bluuebunny/crossref_metadata_2025_split huggingface dataset:
The human preference for symmetric walking often disappears when one leg is constrained
Authors: Browne Michael G. , Smock Cameron S. , Roemmich Ryan T. 
Published: November 2020

Key points
We hypothesized that minimization of metabolic power could drive people to walk asymmetrically when one leg is constrained
We studied healthy young adults and independently constrained one or both step lengths to be markedly shorter or longer than preferred using visual feedback
When one leg was constrained to take a shorter or longer step than preferred, asymmetric walking patterns were less metabolically costly than symmetric walking patterns
When one leg was constrained to take a shorter or longer step than preferred and the other leg was allowed to move freely, most participants naturally adopted an asymmetric gait
People may prefer to walk asymmetrically to minimize metabolic power when the function of one leg is constrained during fixed‐speed treadmill walking
AbstractThe bilateral symmetry inherent in healthy human walking is often disrupted in clinical conditions that primarily affect one leg (e.g. stroke). This seems intuitive: with one leg constrained, gait becomes asymmetric. However, the emergence of asymmetry is not inevitable. Consider that symmetric walking could be preserved by matching the movement of the unconstrained leg to that of the constrained leg. While this is theoretically possible, it is rarely observed in clinical populations. Here, we hypothesized that minimization of metabolic power could drive people to walk asymmetrically when one leg is constrained, even when symmetric walking remains possible. We tested this hypothesis by performing two experiments in healthy adults. In Experiment 1, we constrained one step to be markedly shorter or longer than preferred. We observed that participants could significantly reduce metabolic power by adopting an asymmetric gait (one short/long step, one preferred step) rather than maintaining a symmetric gait (bilateral short/long steps). Indeed, when allowed to walk freely in this situation, participants naturally adopted a less effortful asymmetric gait. In Experiment 2, we applied a milder constraint that more closely approximated magnitudes of step length asymmetry that are observed in clinical populations. Responses in this experiment were more heterogeneous, though most participants adopted an asymmetric gait. These findings support two central conclusions: (1) symmetry is not necessarily energetically optimal in constrained human walking, and (2) people may prefer to walk asymmetrically to minimize metabolic power when one leg is constrained during fixed‐speed treadmill walking, especially when the constraint is large.
The Influence of Sagittal Plane Hip Position on Lower-Extremity Muscle Activity and Torque Output
Authors: Glaviano Neal R. , Bazett-Jones David M. 
Published: November 2020

Context: Hip muscle strength has previously been evaluated in various sagittal plane testing positions. Altering the testing position appears to have an influence on hip muscle torque during hip extension, abduction, and external rotation. However, it is unknown how altering the testing position influences hip muscle activity during these commonly performed assessments. Objectives: To evaluate how hip sagittal plane position influences hip muscle activation and torque output. Study Design: Cross-sectional. Setting: Laboratory. Patients or Other Participants: A total of 22 healthy females (age = 22.1 [1.4] y; mass = 63.4 [11.3] kg; height = 168.4 [6.2] cm) were recruited. Intervention: None. Main Outcome Measures: Participants completed isometric contractions with surface electromyography on the superior and inferior gluteus maximus; anterior, middle, and posterior gluteus medius; biceps femoris, semitendinosus, adductor longus, and tensor fascia latae. Extension and external rotation were tested in 0°, 45°, and 90° of hip flexion and abduction was tested in −5°, 0°, and 45° of hip flexion. Repeated-measures analysis of variances were used for statistical analysis (P ≤ .01). Results: Activation of gluteal (P < .007), semitendinosus (P = .002), and adductor longus (P = .001) muscles were lesser for extension at 90° versus less flexed positions. Adductor longus activity was greatest during 90° of hip flexion for external rotation torque testing (P < .001). Tensor fascia latae (P < .001) and gluteus maximus (P < .001) activities were greater in 45° of hip flexion. Significant differences in extension (P < .001) and abduction (P < .001) torque were found among positions. Conclusions: Position when assessing hip extension and abduction torque has an influence on both muscle activity and torque output but only muscle activity for hip external rotation torque. Clinicians should be aware of the influence of position on hip extension, abduction, and external rotation muscle testing and select a position most in line with their clinical goals.
A 3 b.y. record of a biotic influence on terrestrial weathering
Authors: Beaty Brian J. , Planavsky Noah J. 
Published: November 2020

Abstract
Organic acids secreted by plants and microorganisms are ubiquitous in modern soils. These acids possess a particularly strong binding affinity for aluminum, accelerating its release from mineral surfaces and driving its preferential loss relative to immobile elements such as titanium. Aluminum-titanium (Al-Ti) decoupling in ancient soils may therefore serve as a tracer of a biotic influence on terrestrial weathering in Earth’s past. To explore this idea, we used a mass balance approach to quantify Al mobility in 33 definitive and chronologically well-constrained paleosols spanning the Archean to Miocene. We estimated expected Al release for a given weathering intensity under abiotic conditions using previously established experimental relationships between the relative losses of Al and magnesium (Mg), a mobile element with a much lower organic acid binding affinity. We report Al release likely attributable to organic acid weathering in all paleosols, with net loss in 13, net gain in 16, and a balance between loss and gain in four. This provides a new line of support for a significant terrestrial biosphere as far back as the mid-Archean. Interestingly, there is no statistically significant change in Al mobility across major transitions such as the Great Oxidation Event or the Paleozoic spread of vascular plants. This controversially suggests that localized organic acid weathering, at least within the surface environments captured by the paleosol record, may have been as common on early Earth as it is today.
The role of megacontinents in the supercontinent cycle
Authors: Wang Chong , Mitchell Ross N. , Murphy J. Brendan , Peng Peng , Spencer Christopher J. 
Published: November 2020

Abstract
Supercontinent Pangea was preceded by the formation of Gondwana, a “megacontinent” about half the size of Pangea. There is much debate, however, over what role the assembly of the precursor megacontinent played in the Pangean supercontinent cycle. Here we demonstrate that the past three cycles of supercontinent amalgamation were each preceded by ∼200 m.y. by the assembly of a megacontinent akin to Gondwana, and that the building of a megacontinent is a geodynamically important precursor to supercontinent amalgamation. The recent assembly of Eurasia is considered as a fourth megacontinent associated with future supercontinent Amasia. We use constraints from seismology of the deep mantle for Eurasia and paleogeography for Gondwana to develop a geodynamic model for megacontinent assembly and subsequent supercontinent amalgamation. As a supercontinent breaks up, a megacontinent assembles along the subduction girdle that encircled it, at a specific location where the downwelling is most intense. The megacontinent then migrates along the girdle where it collides with other continents to form a supercontinent. The geometry of this model is consistent with the kinematic transitions from Rodinia to Gondwana to Pangea.
Can we relate the surface expression of dike-induced normal faults to subsurface dike geometry?
Authors: Magee Craig , Jackson Christopher A.-L. 
Published: November 2020

AbstractMany igneous dikes do not reach the surface, instead triggering normal faulting and graben formation in overlying rock. The surface expression of these dike-induced faults provides important records of active and ancient diking. For example, surface measurements of graben half-widths have been used to estimate dike upper-tip depths by projecting faults straight downdip, whereas extension measured at the surface across dike-induced fault pairs (i.e., their cumulative heave) is considered a proxy for dike thickness. We use three-dimensional seismic reflection data to test how the surface expression of two buried dike-induced faults relates to dike geometry. The dike-induced faults are nonplanar, suggesting fault dips should not be assumed constant when using graben half-widths to estimate dike depth. Multiple displacement maxima occur across the dike-induced faults, but rarely at their lower or upper tips, suggesting they formed through linkage of isolated faults that nucleated between the dike and free surface. Fault heave is greatest where these subsurface displacement maxima occur, meaning the cumulative heave of the dike-induced fault pair measured at the syn-faulting free surface underestimates their total extension and poorly reflects dike thickness. Our results imply that at-surface analyses of dike-induced fault geometry cannot be used to estimate key dike parameters without a priori knowledge of fault structure and kinematics or host rock lithological variations.
Association between neuraxial anaesthesia or general anaesthesia for lower limb revascularisation surgery in adults and clinical outcomes: population based comparative effectiveness study
Authors: Roberts Derek J , Nagpal Sudhir K , Kubelik Dalibor , Brandys Timothy , Stelfox Henry T , Lalu Manoj M , Forster Alan J , McCartney Colin JL , McIsaac Daniel I 
Published: November 2020

Abstract

Objective
To examine the associations between neuraxial anaesthesia or general anaesthesia and clinical outcomes, length of hospital stay, and readmission in adults undergoing lower limb revascularisation surgery.

Design
Comparative effectiveness study using linked, validated, population based databases.

Setting
Ontario, Canada, 1 April 2002 to 31 March 2015.

Participants
20 988 patients Ontario residents aged 18 years or older who underwent their first lower limb revascularisation surgery in hospitals performing 50 or more of these surgeries annually.

Main outcome measures
Primary outcome was 30 day all cause mortality. Secondary outcomes were in-hospital cardiopulmonary and renal complications, length of hospital stay, and 30 day readmissions. Multivariable, mixed effects regression models, adjusting for patient, procedural, and hospital characteristics, were used to estimate associations between anaesthetic technique and outcomes. Robustness of analyses were evaluated by conducting instrumental variable, propensity score matched, and survival sensitivity analyses.

Results
Of 20 988 patients who underwent lower limb revascularisation surgery, 6453 (30.7%) received neuraxial anaesthesia and 14 535 (69.3%) received general anaesthesia. The percentage of neuraxial anaesthesia use ranged from 0.6% to 90.6% across included hospitals. Furthermore, use of neuraxial anaesthesia declined by 17% over the study period. Death within 30 days occurred in 204 (3.2%) patients who received neuraxial anaesthesia and 646 (4.4%) patients who received general anaesthesia. After multivariable, multilevel adjustment, use of neuraxial anaesthesia compared with use of general anaesthesia was associated with decreased 30 day mortality (absolute risk reduction 0.72%, 95% confidence interval 0.65% to 0.79%; odds ratio 0.68, 95% confidence interval 0.57 to 0.83; number needed to treat to prevent one death=139). A similar direction and magnitude of association was found in instrumental variable, propensity score matched, and survival analyses. Use of neuraxial anaesthesia compared with use of general anaesthesia was also associated with decreased in-hospital cardiopulmonary and renal complications (odds ratio 0.73, 0.63 to 0.85) and a reduced length of hospital stay (−0.5 days, −0.3 to−0.6 days).

Conclusions
Use of neuraxial anaesthesia compared with general anaesthesia for lower limb revascularisation surgery was associated with decreased 30 day mortality and hospital length of stay. These findings might have been related to reduced cardiopulmonary and renal complications after neuraxial anaesthesia and support the increased use of neuraxial anaesthesia in patients undergoing these surgeries until the results of a large, confirmatory randomised trial become available.
SMART Vaccines 2.0 decision-support platform: a tool to facilitate and promote priority setting for sustainable vaccination in resource-limited settings
Authors: McCormick Benjamin J J , Waiswa Peter , Nalwadda Celia , Sewankambo Nelson K , Knobler Stacey L 
Published: November 2020

In resource-constrained environments, priority setting is critical to making sustainable decisions for introducing new and underused vaccines and choosing among vaccine products. Donor organisations and national governments in low-income and middle-income countries (LMICs) recognise the need to support prioritisation of vaccine decisions driven by local health system capacity, epidemiology and financial sustainability.Successful efforts have supported the establishment of National Immunisation Technical Advisory Groups (NITAGs) to undertake evidence-informed decision making (EIDM) in LMICs. Now, attention is increasingly focused on supporting their function to leverage local expertise and priorities. EIDM and priority-setting functions are complex and dynamic processes. Here, we report a pilot of a web-based decision-support tool. Applying tenets of multicriteria decision analysis, SMART Vaccines 2.0 supported transparent, reproducible and evidence-informed priority setting with an easy-to-use interface and shareable outputs.The pilot was run by the Uganda NITAG who were requested by the Ministry of Health (MOH) in 2016 to produce recommendations on the prioritised introduction of five new vaccines. The tool was acceptable to the NITAG and supported their recommendations to the MOH. The tool highlighted sensitivity in the prioritisation process to the inherent biases of different stakeholders. This feature also enabled examination of the implications of data uncertainty. Feedback from users identified areas where the tool could more explicitly support evidence-to-recommendation frameworks, ultimately informing the next generation of the platform, PriorityVax.Country ownership and priority setting in vaccine decisions are central to sustainability. PriorityVax promotes auditable and rigorous deliberations; enables and captures the decision matrix of users; and generates shareable documentation of the process.
Relative contributions of family history and a polygenic risk score on COPD and related outcomes: COPDGene and ECLIPSE studies
Authors: Moll Matthew , Lutz Sharon M. , Ghosh Auyon J. , Sakornsakolpat Phuwanat , Hersh Craig P. , Beaty Terri H. , Dudbridge Frank , Tobin Martin D. , Mittleman Murray A. , Silverman Edwin K. , Hobbs Brian D. , Cho Michael H. 
Published: November 2020

IntroductionFamily history is a risk factor for chronic obstructive pulmonary disease (COPD). We previously developed a COPD risk score from genome-wide genetic markers (Polygenic Risk Score, PRS). Whether the PRS and family history provide complementary or redundant information for predicting COPD and related outcomes is unknown.MethodsWe assessed the predictive capacity of family history and PRS on COPD and COPD-related outcomes in non-Hispanic white (NHW) and African American (AA) subjects from COPDGene and ECLIPSE studies. We also performed interaction and mediation analyses.ResultsIn COPDGene, family history and PRS were significantly associated with COPD in a single model (PFamHx<0.0001; PPRS<0.0001). Similar trends were seen in ECLIPSE. The area under the receiver operator characteristic curve for a model containing family history and PRS was significantly higher than a model with PRS (p=0.00035) in NHWs and a model with family history (p<0.0001) alone in NHWs and AAs. Both family history and PRS were significantly associated with measures of quantitative emphysema and airway thickness. There was a weakly positive interaction between family history and the PRS under the additive, but not multiplicative scale in NHWs (relative excess risk due to interaction=0.48, p=0.04). Mediation analyses found that a significant proportion of the effect of family history on COPD was mediated through PRS in NHWs (16.5%, 95% CI 9.4% to 24.3%), but not AAs.ConclusionFamily history and the PRS provide complementary information for predicting COPD and related outcomes. Future studies can address the impact of obtaining both measures in clinical practice.
NAIL: an evolutionarily conserved lncRNA essential for licensing coordinated activation of p38 and NFκB in colitis
Authors: Akıncılar Semih Can , Wu Lele , NG Qin Feng , Chua Joelle Yi Heng , Unal Bilal , Noda Taichi , Chor Wei Hong Jeff , Ikawa Masahito , Tergaonkar Vinay 
Published: November 2020

ObjectiveNFκB is the key modulator in inflammatory disorders. However, the key regulators that activate, fine-tune or shut off NFκB activity in inflammatory conditions are poorly understood. In this study, we aim to investigate the roles that NFκB-specific long non-coding RNAs (lncRNAs) play in regulating inflammatory networks.DesignUsing the first genetic-screen to identify NFκB-specific lncRNAs, we performed RNA-seq from thep65-/-andIkkβ-/-mouse embryonic fibroblasts and report the identification of an evolutionary conserved lncRNA designatedmNAIL(mice) orhNAIL(human).hNAILis upregulated in human inflammatory disorders, including UC. We generatedmNAILΔNFκBmice, wherein deletion of two NFκB sites in the proximal promoter ofmNAILabolishes its induction, to study its function in colitis.ResultsNAILregulates inflammation via sequestering and inactivating Wip1, a known negative regulator of proinflammatory p38 kinase and NFκB subunit p65. Wip1 inactivation leads to coordinated activation of p38 and covalent modifications of NFκB, essential for its genome-wide occupancy on specific targets.NAILenables an orchestrated response for p38 and NFκB coactivation that leads to differentiation of precursor cells into immature myeloid cells in bone marrow, recruitment of macrophages to inflamed area and expression of inflammatory genes in colitis.ConclusionNAILdirectly regulates initiation and progression of colitis and its expression is highly correlated with NFκB activity which makes it a perfect candidate to serve as a biomarker and a therapeutic target for IBD and other inflammation-associated diseases.
Preclinical platform for long-term evaluation of immuno-oncology drugs using hCD34+ humanized mouse model
Authors: Park Nahee , Pandey Kamal , Chang Sei Kyung , Kwon Ah-Young , Cho Young Bin , Hur Jin , Katwal Nar Bahadur , Kim Seung Ki , Lee Seung Ah , Son Gun Woo , Jo Jong Min , Ahn Hee Jung , Moon Yong Wha 
Published: November 2020

BackgroundWell-characterized preclinical models are essential for immune-oncology research. We investigated the feasibility of our humanized mouse model for evaluating the long-term efficacy of immunotherapy and biomarkers.MethodsHumanized mice were generated by injecting human fetal cord blood-derived CD34+ hematopoietic stem cells to NOD-scid IL2rγnull (NSG) mice myeloablated with irradiation or busulfan. The humanization success was defined as a 25% or higher ratio of human CD45+ cells to mice peripheral blood mononuclear cells.ResultsBusulfan was ultimately selected as the appropriate myeloablative method because it provided a higher success rate of humanization (approximately 80%) and longer survival time (45 weeks). We proved the development of functional T cells by demonstrating the anticancer effect of the programmed cell death-1 (PD-1) inhibitor in our humanized mice but not in non-humanized NSG mice. After confirming the long-lasting humanization state (45 weeks), we further investigated the response durability of the PD-1 inhibitor and biomarkers in our humanized mice. Early increase in serum tumor necrosis factor α levels, late increase in serum interleukin 6 levels and increase in tumor-infiltrating CD8+ T lymphocytes correlated more with a durable response over 60 days than with a non-durable response.ConclusionsOur CD34+ humanized mouse model is the first in vivo platform for testing the long-term efficacy of anticancer immunotherapies and biomarkers, given that none of the preclinical models has ever been evaluated for such a long duration.
Plaque morphology in acute symptomatic intracranial atherosclerotic disease
Authors: Leung Thomas W , Wang Li , Zou Xinying , Soo Yannie , Pu Yuehua , Ip Hing Lung , Chan Anne , Au Lisa Wing Chi , Fan Florence , Ma Sze Ho , Ip Bonaventure , Ma Karen , Lau Alexander Yuk-lun , Leung Howan , Hui Kwok Fai , Li Richard , Li Siu Hung , Fu Michael , Fong Wing Chi , Liu Jia , Mok Vincent , Wong Ka Sing Lawrence , Miao Zhongrong , Ma Ning , Yu Simon C H , Leng Xinyi 
Published: November 2020

BackgroundIntracranial atherosclerotic disease (ICAD) is globally a major ischaemic stroke subtype with high recurrence. Understanding the morphology of symptomatic ICAD plaques, largely unknown by far, may help identify vulnerable lesions prone to relapse.MethodsWe prospectively recruited patients with acute ischaemic stroke or transient ischaemic attack attributed to high-grade ICAD (60%–99% stenosis). Plaque morphological parameters were assessed in three-dimensional rotational angiography, including surface contour, luminal stenosis, plaque length/thickness, upstream shoulder angulation, axial/longitudinal plaque distribution and presence of adjoining branch atheromatous disease (BAD). We compared morphological features of smooth, irregular and ulcerative plaques and correlated them with cerebral ischaemic lesion load downstream in MRI.ResultsAmong 180 recruited patients (median age=60 years; 63.3% male; median stenosis=75%), plaque contour was smooth (51 (28.3%)), irregular (101 (56.1%)) or ulcerative (28 (15.6%)). Surface ulcers were mostly at proximal (46.4%) and middle one-third (35.7%) of the lesions. Most (84.4%) plaques were eccentric, and half had their maximum thickness over the distal end. Ulcerative lesions were thicker (medians 1.6 vs 1.3 mm; p=0.003), had steeper upstream shoulder angulation (56.2° vs 31.0°; p<0.001) and more adjoining BAD (83.3% vs 57.0%; p=0.033) than non-ulcerative plaques. Ulcerative plaques were significantly associated with coexisting acute and chronic infarcts downstream (35.7% vs 12.5%; adjusted OR 4.29, 95% CI 1.65 to 11.14, p=0.003). Sensitivity analyses in patients with anterior-circulation ICAD lesions showed similar results in the associations between the plaque types and infarct load.ConclusionsUlcerative intracranial atherosclerotic plaques were associated with vulnerable morphological features and had a higher cumulative infarct load downstream.