bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reopening Interventional Pain Practices during the Early Phase of the COVID-19 Global Pandemic
Authors: Huynh Lisa , Chang Richard G , Chhatre Akhil , Sayeed Yusef , MacVicar John , McCormick Zachary L , Duszynski Belinda , Smith Clark 
Published: January 2021

Abstract

Objective
Examine how interventional pain physicians navigated the early phase of reopening practices during the coronavirus disease 2019 (COVID-19) pandemic.

Methods
In June/July 2020, Spine Intervention Society members were queried about practice demographics, perception of COVID-19 prevalence, financial impact, and implementation of new tools and procedures when re-opening practices.

Results
Of the 2,295 members approached, 195 (8%) completed the survey. A majority (71%) reported using risk stratification tools and changing scheduling patterns. Nearly 70% performed initial assessments via telehealth and 87% for follow-up encounters. More than 80% performed symptom/temperature checks upon in-person clinic/facility entrance, and 63% screened patients via phone. Most (58%) did not test patients for COVID-19 for office visits, while 38% tested only if symptomatic. For epidural injections, intra-articular injections, and radiofrequency neurotomy procedures, 43% reported not testing patients, while 36% tested patients only if symptomatic. Most (70%) required patients to wear a mask upon entering the clinic/facility. For nonprocedure encounters, respondents used surgical masks (85%), gloves (35%), face shields/goggles (24%), N95 respirators (15%), and gowns (6%). Some (66%) discussed unique COVID-19 risks/complications and 26% provided written information. Most did not make changes to steroid dosage (67%) or peri-procedural anticoagulation management (97%). The vast majority (81%) estimated that COVID-19 will have a moderate-severe financial impact on their practice.

Conclusions
COVID-19 has dramatically affected interventional pain practices with regard to telehealth, in-clinic precautions, screening/testing protocols, and patient counseling. Practice patterns will continue to evolve as we learn more about the disease and improve methods to provide safe and effective care.
Using 3-Dimensional Motion Analysis to Optimize Treatment Planning for a Patient With Dropfoot: Case Report
Authors: Feng Jing , Bompiani Erin , Coats Scott , Patrick Do K , Aiona Michael 
Published: January 2021

Abstract

Objective
This study demonstrated the use of computerized motion analysis to assist in evidence-based clinical decision-making.

Case Description
A 15-year-old girl who had right hemiparesis after a stroke was referred for 3-dimensional computerized motion analysis to determine the effect of 3 devices intended to control her dropfoot and to assist in developing a treatment plan. Four conditions were tested and compared: barefoot, lateral support ankle brace, functional electrical stimulation (FES) device, and dropfoot cuff.

Results
Kinematics showed the right ankle had significant dropfoot during swing phase (32.7 degrees of plantarflexion at terminal swing) in barefoot. The lateral support ankle brace, FES device, and dropfoot cuff reduced terminal swing plantarflexion to 27.2 degrees, 17.6 degrees, and 15.3 degrees, respectively, though ankle kinematics remained abnormal because of inadequate dorsiflexion. Improvements in gait variable score with FES (−8.2 degrees) or dropfoot cuff (−8.7 degrees) were significantly more than that with the lateral support brace (−2.2 degrees), and the difference in gait variable score between FES and dropfoot cuff was insignificant. Compared with the barefoot condition, the lateral support brace condition did not show a clinically significant difference in gait profile score; however, the gait profile scores of both FES and dropfoot cuff conditions showed clinically significant improvement (−1.7 degrees and −2.1 degrees, respectively).

Conclusion
Objective data delineated subtle changes among 3 devices and led to the recommendation to discontinue the lateral support ankle brace, continue using her night ankle-foot orthosis and FES device, with the dropfoot cuff as a backup when she feels leg fatigue or skin irritation, and consider serial casting or surgical calf lengthening.

Impact
Computerized motion analysis provides quantitative evaluation of subtle differences in the effect of braces with different designs, which are hard for the human eye to discern. The objective data inform and validate treatment decision-making. The recommendations were made as a result of evidence-based practice.
THE UNIFIED INTERACTION MODEL: SIMULATIONS OF TL DOSE RESPONSE AND EXPERIMENTAL VERIFICATION OF INTENDED DOSE RESPONSE LINEARITY BY POSTIRRADIATION PHOTON EXCITATION
Authors: Ginzburg Dimitry , Oster Leonid , Biderman Shlomo , Reshes Galina , Eliyahu Ilan 
Published: January 2021

Abstract
The Unified Interaction Model (UNIM) simulates the linear/supralinear dose response of the glow peaks of LiF:Mg,Ti (TLD-100) and other thermoluminescent materials and the dependence of the supralinearity on photon/electron energy. The UNIM is based on the radiation action of spatially correlated trapping centres (TCs) and luminescent centres (LCs), which results in localised (geminate) electron/hole recombination by quantum mechanical tunnelling. The linear dose response is mainly attributed to geminate recombination. UNIM simulations of the dose response of glow peak 5 in LiF:Mg,Ti following 500 and 8 keV electron/photon irradiation are discussed. In addition, simulations of postirradiation photo-excitation that redistribute the electrons and holes in the various TCs and LCs are demonstrated to extend the region of linear dose response and reduce the supralinearity. Experimental verification of dose–response linearity for levels of dose ≤30 Gy following both 3.65 and 5 eV photon excitation is presented.
Dynamics of above- and belowground responses of silver birch saplings and soil gases to soil freezing and waterlogging during dormancy
Authors: Repo Tapani , Domisch Timo , Roitto Marja , Kilpeläinen Jouni , Wang Ai-Fang , Piirainen Sirpa , Heiskanen Juha , Makita Naoki , Lehto Tarja , Sutinen Sirkka 
Published: January 2021

Abstract
Winter precipitation and soil freeze–thaw events have been predicted to increase in boreal regions with climate change. This may expose tree roots to waterlogging (WL) and soil freezing (Fr) more than in the current climate and therefore affect tree growth and survival. Using a whole-tree approach, we studied the responses of silver birch (Betula pendula Roth.) saplings, growing in mineral soil, to 6-week Fr and WL in factorial combinations during dormancy, with accompanying changes in soil gas concentrations.
Physiological activation (dark-acclimated chlorophyll fluorescence and chlorophyll content index) and growth of leaves and shoot elongation and stem diameter growth started earlier in Fr than NoFr (soil not frozen). The starch content of leaves was temporarily higher in Fr than NoFr in the latter part of the growing season. Short and long root production and longevity decreased, and mortality increased by soil Fr, while there were no significant effects of WL. Increased fine root damage was followed by increased compensatory root growth. At the beginning of the growing season, stem sap flow increased fastest in Fr + WL, with some delay in both NoWL (without WL) treatments. At the end of the follow-up growing season, the hydraulic conductance and impedance loss factor of roots were higher in Fr than in NoFr, but there were no differences in above- and belowground biomasses. The concentration of soil carbon dioxide increased and methane decreased by soil Fr at the end of dormancy. At the beginning of the growing season, the concentration of nitrous oxide was higher in WL than in NoWL and higher in Fr than in NoFr. In general, soil Fr had more consistent effects on soil greenhouse gas concentrations than WL. To conclude, winter-time WL alone is not as harmful for roots as WL during the growing season.
Pollination promotes ABA synthesis but not sexual reproduction in the apomictic speciesZanthoxylum bungeanumMaxim.
Authors: Fei Xitong , Shi Qianqian , Lei Yu , Wang Shujie , Qi Yichen , Hu Haichao , Wei Anzhi 
Published: January 2021

AbstractApomixis is a form of reproduction that does not involve the fertilization of female gametes by male gametes but instead involves the production of offspring directly from the female parent. The offspring of apomixis are genetically identical to the female parent and inherit its traits. Therefore, apomixis has great potential for application to agricultural genetic breeding. However, it remains unclear whether apomictic species require pollination, and the impacts of pollination on such species are poorly understood. We investigated the effects of pollination on the apomictic species Zanthoxylum bungeanum Maxim. by analyzing its fertilization process, assembling its transcriptome, and measuring hormone concentrations, fruit setting rate and gene expression levels. Transcriptome sequencing of pollinated and unpollinated fruits resulted in a total of 69,131 PacBio reads. Of these, 7102 genes were up-regulated and 6491 genes were down-regulated. Analysis of the differentially expressed genes (DEGs) and construction of a weighted gene co-expression network showed that many DEGs were involved in plant hormone signal transduction, suggesting that hormonal signaling during development differs between pollinated and unpollinated fruit. The germination rate of Z. bungeanum pollen in vitro was only 11%, and pollen could not germinate in the embryo sac to complete fertilization. Although pollination did not enable Z. bungeanum to complete the sexual reproduction process, it significantly increased abscisic acid (ABA) concentration and fruit setting rate. Spraying 100 μg l−1 ABA also significantly increased the fruit setting rate. Therefore, ABA appears to be a key factor in the regulation of fruit setting in apomictic Z. bungeanum. Based on these results, we suggest that some male plants be cultivated in Z. bungeanum plantations or exogenous ABA be sprayed to increase the likelihood of pollination and thereby increase the fruit setting rate.
Prediction of individuals at high-risk of chronic kidney disease during treatment with lithium for bipolar disorder
Authors: Hayes Joseph F , Osborn David PJ , Francis Emma , Ambler Gareth , Tomlinson Laurie A , Boman Magnus , Wong Ian , Geddes John , Dalman Christina , Lewis Glyn 
Published: January 2021

AbstractBackgroundLithium is the most effective treatment in bipolar disorder. Its use is limited by concerns about risk of chronic kidney disease (CKD). We aimed to develop a model to predict risk of CKD following lithium treatment initiation, by identifying individuals with a high-risk trajectory of renal function.MethodsWe used United Kingdom Clinical Practice Research Datalink (CPRD) electronic heath records (EHRs) from 2000-2018. CPRD Aurum for prediction model development and CPRD Gold for external validation. We used elastic net to generate a prediction model from potential features. We performed discrimination and calibration assessments in an external validation data set.We included all patients aged ≥16 with bipolar disorder prescribed lithium. To be included patients had to have ≥1 year of follow-up before lithium initiation, ≥3 estimated glomerular filtration rate (eGFR) measures after lithium initiation (to be able to determine a trajectory) and a normal (≥60 mL/min/1.73m2) eGFR at lithium initiation (baseline). In the Aurum development cohort 1609 fulfilled these criteria. The Gold external validation cohort included 934 patients.We included 44 potential baseline features in the prediction model, including sociodemographic, mental and physical heath and drug treatment characteristics. We compared a full model with the 3-variable five-year kidney failure risk equation (KFRE) and a 3-variable elastic net model.We used group-based trajectory modelling to identify latent trajectory groups for eGFR. We were interested in the group with deteriorating renal function (the high-risk group).FindingsThe high-risk group included 191 (11.87%) of the Aurum cohort and 137 (14.67%) of the Gold cohort, of these 168 (87.96%) and 117 (85.40%) respectively developed CKD 3a or more severe during follow-up. The model, developed in Aurum, had a ROC area of 0.879 (95%CI 0.853-0.904) in the Gold external validation data set. At the empirical optimal cut-point defined in the development dataset, the model had a sensitivity of 0. 91 (95%CI 0.84-0.97) and a specificity of 0.74 (95% CI 0.67-0.82). However, a 3-variable elastic net model (including only age, sex and baseline eGFR) performed similarly well (ROC area 0.888; 95%CI 0.864-0.912), as did the KFRE (ROC area 0.870; 95%CI 0.841-0.898).ConclusionsIndividuals at high-risk of a poor trajectory of renal function can be identified before initiation of lithium treatment by a simple equation including age, sex and baseline eGFR. We did not identify strong predicters of renal impairment specific to lithium treated patients.
Agonistic CD40 antibody therapy induces tertiary lymphoid structures but impairs the response to immune checkpoint blockade in glioma
Authors: van Hooren Luuk , Vaccaro Alessandra , Ramachandran Mohanraj , Vazaios Konstantinos , Libard Sylwia , van de Walle Tiarne , Georganaki Maria , Huang Hua , Pietilä Ilkka , Lau Joey , Ulvmar Maria H. , Karlsson Mikael C.I. , Zetterling Maria , Mangsbo Sara M. , Jakola Asgeir S. , Bontell Thomas Olsson , Smits Anja , Essand Magnus , Dimberg Anna 
Published: January 2021

AbstractGliomas are brain tumors characterized by immunosuppression. Immunostimulatory agonistic CD40 antibodies (αCD40) are in clinical development for solid tumors but are yet to be evaluated for glioma. Here, systemic delivery of αCD40 led to cytotoxic T cell dysfunction and impaired the response to immune checkpoint inhibitors in preclinical glioma models. This was associated with an accumulation of suppressive CD11b+B cells. However, αCD40 also induced tertiary lymphoid structures (TLS). In human glioma, TLS correlated with increased T cell infiltration indicating enhanced immune responses. Our work unveils the pleiotropic effects of αCD40 therapy in glioma, which is of high clinical relevance.
RASSF1C oncogene elicits amoeboid invasion, cancer stemness and invasive EVs via a novel SRC/Rho axis
Authors: Tognoli Maria Laura , Vlahov Nikola , Steenbeek Sander , Grawenda Anna M. , Eyres Michael , Cano-Rodriguez David , Scrace Simon , Kartsonaki Christiana , von Kriegsheim Alex , Willms Eduard , Wood Matthew J. , Rots Marianne G. , van Rheenen Jacco , O’Neill Eric , Pankova Daniela 
Published: January 2021

AbstractCell plasticity is a crucial hallmark leading to cancer metastasis. Upregulation of Rho/ROCK pathway drives actomyosin contractility, protrusive forces and contributes to the occurrence of highly invasive amoeboid cells in tumors. Cancer stem cells are similarly associated with metastasis, but how these populations arise in tumors is not fully understood. Here we show that the novel oncogene RASSF1C drives mesenchymal to amoeboid transition and stem cell attributes in breast cancer cells. Mechanistically, RASSF1C activates Rho/ROCK via SRC mediated RhoGDI inhibition, resulting in generation of actomyosin contractility. Moreover, we demonstrate that amoeboid cells display the cancer stem cell markers CD133, ALDH1 and the pluripotent marker Nanog; are accompanied by higher invasive potentialin vitroandin vivo;and employ extracellular vesicles to transfer the invasive phenotype to target cells and tissue. Importantly, the underlying RASSF1C driven biological processes concur to explain clinical data: namely, methylation of the RASSF1C promoter correlates with better survival in early stage breast cancer patients. Therefore, we propose the use ofRASSF1gene promoter methylation status as a biomarker for patient stratification.
Increased sensitivity to strong perturbations in a whole-brain model of LSD
Authors: Jobst Beatrice M. , Atasoy Selen , Ponce-Alvarez Adrián , Sanjuán Ana , Roseman Leor , Kaelen Mendel , Carhat-Harris Robin , Kringelbach Morten L. , Deco Gustavo 
Published: January 2021

AbstractLysergic acid diethylamide (LSD) is a potent psychedelic drug, which has seen a revival in clinical and pharmacological research within recent years. Human neuroimaging studies have shown fundamental changes in brain-wide functional connectivity and an expansion of dynamical brain states, thus raising the question about a mechanistic explanation of the dynamics underlying these alterations. Here, we applied a novel perturbational approach based on a whole-brain computational model, which opens up the possibility to externally perturb different brain regions in silico and investigate differences in dynamical stability of different brain states, i.e. the dynamical response of a certain brain region to an external perturbation. After adjusting the whole-brain model parameters to reflect the dynamics of functional magnetic resonance imaging (fMRI) BOLD signals recorded under the influence of LSD or placebo, perturbations of different brain areas were simulated by either promoting or disrupting synchronization in the regarding brain region. After perturbation offset, we quantified the recovery characteristics of the brain area to its basal dynamical state with the Perturbational Integration Latency Index (PILI) and used this measure to distinguish between the two brain states. We found significant changes in dynamical complexity with consistently higher PILI values after LSD intake on a global level, which indicates a shift of the brain’s global working point further away from a stable equilibrium as compared to normal conditions. On a local level, we found that the largest differences were measured within the limbic network, the visual network and the default mode network. Additionally, we found a higher variability of PILI values across different brain regions after LSD intake, indicating higher response diversity under LSD after an external perturbation. Our results provide important new insights into the brain-wide dynamical changes underlying the psychedelic state - here provoked by LSD intake - and underline possible future clinical applications of psychedelic drugs in particular psychiatric disorders.HighlightsNovel offline perturbational method applied on functional magnetic resonance imaging (fMRI) data under the effect of lysergic acid diethylamide (LSD)Shift of brain’s global working point to more complex dynamics after LSD intakeConsistently longer recovery time after model perturbation under LSD influenceStrongest effects in resting state networks relevant for psychedelic experienceHigher response diversity across brain regions under LSD influence after an external in silico perturbation
COVID-19 virtual patient cohort reveals immune mechanisms driving disease outcomes
Authors: Jenner Adrianne L. , Aogo Rosemary A. , Alfonso Sofia , Crowe Vivienne , Smith Amanda P. , Morel Penelope A. , Davis Courtney L. , Smith Amber M. , Craig Morgan 
Published: January 2021

AbstractTo understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results indicate that virtual patients with low production rates of infected cell derived IFN subsequently experienced highly inflammatory disease phenotypes, compared to those with early and robust IFN responses. In thesein silicopatients, the maximum concentration of IL-6 was also a major predictor of CD8+T cell depletion. Our analyses predicted that individuals with severe COVID-19 also have accelerated monocyte-to-macrophage differentiation that was mediated by increased IL-6 and reduced type I IFN signalling. Together, these findings identify biomarkers driving the development of severe COVID-19 and support early interventions aimed at reducing inflammation.Author summaryUnderstanding of how the immune system responds to SARS-CoV-2 infections is critical for improving diagnostic and treatment approaches. Identifying which immune mechanisms lead to divergent outcomes can be clinically difficult, and experimental models and longitudinal data are only beginning to emerge. In response, we developed a mechanistic, mathematical and computational model of the immunopathology of COVID-19 calibrated to and validated against a broad set of experimental and clinical immunological data. To study the drivers of severe COVID-19, we used our model to expand a cohort of virtual patients, each with realistic disease dynamics. Our results identify key processes that regulate the immune response to SARS-CoV-2 infection in virtual patients and suggest viable therapeutic targets, underlining the importance of a rational approach to studying novel pathogens using intra-host models.
Quantification of fast molecular adhesion by fluorescence footprinting
Authors: Yasunaga Adam B. , Li Isaac T.S. 
Published: January 2021

AbstractRolling adhesion is a unique process in which the adhesion events are short-lived and operate under highly non-equilibrium conditions. These characteristics pose a challenge in molecular force quantification, wherein situmeasurement of such forces cannot be achieved with most molecular force sensors that probe near equilibrium. In this report, we demonstrated a quantitative adhesion footprint assay combining DNA-based non-equilibrium force probes and modelling to measure the molecular force involved in fast rolling adhesion. We were able to directly profile the ensemble molecular force distribution during rolling adhesion with a dynamic range between 0 – 18 pN. Our results showed that the shear stress driving bead rolling motility directly controls the molecular tension on the probe-conjugated adhesion complex. Furthermore, the shear stress can steer the dissociation bias of components within the molecular force probe complex, favouring either DNA probe dissociation or receptor-ligand dissociation.
Kinetic and structural mechanism for DNA unwinding by a non-hexameric helicase
Authors: Carney Sean P. , Ma Wen , Whitley Kevin D. , Jia Haifeng , Lohman Timothy M. , Luthey-Schulten Zaida , Chemla Yann R. 
Published: January 2021

AbstractUvrD, a model for non-hexameric Superfamily 1 helicases, utilizes ATP hydrolysis to translocate stepwise along single-stranded DNA and unwind the duplex. To dissect the mechanism underlying DNA unwinding, we use optical tweezers to measure directly the stepping behavior of UvrD as it processes a DNA hairpin and show that UvrD exhibits a variable step size averaging ~3 base pairs. Analyzing stepping kinetics across ATP reveals the type and number of catalytic events that occur with different step sizes. These single-molecule data reveal a mechanism in which UvrD moves one base pair at a time but sequesters the nascent single strands, releasing them non-uniformly after a variable number of catalytic cycles. Molecular dynamics simulations point to a structural basis for this behavior, identifying the protein-DNA interactions responsible for strand sequestration. Based on structural and sequence alignment data, we propose that this stepping mechanism may be conserved among other non-hexameric helicases.