bluuebunny/crossref_metadata_2025_split huggingface dataset:
The expanding world of tissue‐resident macrophages
Authors: Jenkins Stephen J. , Allen Judith E. 
Published: June 2021

AbstractThe term ‘macrophage’ encompasses tissue cells that typically share dependence on the same transcriptional regulatory pathways (e.g. the transcription factor PU.1) and growth factors (e.g. CSF1/IL‐34). They share a core set of functions that largely arise from a uniquely high phagocytic capacity manifest in their ability to clear dying cells, pathogens and scavenge damaged, toxic or modified host molecules. However, macrophages demonstrate a remarkable degree of tissue‐specific functionality and have diverse origins that vary by tissue site and inflammation status. With our understanding of this diversity has come an appreciation of the longevity and replicative capacity of tissue‐resident macrophages and thus the realisation that macrophages may persist through tissue perturbations and inflammatory events with important consequences for cell function. Here, we discuss our current understanding of the parameters that regulate macrophage survival and function, focusing on the relative importance of the tissue environment versus cell‐intrinsic factors, such as origin, how long a cell has been resident within a tissue and prior history of activation. Thus, we reconsider the view of macrophages as wholly plastic cells and raise many unanswered questions about the relative importance of cell life‐history versus environment in macrophage programming and function.
Mechanism of action of PD‐1 receptor/ligand targeted cancer immunotherapy
Authors: Borst Jannie , Busselaar Julia , Bosma Douwe M. T. , Ossendorp Ferry 
Published: June 2021

AbstractImmunotherapy targeting the Programmed Death (PD‐1) receptor/ligand (L) “checkpoint” rapidly gains ground in the treatment of many cancer types. To increase treatment scope and efficacy, predictive biomarkers and rational selection of co‐treatments are required. To meet these demands, we must understand PD‐1 function in detail. We here outline recent insights into the regulation of the CD8+ T cell response by PD‐1. The prevailing view has been that blockade of PD‐1/ligand (L) interaction “reinvigorates” cytotoxic T lymphocytes (CTL) that were rendered dysfunctional in the tumor microenvironment (TME). However, this review stresses that tumors continuously communicate with adjacent draining lymph nodes (LNs) and that the PD‐1 checkpoint also operates during T cell priming. We clarify the role of the PD‐(L)1 system at the T cell/DC interface, where it regulates T cell receptor (TCR) signaling and CD28 costimulation and thus controls activation of tumor‐specific T cells. We also highlight the importance of CD4+ T cell help during priming, which allows DCs to provide other costimulatory and cytokine signals required for optimal CTL differentiation and likely avoidance of a dysfunctional state. Therefore, we pose that PD‐(L)1 blockade should exploit LN function and be combined with “help” signals to optimize CTL efficacy.
Deletion of TLR2+ erythro‐myeloid progenitors leads to embryonic lethality in mice
Authors: Splichalova Iva , Balounová Jana , Vobořil Matouš , Brabec Tomas , Sedlacek Radislav , Filipp Dominik 
Published: June 2021

AbstractEarly embryonic hematopoiesis in mammals is defined by three successive waves of hematopoietic progenitors which exhibit a distinct hematopoietic potential and provide continuous support for the development of the embryo and adult organism. Although the functional importance of each of these waves has been analyzed, their spatio‐temporal overlap and the lack of wave‐specific markers hinders the accurate separation and assessment of their functional roles during early embryogenesis. We have recently shown that TLR2, in combination with c‐kit, represents the earliest signature of emerging precursors of the second hematopoietic wave, erythro‐myeloid precursors (EMPs). Since the onset of Tlr2 expression distinguishes EMPs from primitive progenitors which coexist in the yolk sac from E7.5, we generated a novel transgenic “knock in” mouse model, Tlr2Dtr , suitable for inducible targeted depletion of TLR2+ EMPs. In this model, the red fluorescent protein and diphtheria toxin receptor sequences are linked via a P2A sequence and inserted into the Tlr2 locus before its stop codon. We show that a timely controlled deletion of TLR2+ EMPs in Tlr2Dtr embryos results in a marked decrease in both erythroid as well as myeloid lineages and, consequently, in embryonic lethality peaking before E13.5. These findings validate the importance of EMPs in embryonic development.
Effectiveness of stratified treatment for back pain in Danish primary care: A randomized controlled trial
Authors: Morsø Lars , Olsen Rose Kim , Schiøttz‐Christensen Berit , Sowden Gail , Søndergaard Jens , Christiansen David H. 
Published: June 2021

AbstractBackgroundA randomized controlled trial (RCT) of stratified care demonstrated superior clinical outcomes and cost‐effectiveness for low back pain (LBP) patients in UK primary care. This is the first study in Europe, outside of the original UK study, to investigate the clinical efficacy and cost‐effectiveness of stratified care compared with current practice for patients with non‐specific LBP.MethodsThe study was a two‐armed RCT. Danish primary care patients with LBP were randomized to stratified care (n = 169) or current practice (n = 164). Primary outcomes at 3‐ and 12‐months' follow‐up were Roland Morris Disability Questionnaire (RDMQ), patient‐reported global change and time off work. Secondary outcomes included pain intensity, patient satisfaction, healthcare resource utilization and quality‐adjusted life years.ResultsIntention‐to‐treat analyses found no between‐group difference in RMDQ scores at 3 months (0.5, 95% CI −1.8 to 0.9) or 12 months (0.4, −2.1 to 1.3). No overall differences were found between the arms at 3 and 12 months with respect to time off work or secondary outcomes. Stratified care intervention resulted in significantly fewer treatment sessions (3.5 [SD 3.1] vs. 4.5 [3.5]) and significantly lower total healthcare costs (€) (13.4 [529] vs. 228 [830], p = .002). There was no difference in cost‐effectiveness (0.09, 0.05 to 0.13 vs. 0.10, 0.07–0.14, p = .70).ConclusionsThere was no significant difference in clinical outcomes between patients with non‐specific LBP receiving stratified care and those receiving current practice. However, stratified care may reduce total healthcare costs if implemented in Danish primary care.SignificanceStratified care for low back pain based on risk profile is recommended by recent evidence based clinical guidelines. This study is the first broad replication of the STarT Back Trial in Europe. Therefore, the study adds to the body of knowledge evaluating the effectiveness of stratified care for low back pain in primary care, and provides insight into the effects of stratification on clinical practice.
Estimation of story drift directly from acceleration records for post‐earthquake safety evaluations of buildings
Authors: Huang Shieh‐Kung , Chao Shu‐Hsien , Huang Jyun‐Yan , Chang Yu‐Wen , Loh Chin‐Hsiung 
Published: June 2021

AbstractStory and roof drift ratios play a key role in the assessment of the structural damage of a building if structural displacement can be measured or calculated. In general, for building seismic monitoring, accelerometers are used to compile the responses for analysis instead of using displacement meters because they are more cost effective. Therefore, an accurate estimate of the displacement response of a building using acceleration measurements will be helpful for the rapid assessment of the damage to its structure after an earthquake. In this study, the combination of an algorithm with singular spectrum analysis (SSA) and an integration scheme is proposed to estimate structural displacement directly from acceleration measurements. The SSA was conducted with varying sizes of the data trajectory matrix, using the approximation part as a weighting factor and the detailed part to integrate for the temporary displacement, to obtain a final weighted temporary displacement. The proposed algorithm was verified using the shaking table test data for four large‐scale reinforced concrete frames. Through the proposed method, both the displacement waveform and the induced residual displacement after earthquake excitations can be estimated. The application of the proposed algorithm to building seismic response data is also discussed.
Microplastic Fibers Increase Sublethal Effects of AgNP and AgNO3 in Daphnia magna by Changing Cellular Energy Allocation
Authors: Tourinho Paula S. , Silva Ana Rita R. , Santos Cátia S.A. , Prodana Marija , Ferreira Violeta , Habibullah Giyaullah , Kočí Vladimír , van Gestel Cornelis A.M. , Loureiro Susana 
Published: June 2021

Abstract
The effects of combined exposure to microplastics and contaminants are still not completely understood. To fill this gap, we assessed the effects of polyethylene terephthalate microplastic fibers (100 mg/L; 360 µm average length) on the toxicity of silver nanoparticles (AgNPs; 32 nm) and silver nitrate (AgNO3; 0.1–10 µg Ag/L) to Daphnia magna. Acute immobilization (median effect concentration [EC50]) and cellular energy allocation (CEA; ratio between available energy and energy consumption) were determined in neonates (&lt;24 h old) and juveniles (7 d old), respectively. The 48-h EC50 for AgNP and AgNO3 (2.6 and 0.67 µg Ag/L, respectively) was not affected by the presence of microplastic fibers (2.2 and 0.85 µg Ag/L, respectively). No decrease in the available energy was observed: lipid, carbohydrate, and protein contents were unaffected. However, a significant increase in energy consumption was observed in animals exposed to AgNO3 (250% compared with control) and to the combination of microplastic fibers with AgNP (170%) and AgNO3 (260%). The exposure to microplastic fibers alone or in combination with both Ag forms decreased the CEA (values were 55–75% of control values). Our results show that after short-term exposure (48 h), microplastic fibers increased Ag toxicity at a subcellular level (i.e., CEA), but not at the individual level (i.e., immobilization). These results highlight the importance of combining different levels of biological organization to fully assess the ecotoxicological effects of plastics in association with environmental contaminants. Environ Toxicol Chem 2022;41:896–904. © 2021 SETAC
Ophthalmic changes in a spaceflight analog are associated with brain functional reorganization
Authors: McGregor Heather R. , Lee Jessica K. , Mulder Edwin R. , De Dios Yiri E. , Beltran Nichole E. , Kofman Igor S. , Bloomberg Jacob J. , Mulavara Ajitkumar P. , Smith Scott M. , Zwart Sara R. , Seidler Rachael D. 
Published: June 2021

AbstractFollowing long‐duration spaceflight, some astronauts exhibit ophthalmic structural changes referred to as Spaceflight Associated Neuro‐ocular Syndrome (SANS). Optic disc edema is a common sign of SANS. The origin and effects of SANS are not understood as signs of SANS have not manifested in previous spaceflight analog studies. In the current spaceflight analog study, 11 subjects underwent 30 days of strict head down‐tilt bed rest in elevated ambient carbon dioxide (HDBR+CO2). Using functional magnetic resonance imaging (fMRI), we acquired resting‐state fMRI data at 6 time points: before (2), during (2), and after (2) the HDBR+CO2 intervention. Five participants developed optic disc edema during the intervention (SANS subgroup) and 6 did not (NoSANS group). This occurrence allowed us to explore whether development of signs of SANS during the spaceflight analog impacted resting‐state functional connectivity during HDBR+CO2. In light of previous work identifying genetic and biochemical predictors of SANS, we further assessed whether the SANS and NoSANS subgroups exhibited differential patterns of resting‐state functional connectivity prior to the HDBR+CO2 intervention. We found that the SANS and NoSANS subgroups exhibited distinct patterns of resting‐state functional connectivity changes during HDBR+CO2 within visual and vestibular‐related brain networks. The SANS and NoSANS subgroups also exhibited different resting‐state functional connectivity prior to HDBR+CO2 within a visual cortical network and within a large‐scale network of brain areas involved in multisensory integration. We further present associations between functional connectivity within the identified networks and previously identified genetic and biochemical predictors of SANS. Subgroup differences in resting‐state functional connectivity changes may reflect differential patterns of visual and vestibular reweighting as optic disc edema develops during the spaceflight analog. This finding suggests that SANS impacts not only neuro‐ocular structures, but also functional brain organization. Future prospective investigations incorporating sensory assessments are required to determine the functional significance of the observed connectivity differences.
Anticipating control over aversive stimuli is mediated by the medial prefrontal cortex: An fMRI study with healthy adults
Authors: Wade‐Bohleber Laura Maria , Haugg Amelie , Huber Sabrina , Ernst Jutta , Grimm Simone , Recher Dominique , Richter Andre , Seifritz Erich , Boeker Heinz , Northoff Georg 
Published: June 2021

AbstractThe anticipation of control over aversive events in life is relevant for our mental health. Insights on the underlying neural mechanisms remain limited. We developed a new functional magnetic resonance imaging (fMRI) task that uses auditory stimuli to explore the neural correlates of (1) the anticipation of control over aversion and (2) the processing of aversion. In a sample of 25 healthy adults, we observed increased neural activation in the medial prefrontal cortex (ventromedial prefrontal cortex and rostral anterior cingulate cortex), other brain areas relevant for reward anticipation (ventral striatum, brainstem [ventral tegmental area], midcingulate cortex), and the posterior cingulate cortex when they anticipated control over aversion compared with anticipating no control (1). The processing of aversive sounds compared to neutral sounds (2) was associated with increased neural activation in the bilateral posterior insula. Our findings provide evidence for the important role of medial prefrontal regions in control anticipation and highlight the relevance of conceiving the neural mechanisms involved within a reward‐based framework.
The short‐term impact of a malaria elimination initiative in Southern Mozambique: Application of the synthetic control method to routine surveillance data
Authors: Thomas Ranjeeta , Cirera Laia , Brew Joe , Saúte Francisco , Sicuri Elisa 
Published: June 2021

AbstractIn public health epidemiology, quasi‐experimental methods are widely used to estimate the causal impacts of interventions. In this paper, we demonstrate the contribution the synthetic control method (SCM) can make in evaluating public health interventions, when routine surveillance data are available and the validity of other quasi‐experimental approaches may be in question. In our application, we evaluate the short‐term effects of a large‐scale Mass Drug Administration (MDA) based malaria elimination initiative in Southern Mozambique. We apply the SCM to district level weekly malaria incidence data and compare the observed reduction in age group specific malaria incidence. Between August 2015 and April 2017, a total of 13,322 (78%) cases of malaria were averted relative to the synthetic control. During the peak malaria seasons, the elimination initiative resulted in an 87% reduction in Year 1 (December 2015–April 2016), and 79% reduction in Year 2 (December 2016–April 2017). Comparison with an interrupted time series approach shows the SCM accounts for pre‐intervention trends in the data and post‐intervention weather events influencing malaria cases. We conclude MDA brought about a drastic reduction in malaria burden and can be a useful addition to existing (or new) vector control strategies and tools in accelerating towards elimination.
Oncologic outcomes of transoral robotic surgery for HPV‐negative oropharyngeal carcinomas
Authors: Parhar Harman S. , Weinstein Gregory S. , O'Malley Bert W. , Shimunov David , Rassekh Christopher H. , Chalian Ara A. , Newman Jason G. , Basu Devraj , Cannady Steven B. , Rajasekaran Karthik , Lin Alexander , Lukens John N. , Swisher‐McClure Samuel , Cohen Roger B. , Bauml Joshua M. , Aggrawal Charu , Brody Robert M. 
Published: June 2021

AbstractBackgroundPatients with human papillomavirus (HPV)‐negative oropharyngeal squamous cell carcinoma (OPSCC) continue to experience disappointing outcomes following chemoradiotherapy (CRT) and appreciable morbidity following historical surgical approaches. We aimed to investigate the oncologic outcomes and perioperative morbidity of a transoral robotic surgery (TORS) approach to surgically resectable HPV‐negative OPSCC.MethodsRetrospective analysis HPV‐negative OPSCC patients who underwent TORS, neck dissection and pathology‐guided adjuvant therapy (2005–2017).ResultsFifty‐six patients (91.1% stage III/IV) were included. Three‐year overall survival, locoregional control, and disease‐free survival were 85.5%, 84.4%, and 73.6%, respectively (median follow‐up 30.6 months, interquartile range 18.4–66.6). Eighteen (32.1%) patients underwent adjuvant radiotherapy and 20 (39.3%) underwent adjuvant CRT. Perioperative mortality occurred in one (1.8%) patient and hemorrhage occurred in two (3.6%) patients. Long‐term gastrostomy and tracheostomy rates were 5.4% and 0.0%, respectively.ConclusionThe TORS approach for resectable HPV‐negative OPSCC can achieve encouraging oncologic outcomes with infrequent morbidity.
Distinct patterns of hippocampal activity associated with color and spatial source memory
Authors: Fritch Haley A. , Thakral Preston P. , Slotnick Scott D. , Ross Robert S. 
Published: June 2021

AbstractThe hippocampus is known to be involved in source memory across a wide variety of stimuli and source types. Thus, source memory activity in the hippocampus is thought to be domain‐general such that different types of source information are similarly processed in the hippocampus. However, there is some evidence of domain‐specificity for spatial and temporal source information. The current fMRI study aimed to determine whether patterns of activity in the hippocampus differed for two types of visual source information: spatial location and background color. Participants completed three runs of a spatial memory task and three runs of a color memory task. During the study phase, 32 line drawings of common objects and animals were presented to either the left or right of fixation for the spatial memory task or on either a red or green background for the color memory task. During the test phase of both tasks, 48 object word labels were presented in the center of the screen and participants classified the corresponding item as old and previously on the “left”/on a “green” background, old and previously on the “right”/on a “red” background, or “new.” Two analysis methods were employed to assess whether hippocampal activity differed between the two source types: a general linear model analysis and a classification‐based searchlight multivoxel pattern analysis (MVPA). The searchlight MVPA revealed that activity associated with spatial memory and color memory could be classified with above‐chance accuracy in a region of the right anterior hippocampus, and a follow‐up analysis revealed that there was a significant effect of memory accuracy. These results indicate that different types of source memory are represented by distinct patterns of activity in the hippocampus.
Molecular classification of aggressive lymphomas—past, present, future
Authors: Wienand Kirsty , Chapuy Björn 
Published: June 2021

AbstractAggressive large B‐cell lymphomas (LBCLs) represent a frequent but clinically and molecularly heterogeneous group of tumors. Technological advances over the last decades prompted the development of different classification schemas to either sharpen diagnoses, dissect molecular heterogeneity, predict outcome, or identify rational treatment targets. Despite increased diagnostic precision and a noticeably improved molecular understanding of these lymphomas, clinical perspectives of patients largely remain unchanged. Recently, finished comprehensive genomic studies discovered genetically defined LBCL subtypes that predict outcome, provide insight into lymphomagenesis, and suggest rational therapies with the hope of generating patient‐tailored treatments with increased perspective for patients in greatest need. Current and future efforts integrate multiomics studies and/or leverage single‐cell technologies and will provide us with an even more fine‐grained picture of LBCL biology. Here, we highlight examples of how high‐throughput technologies aided in a better molecular understanding of LBCLs and provide examples of how to select rationally designed targeted treatment approaches that might personalize LBCL treatment and eventually improve patients' perspective in the near future.
Tobacco purchasing motivations and behaviours in alcohol‐licensed venues: A cross sectional survey of Australian young adults
Authors: Watts Christina , Burton Suzan , Egger Sam , Freeman Becky 
Published: June 2021

AbstractIssue addressedThe widespread retail availability of tobacco contributes to increased tobacco consumption and undermines quit attempts. Given the ready availability of tobacco in alcohol‐licensed venues which young adults frequent, tobacco sales in these venues are likely to influence the purchase and consumption of tobacco by young adults. This study aimed to investigate Australian young adults' tobacco purchasing motivations and behaviours in alcohol‐licensed venues.MethodsA cross‐sectional survey was conducted with a sample of 18‐ to 30‐year‐old Australians (n = 307) who had purchased tobacco at an alcohol‐licensed venue within the previous 6 months. Purchaser characteristics, levels of alcohol consumption and whether the purchase was planned were assessed, along with anticipated responses to tobacco sales ceasing at the venue.ResultsThe majority of participants (57%) reported their recent cigarette purchase at an alcohol‐licensed venue as unplanned. Area of residence was the only characteristic associated with an unplanned purchase, with those living in urban areas significantly less likely to have made an unplanned purchase than regional participants (OR = 0.51, 95% CI [0.29, 0.89]). During the occasion when the tobacco purchase was made, the majority of participants (51%) had consumed five or more standard alcoholic drinks. If tobacco sales ceased at the venue, 22% indicated they would stay and not smoke.ConclusionsUnplanned tobacco purchases appear to be influenced by the alcohol‐licensed settings, rather than socio‐demographic factors associated with the individual.So what?Policies that restrict the sale of tobacco in alcohol‐licensed venues are likely to reduce tobacco consumption among young adults and support smokers to quit.
Gender inequalities in time spent doing housework by children in Ireland: A nationally representative sample across two time points
Authors: O'Reilly Caoimhe , Quayle Michael 
Published: June 2021

AbstractGender inequality in housework divisions is persistent. This study examined early‐emerging patterns in gender roles via children's gendered housework time in the Irish context using time‐use diary and questionnaire data, controlling for key demographic variables. This study utilized longitudinal “Growing up in Ireland” data, comparing the same children's behaviour at age 9 and 13. Participants were a nationally representative, weighted sample of school going children living in Ireland, including 4,135 girls, 3,831 boys and their caregivers. The results highlight that inequalities in domestic chores occur at nine and are even greater at 13: girls do more housework and children tend to do “gender typical” chores. Consequences are discussed in relation to gender inequality and policy implications.