bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain capillary obstruction as a novel mechanism of anti-CD19 CAR T cell neurotoxicity
Authors: Faulhaber Lila D , Hartsuyker Kendra Jae , Phuong Anthea Q , Cho Yeheun , Mand Katie K , Harper Stuart D , Olson Aaron K , Garden Gwenn A , Shih Andy Y , Gust Juliane 
Published: May 2021

AbstractImmunotherapy for hematologic malignancies with CD19-directed CAR T cells is associated with neurotoxicity in about 40% of patients. Systemic cytokine release syndrome, endothelial activation, and disruption of endothelial integrity have all been associated with neurotoxicity, but it remains unclear how these mechanisms interact and how they lead to neurologic dysfunction. We developed a syngeneic mouse model which manifests systemic cytokine release and behavioral abnormalities within 3-5 days after infusion of high-dose murine CD19-CAR T cells. Histologic examination revealed widespread brain hemorrhages, diffuse extravascular IgG deposition, loss of capillary pericyte coverage and increased prevalence of string capillaries. In vivo two-photon imaging of blood flow revealed plugging of >10% of capillaries by leukocytes, associated with regions of localized hypoxia. These data reveal capillary obstruction and associated brain hypoxia and microvascular decline as a potential basis for neurotoxicity during CD19-CAR T cell treatment in humans, which may be amenable to therapeutic interventions.
A comparison of shear- and compression-induced mechanotransduction in SW1353 chondrocytes
Authors: Welhaven Hope D. , McCutchen Carley N. , June Ronald K. 
Published: May 2021

AbstractMechanotransduction is a biological phenomenon where mechanical stimuli are converted to biochemical responses. A model system for studying mechanotransduction are the chondrocytes of articular cartilage. Breakdown of this tissue results in decreased mobility, increased pain, and reduced quality of life. Either disuse or overloading can disrupt cartilage homeostasis, but physiological cyclical loading promotes cartilage homeostasis. To model this, we exposed SW1353 cells to cyclical mechanical stimuli, shear and compression, for different durations of time (15 and 30 min). By utilizing liquid chromatography-mass spectroscopy (LC-MS), metabolomic profiles were generated detailing metabolite features and biological pathways that are altered in response to mechanical stimulation. In total, 1,457 metabolite features were detected. Statistical analyses identified several pathways of interest. Taken together, differences between experimental groups were associated with inflammatory pathways, lipid metabolism, beta-oxidation, central energy metabolism, and amino acid production. These findings expand our understanding of chondrocyte mechanotransduction under varying loading conditions and time periods.
Cause-specific student absenteeism monitoring in K-12 schools for detection of increased influenza activity in the surrounding community - Dane County, Wisconsin, 2014-2020
Authors: Temte Jonathan L. , Barlow Shari , Goss Maureen , Temte Emily , Schemmel Amber , Bell Cristalyne , Reisdorf Erik , Shult Peter , Wedig Mary , Haupt Thomas , Conway James H. , Gangnon Ronald , Uzicanin Amra 
Published: May 2021

ABSTRACTBackgroundSchools are primary venues of influenza amplification with secondary spread to communities. We assessed K-12 student absenteeism monitoring as a means for early detection of influenza activity in the community.Materials and MethodsBetween September 2014 and March 2020, we conducted a prospective observational study of all-cause (a-TOT), illness-associated (a-I), and influenza-like illness–associated (a-ILI) absenteeism within the Oregon School District (OSD), Dane County, Wisconsin. Absenteeism was reported through the electronic student information system. Students were visited at home where pharyngeal specimens were collected for influenza RT-PCR testing. Surveillance of medically-attended laboratory-confirmed influenza (MAI) occurred in five primary care clinics in and adjoining OSD. Poisson general additive log linear regression models of daily counts of absenteeism and MAI were compared using correlation analysis.FindingsInfluenza was detected in 723 of 2,378 visited students, and in 1,327 of 4,903 MAI patients. Over six influenza seasons, a-ILI was significantly correlated with MAI in the community (r = 0.57; 95% CI: 0.53—0.63) with a one-day lead time and a-I was significantly correlated with MAI in the community (r = 0.49; 0.44-0.54) with a 10-day lead time, while a-TOT performed poorly (r = 0.27; 0.21—0.33), following MAI by six days.DiscussionSurveillance using cause-specific absenteeism was feasible and performed well over a study period marked by diverse presentations of seasonal influenza. Monitoring a-I and a-ILI can provide early warning of seasonal influenza in time for community mitigation efforts.
Attentional brain rhythms during prolonged cognitive activity
Authors: Gaillard C. , De Sousa C. , Amengual J. , Loriette C. , Ziane C. , Hadj Hassen S. Ben , Di Bello F. , Hamed S. Ben 
Published: May 2021

AbstractAs routine and lower demand cognitive tasks are taken over by automated assistive systems, human operators are increasingly required to sustain cognitive demand over long periods of time. This has been reported to have long term adverse effects on cardiovascular and mental health. However, it remains unclear whether prolonged cognitive activity results in a monotonic decrease in the efficiency of the recruited brain processes, or whether the brain is able to sustain functions over time spans of one hour and more. Here, we show that during working sessions of one hour or more, contrary to the prediction of a monotonic decline, behavioral performance in both humans and non-human primates consistently fluctuates between periods of optimal and suboptimal performance at a very slow rhythm ofcirca5 cycles per hour. These fluctuations are observed in both high attentional (in non-human primates) and low attentional (in humans) demand conditions. They coincide with fluctuations in pupil diameter, indicating underlying changes in arousal and information-processing load. Accordingly, we show that these rhythmic behavioral fluctuations correlate, at the neurophysiological level, with fluctuations in the informational attention orientation and perception processing capacity of prefrontal neuronal populations. We further identify specific markers of these fluctuations in LFP power, LFP coherence and spike-field coherence, pointing towards long-range rhythmic modulatory inputs to the prefrontal cortex rather than a local prefrontal origin. These results shed light on the resilience of brain mechanisms to sustained effort and have direct implications on how to optimize high cognitive demand working and learning environments.
Climate change and the complex dynamics of green spruce aphid–spruce plantation interactions
Authors: Thornley John H. M. , Newman Jonathan A. 
Published: May 2021

AbstractAphids can have a significant impact on the growth and commercial yield of spruce plantations. Here we develop a mechanistic deterministic mathematical model for the dynamics of the green spruce aphid (Elatobium abietumWalker) growing on Sitka spruce (Picea sitchensis(Bong.) Carr.). These grow in a northern British climate in managed plantations, with planting, thinning and a 60-year rotation. Aphid infestation rarely kills the tree but can reduce growth by up to 55%. We used the Edinburgh Forest Model (efm) to simulate spruce tree growth. The aphid sub-model is described in detail in an appendix. The only environmental variable which impacts immediately on aphid dynamics is air temperature which varies diurnally and seasonally. The efm variables that are directly significant for the aphid are leaf area and phloem nitrogen and carbon. Aphid population predictions include dying out, annual, biennual and other complex patterns, including chaos. Predicted impacts on plantation yield of managed forests can be large and variable, as has been observed; they are also much affected by temperature, CO2concentration and other climate variables. However increased CO2concentration appears to ameliorate the severity of the effects of increasing temperatures coupled to worsening aphid infestations on plantation yield.
Confounds of using theunc-58selection marker highlights the importance of genotyping co-CRISPR genes
Authors: Rawsthorne-Manning Helena , Calahorro Fernando , Izquierdo Patricia Gonzalez , Holden-Dye Lindy , O’Connor Vincent , Dillon James 
Published: May 2021

AbstractMultiple advances have been made to increase the efficiency of CRISPR/Cas9 editing using the model genetic organismCaenorhabditis elegans(C. elegans). Here we report on the use of co-CRISPR ‘marker’ genes: worms in which co-CRISPR events have occurred have overt, visible phenotypes which facilitates the selection of worms that harbour CRISPR events in the target gene. Mutation in the co-CRISPR gene is then removed by outcrossing to wild type but this can be challenging if the CRISPR and co-CRISPR gene are hard to segregate. However, outcrossing can be avoided by selecting worms of wild type appearance from a ‘jackpot’ brood. These are broods in which a high proportion of the progeny of a single injected worm display the co-CRISPR phenotype suggesting high CRISPR efficiency. This can deliver worms that harbour the desired mutation in the target gene locus without the co-CRISPR mutation. We have successfully generated a discrete mutation in theC. elegans nlg-1gene using this method. However, in the process of sequencing to authenticate editing in thenlg-1gene we discovered genomic rearrangements that arise at the co-CRISPR geneunc-58that by visual observation were phenotypically silent but nonetheless resulted in a significant reduction in motility scored by thrashing behaviour. This highlights that careful consideration of the hidden consequences of co-CRISPR mediated genetic changes should be taken before downstream analysis of gene function. Given this, we suggest sequencing of co-CRISPR genes following CRISPR procedures that utilise phenotypic selection as part of the pipeline.
Structural mechanisms for gating and ion selectivity of the human polyamine transporter ATP13A2
Authors: Tillinghast Jordan , Bowser Darren , Lee Kenneth Pak Kin 
Published: May 2021

SummaryMutations in ATP13A2, also known as PARK9, cause a rare monogenic form of juvenile onset Parkinson’s disease named Kufor-Rakeb syndrome and other neurodegenerative diseases. ATP13A2 encodes a neuroprotective P5B P-type ATPase highly enriched in the brain that mediates selective import of spermine ions from lysosomes into the cytosol via an unknown mechanism. Here we present three structures of human ATP13A2 bound to an ATP analogue or to spermine in the presence of phosphomimetics determined by electron cryo-microscopy. ATP13A2 autophosphorylation opens a lysosome luminal gate to reveal a narrow lumen access channel that holds a spermine ion in its entrance. ATP13A2’s architecture establishes physical principles underlying selective polyamine transport and anticipates a “pump-channel” intermediate that could function as a counter-cation conduit to facilitate lysosome acidification. Our findings establish a firm foundation to understand ATP13A2 mutations associated with disease and bring us closer to realizing ATP13A2’s potential in neuroprotective therapy.HighlightsStructures of the Parkinson’s disease-associated polyamine transporter ATP13A2Structures of three transport cycle intermediates reveal the gating mechanismArchitecture of the polyamine binding site reveals mechanisms for ion selectivityThe polyamine binding site’s location anticipates an ion channel-like mechanism
Regional Differences in Brain Plasticity and Behaviour as a Function of Sex and Enrichment Type: Oxytocin Matters
Authors: Faraji Jamshid , Lotfi Hamid , Moharrerie Alireza , Jafari S. Yaghoob , Soltanpour Nasrin , Tamannaiee Rosa , Marjani Kameran , Roudaki Shabnam , Naseri Farhad , Moeeini Reza , Metz Gerlinde A.S. 
Published: May 2021

AbstractThe early environment is critical to brain development, but the relative contribution of physical vs. social stimulation is unclear. Here, we investigated in male and female rats the response to early physical and social environmental enrichment in relation to oxytocin (OT) and brain-derived neurotrophic factor (BDNF) expression. The findings show that males and females respond differently to prolonged sensorimotor stimulation from postnatal day 21-110 in terms of functional, structural and molecular changes in the hippocampus vs. medial prefrontal cortex (mPFC). Physical enrichment promoted motor and cognitive functions and hippocampal BDNF mRNA and protein expression in both sexes. Combined physical and social enrichment, however, promoted functional and structural gain predominantly in females. These changes were accompanied by elevated plasma oxytocin (OT) levels and BDNF mRNA expression in the mPFC while the hippocampus was not affected. Administration of an OT antagonist in females blocked the beneficial effects of enrichment and led to reduced cortical BDNF signaling. These findings suggest that an OT-based mechanism selectively stimulates a region-specific BDNF response which is dependent on the type of experience.
A novel class of human milk oligosaccharides based on 6’- galactosyllactose and containing N-acetylglucosamine branches extended by oligogalactoses
Authors: Hanisch Franz-Georg , Kunz Clemens 
Published: May 2021

AbstractHuman milk oligosaccharides (HMOs) have attracted much attention in recent years not only as a prebiotic factor, but in particular as an essential component in infant nutrition related to their impact in innate immunity. The backbone structures of complex HMOs generally contain single or repetitive lacto-N-biose (type 1) or lactosamine (type 2) units in either linear or branched chains extending from a lactose core. While all known branched structures originate from 3,6-substitution of the lactosyl core galactose, we here describe a new class of HMOs that tentatively branch at terminal galactose of 6’-galactosyllactose. Another novel feature of this class of HMOs was found in linear oligo-galactosyl chains linked to one of the N-acetylglucosamine (GlcNAc) branches. The novel structures exhibit general formulas with hexose vs. hexosamine contents of 5/2 to 8/2 and can be designated as high-galactose (HG)-HMOs. In addition, up to three fucosyl residues are linked to the octa- to dodecasaccharides, which were detected in two human milk samples from Lewis blood group defined donors. Structural analyses of methylated glycans and their alditols comprised MALDI mass spectrometry, ESI-(CID)MS and linkage analyses by GC-MS of the derived partially methylated alditol acetates. Enzymatic degradation by application of β1-3,4-specific galactosidase supported the presence of terminal galactose linked β1−6 to one of the two GlcNAc branches.
New developments in institutional research on performance measurement and management in the public sector
Authors: Modell Sven 
Published: May 2021

PurposeThis paper reviews and reflects on institutional research on performance measurement and management (PMM) in the public sector emerging over the past decade and discusses potential extensions of this body of research.Design/methodology/approachThe paper takes the form of a reflective review with an emphasis on how institutional theory has been used in PMM research in the public sector.FindingsAlthough institutional research on PMM in the public sector has continued to grow over the past decade, much of this research still pays relatively one-sided attention to the influence of pre-existing institutions on PMM practices and has left the constitutive effects of such practices under-researched. In order to address this shortcoming and nurture research that pays more equal attention to the institutional effects on and of PMM practices, a research agenda based on dialogue with the sociology of valuation and valuation studies is outlined. Such research is arguably well-suited for examining emerging themes in the public sector accounting and management literatures centred on the publicness of public service provision and notions of organisational hybridity.Research limitations/implicationsThe paper offers a starting point for research that can provide a more holistic and dynamic perspective on how PMM practices are implicated in the shaping of institutional fields over time.Originality/valueThe paper continues to advance an established research agenda in the public sector accounting and management literatures whilst suggesting ways of extending this research agenda.
Treatment options for DOCK8 deficiency‐related severe dermatitis
Authors: Ollech Ayelet , Mashiah Jacob , Lev Atar , Simon Amos J. , Somech Raz , Adam Etai , Barzilai Aviv , Hagin David , Greenberger Shoshana 
Published: May 2021

AbstractBackgroundCutaneous manifestations of dedicator of cytokinesis 8 gene (DOCK8) deficiency, a combined type of T and B cell immunodeficiency, previously designated as autosomal recessive hyper IgE syndrome, includes dermatitis and skin infections. There are limited treatment options for dermatitis related to the syndrome.ObjectiveTo describe a cohort of patients with DOCK8 deficiency with a focus on the treatment of their cutaneous manifestations.MethodsA retrospective study on all children with the genetic diagnosis of DOCK8 deficiency treated at the Sheba Medical Center between 1/1/2003 and 1/1/2021 was preformed. Collected data included: demographic features, family history, laboratory, genetic testing, skin manifestations, treatment, and disease course. Description of two cases of severe recalcitrant dermatitis treated with dupilumab is detailed.ResultsNine children with a genetic diagnosis of DOCK8 deficiency were included, of whom six were girls (66%) with a median age of 8.5 (±2.2 SD) years. The median age at diagnosis was 2.8 (±2.6 SD) years. Six patients were born to consanguineous parents. Five out of six patients who received hematopoietic stem cell transplantation (HSCT) had a complete response, and one was recently transplanted. Of note, two patients, while awaiting HSCT, were treated with dupilumab for their severe dermatitis resulting in a marked improvement of the cutaneous manifestations and pruritus.ConclusionsHematopoietic stem cell transplantation is the gold standard and most effective therapy for patients with DOCK8 deficiency. Dupilumab, a biological therapy indicated for atopic dermatitis and other Th2 derived dermatoses, is an excellent option for dermatitis in patients with DOCK8 deficiency and can be used as a bridge before HSCT. Larger studies are needed to confirm this observation.
Conventional and simple methods of measuring esophageal nocturnal baseline impedance show excellent agreement
Authors: Park Jin‐soo , Van der Wall Hans , Falk Gregory Leighton 
Published: May 2021

ObjectivesMean nocturnal baseline impedance (MNBI) shows promise in investigating reflux disease by reflecting esophageal mucosal integrity. This study aimed to measure MNBI by both conventional and simple methods in patients with laryngopharyngeal reflux (LPR) and gastroesophageal reflux disease (GERD) in order to evaluate the efficacy of the simple measurement method.MethodsAltogether 187 patients were divided into LPR (n = 105) or GERD (n = 82) groups according to their predominant symptom profile, and underwent off‐therapy impedance‐pH monitoring. MNBI was measured by both the conventional and simple methods. The Bland‐Altman plots were constructed to assess mean differences and to identify bias in the two measurement methods.ResultsFor the two measurement methods, mean difference was (−89 ± 328) Ω in the distal esophagus, (−6 ± 653) Ω in the proximal esophagus, and (128 ± 577) Ω in the pharynx, respectively. There was a strong correlation between conventional and simple MNBI values, with the coefficient of 0.940 in the distal esophagus, 0.463 in the proximal esophagus, and 0.712 in the pharynx (all P < 0.001).ConclusionsThere was an excellent agreement between the conventional and simple methods of MNBI measurement, with no evidence of proportional bias. Conventional and simple MNBI values correlated excellently in the distal esophagus and moderately well in the proximal esophagus and pharynx. This study supports the use of the simple method of measuring MNBI to enhance diagnoses of reflux disease.
A Global Agenda for Household Water Security: Measurement, Monitoring, and Management
Authors: Wutich Amber , Jepson Wendy E. , Stoler Justin , Thomson Patrick , Kooy Michelle , Brewis Alexandra , Staddon Chad , Meehan Katie 
Published: May 2021

AbstractWater scholarship has advanced considerably in recent decades. Despite this remarkable progress, water challenges may be growing more quickly than our capacity to solve them. While much progress has been made toward achieving Sustainable Development Goal 6 — water and sanitation for all — new stressors have emerged to threaten this progress. Far from being a problem of the Global South, recent research shows that water insecurity is very much a global phenomenon — and one that has been, until recently, seriously neglected in the Global North. This indicates a strong need for innovative measurement of who experiences water insecurity, new approaches for monitoring the efficacy of water interventions, and more effective management of complex, mobile, and multiple water infrastructures to achieve water security. In this paper, we introduce the Household Water Insecurity approach to addressing these concerns. First, we suggest ways to improve the measurement of water insecurity — pinpointing problems at the household and individual levels — in ways that can inform policymaking with improved precision. Second, we discuss ways that new information and communication technology can improve monitoring and indicate where water infrastructure repairs and investments are most needed. Third, we highlight the need for new approaches to managing complex water infrastructures in more inclusive and democratic ways.
Concealing researcher identity in fieldwork and social media: Sexuality and speaking for participants
Authors: Sou Gemma 
Published: May 2021

AbstractResearchers often conceal or reveal parts of their identity to ensure the success of fieldwork. Yet, connection between researchers and research participants can now be maintained via social networking sites. This raises new questions about the ethics and practicalities of negotiating identity during and after fieldwork. The paper draws on a narrative ethnography of concealing my lesbian identity during and after ethnographic research in Bolivia. I demonstrate that in a socially mediated world the “curation” of researcher identity is no longer temporally and geographically bound to the periods and locales of fieldwork. Second, I argue that a researcher's decision to conceal elements of their identity may be informed by essentialist assumptions about research participants. Third, researchers may effectively colonise and silence research participants because they speak for them and remove any opportunity for participants to respond to the element of the researcher's identity being hidden, such as sexuality, class, or religion.