bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular O‐Glycome Reporter/Amplification (CORA): Analytical and Preparative Tools to Study Mucin‐Type O‐Glycans of Living Cells
Authors: Kudelka Matthew R. , Li Zhonghua , Chernova Tatiana A. , Smith David F. , Song Xuezheng , Cummings Richard D. , Ju Tongzhong
Published: June 2021

Mucin‐type O‐glycosylation (O‐glycans, O‐glycome) is among the most biologically important post‐translational modification in glycoproteins but O‐glycan structural diversity and expression are poorly understood due to the inadequacy of current analytical methods. We recently developed a new tool termed cellular O‐glycome reporter/amplification (CORA), which uses O‐glycan precursors, benzyl‐α‐GalNAc (Bn‐α‐GalNAc) or azido‐Bn‐α‐GalNAc (N3‐Bn‐α‐GalNAc), as surrogates of protein O‐glycosylation. Living cells metabolically convert these precursors to all types of O‐GalNAc glycans representative of the cells’ capabilities. The amplification and secretion of the O‐glycome products greatly facilitates their analysis and functional studies. Here we describe protocols for analytical and preparative applications. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. This article is a U.S. Government work and is in the public domain in the USA.

Basic Protocol 1: Cellular O‐glycome reporter/amplification for the analysis of mucin‐type O‐glycans from living cells

Basic Protocol 2: Preparation of cellular O‐glycans from living cells for functional glycomics and glycan microarrays

Basic Protocol 3: Conjugation of cellular O‐glycans with a bifunctional fluorescent tag

Basic Protocol 4: 2D‐HPLC purification and MALDI‐TOF/MS identification of individual PYAB‐Bn‐O‐glycan
Electrophysiologic Analysis of Tight Junction Size and Charge Selectivity
Authors: Shashikanth Nitesh , Rizzo Heather E. , Pongkorpsakol Pawin , Heneghan John F. , Turner Jerrold R.
Published: June 2021

Tight junctions form selectively permeable barriers that limit paracellular flux across epithelial‐lined surfaces. Rather than being absolute barriers, tight junctions in many tissues allow ions, water, and other small molecules to cross on the basis of size and charge selectivity via the high‐capacity pore pathway. Most probes currently used to assess tight junction permeability exceed the maximum size capacity of the pore pathway. As a result, available analytical tools have generally been limited to measurement of transepithelial electrical resistances. These provide no information regarding size selectivity and, therefore, cannot be used to distinguish between the pore pathway and the leak pathway, a low‐capacity route that accommodates larger macromolecules. This article describes use of dilution potential and bi‐ionic potential measurements for analysis of tight junction size and charge selectivity within monolayers of cultured epithelial cells. © 2021 Wiley Periodicals LLC.

This article was corrected on 25 August 2021. See the end of the full text for details.

Basic Protocol 1: Culture of MDCK monolayers on semipermeable supports and induction of claudin‐2 expression

Basic Protocol 2: Configuring voltage/current clamp and other equipment

Basic Protocol 3: Measuring dilution and bi‐ionic potentials

Basic Protocol 4: Calculating ion permeabilities and pore diameter

Support Protocol: Preparation of agar bridges and electrophysiology rig setup
Fission Yeast Schizosaccharomyces pombe: A Unicellular “Micromammal” Model Organism
Authors: Vyas Aditi , Freitas Anna V. , Ralston Zachary A. , Tang Zhaohua
Published: June 2021

The fission yeast Schizosaccharomyces pombe is a rod‐shaped unicellular eukaryote, well known for its contributions as a model organism for our understanding of regulation and conservation of the eukaryotic cell cycle. As a yeast divergent from the budding yeast Saccharomyces cerevisiae, S. pombe shares more common features with humans including gene structures, chromatin dynamics, and the prevalence of introns, as well as the control of gene expression through pre‐mRNA splicing, epigenetic gene silencing, and RNAi pathways. With the advent of new methodologies for research, S. pombe has become an increasingly used model to investigate various molecular and cellular processes over the last 50 years. Also, S. pombe serves as an excellent system for undergraduate students to obtain hands‐on research experience. Versatile experimental approaches are amenable using the fission yeast system due to its relative ease of maintenance, its inherent cellular properties, its power in classic and molecular genetics, and its feasibility in genomics and proteomics analyses. This article provides an overview of S. pombe’s rise as a valuable model organism and presents examples to highlight the significance of S. pombe as a unicellular “micromammal” in investigating biological questions. We especially focus on the advantages of and the advancements in using fission yeast for studying biological processes that are characteristic of metazoans to decipher the underlining molecular mechanisms fundamental to all eukaryotes. © 2021 Wiley Periodicals LLC.

This article was corrected on 21 July 2021. See the end of the full text for details.
Understanding the Evolution of Cobalt‐Based Metal‐Organic Frameworks in Electrocatalysis for the Oxygen Evolution Reaction
Authors: Cai Xiaowei , Peng Fei , Luo Xingyu , Ye Xuejie , Zhou Junxi , Lang Xiaoling , Shi Meiqin
Published: June 2021

Metal‐organic frameworks (MOFs) have attracted increasing attention as a promising electrode material for the oxygen evolution reaction (OER). Comprehending catalytic mechanisms in the OER process is of key relevance for the design of efficient catalysts. In this study, two types of Co based MOF with different organic ligands (ZIF‐67 and CoBDC; BDC=1,4‐benzenedicarboxylate) are synthesized as OER electrocatalysts and their electrochemical behavior is studied in alkaline solution. Physical characterization indicates that ZIF‐67, with tetrahedral Co sites, transforms into α‐Co(OH)2 on electrochemical activation, which provides continuous active sites in the following oxidation, whereas CoBDC, with octahedral sites, evolves into β‐Co(OH)2 through hydrolysis, which is inert for the OER. Electrochemical characterization reveals that Co sites coordinated by nitrogen from imidazole ligands (Co−N coordination) are more inclined to electrochemical activation than Co−O sites. The successive exposure and accumulation of real active sites is responsible for the gradual increase in activity of ZIF‐67 in OER. This work not only indicates that CoMOFs are promising OER electrocatalysts but also provides a reference system to understand how metal coordination in MOFs affects the OER process.
Fine resolution smart force sensor based on lever arm mechanism using shape memory alloy spring
Authors: G. Then Mozhi , M. Banu Sundareswari , K. Dhanalakshmi
Published: June 2021

A novel force measurement technique using the variable resistance property of shape memory alloy (SMA) spring is presented. The unique abilities of SMA, a smart material make it a potential candidate to construct actuators and dampers and of late is added to the domain of sensing technology in the design of creative sensing systems. The sensing mechanism is realized using a lever arm made of less stiff acrylic material; one of the links of the lever arm is integrated with an SMA spring actuator that is connected perpendicular to the stationary base, and the unknown load is placed at the other link; the force due to the measurand and the transmitted force act on the arms of the lever. The displacement due to the application of force on one of the flexible arms causes a variation in the strain that leads to resistance variation of the Joule‐heated SMA spring attached at the other arm. The active sensor possesses static and dynamic sensing capabilities and can detect force in the range of a few millinewtons, and the sensor design is validated from the experimental measurements and analytical results. The performance of the sensor is evaluated from its static and dynamic characteristics and depicts promising results. The design methodology of the sensor mechanism and selection of material suitable to offer flexible transformation of force leads to the development of a force sensor with fine resolution.
Power and area‐efficient static current mode logic frequency divider in 180‐nm complementary metal‐oxide‐semiconductor technology
Authors: Maity Subhanil , Jana Sanjay Kumar , Som Indranil , Bhattacharyya Tarun Kanti
Published: June 2021

This paper presents power and area optimized, high‐speed metal‐oxide‐semiconductor (MOS) current mode logic (MCML)‐based frequency dividers. Each differential pair in the divider is sized separately to minimize the overall power consumption. The divide‐by‐2 frequency divider has been realized in a 180‐nm complementary MOS (CMOS) process technology, and postlayout simulation results show that the proposed frequency divider can work up to an operating frequency of 18.8 GHz in the worst‐case process corner with a maximum power dissipation of 1.715 mW under 1.8‐V supply. It gives a bandwidth of 19.9 GHz which ranges from 1 to 20.9 GHz. The divider occupies a 0.106 × 0.09 mm2 area. The performance corresponds to the figure of merit (FoM) of 43.61 dB. The same optimized latches and two EX‐OR gates are used to design a divide‐by‐5 frequency divider that is also realized in 180‐nm CMOS process technology. The postlayout simulation results show that the proposed divide‐by‐5 frequency divider can faithfully work up to an operating frequency of 12.12 GHz in worst‐case process corner with an excellent power head performance. The maximum power dissipation of the core circuit is 1.39 mW under 1.8‐V supply. It occupies a 0.166 × 0.116 mm2 area. The performance corresponds to the FoM of 26.56 dB which compares favorably with the state of the art.
A survey on nature‐inspired algorithms and its applications in the Internet of Vehicles
Authors: Sharma Surbhi , Kaushik Baijnath
Published: June 2021

The concept of the Internet of Vehicles (IoV) was evolved to cater to the increasing demands of emerging and advanced vehicular applications such as intelligent transportation systems (ITS). IoV plays a vital role in the development of smart cities and smart transportation. As IoV involves real‐time data, so efficient routing mechanisms, as well as secure protocols, are very much needed to enhance the efficiency and security of the IoV network. In the existing literature, numerous researchers have focused on enhancing the efficiency of the IoV network. However, there still exist some flaws keeping in view the new security vulnerabilities that keep on emerging. So, there is a need to optimize the capabilities of existing frameworks for dealing with such issues. Nature‐inspired algorithms are a category of powerful tools to solve problems of optimization. In this first of its kind state‐of‐the‐art study, the potential of applicability of nature‐inspired algorithms in IoV networks for improving the overall performance of IoV is explored. First, various categories of nature‐inspired algorithms are presented to make the readers well acquainted with the concepts of nature‐inspired algorithms. Different nature‐inspired algorithms having their applicability in different aspects of IoV are studied with a special focus on security, routing, and parking space management for strengthening the existing IoV network. Various open issues and research challenges in the use of different nature‐inspired algorithms in IoV are also presented. Based upon the study conducted, it has been analyzed that nature‐inspired algorithms can optimize the overall performance of IoV networks.
Dasatinib protects against acute respiratory distress syndrome via Nrf2‐regulated M2 macrophages polarization
Authors: Liu Zishuang , Chen Shanshan , Zhang Xinfeng , Liu Fangfang , Yang Kai , Du Ge , Rui Xi
Published: June 2021

Dasatinib, a tyrosine kinase inhibitor, has a protective effect on experimental acute respiratory distress syndrome (ARDS). This study investigated the effect and mechanism of dasatinib in ARDS. C57BL/6 mice were administered with dasatinib (1 and 10 mg/kg) after lipopolysaccharide (LPS) treatment to evaluate the effect of dasatinib on white blood cells (WBC), neutrophils, lymphocytes and macrophages in bronchoalveolar lavage fluid (BALF). The levels and mRNA expressions of inflammation‐related cytokines in lung tissues and RAW 264.7 cells were detected by enzyme‐linked immunosorbent assay and quantitative real‐time PCR, respectively. The protein expressions of nuclear factor E2‐related factor 2 (Nrf2) and heme oxygenase 1 (HO1) were determined by Western blot. MTT assay was performed to detect the viability of RAW 264.7 cell. Rescue experiments were used to assess the effect of Nrf2 silencing on the LPS‐ and dasatinib‐treated mice. Under LPS treatment, levels of the WBC, neutrophils, lymphocytes and macrophages in BALF and mRNA expressions of IL‐6, TNF‐α and IL‐10 as well as expression of iNOS were increased, but the expression of arginase‐1 was inhibited, while no obvious changes of the protein expressions of Nrf2 and HO1 were observed. Dasatinib partially reversed the effects of LPS above, and further promoted the mRNA expression of IL‐10 and the protein expressions of Nrf2 and HO1, while Nrf2 silencing counteracted the effect of dasatinib. Dasatinib induced the polarization of M2 subtype of macrophages and alleviated LPS‐induced ARDS through activating Nrf2 signaling pathway, which may provide a new strategy for the treatment of ARDS.
Use ADA settlement agreements as a guide for monitoring compliance
Authors: Charmatz Marc
Published: June 2021

The United States Department of Justice has recently settled two complaints against colleges under Title II of the Americans with Disabilities Act — United States of America and Tidewater Community College, DJ #204‐79‐334 (see https://www.ada.gov/tidewater_cc_sa.html) and United States of America and Central Texas College of Killeen (see https://www.ada.gov/ctc_sa.html).
Unraveling the roles of genotype and environment in the expression of plant defense phenotypes
Authors: Potts Abigail S. , Hunter Mark D.
Published: June 2021

Phenotypic variability results from interactions between genotype and environment and is a major driver of ecological and evolutionary interactions. Measuring the relative contributions of genetic variation, the environment, and their interaction to phenotypic variation remains a fundamental goal of evolutionary ecology.

In this study, we assess the question: How do genetic variation and local environmental conditions interact to influence phenotype within a single population? We explored this question using seed from a single population of common milkweed,Asclepias syriaca, in northern Michigan. We first measured resistance and resistance traits of 14 maternal lines in two common garden experiments (field and greenhouse) to detect genetic variation within the population. We carried out a reciprocal transplant experiment with three of these maternal lines to assess effects of local environment on phenotype. Finally, we compared the phenotypic traits measured in our experiments with the phenotypic traits of the naturally growing maternal genets to be able to compare relative effect of genetic and environmental variation on naturally occurring phenotypic variation. We measured defoliation levels, arthropod abundances, foliar cardenolide concentrations, foliar latex exudation, foliar carbon and nitrogen concentrations, and plant growth.

We found a striking lack of correlation in trait expression of the maternal lines between the common gardens, or between the common gardens and the naturally growing maternal genets, suggesting that environment plays a larger role in phenotypic trait variation of this population. We found evidence of significant genotype‐by‐environment interactions for all traits except foliar concentrations of nitrogen and cardenolide. Milkweed resistance to chewing herbivores was associated more strongly with the growing environment. We observed no variation in foliar cardenolide concentrations among maternal lines but did observe variation among maternal lines in foliar latex exudation.

Overall, our data reveal powerful genotype‐by‐environment interactions on the expression of most resistance traits in milkweed.
Migration efficiency sustains connectivity across agroecological networks supporting sandhill crane migration
Authors: Donnelly J. Patrick , King Sammy L. , Knetter Jeff , Gammonley James H. , Dreitz Victoria J. , Grisham Blake A. , Nowak M. Cathy , Collins Daniel P.
Published: June 2021

Preserving avian flyway connectivity has long been challenged by our capacity to meaningfully quantify continental habitat dynamics and bird movements at temporal and spatial scales underlying long‐distance migrations. Waterbirds migrating hundreds or thousands of kilometers depend on networks of wetland stopover sites to rest and refuel. Entire populations may rely on discrete wetland habitats, particularly in arid landscapes where the loss of limited stopover options can have disproportionately high impacts on migratory cost. Here, we examine flyway connectivity in water‐limited ecosystems of western North America using 108 GPS tagged greater sandhill cranes. Bird movements were used to reconstruct wetland stopover networks across three geographically unique sub‐populations spanning 12 U.S.–Mexican states and Canadian provinces. Networks were monitored with remote sensing to identify long‐term (1988–2019) trends in wetland and agricultural resources supporting migration and evaluated using network theory and centrality metrics as a measure of stopover site importance to flyway connectivity. Sandhill crane space use was analyzed in stopover locations to identify important ownership and landscape factors structuring bird distributions. Migratory efficiency was the primary mechanism underpinning network function. A small number of key stopover sites important to minimizing movement cost between summering and wintering locations were essential to preserving flyway connectivity. Localized efficiencies were apparent in stopover landscapes given prioritization of space use by birds where the proximity of agricultural food resources and flooded wetlands minimized daily movements. Model depictions showing wetland declines from 16% to 18% likely reflect a new normal in landscape drying that could decouple agriculture–waterbird relationships as water scarcity intensifies. Sustaining network resilience will require conservation strategies to balance water allocations preserving agricultural and wetlands on private lands that accounted for 67–96% of habitat use. Study outcomes provide new perspectives of agroecological relationships supporting continental waterbird migration needed to prioritize conservation of landscapes vital to maintaining flyway connectivity.
Evaluating probabilistic ecological forecasts
Authors: Simonis Juniper L. , White Ethan P. , Ernest S. K. Morgan
Published: June 2021

Probabilistic near‐term forecasting facilitates evaluation of model predictions against observations and is of pressing need in ecology to inform environmental decision‐making and effect societal change. Despite this imperative, many ecologists are unfamiliar with the widely used tools for evaluating probabilistic forecasts developed in other fields. We address this gap by reviewing the literature on probabilistic forecast evaluation from diverse fields including climatology, economics, and epidemiology. We present established practices for selecting evaluation data (end‐sample hold out), graphical forecast evaluation (times‐series plots with uncertainty, probability integral transform plots), quantitative evaluation using scoring rules (log, quadratic, spherical, and ranked probability scores), and comparing scores across models (skill score, Diebold–Mariano test). We cover common approaches, highlight mathematical concepts to follow, and note decision points to allow application of general principles to specific forecasting endeavors. We illustrate these approaches with an application to a long‐term rodent population time series currently used for ecological forecasting and discuss how ecology can continue to learn from and drive the cross‐disciplinary field of forecasting science.
The Effect of ThyroidߚStimulating Hormone on Stage of Differentiated Thyroid Carcinoma
Authors: Soleimanisardoo Laya , Rouhani Mohsen , Sardoo Fatemeh Soleymani , Gozashti Mohammad Hossein
Published: June 2021

Introduction

Thyroid cancer is the most common endocrine malignancy, and it has the fastest increase rate in incidence in both sexes, with a yearly increase of 3% over the last decade. Thyroid‐stimulating hormone (TSH) is the main driver for the thyroid gland to produce thyroid hormone. The main purpose of this study was to assess the relationship between serum TSH level and the stage of malignancy in patients with differentiated thyroid cancer.

Methods

This cross‐sectional study was performed on 77 patients with thyroid cancer. The demographic characteristics, TSH level and stage of malignancy were recorded for all patients in the data collection form. The data analysis was conducted by descriptive statistics using SPSS 20.0 software.

Results

The results show a significant relationship (p‐value = .025) between the malignancy stage and serum TSH level. The mean TSH level in patients of stage 3 (5.70 ± 2.03) was significantly higher than patients in stage 2 (2.58 ± 0.52) and stage 1 (2.33 ± 0.28). No significant relationship was observed between the age of patients and serum TSH level. Although the mean serum TSH level in men (3.61 ± 0.98) was higher than in women (2.52 ± 0.25), the difference was not statistically significant.

Conclusions

According to the results of this study, serum TSH level can be considered as a predictor of the stage of differentiated thyroid cancer. Therefore, it can be used to predict the likelihood of cancer and improve the outcome and extent of thyroidectomy in patients with thyroid cancer.
Hierarchically Micro/Nanostructured Current Collectors Induced by Ultrafast Femtosecond Laser Strategy for High‐Performance Lithium‐ion Batteries
Authors: Wang Yaya , Zhao Zexu , Zhong Jiang , Wang Tao , Wang Lei , Xu Hanjiao , Cao Jinhui , Li Jinhao , Zhang Guanhua , Fei Huilong , Zhu Jian
Published: June 2021

Commercial Cu and Al current collectors for lithium‐ion batteries (LIBs) possess high electrical conductivity, suitable chemical and electrochemical stability. However, the relatively flat surface of traditional current collectors causes weak bonding strength and poor electrochemical contact between current collectors and electrode materials, resulting in potential detachment of active materials and rapid capacity degradation during extended cycling. Here, we report an ultrafast femtosecond laser strategy to manufacture hierarchical micro/nanostructures on commercial Al and Cu foils as current collectors for high‐performance LIBs. The hierarchically micro/nanostructured current collectors (HMNCCs) with high surface area and roughness offer strong adhesion to active materials, fast electronic delivery of entire electrodes, significantly improving reversible capacities and cyclic stability of HMNCCs based LIBs. Consequently, LiNi0.5Co0.2Mn0.3O2 (NCM523) cathode with Al HMNCC generated a high reversible capacity after 200 cycles (25% higher than that of cathode with Al CC). Besides, graphite anode with Cu HMNCC also maintained prominent reversible capacity even after 600 cycles. Moreover, the full cell assembled by graphite anode with Cu HMNCC and NCM523 cathode with Al HMNCC achieved high reversible capacity and remarkable cycling stability under industrial‐grade mass loading. This study provides promising candidate for achieving high‐performance LIBs current collectors.
Air‐Processed Efficient Organic Solar Cells from Aromatic Hydrocarbon Solvent without Solvent Additive or Post‐Treatment: Insights into Solvent Effect on Morphology
Authors: Ma Ruijie , Yang Tao , Xiao Yiqun , Liu Tao , Zhang Guangye , Luo Zhenghui , Li Gang , Lu Xinhui , Yan He , Tang Bo
Published: June 2021

Most of the recent organic solar cells (OSCs) with top‐of‐the‐line efficiencies are processed from organic solvents with a high vapor pressure such as CF in nitrogen‐filled glovebox, which is not feasible for large‐area manufacturing. Herein, we cast active layers with both aromatic hydrocarbon solvents and halogenated solvents without any solvent additive or post‐treatment, as well as interlayers with water and methanol in air (35% relative humidity) for efficient OSCs, except cathode electrode's evaporation is in vacuum. Compared to the PM6:Y6 system that is processed from CF, the PM6:BTP‐ClBr2 system demonstrates good efficiency of 16.28% processed from CB and the device based on PM6:BTP‐4Cl achieves 16.33% using TMB as its solvent for the active layer. These are among the highest efficiencies for CB‐ and TMB‐processed binary OSCs to date. The molecular packing and phase separation length scales of each combination depend strongly on the solvent, and the overall morphology is the result of the interplay between solvent evaporation (kinetics) and materials miscibility (thermodynamics). Different solvents are required to realize the optimal morphology due to the different miscibility between the donor and acceptor. Finally, 17.36% efficiency was achieved by incorporating PC71BM for TMB‐processed devices. Our result provides insights into the effect of processing solvent and shows the potential of realizing high‐performance OSCs in conditions relevant for industrial fabrication.
The expanding world of tissue‐resident macrophages
Authors: Jenkins Stephen J. , Allen Judith E.
Published: June 2021

The 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

Immunotherapy 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

Early 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

Background

A 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.

Methods

The 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.

Results

Intention‐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).

Conclusions

There 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.

Significance

Stratified 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

Story 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

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 (<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

Following 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

The 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

In 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

Background

Patients 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.

Methods

Retrospective analysis HPV‐negative OPSCC patients who underwent TORS, neck dissection and pathology‐guided adjuvant therapy (2005–2017).

Results

Fifty‐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.

Conclusion

The 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

The 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

Aggressive 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.