bluuebunny/crossref_metadata_2025 huggingface dataset:
Political Obfuscation and Literary Ambiguity
Authors: Bauer Matthias , Zirker Angelika
Published: October 2022

In this paper, we are addressing the relationship between ambiguity and obscurity by comparing political with literary use of language. In particular, we are considering contexts in which ambiguity, deriving from underspecification, is strategically used as a device to establish a certain degree of obscurity. We suggest that this strategy is based on an undeclared identification of meanings that are in fact distinct, thus creating false or at least misleading impressions. By contrast, we present literary strategies of ambiguity which also work with combinations of meanings. While the strategies share this combination, they differ vastly in purpose and effect. Our examples are taken from Boris Johnson’s 2021 »Levelling Up«-Speech as well as from poetry and plays by William Shakespeare. Their comparison proves to be particularly fruitful when it comes to conceptualising the ambiguities of »levelling (up)« and their uses in context.
Application of Sustainable Procurement Policy to Improve the Circularity of Construction and Demolition Waste Resources in Australia
Authors: Shooshtarian Salman , Maqsood Tayyab , Wong Peter S. P. , Bettini Louis
Published: October 2022

The sustainable management of construction and demolition (C&D) necessitates efficient waste minimisation policies. Sustainable procurement of recycled waste products (RWPs) is an encouragement-based policy approach that can serve this purpose. This policy aids stakeholders in enhancing the circular economy (CE) in the built environment (BE) sector. However, this procurement method is yet to be successfully adapted globally or in Australia. Hence, this study was conducted to shed light on the use of sustainable procurement in the Australian BE sector. Based on a mixed-methods methodology, 49 relevant academic, industry and government publications were analysed during the review process. The findings reveal that the two most significant obstacles are the lack of supportive organisational culture and uncertainty about RWP quality. In addition, implementing clear and supporting regulations and maintaining transparency and good governance are identified as the two most important enablers. A model was proposed to facilitate the adoption of sustainable procurement, based on the research findings. The study includes a number of suggestions to encourage the acquisition of C&D RWPs for construction projects. This review is anticipated to contribute to three areas: sustainable procurement theory, policy development, and BE sector practice.
Evidence of male alliance formation in a small dolphin community
Authors: Chabanne Delphine B. H. , Krützen Michael , Finn Hugh , Allen Simon J.
Published: October 2022

The photo-identification of uniquely marked individuals has revealed much about mammalian behaviour and social structure in recent decades. In bottlenose dolphins (Tursiopsspp.), for example, the long-term tracking of individuals has unveiled considerable variation in social structure among populations and various spatio-temporal aspects of group formation. In this study, we investigated associations among individual males in a small community of Indo-Pacific bottlenose dolphins (T. aduncus) residing in an urbanized estuary in southwestern Australia. Given the relative proximity of our study area to other populations in which complex male alliances form for the purpose of mate acquisition, we used long-term photo-identification records and social analyses to assess whether such alliances also occur in smaller and more isolated settings. Our work revealed strong social bonds and long-term, non-random associations among individual males, suggesting the occurrence of male alliances. Behavioural observations of alliances interacting with potentially receptive adult females from the estuary community and from adjacent communities, and exhibiting sexual display behaviours near females, suggest that these alliances occur in a reproductive context. As the first formal analysis indicating the occurrence of male alliances outside Shark Bay along the vast western coastline of Australia, this study complements previous research and extends our understanding of the evolutionary and ecological processes that drive alliance formation.
Generalized Cubic Pythagorean Fuzzy Aggregation Operators and their Application to Multi-attribute Decision-Making Problems
Authors: Amin Fazli , Rahim Muhammad , Ali Asad , Ameer Eskandar
Published: October 2022

Cubic Pythagorean fuzzy (CPF) set (CPFS) is a hybrid set that can hold much more information and can be used to describe both an interval-valued Pythagorean fuzzy set (IVPFS) and Pythagorean fuzzy set (PFS) at the same time to handle data uncertainties. Based on it, the present study is classified into three phases. The first phase is to modify the existing operational laws and aggregation operators (AOs) in the article presented by Abbas et al. (Journal of Intelligent & Fuzzy Systems, vol. 37, no. 1, pp. 1529–1544, (2019)). The main objective of improved operational laws is to eliminate the flows and ambiguities in existing AOs. Secondly, based on these laws, various AOs to aggregate the information are acquired along with their requisite properties and relations. Lastly, an approach for interpreting the multi-attribute decision-making (MCDM) problem based on the stated operators is given and illustrated with an example. Some of the existing models are used to perform a comprehensive comparative analysis to demonstrate their impacts.
Cost-effectiveness of psychological intervention within services for depression delivered by primary care workers in Nepal: economic evaluation of a randomized control trial
Authors: Aldridge L. R. , Luitel N. P. , Jordans M. J. D. , Bass J. K. , Patenaude B.
Published: October 2022

Background

Integrating services for depression into primary care is key to reducing the treatment gap in low- and middle-income countries. We examined the value of providing the Healthy Activity Programme (HAP), a behavioral activation psychological intervention, within services for depression delivered by primary care workers in Chitwan, Nepal using data from the Programme for Improving Mental Health Care.

Methods

People diagnosed with depression were randomized to receive either standard treatment (ST), comprised of psychoeducation, antidepressant medication, and home-based follow up, or standard treatment plus psychological intervention (T + P). We estimated incremental costs and health effects of T + P compared to ST, with quality adjusted life years (QALYs) and depression symptom scores over 12 months as health effects. Nonparametric uncertainty analysis provided confidence intervals around each incremental effectiveness ratio (ICER); results are presented in 2020 international dollars.

Results

Sixty participants received ST and 60 received T + P. Implementation costs (ST = $329, T + P = $617) were substantially higher than service delivery costs (ST = $18.7, T + P = $22.4) per participant. ST and T + P participants accrued 46.5 and 49.4 QALYs, respectively. The ICERs for T + P relative to ST were $4422 per QALY gained (95% confidence interval: $2484 to $9550) – slightly above the highly cost-effective threshold – and −$53.21 (95% confidence interval: −$105.8 to −$30.2) per unit change on the Patient Health Questionnaire.

Conclusion

Providing HAP within integrated depression services in Chitwan was cost-effective, if not highly cost-effective. Efforts to scale up integrated services in Nepal and similar contexts should consider including evidence-based psychological interventions as a part of cost-effective mental healthcare for depression.
Debasement and demography in England and France in the Later Middle Ages
Authors: Mayhew Nick , Ball Katherine
Published: October 2022

England recovered slowly after the Black Death, but countries which debased more saw rising prices and earlier population growth and economic recovery. We examine debasement in England, France, Flanders, and Scotland, emphasising the importance of nominal prices and governments’ role in determining and enforcing monetary policy. Money, as well as demography, strongly influenced the behaviour of prices in later medieval Europe, and price changes had profound economic effects. Population levels depend on mortality and fertility. It is not clear that mortality in England was more severe than elsewhere, but the English economic recession could have affected fertility and nuptiality.
Observations of High Densities at Low Altitudes in the Nightside Ionosphere of Mars by the MAVEN Radio Occultation Science Experiment (ROSE)
Authors: Withers P. , Felici M. , Mendillo M. , Vogt M. F. , Barbinis E. , Kahan D. , Oudrhiri K. , Gray C. , Lee C. O. , Xu S. , Lester M. , Sanchez‐Cano B. , Jakosky B. M. , Curry S.
Published: October 2022

Unusually large peak electron density values of ∼5 × 1010 m−3 are sporadically observed in the nightside ionosphere of Mars in regions of strong and open crustal magnetic field. However, the associated vertical structure of the ionosphere has not previously been observed. Here, we present three vertical electron density profiles from the nightside ionosphere of Mars that have comparably large values of peak electron density. They were acquired by the Radio Occultation Science Experiment on the MAVEN spacecraft on 23, 24, and 29 March 2021. In these profiles, the peak density is large (2–4 × 1010 m−3), the peak altitude is low (60–90 km), and the plasma layer is broad (full width at half maximum greater than 100 km, Chapman layer lengthscale of ∼30 km). Even if the peak altitude is at the upper end of this range, 90 km, the plasma density at 60 km would still be large, approximately 70% of the peak density. These findings hold even if the ionosphere was patchy, not spherically symmetric, during these observations. These three profiles were acquired at times when fluxes of energetic protons, but not electrons, were enhanced above background levels. The apparent association of large nightside electron density values with protons, rather than electrons, is contrary to previous findings.
Topology of Magnetic and Velocity Fields at Kinetic Scales in Incompressible Plasma Turbulence
Authors: Zhang J. , Huang S. Y. , Sahraoui F. , Andrés N. , Yuan Z. G. , Jiang K. , Xu S. B. , Wei Y. Y. , Xiong Q. Y. , Wang Z. , Lin R. T. , Yu L.
Published: October 2022

The topology of the magnetic and velocity fields at the kinetic scales are investigated in the context of nearly incompressible magnetosheath plasma turbulence. Using the unprecedented high‐resolution data from the Magnetospheric MultiScale mission, the joint probability distribution functions of geometrical invariants characterizing the magnetic and velocity fields gradient tensor at the kinetic scales are computed. The topological features of the magnetic and velocity field gradient tensors and their symmetric component tensors present axisymmetric distribution patterns, indicating that the structure of the plasma turbulence at the kinetic scales are different from those in hydrodynamic and magnetohydrodynamic turbulence. Moreover, a strong correlation between the straining and rotational parts of the magnetic and velocity field gradient tensors was found, which manifests the dominance of sheet‐like structures at the kinetic‐scales dissipation in incompressible plasma turbulence.
Inception of Regular Valley Spacing in Fluvial Landscapes: A Linear Stability Analysis
Authors: Anand Shashank Kumar , Bonetti Sara , Camporeale Carlo , Porporato Amilcare
Published: October 2022

Incipient valley formation in mountainous landscapes is often associated with their presence at a regular spacing under diverse hydroclimatic forcings. Here we provide a formal linear stability theory for a landscape evolution model representing the action of tectonic uplift, diffusive soil creep, and detachment‐limited fluvial erosion. For configurations dominated by only one horizontal length scale, a single dimensionless quantity characterizes the overall system dynamics based on model parameters and boundary conditions. The stability analysis is conducted for smooth and symmetric hillslopes along a long mountain ridge to study the impact of the erosion law form on regular first‐order valley formation. The results provide the critical condition when smooth landscapes become unstable and give rise to a characteristic length scale for incipient valleys, which is related to the scaling exponents that couple fluvial erosion to the specific drainage area and the local slope. The valley spacing at first instability is uniquely related to the ratio of the scaling exponents and widens with an increase in this ratio. We find compelling evidence of sediment transport by diffusive creep and fluvial erosion coupled with the specific drainage area equation as a sufficient mechanism for first‐order valley formation. We finally show that the predictions of the linear stability analysis conform with the results of numerical simulations for different degrees of nonlinearity in the erosion law and agree well with topographic data from a natural landscape.
A Large Simulation Set of Geomagnetic Storms—Can Simulations Predict Ground Magnetometer Station Observations of Magnetic Field Perturbations?
Authors: Al Shidi Q. , Pulkkinen T. , Toth G. , Brenner A. , Zou S. , Gjerloev J.
Published: October 2022

We use the Space Weather Modeling Framework Geospace configuration to simulate a total of 122 storms from the period 2010–2019. With the focus on the storm main phase, each storm period was run for 54 hr starting from 6 hr prior to the start of the Dst depression. The simulation output of ground magnetic variations, ΔBH in particular, were compared with ground magnetometer station data provided by SuperMAG to statistically assess the Geospace model regional magnetic perturbation prediction performance. Our results show that the regional predictions at mid‐latitudes are quite accurate, but the high‐latitude regional disturbances are still difficult to predict.
Two kinds of transcription factors mediate chronic morphine-induced decrease in miR-105 in medial prefrontal cortex of rats
Authors: Zhang Junfang , Guo Xinli , Cai Zhangyin , Pan Yan , Yang Hao , Fu Yali , Cao Zixuan , Wen Yaxian , Lei Chao , Chu Chenshan , Yuan Yu , Cui Dongyang , Gao Pengyu , Lai Bin , Zheng Ping
Published: October 2022

Chronic morphine administration alters gene expression in different brain regions, an effect which may contribute to plastic changes associated with addictive behavior. This change in gene expression is most possibly mediated by addictive drug-induced epigenetic remodeling of gene expression programs. Our previous studies showed that chronic morphine-induced decrease of miR-105 in the medial prefrontal cortex (mPFC) contributed to context-induced retrieval of morphine withdrawal memory. However, how chronic morphine treatment decreases miR-105 in the mPFC still remains unknown. The present study shows that chronic morphine induces addiction-related change in miR-105 in the mPFC via two kinds of transcription factors: the first transcription factor is CREB activated by mu receptors-ERK-p90RSK signaling pathway and the second transcription factor is glucocorticoid receptor (GR), which as a negative transcription factor, mediates chronic morphine-induced decrease in miR-105 in the mPFC of rats.
Nrf2 regulates the arginase 1+ microglia phenotype through the initiation of TREM2 transcription, ameliorating depression-like behavior in mice
Authors: He Lujuan , Zheng Yi , Huang Lixuan , Ye Jingyi , Ye Yinyi , Luo Hanyue , Chen Xi , Yao Wei , Chen Jiaxu , Zhang Ji-chun
Published: October 2022

The expression of the triggering receptor on myeloid cell-2 (TREM2) knockdown in microglia from the lateral habenula (LHb) reportedly induces depression-like behaviors in mice. However, the key molecular mechanism that mediates major depressive disorder (MDD) pathogenesis remains elusive. We herein show that Nrf2 regulates TREM2 transcription and effects TREM2 mRNA and protein expression. The activation of Nrf2 by sulforaphane (Nrf2 activator) increases the microglial arginase 1+ phenotype by initiating TREM2 transcription in the medial prefrontal cortex (mPFC) and ameliorates depression-like behavior in CSDS mice. The knockout of Nrf2 decreases TREM2 and the microglial arginase 1+ phenotype in the mPFC of Nrf2 KO mice with depression-like behavior. Downregulating TREM2 expression decreases the microglial arginase 1+ phenotype in the mPFC, resulting in depression-like behavior in SFN-treated CSDS mice. Finally, the knockout of Nrf2 and downregulation of TREM2 expression decreases the microglial arginase 1+ phenotype in the mPFC of Nrf2 KO mice and SFN-treated CSDS mice were associated with the brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling pathway. These data indicate that alterations in the interaction between Nrf2 and TREM2 may play a role in the pathophysiology of depression-like behavior in mice.
Impact of the COVID-19 pandemic on the research activities of UK ophthalmologists
Authors: Hogg H. D. J. , Low L. , Self J. E. ,   Royal College of Ophthalmologists’ Academic and Research Subcommittee, Allen Louise , Atan Denize , Bourne Rupert R. A. , Dick Andrew D. , Foster Paul J. , Gale Richard P. , Hammond Christopher J. , Megaw Roly , Moosajee Mariya , Sivaprasad Sobha , Rahi J. S.
Published: October 2022

Background

The COVID-19 pandemic has impacted negatively on many areas of biomedical research and there is concern that academic recovery will take several years. This survey aimed to define the impact of the COVID-19 pandemic on UK ophthalmologists’ research activities and understand the implications for recovery.

Methods

An online survey comprising multiple choice and free-text questions was designed, piloted and then distributed to Royal College of Ophthalmologists (RCOphth) members in January 2021. Respondent characteristics, research expectations and experiences through the pandemic were captured. Descriptive and comparative statistics were applied to quantitative data alongside content analysis of qualitative data.

Results

In total, 148 respondents (3.7% of RCOphth membership) comprised 46 trainees (31.1%), 97 consultants (65.5%) and 5 SAS doctors (3.4%); 54 had clinical-academic roles (36.5%) and 65/94 (69.1%) ophthalmologists with fully clinical posts identified as research-active. Of 114 research-active respondents, 104 (91.2%) reported an impact on their research from COVID-19; negative impacts included loss of research time (n = 69), research delays (n = 96) and funding shortfalls (n = 63). Content analysis identified five common themes; type of research activity, clinical demands, institutional challenges, COVID-19 alignment and work-life balance.

Conclusions

UK ophthalmology research has been adversely impacted by the pandemic. A substantial proportion of UK ophthalmologists are research active, but 20.4% of those surveyed felt that the pandemic had made research less attractive. Strategic steps must be taken to nurture UK ophthalmologists’ engagement with research, especially for those who currently do no research, if the profession is to align itself with the Government vision of ‘Research for All’.
Prolonged in situ self-healing in structural composites via thermo-reversible entanglement
Authors: Snyder Alexander D. , Phillips Zachary J. , Turicek Jack S. , Diesendruck Charles E. , Nakshatrala Kalyana B. , Patrick Jason F.
Published: October 2022

Natural processes continuously degrade a material’s performance throughout its life cycle. An emerging class of synthetic self-healing polymers and composites possess property-retaining functions with the promise of longer lifetimes. But sustained in-service repair of structural fiber-reinforced composites remains unfulfilled due to material heterogeneity and thermodynamic barriers in commonly cross-linked polymer-matrix constituents. Overcoming these inherent challenges for mechanical self-recovery is vital to extend in-service operation and attain widespread adoption of such bioinspired structural materials. Here we transcend existing obstacles and report a fiber-composite capable of minute-scale and prolonged in situ healing — 100 cycles: an order of magnitude higher than prior studies. By 3D printing a mendable thermoplastic onto woven glass/carbon fiber reinforcement and co-laminating with electrically resistive heater interlayers, we achieve in situ thermal remending of internal delamination via dynamic bond re-association. Full fracture recovery occurs below the glass-transition temperature of the thermoset epoxy-matrix composite, thus preserving stiffness during and after repair. A discovery of chemically driven improvement in thermal remending of glass- over carbon-fiber composites is also revealed. The marked lifetime extension offered by this self-healing strategy mitigates costly maintenance, facilitates repair of difficult-to-access structures (e.g., wind-turbine blades), and reduces part replacement, thereby benefiting economy and environment.
Formation of supramolecular channels by reversible unwinding-rewinding of bis(indole) double helix via ion coordination
Authors: Mondal Debashis , Ahmad Manzoor , Dey Bijoy , Mondal Abhishek , Talukdar Pinaki
Published: October 2022

Stimulus-responsive reversible transformation between two structural conformers is an essential process in many biological systems. An example of such a process is the conversion of amyloid-β peptide into β-sheet-rich oligomers, which leads to the accumulation of insoluble amyloid in the brain, in Alzheimer’s disease. To reverse this unique structural shift and prevent amyloid accumulation, β-sheet breakers are used. Herein, we report a series of bis(indole)-based biofunctional molecules, which form a stable double helix structure in the solid and solution state. In presence of chloride anion, the double helical structure unwinds to form an anion-coordinated supramolecular polymeric channel, which in turn rewinds upon the addition of Ag+ salts. Moreover, the formation of the anion-induced supramolecular ion channel results in efficient ion transport across lipid bilayer membranes with excellent chloride selectivity. This work demonstrates anion-cation-assisted stimulus-responsive unwinding and rewinding of artificial double-helix systems, paving way for smart materials with better biomedical applications.
B cells oppose Mycoplasma pneumoniae vaccine enhanced disease and limit bacterial colonization of the lungs
Authors: Gavitt Tyler D. , Mara Arlind B. , Goodridge Meagan L. , Ozyck Rosemary Grace , Reinhardt Emily , Miller Jeremy M. , Hunte Morgan , Tulman Edan R. , Frasca Jr Salvatore , Silbart Lawrence K. , Geary Steven J. , Szczepanek Steven M.
Published: October 2022

Development of an effective vaccine for Mycoplasma pneumoniae has been hindered by reports of Vaccine Enhanced Disease (VED) in test subjects vaccinated and challenged in studies conducted in the 1960s. The exact mechanism of disease exacerbation has yet to be fully described, but host immune responses to Lipid-Associated Membrane Proteins (LAMPs) lipoprotein lipid moieties have been implicated. LAMPs-induced exacerbation appears to involve helper T cell recall responses, due in part to their influence on neutrophil recruitment and subsequent inflammatory responses in the lung. Herein, we characterized the functions of host B cell responses to M. pneumoniae LAMPs and delipidated-LAMPs (dLAMPs) by conducting passive transfer and B cell depletion studies to assess their contribution to disease exacerbation or protection using a BALB/c mouse model. We found that antibody responses to M. pneumoniae LAMPs and dLAMPs differ in magnitude, but not in isotype or subclass. Passive transfer, dLAMP denaturation, and monoclonal antibody studies indicate that antibodies do not cause VED, but do appear to contribute to control of bacterial loads in the lungs. Depletion of B cells prior to LAMPs-vaccination results in significantly enhanced pathology in comparison to B cell competent controls, suggesting a possible regulatory role of B cells distinct from antibody secretion. Taken together, our findings suggest that B cell antibody responses to M. pneumoniae contribute to, but are insufficient for protection against challenge on their own, and that other functional properties of B cells are necessary to limit exacerbation of disease in LAMPs-vaccinated mice after infection.
Characterization of an Escherichia coli-derived triple-type chimeric vaccine against human papillomavirus types 39, 68 and 70
Authors: Qian Ciying , Yang Yurou , Xu Qin , Wang Zhiping , Chen Jie , Chi Xin , Yu Miao , Gao Fei , Xu Yujie , Lu Yihan , Sun Hui , Shen Jingjia , Wang Daning , Zhou Lizhi , Li Tingting , Wang Yingbin , Zheng Qingbing , Yu Hai , Zhang Jun , Gu Ying , Xia Ningshao , Li Shaowei
Published: October 2022

In vaccinology, a potent immunogen has two prerequisite attributes—antigenicity and immunogenicity. We have rational designed a triple-type HPV vaccine against HPV58, −33 and −52 covered in Gardasil 9 based on the sequence homology and similar surface loop structure of L1 protein, which is related to cross-type antigenicity. Here, we design another triple-type vaccine against non-vaccine types HPV39, −68 and −70 by immunogenicity optimization considering type specific immunodominant epitopes located in separate region for different types. First, we optimized the expression of wild-type HPV39, −68 and −70 L1-only virus-like particles (VLPs) in E. coli through N-terminal truncation of HPV L1 proteins and non-fusion soluble expression. Second, based on genetic relationships and an L1 homologous loop-swapping rationale, we constructed several triple-type chimeric VLPs for HPV39, −68 and −70, and obtained the lead candidate named H39–68FG-70DE by the immunogenicity optimization using reactivity profile of a panel type-specific monoclonal antibodies. Through comprehensive characterization using various biochemical, VLP-based analyses and immune assays, we show that H39–68FG-70DE assumes similar particulate properties as that of its parental VLPs, along with comparable neutralization immunogenicity for all three HPV types. Overall, this study shows the promise and translatability of an HPV39/68/70 triple-type vaccine, and the possibility of expanding the type-coverage of current HPV vaccines. Our study further expanded the essential criteria on the rational design of a cross-type vaccine, i.e. separate sites with inter-type similar sequence and structure as well as type-specific immunodominant epitope to be clustered together.
Toxoplasmosis vaccines: what we have and where to go?
Authors: Zhang Yizhuo , Li Dan , Lu Shaohong , Zheng Bin
Published: October 2022

Despite recent major advances in developing effective vaccines against toxoplasmosis, finding new protective vaccination strategies remains a challenging and elusive goal as it is critical to prevent the disease. Over the past few years, various experimental approaches have shown that developing an effective vaccine against T. gondii is achievable. However, more remains unknown due to its complicated life cycle, difficulties in clinical translation, and lack of a standardized platform. This minireview summarizes the recent advances in the development of T. gondii vaccines and the main obstacles to developing a safe, effective and durable T. gondii vaccine. The successes and failures in developing and testing vaccine candidates for the T. gondii vaccine are also discussed, which may facilitate the future development of T. gondii vaccines.
A split, conditionally active mimetic of IL-2 reduces the toxicity of systemic cytokine therapy
Authors: Quijano-Rubio Alfredo , Bhuiyan Aladdin M. , Yang Huilin , Leung Isabel , Bello Elisa , Ali Lestat R. , Zhangxu Kevin , Perkins Jilliane , Chun Jung-Ho , Wang Wentao , Lajoie Marc J. , Ravichandran Rashmi , Kuo Yun-Huai , Dougan Stephanie K. , Riddell Stanley R. , Spangler Jamie B. , Dougan Michael , Silva Daniel-Adriano , Baker David
Published: October 2022

The therapeutic potential of recombinant cytokines has been limited by the severe side effects of systemic administration. We describe a strategy to reduce the dose-limiting toxicities of monomeric cytokines by designing two components that require colocalization for activity and that can be independently targeted to restrict activity to cells expressing two surface markers. We demonstrate the approach with a previously designed mimetic of cytokines interleukin-2 and interleukin-15—Neoleukin-2/15 (Neo-2/15)—both for trans-activating immune cells surrounding targeted tumor cells and for cis-activating directly targeted immune cells. In trans-activation mode, tumor antigen targeting of the two components enhanced antitumor activity and attenuated toxicity compared with systemic treatment in syngeneic mouse melanoma models. In cis-activation mode, immune cell targeting of the two components selectively expanded CD8+ T cells in a syngeneic mouse melanoma model and promoted chimeric antigen receptor T cell activation in a lymphoma xenograft model, enhancing antitumor efficacy in both cases.
Multifactorial profiling of epigenetic landscapes at single-cell resolution using MulTI-Tag
Authors: Meers Michael P. , Llagas Geneva , Janssens Derek H. , Codomo Christine A. , Henikoff Steven
Published: October 2022

Chromatin profiling at locus resolution uncovers gene regulatory features that define cell types and developmental trajectories, but it remains challenging to map and compare different chromatin-associated proteins in the same sample. Here we describe Multiple Target Identification by Tagmentation (MulTI-Tag), an antibody barcoding approach for profiling multiple chromatin features simultaneously in single cells. We optimized MulTI-Tag to retain high sensitivity and specificity, and we demonstrate detection of up to three histone modifications in the same cell: H3K27me3, H3K4me1/2 and H3K36me3. We apply MulTI-Tag to resolve distinct cell types and developmental trajectories; to distinguish unique, coordinated patterns of active and repressive element regulatory usage associated with differentiation outcomes; and to uncover associations between histone marks. Multifactorial epigenetic profiling holds promise for comprehensively characterizing cell-specific gene regulatory landscapes in development and disease.
Incorporating the image formation process into deep learning improves network performance
Authors: Li Yue , Su Yijun , Guo Min , Han Xiaofei , Liu Jiamin , Vishwasrao Harshad D. , Li Xuesong , Christensen Ryan , Sengupta Titas , Moyle Mark W. , Rey-Suarez Ivan , Chen Jiji , Upadhyaya Arpita , Usdin Ted B. , Colón-Ramos Daniel Alfonso , Liu Huafeng , Wu Yicong , Shroff Hari
Published: October 2022

We present Richardson–Lucy network (RLN), a fast and lightweight deep learning method for three-dimensional fluorescence microscopy deconvolution. RLN combines the traditional Richardson–Lucy iteration with a fully convolutional network structure, establishing a connection to the image formation process and thereby improving network performance. Containing only roughly 16,000 parameters, RLN enables four- to 50-fold faster processing than purely data-driven networks with many more parameters. By visual and quantitative analysis, we show that RLN provides better deconvolution, better generalizability and fewer artifacts than other networks, especially along the axial dimension. RLN outperforms classic Richardson–Lucy deconvolution on volumes contaminated with severe out of focus fluorescence or noise and provides four- to sixfold faster reconstructions of large, cleared-tissue datasets than classic multi-view pipelines. We demonstrate RLN’s performance on cells, tissues and embryos imaged with widefield-, light-sheet-, confocal- and super-resolution microscopy.
Amino acids for the prevention of mortality and morbidity in preterm infants: a systematic review and network meta-analysis
Authors: Wang Xiaoqin , Sadeghirad Behnam , Morgan Rebecca L. , Zeratkaar Dena , Chang Yaping , Crandon Holly N. , Couban Rachel , Foroutan Farid , Florez Ivan D.
Published: October 2022

To determine the effectiveness and safety of amino acids in preventing the mortality and morbidity among preterm infants. We conducted a systematic review and network meta-analysis. We searched MEDLINE, EMBASE, Web of Science, CINAHL, Scopus, Cochrane, and Google Scholar, and grey literature, from databases inception to January 2021. We included randomized trials that evaluated any amino acids on preterm or low-birth weight infants. We performed frequentist pairwise and network meta-analyses and used the GRADE methodology to assess the certainty of the evidence and provide a summary of the results.We included 18 trials (3702 infants). Low certainty evidence showed that there seems to be no benefit for arginine, glutamine, or N-acetylcysteine in reducing all-cause mortality. Oral arginine likely results in reduction of necrotizin enterocolitis (NEC) stage ≥ II (OR 0.48; 95% CI 0.26–0.90; moderate certainty). Oral glutamine may reduce the likelihood of developing late-onset sepsis (LOS) compared to placebo (OR 0.62; 95% CI 0.47–0.82; low certainty); and likely reduces time to reach full enteral feeding (MD = − 2.63 days; 95% CI − 4.99 to − 0.27; moderate certainty). Amino acids may have no effect on mortality. Oral arginine may reduce severe NEC, and oral glutamine may reduce LOS and the time to reach full feeding.

Systematic review registration: PROSPERO registration number: CRD4201603873.
Increased retinal drusen in IgA glomerulonephritis are further evidence for complement activation in disease pathogenesis
Authors: Harraka P. , Wightman Tony , Akom Sarah , Sandhu Kieran , Colville Deb , Catran Andrew , Langsford David , Pianta Timothy , Barit David , Ierino Frank , Skene Alison , Mack Heather , Savige Judy
Published: October 2022

Drusen are retinal deposits comprising cell debris, immune material and complement that are characteristic of macular degeneration but also found in glomerulonephritis. This was a pilot cross-sectional study to determine how often drusen occurred in IgA glomerulonephritis and their clinical significance. Study participants underwent non-mydriatic retinal photography, and their deidentified retinal images were examined for drusen by two trained graders, who compared central drusen counts, counts ≥ 10 and drusen size with those of matched controls. The cohort comprised 122 individuals with IgA glomerulonephritis including 89 males (73%), 49 individuals (40%) of East Asian or Southern European ancestry, with an overall median age of 54 years (34–64), and median disease duration of 9 years (4–17). Thirty-nine (33%) had an eGFR < 60 ml/min/1.73 m2 and 72 had previously reached kidney failure (61%). Overall mean drusen counts were higher in IgA glomerulonephritis (9 ± 27) than controls (2 ± 7, p < 0.001). Central counts ≥ 10 were also more common (OR = 3.31 (1.42–7.73, p = 0.006), and were associated with longer disease duration (p = 0.03) but not kidney failure (p = 0.31). Larger drusen were associated with more mesangial IgA staining (p = 0.004). Increased drusen counts were also present in IgA glomerulonephritis secondary to Crohn’s disease but not with Henoch-Schonlein purpura. The finding of retinal drusen in IgA glomerulonephritis is consistent with complement activation and represents a model for better understanding glomerular immune deposition and a supporting argument for treatment with anti-complement therapies.
Transmittance properties of one-dimensional metamaterial nanocomposite photonic crystal in GHz range
Authors: Mohamed Aliaa G. , Elsayed Hussein A. , Mehaney Ahmed , Aly Arafa H. , Sabra Walied
Published: October 2022

We have theoretically demonstrated and explored the transmittance characteristics of a one-dimensional binary photonic crystal composed of metamaterial (MM) and nanocomposite (NC) layers. The NC layer was designed from silver nanoparticles (Ag-NPs) in a host material as Yttrium oxide (Y2O3). Using the transfer matrix approach (TMM), the optical properties of a one-dimensional binary periodic structure having MM and NC layers in the Giga Hertz (GHz) range were examined. The filling fractions of nanoparticles have been explored to see their effect on the effective permittivity of NC materials. Furthermore, the transmittance properties of the suggested structure were investigated at various incident angles for the transverse electric (TE) polarization. In addition to that, different parameters, such as the thickness of the MM layer, the permittivity of the host dielectric material, the filling fraction, and the thickness of the NC layer are also taken into account. We also discussed the effect of these parameters on the width of the photonic bandgap (PBG). With the optimum values of the optical parameters of NC layer, this research could open the way for better photonic crystal circuits, splitters, switches and others.
Network analysis reveals that the tumor suppressor lncRNA GAS5 acts as a double-edged sword in response to DNA damage in gastric cancer
Authors: Gupta Shantanu , Panda Pritam Kumar , Luo Wei , Hashimoto Ronaldo F. , Ahuja Rajeev
Published: October 2022

The lncRNA GAS5 acts as a tumor suppressor and is downregulated in gastric cancer (GC). In contrast, E2F1, an important transcription factor and tumor promoter, directly inhibits miR-34c expression in GC cell lines. Furthermore, in the corresponding GC cell lines, lncRNA GAS5 directly targets E2F1. However, lncRNA GAS5 and miR-34c remain to be studied in conjunction with GC. Here, we present a dynamic Boolean network to classify gene regulation between these two non-coding RNAs (ncRNAs) in GC. This is the first study to show that lncRNA GAS5 can positively regulate miR-34c in GC through a previously unknown molecular pathway coupling lncRNA/miRNA. We compared our network to several in-vivo/in-vitro experiments and obtained an excellent agreement. We revealed that lncRNA GAS5 regulates miR-34c by targeting E2F1. Additionally, we found that lncRNA GAS5, independently of p53, inhibits GC proliferation through the ATM/p38 MAPK signaling pathway. Accordingly, our results support that E2F1 is an engaging target of drug development in tumor growth and aggressive proliferation of GC, and favorable results can be achieved through tumor suppressor lncRNA GAS5/miR-34c axis in GC. Thus, our findings unlock a new avenue for GC treatment in response to DNA damage by these ncRNAs.
Osteopenia is associated with inferior survival in patients undergoing partial hepatectomy for hepatocellular carcinoma
Authors: Meister Franziska Alexandra , Verhoeven Suekran , Mantas Anna , Liu Wen-Jia , Jiang Decan , Heij Lara , Heise Daniel , Bruners Philipp , Lang Sven Arke , Ulmer Tom Florian , Neumann Ulf Peter , Bednarsch Jan , Czigany Zoltan
Published: October 2022

Osteopenia is known to be associated with clinical frailty which is linked to inferior outcomes in various clinical scenarios. However, the exact prognostic value of osteopenia in patients undergoing curative intent-surgery for hepatocellular carcinoma (HCC) is not completely understood. This retrospective study was conducted in a cohort of 151 patients who underwent partial hepatectomy for HCC in curative intent at a German university medical center (05/2008–12/2019). Preoperative computed tomography-based segmentation was used to assess osteopenia, and the prognostic impact of pathological changes in bone mineral density (BMD) on perioperative morbidity, mortality, and long-term oncological outcome was analyzed. Five-year overall survival of osteopenic patients was significantly worse compared to those with normal BMD (29% vs. 65%, p = 0.014). In line with this, the probability of disease-free survival at 5 years was significantly worse for patients with osteopenia (21% vs. 64%, p = 0.005). In our multivariable model, osteopenia was confirmed as an independent risk-factor for inferior overall survival (Hazard-ratio 7.743, p = 0.002). Concerning perioperative complications, osteopenic patients performed slightly worse, even though no statistical difference was detected (Clavien-Dindo ≥ 3b; 21% vs. 9%, p = 0.139). The present study confirms osteopenia as an independent risk-factor for inferior survival in patients undergoing partial hepatectomy for HCC in a European cohort. Further studies are warranted to validate these findings.
Point cloud registration of arrester based on scale-invariant points feature histogram
Authors: Zhu Wen , Chen Lingchao , Hou Beiping , Li Weihan , Chen Tianliang , Liang Shixiong
Published: October 2022

Arrester is an important lightning protection device in the electrical field. The parameters of arrester such as creepage distance, umbrella distance and diameter are important for product quality, but they are difficult to measure because the shape of arrester is irregular. However, the three-dimensional (3D) reconstruction technique is efficient in measuring arrester parameters. The uniform distributed structure of umbrella skirt on the arrester surface restrict the registration of point cloud. In this paper, a scale-invariant points features histogram (SIPFH) descriptor is proposed; the descriptor combines the characteristics of Scale-invariant Feature Transform (SIFT) and fast point feature histogram (FPFH). Moreover, the improved Levenberg-Marquardt (LM) algorithm is presented, the maximum distance of corresponding points in the iterative process is adjusted to realize the local optimization. The point cloud registration method consists of two parts: primary registration method based on SIPFH, and secondary registration method based on improved LM algorithm. Point clouds of different arresters are collected to establish datasets, some of which have interference. Experimental results indicate that the root mean square error of the method is less than 0.02 m; the average running time is 2.7 s, which is$$41.4\%$$41.4%of the conventional method based on FPFH.
Persistent muscle hyperalgesia after adolescent stress is exacerbated by a mild-nociceptive input in adulthood and is associated with microglia activation
Authors: Singaravelu Sathish Kumar , Goitom Alexander Dawit , Graf Akseli Petteri , Moerz Handan , Schilder Andreas , Hoheisel Ulrich , Spanagel Rainer , Treede Rolf-Detlef
Published: October 2022

Non-specific low back pain (LBP) is a major global disease burden and childhood adversity predisposes to its development. The mechanisms are largely unknown. Here, we investigated if adversity in young rats augments mechanical hyperalgesia and how spinal cord microglia contribute to this. Adolescent rats underwent restraint stress, control animals were handled. In adulthood, all rats received two intramuscular injections of NGF/saline or both into the lumbar multifidus muscle. Stress induced in rats at adolescence lowered low back pressure pain threshold (PPT; p = 0.0001) and paw withdrawal threshold (PWT; p = 0.0007). The lowered muscle PPT persisted throughout adulthood (p = 0.012). A subsequent NGF in adulthood lowered only PPT (d = 0.87). Immunohistochemistry revealed changes in microglia morphology: stress followed by NGF induced a significant increase in ameboid state (p < 0.05). Repeated NGF injections without stress showed significantly increased cell size in surveilling and bushy states (p < 0.05). Thus, stress in adolescence induced persistent muscle hyperalgesia that can be enhanced by a mild-nociceptive input. The accompanying morphological changes in microglia differ between priming by adolescent stress and by nociceptive inputs. This novel rodent model shows that adolescent stress is a risk factor for the development of LBP in adulthood and that morphological changes in microglia are signs of spinal mechanisms involved.
Sleep pattern, healthy lifestyle and colorectal cancer incidence
Authors: Chen Jie , Chen Nanqian , Huang Tao , Huang Ninghao , Zhuang Zhenhuang , Liang Hailun
Published: October 2022

Researchers have identified an association between lifestyle factors and colorectal cancer (CRC) risk. This study examined the relationship between sleep patterns and CRC events. 392,252 individuals were sampled from the UK Biobank. Chronotype, sleep duration, insomnia, snoring, and excessive daytime sleepiness were combined to measure a healthy sleep score. A number of healthy sleep factors were defined, along with factors for healthy lifestyle scores. Using Cox proportional hazards regression, computed hazard ratios (HRs) were used to examine the associations between sleep patterns, healthy lifestyles, and the incidence of CRC. Healthy sleep scores were inversely associated with CRC events. The HRs for CRC were 0.90 (95% CI, 0.88–0.92) and 0.95 (95% CI, 0.92–0.98) for a 1-point healthy sleep score increase among males and females. When analyzing sleep components, sleeping 7–8 h/day, no frequent insomnia, no snoring, and no frequent daytime sleepiness were independently associated with a 9%, 14%, 8%, and 14% lower risk of CRC, respectively, whilst healthy lifestyle scores were inversely associated with CRC incidence across all models. Sleep pattern and lifestyle are significantly correlated with CRC risk. The healthier the subject’s lifestyle and sleep pattern, the lower their CRC risk.
Non-invasive brain stimulation modulates GABAergic activity in neurofibromatosis 1
Authors: Garg Shruti , Williams Steve , Jung JeYoung , Pobric Gorana , Nandi Tulika , Lim Ben , Vassallo Grace , Green Jonathan , Evans D. Gareth , Stagg Charlotte J. , Parkes Laura M. , Stivaros Stavros
Published: October 2022

Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive phenotypes common to neurodevelopmental conditions such as autism. GABAergic dysregulation underlies working memory impairments seen in NF1. This mechanistic experimental study investigates whether application of anodal transcranial direct current stimulation (atDCS) can modulate GABA and working memory in NF1. Thirty-one NF1 adolescents 11–18 years, were recruited to this single-blind sham-controlled cross-over randomized trial. AtDCS or sham stimulation was applied to the left Dorsolateral Prefrontal Cortex (DLPFC) and MR Spectroscopy was collected before and after intervention in the left DLPFC and occipital cortex. Task-related functional MRI was collected before, during, and after stimulation. Higher baseline GABA+ in the left DLPFC was associated with faster response times on baseline working memory measures. AtDCS was seen to significantly reduced GABA+ and increase brain activation in the left DLPFC as compared to sham stimulation. Task performance was worse in the aTDCS group during stimulation but no group differences in behavioural outcomes were observed at the end of stimulation. Although our study suggests aTDCS modulates inhibitory activity in the DLPFC, further work is needed to determine whether repeated sessions of atDCS and strategies such as alternating current stimulation offer a better therapeutic approach.