bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of metabolic ecosystem in cancer progression — metabolic plasticity and mTOR hyperactivity in tumor tissues
Authors: Sebestyén Anna , Dankó Titanilla , Sztankovics Dániel , Moldvai Dorottya , Raffay Regina , Cervi Catherine , Krencz Ildikó , Zsiros Viktória , Jeney András , Petővári Gábor
Published: January 2022

Despite advancements in cancer management, tumor relapse and metastasis are associated with poor outcomes in many cancers. Over the past decade, oncogene-driven carcinogenesis, dysregulated cellular signaling networks, dynamic changes in the tissue microenvironment, epithelial-mesenchymal transitions, protein expression within regulatory pathways, and their part in tumor progression are described in several studies. However, the complexity of metabolic enzyme expression is considerably under evaluated. Alterations in cellular metabolism determine the individual phenotype and behavior of cells, which is a well-recognized hallmark of cancer progression, especially in the adaptation mechanisms underlying therapy resistance. In metabolic symbiosis, cells compete, communicate, and even feed each other, supervised by tumor cells. Metabolic reprogramming forms a unique fingerprint for each tumor tissue, depending on the cellular content and genetic, epigenetic, and microenvironmental alterations of the developing cancer. Based on its sensing and effector functions, the mechanistic target of rapamycin (mTOR) kinase is considered the master regulator of metabolic adaptation. Moreover, mTOR kinase hyperactivity is associated with poor prognosis in various tumor types. In situ metabolic phenotyping in recent studies highlights the importance of metabolic plasticity, mTOR hyperactivity, and their role in tumor progression. In this review, we update recent developments in metabolic phenotyping of the cancer ecosystem, metabolic symbiosis, and plasticity which could provide new research directions in tumor biology. In addition, we suggest pathomorphological and analytical studies relating to metabolic alterations, mTOR activity, and their associations which are necessary to improve understanding of tumor heterogeneity and expand the therapeutic management of cancer.
Study of trace metal contamination and ecological risk assessment in the sediments of a tropical river estuary, Southwestern India
Authors: Nishitha D’Souza , Amrish Vadakkeveedu Narayan , Arun Kumar , Warrier Anish Kumar , Udayashankar Harikripa Narayana , Balakrishna Keshava
Published: January 2022

The present study aims to assess the extent of trace metal pollution in the sediments of Sita-Swarna estuary, west coast of India, and investigate their possible ecological risk on the aquatic environment. The sediment cores were analyzed for sand, silt, clay, organic carbon, and trace metals (Al, Fe, Mn, As, Cd, Co, Zn, Pb, Ni, Cr, and Cu) at 2-cm intervals. The study revealed that sediments have deposited in relatively violent to very violent hydrodynamic energy conditions. Factor analysis indicated that the metal distribution is mainly controlled by Fe–Mn oxyhydroxides and organic carbon. Further, the geochemical approach, pollution indices, and statistical evaluation revealed moderate pollution in the catchment. From an ecotoxicological perspective, the estimated risk index (RI) value was found to less than 150, indicating low risk for aquatic life. Thus, this baseline study would help to adopt strategies in pollution control and protect the fragile marine environment.
The Habituation Process in Two Groups of Wild Moor Macaques (Macaca maura)
Authors: Hernández Tienda Clara , Majolo Bonaventura , Romero Teresa , Illa Maulany Risma , Oka Ngakan Putu , Beltrán Francés Víctor , Gregorio Hernández Elisa , Gómez-Melara Jose , Llorente Miquel , Amici Federica
Published: January 2022

When studying animal behavior in the wild, some behaviors may require observation from a relatively short distance. In these cases, habituation is commonly used to ensure that animals do not perceive researchers as a direct threat and do not alter their behavior in their presence. However, habituation can have significant effects on the welfare and conservation of the animals. Studying how nonhuman primates react to the process of habituation can help to identify the factors that affect habituation and implement habituation protocols that allow other researchers to speed up the process while maintaining high standards of health and safety for both animals and researchers. In this study, we systematically described the habituation of two groups of wild moor macaques (Macaca maura), an Endangered endemic species of Sulawesi Island (Indonesia), to assess the factors that facilitate habituation and reduce impact on animal behavior during this process. During 7 months, we conducted behavioral observations for more than 7,872 encounters and an average of 120 days to monitor how macaque behavior toward researchers changed through time in the two groups under different conditions. We found that both study groups (N = 56, N = 41) became more tolerant to the presence of researchers during the course of the habituation, with occurrence of neutral group responses increasing, and minimum distance to researchers and occurrence of fearful group responses decreasing through time. These changes in behavior were predominant when macaques were in trees, with better visibility conditions, when researchers maintained a longer minimum distance to macaques and, unexpectedly, by the presence of more than one researcher. By identifying these factors, we contribute to designing habituation protocols that decrease the likelihood of fearful responses and might reduce the stress experienced during this process.
Not Getting Stuck in Dryness - Strategies for Coping with Phases of Spiritual Dryness Among Religious Brothers and Sisters in Germany—Findings from Qualitative Interviews
Authors: Gerundt Mareike , Beerenbrock Yvonne , Büssing Arndt
Published: January 2022

Many believers experience phases of spiritual dryness in their lives coupled with feelings of exhaustion, confusion, and emotional emptiness. Even religious sisters and brothers experience such phases. But how do they cope with phases of spiritual dryness, and what resources do they use to overcome them? In a qualitative study, 30 religious brothers and sisters utilized four main categories of resources: internal reflective resources, internal spiritual resources, external personal resources, and external other resources. A primary strategy does not seem to exist for overcoming phases of spiritual dryness. In the context of this study, therefore, several resources emerged that were used in accordance with the triggers and were applied against the background of the life situation, context and attitudes, perceptions, behavioral competencies, resources, and abilities of the person concerned.
Muscle force estimation from lower limb EMG signals using novel optimised machine learning techniques
Authors: Mokri Chiako , Bamdad Mahdi , Abolghasemi Vahid
Published: January 2022

The main objective of this work is to establish a framework for processing and evaluating the lower limb electromyography (EMG) signals ready to be fed to a rehabilitation robot. We design and build a knee rehabilitation robot that works with surface EMG (sEMG) signals. In our device, the muscle forces are estimated from sEMG signals using several machine learning techniques, i.e. support vector machine (SVM), support vector regression (SVR) and random forest (RF). In order to improve the estimation accuracy, we devise genetic algorithm (GA) for parameter optimisation and feature extraction within the proposed methods. At the same time, a load cell and a wearable inertial measurement unit (IMU) are mounted on the robot to measure the muscle force and knee joint angle, respectively. Various performance measures have been employed to assess the performance of the proposed system. Our extensive experiments and comparison with related works revealed a high estimation accuracy of 98.67% for lower limb muscles. The main advantage of the proposed techniques is high estimation accuracy leading to improved performance of the therapy while muscle models become especially sensitive to the tendon stiffness and the slack length.
Pensions and the Extending Working Lives Agenda in the UK: The Impact on Women
Authors: Foster Liam
Published: January 2022

Extending working lives (EWLs) has been a key policy response to the challenges presented by an ageing population in the United Kingdom (UK). This includes the use of pension policies to encourage working longer. However, opportunities and experiences of EWLs are not equal. While much has been written about EWLs more broadly, limited attention has been paid to connecting those EWLs policies associated with pensions and their potentially unequal impact on women. This article aims to address this gap, taking a feminist political-economy perspective to explore the structural constraints that shape EWLs and pensions. Initially it briefly introduces the EWLs agenda, before focussing on pension developments and their implications for EWLs, considering the gendered nature of these policies. Finally, it touches upon potential policy measures to mitigate the impact of these developments on women. It demonstrates how women’s existing labour market and pension disadvantages have been largely overlooked in the development of EWLs policy, perpetuating or expanded many women’s financial inequalities in later life. It highlights the need for a greater focus on gendered pension differences in developing EWLs policy to ensure women’s circumstances are not adversely impacted on.
Impact of Mindfulness Training on Spanish Police Officers’ Mental and Emotional Health: a Non-Randomized Pilot Study
Authors: Navarrete Jaime , García-Salvador Miguel Ángel , Cebolla Ausiàs , Baños Rosa
Published: January 2022

Objectives

The purpose of this exploratory non-randomized controlled study was to determine the acceptance and effectiveness of an 8-week mindfulness-based intervention (MBI) co-designed by a police officer.

Methods

A pretest-posttest control group design was followed. Participants (MBI group = 20; control group = 18) answered baseline and post-training self-reported measures. In addition, the weekly emotional state of the MBI group was collected. Paired-samplest-test and analysis of covariance were performed for pre-post within-group and between-group differences, respectively, as well as linear mixed effects analysis of repeated measures for week-by-week data.

Results

High acceptance and attendance rates, as well as significant pre-post within-group differences in the MBI group in mindfulness (η2= 0.43), self-compassion (η2= 0.43), depression (η2= 0.54), anxiety (η2= 0.46), stress (η2= 0.51), difficulties in emotion regulation, sleep quality (η2= 0.57), and burnout (η2= 0.31–0.47), were identified. Moreover, police officers who underwent the MBI experienced a week by week decrease of anger, disgust, anxiety, sadness, and desire. Finally, after adjusting for pre-test scores, significant between-group differences were found in the way of attending to internal and external experiences (observing mindfulness facet;ηp2= 0.21), depression symptoms (ηp2= 0.23), general distress (ηp2= 0.24), and the degree of physical and psychological exhaustion (personal burnout;ηp2= 0.20).

Conclusions

The preliminary effectiveness of this MBI on psychopathology and quality of life outcomes in Spanish police officers was discussed. Previous evidence regarding the promising use of MBIs in this population was supported.
An Accelerated Thrombosis Model for Computational Fluid Dynamics Simulations in Rotary Blood Pumps
Authors: Blum Christopher , Groß-Hardt Sascha , Steinseifer Ulrich , Neidlin Michael
Published: January 2022

Purpose

Thrombosis ranks among the major complications in blood-carrying medical devices and a better understanding to influence the design related contribution to thrombosis is desirable. Over the past years many computational models of thrombosis have been developed. However, numerically cheap models able to predict localized thrombus risk in complex geometries are still lacking. The aim of the study was to develop and test a computationally efficient model for thrombus risk prediction in rotary blood pumps.

Methods

We used a two-stage approach to calculate thrombus risk. The first stage involves the computation of velocity and pressure fields by computational fluid dynamic simulations. At the second stage, platelet activation by mechanical and chemical stimuli was determined through species transport with an Eulerian approach. The model was compared with existing clinical data on thrombus deposition within the HeartMate II. Furthermore, an operating point and model parameter sensitivity analysis was performed.

Results

Our model shows good correlation (R2> 0.93) with clinical data and identifies the bearing and outlet stator region of the HeartMate II as the location most prone to thrombus formation. The calculation of thrombus risk requires an additional 10–20 core hours of computation time.

Conclusion

The concentration of activated platelets can be used as a surrogate and computationally low-cost marker to determine potential risk regions of thrombus deposition in a blood pump. Relative comparisons of thrombus risk are possible even considering the intrinsic uncertainty in model parameters and operating conditions.
Nano-enhanced biolubricant in sustainable manufacturing: From processability to mechanisms
Authors: Zhang Yanbin , Li Hao Nan , Li Changhe , Huang Chuanzhen , Ali Hafiz Muhammad , Xu Xuefeng , Mao Cong , Ding Wenfeng , Cui Xin , Yang Min , Yu Tianbiao , Jamil Muhammad , Gupta Munish Kumar , Jia Dongzhou , Said Zafar
Published: January 2022

To eliminate the negative effect of traditional metal-working fluids and achieve sustainable manufacturing, the usage of nano-enhanced biolubricant (NEBL) is widely researched in minimum quantify lubrication (MQL) machining. It’s improved tool wear and surface integrity have been preliminarily verified by experimental studies. The previous review papers also concluded the major influencing factors of processability including nano-enhancer and lubricant types, NEBL concentration, micro droplet size, and so on. Nevertheless, the complex action of NEBL, from preparation, atomization, infiltration to heat transfer and anti-friction, is indistinct which limits preparation of process specifications and popularity in factories. Especially in the complex machining process, in-depth understanding is difficult and meaningful. To fill this gap, this paper concentrates on the comprehensive quantitative assessment of processability based on tribological, thermal, and machined surface quality aspects for NEBL application in turning, milling, and grinding. Then it attempts to answer mechanisms systematically considering multi-factor influence of molecular structure, physicochemical properties, concentration, and dispersion. Firstly, this paper reveals advanced lubrication and heat transfer mechanisms of NEBL by quantitative comparison with biolubricant-based MQL machining. Secondly, the distinctive filmformation, atomization, and infiltration mechanisms of NEBL, as distinguished from metal-working fluid, are clarified combining with its unique molecular structure and physical properties. Furtherly, the process optimization strategy is concluded based on the synergistic relationship analysis among process variables, physicochemical properties, machining mechanisms, and performance of NEBL. Finally, the future development directions are put forward aiming at current performance limitations of NEBL, which requires improvement on preparation and jet methods respects. This paper will help scientists deeply understand effective mechanism, formulate process specifications, and find future development trend of this technology.
The Secondary Harms of Parental Substance Use on Children’s Educational Outcomes: A Review
Authors: Lowthian Emily
Published: January 2022

Parental substance use, that is alcohol and illicit drugs, can have a deleterious impact on child health and wellbeing. An area that can be affected by parental substance use is the educational outcomes of children. Current reviews of the literature in the field of parental substance use and children's educational outcomes have only identified a small number of studies, and most focus on children's educational attainment. To grasp the available literature, the method from Arksey and O’Malley (2005) was used to identify literature. Studies were included if they were empirical, after 1950, and focused on children’s school or educational outcomes. From this, 51 empirical studies were identified which examined the relationship between parental alcohol and illicit drug use on children’s educational outcomes. Five main themes emerged which included attainment, behavior and adjustment, attendance, school enjoyment and satisfaction, academic self-concept, along with other miscellaneous outcomes. This paper highlights the main findings of the studies, the gaps in the current literature, and the challenges presented. Recommendations are made for further research and interventions in the areas of parental substance use and child educational outcomes specifically, but also for broader areas of adversity and child wellbeing.
Edge Learning for Distributed Big Data Analytics
Authors: Guo Song , Qu Zhihao
Published: January 2022

Discover this multi-disciplinary and insightful work, which integrates machine learning, edge computing, and big data. Presents the basics of training machine learning models, key challenges and issues, as well as comprehensive techniques including edge learning algorithms, and system design issues. Describes architectures, frameworks, and key technologies for learning performance, security, and privacy, as well as incentive issues in training/inference at the network edge. Intended to stimulate fruitful discussions, inspire further research ideas, and inform readers from both academia and industry backgrounds. Essential reading for experienced researchers and developers, or for those who are just entering the field.
Expanding Paleoindian Diet Breadth: Paleoethnobotany of Connley Cave 5, Oregon, USA
Authors: McDonough Katelyn N. , Kennedy Jaime L. , Rosencrance Richard L. , Holcomb Justin A. , Jenkins Dennis L. , Puseman Kathryn
Published: January 2022

Paleoethnobotanical perspectives are essential for understanding past lifeways yet continue to be underrepresented in Paleoindian research. We present new archaeobotanical and radiocarbon data from combustion features within stratified cultural components at Connley Caves, Oregon, that reaffirm the inclusion of plants in the diet of Paleoindian groups. Botanical remains from three features in Connley Cave 5 show that people foraged for diverse dryland taxa and a narrow range of wetland plants during the summer and fall months. These data add new taxa to the known Pleistocene food economy and support the idea that groups equipped with Western Stemmed Tradition toolkits had broad, flexible diets. When viewed continentally, this work contributes to a growing body of research indicating that regionally adapted subsistence strategies were in place by at least the Younger Dryas and that some foragers in the Far West may have incorporated a wider range of plants including small seeds, leafy greens, fruits, cacti, and geophytes into their diet earlier than did Paleoindian groups elsewhere in North America. The increasing appearance of diverse and seemingly low-ranked resources in the emerging Paleoindian plant-food economy suggests the need to explore a variety of nutritional variables to explain certain aspects of early foraging behavior.
The Conceptual Problems Arising from Legal Pluralism
Authors: Fabra-Zamora Jorge Luis
Published: January 2022

This paper argues that analytical jurisprudence has been insufficiently attentive to three significant puzzles highlighted by the legal pluralist tradition: the existence of commonalities between different types of law, the possibility of a distinction between law and non-law, and the explanatory centrality of the state. I further argue that the resolution of these questions sets the stage for a renewed agenda of analytical jurisprudence and has to be considered in attempts for reconciliation between the academic traditions of analytical jurisprudence and legal pluralism, often called “pluralist jurisprudence.” I also argue that the resolution of these problems affects the empirical, doctrinal, and politico-moral inquiries about legal pluralism.
The Attorney General, Politics, and the Public Interest: Contributions to an Evolving Constitutional Convention
Authors: Murphy Michael
Published: January 2022

The prosecutorial independence of the Attorney General (AG) is a firmly established constitutional convention in Canada, but it is also an evolving convention, subject to ongoing contestation and debate. This article is a contribution to that debate. It defends a normative constitutional framework wherein the AG’s authority to make final decisions in matters of criminal prosecution is balanced against a corresponding duty to consult with cabinet and the prime minister on the public interest implications of prosecutorial decisions when the circumstances warrant. Within this normative framework, respectful contestation and debate amongst ministers, the prime minister, and the AG in determining the public interest merits of prosecution is welcomed, even encouraged, and if conducted with the requisite integrity, objectivity, and transparency, it is regarded not as a threat but as a valuable check and balance on AG independence and an indispensable form of quality control on the exercise of prosecutorial discretion.
Board Games: Antecedents of Australia’s Interlocking Directorates, 1910–2018
Authors: Wright Claire E. F.
Published: January 2022

Interlocking directorates can encourage innovation, cooperation, and adherence to best practices or can contribute to collusion, corruption, and the stagnation of ideas. Research has identified the contingent nature of director networks, with outcomes dependent on the nature of the tie; the firms and individuals involved; and the institutional, sociopolitical, and cultural context. Distinguishing between helpful and harmful interlocks thus requires understanding the foundations on which they were built. This article is the first systematic, longitudinal analysis of the antecedents of interlocking directorates in Australia, complementing substantial international efforts to understand and compare director networks across the twentieth century. The network has been characterized by a relatively consistent long-run level of connection but substantial variation in the causes of interlocks. The director network in Australia has responded to the pragmatics of the board member occupation, with corporate governance regulations, the progress of the professions, banking and prudential practices, and the form of large organizations encouraging ties that were built on professional expertise and geographic proximity. These findings are important for policy makers, regulatory bodies, and scholars, highlighting the importance of understanding the contextual foundations of interlocks when assessing their potential for harm.
Restricted vision: Censorship and cinematic resistance in Thailand
Authors: Viernes Noah Keone
Published: January 2022

Film censorship screens the nation as a ‘way of seeing’ that is both fundamental to the art of governance and vulnerable to the flexibility of contemporary global images. In Thailand, this historically-conditioned regime arose in the geopolitics of the 1930 Film Act, the Motion Pictures and Video Act of 2008, and a coterminous regulation of visuality as a form of cultural governance. I pursue a close reading of two banned films by Apichatpong Weerasethakul and Nontawat Numbenchapol, respectively, to illustrate the aesthetics of film censorship in light of the development of a national cinema, especially to consider the strategies that film-makers use to negotiate the governance of vision.
#yeeyeenation
Authors: Putcha Rumya S.
Published: January 2022

Using methods from country music studies, performance studies, hashtag ethnography, and Black Feminist Thought (BFT), this article employs sonic, discursive, and social media analysis to examine performances of White masculinity known as “country boys.” In the opening sections, I describe examples of country boys that emerge from Texas A&M University (College Station), bringing together confederate statues and the men who identify with and defend such statues. I then turn my focus to critical analysis of one country boy in particular: county music singer, brand progenitor, and Texas icon, Granger Smith a.k.a. Earl Dibbles Jr. Highlighting the importance of country boys to the cultural identity of Texas A&M University, I argue that White publics aggregate and accrue racialized and gendered meaning in social media spaces through signs associated with Smith like the hashtag #yeeyeenation. Such signs are predicated on and normalize a rhetoric—in this case, that something or someone “is not racist”—even in the face of evidence to the contrary. Extending the insights of scholarship on the former Confederacy to contemporary country music cultures and to the present political moment, this article interrogates how White identities and related genealogies in the U.S. context are not simply established to sanitize and excuse expressions of racist, gendered, and exclusionary thought, but are sustained by aestheticized deceptions. I refer to these deceptions as mythopoetics. In this article I demonstrate how Smith’s success, particularly since he is best known for his “redneck” alter-ego, Earl Dibbles Jr., is a testament to the power and reach of mythopoetics in a hegemonic White and heteropatriarchal society. I argue that mythopoetics are not only essential to majoritarian cultural formations today, but also normalize White supremacy to such a point that its violence can circulate without consequence and in plain sight.
Associations between body composition, fat distribution and metabolic consequences of excess adiposity with severe COVID-19 outcomes: observational study and Mendelian randomisation analysis
Authors: Gao Min , Wang Qin , Piernas Carmen , Astbury Nerys M. , Jebb Susan A. , Holmes Michael V. , Aveyard Paul
Published: January 2022

Background

Higher body mass index (BMI) and metabolic consequences of excess weight are associated with increased risk of severe COVID-19, though their mediating pathway is unclear.

Methods

A prospective cohort study included 435,504 UK Biobank participants. A two-sample Mendelian randomisation (MR) study used the COVID-19 Host Genetics Initiative in 1.6 million participants. We examined associations of total adiposity, body composition, fat distribution and metabolic consequences of excess weight, particularly type 2 diabetes, with incidence and severity of COVID-19, assessed by test positivity, hospital admission, intensive care unit (ICU) admission and death.

Results

BMI and body fat were associated with COVID-19 in the observational and MR analyses but muscle mass was not. The observational study suggested the association with central fat distribution was stronger than for BMI, but there was little evidence from the MR analyses than this was causal. There was evidence that strong associations of metabolic consequences with COVID-19 outcomes in observational but not MR analyses. Type 2 diabetes was strongly associated with COVID-19 in observational but not MR analyses. In adjusted models, the observational analysis showed that the association of BMI with COVID-19 diminished, while central fat distribution and metabolic consequences of excess weight remained strongly associated. In contrast, MR showed the reverse, with only BMI retaining a direct effect on COVID-19.

Conclusions

Excess total adiposity is probably casually associated with severe COVID-19. Mendelian randomisation data do not support causality for the observed associations of central fat distribution or metabolic consequences of excess adiposity with COVID-19.
High-throughput volumetric adaptive optical imaging using compressed time-reversal matrix
Authors: Lee Hojun , Yoon Seokchan , Loohuis Pascal , Hong Jin Hee , Kang Sungsam , Choi Wonshik
Published: January 2022

Deep-tissue optical imaging suffers from the reduction of resolving power due to tissue-induced optical aberrations and multiple scattering noise. Reflection matrix approaches recording the maps of backscattered waves for all the possible orthogonal input channels have provided formidable solutions for removing severe aberrations and recovering the ideal diffraction-limited spatial resolution without relying on fluorescence labeling and guide stars. However, measuring the full input–output response of the tissue specimen is time-consuming, making the real-time image acquisition difficult. Here, we present the use of a time-reversal matrix, instead of the reflection matrix, for fast high-resolution volumetric imaging of a mouse brain. The time-reversal matrix reduces two-way problem to one-way problem, which effectively relieves the requirement for the coverage of input channels. Using a newly developed aberration correction algorithm designed for the time-reversal matrix, we demonstrated the correction of complex aberrations using as small as 2% of the complete basis while maintaining the image reconstruction fidelity comparable to the fully sampled reflection matrix. Due to nearly 100-fold reduction in the matrix recording time, we could achieve real-time aberration-correction imaging for a field of view of 40 × 40 µm2 (176 × 176 pixels) at a frame rate of 80 Hz. Furthermore, we demonstrated high-throughput volumetric adaptive optical imaging of a mouse brain by recording a volume of 128 × 128 × 125 µm3 (568 × 568 × 125 voxels) in 3.58 s, correcting tissue aberrations at each and every 1 µm depth section, and visualizing myelinated axons with a lateral resolution of 0.45 µm and an axial resolution of 2 µm.
A customizable, low-power, wireless, embedded sensing platform for resistive nanoscale sensors
Authors: Nedelcu Stefan , Thodkar Kishan , Hierold Christofer
Published: January 2022

Customizable, portable, battery-operated, wireless platforms for interfacing high-sensitivity nanoscale sensors are a means to improve spatiotemporal measurement coverage of physical parameters. Such a platform can enable the expansion of IoT for environmental and lifestyle applications. Here we report a platform capable of acquiring currents ranging from 1.5 nA to 7.2 µA full-scale with 20-bit resolution and variable sampling rates of up to 3.125 kSPS. In addition, it features a bipolar voltage programmable in the range of −10 V to +5 V with a 3.65 mV resolution. A Finite State Machine steers the system by executing a set of embedded functions. The FSM allows for dynamic, customized adjustments of the nanosensor bias, including elevated bias schemes for self-heating, measurement range, bandwidth, sampling rate, and measurement time intervals. Furthermore, it enables data logging on external memory (SD card) and data transmission over a Bluetooth low energy connection. The average power consumption of the platform is 64.5 mW for a measurement protocol of three samples per second, including a BLE advertisement of a 0 dBm transmission power. A state-of-the-art (SoA) application of the platform performance using a CNT nanosensor, exposed to NO2 gas concentrations from 200 ppb down to 1 ppb, has been demonstrated. Although sensor signals are measured for NO2 concentrations of 1 ppb, the 3σ limit of detection (LOD) of 23 ppb is determined (1σ: 7 ppb) in slope detection mode, including the sensor signal variations in repeated measurements. The platform’s wide current range and high versatility make it suitable for signal acquisition from resistive nanosensors such as silicon nanowires, carbon nanotubes, graphene, and other 2D materials. Along with its overall low power consumption, the proposed platform is highly suitable for various sensing applications within the context of IoT.
Public understanding of intersex: an update on recent findings
Authors: Hegarty Peter , Smith Annette
Published: January 2022

Surgical interventions on infants with intersex characteristics are considered justified by some on the grounds that they carry a high risk of intolerable stigma. However, public understanding of intersex and its medicalization are under-researched. We review recent qualitative and quantitative studies of the understandings of intersex and its medicalization among people who have no particular professional or public experience of intersex. First, such laypeople reason about clinical dilemmas by drawing on values in similar ways as expert healthcare professionals do. Second, laypeople can over-estimate the utility of current ‘umbrella terms,’ includingintersex, for people with direct familial experience of intersex. Third, beliefs about good and bad effects of medical intervention are affected by framing intersex as either a medical condition or the natural basis for a social identity. Fourth, sexual identity is the best evidenced predictor of opinions about early surgical intervention and its legal limitation on human rights grounds. We argue that possible stigmatizing reactions from the public may not be a solid basis on which to justify early surgical intervention on intersex characteristics.
Transcriptional programs regulating neuronal differentiation are disrupted in DLG2 knockout human embryonic stem cells and enriched for schizophrenia and related disorders risk variants
Authors: Sanders Bret , D’Andrea Daniel , Collins Mark O. , Rees Elliott , Steward Tom G. J. , Zhu Ying , Chapman Gareth , Legge Sophie E. , Pardiñas Antonio F. , Harwood Adrian J. , Gray William P. , O’Donovan Michael C. , Owen Michael J. , Errington Adam C. , Blake Derek J. , Whitcomb Daniel J. , Pocklington Andrew J. , Shin Eunju
Published: January 2022

Coordinated programs of gene expression drive brain development. It is unclear which transcriptional programs, in which cell-types, are affected in neuropsychiatric disorders such as schizophrenia. Here we integrate human genetics with transcriptomic data from differentiation of human embryonic stem cells into cortical excitatory neurons. We identify transcriptional programs expressed during early neurogenesis in vitro and in human foetal cortex that are down-regulated in DLG2−/− lines. Down-regulation impacted neuronal differentiation and maturation, impairing migration, morphology and action potential generation. Genetic variation in these programs is associated with neuropsychiatric disorders and cognitive function, with associated variants predominantly concentrated in loss-of-function intolerant genes. Neurogenic programs also overlap schizophrenia GWAS enrichment previously identified in mature excitatory neurons, suggesting that pathways active during prenatal cortical development may also be associated with mature neuronal dysfunction. Our data from human embryonic stem cells, when combined with analysis of available foetal cortical gene expression data, de novo rare variants and GWAS statistics for neuropsychiatric disorders and cognition, reveal a convergence on transcriptional programs regulating excitatory cortical neurogenesis.
The genetic architecture underlying prey-dependent performance in a microbial predator
Authors: Stewart Balint , Gruenheit Nicole , Baldwin Amy , Chisholm Rex , Rozen Daniel , Harwood Adrian , Wolf Jason B. , Thompson Christopher R. L.
Published: January 2022

Natural selection should favour generalist predators that outperform specialists across all prey types. Two genetic solutions could explain why intraspecific variation in predatory performance is, nonetheless, widespread: mutations beneficial on one prey type are costly on another (antagonistic pleiotropy), or mutational effects are prey-specific, which weakens selection, allowing variation to persist (relaxed selection). To understand the relative importance of these alternatives, we characterised natural variation in predatory performance in the microbial predatorDictyostelium discoideum. We found widespread nontransitive differences among strains in predatory success across different bacterial prey, which can facilitate stain coexistence in multi-prey environments. To understand the genetic basis, we developed methods for high throughput experimental evolution on different prey (REMI-seq). Most mutations (~77%) had prey-specific effects, with very few (~4%) showing antagonistic pleiotropy. This highlights the potential for prey-specific effects to dilute selection, which would inhibit the purging of variation and prevent the emergence of an optimal generalist predator.
Structure and function of a family of tick-derived complement inhibitors targeting properdin
Authors: Braunger Katharina , Ahn Jiyoon , Jore Matthijs M. , Johnson Steven , Tang Terence T. L. , Pedersen Dennis V. , Andersen Gregers R. , Lea Susan M.
Published: January 2022

Activation of the serum-resident complement system begins a cascade that leads to activation of membrane-resident complement receptors on immune cells, thus coordinating serum and cellular immune responses. Whilst many molecules act to control inappropriate activation, Properdin is the only known positive regulator of the human complement system. By stabilising the alternative pathway C3 convertase it promotes complement self-amplification and persistent activation boosting the magnitude of the serum complement response by all triggers. In this work, we identify a family of tick-derived alternative pathway complement inhibitors, hereafter termed CirpA. Functional and structural characterisation reveals that members of the CirpA family directly bind to properdin, inhibiting its ability to promote complement activation, and leading to potent inhibition of the complement response in a species specific manner. We provide a full functional and structural characterisation of a properdin inhibitor, opening avenues for future therapeutic approaches.
Model-based evaluation of alternative reactive class closure strategies against COVID-19
Authors: Liu Quan-Hui , Zhang Juanjuan , Peng Cheng , Litvinova Maria , Huang Shudong , Poletti Piero , Trentini Filippo , Guzzetta Giorgio , Marziano Valentina , Zhou Tao , Viboud Cecile , Bento Ana I. , Lv Jiancheng , Vespignani Alessandro , Merler Stefano , Yu Hongjie , Ajelli Marco
Published: January 2022

There are contrasting results concerning the effect of reactive school closure on SARS-CoV-2 transmission. To shed light on this controversy, we developed a data-driven computational model of SARS-CoV-2 transmission. We found that by reactively closing classes based on syndromic surveillance, SARS-CoV-2 infections are reduced by no more than 17.3% (95%CI: 8.0–26.8%), due to the low probability of timely identification of infections in the young population. We thus investigated an alternative triggering mechanism based on repeated screening of students using antigen tests. Depending on the contribution of schools to transmission, this strategy can greatly reduce COVID-19 burden even when school contribution to transmission and immunity in the population is low. Moving forward, the adoption of antigen-based screenings in schools could be instrumental to limit COVID-19 burden while vaccines continue to be rolled out.
Minimal genetically encoded tags for fluorescent protein labeling in living neurons
Authors: Arsić Aleksandra , Hagemann Cathleen , Stajković Nevena , Schubert Timm , Nikić-Spiegel Ivana
Published: January 2022

Modern light microscopy, including super-resolution techniques, has brought about a demand for small labeling tags that bring the fluorophore closer to the target. This challenge can be addressed by labeling unnatural amino acids (UAAs) with bioorthogonal click chemistry. The minimal size of the UAA and the possibility to couple the fluorophores directly to the protein of interest with single-residue precision in living cells make click labeling unique. Here, we establish click labeling in living primary neurons and use it for fixed-cell, live-cell, dual-color pulse–chase, and super-resolution microscopy of neurofilament light chain (NFL). We also show that click labeling can be combined with CRISPR/Cas9 genome engineering for tagging endogenous NFL. Due to its versatile nature and compatibility with advanced multicolor microscopy techniques, we anticipate that click labeling will contribute to novel discoveries in the neurobiology field.
Decoupling of inorganic and organic carbon during slab mantle devolatilisation
Authors: Bouilhol P. , Debret B. , Inglis E. C. , Warembourg M. , Grocolas T. , Rigaudier T. , Villeneuve J. , Burton K. W.
Published: January 2022

Serpentinites are an important sink for both inorganic and organic carbon, and their behavior during subduction is thought to play a fundamental role in the global cycling of carbon. Here we show that fluid-derived veins are preserved within the Zermatt-Saas ultra-high pressure serpentinites providing key evidence for carbonate mobility during serpentinite devolatilisation. We show through the O, C, and Sr isotope analyses of vein minerals and the host serpentinites that about 90% of the meta-serpentinite inorganic carbon is remobilized during slab devolatilisation. In contrast, graphite-like carbonaceous compounds remain trapped within the host rock as inclusions within metamorphic olivine while the bulk elemental and isotope composition of organic carbon remains relatively unchanged during the subduction process. This shows a decoupling behavior of carbon during serpentinite dehydration in subduction zones. This process will therefore facilitate the transfer of inorganic carbon to the mantle wedge and the preferential slab sequestration of organic carbon en route to the deep mantle.
Uncovering the reaction mechanism behind CoO as active phase for CO2 hydrogenation
Authors: Have Iris C. ten , Kromwijk Josepha J. G. , Monai Matteo , Ferri Davide , Sterk Ellen B. , Meirer Florian , Weckhuysen Bert M.
Published: January 2022

Transforming carbon dioxide into valuable chemicals and fuels, is a promising tool for environmental and industrial purposes. Here, we present catalysts comprising of cobalt (oxide) nanoparticles stabilized on various support oxides for hydrocarbon production from carbon dioxide. We demonstrate that the activity and selectivity can be tuned by selection of the support oxide and cobalt oxidation state. Modulated excitation (ME) diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) reveals that cobalt oxide catalysts follows the hydrogen-assisted pathway, whereas metallic cobalt catalysts mainly follows the direct dissociation pathway. Contrary to the commonly considered metallic active phase of cobalt-based catalysts, cobalt oxide on titania support is the most active catalyst in this study and produces 11% C2+ hydrocarbons. The C2+ selectivity increases to 39% (yielding 104 mmol h−1 gcat−1 C2+ hydrocarbons) upon co-feeding CO and CO2 at a ratio of 1:2 at 250 °C and 20 bar, thus outperforming the majority of typical cobalt-based catalysts.
The self-management abilities test (SMAT): a tool to identify the self-management abilities of adults with bronchiectasis
Authors: Smalley Katelyn R. , Aufegger Lisa , Flott Kelsey , Mayer Erik K. , Darzi Ara
Published: January 2022

Bronchiectasis is an increasingly common chronic respiratory disease which requires a high level of patient engagement in self-management. Whilst the need for self-management has been recognised, the knowledge and skills needed to do so— and the extent to which patients possess these—has not been well-specified. On one hand, understanding the gaps in people’s knowledge and skills can enable better targeting of self-management supports. On the other, clarity about what they do know can increase patients’ confidence to self-manage. This study aims to develop an assessment of patients’ ability to self-manage effectively, through a consensus-building process with patients, clinicians and policymakers. The study employs a modified, online three-round Delphi to solicit the opinions of patients, clinicians, and policymakers (N = 30) with experience of bronchiectasis. The first round seeks consensus on the content domains for an assessment of bronchiectasis self-management ability. Subsequent rounds propose and refine multiple-choice assessment items to address the agreed domains. A group of ten clinicians, ten patients and ten policymakers provide both qualitative and quantitative feedback. Consensus is determined using content validity ratios. Qualitative feedback is analysed using the summative content analysis method. Overarching domains are General Health Knowledge, Bronchiectasis-Specific Knowledge, Symptom Management, Communication, and Addressing Deterioration, each with two sub-domains. A final assessment tool of 20 items contains two items addressing each sub-domain. This study establishes that there is broad consensus about the knowledge and skills required to self-manage bronchiectasis effectively, across stakeholder groups. The output of the study is an assessment tool that can be used by patients and their healthcare providers to guide the provision of self-management education, opportunities, and support.
An immunologically active, adipose-derived extracellular matrix biomaterial for soft tissue reconstruction: concept to clinical trial
Authors: Anderson Amy E. , Wu Iwen , Parrillo Alexis J. , Wolf Matthew T. , Maestas David R. , Graham Ian , Tam Ada J. , Payne Rachael M. , Aston Jeffrey , Cooney Carisa M. , Byrne Patrick , Cooney Damon S. , Elisseeff Jennifer H.
Published: January 2022

Soft tissue reconstruction remains an intractable clinical challenge as current surgical options and synthetic implants may produce inadequate outcomes. Soft tissue deficits may be surgically reconstructed using autologous adipose tissue, but these procedures can lead to donor site morbidity, require multiple procedures, and have highly variable outcomes. To address this clinical need, we developed an “off-the-shelf” adipose extracellular matrix (ECM) biomaterial from allograft human tissue (Acellular Adipose Tissue, AAT). We applied physical and chemical processing methods to remove lipids and create an injectable matrix that mimicked the properties of lipoaspirate. Biological activity was assessed using cell migration and adipogenesis assays. Characterization of regenerative immune properties in a murine muscle injury model revealed that allograft and xenograft AAT induced pro-regenerative CD4+ T cells and macrophages with xenograft AAT additionally attracting eosinophils secreting interleukin 4 (Il4). In immunocompromised mice, AAT injections retained similar volumes as human fat grafts but lacked cysts and calcifications seen in the fat grafts. The combination of AAT with human adipose-derived stem cells (ASCs) resulted in lower implant volumes. However, tissue remodeling and adipogenesis increased significantly in combination with ASCs. Larger injected volumes of porcine-derived AAT demonstrated biocompatibility and greater retention when applied allogeneicly in Yorkshire cross pigs. AAT was implanted in healthy volunteers in abdominal tissue that was later removed by elective procedures. AAT implants were well tolerated in all human subjects. Implants removed between 1 and 18 weeks demonstrated increasing cellular infiltration and immune populations, suggesting continued tissue remodeling and the potential for long-term tissue replacement.