bluuebunny/crossref_metadata_2025 huggingface dataset:
The interaction between suicidal ideation, insomnia symptoms, and student status
Authors: Stevenson Jodie C. , Irvine Kamila , Allen Sarah , Akram Umair
Published: November 2021

Evidence demonstrates increased vulnerability to thoughts and behaviors related to suicide (i.e., suicidal ideation) in students. This study examined the interaction between insomnia-symptoms and student-status (students vs. non-students) on reports of suicidal thoughts of behaviors. A total of 363 (N = 363) university students and 300 (N = 300) members of the general population provided complete data on measures of insomnia-symptoms and suicidal ideation. Students indicated greater reports of both total and lifetime ideation while also considering suicidal behavior within the past year. However, no differences were observed in reports of possible future attempt(s) and the disclosure of suicidal thoughts and behaviors to another person. Moreover, students presenting concurrent symptoms of insomnia reported significantly elevated levels of suicidal ideation relative to nonstudents. These outcomes highlight the possible role of insomnia symptoms in accentuating suicidal thoughts and behaviors in the student population.
Competition between protons and substrate for binding to the major facilitator superfamily multidrug/H+ antiporter MdtM – RETRACTED
Authors: Law Christopher J.
Published: November 2021

Proton electrochemical gradient-driven multidrug efflux activity of representatives of the major facilitator superfamily (MFS) of secondary active transporters contributes to antimicrobial resistance of pathogenic bacteria. Integral to the mechanism of these transporters is a proposed competition between substrate and protons for the binding site of the protein. The current work investigated the competition between protons and antimicrobial substrate for binding to the Escherichia coli MFS multidrug/H+ antiporter MdtM by measuring the quench of intrinsic protein fluorescence upon titration of substrate tetraphenylphosphonium into a solution of purified MdtM over a range of pH values between pH 8.8 and 5.9. The results, which revealed that protons inhibit binding of substrate to MdtM in a competitive manner, are consistent with those reported in a study on the related MFS multidrug/H+ antiporter MdfA and provide further evidence that competition for binding between substrate and protons is a general feature of secondary multidrug efflux.
Shock identification and classification in 2D magnetohydrodynamiccompressible turbulence—Orszag–Tang vortex
Authors: Snow Ben , Hillier Andrew , Murtas Giulia , Botha Gert J. J.
Published: November 2021

Compressible magnetohydrodynamic (MHD) turbulence is a common feature of astrophysical systems such as the solar atmosphere and interstellar medium. Such systems are rife with shock waves that can redistribute and dissipate energy. For an MHD system, three broad categories of shocks exist (slow, fast, and intermediate); however, the occurrence rates of each shock type are not known for turbulent systems. Here, we present a method for detecting and classifying the full range of MHD shocks applied to the Orszag–Tang vortex. Our results show that the system is dominated by fast and slow shocks, with far less-frequent intermediate shocks appearing most readily near magnetic reconnection sites. We present a potential mechanism that could lead to the formation of intermediate shocks in MHD systems, and study the coherency and abundances of shocks in compressible MHD turbulence.
A systematic review and meta-analysis of diagnostic test accuracy studies of self-report screening instruments for common mental disorders in Arabic-speaking adults
Authors: de Graaff Anne M. , Cuijpers Pim , Leeflang Mariska , Sferra Irene , Uppendahl Jana R. , de Vries Ralph , Sijbrandij Marit
Published: November 2021

Background

Self-report screening instruments are frequently used as scalable methods to detect common mental disorders (CMDs), but their validity across cultural and linguistic groups is unclear. We summarized the diagnostic accuracy of brief questionnaires on symptoms of depression, anxiety and posttraumatic stress disorder (PTSD) among Arabic-speaking adults.

Methods

Five databases were searched from inception to 22 January 2021 (PROSPERO: CRD42018070645). Studies were included when diagnostic accuracy of brief (maximally 25 items) psychological questionnaires was assessed in Arabic-speaking populations and the reference standard was a clinical interview. Data on sensitivity/specificity, area under the curve, and data to generate 2 × 2 tables at various thresholds were extracted. Meta-analysis was performed using the diagmeta package in R. Quality of studies was assessed with QUADAS-2.

Results

Thirty-two studies (Nparticipants= 4042) reporting on 17 questionnaires with 5–25 items targeting depression/anxiety (n= 14), general distress (n= 2), and PTSD (n= 1) were included. Seventeen studies (53%) scored high risk on at least two QUADAS-2 domains. The meta-analysis identified an optimal threshold of 11 (sensitivity 76.9%, specificity 85.1%) for the Edinburgh Postnatal Depression Scale (EPDS) (nstudies= 7,nparticipants= 711), 7 (sensitivity 81.9%, specificity 87.6%) for the Hospital Anxiety and Depression Scale (HADS) anxiety subscale and 6 (sensitivity 73.0%, specificity 88.6%) for the depression subscale (nstudies= 4,nparticipants= 492), and 8 (sensitivity 86.0%, specificity 83.9%) for the Self-Reporting Questionnaire (SRQ-20) (nstudies= 4,nparticipants= 459).

Conclusion

We present optimal thresholds to screen for perinatal depression with the EPDS, anxiety/depression with the HADS, and CMDs with the SRQ-20. More research on Arabic-language questionnaires, especially those targeting PTSD, is needed.
Thin-film Rayleigh–Taylor instability in the presence of a deep periodic corrugated wall
Authors: Dinesh B. , Corbin T. , Narayanan R.
Published: November 2021

Rayleigh–Taylor instability of a thin liquid film overlying a passive fluid is examined when the film is attached to a periodic wavy deep corrugated wall. A reduced-order long-wave model shows that the wavy wall enhances the instability toward rupture when the interface pattern is sub-harmonic to the wall pattern. An expression that approximates the growth constant of instability is obtained for any value of wall amplitude for the special case when the wall consists of two full waves and the interface consists of a full wave. Nonlinear computations of the interface evolution show that sliding is arrested by the wavy wall if a single liquid film residing over a passive fluid is considered but not necessarily when a bilayer sandwiched by a top wavy wall and bottom flat wall is considered. In the latter case interface tracking shows that primary and secondary troughs will evolve and subsequently slide along the flat wall due to symmetry-breaking. It is further shown that this sliding motion of the interface can ultimately be arrested by the top wavy wall, depending on the holdup of the fluids. In other words, there exists a critical value of the interface position beyond which the onset of the sliding motion is observed and below which the sliding is always arrested.
The Aloneness Argument fails
Authors: Pawl Timothy Joseph , Grant W. Matthews
Published: November 2021

Schmid and Mullins present what they call ‘the Aloneness Argument’ for the inconsistency of four theses from classical theism: the doctrine of divine simplicity, the doctrine of divine omniscience, the claim that God is free to create or not to create, and the claim that it is possible that God and nothing but God exist. We deny that they have shown an inconsistency between these theses. We maintain that, depending on how certain premises are interpreted, one or another premise is false. We also offer a positive proposal regarding a simple God's knowledge that he is alone in a world where he doesn't create anything.
To what extent does early childhood education policy in Australia recognise and propose action on the social determinants of health and health equity?
Authors: VAN EYK HELEN , BAUM FRAN , FISHER MATT , MACDOUGALL COLIN , LAWLESS ANGELA
Published: November 2021

Early childhood education (ECE) and development is internationally recognised as important to child health and wellbeing and to enabling children to become healthy productive adults. This paper analyses Australian ECE policy current in 2019. It uses the institutional framework of ideas, actors and institutions to determine the extent to which ECE policy recognises and acts on social determinants of health and health equity. We found that the policies supported integrated approaches, intersectoral collaboration and partnerships with parents and families. Evidence was important in formulating the ideas underpinning ECE policy. ECE was widely recognised as a social determinant of health, and the impacts of other social determinants of health and health equity were acknowledged. The ECE policies tended to be future-focused and not respond to social determinants that influence children and their families in the present time. The policies lacked strategies to address social determinants, or to engage with other sectors for this purpose. While some policies focused on breaking the cycle of disadvantage, they did not explore potential policy responses to pathways from intergenerational disadvantage to reduce poverty. Despite this, Australian ECE policy has achieved significant coherence, with shared understandings of the purpose and benefits of ECE.
Numerical and experimental performance estimation for a ExoFing - 2 DOFs finger exoskeleton
Authors: Carbone G , Ceccarelli M , Capalbo C. E. , Caroleo G , Morales-Cruz C
Published: November 2021

This paper presents a numerical and experimental validation of ExoFing, a two-degrees-of-freedom finger mechanism exoskeleton. The main functionalities of this device are investigated by focusing on its kinematic model and by computing its main operation characteristics via numerical simulations. Experimental tests are designed and carried out for validating both the engineering feasibility and effectiveness of the ExoFing system aiming at achieving a human index finger motion assistance with cost-oriented and user-friendly features.
Cell and Tissue Imaging by TOF-SIMS and MALDI-TOF: An Overview for Biological and Pharmaceutical Analysis
Authors: Noun Manale , Akoumeh Rayane , Abbas Imane
Published: November 2021

The potential of mass spectrometry imaging (MSI) has been demonstrated in cell and tissue research since 1970. MSI can reveal the spatial distribution of a wide range of atomic and molecular ions detected from biological sample surfaces, it is a powerful and valuable technique used to monitor and detect diverse chemical and biological compounds, such as drugs, lipids, proteins, and DNA. MSI techniques, notably matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) and time of flight secondary ion mass spectrometry (TOF-SIMS), witnessed a dramatic upsurge in studying and investigating biological samples especially, cells and tissue sections. This advancement is attributed to the submicron lateral resolution, the high sensitivity, the good precision, and the accurate chemical specificity, which make these techniques suitable for decoding and understanding complex mechanisms of certain diseases, as well as monitoring the spatial distribution of specific elements, and compounds. While the application of both techniques for the analysis of cells and tissues is thoroughly discussed, a briefing of MALDI-TOF and TOF-SIMS basis and the adequate sampling before analysis are briefly covered. The importance of MALDI-TOF and TOF-SIMS as diagnostic tools and robust analytical techniques in the medicinal, pharmaceutical, and toxicology fields is highlighted through representative published studies.
Who is a civilian in Afghanistan?
Authors: Voudouri Ioanna
Published: November 2021

Despite the existence of a definition of civilian status in international humanitarian law (IHL), differences in the application of this definition – both in theory and in practice – continue to be observed. One of the contexts where these differences remain palpable (and do so for various fighting parties) is Afghanistan, a country where civilian harm has remained high for several years. This article explores the legal concepts of civilian and civilian population, including how they have been formed and interpreted and, ultimately, what protection they afford to persons who belong in these categories. The second part of the article brings these questions into the Afghan context, one that is complex and where cultural and religious implications should not be overlooked. Public statements, reports and codes of fighting parties in the country which touch upon civilian status are presented, followed by the civilian experience in Afghanistan, particularly focusing on the reported harm. Ultimately, it is proposed that despite the factual and contextual confusion, the existing legal rules and interpretations, when applied in good faith, suffice to ensure both that those who are civilians under IHL are protected and that the threats which some civilians’ behaviour might pose can be effectively addressed without a status change.
A comparative review of artificial muscles for microsystem applications
Authors: Shi Mayue , Yeatman Eric M.
Published: November 2021

Artificial muscles are capable of generating actuation in microsystems with outstanding compliance. Recent years have witnessed a growing academic interest in artificial muscles and their application in many areas, such as soft robotics and biomedical devices. This paper aims to provide a comparative review of recent advances in artificial muscle based on various operating mechanisms. The advantages and limitations of each operating mechanism are analyzed and compared. According to the unique application requirements and electrical and mechanical properties of the muscle types, we suggest suitable artificial muscle mechanisms for specific microsystem applications. Finally, we discuss potential strategies for energy delivery, conversion, and storage to promote the energy autonomy of microrobotic systems at a system level.
Cortical complexity in world trade center responders with chronic posttraumatic stress disorder
Authors: Kritikos Minos , Clouston Sean A. P. , Huang Chuan , Pellecchia Alison C. , Mejia-Santiago Stephanie , Carr Melissa A. , Kotov Roman , Lucchini Roberto G. , Gandy Samuel E. , Bromet Evelyn J. , Luft Benjamin J.
Published: November 2021

Approximately 23% of World Trade Center (WTC) responders are experiencing chronic posttraumatic stress disorder (PTSD) associated with their exposures at the WTC following the terrorist attacks of 9/11/2001, which has been demonstrated to be a risk factor for cognitive impairment raising concerns regarding their brain health. Cortical complexity, as measured by analyzing Fractal Dimension (FD) from T1MRI brain images, has been reported to be reduced in a variety of psychiatric and neurological conditions. In this report, we hypothesized that FD would be also reduced in a case-control sample of 99 WTC responders as a result of WTC-related PTSD. The results of our surface-based morphometry cluster analysis found alterations in vertex clusters of complexity in WTC responders with PTSD, with marked reductions in regions within the frontal, parietal, and temporal cortices, in addition to whole-brain absolute bilateral and unilateral complexity. Furthermore, region of interest analysis identified that the magnitude of changes in regional FD severity was associated with increased PTSD symptoms (reexperiencing, avoidance, hyperarousal, negative affect) severity. This study confirms prior findings on FD and psychiatric disorders and extends our understanding of FD associations with posttraumatic symptom severity. The complex and traumatic experiences that led to WTC-related PTSD were associated with reductions in cortical complexity. Future work is needed to determine whether reduced cortical complexity arose prior to, or concurrently with, onset of PTSD.
Lightwave-driven scanning tunnelling spectroscopy of atomically precise graphene nanoribbons
Authors: Ammerman S. E. , Jelic V. , Wei Y. , Breslin V. N. , Hassan M. , Everett N. , Lee S. , Sun Q. , Pignedoli C. A. , Ruffieux P. , Fasel R. , Cocker T. L.
Published: November 2021

Atomically precise electronics operating at optical frequencies require tools that can characterize them on their intrinsic length and time scales to guide device design. Lightwave-driven scanning tunnelling microscopy is a promising technique towards this purpose. It achieves simultaneous sub-ångström and sub-picosecond spatio-temporal resolution through ultrafast coherent control by single-cycle field transients that are coupled to the scanning probe tip from free space. Here, we utilize lightwave-driven terahertz scanning tunnelling microscopy and spectroscopy to investigate atomically precise seven-atom-wide armchair graphene nanoribbons on a gold surface at ultralow tip heights, unveiling highly localized wavefunctions that are inaccessible by conventional scanning tunnelling microscopy. Tomographic imaging of their electron densities reveals vertical decays that depend sensitively on wavefunction and lateral position. Lightwave-driven scanning tunnelling spectroscopy on the ångström scale paves the way for ultrafast measurements of wavefunction dynamics in atomically precise nanostructures and future optoelectronic devices based on locally tailored electronic properties.
The role of urban trees in reducing land surface temperatures in European cities
Authors: Schwaab Jonas , Meier Ronny , Mussetti Gianluca , Seneviratne Sonia , Bürgi Christine , Davin Edouard L.
Published: November 2021

Urban trees influence temperatures in cities. However, their effectiveness at mitigating urban heat in different climatic contexts and in comparison to treeless urban green spaces has not yet been sufficiently explored. Here, we use high-resolution satellite land surface temperatures (LSTs) and land-cover data from 293 European cities to infer the potential of urban trees to reduce LSTs. We show that urban trees exhibit lower temperatures than urban fabric across most European cities in summer and during hot extremes. Compared to continuous urban fabric, LSTs observed for urban trees are on average 0-4 K lower in Southern European regions and 8-12 K lower in Central Europe. Treeless urban green spaces are overall less effective in reducing LSTs, and their cooling effect is approximately 2-4 times lower than the cooling induced by urban trees. By revealing continental-scale patterns in the effect of trees and treeless green spaces on urban LST our results highlight the importance of considering and further investigating the climate-dependent effectiveness of heat mitigation measures in cities.
Desmoplakin and periplakin genetically and functionally contribute to eosinophilic esophagitis
Authors: Shoda Tetsuo , Kaufman Kenneth M. , Wen Ting , Caldwell Julie M. , Osswald Garrett A. , Purnima Pathre , Zimmermann Nives , Collins Margaret H. , Rehn Kira , Foote Heather , Eby Michael D. , Zhang Wenying , Ben-Baruch Morgenstern Netali , Ballaban Adina Y. , Habel Jeff E. , Kottyan Leah C. , Abonia J. Pablo , Mukkada Vincent A. , Putnam Philip E. , Martin Lisa J. , Rothenberg Marc E.
Published: November 2021

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease with a complex underlying genetic etiology. Herein, we conduct whole-exome sequencing of a multigeneration EoE pedigree (discovery set) and 61 additional multiplex families with EoE (replication set). A series of rare, heterozygous, missense variants are identified in the genes encoding the desmosome-associated proteins DSP and PPL in 21% of the multiplex families. Esophageal biopsies from patients with these variants retain dilated intercellular spaces and decrease DSP and PPL expression even during disease remission. These variants affect barrier integrity, cell motility and RhoGTPase activity in esophageal epithelial cells and have increased susceptibility to calpain-14–mediated degradation. An acquired loss of esophageal DSP and PPL is present in non-familial EoE. Taken together, herein, we uncover a pathogenic role for desmosomal dysfunction in EoE, providing a deeper mechanistic understanding of tissue-specific allergic responses.
The shallow structure of Mars at the InSight landing site from inversion of ambient vibrations
Authors: Hobiger M. , Hallo M. , Schmelzbach C. , Stähler S. C. , Fäh D. , Giardini D. , Golombek M. , Clinton J. , Dahmen N. , Zenhäusern G. , Knapmeyer-Endrun B. , Carrasco S. , Charalambous C. , Hurst K. , Kedar S. , Banerdt W. B.
Published: November 2021

Orbital and surface observations can shed light on the internal structure of Mars. NASA’s InSight mission allows mapping the shallow subsurface of Elysium Planitia using seismic data. In this work, we apply a classical seismological technique of inverting Rayleigh wave ellipticity curves extracted from ambient seismic vibrations to resolve, for the first time on Mars, the shallow subsurface to around 200 m depth. While our seismic velocity model is largely consistent with the expected layered subsurface consisting of a thin regolith layer above stacks of lava flows, we find a seismic low-velocity zone at about 30 to 75 m depth that we interpret as a sedimentary layer sandwiched somewhere within the underlying Hesperian and Amazonian aged basalt layers. A prominent amplitude peak observed in the seismic data at 2.4 Hz is interpreted as an Airy phase related to surface wave energy trapped in this local low-velocity channel.
Adaptation, spread and transmission of SARS-CoV-2 in farmed minks and associated humans in the Netherlands
Authors: Lu Lu , Sikkema Reina S. , Velkers Francisca C. , Nieuwenhuijse David F. , Fischer Egil A. J. , Meijer Paola A. , Bouwmeester-Vincken Noortje , Rietveld Ariene , Wegdam-Blans Marjolijn C. A. , Tolsma Paulien , Koppelman Marco , Smit Lidwien A. M. , Hakze-van der Honing Renate W. , van der Poel Wim H. M. , van der Spek Arco N. , Spierenburg Marcel A. H. , Molenaar Robert Jan , Rond Jan de , Augustijn Marieke , Woolhouse Mark , Stegeman J. Arjan , Lycett Samantha , Oude Munnink Bas B. , Koopmans Marion P. G.
Published: November 2021

In the first wave of the COVID-19 pandemic (April 2020), SARS-CoV-2 was detected in farmed minks and genomic sequencing was performed on mink farms and farm personnel. Here, we describe the outbreak and use sequence data with Bayesian phylodynamic methods to explore SARS-CoV-2 transmission in minks and humans on farms. High number of farm infections (68/126) in minks and farm workers (>50% of farms) were detected, with limited community spread. Three of five initial introductions of SARS-CoV-2 led to subsequent spread between mink farms until November 2020. Viruses belonging to the largest cluster acquired an amino acid substitution in the receptor binding domain of the Spike protein (position 486), evolved faster and spread longer and more widely. Movement of people and distance between farms were statistically significant predictors of virus dispersal between farms. Our study provides novel insights into SARS-CoV-2 transmission between mink farms and highlights the importance of combining genetic information with epidemiological information when investigating outbreaks at the animal-human interface.
Identification of disease-linked hyperactivating mutations in UBE3A through large-scale functional variant analysis
Authors: Weston Kellan P. , Gao Xiaoyi , Zhao Jinghan , Kim Kwang-Soo , Maloney Susan E. , Gotoff Jill , Parikh Sumit , Leu Yen-Chen , Wu Kuen-Phon , Shinawi Marwan , Steimel Joshua P. , Harrison Joseph S. , Yi Jason J.
Published: November 2021

The mechanisms that underlie the extensive phenotypic diversity in genetic disorders are poorly understood. Here, we develop a large-scale assay to characterize the functional valence (gain or loss-of-function) of missense variants identified in UBE3A, the gene whose loss-of-function causes the neurodevelopmental disorder Angelman syndrome. We identify numerous gain-of-function variants including a hyperactivating Q588E mutation that strikingly increases UBE3A activity above wild-type UBE3A levels. Mice carrying the Q588E mutation exhibit aberrant early-life motor and communication deficits, and individuals possessing hyperactivating UBE3A variants exhibit affected phenotypes that are distinguishable from Angelman syndrome. Additional structure-function analysis reveals that Q588 forms a regulatory site in UBE3A that is conserved among HECT domain ubiquitin ligases and perturbed in various neurodevelopmental disorders. Together, our study indicates that excessive UBE3A activity increases the risk for neurodevelopmental pathology and suggests that functional variant analysis can help delineate mechanistic subtypes in monogenic disorders.
Discrete regulatory modules instruct hematopoietic lineage commitment and differentiation
Authors: Georgolopoulos Grigorios , Psatha Nikoletta , Iwata Mineo , Nishida Andrew , Som Tannishtha , Yiangou Minas , Stamatoyannopoulos John A. , Vierstra Jeff
Published: November 2021

Lineage commitment and differentiation is driven by the concerted action of master transcriptional regulators at their target chromatin sites. Multiple efforts have characterized the key transcription factors (TFs) that determine the various hematopoietic lineages. However, the temporal interactions between individual TFs and their chromatin targets during differentiation and how these interactions dictate lineage commitment remains poorly understood. Here we perform dense, daily, temporal profiling of chromatin accessibility (DNase I-seq) and gene expression changes (total RNA-seq) along ex vivo human erythropoiesis to comprehensively define developmentally regulated DNase I hypersensitive sites (DHSs) and transcripts. We link both distal DHSs to their target gene promoters and individual TFs to their target DHSs, revealing that the regulatory landscape is organized in distinct sequential regulatory modules that regulate lineage restriction and maturation. Finally, direct comparison of transcriptional dynamics (bulk and single-cell) and lineage potential between erythropoiesis and megakaryopoiesis uncovers differential fate commitment dynamics between the two lineages as they exit the stem and progenitor stage. Collectively, these data provide insights into the temporally regulated synergy of thecis- and thetrans-regulatory components underlying hematopoietic lineage commitment and differentiation.
Mapping enzyme catalysis with metabolic biosensing
Authors: Xu Linfeng , Chang Kai-Chun , Payne Emory M. , Modavi Cyrus , Liu Leqian , Palmer Claire M. , Tao Nannan , Alper Hal S. , Kennedy Robert T. , Cornett Dale S. , Abate Adam R.
Published: November 2021

Enzymes are represented across a vast space of protein sequences and structural forms and have activities that far exceed the best chemical catalysts; however, engineering them to have novel or enhanced activity is limited by technologies for sensing product formation. Here, we describe a general and scalable approach for characterizing enzyme activity that uses the metabolism of the host cell as a biosensor by which to infer product formation. Since different products consume different molecules in their synthesis, they perturb host metabolism in unique ways that can be measured by mass spectrometry. This provides a general way by which to sense product formation, to discover unexpected products and map the effects of mutagenesis.
Long-term repair of porcine articular cartilage using cryopreservable, clinically compatible human embryonic stem cell-derived chondrocytes
Authors: Petrigliano Frank A. , Liu Nancy Q. , Lee Siyoung , Tassey Jade , Sarkar Arijita , Lin Yucheng , Li Liangliang , Yu Yifan , Geng Dawei , Zhang Jiankang , Shkhyan Ruzanna , Bogdanov Jacob , Van Handel Ben , Ferguson Gabriel B. , Lee Youngjoo , Hinderer Svenja , Tseng Kuo-Chang , Kavanaugh Aaron , Crump J. Gage , Pyle April D. , Schenke-Layland Katja , Billi Fabrizio , Wang Liming , Lieberman Jay , Hurtig Mark , Evseenko Denis
Published: November 2021

Osteoarthritis (OA) impacts hundreds of millions of people worldwide, with those affected incurring significant physical and financial burdens. Injuries such as focal defects to the articular surface are a major contributing risk factor for the development of OA. Current cartilage repair strategies are moderately effective at reducing pain but often replace damaged tissue with biomechanically inferior fibrocartilage. Here we describe the development, transcriptomic ontogenetic characterization and quality assessment at the single cell level, as well as the scaled manufacturing of an allogeneic human pluripotent stem cell-derived articular chondrocyte formulation that exhibits long-term functional repair of porcine articular cartilage. These results define a new potential clinical paradigm for articular cartilage repair and mitigation of the associated risk of OA.
Table to text generation with accurate content copying
Authors: Yang Yang , Cao Juan , Wen Yujun , Zhang Pengzhou
Published: November 2021

Generating fluent, coherent, and informative text from structured data is called table-to-text generation. Copying words from the table is a common method to solve the “out-of-vocabulary” problem, but it’s difficult to achieve accurate copying. In order to overcome this problem, we invent an auto-regressive framework based on the transformer that combines a copying mechanism and language modeling to generate target texts. Firstly, to make the model better learn the semantic relevance between table and text, we apply a word transformation method, which incorporates the field and position information into the target text to acquire the position of where to copy. Then we propose two auxiliary learning objectives, namely table-text constraint loss and copy loss. Table-text constraint loss is used to effectively model table inputs, whereas copy loss is exploited to precisely copy word fragments from a table. Furthermore, we improve the text search strategy to reduce the probability of generating incoherent and repetitive sentences. The model is verified by experiments on two datasets and better results are obtained than the baseline model. On WIKIBIO, the result is improved from 45.47 to 46.87 on BLEU and from 41.54 to 42.28 on ROUGE. On ROTOWIRE, the result is increased by 4.29% on CO metric, and 1.93 points higher on BLEU.
Psychedelics alter metaphysical beliefs
Authors: Timmermann Christopher , Kettner Hannes , Letheby Chris , Roseman Leor , Rosas Fernando E. , Carhart-Harris Robin L.
Published: November 2021

Can the use of psychedelic drugs induce lasting changes in metaphysical beliefs? While it is popularly believed that they can, this question has never been formally tested. Here we exploited a large sample derived from prospective online surveying to determine whether and how beliefs concerning the nature of reality, consciousness, and free-will, change after psychedelic use. Results revealed significant shifts away from ‘physicalist’ or ‘materialist’ views, and towards panpsychism and fatalism, post use. With the exception of fatalism, these changes endured for at least 6 months, and were positively correlated with the extent of past psychedelic-use and improved mental-health outcomes. Path modelling suggested that the belief-shifts were moderated by impressionability at baseline and mediated by perceived emotional synchrony with others during the psychedelic experience. The observed belief-shifts post-psychedelic-use were consolidated by data from an independent controlled clinical trial. Together, these findings imply that psychedelic-use may causally influence metaphysical beliefs—shifting them away from ‘hard materialism’. We discuss whether these apparent effects are contextually independent.
Pulse arrival time as a surrogate of blood pressure
Authors: Finnegan Eoin , Davidson Shaun , Harford Mirae , Jorge João , Watkinson Peter , Young Duncan , Tarassenko Lionel , Villarroel Mauricio
Published: November 2021

Various models have been proposed for the estimation of blood pressure (BP) from pulse transit time (PTT). PTT is defined as the time delay of the pressure wave, produced by left ventricular contraction, measured between a proximal and a distal site along the arterial tree. Most researchers, when they measure the time difference between the peak of the R-wave in the electrocardiogram signal (corresponding to left ventricular depolarisation) and a fiducial point in the photoplethysmogram waveform (as measured by a pulse oximeter attached to the fingertip), describe this erroneously as the PTT. In fact, this is the pulse arrival time (PAT), which includes not only PTT, but also the time delay between the electrical depolarisation of the heart’s left ventricle and the opening of the aortic valve, known as pre-ejection period (PEP). PEP has been suggested to present a significant limitation to BP estimation using PAT. This work investigates the impact of PEP on PAT, leading to a discussion on the best models for BP estimation using PAT or PTT. We conducted a clinical study involving 30 healthy volunteers (53.3% female, 30.9 ± 9.35 years old, with a body mass index of 22.7 ± 3.2 kg/m$$^{2}$$

2

). Each session lasted on average 27.9 ± 0.6 min and BP was varied by an infusion of phenylephrine (a medication that causes venous and arterial vasoconstriction). We introduced new processing steps for the analysis of PAT and PEP signals. Various population-based models (Poon, Gesche and Fung) and a posteriori models (inverse linear, inverse squared and logarithm) for estimation of BP from PTT or PAT were evaluated. Across the cohort, PEP was found to increase by 5.5 ms ± 4.5 ms from its baseline value. Variations in PTT were significantly larger in amplitude, − 16.8 ms ± 7.5 ms. We suggest, therefore, that for infusions of phenylephrine, the contribution of PEP on PAT can be neglected. All population-based models produced large BP estimation errors, suggesting that they are insufficient for modelling the complex pathways relating changes in PTT or PAT to changes in BP. Although PAT is inversely correlated with systolic blood pressure (SBP), the gradient of this relationship varies significantly from individual to individual, from − 2946 to − 470.64 mmHg/s in our dataset. For the a posteriori inverse squared model, the root mean squared errors (RMSE) for systolic and diastolic blood pressure (DBP) estimation from PAT were 5.49 mmHg and 3.82 mmHg, respectively. The RMSEs for SBP and DBP estimation by PTT were 4.51 mmHg and 3.53 mmHg, respectively. These models take into account individual calibration curves required for accurate blood pressure estimation. The best performing population-based model (Poon) reported error values around double that of the a posteriori inverse squared model, and so the use of population-based models is not justified.
Network analysis of trauma in patients with early-stage psychosis
Authors: Chung Young-Chul , Yun Je-Yeon , Nguyen Thong Ba , Rami Fatima Zahra , Piao Yan Hong , Li Ling , Lee Bomi , Kim Woo-Sung , Sui Jing , Kim Sung-Wan , Lee Bong Ju , Kim Jung Jin , Yu Je-Chun , Lee Kyu Young , Won Seung-Hee , Lee Seung-Hwan , Kim Seung-Hyun , Kang Shi Hyun , Kim Eui Tae
Published: November 2021

Childhood trauma (ChT) is a risk factor for psychosis. Negative lifestyle factors such as rumination, negative schemas, and poor diet and exercise are common in psychosis. The present study aimed to perform a network analysis of interactions between ChT and negative lifestyle in patients and controls. We used data of patients with early-stage psychosis (n = 500) and healthy controls (n = 202). Networks were constructed using 12 nodes from five scales: the Brief Core Schema Scale (BCSS), Brooding Scale (BS), Dietary Habits Questionnaire, Physical Activity Rating, and Early Trauma Inventory Self Report-Short Form (ETI). Graph metrics were calculated. The nodes with the highest predictability and expected influence in both patients and controls were cognitive and emotional components of the BS and emotional abuse of the ETI. The emotional abuse was a mediator in the shortest pathway connecting the ETI and negative lifestyle for both groups. The negative others and negative self of the BCSS mediated emotional abuse to other BCSS or BS for patients and controls, respectively. Our findings suggest that rumination and emotional abuse were central symptoms in both groups and that negative others and negative self played important mediating roles for patients and controls, respectively.

Trial Registration: ClinicalTrials.gov identifier: CUH201411002.
RNA G-quadruplex structures control ribosomal protein production
Authors: Varshney Dhaval , Cuesta Sergio Martinez , Herdy Barbara , Abdullah Ummi Binti , Tannahill David , Balasubramanian Shankar
Published: November 2021

Four-stranded G-quadruplex (G4) structures form from guanine-rich tracts, but the extent of their formation in cellular RNA and details of their role in RNA biology remain poorly defined. Herein, we first delineate the presence of endogenous RNA G4s in the human cytoplasmic transcriptome via the binding sites of G4-interacting proteins, DDX3X (previously published), DHX36 and GRSF1. We demonstrate that a sub-population of these RNA G4s are reliably detected as folded structures in cross-linked cellular lysates using the G4 structure-specific antibody BG4. The 5′ UTRs of protein coding mRNAs show significant enrichment in folded RNA G4s, particularly those for ribosomal proteins. Mutational disruption of G4s in ribosomal protein UTRs alleviates translation in vitro, whereas in cells, depletion of G4-resolving helicases or treatment with G4-stabilising small molecules inhibit the translation of ribosomal protein mRNAs. Our findings point to a common mode for translational co-regulation mediated by G4 structures. The results reveal a potential avenue for therapeutic intervention in diseases with dysregulated translation, such as cancer.
Effect of initial switch-on within 24 hours of cochlear implantation using slim modiolar electrodes
Authors: Sunwoo Woongsang , Jeon Hyoung Won , Choi Byung Yoon
Published: November 2021

Reducing electrode impedance is an important factor in improving the functional benefits of cochlear implants (CIs). The immediate effect of early switch-on within 24 h of surgery on impedance among CI recipients with various types of electrodes has been reported previously; however, the immediate change and the evolution of electrode impedances of slim modiolar electrodes after early switch-on within 24 h of implantation has not. Therefore, the focus of this retrospective cohort study of CI patients was to compare the effect of early switch-on (n = 36) and conventional switch-on (n = 72) 2–4 weeks post-operation on impedance. Compared with impedance measured intraoperatively, our results demonstrate a significant decrease in impedance from 11.5 to 8.9 kΩ (p < 0.001) at 2–4 weeks after implantation in the early switch-on group, which sharply contrasted with elevated impedance values for conventional switch-on 2–4 weeks after implantation (from 10.7 to 14.2 kΩ, p = 0.001). Notably, a comparatively lower impedance than the conventional switch-on protocol was observed for up to 2 months post-operation. Most importantly, a much earlier stabilization of impedance can be achieved with the early switch-on protocol coupled with the slim modiolar electrode array compared to the conventional switch-on protocol, offering the advantage of reducing the number of required mapping sessions in the early stages of rehabilitation.
A novel comparative case study of entropy generation for natural convection flow of proportional-Caputo hybrid and Atangana baleanu fractional derivative
Authors: khan Dolat , Kumam Poom , Watthayu Wiboonsak
Published: November 2021

This article focused on the comparative study of entropy generation for natural convection flow of the newly proportional Caputo hybrid and Atangana baleanu fractional derivative. The governing equation is formed as the set of partial differential equations with the physical boundary conditions. The report of entropy generation is investigated for the first time for proportional–Caputo hybrid model and comparison are sorts out with generalized Atangana baleanu fractional derivative. The Bejan number is also compared for the mention fractional derivatives. Graphs show the impact of various factors on the minimization and maximizing of entropy production. The newly proportional Caputo hybrid operator has a good memory effect rather than Atangana baleanu fractional operator.
A 3D primary human cell-based in vitro model of non-alcoholic steatohepatitis for efficacy testing of clinical drug candidates
Authors: Ströbel Simon , Kostadinova Radina , Fiaschetti-Egli Katia , Rupp Jana , Bieri Manuela , Pawlowska Agnieszka , Busler Donna , Hofstetter Thomas , Sanchez Katarzyna , Grepper Sue , Thoma Eva
Published: November 2021

Non-alcoholic steatohepatitis (NASH) is a progressive and severe liver disease, characterized by lipid accumulation, inflammation, and downstream fibrosis. Despite its increasing prevalence, there is no approved treatment yet available for patients. This has been at least partially due to the lack of predictive preclinical models for studying this complex disease. Here, we present a 3D in vitro microtissue model that uses spheroidal, scaffold free co-culture of primary human hepatocytes, Kupffer cells, liver endothelial cells and hepatic stellate cells. Upon exposure to defined and clinically relevant lipotoxic and inflammatory stimuli, these microtissues develop key pathophysiological features of NASH within 10 days, including an increase of intracellular triglyceride content and lipids, and release of pro-inflammatory cytokines. Furthermore, fibrosis was evident through release of procollagen type I, and increased deposition of extracellular collagen fibers. Whole transcriptome analysis revealed changes in the regulation of pathways associated with NASH, such as lipid metabolism, inflammation and collagen processing. Importantly, treatment with anti-NASH drug candidates (Selonsertib and Firsocostat) decreased the measured specific disease parameter, in accordance with clinical observations. These drug treatments also significantly changed the gene expression patterns of the microtissues, thus providing mechanisms of action and revealing therapeutic potential. In summary, this human NASH model represents a promising drug discovery tool for understanding the underlying complex mechanisms in NASH, evaluating efficacy of anti-NASH drug candidates and identifying new approaches for therapeutic interventions.
Low-frequency exercise training improves cardiovascular fitness and strength during treatment for breast cancer: a single-arm intervention study
Authors: Bell Kirsten E. , Pfeiffer Amanda G. , Schmidt Schuyler , Bos Lisa , Russell Caryl , Barnes Tyler , Di Sebastiano Katie M. , Avrutin Egor , Gibson Marielle , Dubin Joel A. , Mourtzakis Marina
Published: November 2021

Aerobic and resistance exercise during and after cancer treatment are important for health-related outcomes, however treatment-specific barriers may inhibit adherence. We explored the effect of lower-frequency exercise training on fitness, body composition, and metabolic markers (i.e. glucose and lipids) in a group of recently diagnosed breast cancer patients. Fifty-two females ≥ 18 years with stage I–IIIB breast cancer were instructed to attend 2 cardiovascular and strength training sessions/week over 12 weeks, but program length was expanded as needed to accommodate missed sessions. Pre- and post-intervention, we measured: (1) cardiovascular fitness, (2) isometric strength, (3) body composition (dual-energy X-ray absorptiometry), and (4) fasting glucose, insulin, c-peptide, and lipids. Pre-intervention, participants were 53 ± 10 years old (mean ± SD) and overweight (BMI: 27.5 ± 5.4 kg m−2, 40.1 ± 6.5% body fat). Forty participants completed the program over a median 20 weeks (range: 13–32 weeks, median frequency: 1.2 sessions/week), over which predicted VO2peak improved by 7% (2.2[0.1–4.4] mL/kg/min) (delta[95% CI]), and strength increased by 7–9% (right arm: 2.3[0.1–4.5] N m; right leg: 7.9[2.1–13.7] N m; left leg: 7.8[1.9–13.7] N m). Body composition and metabolic markers were unchanged. An exercise frequency of 1.2 sessions/week stimulated significant improvements in fitness, and may represent a practical target for patients during active treatment.
A novel role for vaping in mitochondrial gene dysregulation and inflammation fundamental to disease development
Authors: Tommasi Stella , Pabustan Niccolo , Li Meng , Chen Yibu , Siegmund Kimberly D. , Besaratinia Ahmad
Published: November 2021

We constructed and analyzed the whole transcriptome in leukocytes of healthy adult vapers (with/without a history of smoking), ‘exclusive’ cigarette smokers, and controls (non-users of any tobacco products). Furthermore, we performed single-gene validation of expression data, and biochemical validation of vaping/smoking status by plasma cotinine measurement. Computational modeling, combining primary analysis (age- and sex-adjusted limmaVoom) and sensitivity analysis (cumulative e-liquid- and pack-year modeling), revealed that ‘current’ vaping, but not ‘past’ smoking, is significantly associated with gene dysregulation in vapers. Comparative analysis of the gene networks and canonical pathways dysregulated in vapers and smokers showed strikingly similar patterns in the two groups, although the extent of transcriptomic changes was more pronounced in smokers than vapers. Of significance is the preferential targeting of mitochondrial genes in both vapers and smokers, concurrent with impaired functional networks, which drive mitochondrial DNA-related disorders. Equally significant is the dysregulation of immune response genes in vapers and smokers, modulated by upstream cytokines, including members of the interleukin and interferon family, which play a crucial role in inflammation. Our findings accord with the growing evidence on the central role of mitochondria as signaling organelles involved in immunity and inflammatory response, which are fundamental to disease development.
Unique pattern of histogenesis of the parakeratinized epithelium on lingual prominence in the domestic goose embryos (Anser anser f. domestica)
Authors: Skieresz-Szewczyk Kinga , Jackowiak Hanna , Ratajczak Marlena
Published: November 2021

A triangular lingual prominence (LP) is a characteristic part of the tongue in Anseriformes containing adipose tissue. The parakeratinized epithelium (PEp) covers the LP. Studies aimed to describe the histogenesis of PEp during the process of the intensive formation of the LP in domestic goose during embryonic period and to determine the structural readiness to perform a protective function. The study were conducted by using LM, SEM and TEM technique. The results revealed that on day 16th the undifferentiated epithelium of LP transformed into the typical avian multilayered epithelium. Contrary to pattern of histogenesis of parakeratinized epithelium on the lingual body, on the medial and lateral areas of the elongating and bulging LP were formed epithelial furrows. Which around 20th day, on lateral areas of LP deepened up to half of epithelium, whereas on the medial area began to fade. The ultrastructure of cells lying in furrows indicated progressive apoptosis-like degeneration. On the 25th day, shallow furrows were only present on lateral areas, where bulging of LP was continued. Whereas the epithelium on medial area started cornification by the accumulation of cytokeratin fibers. Lack of the periderm during the development of the PEp of the LP indicated its endodermal origin.