bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient and accurate prediction of protein structure using RoseTTAFold2
Authors: Baek Minkyung , Anishchenko Ivan , Humphreys Ian R. , Cong Qian , Baker David , DiMaio Frank
Published: May 2023

AlphaFold2 and RoseTTAFold predict protein structures with very high accuracy despite substantial architecture differences. We sought to develop an improved method combining features of both. The resulting method, RoseTTAFold2, extends the original three-track architecture of RoseTTAFold over the full network, incorporating the concepts of Frame-aligned point error, recycling during training, and the use of a distillation set from AlphaFold2. We also took from AlphaFold2 the idea of structurally coherent attention in updating pair features, but using a more computationally efficient structure-biased attention as opposed to triangle attention. The resulting model has the accuracy of AlphaFold2 on monomers, and AlphaFold2-multimer on complexes, with better computational scaling for large proteins and complexes. This excellent performance is achieved without hallmark features of AlphaFold2, invariant point attention and triangle attention, indicating that these are not essential for high accuracy prediction. Almost all recent work on protein structure prediction has re-used the basic AlphaFold2 architecture; our results show that excellent performance can be achieved with a broader class of models, opening the door for further exploration.
Oxaliplatin-induced cardiotoxicity in mice is connected to the changes in energy metabolism in the heart tissue
Authors: Du Junwei , Sudlow Leland C. , Shahverdi Kiana , Zhou Haiying , Michie Megan , Schindler Thomas H. , Mitchell Joshua D. , Mollah Shamim , Berezin Mikhail Y.
Published: May 2023

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. At high cumulative dosage, the negative effect of oxaliplatin on the heart becomes evident and is linked to a growing number of clinical reports. The aim of this study was to determine how chronic oxaliplatin treatment causes the changes in energy-related metabolic activity in the heart that leads to cardiotoxicity and heart damage in mice. C57BL/6 male mice were treated with a human equivalent dosage of intraperitoneal oxaliplatin (0 and 10 mg/kg) once a week for eight weeks. During the treatment, mice were followed for physiological parameters, ECG, histology and RNA sequencing of the heart. We identified that oxaliplatin induces strong changes in the heart and affects the heart’s energy-related metabolic profile. Histological post-mortem evaluation identified focal myocardial necrosis infiltrated with a small number of associated neutrophils. Accumulated doses of oxaliplatin led to significant changes in gene expression related to energy related metabolic pathways including fatty acid (FA) oxidation, amino acid metabolism, glycolysis, electron transport chain, and NAD synthesis pathway. At high accumulative doses of oxaliplatin, the heart shifts its metabolism from FAs to glycolysis and increases lactate production. It also leads to strong overexpression of genes in NAD synthesis pathways such asNmrk2. Changes in gene expression associated with energy metabolic pathways can be used to develop diagnostic methods to detect oxaliplatin-induced cardiotoxicity early on as well as therapy to compensate for the energy deficit in the heart to prevent heart damage.

Significance Statement

This study uncovers the detrimental impact of chronic oxaliplatin treatment on heart metabolism in mice, linking high accumulative dosages to cardiotoxicity and heart damage. By identifying significant changes in gene expression related to energy metabolic pathways, the findings pave the way for the development of diagnostic methods to detect oxaliplatin-induced cardiotoxicity at an early stage. Furthermore, these insights may inform the creation of therapies that compensate for the energy deficit in the heart, ultimately preventing heart damage and improving patient outcomes in cancer treatment.
Young gene HP6/Umbrea is dispensable for viability and fertility
Authors: Grill Sherilyn , Riley Ashley , Selvaraj Monica , Lehmann Ruth
Published: May 2023

Studies of the young gene Heterochromatin Protein 6 (HP6) have challenged the dogma that essential functions are only seen in genes with a long evolutionary history. Based on its prominent expression in Drosophila germ cells, we asked if HP6 might play a role in germline development. Surprisingly, we found that CRISPR-generated HP6 null mutants are viable and fertile. We identified an independent lethal allele and an RNAi off-target effect that prevented accurate interpretation of HP6 essentiality in previous studies. We found that the vast majority of young essential genes were viable when tested with orthologous methods. Together our data call into question the frequency with which young genes gain essential functions.
Various Cell Types in the Bone Marrow sustain Primary B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Smeets Mandy W. E. , van de Ven Cesca , Orsel Jan , Reichert Caitlin E. J. , Boeree Aurélie , Boer Judith , den Boer Monique L.
Published: May 2023

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) originates from the bone marrow, which besides hematopoietic cells also contains different (supportive) cell types, including mesenchymal stromal cells (MSCs), osteocytes, chondrocytes, fibroblasts, and adipocytes. These (supportive) cell types create a bone marrow microenvironment that facilitates leukemogenesis and provide a survival benefit to leukemic cells that also affects the response to chemotherapeutic drugs. We here show that the survival benefit provided by supportive tissues does not depend on the type of supportive cells and does not differ between supportive cells collected at the time of full leukemia (diagnosis), at end of consolidation therapy or from healthy controls. The need for supportive cells, however, clearly differed between subtypes of BCP-ALL, withBCR-ABL1-positive andTCF3-PBX1-positive subtypes being the most dependent on this support. Various supportive cell types provided a survival benefit to BCP-ALL cells, with a median benefit of 18% (chondrocytes) and 30-36% (MSCs, osteocytes, and fibroblasts), which was not observed for mature adipocytes. This benefit was direct cell-cell contact dependent and decreased upon physical separation of cell populations in a transwell setting. BCP-ALL cells in contrast to MSCs and the other supportive tissue types hardly produce cyto-/chemokines. The secretome of MSCs changed upon co-culture with BCP-ALL cells resulting in 1.2-fold to 1.4-fold (median) higher levels for the cyto-/chemokines IL6, CCL22, CXCL10, and CXCL5. Together, these data suggest that BCP-ALL cells manipulate different components of the bone marrow supportive tissues via direct cell-cell contact which favors the survival of leukemic cells. This strengthens our earlier observation that BCP-ALL cells hijack the bone marrow microenvironment and offers the perspective that interference with this stromal interaction and/or released cyto-/chemokines may be of additive value in the treatment of BCP-ALL.
How human-derived brain organoids are built differently from brain organoids derived of genetically-close relatives: A multi-scale hypothesis
Authors: Zhang Tao , Gupta Sarthak , Lancaster Madeline A. , Schwarz J. M.
Published: May 2023

How genes affect tissue scale organization remains a longstanding biological puzzle. As experimental efforts are underway to solve this puzzle via quantification of gene expression, chromatin organization, cellular structure, and tissue structure, computational modeling efforts remain far behind. To help accelerate the computational modeling efforts, we review two recent publications, the first on a cellular-based model for tissues and the second on a model of a cell nucleus that includes a lamina shell and chromatin. We then address how the two models can be combined to ultimately test multiscale hypotheses linking the chromatin scale and the tissue scale. To be concrete, we turn to anin vitrosystem for the brain known as a brain organoid. We provide a multiscale hypothesis to distinguish structural differences between brain organoids built from induced-pluripotent human stem cells and from induced-pluripotent gorilla and chimpanzee stem cells. Recent experiments discover that a cell fate transition from neuroepithelial cells to radial glial cells includes a new intermediate state that is delayed in human-derived brain organoids as compared to their genetically-close relatives, which significantly narrows and lengthens the cells on the apical side [1]. Additional experiments revealed that the protein ZEB2 plays a major role in the emergence of this new intermediate state with ZEB2 mRNA levels peaking at the onset of the emergence [1]. We postulate that the enhancement of ZEB2 expression driving this intermediate state is potentially due to chromatin reorganization. More precisely, there exists critical strain triggering the reorganization that is higher for human-derived stem cells, thereby resulting in a delay. Such a hypothesis can readily be tested experimentally within individual cells and within brain organoids as well as computationally to help work towards solving the gene-to-tissue organization puzzle.
Brainways: An AI-based Tool for Automated Registration, Quantification and Generation of Brain-wide Activity Networks Based on Fluorescence in Coronal Slices
Authors: Kantor Ben , Ben-Ami Bartal Inbal
Published: May 2023

A central current trend in neuroscience involves the identification of brain-wide neural circuits associated with complex behavior. A major challenge for this approach involves the laborious process for registration and quantification of fluorescence on histological brain slices, as well as the difficulty of deriving functional insight from the complex resulting datasets. As a solution, we developed Brainways, a simple-to-use AI-based open-source software for the identification of neural networks involved in a specific behavior, from digital images to network analysis. Brainways offers automatic registration of coronal slices to any 3D brain atlas, and provides quantification of fluorescent markers (e.g. activity marker, tracer) per region, as well as statistical comparisons with visual mapping of contrasts between conditions. A built-in partial least squares task analysis provides the neural patterns associated with a specific contrast, as well as network graph analysis representing functional connectivity. Trained on atlases for rats and mice, Brainways currently provides above 80% atlas registration accuracy and allows the user to easily adjust the outputs for better fit. Below, a case study validation of Brainways is demonstrated on a previously published data set describing the neural correlates of empathic helping behavior in rats. The original results were successfully replicated and expanded upon, due to the exponentially larger sample size that covered over a 100 times more brain tissue compared to the original manual sampling. Brainways thus provides a fast, accurate solution for quantification of large-scale projects and facilitates novel neurobiological insights about the structural and functional neural networks involved in complex behavior. Brainways has a highly accessible GUI and is functionality exposed through a Python-based API, which can be enhanced for different applications.
Model matters: Differential outcomes in traumatic optic neuropathy pathophysiology between blunt and blast-wave mediated head injuries
Authors: Hetzer S.M. , O’Connell C. , Lallo V. , Robson M. , Evanson N.K.
Published: May 2023

Over 3 million people in the United States live with long-term disability as a result of a traumatic brain injury (TBI). The purpose of this study was to characterize and compare two different animal models of TBI (blunt head trauma and blast TBI) to determine common and divergent characteristics of these models. With recent literature reviews noting the prevalence of visual system injury in animal models of TBI, coupled with clinical estimates of 50-75% of all TBI cases, we decided to assess commonalities, if they existed, through visual system injury. Blast, repeat blast, and blunt injury were induced in adult male mice to observe and quantify visual deficits. Retinal ganglion cell loss and axonal degeneration in the optic tract, superior colliculus, and lateral geniculate nuclei were examined to trace injury outcomes throughout major vision-associated areas. Optokinetic response, immunohistochemistry, and western blots were analyzed. Where a single blunt injury produces significant visual deficits a single blast injury appears to have less severe visual consequences. Visual deficits after repeat blasts are similar to a single blast. Single blast injury induces contralateral damage to right optic chiasm and tract whereas bilateral injury follows a single blunt injury. Repeat blast injuries are required to see degeneration patterns in downstream regions similar to the damage seen in a single blunt injury. This finding is further supported by Amyloid Precursor Protein (APP) staining in injured cohorts. Blunt injured groups present with staining 1.2 mm of the optic nerve, indicating axonal breakage closer to the optic chiasm. In blast groups, APP was identifiable in a bilateral pattern only in the geniculate nucleus. Evidence for unilateral neuronal degeneration in brain tissue with bilateral axonal ruptures are pivotal discoveries in this model differentiation. Analysis of the two injury models suggest there is a significant difference in the histological outcomes dependent on injury type, though visual system injury is likely present in more cases than are currently diagnosed clinically.
Does COVID-19 pandemic spur digital business transformation? Evidence from selected MENA countries
Authors: Mustafa Ali Mohammed Elhaj , Ebaidalla Ebaidalla M.
Published: May 2023

Purpose

In the light of high reliance on digital technology to mitigate the consequences of the coronavirus disease 2019 (COVID-19) pandemic and its containment measures, this study investigates the factors influencing firms' decision to adopt digital technologies during COVID-19 in four Middle East and Northern African (MENA) countries, namely, Egypt, Jordan, Morocco and Tunisia.

Design/methodology/approach

The study used the International Labour Organization (ILO)/Economic Research Forum (ERF) COVID-19 - MENA Monitor Enterprise Survey (CMMENT), comprising 5,480 firms, surveyed during 2020–2021. The empirical model is estimated using the linear probability model (LPM) to address the problem of unobserved heterogeneity between firms, countries, and time.

Findings

The results revealed that firm characteristics, such as firm size and foreign ownership, encourage digital transformation in the business sector. Moreover, firms that face challenges during the pandemic, comply with the containment measures, and receive government assistance are more likely to adopt digital solutions. Furthermore, the results indicated that firms operating in services sector have a higher likelihood to adopt digital technology. Disaggregating the total sample into several sub-samples, the results are robust across countries and technology types, supporting the initial hypothesis that COVID-19 encourages digital transformation in the MENA region.

Originality/value

The study has numerous contributions. First, to the best of the authors' knowledge, this is the sole study that uses micro data collected during the COVID-19 to examine the factors influencing firms' decision to adopt and invest in digital solutions in the MENA countries. Second, the paper employs the LPM estimator to address the issue of unobserved heterogeneity between firms, countries and time. Finally, the paper offers some practical recommendations for accelerating digital transformation in MENA region.
The impact of earnings quality on corporate cash holdings: evidence from an emerging economy
Authors: Al-Haddad Lara , Al-Ghoul Shadi
Published: May 2023

Purpose

This study aims to inspect the impact of earnings quality on corporate cash holdings of Jordanian companies listed on the Amman Stock Exchange.

Design/methodology/approach

This study examines a large sample of (98) Jordanian companies listed on the Amman Stock Exchange during the period that ranges from 2009 to 2019. Earnings quality was computed using two different methods; firstly, through the absolute abnormal discretionary accruals (as an inverse measure of earnings quality), which were estimated using the Dechow et al.’s (1995) cross-sectional version of the Modified Jones model and the Kothari et al. (2005) model; and secondly, through earnings persistence as a direct measure of earnings quality.

Findings

The empirical results of this study reveal that poor accounting quality (high levels of abnormal discretionary accruals) is associated with higher levels of cash holdings, implying that as the quality of earnings decreases, the harmful effects of information asymmetry and adverse selection costs will increase, leading, therefore, Jordanian companies to increase their corporate cash holdings levels to act as a buffer against any cash shortages. Further, the authors document that higher accounting quality (more persistent earnings) is associated with lower levels of cash holdings. In addition, this study found that earnings quality negatively and significantly affects the cash holdings of profitable companies in Jordan. Thus, earnings quality appeared to be a significant determinant of cash holdings for profit-making companies but not for companies enduring losses.

Originality/value

This study contributes to the limited evidence that investigates the relationship between earnings quality and corporate cash holdings. Where the majority of previous studies have focused on developed economies, to the best of the authors’ knowledge, this study is the first in Jordan to comprehensively explore the relationship between earnings quality, computed by the absolute abnormal discretionary accruals and earnings persistence, and corporate cash holdings. Also, it is the first to explore the nature of the earnings quality-cash holding nexus in loss-making companies compared with their profit-making counterparts to the best of the authors’ knowledge. The results of this study have important policy implications for managers, creditors, investors and academics in Jordan and other emerging economies that share similar characteristics.
Emotional robustness in times of crisis: the effects of venture funding on the digital communication styles of entrepreneurs
Authors: Kaiser Manuel , Kuckertz Andreas
Published: May 2023

Purpose

Entrepreneurial communication describes the communication activities of entrepreneurs and is an essential tool for entrepreneurs to build relationships. However, there is a lack of research regarding how entrepreneurs adapt their communication styles in times of crisis. Nevertheless, entrepreneurial communication during a crisis is essential because entrepreneurs must continue communicating with their stakeholders and be visible. In this regard, communication has the central aim of preventing the startup from suffering any damage that may result from the crisis. Thus, the present paper explores potential shifts in the communication styles of entrepreneurs during the first wave of the COVID-19 pandemic.

Design/methodology/approach

The authors examined the digital footprints of 780 entrepreneurs based in the USA on the social network Twitter. This study used a longitudinal dataset with the software Linguistic Inquiry and Word Count (LIWC) to analyze 110,283 tweets sent pre-crisis and during the first wave of COVID-19.

Findings

The results of the exploratory analysis revealed a connection between crisis and both analytical thinking and emotional responses. In the case of emotions, the results also suggest that entrepreneurs who had already received funding from venture capital investors remained emotionally robust during the crisis, as evidenced by the expression of more positive emotions compared to entrepreneurs without funding.

Originality/value

This study contributes to the understanding of entrepreneurial communication and adds the context of an exogenous shock to this research stream. Furthermore, this study highlights the effects of venture funding on the digital communication style of entrepreneurs, especially in the context of expressed emotions, and suggests emotional robustness for these entrepreneurs.
Factors and key interactions influencing successful employment outcomes for people with disabilities
Authors: Ikutegbe Paul , Randle Melanie , Sheridan Lynnaire , Gordon Robert , Dolnicar Sara
Published: May 2023

Responding to the UN Convention on the Rights of People with Disabilities, many countries are trying to improve economic and social participation for people with disabilities. Yet, workforce participation remains substantially lower for people with disabilities than for people without disabilities. Building on a recently developed model of factors that influence mainstream employment outcomes for people with disabilities, this study utilises the social model of disability to examine the perceived relative importance of each factor and the interactions between them. We conducted 47 semi‐structured interviews with people with disabilities, employers and disability employment services providers to identify eight factors that were most important in achieving successful employment outcomes: nature of the disability, disability disclosure, personal motivation, employer attitudes, job characteristics, corporate culture and climate, government support and societal attitudes. Eight interactions between the factors were also identified. Findings provide insights that can guide the implementation of structural changes to ensure better employment outcomes for people with disabilities.
Single‐cell transcriptomic landscape of peripheral blood cells provides insights into adaptation of red‐eared sliders (Trachemys scripta elegans)
Authors: GUO Rui , MA Guangwei , ZHAI Xiaofei , SHI Haitao , WANG Jichao
Published: May 2023

Red‐eared sliders (Trachemys scripta elegans), as one of the 100 most threatening aliens, have stronger immunity than the native species in response to environmental stress. Blood cells are an important component of immunity in the body. However, the blood cell researches of turtle are still in the traditional blood cell classification and morphological structure observation. Furthermore, turtle granulocytes cannot be accurately identified using traditional methods. Single‐cell RNA sequencing techniques have been successfully implemented to study cells based on the mRNA expression patterns of each cell. The present study profiled the transcriptomes of peripheral blood cells in red‐eared sliders to construct a single‐cell transcriptional landscape of the different cell types and explored environmental adaptation mechanism from the perspective of hematology. All 14 transcriptionally distinct clusters (platelets, erythrocytes1, erythrocytes2, CSF1R monocytes, POF1B monocytes, neutrophils, GATA2high basophils, GATA2low basophils, CD4 T cells, CD7 T cells, B cells, ACKR4 cells, serotriflin cells, and ficolin cells) were identified in the peripheral blood cells of the red‐eared sliders. In particular, a subtype of erythrocytes (erythrocytes1) that expressed immune signals was identified. Peripheral blood cells were grouped into three lineages: platelet, erythroid/lymphoid, and myeloid cell lineages. Furthermore, based on differentiation trajectory and up‐regulated gene expression, ACKR4 cells were newly identified as lymphocytes, and serotriflin and ficolin cells as granulocytes. The single‐cell transcriptional atlas of the peripheral blood cells in red‐eared sliders provided in the present study will offer a comprehensive transcriptome reference for the exploration of physiological and pathological hematology in this species.
Insights from basic adjunctive examinations of GCK‐MODY, HNF1A‐MODY, and type 2 diabetes: A systemic review and meta‐analysis
Authors: Liu Jing , Xiao Xinhua , Zhang Qian , Yu Miao
Published: May 2023

Background

Glucokinase maturity‐onset diabetes of the young (GCK‐MODY) is difficult to distinguish from other diabetic forms. This article aims to characterize the differences in results from routine examinations between GCK‐MODY and hepatocyte nuclear factor 1‐α (HNF1A)‐MODY or type 2 diabetes (T2D) patients in different periods of diabetes.

Methods

Ovid Medline, Embase, and the Cochrane Library were searched up until October 9, 2022 for articles containing baseline characteristics of GCK‐MODY, HNF1A‐MOFY, and T2D, excluding pregnant women. The pooled standardized mean differences were derived using a random‐effects model.

Results

Compared to HNF1A‐MODY, GCK‐MODY patients had lower indicators of glucose metabolism. Total triglycerides (TG) (−0.93 [−1.66, −0.21] mmol/l) were consistently lower in GCK‐MODY patients in the all‐family‐members subgroup analysis. Compared to T2D, GCK‐MODY patients were younger at diagnosis and had lower body mass index (BMI), lower high‐sensitivity C‐reactive protein (hsCRP) (−0.60 [−0.75, −0.44] mg/l), lower fasting C‐peptide (FCP), and lower 2‐hour postprandial glucose (2‐h PG). Indicators of glycated hemoglobin (HbA1c) and fasting blood glucose (FPG) were consistently lower in subgroup studies with all family members of GCK‐MODY patients as well.

Conclusions

Lower HbA1c, FPG, 2‐h PG, and change in 2‐h PG may help to diagnose GCK‐MODY differentially from HNF1A‐MODY at an early stage, and lower TG may strengthen such a diagnosis in the follow‐up stages. Younger age combined with lower BMI, FCP, hsCRP, and 2‐h PG may be useful to distinguish GCK‐MODY from MODY‐like T2D, whereas results of glucose metabolism indicators such as HbA1c and FPG may not help physicians until after a long follow‐up period.
Extracellular flux analysis in intact cardiac tissue slices—A novel tool to investigate cardiac substrate metabolism in mouse myocardium
Authors: Bottermann Katharina , Spychala Andre , Eliacik Asena , Amin Ehsan , Moussavi‐Torshizi S. Erfan , Klöcker Nikolaj , Gödecke Axel , Heinen Andre
Published: May 2023

Aim

Cardiac pathologies are accompanied by alterations in substrate metabolism, and extracellular flux analysis is a standard tool to investigate metabolic disturbances, especially in immortalized cell lines. However, preparations of primary cells, such as adult cardiomyocytes require enzymatic dissociation and cultivation affecting metabolism. Therefore, we developed a flux analyzer‐based method for the assessment of substrate metabolism in intact vibratome‐sliced mouse heart tissue.

Methods

Oxygen consumption rates were determined using a Seahorse XFe24‐analyzer and “islet capture plates.” We demonstrate that tissue slices are suitable for extracellular flux analysis and metabolize both free fatty acids (FFA) and glucose/glutamine. Functional integrity of tissue slices was proven by optical mapping‐based assessment of action potentials. In a proof‐of‐principle approach, the sensitivity of the method was tested by analyzing substrate metabolism in the remote myocardium after myocardial infarction (I/R).

Results

Here, I/R increased uncoupled OCR compared with sham animals indicating a stimulated metabolic capacity. This increase was caused by a higher glucose/glutamine metabolism, whereas FFA oxidation was unchanged.

Conclusion

In conclusion, we describe a novel method to analyze cardiac substrate metabolism in intact cardiac tissue slices by extracellular flux analysis. The proof‐of‐principle experiment demonstrated that this approach has a sensitivity allowing the investigation of pathophysiologically relevant disturbances in cardiac substrate metabolism.
Fostering innovation to solve the biomechanics of microbe–host interactions: Focus on the adhesive forces underlying Apicomplexa parasite biology
Authors: Vigetti Luis , Tardieux Isabelle
Published: May 2023

The protozoa, Toxoplasma gondii and Plasmodium spp., are preeminent members of the Apicomplexa parasitic phylum in large part due to their public health and economic impact. Hence, they serve as model unicellular eukaryotes with which to explore the repertoire of molecular and cellular strategies that specific developmental morphotypes deploy to timely adjust to their host(s) in order to perpetuate. In particular, host tissue‐ and cell‐invasive morphotypes termed zoites alternate extracellular and intracellular lifestyles, thereby sensing and reacting to a wealth of host‐derived biomechanical cues over their partnership. In the recent years, biophysical tools especially related to real time force measurement have been introduced, teaching us how creative are these microbes to shape a unique motility system that powers fast gliding through a variety of extracellular matrices, across cellular barriers, in vascular systems or into host cells. Equally performant was this toolkit to start illuminating how parasites manipulate their hosting cell adhesive and rheological properties to their advantage. In this review, besides highlighting major discoveries along the way, we discuss the most promising development, synergy, and multimodal integration in active noninvasive force microscopy methods. These should in the near future unlock current limitations and allow capturing, from molecules to tissues, the many biomechanical and biophysical interplays over the dynamic host and microbe partnership.
Sleep, oscillations, and epilepsy
Authors: Bernard Christophe , Frauscher Birgit , Gelinas Jennifer , Timofeev Igor
Published: May 2023

Sleep and wake are defined through physiological and behavioral criteria and can be typically separated into non‐rapid eye movement (NREM) sleep stages N1, N2, and N3, rapid eye movement (REM) sleep, and wake. Sleep and wake states are not homogenous in time. Their properties vary during the night and day cycle. Given that brain activity changes as a function of NREM, REM, and wake during the night and day cycle, are seizures more likely to occur during NREM, REM, or wake at a specific time? More generally, what is the relationship between sleep–wake cycles and epilepsy? We will review specific examples from clinical data and results from experimental models, focusing on the diversity and heterogeneity of these relationships. We will use a top‐down approach, starting with the general architecture of sleep, followed by oscillatory activities, and ending with ionic correlates selected for illustrative purposes, with respect to seizures and interictal spikes. The picture that emerges is that of complexity; sleep disruption and pathological epileptic activities emerge from reorganized circuits. That different circuit alterations can occur across patients and models may explain why sleep alterations and the timing of seizures during the sleep–wake cycle are patient‐specific.
Generating instability? The impact of the EU's hybrid migration governance in Turkey, Lebanon and Jordan
Authors: Cooper Luke , Nimer Maissam
Published: May 2023

This article analyses the migration agreements between the European Union (EU) and Turkey, Lebanon and Jordan. These international policy frameworks were negotiated in tandem with one another, and all were announced in 2016. Drawing on fieldwork conducted in the three countries, the article argues that they fuse humanitarian elements with a bloc‐based security logic in an ad‐hoc mix that lacks substantive legitimacy in the three states, rendering the frameworks unstable. The article introduces the idea of hybrid migration governance which we have developed inductively to conceptualise the empirical findings from our fieldwork, building on existing work on hybridity in the conflict and security studies literature and Nora Stel's conception of governance as the ability to shape the field of action of others. In our usage, hybrid migration governance refers to the efficacy of EU intervention in the institutional management of migration in the three case study countries (‘shaping the field of action’), the ‘frozen’ character of the societal relations formed through this process and their underlying lack of domestic legitimacy. In conclusion, we argue that hybrid migration governance poses problem for the EU's ‘Barcelona’ conception of human security, because rather than expanding the bloc's ‘zone of security’ to the international neighbourhood, these policies have generated downstream security‐risks.
ON THE DISTRIBUTIONAL EFFECTS OF INTERNATIONAL TARIFFS
Authors: Carroll Daniel , Hur Sewon
Published: May 2023

We provide a quantitative analysis of the distributional effects of the 2018 increase in tariffs by the United States and its major trading partners. We build a trade model with incomplete asset markets and households that are heterogeneous in their age, income, wealth, and labor skill. When tariff revenues are used to reduce distortionary taxes on consumption, labor, and capital income, the average welfare loss from the trade war is equivalent to a permanent 0.1% reduction in consumption. Much larger welfare losses are concentrated among retirees and low‐wealth households, whereas only wealthy households experience a welfare gain.
Purification and concentration of infectious koi herpesvirus using steric exclusion chromatography
Authors: Eilts Friederike , Jordan Lisa K. , Harsy Yasmina M. J. , Bergmann Sven M. , Becker Anna M. , Wolff Michael W.
Published: May 2023

Koi herpesvirus (KHV) is the causative agent of a koi herpesvirus disease (KHVD) inducing high mortality rates in common carp and koi (Cyprinus carpio). No widespread effective vaccination strategy has been implemented yet, which is partly due to side effects of the immunized fish. In this study, we present an evaluation of the purification of infectious KHV from host cell protein and DNA, using the steric exclusion chromatography. The method is related to conventional polyethylene glycol (PEG) precipitation implemented in a chromatographic set‐up and has been applied for infectious virus particle purification with high recoveries and impurity removal. Here, we achieved a yield of up to 55% of infectious KHV by using 12% PEG (molecular weight of 6 kDa) at pH 7.0. The recoveries were higher when using chromatographic cellulose membranes with 3–5 μm pores in diameter instead of 1 μm. The losses were assumed to originate from dense KHV precipitates retained on the membranes. Additionally, the use of >0.6 M NaCl was shown to inactivate infectious KHV. In summary, we propose a first step towards a purification procedure for infectious KHV with a possible implementation in fish vaccine manufacturing.
Methods to assess ambivalence towards food and diet: a scoping review
Authors: Hayashi Daisuke , Carvalho Samantha Dalbosco Lins , Ribeiro Paula Aver Bretanha , Rodrigues Roberta Cunha Matheus , São‐João Thaís Moreira , Lavoie Kim , Bacon Simon , Cornélio Marilia Estevam
Published: May 2023

Background

Ambivalence towards food and diet, which favours behavioural inertia, might be a barrier to adopting healthier eating behaviours. Measuring it can help researchers to better understand its relationship with behaviour change and design interventions aimed at resolving it. In this scoping review, we map and describe methods and tools employed in studies to assess, measure or classify the ambivalence of participants towards food‐ and diet‐related attitude objects.

Methods

In accordance with Joanna Briggs Institute guidance for conducting scoping reviews, we retrieved peer‐reviewed studies from MEDLINE, CINAHL, PsycINFO, Web of Science, FSTA and Food Science Source and preprints from PsyArXiv and MedRxiv. Two independent reviewers screened the articles. We considered for inclusion peer‐reviewed studies and preprints that assessed the ambivalence of participants of any age, sex or sociodemographic group towards food and diet.

Results

We included 45 studies published between 1992 and 2022, which included participants from 17 countries. Eighteen methods were employed across the included studies to assess different types of ambivalence (felt, potential or cognitive–affective), the most frequent of which were the Griffin Index, the Subjective Ambivalence Questionnaire, the MouseTracker Paradigm and the Orientation to Chocolate Questionnaire.

Conclusion

This scoping review identified several methods and tools to assess different types of ambivalence towards food‐ and diet‐related objects, providing an array of options for future studies.
EGF coating of titanium surfaces modulates cytokines in oral mucosal primary cells exposed to TNF‐α
Authors: Pansani Taisa Nogueira , Basso Fernanda Gonçalves , Cardoso Laís Medeiros , de Souza Costa Carlos Alberto
Published: May 2023

Objective

This study assessed the metabolism of oral mucosal cells cultured on titanium discs (Ti) coated (or not) with epidermal growth factor (EGF) and exposed to tumor necrosis factor alpha (TNF‐α).

Methods

Fibroblasts or keratinocytes were seeded on Ti coated or not with EGF, and then exposed to 100 ng/mL of TNF‐α for 24 h. Groups were established: G1: Ti (control); G2: Ti + TNF‐α; G3: Ti + EGF; and G4: Ti + EGF + TNF‐α. Both cell lines were evaluated for: viability (AlamarBlue®, n = 8); interleukin 6 and 8 (IL‐6, IL‐8) gene expression (qPCR, n = 5), and protein synthesis (ELISA, n = 6). For keratinocytes cells, the matrix metalloproteinase type 3 (MMP‐3) was evaluated by qPCR (n = 5) and ELISA (n = 6). A 3‐D culture of fibroblasts was analyzed by confocal microscopy. The data were subjected to ANOVA analysis, α = 5%.

Results

Increased cell viability was observed in all groups compared with G1. Enhanced gene expression and synthesis of IL‐6 and IL‐8 by fibroblasts and keratinocytes in G2 and modulation of hIL‐6 gene expression in G4 was noted. Modulation of IL‐8 synthesis occurred in keratinocytes in G3 and G4. Keratinocytes in G2 showed enhanced gene expression of hMMP‐3. A 3‐D culture showed more cells in G3. Fibroblasts in G2 exhibited disrupted cytoplasmic membrane. Cells in G4 showed elongated morphology with intact cytoplasm.

Conclusions

EGF coating increases cell viability and modulates the response of oral cells exposed to an inflammatory stimulus.
Banana bunchy top disease in Africa—Predicting continent‐wide disease risks by combining survey data and expert knowledge
Authors: Bouwmeester Hein , Blomme Guy , Omondi Aman Bonaventure , Ocimati Walter
Published: May 2023

Across Africa, banana bunchy top disease (BBTD) severely impacts banana production and livelihoods of millions of smallholder farmers. Mapping vulnerability of landscapes to monitor BBTD establishment and spread is crucial for proactive measures of disease exclusion. To highlight current and future risks of BBTD in Africa, the relationship between 1160 field observations from 14 BBTD surveys and environmental covariate maps was determined using logistic regression. From these relationships, we inferred the environmental suitability of the African landscape for the possible wider spread of BBTD. Using this information and expert knowledge, we generated a map highlighting the main banana production areas at risk of BBTD entry and establishment. We combined these maps to create a priority map that highlights the areas that need most attention in combating BBTD through surveillance and measures to prevent its spread. Our analysis shows that BBTD is widespread across tropical Africa, with dispersal over several hotspots. Central and Western Africa are most favourable for the development of BBTD. Central, West and South‐East Africa are most at risk of BBTD entry and initial establishment. Areas in West and Central Africa, in the Great Lakes Region in Eastern Africa and in South‐East Africa, particularly in Malawi and Mozambique, score high on the prioritization index for surveillance and mitigation efforts. Recent reports of BBTD presence in north‐western Uganda and western Tanzania support these risk predictions. For these and other not‐yet‐infected areas, measures for close surveillance and proactive management of the disease are needed.
Technology adoption in autocratic economies: The role of fiscal capacity
Authors: Janus Thorsten
Published: May 2023

What determines technology in autocratic regimes? In this paper, I assume that a rent‐extracting regime can adopt technology from the global technology frontier, tax‐paying citizens can oust the regime, and technology can decrease the ousting cost. I show that a lack of fiscal capacity can increase technology by preventing the ousting constraint from binding. Consistent with this prediction, tax collections and total factor productivity are negatively related in autocratic regimes. Extensions show that natural resources can divorce fiscal revenues from technology, which can encourage technology blocking. However, if technology adoption is socially costly, autocratic regimes can adopt too much technology.
Edgeworth's taxation paradox when firms engage in cost‐reducing investment
Authors: Hamada Kojun , Ohkawa Takao , Okamura Makoto
Published: May 2023

This study examines whether and when Edgeworth's taxation paradox, that taxation decreases the equilibrium price, occurs in a free‐entry Cournot oligopoly with cost‐reducing investment. In contrast to the fact that no paradox occurs in the short‐run equilibrium, the paradox can occur in the long‐run equilibrium, in which the number of firms is endogenous. However, the conditions under which the paradox occurs are restrictive when there is no investment. By incorporating cost‐reducing investments into the model, we demonstrate that the paradox is likely to occur under less restrictive conditions, irrespective of whether the tax is specific or ad valorem.
Split‐face evaluation: Gluconolactone plus oxybrasion versus gluconolactone plus microneedling. The effects on skin parameters
Authors: Jarząbek‐Perz Sylwia , Dziedzic Marta , Kołodziejczak Anna , Rotsztejn Helena
Published: May 2023

Background

The application of polyhydroxy acids and alpha‐hydroxy acids to the skin is often used in cosmetology. To enhance the effect of gluconolactone chemical peeling, a combined method including water‐oxygen oxybrasion or microneedle mesotherapy can be used.

Objectives

To evaluate skin parameters such as hydration, sebum, pH and TEWL after application of a 10% gluconolactone chemical peel in combination with oxybrasion and microneedling.

Materials and methods

Twenty‐one Caucasian women participated in the study. A series of three split face treatments was carried out at 1‐week intervals. Oxybrasion was performed on the right side of the face and micro‐needle mesotherapy on the left side. A 10% gluconolactone solution was applied to the entire face. Before the first and third treatments and 2 weeks after the last treatment, skin parameters were evaluated. Photographic documentation was also made before and after the treatment series.

Results and conclusion

Evaluation of skin parameters using Courage & Khazaka 580 Multi Probe Adapter probes (Courage + Khazaka electronic GmbH, Cologne, Germany) showed an increase in hydration and a decrease in sebum, pH and TEWL for both treatments. There were no statistically significant differences between the treatments. Combining chemical peeling of gluconolactone with oxybrasion and microneedle mesotherapy is a good method to seal the hydrolipid barrier and increase skin hydration.
The novel HLA‐C*06:02:105 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual
Authors: An Lin , Ding Pei‐pei , Xu Xiang , Tu Xiao‐nian , Zheng Zhong‐zheng
Published: May 2023

HLA‐C*06:02:105 differs from HLA‐C*06:02:01:01 by one nucleotide in exon 1.
Characterization of a novel HLA‐C allele, HLA‐C*05:278N
Authors: Devriese Magali , Da Silva Sephora , Carmagnat Maryvonnick , Taupin Jean‐Luc
Published: May 2023

The novel HLA‐C*05:278N allele has a premature stop codon in exon 4.
High resolution acoustic identification of clusters of small blockages in fluid-filled pipe using maximum likelihood estimation
Authors: Nasraoui Saber , Louati Moez , Ghidaoui Mohamed S.
Published: May 2023

This paper presents a method for identifying a cluster of small blockages (i.e., blockages with length on the order of centimeters and radial extent on the order of millimeters and separated by a distance on the order of few centimeters) in pressurized fluid-filled pipes using sound waves. This focus on defects with small scale, and, thus, small scattering strength is exploited to develop a Neumann series solution for the scattered acoustic wave field. The probing waves are such that the Helmholtz number (ratio of blockage longitudinal length scale and probing acoustic wavelength) is of order 1 or larger. A high resolution inverse technique for identifying a cluster of small blockages based on the maximum likelihood estimation principle is developed. The proposed technique uses two-dimensional search space to resolve each blockage in the cluster and requires a single measurement point only. The method is successfully tested through both numerical and laboratory experiments. The proposed methodology allows an early identification of a cluster of small defects and leads to reliable condition assessment of pipelines, which is necessary to inform decisions as to when remedial actions are required.
Development, Evaluation, and Multisite Deployment of a Machine Learning Decision Tree Algorithm To Optimize Urinalysis Parameters for Predicting Urine Culture Positivity
Authors: Seheult Jansen N. , Stram Michelle N. , Contis Lydia , Pontzer Raymond E. , Hardy Stephanie , Wertz William , Baxter Carla M. , Ondras Michael , Kip Paula L. , Snyder Graham M. , Pasculle A. William
Published: May 2023

PittUDT, a recursive partitioning decision tree algorithm for predicting urine culture (UC) positivity based on macroscopic and microscopic urinalysis (UA) parameters, was developed in support of a broader system-wide diagnostic stewardship initiative to increase appropriateness of UC testing. Reflex algorithm training utilized results from 19,511 paired UA and UC cases (26.8% UC positive); the average patient age was 57.4 years, and 70% of samples were from female patients.
Hepatitis B Virus Genotype E/A Recombinants from Blood Donors in Beira, Mozambique
Authors: Tyler Barbara , Meeds Heidi L. , Odegard Elizabeth A. , Ismael Nalia , Vubil Adolfo , Zicai Ana Flora , Mabunda Nédio , Blackard Jason T.
Published: May 2023

Hepatitis B virus (HBV) is endemic in many parts of sub-Saharan Africa. Here, we present 5 full-length HBV recombinant genomes from blood donors in Beira, Mozambique. The genomes are recombinants between genotypes E and A and are distantly related to one another, based on their genetic distances.
Supplemental Material: Southwest Borneo, an autochthonous Pangea-Eurasia assembly proxy: Insights from detrital zircon record
Authors: Quek Long Xiang , Li Shan , al. et
Published: May 2023

Figures S1–S2, Data Sets S1–S2, data sources, and methods. 
Supplemental Material: Mud volcanoes guided by thrusting in compressional settings
Authors: Soto Juan I. , Hudec Michael
Published: May 2023

Additional information about the study area, the 3-D seismic dataset and interpretation, and the details of the fold measurements. 
Supplemental Material: Boninitic melt percolation makes depleted mantle wedges rich in silica
Authors: Chen Ming , al. et
Published: May 2023

Samples and petrography, analytical and modelling procedures, major-element results of silicate minerals, compiled data sources, supplementary figures and tables, and spot locations for electron microprobe analyses.  