bluuebunny/crossref_metadata_2025 huggingface dataset:
Amino acid substitutions hydrophilizing the core of titin domains cause dilated cardiomyopathy
Authors: Martinez-Martin Ines , Crousilles Audrey , Ochoa Juan Pablo , Velazquez-Carreras Diana , Mortensen Simon A. , Herrero-Galan Elias , Dominguez Fernando , Garcia-Pavia Pablo , de Sancho David , Wilmanns Matthias , Alegre-Cebollada Jorge
Published: June 2023

The underlying genetic defect in most cases of dilated cardiomyopathy (DCM), a common inherited heart disease, remains unknown. Intriguingly, many patients carry single missense variants of uncertain pathogenicity targeting the giant protein titin, a fundamental sarcomere component. To explore the deleterious potential of these variants, we first solved the wild-type and mutant crystal structures of I21, the titin domain targeted by pathogenic variant p.C3575S. Although both structures are remarkably similar, the increase in hydrophilicity of deeply buried position 3575 strongly destabilizes the mutant domain, a scenario supported by molecular dynamics simulations and by biochemical assays that show no disulfide involving C3575. Prompted by these observations, we have found that thousands of similar hydrophilizing variants associate specifically with DCM. Hence, our results imply that titin domain destabilization causes DCM, a conceptual framework that not only informs pathogenicity assessment of gene variants but also points to therapeutic strategies counterbalancing protein destabilization.
Small regulatory RNAs are mediators of theStreptococcus mutansSloR regulon
Authors: Drummond India Y. , DePaolo Alessandra , Krieger Madeline , Driscoll Heather , Eckstrom Korin , Spatafora Grace A.
Published: June 2023

Dental caries is among the most prevalent chronic infectious diseases worldwide.Streptococcus mutans, the chief causative agent of caries, uses a 25 kDa manganese dependent SloR protein to coordinate the uptake of essential manganese with the transcription of its virulence attributes. Small non-coding RNAs (sRNAs) can either enhance or repress gene expression and reports in the literature ascribe an emerging role for sRNAs in the environmental stress response. Herein, we identify 18-50 nt sRNAs as mediators of theS. mutansSloR and manganese regulons. Specifically, the results of sRNA-seq revealed 56 sRNAs inS. mutansthat were differentially transcribed in the SloR-proficient UA159 and SloR-deficient GMS584 strains, and 109 sRNAs that were differentially expressed in UA159 cells grown in the presence of low versus high manganese. We describe SmsR1532 and SmsR1785 as SloR- and/or manganese-responsive sRNAs that are processed from large transcripts, and that bind SloR directly in their promoter regions. The predicted targets of these sRNAs include regulators of metal ion transport, growth management via a toxin-antitoxin operon, and oxidative stress tolerance. These findings support a role for sRNAs in coordinating intracellular metal ion homeostasis with virulence gene control in an important oral cariogen.

IMPORTANCE

Small regulatory RNAs (sRNAs) are critical mediators of environmental signaling, particularly in bacterial cells under stress, but their role inStreptococcus mutansis poorly understood.S. mutans,the principal causative agent of dental caries, uses a 25 kDa manganese-dependent protein, called SloR, to coordinate the regulated uptake of essential metal ions with the transcription of its virulence genes. In the present study, we identified and characterize sRNAs that are both SloR- and manganese-responsive. Taken together, this research can elucidate the details of regulatory networks that engage sRNAs in an important oral pathogen, and that can enable the development of an effective anti-caries therapeutic.
The small protein MntS evolved from a signal peptide and acquired a novel function regulating manganese homeostasis inEscherichia coli
Authors: Wright Zachary , Seymour Mackenzie , Paszczak Kalista , Truttmann Taylor , Senn Katherine , Stilp Samuel , Jansen Nickolas , Gosz Magdalyn , Goeden Lindsay , Anantharaman Vivek , Aravind L. , Waters Lauren S.
Published: June 2023

Small proteins (< 50 amino acids) are emerging as ubiquitous and important regulators in organisms ranging from bacteria to humans, where they commonly bind to and regulate larger proteins during stress responses. However, fundamental aspects of small proteins, such as their molecular mechanism of action, downregulation after they are no longer needed, and their evolutionary provenance are poorly understood. Here we show that the MntS small protein involved in manganese (Mn) homeostasis binds and inhibits the MntP Mn transporter. Mn is crucial for bacterial survival in stressful environments, but is toxic in excess. Thus, Mn transport is tightly controlled at multiple levels to maintain optimal Mn levels. The small protein MntS adds a new level of regulation for Mn transporters, beyond the known transcriptional and post-transcriptional control. We also found that MntS binds to itself in the presence of Mn, providing a possible mechanism of downregulating MntS activity to terminate its inhibition of MntP Mn export. MntS is homologous to the signal peptide of SitA, the periplasmic metal-binding subunit of a Mn importer. Remarkably, the homologous signal peptide regions can substitute for MntS, demonstrating a functional relationship between MntS and these signal peptides. Conserved gene-neighborhoods support that MntS evolved from an ancestral SitA, acquiring a life of its own with a distinct function in Mn homeostasis.

Significance

This study demonstrates that the MntS small protein binds and inhibits the MntP Mn exporter, adding another layer to the complex regulation of Mn homeostasis. MntS also interacts with itself in cells with Mn, which could prevent it from regulating MntP. We propose that MntS and other small proteins might sense environmental signals and shut off their own regulation via binding to ligands (e.g., metals) or other proteins. We also provide evidence that MntS evolved from the signal peptide region of the Mn importer, SitA. Homologous SitA signal peptides can recapitulate MntS activities, showing that they have a second function beyond protein secretion. Overall, we establish that small proteins can emerge and develop novel functionalities from gene remnants.
Structural characterization of ligand binding and pH-specific enzymatic activity of mouse Acidic Mammalian Chitinase
Authors: Díaz Roberto Efraín , Ecker Andrew K. , Correy Galen J. , Asthana Pooja , Young Iris D. , Faust Bryan , Thompson Michael C. , Seiple Ian B. , Van Dyken Steven J. , Locksley Richard M. , Fraser James S.
Published: June 2023

Chitin is an abundant biopolymer and pathogen-associated molecular pattern that stimulates a host innate immune response. Mammals express chitin-binding and chitin-degrading proteins to remove chitin from the body. One of these proteins, Acidic Mammalian Chitinase (AMCase), is an enzyme known for its ability to function under acidic conditions in the stomach but is also active in tissues with more neutral pHs, such as the lung. Here, we used a combination of biochemical, structural, and computational modeling approaches to examine how the mouse homolog (mAMCase) can act in both acidic and neutral environments. We measured kinetic properties of mAMCase activity across a broad pH range, quantifying its unusual dual activity optima at pH 2 and 7. We also solved high resolution crystal structures of mAMCase in complex with oligomeric GlcNAcn, the building block of chitin, where we identified extensive conformational ligand heterogeneity. Leveraging these data, we conducted molecular dynamics simulations that suggest how a key catalytic residue could be protonated via distinct mechanisms in each of the two environmental pH ranges. These results integrate structural, biochemical, and computational approaches to deliver a more complete understanding of the catalytic mechanism governing mAMCase activity at different pH. Engineering proteins with tunable pH optima may provide new opportunities to develop improved enzyme variants, including AMCase, for therapeutic purposes in chitin degradation.
The ghrelin receptor GHSR has two efficient agonists in an ancient fish species
Authors: Li Hao-Zheng , Wang Ya-Fen , Zheng Yong-Shan , Liu Ya-Li , Xu Zeng-Guang , Guo Zhan-Yun
Published: June 2023

The gastric peptide ghrelin and its receptor GHSR have important functions in energy metabolism. Recently, liver-expressed antimicrobial peptide 2 (LEAP2) was identified as an endogenous antagonist for GHSR. Ghrelin, LEAP2, and GHSR are ubiquitously present from fishes to mammals and are highly conserved in evolution. However, our recent study suggested that GHSRs from the Actinopterygii fishDanio rerio(zebrafish) andLarimichthys crocea(large yellow croaker) have lost their binding to ghrelin, despite binding normally to LEAP2. Do these fish GHSRs use another peptide as their agonist? To answer this question, in the present study, we tested to two fish motilins that are closely related to ghrelin. In ligand binding and activation assays, the fish GHSRs fromD. rerioandL. croceadisplayed no detectable or very low binding to all tested motilins; however, the GHSR from the Sarcopterygii fishLatimeria chalumnae(coelacanth) bound to its motilin with high affinity and was efficiently activated by it. Therefore, it seemed that motilin is not a ligand for GHSR inD. rerioandL. crocea, but is an efficient agonist for GHSR inL. chalumnae, which is known as a ‘living fossil’ and is believed to be one of the closest fish ancestors of tetrapods. The results of present study suggested that in ancient fishes, GHSR had two efficient agonists, ghrelin and motilin; however, this feature might be only preserved in some extant fishes with ancient evolutionary origins. Our present work shed new light on the ligand usage of GHSR in different fish species and in evolution.
Mutant Huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure
Authors: Lisowski Pawel , Lickfett Selene , Rybak-Wolf Agnieszka , Le Stephanie , Dykstra Werner , Mlody Barbara , Menacho Carmen , Roth Philipp , Richter Yasmin , Kulka Linda A. M. , Glazar Petar , Wu Haijia , Meierhofer David , Legnini Ivano , Otto Max , Miller Duncan , Neuendorf Nancy , Hahn Tobias , Telugu Narasimha Swamy , Böddrich Annett , Mayatepek Ertan , Diecke Sebastian , Olzscha Heidi , Kirstein Janine , Kühn Ralf , Cambridge Sidney , Rajewsky Nikolaus , Wanker Erich E. , Priller Josef , Metzger Jakob J. , Prigione Alessandro
Published: June 2023

Expansion of the glutamine tract (poly-Q) in the protein Huntingtin (HTT) causes the neurodegenerative disorder Huntington’s disease (HD). Emerging evidence suggests that mutant HTT (mHTT) disrupts brain development. To gain mechanistic insights into the neurodevelopmental impact of human mHTT, we engineered induced pluripotent stem cells to introduce a biallelic or monoallelic mutant 70Q expansion or to remove the poly-Q tract of HTT. 70Q introduction caused aberrant development of cerebral organoids with loss of neural progenitor organization. The early neurodevelopmental signature of mHTT highlighted the dysregulation of the protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2), a transcription factor involved in mitochondrial integrated stress response. CHCHD2 repression was associated with abnormal mitochondrial morpho-dynamics and elevated resting energy expenditure. Elimination of the poly-Q tract of HTT normalized CHCHD2 expression and mitochondrial defects. Hence, mHTT-mediated disruption of human neurodevelopment is paralleled by aberrant neurometabolic programming mediated by dysregulation of CHCHD2, which could then serve as an early intervention target for HD.
A Pumpless, High-Throughput Microphysiological System Confirms Enteric Innervation of Duodenal Epithelium Strengthens the Barrier Function
Authors: Nichols Kyla N. , Snyder Jessica R. , Koppes Ryan A. , Koppes Abigail N.
Published: June 2023

Enteric neurons, diverse in function and great in number, are heavily involved in homeostasis within the small intestine and their dysregulation has been implicated in gastrointestinal disorders and neurodegenerative diseases. Innovations in biofabrication have resulted in advances for in vitro models of the gut, however the majority lack enteric innervation, limiting therapeutic screening and discovery. Here, we present a high-throughput co-cultured microphysiological system (MPS), or organ chip, that supports a primary epithelial monolayer that directly interfaces with a three-dimensional hydrogel containing a primary enteric neuron culture, mimicking the close proximity present in vivo. The acrylic MPS device was fabricated with our established and cost-effective laser cut and assemble method. We have expanded this technology to include up to twelve 3D MPSs per device within the footprint of a traditional well-plate, supporting high-throughput experimentation. The inclusion of this 3D microtissue does not hinder physiologically relevant flow, standard measures of barrier function, and microscopy techniques. The device features gravity-driven flow to induce physiological shear stress on the epithelium culture and provide continuous nutrient presentation. Results show the intestinal and neural tissue maintained expected morphologies over an experimental timeline of ten days. Proximal enteric neurons extend neurites through the 3D hydrogel towards the epithelial monolayer. Barrier function was confirmed with both Transepithelial Electrical Resistance (TEER) and Lucifer Yellow diffusion on-chip. TEER confirmed a significantly more substantial barrier integrity in co-cultures compared to baseline values (1.25-fold) in epithelial cell-only. Lucifer yellow permeability assays performed in parallel supported the TEER results, with an 11.8% lower permeability of the co-cultured group than the epithelium only. The presence of the ENS on chip results in a significant (1.4 fold) reduction in epidermal growth factor (EGF). This is the first high-throughput, innervated gut on a chip device that demonstrates the importance of the autonomic nervous system on EGF expression and possibly epithelial renewal in vitro. Innervation is essential to create more biomimetic and physiologically relevant in vitro models for biological and pharmacological assays.
Persistent biofluid small molecule alterations induced byTrypanosoma cruziinfection are not restored by antiparasitic treatment
Authors: Dean Danya A. , Roach Jarrod , vonBargen Rebecca Ulrich , Xiong Yi , Kane Shelley S. , Klechka London , Wheeler Kate , Sandoval Michael Jimenez , Lesani Mahbobeh , Hossain Ekram , Katemauswa Mitchelle , Schaefer Miranda , Harris Morgan , Barron Sayre , Liu Zongyuan , Pan Chongle , McCall Laura-Isobel
Published: June 2023

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Chagas Disease (CD), caused byTrypanosoma cruzi (T. cruzi)protozoa, is a complicated parasitic illness with inadequate medical measures for diagnosing infection and monitoring treatment success. To address this gap, we analyzed changes in the metabolome ofT. cruzi-infected mice via liquid chromatography tandem mass spectrometry analysis of clinically-accessible biofluids: saliva, urine, and plasma. Urine was the most indicative of infection status, across mouse and parasite genotypes. Metabolites perturbed by infection in the urine include kynurenate, acylcarnitines, and threonylcarbamoyladenosine. Based on these results, we sought to implement urine as a tool for assessment of CD treatment success. Strikingly, it was found that mice with parasite clearance following benznidazole antiparasitic treatment had comparable overall urine metabolome to mice that failed to clear parasites. These results match with clinical trial data in which benznidazole treatment did not improve patient outcomes in late-stage disease. Overall, this study provides insights into new small molecule-based CD diagnostic methods and a new approach to assess functional treatment response.
Evaluating the Performance of the Astral Mass Analyzer for Quantitative Proteomics Using Data Independent Acquisition
Authors: Heil Lilian R. , Damoc Eugen , Arrey Tabiwang N. , Pashkova Anna , Denisov Eduard , Petzoldt Johannes , Peterson Amelia C. , Hsu Chris , Searle Brian C. , Shulman Nicholas , Riffle Michael , Connolly Brian , MacLean Brendan X. , Remes Philip M. , Senko Michael W. , Stewart Hamish I. , Hock Christian , Makarov Alexander A. , Hermanson Daniel , Zabrouskov Vlad , Wu Christine C. , MacCoss Michael J.
Published: June 2023

We evaluate the quantitative performance of the newly released Asymmetric Track Lossless (Astral) analyzer. Using data independent acquisition, the Thermo Scientific™ Orbitrap™ Astral™ mass spectrometer quantifies 5 times more peptides per unit time than state-of-the-art Thermo Scientific™ Orbitrap™ mass spectrometers, which have long been the gold standard for high resolution quantitative proteomics. Our results demonstrate that the Orbitrap Astral mass spectrometer can produce high quality quantitative measurements across a wide dynamic range. We also use a newly developed extra-cellular vesicle enrichment protocol to reach new depths of coverage in the plasma proteome, quantifying over 5,000 plasma proteins in a 60-minute gradient with the Orbitrap Astral mass spectrometer.
Social media celebrities' influence on youths' diet behaviors: a gender study based on the AIDA marketing communication model
Authors: Wong Ivan Ho San , Fan Chi Man , Chiu Dickson K.W. , Ho Kevin K.W.
Published: June 2023

Purpose

Social media celebrities are getting popular in promotions, and more people have experienced social media to receive information on diet and health tips. This research presents a study showing how social media can influence young people's diet behavior through collaboration with social media celebrities.

Design/methodology/approach

Through recruiting on various social media and online education forums, this research recruited 196 young Hongkongers to participate in an online survey developed based on the AIDA (Action, Interest, Desire, Attention) marketing communication model on how youths access diet information from social media celebrities in Hong Kong.

Findings

Hong Kong youths consume diet information from social media celebrities through instant messaging systems, social networking sites and online videos, and, in particular, information on food calories and nutrition. However, sponsorship from vendors would decrease their desire to agree with the messages from social media celebrities. After receiving this information, some participants would follow tips and guides from social media celebrities. However, they seldom share such information. Interestingly, males are more willing to follow these tips and guides.

Originality/value

First, this study fills the gap of prior research, which did not study much on how social media celebrities contribute to diet promotion to youths in Asia. Second, through the AIDA Model, this study shows how social media can affect the awareness and accessibility of diet information by young Hongkongers, followed by initiating their interest in this topic and retrieving more relevant information. Furthermore, the authors further understand their desire to follow and improve their behavior as promoted by social media influencers and how they practice such behavior. Based on these findings, health-related brands could consider using social media influencers helping to promote their products and services, and these brands could further use social media to secure customer engagement.
Struggling or juggling: work-life balance challenges of Western self-initiated women expatriates in the United Arab Emirates
Authors: Tahir Rizwan
Published: June 2023

Purpose

This qualitative study is grounded on in-depth interviews with 30 Western women self-initiated expatriate (SIEs) currently living and working in the UAE. When selecting the interviewees, the author used purposeful sampling to ensure a diverse sample of interviewees with respect to nationality, age, gender and occupation.

Design/methodology/approach

The present study, drawing on boundary theory, aims to investigate the work–life balance (WLB) of Western women SIEs regarding how these women construct and manage the borders between the non-work and work lives in the United Arab Emirates (UAE).

Findings

The results demonstrate that women SIEs experience conflicts and enrichment during overseas employment. Both directions – the impact flowing from working life to personal life and vice versa – were significant. Different career and life phases appeared to be crucial to these experiences. The study also found that some women SIEs in the UAE experience high pressure in the WLB approaches, which are primarily impacted by the specific work–life environment in the UAE. Mostly, work–life boundaries are culturally and socially induced. Hence, many women SIEs encounter disparities between the robust work–life separations in the home country compared to the host country; women SIEs, therefore, need to relax the boundaries to adapt to the competitive work–life environment in the UAE.

Originality/value

The present study contributes to research on work–life boundary management approaches in local settings, such as UAE, by analyzing cross-cultural and individual dimensions. Moreover, although women are still a minority among SIEs, the number of women is increasing. As prior studies have mainly focused on male SIEs, more research is required focusing specifically on women with overseas jobs. The present study endeavors to fill this research gap.
How does terrorism hollow out the sustainable economic growth in Big Ten Countries?
Authors: Keser Ahmet , Cutcu Ibrahim , Tiwari Sunil , Eren Mehmet Vahit , Askar S.S. , Abouhawwash Mohamed
Published: June 2023

Purpose

The main objective of this research is to investigate if there is a long-term relationship between “terrorism” and sustainable “economic growth” in Big Ten Countries.

Design/methodology/approach

The data was tested via Panel ARDL Analysis. The growth rate (GR) is the dependent variable, and the “Global Terror Index (GTI)” is the independent variable as the terror indicator. The ratio of Foreign Direct Investment (FDI) to the Gross Domestic Product (GDP), and the ratio of External Balance (EB) to Gross Domestic Product (GDP) are included in the model as the control variables due to their effect on the growth rate. A Panel ARDL analysis is conducted to examine the existence of long-term co-integration between terror and the economy. The planning of the study, the formation of its theoretical and conceptual framework, and the literature research were carried out in 2 months, and the collection of data, the creation of the methodology and the analysis of the analyzes were carried out in 2 months, the interpretation of the findings and the development of policy recommendations were carried out within a period of 1 month. The entire study was completed in a total of 5 months.

Findings

Results showed that “Terror” has a negative impact on “Growth Rate” in the long term while “External Balance” and “Foreign Direct Investment” positively affect the Growth Rate. The coefficients for the short term are not statistically significant.

Research limitations/implications

The sample is only limited to Big Ten including China, India, Indonesia, South Korea, Argentina, Brazil, Mexico, Turkey, Poland and South Africa. The period for annual data collection covers the years between 2002 and 2019 and due to the unavailability of data.

Practical implications

Considering the risks and the mutual negative effect that turns into a vicious circle between terrorism and the economy, it is necessary to eliminate the problems that cause terrorism in the mentioned countries, on the one hand, and to develop policies that will improve economic performance on the other.

Social implications

Trustful law enforcement bodies have to be established and supported by all technological means to prevent terror. The conditions causing terror have to be investigated carefully and the problems causing terror or internal conflict have to be solved. International cooperation against terrorism has to be strengthened and partnerships, information, experience sharing have to be supported at the maximum levels.

Originality/value

It is certain that terror might have a negative influence on the performance of economies. But the limited number of studies within this vein and the small size of their sample groups mostly including single-country case studies require conducting a study by using a larger sample group of countries. Big Ten here represents at least half of the population of the world and different regions of the Globe.
Corporate governance, enforcement institutions and corporate liquidity in the MENA region
Authors: Mertzanis Charilaos , Ellili Nejla , Marashdeh Hazem , Nobanee Haitham
Published: June 2023

Purpose

The study examines the effects of corporate governance and countrywide institutions and risk factors on corporate liquidity.

Design/methodology/approach

Using firm-level data, the authors analyze the effect of corporate governance and various economic, regulatory and social institutions on the liquidity of firms operating in the Middle East and North Africa (MENA) region. The authors use fixed-effects, firm-specific and country-level controls, disaggregated analysis, sensitivity and endogeneity analysis to test the robustness of the estimates.

Findings

The corporate governance characteristics of firms influence in diverse ways their liquidity decisions. The independence and diversity of the board and institutional ownership are especially strong predictors. The effect also depends on the size of the firm and the degree of economic development and exhibits time sensitivity and nonlinearity. Enforcement institutions and risk factors play a strong role.

Originality/value

The analysis contributes to the literature by using a large sample of countries and firms over a larger period, distinguishing between poorer and richer countries and using sensitivity and endogeneity analysis. The analysis considers explicitly the role of regulatory and enforcement conditions, social structures and religious beliefs.
Single fetal demise in monochorionic twins: How to predict cerebral injury in the survivor co‐twin?
Authors: Duyos Inmaculada , Ordás Polán , Herrero Beatriz , Rodriguez Roberto , Cabrero Miguel Jesús , Fernández‐Zubillaga Amelia , Diez Sebastian Jesús Benito , De La Calle María , Bartha José Luis , Antolín Eugenia
Published: June 2023

Introduction

The aims of the study were to evaluate perinatal outcome in monochorionic (MC) twins complicated with single intrauterine fetal death, spontaneously vs after fetal therapy, and to assess antenatal events that increase the risk of cerebral injury.

Material and methods

Historical cohort study of MC pregnancies with single intrauterine fetal death diagnosed or referred to a tertiary referral hospital (2012–2020). Adverse perinatal outcome included termination of pregnancy, perinatal death, abnormal fetal or neonatal neuroimaging and abnormal neurological development.

Results

A total of 68 MC pregnancies with single intrauterine fetal death after 14 weeks of gestation were included. Sixty‐five (95.6%) occurred in complicated MC pregnancies (twin to twin transfusion syndrome: 35/68 [51.5%]; discordant malformation: 13/68 [19.1%], selective intrauterine growth restriction: 10/68 [14.7%], twin reversed arterial perfusion sequence: 5/68 [7.3%] and cord entanglement in monoamniotic twins: 2/68 [2.94%]). In 52 cases (76.5%) single intrauterine fetal demise occurred after fetal therapy and in 16 (23.5%) occurred spontaneously. Cerebral damage included 14/68 cases (20.6%): 6/68 cases (8.82%) were prenatal lesions and 8/68 cases (11.8%) were postnatal. Risk of cerebral damage tended to be higher in the spontaneous death group (6/16, 37.5%) compared to the therapy‐group (8/52, 15.38%) (p = 0.07). The risk increased with gestational age at intrauterine death (OR 1.21, 95% CI: 1.04–1.41, p = 0.014) and was higher in those surviving co‐twins who developed anemia (OR 9.27, 95% CI: 1.50–57.12, p = 0.016). Pregnancies complicated with selective intrauterine growth restriction tended to be at higher risk for neurological damage (OR 2.85, 95% CI: 0.68–11.85, p = 0.15). Preterm birth rate (<37 weeks of pregnancy) was 61.7% (37/60). Seven of eight postnatal cerebral lesions (87.5%) were related to extreme prematurity. Overall perinatal survival rate was 88.3% (57/68) and 7% (4/57) of children had an abnormal neurological outcome.

Conclusions

Risk of cerebral damage in single intrauterine fetal death is especially high when it occurs spontaneously. Gestational age at single intrauterine fetal death, selective intrauterine growth restriction and anemia of the surviving co‐twin are the main predictors for prenatal lesions and might be useful in parent counseling. Abnormal postnatal neurological outcome is closely related to extreme prematurity.
Intravenous leiomyomatosis involving the right heart: Comprehensive evaluation using echocardiography combined with abdominal ultrasonography
Authors: Han Xuefang , Nie Fang , Li Jing , Zhao Yinglu , Wang Xiaofeng
Published: June 2023

Intravenous leiomyomatosis (IVL) is a rare condition characterized by a tumor that originates within a pelvic vein wall or the uterine smooth muscle, with extension into the right heart (referred to as intracardiac leiomyomatosis) in approximately 10% of all IVL cases. Usually, computed tomography (CT) or magnetic resonance imaging (MRI) is performed for diagnostic imaging of IVL. Notably, this neoplasm presents with characteristic ultrasonographic findings. In this report, we present the case of a 49‐year‐old woman with IVL, which extended into the right heart. Echocardiography combined with abdominal ultrasonography was useful to outline the course of the tumor from the right heart to the uterus. Our findings suggest that in addition to CT or MRI, ultrasonography shows high diagnostic value in cases of IVL, and ultrasonography combined with CT or MRI can further improve the preoperative diagnosis rate of IVL.
A new contextual and comprehensive application of the UTAUT2 model post‐COVID‐19 pandemic in higher education
Authors: Narayan Jashwini , Naidu Samantha
Published: June 2023

This study examines tertiary students' behavioural intention to resume face‐to‐face mode of study, post‐COVID‐19. A modified UTAUT2 model of nine factors and a moderator is used to investigate the impact of these factors on developing country's tertiary students' behavioural intention. The influence of these students' behavioural intention on se behaviour is also examined. Using a quantitative research approach, data were gathered from 419 students at a regional university using convenience sampling technique. Data were analysed to test and validate the proposed model using covariance‐based structural equation modelling. The study's findings reveal significant positive relationships between social influence, hedonic motivation, facilitating conditions, commitment, behavioural intention and use behaviour. However, it did not find performance expectancy, effort expectancy, price value, trust and comfortability, reporting any significant positive influence on behavioural intentions. Additionally, the moderating analysis shows that COVID‐19 fear did not moderate or strengthen the association between behavioural intentions and use behaviour, given the insignificant interaction effect of COVID‐19 fear. This study provides novelty in the contextual application of the modified UTAUT2 model, post‐COVID‐19. The addition of three additional constructs (trust, commitment and comfortability) has further improved the predictive power of the model. Lastly, the new construct that emerged in recent literature, COVID‐19 fear, has been tested for the first time within the UTAUT2 model as a moderator between behavioural intentions and use behaviour. In terms of practical implications, this study first adds to the current literature on higher education, after the COVID‐19 situation, being useful to education scholars. Second, it also offers specific suggestions to educational institutions and policymakers who fund universities. Such suggestions include: involving students' families in orientation and open day events, featuring family and friend support in promotional activities, upgrading facilities, including more teaching and learning sessions with team‐based assessments, encouraging comfortable interactions and continuously practising COVID‐19 safety protocols.
Supplemental Material: Juvenile hafnium isotopic compositions recording a late Carboniferous–Early Triassic retreating subduction in the southern Central Asian Orogenic Belt: A case study from the southern Alxa
Authors: Zheng  , al. et
Published: June 2023

Analytical methods, U–Pb geochronological data, zircon Lu–Hf-O isotopic compositions, whole-rock major and trace element data are presented in the Supplemental Material.
Supplemental Material: Stratigraphy around the Cretaceous-Paleogene boundary in sediment cores from the Lord Howe Rise, Southwest Pacific
Authors: Kuroda Junichiro , al. et
Published: June 2023

Tables S1–S4 and Figures S1–S2.
Effects of Probiotics, Prebiotics, and Synbiotics as an Alternative to Antibiotics on Growth and Blood Profile of Nile Tilapia (Oreochromis niloticus)
Authors: Munni Marjana Jannat , Akther Kazi Rabeya , Ahmed Shamim , Hossain Mohammad Amzad , Roy Nirmal Chandra
Published: June 2023

The purpose of this study is to compare the effects of probiotics, prebiotics, and their synergism against antibiotics on the growth performance and hematology of Nile tilapia (Oreochromis niloticus). The study was designed by using five treatments over 75 days in which TCon (control), TAnt (antibiotics: Cotrim vet), TPro (commercial probiotics: pond care), TPre (prebiotics: spirulina), and TSyn (synbiotic: probiotic and prebiotic) were used. All the treatments showed significant (

P

 < 0.05) improvements in growth and feed utilization parameters. The highest mean final growth was found in TSyn (13.79 ± 0.11) and then in TPre (13.61 ± 0.02), TPro (13.22 ± 0.12), TAnt (10.04 ± 0.7), and TCon (8.89 ± 0.19). Weight gain and specific growth rate were significantly (

P

 < 0.05) different between treatments. The food conversion ratio varied significantly (

P

 < 0.05) across treatments and the lowest value was observed in TPro (1.13 ± 0.021). The protein efficiency ratio (PER) was significantly (

P

 < 0.05) different between treatments and the highest value was in TPro (3.1 ± 0.05). The survival rate was not significantly (

P

 < 0.05) different between treatments. The highest white blood cell (WBC) counts were found in TSyn (12.63 ± 0.11) followed by TPre (12.6 ± 0.2), TPro (12.32 ± 0.12), TCon (12.16 ± 0.105), and TAnt (11.03 ± 0.46). The values of red blood cells and platelets were not statistically significant (

P

 < 0.05) among the different treatments. However, all treatments showed normal hepatocyte structure in liver tissue histology, and intense hepatic lipid vacuoles in TSyn indicated improved growth. The higher growth performance and feed utilization values were observed in probiotics, prebiotics, and their synergism units compared to antibiotic treatment. Therefore, probiotics, prebiotics, and their synergism can be used as an alternative to antibiotics in tilapia aquaculture.
AhR and HIF-1α Signaling Pathways in Benign Meningioma under Hypoxia
Authors: Perepechaeva Maria L. , Klyushova Lyubov S. , Grishanova Alevtina Y.
Published: June 2023

The role of hypoxia in benign meningiomas is less clear than that in the malignant meningiomas. Hypoxia-induced transcription factor 1 subunit alpha (HIF-1α) and its downstream signaling pathways play a central role in the mechanism of hypoxia. HIF-1α forms a complex with the aryl hydrocarbon receptor nuclear translocator (ARNT) protein and can compete for ARNT with aryl hydrocarbon receptor (AhR). In this work, the status of HIF-1α- and AhR-dependent signaling pathways was investigated in World Health Organization (WHO) grade 1 meningioma and patient-derived tumor primary cell culture under hypoxic conditions. mRNA levels of HIF-1α, AhR, and of their target genes as well as of ARNT and nuclear receptor coactivator NCOA2 were determined in tumor tissues from patients in whom the tumor was promptly removed either with or without prior endovascular embolization. Using the patient-derived nonembolized tumor primary cell culture, the effects of a hypoxia mimetic cobalt chloride (CoCl2) and an activator of the AhR signaling pathway benzo(α)pyrene (B[a]P) on mRNA levels of HIF-1α, AhR, and their target genes were investigated. Our findings show active functioning of AhR signaling in meningioma tissue of patients with tumor embolization and crosstalk between HIF-1α and AhR signaling in meningeal cells under hypoxia.
SS-31 alleviated nociceptive responses and restored mitochondrial function in a headache mouse model via Sirt3/Pgc-1α positive feedback loop
Authors: Shan Zhengming , Wang Yajuan , Qiu Tao , Zhou Yanjie , Zhang Yu , Hu Luyu , Zhang Lili , Liang Jingjing , Ding Man , Fan Shanghua , Xiao Zheman
Published: June 2023

Migraine is the second highest cause of disability worldwide, bringing a huge socioeconomic burden. Improving mitochondrial function has promise as an effective treatment strategy for migraine. Szeto-Schiller peptide (SS-31) is a new mitochondria-targeted tetrapeptide molecule that has been shown to suppress the progression of diseases by restoring mitochondrial function, including renal disease, cardiac disease, and neurodegenerative disease. However, whether SS-31 has a therapeutic effect on migraine remains unclear. The aim of this study is to clarify the treatment of SS-31 for headache and its potential mechanisms. Here we used a mouse model induced by repeated dural infusion of inflammatory soup (IS), and examined roles of Sirt3/Pgc-1α positive feedback loop in headache pathogenesis and mitochondrial function. Our results showed that repeated IS infusion impaired mitochondrial function, mitochondrial ultrastructure and mitochondrial homeostasis in the trigeminal nucleus caudalis (TNC). These IS-induced damages in TNC were reversed by SS-31. In addition, IS-induced nociceptive responses were simultaneously alleviated. The effects of SS-31 on mitochondrial function and mitochondrial homeostasis (mainly mitochondrial biogenesis) were attenuated partially by the inhibitor of Sirt3/Pgc-1α. Overexpression of Sirt3/Pgc-1α increased the protein level of each other. These results indicated that SS-31 alleviated nociceptive responses and restored mitochondrial function in an IS-induced headache mouse model via Sirt3/Pgc-1α positive feedback loop. SS-31 has the potential to be an effective drug candidate for headache treatment.

Graphical Abstract
Home confinement’s impact on myopia control by using orthokeratology in school-aged children
Authors: Zhang Boyuan , Liao Hongfei , Xiong Fen , Mao Tian , Wu Lili , Li Yue , Xiong Chao
Published: June 2023

Background

Home confinement during the epidemic has a significant impact on the lifestyle and behavior of school-aged children, who have exhibited an increase in the prevalence and development of myopia. Our research will look at if home confinement will affect school-aged children on myopia control with orthokeratology.

Method

Data on axial length was gathered from school-aged children who had received OK lenses treatment. The entire data was separated into subgroups based on gender, age, and initial refraction, and the AL changes for each period were calculated using the formula defined in our study. Finally, the acquired data will be examined using various statistical approaches, and the ideas of slow, moderate, and rapid myopia progression will be applied to our study.

Result

A total of 258 study subjects met the requirements to be included in the study. We discovered that the percentage of rapid myopia growth increased during the epidemic. In addition, the AL changes before and during the epidemic were found to be statistically significant in 171 subjects in the overall data. (P = 0.041) In the high age group, the AL changes before and during the epidemic、(P = 0.033) before and after the epidemic (P = 0.023) were found to be statistically significant. The AL changes before and during the epidemic (P = 0.035) were shown to be statistically significant in the moderate myopia group. Finally, we did not find statistically significant results for other groups.

Conclusion

We cannot conclude that home confinement did have a negative impact on myopia control with orthokeratology in school-aged children. But we found there was an increase in the percentage of patients with OK treatment that had fast myopia progression during the confinement. We also observed that older children with higher initial refraction were more likely to be affected by home confinement.
Tridimensional assessment of the mandibular angle in patients with different skeletal patterns by cone-beam computed tomography scans: a retrospective study
Authors: Miranda-Viana Murilo , Moreira Gabriel Mosso , de Souza Larissa Moreira , Nejaim Yuri , Haiter-Neto Francisco , Freitas Deborah Queiroz
Published: June 2023

Background

Since the muscles of chewing are involved in the region of the mandibular angle, important structures in surgical and orthodontic procedures, to study its morphological aspects and the possible influence of different patterns of skeletal development would be of interest. Thus, this study aimed to assess the influence of patient characteristics - such as sex, skeletal malocclusion (Class I, Class II, and Class III) and facial type (brachycephalic, mesocephalic, and dolichocephalic) - on the width, height, thickness, and volume of the mandibular angle, using cone-beam computed tomography (CBCT) scans.

Methods

CBCT scans were assessed − 144 men and 154 women, total of 298 - and classified according to skeletal patterns (skeletal malocclusions and facial types). Width, height, and thickness of the mandibular angle were measured using OnDemand 3D software. The volumetric measures of the mandibular angle were obtained using the ITK-SNAP software. Analysis of Variance (multiway ANOVA) with Tukey’s post-hoc test compared the data, with a 5% significance level.

Results

Among the factors studied, sex significantly influenced all the analyzed variables (height, width, thickness, and volume of the mandibular angle) (p < 0.05); in general, male individuals presented higher values than females. In some cases, the skeletal malocclusion and facial type factors influenced only the width and height variables (p < 0.05); in general, the Class III and dolichocephalic individuals presented higher values in relation to the other types of skeletal malocclusions and facial types.

Conclusions

Variations in the craniofacial growth pattern, considering the different skeletal malocclusions and facial types, had some influence in the width and height dimensions of the mandibular angle. Furthermore, sex influenced all the studied variables.
Application of the Khorana score for cancer-associated thrombosis prediction in patients of East Asian ethnicity undergoing ambulatory chemotherapy
Authors: Ha Hyerim , Ko Yeh-Hee , Kim Kwangsoo , Hong Junshik , Lee Gyeong-Won , Jeong Seong Hyun , Bang Soo-Mee , Yoon Sung-Soo
Published: June 2023

Background

The Khorana score (KS) has not been well studied in East Asian cancer patients, who have different genetic backgrounds for inherited thrombophilia, body metabolism, and cancer epidemiology.

Methods

By using the Common Data Model, we retrospectively collected deidentified data from 11,714 consecutive newly diagnosed cancer patients who underwent first-line chemotherapy from December 2015 to December 2021 at a single institution in Korea, and we applied the KS for cancer-associated thrombosis (CAT) prediction. Age at diagnosis, sex, and use of highly thrombogenic chemotherapeutics were additionally investigated as potential risk factors for CAT development.

Results

By 6 months after chemotherapy initiation, 207 patients (1.77%) experienced CAT. Only 0.4% had a body mass index (BMI) ≥ 35 kg/m2 and changing the cutoff to 25 kg/m2 improved the prediction of CAT. Age ≥ 65 years and the use of highly thrombogenic chemotherapeutics were independently associated with CAT development. KS values of 1 ~ 2 and ≥ 3 accounted for 52.3% and 7.6% of all patients, respectively, and the incidence of CAT in these groups was 2.16% and 4.16%, respectively, suggesting a lower incidence of CAT in the study population than in Westerners. The KS component regarding the site of cancer showed a good association with CAT development but needed some improvement.

Conclusion

The KS was partially validated to predict CAT in Korean cancer patients undergoing modern chemotherapy. Modifying the BMI cutoff, adding other risk variables, and refining the use of cancer-site data for CAT risk prediction may improve the performance of the KS for CAT prediction in East Asian patients.
Characteristics of rapid cycling in 1261 bipolar disorder patients
Authors: Miola Alessandro , Tondo Leonardo , Pinna Marco , Contu Martina , Baldessarini Ross J.
Published: June 2023

Background

Rapid-cycling (RC; ≥ 4 episodes/year) in bipolar disorder (BD) has been recognized since the 1970s and associated with inferior treatment response. However, associations of single years of RC with overall cycling rate, long-term morbidity, and diagnostic subtypes are not clear.

Results

We compared descriptive and clinical characteristics in 1261 BD patients with/without RC, based on history and prospective follow-up for several years. RC in any previous year was identified in 9.36% of BD subjects (3.74% in BD1, 15.2% BD2), and somewhat more among women than men. RC-BD subjects had 3.21-fold greater average prospective annual rates of recurrence but not hospitalizations, had less difference in %-time-ill, received more mood-stabilizing treatments, and had greater suicidal risk, lacked familial psychiatric illnesses, had more cyclothymic temperament, were more likely to be married, had more siblings and children, experienced early sexual abuse, but were less likely to abuse drugs (not alcohol) or smoke. In multivariable regression modeling, older age, mood-switching with antidepressants, and BD2 > BD1 diagnosis, as well as more episodes/year were independently associated with RC. Notably, prospective mean recurrence rates were below 4/year in 79.5% of previously RC patients, and below 2/year in 48.1%.

Conclusions

Lifetime risk of RC in BD was 9.36%, more likely in women, with older age, and in BD2 > BD1. With RC, recurrence rates were much higher, especially for depression with less effect on %-time ill, suggesting shorter episodes. Variable associations with unfavorable outcomes and prospective recurrence rates well below 4/year in most previously RC patients indicate that RC was not a sustained characteristic and probably was associated with use of antidepressants.