bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of animated stories to improve music education practices of trainee primary school teachers in Spain
Authors: Esteve-Faubel José María , Botella-Quirant María Teresa , Esteve-Faubel Rosa Pilar
Published: July 2023

This article analyses an interdisciplinary educational experience combining music, ICT, language and art to create an animated story with active listening as a means of improving knowledge of music education practices. The method consisted of a qualitative, exploratory and descriptive study, with a semi-structured open-ended interview and analysis of the corresponding portfolio by both students and teachers with the aim of encouraging systematic reflection on practices and optimising teaching-learning in the nature of action research. The research population consisted of 104 students of the Bachelor’s Degree in Teaching of the Faculty of Education of the University of Alicante (Spain). The results indicated an improvement in music education practices relating to active listening following the pedagogical intervention, leading to the conclusion that inclusion of ICT in music education facilitates real and effective insertion and enhances students’ autonomy in the process of acquisition of musical skills.
Using Travel Diaries to Examine the Extent to Which Older Adult Centres Are a Focal Point for Recreation and Social Activities
Authors: Sheppard Christine L. , Myers Anita M. , Hesjedahl Sue
Published: July 2023

This study aimed to better understand the extent to which older adult centres are a focal point for recreation and social activities for their members. Travel diaries completed by 261 members of 12 older adult centres across Ontario provided comprehensive and real-time (24-hour) data over two consecutive weeks concerning time away from home, trip purposes, and modes of travel. The data showed that nearly one-third of their trips included a stop at their older adult centre. Three-quarters also went to other community venues over the study period, possibly to access amenities (e.g., pools) not available at their centre. Notwithstanding, their local older adult centre was still a focal point in out-of-home travel, particularly for potentially more vulnerable older adults, including those who were non-drivers, had less education, and felt lonelier. The diaries also substantiated the importance of time spent socializing with peers and staff at the centre, apart from formal program participation.
Law, Courts, and Constitutions in Twentieth-Century South Asia
Authors: Saxena Saumya , McClure Alastair
Published: July 2023

This special issue brings together scholars from multiple disciplines and with varied research and geographic expertise to study the historical role played by the law in governing the political, social, and cultural life of twentieth-century South Asia. These articles have not emerged in a vacuum, but rather build on an exciting turn in South Asian history that is placing new focus on the legal and constitutional work that accompanied the post-colonial moment. This introduction examines some of the important historiographical and methodological interventions made by scholars working in this field, before outlining the specific themes connecting the articles in this issue.
Preventing child welfare reinvolvement: The efficacy of the Reminiscing and Emotion Training intervention
Authors: Edler Katherine , Behrens Brigid , Jacques Karen P. , Valentino Kristin
Published: July 2023

Child maltreatment is a pathogenic relational experience that creates risk for physical and psychological health difficulties throughout the lifespan. The Reminiscing and Emotion Training intervention (RET) was developed to support maltreated children’s healthy development by improving parenting behavior among maltreating mothers. Here, we evaluated whether RET was associated with reductions in child welfare reinvolvement over the course of two years. The sample included 165 maltreating and 83 nonmaltreating mothers and their 3- to 6-year-old children who were enrolled in a longitudinal randomized controlled trial of RET. Maltreating mother–child dyads were randomly assigned to receive RET or an active control condition (community standard [CS]). Nonmaltreating dyads were a separate control group (nonmaltreating control). Comparing CS and RET dyads, there was a significant effect of RET on frequency of child welfare reinvolvement (substantiations and unsubstantiated assessments) during the two years following dyads’ enrollment in the intervention, t(163) = 2.02, p < .05, Cohen’s d = 0.32. There was a significant indirect effect of RET on child welfare reinvolvement through maternal sensitive guidance during reminiscing [95% CI −0.093, −0.007]. Results provide support for the efficacy of RET in preventing child welfare reinvolvement.
Effects of abstract versus concrete rumination about anger on affect
Authors: Heinzel Carlotta V. , Moulds Michelle , Kollárik Martin , Lieb Roselind , Wahl Karina
Published: July 2023

Background:

The processing-mode theory of rumination proposes that an abstract mode of rumination results in more maladaptive consequences than a concrete ruminative mode. It is supported by evidence mostly from the area of depression and little is known of the relative consequences of abstract versus concrete rumination for anger.

Aims:

We investigated the differential effects of abstract versus concrete rumination about anger on individuals’ current affect. We hypothesized that abstract rumination would increase current anger and negative affect, and decrease positive affect, to a greater extent than concrete rumination.

Method:

In a within-subject design, 120 participants were instructed to focus on a past social event that resulted in intense anger and then to ruminate about the event in both an abstract and a concrete mode, in a randomly assigned order. Current anger, negative and positive affect were assessed before and after each rumination phase.

Results:

Anger and negative affect increased and positive affect decreased from pre- to post-rumination. Contrary to expectations, these patterns were observed irrespective of the ruminative mode induced.

Conclusions:

This initial study does not support the hypothesis that abstract and concrete rumination about anger have different consequences for current affect. Replications and more extensive designs are needed.
Structural reality and architectural editing: the four invisible columns of the Sydney Opera House
Authors: Tombesi Paolo , Stracchi Paolo , Cardellicchio Luciano
Published: July 2023

In modern architectural debate, buildings are made by their description in the literature as much as they are defined by the reality of their construction. On this point, a relatively small glitch in the celebratory narrative of the roof of the Sydney Opera House – four columns that do not appear in the descriptions of the building – offers the opportunity to reflect on the generation of architecture’s canons and perhaps the perceived need to elevate the subject matter by abstracting the engineering of its construction. While questioning the reasons for the absence of the columns from the biographies of the building, the article articulates the value of embracing even the smaller details in projects' histories.
How healthy and affordable are foods and beverages sold in school canteens? A cross-sectional study comparing menus from Victorian primary schools
Authors: Hill Amy , Blake Miranda , Alston Laura Veronica , Nichols Melanie S , Bell Colin , Fraser Penny , Le Ha ND , Strugnell Claudia , Allender Steven , Bolton Kristy A
Published: July 2023

Objective:

Government policy guidance in Victoria, Australia, encourages schools to provide affordable, healthy foods in canteens. This study analysed the healthiness and price of items available in canteens in Victorian primary schools and associations with school characteristics.

Design:

Dietitians classified menu items (main, snack and beverage) using the red, amber and green traffic light system defined in the Victorian government’s School Canteens and Other School Food Services Policy. This system also included a black category for confectionary and high sugar content soft drinks which should not be supplied. Descriptive statistics and regressions were used to analyse differences in the healthiness and price of main meals, snacks and beverages offered, according to school remoteness, sector (government and Catholic/independent) size, and socio-economic position.

Setting:

State of Victoria, Australia

Participants:

A convenience sample of canteen menus drawn from three previous obesity prevention studies in forty-eight primary schools between 2016 and 2019.

Results:

On average, school canteen menus were 21 % ‘green’ (most healthy – everyday), 53 % ‘amber’ (select carefully), 25 % ‘red’ (occasional) and 2 % ‘black’ (banned) items, demonstrating low adherence with government guidelines. ‘Black’ items were more common in schools in regional population centres. ‘Red’ main meal items were cheaper than ‘green’% (mean difference –$0·48 (95 % CI –0·85, –0·10)) and ‘amber’ –$0·91 (–1·27, –0·57)) main meal items. In about 50 % of schools, the mean price of ‘red’ main meal, beverages and snack items were cheaper than ‘green’ items, or no ‘green’ alternative items were offered.

Conclusion:

In this sample of Victorian canteen menus, there was no evidence of associations of healthiness and pricing by school characteristics except for regional centres having the highest proportion of ‘black’ (banned) items compared with all other remoteness categories examined. There was low adherence with state canteen menu guidelines. Many schools offered a high proportion of ‘red’ food options and ‘black’ (banned) options, particularly in regional centres. Unhealthier options were cheaper than healthy options. More needs to be done to bring Victorian primary school canteen menus in line with guidelines.
Observation of ~100% valley-coherent excitons in monolayer MoS2 through giant enhancement of valley coherence time
Authors: Gupta Garima , Watanabe Kenji , Taniguchi Takashi , Majumdar Kausik
Published: July 2023

In monolayer transition metal dichalcogenide semiconductors, valley coherence degrades rapidly due to a combination of fast scattering and inter-valley exchange interaction. This leads to a sub-picosecond valley coherence time, making coherent manipulation of exciton a highly challenging task. Using monolayer MoS2 sandwiched between top and bottom graphene, here we demonstrate fully valley-coherent excitons by observing ~100% degree of linear polarization in steady state photoluminescence. This is achieved in this unique design through a combined effect of (a) suppression in exchange interaction due to enhanced dielectric screening, (b) reduction in exciton lifetime due to a fast inter-layer transfer to graphene, and (c) operating in the motional narrowing regime. We disentangle the role of the key parameters affecting valley coherence by using a combination of calculation (solutions of Bethe-Salpeter and Maialle-Silva-Sham equations) and a careful choice of design of experiments using four different stacks with systematic variation of screening and exciton lifetime. To the best of our knowledge, this is the first report in which the excitons are found to be valley coherent in the entire lifetime in monolayer semiconductors, allowing optical readout of valley coherence possible.
Anatomical and molecular characterization of parvalbumin-cholecystokinin co-expressing inhibitory interneurons: implications for neuropsychiatric conditions
Authors: Grieco Steven F. , Johnston Kevin G. , Gao Pan , Garduño B. Maximiliano , Tang Bryan , Yi Elsie , Sun Yanjun , Horwitz Gregory D. , Yu Zhaoxia , Holmes Todd C. , Xu Xiangmin
Published: July 2023

Inhibitory interneurons are crucial to brain function and their dysfunction is implicated in neuropsychiatric conditions. Emerging evidence indicates that cholecystokinin (CCK)-expressing interneurons (CCK+) are highly heterogenous. We find that a large subset of parvalbumin-expressing (PV+) interneurons express CCK strongly; between 40 and 56% of PV+ interneurons in mouse hippocampal CA1 express CCK. Primate interneurons also exhibit substantial PV/CCK co-expression. Mouse PV+/CCK+ and PV+/CCK- cells show distinguishable electrophysiological and molecular characteristics. Analysis of single nuclei RNA-seq and ATAC-seq data shows that PV+/CCK+ cells are a subset of PV+ cells, not of synuclein gamma positive (SNCG+) cells, and that they strongly express oxidative phosphorylation (OXPHOS) genes. We find that mitochondrial complex I and IV-associated OXPHOS gene expression is strongly correlated with CCK expression in PV+ interneurons at both the transcriptomic and protein levels. Both PV+ interneurons and dysregulation of OXPHOS processes are implicated in neuropsychiatric conditions, including autism spectrum (ASD) disorder and schizophrenia (SCZ). Analysis of human brain samples from patients with these conditions shows alterations in OXPHOS gene expression. Together these data reveal important molecular characteristics of PV-CCK co-expressing interneurons and support their implication in neuropsychiatric conditions.
Is 1:1000 adrenaline as a topical haemostat an effective alternative to control bleeding in dentistry and oral surgery?
Authors: Aslam Raj D. , Liew Jonathan , Besi Eleni
Published: July 2023

Minor oral surgery can give rise to bleeding intra- and post-operatively. This can be minimal in most patients; however, it can be more problematic in patients with impaired clotting disorders, liver disease, or taking any form of anticoagulation therapy. Haemostatic agents are available to overcome such bleeding risks. The topical application of 1:1000 adrenaline used in medicine can be considered for use in dentistry. Adrenaline is widely used within medicine, surgery and dentistry. Examples include its use in local anaesthetic agents, in the management of anaphylaxis and as part of the cardiopulmonary resuscitation algorithm. 1:1000 adrenaline used topically for ear, nose and throat surgeries has shown improved visual fields during surgery with better surgical outcomes. It is relatively safe, but in patients with cardiovascular comorbidities, it should be practised with caution. This has precipitated the idea for its use within oral surgical procedures, including canine exposures, third molar surgery, root displacement into the antrum and periapical surgery. The haemostatic effect of 1:1000 adrenaline as an alternative should be considered in operative dentistry and oral surgery to aid in haemostasis and improve intra-operative visualisation, reducing the risk of iatrogenic damage and bleeding, thereby improving treatment outcomes.
The underestimated impact of excess body weight on colorectal cancer risk: Evidence from the UK Biobank cohort
Authors: Safizadeh Fatemeh , Mandic Marko , Pulte Dianne , Niedermaier Tobias , Hoffmeister Michael , Brenner Hermann
Published: July 2023

Background

The association between excess weight and colorectal cancer (CRC) risk may have been underestimated due to potential weight loss during pre-clinical sojourn time of CRC. We aimed to investigate this association and the corresponding population attributable fraction (PAF), accounting for prediagnostic weight loss.

Methods

Data from the UK Biobank prospective cohort were used. Multivariable adjusted hazard ratios (HR) and their 95% confidence intervals (CI) for various periods of follow-up and the corresponding PAF of excess weight were calculated.

Results

During a median of 10.0 years of follow-up, of 453,049 participants, 4794 developed CRC. The excess weight–CRC association became substantially stronger with including increasing lengths of follow-up in the analyses and further excluding the initial years of follow-up. HRs (95% CIs) for overweight and obesity were 1.06 (0.97–1.16) and 1.14 (1.03–1.26) after 7 years of follow-up, 1.13 (1.05–1.21) and 1.23 (1.14–1.33) when including complete follow-up length, and 1.26 (1.12–1.43) and 1.42 (1.24–1.63) when excluding the initial 7 years of follow-up. The corresponding PAFs of excess weight were estimated as 6.8%, 11.3%, and 19.0%, respectively.

Conclusions

Comprehensive consideration of the potential effect of prediagnostic weight loss discloses a much stronger impact of excess body weight on CRC risk than previously assumed.
Transglutaminase 2 is associated with adverse colorectal cancer survival and represents a therapeutic target
Authors: Malkomes Patrizia , Lunger Ilaria , Oppermann Elsie , Lorenz Johannes , Faqar-Uz-Zaman Sara Fatima , Han Jiaoyan , Bothur Sabrina , Ziegler Paul , Bankov Katrin , Wild Peter , Bechstein Wolf Otto , Rieger Michael A.
Published: July 2023

Molecular markers for predicting prognosis of colorectal cancer (CRC) patients are urgently needed for effective disease management. We reported previously that the multifunctional enzyme Transglutaminase 2 (TGM2) is essential for CRC cell survival by inactivation of the tumor suppressor p53. Based on these data, we determined the clinical relevance of TGM2 expression and explored its potential as prognostic marker and therapeutic target in CRC. We profiled TGM2 protein expression in tumor samples of 279 clinically characterized CRC patients using immunohistochemical staining. TGM2 expression was upregulated in matched tumor samples in comparison to normal tissue. A strong TGM2 expression was associated with advanced tumor stages and predicted worse prognosis regarding progression-free and overall-survival, even at early stages. Inhibition of TGM2 in CRC cell lines by the inhibitors LDN27219 and Tyrphostin resulted in a strong reduction of cancer cell proliferation and tumorsphere formation in vitro by induction of p53-mediated apoptosis. Primary patient-derived tumorsphere formation was significantly reduced by inhibition of TGM2. Treatment of mice with TGM2 inhibitors exhibited a significant deceleration of tumor progression. Our data indicate that high TGM2 expression in CRC is associated with worse prognosis and may serve as a therapeutic target in CRC patients with strong TGM2 expression.
Aberrant Akt2 signaling in the RPE may contribute to retinal fibrosis process in diabetic retinopathy
Authors: Daley Rachel , Maddipatla Vishnu , Ghosh Sayan , Chowdhury Olivia , Hose Stacey , Zigler J. Samuel , Sinha Debasish , Liu Haitao
Published: July 2023

Diabetic Retinopathy (DR) is a complication of diabetes that causes blindness in adults. Retinal fibrosis is closely associated with developing proliferative diabetic retinopathy (PDR). Clinical studies have shown that fibrotic membranes exhibit uncontrolled growth in PDR and contribute to retinal detachment from RPE cells, ultimately leading to vision loss. While anti-VEGF agents and invasive laser treatments are the primary treatments for PDR, retinal fibrosis has received minimal attention as a potential target for therapeutic intervention. Therefore, to investigate the potential role of Akt2 in the diabetes-induced retinal fibrosis process, we generated RPE-specific Akt2 conditional knockout (cKO) mice and induced diabetes in these mice and Akt2fl/fl control mice by intraperitoneal injection of streptozotocin. After an 8-month duration of diabetes (10 months of age), the mice were euthanized and expression of tight junction proteins, epithelial–mesenchymal transition (EMT), and fibrosis markers were examined in the RPE. Diabetes induction in the floxed control mice decreased levels of the RPE tight junction protein ZO-1 and adherens junction proteins occludin and E-cadherin; these decreases were rescued in Akt2 cKO diabetic mice. Loss of Akt2 also inhibited diabetes-induced elevation of RNA and protein levels of the EMT markers Snail/Slug and Twist1 in the RPE as compared to Akt2fl/fl diabetic mice. We also found that in Akt2 cKO mice diabetes-induced increase of fibrosis markers, including collagen IV, Connective tissue growth factor (CTGF), fibronectin, and alpha-SMA was attenuated. Furthermore, we observed that high glucose-induced alterations in EMT and fibrosis markers in wild-type (WT) RPE explants were rescued in the presence of PI3K and ERK inhibitors, indicating diabetes-induced retinal fibrosis may be mediated via the PI3K/Akt2/ERK signaling, which could provide a novel target for DR therapy.
EMQN: Recommendations for genetic testing in inherited cardiomyopathies and arrhythmias
Authors: Hayesmoore Jesse B. , Bhuiyan Zahurul A. , Coviello Domenico A. , du Sart Desirée , Edwards Matthew , Iascone Maria , Morris-Rosendahl Deborah J. , Sheils Katie , van Slegtenhorst Marjon , Thomson Kate L.
Published: July 2023

Inherited cardiomyopathies and arrhythmias (ICAs) are a prevalent and clinically heterogeneous group of genetic disorders that are associated with increased risk of sudden cardiac death and heart failure. Making a genetic diagnosis can inform the management of patients and their at-risk relatives and, as such, molecular genetic testing is now considered an integral component of the clinical care pathway. However, ICAs are characterised by high genetic and allelic heterogeneity, incomplete / age-related penetrance, and variable expressivity. Therefore, despite our improved understanding of the genetic basis of these conditions, and significant technological advances over the past two decades, identifying and recognising the causative genotype remains challenging. As clinical genetic testing for ICAs becomes more widely available, it is increasingly important for clinical laboratories to consolidate existing knowledge and experience to inform and improve future practice. These recommendations have been compiled to help clinical laboratories navigate the challenges of ICAs and thereby facilitate best practice and consistency in genetic test provision for this group of disorders. General recommendations on internal and external quality control, referral, analysis, result interpretation, and reporting are described. Also included are appendices that provide specific information pertinent to genetic testing for hypertrophic, dilated, and arrhythmogenic right ventricular cardiomyopathies, long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia.
Full-field stimulus threshold testing: a scoping review of current practice
Authors: Shi Linda F. , Hall Amanda J. , Thompson Dorothy A.
Published: July 2023

The full-field stimulus threshold (FST) is a psychophysical measure of whole-field retinal light sensitivity. It can assess residual visual function in patients with severe retinal disease and is increasingly being adopted as an endpoint in clinical trials. FST applications in routine ophthalmology clinics are also growing, but as yet there is no formalised standard guidance for measuring FST. This scoping review explored current variability in FST conduct and reporting, with an aim to inform further evidence synthesis and consensus guidance. A comprehensive electronic search and review of the literature was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews (PRISMA-ScR) checklist. Key source, participant, methodology and outcomes data from 85 included sources were qualitatively and quantitatively compared and summarised. Data from 85 sources highlight how the variability and insufficient reporting of FST methodology, including parameters such as units of flash luminance, colour, duration, test strategy and dark adaptation, can hinder comparison and interpretation of clinical significance across centres. The review also highlights an unmet need for paediatric-specific considerations for test optimisation. Further evidence synthesis, empirical research or structured panel consultation may be required to establish coherent standardised guidance on FST methodology and context or condition dependent modifications. Consistent reporting of core elements, most crucially the flash luminance equivalence to 0 dB reference level is a first step. The development of criteria for quality assurance, calibration and age-appropriate reference data generation may further strengthen rigour of measurement.
RAGE inhibitor TTP488 (Azeliragon) suppresses metastasis in triple-negative breast cancer
Authors: Magna Melinda , Hwang Gyong Ha , McIntosh Alec , Drews-Elger Katherine , Takabatake Masaru , Ikeda Adam , Mera Barbara J. , Kwak Taekyoung , Miller Philip , Lippman Marc E. , Hudson Barry I.
Published: July 2023

Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic cancer subtype, which is generally untreatable once it metastasizes. We hypothesized that interfering with the Receptor for Advanced Glycation End-products (RAGE) signaling with the small molecule RAGE inhibitors (TTP488/Azeliragon and FPS-ZM1) would impair TNBC metastasis and impair fundamental mechanisms underlying tumor progression and metastasis. Both TTP488 and FPS-ZM1 impaired spontaneous and experimental metastasis of TNBC models, with TTP488 reducing metastasis to a greater degree than FPS-ZM1. Transcriptomic analysis of primary xenograft tumor and metastatic tissue revealed high concordance in gene and protein changes with both drugs, with TTP488 showing greater potency against metastatic driver pathways. Phenotypic validation of transcriptomic analysis by functional cell assays revealed that RAGE inhibition impaired TNBC cell adhesion to multiple extracellular matrix proteins (including collagens, laminins, and fibronectin), migration, and invasion. Neither RAGE inhibitor impaired cellular viability, proliferation, or cell cycle in vitro. Proteomic analysis of serum from tumor-bearing mice revealed RAGE inhibition affected metastatic driver mechanisms, including multiple cytokines and growth factors. Further mechanistic studies by phospho-proteomic analysis of tumors revealed RAGE inhibition led to decreased signaling through critical BC metastatic driver mechanisms, including Pyk2, STAT3, and Akt. These results show that TTP488 impairs metastasis of TNBC and further clarifies the signaling and cellular mechanisms through which RAGE mediates metastasis. Importantly, as TTP488 displays a favorable safety profile in human studies, our study provides the rationale for evaluating TTP488 in clinical trials to treat or prevent metastatic TNBC.
Cortex-wide topography of 1/f-exponent in Parkinson’s disease
Authors: Helson Pascal , Lundqvist Daniel , Svenningsson Per , Vinding Mikkel C. , Kumar Arvind
Published: July 2023

Parkinson’s disease (PD) is a progressive and debilitating brain disorder. Besides the characteristic movement-related symptoms, the disease also causes decline in sensory and cognitive processing. The extent of symptoms and brain-wide projections of neuromodulators such as dopamine suggest that many brain regions are simultaneously affected in PD. To characterise brain-wide disease-related changes in neuronal function, we analysed resting state magnetoencephalogram (MEG) from two groups: PD patients and healthy controls. Besides standard spectral analysis, we quantified the aperiodic components (κ, λ) of the neural activity by fitting a power law κ/fλ – f is the frequency, κ and λ are the fitting parameters—to the MEG power spectrum and studied its relationship with age and Unified Parkinson’s Disease Rating Scale (UPDRS). Consistent with previous results, the most significant spectral changes were observed in the high theta/low-alpha band (7–10 Hz) in all brain regions. Furthermore, analysis of the aperiodic part of the spectrum showed that in all but frontal regions λ was significantly larger in PD patients than in control subjects. Our results indicate that PD is associated with significant changes in aperiodic activity across the whole neocortex. Surprisingly, even early sensory areas showed a significantly larger λ in patients than in healthy controls. Moreover, λ was not affected by the Levodopa medication. Finally, λ was positively correlated with patient age but not with UPDRS-III. Because λ is closely associated with excitation-inhibition balance, our results propose new hypotheses about neural correlates of PD in cortical networks.
Profound structural conservation of chemically cross-linked HIV-1 envelope glycoprotein experimental vaccine antigens
Authors: Martin Gregory M. , Russell Rebecca A. , Mundsperger Philip , Harris Scarlett , Jovanoska Lu , Trajano Luiza Farache , Schiffner Torben , Fabian Katalin , Tolazzi Monica , Scarlatti Gabriella , McFarlane Leon , Cheeseman Hannah , Aldon Yoann , Schermer Edith E. , Breemen Marielle , Sliepen Kwinten , Katinger Dietmar , Kunert Renate , Sanders Rogier W. , Shattock Robin , Ward Andrew B. , Sattentau Quentin J.
Published: July 2023

Chemical cross-linking is used to stabilize protein structures with additional benefits of pathogen and toxin inactivation for vaccine use, but its use has been restricted by the potential for local or global structural distortion. This is of particular importance when the protein in question requires a high degree of structural conservation for inducing a biological outcome such as the elicitation of antibodies to conformationally sensitive epitopes. The HIV-1 envelope glycoprotein (Env) trimer is metastable and shifts between different conformational states, complicating its use as a vaccine antigen. Here we have used the hetero-bifunctional zero-length reagent 1-Ethyl-3-(3-Dimethylaminopropyl)-Carbodiimide (EDC) to cross-link two soluble Env trimers, selected well-folded trimer species using antibody affinity, and transferred this process to good manufacturing practice (GMP) for experimental medicine use. Cross-linking enhanced trimer stability to biophysical and enzyme attack. Cryo-EM analysis revealed that cross-linking retained the overall structure with root-mean-square deviations (RMSDs) between unmodified and cross-linked Env trimers of 0.4–0.5 Å. Despite this negligible distortion of global trimer structure, we identified individual inter-subunit, intra-subunit, and intra-protomer cross-links. Antigenicity and immunogenicity of the trimers were selectively modified by cross-linking, with cross-linked ConS retaining bnAb binding more consistently than ConM. Thus, the EDC cross-linking process improves trimer stability whilst maintaining protein folding, and is readily transferred to GMP, consistent with the more general use of this approach in protein-based vaccine design.
A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts
Authors: Chen J. , Neil J. A. , Tan J. P. , Rudraraju R. , Mohenska M. , Sun Y. B. Y. , Walters E. , Bediaga N. G. , Sun G. , Zhou Y. , Li Y. , Drew D. , Pymm P. , Tham W. H. , Wang Y. , Rossello F. J. , Nie G. , Liu X. , Subbarao K. , Polo J. M.
Published: July 2023

SARS-CoV-2 infection causes COVID-19. Several clinical reports have linked COVID-19 during pregnancy to negative birth outcomes and placentitis. However, the pathophysiological mechanisms underpinning SARS-CoV-2 infection during placentation and early pregnancy are not clear. Here, to shed light on this, we used induced trophoblast stem cells to generate an in vitro early placenta infection model. We identified that syncytiotrophoblasts could be infected through angiotensin-converting enzyme 2 (ACE2). Using a co-culture model of vertical transmission, we confirmed the ability of the virus to infect syncytiotrophoblasts through a previous endometrial cell infection. We further demonstrated transcriptional changes in infected syncytiotrophoblasts that led to impairment of cellular processes, reduced secretion of HCG hormone and morphological changes vital for syncytiotrophoblast function. Furthermore, different antibody strategies and antiviral drugs restore these impairments. In summary, we have established a scalable and tractable platform to study early placental cell types and highlighted its use in studying strategies to protect the placenta.
The benefits and struggles of FAIR data: the case of reusing plant phenotyping data
Authors: Papoutsoglou Evangelia A. , Athanasiadis Ioannis N. , Visser Richard G. F. , Finkers Richard
Published: July 2023

Plant phenotyping experiments are conducted under a variety of experimental parameters and settings for diverse purposes. The data they produce is heterogeneous, complicated, often poorly documented and, as a result, difficult to reuse. Meeting societal needs (nutrition, crop adaptation and stability) requires more efficient methods toward data integration and reuse. In this work, we examine what “making data FAIR” entails, and investigate the benefits and the struggles not only of reusing FAIR data, but also making data FAIR using genotype by environment and QTL by environment interactions for developmental traits in potato as a case study. We assume the role of a scientist discovering a phenotypic dataset on a FAIR data point, verifying the existence of related datasets with environmental data, acquiring both and integrating them. We report and discuss the challenges and the potential for reusability and reproducibility of FAIRifying existing datasets, using metadata standards such as MIAPPE, that were encountered in this process.
Chromosome-level genome assembly of the sea cucumber Apostichopus japonicus
Authors: Sun Lina , Jiang Chunxi , Su Fang , Cui Wei , Yang Hongsheng
Published: July 2023

Sea cucumber is a morphologically diverse and ecologically important clade of echinoderms. The sea cucumber Apostichopus japonicus is the most economically valuable species of sea cucumber. The initial assembly of the A. japonicus genome was released in 2017. However, this genome assembly is fragmented and lacks relative position information of genes on chromosomes. In this study, we produced a high-quality chromosome-level genome of A. japonicus using Pacbio HiFi long-reads and Hi-C sequencing data. The assembled A. japonicus genome spanned 671.60 Mb with a contig N50 size of 17.20 Mb and scaffold N50 size of 29.65 Mb. A total of 99.9% of the assembly was anchored to 23 chromosomes. In total, 19,828 genes were annotated, and 97.2% of BUSCO genes were fully represented. This high-quality genome of A. japonicus will not only aid in the development of sustainable aquaculture practices, but also lay a foundation for a deeper understanding of their genetic makeup, evolutionary history, and ecological adaptation.
Individual-level precision diagnosis for coronavirus disease 2019 related severe outcome: an early study in New York
Authors: Huang Chaorui C. , Xu Hong
Published: July 2023

Because of inadequate information provided by the on-going population level risk analyses for Coronavirus disease 2019 (COVID-19), this study aimed to evaluate the risk factors and develop an individual-level precision diagnostic method for COVID-19 related severe outcome in New York State (NYS) to facilitate early intervention and predict resource needs for patients with COVID-19. We analyzed COVID-19 related hospital encounter and hospitalization in NYS using Statewide Planning and Research Cooperative System hospital discharge dataset. Logistic regression was performed to evaluate the risk factors for COVID-19 related mortality. We proposed an individual-level precision diagnostic method by taking into consideration of the different weights and interactions of multiple risk factors. Age was the greatest risk factor for COVID-19 related fatal outcome. By adding other demographic variables, dyspnea or hypoxemia and multiple chronic co-morbid conditions, the model predictive accuracy was improved to 0.85 (95% CI 0.84–0.85). We selected cut-off points for predictors and provided a general recommendation to categorize the levels of risk for COVID-19 related fatal outcome, which can facilitate the individual-level diagnosis and treatment, as well as medical resource prediction. We further provided a use case of our method to evaluate the feasibility of public health policy for monoclonal antibody therapy.
Extremely large Lamb shift in a deep-strongly coupled circuit QED system with a multimode resonator
Authors: Ao Ziqiao , Ashhab Sahel , Yoshihara Fumiki , Fuse Tomoko , Kakuyanagi Kosuke , Saito Shiro , Aoki Takao , Semba Kouichi
Published: July 2023

We report experimental and theoretical results on the extremely large Lamb shift in a multimode circuit quantum electrodynamics (QED) system in the deep-strong coupling (DSC) regime, where the qubit-resonator coupling strength is comparable to or larger than the qubit and resonator frequencies. The system comprises a superconducting flux qubit (FQ) and a quarter-wavelength coplanar waveguide resonator ($$\lambda /4$$

λ
/
4

CPWR) that are coupled inductively through a shared edge that contains a Josephson junction to achieve the DSC regime. Spectroscopy is performed around the frequency of the fundamental mode of the CPWR, and the spectrum is fitted by the single-mode quantum Rabi Hamiltonian to obtain the system parameters. Since the qubit is also coupled to a large number of higher modes in the resonator, the single-mode fitting does not provide the bare qubit energy but a value that incorporates the renormalization from all the other modes. We derive theoretical formulas for the Lamb shift in the multimode resonator system. As shown in previous studies, there is a cut-off frequency $$\omega _{\textrm{cutoff}}$$

ω
cutoff

for the coupling between the FQ and the modes in the CPWR, where the coupling grows as $$\sqrt{\omega _n}$$

ω
n

for $$\omega _n/\omega _{\textrm{cutoff}}\ll 1$$

ω
n

/

ω
cutoff

≪
1

and decreases as $$1/\sqrt{\omega _n}$$

1
/

ω
n

for $$\omega _n/\omega _{\textrm{cutoff}}\gg 1$$

ω
n

/

ω
cutoff

≫
1

. Here $$\omega _n$$

ω
n

is the frequency of the nth mode. The cut-off effect occurs because the qubit acts as an obstacle for the current in the resonator, which suppresses the current of the modes above $$\omega _{\textrm{cutoff}}$$

ω
cutoff

at the location of the qubit and results in a reduced coupling strength. Using our observed spectrum and theoretical formulas, we estimate that the Lamb shift from the fundamental mode is 82.3% and the total Lamb shift from all the modes is 96.5%. This result illustrates that the coupling to the large number of modes in a CPWR yields an extremely large Lamb shift but does not suppress the qubit energy to zero, which would happen in the absence of a high-frequency cut-off.
Comparative hydrodynamic and nanoscale imaging study on the interactions of teicoplanin-A2 and bovine submaxillary mucin as a model ocular mucin
Authors: Chun Taewoo , Pattem Jacob , Gillis Richard B. , Dinu Vlad T. , Yakubov Gleb E. , Corfield Anthony P. , Harding Stephen E.
Published: July 2023

Glycopeptide antibiotics are regularly used in ophthalmology to treat infections of Gram-positive bacteria. Aggregative interactions of antibiotics with mucins however can lead to long exposure and increases the risk of resistant species. This study focuses on the evaluation of potential interactions of the last line of defence glycopeptide antibiotic teicoplanin with an ocular mucin model using precision matrix free hydrodynamic and microscopic techniques: sedimentation velocity in the analytical ultracentrifuge (SV-AUC), dynamic light scattering (DLS) and atomic force microscopy (AFM). For the mixtures of teicoplanin at higher doses (1.25 mg/mL and 12.5 mg/mL), it was shown to interact and aggregate with bovine submaxillary mucin (BSM) in the distributions of both sedimentation coefficients by SV-AUC and hydrodynamic radii by DLS. The presence of aggregates was confirmed by AFM for higher concentrations. We suggest that teicoplanin eye drop formulations should be delivered at concentrations of < 1.25 mg/mL to avoid potentially harmful aggregations.
Region of interest (ROI) selection using vision transformer for automatic analysis using whole slide images
Authors: Hossain Md Shakhawat , Shahriar Galib Muhammad , Syeed M. M. Mahbubul , Uddin Mohammad Faisal , Hasan Mahady , Shivam Shingla , Advani Suresh
Published: July 2023

Selecting regions of interest (ROI) is a common step in medical image analysis across all imaging modalities. An ROI is a subset of an image appropriate for the intended analysis and identified manually by experts. In modern pathology, the analysis involves processing multidimensional and high resolution whole slide image (WSI) tiles automatically with an overwhelming quantity of structural and functional information. Despite recent improvements in computing capacity, analyzing such a plethora of data is challenging but vital to accurate analysis. Automatic ROI detection can significantly reduce the number of pixels to be processed, speed the analysis, improve accuracy and reduce dependency on pathologists. In this paper, we present an ROI detection method for WSI and demonstrated it for human epidermal growth factor receptor 2 (HER2) grading for breast cancer patients. Existing HER2 grading relies on manual ROI selection, which is tedious, time-consuming and suffers from inter-observer and intra-observer variability. This study found that the HER2 grade changes with ROI selection. We proposed an ROI detection method using Vision Transformer and investigated the role of image magnification for ROI detection. This method yielded an accuracy of 99% using 20 × WSI and 97% using 10 × WSI for the ROI detection. In the demonstration, the proposed method increased the diagnostic agreement to 99.3% with the clinical scores and reduced the time to 15 seconds for automated HER2 grading.
Comparing machine learning algorithms to predict COVID‑19 mortality using a dataset including chest computed tomography severity score data
Authors: Zakariaee Seyed Salman , Naderi Negar , Ebrahimi Mahdi , Kazemi-Arpanahi Hadi
Published: July 2023

Since the beginning of the COVID-19 pandemic, new and non-invasive digital technologies such as artificial intelligence (AI) had been introduced for mortality prediction of COVID-19 patients. The prognostic performances of the machine learning (ML)-based models for predicting clinical outcomes of COVID-19 patients had been mainly evaluated using demographics, risk factors, clinical manifestations, and laboratory results. There is a lack of information about the prognostic role of imaging manifestations in combination with demographics, clinical manifestations, and laboratory predictors. The purpose of the present study is to develop an efficient ML prognostic model based on a more comprehensive dataset including chest CT severity score (CT-SS). Fifty-five primary features in six main classes were retrospectively reviewed for 6854 suspected cases. The independence test of Chi-square was used to determine the most important features in the mortality prediction of COVID-19 patients. The most relevant predictors were used to train and test ML algorithms. The predictive models were developed using eight ML algorithms including the J48 decision tree (J48), support vector machine (SVM), multi-layer perceptron (MLP), k-nearest neighbourhood (k-NN), Naïve Bayes (NB), logistic regression (LR), random forest (RF), and eXtreme gradient boosting (XGBoost). The performances of the predictive models were evaluated using accuracy, precision, sensitivity, specificity, and area under the ROC curve (AUC) metrics. After applying the exclusion criteria, a total of 815 positive RT-PCR patients were the final sample size, where 54.85% of the patients were male and the mean age of the study population was 57.22 ± 16.76 years. The RF algorithm with an accuracy of 97.2%, the sensitivity of 100%, a precision of 94.8%, specificity of 94.5%, F1-score of 97.3%, and AUC of 99.9% had the best performance. Other ML algorithms with AUC ranging from 81.2 to 93.9% had also good prediction performances in predicting COVID-19 mortality. Results showed that timely and accurate risk stratification of COVID-19 patients could be performed using ML-based predictive models fed by routine data. The proposed algorithm with the more comprehensive dataset including CT-SS could efficiently predict the mortality of COVID-19 patients. This could lead to promptly targeting high-risk patients on admission, the optimal use of hospital resources, and an increased probability of survival of patients.
A longitudinal transcriptomic analysis from unfed to post-engorgement midguts of adult female Ixodes scapularis
Authors: Lu Stephen , Martins Larissa A. , Kotál Jan , Ribeiro José M. C. , Tirloni Lucas
Published: July 2023

The hematophagy behavior has evolved independently several times within the Arthropoda phylum. Interestingly, the process of acquiring a blood meal in ticks is considerably distinct from that observed in other blood-feeding arthropods. Instead of taking seconds to minutes to complete a blood meal, an adult female Ixodes scapularis tick can remain attached to its host for numerous days. During this extended feeding period, the tick undergoes drastic morphological changes. It is well established that the tick midgut plays a pivotal role not only in blood meal digestion but also in pathogen acquisition and transmission. However, our understanding of the underlying molecular mechanisms involved in these events remains limited. To expedite tick research, we conducted a comprehensive longitudinal RNA-sequencing of the tick midgut before, during, and after feeding. By collecting ticks in different feeding stages (unfed, slow feeding, rapid feeding, and early post-detached), we obtained a comprehensive overview of the transcripts present in each stage and the dynamic transcriptional changes that occur between them. This provides valuable insights into tick physiology. Additionally, through unsupervised clustering, we identified transcripts with similar patterns and stage-specific sequences. These findings serve as a foundation for selecting targets in the development of anti-tick control strategies and facilitate a better understanding of how blood feeding and pathogen infection impact tick physiology.
Pre-ceramic polymer-assisted nucleation and growth of copper sulfide nanoplates
Authors: Loughney Patricia A. , Martin Kara L. , Cuillier Paul , Trigg Edward B. , Posey Nicholas D. , Dickerson Matthew B. , Pruyn Timothy L. , Doan-Nguyen Vicky
Published: July 2023

Polymer-derived ceramics derived from pre-ceramic polymers (PCPs), have access to several form factors and are highly tunable systems. Tunability can be further expanded with the incorporation of functional nanoparticle fillers throughout the matrix for advanced nanocomposite polymer-derived ceramic development. However, capping ligands used in nanoparticle syntheses mix unfavorably with PCPs, giving aggregated filler material and diminished properties. To control dispersion, secondary nanoparticle processing is performed by adhering PCP-miscible caps to the surface after synthesis. This often sacrifices size control established for small nanoparticles (<10 nm). Herein, we successfully eliminate the need for extra nanoparticle processing through the development of a one-pot, copper sulfide synthesis in which a PCP assists the stable formation of nanoparticles and serves as the final graft molecule. We monitor the success of this methodology and the PCP’s role in the reaction through several characterization methods probing both the nanoparticle core and polymer graft.
Engineering a gold nanoparticles-carbon dots nanocomposite with pH-flexibility for monitoring hydrogen peroxide released from living cells
Authors: Xu Hongmei , Guo Lili , Duan Weijiang , Liu Yang , Shuang Shaomin , Dong Chuan
Published: July 2023

The Au-CDs nanocomposite with efficient photo-oxidation activity at neutral pH was constructed for the colorimetric assessment of H2O2.
Sensitive detection of synthetic cannabinoids in human blood using magnetic polydopamine molecularly imprinted polymer nanocomposites
Authors: Li Jiajia , Wang Yong , Liu Anran , Liu Songqin
Published: July 2023

A method for the sensitive HPLC-MS detection of various synthetic cannabinoids in human blood has been developed based on magnetic ferric oxide and polydopamine MIP nanocomposites.
Three dimensional cyclic trinuclear units based metal–covalent organic frameworks for electrochemical CO2RR
Authors: Liu Zhenli , Yan Shichen , Fang Qianrong , Wang Yaobing , Yuan Daqiang
Published: July 2023

The construction of 3D-CTU-MCOF and its application in electrochemical CO2RR.
Photodissociation dynamics and UV absorption spectrum of acetone oxide (CH3)2COO
Authors: Nikoobakht Behnam , Köppel Horst
Published: July 2023

The photodynamics and B1A′ ← X1A′ absorption spectrum of acetone oxide, (CH3)2COO, are studied theoretically from first principles.