bluuebunny/crossref_metadata_2025 huggingface dataset:
PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune liver disease
Authors: Kocheise Lorenz , Piseddu Ignazio , Vonderlin Joscha , Tjwa Eric T , Buescher Gustav , Meunier Lucy , Goeggelmann Pia , Fianchi Francesca , Dumortier Jérôme , Riveiro-Barciela Mar , Gevers Tom JG , Beretta-Piccoli Benedetta Terziroli , Londoño Maria-Carlota , Frankova Sona , Roesner Thomas , Joerg Vincent , Schmidt Constantin , Glaser Fabian , Sutter Jan P , Fründt Thorben W , Lohse Ansgar W , Huber Samuel , von Felden Johann , Sebode Marcial , Schulze Kornelius
Published: July 2023

Background

Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many malignancies in recent years. However, immune-related adverse events (irAE) are a frequent concern in clinical practice. The safety profile of ICI for the treatment of malignancies in patients diagnosed with autoimmune liver disease (AILD) remains unclear. Due to this uncertainty, these patients were excluded from ICI clinical trials and ICI are withheld from this patient group. In this retrospective multicenter study, we assessed the safety of ICI in patients with AILD.

Methods

We contacted tertiary referral hospitals for the identification of AILD patients under ICI treatment in Europe via the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Fourteen centers contributed data on AILD patients with malignancies being treated with ICI, another three centers did not treat these patients with ICI due to fear of irAEs.

Results

In this study, 22 AILD patients under ICI treatment could be identified. Among these patients, 12 had primary biliary cholangitis (PBC), five had primary sclerosing cholangitis (PSC), four had autoimmune hepatitis (AIH), and one patient had an AIH-PSC variant syndrome. Eleven patients had hepatobiliary cancers and the other 11 patients presented with non-hepatic tumors. The applied ICIs were atezolizumab (n=7), durvalumab (n=5), pembrolizumab (n=4), nivolumab (n=4), spartalizumab (n=1), and in one case combined immunotherapy with nivolumab plus ipilimumab. Among eight patients who presented with grade 1 or 2 irAEs, three demonstrated liver irAEs. Cases with grades ≥ 3 irAEs were not reported. No significant changes in liver tests were observed during the first year after the start of ICI.

Conclusions

This European multicenter study demonstrates that PD-1/PD-L1 inhibitors appear to be safe in patients with AILD. Further studies on the safety of more potent dual immune checkpoint therapy are needed. We conclude that immunotherapy should not categorically be withheld from patients with AILD.
Predicting prenatal depression and assessing model bias using machine learning models
Authors: Huang Yongchao , Alvernaz Suzanne , Kim Sage J. , Maki Pauline , Dai Yang , Peñalver Bernabé Beatriz
Published: July 2023

Perinatal depression (PND) is one of the most common medical complications during pregnancy and postpartum period, affecting 10-20% of pregnant individuals. Black and Latina women have higher rates of PND, yet they are less likely to be diagnosed and receive treatment. Machine learning (ML) models based on Electronic Medical Records (EMRs) have been effective in predicting postpartum depression in middle-class White women but have rarely included sufficient proportions of racial and ethnic minorities, which contributed to biases in ML models for minority women. Our goal is to determine whether ML models could serve to predict depression in early pregnancy in racial/ethnic minority women by leveraging EMR data. We extracted EMRs from a hospital in a large urban city that mostly served low-income Black and Hispanic women (N=5,875) in the U.S. Depressive symptom severity was assessed from a self-reported questionnaire, PHQ-9. We investigated multiple ML classifiers, used Shapley Additive Explanations (SHAP) for model interpretation, and determined model prediction bias with two metrics, Disparate Impact, and Equal Opportunity Difference. While ML model (Elastic Net) performance was low (ROCAUC=0.67), we identified well-known factors associated with PND, such as unplanned pregnancy and being single, as well as underexplored factors, such as self-report pain levels, lower levels of prenatal vitamin supplement intake, asthma, carrying a male fetus, and lower platelet levels blood. Our findings showed that despite being based on a sample mostly composed of 75% low-income minority women (54% Black and 27% Latina), the model performance was lower for these communities. In conclusion, ML models based on EMRs could moderately predict depression in early pregnancy, but their performance is biased against low-income minority women.
Plasma α-synuclein domain profiles across α-synucleinopathies
Authors: Pons Marie-Laure , Mohaupt Pablo , Vialaret Jérôme , Mondesert Etienne , Vignon Margaux , Coppens Salomé , Stéphane Moreau , Lehmann Sylvain , Hirtz Christophe
Published: July 2023

Background

The differential diagnosis of α-synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), is challenging due to overlapping clinical features and the current lack of reliable biomarkers. The primary diagnostic approach remains clinical, underscoring the need for objective biomarkers that can distinguish between these diseases. This study profiles α-synuclein peptides in plasma to explore potential disease-specific patterns.

Methods

We developed a targeted mass spectrometry-based assay to profile α-synuclein in plasma samples from PD (n=82), DLB (n=32), MSA (n=8), and controls (n=21). The assay quantifies non-modified peptides specifically derived from the N-terminus and NAC domain, regions implicated in aggregate formation, to assess potential disease-specific peptide patterns.

Results

No significant differences in peptide levels were observed between the disease groups, indicating consistent N-terminus and NAC domain profiles among α-synucleinopathies. However, a peptide within the NAC domain showed distinct patterns in MSA compared to other groups, which may reflect unique pathological processes.

Conclusions

This study provides the first blood-based assessment of α-synuclein peptide profiles, establishing a basis for future research into α-synucleinopathies. Refining the assay to include post-translationally modified peptides may enhance understanding of disease mechanisms and improve biomarker development.
Learning a deep language model for microbiomes: the power of large scale unlabeled microbiome data
Authors: Pope Quintin , Varma Rohan , Tataru Chritine , David Maude , Fern Xiaoli
Published: July 2023

We use open source human gut microbiome data to learn a microbial “language” model by adapting techniques from Natural Language Processing (NLP). Our microbial “language” model is trained in a self-supervised fashion (i.e., without additional external labels) to capture the interactions among different microbial taxa and the common compositional patterns in microbial communities. The learned model produces contextualized taxa representations that allow a single microbial taxon to be represented differently according to the specific microbial environment it appears in. The model further provides a sample representation by collectively interpreting different microbial taxa in the sample and their interactions as a whole. We show that, compared to baseline representations, our sample representation consistently leads to improved performance for multiple prediction tasks including predicting Irritable Bowel Disease (IBD) and diet patterns. Coupled with a simple ensemble strategy, it produces a highly robust IBD prediction model that generalizes well to microbiome data independently collected from different populations with substantial distribution shift.

We visualize the contextualized taxa representations and find that they exhibit meaningful phylum-level structure, despite never exposing the model to such a signal. Finally, we apply an interpretation method to highlight microbial taxa that are particularly influential in driving our model’s predictions for IBD.

Author summary

Human microbiomes and their interactions with various body systems have been linked to a wide range of diseases and lifestyle variables. To understand these links, citizen science projects such as the American Gut Project (AGP) have provided large open-source datasets for microbiome investigation. In this work we leverage such open-source data and learn a “language” model for human gut microbiomes using techniques derived from natural language processing. We train the “language” model to capture the interactions among different microbial taxa and the common compositional patterns that shape gut microbiome communities. By considering the entirety of taxa within a sample and their interactions, our model produces a representation that enables contextualized interpretation of individual microbial taxa within their microbial environment. We demonstrate that our sample representation enhances prediction performance compared to baseline methods across multiple microbiome tasks including prediction of Irritable Bowel Disease (IBD) and diet patterns. Furthermore, our learned representation yields a robust IBD prediction model that generalizes well to independent data collected from different populations. To gain insight into our model’s workings, we present interpretation results that showcase its ability to learn biologically meaningful representations.
Identification of anti-pathogenic activity amongin silicopredicted small molecule inhibitors ofPseudomonas aeruginosaLasR or Nitric Oxide Reductase (NOR)
Authors: Gajera Gemini , Henriksen Niel , Cox Bryan , Kothari Vijay
Published: July 2023

Antibiotic resistantPseudomonas aeruginosastrains cause considerable morbidity and mortality. Identification of novel targets in this notorious pathogen is urgently warranted to facilitate discovery of new anti-pathogenic agents acting against it. Attacking non-essential targets is believed to be a potential anti-virulence strategy. This study attempted to identify small molecule inhibitors of two important proteins LasR and nitric oxide reductase (NOR) inP. aeruginosa. This bacterial pathogen possesses multiple quorum sensing (QS) systems to regulate expression of many of its genes including those associated with virulence. Among these QS systems, ‘Las’ system can be said to be the ‘master’ regulator, whose receptor protein is LasR. Similarly, NOR plays crucial role in detoxification of reactive nitrogen species. This study attemptedin silicoidentification of potential LasR or NOR inhibitors through a virtual screen employing AtomNet®, a proprietary deep learning neural network. Following virtual screening of a large number of compounds for their affinity to LasR or NOR, a final subset of <100 compounds was created by clustering and filtering the top scoring compounds. These compounds were evaluated for theirin vivoanti-pathogenic activity by challenging the model hostCaenorhabditis eleganswithP. aeruginosain presence or absence of test compounds. Survival of the worm population in 24-well assay plates was monitored over a period of 5 days microscopically. Of the 96 predicted LasR inhibitors, 11 exhibited anti-Pseudomonasactivity (23-96% inhibition of bacterial virulence as per third-day end point) at 25-50 µg/ml. Of the 85 predicted NOR inhibitors, 8 exhibited anti-Pseudomonasactivity (40-85% inhibition of bacterial virulence as per second-day end point) at 25-50 µg/ml. Further investigation on molecular mode of action of active compounds is warranted.
Voltage tunes mGlu5 receptor function, impacting synaptic transmission
Authors: Boutonnet Marin , Carpena Camille , Bouquier Nathalie , Chastagnier Yan , Font-Ingles Joan , Moutin Enora , Tricoire Ludovic , Chemin Jean , Perroy Julie
Published: July 2023

Voltage sensitivity is a common feature of many membrane proteins, including some G-protein coupled receptors (GPCRs). However, the functional consequences of voltage sensitivity in GPCRs are not well understood.

In this study, we investigated the voltage sensitivity of the post-synaptic metabotropic glutamate receptor mGlu5 and its impact on synaptic transmission. Using biosensors and electrophysiological recordings in non-excitable HEK293T cells or neurons, we found that mGlu5 receptor function is optimal at resting membrane potentials. We observed that membrane depolarization significantly reduced mGlu5 receptor activation, Gq-PLC/PKC stimulation, Ca2+release, and mGlu5 receptor-gated currents through TRPC6 channels or NMDA receptors. Notably, we report a previously unknown activity of the NMDA receptor at the resting potential of neurons, enabled by mGlu5.

Our findings suggest that mGlu5 receptor activity is directly regulated by membrane voltage which may have a significant impact on synaptic processes and pathophysiological functions.
In vivomarker of brainstem myelin is associated to quantitative sleep parameters in healthy young men
Authors: Talwar Puneet , Deantoni Michele , Van Egroo Maxime , Muto Vincenzo , Chylinski Daphne , Koshmanova Ekaterina , Jaspar Mathieu , Meyer Christelle , Degueldre Christian , Berthomier Christian , Luxen André , Salmon Eric , Collette Fabienne , Dijk D.-J. , Schmidt Christina , Phillips Christophe , Maquet Pierre , Sherif Siya , Vandewalle Gilles
Published: July 2023

Brain structural integrity has been suggested to contribute to the variability in human sleep quality and composition. The associations between sleep parameters and the regional integrity of subcortical structures implicated in sleep-wake regulation remain, however, largely unexplored. The present study aimed at assessing association between quantitative Magnetic Resonance Imaging (qMRI)-derived marker of the myelin content of the brainstem with the variability in the sleep electrophysiology in a large sample of healthy young men (N=321;∼22y). Generalized Additive Model for Location, Scale and Shape (GAMLSS) was used to seek associations between sleep metrics and Magnetisation Transfer saturation (MTsat) qMRI values, proxy for myelin content. Separate GAMLSS revealed that sleep onset latency and slow wave sleep intensity were significantly associated with MTsat-derived myelin estimates in the brainstem (pcorrected≤.03), with overall higher MTsat value associated with values reflecting better sleep quality. The association changed with age, however (MTsat-by-age interaction - pcorrected≤.03), with higher MTsat value linked to better values in the two sleep metrics in the individuals of our sample aged ∼18 to 20y. Similar associations were detected across different parts of the brainstem (pcorrected≤.03), suggesting that the overall maturation and integrity of the brainstem was associated with both sleep metrics. Our results suggest that myelination of the many reticular nuclei of the brainstem essential to regulation of sleep is associated with inter-individual differences in sleep characteristics during early adulthood. They may have implications for sleep disorders or neurological diseases related to myelin.
Phase separation of ecDNA aggregates establishesin-transcontact domains boosting selectiveMYCregulatory interactions
Authors: Conte Mattia , Matteuzzi Tommaso , Esposito Andrea , Chiariello Andrea M. , Bianco Simona , Vercellone Francesca , Nicodemi Mario
Published: July 2023

Extrachromosomal DNAs (ecDNAs) are found in the nucleus of an array of human cancer cells where they can form clusters that were associated to oncogene overexpression, as they carry genes andcis-regulatory elements. Yet, the mechanisms of aggregation and gene amplification beyond copy-number effects remain mostly unclear. Here, we investigate, at the single molecule level,MYC-harboring ecDNAs of COLO320-DM colorectal cancer cells by use of a minimal polymer model of the interactions of ecDNA BRD4 binding sites and BRD4 molecules. We find that BRD4 induces ecDNAs phase separation, resulting in the self-assembly of clusters whose predicted structure is validated against HiChIP data (Hung et al., 2021). Clusters establishin-transassociated contact domains (I-TADs) enriched, beyond copy number, in regulatory contacts among specific ecDNA regions, encompassing itsPVT1-MYCfusions but not its other canonicalMYCcopy. That explains why the fusions originate most of ecDNAMYCtranscripts (Hung et al., 2021), and shows that ecDNA clusteringper seis important but not sufficient to amplify oncogene expression beyond copy-number, reconciling opposite views on the role of clusters (Hung et al., 2021; Zhu et al., 2021; Purshouse et al. 2022). Regulatory contacts become strongly enriched as soon as half a dozen ecDNAs aggregate, then saturate because of steric hindrance, highlighting that even cells with few ecDNAs can experience pathogenicMYCupregulations. To help drug design and therapeutic applications, with the model we dissect the effects of JQ1, a BET inhibitor. We find that JQ1 reverses ecDNA phase separation hence abolishing I-TADs and extra regulatory contacts, explaining how in COLO320-DM cells it reducesMYCtranscription (Hung et al., 2021).
Three-step docking by WIPI2, ATG16L1 and ATG3 delivers LC3 to the phagophore
Authors: Rao Shanlin , Strong Lisa M. , Ren Xuefeng , Skulsuppaisarn Marvin , Lazarou Michael , Hurley James H. , Hummer Gerhard
Published: July 2023

The covalent attachment of ubiquitin-like LC3 proteins prepares the autophagic membrane for cargo recruitment. We resolve key steps in LC3 lipidation by combining molecular dynamics simulations and experimentsin vitroandin cellulo. We show how the E3-like ligase ATG12– ATG5-ATG16L1 in complex with the E2-like conjugase ATG3 docks LC3 onto the membrane in three steps by (1) the PI(3)P effector protein WIPI2, (2) helix α2 of ATG16L1, and (3) a membrane-interacting surface of ATG3. Phosphatidylethanolamine (PE) lipids concentrate in a region around the thioester bond between ATG3 and LC3, highlighting residues with a possible role in the catalytic transfer of LC3 to PE, including two conserved histidines. In a near-complete pathway from the initial membrane recruitment to the LC3 lipidation reaction, the three-step targeting of the ATG12–ATG5-ATG16L1 machinery establishes a high level of regulatory control.
Non-cell autonomous cardiomyocyte regulation complicates gene supplementation therapy forLMNAcardiomyopathy
Authors: Sun Yueshen , Guo Congting , Chen Zhan , Lin Junsen , Yang Luzi , Zhang Yueyang , Wu Chenyang , Zhao Dongyu , Jardin Blake , Pu William T. , Zhao Mingming , Dong Erdan , Hu Xiaomin , Zhang Shuyang , Guo Yuxuan
Published: July 2023

Aims

Recombinant adeno-associated viruses (rAAVs) are federally approved gene delivery vectors for in vivo gene supplementation therapy. Loss-of-function truncating variants ofLMNA, the coding gene for Lamin-A/C, are one of the primary causes of inherited dilate cardiomyopathy (DCM). Here we aim to study whether AAV-basedLMNAsupplementation could treatLMNAdeficiency-triggered cardiac defects.

Methods and Results

We compared whole-body, cardiomyocyte-specific and genetic-mosaic mouse models that carryLmnatruncating variants at the same genetic loci and uncovered primarily a non-cell autonomous impact ofLmnaon cardiomyocyte maturation. Whole-body lamin-A supplementation by rAAVs moderately rescued the cardiac defects inLmnagermline mutants. By contrast, cardiomyocyte-specific lamin-A addback failed to restore the cardiomyocyte growth defects. A Cre-loxP-based AAV vector that expresses lamin-A throughout the body but excluding the heart was able to restore cardiomyocyte growth inLmnagermline mutants.

Conclusions

Lmnaregulates cardiomyocyte growth non-cell autonomously. Non-myocytes are the key cell targets for a successful gene therapy forLMNA-associated cardiac defects.

Translational perspective

LMNAtruncating mutations are among the major causes of inherited DCM. AAV gene supplementation therapy is emerging as a promising strategy to treat genetic cardiomyopathy, but whether this strategy is suitable forLMNAcardiomyopathy remained unclear. Our study counterintuitively showed that the cardiomyocytes are not necessarily the correct therapeutic cell targets for AAV-based treatment ofLMNAcardiomyopathy. By contrast, careful elucidation of cell-autonomous versus non-cell-autonomous gene functions is essential for the proper design of a gene supplementation therapy for cardiomyopathy.

Graphical Abstract
Stress analysis of aluminium die-cast parts including the STL-data of pores
Authors: Gabbert Ulrich , Ringwelski Stefan , Würkner Mathias , Kittsteiner Mario
Published: July 2023

Purpose

Pores and shrink holes are unavoidable defects in the die-casting mass production process which may significantly influence the strength, fatigue and fracture behaviour as well as the life span of structures, especially if they are subjected to high static and dynamic loads. Such defects should be considered during the design process or after production, where the defects could be detected with the help of computed tomography (CT) measurements. However, this is usually not done in today's mass production environments. This paper deals with the stress analysis of die-cast structural parts with pores found from CT measurements or that are artificially placed within a structure.

Design/methodology/approach

In this paper the authors illustrate two general methodologies to take into account the porosity of die-cast components in the stress analysis. The detailed geometry of a die-cast part including all discontinuities such as pores and shrink holes can be included via STL data provided by CT measurements. The first approach is a combination of the finite element method (FEM) and the finite cell method (FCM), which extends the FEM if the real geometry cuts finite elements. The FCM is only applied in regions with pores. This procedure has the advantage that all simulations with different pore distributions, real or artificial, can be calculated without changing the base finite element mesh. The second approach includes the pore information as STL data into the original CAD model and creates a new adapted finite element mesh for the simulation. Both methods are compared and evaluated for an industrial problem.

Findings

The STL data of defects which the authors received from CT measurements could not be directly applied without repairing them. Therefore, for FEM applications an appropriate repair procedure is proposed. The first approach, which combines the FEM with the FCM, the authors have realized within the commercial software tool Abaqus. This combination performs well, which is demonstrated for test examples, and is also applied for a complex industrial project. The developed in-house code still has some limitations which restrict broader application in industry. The second pure FEM-based approach works well without limitations but requires increasing computational effort if many different pore distributions are to be investigated.

Originality/value

A new simulation approach which combines the FEM with the FCM has been developed and implemented into the commercial Abaqus FEM software. This approach the authors have applied to simulate a real engineering die-cast structure with pores. This approach could become a preferred way to consider pores in practical applications, where the porosity can be derived either from CT measurements or are artificially adopted for design purposes. The authors have also shown how pores can be considered in the standard FEM analysis as well.
Dynamic association between phonemic awareness and disordered speech recognition moderated by transcription training
Authors: Chen Yu‐Ju , Yeh Lili
Published: July 2023

Background

Phonetic transcription of disordered speech samples is especially crucial for the assessment and treatment of functional or organic speech‐sound disorders. Previous studies show that students who struggle with the identification and segmentation of speech sounds are more likely to encounter difficulties with clinical phonetic transcription.

Aims

To clarify the connection between phonemic awareness and phonetic transcription in Mandarin‐speaking undergraduate students, as well as the improvement of these skills after phonetic transcription training.

Methods & Procedures

A pretest–post‐test design was adopted for this study. The experimental group (n = 38) consisted of students majoring in audiology and speech–language pathology who were given 12 weeks of transcription training. The control group (n = 33) consisted of audiology and speech–language pathology majors who completed the same module a year earlier without undergoing the transcription training. Two instruments were used to assess their skills: (1) the Phonemic Awareness Skill Test (PA test) and (2) the Phonetic Transcription Skill Test (PT test) designed for the purposes of the present study.

Outcomes & Results

Performance on most subtests of the PT and PA tests improved significantly at post‐test for the experiment group, although only PT training was provided. After phonetic transcription training, the relationship between phonemic addition abilities and phonetic transcription strengthened. Phonemic identification was found to be a predictor of undergraduate students’ PT skills of disordered speech samples.

Conclusions & Implications

Results from this study provide insights into the role of phonetic transcription training in improving phonemic awareness and phonetic transcription skills.

What This Paper Adds

What is already known on the subject

Phonetic transcription of disordered speech samples is especially crucial for the assessment and treatment of functional or organic speech‐sound disorders. Phonemic awareness is not only an essential ability for reading alphabetic language but also associated with acquiring phonetic transcription skills.

What this paper adds to existing knowledge

A dynamically changing association between phonemic transcription and phonetic transcription during transcription training was reported. Phonetic transcription training of disordered speech samples acted as a driving force for deeper relationships between the two skills.

What are the potential or actual clinical implications of this work?

Training phonetic recognition and transcription equips future and practising speech–language pathologists with better skills in managing speech‐sound disorders. Implications for phonemic awareness training also have the potential to extend to the literacy skills of alphabetic language speakers.
Intravenous immunoglobulin and rituximab in a treatment‐refractory COVID‐19‐associated central nervous system vasculitis: A case report and literature review
Authors: Mutlu Onur Anil , İriş Merve , Erener Nursena , Kizilkiliç Osman , Işlak Civan , Seyahi Emire , Saip Sabahattin , Uygunoğlu Uğur
Published: July 2023

Central nervous system (CNS) vasculitis is an uncommon inflammatory disease that affects the brain and spinal cord. It might present with headache, focal neurological deficits, seizures and encephalopathy. CNS vasculitis might be triggered by systemic vasculitides, connective tissue diseases, malignancies and infectious agents, including severe acute respiratory syndrome coronavirus 2. Diagnosis requires a combination of clinical presentation, serological and cerebral spinal fluid analysis, radiological findings (magnetic resonance imaging and conventional angiography), and brain biopsy. In the lack of randomized prospective studies, the treatment approach is based on retrospective cohort studies, anecdotal reports and therapeutic approaches derived from other vasculitides. In this report, we present a case of a 55‐year‐old man who presented with hemiparesthesia 39 days after coronavirus disease 2019 (COVID‐19) infection. During the disease course, the patient developed right‐sided hemiparesis and was referred to our center. Conventional angiogram suggested CNS vasculitis. After an extensive work‐up, systemic vasculitis was excluded. Despite having been treated with pulse steroid and cyclophosphamide, the patient experienced relapses. As we administered intravenous immunoglobulin and rituximab, remission was achieved both in clinical and radiological aspects. In this study, we present the first case of treatment‐refractory CNS vasculitis associated with COVID‐19, which was treated successfully with intravenous immunoglobulin and rituximab. Second, we report a review of COVID‐19‐related CNS vasculitis articles and applied treatment strategies published in English. To elucidate the mechanism of COVID‐19‐related CNS vasculitis, further research is needed.
Ephemeral promises of happiness: Coming out in the Australian accounting profession into the late 2010s
Authors: Egan Matthew , Voss Barbara de Lima
Published: July 2023

This interview‐based study explores how shifting promises of happiness impact on LGBTIQ+ individuals within the workplace. Our study situates within the “Big 4” Australian professional service firms at a time of significant political change, centered around the legislating of marriage equality in 2017. Together with statements of support issued by each of these firms, these moves offered an increasing sense that secure promises of happiness were now offered to “out” LGBTIQ+ staff. A shifting of hetero‐cis normativities was suggested, offering some sense of greater safety, visibility, connection, and acceptance within these workplaces. However, these promises of happiness remained precarious and did little for issues that mattered most (including promotion), particularly individuals of intersectionality, including ethnically diverse and female individuals.
Polynomial ergodicity of an SIRS epidemic model with density‐dependent demographics
Authors: Lan Guijie , Yuan Sanling
Published: July 2023

In this paper, a stochastic susceptible‐infective‐recovered‐susceptible (SIRS) model with density‐dependent demographics is proposed to study the dynamics of transmission of infectious diseases under stochastic environmental fluctuations. We demonstrate that the position of the basic reproduction number with respect to 1 is the threshold between extinction and persistence of the disease under mild extra conditions. That is, under mild extra conditions, when , the disease is eradicated with probability 1; when , the disease is persistent almost surely and the Markov process has a unique stationary distribution and is polynomial ergodic. As an application, we use the 2017 influenza A data from Western Asia to estimate the parameter values of the model and based on that investigate the effect of random noises on the dynamics of the model. Our study reveals that the basic reproduction number is negatively correlated with the noise intensity for the infected but positively correlated with that for the susceptible population, which are different from the findings obtained in the existing literature.
The COPII subunit CsSEC23 mediates fruit glossiness in cucumber
Authors: Gao Luyao , Cao Jiajian , Gong Siyu , Hao Ning , Du Yalin , Wang Chunhua , Wu Tao
Published: July 2023

To improve our understanding of the mechanism underlying cucumber glossiness regulation, a novel cucumber mutant with a glossy peel (Csgp) was identified. MutMap, genotyping, and gene editing results demonstrated that CsSEC23, which is the core component of COPII vesicles, mediates the glossiness of cucumber fruit peel. CsSEC23 is functionally conserved and located in the Golgi and endoplasmic reticulum. CsSEC23 could interact with CsSEC31, but this interaction was absent in the Csgp mutant, which decreased the efficiency of COPII vesicle transportation. Genes related to wax and cutin transport were upregulated in the Csgp mutant, and the cuticle structure of the Csgp‐mutant peel became thinner. Moreover, the wax and cutin contents were also changed due to CsSEC23 mutation. Taken together, the results obtained from this study revealed that CsSEC23 mediates cucumber glossiness, and this mediating might be affected by COPII vesicle transportation.
Development of a Questionnaire to Assess Self-Esteem in the Teaching Profession
Authors: Yamasaki Katsuyuki , Uchida Kanako
Published: July 2023

Schoolteachers in Japan frequently suffer from mental health problems, resulting in a high rate of leaves of absence from work. Considering the poor condition of Japanese teachers, this study aimed to develop a questionnaire to assess self-esteem in the teaching profession for students in teacher training courses at university. As self-esteem is generally associated with health and adaptation, improving teachers’ working conditions and enhancing their self-esteem are expected. First, we created an original version of the questionnaire taking into consideration the content validity. Thereafter, a web-based survey was conducted among registered participants of a survey company in Japan. The final sample for analysis consisted of 422 participants (176 males and 246 females). The results showed factorial validity through exploratory and confirmatory factor analyses, along with internal consistency and an undistorted distribution of scores for the normal distribution. Thus, the “Self-Esteem Questionnaire in the Teaching Profession (SEQ-TP)” that includes twelve items with the score range of 12 to 84 was completed for future study. Finally, the limitations of this study are discussed, along with possibilities for future research.
Cross‐talk between zinc and calcium regulates ion transport: A role for the zinc receptor, ZnR/GPR39
Authors: Hershfinkel Michal
Published: July 2023

Zinc is essential for many physiological functions, with a major role in digestive system, skin health, and learning and memory. On the cellular level, zinc is involved in cell proliferation and cell death. A selective zinc sensing receptor, ZnR/GPR39 is a Gq‐coupled receptor that acts via the inositol trisphosphate pathway to release intracellular Ca2+. The ZnR/GPR39 serves as a mediator between extracellular changes in Zn2+ concentration and cellular Ca2+ signalling. This signalling pathway regulates ion transporters activity and thereby controls the formation of transepithelial gradients or neuronal membrane potential, which play a fundamental role in the physiological function of these tissues. This review focuses on the role of Ca2+ signalling, and specifically ZnR/GPR39, with respect to the regulation of the Na+/H+ exchanger, NHE1, and of the K+/Cl− cotransporters, KCC1‐3, and also describes the physiological implications of this regulation.

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Intestinal microRNAs and bacterial taxa in juvenile mice are associated, modifiable by allochthonous lactobacilli, and affect postnatal maturation
Authors: Taibi Amel , Tokar Tomas , Tremblay Julien , Gargari Giorgio , Streutker Catherine J. , Li Bo , Pierro Agostino , Guglielmetti Simone , Tompkins Thomas A. , Jurisica Igor , Comelli Elena M.
Published: July 2023

The interplay between the intestinal microbiota and host is critical to intestinal ontogeny and homeostasis. MicroRNAs (miRNAs) may be an underlying link. Intestinal miRNAs are microbiota-dependent and, when shed in the lumen, affect resident microorganisms. Yet, longitudinal relationships between intestinal tissue miRNAs, luminal miRNAs, and luminal microorganisms have not been elucidated, especially in early life. Here, we investigated the postnatal cecal miRNA and microbiota populations, their relationship, and their impact on intestinal maturation in specific pathogen-free mice; we also assessed if they can be modified by intervention with allochthonous probiotic lactobacilli. We report that cecal and cecal content miRNA and microbiota signatures are temporally regulated, correlated, and modifiable by probiotics with implications for intestinal maturation. These findings help understand causal relationships within the gut ecosystem and provide a basis for preventing and managing their alterations in diseases throughout life.

IMPORTANCE

The gut microbiota affects intestinal microRNA (miRNA) signatures and is modified by host-derived luminal miRNA. This suggests the existence of close miRNA-microbiota relationships that are critical to intestinal homeostasis. However, an integrative analysis of these relationships and their evolution during intestinal postnatal maturation is lacking. We provide a system-level longitudinal analysis of miRNA-microbiota networks in the intestine of mice at the weaning transition, including tissue and luminal miRNA and luminal microbiota. To address causality and move toward translational applications, we used allochthonous probiotic lactobacilli to modify these longitudinal relationships and showed that they are critical for intestinal maturation in early life. These findings contribute to understand mechanisms that underlie the maturation of the intestinal ecosystem and suggest that interventions aiming at maintaining, or restoring, homeostasis cannot prescind from considering relationships among its components.
Comprehensive imaging in patients with suspected pulmonary arterial hypertension
Authors: Crisan Simina , Baghina Ruxandra-Maria , Luca Silvia Ana , Cozlac Alina-Ramona , Negru Alina-Gabriela , Vacarescu Cristina , Lazar Mihai-Andrei , Luca Constantin-Tudor , Gaita Dan
Published: July 2023

Currently, several imaging techniques are being used for a comprehensive evaluation of patients with suspected pulmonary hypertension (PH), in order to provide information that may clarify the presence and identify the aetiology of this complex pathology. The current paper is focused on recent updates regarding the importance of comprehensive imaging techniques for patients with suspected PH. Transthoracic echocardiography that can mainly detect right ventricle pressure overload and dysfunction is the cornerstone of imaging evaluation, while right heart catheterisation remains the gold standard assessment method. Chest radiography that may exclude pleuroparenchymal lung diseases, CT, the primary imaging modality for the assessment of lung parenchyma and CT pulmonary angiography, that allows for the non-invasive assessment of the pulmonary arteries, are equally important. Imaging techniques like dual-energy CT, single photon emission CT and ventilation perfusion scan may provide accurate diagnostic information for patients with chronic thromboembolic PH. Cardiac MRI provides the most accurate three-dimensional characterisation of the right ventricle. Accurate use of diagnostic imaging algorithms allows early detection of the disease, with the constant goal of improved PH patients prognosis.
On strict-double-bound graphs and Cartesian products of paths and cycles
Authors: Egawa Yoshimi , Ogawa Kenjiro , Ozeki Kenta , Tagusari Satoshi , Tsuchiya Morimasa
Published: July 2023

For a poset [Formula: see text] the strict-double-bound graph ([Formula: see text]) of [Formula: see text] is the graph with the vertex set [Formula: see text] such that [Formula: see text] if and only if [Formula: see text] and there exist [Formula: see text] and [Formula: see text] distinct from [Formula: see text] and [Formula: see text] such that [Formula: see text] and [Formula: see text] For a connected graph [Formula: see text], the strict-double-bound number [Formula: see text] is defined as [Formula: see text] there exists a poset [Formula: see text] such that sDB([Formula: see text]) [Formula: see text], where [Formula: see text] is the graph with [Formula: see text] vertices and no edges. In this paper we deal with the strict-double-bound numbers of Cartesian products of graphs. We show that [Formula: see text] for [Formula: see text], [Formula: see text] for [Formula: see text], and [Formula: see text] for [Formula: see text].
Evolutionary Algorithm with Graph Neural Network Driven Cyberbullying Detection on Low Resource Asian Languages
Authors: Rasool Hussein Ali , Aldolaimy Firas , Hasan Forat Falih , Alsalamy Ali H. , Saleem Munqith , Alkhayyat Ahmed Hussein , Sharma Moolchand
Published: July 2023

ICT is widely adopted by Asian youth and is utilized by people of all ages across the continent. Despite its many advantages, unethical ICT usage can lead to many complications. A harmful application of ICT for social communication and engagement is cyberbullying. Simply adhering to the generally accepted norms and guidelines for cybersecurity will not protect you from cybercrime. Even well-known social media stages like Twitter are safe from this attack. Natural language processing (NLP) research on cyberbullying detection has become popular recently. Even though old-style NLP procedures have become highly cyberbullying, there are still hurdles to overcome. These include the limited character count allowed by social media platforms, an imbalance among comments, ambiguity, and unnecessary use of slang. Models based on (CNNs), Multilayer Perceptrons (MLPs), and (RNNs), have recently shown encouraging results in a variety of NLP tasks. With this motivation, this research develops an African vulture optimization algorithm with a graph neural network-based cyberbullying detection and classification (AVOAGNN-CBDC) model. The proposed AVOAGNN-CBDC technique mainly intends to detect and classify cyberbullying. The AVOAGNN-CBDC technique undergoes data preprocessing in different stages and a FastText-based word embedding process to achieve this. Besides, the AVOAGNN-CBDC technique employs the GNN model for cyberbullying detection and classification. Finally, the AVOA is used for the optimal parameter selection of the GNN model, which helps achieve improved classification performance. The experimental result investigation of the AVOAGNN-CBDC technique is tested on the cyberbullying dataset, and the outcomes highlighted the supremacy of the AVOAGNN-CBDC technique in terms of several measures.
Triplosphaeria guizhouensis sp. nov. (Tetraplosphaeriaceae, Pleosporales), a novel taxon from freshwater habitat in Guizhou Province, China
Authors: LIU LING-LING , FENG YAO , WEI QUAN-QUAN , ZHANG MENG , GU XIAO-FENG , LIU ZUO-YI , GOU JIU-LAN
Published: July 2023

During our survey of the taxonomy and diversity of freshwater fungi of Guizhou Province, China, a Tetraploa-like taxon was collected from stream in China. The taxon has quite smaller, oblong, dark brown to black, three or four-columned conidia with three or four setose appendages. Phylogenetic analyses of combined LSU, SSU, ITS, tef1-α and β-tubulin sequence data revealed that the newly obtained isolate clustered as a monophyletic clade with the species of Triplosphaeria with strong statistical support (98% ML BS/1.0 PP). Based on the morphological comparison and multi-locus phylogeny, we introduce T. guizhouensis as a new species in Triplosphaeria. The description and illustration of the newly discovered taxon, and updated backbone tree of Tetraplosphaeriaceae are provided.
A new and possibly carnivorous species of Crepidorhopalon (Linderniaceae) from Mozambique
Authors: FISCHER EBERHARD , WURSTEN BART , DARBYSHIRE IAIN
Published: July 2023

The new species Crepidorhopalon droseroides from Mozambique is described and illustrated. It represents the third strict Mozambique endemic in Linderniaceae, and it differs from all known species of Crepidorhopalon in the long sticky glandular hairs. The hypothesis that the species may be carnivorous is discussed. The Conservation Status is preliminarily assessed.
The Adjoint-Based Favorable Winds for the Generation of the Central Pacific El Niño
Authors: Yang Weisheng , Liu Chuanyu , Köhl Armin , Wang Jin , Wang Xin , Wang Fan
Published: July 2023

Central Pacific (CP) El Niño (i.e., CP El Niño) events have occurred more frequently during recent decades. Wind stress patterns are argued to have significant effects on the generation and evolution of CP El Niño. However, the winds differ in different CP El Niño events, making it hard in previous studies to avoid overgeneralizing the timing and location of the winds that indeed matter. In this study, the theoretically favorable wind perturbations (FWPs) that may warm the Niño-4 region, in terms of their directions, horizontal structures, and bounds, in each month before the peak month (December) of CP El Niños are determined, using an adjoint sensitivity method. The mechanisms of the FWPs are interpreted. Primarily, zonal temperature advection via the equatorial wave–associated velocity anomalies is responsible. In particular, easterly FWPs over the central equatorial Pacific with off-equatorial westerly FWPs (constituting a wind structure with a strong north–south gradient) during the first half year can play a positive role in warming the Niño-4 region and so can the westerly FWPs over the western tropical Pacific, while westerly FWPs in the western-central tropical Pacific in the second half year show higher efficiency. Meanwhile, the particular wind structure of the first half year (i.e., the easterly anomaly over the central equatorial Pacific with strong wind stress curl off the equator) has also been verified to be able to produce a CP-type warming in an intermediate coupled model (ICM); similar wind stress anomalies had been observed in some CP El Niño events. Thus, the FWPs provide helpful guidance in analyzing the generation and evolving processes of the wind-driven CP El Niño.
Social determinants associated with psychological distress in children and adolescents during and after the first COVID-19-related lockdown in France: results from the CONFEADO study
Authors: Estevez Mégane , Oppenchaim Nicolas , Rezzoug Dalila , Laurent Isaura , Domecq Sandrine , Khireddine-Medouni Imane , Thierry Xavier , Galera Cédric , De Stefano Carla , Vandentorren Stéphanie
Published: July 2023

Background

This study aimed to analyze the parental socio-demographic characteristics of children and adolescents aged 9 to 18 years old, as well as the living and housing conditions associated with the psychological distress in these two sub-populations during and after France’s first national COVID-19-related lockdown in spring 2020.

Methods

We used data from the cross-sectional, observational, web-based study CONFEADO, which collected data on children and adolescents’ living and housing conditions and socio-demographic characteristics as well as those of their parents. It also collected data on children’s and adolescents’ health behaviors and psychological distress. We assessed psychological distress using the 10-item Children and Adolescents Psychological Distress Scale (CAPDS-10), and performed a multinomial logistic regression.

Results

A total of 2882 children and adolescents were included in the present study. Factors associated with moderate psychological distress included being a female, parental financial difficulties, a lack of a private living space at home for the child/adolescent, and the following child health behaviors: no leisure or recreational activities with adults in the household, doing less than one hour of school homework a day, and not going outside during the lockdown. Severe psychological distress was associated with the parent’s occupation (especially essential frontline workers), a lack of a private living space at home for the child/adolescent, and the following child health behaviors: spending over 5 h a day on social media, doing less than one hour of school homework a day, and no leisure or recreational activities with adults in the household.

Conclusions

This study emphasizes the impact of housing and living conditions, as well as parents’ socio-economic characteristics on children’s health behaviors and psychological needs during the first COVID-19-related lockdown in France. Our results suggest that health policies implemented during future pandemics should consider these structural social determinants to prevent severe psychological distress in children and adolescents.