bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the function of Pax5 in development of docetaxel-resistant neuroendocrine-like prostate cancers
Authors: Bhattacharya Sreyashi , Harris Hannah L. , Islam Ridwan , Bodas Sanika , Polavaram Navatha , Mishra Juhi , Das Dipanwita , Seshacharyulu Parthasarathy , Kalluchi Achyuth , Pal Anirban , Kohli Manish , Lele Subodh M. , Muders Michael , Batra Surinder K. , Ghosh Paramita M. , Datta Kaustubh , Rowley M. Jordan , Dutta Samikshan
Published: August 2024

Resistance to the current Androgen Receptor Signaling Inhibitor (ARSI) therapies has led to higher incidences of therapy-induced neuroendocrine-like prostate cancer (t-NEPC). This highly aggressive subtype with predominant small-cell-like characteristics is resistant to taxane chemotherapies and has a dismal overall survival. t-NEPCs are mostly treated with platinum-based drugs with a combination of etoposide or taxane and have less selectivity and high systemic toxicity, which often limit their clinical potential. During t-NEPC transformation, adenocarcinomas lose their luminal features and adopt neuro-basal characteristics. Whether the adaptive neuronal characteristics of t-NEPC are responsible for such taxane resistance remains unknown. Pathway analysis from patient gene-expression databases indicates that t-NEPC upregulates various neuronal pathways associated with enhanced cellular networks. To identify transcription factor(s) (TF) that could be important for promoting the gene expression for neuronal characters in t-NEPC, we performed ATAC-Seq, acetylated-histone ChIP-seq, and RNA-seq in our NE-like cell line models and analyzed the promoters of transcriptionally active and significantly enriched neuroendocrine-like (NE-like) cancer-specific genes. Our results indicate that Pax5 could be an important transcription factor for neuronal gene expression and specific to t-NEPC. Pathway analysis revealed that Pax5 expression is involved in axonal guidance, neurotransmitter regulation, and neuronal adhesion, which are critical for strong cellular communications. Further results suggest that depletion of Pax5 disrupts neurite-mediated cellular communication in NE-like cells and reduces surface growth factor receptor activation, thereby, sensitizing them to docetaxel therapies. Moreover, t-NEPC-specific hydroxymethylation of Pax5 promoter CpG islands favors Pbx1 binding to induce Pax5 expression. Based on our study, we concluded that continuous exposure to ARSI therapies leads to epigenetic modifications and Pax5 activation in t-NEPC, which promotes the expression of genes necessary to adopt taxane-resistant NE-like cancer. Thus, targeting the Pax5 axis can be beneficial for reverting their taxane sensitivity.
A novel protein encoded by circCOPA inhibits the malignant phenotype of glioblastoma cells and increases their sensitivity to temozolomide by disrupting the NONO–SFPQ complex
Authors: Peng Dazhao , Wei Cheng , Jing Boyuan , Yu Runze , Zhang Zhenyu , Han Lei
Published: August 2024

Glioblastoma (GBM) represents a primary malignant brain tumor. Temozolomide resistance is a major hurdle in GBM treatment. Proteins encoded by circular RNAs (circRNAs) can modulate the sensitivity of multiple tumor chemotherapies. However, the impact of circRNA-encoded proteins on GBM sensitivity to temozolomide remains unknown. Herein, we discover a circRNA (circCOPA) through the circRNA microarray profile in GBM samples, which can encode a novel 99 amino acid protein (COPA-99aa) through its internal ribosome entry site. Functionally, circCOPA overexpression in GBM cells inhibits cell proliferation, migration, and invasion in vitro and growth in vivo. Rather than itself, circCOPA mainly functions as a suppressive effector by encoding COPA-99aa. Moreover, we reveal that circCOPA is downregulated in GBM tissues and high expression of circCOPA is related to a better prognosis in GBM patients. Mechanistically, a heteromer of SFPQ and NONO is required for double-strand DNA break repair. COPA-99aa disrupts the dimerization of NONO and SFPQ by separately binding with the NONO and SFPQ proteins, thus resulting in the inhibition of proliferation or invasion and the increase of temozolomide-induced DNA damage in GBM cells. Collectively, our data suggest that circCOPA mainly contributes to inhibiting the GBM malignant phenotype through its encoded COPA-99aa and that COPA-99aa increases temozolomide-induced DNA damage by interfering with the dimerization of NONO and SFPQ. Restoring circCOPA or COPA-99aa may increase the sensitivity of patients to temozolomide.
Efficacy of periodontal treatment modalities in Down syndrome patients: a systematic review and meta-analysis
Authors: Yehia Zakaria , Silbereisen Angelika , Koletsi Despina , Arabzadehtousi Mahla , Tsilingaridis Georgios , Bostanci Nagihan
Published: August 2024

Objective

The systematic review aimed to review the existing evidence, to identify and appraise the effectiveness of periodontal prevention and treatment modalities in individuals diagnosed with Down syndrome (DS) and to determine the estimates of the effects of implemented periodontal prevention and treatment strategies compared to chromosomally normal (CN) individuals.

Methodology

The systematic review was conducted and reported in conformity with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. The study protocol was registered in the Open Science Framework. Electronic and manual searches, in accordance with PICO framework and delineated inclusion/exclusion criteria, were conducted in multiple databases.

Results

The initial search identified 11,704 studies. After removing duplicates, 9,048 remained. Title and abstract screening narrowed these to 281 for full-text review. Ultimately, 16 studies met the inclusion criteria, with 4 eligible for quantitative data synthesis. Results of the meta-analysis indicated that professional tooth cleaning in combination with oral hygiene reinforcement was less effective in the reduction of PPD in patients with DS compared to those without DS (Mean difference (MD): 0.23; 95% Confidence Interval (CI): 0.14 to 0.32; p < 0.001).

Discussion

These findings suggest that conventional periodontal treatment is less effective in managing periodontitis in patients with DS. Thus, tailored periodontal care strategies that address the specific needs of individuals with DS should be implemented to improve treatment outcomes for this population The presence of moderate to high risk of bias in the included studies underscores the need for rigorously designed research that minimizes bias through effective blinding, randomization, control of confounding factors, and inclusion of diverse treatment outcomes to further investigate these associations.

Conclusion

Based on the best available evidence, professional tooth cleaning combined with oral hygiene instructions appears to be less effective in reducing pocket depths in individuals with DS compared to those without DS. https://doi.org/10.17605/OSF.IO/UXTCG
Lentiviral vector gene therapy and CFTR modulators show comparable effectiveness in cystic fibrosis rat airway models
Authors: McCarron Alexandra , Ling Kak-Ming , Montgomery Samuel T. , Martinovich Kelly M. , Cmielewski Patricia , Rout-Pitt Nathan , Kicic Anthony , Parsons David , Donnelley Martin
Published: August 2024

Mutation-agnostic treatments such as airway gene therapy have the potential to treat any individual with cystic fibrosis (CF), irrespective of their CF transmembrane conductance regulator (CFTR) gene variants. The aim of this study was to employ two CF rat models, Phe508del and CFTR knockout (KO), to assess the comparative effectiveness of CFTR modulators and lentiviral (LV) vector-mediated gene therapy. Cells were isolated from the tracheas of rats and used to establish air-liquid interface (ALI) cultures. Phe508del rat ALIs were treated with the modulator combination, elexacaftor-tezacaftor-ivacaftor (ETI), and separate groups of Phe508del and KO tracheal epithelial cells were treated with LV-CFTR followed by differentiation at ALI. Ussing chamber measurements were performed to assess CFTR function. ETI-treated Phe508del ALI cultures demonstrated CFTR function that was 59% of wild-type level, while gene-addition therapy restored Phe508del to 68% and KO to 47% of wild-type level, respectively. Our findings show that rat Phe508del-CFTR protein can be successfully rescued with ETI treatment, and that CFTR gene-addition therapy provides significant CFTR correction in Phe508del and KO ALI cultures to levels that were comparable to ETI. These findings highlight the potential of an LV vector-based gene therapy for the treatment of CF lung disease.
18F-FDG-PET/MR imaging to monitor disease activity in large vessel vasculitis
Authors: Pugh Dan , Patel Dilip , Macnaught Gillian , Czopek Alicja , Bruce Lorraine , Donachie James , Gallacher Peter J. , Tan Sovira , Ahlman Mark , Grayson Peter C. , Basu Neil , Dhaun Neeraj
Published: August 2024

Disease-monitoring in large vessel vasculitis (LVV) is challenging. Simultaneous18F-fluorodeoxyglucose positron emission tomography with magnetic resonance imaging (PET/MRI) provides functional assessment of vascular inflammation alongside high-definition structural imaging with a relatively low burden of radiation exposure. Here, we investigate the ability of PET/MRI to monitor LVV disease activity longitudinally in a prospective cohort of patients with active LVV. We demonstrate that both the PET and MRI components of the scan can distinguish active from inactive disease using established quantification methods. Using logistic-regression modelling of PET/MRI metrics, we devise a novel PET/MRI-specificVasculitisActivity usingMRPET (VAMP) score which is able to distinguish active from inactive disease with more accuracy than established methods and detects changes in disease activity longitudinally. These findings are evaluated in an independent validation cohort. Finally, PET/MRI improves clinicians’ assessment of LVV disease activity and confidence in disease management, as assessed via clinician survey. In summary, PET/MRI may be useful in tracking disease activity and assessing treatment-response in LVV. Based on our findings, larger, prospective studies assessing PET/MRI in LVV are now warranted.
A ventromedial visual cortical ‘Where’ stream to the human hippocampus for spatial scenes revealed with magnetoencephalography
Authors: Rolls Edmund T. , Yan Xiaoqian , Deco Gustavo , Zhang Yi , Jousmaki Veikko , Feng Jianfeng
Published: August 2024

The primate including the human hippocampus implicated in episodic memory and navigation represents a spatial view, very different from the place representations in rodents. To understand this system in humans, and the computations performed, the pathway for this spatial view information to reach the hippocampus was analysed in humans. Whole-brain effective connectivity was measured with magnetoencephalography between 30 visual cortical regions and 150 other cortical regions using the HCP-MMP1 atlas in 21 participants while performing a 0-back scene memory task. In a ventromedial visual stream, V1–V4 connect to the ProStriate region where the retrosplenial scene area is located. The ProStriate region has connectivity to ventromedial visual regions VMV1–3 and VVC. These ventromedial regions connect to the medial parahippocampal region PHA1–3, which, with the VMV regions, include the parahippocampal scene area. The medial parahippocampal regions have effective connectivity to the entorhinal cortex, perirhinal cortex, and hippocampus. In contrast, when viewing faces, the effective connectivity was more through a ventrolateral visual cortical stream via the fusiform face cortex to the inferior temporal visual cortex regions TE2p and TE2a. A ventromedial visual cortical ‘Where’ stream to the hippocampus for spatial scenes was supported by diffusion topography in 171 HCP participants at 7 T.
Improving genetic risk modeling of dementia from real-world data in underrepresented populations
Authors: Fu Mingzhou , Valiente-Banuet Leopoldo , Wadhwa Satpal S. , Pasaniuc Bogdan , Vossel Keith , Chang Timothy S.
Published: August 2024

Genetic risk modeling for dementia offers significant benefits, but studies based on real-world data, particularly for underrepresented populations, are limited. We employ an Elastic Net model for dementia risk prediction using single-nucleotide polymorphisms prioritized by functional genomic data from multiple neurodegenerative disease genome-wide association studies. We compare this model with APOE and polygenic risk score models across genetic ancestry groups (Hispanic Latino American sample: 610 patients with 126 cases; African American sample: 440 patients with 84 cases; East Asian American sample: 673 patients with 75 cases), using electronic health records from UCLA Health for discovery and the All of Us cohort for validation. Our model significantly outperforms other models across multiple ancestries, improving the area-under-precision-recall curve by 31–84% (Wilcoxon signed-rank test p-value <0.05) and the area-under-the-receiver-operating characteristic by 11–17% (DeLong test p-value <0.05) compared to the APOE and the polygenic risk score models. We identify shared and ancestry-specific risk genes and biological pathways, reinforcing and adding to existing knowledge. Our study highlights the benefits of integrating functional mapping, multiple neurodegenerative diseases, and machine learning for genetic risk models in diverse populations. Our findings hold potential for refining precision medicine strategies in dementia diagnosis.
SARS-CoV-2 infection results in a unique lung proteome long after virus resolution in the hamster
Authors: Boese Amrit S. , Warner Bryce M. , McQueen Peter , Vendramelli Robert , Tailor Nikesh , Griffin Bryan D. , Chan Mable , Audet Jonathan , Leung Anders , McCorrister Stuart , Grant Chris , Westmacott Garrett , Kobasa Darwyn
Published: August 2024

Long COVID or post-acute sequelae of COVID-19 (PASC) remains an ongoing public health issue that causes impairment for those afflicted and diminishes their ability to contribute to society. To address the host response underpinning respiratory PASC, we used the Golden Syrian hamster model infected with ancestral SARS-CoV-2 and examined its lung proteome in a longitudinal experiment. We infected young 6-week old male and female hamsters with 105 TCID50 of virus via the intranasal route and sampled the lung at 1, 3, 5, and 31 days post infection (dpi). We compared the infected lung proteome to that of uninfected sex-matched controls. We found almost no differences in protein levels at 1 dpi, with hundreds at 3 dpi, and thousands at 5 dpi. Many overlapping differential protein levels and pathways were seen in both sexes at 3 and 5 dpi including the Coagulation and Complement cascades. Notably, we found differences between the sexes at 31 dpi which included many targets with decreased levels of protein in the males. We also noted an increase in 7 proteins in both sexes at 31 dpi including proteins responsible for airway mucosal layer integrity such as Mucin 5B and Calcium-activated chloride channel regulator 1. Longitudinally, 38 proteins were changed in levels across more than one timepoint in the males but only three proteins were in the females, Secretoglobin family 1 A member 1, Poly [ADP-ribose] polymerase, and Apolipoprotein D. Overall, we show that there are changes to the lung proteome at 31 dpi, a time when no SARS-CoV-2 remains, and that there are sex differences in that proteome after infection with the ancestral strain. We conclude that biological sex should be examined as a variable when testing medical countermeasures for PASC in the Golden Syrian hamster due to host differences between the sexes.
Sociology, Human Rights, and Religious Freedom
Authors: Breskaya Olga , Giordan Giuseppe , Richardson James T
Published: August 2024

This chapter addresses two questions: Why did it take so long for sociology to be applied to the study of religious freedom, and how has it already contributed to the study of human rights? First, the chapter outlines the multiple difficulties of theorizing human rights in the framework of sociology and considers recent sociological arguments in favor of the value-laden, socially practiced, and culturally conditioned nature of rights. Second, it discusses the sociolegal conception of the norm-making process as introduced by sociologist Gurvitch along with his “continuum of freedom,” applying it to the analysis of practices of religious freedom. Third, it overviews Luhmann’s sociological perspective concerning human rights, considered not only as legal principles but also in terms of social institutions. Finally, it addresses the sociological analysis of religious freedom within the framework of secularization and rational choice theory specifying a sociological perspective to the study of religious freedom.
grenedalf: population genetic statistics for the next generation of pool sequencing
Authors: Czech Lucas , Spence Jeffrey P , Expósito-Alonso Moisés
Published: August 2024

Pool sequencing is an efficient method for capturing genome-wide allele frequencies from multiple individuals, with broad applications such as studying adaptation in Evolve-and-Resequence experiments, monitoring of genetic diversity in wild populations, and genotype-to-phenotype mapping. Here, we present grenedalf, a command line tool written in C++ that implements common population genetic statistics such as θ, Tajima’s D, and FST for Pool sequencing. It is orders of magnitude faster than current tools, and is focused on providing usability and scalability, while also offering a plethora of input file formats and convenience options.

Availability and implementation

grenedalf is published under the GPL-3, and freely available at github.com/lczech/grenedalf.
Lichen planus following COVID-19 vaccination: a narrative review
Authors: D’Agostino Michela , Martora Fabrizio , Megna Matteo , Napolitano Maddalena , Potestio Luca
Published: August 2024

Lichen planus (LP) is an inflammatory disease that afflicts the skin, mucous membranes and cutaneous appendages. Moreover, LP represents a prototype of lichenoid dermatosis, being characterized by the presence of a dense dermal cell infiltrate. Although most cases of LP are idiopathic, infectious and drug-related factors must also be considered in the aetiology. In this context, the occurrence of LP and lichenoid drug eruptions following different types of vaccination is a possible event. Therefore, the aim of our review is to provide a broad perspective to clinicians by analysing the current literature of cases of LP and lichenoid eruptions following COVID-19 vaccination, and also investigating the possible pathogenetic mechanisms underlying this phenomenon. In total, 61 cases of LP and lichenoid eruption following COVID-19 vaccination have been collected. However, the number of cases of LP and lichenoid drug eruption is extremely low compared with the number of vaccines administered overall, suggesting that the risk of LP and lichenoid eruption following COVID-19 vaccination is extremely low. Certainly, further studies are desirable to identify the population most at risk and the possibility of taking preventive measures.
Transportable, portable, wearable and (partially) implantable haemodialysis systems: comparison of technologies and readiness levels
Authors: Wieringa Fokko P , Bolhuis Dian , Søndergaard Henning , Ash Stephen R , Cummins Cian , Gerritsen Karin G F , Vollenbroek Jeroen , Irmak Tugrul
Published: August 2024

Background

Dialysis modalities and their various treatment schedules result from complex compromises (‘trade-offs’) between medical, financial, technological, ergonomic, and ecological factors. This study targets summarizing the mutual influence of these trade-offs on (trans)portable, wearable, or even (partially) implantable haemodialysis (HD) systems, identify what systems are in development, and how they might improve quality of life (QoL) for patients with kidney failure.

Methods

HD as defined by international standard IEC 60601–2-16 was applied on a PUBMED database query regarding (trans)portable, wearable, and (partly) implantable HD systems. Out of 159 search results, 24 were included and scanned for specific HD devices and/or HD systems in development. Additional information about weight, size, and development status was collected by the internet and/or contacting manufacturers. International airplane hand baggage criteria formed the boundary between transportable and portable. Technology readiness levels (TRLs) were assigned by combining TRL scales from the European Union and NATO medical staff.

Results

The query revealed 13 devices/projects: seven transportable (six TRL9, one TRL5); two portable (one TRL6–7, one TRL4); two wearable (one TRL6, one frozen); and two partly implantable (one TRL4–5, one TRL2–3).

Discussion

Three main categories of technical approaches were distinguished: single-pass, dialysate regenerating, and implantable HD filter with extracorporeal dialysate regeneration (in climbing order of mobility).

Conclusions

Kidneys facilitate mobility by excreting strongly concentrated waste solutes with minimal water loss. Mimicking this kidney function can increase HD system mobility. Dialysate-regenerating HD systems are enablers for portability/wearability and, combined with durable implantable HD filters (once available), they may enable HD without needles or intravascular catheters. However, lack of funding severely hampers progress.
Burden of risk factors in women and men with unrecognized myocardial infarction: a systematic review and meta-analysis
Authors: van Oortmerssen Julie A E , Ntlapo Noluthando , Tilly Martijn J , Bramer Wichor M , den Ruijter Hester M , Boersma Eric , Kavousi Maryam , Roeters van Lennep Jeanine E
Published: August 2024

Unrecognized myocardial infarction (MI) is an MI that remains undetected in the acute phase and is associated with an unfavourable prognosis. With this systematic review and meta-analysis, we evaluated the burden of cardiovascular risk factors in individuals with unrecognized MI. We searched general population-based cohort studies diagnosing unrecognized MI by electrocardiogram or myocardial imaging up to 24 November 2023. Pooled mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs) were determined, and random-effects meta-analyses were performed. Fourteen cohort studies were included involving 200 450 individuals (mean age 62.8 ± 9.9 years, 56.0% women), among which 4322 (2.2%) experienced unrecognized MI (mean age 66.3 ± 8.2 years, 47.8% women) and 4653 (2.1%) recognized MI (mean age 68.5 ± 7.3 years, 33.8% women). Compared to individuals without MI, those with unrecognized MI had higher body mass index (MD 0.27, 95% CI 0.16–0.39) and systolic blood pressure (MD 4.48, 95% CI 2.81–6.15) levels, and higher prevalence of hypertension (RR 1.27, 95% CI 1.06–1.51) and diabetes mellitus (RR 1.67, 95% CI 1.36–2.06). Furthermore, individuals with unrecognized MI had lower prevalence of hypertension (RR 0.92, 95% CI 0.88–0.97) and diabetes mellitus (RR 0.80, 95% CI 0.70–0.92). Individuals with unrecognized MI are characterized by a substantial burden of metabolic risk factors. Our findings suggest insufficient recognition and management of cardiovascular risk factors among individuals with unrecognized MI.
Oligonucleotide-based CRISPR-Cas9 toolbox for efficient engineering of Komagataella phaffii
Authors: Strucko Tomas , Gadar-Lopez Adrian-E , Frøhling Frederik B , Frost Emma T , Iversen Esther F , Olsson Helen , Jarczynska Zofia D , Mortensen Uffe H
Published: August 2024

Komagataella phaffii (Pichia pastoris) is a methylotrophic yeast that is favored by industry and academia mainly for expression of heterologous proteins. However, its full potential as a host for bioproduction of valuable compounds cannot be fully exploited as genetic tools are lagging behind those that are available for baker’s yeast. The emergence of CRISPR-Cas9 technology has significantly improved the efficiency of gene manipulations of K. phaffii, but improvements in gene-editing methods are desirable to further accelerate engineering of this yeast. In this study, we have developed a versatile vector-based CRISPR-Cas9 method and showed that it works efficiently at different genetic loci using linear DNA fragments with very short targeting sequences including single-stranded oligonucleotides. Notably, we performed site-specific point mutations and full gene deletions using short (90 nt) single-stranded oligonucleotides at very high efficiencies. Lastly, we present a strategy for transient inactivation of nonhomologous end-joining (NHEJ) pathway, where KU70 gene is disrupted by a visual marker (uidA gene). This system enables precise CRISPR-Cas9-based editing (including multiplexing) and facilitates simple reversion to NHEJ-proficient genotype. In conclusion, the tools presented in this study can be applied for easy and efficient engineering of K. phaffii strains and are compatible with high-throughput automated workflows.
EARA2024: a new radially anisotropic seismic velocity model for the crust and upper mantle beneath East Asia and Northwestern pacific subduction zones
Authors: Xi Ziyi , Chen Min , Wei Songqiao Shawn , Li Jiaqi , Zhou Tong , Wang Baoshan , Kim YoungHee
Published: August 2024

We present a new 3-D radially anisotropic seismic velocity model EARA2024 of the crust and mantle beneath East Asia and the northwestern Pacific using adjoint full-waveform inversion tomography. We construct the EARA2024 model by iteratively minimizing the waveform similarity misfit between the synthetic and observed waveforms from 142 earthquakes recorded by about 2000 broad-band stations in East Asia. Compared to previous studies, this new model renders significantly improved images of the subducted oceanic plate in the upper mantle, mantle transition zone, and uppermost lower mantle along the Kuril, Japan, Izu-Bonin and Ryukyu Trenches. Complex slab deformation and break-offs are observed at different depths. Moreover, our model provides new insights into the origins of intraplate volcanoes in East Asia, including the Changbaishan, Datong-Fengzhen, Tengchong and Hainan volcanic fields.
High-precision vertical deformation of the Chinese mainland constrained by levelling and GNSS data
Authors: Wu Yanqiang , Su Guangli , Nie Jianliang , Chen Changyun , Chen Zhaohui , Yu Huazhi , Yin Haiquan , Chang Liu , Tang Zheng , Pang Yajin , Liang Hongbao , Bo Wanju
Published: August 2024

A high-precision and high-resolution vertical velocity for the Chinese mainland is obtained by integrating precise levelling and Global Navigation Satellite System data, using a Helmert joint adjustment method. The results show that the surface vertical rates range between −3.0 and 3.9 mm yr−1 with continuous deformation in most areas, except the obvious subsidence at the rates of −15.0 to −94.2 mm yr−1 induced by groundwater exploitation in the North China Plain. Particularly, the central and southern Tibet, Tien Shan, Alashan, Ordos, eastern Cathaysia and Northeast China uplift at the rates of 0.5–3.9 mm yr−1; the southeastern Tibetan Plateau, Sichuan basin and Yangtze block are dominated by surface subsidence at the rates of −3.3 to −0.5 mm yr−1. Furthermore, the vertical rates vary little between the eastern and western regions of the Chinese mainland despite their pronounced differences in horizontal deformations. The effects of gravity isostasy and non-tectonic factors, including the environmental mass loads, Glacier Isostatic Adjustment (GIA), poroelastic expansion/compression, and mining operations have partially contributed to the vertical deformation of the Chinese mainland. Overall, this velocity reflects the complicated deformation features induced by the multiple geodynamic processes of the Chinese mainland. These geodynamic processes include isostasy, orogenic processes and geothermal anomalies associated with slab subduction/plate collision.
Potential therapeutic use of dermaseptin S4 from the frog Phyllomedusa sauvagii and its derivatives against bacterial pathogens in fish
Authors: Braik Afef , Serna-Duque John Alberto , Nefzi Adel , Aroui Sonia , Esteban María Ángeles
Published: August 2024

Aim

Dermaseptins are one of the main families of antimicrobial peptides (AMPs) derived from the skin secretions of Hylidae frogs. Among them, dermaseptin S4 (DS4) is characterized by its broad-spectrum of activity against bacteria, protozoa, and fungi. In this study, the physicochemical properties of the native peptide DS4 (1–28) and two derivatives [DS4 (1–28)a and DS4 (1–26)a] isolated from the skin of the frog Phyllomedusa sauvagii were investigated and their antimicrobial properties against two marine pathogenic bacteria (Vibrio harveyi and Vibrio anguillarum) were examined.

Methods and results

The results indicate that the peptide DS4 (1–26)a has high-antibacterial activity against the tested strains and low-hemolytic activity (<30% lysis at the highest tested concentration of 100 µg/mL) compared to the other two peptides tested. In addition, all three peptides affect the membrane and cell wall integrity of both pathogenic bacteria, causing leakage of cell contents, with DS4 (1–26)a having the most severe impact. These skills were corroborated by transmission electron microscopy and by the variation of cations in their binding sites due to the effects caused by the AMPs.

Conclusions

These results suggest that DS4 and its derivatives, in particular the truncated and amidated peptide DS4 (1–26)a could be effective in the treatment of infections caused by these marine pathogenic bacteria. Future studies are required to validate the use of DS4  in vivo for the prevention of bacterial diseases in fish.
Brighteness-dependent visual attractiveness of the human body for horse flies (Diptera: Tabanidae): a field experiment
Authors: Balogh Attila , Kúdela Matúš
Published: August 2024

The landing patterns of blood-sucking females (Diptera: Tabanidae) are largely influenced by their visual perceptions. When attacking humans, the shape of different body parts and overall brightness of the body could be the factors determining the place of blood-sucking. The visual attractiveness of the human body for tabanids was investigated through a black and a white mannequin in the Danube floodplain, Slovakia. The mannequins were covered by glue once a week. On both of the mannequins, 332 horse flies were stuck. The trapped horse flies on the mannequins belong to the genera Tabanus Linnaeus, 1758, Hybomitra Enderlein, 1922, Chrysops Meigen, 1803, Haematopota Linnaeus, 1758 and Atylotus (Linnaeus, 1767). Based on the trapped tabanids, the black mannequin is 6.06 times more attractive than the white one. The most tabanid carcasses were found on the lower limbs (56.32%) and the least occurred on the head (2.1%), the difference in their occurrence between the lower limbs and head of both mannequins was significant (P < 0.001). A similar significant difference was observed on certain parts of both mannequins on the taxonomical level of the genera Tabanus, Hybomitra, and Atylotus, the carcasses of which aggregated mostly on the lower limbs, rather than on the upper limbs and head.
Molecular and serological detection of Leishmania infantum (Trypanosomatida: Trypanosomatidae) in domestic dogs in Manaus city, Amazonas, Brazil
Authors: Nascimento de Campos Hevila Gabrieli , Gennari Solange Maria , da Silva Ryan Emiliano , Soares Herbert Sousa , Costa Jaciara de Oliveira Jorge , de Azevedo Sergio Santos , Marcili Arlei
Published: August 2024

Leishmaniasis are zoonosis widely spread in Brazil, caused by the protozoan of the genus Leishmania, which includes several species. The disease manifests itself in the visceral or tegumentary form, and the main reservoir is the dogs. Manaus is the largest city in the Brazilian Amazon region, and despite the importance of the municipality, practically nothing is known about leishmaniosis in humans and animals. The objective of this study was to evaluate the occurrence and risk factors associated with the presence of Leishmania infantum in domiciliated dogs from Manaus. Molecular (polymerase chain reaction) and serological (immunofluorescent antibody test) methods were used as an indication of the circulation of the parasite. Blood samples for 154 domiciled dogs were obtained, and prevalence ratio and analysis of the variables were performed. Serum antibodies anti-Leishmania spp. were detected in 20.8% (95% CI: 14.4%–27.2%). Access to the street and zone of residence (P < 0.01) were associated with higher seropositivity. Molecular diagnosis for L. infantum detected positivity in 60 (39%) of the 154 (95% CI: 31.3%–46.7%) animals, and the variables street access, contact with dogs, and zone of residence were associated with higher frequencies of positivity (P < 0.05). Both serology and molecular diagnosis detected positive dogs in the municipality. This is the first description of the circulation of L. infantum infecting dogs in Manaus. As the municipality is classified as nonendemic, studies of isolation and characterization of the isolate must be done urgently.
Narrating the Client: How stories of parental influence impact teacher professionalism
Authors: Eklund Sanna
Published: August 2024

This article examines how teachers engage in symbolic institutional work to address client influence, and how this impacts teacher professionalism. The study delves into an intriguing empirical field, using the Swedish school system as an illustrative case for studying the development of professionalism within a highly marketized context. The research employed interviews, observations, and shadowing, enabling a deeper understanding of the symbolic institutional work in a complex institutional environment where market and professional logic collide. The findings demonstrate how teachers utilize a narrative of a threatening and demanding client, which helps them distance themselves from market logic and resist adapting to it in their professionalism. However, there are also indications of a different narrative, where some teachers embrace and integrate client influence as a natural part of their professionalism. Additionally, there is also a form of ambivalence, where teachers are moving between different narratives. By investigating how professionals engage in these narratives, the article provides insights into understudied dimensions within the concept of professionalism. While the existence of different narratives highlights the complexity and fragility of institutional work, the inclination towards distancing from clients illustrates a preservation of traditional professionalism rather than a shift towards the ‘new professionalism’ described in previous literature.
Achieving a cure for anastomotic leakage following laparoscopic low anterior resection for rectal cancer using an endoscopic closure device, a MANTIS clip
Authors: Horikawa Daisuke , Takahata Hiroki , Fujiwara Yasuhiro
Published: August 2024

Anastomotic leakage (AL) following low anterior resection (LAR) for rectal cancer is a major complication. While most reports focus on the closure of AL using over-the-scope clip (OTSC), few reports are available on the use of through-the-scope clip (TTSC). This is because TTSC is not typically designed for full-thickness closure, unlike OTSC. However, a MANTIS clip, categorized as TTSC, is indicated for full-thickness closure. A 73-year-old man diagnosed with AL 7 days postoperatively following laparoscopic LAR underwent laparoscopic drainage and ileostomy the next day. Although the drainage led to the shrinkage of the fistula, it persisted even after 2 months. Consequently, the fistula orifice was closed using a MANTIS clip under colonoscopy and radiography. Two days later, the patient was discharged. The drain was withdrawn cautiously to prevent residual fistula and removed completely on day 29. This report highlights our experience in using a MANTIS clip for AL following LAR.
Prospects for neutron star parameter estimation using gravitational waves from f modes associated with magnetar flares
Authors: Ball Matthew , Frey Raymond , Merfeld Kara
Published: August 2024

Magnetar vibrational modes are theorized to be associated with energetic X-ray flares. Regular searches for gravitational waves from these modes have been performed by Advanced LIGO (Laser Interferometer Gravitational-wave Observatory) and Advanced Virgo, with no detections so far. Presently, search results are given in upper limits on the root sum square of the integrated gravitational-wave strain. However, the increased sensitivity of current detectors and the promise of future detectors invite the consideration of more astrophysically motivated methods. We present a framework for augmenting gravitational-wave searches to measure or place direct limits on magnetar astrophysical properties in various search scenarios using a set of phenomenological and analytical models.
Probing the spatial and velocity anisotropies in stellar haloes from the Aquarius simulations
Authors: Mondal Amit , Pandey Biswajit
Published: August 2024

We analyse the spatial anisotropy and the velocity anisotropy in a set of mock stellar haloes from the Aquarius simulations. The spatial anisotropy in each mock stellar halo rises progressively with the increasing distance from the halo centre, eventually reaching a maximum near the periphery. Excluding the bound satellites leads to a significant reduction of the spatial anisotropy in each halo. We compare the measured anisotropy in the mock stellar haloes with that from their sphericalized versions where all the shape- and substructure-induced anisotropies are erased. The growth of spatial anisotropy persists throughout the entire halo when the bound satellites are present but remains limited within the inner halo (${\lt} 60 \, {h^{-1}\, {\rm kpc}}$) after their exclusion. This indicates that the spatial anisotropy in the inner halo is induced by the diffuse substructures and the halo shape, whereas the outer halo anisotropy is dominated by the bound satellites. We find that the outer parts of the stellar halo are kinematically colder than the inner regions. The stellar orbits are predominantly radial, but they become rotationally dominated at certain radii that are marked by the prominent dips in the velocity anisotropy. Most of these dips disappear after the removal of the satellites. A few shallow dips arise occasionally due to the presence of diffuse streams and clouds. Our analysis suggests that a combined study of the spatial and velocity anisotropies can reveal the structure and the assembly history of the stellar haloes.
BASILISK II. Improved constraints on the galaxy–halo connection from satellite kinematics in SDSS
Authors: Mitra Kaustav , van den Bosch Frank C , Lange Johannes U
Published: August 2024

Basilisk is a novel Bayesian hierarchical method for inferring the galaxy–halo connection, including its scatter, using the kinematics of satellite galaxies extracted from a redshift survey. In this paper, we introduce crucial improvements, such as updated central and satellite selection, advanced modelling of impurities and interlopers, extending the kinematic modelling to fourth order by including the kurtosis of the line-of-sight velocity distribution, and utilizing satellite abundance as additional constraint. This drastically enhances Basilisk’s performance, resulting in an unbiased recovery of the full conditional luminosity function (central and satellite) and with unprecedented precision. After validating Basilisk’s performance using realistic mock data, we apply it to the SDSS-DR7 data. The resulting inferences on the galaxy–halo connection are consistent with, but significantly tighter than, previous constraints from galaxy group catalogues, galaxy clustering, and galaxy–galaxy lensing. Using full projected phase-space information, Basilisk breaks the mass-anisotropy degeneracy, thus providing precise global constraint on the average orbital velocity anisotropy of satellite galaxies across a wide range of halo masses. Satellite orbits are found to be mildly radially anisotropic, in good agreement with the mean anisotropy for subhaloes in dark matter-only simulations. Thus, we establish Basilisk as a powerful tool that is not only more constraining than other methods on similar volumes of data, but crucially, is also insensitive to halo assembly bias which plagues the commonly used techniques like galaxy clustering and galaxy–galaxy lensing.
A digital-twin platform for cryospheric disaster warning
Authors: Cui Yifei , Li Yao , Tang Hui , Turowski Jens M , Yan Yan , Bazai Nazir Ahmed , Wei Ruilong , Li Li
Published: August 2024

With increasing glacial hazards due to global climate warming, a promising digital-twin-based platform has been proposed for early warning of cryospheric disasters.
Impact of compression forces on different mesenchymal stem cell types regarding orthodontic indication
Authors: Radermacher Chloé , Craveiro Rogerio B , Jahnen-Dechent Wilhelm , Beier Justus P , Bülow Astrid , Wolf Michael , Neuss Sabine
Published: August 2024

The potential of stem cells, for example upper periodontal ligament stem cells from the maxilla (u-PDLSC) and from the mandible (l-PDLSC), adipose-derived mesenchymal stem cells (AD-MSC), and bone marrow-derived mesenchymal stem cells (BM-MSC), with respect to periodontal remodeling and orthodontic treatment is of great importance. In this work, we focus on the comprehensive adaptability of different stem cell types to mechanical forces with the aim to better understanding cell behavior and to refine a new mechanistic approach to investigate periodontal remodeling. We comprehensively analyze stem cells and observe distinct morphological and proliferation changes under compression in dependence on stem cell type. The cell signaling of extracellular signal-regulated kinase (ERK) and protein kinase B, also called AKT, and their respective phosphorylation shows diverse responses to compression. Additionally, vascular endothelial growth factor and hepatocyte growth factor secretion were reduced under mechanical stress in all cell types, with cell-specific variations. Osteoprotegerin secretion was reduced under compression, particularly in u-PDLSC. At least, diverse soluble receptors of NF-kB-ligand secretion patterns among cell types under pressure were observed, providing crucial insights into bone metabolism. These findings offer a deeper understanding of the behavior of mesenchymal stem cells under mechanical stimuli, highlighting their roles in bone remodeling, wound healing, and tissue regeneration in orthodontic and regenerative medicine contexts. Our results underscore the potential of u-PDLSC, l-PDLSC, and AD-MSC in periodontal regeneration, with AD-MSC showing notable resilience under compression, indicating its promising role for further investigation for orthodontic research. While these findings are encouraging, further research is essential to fully comprehend the mechanism of stem cell-based periodontal therapies.
Wheat Stripe Rust Inoculum from the Southwest Dispersed to the East Huang-Huai-Hai Region Through Southern Anhui in China
Authors: Huang Liang , Zhao Wuchao , Xia Chongjing , Zhao Na , Li Hongfu , Sun Zhenyu , Yang Lijun , Li Mingju , Chen Wen , Yang Fang , Zhang Hao , Chen Wanquan , Liu Taiguo
Published: August 2024

Stripe rust, caused by Puccinia striiformis f. sp. tritici, is a continuous threat to global wheat production. In 2021, the epidemic of wheat stripe rust in China affected approximately 4.5 million hectares, resulting in severe yield losses. When confronted with the epidemic, tracing the sources of the pathogen can offer valuable insights for disease prevention and control. This study was conducted to analyze the genetic structure, aerodynamics, geographical features, and cultivation practices of the pathogen population in various wheat-producing regions and to further reveal the spread patterns of the stripe rust pathogens in China. The findings indicated an overall trend of the pathogen dissemination from the west to the east. The pathogen was primarily spread from the northwestern region to the Huang-Huai-Hai region through the Guanzhong Plain and the NanXiang Plain. Meanwhile, the pathogen also spread eastward from the southwestern region to the lower reaches of the Yangtze River, using the Jianghan Plain as a bridge and the Yangtze River Valley in southwestern Anhui as the main pathway. Furthermore, the pathogen spread northward into Shandong under the driving force of the southeast winds. The findings of this study may provide valuable insights for the integrated management of wheat stripe rust in China.
Integrative single-cell and spatial transcriptomic analyses identify a pathogenic cholangiocyte niche and TNFRSF12A as therapeutic target for biliary atresia
Authors: Xiao Man-Huan , Ma Dong , Wu Sihan , Huang Zaoli , Liang Peishi , Chen Huadong , Zhong Zhihai , Li Wei , Wang Fen , Tang Yanlai , Liu Juncheng , Jiang Hong , Feng Xuyang , Luo Zhenhua
Published: August 2024

Background and Aims:

Biliary atresia (BA) is a devastating fibroinflammatory biliary disease that is the leading indication for pediatric liver transplants worldwide. Although cholangiocytes are the primary target cells, the pathogenic mechanisms involving cholangiocytes remain elusive. Here, we aimed to characterize the pathogenic role of cholangiocytes in BA.

Approach and Results:

Integration of single-cell RNA sequencing of 12 liver tissues (from 9 BA and 3 controls) and the spatial transcriptome of another four liver sections (from 2 BA and 2 controls) provided a comprehensive spatial liver cell atlas of BA. In particular, we identified a cholangiocyte-enriched spatial niche with infiltration of activated HSCs, activated portal fibroblasts, macrovascular endothelial cells, and TREM2+ macrophages that were elevated in the portal triad of BA. This niche was positively correlated with bile duct profiles, liver fibrosis, and poor survival in 2 independent cohorts of patients with BA. Using integrative bioinformatics analyses to mine the cell-cell communication and regulatory network in BA cholangiocytes, we uncovered the fibroinflammatory phenotype of cholangiocytes with TNFSF12-TNFRSF12A as a significant signal. Genetic ablation or blockade of TNFRSF12A suppresses liver injury, inflammation, and bile duct profiles in a mouse model of disease. Using human biliary organoids, we revealed that BA organoids expressed higher levels of CCL2 in response to TNFSF12 stimulation and promoted monocyte chemotaxis via the CCL2-CCR2 axis.

Conclusions:

Pathogenic cholangiocytes-enriched niche identifies TNFRSF12A as a potential therapeutic target for BA.