bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial communities in Asecodes hispinarum (Hymenoptera: Eulophidae) and its host Brontispa longissima (Coleoptera: Chrysomelidae), with comparison of Wolbachia dominance
Authors: Yang Sheng-Yuan , Lin Yu-Ying , Hao Zheng , Li Zi-Jie , Peng Zheng-Qiang , Jin Tao
Published: November 2024

The endoparasitoid Asecodes hispinarum (Bouček) (Hymenoptera: Eulophidae) serves as an effective biological control agent against Brontispa longissima (Gestro) (Coleoptera: Chrysomelidae), a notorious palm pest. Endosymbionts found in parasitoids and their hosts have attracted significant attention due to their substantial influence on biocontrol efficacy. In this study, we employed 16S rRNA sequencing, polymerase chain reaction, and fluorescence in situ hybridization to assess the symbiotic bacteria composition, diversity, phylogeny, and localization in A. hispinarum and its host B. longissima. Our findings showed significant differences in the richness, diversity, and composition of symbiotic bacteria among different life stages of B. longissima. Notably, the bacterial richness, diversity, and composition of A. hispinarum was similar to that of B. longissima. Firmicutes and Proteobacteria were the dominant phyla, while Wolbachia was the dominant genera across the parasitoid and host. It was discovered for the first time that Wolbachia was present in A. hispinarum with a high infection rate at ≥ 96.67%. Notably, the Wolbachia strain in A. hispinarum was placed in supergroup A, whereas it was categorized under supergroup B in B. longissima. Furthermore, Wolbachia is concentrated in the abdomen of A. hispinarum, with particularly high levels observed in the ovipositors of female adults. These findings highlight the composition and diversity of symbiotic bacteria in both A. hispinarum and its host B. longissima, providing a foundation for the development of population regulation strategies targeting B. longissima.
Resveratrol potentiates BCG-induced trained immunity in human monocytes
Authors: Bulut Ozlem , Baydemir Ilayda , Kilic Gizem , Domínguez-Andrés Jorge , Netea Mihai G
Published: November 2024

Resveratrol is a natural polyphenol derived from plants such as grapes and berries. In addition to its role in plants during injury and infection, various cardioprotective, neuroprotective, and longevity-promoting effects were reported in diverse model organisms. The primary target of resveratrol is the deacetylase Sirtuin 1, which regulates many immunological processes, including BCG-induced trained immunity response in humans. We, therefore, investigated the effect of resveratrol on trained immunity induced by BCG, β-glucan (BG), Candida albicans, or oxidized low-density lipoprotein (oxLDL). Using an in vitro model of trained immunity with monocytes obtained from healthy donors, we demonstrate that resveratrol amplifies BCG-induced trained immunity regarding IL-6 and TNFα production after a secondary challenge. Although resveratrol did not improve and even limited glycolysis, oxidative phosphorylation, and reactive oxygen species production, it enhanced the permissive epigenetic mark H3K27Ac on IL-6 and TNFα promoters. In contrast to BCG-induced trained immunity, resveratrol potently inhibited training induced by BG, C. albicans, oxLDL, and muramyl dipeptide, a peptidoglycan component of BCG. Resveratrol's unique boosting effect on BCG training depended on BCG being alive and metabolically active. These results suggest that resveratrol might amplify the effects of BCG vaccination, which should be mechanistically characterized further. In addition, resveratrol could alleviate oxLDL-induced training of innate immune cells in atherosclerosis, and in vivo studies of trained immunity combined with resveratrol are warranted to explore these therapeutic possibilities.
Piezo1 restrains proinflammatory response but is essential in T-cell–mediated immunopathology
Authors: Choi Sung Hee , Santin Alicia , Myers Jay T , Kim Byung-Gyu , Eid Saada , Tomchuck Suzanne L , Kingsley Daniel T , Huang Alex Y
Published: November 2024

Piezo1 is a mechanosensitive, nonselective Ca2+ channel that is broadly expressed in CD4+ T cells. Using lineage-specific Piezo1 knockout mice (Piezo1cKO), we show that loss of Piezo1 in CD4+ T cells significantly increased IFNγ and IL-17 production in vitro under TH1 and TH17 polarizing conditions, respectively. Despite their intrinsic proinflammatory phenotype, Piezo1cKO T cells are incapable of establishing disease in vivo in 3 separate adoptive transfer T-cell–mediated inflammatory mouse models, including experimental autoimmune encephalomyelitis, inflammatory bowel disease, and graft-vs-host disease. These phenomena coincided with a decreased effector memory (CD44hiCD62Llo) CD4+ T-cell pool derived from donor Piezo1cKO T cells, an observation related to intrinsic T-cell fitness, as a cotransfer inflammatory bowel disease mouse model revealed a deficiency in the CD4+ effector memory population derived only from the naive Piezo1cKO but a not coinfused Piezo1WT CD4+ T-cell source. Taken together, our results support Piezo1 as restraining proinflammatory T-cell differentiation while contributing to the generation and persistence of the effector memory pool during CD4+ T-cell–mediated immunopathology.
County-level racial disparities in prostate cancer–specific mortality from 2005 to 2020
Authors: Washington III Samuel L , Fakunle Mary , Wang Lufan , Braun Avery E , Leapman Michael , Cowan Janet E , Cooperberg Matthew R
Published: November 2024

Background

Local conditions where people live continue to influence prostate cancer outcomes. By examining local characteristics associated with trends in Black-White differences in prostate cancer–specific mortality over time, we aim to identify factors driving county-level prostate cancer–specific mortality disparities over a 15-year period.

Methods

We linked county-level data (Area Health Resource File) with clinicodemographic data of men with prostate cancer (Surveillance, Epidemiology, and End Results registry) from 2005 to 2020. Generalized linear mixed models evaluated associations between race and county-level age-standardized prostate cancer–specific mortality, adjusting for age; year of death; rurality; county-level education; income; uninsured rates; and densities of urologists, radiologists, primary care practitioners, and hospital beds.

Results

In 1085 counties, 185 390 patients were identified of which 15.8% were non-Hispanic Black. Racial disparities in prostate cancer–specific mortality narrowed from 2005 to 2020 (25.4 per 100 000 to 19.2 per 100 000 overall, 57.9 per 100 000 to 38 per 100 000 for non-Hispanic Black patients, and 23.4 per 100 000 to 18.3 per 100 000 for non-Hispanic White patients). For non-Hispanic Black and non-Hispanic White patients, county prostate cancer–specific mortality changes varied greatly (-65% to +77% and -61% to +112%, respectively). From 2016 to 2020, non-Hispanic Black patients harbored greater prostate cancer–specific mortality risk (relative risk = 2.09, 95% confidence interval [CI] = 2.01 to 2.18); higher radiation oncologist density was associated with lower mortality risk (relative risk = 0.93, 95% CI = 0.89 to 0.98), while other practitioner densities were not.

Conclusion

Although overall rates improved, specific counties experienced worsening race-based disparities over time. Identifying locations of highest (and lowest) mortality disparities remains critical to development of location-specific solutions to racial disparities in prostate cancer outcomes.
Predictors of duty sex frequency in women
Authors: Metcalfe Kate B , Kilimnik Chelsea D , Meston Cindy M
Published: November 2024

Background

Duty Sex—the act of engaging in sex out of a sense of duty or obligation to a partner—is a commonly reported reason why women have sex, with studies indicating associations between Duty Sex and sexual dysfunction, as well as nonconsensual sexual experiences (NSEs).

Aim

This study sought to examine the associations between Duty Sex frequency, sexual function, and NSEs using comprehensive, validated measures of sexual function and NSE histories in a large community sample of women.

Methods

Six hundred and fifty-eight women with (n = 293) and without (n = 365) NSE histories completed measures of sexual function and sexual motivations.

Results

Women with NSE histories reported more sexual pain, lower sexual satisfaction, and more frequent Duty Sex. The relation between NSE history and Duty Sex remained after controlling for the variance in sexual function. The type of NSE behavior, but not the timing of the first NSE nor the perceived impact of the experience, predicted Duty Sex frequency.

Clinical implications

Clinicians should consider sexual motivations, particularly Duty Sex, when treating women with NSE histories or who experience sexual dysfunction.

Strengths and Limitations

To our knowledge, this was the first study to examine how NSEs relate to all domains of sexual function and sexual motives, revealing a link between NSEs, sexual function, and Duty Sex. However, we were unable to account for what percentage of sexual encounters are considered Duty Sex. Therefore, our measurement of Duty Sex lacks specificity, which may explain the relatively low variance accounted for by the models in our analyses.

Conclusions

There are consequences of NSEs, including difficulties with communicating sexual boundaries and impairment of sexual function, that may contribute to the increased likelihood of engaging in Duty Sex.
β-Aminobutyric acid-induced resistance in postharvest peach fruit involves interaction between the MAPK cascade and SNARE13 protein in the salicylic acid-dependent pathway
Authors: Li Chunhong , Wang Kaituo , Lei Changyi , Zou Yanyu , Yang Sisi , Xiang Fei , Li Meilin , Zheng Yonghua
Published: November 2024

The inducer β-aminobutyric acid (BABA) participates in the immune response in various plants. However, the specific mitogen-activated protein kinase (MAPK) cascade involved in BABA-induced resistance (BABA-IR) has not yet been elucidated. Here, peach (Prunus persica) fruits treated with the BABA exhibited pattern-triggered immunity defense against Rhizopus stolonifer, accompanied by the generation of reactive oxygen species and activation of a MAPK cascade. Transcriptome sequencing suggested that a total of 15 MAPK kinase kinase (PpMAPKKK)/MAPK kinase (PpMAPKK)/PpMAPK genes were involved in BABA-IR in peach fruit. Further qRT-PCR analysis showed that the transcript profiles of PpMAPKKK3, PpMAPKK5, and PpMAPK1 were elevated. Subsequently, yeast two-hybrid, luciferase complementation imaging, pull-down, and in vitro phosphorylation assays were conducted to characterize the complete MAPK cascade (PpMAPKKK3–PpMAPKK5–PpMAPK1) involved in peach fruit. Moreover, the downstream events of MAPK1 include the involvement of SNARE13 and the corresponding NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1)-responsive defense. Single silencing of MAPKKK3, MAPKK5, or MAPK1 and double silencing of MAPKKK3 and MAPKK5 or MAPKK5 and MAPK1 resulted in enhanced susceptibility to the fungus R. stolonifer in mutants and attenuated salicylic acid (SA)-dependent defense gene expression. In contrast, the homologous or heterologous overexpression of PpSNARE13 in peach fruit or Arabidopsis led to an enhanced SA pool and elevated expression of pathogenesis related (PR) genes. Reciprocally, the ppsnare13cas9 mutants were generally compromised in the priming of SA-dependent resistance. Therefore, the MAPKKK3–MAPKK5–MAPK1 cascade contributed to pattern-triggered immunity signal transduction in BABA-elicited peach fruit, by combination with downstream events such as SNARE13, NPR1, and SA-dependent signaling.
Wave Optical Modeling of the SEM Column From Source to Specimen
Authors: Kamal Surya , Zhou Yongjian , Gong Zizhou
Published: November 2024

Probe formation in scanning electron microscope (SEM) is often reduced to objective lens action modeling based on a point-spread function or Fourier transforms. In this study, we present the first complete wave optical modeling of the whole SEM column based on plane-by-plane propagation of the electron beam wavefunction without simplifying the optical system. We identify the challenges in plane-by-plane beam propagation and show how sampling limitations produce aliased results. Through a careful selection and combination of propagators, we have developed a general wave optical propagation method that is able to overcome the aliasing problem to achieve the appropriate probe widths. Using a two-step propagator, we show that it is possible to model the electron beam distribution throughout the column from the virtual source plane to the specimen plane. We also show that our results from the wave optical simulations are consistent with the geometrical theory of probe formation. Finally, as a direct application of this method, we demonstrated that the combined effect of aberrations in the condenser lens and the probe forming objective lens cannot be accurately represented using only the objective lens. Designing beam shaping experiments and studying the effect of partial coherence can be some novel applications.
Why Introduce Psychological Techniques into Clinical Practice?
Authors: Doleys Daniel M.
Published: November 2024

This introductory chapter provides context for the importance of appropriate clinician–patient communication, discusses the role of pain psychology in clinical practice, and explains the rationale for the book. It reaffirms the complexity of the clinician–patient interaction but also provides some insight as to how a thoughtful and well-formulated approach to the patient can maximize the impact of one’s time with the patient. A variety of different clinician–patient interaction philosophies and styles have been investigated. Those proven to be most beneficial to the clinician and patients are highlighted. By its very nature, the clinician–patient interaction is a psychological event. Understanding the context and nuances of this event will ultimately save time as well as improve patient satisfaction, the outcome of treatment, and stress level of the clinician. The point at which it is advisable to involve a trained psychologist, and how to locate one, is discussed. Encouraging the use of techniques from multiple disciplines, educating the patient regarding the complex and dynamic nature of chronic pain, and fostering the sharing of responsibility are outlined as hallmarks of an effective interaction.
Variations of flare energy release behaviour and magnetic loop characteristics versus absolute stellar parameters
Authors: Yoldaş E , Dal H A
Published: November 2024

In this paper, we examine how stellar flare activity varies with evolution stage, rotation period, and spectral type. To do this, we examine the distributions of the flare equivalent duration on a logarithmic scale, which we consider as an indicator of the maximum energy level that a star can reach in white-light flares. We conduct these analyses using two distinct statistical models of data obtained from white-light flare patrols of 33 stars. These models are the one-phase exponential association (OPEA) and cumulative flare frequency models. The results show that the value of the OPEA model parameter Plateau has a linear relationship with the stellar B – V colour index and the rotation period. In addition, it is shown that flare time-scales, and therefore the maximum magnetic loop height that stars can have, vary according to the evolutionary stage of the star. Finally, it is concluded that the cumulative flare frequency parameters of the stars are not as effective as the OPEA parameters at exhibiting these variations.
The PRIDE database at 20 years: 2025 update
Authors: Perez-Riverol Yasset , Bandla Chakradhar , Kundu Deepti J , Kamatchinathan Selvakumar , Bai Jingwen , Hewapathirana Suresh , John Nithu Sara , Prakash Ananth , Walzer Mathias , Wang Shengbo , Vizcaíno Juan Antonio
Published: November 2024

The PRoteomics IDEntifications (PRIDE) database (https://www.ebi.ac.uk/pride/) is the world’s leading mass spectrometry (MS)-based proteomics data repository and one of the founding members of the ProteomeXchange consortium. This manuscript summarizes the developments in PRIDE resources and related tools for the last three years. The number of submitted datasets to PRIDE Archive (the archival component of PRIDE) has reached on average around 534 datasets per month. This has been possible thanks to continuous improvements in infrastructure such as a new file transfer protocol for very large datasets (Globus), a new data resubmission pipeline and an automatic dataset validation process. Additionally, we will highlight novel activities such as the availability of the PRIDE chatbot (based on the use of open-source Large Language Models), and our work to improve support for MS crosslinking datasets. Furthermore, we will describe how we have increased our efforts to reuse, reanalyze and disseminate high-quality proteomics data into added-value resources such as UniProt, Ensembl and Expression Atlas.
RNA G-quadruplex formation in biologically important transcribed regions: can two-tetrad intramolecular RNA quadruplexes be formed?
Authors: Basu Pritha , Kejnovská Iva , Gajarský Martin , Šubert Denis , Mikešová Tereza , Renčiuk Daniel , Trantírek Lukáš , Mergny Jean-Louis , Vorlíčková Michaela
Published: November 2024

G-quadruplexes (G4s) formed within RNA are emerging as promising targets for therapeutic intervention in cancer, neurodegenerative disorders and infectious diseases. Sequences containing a succession of short GG blocks, or uneven G-tract lengths unable to form three-tetrad G4s (GG motifs), are overwhelmingly more frequent than canonical motifs involving multiple GGG blocks. We recently showed that DNA is not able to form stable two-tetrad intramolecular parallel G4s. Whether RNA GG motifs can form intramolecular G4s under physiological conditions and play regulatory roles remains a burning question. In this study, we performed a systematic analysis and experimental evaluation of a number of biologically important RNA regions involving RNA GG motifs. We show that most of these motifs do not form stable intramolecular G4s but need to dimerize to form stable G4 structures. The strong tendency of RNA GG motif G4s to associate may participate in RNA-based aggregation under conditions of cellular stress.
The first chicken oocyte nucleus whole transcriptomic profile defines the spectrum of maternal mRNA and non-coding RNA genes transcribed by the lampbrush chromosomes
Authors: Krasikova Alla , Kulikova Tatiana , Schelkunov Mikhail , Makarova Nadezhda , Fedotova Anna , Plotnikov Vladimir , Berngardt Valeria , Maslova Antonina , Fedorov Anton
Published: November 2024

Lampbrush chromosomes, with their unusually high rate of nascent RNA synthesis, provide a valuable model for studying mechanisms of global transcriptome up-regulation. Here, we obtained a whole-genomic profile of transcription along the entire length of all lampbrush chromosomes in the chicken karyotype. With nuclear RNA-seq, we obtained information about a wider set of transcripts, including long non-coding RNAs retained in the nucleus and stable intronic sequence RNAs. For a number of protein-coding genes, we visualized their nascent transcripts on the lateral loops of lampbrush chromosomes by RNA-FISH. The set of genes transcribed on the lampbrush chromosomes is required for basic cellular processes and is characterized by a broad expression pattern. We also present the first high-throughput transcriptome characterization of miRNAs and piRNAs in chicken oocytes at the lampbrush chromosome stage. Major targets of predicted piRNAs include CR1 and long terminal repeat (LTR) containing retrotransposable elements. Transcription of tandem repeat arrays was demonstrated by alignment against the whole telomere-to-telomere chromosome assemblies. We show that transcription of telomere-derived RNAs is initiated at adjacent LTR elements. We conclude that hypertranscription on the lateral loops of giant lampbrush chromosomes is required for synthesizing large amounts of transferred to the embryo maternal RNA for thousands of genes.
Recruitment of homodimeric proneural factors by conserved CAT–CAT E-boxes drives major epigenetic reconfiguration in cortical neurogenesis
Authors: de Martin Xabier , Oliva Baldomero , Santpere Gabriel
Published: November 2024

Proneural factors of the basic helix–loop–helix family coordinate neurogenesis and neurodifferentiation. Among them, NEUROG2 and NEUROD2 subsequently act to specify neurons of the glutamatergic lineage. Disruption of these factors, their target genes and binding DNA motifs has been linked to various neuropsychiatric disorders. Proneural factors bind to specific DNA motifs called E-boxes (hexanucleotides of the form CANNTG, composed of two CAN half sites on opposed strands). While corticogenesis heavily relies on E-box activity, the collaboration of proneural factors on different E-box types and their chromatin remodeling mechanisms remain largely unknown. Here, we conducted a comprehensive analysis using chromatin immunoprecipitation followed by sequencing (ChIP-seq) data for NEUROG2 and NEUROD2, along with time-matched single-cell RNA-seq, ATAC-seq and DNA methylation data from the developing mouse cortex. Our findings show that these factors are highly enriched in transiently active genomic regions during intermediate stages of neuronal differentiation. Although they primarily bind CAG-containing E-boxes, their binding in dynamic regions is notably enriched in CAT–CAT E-boxes (i.e. CATATG, denoted as 5′3′ half sites for dimers), which undergo significant DNA demethylation and exhibit the highest levels of evolutionary constraint. Aided by HT-SELEX data reanalysis, structural modeling and DNA footprinting, we propose that these proneural factors exert maximal chromatin remodeling influence during intermediate stages of neurogenesis by binding as homodimers to CAT–CAT motifs. This study provides an in-depth integrative analysis of the dynamic regulation of E-boxes during neuronal development, enhancing our understanding of the mechanisms underlying the binding specificity of critical proneural factors.
Pairpot: a database with real-time lasso-based analysis tailored for paired single-cell and spatial transcriptomics
Authors: Ruan Zhihan , Lin Fan , Zhang Zhenjie , Cao Jiayue , Xiang Wenting , Wei Xiaoyi , Liu Jian
Published: November 2024

Paired single-cell and spatially resolved transcriptomics (SRT) data supplement each other, providing in-depth insights into biological processes and disease mechanisms. Previous SRT databases have limitations in curating sufficient single-cell and SRT pairs (SC–SP pairs) and providing real-time heuristic analysis, which hinder the effort to uncover potential biological insights. Here, we developed Pairpot (http://pairpot.bioxai.cn), a database tailored for paired single-cell and SRT data with real-time heuristic analysis. Pairpot curates 99 high-quality pairs including 1,425,656 spots from 299 datasets, and creates the association networks. It constructs the curated pairs by integrating multiple slices and establishing potential associations between single-cell and SRT data. On this basis, Pairpot adopts semi-supervised learning that enables real-time heuristic analysis for SC–SP pairs where Lasso-View refines the user-selected SRT domains within milliseconds, Pair-View infers cell proportions of spots based on user-selected cell types in real-time and Layer-View displays SRT slices using a 3D hierarchical layout. Experiments demonstrated Pairpot’s efficiency in identifying heterogeneous domains and cell proportions.
Diverse intrinsic properties shape transcript stability and stabilization in Mycolicibacterium smegmatis
Authors: Sun Huaming , Vargas-Blanco Diego A , Zhou Ying , Masiello Catherine S , Kelly Jessica M , Moy Justin K , Korkin Dmitry , Shell Scarlet S
Published: November 2024

Mycobacteria regulate transcript degradation to facilitate adaptation to environmental stress. However, the mechanisms underlying this regulation are unknown. Here we sought to gain understanding of the mechanisms controlling mRNA stability by investigating the transcript properties associated with variance in transcript stability and stress-induced transcript stabilization. We measured mRNA half-lives transcriptome-wide in Mycolicibacterium smegmatis in log phase growth and hypoxia-induced growth arrest. The transcriptome was globally stabilized in response to hypoxia, but transcripts of essential genes were generally stabilized more than those of non-essential genes. We then developed machine learning models that enabled us to identify the non-linear collective effect of a compendium of transcript properties on transcript stability and stabilization. We identified properties that were more predictive of half-life in log phase as well as properties that were more predictive in hypoxia, and many of these varied between leadered and leaderless transcripts. In summary, we found that transcript properties are differentially associated with transcript stability depending on both the transcript type and the growth condition. Our results reveal the complex interplay between transcript features and microenvironment that shapes transcript stability in mycobacteria.
Phase II trial of pathology-based tripartite treatment stratification for patients with CNS germ cell tumors: A long-term follow-up study
Authors: Takami Hirokazu , Matsutani Masao , Suzuki Tomonari , Takabatake Kazuhiko , Fujimaki Takamitsu , Okamoto Michinari , Yamaguchi Shigeru , Kanamori Masayuki , Matsuda Kenichiro , Sonoda Yukihiko , Natsumeda Manabu , Ichinose Toshiya , Nakada Mitsutoshi , Muroi Ai , Ishikawa Eiichi , Takahashi Masamichi , Narita Yoshitaka , Tanaka Shota , Saito Nobuhito , Higuchi Fumi , Shin Masahiro , Mineharu Yohei , Arakawa Yoshiki , Kagawa Naoki , Kawabata Shinji , Wanibuchi Masahiko , Takayasu Takeshi , Yamasaki Fumiyuki , Fujii Kentaro , Ishida Joji , Date Isao , Miyake Keisuke , Fujioka Yutaka , Kuga Daisuke , Yamashita Shinji , Takeshima Hideo , Shinojima Naoki , Mukasa Akitake , Asai Akio , Nishikawa Ryo
Published: November 2024

Background

A previous Phase II clinical trial, conducted from 1995 to 2003, evaluated CNS germ cell tumors (GCTs) using a three-group treatment stratification based on histopathology. The primary objective of the study was to assess the long-term efficacy of standardized treatment regimens, while the secondary objective focused on identifying associated long-term complications.

Methods

A total of 228 patients were classified into 3 groups for treatment: germinoma (n = 161), intermediate prognosis (n = 38), and poor prognosis (n = 28), excluding one mature teratoma case. Treatment involved stratified chemotherapy regimens and varied radiation doses/coverage. Clinical data was retrospectively analyzed at a median follow-up of 18.5 years.

Results

The treatment outcomes for germinoma, with or without syncytiotrophoblastic giant cells, were similar. The 10- and 20-year event-free survival rates for the germinoma, intermediate, and poor prognosis groups were 82/76/49% and 73/66/49%, respectively. Overall survival (OS) rates were 97/87/61% at 10 years and 92/70/53% at 20 years. Germinomas in the basal ganglia, treated without whole-brain radiation therapy (WBRT), frequently relapsed but were effectively managed with subsequent WBRT. Deaths in germinoma cases had varied causes, whereas deaths in the poor prognosis group were predominantly disease-related. Nineteen treatment-related complications were identified in 16 patients, with cumulative event rates of 1.9% at 10 years and 11.3% at 20 years. OS rates at 1 and 2 years post-relapse for tumors initially classified as germinoma, intermediate, and poor prognosis were 94/88/18% and 91/50/9%, respectively.

Conclusions

Initial treatment intensity is crucial for managing non-germinomatous GCTs, while long-term follow-up for relapse and complications is imperative in germinomas. Irradiation extending beyond the immediate tumor site is essential for basal ganglia germinomas. Addressing relapse in non-germinomatous GCT remains a significant challenge.
Systematic review and meta-analysis on the mental health of emergency and urgent call-handlers and dispatchers
Authors: Osório C , Talwar S , Stevelink S A M , Sihre H K , Lamb D , Billings J
Published: November 2024

Background

Call-handlers and dispatchers (CHDs) working in specialized emergency and urgent communication centres are essential in supporting public safety and health. Evidence suggests that these professionals are at increased risk of mental health conditions, including post-traumatic stress disorder (PTSD), depression, anxiety and alcohol abuse among other conditions; however, reliable prevalence estimates remain undetermined.

Aims

We provide the estimated pooled prevalence for PTSD, depression, anxiety and hazardous drinking among emergency and urgent CHDs globally.

Methods

We searched 10 electronic databases, grey literature and the Annals of Emergency Dispatch and Response. Eligible studies reported original quantitative data and used validated self-reported measures on the prevalence of mental health conditions of interest (i.e. PTSD, depression, anxiety and alcohol use) within CHD professionals. Three reviewers independently screened results for eligibility. Prevalence estimates were pooled using random-effects meta-analyses.

Results

In total, 16 857 references were retrieved. From these, 183 full-text articles were assessed for eligibility, of which 37 articles were included in this systematic review, and 13 articles provided necessary quantitative information for meta-analyses. In total, 7759 CHDs were considered across nine different countries. The overall pooled prevalence for PTSD was 17.8% (95% confidence interval [CI] 12.4−24.0%), depression was 28.2% (95% CI 20.7–36.2%), anxiety was 17.2% (95% CI 6.6–31.5%) and hazardous drinking was 17.8% (95% CI 6.9–32.2%).

Conclusions

These findings indicate CHDs are at significant risk of mental health problems. Further quantitative and qualitative research is warranted to help understand the psychological risks of working as a CHD and guide appropriate psychological support.
Galaxy morphologies revealed with Subaru HSC and super-resolution techniques. II. Environmental dependence of galaxy mergers at z ∼ 2–5
Authors: Shibuya Takatoshi , Ito Yohito , Asai Kenta , Kirihara Takanobu , Fujimoto Seiji , Toba Yoshiki , Miura Noriaki , Umayahara Takuya , Iwadate Kenji , Ali Sadman S , Kodama Tadayuki
Published: November 2024

We super-resolve the seeing-limited Subaru Hyper Suprime-Cam (HSC) images for 32187 galaxies at $z\sim 2$–5 using three techniques, namely, the classical Richardson–Lucy (RL) point spread function (PSF) deconvolution, sparse modeling, and generative adversarial networks, to investigate the environmental dependence of galaxy mergers. These three techniques generate overall similar high spatial resolution images but with some slight differences in galaxy structures; for example, more residual noises are seen in the classical RL PSF deconvolution. To alleviate the disadvantages of each technique, we create combined images by averaging over the three types of super-resolution images, resulting in galaxy substructures resembling those seen in the Hubble Space Telescope images. Using the combined super-resolution images, we measure the relative galaxy major merger fraction corrected for the chance projection effect, $f_{\rm merger}^{\rm rel,col}$, for galaxies in the $\sim$300 deg$^2$ area data of the HSC Strategic Survey Program and the CFHT Large Area U-band Survey. Our $f_{\rm merger}^{\rm rel,col}$ measurements at $z\sim 3$ validate previous findings showing that $f_{\rm merger}^{\rm rel,col}$ is higher in regions with a higher galaxy overdensity $\delta$ at $z\sim 2$–3. Thanks to the large galaxy sample, we identify a nearly linear increase in $f_{\rm merger}^{\rm rel,col}$ with increasing $\delta$ at $z\sim 4$–5, providing the highest-z observational evidence that galaxy mergers are related to $\delta$. In addition to our $f_{\rm merger}^{\rm rel,col}$ measurements, we find that the galaxy merger fractions in the literature also broadly align with the linear $f_{\rm merger}^{\rm rel,col}$–$\delta$ relation across a wide redshift range of $z\sim 2$–5. This alignment suggests that the linear $f_{\rm merger}^{\rm rel,col}$–$\delta$ relation can serve as a valuable tool for quantitatively estimating the contributions of galaxy mergers to various environmental dependences. This super-resolution analysis can be readily applied to datasets from wide field-of-view space telescopes such as Euclid and Roman.
A seed-specific DNA-binding with One Finger transcription factor, RPBF, positively regulates galactinol synthase to maintain seed vigour in rice
Authors: Sonowal Kaberi , Gandass Nishu , Kamble Nitin Uttam , Mehta Kritika , Pandey Ajay Kumar , Salvi Prafull
Published: November 2024

Seed vigour and longevity are intricate yet indispensable physiological traits for agricultural crops, as they play a crucial role in facilitating the successful emergence of seedlings and exert a substantial influence on crop productivity. Transcriptional regulation plays an important role in seed development, maturation, and desiccation tolerance, which are important attributes for seed vigour and longevity. Here, we have investigated the regulatory role of the seed-specific DNA-binding with One Finger (DOF) transcription factor and the rice prolamin box binding factor (RPBF) in seed vigour. RPBF modulates the transcription of galactinol synthase (GolS) and improves seed vigour. The promoter region of GolS-encoding genes from different species was enriched with DOF-binding sites, and the expression levels of both RPBF; OsGolS were found to enhance during seed development. Furthermore, direct interaction of RPBF with the OsGolS promoter has been demonstrated through multiple approaches: yeast one-hybrid assays, in planta promoter–GUS assays, dual luciferase assay, and in silico molecular docking. To assess functionality, Agrobacterium-mediated genetic transformation of rice was performed to generate the RNAi lines with reduced RPBF expression. In these RNAi lines, a reduction in both galactinol and raffinose content was observed. Since galactinol and raffinose are known contributors to seed vigour, the T2-transgenic lines were assessed for vigour and viability. For this, RNAi seeds were subjected to accelerated ageing by exposing them to high relative humidity and temperature, followed by scoring the germination and viability potential. Tetrazolium and seed germination assay revealed that the RNAi seeds were more sensitive to ageing compared to their wild-type and vector control counterparts. Collectively, this is the first report demonstrating that the DOF transcription factor RPBF controls the seed vigour through transcriptional regulation of GolS.
Jasmonate induces translation of the Arabidopsis transfer RNA-binding protein YUELAO1, which activates MYC2 in jasmonate signaling
Authors: Wang Jiahui , Li Yuanyuan , Hu Yanru , Zhu Sirui
Published: November 2024

Jasmonate is ubiquitous in the plant kingdom and regulates multiple physiological processes. Although jasmonate signaling has been thoroughly investigated in Arabidopsis thaliana, most studies have focused on the transcriptional mechanisms underlying various jasmonate responses. It remains unclear whether (and how) translation-related pathways help improve transcription efficiency to modulate jasmonate signaling, which may enable plants to respond to stressful conditions effectively. Here, we demonstrate that jasmonate induces translation of the transfer RNA (tRNA)-binding protein YUELAO 1 (YL1) via a specific region in its 3′ untranslated region (3′ UTR). YL1 and its homolog YL2 redundantly stimulate jasmonate responses such as anthocyanin accumulation and root growth inhibition, with the YL1 3′ UTR being critical for YL1-promoted jasmonate responses. Once translated, YL1 acts as an activator of the MYC2 transcription factor through direct interaction, and disrupting YL1 3′ UTR impairs the YL1-mediated transcriptional activation of MYC2. YL1 enhances jasmonate responses mainly in a MYC2-dependent manner. Together, these findings reveal a translational mechanism involved in jasmonate signaling and advance our understanding of the transcriptional regulation of jasmonate signaling. The YL1 3′ UTR acts as a crucial signal transducer that integrates translational and transcriptional regulation, allowing plants to respond to jasmonate in a timely fashion.
The NIH HEAL pain common data elements (CDE): a great start but a long way to the finish line
Authors: Adams Meredith C B , Hassett Afton L , Clauw Daniel J , Hurley Robert W
Published: November 2024

Background

The National Institutes of Health (NIH) Pain Common Data Elements (CDEs) provide a standardized framework for pain research, but their implementation and interpretation present challenges.

Objectives

To review the NIH CDE Program’s selected pain domains, provide best practices for implementing required questions, and offer a checklist for appropriate CDE use in clinical trials and secondary data analysis. This work analyzed the 10 core pain research domains selected by the NIH CDE Program and discuss their limitations and considerations for use.

Results

The manuscript provides an overview of the 10 core pain research domains, including pain intensity, interference, physical function, sleep, catastrophizing, depression, anxiety, global impression of change, substance use screening, and quality of life. It offers sample scenarios for implementing required questions and presents a checklist to guide researchers in using pain CDEs effectively for clinical trials and secondary data analysis.

Conclusion

Key challenges identified include contextual variability, lack of validation across all pain conditions and populations, and potential misuse or misinterpretation of measures. This work proposes solutions such as supplementary measures, context-specific guidance, comprehensive training programs, and ongoing refinement of the CDE framework. While NIH Pain CDEs are valuable tools for standardizing pain assessment in research, addressing challenges in their implementation and interpretation is crucial for improving the consistency, validity, and interpretability of pain research data, ultimately advancing the field and enhancing patient care.
Deep learning assessment of disproportionately enlarged subarachnoid-space hydrocephalus in Hakim’s disease or idiopathic normal pressure hydrocephalus
Authors: Yamada Shigeki , Ito Hirotaka , Iseki Chifumi , Kondo Toshiyuki , Yamanaka Tomoyasu , Tanikawa Motoki , Otani Tomohiro , Ii Satoshi , Ohta Yasuyuki , Watanabe Yoshiyuki , Wada Shigeo , Oshima Marie , Mase Mitsuhito
Published: November 2024

Background

Disproportionately enlarged subarachnoid-space hydrocephalus (DESH) is a key feature of Hakim’s disease (synonymous with idiopathic normal pressure hydrocephalus; iNPH). However, it previously had been only subjectively evaluated.

Purpose

This study aims to evaluate the usefulness of MRI indices, derived from deep learning segmentation of cerebrospinal fluid (CSF) spaces, for DESH detection and to establish their optimal thresholds.

Materials and Methods

This study retrospectively enrolled a total of 1009 participants, including 77 patients diagnosed with Hakim’s disease, 380 healthy volunteers, 163 with mild cognitive impairment, 256 with Alzheimer’s disease, and 217 with other types of neurodegenerative diseases. DESH, ventriculomegaly, tightened sulci in the high convexities, and Sylvian fissure dilatation were evaluated on three-dimensional T1-weighted MRI by radiologists. The total ventricles, high-convexity part of the subarachnoid space, and Sylvian fissure and basal cistern were automatically segmented using the CSF Space Analysis application (FUJIFILM Corporation). Moreover, DESH, Venthi, and Sylhi indices were calculated based on these 3 regions. The area under the receiver-operating characteristic curves of these indices and region volumes (volume ratios) for DESH detection were calculated.

Results

Of the 1009 participants, 101 (10%) presented with DESH. The DESH, Venthi, and Sylhi indices performed well with 95.0%-96.0% sensitivity and 91.5%-96.8% specificity at optimal thresholds. All patients with Hakim’s disease were diagnosed with DESH, despite variations in severity. In patients with Hakim’s disease, with or without Alzheimer’s disease, the DESH index and total ventricular volume were significantly higher compared to patients with Alzheimer’s disease, although the total intracranial cerebrospinal fluid volume was significantly lower.

Conclusion

DESH, Venthi, and Sylhi indices, and the volumes and volume ratios of the ventricle and high-convexity part of the subarachnoid space computed using deep learning were useful for the DESH detection that may help to improve the diagnosis of Hakim’s disease (ie, iNPH).
Telitacicept add-on therapy in refractory idiopathic inflammatory myopathy: insights from a pilot study
Authors: Gao Huajie , Lin Jing , Yang Mengge , Gui Mengcui , Ji Suqiong , Bu Bitao , Li Yue
Published: November 2024

Objectives

This study aimed to evaluate the therapeutic efficacy of telitacicept based on the conventional treatment in adults with idiopathic inflammatory myopathy (IIM), focusing on its impact on clinical manifestations.

Methods

IIM patients who had been treated with telitacicept for at least 3 months based on the conventional treatment from January 2023 to January 2024 were included in this study. The clinical response to telitacicept was determined based on the ACR/EULAR criteria for minimal, moderate and major improvement in the Total Improvement Score. Disease activity was monitored using core set measures, while myositis damage was assessed with established assessment tools. The Manual Muscle Test for eight muscle groups (MMT-8) was used to assess the muscle performance.

Results

A total of 11 patients administered with telitacicept (160 mg per week) were included in this study. Post-treatment assessments revealed improvements in all patients according to ACR/EULAR criteria. Notably, there was a significant reduction in the prednisone dosage from baseline to last visit [27.05 (12.47) to 12.05 (7.32) mg; P < 0.005]. An enhancement was observed in the MMT-8 score [which improved from 109.18 (14.18) to 137.64 (15.28); P < 0.005], and there was a reduction in creatine kinase level [from 2670.27 (2675.00) to 561.09 (754.09) U/l; P < 0.05].

Conclusion

Telitacicept demonstrated effectiveness in treating refractory inflammatory myopathy, contributing to a significant reduction in steroid dosage among the patients. These findings highlight the potential of telitacicept as a valuable therapeutic option in the management of IIM.
Impact of structural severity on outcomes in knee osteoarthritis: an analysis of data from phase 2 and phase 3 lorecivivint clinical trials
Authors: Tambiah Jeyanesh , Kennedy Sarah , Swearingen Christopher , McAlindon Timothy , Yazici Yusuf
Published: November 2024

Objective

Developing knee osteoarthritis (OA) treatments is challenging due to assessing pain and joint structure outcomes within a highly heterogeneous disease. Lorecivivint (LOR), an intra-articular CLK/DYRK inhibitor, modulates Wnt and inflammatory pathways. This review analysis of LOR 0.07 mg trial data aims to describe the potential impact of baseline joint structure on OA pain response.

Methods

Two Phase 2 and two Phase 3 trials enrolled knee OA patients with Kellgren-Lawrence (KL) Grades 2–3 and Pain Numeric Rating Scale [NRS (0–10)] ≥ 4 to ≤8 in their target knee. Cumulative frequency distribution plots by KL grade summarized the percentages of patients with medial joint space width (medial JSW) < 3 mm. Osteoarthritis Research Society International Joint Space Narrowing grades and treatment responses in trials capturing Pain NRS were similarly summarized. Pain outcome changes were estimated using baseline adjusted ANCOVA.

Results

Compared with phase 2 trials, the phase 3 trials had an increased proportion of patients with baseline medial JSW <3 mm. LOR demonstrated beneficial treatment effects vs placebo in KL 2 subgroups, which were found to have higher proportions of baseline medial JSW >3 mm, apart from one Phase 3 trial with advanced structural knee OA.

Conclusion

Baseline medial JSWs were heterogeneous across trials despite KL inclusion criteria. LOR demonstrated greater symptomatic improvements in patients with less structurally advanced disease, indicative of an association between OA structural damage and pain. Early treatment interventions may improve outcomes and provide insight for future OA trial inclusion criteria development.

Trial registration

OA-02, NCT02536833; OA-04, NCT03122860; OA-10, NCT04385303; OA-11, NCT03928184.
The lasting legacy of Charles Fisher (1908–1988), pioneering sleep laboratory scientist and sleep medicine psychiatrist
Authors: Schenck Carlos H , Provini Federica , Eiser Alan S
Published: November 2024

Charles Fisher is a pioneering historical figure in sleep laboratory research and sleep medicine who distinguished himself in nine areas: (1) he first documented nocturnal sleep-onset rapid eye movement (REM) sleep periods in narcoleptic patients; (2) he published the first case of polysomnography (PSG) documented acute REM sleep behavior disorder (RBD) that was triggered by sudden withdrawal from a monoamine oxidase inhibitor in 1978, 8 years before the formal identification of RBD; (3) he worked with Roffwarg and Dement on the early delineation of the ontogeny of the human sleep cycle; (4) he first demonstrated that benzodiazepine (diazepam) therapy was effective in controlling night terrors together with suppression of stage 4 non-rapid eye movement (NREM) sleep, and he was also an early investigator of night terrors as phenomena emerging from stage 4 NREM sleep, without dreaming, as had been traditionally assumed; (5) he collaborated with another pioneering sleep medicine physician, William C. Dement on studies focused on REM sleep deprivation and dreaming at Fisher’s Mt. Sinai Hospital sleep laboratory in New York City; (6) he published the first PSG-documented case of sleep-related (psychogenic) dissociative disorder in 1976; (7) he first documented that typical nightmares (“anxiety dreams”) occurred during REM sleep; (8) he conducted some of the earliest research, beginning in 1965, that documented cycles of nocturnal penile tumescence emerging in conjunction with REM sleep cycles; and (9) he conducted similar early studies of female sexual arousal during sleep that occurred predominantly in REM sleep.
HSP70 promotes amino acid‐dependent mTORC1 signaling by mediating CHIP‐induced NPRL2 ubiquitination and degradation
Authors: Gao Jianfang , Lin Mingjun , Qing Jina , Li Hongxia , Zeng Xiao , Yuan Wuzhou , Li Tingting , He Shanping
Published: November 2024

Mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth and its dysregulation leads to a variety of human diseases. Although NPRL2, an essential component of the GATOR1 complex, is reported to effectively suppress amino acid‐induced mTORC1 activation, the regulation of NPRL2 protein stability is unclear. In this study, we show that chaperon‐associated ubiquitin ligase CHIP interacts with NPRL2 and promotes its polyubiquitination and proteasomal degradation. Moreover, HSP70 mediates CHIP‐induced ubiquitination and degradation of NPRL2. Consistently, overexpression of HSP70 enhances whereas HSP70 depletion inhibits amino acid‐induced mTORC1 activation. Accordingly, knockdown of HSP70 promotes basal autophagic flux, and inhibits cell growth and proliferation. Taken together, these results demonstrated that HSP70 is a novel activator of mTORC1 through mediating CHIP‐induced ubiquitination and degradation of NPRL2.