bluuebunny/crossref_metadata_2025_split huggingface dataset:
The phage protein paratox is a multifunctional metabolic regulator of Streptococcus
Authors: Muna Tasneem Hassan , Rutbeek Nicole R , Horne Julia , Lao Ying W , Krokhin Oleg V , Prehna Gerd 
Published: December 2024

Abstract
Streptococcus pyogenes, or Group A Streptococcus (GAS), is a commensal bacteria and human pathogen. Central to GAS pathogenesis is the presence of prophage encoded virulence genes. The conserved phage gene for the protein paratox (Prx) is genetically linked to virulence genes, but the reason for this linkage is unknown. Prx inhibits GAS quorum sensing and natural competence by binding the transcription factor ComR. However, inhibiting ComR does not explain the virulence gene linkage. To address this, we took a mass spectrometry approach to search for other Prx interaction partners. The data demonstrates that Prx binds numerous DNA-binding proteins and transcriptional regulators. We show binding of Prx in vitro with the GAS protein Esub1 (SpyM3_0890) and the phage protein JM3 (SpyM3_1246). An Esub1:Prx complex X-ray crystal structure reveals that Esub1 and ComR possess a conserved Prx-binding helix. Computational modelling predicts that the Prx-binding helix is present in several, but not all, binding partners. Namely, JM3 lacks the Prx-binding helix. As Prx is conformationally dynamic, this suggests partner-dependent binding modes. Overall, Prx acts as a metabolic regulator of GAS to maintain the phage genome. As such, Prx maybe a direct contributor to the pathogenic conversion of GAS.
SLAM-seq reveals independent contributions of RNA processing and stability to gene expression in African trypanosomes
Authors: Luzak Vanessa , Osses Esteban , Danese Anna , Odendaal Christoff , Cosentino Raúl O , Stricker Stefan H , Haanstra Jurgen R , Erhard Florian , Siegel T Nicolai 
Published: December 2024

Abstract
Gene expression is a multi-step process that converts DNA-encoded information into proteins, involving RNA transcription, maturation, degradation, and translation. While transcriptional control is a major regulator of protein levels, the role of post-transcriptional processes such as RNA processing and degradation is less well understood due to the challenge of measuring their contributions individually. To address this challenge, we investigated the control of gene expression in Trypanosoma brucei, a unicellular parasite assumed to lack transcriptional control. Instead, mRNA levels in T. brucei are controlled by post-transcriptional processes, which enabled us to disentangle the contribution of both processes to total mRNA levels. In this study, we developed an efficient metabolic RNA labeling approach and combined ultra-short metabolic labeling with transient transcriptome sequencing (TT-seq) to confirm the long-standing assumption that RNA polymerase II transcription is unregulated in T. brucei. In addition, we established thiol (SH)-linked alkylation for metabolic sequencing of RNA (SLAM-seq) to globally quantify RNA processing rates and half-lives. Our data, combined with scRNA-seq data, indicate that RNA processing and stability independently affect total mRNA levels and contribute to the variability seen between individual cells in African trypanosomes.
Pediatric brain tumor classification using deep learning on MR images with age fusion
Authors: Tampu Iulian Emil , Bianchessi Tamara , Blystad Ida , Lundberg Peter , Nyman Per , Eklund Anders , Haj-Hosseini Neda 
Published: December 2024

Abstract

Purpose
To implement and evaluate deep learning-based methods for the classification of pediatric brain tumors (PBT) in magnetic resonance (MR) data.

Methods
A subset of the “Children’s Brain Tumor Network” dataset was retrospectively used (n = 178 subjects, female = 72, male = 102, NA = 4, age range [0.01, 36.49] years) with tumor types being low-grade astrocytoma (n = 84), ependymoma (n = 32), and medulloblastoma (n = 62). T1w post-contrast (n = 94 subjects), T2w (n = 160 subjects), and apparent diffusion coefficient (ADC: n = 66 subjects) MR sequences were used separately. Two deep learning models were trained on transversal slices showing tumor. Joint fusion was implemented to combine image and age data, and 2 pre-training paradigms were utilized. Model explainability was investigated using gradient-weighted class-activation mapping (Grad-CAM), and the learned feature space was visualized using principal component analysis (PCA).

Results
The highest tumor-type classification performance was achieved when using a vision transformer model pre-trained on ImageNet and fine-tuned on ADC images with age fusion (Matthews correlation coefficient [MCC]: 0.77 ± 0.14, Accuracy: 0.87 ± 0.08), followed by models trained on T2w (MCC: 0.58 ± 0.11, Accuracy: 0.73 ± 0.08) and T1w post-contrast (MCC: 0.41 ± 0.11, Accuracy: 0.62 ± 0.08) data. Age fusion marginally improved the model’s performance. Both model architectures performed similarly across the experiments, with no differences between the pre-training strategies. Grad-CAMs showed that the models’ attention focused on the brain region. PCA of the feature space showed greater separation of the tumor-type clusters when using contrastive pre-training.

Conclusion
Classification of PBT on MR images could be accomplished using deep learning, with the top-performing model being trained on ADC data, which radiologists use for the clinical classification of these tumors.
Neuroimaging of postoperative pediatric cerebellar mutism syndrome: a systematic review
Authors: Obdeijn Iris V , van Baarsen Kirsten M , Avula Shivaram , Toescu Sebastian , Lequin Maarten H , Hoving Eelco W , Partanen Marita 
Published: December 2024

Abstract

Background
Postoperative pediatric cerebellar mutism syndrome (ppCMS) poses serious morbidity after posterior fossa tumor surgery. Neuroimaging studies aim to understand its pathophysiology, yet these vary in methodology and outcome measures. Therefore, we systematically reviewed the current literature to evaluate the evidence for differences in neuroimaging features between children with and without ppCMS.

Methods
Following PRISMA guidelines, a systematic review was conducted by searching for original articles on neuroimaging in children undergoing posterior fossa tumor surgery, comparing patients with and without ppCMS. Articles were selected based on predefined eligibility criteria. Data were systematically extracted, and risk of bias was evaluated.

Results
From the 866 articles identified, 50 studies fulfilled the inclusion criteria. Studies were categorized into 3 imaging domains: structural, diffusion, and functional imaging. Risk of bias assessment revealed a medium risk in most articles, predominantly due to unclear ppCMS definition and qualitative image analysis without blinding for ppCMS diagnosis. Preoperative structural imaging showed the association of ppCMS with midline tumor localization and involvement of the brainstem, superior cerebellar peduncle (SCP), or middle cerebellar peduncle. Postoperative structural and diffusion imaging highlighted SCP injury with reduced white matter integrity, while functional imaging demonstrated hypoperfusion in frontal lobes. Late follow-up showed T2-weighted hyperintensities in the inferior olivary nuclei of ppCMS patients.

Conclusion
Neuroimaging features suggest that ppCMS is associated with efferent cerebellar pathway injury and hypoperfusion in frontal lobes, with level 2 a/b evidence. Large-scale prospective longitudinal neuroimaging studies comparing pre- and postoperative imaging are needed to further elucidate the pathophysiological mechanism of ppCMS.
How do I prescribe and manage mIDH inhibitors in patients with IDH-mutant glioma?
Authors: Still Megan E H , Moor Rachel S F , Ghiaseddin Ashley P , Leibetseder Annette , Hottinger Andreas F , Berghoff Anna , Leung Denise 
Published: December 2024

Abstract
Recent interest has been in using mIDH inhibitors in patients with IDH-mutant gliomas. This review paper summarizes the indications, side effects, recommended dosing, and management for patients on ivosidenib and vorasidenib.
An evidence-based framework for postoperative surveillance of meningioma
Authors: Owusu-Adjei Brittany , Lim Jeewoo C , Hou Connie C , Mietus Constance J , Daci Rrita , Lambert William , Qureshi Hanya , Berry Bethany C , Marasco Madison R B , Paul Umika , Sirianni Rachael W , Johnson Mark D 
Published: December 2024

Abstract

Background
Meningiomas frequently recur after surgery. Existing guidelines for postoperative surveillance are based on customary practices or limited data. This may result in excessive or inadequate surveillance.

Methods
We compared 8 studies involving 1519 resected meningiomas with postoperative follow-up ranging from 7 to 23 years. Meningiomas were stratified using the World Health Organization and Simpson grading systems, and progression-free survival data were compared. Recurrence patterns were validated using 2 additional studies involving 2463 meningiomas.

Results
Incompletely resected meningiomas of all grades displayed recurrences throughout the observation period. The 5-year and 10-year cumulative incidence of recurrence for completely resected Grade 1 meningiomas was 10% and 20%, with no recurrences beyond 11 years. For completely resected Grade 2 meningiomas, the 5-year and 10-year cumulative incidence of recurrence was 24% and 50%, with ongoing recurrences throughout the observation period. Elevated recurrence rates for Grade 1/2 meningiomas persisted beyond 5 years. For completely resected Grade 3 meningiomas, the 5-year cumulative incidence of recurrence was 63%, and all recurred before 10 years.

Conclusions
Postoperative magnetic resonance imaging (MRI) at 48 h to determine the extent of resection and at 4 months to detect rapid regrowth is recommended. For completely resected Grade 1 meningiomas, annual MRI followed by discontinuation of surveillance if there is no recurrence after 11 years is reasonable. For completely resected Grade 2 meningiomas, annual MRI indefinitely is recommended. For Grade 3 meningiomas, MRI every 3-4 months for 2 years, followed by every 6 months indefinitely, is recommended. Incompletely resected meningiomas should be followed indefinitely.
Risk factors for type I leptomeningeal metastasis derived from non-small cell lung cancer and the impact of treatment for brain metastases on its development
Authors: Iuchi Toshihiko , Shingyoji Masato , Mizuno Satoko , Ashinuma Hironori , Hasegawa Yuzo , Setoguchi Taiki , Hosono Junji , Sakaida Tsukasa 
Published: December 2024

Abstract

Background
Preventing Type I leptomeningeal metastasis (LM) is critical when treating brain metastases (BMs). The aim of this study was to extract risk factors for Type I LM and to clarify the optimal treatment for BMs from the perspective of Type I LM prevention.

Methods
The clinical course of consecutive cases of BMs derived from non-small cell lung cancer (NSCLC) treated at our hospital was retrospectively evaluated. The relationship between clinicopathological factors, including molecular background, and Type I LM development was verified. In addition, the difference in the time to Type I LM because of treatment for BMs was evaluated to clarify the effectiveness of each treatment in preventing Type I LM.

Results
Of 784 patients with BMs, 44 exhibited Type I LM at the onset of BMs. Poor performance status (P &lt; .0001) and mutated epidermal growth factor receptor (EGFR) gene (P = .004) were significant risk factors for Type I LM. Among the 740 patients without LMC at diagnosis, 85 developed Type I LM. Younger age (P = .011) and mutated EGFR (P &lt; .0001) were risk factors for developing LMC after BMs. Osimertinib reduced the incidence of Type I LM (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.24-0.97) in EGFR-mutated cases. Immune checkpoint inhibitors (ICIs) showed a tendency to prolong the time to Type I LM (HR: 0.15; 95% CI: 0.02-1.11) in EGFR-wild-type cases.

Conclusions
Patients with EGFR-mutated NSCLC are prone to developing Type I LM. Osimertinib for EGFR-mutated cases and ICIs are expected to prevent Type I LM after the diagnosis of BMs.
Cascade specific endogenous Fe3+ interference and in situ catalysis for tumor therapy with stemness suppression
Authors: Chen Jiajie , Wang Yitong , Huang Jian , Yang Zhibo , Niu Huicong , Su Xiaolian , Huang Jimin , Ma Hongshi , Zhu Yufang , Wu Chengtie , Shi Jianlin 
Published: December 2024

ABSTRACT
Cancer stem-like cells (CSCs), featuring high tumorigenicity and invasiveness, are one of the critical factors leading to the failure of clinical cancer treatment such as metastasis and recurrence. However, current strategies suffer from the low stemness-inhibiting efficacy on CSCs by conventional molecular agents and the poor lethal effects against bulk tumor cells. Here we engineer a coordination nanomedicine by 2,5-dihydroxyterephthalic acid (DHT) complexing zinc ions (Zn2+) as a double-effect nanodisrupter of tumor iron (Fe) and redox homeostasis for catalysis-boosted tumor therapy with stemness inhibition. Taking advantage of the much higher binding force of DHT toward Fe3+, this nanomedicine can specifically chelate endogenous Fe3+ into its nanostructure and release Zn2+, and the in situ formed hexacoordinated Fe-DHT conformation is of much enhanced reducibility in order to promote reactive oxygen species (ROS) production in tumors. The nanomedicine-mediated Fe depletion and ROS generation collectively induce CSC differentiation via downregulating the Wnt signaling and inducing forkhead box O3 (FoxO3) activation, respectively. Notably, the combined tumor-selective ROS generation and Zn2+-induced antioxidation dysfunction potently trigger intratumoral oxidative damage leading to both cellular apoptosis and ferroptosis. This nanomedicine, capable of synchronously treating CSCs and bulk tumor cells, has been demonstrated to effectively inhibit the growth, postoperative recurrence and metastasis of orthotopic triple-negative breast tumors in vivo, offering an encouraging candidate of cancer therapeutic agents for treating CSCs-enriched malignancy.
Constructing new-generation ion exchange membranes under confinement regime
Authors: Li Xingya , Zuo Peipei , Ge Xiaolin , Yang Zhengjin , Xu Tongwen 
Published: December 2024

ABSTRACT
Ion exchange membranes (IEMs) enable fast and selective ion transport and the partition of electrode reactions, playing an important role in the fields of precise ion separation, renewable energy storage and conversion, and clean energy production. Traditional IEMs form ion channels at the nanometer-scale via the assembly of flexible polymeric chains, which are trapped in the permeability/conductivity and selectivity trade-off dilemma due to a high swelling propensity. New-generation IEMs have shown great potential to break this intrinsic limitation by using microporous framework channels for ion transport under a confinement regime. In this Review, we first describe the fundamental principles of ion transport in charged channels from nanometer to sub-nanometer scale. Then, we focus on the construction of new-generation IEMs and highlight the microporous confinement effects from sub-2-nm to sub-1-nm and further to ultra-micropores. The enhanced ion transport properties brought by the intense size sieving and channel interaction are elucidated, and the corresponding applications including lithium separation, flow battery, water electrolysis, and ammonia synthesis are introduced. Finally, we prospect the future development of new-generation IEMs with respect to the intricate microstructure observation, in-situ ion transport visualization, and large-scale membrane fabrication.
Principle-based adept predictions of global warming from climate mean states
Authors: Cai Ming , Hu Xiaoming , Sun Jie , Hu Yongyun , Liu Guosheng , Wu Zhaohua , Ding Feng , Kang Wanying 
Published: December 2024

ABSTRACT
Distinguishing anthropogenic warming from natural variability and reducing uncertainty in global-warming projections continue to present challenges. Here, we introduce a novel principle-based framework for predicting global warming from climate mean states that is based solely on carbon-dioxide-increasing scenarios without running climate models and relying on statistical trend analysis. By applying this framework to the climate mean state of 1980–2000, we accurately capture the subsequent global warming (0.403 K predicted versus 0.414 K observed) and polar warming amplification patterns. Our predictions from climate mean states of individual models not only exhibit a high map-correlation skill that is comparable to that of individual Coupled Model Intercomparison Project Phase 6 models for the observed warming, but also capture the temporal pace of their warming under the 1% annual CO2-increasing scenario. This work provides the first principle-based confirmation that anthropogenic greenhouse gases are the primary cause of the observed global warming from 1980–2000 to 2000–2020, independently of climate models and statistical analysis.
Long COVID in healthcare workers: longitudinal mixed-methods study
Authors: Grant A , Adams N N , MacIver E , Skåtun D , Scott N , Kennedy C , Douglas F , Hernandez-Santiago V , Torrance N 
Published: December 2024

Abstract

Background
Healthcare workers (HCWs) report higher rates of long coronavirus disease (COVID) (LC) than other occupational groups. It is still unclear whether LC is a lifelong condition. Workforce shortfalls are apparent due to sick leave, reduced hours and lower productivity.

Aims
To investigate the lived experience of LC on a range of HCWs, including impact on health-related quality-of-life (HRQL), use of health services, working and personal lives and household finances.

Methods
Longitudinal mixed methods with online surveys and qualitative interviews 6-months apart. HCWs including healthcare professionals, ancillary and administration staff who self-report LC were recruited through social media and National Health Service channels. Interviewees were purposively sampled from survey responses.

Results
The first survey was completed by 471 HCWs (S1) and 302 (64%) the follow-up (S2). A total of 50 HCWs were interviewed initially and 44 at second interview. All participants experienced various relapsing, remitting, changing and prolonged LC symptoms (mean 7.1 [SD 4.8] at S2) and a third reported day-to-day activities ‘limited a lot’. Most participants were working in a reduced capacity: reduced hours, different role or location. Healthcare was limited, and often unsatisfactory. Participants feared reinfection, their future, ability to work and financial security (59% (n = 174) at S2). They experienced stigma, distress, grief for their former self and some felt unsupported, however, as awareness of LC grew some experienced improved understanding and support.

Conclusions
Most participants continued working, managing complex and dynamic symptoms effecting their everyday life and ability to work. Most did not report significant improvements over time and feared for their future and financial security.
Utility of 18F-Fluorodeoxyglucose Positron Emission Tomography in Evaluating Disseminated Nontuberculous Mycobacterial Infection in Patients With Anti-interferon-γ Autoantibodies
Authors: Chuang Pei-Ju , Lan Wei-Cheng , Cheng Mei-Fang , Huang Chun-Kai , Hong Tzu-Chan , Lin Chi-Ying , Huang Yu-Shan , Chen Pao-Yu , Wu Un-In , Wang Jann-Tay , Sheng Wang-Huei , Chen Yee-Chun , Chang Shan-Chwen 
Published: December 2024

Abstract

Background
Managing disseminated nontuberculous mycobacterial (NTM) infection in patients with neutralizing anti-interferon-γ autoantibodies (AIGAs) poses substantial challenges due to the lack of established treatment guidance and predictive tools for clinical outcomes. In this study, we investigated the utility of 18F-fluorodeoxyglucose (2-[18F]FDG) positron emission tomography (PET) in guiding treatment decisions, with a focus on its ability to predict rehospitalization outcomes.

Methods
We conducted a post hoc analysis of the first available 2-[18F]FDG PET scans of patients with AIGAs and disseminated NTM infection from a prospective observational multicenter cohort. Cox proportional hazards regression was used to determine predictors for disease-related rehospitalization within 1 year of the examination.

Results
Of the patients with AIGAs evaluated, 41.9% required rehospitalization within 1 year following the initial 2-[18F]FDG PET evaluation. Slowly growing mycobacteria were isolated in 64.5% of patients. Multivariable analysis identified splenic involvement (adjusted hazard ratio, 7.97; 95% CI, 2.34–27.16; P &lt; .001) as a significant predictor of disease-related rehospitalization within 1 year following the examination. Moreover, mediastinal node involvement (adjusted odds ratio, 14.77; 95% CI, 1.01–216.76; P = .049) and axial skeleton involvement (adjusted odds ratio, 14.93; 95% CI, 1.11–201.43; P = .042) were significantly associated with the isolation of slowly growing mycobacteria.

Conclusions
2-[18F]FDG PET appears useful in initial evaluation of disease extent and microbiology in patients with AIGAs and disseminated NTM infection. Identifying splenic involvement through this modality may help recognize patients at increased risk of disease-related rehospitalization within 1 year. These findings suggest that 2-[18F]FDG PET could inform management decisions in this challenging population.
Long-term Risk of Infection Among Patients Colonized With Antimicrobial-Resistant Pathogens: A Population-wide Cohort Study
Authors: Blagojevic Christina , Brown Kevin A , Diong Christina , Fridman Daniel J , Johnstone Jennie , Langford Bradley J , Lee Samantha M , MacFadden Derek R , Schwartz Kevin L , Daneman Nick 
Published: December 2024

Abstract

Background
Antimicrobial-resistant (AMR) pathogens represent an ongoing global health burden. Colonization is often a prerequisite for infection, but the risk of infection after AMR colonization is not well understood. Using population-level health administrative data, we sought to investigate the risk of infection with the same AMR organism after detection of colonization.

Methods
We conducted a retrospective population-wide cohort study among residents of Ontario, Canada, over a 5-year period to determine the risk of infection after detection of colonization with the following AMR pathogens: methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, extended-spectrum β-lactamase–producing Enterobacterales, and carbapenemase-producing Enterobacterales. We also examined the effects of age, sex, and health care setting of colonization detection on subsequent infection risk.

Results
There were 69 998 individuals with a positive AMR pathogen surveillance test result during the study period, 15.6% of which subsequently developed a sterile or nonsterile site infection within a median 57 days (IQR, 11–228). Infection rates varied among organisms: 18.3% for methicillin-resistant S aureus within a median 57 days (IQR, 10–239), 2.8% for vancomycin-resistant Enterococcus within a median 37 days (IQR, 11–119), 21.5% for extended-spectrum β-lactamase–producing Enterobacterales within a median 71 days (IQR, 18–231), and 20.3% for carbapenemase-producing Enterobacterales within a median 10 days (IQR, 3–42). A positive surveillance test result detected in a hospital was associated with increased infection risk after colonization as compared with the community setting.

Conclusions
The overall infection rate after colonization with an AMR pathogen was high for most organisms, highlighting the importance of detecting colonization from both an infection control and empiric antibiotic selection perspective.