bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel molecular subtypes of intracranial germ cell tumors expand therapeutic opportunities
Authors: Li Bo , Zhao Shuang , Li Shouwei , Li Chunde , Liu Wei , Li Lin , Cui Bowen , Liu Xing , Chen Huiyuan , Zhang Jing , Ren Yin , Liu Fei , Yang Ming , Jiang Tao , Liu Yu , Qiu Xiaoguang 
Published: March 2024

Abstract

Background
Intracranial germ cell tumors (IGCTs) are a rare group of malignancies that are clinically classified as germinomas and nongerminomatous germ cell tumors (NGGCTs). Previous studies have found that somatic mutations involving the mitogen-activated protein kinase/mTOR signaling pathway are common early events. However, a comprehensive genomic understanding of IGCTs is still lacking.

Methods
We established a cohort including over 100 IGCTs and conducted genomic and transcriptomic sequencing.

Results
We identified novel recurrent driver genomic aberrations, including USP28 truncation mutations and high-level copy number amplification of KRAS and CRKL caused by replication of extrachromosomal DNA. Three distinct subtypes associated with unique genomic and clinical profiles were identified with transcriptome analysis: Immune-hot, MYC/E2F, and SHH. Both immune-hot and MYC/E2F were predominantly identified in germinomas and shared similar mutations involving the RAS/MAPK signaling pathway. However, the immune-hot group showed an older disease onset age and a significant immune response. MYC/E2F was characterized by a younger disease onset age and increased genomic instability, with a higher proportion of tumors showing whole-genome doubling. Additionally, the SHH subtype was mostly identified in NGGCTs.

Conclusions
Novel genomic aberrations and molecular subtypes were identified in IGCTs. These findings provide molecular basis for the potential introduction of new treatment strategies in this setting.
Plasma ctDNA liquid biopsy of IDH1, TERTp, and EGFRvIII mutations in glioma
Authors: Jones Jordan J , Nguyen Hong , Wong Stephen Q , Whittle James , Iaria Josie , Stylli Stanley , Towner James , Pieters Thomas , Gaillard Frank , Kaye Andrew H , Drummond Katharine J , Morokoff Andrew P 
Published: March 2024

Abstract

Background
Circulating tumor DNA has emerging clinical applications in several cancers; however, previous studies have shown low sensitivity in glioma. We investigated if 3 key glioma gene mutations IDH1, TERTp, and EGFRvIII could be reliably detected in plasma by droplet digital polymerase chain reaction (ddPCR) thereby demonstrating the potential of this technique for glioma liquid biopsy.

Methods
We analyzed 110 glioma patients from our biobank with a total of 359 plasma samples (median 4 samples per patient). DNA was isolated from plasma and analyzed for IDH1, TERTp, and EGFRvIII mutations using ddPCR.

Results
Total cfDNA was significantly associated with tumor grade, tumor volume, and both overall and progression-free survival for all gliomas as well as the grade 4 glioblastoma subgroup, but was not reliably associated with changes in tumor volume/progression during the patients’ postoperative time course. IDH1 mutation was detected with 84% overall sensitivity across all plasma samples and 77% in the preoperative samples alone; however, IDH1 mutation plasma levels were not associated with tumor progression or survival. IDH1m plasma levels were not associated with pre- or postsurgery progression or survival. The TERTp C228T mutation was detected in the plasma ctDNA in 88% but the C250T variant in only 49% of samples. The EGFRvIII mutation was detected in plasma in 5 out of 7 patients (71%) with tissue EGFRvIII mutations in tumor tissue.

Conclusions
Plasma ctDNA mutations detected with ddPCR provide excellent diagnostic sensitivity for IDH1, TERTp-C228T, and EGFRvIII mutations in glioma patients. Total cfDNA may also assist with prognostic information. Further studies are needed to validate these findings and the clinical role of ctDNA in glioma.
An Analysis of Social Determinants of Health and Their Implications for Hepatitis C Virus Treatment in People Who Inject Drugs: The Case of Baltimore
Authors: Gonzalez Corro Luis A , Zook Katie , Landry Miles , Rosecrans Amanda , Harris Robert , Gaskin Darrell , Falade-Nwulia Oluwaseun , Page Kathleen R , Lucas Gregory M 
Published: March 2024

Abstract

Background
Sixty-eight percent of the nearly 3.5 million people living with hepatitis C virus (HCV) in the United States are people who inject drugs (PWID). Despite effective treatments, uptake remains low in PWID. We examined the social determinants of health (SDoH) that affect the HCV care cascade.

Methods
We conducted a secondary analysis of data from 720 PWID in a cluster-randomized trial. We recruited PWID from 12 drug-affected areas in Baltimore. Inclusion criteria were injection in the prior month or needle sharing in the past 6 months. Intake data consisted of a survey and HCV testing. Focusing on SDoH, we analyzed self-report of (1) awareness of HCV infection (in those with active or previously cured HCV) and (2) prior HCV treatment (in the aware subgroup). We used descriptive statistics and logistic regression for statistical analyses.

Results
The 342 participants were majority male and Black with a median age of 52 years. Women were more likely to be aware of their status but less likely to be treated. Having a primary care provider and HIV-positive status were associated with increased awareness and treatment. Unhoused people had 51% lower odds of HCV treatment. People who reported that other PWID had shared their HCV status with them had 2.3-fold higher odds of awareness of their own status.

Conclusions
Further study of gender disparities in HCV treatment access is needed. Increased social support was associated with higher odds of HCV treatment, suggesting an area for future interventions. Strategies to identify and address SDoH are needed to end HCV.
A Machine Learning-Based Thermobarometer for Magmatic Liquids
Authors: Weber Gregor , Blundy Jon 
Published: March 2024

Abstract
Experimentally calibrated models to recover pressures and temperatures of magmas are widely used in igneous petrology. However, large errors, especially in barometry, limit the capacity of these models to resolve the architecture of crustal igneous systems. Here, we apply machine learning to a large experimental database to calibrate new regression models that recover P–T of magmas based on melt composition plus associated phase assemblage. The method is applicable to compositions from basalt to rhyolite, pressures from 0.2 to 15 kbar, and temperatures of 675°C to 1400°C. Testing and optimisation of the model with a filter that removes estimates with standard deviation above the 50th percentile show that pressures can be recovered with root-mean-square-error (RMSE) of 1.1 to 1.3 kbar and errors on temperature estimates of 21°C. Our findings demonstrate that, given constraints on the coexisting mineral assemblage, melt chemistry is a reliable recorder of magmatic variables. This is a consequence of the relatively low thermodynamic variance of natural magma compositions despite their relatively large number of constituent oxide components. We apply our model to two contrasting cases with well-constrained geophysical information: Mount St. Helens volcano (USA), and Askja caldera in Iceland. Dacite whole-rocks from Mount St Helens erupted 1980 to 1986, inferred to represent liquids extracted from cpx–hbl–opx–plag–mt–ilm mush, yield melt extraction source pressures of 5.1 to 6.7 kbar in excellent agreement with geophysical constraints. Melt inclusions and matrix glasses record lower pressures (0.7–3.8 kbar), consistent with magma crystallisation within the upper reaches of the imaged geophysical anomaly and during ascent. Magma reservoir depth estimates for historical eruptions from Askja match the location of seismic wave speed anomalies. Vp/Vs anomalies at 5 to 10 km depth correspond to hot (~990°C) rhyolite source regions, while basaltic magmas (~1120°C) were stored at 7 to 17 km depth under the caldera. These examples illustrate how our model can link petrology and geophysics to better constrain the architecture of volcanic feeding systems. Our model (MagMaTaB) is accessible through a user-friendly web application (https://igdrasil.shinyapps.io/MagmaTaBv4/).
AraLeTA: An Arabidopsis leaf expression atlas across diurnal and developmental scales
Authors: Vong Gina Y W , McCarthy Kayla , Claydon Will , Davis Seth J , Redmond Ethan J , Ezer Daphne 
Published: March 2024

Abstract
Mature plant leaves are a composite of distinct cell types, including epidermal, mesophyll, and vascular cells. Notably, the proportion of these cells and the relative transcript concentrations within different cell types may change over time. While gene expression data at a single-cell level can provide cell-type-specific expression values, it is often too expensive to obtain these data for high-resolution time series. Although bulk RNA-seq can be performed in a high-resolution time series, RNA-seq using whole leaves measures average gene expression values across all cell types in each sample. In this study, we combined single-cell RNA-seq data with time-series data from whole leaves to assemble an atlas of cell-type-specific changes in gene expression over time for Arabidopsis (Arabidopsis thaliana). We inferred how the relative transcript concentrations of different cell types vary across diurnal and developmental timescales. Importantly, this analysis revealed 3 subgroups of mesophyll cells with distinct temporal profiles of expression. Finally, we developed tissue-specific gene networks that form a community resource: an Arabidopsis Leaf Time-dependent Atlas (AraLeTa). This allows users to extract gene networks that are confirmed by transcription factor–binding data and specific to certain cell types at certain times of day and at certain developmental stages. AraLeTa is available at https://regulatorynet.shinyapps.io/araleta/.
The role of long noncoding RNA MEG3 in fibrosis diseases
Authors: Wu Wenlong , Zhou Sijing , Fei Guanghe , Wang Ran 
Published: March 2024

Abstract
Fibrosis is a prevalent pathological condition observed in various organs and tissues. It primarily arises from the excessive and abnormal accumulation of the extracellular matrix, resulting in the structural and functional impairment of tissues and organs, which can culminate in death. Many forms of fibrosis, including liver, cardiac, pulmonary, and renal fibrosis, are considered irreversible. Maternally expressed gene 3 (MEG3) is an imprinted RNA gene. Historically, the downregulation of MEG3 has been linked to tumor pathogenesis. However, recent studies indicate an emerging association of MEG3 with fibrotic diseases. In this review, we delve into the current understanding of MEG3’s role in fibrosis, aiming to shed light on the molecular mechanisms of fibrosis and the potential of MEG3 as a novel therapeutic target.
Characteristics of long COVID in patients with autoimmune rheumatic diseases: a systematic review and meta-analysis
Authors: Chen Der-Yuan , Huang Po-I , Tang Kuo-Tung 
Published: March 2024

Abstract

Objectives
Numerous cases of long coronavirus disease (long COVID) have been reported in patients with autoimmune rheumatic diseases (ARDs). Despite the reviews on clinical manifestations of long COVID in the general population, systematic reviews on ARD patients are scarce. Herein, we conducted a systematic review and meta-analysis on the prevalence and characteristics of long COVID in ARD patients.

Methods
We searched the literature in PubMed and Embase as of 27 December 2022. Cohort, cross-sectional and case–control studies relevant to long COVID in ARD patients were collected. Stratification based on the severity of COVID infection and subtypes of rheumatic diseases [systemic autoimmune rheumatic disease (SARD) vs non-autoimmune rheumatic disease (NARD)] was also undertaken. A random-effects model was used in the meta-analysis.

Results
A total of 15 relevant studies were identified from the literature. The prevalence of long COVID was 56% (95% CI 34, 76) in 2995 patients. Hospitalized COVID patients had a higher proportion of long COVID than non-hospitalized patients. The prevalence of long COVID was similar between SARD and NARD patients. In terms of symptoms, fatigue, arthralgia and pain were commonly reported in long COVID patients with ARDs.

Conclusion
The characteristics of long COVID in ARD patients are generally similar to those in the general population despite a higher prevalence and a higher proportion of arthralgia and pain.
Inclusion-body myositis associated with Sjögren’s disease: clinical characteristics and comparison with other Sjögren-associated myositis
Authors: Astouati Quentin , Machet Thomas , Houssais Camille , Noury Jean-Baptiste , Allenbach Yves , Gallay Laure , Quere Baptiste , Assan Florence , Benveniste Olivier , Broner Jonathan , Duffau Pierre , Espitia Alexandra , Grasland Anne , Hayem Gilles , Le Guern Véronique , Martis Nihal , Mariampillai Kuberaka , Nocturne Gaëtane , Mariette Xavier , Meyer Alain , Mulleman Denis , Devauchelle-Pensec Valérie , Collet Aurore , Launay David , Hachulla Eric , Cornec Divi , Guellec Dewi , Sanges Sébastien 
Published: March 2024

Abstract

Objectives
To describe the characteristics of patients with Sjögren’s disease (SjD) and inclusion-body myositis (IBM), and how they compare to SjD patients with other inflammatory myopathies (IM).

Methods
Patients were retrospectively recruited from 13 French centres and included if they met the ACR/EULAR criteria for SjD and for IM. They were categorized as SjD-IBM if sub-criteria for IBM were met, or as SjD-other IM if not.

Results
SjD-IBM patients (n = 22) were mostly females (86%), with a median [Q1; Q3] age of 54 [38.5; 64] years at SjD diagnosis, and 62 [46.5; 70] years at first IBM symptoms. Although most patients displayed glandular and immunological abnormalities, additional extra-glandular manifestations were uncommon, resulting in moderate disease activity at SjD diagnosis (ESSDAI 5.5 [1; 7.8]). Classic IBM features were frequent, such as progressive symptom onset (59%), asymmetrical (27%) and distal (32%) involvements, dysphagia (41%), low CPK (386.5 [221.8; 670.5] UI/l) and CRP (3.0 [3; 8.5] mg/l) levels. Immunosuppressants were reported as efficient in 55% of cases. Compared with SjD-IBM patients, SjD patients with other IM (n = 50) were significantly younger, displayed more frequent additional extra-glandular disease, higher ESSDAI score (11 [3; 30]), shorter delay between SjD diagnosis and myositis onset (0 [−0.5; 26]), more frequent CPK values over 1000 UI/l (36%), and less frequent classic IBM features.

Conclusion
IBM can occur in SjD patients, with muscle features reminiscent of classic sporadic IBM characteristics, but mostly affecting women. In SjD patients with muscle involvement, extra-glandular manifestations, high ESSDAI score, elevated CPK values and shorter delay after SjD diagnosis plead against IBM.
Loneliness in the Daily Lives of People With Mood and Psychotic Disorders
Authors: Moran Erin K , Shapiro Madelyn , Culbreth Adam J , Nepal Subigya , Ben-Zeev Dror , Campbell Andrew , Barch Deanna M 
Published: March 2024

Abstract

Background and Hypothesis
Loneliness, the subjective experience of feeling alone, is associated with physical and psychological impairments. While there is an extensive literature linking loneliness to psychopathology, limited work has examined loneliness in daily life in those with serious mental illness. We hypothesized that trait and momentary loneliness would be transdiagnostic and relate to symptoms and measures of daily functioning.

Study Design
The current study utilized ecological momentary assessment and passive sensing to examine loneliness in those with schizophrenia (N = 59), bipolar disorder (N = 61), unipolar depression (N = 60), remitted unipolar depression (N = 51), and nonclinical comparisons (N = 82) to examine relationships of both trait and momentary loneliness to symptoms and social functioning in daily life.

Study Results
Findings suggest that both trait and momentary loneliness are higher in those with psychopathology (F(4,284) = 28.00, P &lt; .001, ηp2 = 0.27), and that loneliness significantly relates to social functioning beyond negative symptoms and depression (β = −0.44, t = 6.40, P &lt; .001). Furthermore, passive sensing measures showed that greater movement (β = −0.56, t = −3.29, P = .02) and phone calls (β = −0.22, t = 12.79, P = .04), but not text messaging, were specifically related to decreased loneliness in daily life. Individuals higher in trait loneliness show stronger relationships between momentary loneliness and social context and emotions in everyday life.

Conclusions
These findings provide further evidence pointing to the importance of loneliness transdiagnostically and its strong relation to social functioning. Furthermore, we show that passive sensing technology can be used to measure behaviors related to loneliness in daily life that may point to potential treatment implications or early detection markers of loneliness.
An online behavioral self-help intervention rapidly improves acute insomnia severity and subjective mood during the coronavirus disease-2019 pandemic: a stratified randomized controlled trial
Authors: Elder Greg J , Santhi Nayantara , Robson Amelia R , Alfonso-Miller Pamela , Spiegelhalder Kai , Ellis Jason G 
Published: March 2024

Abstract

Study Objectives
Stressful life events, such as the coronavirus disease-2019 (COVID-19) pandemic, can cause acute insomnia. Cognitive behavioral therapy for acute insomnia is effective but is both time and resource-intensive. This study investigated if an online behavioral self-help intervention, which has been successfully used alongside sleep restriction for acute insomnia, reduced insomnia severity and improved mood in acute insomnia. This study also assessed good sleepers to explore if a “sleep vaccination” approach was feasible.

Methods
In this online stratified randomized controlled trial, 344 participants (103 good sleepers and 241 participants with DSM-5 acute insomnia) were randomized to receive the intervention/no intervention (good sleepers) or intervention/intervention after 28 days (poor sleepers). Insomnia severity was assessed using the ISI (primary outcome), and anxiety and depression using the GAD-7/PHQ-9 (secondary outcomes) at baseline, 1 week, 1 month, and 3-month follow-up.

Results
In people with acute insomnia, relative to baseline, there were significant reductions in ISI (dz = 1.17), GAD-7 (dz = 0.70), and PHQ-9 (dz = 0.60) scores at 1-week follow-up. ISI, GAD-7, and PHQ-9 scores were significantly lower at all follow-up time points, relative to baseline. Subjective diary-derived sleep continuity was unaffected. No beneficial effects on sleep or mood were observed in good sleepers.

Conclusions
An online behavioral self-help intervention rapidly reduces acute insomnia severity (within 1 week), and benefits mood in people with acute insomnia. These beneficial effects are maintained up to 3 months later. Although the use of the intervention is feasible in good sleepers, their subjective sleep was unaffected.

Clinical Trial registration
Testing an early online intervention for the treatment of disturbed sleep during the COVID-19 pandemic; prospectively registered at ISRCTN on 8 April 2020 (identifier: ISRCTN43900695).
HDAC3 promotes Sertoli cell maturation and maintains the blood–testis barrier dynamics
Authors: Liu Mengrou , He Qing , Yuan Zihan , Chen Niuniu , Ren Sen , Du Qian , Wang Yanfeng , Han Shenglin , Xu Chen , Lu Luyang , Sun Zheng , Guan Yongjuan , Xie Jie , Guan Yichun , Ye Lan 
Published: March 2024

AbstractGerm cell development depends on the capacity of somatic Sertoli cells to undergo differentiation into a mature state and establish a germ cell‐specific blood–testis barrier (BTB). The BTB structure confers an immunological barrier for meiotic and postmeiotic germ cells, and its dynamic permeability facilitates a transient movement of preleptotene spermatocytes through BTB to enter meiosis. However, the regulatory factors involved in Sertoli cell maturation and how BTB dynamics coordinate germ cell development remain unclear. Here, we found a histone deacetylase HDAC3 abundantly expresses in Sertoli cells and localizes in both cytoplasm and nucleus. Sertoli cell‐specific Hdac3 knockout in mice causes infertility with compromised integrity of blood–testis barrier, leading to germ cells unable to traverse through BTB and an accumulation of preleptotene spermatocytes in juvenile testis. Mechanistically, nuclear HDAC3 regulates the expression program of Sertoli cell maturation genes, and cytoplasmic HDAC3 forms a complex with the gap junction protein Connexin 43 to modulate the BTB integrity and dynamics through regulating the distribution of tight junction proteins. Our findings identify HDAC3 as a critical regulator in promoting Sertoli cell maturation and maintaining the homeostasis of the blood–testis barrier.
Phenotypic and functional exhaustion of circulating CD3+CD56+NKT‐like cells in colorectal cancer patients
Authors: Cao Kangli , Wang Xiaowei , Wang Hui , Xu Cairui , Ma Along , Zhang Yuntao , Zheng Meijuan , Xu Yuanhong , Tang Ling 
Published: March 2024

AbstractCD3+CD56+ NKT‐like cells are crucial to antitumor immune surveillance and defense. However, research on circulating NKT‐like cells in colorectal cancer (CRC) patients is limited. This investigation selected 113 patients diagnosed with primary CRC for preoperative peripheral blood collection. The blood from 106 healthy donors at the physical examination center was acquired as a healthy control (HC). The distribution of lymphocyte subsets, immunophenotype, and functional characteristics of NKT‐like cells was comprehensively evaluated. Compared to HC, primary CRC patients had considerably fewer peripheral NKT‐like cells in frequency and absolute quantity, and the fraction of NKT‐like cells was further reduced in patients with vascular invasion compared to those without. The NKT‐like cells in CRC patients had a reduced fraction of the activating receptor CD16, up‐regulated expression of inhibitory receptors LAG‐3 and NKG2A, impaired production of TNF‐α and IFN‐γ, as well as degranulation capacity. Moreover, the increased frequency of NKG2A+ NKT‐like cells and the decreased expression of activation‐related molecules were significantly correlated with tumor progression. In detail, NKG2A+ NKT‐like cells indicated increased PD‐1 and Tim‐3 and reduced TNF‐α than NKG2A− subgroup. Blocking NKG2A in vitro restored cytokine secretion capacity in NKT‐like cells from CRC patients. Altogether, this research revealed that circulating NKT‐like cells in CRC patients exhibited suppressive phenotype and functional impairment, which was more pronounced in NKG2A+ NKT‐like cells. These findings suggest that NKG2A blockade may restore anti‐tumor effector function in NKT‐like cells, which provides a potential target for immunotherapy in CRC patients.