bluuebunny/crossref_metadata_2025 huggingface dataset:
Proposal of Paradevosia tibetensis (Wang et al. 2015) comb. nov. by transferring the species Youhaiella tibetensis to the genus Paradevosia
Authors: Li Meng-Syun
Published: January 2025

The authors of a recent study in this journal in which the union of the genera Youhaiella and Paradevosia was proposed wrongfully indicated the correct generic name that should be used. According to Rule 24b(4) of the International Code of Nomenclature of Prokaryotes, Paradevosia Geng et al. 2015 has priority over Youhaiella Wang et al. 2015. Hence, a new combination is needed for the species that contains Youhaiella tibetensis F4T, and in this letter, Paradevosia tibetensis (Wang et al. 2015) comb. nov. is proposed by correctly adopting the earliest legitimate generic name.
Jannaschia maritima sp. nov., a novel marine bacterium isolated from the biofilm of concrete breakwater structures
Authors: Feng Hao , Liang Shuyi , Li Ruisi , Wang Hui , Cai Runlin
Published: January 2025

Marine biofilms were newly revealed as a bank of hidden microbial diversity and functional potential. In this study, a Gram-stain-negative, aerobic, oval and non-motile bacterium, designated LMIT008T, was isolated from the biofilm of concrete breakwater structures located in the coastal area of Shantou, PR China. Strain LMIT008T was found to grow at salinities of 1–7% NaCl, at pH 5–8 and at temperatures 10–40 °C. Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain LMIT008T belonged to the genus Jannaschia and was closely related to the type strains Jannaschia aquimarina KCTC23555T (96.03%) and Jannaschia marina SHC-163T (95.31%). The draft genome size of the strain LMIT008T was 3.67 Mbp, and the genomic DNA G+C content was 69.83 mol%. The average nucleotide identity value between strain LMIT008T and the closely related type strain J. aquimarina KCTC23555T was 74.82%. The predominant cellular fatty acids were identified as summed feature 8 (C18 : 1
 ω7c/C18 : 1
 ω6c) and C18 : 0, and the major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and phosphatidylcholine. Ubiquinone-10 (Q-10) is the sole respiratory quinone. Further, genomic analysis of strain LMIT008T showed that the strain harbours abundant genes associated with biofilm formation and environmental adaption, explaining the potential strategies for living on concrete breakwater structures. Based on the morphological, phylogenetic, chemotaxonomic and phenotypic characterization, the strain LMIT008T was considered to represent a novel species in the genus of Jannaschia, for which the name Jannaschia maritima sp. nov. was proposed, with LMIT008T (=MCCC 1K08854T=KCTC 8321T) as the type strain.
Leukocyte Count Is Better than LDL-C as Predictor of Novel Carotid Atherosclerosis
Authors: Li Y , Cao H , Ding L , Naren T G , Zhang Q Q , Wang Z
Published: January 2025

Background

This continuous retrospective cohort study aims to(1)screen the risk factors and cut-off values of initial occurrence of carotid atherosclerosis(CAS) and(2)identify whether the pathological procession of CAS is from carotid intima-media thickening(C-IMT) to carotid plaques CAP).

Methods

Between 2015 and 2024, the characteristics were recorded at three time points, which were the meaningful time point for the first new appearance of CAS or not, the baseline time point for the previous closest normal carotid status, and the validated time point for the first confirming the meaningful results. Statistics analyses, including student’s t test, Mann-Whitney U test, and Chi-square test, assessed the different results between observation group and healthy controls. Logistic regression, Cox regression, ROC curves and Kaplan-Meier analysis were used for screening the risk factors and cut-off points. Repeated-measures ANOVA was used for comparison between the groups and within each group.

Results

Of 3583 recruited participants, the final study analyses included 1141 individuals, there was no significant change in the proportion of C-IMT and CAP during continuous observation of a 1.04 years (P=0.561). After performed Propensity score matching for age and gender, leukocyte count 5.00*109/L and low-density lipoprotein cholesterol (LDL-C) 125.1mg/dl were significantly associated with the new appearance of CAS over a 1.09 years follow-up period compared to the reference group. Leukocyte count high level group was associated with CAS (log-rank P=0.01), nevertheless LDL-C was no significant difference (log-rank P=0.055).

Conclusions

Middle aged adults(aged 49.6± 8.0)with leukocyte count above 5.00*109/L were more likely progress CAS after an average of 1.09 years. CAS new lesions had no obvious specificity and no significant changes were found after an average of 1.04 years. This study identified early specific markers that predict the appearance of CAS in order to guide the timing of early lifestyle interventions.
Inversions Dominate Evolution in the Highly Admixed European Sardine (Sardina pilchardus)
Authors: Sabatino SJ , Cabezas M. P , Pereira P , Garrido S , Múrias A , Carneiro M , Talhadas PJ , Louro B , Cox C , Canário AVM , Veríssimo A
Published: January 2025

Inversions can play key roles in the genetic architecture of adaptation, but the scale of their effects across different species remains poorly understood. Here, we use whole- genome sequencing to investigate the influence of inversions on the population genomics of the r-selected European sardine (Sardina pilchardus). Allele frequency differences from millions of SNPs across 34 populations spanning the species’ range were analyzed. Genomic scans identified several extreme outlier regions overlapping chromosome-scale inversions, collectively representing over half the genome. Our findings suggest these inversions are associated with locally adapted life history strategies. First, SNPs within outlier regions containing inversions exhibited striking allele frequency differences between Atlantic and Mediterranean sardines, which differ in key adaptive life history traits. In the Atlantic, inversion allele frequencies varied latitudinally, while in the Mediterranean, they shifted longitudinally, aligning with temperature and oceanographic features that influence sardine life history strategies. Moreover, adjacent populations in contrasting environments displayed pronounced allele frequency differences in inversions. These spatial patterns of allele frequencies sharply contrasted with those based on neutral loci, indicating they are driven by selection. After rigorously filtering SNPs affected by selection and inversions, sardine populations showed high admixture across their range but significant population structure and isolation by distance, especially in the Mediterranean. This study demonstrates that inversions can shape genome-wide patterns of genetic diversity and population structure in highly admixed r-selected marine species. These findings also offer crucial insights for stock delimitation and management of this commercially valuable species in the face of climate change.
The Brugada syndrome associated geneWT1impacts onSCN5Aexpression and cardiac conduction
Authors: Marsman E. Madelief J. , Offerhaus Joost A. , Mengarelli Isabella , Beekman Leander , Wilde Lisanne M.W. , Casini Simona , Goumans Marie-José , Verkerk Arie O. , Jurgens Sean J. , Wilde Arthur A.M. , Boukens Bastiaan J. , Remme Carol Ann , Bezzina Connie R. , Bosada Fernanda M.
Published: January 2025

Brugada syndrome (BrS) is an inherited cardiac arrhythmic disorder caused by conduction slowing primarily affecting the right ventricular (RV) outflow tract (RVOT). A recent genome-wide association study (GWAS) implicated a genomic region in chromosome 11, overlapping the transcription factorWT1, in BrS susceptibility. Here, we investigated the role ofWT1on cardiac conduction using a heterozygous knockout mouse model (Wt1+/-). Transcriptomic analysis revealed increasedScn5aexpression predominantly inWt1+/-cardiomyocytes of the (sub)epicardium of the RV and RVOT without any changes in electrical properties. To unmask an effect on cardiac conduction, we performed optical mapping in a severely challenged setting offered byScn5ahaploinsufficiency, ageing, and exposure to the sodium channel blocker ajmaline and found that diminishedWt1improved the observed slowed conduction. Examination of human single-nuclei cardiac datasets indicated a strong negative correlation betweenWT1andSCN5Aexpression. In line with this observation, cardiac samples from patients with mutations inSCN5Ashowed increased WT1 protein abundance in histological sections, suggesting that increasedWT1, and not loss, is associated with BrS pathophysiology. By deleting the mouse orthologue of a BrS-associated noncoding region (RE) harboring a candidate regulatory element, we established that this RE controls expression ofWt1specifically in the (sub)epicardium of the RV. Lastly, transient overexpression ofWT1in hiPSC-derived cardiomyocytes resulted in reduced sodium current density. Our study therefore identifies the transcription factorWT1as a novel contributor to the pathophysiology of BrS, at least in part, throughSCN5A.
An adversarial scheme for integrating multi-modal data on protein function
Authors: Nasser Rami , Schaffer Leah V , Ideker Trey , Sharan Roded
Published: January 2025

In order to begin to decipher the structure of the cell, we need to integrate multiple types of data of different scales on subcellular organization. Such integration requires dealing with multiple data modalities and with missing data. To this end, we developed MIRAGE, a multi-modal generative model for integrating protein sequence, protein-protein interaction and protein localization data. Our approach successfully learns a joint embedding space that captures the complex relationships between these diverse modalities. We evaluate our model’s performance against existing methods, obtaining superior performance in several key tasks, including protein function prediction and module detection. MIRAGE source code is available athttps://github.com/raminass/MIRAGE.
Modular DNA Barcoding of Nanobodies Enables Multiplexedin situProtein Imaging and High-throughput Biomolecule Detection
Authors: Zhong Shilin , Wang Ruiyu , Gao Xinwei , Guo Qingchun , Lin Rui , Luo Minmin
Published: January 2025

Immunodetection methods based on antibody-antigen interactions are routinely used in biological and clinical laboratories. DNA-labeled antibodies offer the advantage of simultaneous detection of multiple target molecules via orthogonal DNA barcode sequences. However, current methods for antibody-DNA conjugation typically involve non-site-specific modifications tailored for each specific application, a process that is labor-intensive and often compromises antibody affinity and specificity. To overcome these limitations, here we present a modular, site-specific, and cost-efficient DNA tagging strategy — multiplexed and modular barcoding of antibodies (MaMBA). Utilizing nanobodies as modular adaptors, MaMBA enables direct site-specific labeling of off-the-shelf IgG antibodies with a one-component design. We first applied MaMBA to develop themisHCR method for highly multiplexedin situprotein imaging via orthogonal hybridization chain reaction (HCR). We then introduced a cleavable version of MaMBA, which allows iterative use of the same HCR probes sets, thereby enhancing the multiplexity ofmisHCR (misHCRn).misHCRnachieves simultaneous labeling of 12 different target molecules within the same mouse brain sections. We further extended the cleavable MaMBA to develop the barcode-linked immunosorbent assay (BLISA) for multiplexed and high-throughput biomolecule detections. By combining BLISA with next-generation sequencing, we successfully measured SARS-CoV-2 IgG and HBV-associated antigens in a large number of human serum samples. Additionally, we demonstrated a small-scale drug screen by using BLISA to simultaneously detect eight protein targets. In conclusion, MaMBA offers a highly modular and easily adaptable approach for antibody DNA-barcoding, which can be broadly applied in basic research and clinical diagnostics.
Transcriptional Landscape of THAP9 across Oligodendrocyte Developmental Stages: Molecular Mechanisms and Network Analysis
Authors: Bhardwaj Tanuja , Patel Dhrumi , Majumdar Sharmistha
Published: January 2025

Oligodendrocyte maturation and myelination are critical processes in human neurodevelopment, and their dysregulation is linked to numerous neurological disorders. While model organisms have provided insight into these processes, human-specific regulatory mechanisms remain poorly understood. This study investigated human THAP9, a protein homologous to theDrosophilaP-element transposase, whose function in oligodendrocytes remains unknown. An analysis of publicly available RNA-sequencing data and H3K27ac ChIP-sequencing data from oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes (MOs) revealed significant upregulation of THAP9 during oligodendrocyte maturation. Co-expression analysis demonstrated a strong correlation with established markers of oligodendrocyte development, including myelin-associated genes (MOG, MBP) and key transcriptional regulators (PDGFRA, SOX5, SOX6, SOX11). THAP9 lacks homologues in mice, highlighting potential human-specific mechanisms in oligodendrocyte development and emphasising the importance of studying species-specific factors in neurodevelopment.. Our findings suggest that THAP9 is a novel human-specific regulator of oligodendrocyte maturation and opens new avenues for studying myelination disorders.
A Randomized Double-Blind Phase 2 Clinical Trial Treating Cervical Intraepithelial Neoplasia 2/3 with PepCan orCandida
Authors: Nakagawa Mayumi , Evans Teresa , Bimali Milan , Coleman Hannah , Crane Jasmine , Darwish Nadia , Faulkner Jennifer L. , Jones Amy , Kelly Haley , Lieblong Benjamin J. , Lu Yong-Chen , Marsh Keanna , Nookaew Intawat , Quick Charles M. , Ussery David , Robeson Michael , Shah Sumit , Shibata Takeo , Williams Heather R. , Greenfield William
Published: January 2025

PURPOSE

A non-surgical alternative for treating cervical intraepithelial neoplasia (CIN) 2/3 is an unmet need due to a risk of cervical incompetency.

METHODS

PepCan consists of four human papillomavirus (HPV) type 16 E6 peptides and aCandidaskin testing reagent (adjuvant). In this randomized, double-blind Phase 2 study, women with biopsy-confirmed CIN2/3 were treated with PepCan orCandidaat one to one ratio. Four intradermal injections were given every 3 weeks, with observation visits at 6 and 12 months post-vaccination. Quadrant biopsies were performed at the 12-month visit, and those whose lesions regressed to no CIN were considered to be complete responders. Regression rates of each treatment group were compared to that of a historical placebo group.

RESULTS

With the intention-to-treat analysis, PepCan (n=39) showed 30.8% efficacy (95% confidence interval [CI], 17 to 47.6;p=0.25) whileCandida(n=42) demonstrated 47.6% efficacy (95% CI, 32 to 63.6;p<0.001). Likewise, with the per-protocol analysis, PepCan (n=24) showed 45.8% efficacy (95% CI, 25.6 to 67.2;p=0.08) andCandida(n=29) showed 62.1% efficacy (95% CI, 42.3 to 79.3;p<0.001). There was no difference between efficacy of PepCan andCandida. No dose-limiting toxicity was observed. HPV-specific T cell responses were elicited in both groups. Vaccine-induced HPV-specific CD4 and CD8 T cells were present in cervix regardless of histological response. Single-cell RNA-seq revealed increased expression of granzymes, CCR5, and EOMES in HPV-specific CD8-positive T cells of a histological responder, compared to non-responders. Six cytokines (CCL4, CCL5, interleukin-9, lymphotoxin-α, platelet-derived growth factor-ββ, tumor growth factor-β1) were significantly decreased in bothCandidarecipients and histological responders suggesting thatCandidamay possibly exert its anti-tumor effects through these systemic mediators.

CONCLUSIONS

Candidamay be effective in inducing histological regression. PepCan andCandidatreatments are safe.Candidashould be evaluated in a Phase 3 trial as a potential new treatment for CIN2/3.
Clinical aspects and serodiagnosis of myasthenia gravis in Algerian patients: a prospective study on a small group of patients
Authors: Bouchtout Mohamed Nadji , Phillips William D , Attal Elias , Daoudi Smail , Kechoud Sarah , Reddel Stephen W , Touil-Boukoffa Chafia , Attal Nabila , Raache Rachida
Published: January 2025

Myasthenia gravis (MG) is a clinically heterogeneous disease, and its diagnosis relies primarily on serological tests such as ELISA and RIPA. This study reports the clinical characteristics of a cohort of Algerian patients with MG and evaluates the diagnostic accuracy of ELISA and RIPA for detecting anti-AChR and anti-MuSK autoantibodies. Serological analyses were performed using ELISA, RIPA, and cell-based assays (CBA) in a subset of 23 patients. Algerian MG patients did not exhibit any specific clinical features compared to other populations. The results demonstrated a good correlation between ELISA and RIPA for anti-AChR and anti-MuSK autoantibodies. However, 100% of patients with generalized MG and none of those with ocular MG were positive for anti-AChR by ELISA, compared to 83.3% and 40% by RIPA, respectively. None of the 23 patients were positive for anti-MuSK by RIPA or an in-house CBA. These findings suggest that anti-AChR ELISA may serve as a reliable diagnostic tool for MG in settings where RIPA is unavailable. Combining clinical and electrophysiological findings with serological testing may enhance the accuracy of MG diagnosis.
Synergistic impact of CAG intermediate alleles in theHTTgene and microRNA dysregulation exacerbates spliceosome impairment and accelerates Tau pathology in the caudate nucleus of late-onset Alzheimer’s disease
Authors: Castilla-Silgado Juan , Perez-Oliveira Sergio , Pinto-Hernandez Paola , Fernandez-Sanjurjo Manuel , Corte-Torres Maria Daniela , Iglesias-Gutierrez Eduardo , Menendez-Gonzalez Manuel , Alvarez Victoria , Tomas-Zapico Cristina
Published: January 2025

Background

Late-onset Alzheimer’s disease (LOAD) accounts for more than 95% of AD cases. Previously, we have described that 6% of AD patients present CAG intermediate alleles in the huntingtin gene (HTT IAs). The caudate nucleus, the most affected region in Huntington’s disease, is highly sensitive to theseHTTCAG expansions, as they can induce epigenetic changes, including altered microRNA profiles. All this implies a potential source of gene expression deregulation, affecting disease onset and/or progression in LOAD patients withHTT IAs.

Methods

We genotypedHTTCAG repeats and Apolipoprotein E (APOE) inpostmortembrain frozen samples from 323 LOAD patients and 335 healthy controls. From them, we selected caudate samples ofHTT IAcarrier and non-carrier LOAD patients and controls, with neuropathological study, and performed next-generation microRNA sequencing,in silicotarget prediction and pathway analysis, followed by molecular and histopathological studies.

Results

Our study revealed that the presence ofHTT IAsdecreases survival in LOAD patients after disease onset. MicroRNA profiles in the caudate nucleus are altered in all LOAD compared to the control cases but are more pronounced inHTT IAscarriers.In silicoanalysis suggests that the microRNAs expressed differentially inHTT IAscarriers regulate key components of the spliceosome, affecting splicing factors of the SRSF family or the nuclear FUS-SFPQ complex, which was confirmed by different techniques. This leads to an increase in Tau 3R protein, conducting to a higher presence of ghost tangles, the last state of neurofibrillary tangles, in LOAD patients withHTT IAs. In addition, they also present a higher number of HTT-positive neurons in a CAG repeat expansion-dependent manner.

Conclusions

Our findings demonstrate a synergistic effect ofHTT IAsand miRNAs deregulation in the evolution of tau pathology, which could be related to an accelerated misprocessing and subsequent aggregation of the Tau 3R isoform, favoring a subsequent faster disease progression. The incorporation of genetic screening forHTTalleles into clinical practice would allow a more accurate classification of LOAD patients, facilitating the design of personalized therapeutic interventions and improving the prospects for the management of this debilitating disease.
Generalized Linear Mixed Model Approach for Analyzing Water, Sanitation, and Hygiene Facilities in Bangladesh: Insights from BDHS 2022 Data
Authors: Mim Mahmila Sanjana , Rahaman Lutfor , Sajib Anamul Haque
Published: January 2025

This study aims to identify key determinants and barriers to effective WASH facilities in Bangladesh, crucial for preventing health issues and ensuring fair access. For identifying the vital factors associated with access to WASH facilities, data obtained from Bangladesh Demographic and Health Survey (BDHS) 2022 have been analyzed. Since the survey employed a two-stage stratified clustered sampling approach, the responses from each cluster are likely to be correlated and exhibit variation between clusters, reflecting the inherent heterogeneity. To overcome this problem and incorporate cluster effect along with fixed effects, Generalized Linear Mixed Model (GLMM) for binary response has been employed rather than the conventional fixed effect logistic regression model for analyzing individual and combined basic WASH facilities in Bangladesh. The superiority of GLMM over fixed effect logistic regression model for binary response have been observed based on Akaike Information Criterion (AIC) and likelihood ratio test (LRT). The study shows that, age of household head, partner’s education level, media exposure, women empowerment, wealth index, mother’s age and mother’s education of children under 5 had significant association with basic handwashing facility. Basic sanitation facility was associated with division, place of residence, sex and age of the household head, household size, partner’s education level, working status, wealth index, mother’s age, and mother’s education of children under 5. Wealth index significantly affected the access to basic drinking water facility. Moreover, combined WASH facilities were influenced by the sex and age of the household head, household size, partner’s education level, working status, media exposure, wealth index, mother’s age, and mother’s education of children under 5. Findings of this study can be used to enhance accessibility to basic WASH facilities, contributing to the achievement of 6thSustainable Development Goal (SDG).
Optimizing Transfection Efficiency in Primary Human Splenic Fibroblast Cells
Authors: Kaur Ashpreet , Assogba Victoria A. , Assogba Jovy M. G. , Assogba Barnabe D.
Published: January 2025

Transfection, a fundamental molecular biology technique, is crucial in introducing foreign DNA into cells. Despite its pivotal importance, mastering this technique remains a formidable challenge. In this study, we employed the calcium phosphate reagent and conducted a systematic exploration through time-dependent experiments to assess its impact on human primary splenic fibroblast cells (HSFC). The results precisely delineate optimal time frames for achieving enhanced transfection efficiency, offering conclusive evidence for the efficacy of calcium phosphate in transient transfection within the cells. The data significantly advances our comprehension of HSFC reactions, contributing to refining transfection methodologies with broader implications for biomedical applications.
Comparative analysis of cerebrospinal fluid neurofilament medium, light and heavy chain in neurodegenerative diseases using a novel assay for the detection of neurofilament medium chain
Authors: Fazeli Badrieh , Botzenhardt Sara , Bachhuber Franziska , Klassen Paula , Klose Veronika , Dorst Johannes , Wiesenfarth Maximilian , Uzelac Zeljko , Jesse Sarah , Brenner David , Anderl-Straub Sarah , Ludolph Albert C. , Otto Markus , Weishaupt Jochen , Tumani Hayrettin , Halbgebauer Steffen
Published: January 2025

Objective

Neurofilaments are key axonal proteins, with neurofilament light (NfL) and heavy (NfH) chain recognized as promising biomarkers for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). However, neurofilament medium chain (NfM) remained previously underexplored due to a lack of quantitative assays. In this study, we developed a sensitive immunoassay to measure NfM in cerebrospinal fluid (CSF) and analyzed its levels in ALS, Alzheimer’s disease (AD), frontotemporal dementia (FTD), and Lewy body dementia (LBD). Correlations among neurofilaments and their diagnostic performance were also evaluated.

Methods

In this study CSF levels of three neurofilament proteins were measured in 271 participants, including patients with ALS (n=91), AD (n=25), FTD (n=38), LBD (n=18), non-neurodegenerative controls (CTRL, n=51), and 48 individuals initially evaluated for ALS but ultimately diagnosed with other conditions (CTRL.DD).

Results

All three neurofilaments were significantly elevated in ALS compared to CTRL and CTRL.DD groups (p<0.0001 for both), with NfM and NfL also increased in FTD (p<0.0001 for both) and AD (NfM, p=0.0017; NfL, p=0.0135 ) compared to CTRL. NfH demonstrated the greatest distinction between ALS and FTD (p<0.0001). Strong correlations were observed among neurofilament subunits, particularly between NfM and NfL (r=0.94, 95% CI: 0.93-0.96, p<0.0001). All neurofilaments effectively distinguished ALS from CTRL and CTRL.DD, with AUC values ranging from 0.92 to 0.99. NfM and NfL showed high accuracy in differentiating AD (NfM, AUC: 0.89; NfL, AUC: 0.90) and FTD (NfM, AUC: 0.91; NfL, AUC: 0.92) from CTRL, while NfH best separated ALS from FTD (AUC: 0.96).

Conclusion

This study provides the first quantitative comparison of NfM with NfL and NfH in a neurodegenerative cohort, highlighting its potential diagnostic value. Further research with larger cohorts, longitudinal studies, and investigations into neurofilament distribution in different compartments is needed to clarify the distinct roles of NfM, NfL, and NfH in the diagnosis and treatment of neurological diseases.
Harnessing Artificial Intelligence for Accurate Diagnosis and Radiomics Analysis of Combined Pulmonary Fibrosis and Emphysema: Insights from a Multicenter Cohort Study
Authors: Zhang Shichen , Wang Hongqiu , Tang Haiyun , Li Xiaoqin , Wu Nian-Wei , Li Bo , Chen Xin , Chen Kaishi , Xie Baosong , Zhou Aiyuan , Mo Chunheng
Published: January 2025

Combined Pulmonary Fibrosis and Emphysema (CPFE), recognized as a distinct pulmonary syndrome in 2022, is characterized by unique clinical features and pathogenesis that can lead to respiratory failure and death. However, the diagnosis of CPFE presents significant challenges that impede effective treatment. Here, we assembled a multicenter dataset of three-dimensional (3D) computed tomography (CT) images of patients lungs from multiple hospitals across different provinces in China, including Xiangya Hospital, West China Hospital, and Fujian Provincial Hospital. Utilizing this dataset, we developed CPFENet, a deep learning-assisted diagnostic model specifically designed for CPFE patients. This model accurately classifies patients into CPFE, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis based on 3D CT data, demonstrating diagnostic performance comparable to that of professional radiologists. Furthermore, we extracted radiomic features from the 3D CT images to generate a CPFE score, a robust and efficient metric for characterizing the presence of CPFE. Using this score, we identified significant differences in CPFE scores between genders. To validate our findings, we retrospectively analyzed the gender distribution of patients across the participating hospitals, corroborating the accuracy of our results. Overall, our study represents the first multicenter systematic investigation of CPFE, providing a diagnostic model and clinical indicators that enable accurate classification and characterization of the syndrome. This research offers a valuable direction and benchmark for future studies on CPFE, potentially facilitating the development of targeted therapeutic strategies and improving patient outcomes.
Genetic prediction and adverse selection
Authors: Azevedo Eduardo , Beauchamp Jonathan , Karlsson Linnér Richard
Published: January 2025

The predictive power of genetic data has been increasing rapidly and is reaching levels of clinical utility for many diseases. Meanwhile, many jurisdictions have banned insurers from utilizing genetic information. This has led to concerns that further improvements in genetic prediction will lead to adverse selection. We make three contributions to this debate. First, we develop a method to measure the amount of selection in an insurance market where consumers have access to current genetic prediction technology. Second, we extend the method to estimate the amount of selection given expected improvements in genetic prediction technology. Third, using the UK Biobank dataset with nearly 500,000 genotyped individuals, we apply the method to the critical illness insurance market. We find that expected improvements in genetic prediction are likely to lead to unsustainably high levels of selection and thus threaten the viability of the market. We discuss policy implications.
Pharmacokinetic analysis of carboplatin and fluorescein brain permanence following ultrasound-based blood-brain barrier opening
Authors: Habashy Karl J. , Synold Timothy W. , Feng Ye , Gomez Cristal , Amidei Christina , Ward Rachel , VanderMolen Sarah , Zarrieneh Ashkan , Kim Kwang-Soo , Arrieta Victor A. , Fares Jawad , Burdett Kirsten B. , Zhang Hui , Dmello Crismita , Chen Li , Bebawy John F. , Canney Michael , Stupp Roger , Badie Behnam , Portnow Jana , Sonabend Adam M.
Published: January 2025

Background

The blood-brain barrier (BBB) impedes the passage of most circulating drugs into the brain. Low-intensity pulsed ultrasound with microbubbles (LIPU/MB) transiently opens the BBB, improving parenchymal drug penetration. Parenchymal drug permanence upon short-lived BBB opening is unknown. We compared the parenchymal permanence of temozolomide, carboplatin, and fluorescein, and investigated the effect of LIPU/MB on the concentration of carboplatin and fluorescein.

Methods

We analyzed four patients who underwent intraoperative LIPU/MB with intravenous administration of carboplatin and fluorescein in theNCT04528680clinical trial. Microdialysis catheters were implanted into sonicated and non-sonicated brain and measured drug levels over 24 hours. Published data from a microdialysis study of temozolomide without LIPU/MB were used for comparison.

Results

LIPU/MB led to sustained elevated parenchymal drug concentrations, achieving 3.1-fold increase in brain-to-plasma AUC for carboplatin and fluorescein (P = 0.03). Compared to non-sonicated brain, sonicated brain had higher concentrations of carboplatin for 11 hours, and fluorescein for 5 hours. Drug levels in the sonicated brain exceeded their plasma concentrations at 21 hours and 7 hours, for carboplatin and fluorescein, respectively. In non-sonicated brain, drug half-life was longest for fluorescein (13.6 ± 11.0 hours), followed by carboplatin (5.1 ± 1.9 hours) and temozolomide (2.9 ± 1.6 hours). Sonication did not affect parenchymal drug half-life.

Conclusion

Following LIPU/MB, BBB-impermeable drugs exhibit sustained elevated parenchymal concentrations surpassing their plasma levels, highlighting the bi-directional restriction of drug passage by the BBB. Future studies are warranted to explore drug trapping and the efficacy of sustained exposure to cytotoxic drugs for the treatment of brain-infiltrating tumors.
From Abstainers to Dependent Drinkers: Alcohol Consumption Patterns and Risk Factors Among Portuguese University Students
Authors: Saldanha Lucas , Crego Alberto , Almeida-Antunes Natália , Rodrigues Rui , Sampaio Adriana , López-Caneda Eduardo
Published: January 2025

Background

Alcohol is the most widely consumed psychoactive substance worldwide. In Portugal, alcohol consumption is deeply embedded in social and cultural practices, contributing to high prevalence rates among university students, with binge drinking emerging as a predominant consumption pattern. Despite the associations between this drinking behaviour and numerous social, physical, and psychological problems, research on alcohol consumption in Portuguese university populations remains limited. Thus, this study aimed to provide a comprehensive description of alcohol use patterns among a large sample of Portuguese university students, focusing on adolescents and young adults.

Methods

A total of 1,746 students, aged 17-24 years, were surveyed using the Alcohol Use Disorders Identification Test (AUDIT) and additional questionnaires regarding socio-demographic information, alcohol and illicit drug use, smoking habits, and alcohol cravings. Students were classified into five drinking groups: Abstainers (16.8%), Moderate Drinkers (35.1%), Hazardous Drinkers (25.8%), Binge Drinkers (20.8%), and Dependent Drinkers (1.5%). Statistical analyses included descriptive statistics, group comparisons, and multinomial logistic regressions to obtain Odds Ratios (ORs) for group membership.

Results

Alcohol consumption was reported by 83.2% of students over the past year. Nearly 47% of students revealed harmful drinking patterns, and 1.5% exhibited symptoms of alcohol dependence. A progressive increase in the severity of alcohol consumption characteristics was observed across the groups, with Dependent Drinkers reporting the highest levels overall. Significant predictors of group membership included polydrug use, standard weekly consumption, earlier drinking onset, and higher levels of alcohol craving. Polydrug use, reported by 27.3% of students, was the strongest predictor for being a Hazardous Drinker (OR = 10.75), Binge Drinker (OR = 13.20), and Dependent Drinker (OR = 21.40). Binge Drinkers displayed standard weekly consumption and craving levels comparable to Dependent Drinkers, while Moderate Drinkers exhibited the least risky patterns, including a later age of onset of drinking. Male students reported significantly greater consumption and craving levels than their female peers.

Conclusions

This study highlights the prevalence of harmful drinking behaviours among Portuguese university students and identifies critical risk factors, such as polydrug use and early drinking onset. These findings underscore the need for prevention programmes focused on delaying the onset of alcohol use, reducing polydrug use, and promoting healthier behaviours within academic settings.
Computationally-designed aptamers targeting RAD51-BRCA2 interaction inhibit RAD51 nuclear recruitment
Authors: Milordini Giulia , Zacco Elsa , Armaos Alexandros , Di Palma Francesco , Masi Mirco , Gilodi Martina , Rupert Jakob , Broglia Laura , Varignani Giulia , Oneto Michele , Scotto Marco , Marotta Roberto , Girotto Stefania , Cavalli Andrea , Tartaglia Gian Gaetano
Published: January 2025

The interaction between RAD51 and BRCA2 plays a key role in homologous recombination (HR), a critical DNA repair mechanism essential for the survival of cancer cells. Disrupting this interaction increases the sensitivity of cancer cells to chemotherapeutic agents. Here, we employedin silicomethods to design a novel class of aptamers—customized single-stranded oligonucleotides—specifically engineered to bind RAD51. These aptamers were developed with the aim of selectively modulating RAD51’s nuclear recruitment and its role in DNA repair processes. The leading candidate displays high affinity for RAD51, competing with BRCA2 for the same interaction sitein vitro, as confirmed through biolayer interferometry (BLI) and fluorescence lifetime imaging microscopy (FLIM). We tested the efficacy of the leading aptamer in pancreatic cancer cells and observed that it significantly impedes RAD51 nuclear localization, reduces homologous recombination (HR) efficiency, and increases DNA damage. Critically, our aptamer potentiates the cytotoxicity of the PARP inhibitor olaparib, exploiting synthetic lethality (SL) to induce cancer cell death. Our study showcases an aptamer-based approach for selectively targeting protein interactions within DNA repair pathways, introducing a promising avenue for SL-based treatments applicable to a wide range of cancers.
A formal model of anxiety disorders based on the neural circuit dynamics of the fear and extinction circuits
Authors: Rubin Alan Lawrence , Walth Mark
Published: January 2025

The pathophysiology of anxiety disorders is the outcome of an imbalance of the fear-anxiety circuit and the extinction circuit. We present a formal model using nonlinear dynamics and network theory, which captures the dynamic interactions of the key nodes of the anxiety and extinction networks. This rudimentary model can be modified by newer data. These core nodes consist of the cells of the paraventricular nucleus of the thalamus coding negative valence, the neurons of the basal-lateral amygdala coding negative valence (Rspo2+), the anterior cingulate cortex, the ventral hippocampus neurons coding fear memories, the somatostatin expressing cells of the lateral segment of the central amygdala, the medial segment of the central nucleus of the amygdala-bed nucleus of the stria terminalis and their target nodes. The extinction network consists primarily of the paraventricular thalamic cells coding positive valence, (Ppp1r1b+) cells of the basolateral amygdala coding positive valence, the ventromedial prefrontal cortex, the PKCδ cells of the lateral segment of the central amygdala, and the intercalated cells.

Human and non-human animal genetic and epigenetic studies point to deficiencies in brain-derived neurotrophic factor and neurotrophic receptor kinase tyrosine 2 production in key nodes causing reduced plasticity extinction network plasticity and leading to a weakened extinction response.

We rely primarily on the neurophysiological studies of non-human animal models since nodes generating fear/anxiety and extinction responses are highly conserved across species and equivalent nodes are present within analogous circuits of the human brain. The results are confirmed, where possible by human functional magnetic resonance imaging studies.

We believe this simplified model is of heurist value and can lead to a more consistent focus on physiologically based pathophysiology. This would lead to treatments to reverse the pathologic physiology produced by genetic and epigenetic abnormalities, and greater efforts to directly correct pathologic circuit activity through direct interventions such as transcranial magnetic stimulation.

Significance

We believe this simplified model is of heurist value and can lead to a more consistent focus on physiologically based pathophysiology. This would lead to treatments to reverse the pathologic physiology produced by genetic and epigenetic abnormalities, and greater efforts to directly correct pathologic circuit activity through direct interventions such as transcranial magnetic stimulation.
Postnatal interaction of size and shape in the human endocranium and brain structures
Authors: Takagi Kuranosuke , Kondo Osamu
Published: January 2025

The uniqueness of human brain growth and development has been considered promising to understand the advanced cognitive ability of humans. Compared with that of chimpanzees, the human endocranium undergoes several characteristic shape changes immediately after birth, which has been termed “endocranial globularization.” However, how the brain structures and surrounding neurocranium interact with each other during early development in the context of brain–neurocranium integration remains to be investigated. We observed shape changes in the human brain and endocranium during postnatal development using magnetic resonance imaging, and analyzed spatial constraints and interactions among subdivisions of the brain influencing endocranial morphology. Our results suggest that during postnatal development, the relative size changes of supratentorial and infratentorial regions and the cranial base largely constrain brain and endocranium shape. Specifically, a disproportionate increase in the size of the cerebellum relative to the cranial base affects infratentorial spatial packing constraints in neonates, causing inferoposterior expansion of the posterior cranial fossa and coronal reorientation of the petrous bone without lateral opening of the tentorium cerebelli. The dramatic size increase of the cerebellum relative to the cranial base immediately after birth is inferred to be characteristic of human development, which corresponds to previously observed bony shape changes.
The effects of task similarity during representation learning in brains and neural networks
Authors: Menghi Nicholas , Johnston William Jeffrey , Vigano' Simone , Hinrichs Max Andreas Bosse , Maess Burkhard , Fusi Stefano , Doeller Christian F
Published: January 2025

The complexity of our environment poses significant challenges for adaptive behavior. Recognizing shared structures across tasks can theoretically improve learning through generalization. However, how such shared representations emerge and influence performance remains poorly understood. Contrary to expectations, our findings revealed that individuals trained on tasks with similar low-dimensional structures performed worse than those trained on dissimilar tasks. Magnetoencephalography revealed correlated neural representations in the same-structure group and anticorrelated ones in the different-structure group. Crucially, practice reduced this performance gap and shifted the neural representations of the tasks in the same-structure group towards anticorrelation, like those in the different-structure group. A neural network model trained on similar tasks replicated these findings: tasks with similar structures require more iterations to orthogonalize their representations. These results highlight a complex interplay between task similarity, neural dynamics, and behavior, challenging traditional assumptions about learning and generalization.
Neuropeptidergic circuit modulation of developmental sleep inDrosophila
Authors: Hemmi Chikayo , Ishii Kenichi , Motoyoshi Mana , Tsuji Masato , Emoto Kazuo
Published: January 2025

Sleep-wakefulness regulation dynamically evolves along development in flies, fish, and humans. While the mechanisms regulating sleep in adults are relatively well understood, little is known about their counterparts in early developmental stages. Here, we report a neuropeptidergic circuitry that modulates sleep in developingDrosophilalarvae. Through an unbiased screen, we identified the neuropeptide Hugin and its receptor PK2-R1 as critical regulators of larval sleep. Our data suggest that HugPC neurons secrete Hugin peptides to activate insulin-producing cells (IPCs), which express a Hugin receptor PK2-R1. IPCs, in turn, releaseDrosophilainsulin-like peptides (Dilps) to regulate sleep. We further show that the Hugin/PK2-R1 axis is dispensable for adult sleep control. Our findings thus reveal the neuromodulatory circuitry regulating larval sleep, highlighting differential impacts of the same modulatory axis on developmental sleep and adult sleep.
Lysosomal Glucocerebrosidase is needed for ciliary Hedgehog signaling: A convergent pathway to Parkinson’s disease
Authors: Nair Sreeja V. , Jaimon Ebsy , Adhikari Ayan , Nikoloff Jonas , Pfeffer Suzanne R.
Published: January 2025

Mutations inLRRK2andGBA1are the most common genetic causes of familial Parkinson’s disease. Previously, we showed that pathogenicLRRK2mutations inhibit primary cilia formation in rare interneurons and astrocytes of the mouse and human dorsal striatum. This blocks Hedgehog signaling and reduces synthesis of neuroprotective GDNF and NRTN, which support neurons vulnerable in PD. Here we show thatGBA1mutations also impair Hedgehog signaling through a distinct mechanism. Loss ofGBA1activity decreases accessible cholesterol in primary cilia of cultured cells, thereby disrupting Hedgehog signaling. In the mouse striatum,Gba1mutations result in reduced Hedgehog-inducedGdnfRNA expression in cholinergic interneurons, despite having no detectable impact on cilia formation. Also, bothLrrk2andGba1mutations suppress Hedgehog-inducedBdnfexpression in striatal astrocytes. These findings underscore the role of Hedgehog signaling in the nigrostriatal circuit and reveal a convergent mechanism by which distinct mutations may contribute to PD pathogenesis.
Low-temperature state in strontium titanate microcrystals using
in situ
multireflection Bragg coherent x-ray diffraction imaging
Authors: Yang David , Suzana Ana F. , Wu Longlong , Ha Sung Soo , Choi Sungwook , Ngo Hieu Minh , Nawaz Muhammad Mahmood , Kim Hyunjung , Liu Jialun , Treuherz Daniel , Zhang Nan , An Zheyi , Nisbet Gareth , Porter Daniel G. , Robinson Ian K.
Published: January 2025

Strontium titanate is a classic quantum paraelectric oxide material that has been widely studied in bulk and thin films. It exhibits a well-known cubic-to-tetragonal antiferrodistortive phase transition at 105 K, characterized by the rotation of oxygen octahedra. A possible second phase transition at lower temperature is suppressed by quantum fluctuations, preventing the onset of ferroelectric order. However, recent studies have shown that ferroelectric order can be established at low temperatures by inducing strain and other means. Here, we used multireflection Bragg coherent x-ray diffraction imaging to measure the strain and rotation tensors for two strontium titanate microcrystals at low temperature. We observe strains induced by dislocations and inclusion-like impurities in the microcrystals. Based on radial magnitude plots, these strains increase in magnitude and spread as the temperature decreases. Pearson's correlation heat maps show a structural transition at 50 K, which could possibly be the formation of a low-temperature ferroelectric phase in the presence of strain. We do not observe any change in local strains associated with the tetragonal phase transition at 105 K.

Published by the American Physical Society
2025
Bridging correlation and spectroscopy measurements to access the hadron interaction behind molecular states: The case of the
Ξ(1620)
and
Ξ(1690)
in the
K−Λ
system
Authors: Feijoo A. , Sarti V. Mantovani , Nieves J. , Ramos A. , Vidaña I.
Published: January 2025

We study the compatibility between the K−Λ correlation function, recently measured by the ALICE collaboration, and the LHCb K−Λ invariant mass distribution obtained in the Ξb−→J/ψΛK− decay. The K−Λ invariant mass distribution associated with the Ξb− decay has been calculated within the framework of unitary effective field theories using two models, one of them constrained by the K−Λ correlation function. We consider two degenerate pentaquark Pcs states in the J/ψΛ scattering amplitude which allows us to investigate their impact on both the K−Λ and J/ψΛ mass distributions assuming different spin-parity quantum numbers and multiplicity. Without any fitting procedure, the K−Λ model is able to better reproduce the experimental K−Λ mass spectrum in the energy region above 1680 MeV as compared to previous unitarized scattering amplitudes constrained to a large amount of experimental data in the neutral S=−1 meson-baryon sector. We observe a tension between our model and the LHCb K−Λ distribution in the region close to threshold, largely dominated by the presence of the still poorly known Ξ(1620) state. We discuss in detail the different production mechanisms probed via femtoscopy and spectroscopy that could provide valid explanations for such disagreement, indicating the necessity to employ future correlation data in other S=−2 channels such as πΞ and K¯Σ.

Published by the American Physical Society
2025