bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulation of neuropilin-2 expression in inhibitory neurons impairs hippocampal circuit development and enhances risk for autism-related behaviors and seizures
Authors: Subramanian Deepak , Eisenberg Carol , Huang Andrew , Baek Jiyeon , Naveed Haniya , Komatireddy Samiksha , Shiflett Michael W. , Tran Tracy S. , Santhakumar Vijayalakshmi 
Published: November 2024

AbstractDysregulation of development, migration, and function of interneurons, collectively termed interneuronopathies, have been proposed as a shared mechanism for autism spectrum disorders (ASDs) and childhood epilepsy. Neuropilin-2 (Nrp2), a candidate ASD gene, is a critical regulator of interneuron migration from the median ganglionic eminence (MGE) to the pallium, including the hippocampus. While clinical studies have identified Nrp2 polymorphisms in patients with ASD, whether selective dysregulation of Nrp2-dependent interneuron migration contributes to pathogenesis of ASD and enhances the risk for seizures has not been evaluated. We tested the hypothesis that the lack of Nrp2 in MGE-derived interneuron precursors disrupts the excitation/inhibition balance in hippocampal circuits, thus predisposing the network to seizures and behavioral patterns associated with ASD. Embryonic deletion of Nrp2 during the developmental period for migration of MGE derived interneuron precursors (iCKO) significantly reduced parvalbumin, neuropeptide Y, and somatostatin positive neurons in the hippocampal CA1. Consequently, when compared to controls, the frequency of inhibitory synaptic currents in CA1 pyramidal cells was reduced while frequency of excitatory synaptic currents was increased in iCKO mice. Although passive and active membrane properties of CA1 pyramidal cells were unchanged, iCKO mice showed enhanced susceptibility to chemically evoked seizures. Moreover, iCKO mice exhibited selective behavioral deficits in both preference for social novelty and goal-directed learning, which are consistent with ASD-like phenotype. Together, our findings show that disruption of developmental Nrp2 regulation of interneuron circuit establishment, produces ASD-like behaviors and enhanced risk for epilepsy. These results support the developmental interneuronopathy hypothesis of ASD epilepsy comorbidity.
Combining tissue biomarkers with mpMRI to diagnose clinically significant prostate cancer. Analysis of 21 biomarkers in the PICTURE study
Authors: Stopka-Farooqui Urszula , Stavrinides Vasilis , Simpson Benjamin S. , Qureshi Hania , Carmona Echevierra Lina M. , Pye Hayley , Ahmed Zeba , Alawami Mohammed F. , Kay Jonathan D. , Olivier Jonathan , Heavey Susan , Patel Dominic , Freeman Alex , Haider Aiman , Moore Caroline M. , Ahmed Hashim U. , Whitaker Hayley C. 
Published: November 2024

Abstract
Background
Serum PSA and digital rectal examination remain the key diagnostic tools for detecting prostate cancer. However, due to the limited specificity of serum PSA, the applicability of this marker continues to be controversial. Recent use of image-guided biopsy along with pathological assessment and the use of biomarkers has dramatically improved the diagnosis of clinically significant cancer. Despite the two modalities working together for diagnosis biomarker research often fails to correlate findings with imaging.

Methods and results
We looked at 21 prostate cancer biomarkers correlating our results with mpMRI data to investigate the hypothesis that biomarkers along with mpMRI data make a powerful tool to detect clinically significant prostate cancer. Biomarkers were selected based on the existing literature. Using a tissue microarray comprised of samples from the PICTURE study, with biopsies at 5 mm intervals and mpMRI data we analysed which biomarkers could differentiate benign and malignant tissue. Biomarker data were also correlated with pathological grading, mpMRI, serum PSA, age and family history. AGR2, CD10 and EGR protein expression was significantly different in both matched malignant and benign tissues. AMACR, ANPEP, GDF15, MSMB, PSMA, PTEN, TBL1XR1, TP63, VPS13A and VPS28 showed significantly different expression between Gleason grades in malignant tissue. The majority of the biomarkers tested did not correlate with mpMRI data. However, CD10, KHDRBS3, PCLAF, PSMA, SIK2 and GDF15 were differentially expressed with prostate cancer progression. AMACR and PTEN were identified in both pathological and image data evaluation.

Conclusions
There is a high demand to develop biomarkers that would help the diagnosis and prognosis of prostate cancer. Tissue biomarkers are of particular interest since immunohistochemistry remains a cheap, reliable method that is widely available in pathology departments. These results demonstrate that testing biomarkers in a cohort consistent with the current diagnostic pathway is crucial to identifying biomarker with potential clinical utility.
PCK1 as a target for cancer therapy: from metabolic reprogramming to immune microenvironment remodeling
Authors: Liu Na , Zhu Xiao-ren , Wu Chang-ying , Liu Yuan-yuan , Chen Min-bin , Gu Jin-hua 
Published: November 2024

AbstractRecently, changes in metabolites and metabolism-related enzymes related to tumor cell proliferation, metastasis, drug resistance, and immunosuppression have become a research hotspot, and researchers have attempted to determine the clinical correlation between specific molecular lesions and metabolic phenotypes. Convincing evidence shows that metabolic reprogramming is closely related to the proliferation, invasion, metastasis, and poor prognosis of malignant tumors. Therefore, targeting metabolic reprogramming is a new direction for cancer treatment. However, how molecular alterations in tumors contribute to metabolic diversity and unique targeting dependencies remains unclear. A full understanding of the underlying mechanisms of metabolic reprogramming in cancer may lead to better identification of therapeutic targets and the development of therapeutic strategies. Evidence for the importance of PCK1, a phosphoenolpyruvate carboxykinase 1, in tumorigenesis and development is accumulating. PCK1 can regulate cell proliferation and metastasis by remodeling cell metabolism. Additionally, PCK1 has “nonclassical” nonmetabolic functions, involving the regulation of gene expression, angiogenesis, epigenetic modification, and other processes, and has an impact on cell survival, apoptosis, and other biological activities, as well as the remodeling of the tumor immune microenvironment. Herein, we provide a comprehensive overview of the functions of PCK1 under physiological and pathological conditions and suggest that PCK1 is a potential target for cancer therapy. We also propose a future exploration direction for targeting PCK1 for cancer therapy from a clinical perspective. Finally, in view of the collective data, the results of our discussion suggest the potential clinical application of targeted PCK1 therapy in combination with chemotherapy and immunotherapy for cancer treatment.
Viral sequence determines HLA-E-restricted T cell recognition of hepatitis B surface antigen
Authors: Murugesan Gavuthami , Paterson Rachel L. , Kulkarni Rakesh , Ilkow Veronica , Suckling Richard J. , Connolly Mary M. , Karuppiah Vijaykumar , Pengelly Robert , Jadhav Archana , Donoso Jose , Heunis Tiaan , Bunjobpol Wilawan , Philips Gwilym , Ololade Kafayat , Kay Daniel , Sarkar Anshuk , Barber Claire , Raj Ritu , Perot Carole , Grant Tressan , Treveil Agatha , Walker Andrew , Dembek Marcin , Gibbs-Howe Dawn , Hock Miriam , Carreira Ricardo J. , Atkin Kate E. , Dorrell Lucy , Knox Andrew , Leonard Sarah , Salio Mariolina , Godinho Luis F. 
Published: November 2024

AbstractThe non-polymorphic HLA-E molecule offers opportunities for new universal immunotherapeutic approaches to chronic infectious diseases. Chronic Hepatitis B virus (HBV) infection is driven in part by T cell dysfunction due to elevated levels of the HBV envelope (Env) protein hepatitis B surface antigen (HBsAg). Here we report the characterization of three genotypic variants of an HLA-E-binding HBsAg peptide, Env371-379, identified through bioinformatic predictions and verified by biochemical and cellular assays. Using a soluble affinity-enhanced T cell receptor (TCR) (a09b08)-anti-CD3 bispecific molecule to probe HLA-E presentation of the Env371-379 peptides, we demonstrate that only the most stable Env371-379 variant, L6I, elicits functional responses to a09b08-anti-CD3-redirected polyclonal T cells co-cultured with targets expressing endogenous HBsAg. Furthermore, HLA-E-Env371-379 L6I-specific CD8+ T cells are detectable in HBV-naïve donors and people with chronic HBV after in vitro priming. In conclusion, we provide evidence for HLA-E-mediated HBV Env peptide presentation, and highlight the effect of viral mutations on the stability and targetability of pHLA-E molecules.
Analysis of complex excitation patterns using Feynman-like diagrams
Authors: Arno Louise , Kabus Desmond , Dierckx Hans 
Published: November 2024

AbstractMany extended chemical and biological systems self-organise into complex patterns that drive the medium behaviour in a non-linear fashion. An important class of such systems are excitable media, including neural and cardiac tissues. In extended excitable media, wave breaks can form rotating patterns and turbulence. However, the onset, sustaining and elimination of such complex patterns is currently incompletely understood. The classical theory of phase singularities in excitable media was recently challenged, as extended lines of conduction block were identified as phase discontinuities. Here, we provide a theoretical framework that captures the rich dynamics in excitable systems in terms of three quasiparticles: heads, tails, and pivots. We propose to call these quasiparticles ‘cardions’. In simulations and experiments, we show that these basic building blocks combine into at least four different bound states. By representing their interactions similarly to Feynman diagrams in physics, the creation and annihilation of vortex pairs are shown to be sequences of dynamical creation, annihilation, and recombination of the identified quasiparticles. We draw such diagrams for numerical simulations, as well as optical voltage mapping experiments performed on cultured human atrial myocytes (hiAMs). Our results provide a new, unified language for a more detailed theory, analysis, and mechanistic insights of dynamical transitions in excitation patterns.
Optimizing energy-efficient grid performance: integrating electric vehicles, DSTATCOM, and renewable sources using the Hippopotamus Optimization Algorithm
Authors: Abdelaziz M. A. , Ali A. A. , Swief R. A. , Elazab Rasha 
Published: November 2024

AbstractThe rapid increase in renewable energy integration and electric vehicle (EV) adoption creates significant challenges for the stability and efficiency of power distribution networks. This study addresses the need for optimized placement and sizing of Electric Vehicle Charging Stations (EVCSs), photovoltaic (PV) systems, and Distribution Static Compensators (DSTATCOMs) to enhance grid performance. The motivation for this work arises from the fluctuating nature of renewable energy generation and the unpredictable demands of EV charging, which strain existing infrastructure. To address these challenges, we propose a novel optimization framework that introduces the Renewable Distributed Generation Hosting Factor (RDG-HF) and Electric Vehicle Hosting Factor (EV-HF) as key metrics. These metrics, combined with the Hippopotamus Optimization Algorithm (HO), enable strategic planning within the IEEE 69-bus system. Simulation results demonstrate that the integrated placement of EVCSs, PVs, and DSTATCOMs reduces power losses by up to 31.5% and reactive power losses by up to 29.2%. An economic analysis further reveals payback periods ranging from 2.7 to 10.4 years and potential profits of up to $1,052,365 over 25 years. These findings highlight the importance of optimized integration in improving both technical performance and long-term economic benefits for distribution networks.
Different dynamics of soluble inflammatory mediators after clearance of respiratory SARS-CoV-2 versus blood-borne hepatitis C virus infections
Authors: Zeuzem Antonia , Kumar Saumya Dileep , Oltmanns Carlos , Witte Moana , Mischke Jasmin , Drick Nora , Fuge Jan , Pink Isabell , Tauwaldt Jan , Debarry Jennifer , Illig Thomas , Wedemeyer Heiner , Maasoumy Benjamin , Li Yang , Kraft Anke R. M. , Cornberg Markus 
Published: November 2024

AbstractViral infections can be acute or chronic, with the immune system pivotal in immunopathogenesis. The potential reversibility of inflammation post-viral elimination is of current interest. This study compares the dynamics of soluble inflammatory mediators (SIM) during and after respiratory infections with SARS-CoV-2 and blood-borne acute and chronic hepatitis C virus (HCV) infections. The study included patients with acute HCV (n = 29), chronic HCV (n = 54), and SARS-CoV-2 (n = 39 longitudinal, n = 103 cross-sectional), along with 30 healthy controls. Blood samples were collected at baseline, end of treatment/infection, and during follow-up (up to 9 months). SIMs were quantified using the HD-SP-X Imaging and Analysis System™. At baseline, SIM profiles in acute SARS-CoV-2 and HCV infections were significantly elevated compared with controls. During follow-up, SIM decline was less pronounced in acute and chronic HCV infections after successful therapy than in SARS-CoV-2 infections. Most SIM in the SARS-CoV-2 cohort normalized within 3 months. In chronic HCV, SIM were higher in cirrhotic than noncirrhotic patients post-HCV elimination. Dynamics of SIM after viral elimination vary between blood-borne acute and chronic HCV infections and respiratory SARS-CoV-2 infections. Immunological imprints 3–9 months after HCV elimination appear more pronounced than after SARS-CoV-2 infection.
Question framing affects accurate-inaccurate discrimination in responses to sharing questions, but not in responses to accuracy questions
Authors: Bell Raoul , Buchner Axel 
Published: November 2024

AbstractPrevious research suggests that even when people are capable of judging to the best of their knowledge whether claims are accurate or inaccurate, they do not sufficiently discriminate between accurate and inaccurate information when asked to consider whether they would share stories on social media. However, question framing (“To the best of your knowledge…”, “Would you consider…?”) differed between the questions about accuracy and the questions about sharing. Here we examine the effects of question framing on responses to accuracy questions and responses to sharing questions. The framing of accuracy questions had no effect on accurate-inaccurate discrimination. In contrast, accurate-inaccurate discrimination in response to sharing questions increased when participants were asked to respond, to the best of their knowledge, whether they would share claims compared to when they were asked whether they would consider sharing stories. At a theoretical level, the findings support the inattention-based account, according to which contextual cues shifting the focus toward accuracy can enhance accurate-inaccurate discrimination in sharing responses. At a methodological level, these findings suggest that researchers should carefully attend to the verbal framing of questions about sharing information on social media, as the framing may significantly influence participants’ focus on accuracy.
Structural insight into Okazaki fragment maturation mediated by PCNA-bound FEN1 and RNaseH2
Authors: Tian Yuhui , Li Ningning , Li Qing , Gao Ning 
Published: November 2024

Abstract
PCNA is a master coordinator of many DNA-metabolic events. During DNA replication, the maturation of Okazaki fragments involves at least four DNA enzymes, all of which contain PCNA-interacting motifs. However, the temporal relationships and functional modulations between these PCNA-binding proteins are unclear. Here, we developed a strategy to purify endogenous PCNA-containing complexes from native chromatin, and characterized their structures using cryo-EM. Two structurally resolved classes (PCNA-FEN1 and PCNA-FEN1-RNaseH2 complexes) have captured a series of 3D snapshots for the primer-removal steps of Okazaki fragment maturation. These structures show that product release from FEN1 is a rate-liming step. Furthermore, both FEN1 and RNaseH2 undergo continuous conformational changes on PCNA that result in constant fluctuations in the bending angle of substrate DNA at the nick site, implying that these enzymes could regulate each other through conformational modulation of the bound DNA. The structures of the PCNA-FEN1-RNaseH2 complex confirm the toolbelt function of PCNA and suggests a potential unrecognized role of RNaseH2, as a dsDNA binding protein, in promoting the 5′-flap cleaving activity of FEN1.
Interleukin-2-mediated NF-κB-dependent mRNA splicing modulates interferon gamma protein production
Authors: Van Gelder Rachel D , Gokhale Nandan S , Genoyer Emmanuelle , Omelia Dylan S , Anderson Stephen K , Young Howard A , Savan Ram 
Published: November 2024

AbstractInterferon-gamma (IFNγ) is a pleiotropic cytokine produced by natural killer (NK) cells during the early infection response. IFNγ expression is tightly regulated to mount sterilizing immunity while preventing tissue pathology. Several post-transcriptional effectors dampen IFNγ expression through IFNG mRNA degradation. In this study, we identify mRNA splicing as a positive regulator of IFNγ production. While treatment with the combination of IL-12 and IL-2 causes synergistic induction of IFNG mRNA and protein, defying transcription-translation kinetics, we observe that NK cells treated with IL-12 alone transcribe IFNG with introns intact. When NK cells are treated with both IL-2 and IL-12, IFNG transcript is spliced to form mature mRNA with a concomitant increase in IFNγ protein. We find that IL-2-mediated intron splicing occurs independently of nascent transcription but relies upon NF-κB signaling. We propose that while IL-12 transcriptionally induces IFNG mRNA, IL-2 signaling stabilizes IFNG mRNA by splicing detained introns, allowing for rapid IFNγ protein production. This study uncovers a novel role for cytokine-induced splicing in regulating IFNγ through a mechanism potentially applicable to other inflammatory mediators.
The Lyman Alpha Reference Sample
Authors: Le Reste A. , Hayes M. J. , Cannon J. M. , Melinder J. , Runnholm A. , Rivera-Thorsen T. E. , Östlin G. , Adamo A. , Herenz E. C. , Schaerer D. , Scarlata C. , Kunth D. 
Published: November 2024

Context. The Lyman-α (Lyα) line of hydrogen is a well-known tracer of galaxies at high redshift. However, the connection between Lyα observables and galaxy properties has not been fully established, limiting the use of the line to probe the physics of galaxies.
Aims. Here, we derive the global neutral hydrogen gas (HI) properties of nearby Lyα-emitting galaxies to assess the impact of neutral gas on the Lyα output of galaxies.
Methods. We observed the 21 cm line emission using the Karl G. Jansky Very Large Array in D-array configuration (∼55″ resolution, ∼38 kpc) for 37 star-forming galaxies with available Hubble Space Telescope (HST) Lyα imaging from the Lyman Alpha Reference Samples.
Results. We detected 21 cm emission for 33 out of the 37 galaxies observed. We found no significant correlation of global HI properties (including HI mass, column density, gas fraction, depletion time, line width, or velocity shift between HI and Lyα), with the Lyα luminosity, escape fractions, or equivalent widths (EW) derived with HST photometry. Additionally, both Lyα-emitters and weak or non-emitters are distributed evenly along the HI parameter space of optically selected z = 0 galaxies. Around 74% of the sample is undergoing galaxy interaction, this fraction is higher for Lyα-emitters (83% for galaxies with EW ≥ 20 Å) than for weak or non-emitters (70%). Nevertheless, galaxies identified as interacting have Lyα and HI properties statistically consistent with those of non-interacting galaxies.
Conclusions. Our results show that global HI properties (on scales > 30kpc) have little direct impact on the Lyα output from galaxies. Instead, HI likely regulates Lyα emission on small scales: statistical comparisons of Lyα and high angular resolution 21 cm observations are required to fully assess the role of HI in Lyα radiative transfer. While our study indicates that major and minor galaxy mergers could play a role in the emission of Lyα photons in the Local Universe, especially for galaxies with high HI fractions, the line of sight that a system is observed through ultimately determines the Lyα observables.
Telemedizin und Telemonitoring zur Überwachung von Vitalparametern – eine medizinrechtliche Betrachtung
Authors: Jorzig Alexandra , Schneider Hendrik 
Published: November 2024

ZusammenfassungTelemedizin hat in den letzten Jahren aufgrund der Digitalisierung, des anhaltenden Ärztemangels und der Coronapandemie eine rasante Entwicklung durchlaufen. Sie bietet Patienten die Möglichkeit, medizinische Dienstleistungen aus der Ferne zu nutzen. Parallel dazu hat sich die künstliche Intelligenz (KI) als Diagnosetool und Instrument zur Überwachung von Vitalparametern etabliert. Diese Technologien versprechen nicht nur eine Verbesserung der Gesundheitsversorgung (z. B. im Rahmen der personalisierten und prädiktiven Analyse von Gesundheitsdaten), sondern werfen auch komplexe ethische und rechtliche Fragen auf.
Association of Circulating Homocysteine Level with the Risk of
Nephropathy in Type 2 Diabetes Mellitus: A Meta-Analysis
Authors: Zhu Manli , Fan Yandong 
Published: November 2024

AbstractThe objective of the study was to explore the association between homocysteine
(Hcy) levels and the risk of type 2 diabetic nephropathy (T2DN). PubMed, Web of
Science, Cochrane Library, and Embase databases were searched to collect
literature on the association between Hcy levels and the risk of T2DN. The
retrieval period was from the establishment of the database to September 10,
2024. Stata 15.0 statistical software was used for data analysis. Type II
diabetes without nephropathy was considered the control group, and
microalbuminuria and macroalbuminuria were included in the experimental group.
Fourteen articles were included in this meta-analysis. The results of the
meta-analysis showed that compared with the control group, the level of Hcy in
the T2DN group with microalbuminuria [Weighted mean difference (WMD)=2.50, 95%
confidence interval (CI): 1.49–3.51, p<0.001] and the group with
macroalbuminuria (WMD=3.38, 95% CI: 1.95–4.82) was significantly increased.
Compared with the T2DN microalbuminuria group, the Hcy level in the T2DN
macroalbuminuria group was considerably higher (WMD=2.12, 95% CI: 0.80–3.44,
p<0.001). High homocysteine levels were associated with an increased risk of
T2DN (OR=1.36, 95% CI: 1.20–1.54, p<0.001). In conclusion, circulating Hcy
levels are significantly associated with the severity of T2DN. In addition,
there was a significant association between high Hcy levels and an increased
risk of T2DN.