bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network topology and metabolic alterations in early- and mid-stage Parkinson’s disease: insights from fluorodeoxyglucose PET imaging
Authors: Li Min , Liu Jianpeng , Lv Rongbin , Liu Fangfei , Wang Guangbin , Wang Jiyuan , Cheng Juan , Jia Mingsheng , Wang Na , Liu Shuyong 
Published: January 2025

Objectives
Parkinson’s disease (PD) is a neurodegenerative disorder with distinct metabolic alterations in the brain, which are detectable via 18F-FDG PET. This study aims to delineate glucose metabolism patterns and network topology changes across early- and mid-stage PD patients.

Methods
A total of 80 PD patients (Hoehn–Yahr stages 1–3) were retrospectively analyzed, including 40 early-stage and 40 mid-stage cases, along with 40 age-matched healthy controls. All participants underwent 18F-FDG PET imaging. The brain metabolic activity was quantified, and network topology was assessed using graph theory metrics. Statistical comparisons between PD stages and control groups were performed to identify significant differences in metabolic patterns and network alterations.

Results
Early-stage PD patients exhibited hypermetabolism in regions such as the pons and thalamus, with significant differences in metabolic activity compared with controls. Mid-stage PD patients showed more extensive hypermetabolism in the pons, right cerebellum, and putamen, alongside hypometabolism in the cuneus and calcarine regions. Hub node connectivity analysis revealed decreased connectivity in temporal and occipital lobes for both stages, while the limbic and frontal lobes showed enhanced connectivity. Compared with early-stage PD, mid-stage PD had reduced connectivity in the limbic system but increased in the frontal and occipital lobes.

Conclusions

18F-FDG PET imaging reveals progressive metabolic disruptions and network changes in PD, offering potential biomarkers for disease staging and therapeutic targeting, while also aiding in the understanding of disease progression and guiding therapeutic interventions.
Friend or Foe? Safety and Efficacy of Hepatitis B Viremic Solid Organ Allograft into Seronegative Recipients
Authors: Pratt Catherine G , Noriega Nicolas , Delman Aaron M , Moore Allison N , Bari Khurram , Luckett Keith , Kaiser Tiffany E , Quillin Ralph C , Cuffy Madison C , Shah Shimul A 
Published: January 2025

Background:
Long-term outcomes of HBV nucleic acid test (NAT)-positive (+) allograft use in seronegative liver transplant (LT) and kidney transplant (KT) recipients remains unknown despite being incorporated into practice by select centers. This study compares long-term outcomes between HBV NAT+ and NAT-negative (–) allografts in seronegative recipients.

Study Design:
All recipients of an HBV core antibody-positive (HBcAb+) LT or KT were prospectively evaluated at a single transplant center from 6/2015-3/2023 and compared by NAT status. Study endpoints were post-transplant viremia, patient, and graft survival.

Results:
144 HBcAb+ LT and 220 HBcAb+ KT were performed including 57 (39.6%) NAT+ LT’s and 123 (55.9%) NAT+ KT’s with a median follow-up of 36 months. 14.8% of NAT+ and 3.5% of NAT– LTs experienced post-transplant viremia (p=0.004). At the time of last follow-up, 100% of NAT+ and 98.9% of NAT– LT recipients had undetectable HBV DNA (p=0.31). 4.1% of NAT+ and 6.2% of NAT– KTs experienced post-transplant viremia (p=0.12). At the time of last follow-up, 100% of NAT+ and 96.9% of NAT– KT recipients had undetectable HBV DNA (p=0.85). LT and KT patient and graft survival were not different between groups (p>0.05).

Conclusion:
With close surveillance, HBV seronegative recipients transplanted with NAT+ allografts can develop viremia which can be cleared with antiviral therapy. This is the first and largest single-center study reporting longer-term experience with HBV NAT+ allografts in seronegative recipients demonstrating the safe expansion of the donor pool.
DiffHiChIP: Identifying differential chromatin contacts from HiChIP data
Authors: Bhattacharyya Sourya , Salgado Figueroa Daniela , Georgopoulos Katia , Ay Ferhat 
Published: January 2025

ABSTRACTHigh-resolution conformation capture assays such as HiChIP are commonly used for profiling chromatin loops amongcis-regulatory elements including enhancers and promoters. Detection of differential loops between two conditions (e.g., same cell type different genotypes or before/after perturbations) help contextualize condition-specific activities of genes in connection with suchcis-regulatory elements. Existing differential loop callers for HiChIP data employ count-based models that are designed with gene expression data in mind and, hence, do not account for the distance decay of contact counts from HiChIP data. These approaches are not ideal for detection of differential long-range (>400Kb) loops, a limitation that persists even with the use of implicit or explicit corrections for this distance effect. We have implemented DiffHiChIP, the first comprehensive framework to call differential loops from HiChIP and similar 3C protocols. DiffHiChIP supports both DESeq2 and edgeR using either complete contact map or a subset of contacts (filtered) for background estimation, incorporates edgeR with generalized linear model (GLM) using either quasi-likelihood F-test or likelihood ratio test, and implements independent hypothesis weighting (IHW) as well as a distance stratification technique for modeling distance decay of contacts in estimating their statistical significance. Our results on 5 different datasets, each with two conditions or cell types, suggest that edgeR GLM-based models with IHW correction capture differential interactions, including long-range, that are supported by published Hi-C data and reference studies. Given the increasing trend of generating and utilizing HiChIP data for modeling chromatin regulation, DiffHiChIP promises to have broad impact and utility in this field.
The mechanism of DRB7.2:DRB4 mediated sequestering of endogenous inverted-repeat dsRNA precursors in plants
Authors: Paturi Sneha , Patra Debadutta , Behera Priti Chanda , Aute Ramdas , Waghela Nilam , Kinatukara Priyadarshan , Deshmukh Mandar V. 
Published: January 2025

ABSTRACTNoncoding transcribable inverted repeat sequences are vital in genome stability, regulation of transposable elements, mutations, and diseases in eukaryotes. In vascular plants, dsRNA Binding Proteins (dsRBPs), DRB7.2 and DRB4, inhibit Dicer-like-protein 3 (DCL3) to stall endogenous inverted-repeat dsRNA (endo-IR dsRNA) mediated gene silencing. As dsRBPs generally assist Dicers, the inhibition of DCL3 by a dsRBP complex is quite enigmatic. Here, we explore how the DRB7.2:DRB4 complex sequesters substrate dsRNA of DCL3 using a structure-based mechanistic approach. Intriguingly, the crucial step of endo-IR dsRNA precursor sequestration is the high affinity complex formation of interacting domains of DRB7.2 (DRB7.2M) and DRB4 (DRB4D3). Next, we establish that DRB7.2 simultaneously interacts with DRB4 and endo-IR dsRNA precursors, where DRB4 contributes towards enhancement in the affinity of the complex with dsRNA, thereby impairing DCL3 mediated cleavage of endo-IR dsRNA precursors. The uniqueness of the DRB4D3 structure implies that the trans-acting (tasi)/siRNA initiation complex formed by DCL4:DRB4 in plants is diverse from its non-plant higher eukaryotes. Overall, we present considerable insights into endo-IR dsRNA precursors regulation in plants and indicate a differential evolution of RNAi initiation complexes between plants and other higher eukaryotes.
Disrupted α-ketoglutarate homeostasis trains monocyte-derived macrophages towards M2-like phenotype in long-term treated HIV-infection
Authors: Escós Alejandra , Ambikan Anoop T , Schulster Sabrina , Svensson Akusjärvi Sara , Gelpi Marco , Mansouri Siavash , Naval Prajakta , Júnior Ronaldo Lira , Sood Vikas , Knudsen Andreas D. , Pathade Pratik P. , Mikaeloff Flora , Høgh Julie , Lourda Magda , Vesterbacka Jan , Nowak Piotr , Benfield Thomas , Pawar Vinay , Weiss Siegfried , Muvva Jagadeeswara Rao , Végvári Ákos , Gupta Soham , Savai Rajkumar , Nielsen Susanne D. , Neogi Ujjwal 
Published: January 2025

AbstractCells of the myeloid lineage, particularly monocytes and macrophages, play a key role in HIV infection by contributing to viral replication, immune response, and maintaining immune balance during suppressive therapy. We hypothesized that metabolic reprogramming and altered chemokine signaling in people living with HIV (PWH) on long-term antiretroviral therapy (ART) affect monocyte transport and polarization due to ongoing inflammation. Therefore, the present study aimed to identify the mechanism of impaired monocyte/macrophage function in PWH on well-treated ART that can lead to clinical intervention strategies to improve health. Single-cell RNA sequencing, immune-phenotyping, and metabolic modeling identified altered expression of chemokine and metabolite receptors and altered metabolic flux in PWH monocytes that decreased monocyte migration. The plasma secretome revealed a nonclassical inflammatory microenvironment in PWH. Integrative multi-omics and single-cell proteomics of differentiated monocyte-derived macrophages (MDMs) detected metabolic reprogramming orchestrated by α-ketoglutarate (AKG) that affected macrophage function and HIV infection. Increased levels of AKG in plasma were shown to occur in PWH under ART. Therefore, when differentiating MDM with serum from PWH or AKG, macrophage function was found polarized towards an M2-like state. AKG alone was shown to increase CCR5 levels and increase HIV-1 infection in MDM. Here, we utilize systems biology-driven identification and ex vivo assays to show impaired macrophage polarization, due to metabolic training, can leads to a low-grade nonclassical inflammatory environment in well-treated PWH.
PAX3-FOXO1 drives targetable cell state-dependent metabolic vulnerabilities in rhabdomyosarcoma
Authors: Paras Katrina I. , Brunner Julia S. , Boyer Jacob A. , Montero Angela M. , Jackson Benjamin T. , Chakraborty Sangita , Xie Abigail , Guillan Kristina , Siddiquee Armaan , Torres Lourdes Pajuelo , Rabinowitz Joshua D. , Kung Andrew , You Daoqi , Cruz Filemon Dela , Finley Lydia W. S. 
Published: January 2025

AbstractPAX3-FOXO1, an oncogenic transcription factor, drives a particularly aggressive subtype of rhabdomyosarcoma (RMS) by enforcing gene expression programs that support malignant cell states. Here we show that PAX3-FOXO1+RMS cells exhibit altered pyrimidine metabolism and increased dependence on enzymes involved inde novopyrimidine synthesis, including dihydrofolate reductase (DHFR). Consequently, PAX3-FOXO1+cells display increased sensitivity to inhibition of DHFR by the chemotherapeutic drug methotrexate, and this dependence is rescued by provision of pyrimidine nucleotides. Methotrexate treatment mimics the metabolic and transcriptional impact ofPAX3-FOXO1silencing, reducing expression of genes related to PAX3-FOXO1-driven malignant cell states. Accordingly, methotrexate treatment slows growth of multiple PAX3-FOXO1+tumor xenograft models, but not fusion-negative counterparts. Taken together, these data demonstrate that PAX3-FOXO1 induces cell states characterized by altered pyrimidine dependence and nominate methotrexate as an addition to the current therapeutic arsenal for treatment of these malignant pediatric tumors.
Sex does not Influence Neuronal Autophagy throughout Aging in Mice
Authors: Rodriguez Mya N , Stavoe Andrea KH 
Published: January 2025

ABSTRACTAutophagy is critical for the homeostasis and function of neurons, as misregulation of autophagy has been implicated in age-related neurodegenerative diseases and neuron-specific knockdown of early autophagy genes results in early neurodegeneration in mice. We previously found that autophagosome formation decreases with age in murine neurons. Sex differences have been intensely studied in neurodegenerative diseases, but whether sex differences influence autophagy at the neuronal level have not been investigated. We compared protein expression of 22 autophagy components between neural tissues of female and male mice across development and aging. We found minimal sex-related differences in autophagy protein expression throughout the murine lifespan. Additionally, we assayed the recruitment of autophagy complexes and autophagosome biogenesis; we found no sex-dependent differences in multiple stages of autophagosome formation in neurons, independent of age. Our data suggest that biological sex does not influence autophagosome formation in neurons across development and aging.
Constitutive expression of cardiomyocyte Klf9 precipitates metabolic dysfunction and spontaneous heart failure
Authors: Thakkar Chandni , Alikunju Saleena , Venkatasubramanium Aishwarya , Yang Zhi , Sayed Nazish , Abdellatif Maha , Sayed Danish 
Published: January 2025

AbstractMetabolic adaptations and flexibility during development and disease play an essential in cardiomyocyte function and survival. We recently reported Glucocorticoid receptor (GR)-Krüppel-like factor 9 (Klf9) axis in mediating metabolic adaptations in cardiomyocytes stimulated with Dexamethasone. Klf9 expression decreases in hypertrophic and failing hearts, suggesting its importance in cardiac homeostasis and its potential contribution to dysfunction under pressure overload. Genome wide Klf9 occupancy in adult hearts revealed 2,242 genes directly associated with Klf9, with enrichment in metabolic pathways, autophagy, ubiquitin-mediated proteolysis, and cellular senescence. We generated and characterized a conditional cardiac specific Klf9 knock-In (Klf9KI) mice, which developed progressive cardiac hypertrophy, cardiac dysfunction and cardiac failure by 8wks of age, with mortality by 12-14wks. RNA-seq analysis at 1wk, 4wks, and 8wks showed stage-specific transcriptional changes. At 1 week, 64.81% of differentially expressed genes were downregulated, aligning with Klf9’s predicted role as a transcriptional repressor. At 4wks and 8wks, more genes were upregulated, suggesting more of secondary targets in response to cardiac phenotype. KEGG pathway analysis showed dysregulation in lipid, carbohydrate and glutathione metabolism, transcriptional regulation, apoptosis, and innate immunity. Untargeted Metabolomics at 4wks identified significant alterations in tissue metabolite levels, particularly in pathways involving fatty acid metabolism, amino acids, and glucose, correlating with transcriptome data. Mitochondrial function assays revealed progressive dysregulation. At 2 weeks, complex I activity was significantly reduced, while complex II and IV activities were partially preserved. By 4 weeks, all measured respiratory complexes showed significant declines, consistent with decline in mitochondrial function. These mitochondrial deficits preceded overt cardiac dysfunction and likely contributed to the development of hypertrophy and failure. In conclusion, constitutive Klf9 overexpression disrupts transcriptional and metabolic homeostasis, driving progressive hypertrophy, cardiac dysfunction, and failure.
The liver clock tunes transcriptional rhythms in skeletal muscle to regulate mitochondrial function
Authors: Sica Valentina , Sato Tomoki , Tsialtas Ioannis , Hernandez Sophia , Chen Siwei , Baldi Pierre , Muñoz Cánoves Pura , Sassone-Corsi Paolo , Koronowski Kevin B. , Smith Jacob G. 
Published: January 2025

ABSTRACTCircadian clocks present throughout the brain and body coordinate diverse physiological processes to support daily homeostasis and respond to changing environmental conditions. The local dependencies within the mammalian clock network are not well defined. We previously demonstrated that the skeletal muscle clock controls transcript oscillations of genes involved in fatty acid metabolism in the liver, yet whether the liver clock also regulates the muscle was unknown. Here, we use hepatocyte-specificBmal1KO mice (Bmal1hep-/-) and reveal that approximately one third of transcriptional rhythms in skeletal muscle are regulated by the liver clock vivo. Treatment of myotubes with serum harvested fromBmal1hep-/-mice inhibited expression of genes involved in metabolic pathways, including oxidative phosphorylation. Overall, the transcriptional changes induced by liver clock-driven endocrine-communication revealed from our in vitro system were small in magnitude, leading us to surmise that the liver clock acts to fine-tune metabolic gene expression in muscle. Strikingly, treatment of myotubes with serum fromBmal1hep-/-mice inhibited mitochondrial ATP production compared to WT and this effect was only observed with serum harvested during the active phase. Overall, our results reveal communication between the liver clock and skeletal muscle–uncovering a bidirectional endocrine communication pathway dependent on clocks in these two key metabolic tissues. Targeting liver and muscle circadian clocks may represent a potential avenue for exploration for diseases associated with dysregulation of metabolism in these tissues.
Decreased KCC2 expression in the human spinal dorsal horn associated with chronic pain and long-term opioid use
Authors: Davis Olivia C , Ferland Samuel , Lorenzo Louis-Etienne , Murray-Lawson Clare , Shiers Stephanie , Yousuf Muhammad Saad , Dedek Annemarie , Tsai Eve C. , Vines Erin , Horton Peter , Cervantes Anna , Khan Tariq , Funk Geoffrey , Dussor Gregory , Godin Antoine G. , Ferrini Francesco , De Koninck Yves , Hildebrand Michael E. , Price Theodore J. 
Published: January 2025

AbstractLoss of GABAergic and glycinergic inhibitory efficacy in the spinal dorsal horn is associated with neuropathic pain and opioid-induced hyperalgesia in rodent models. Downregulation of the KCC2 chloride extrusion transporter is a key mechanism underlying this decreased inhibitory efficacy, but to-date there is no evidence supporting or opposing this hypothesis in humans. Here we demonstrate that KCC2 expression is decreased in superficial dorsal horn neurons of organ donors who died with a documented history of pain, or of long-term opioid use. We show profoundly decreased KCC2 dorsal horn membrane expression in a primary cohort associated with either chronic pain or opioid use, and in a replication cohort of mixed chronic pain and opioid use history. These results show that decreased dorsal horn inhibitory efficacy likely promotes chronic pain in humans and support the development of therapeutics augmenting KCC2 function as a treatment for chronic pain and opioid use disorders.
Takens’ theorem to assess EEG traces: regional variations in brain dynamics
Authors: Tozzi Arturo , Jaušovec Ksenija 
Published: January 2025

ABSTRACTTakens’ theorem (TT) proves that the behaviour of a dynamical system can be effectively reconstructed within a multidimensional phase space. This offers a comprehensive framework for examining temporal dependencies, dimensional complexity and predictability of time series data. We applied TT to investigate the physiological regional differences in EEG brain dynamics of healthy subjects, focusing on three key channels: FP1 (frontal region), C3 (sensorimotor region), and O1 (occipital region). We provided a detailed reconstruction of phase spaces for each EEG channel using time-delay embedding. The reconstructed trajectories were quantified through measures of trajectory spread and average distance, offering insights into the temporal structure of brain activity that traditional linear methods struggle to capture. Variability and complexity were found to differ across the three regions, revealing notable regional variations. FP1 trajectories exhibited broader spreads, reflecting the dynamic complexity of frontal brain activity associated with higher cognitive functions. C3, involved in sensorimotor integration, displayed moderate variability, reflecting its functional role in coordinating sensory inputs and motor outputs. O1, responsible for visual processing, showed constrained and stable trajectories, consistent with repetitive and structured visual dynamics. These findings align with the functional specialization of different cortical areas, suggesting that the frontal, sensorimotor and occipital regions operate with autonomous temporal structures and nonlinear properties. This distinction may have significant implications for advancing our understanding of normal brain function and enhancing the development of brain-computer interfaces. In sum, we demonstrated the utility of TT in revealing regional variations in EEG traces, underscoring the value of nonlinear dynamics.
AuthormetriX: Automated Calculation of Individual Authors’ Non-Inflationary Credit-Allocation Schemas’ and Collaboration Metrics from a Scopus Corpus
Authors: Adeosun Samuel O. 
Published: January 2025

AbstractBackgroundPublication count is the currency in academia, but the most widely used whole count method is considered unfair and inflationary. Several non-inflationary author credit-allocation schemas (NIACAS) have been proposed, but none is widely adopted in practice (e.g., in evaluating faculty scholarly productivity) or in bibliometric research. This low adoption and implementation rate may be due to the complexity in operationalizing the schemas.AimTo develop an application that automates the calculation of individual authors’ scholarly output metrics based on multiple NIACAS.MethodPublished formulas of NIACAS were written as Python functions wrapped in a Streamlit user interface that takes .csvfiles of the relevant corpus, and a list of author’s Scopus IDs as inputs. The functions calculate the authors’ output metrics based on NIACAS including first- and last-author straight counts, arithmetic, golden share, and multiple variations of fractional, geometric, and harmonic schemas. Collaboration metrics are also calculated. Secondary features include modelers for author counts and schemas. In a use-case, absolute rank displacement (ARD) and actual contribution proportions (ACP) were compared between highly cited clinical medicine researchers and highh-index pharmacy practice faculty populations.ResultsAuthormetriX accurately calculates individual authors’ aggregate scholarly output based on 14 NIACAS, from the file inputs. There were schema and population differences in ACP, but only schema differences in ARD within the populations studied.ConclusionsAuthormetriX simplifies the implementation of non-inflationary author credit-allocation schemas and will facilitate their broader adoption in practice and bibliometric research. AuthormetriX is freely available athttps://sadeosun-a-uthormetrix-v1.streamlit.app/.