bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diminished DNA binding affinity of DMRT1 caused by heterozygous DM domain mutations is a cause of male infertility
Authors: Marić Tihana , Castillo-Madeen Helen , Klarić Monika Logara , Barišić Antun , Trgovec-Greif Lovro , Murphy Mark W , Juchnewitsch Anna-Grete , Lillepea Kristiina , Dutta Avirup , Žunić Lucija , Stendahl Alexandra M , Punab Margus , Pomm Kristjan , Mendoza Daniel M , Lopes Alexandra M , Šorgić Ana Merkler , Vugrek Oliver , Gonçalves Joao , Almstrup Kristian , Aston Kenneth I , Belužić Robert , Ježek Davor , Bertoša Branimir , Laan Maris , Bojanac Ana Katušić , Conrad Donald F , Barbalić Maja 
Published: January 2025

Abstract
The most severe form of male infertility is idiopathic non-obstructive azoospermia (NOA), a complete sperm absence in the ejaculate. We performed exome sequencing in the Croatian infertile brothers with NOA and found a variant in DMRT1 (Doublesex and mab-3 related transcription factor 1) gene that was further assessed by the EMSA assay and molecular dynamic simulations. We additionally screened for DMRT1 mutations in 1940 infertile men diagnosed with spermatogenic failure, 644 normozoospermic controls, and 105 females with primary ovarian insufficiency (POI) recruited to the GEnetics of Male INfertility Initiative (GEMINI) or Estonian Andrology (ESTAND) cohorts. DMRT1 p.Pro74Leu (chr9:g.842059C &gt; T) variant was detected in infertile brothers in the highly conserved position within the DNA binding DM domain of the protein. EMSA assay showed reduced DNA binding of DMRT1P74L and molecular dynamic simulations showed differences in structural and dynamical properties between the wild type protein and DMRT1P74L. Plausible disease-causing DMRT1 variants were only identified in infertile men (13/1940; 0.67%), and none in 639 fertile controls. Burden testing showed an excess of rare deleterious DM domain mutations in the infertility cohort compared to gnomAD v.4.0 population-based controls (Fisher’s exact test, p = 1.44 x 10−5). Three rare deleterious variants in DMRT1 were found in 104 cases of POI. The findings of this study strengthen the evidence of DMRT1 variants being a causal factor for male infertility and provide the distribution of likely pathogenic variants across the gene. This is also the first study to suggest that DMRT1 variants may also be linked to POI.
Decanoylcarnitine Improves Liver Mitochondrial Dysfunction in Hepatitis B Virus Infection by Enhancing Fatty Acid β-Oxidation
Authors: Sun Ye , Chen Qingling , Liu Yuxiao , Jiao Mengfan , Dai Zixing , Hou Xiaoxue , Liu Rui , Li Yuwen , Zhu Chuanlong 
Published: January 2025

Abstract

Background
The incidence of metabolic-associated steatotic liver disease in patients with chronic hepatitis B is increasing annually; however, the interaction between hepatitis B virus (HBV) infection and lipid metabolism remains unclear. This study attempted to clarify whether fatty acid metabolism regulation could alleviate mitochondrial dysfunction caused by HBV infection.

Methods
A public gene set of human livers was analyzed, and a proteomic analysis on mouse livers was conducted to explore metabolic disorders and affected organelles associated with HBV infection. The effect of decanoylcarnitine on fatty acid β-oxidation and mitochondria was investigated in vivo and in vitro. The pathways involved were shown by proteomic analysis and confirmed by Western blot.

Results
HBV infection could cause fatty acid β-oxidation disorder and mitochondrial dysfunction in vivo and in vitro. CPT1A overexpression could improve mitochondrial function in hepatocytes. Furthermore, decanoylcarnitine supplementation could activate CPT1A expression, thus improving fatty acid metabolism and repairing mitochondrial dysfunction. Proteomic analysis of mouse livers suggests that decanoylcarnitine stimulates the peroxisome proliferator–activated receptor (PPAR) signaling pathway, and PPARα was the most important among PPARs.

Conclusions
Impaired fatty acid metabolism and mitochondrial dysfunction in hepatocytes caused by HBV infection could be partially restored by exogenous supplementation of decanoylcarnitine. This work elucidates the therapeutic potential of decanoylcarnitine in HBV infection and provides a new approach for diseases related to mitochondrial dysfunction.
Abundant and active community members respond to diel cycles in hot spring phototrophic mats
Authors: Shelton Amanda N , Yu Feiqiao B , Grossman Arthur R , Bhaya Devaki 
Published: January 2025

Abstract
Photosynthetic microbial mats in hot springs can provide insights into the diel behaviors of communities in extreme environments. In this habitat, photosynthesis dominates during the day, leading to super-oxic conditions, with a rapid transition to fermentation and anoxia at night. Multiple samples were collected from two springs over several years to generate metagenomic and metatranscriptomic datasets. Metagenome-assembled genomes comprised 71 taxa (in 19 different phyla), of which 12 core taxa were present at high abundance in both springs. The eight most active taxa identified by metatranscriptomics were an oxygenic cyanobacterium (Synechococcus sp.), five anoxygenic phototrophs from three different phyla, and two understudied heterotrophs from phylum Armatimonadota. In all eight taxa, a significant fraction of genes exhibited a diel expression pattern, although peak timing varied considerably. The two abundant heterotrophs exhibit starkly different peak timing of expression, which we propose is shaped by their metabolic and genomic potential to use carbon sources that become differentially available during the diel cycle. Network analysis revealed pathway expression patterns that had not previously been linked to diel cycles, including ribosome biogenesis and chaperones. This provides a framework for analyzing metabolically coupled communities and the dominant role of the diel cycle.
Pacmanvirus isolated from the Lost City hydrothermal field extends the concept of transpoviron beyond the family Mimiviridae
Authors: Santini Sébastien , Lartigue Audrey , Alempic Jean-Marie , Couté Yohann , Belmudes Lucid , Brazelton William J , Lang Susan Q , Claverie Jean-Michel , Legendre Matthieu , Abergel Chantal 
Published: January 2025

Abstract
The microbial sampling of submarine hydrothermal vents remains challenging, with even fewer studies focused on viruses. Here we report what is to our knowledge the first isolation of a eukaryotic virus from the Lost City hydrothermal field, by co-culture with the laboratory host Acanthamoeba castellanii. This virus, named pacmanvirus lostcity, is closely related to previously isolated pacmanviruses (strains A23 and S19), clustering in a divergent clade within the long-established family Asfarviridae. The icosahedral particles of this virus are 200 nm in diameter, with an electron-dense core surrounded by an inner membrane. The viral genome of 395 708 bp (33% G + C) has been predicted to encode 473 proteins. However, besides these standard properties, pacmanvirus lostcity was found to be associated with a new type of selfish genetic element, 7 kb in length, whose architecture and gene content are reminiscent of those of transpovirons, hitherto specific to the family Mimiviridae. As in previously described transpovirons, this selfishg genetic element propagates as an episome within its host virus particles and exhibits partial recombination with its genome. In addition, an unrelated episome with a length of 2 kb was also found to be associated with pacmanvirus lostcity. Together, the transpoviron and the 2-kb episome might participate in exchanges between pacmanviruses and other DNA virus families. It remains to be elucidated if the presence of these mobile genetic elements is restricted to pacmanviruses or was simply overlooked in other members of the Asfarviridae.
Inflation and Monetary Policy in a Low-Income and Fragile State: The Case of Guinea
Authors: Carrière-Swallow Yan , Koumtingué Nelnan Fidèle , Weber Sebastian 
Published: January 2025

ABSTRACT
Inflation in low-income countries is often high and volatile, driven by external shocks. In addition, inflation in fragile states is affected by highly volatile domestic factors that complicate monetary policy's ability to deliver price stability. We estimate the drivers of inflation in Guinea since the early 2000s, a period in which the country suffered major shocks from pandemics, commodity price movements, and multiple military coups, and during which inflation averaged 12%. Results confirm that global commodity and transport prices account for a large share of the variation in inflation. The contribution of monetary policy shocks to inflation is moderate, reflecting its broadly neutral stance throughout most of the last two decades. However, monetary policy has occasionally made larger contributions to inflation, and recently helped contain price pressures from high commodity prices. The effectiveness of monetary policy reflects a strong relationship between monetary aggregates and the exchange rate.
Paradoxical combination of osteosclerosis and osteopenia in an adult woman with biallelic TNFRSF11A loss-of-function variants escaping nonsense-mediated decay
Authors: Gajewski Dario , Hennig Anna Floriane , Grün Regina , Siggelkow Heide , Vishnolia Svenja , Bastian Leonard , Taipaleenmäki Hanna , Schulz Ansgar , Kornak Uwe , Hesse Eric 
Published: January 2025

Abstract
Osteoclasts are essential for bone resorption, playing a crucial role in skeletal development, homeostasis, and remodeling. Their differentiation depends on the RANK receptor encoded by the TNFRSF11A gene, with defects in this gene linked to osteoclast-poor sclerosing skeletal dysplasias. This report presents a 37-yr-old woman with normal height, valgus deformities that were treated surgically, frequent fractures, scoliosis, mildly elevated BMD, sclerotic diaphyseal bone, and metaphyseal widening. Initially suspected of having dysosteosclerosis, her diagnosis shifted toward Pyle disease due to the valgus deformity and prominent metaphyseal widening and translucency. Genetic analysis identified 2 pathogenic TNFRSF11A variants: a nonsense mutation c.1093G&gt;T, p.(Glu365*) and a frameshift mutation c.1266_1268delinsCC, p.(Leu422Phefs*104). Thus, genetic and clinical assessment converged on the diagnosis of a mild form of dysosteosclerosis. Both mutations introduced premature stop codons but escaped complete nonsense-mediated decay, potentially permitting residual protein function. Analysis of patient-derived osteoclasts cultured on glass surfaces showed partial differentiation. However, in vitro resorptive function was strongly impaired, which was clinically reflected by reduced serum concentration of the bone resorption marker CTx. Despite this impairment, the retained residual resorptive function likely explains the patient’s relatively mild clinical presentation. These findings underscore the complex genetic interactions that affect osteoclast function, leading to a spectrum of phenotypes in osteoclast-related bone disorders.
Optimization using kriging metamodel and CMA-ES to improve temperature uniformity of electric vehicle liquid-cooled cylindrical Li-ion battery BTMS
Authors: Park Seokjun , Lee Hamin , Park Cheonha , An Jaewook , Kim Chang-Wan 
Published: January 2025

Abstract
Temperature uniformity in Li-ion battery thermal management systems (BTMS) is crucial for achieving thermal safety and optimal performance in electric vehicles. This study proposes a method to enhance the temperature uniformity of a liquid-cooled BTMS by using a kriging metamodel and the covariance matrix adaptation evolution strategy (CMA-ES). The heat generation rate of the battery was determined based on voltage and current data, followed by thermal fluid analysis to evaluate the cooling performance. Key design variables included the outer and inner dimensions of the cooling plate and the coolant flow rate, constrained by the BTMS mass. The kriging metamodel was used to reduce computational costs significantly, while CMA-ES provided a robust optimization method capable of efficiently handling complex, multimodal design spaces. The combined approach resulted in a 21.15% reduction in temperature difference without increasing the BTMS mass, demonstrating the effectiveness of this optimization strategy in improving the thermal management of Li-ion battery modules.
Thymic Eosinophils: What Are You Doing Here?
Authors: Gatti Dominique M , Reynolds Lisa A 
Published: January 2025

Abstract
The thymus is a primary lymphoid organ where major types of T lymphocytes undergo essential developmental processes. Eosinophils are among the cell types present in microenvironments within the thymus, and perhaps surprisingly, the role of thymic eosinophils, especially during homeostatic conditions, remains unclear. Major physiological events impact thymic organization and function throughout life: including age-related involution, pregnancy, and exposure to chemotherapy or radiation. In this Review, we summarize literature that has explored factors that regulate the accumulation, phenotype, and location of thymic eosinophils during homeostatic development and during conditions where homeostasis is perturbed. Further, we discuss the current theories as to the function of thymic eosinophils, and we consider how the heterogeneity of thymic eosinophil populations may reflect a temporal, spatial, and situational multi-functionality of thymic eosinophils.
Under the Moon’s Healing Influence: George MacDonald’s Literary Re-envisioning of Women’s Health
Authors: Little Ariel 
Published: January 2025

Abstract
This article demonstrates how the work of fantasist George MacDonald interacted with Victorian debates regarding women’s health. Participating in the trend to interpret MacDonald’s fiction as invested in contemporary societal issues, I bring to the forefront MacDonald’s interest in women’s rights and alternative medicine. Emphasizing MacDonald’s belief in the persuasive power of appealing indirectly to the imagination, I argue that MacDonald aimed to participate in women’s health reform through his short fiction. Focusing on works published between 1850 and 1880, I discuss MacDonald’s fairy tales in conjunction with his realist fiction in order to discern a pattern of literary tropes, such as the cursed princess, deployed to subvert dominant medical views of women’s bodies. I consider how MacDonald represents elements of Victorian medicine, such as the clinical objectification of patients, the medicalization of disability, and the early social eugenics movement. In his countercultural representation of impaired female characters as empowered heroines, I argue that MacDonald challenges the medical stigmatization of women’s bodies. This article also considers how MacDonald challenges the interventionism of Victorian allopathy by celebrating the practices of established alternative approaches, such as homeopathy and hydropathy. As an early proponent of bibliotherapy, MacDonald demonstrates his belief in the healing potential of narrative both within the context of his narratives and in his use of narrative to improve women’s health practices.
Benchmarking cross-species single-cell RNA-seq data integration methods: towards a cell type tree of life
Authors: Zhong Huawen , Han Wenkai , Gomez-Cabrero David , Tegner Jesper , Gao Xin , Cui Guoxin , Aranda Manuel 
Published: January 2025

Abstract
Cross-species single-cell RNA-seq data hold immense potential for unraveling cell type evolution and transferring knowledge between well-explored and less-studied species. However, challenges arise from interspecific genetic variation, batch effects stemming from experimental discrepancies and inherent individual biological differences. Here, we benchmarked nine data-integration methods across 20 species, encompassing 4.7 million cells, spanning eight phyla and the entire animal taxonomic hierarchy. Our evaluation reveals notable differences between the methods in removing batch effects and preserving biological variance across taxonomic distances. Methods that effectively leverage gene sequence information capture underlying biological variances, while generative model-based approaches excel in batch effect removal. SATURN demonstrates robust performance across diverse taxonomic levels, from cross-genus to cross-phylum, emphasizing its versatility. SAMap excels in integrating species beyond the cross-family level, especially for atlas-level cross-species integration, while scGen shines within or below the cross-class hierarchy. As a result, our analysis offers recommendations and guidelines for selecting suitable integration methods, enhancing cross-species single-cell RNA-seq analyses and advancing algorithm development.
High-dose MTX-based polychemotherapy for primary CNS lymphoma in younger patients: Long-term efficacy of the modified Bonn protocol
Authors: Zeyen Thomas , Weller Johannes , Schneider Matthias , Potthoff Anna-Laura , Schaub Christina , Roever Lea , Gkika Eleni , Vatter Hartmut , Holderried Tobias A W , Brossart Peter , Herrlinger Ulrich , Schaefer Niklas 
Published: January 2025

Abstract

Background
Polychemotherapy based on high-dose methotrexate (HD-MTX) is the standard therapy for newly diagnosed younger patients (&lt;65 years) with primary CNS lymphoma (PCNSL). In the modified Bonn protocol, consolidation therapy consists of intraventricular chemotherapy that is added to the continuation of HD-MTX-based chemotherapy. This study investigates the efficacy and toxicity of the modified Bonn protocol in first-line therapy of young patients with PCNSL.

Methods
All consecutive immunocompetent patients aged &lt;65 years who were newly diagnosed with PCNSL from 2012 to 2021 and started first-line therapy with the modified Bonn protocol at the Neurooncology Center Bonn were included in this retrospective analysis. Treatment comprised 3 courses of rituximab/HD-MTX/IFO followed by consolidation therapy with 2 courses of HD-AraC and 2 courses of HD-MTX/IFO, including intrathecal MTX and intrathecal AraC. Progression-free and overall survival were evaluated.

Results
Forty-three patients were included. Thirty-seven patients (86%) reached intrathecal consolidation therapy. Grade 3/4 toxicity was observed in 58.1%. The median PFS was 102.8 months; 5-year OS rate was 76% (median not reached). Eighteen patients developing refractory/relapsed PCNSL received second-line therapy using the modified Freiburg protocol (AraC/TT +/- HD-MTX/rituximab followed by BCNU/TT-based HD-ASCT). A second relapse was observed in 11/18 patients (median follow-up of 17 months (IQR 5-43.7 months)).

Conclusions
First-line treatment of PCNSL with the modified Bonn protocol is highly effective. The outcome compares well with other seemingly more toxic PCNSL protocols for younger patients. In patients with disease recurrence, second-line therapy according to the modified Freiburg protocol appears to be effective.
An epH-driven DNA nanodevice for impeding metastasis in vivo by selectively blocking cell signaling
Authors: Yuan Kun , Meng Hong-Min , Sun Hongzhi , Qu Lingbo , Li Zhaohui , Tan Weihong 
Published: January 2025

Abstract
Invasion and metastasis dominate tumor progression, causing a substantial proportion of cancer-related deaths. However, the efficacy of current antimetastatic treatments is hampered by the dearth of targeted therapeutics. Recently developed synthetic-receptor toolkits offer potential for artificially regulating cellular behavior. However, to the best of our knowledge, none has yet successfully suppressed tumor metastasis in vivo. Here, we report the first extracellular pH (epH)-driven DNA nanodevice for use in antimetastatic treatment in vivo by manipulating heterogeneous receptors on the tumor cell surface. This DNA nanodevice was constructed by partially locking tumorigenic receptor-specific aptamers with two i-motifs. Acidic extracellular pH induced dynamic allosteric reassembly within the nanodevice. The restructured nanodevice enabled oligomerization of c-Met and TfR, which inhibited tumor metastasis by blocking the HGF/c-Met signaling pathway. A suppressive efficacy of 86.25% was verified in an early hepatocarcinoma-pulmonary-metastasis mouse model. Such impressive antimetastatic efficacy suggests an efficient paradigm for developing adaptive antimetastatic therapeutics.
Systems analysis of long-term heat stress responses in the C4 grass Setaria viridis
Authors: Zhang Peng , Sharwood Robert , Carroll Adam , Estavillo Gonzalo M , von Caemmerer Susanne , Furbank Robert T 
Published: January 2025

Abstract
Many C4 plants are used as food and fodder crops and often display improved resource use efficiency compared to C3 plants. However, the response of C4 plants to future extreme conditions such as heatwaves is less understood. Here, Setaria viridis, an emerging C4 model grass, was grown under long-term high temperature stress for two weeks (42°C, compared to 28°C). This resulted in stunted growth, but surprisingly had little impact on leaf thickness, leaf area-based photosynthetic rates and bundle sheath leakiness. Dark respiration rates increased and there were major alterations in carbon and nitrogen metabolism in the heat-stressed plants. Abscisic acid and indole-acetic acid–amino acid conjugates accumulated in the heat-stressed plants, consistent with transcriptional changes. Leaf transcriptomics, proteomics and metabolomics analyses were carried out and mapped onto the metabolic pathways of photosynthesis, respiration, carbon/nitrogen metabolism and phytohormone biosynthesis and signaling. An in-depth analysis of correlations between transcripts and their corresponding proteins revealed strong differences between groups in the strengths and signs of correlations. Overall, many stress signaling pathways were upregulated, consistent with multiple signals leading to reduced plant growth. A systems-based model of the plant response to long-term heat stress is presented based on the oxidative stress, phytohormone and sugar signaling pathways.