bluuebunny/crossref_metadata_2025_split huggingface dataset:
A high-fidelity CRISPR-Cas13 system improves abnormalities associated with C9ORF72-linked ALS/FTD
Authors: McCallister Tristan X. , Lim Colin K. W. , Singh Mayuri , Zhang Sijia , Ahsan Najah S. , Terpstra William M. , Xiong Alisha Y. , Zeballos C M. Alejandra , Powell Jackson E. , Drnevich Jenny , Kang Yifei , Gaj Thomas 
Published: January 2025

AbstractAn abnormal expansion of a GGGGCC (G4C2) hexanucleotide repeat in the C9ORF72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two debilitating neurodegenerative disorders driven in part by gain-of-function mechanisms involving transcribed forms of the repeat expansion. By utilizing a Cas13 variant with reduced collateral effects, we develop here a high-fidelity RNA-targeting CRISPR-based system for C9ORF72-linked ALS/FTD. When delivered to the brain of a transgenic rodent model, this Cas13-based platform curbed the expression of the G4C2 repeat-containing RNA without affecting normal C9ORF72 levels, which in turn decreased the formation of RNA foci, reduced the production of a dipeptide repeat protein, and reversed transcriptional deficits. This high-fidelity system possessed improved transcriptome-wide specificity compared to its native form and mediated targeting in motor neuron-like cells derived from a patient with ALS. These results lay the foundation for the implementation of RNA-targeting CRISPR technologies for C9ORF72-linked ALS/FTD.
Structure and catalytic activity of the SAM-utilizing ribozyme SAMURI
Authors: Chen Hsuan-Ai , Okuda Takumi , Lenz Ann-Kathrin , Scheitl Carolin P. M. , Schindelin Hermann , Höbartner Claudia 
Published: January 2025

AbstractRibozymes that catalyze site-specific RNA modification have recently gained increasing interest for their ability to mimic methyltransferase enzymes and for their application to install molecular tags. Recently, we reported SAMURI as a site-specific alkyltransferase ribozyme using S-adenosylmethionine (SAM) or a stabilized analog to transfer a methyl or propargyl group to N3 of an adenosine. Here, we report the crystal structures of SAMURI in the postcatalytic state. The structures reveal a three-helix junction with the catalytic core folded into four stacked layers, harboring the cofactor and the modified nucleotide. Detailed structure–activity analyses explain the cofactor scope and the structural basis for site selectivity. A structural comparison of SAMURI with SAM riboswitches sheds light on how the synthetic ribozyme overcomes the strategies of natural riboswitches to avoid self-methylation. Our results suggest that SAM and its analogs may serve as substrates for various RNA-catalyzed reactions, for which the corresponding ribozymes remain to be identified.
China’s product-level CO2 emissions dataset aligned with national input-output tables from 1997 to 2020
Authors: Li Xinbei , Liu Yu , Zhang Jing , Zhou Meifang , Meng Bo 
Published: January 2025

AbstractCarbon emission research based on input-output tables (IOTs) has received attention, but data quality issues persist due to inconsistencies between the sectoral scopes of energy statistics and IOTs. Specifically, China’s official energy data are reported at the industry level, whereas IOTs are organized by product sectors. Valid IOT-based environmental models require consistent transformation from industry-level to product-level emissions. However, most existing studies overlook this necessary transformation, leading to substantial estimation errors. This study addresses this issue by developing a high-quality, product-level emissions dataset for China, grounded in robust product technology identification derived from IOTs. Our new emissions dataset, aligned with Chinese national IOTs, covers 29 to 34 product sectors across 7 benchmark years from 1997 to 2020. It includes data from 4 to 5 energy sectors and detailed emissions for 18 types of fossil fuels, using both IPCC-default and two China-specific emission factors. This inventory improves product-sector emission accounting and can be integrated into IOT-based climate and energy models, serving as a fundamental database for energy and emission analysis.
Forearm elevation impairs local static handgrip endurance likely through reduction in vascular conductance and perfusion pressure: revisiting Rohmert’s curve
Authors: Heinzl L. , Risse S. , Schwarzbach H. , Hildebrandt O. , Koehler U. , Koenig A. M. , Mahnken A. H. , Kinscherf R. , Hildebrandt W. 
Published: January 2025

AbstractMaximal isometric contraction time (MICT) is critical for most motor tasks and depends on skeletal muscle blood flow at < 40% of maximal voluntary strength (MVC). Whether limb work positions associated with reduced perfusion pressure and facilitated vessel compression affect MICT is largely unknown. In 14 healthy young men we therefore assessed bilateral handgrip MICT at 15, 20, 30, 40, and 70% of MVC in horizontal forearm positions of 0.0, + 27.5 or − 27.5 cm relative to heart level. Forearm blood flow (FBF, venous occlusion plethysmography) and brachial blood pressure were measured repetitively. MICT at 15% MVC was significantly shorter by 66.3 and 86.2 s with forearm position + 27.5 cm (389.6 ± 23.3 s) as compared to 0.0 cm (455.9 ± 34.1 s) and − 27.5 cm (475.8 ± 35.0 s) while MICT at 20–70% MVC was unaffected. Peak FBF at 15% MVC was significantly lower in position + 27.5 cm (11.11 ± 0.92 ml/min/100 ml) compared to 0.0 cm (15.55 ± 0.91 ml/min/100 ml) or − 27.5 cm (14.21 ± 0.59 ml/min/100 ml) and vascular resistance significantly higher in position + 27.5 vs 0.0 or − 27.5 cm. Working position above, but not below heart level may limit MICT at 15% MVC possibly through blood flow reduction arising from increased vascular resistance beside reduced perfusion pressure. Local isometric endurance warrants (re)evaluation regarding hydrostatic/gravitational or other hemodynamic limitations.
The non-nutritive sweetener rebaudioside a enhances phage infectivity
Authors: Marongiu Luigi , Brzozowska Ewa , Brykała Jan , Burkard Markus , Schmidt Herbert , Szermer-Olearnik Bożena , Venturelli Sascha 
Published: January 2025

AbstractNon-nutritive sweeteners (NNS) are widely employed in foodstuffs. However, it has become increasingly evident that their consumption is associated with bacterial dysbiosis, which, in turn, is linked to several health conditions, including a higher risk of type 2 diabetes and cancer. Among the NNS, stevia, whose main component is rebaudioside A (rebA), is gaining popularity in the organic food market segment. While the effect of NNS on bacteria has been established, the impact of these sweeteners on bacterial viruses (phages) has been neglected, even though phages are crucial elements in maintaining microbial eubiosis. The present study sought to provide a proof-of-concept of the impact of NNS on phage infectivity by assessing the binding of rebA to phage proteins involved in the infection process of enteropathogenic bacteria, namely the fiber protein gp17 of Yersinia enterocolitica phage φYeO3-12 and the tubular baseplate protein gp31 of Klebsiella pneumoniae phage 32. We employed docking analysis and a panel of in vitro confirmatory tests (microscale thermophoresis, RedStarch™ depolymerization, adsorption, and lysis rates). Docking analysis indicated that NNS can bind to both fiber and baseplate proteins. Confirmatory assays demonstrated that rebA can bind gp31 and that such binding increased the protein’s enzymatic activity. Moreover, the binding of rebA to gp17 resulted in a decrease in the adsorption rate of the recombinant protein to its host but increased the Yersinia bacteriolysis caused by the whole phage compared to unexposed controls. These results support the hypothesis that NNS can impair phage infectivity, albeit the resulting effect on the microbiome remains to be elucidated.
Otolith chemistry suggests population heterogeneity within a genetically homogeneous Indian scad population along Indian coast
Authors: Jose Anjaly , Sukumaran Sandhya , Raj Neenu , Nisha K. , Varghese Eldho , Laly S. J. , Panda Satyen Kumar , Roul Subal Kumar , Azeez P. Abdul , Kizhakudan Shoba Joe , Gopalakrishnan A. 
Published: January 2025

AbstractThe Indian scad, Decapterus russelli is one of the most exploited pelagic resources of India. Population genetic analyses using mitochondrial and nuclear markers indicated a lack of genetic structuring among populations from Indian waters. As this species is highly migratory, it is also important to establish the environmental influence on its population structure. In the present study, the whole sagittal otolith composition was analysed using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) to assess spatial distribution of D. russelli collected from 4 sites along the Indian coast. Elemental ratios (Ba/Ca, Fe/Ca, K/Ca, Mg/Ca, Na/Ca, Sr/Ca and Zn/Ca) were analysed using univariate and multivariate statistics to determine whether this chemical signature can provide insight into the adaptive patterns. All element/Ca ratios are found to be significantly different between the four sampling locations (ANOVA, p < 0.05; MANOVA, p < 0.05). Five of the element/Ca ratios were found to be significantly different when the data was analysed coastwise (ANOVA, p < 0.05; MANOVA, p < 0.05). The LDA plot also showed the spatial heterogeneity of Element/Ca ratios between the four sampling sites, but some overlaps were also observed, reflecting the migratory ability of the species. This basic information on spatial ecology is required for formulating effective management and conservation strategies for the species.
The E3 ubiquitin ligase MARCH1 mediates downregulation of plasma membrane GABAB receptors under ischemic conditions by inhibiting fast receptor recycling
Authors: Bhat Musadiq A. , Hleihil Mohammad , Mondéjar Irene , Grampp Thomas , Benke Dietmar 
Published: January 2025

AbstractGABAB receptors mediate prolonged inhibition in the brain and are important for keeping neuronal excitation and inhibition in a healthy balance. However, under excitotoxic/ischemic conditions, GABAB receptors are downregulated by dysregulated endocytic trafficking and can no longer counteract the severely enhanced excitation, eventually triggering neuronal death. Recently, we developed interfering peptides targeting protein-protein interactions involved in downregulating the receptors. Treatment with these peptides restored GABAB receptor expression after an ischemic insult and thereby inhibited neuronal overexcitation and progressive neuronal death. In this study, we searched for GABAB receptor interactions that specifically occur under ischemic conditions. We found that the E3 ubiquitin ligase MARCH1 is specifically upregulated under ischemic/excitotoxic conditions. Upregulated MARCH1 interacts with GABAB receptors and triggered downregulation of plasma membrane GABAB receptors by inhibiting fast recycling of the receptors. We developed an interfering peptide that inhibits the MARCH1/GABAB receptor interaction. Treatment of cultured neurons subjected to ischemic stress with this peptide restored receptor expression and as a consequence stopped progressive neuronal death. Thus, inhibiting the interaction of GABAB receptors with MARCH1 to restore cell surface receptor expression might be a promising strategy to prevent progressive neuronal death induced by ischemic conditions.
A hybrid machine learning approach for the personalized prognostication of aggressive skin cancers
Authors: Andrew Tom W. , Alrawi Mogdad , Plummer Ruth , Reynolds Nick , Sondak Vern , Brownell Isaac , Lovat Penny E. , Rose Aidan , Shalhout Sophia Z. 
Published: January 2025

AbstractAccurate prognostication guides optimal clinical management in skin cancer. Merkel cell carcinoma (MCC) is the most aggressive form of skin cancer that often presents in advanced stages and is associated with poor survival rates. There are no personalized prognostic tools in use in MCC. We employed explainability analysis to reveal new insights into mortality risk factors for this highly aggressive cancer. We then combined deep learning feature selection with a modified XGBoost framework, to develop a web-based prognostic tool for MCC termed ‘DeepMerkel’. DeepMerkel can make accurate personalised, time-dependent survival predictions for MCC from readily available clinical information. It demonstrated generalizability through high predictive performance in an international clinical cohort, out-performing current population-based prognostic staging systems. MCC and DeepMerkel provide the exemplar model of personalised machine learning prognostic tools in aggressive skin cancers.
Second harmonic generation imaging reveals entanglement of collagen fibers in the elephant trunk skin dermis
Authors: Schulz Andrew K. , Plotczyk Magdalena , Sordilla Sophia , Gaboriau David C. A. , Boyle Madeline , Singal Krishma , Reidenberg Joy S. , Hu David L. , Higgins Claire A. 
Published: January 2025

AbstractForm-function relationships often have tradeoffs: if a material is tough, it is often inflexible, and vice versa. This is particularly relevant for the elephant trunk, where the skin should be protective yet elastic. To investigate how this is achieved, we used classical histochemical staining and second harmonic generation microscopy to describe the morphology and composition of elephant trunk skin. We report structure at the macro and micro scales, from the thickness of the dermis to the interaction of 10 μm thick collagen fibers. We analyzed several sites along the length of the trunk to compare and contrast the dorsal-ventral and proximal-distal skin morphologies and compositions. We find the dorsal skin of the elephant trunk can have keratin armor layers over 2 mm thick, which is nearly 100 times the thickness of the equivalent layer in human skin. We also found that the structural support layer (the dermis) of the elephant trunk contains a distribution of collagen-I (COL1) fibers in both perpendicular and parallel arrangement. The bimodal distribution of collagen is seen across all portions of the trunk, and is dissimilar from that of human skin where one orientation dominates within a body site. We hypothesize that this distribution of COL1 in the elephant trunk allows both flexibility and load-bearing capabilities. Additionally, when viewing individual fiber interactions of 10 μm thick collagen, we find the fiber crossings per unit volume are five times more common than in human skin, suggesting that the fibers are entangled. We surmise that these intriguing structures permit both flexibility and strength in the elephant trunk. The complex nature of the elephant skin may inspire the design of materials that can combine strength and flexibility.
The Amazonian mangrove systems accumulate and release dissolved neodymium and hafnium to the oceans
Authors: Xu Antao , Hathorne Ed , Seidel Michael , Liu Te , Asp Nils E. , Koschinsky Andrea , Dittmar Thorsten , Frank Martin 
Published: January 2025

AbstractMangroves are essential tropical ecosystems nurturing a wide range of marine biodiversity and counteracting global warming by sequestering atmospheric carbon dioxide. Hence, the export mechanisms and fluxes of particulate and dissolved organic carbon and trace elements from mangroves directly influence coastal productivity, the global carbon cycle and thus global climate, which are, however, not well constrained. Here we find consistent radiogenic neodymium and hafnium isotopic compositions of porewater, sedimentary iron-manganese oxyhydroxides and coastal seawater, suggesting that the Amazonian mangrove belt supplies trace elements through porewater discharge, dissolution of iron-manganese oxyhydroxides and their interactions with seawater. Together, these processes supply 8.4 × 106 g yr-1 dissolved neodymium, equivalent to 64% of the total sources of neodymium to the Amazonian coastal seawater. Globally, mangrove systems along the continental margins contribute 6–9% of the net neodymium input to the ocean, which is similar to the contributions from atmospheric deposition. A contribution of this magnitude is potentially also the case for other trace elements, given the strong correlations between neodymium and iron (Pearson r = 0.92), and manganese (r = 0.75) concentrations across the entire river-ocean section, emphasizing the crucial role of mangrove system inputs in micro-nutrient cycling.
Gene signatures derived from transcriptomic-causal networks stratify colorectal cancer patients for effective targeted therapy
Authors: Yazdani Akram , Lenz Heinz-Josef , Pillonetto Gianluigi , Mendez-Giraldez Raul , Yazdani Azam , Sanoff Hanna , Hadi Reza , Samiei Esmat , Venook Alan P. , Ratain Mark J. , Rashid Naim , Vincent Benjamin G. , Qu Xueping , Wen Yujia , Kosorok Michael , Symmans William F. , Shen John Paul Y. C. , Lee Michael S. , Kopetz Scott , Nixon Andrew B. , Bertagnolli Monica M. , Perou Charles M. , Innocenti Federico 
Published: January 2025

Abstract
Background
Gene signatures derived from transcriptomic-causal networks offer potential for tailoring clinical care in cancer treatment by identifying predictive and prognostic biomarkers. This study aimed to uncover such signatures in metastatic colorectal cancer (CRC) patients to aid treatment decisions.

Methods
We constructed transcriptomic-causal networks and integrated gene interconnectivity into overall survival (OS) analysis to control for confounding genes. This integrative approach involved germline genotype and tumor RNA-seq data from 1165 metastatic CRC patients. The patients were enrolled in a randomized clinical trial receiving either cetuximab or bevacizumab in combination with chemotherapy. An external cohort of paired CRC normal and tumor samples, along with protein-protein interaction databases, was used for replication.

Results
We identify promising predictive and prognostic gene signatures from pre-treatment gene expression profiles. Our study discerns sets of genes, each forming a signature that collectively contribute to define patient subgroups with different prognosis and response to the therapies. Using an external cohort, we show that the genes influencing OS within the signatures, such as FANCI and PRC1, are upregulated in CRC tumor vs. normal tissue. These signatures are highly associated with immune features, including macrophages, cytotoxicity, and wound healing. Furthermore, the corresponding proteins encoded by the genes within the signatures interact with each other and are functionally related.

Conclusions
This study underscores the utility of gene signatures derived from transcriptomic-causal networks in patient stratification for effective therapies. The interpretability of the findings, supported by replication, highlights the potential of these signatures to identify patients likely to benefit from cetuximab or bevacizumab.
Syrian hamsters (Mesocricetus auratus) as an upper respiratory tract model for respiratory syncytial virus infection
Authors: Kolbe Sophie M. , Guilfoyle Kate , Reineking Wencke , van Amerongen Geert , van der Net Guido , Lockow Sandra , Baumgärtner Wolfgang , Ludlow Martin , Osterhaus Albert D.M.E 
Published: January 2025

AbstractRespiratory syncytial virus (RSV) is one of the leading causes of respiratory tract infection in children, immunocompromised individuals and older adults. Vaccines have recently been approved for use in adults and although further efforts to develop suitable interventions for children are ongoing, there are limited animal models for RSV infection. For preclinical efficacy testing of prophylactic and therapeutic treatments cotton rat and ferret models can be used. However, these can be expensive, difficult to source and house, and often have limitations such as insufficient virus replication in the respiratory tract and/or lack of horizontal transmission. In this study, Syrian hamsters (Mesocricetus auratus), which are relatively cheap, easy to source and house, were inoculated intranasally with a recombinant RSV-A-0594 strain expressing EGFP and using virological and pathological analyses. Viral replication was assessed and compared to viral replication in the ferret model. Although there was limited virus infection of the lower respiratory tract of Syrian hamsters, we show that a contemporary recombinant RSV-A strain replicates efficiently in the upper respiratory tract of Syrian hamsters (titers up to 4.5 Log10 TCID50/g and 12 Log10 RNA copies/g). These titers are comparable to those found in the ferret upper respiratory tract tissues post-infection with the same virus strain (up to 6.0 Log10 TCID50/g and 12 Log 10 RNA copies/g). Fluorescent regions indicating virus infection were macroscopically visible under UV-light in the nasal turbinates and histological assessment showed mucosal inflammation with necrotic cells in this tissue. In summary, Syrian hamsters generally displayed less severe systemic and pulmonary changes than ferrets, but do appear to be a promising model for upper respiratory tract infection with RSV.
The Effect of Contralateral Routing of Signal Devices on the Quality of Life of Unilateral Cochlear Implant Recipients and Their Frequent Communication Partners
Authors: Johnson Kate , Jeon Eun Kyung , Dwyer Robert , Agrawal Smita , Gurgel Richard 
Published: January 2025

Purpose:
Unilateral cochlear implant (CI) recipients with limited hearing in the contralateral ear are deprived of the advantages of binaural hearing. To address speech recognition challenges arising from the head shadow effect, a contralateral routing of signal (CROS) device can be used; however, less is known of the broader impact of a CROS device on an individual's quality of life (QoL) or that of their frequent communication partners (FCPs). This preliminary study aimed to evaluate the impact of CROS on speech recognition in noise and its influence on the QoL of unilateral CI recipients and their FCPs.

Method:
This preliminary study enrolled seven adult unilateral CI recipients and their FCPs. All CI recipients were fitted with CROS devices during their initial appointments. Speech recognition testing was conducted in noise with and without the CROS device in a sound booth before a take-home trial. Participants used the CROS devices for approximately 1 year, with device fitting occurring before and continuing during the COVID-19 pandemic. Participants completed two QoL questionnaires, the Auditory Performance and Satisfaction Scale for Single-Sided Deafness (APS-SSD) and the Nijmegen Cochlear Implant Questionnaire (NCIQ), twice: once prior to CROS device use and once after the take-home trial. Additionally, the FCPs of each CI recipient completed the Significant Other Scale of Hearing Disability (SOS-HEAR) Questionnaire twice, once before and once after extended CROS device use.

Results:

When noise was directed toward the CI ear and speech toward the non-CI ear, speech recognition improved by 32% with the CROS device (
p
= .001). CI recipients reported significant median improvement in the “general” domain of the APS-SSD after the take-home trial (Wilcoxon
Z
= 12.0,
p
< .05). FCPs reported a significant median reduction in concerns related to their partner's hearing when the CI recipient used the CROS device (Wilcoxon
Z
= 2.0,
p
< .05).

Conclusions:
This preliminary study demonstrates the benefit of CROS devices for unilateral CI recipients in noisy environments. Additionally, it highlights the positive impact of CROS devices on the QoL of both CI recipients and their FCPs. These findings emphasize the importance of considering CROS devices as a valuable solution for unilateral CI recipients to enhance their hearing experience, overall well-being, and that of their FCPs.