bluuebunny/crossref_metadata_2025_split huggingface dataset:
MRI radiomics to monitor therapeutic outcome of sorafenib plus IHA transcatheter NK cell combination therapy in hepatocellular carcinoma
Authors: Yu Guangbo , Zhang Zigeng , Eresen Aydin , Hou Qiaoming , Garcia Emilie Elizabeth , Yu Zeyang , Abi-Jaoudeh Nadine , Yaghmai Vahid , Zhang Zhuoli 
Published: January 2024

Abstract
Background
Hepatocellular carcinoma (HCC) is a common liver malignancy with limited treatment options. Previous studies expressed the potential synergy of sorafenib and NK cell immunotherapy as a promising approach against HCC. MRI is commonly used to assess response of HCC to therapy. However, traditional MRI-based metrics for treatment efficacy are inadequate for capturing complex changes in the tumor microenvironment, especially with immunotherapy. In this study, we investigated potent MRI radiomics analysis to non-invasively assess early responses to combined sorafenib and NK cell therapy in a HCC rat model, aiming to predict multiple treatment outcomes and optimize HCC treatment evaluations.

Methods
Sprague Dawley (SD) rats underwent tumor implantation with the N1-S1 cell line. Tumor progression and treatment efficacy were assessed using MRI following NK cell immunotherapy and sorafenib administration. Radiomics features were extracted, processed, and selected from both T1w and T2w MRI images. The quantitative models were developed to predict treatment outcomes and their performances were evaluated with area under the receiver operating characteristic (AUROC) curve. Additionally, multivariable linear regression models were constructed to determine the correlation between MRI radiomics and histology, aiming for a noninvasive evaluation of tumor biomarkers. These models were evaluated using root-mean-squared-error (RMSE) and the Spearman correlation coefficient.

Results
A total of 743 radiomics features were extracted from T1w and T2w MRI data separately. Subsequently, a feature selection process was conducted to identify a subset of five features for modeling. For therapeutic prediction, four classification models were developed. Support vector machine (SVM) model, utilizing combined T1w + T2w MRI data, achieved 96% accuracy and an AUROC of 1.00 in differentiating the control and treatment groups. For multi-class treatment outcome prediction, Linear regression model attained 85% accuracy and an AUC of 0.93. Histological analysis showed that combination therapy of NK cell and sorafenib had the lowest tumor cell viability and the highest NK cell activity. Correlation analyses between MRI features and histological biomarkers indicated robust relationships (r = 0.94).

Conclusions
Our study underscored the significant potential of texture-based MRI imaging features in the early assessment of multiple HCC treatment outcomes.
Circulating mitochondria promoted endothelial cGAS-derived neuroinflammation in subfornical organ to aggravate sympathetic overdrive in heart failure mice
Authors: Zhang Shutian , Zhao Dajun , Yang Zhaohua , Wang Fanshun , Yang Shouguo , Wang Chunsheng 
Published: January 2024

Abstract
Background
Sympathoexcitation contributes to myocardial remodeling in heart failure (HF). Increased circulating pro-inflammatory mediators directly act on the Subfornical organ (SFO), the cardiovascular autonomic center, to increase sympathetic outflow. Circulating mitochondria (C-Mito) are the novel discovered mediators for inter-organ communication. Cyclic GMP–AMP synthase (cGAS) is the pro-inflammatory sensor of damaged mitochondria.

Objectives
This study aimed to assess the sympathoexcitation effect of C-Mito in HF mice via promoting endothelial cGAS-derived neuroinflammation in the SFO.

Methods
C-Mito were isolated from HF mice established by isoprenaline (0.0125 mg/kg) infusion via osmotic mini-pumps for 2 weeks. Structural and functional analyses of C-Mito were conducted. Pre-stained C-Mito were intravenously injected every day for 2 weeks. Specific cGAS knockdown (cGAS KD) in the SFO endothelial cells (ECs) was achieved via the administration of AAV9-TIE-shRNA (cGAS) into the SFO. The activation of cGAS in the SFO ECs was assessed. The expression of the mitochondrial redox regulator Dihydroorotate dehydrogenase (DHODH) and its interaction with cGAS were also explored. Neuroinflammation and neuronal activation in the SFO were evaluated. Sympathetic activity, myocardial remodeling, and cardiac systolic dysfunction were measured.

Results
C-Mito were successfully isolated, which showed typical structural characteristics of mitochondria with double-membrane and inner crista. Further analysis showed impaired respiratory complexes activities of C-Mito from HF mice (C-MitoHF) accompanied by oxidative damage. C-Mito entered ECs, instead of glial cells and neurons in the SFO of HF mice. C-MitoHF increased the level of ROS and cytosolic free double-strand DNA (dsDNA), and activated cGAS in cultured brain endothelial cells. Furthermore, C-MitoHF highly expressed DHODH, which interacted with cGAS to facilitate endothelial cGAS activation. C-MitoHF aggravated endothelial inflammation, microglial/astroglial activation, and neuronal sensitization in the SFO of HF mice, which could be ameliorated by cGAS KD in the ECs of the SFO. Further analysis showed C-MitoHF failed to exacerbate sympathoexcitation and myocardial sympathetic hyperinnervation in cGAS KD HF mice. C-MitoHF promoted myocardial fibrosis and hypertrophy, and cardiac systolic dysfunction in HF mice, which could be ameliorated by cGAS KD.

Conclusion
Collectively, we demonstrated that damaged C-MitoHF highly expressed DHODH, which promoted endothelial cGAS activation in the SFO, hence aggravating the sympathoexcitation and myocardial injury in HF mice, suggesting that C-Mito might be the novel therapeutic target for sympathoexcitation in HF.

Graphic Abstract
An unusual diarrheal outbreak in the community in Eastern Thailand caused by Norovirus GII.3[P25]
Authors: Udompat Patpong , Srimuang Krongkan , Doungngern Pawinee , Thippamom Nattakarn , Petcharat Sininat , Rattanatumhi Khwankamon , Khiewbanyang Sirorat , Taweewigyakarn Pantila , Kripattanapong Somkid , Ninwattana Sasiprapa , Supataragul Ananporn , Sterling Spencer L. , Klungthong Chonticha , Joonlasak Khajohn , Manasatienkij Wudtichai , Cotrone Thomas S. , Fernandez Stefan , Wacharapluesadee Supaporn , Putcharoen Opass 
Published: January 2024

Abstract
Background
Sentinel laboratory surveillance for diarrheal disease determined norovirus to be the most common cause of non-bacterial gastroenteritis in people during the COVID-19 pandemic in Thailand. An increase in patients presenting with diarrhea and vomiting in hospitals across Chanthaburi province between December 2021 and January 2022 led to the need for the identification of viral pathogens that may be responsible for the outbreak.

Methods
Fecal samples (rectal swabs or stool) from 93 patients, of which 65 patients were collected during the December 2021 to January 2022 outbreak, were collected and screened for viral infection by real-time RT-PCR. Positive samples for norovirus GII were then genotyped by targeted amplification and sequencing of partial polymerase and capsid genes. Full genome sequencing was performed from the predominant strain, GII.3[P25].

Results
Norovirus was the most common virus detected in human fecal samples in this study. 39 of 65 outbreak samples (60%) and 3 of 28 (10%) non-outbreak samples were positive for norovirus genogroup II. One was positive for rotavirus, and one indicated co-infection with rotavirus and norovirus genogroups I and II. Nucleotide sequences of VP1 and RdRp gene were successfully obtained from 28 of 39 positive norovirus GII and used for dual-typing; 25/28 (89.3%) were GII.3, and 24/28 (85.7) were GII.P25, respectively. Norovirus GII.3[P25] was the predominant strain responsible for this outbreak. The full genome sequence of norovirus GII.3[P25] from our study is the first reported in Thailand and has 98.62% and 98.57% similarity to norovirus found in China in 2021 and the USA in 2022, respectively. We further demonstrate the presence of multiple co-circulating norovirus genotypes, including GII.21[P21], GII.17[P17], GII.3[P12] and GII.4[P31] in our study.

Conclusions
An unusual diarrhea outbreak was found in December 2021 in eastern Thailand. Norovirus strain GII.3[P25] was the cause of the outbreak and was first detected in Thailand. The positive rate during GII.3[P25] outbreak was six times higher than sporadic cases (GII.4), and, atypically, adults were the primary infected population rather than children.
Radiology in conflict: scoping review
Authors: Suji Trisha , Sullivan Richard , Bowsher Gemma 
Published: January 2024

AbstractThe United Nations estimate a quarter of the global population currently lives in violent conflict zones. Radiology is an integral part of any healthcare system, providing vital information to aid diagnosis and treatment of a range of disease and injury. However, its delivery in conflict-affected settings remains unclear. This study aims to understand how radiology services are currently delivered in conflict settings, the challenges of doing so, and potential solutions. A hermeneutic narrative review of multiple databases, including grey literature sources, was undertaken. Key themes were identified, and articles grouped accordingly. Various conflict zones including Gaza, Ukraine, Iraq, Yemen, Afghanistan, and Somalia were identified in literature relating to radiology services. Three key themes were identified: underserving of local medical imaging services, strong presence of military hospitals, and the importance of teleradiology. A severe shortage of radiologists, technicians, and equipment in conflict affected settings are a significant cause of the underserving by local services. Teleradiology has been used to blunt the acuity of the these struggling services, alongside military hospitals which often serve local populations. Radiology faces unique challenges compared to other healthcare services owing to its expensive equipment which is difficult to fund and can be less effective due to international sanctions placed on contrast medium to enhance image quality. Further the equipment is reliant on local infrastructure, e.g., power supply, which can be affected in conflict. Key recommendations to improve radiology services include retention of radiologists within conflict zones, careful allocation of funds to supply necessary imaging machinery, international cooperation to ensure sanctions do not affect sourcing of radiology equipment, special training for military medical teams to help preparedness for the unique demands of the local population, and investment in communication devices, like smartphones, to allow international teleradiology efforts.
Haplotype-resolved assembly of a tetraploid potato genome using long reads and low-depth offspring data
Authors: Serra Mari Rebecca , Schrinner Sven , Finkers Richard , Ziegler Freya Maria Rosemarie , Arens Paul , Schmidt Maximilian H.-W. , Usadel Björn , Klau Gunnar W. , Marschall Tobias 
Published: January 2024

AbstractPotato is one of the world’s major staple crops, and like many important crop plants, it has a polyploid genome. Polyploid haplotype assembly poses a major computational challenge. We introduce a novel strategy for the assembly of polyploid genomes and present an assembly of the autotetraploid potato cultivar Altus. Our method uses low-depth sequencing data from an offspring population to achieve chromosomal clustering and haplotype phasing on the assembly graph. Our approach generates high-quality assemblies of individual chromosomes with haplotype-specific sequence resolution of whole chromosome arms and can be applied in common breeding scenarios where collections of offspring are available.
Quabodepistat in combination with delamanid and bedaquiline in participants with drug-susceptible pulmonary tuberculosis: protocol for a multicenter, phase 2b/c, open-label, randomized, dose-finding trial to evaluate safety and efficacy
Authors: Dawson Rodney , Diacon Andreas H. , Takuva Simbarashe , Liu Yongge , Zheng Bo , Karwe Vatsala , Hafkin Jeffrey 
Published: January 2024

Abstract
Background
Delamanid and bedaquiline are two of the most recently developed antituberculosis (TB) drugs that have been extensively studied in patients with multidrug-resistant TB. There is currently a need for more potent, less-toxic drugs with novel mechanisms of action that can be used in combination with these newer agents to shorten the duration of treatment as well as prevent the development of drug resistance. Quabodepistat (QBS) is a newly discovered inhibitor of decaprenylphosphoryl-β-D-ribose-2′-oxidase, an essential enzyme for Mycobacterium tuberculosis to synthesize key components of its cell wall. The objective of this study is to evaluate the safety, efficacy, and appropriate dosing of a 4-month regimen of QBS in combination with delamanid and bedaquiline in participants with drug-susceptible pulmonary TB in comparison with the 6-month standard treatment (i.e., rifampicin, isoniazid, ethambutol, and pyrazinamide).

Methods
This phase 2b/c, open-label, randomized, parallel group, dose-finding trial will enroll approximately 120 participants (including no more than 15% with human immunodeficiency virus [HIV] coinfection) aged ≥ 18 to ≤ 65 years at screening with newly diagnosed pulmonary drug-sensitive TB from ~8 sites in South Africa. Following a screening period of up to 14 days, eligible participants will be randomized in a ratio of 1:2:2:1 to one of four arms. Randomization will be stratified by HIV status and the presence of bilateral cavitation on a screening chest x-ray. After the end of the treatment period, participants will be followed until 12 months post randomization. The primary efficacy endpoint is the proportion of participants achieving sputum culture conversion in Mycobacteria Growth Indicator Tube by the end of the treatment period. The safety endpoints consist of adverse events, clinical laboratory tests, vital signs, physical examination findings, and electrocardiographic changes.

Discussion
QBS’s potent bactericidal activity and distinct mechanism of action (compared with other TB drugs currently available for human use) may make it an ideal candidate for inclusion in a novel treatment regimen to improve efficacy and potentially prevent resistance to concomitant TB drugs. This trial will assess the effectiveness, safety, and dosing of a new, shorter, QBS-based, combination anti-TB treatment regimen.

Trial status
ClinicalTrials.gov NCT05221502. Registered on February 3, 2022
Non-canonical antigens are the largest fraction of peptides presented by MHC class I in mismatch repair deficient murine colorectal cancer
Authors: Rospo Giuseppe , Chilà Rosaria , Matafora Vittoria , Basso Veronica , Lamba Simona , Bartolini Alice , Bachi Angela , Di Nicolantonio Federica , Mondino Anna , Germano Giovanni , Bardelli Alberto 
Published: January 2024

Abstract
Background
Immunotherapy based on checkpoint inhibitors is highly effective in mismatch repair deficient (MMRd) colorectal cancer (CRC). These tumors carry a high number of mutations, which are predicted to translate into a wide array of neoepitopes; however, a systematic classification of the neoantigen repertoire in MMRd CRC is lacking. Mass spectrometry peptidomics has demonstrated the existence of MHC class I associated peptides (MAPs) originating from non-coding DNA regions. Based on these premises we investigated DNA genomic regions responsible for generating MMRd-induced peptides.

Methods
We exploited mouse CRC models in which the MMR gene Mlh1 was genetically inactivated. Isogenic cell lines CT26 Mlh1+/+ and Mlh1-/- were inoculated in immunocompromised and immunocompetent mice. Whole genome and RNA sequencing data were generated from samples obtained before and after injection in murine hosts. First, peptide databases were built from transcriptomes of isogenic cell lines. We then compiled a database of peptides lost after tumor cells injection in immunocompetent mice, likely due to immune editing. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and matched next-generation sequencing databases were employed to identify the DNA regions from which the immune-targeted MAPs originated. Finally, we adopted in vitro T cell assays to verify whether MAP-specific T cells were part of the in vivo immune response against Mlh1-/- cells.

Results
Whole genome sequencing analyses revealed an unbalanced distribution of immune edited alterations across the genome in Mlh1-/- cells grown in immunocompetent mice. Specifically, untranslated (UTR) and coding regions exhibited the largest fraction of mutations leading to highly immunogenic peptides. Moreover, the integrated computational and LC-MS/MS analyses revealed that MAPs originate mainly from atypical translational events in both Mlh1+/+ and Mlh1-/- tumor cells. In addition, mutated MAPs—derived from UTRs and out-of-frame translation of coding regions—were highly enriched in Mlh1-/- cells. The MAPs trigger T-cell activation in mice primed with Mlh1-/- cells.

Conclusions
Our results suggest that—in comparison to MMR proficient CRC—MMRd tumors generate a significantly higher number of non-canonical mutated peptides able to elicit T cell responses. These results reveal the importance of evaluating the diversity of neoepitope repertoire in MMRd tumors.
Bifurcations, chaotic behavior, sensitivity analysis, and various soliton solutions for the extended nonlinear Schrödinger equation
Authors: ur Rahman Mati , Sun Mei , Boulaaras Salah , Baleanu Dumitru 
Published: January 2024

AbstractIn this manuscript, our primary objective is to delve into the intricacies of an extended nonlinear Schrödinger equation. To achieve this, we commence by deriving a dynamical system tightly linked to the equation through the Galilean transformation. We then employ principles from planar dynamical systems theory to explore the bifurcation phenomena exhibited within this derived system. To investigate the potential presence of chaotic behaviors, we introduce a perturbed term into the dynamical system and systematically analyze the extended nonlinear Schrödinger equation. This investigation is further enriched by the presentation of comprehensive two- and 3D phase portraits. Moreover, we conduct a meticulous sensitivity analysis of the dynamical system using the Runge–Kutta method. Through this analytical process, we confirm that minor fluctuations in initial conditions have only minimal effects on solution stability. Additionally, we utilize the complete discrimination system of the polynomial method to systematically construct single traveling wave solutions for the governing model.
Spatial and temporal patterns of forest fires in the Central Monte: relationships with regional climate
Authors: Villagra Pablo Eugenio , Cesca Erica , Alvarez Leandro Manuel , Delgado Silvia , Villalba Ricardo 
Published: January 2024

Abstract
Background
Natural and anthropogenic wildfires burn large areas of arid and semi-arid forests with significant socio-economic and environmental impacts. Fire regimes are controlled by climate, vegetation type, and anthropogenic factors such as ignition sources and human-induced disturbances. Projections of climate and land-use change suggest that these controlling factors will change, altering fire regimes in the near future. In the southern Central Monte, Mendoza, Argentina, the factors that modulate the fire temporal and spatial variability are poorly understood. We reconstructed the fire history of southeast of Mendoza from 1984 to 2023 and investigated the relationships between fire extent and climate variability at seasonal and interannual scales. Burned areas were determined using Google Earth Engine by processing Landsat 5-TM, Landsat 7-ETM+ , and Landsat 8-OLI-TIRS sensor imagery.

Results
The region exhibited high spatial and temporal variability in fire occurrence, being a mosaic of areas with different fire histories and recovery times. Between 1985 and 2023, fire recurrence ranged from sites unburned to sites with up to 14 fires. The occurrence of large fires was strongly favored by a combination of a year with abundant spring–early summer precipitation, which favors fuel accumulation, followed by a year of low spring–early summer precipitation. Precipitation and burnt area showed a very pronounced 6–7 year cycle, suggesting a dominant climatic control on fire occurrence.

Conclusions
Fire distribution in southeastern Mendoza forests is not homogeneous, resulting in a mosaic of patches with different fire histories. This heterogeneity may be related to vegetation patterns and land use. The temporal variability of fires is strongly influenced by climate variability, which would promote fuel production and subsequent drying. Large fires are concentrated in periods of high interannual precipitation variability. Climate change scenarios predict an increase in temperature and precipitation variability in the region, suggesting future changes in fire dynamics. Our results contribute to the development of fire guidelines for southeastern Mendoza forests, focusing on periods of wet years followed by dry years that favor fire occurrence and spread.
A comparison of raster-based point density calculations to vector-based counterparts as applied to the study of food availability
Authors: Mulrooney Timothy , Akinnusi Samuel , McGinn Christopher , Okoli Chima , Esimaje Tony 
Published: January 2024

Abstract
Background
Proximity to food sources is one of the quantifiable factors measurable across space impacting diet-related health outcomes. Contemporary research has coined the terms ‘food desert’ and ‘food swamp’, sometimes combined with a poverty component, to highlight disproportionate access to healthy and unhealthy food sources. However, there are various ways to measure this proximity—i.e., food availability in this research. Dollar stores such as Dollar General, Family Dollar, and Dollar Tree are one emerging facet of the food environment that provides healthy and unhealthy food options yet have not fully been studied. With more ways to easily measure food availability within the confines of a GIS, this paper proposes a new raster-based Point Density metric to measure the availability of these Dollar stores. In this study, this raster-based metric was calculated for a 6-county region in central North Carolina and compared to six other availability metrics utilized in food security research. A novel Python-based tool to compute the Jaccard Index between these various availability metrics and a matrix to compare these pairwise Jaccard Index calculations was created for this raster-based metric, which is very easy to derive.

Results
Using a pairwise Jaccard Index summarized and then averaged in a correlation table, the Point Density measure rated the highest (.65) when compared to 6 other popular vector-based techniques. Our results showed the density metric performed statistically better than Euclidean distance, drive-time, density, and point-in-polygon vector metrics when measuring availability for Dollar stores in Central North Carolina.

Conclusions
Results reinforce the efficacy of this easy-to-compute metric comparable to vector-based counterparts that require more robust network and/or geoprocessing calculations. Results quantitatively evaluate food availability with an eventual goal of dictating local, regional, and even state-level policy that critically and holistically consider this metric as powerful and convenient metric that can be easily calculated by the lay GIS user and understood by anyone.