bluuebunny/crossref_metadata_2025_split huggingface dataset:
A ketogenic diet enhances fluconazole efficacy in murine models of systemic fungal infection
Authors: Palmucci Julia R. , Sells Blake E. , Giamberardino Charles D. , Toffaletti Dena L. , Dai Baodi , Asfaw Yohannes G. , Dubois Laura G. , Li Zhong , Theriot Barbara , Schell Wiley A. , Hope William , Tenor Jennifer L. , Perfect John R. 
Published: April 2024

ABSTRACT

Invasive fungal infections are a significant public health concern, with mortality rates ranging from 20% to 85% despite current treatments. Therefore, we examined whether a ketogenic diet could serve as a successful treatment intervention in murine models of
Cryptococcus neoformans
and
Candida albicans
infection in combination with fluconazole—a low-cost, readily available antifungal therapy. The ketogenic diet is a high-fat, low-carbohydrate diet that promotes fatty acid oxidation as an alternative to glycolysis through the production of ketone bodies. In this series of experiments, mice fed a ketogenic diet prior to infection with
C. neoformans
and treated with fluconazole had a significant decrease in fungal burden in both the brain (mean 2.66 ± 0.289 log
10
reduction) and lung (mean 1.72 ± 0.399 log
10
reduction) compared to fluconazole treatment on a conventional diet. During
C. albicans
infection, kidney fungal burden of mice in the keto-fluconazole combination group was significantly decreased compared to fluconazole alone (2.37 ± 0.770 log
10
-reduction). Along with higher concentrations of fluconazole in the plasma and brain tissue, fluconazole efficacy was maximized at a significantly lower concentration on a keto diet compared to a conventional diet, indicating a dramatic effect on fluconazole pharmacodynamics. Our findings indicate that a ketogenic diet potentiates the effect of fluconazole at multiple body sites during both
C. neoformans
and
C. albicans
infection and could have practical and promising treatment implications.

IMPORTANCE

Invasive fungal infections cause over 2.5 million deaths per year around the world. Treatments for fungal infections are limited, and there is a significant need to develop strategies to enhance antifungal efficacy, combat antifungal resistance, and mitigate treatment side effects. We determined that a high-fat, low-carbohydrate ketogenic diet significantly potentiated the therapeutic effect of fluconazole, which resulted in a substantial decrease in tissue fungal burden of both
C. neoformans
and
C. albicans
in experimental animal models. We believe this work is the first of its kind to demonstrate that diet can dramatically influence the treatment of fungal infections. These results highlight a novel strategy of antifungal drug enhancement and emphasize the need for future investigation into dietary effects on antifungal drug activity.
Late Triassic paleogeography of southern Laurentia and its fringing arcs: Insights from detrital zircon U-Pb geochronology and Hf isotope geochemistry, Auld Lang Syne basin (Nevada, USA)
Authors: Schwartz Theresa M. , Wyld Sandra J. , Colgan Joseph P. , Prihar Douglas W. 
Published: April 2024

Abstract
Fluvial strata of the Upper Triassic Chinle Formation and Dockum Group, exposed across the Western Interior of North America, have long been interpreted to record a transcontinental river system that connected the ancestral Ouachita orogen of Texas and Oklahoma, USA, to the Auld Lang Syne basin of northwestern Nevada, USA, its inferred marine terminus. Fluvial strata are well-characterized by existing detrital zircon data, but the provenance of the Auld Lang Syne basin is poorly constrained. We present new detrital zircon U-Pb and Hf isotopic data that characterize the provenance of Norian siliciclastic strata that dominate the Auld Lang Syne basin. Mixture modeling of Auld Lang Syne basin data identifies the Alleghany–Ouachita–Marathon belt of eastern Laurentia as a dominant source of sediment, but the presence of Triassic detrital zircon grains in Auld Lang Syne basin strata indicates that at least one peri-Laurentian arc segment had to have also contributed sediment. A comparison of new Hf isotopic data with those characterizing various peri-Laurentian volcanic arcs demonstrates that although multiple arc segments may have simultaneously contributed zircons to the Auld Lang Syne basin, the west Pangean arc of northern Mexico stands out as a unique source of highly evolved Permian to Triassic detrital zircon grains in samples from the Auld Lang Syne basin. Altogether, our data and analyses demonstrate source-to-sink connectivity between the Late Triassic (Norian) Cordilleran margin and remnant late Paleozoic highlands of southern to eastern Laurentia, which ultimately framed a Mississippi River–scale, transcontinental watershed that traversed the topographically subdued Laurentian continental interior.
An enhanced chemical maturation of juvenile arc crust recorded by the Urad Houqi intrusive suite in Langshan arc, Central Asia
Authors: Liu Min , Lai Shao-Cong , Ma Shuai , Zhang Fang-Yi , Zhu Ren-Zhi , Zhu Yu , Qin Jiang-Feng , Xu Bo , Yang Hang 
Published: April 2024

Abstract
Continental arc magmatism is crucial in producing juvenile continental crust of andesitic to dacitic composition, yet its impact on the formation of the modern mature continental crust, which is more enriched in potassic and granitic components, remains poorly understood. We examined a suite comprised of norite gabbro, gabbroic diorite, high-Mg diorite, dioritic enclave, and medium-K to high-K granites (the Urad Houqi suite) from the Langshan arc in the southern Central Asian Orogenic Belt (CAOB). Zircon U-Pb geochronology indicates that the Urad Houqi suite was formed ca. 278–268 Ma by a continuous magmatic event, marking the final episode of the late Paleozoic continental arc magmatism in the southern CAOB induced by the subduction of the Paleo-Asian Ocean. The suite exhibits a more potassic and fertile composition compared to typical continental arc magmas, and shows a continuous increasing K2O/Na2O ratio and incompatible element concentrations, including K, Rb, Th, and U, with increasing SiO2 content. The geochemical evolution of the suite offers valuable insights into the maturation process of the juvenile arc crust. By combining zircon Hf and bulk-rock Sr-Nd-Pb isotope studies, we demonstrated that the various lithologies within the Urad Houqi suite recorded a three-stage enhancement of the geochemical fertility of the juvenile Langshan arc crust: (1) generation of the initially fertile primary melt from the mantle wedge metasomatized by the recycled subducted sediments; (2) trans-crustal open-system hybridization processes, including peritectic reaction and magma mixing, that further fertilized the derived melts in addition to fractional crystallization; and (3) diverse petrogenetic processes that contributed to the fertility of the granitic magmas, including polybaric fractionation of the primary magma, anatexis of ancient crust, and extraction of high-silica melts from the shallow mush system. The three-stage maturation of the juvenile Langshan arc crust was typically coupled with the accelerated subduction of the Paleo-Asian Ocean since the earliest Permian. Our study finds that the Urad Houqi suite can serve as an example of modern continental crust maturation at continental arc settings.
Paediatric medication incident reporting: a multicentre comparison study of medication errors identified at audit, detected by staff and reported to an incident system
Authors: Li Ling , Badgery-Parker Tim , Merchant Alison , Fitzpatrick Erin , Raban Magdalena Z , Mumford Virginia , Metri Najwa-Joelle , Hibbert Peter Damian , Mccullagh Cheryl , Dickinson Michael , Westbrook Johanna I 
Published: April 2024

ObjectivesTo compare medication errors identified at audit and via direct observation with medication errors reported to an incident reporting system at paediatric hospitals and to investigate differences in types and severity of errors detected and reported by staff.MethodsThis is a comparison study at two tertiary referral paediatric hospitals between 2016 and 2020 in Australia. Prescribing errors were identified from a medication chart audit of 7785 patient records. Medication administration errors were identified from a prospective direct observational study of 5137 medication administration doses to 1530 patients. Medication errors reported to the hospitals’ incident reporting system were identified and matched with errors identified at audit and observation.ResultsOf 11 302 clinical prescribing errors identified at audit, 3.2 per 1000 errors (95% CI 2.3 to 4.4, n=36) had an incident report. Of 2224 potentially serious prescribing errors from audit, 26.1% (95% CI 24.3 to 27.9, n=580) were detected by staff and 11.2 per 1000 errors (95% CI 7.6 to 16.5, n=25) were reported to the incident system. Although the prescribing error detection rates varied between the two hospitals, there was no difference in incident reporting rates regardless of error severity. Of 40 errors associated with actual patient harm, only 7 (17.5%; 95% CI 8.7% to 31.9%) were detected by staff and 4 (10.0%; 95% CI 4.0% to 23.1%) had an incident report. None of the 2883 clinical medication administration errors observed, including 903 potentially serious errors and 144 errors associated with actual patient harm, had incident reports.ConclusionIncident reporting data do not provide an accurate reflection of medication errors and related harm to children in hospitals. Failure to detect medication errors is likely to be a significant contributor to low error reporting rates. In an era of electronic health records, new automated approaches to monitor medication safety should be pursued to provide real-time monitoring.
Recurrent RhoGAP gene fusion CLDN18-ARHGAP26 promotes RHOA activation and focal adhesion kinase and YAP-TEAD signalling in diffuse gastric cancer
Authors: Zhang Feifei , Sahu Varun , Peng Ke , Wang Yichen , Li Tianxia , Bala Pratyusha , Aitymbayev Daulet , Sahgal Pranshu , Schaefer Antje , Der Channing J , Ryeom Sandra , Yoon Sam , Sethi Nilay , Bass Adam J , Zhang Haisheng 
Published: April 2024

Objective
Genomic studies of gastric cancer have identified highly recurrent genomic alterations impacting RHO signalling, especially in the diffuse gastric cancer (DGC) histological subtype. Among these alterations are interchromosomal translations leading to the fusion of the adhesion protein CLDN18 and RHO regulator ARHGAP26. It remains unclear how these fusion constructs impact the activity of the RHO pathway and what is their broader impact on gastric cancer development. Herein, we developed a model to allow us to study the function of this fusion protein in the pathogenesis of DGC and to identify potential therapeutic targets for DGC tumours with these alterations.

Design

We built a transgenic mouse model with
LSL-CLDN18-ARHGAP26
fusion engineered into the
Col1A1
locus where its expression can be induced by Cre recombinase. Using organoids generated from this model, we evaluated its oncogenic activity and the biochemical effects of the fusion protein on the RHOA pathway and its downstream cell biological effects in the pathogenesis of DGC.

Results

We demonstrated that induction of
CLDN18-ARHGAP26
expression in gastric organoids induced the formation of signet ring cells, characteristic features of DGC and was able to cooperatively transform gastric cells when combined with the loss of the tumour suppressor gene
Trp53. CLDN18-ARHGAP26
promotes the activation of RHOA and downstream effector signalling. Molecularly, the fusion promotes activation of the focal adhesion kinase (FAK) and induction of the YAP pathway. A combination of FAK and YAP/TEAD inhibition can significantly block tumour growth.

Conclusion

These results indicate that the
CLDN18-ARHGAP26
fusion is a gain-of-function DGC oncogene that leads to activation of RHOA and activation of FAK and YAP signalling. These results argue for further evaluation of emerging FAK and YAP-TEAD inhibitors for these deadly cancers.
Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis
Authors: Liu Jinxia , MacNaughtan Jane , Kerbert Annarein J C , Portlock Theo , Martínez Gonzalez Javier , Jin Yi , Clasen Frederick , Habtesion Abeba , Ji Huoyan , Jin Qin , Phillips Alexandra , De Chiara Francesco , Ingavle Ganesh , Jimenez Cesar , Zaccherini Giacomo , Husi Katherine , Rodriguez Gandia Miguel Angel , Cordero Paul , Soeda Junpei , McConaghy Lynda , Oben Jude , Church Karen , Li Jia V , Wu Haifeng , Jalan Aarti , Gines Pere , Solà Elsa , Eaton Simon , Morgan Carrie , Kowalski Michal , Green Daniel , Gander Amir , Edwards Lindsey A , Cox I Jane , Cortez-Pinto Helena , Avery Thomas , Wiest Reiner , Durand Francois , Caraceni Paolo , Elosua Roberto , Vila Joan , Pavesi Marco , Arroyo Vicente , Davies Nathan , Mookerjee Rajeshwar P , Vargas Victor , Sandeman Susan , Mehta Gautam , Shoaie Saeed , Marchesi Julian , Albillos Agustín , Andreola Fausto , Jalan Rajiv 
Published: April 2024

Objective
Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis.

Design

Performance of Yaq-001 was evaluated
in vitro
. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed.

Results

Yaq-001 exhibited rapid adsorption kinetics for endotoxin.
In vivo
, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial.

Conclusions
This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation.

Trial registration number

NCT03202498
.
Decreased pancreatic amylase activity after acute high-intensity exercise and its effects on post-exercise muscle glycogen recovery
Authors: Kondo Saki , Karasawa Takuya , Koike Atsuko , Tsutsui Momoko , Kunisawa Jun , Terada Shin 
Published: April 2024

Our prior results showed that an acute bout of endurance exercise for 6 h, but not 1 h, decreased pancreatic amylase activity, indicating that acute endurance exercise may affect carbohydrate digestive capacity in an exercise duration-dependent manner. Here, we investigated the effects of acute endurance exercise of different intensities on mouse pancreatic amylase activity. Male C57BL/6J mice performed low- or high-intensity running exercise for 60 min at either 10 (Ex-Low group) or 20 m/min (Ex-High group). The control group comprised sedentary mice. Immediately after acute exercise, pancreatic amylase activity was significantly decreased in the Ex-High group and not the Ex-Low group in comparison with the control group. To determine whether the decreased amylase activity induced by high-intensity exercise influenced muscle glycogen recovery after exercise, we investigated the rates of muscle glycogen resynthesis in Ex-High group mice administered either oral glucose or starch solution (2.0 mg/g body weight) immediately after exercise. The starch-fed mice exhibited significantly lower post-exercise glycogen accumulation rates in the 2-h recovery period compared with the glucose-fed mice. This difference in the glycogen accumulation rate was absent for starch- and glucose-fed mice in the sedentary (no exercise) control group. Furthermore, the plasma glucose AUC during early post-exercise recovery (0–60 min) was significantly lower in the starch-fed mice than in the glucose-fed mice. Thus, our findings suggest that acute endurance exercise diminishes the carbohydrate digestive capacity of the pancreas in a manner dependent on exercise intensity, with polysaccharides leading to delayed muscle glycogen recovery after exercise.
A novel 5,10,15,20-tetrakis-(4-(triazol-1-yl)phenyl)porphyridine compound: Crystal structure, photophysical properties and TDDFT calculations
Authors: Liu Hao-Dong , Shao Xi-Yu , Zeng Long-Hua , Xu Yu-Yue , Liu Cheng , Dai Sheng-Ping , Pan Chang-Wang , Chen Wen-Tong 
Published: April 2024

A novel 5,10,15,20-tetrakis-(4-(triazol-1-yl)phenyl)porphyridine compound, namely, Zn[5,10,15,20-tetrakis-(4-(triazol-1-yl)phenyl)porphyridine] (hereafter tagged as 1) was synthesized through a solvothermal reaction with mixed solvents at 413 K. The X-ray single-crystal structure of compound 1 is featured as a two-dimensional (2D) layer-like structure with the zinc ion located at the center of the 5,10,15,20-tetrakis-(4-(triazol-1-yl)phenyl)porphyridine. The macrocycle of the 5,10,15,20-tetrakis-(4-(triazol-1-yl)phenyl)porphyridine is coplanar. The zinc ion has six coordination and coordinates with three porphyridines. The photoluminescence spectra of compound 1 with DMF solution reveal that it shows upconversion red photoluminescence. The time-dependent density functional theory (TDDFT) calculation confirms that this upconversion red photoluminescence originated from the MLCT process (metal to ligand charge transfer). The CCT (Correlated Color Temperature) is 2200 K and the CIE (Commission Internationale de I’Éclairage) chromaticity coordinate is (0.6311, 0.3595) for compound 1. The UV-vis diffuse reflectance curve measured with a solid state sample reveals that compound 1 possesses a 2.75 eV band gap.
Supplementary Figure 4 from CB307: A Dual Targeting Costimulatory Humabody V<sub>H</sub> Therapeutic for Treating PSMA-Positive Tumors
Authors: Archer Sophie , Brailey Phillip M. , Song Minjung , Bartlett Phillip D. , Figueiredo Ines , Gurel Bora , Guo Christina , Brucklacher-Waldert Verena , Thompson H. Lorraine , Akinwale Jude , Boyle Samantha E. , Rossant Christine , Birkett Neil R. , Pizzey Julia , Maginn Mark , Legg James , Williams Richard , Johnston Colette M. , Bland-Ward Philip , de Bono Johann S. , Pierce Andrew J. 
Published: April 2024

<p>Supplementary Figure 4: Binding kinetics of CB307 to human PSMA, CD137 and serum albumin (HSA)</p>
Abstract LT10: Recurrent FBXW7 Mutations Bypass Wnt/β-catenin Addiction in Cancer
Authors: Zhong Zheng , Virshup David 
Published: April 2024

Abstract
Inactivating mutations in RNF43 or gene fusions involving RSPO2/3 are potent activators of ligand-dependent Wnt signaling and drive multiple human cancers. Pharmacologically targeting the biogenesis of Wnt ligands, e.g., with PORCN inhibitors, is being investigated in clinical trials for treating RNF43-mutant/RSPO-fusion cancers. But, the therapeutic response is heterogeneous. Here we show that the tumor suppressor FBXW7 is frequently mutated in RNF43-mutant/RSPO-fusion tumors. Multiple RNF43-mutant/RSPO-fusion cancers harboring FBXW7 mutations show resistance to Wnt pathway blockade, while silencing FBXW7 by truncation or expressing a hotspot mutant in FBXW7-wildtype tumors leads to intrinsic drug resistance. Mechanistically, inactivation of FBXW7, the substrate recognition component of a SCF E3 ubiquitin ligase complex, stabilizes multiple oncoproteins especially Cyclin E and MYC, and antagonizes the cytostatic effect of Wnt inhibitors in these cancers. Moreover, although FBXW7 mutations do not mitigate β-catenin degradation upon Wnt inhibition, FBXW7 mutants instead lose dependence on β-catenin signaling, accompanied by dedifferentiation and loss of lineage specificity. These FBXW7-mutant Wnt/β-catenin-independent tumors are susceptible to multi-CDK inhibition by dinaciclib that targets both cell cycle and transcription. In summary, this study identifies FBXW7 mutations as a mechanism of Wnt independence and drug resistance in RNF43-mutant/RSPO-fusion cancers and reveals the potential of treating these cancers with multi-CDK inhibitors.
Citation Format: Zheng Zhong, David Virshup. Recurrent FBXW7 Mutations Bypass Wnt/β-catenin Addiction in Cancer [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr LT10.
Abstract P19: Comprehensive Benchmark of Somatic Mutation Callers on Cell-Free DNA Next-Generation Sequencing Data in Cancer Liquid Biopsy
Authors: Carrié Hanaé , Sim Ngak Leng , Wong Pui Mun , Gan Anna , Lau Yi Ting , Poon Polly , Thangaraju Saranya , Tan Iain , Yap Yoon Sim , Wong Limsoon , Skanderup Anders 
Published: April 2024

Abstract
Circulating tumour DNA (ctDNA) has emerged as a rich source of biomarkers in precision oncology. However, ctDNA sequence data is often noisier than that derived from standard tissue biopsies, posing significant challenges for accurate cancer mutation detection. Besides, there is a lack of standardised and unbiased benchmark datasets to evaluate and compare performance of variant callers on ctDNA. To address this issue, we present a novel benchmarking approach and comprehensive benchmark of cancer somatic mutation callers on cell-free DNA (cfDNA) Next Generation Sequencing (NGS) data.
To create a large-scale benchmark dataset, we developed a new methodology using real colorectal cancer patients plasma samples exhibiting either ultra-high and an ultra-low levels of ctDNA. This enabled the generation of dilution series of deep Whole Genome Sequencing (WGS, 150x) and the creation of high-quality consensus ground truth calls.
We evaluated the performance of 9 SNV callers and 7 short INDEL callers frequently used in academic research, including 2 callers that were specifically designed for cfDNA. We further validated our findings at higher depth of coverage using deep Whole Exome Sequencing (WES, &gt;2,000x) data. We further investigated each caller's features to develop practical guidelines for users depending on their application setting: unguided analysis focusing on overall accuracy vs. guided analysis focusing on sensitivity.
Citation Format: Hanaé Carrié, Ngak Leng Sim, Pui Mun Wong, Anna Gan, Yi Ting Lau, Polly Poon, Saranya Thangaraju, Iain Tan, Yoon Sim Yap, Limsoon Wong, Anders Skanderup. Comprehensive Benchmark of Somatic Mutation Callers on Cell-Free DNA Next-Generation Sequencing Data in Cancer Liquid Biopsy [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr P19.