bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paleoseismology of the Marquesado-La Rinconada thrust system, Eastern Precordillera of Argentina
Authors: Rockwell Thomas K. , Costa Carlos H. , Meigs Andrew J. , Ragona Daniel , Owen Lewis A. , Murari Madhav Krishna , Masana Eulalia , Richard Andrés D. 
Published: December 2022

Excavated trenches at two sites across the Marquesado–La Rinconada fault system along the eastern Precordilleran front south of San Juan, Argentina, reveal the earthquake history of this rapidly urbanizing region. Interpretation of earthquakes is based on both the generation of colluvial wedges and upward fault terminations, as well as folding events in fine-grained alluvium ponded behind upslope-facing fault scarps. The ages of the past five interpreted earthquakes at the Loma Negra site are E1 at 2.8 ± 2.8 ka, E2 at 7.1 ± 1.5 ka, E3 at 9.6 ± 1.3 ka, E4 at 14.4 ± 2.1 ka, and E5 at 17.2 ± 3.1 ka. At the Jejenes sites, we documented event ages of 2.7 ± 0.1 ka, 3.9 ± 0.6 ka, 5.9 ± 1.3 ka, and 11.4 ± 4 ka. These results indicate that the recurrence interval along the Marquesado–La Rinconada fault zone averages several thousand years. The inferred displacements at the Jejenes site are about 1.1 m for E1, E3, and E4 and 2.1 m for event E2, whereas the displacements at Loma Negra averaged about 1 m, but the most recent event displays less slip. Notably, the older events seem to have been larger and emergent, whereas the youngest event appears to have been smaller and blind in the ponded sediment; this may partially explain the poor expression of classic colluvial wedges associated with some events. Despite the fact that active surface faulting has an uncertain relationship with the primary seismic sources at depth in the crust, past and future events of Mw∼7.5 are consistent with the length scale of active deformation, the ∼1–2 m slip per event scale of these ruptures, and the size of historical earthquakes.
Validation of automated scoring for learning progression-aligned Next Generation Science Standards performance assessments
Authors: Kaldaras Leonora , Haudek Kevin C. 
Published: December 2022

IntroductionThe Framework for K-12 Science Education promotes supporting the development of knowledge application skills along previously validated learning progressions (LPs). Effective assessment of knowledge application requires LP-aligned constructed-response (CR) assessments. But these assessments are time-consuming and expensive to score and provide feedback for. As part of artificial intelligence, machine learning (ML) presents an invaluable tool for conducting validation studies and providing immediate feedback. To fully evaluate the validity of machine-based scores, it is important to investigate human-machine score consistency beyond observed scores. Importantly, no formal studies have explored the nature of disagreements between human and machine-assigned scores as related to LP levels.MethodsWe used quantitative and qualitative approaches to investigate the nature of disagreements among human and scores generated by two approaches to machine learning using a previously validated assessment instrument aligned to LP for scientific argumentation.ResultsWe applied quantitative approaches, including agreement measures, confirmatory factor analysis, and generalizability studies, to identify items that represent threats to validity for different machine scoring approaches. This analysis allowed us to determine specific elements of argumentation practice at each level of the LP that are associated with a higher percentage of misscores by each of the scoring approaches. We further used qualitative analysis of the items identified by quantitative methods to examine the consistency between the misscores, the scoring rubrics, and student responses. We found that rubrics that require interpretation by human coders and items which target more sophisticated argumentation practice present the greatest threats to the validity of machine scores.DiscussionWe use this information to construct a fine-grained validity argument for machine scores, which is an important piece because it provides insights for improving the design of LP-aligned assessments and artificial intelligence-enabled scoring of those assessments.
Development of Type 1 Diabetes may occur through a Type 2 Diabetes mechanism
Authors: Josefsen Knud , Krogvold Lars , Gerling Ivan C. , Pociot Flemming , Dahl-Jørgensen Knut , Buschard Karsten 
Published: December 2022

BackgroundAt diagnosis of Type 1 Diabetes (T1D), 30% of the beta cells are dormant, i.e. alive, but inactive. This could reduce beta cell destruction, as cellular stress contributes to beta cell damage. However, the beta cells, that are still active, must produce more insulin and are therefore more vulnerable. The inactive beta cells represent a potential for restoring the insulin secretion.MethodsWe analyzed the expression of selected genes in islets from live, newly diagnosed T1D patients from the DiViD study and organ doners with longer duration of T1D, type 2 diabetes (T2D), or no diabetes from the nPOD study. Additionally, analysis of polymorphisms was performed on all the investigated genes.FindingsVarious possibilities were considered for the inactivity of the beta cells: secretion defect, fetal state, hibernation, and insulin resistance. We analyzed genes related to the ceramide and sphingomyelin synthesis and degradation, secretion, circadian rhythm and insulin action, and found changes in T1D islets that resemble fetal dedifferentiation and asynchrony. Furthermore, we found low levels of insulin receptor mRNA in the islets. No polymorphisms were found.InterpretationOur findings suggest a secretion defect, but also fetal dedifferentiation and desynchronization in the inactive beta cells. Together with previous evidence, that predisposing factors for T2D are also present for T1D development, we raise the idea to treat individuals with ongoing T1D development prophylactically with T2D medicine like GLP-1 receptor agonists, metformin, or others, combined with anti-inflammatory compounds, in order to reactivate the dormant beta cells, and to prevent autoimmune destruction. T2D mechanisms during T1D development should be investigated further.
Assessment of immunotherapy response in intracranial malignancy using semi-automatic segmentation on magnetic resonance images
Authors: Tan Jia , Liu Chang , Li Yan , Ma Yiqi , Xie Ruoxi , Li Zheng , Wan Hengjiang , Lui Su , Wu Min 
Published: December 2022

ObjectiveTo explore multi-aspect radiologic assessment of immunotherapy response in intracranial malignancies based on a semi-automatic segmentation technique, and to explore volumetric thresholds with good performance according to RECIST 1.1 thresholds.MethodsPatients diagnosed with intracranial malignancies and treated with immunotherapy were included retrospectively. In all MR images, target lesions were measured using a semi-automatic segmentation technique that could intelligently generate visual diagrams including RECIST 1.1, total volume, and max. 3D diameter. The changes in parameters were calculated for each patient after immunotherapy. The ROC curve was used to analyze the sensitivity and specificity of the size change of the legion. This was useful to find new volumetric thresholds with better efficiency in response assessment. The changes in total volume were assessed by conventional volumetric thresholds, while RECIST 1.1 thresholds were for the max. 3D diameter. A chi-square test was used to compare the concordance and diagnostic correlation between the response assessment results of the three criteria.ResultsA total of 20 cases (average age, 58 years; range, 23 to 84 years) and 58 follow-up MR examinations after immunotherapy were included in the analysis. The P-value of the chi-square test between RECIST 1.1 and total volume is 0 (P &lt;0.05), same as that in RECIST 1.1 and max. 3D diameter. The kappa value of the former two was 0.775, and the kappa value for the latter two was 0.742. The above results indicate a significant correlation and good concordance for all three criteria. In addition, we also found that the volumetric assessment had the best sensitivity and specificity for the immunotherapy response in intracranial malignancies, with a PR threshold of −64.9% and a PD threshold of 21.4%.ConclusionsRadiologic assessment of immunotherapy response in intracranial malignancy can be performed by multiple criteria based on semi-automatic segmentation technique on MR images, such as total volume, max. 3D diameter and RECIST 1.1. In addition, new volumetric thresholds with good sensitivity and specificity were found by volumetric assessment.
Fatty acid metabolism is related to the immune microenvironment changes of gastric cancer and RGS2 is a new tumor biomarker
Authors: Yang Shifeng , Sun Boshi , Li Wenjing , Yang Hao , Li Nana , Zhang Xinyu 
Published: December 2022

BackgroundAlterations in lipid metabolism promote tumor progression. However, the role of lipid metabolism in the occurrence and development of gastric cancer have not been fully clarifiedMethodHere, genes that are related to fatty acid metabolism and differentially-expressed between normal and gastric cancer tissues were identified in the TCGA-STAD cohort. The intersection of identified differentially-expressed genes with Geneset was determined to obtain 78 fatty acid metabolism-related genes. The ConsensusClusterPlus R package was used to perform differentially-expressed genes, which yielded divided two gastric cancer subtypes termed cluster 1 and cluster 2.ResultsPatients in cluster 2 was found to display poorer prognosis than patients in cluster 1. Using machine learning method to select 8 differentially expressed genes among subtypes to construct fatty acid prognostic risk score model (FARS), which was found to display good prognostic efficacy. We also identified that certain anticancer drugs, such as bortezomib, elesclomol, GW843682X, and nilotinib, showed significant sensitivity in the high FARS score group. RGS2 was selected as the core gene upon an analysis of the gastric cancer single-cell, and Western blotting and immunofluorescence staining results revealed high level of expression of this gene in gastric cancer cells. The results of immunohistochemical staining showed that a large amount of RGS2 was deposited in the stroma in gastric cancer. A pan-cancer analysis also revealed a significant association of RGS2 with TMB, TIDE, and CD8+ T-cell infiltration in other cancer types as well. RGS2 may thus be studied further as a new target for immunotherapy in future studies on gastric cancer.ConclusionIn summary, the FARS model developed here enhances our understanding of lipid metabolism in the TME in gastric cancer, and provides a theoretical basis for predicting tumor prognosis and clinical treatment.
Degradable composite aerogel with excellent water-absorption for trace water removal in oil and oil-in-water emulsion filtration
Authors: Lu Hong , Jiang Xueliang , Wang Jintao , Hu Ruofei 
Published: December 2022

In this study, using chitosan (CS) and carboxymethyl cellulose (CMC) as backbone and introducing citric acid (CA)to enhance the electrostatic interaction of the system, citric acid/chitosan/carboxymethyl cellulose (CA/CS/CMC) aerogel is obtained by simple freeze-drying. CA/CS/CMC composite aerogel exhibits light weight, low density, high porosity, outstanding hydrophilic and water retention properties, and satisfactory underwater oleophobicity. The water adsorption capacity of the obtained aerogels can reach 43.87–80.28 g/g, which are far more than that of carboxymethyl cellulose and chitosan aerogels (14.27–20.08 g/g). In addition, with strong hydrophilicity, underwater oleophobicity and water retention endowed by the rough internal microstructure and the rich hydroxyl, amino, and carboxyl groups, the fabricated aerogel can also be used as a filter to achieve effective separation of oil-in-water emulsions and oil/water mixtures. The separation efficiency of aerogel for oil/water mixtures are higher than 90.7%. Because the developed preparation method is green, simple and mild and the raw materials are readily available and environmentally friendly, the obtained CA/CS/CMC aerogel with strong water absorption capacity and good separation efficiency displays a promising application in water-oil separation.
Fusobacterium nucleatum induces colon anastomosis leak by activating epithelial cells to express MMP9
Authors: Shi Shang , Liu Yang , Wang Zhiyue , Jin Xiangren , Yan Wei , Guo Xiao , Lin Baiqiang , Wang Haoran , Li Bowen , Zheng Jianjun , Wei Yunwei 
Published: December 2022

BackgroundDespite advances in anastomotic techniques and perioperative care, the incidence of anastomotic leak (AL) has not substantially decreased over time. Although it is known that AL etiology is multifactorial and the mechanisms involved remain unclear, there is accumulating evidence pointing at AL related to gut microbiota.MethodWe firstly performed a clinical study to analyze the gut microbiota between colorectal cancer patients who developed AL and those who did not (nAL) using 16S-rRNA sequencing and quantitative real-time PCR to identify AL risk bacterial taxa. Then we built a rat anastomosis model and performed a bacteria transplantation to ensure the cause-effect relationship. The anastomotic healing score was used to evaluate the healing of anastomosis. In addition, we assessed the adhesion ability of bacteria by staining with fluorescein isothiocyanate and attachment assay. The expression of matrix metalloproteinase 9 (MMP9) was detected by western blot, and the activity was detected by gelatin zymography.ResultsWe found that the abundance and positive rate of Fusobacterium nucleatum (Fn) were higher in the AL patients. Exposure of the rat’s colon anastomosis to Fn contributes to the loss of submucosa collagen I and III, leading to AL’s pathogenesis. Fn can attach to the gut epithelial cells and stimulate intestinal MMP9 expression in vitro and in vivo. We further confirmed that these effects of Fn depended on the E-cadherin/β-catenin signaling pathway.ConclusionThis work demonstrates that Fn attaches and then stimulates the expression of epithelial cells MMP9 by the E-cadherin/β-catenin signaling pathway. These effects contribute to collagen break down in the intestinal tissue, finally leading to AL.
Endogenous tagging of Unc-13 reveals nanoscale reorganization at active zones during presynaptic homeostatic potentiation
Authors: Dannhäuser Sven , Mrestani Achmed , Gundelach Florian , Pauli Martin , Komma Fabian , Kollmannsberger Philip , Sauer Markus , Heckmann Manfred , Paul Mila M. 
Published: December 2022

IntroductionNeurotransmitter release at presynaptic active zones (AZs) requires concerted protein interactions within a dense 3D nano-hemisphere. Among the complex protein meshwork the (M)unc-13 family member Unc-13 of Drosophila melanogaster is essential for docking of synaptic vesicles and transmitter release.MethodsWe employ minos-mediated integration cassette (MiMIC)-based gene editing using GFSTF (EGFP-FlAsH-StrepII-TEV-3xFlag) to endogenously tag all annotated Drosophila Unc-13 isoforms enabling visualization of endogenous Unc-13 expression within the central and peripheral nervous system.Results and discussionElectrophysiological characterization using two-electrode voltage clamp (TEVC) reveals that evoked and spontaneous synaptic transmission remain unaffected in unc-13GFSTF 3rd instar larvae and acute presynaptic homeostatic potentiation (PHP) can be induced at control levels. Furthermore, multi-color structured-illumination shows precise co-localization of Unc-13GFSTF, Bruchpilot, and GluRIIA-receptor subunits within the synaptic mesoscale. Localization microscopy in combination with HDBSCAN algorithms detect Unc-13GFSTF subclusters that move toward the AZ center during PHP with unaltered Unc-13GFSTF protein levels.
Valorization of whey proteins and beetroot peels to develop a functional beverage high in proteins and antioxidants
Authors: Abdo Eman M. , Allam Marwa G. , Gomaa Mohamed A. E. , Shaltout Omayma E. , Mansour Hanem M. M. 
Published: December 2022

IntroductionAdequate protein and antioxidant intake are crucial for everyone, particularly athletes, to promote muscle performance and prevent muscle damage. Whey proteins are high-quality proteins with high digestibility and bioavailability; beetroot peels are an abundant antioxidant source.MethodsThe present study was designated to develop a functional beverage based on mixing whey protein isolate (5%) with different concentrations of beetroot peel water extract (1, 2.5, and 5%) and flavored with strawberries puree (5%). In addition, we examined the stability of the physicochemical parameters and the bioactive components of the beverages during cold storage (4°C) for 14 days.Results and discussionWhey protein isolates enriched the juices with stable protein content during the storage (4.65–4.69%). Besides, the extract revealed a concentration-dependent effect on the bioactive components, the antioxidant activity, and the microbial load of the juices; it distinguished the fresh juices by high betalains and nitrate content, 87.31–106.44 mg/L and 94.29–112.59 mg/L, respectively. Beverages with 2.5% peel extract (T2) had the preferable sensory attributes compared to control and other treatments. On day 0, phenolics and flavonoids increased in T2 by 44 and 31% compared to the control, which elevated the scavenging activity of the juice (T2) (P &lt; 0.05). At the end of the storage period (14 days), phenolics and flavonoids of T2 recorded their lowest values, 26.23 and 21.75 mg/mL, respectively. However, they stood higher than phenolics (22.21 mg/mL) (p &lt; 0.05) and flavonoids (18.36 mg/mL) (p &gt; 0.05) of control. Similarly, betalains degraded by 45% to reach 47.46 mg/L in T2, which reduced the redness (a*) and increased the yellowness (b*) values.ConclusionConsequently, whey/strawberry/beetroot peel (5: 5: 2.5 w/v/w) in d.H2O is a functional beverage that provides the body with a high-quality protein and a considerable amount of antioxidants.
Agrimol B inhibits colon carcinoma progression by blocking mitochondrial function through the PGC-1α/NRF1/TFAM signaling pathway
Authors: Xiang Dongyang , Yang Wenjuan , Fang Zihan , Mao Jialei , Yan Qiuying , Li Liu , Tan Jiani , Yu Chengtao , Qian Jun , Tang Dongxin , Pan Xiaoting , Cheng Haibo , Sun Dongdong 
Published: December 2022

BackgroundThe activation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) stimulates the transcription of the downstream target proteins, mitochondrial transcription factor A (TFAM) and nuclear respiratory factor 1 (NRF1), which induces mitochondrial biogenesis and promotes colorectal tumorigenesis. Agrimol B (Agr) is a constituent of Agrimonia pilosa Ledeb. that exerts anticancer effects. Herein, we aimed to investigate the antitumor activity of Agr and its mechanism of action.MethodsThe interaction between Agr and PGC-1α was predicted by molecular docking. After the treatment with different concentrations of Agr (0, 144, 288, and 576 nM), the cell viability, migration rate, proliferation rate, and apoptosis rate of human colon cancer HCT116 cells were determined. Mitochondrial activity, cellular reactive oxygen species (ROS), and mitochondrial membrane potential were assessed to measure the regulatory effect of Agr on mitochondrial function. Western blotting (WB) assay was used to examine the expression of PGC-1α, NRF1, and TFAM, as well as of the pro-apoptotic proteins, Bax and Caspase-3, and the antiapoptotic protein (Bcl-2). Finally, subcutaneous tumor xenograft model mice were used to evaluate the effect of Agr on colorectal cancer (CRC) in vivo.ResultsThe molecular docking results revealed a high likelihood of Agr interacting with PGC-1α. Agr inhibited the proliferation and migration of HCT116 cells, promoted ROS production and mitochondrial oxidative stress, inhibited mitochondrial activity, and decreased mitochondrial membrane potential. Agr induced cell apoptosis and, in combination with PGC-1α, impaired mitochondrial biogenesis and suppressed the expression of NRF1 and TFAM. Agr also suppressed the expression of Bcl-2 and Cleaved-Caspase-3 and increased the expression of Bax and Caspase-3. In addition, the in vivo antitumor effect and mechanism of Agr were confirmed by using a subcutaneous tumor xenograft mouse model.ConclusionsOur findings demonstrated that Agr regulates the expression of PGC-1α, thereby inducing mitochondrial dysfunction and promoting tumor cell apoptosis. This work highlights the potential of Agr as a promising therapeutic candidate in CRC.
Clinicopathologic features, treatment, and prognosis of pregnancy-associated breast cancer
Authors: Li Yuechong , Wang Yingjiao , Sun Qiang , Shen Songjie 
Published: December 2022

PurposeTo identify the clinicopathological features, treatment, and prognosis of patients with breast cancer, who were diagnosed during and after pregnancy.MethodsWe searched for patients with pregnancy-associated breast cancer (PABC) using the big data query and analysis system of Peking Union Medical College Hospital from between January 1, 2013, and December 31, 2021, and matched each patient with two non-PABC patients by age at diagnosis, year at diagnosis, and tumor stage. The clinicopathologic features, treatment, and outcomes of breast cancer during pregnancy (BC-P) and breast cancer during the first-year post-partum (BC-PP) were examined retrospectively in two case-control studies.ResultsEighteen BC-P cases, 36 controls for BC-P cases, 62 BC-PP cases, and 124 controls for BC-PP cases were enrolled in our study. The expression of HER-2 and Ki-67 was higher in BC-PP cases than in its controls (P=0.01, 0.018, respectively). Patients with BC-PP were more likely to choose mastectomy than breast-conserving surgery (P=0.001). There were no significant differences in event-free survival (EFS) between patients with BC-P and BC-PP and their controls.ConclusionBC-P and BC-PP patients displayed adverse clinicopathological features in our population. However, when matched by age at diagnosis, year of diagnosis, and tumor stage, BC-P and BC-PP patients did not show inferior outcomes to controls, probably due to aggressive multimodality therapy.
Pharmacokinetics, distribution, metabolism, and excretion of body-protective compound 157, a potential drug for treating various wounds, in rats and dogs
Authors: He Lei , Feng Donglin , Guo Hui , Zhou Yueyuan , Li Zhaozhao , Zhang Kuo , Zhang Wangqian , Wang Shuning , Wang Zhaowei , Hao Qiang , Zhang Cun , Gao Yuan , Gu Jintao , Zhang Yingqi , Li Weina , Li Meng 
Published: December 2022

Body-protective compound (BPC) 157 demonstrates protective effects against damage to various organs and tissues. For future clinical applications, we had previously established a solid-phase synthesis process for BPC157, verified its biological activity in different wound models, and completed preclinical safety evaluations. This study aimed to investigate the pharmacokinetics, excretion, metabolism, and distribution profiles of BPC157. After a single intravenous (IV) administration, single intramuscular (IM) administrations at three doses in successive increments along with repeated IM administrations, the elimination half-life (t1/2) of prototype BPC157 was less than 30 min, and BPC157 showed linear pharmacokinetic characteristics in rats and beagle dogs at all doses. The mean absolute bioavailability of BPC157 following IM injection was approximately 14%–19% in rats and 45%–51% in beagle dogs. Using [3H]-labeled BPC157 and radioactivity examination, we proved that the main excretory pathways of BPC157 involved urine and bile. [3H]BPC157 was rapidly metabolized into a variety of small peptide fragments in vivo, thus forming single amino acids that entered normal amino acid metabolism and excretion pathways. In conclusion, this study provides the first analysis of the pharmacokinetics of BPC157, which will be helpful for its translation in the clinic.