bluuebunny/crossref_metadata_2025_split huggingface dataset:
LHX2 facilitates the progression of nasopharyngeal carcinoma via activation of the FGF1/FGFR axis
Authors: Xie Tao , Du Kunpeng , Liu Wei , Liu Chunshan , Wang Baiyao , Tian Yunhong , Li Rong , Huang Xiaoting , Lin Jie , Jian Haifeng , Zhang Jian , Yuan Yawei 
Published: July 2022

Abstract
Background
Distant metastasis and recurrence remain the main obstacle to nasopharyngeal carcinoma (NPC) treatment. However, the molecular mechanisms underlying NPC growth and metastasis are poorly understood.

Methods
LHX2 expression was examined in NPC cell lines and NPC tissues using quantitative reverse transcription-polymerase chain reaction, western blotting and Immunohistochemistry assay. NPC cells overexpressing or silencing LHX2 were used to perform CCK-8 assay, colony-formation assay, EdU assay, wound-healing and invasion assays in vitro. Xenograft tumour models and lung metastasis models were involved for the in vivo assays. The Gene Set Enrichment Analysis (GSEA), ELISA assay, western blot, chromatin immunoprecipitation (ChIP) assay and Luciferase reporter assay were applied for the downstream target mechanism investigation.

Results
LIM-homeodomain transcription factor 2 (LHX2) was upregulated in NPC tissues and cell lines. Elevated LHX2 was closely associated with poor survival in NPC patients. Ectopic LHX2 overexpression dramatically promoted the growth, migration and invasion of NPC cells both in vitro and in vivo. Mechanistically, LHX2 transcriptionally increased the fibroblast growth factor 1 (FGF1) expression, which in turn activated the phosphorylation of STAT3 (signal transducer and activator of transcription 3), ERK1/2 (extracellular regulated protein kinases 1/2) and AKT signalling pathways in an autocrine and paracrine manner, thereby promoting the growth and metastasis of NPC. Inhibition of FGF1 with siRNA or FGFR inhibitor blocked LHX2-induced nasopharyngeal carcinoma cell growth, migration and invasion.

Conclusions
Our study identifies the LHX2-FGF1-FGFR axis plays a key role in NPC progression and provides a potential target for NPC therapy.
Transepithelial photorefractive keratectomy: a prospective randomized comparative study between the two-step and the single-step techniques
Authors: Abdel-Radi Mahmoud , Shehata Mohamed , Mostafa Magdi Mohammad , Aly Mohamed Omar M. 
Published: July 2022

Abstract
Objectives
To assess and compare the six-month outcome of the two-step transepithelial phototherapeutic keratectomy- photorefractive keratectomy (PTK-PRK) and the single-step transepithelial PRK for myopia and myopic astigmatism.

Methods
A prospective randomized study. The study enrolled 100 eyes of 50 patients with mild to moderate myopia or myopic astigmatism stratified into two groups, PTK-PRK (n = 50 eyes) and single step PRK (n = 50 eyes). Primary outcome measures were visual acuity and manifest refraction. Secondary outcome measures were epithelial healing duration, post-PRK pain scores and 3-month postoperative haze grading.

Results
Preoperative characteristics were similar in both groups (p value > 0.05). The mean uncorrected distance visual acuity (UDVA) at 1 week, 1 month, 3 and 6 months was significantly better in the single-step PRK group than in the two-step PTK-PRK group (p < 0.001). The mean manifest sphere, cylinder and spherical equivalent showed a significant difference at all follow up visits in favour of the single-step PRK (p value < 0.001). Epithelial healing duration was faster in single-step PRK (p value < 0.001). Pain scores were significantly lower following single-step PRK at 8 h, 1 day, 3 days (p value < 0.001) but were similar at the 7th day. Haze scores showed no statistical difference between the two groups at 3-month follow-up.

Conclusion
The two transepithelial PRK techniques were effective in correcting mild to moderate myopia and myopic astigmatism. However, Single-step transepithelial PRK achieved faster visual recovery, better refractive outcome and shorter epithelial healing time with less post-PRK pain.

Clinical trials registry
(Clinical Trials.gov Identifier): NCT04710082.
A quantum dot crossbar with sublinear scaling of interconnects at cryogenic temperature
Authors: Bavdaz P. L. , Eenink H. G. J. , van Staveren J. , Lodari M. , Almudever C. G. , Clarke J. S. , Sebasatiano F. , Veldhorst M. , Scappucci G. 
Published: July 2022

AbstractWe demonstrate a 36 × 36 gate electrode crossbar that supports 648 narrow-channel field effect transistors (FET) for gate-defined quantum dots, with a quadratic increase in quantum dot count upon a linear increase in control lines. The crossbar is fabricated on an industrial 28Si-MOS stack and shows 100% FET yield at cryogenic temperature. We observe a decreasing threshold voltage for wider channel devices and obtain a normal distribution of pinch-off voltages for nominally identical tunnel barriers probed over 1296 gate crossings. Macroscopically across the crossbar, we measure an average pinch-off of 1.17 V with a standard deviation of 46.8 mV, while local differences within each unit cell indicate a standard deviation of 23.1 mV. These disorder potential landscape variations translate to 1.2 and 0.6 times the measured quantum dot charging energy, respectively. Such metrics provide means for material and device optimization and serve as guidelines in the design of large-scale architectures for fault-tolerant semiconductor-based quantum computing.
Strong control of effective radiative forcing by the spatial pattern of absorbing aerosol
Authors: Williams Andrew I. L. , Stier Philip , Dagan Guy , Watson-Parris Duncan 
Published: July 2022

AbstractOver the coming decades, it is expected that the spatial pattern of anthropogenic aerosol will change dramatically and the global aerosol composition will become relatively more absorbing. Yet, the climatic impact of this evolving spatial pattern of absorbing aerosol has received relatively little attention, in particular its impact on global-mean effective radiative forcing. Here, using model experiments, we show that the effective radiative forcing from absorbing aerosol varies strongly depending on their location, driven by rapid adjustments of clouds and circulation. Our experiments generate positive effective radiative forcing in response to aerosol absorption throughout the midlatitudes and most of the tropical regions, and a strong ‘hot spot’ of negative effective radiative forcing in response to aerosol absorption over the tropical Western Pacific. Further, these diverse responses can be robustly attributed to changes in atmospheric dynamics and highlight the importance of this ‘aerosol pattern effect’ for transient forcing from regional biomass-burning aerosol.
Origin and function of activated fibroblast states during zebrafish heart regeneration
Authors: Hu Bo , Lelek Sara , Spanjaard Bastiaan , El-Sammak Hadil , Simões Mariana Guedes , Mintcheva Janita , Aliee Hananeh , Schäfer Ronny , Meyer Alexander M. , Theis Fabian , Stainier Didier Y. R. , Panáková Daniela , Junker Jan Philipp 
Published: July 2022

AbstractThe adult zebrafish heart has a high capacity for regeneration following injury. However, the composition of the regenerative niche has remained largely elusive. Here, we dissected the diversity of activated cell states in the regenerating zebrafish heart based on single-cell transcriptomics and spatiotemporal analysis. We observed the emergence of several transient cell states with fibroblast characteristics following injury, and we outlined the proregenerative function of collagen-12-expressing fibroblasts. To understand the cascade of events leading to heart regeneration, we determined the origin of these cell states by high-throughput lineage tracing. We found that activated fibroblasts were derived from two separate sources: the epicardium and the endocardium. Mechanistically, we determined Wnt signalling as a regulator of the endocardial fibroblast response. In summary, our work identifies specialized activated fibroblast cell states that contribute to heart regeneration, thereby opening up possible approaches to modulating the regenerative capacity of the vertebrate heart.
Chemical acylation of an acquired serine suppresses oncogenic signaling of K-Ras(G12S)
Authors: Zhang Ziyang , Guiley Keelan Z. , Shokat Kevan M. 
Published: July 2022

AbstractDrugs that directly impede the function of driver oncogenes offer exceptional efficacy and a therapeutic window. The recently approved mutant selective small-molecule cysteine-reactive covalent inhibitor of the G12C mutant of K-Ras, sotorasib, provides a case in point. KRAS is the most frequently mutated proto-oncogene in human cancer, yet despite success targeting the G12C allele, targeted therapy for other hotspot mutants of KRAS has not been described. Here we report the discovery of small molecules that covalently target a G12S somatic mutation in K-Ras and suppress its oncogenic signaling. We show that these molecules are active in cells expressing K-Ras(G12S) but spare the wild-type protein. Our results provide a path to targeting a second somatic mutation in the oncogene KRAS by overcoming the weak nucleophilicity of an acquired serine residue. The chemistry we describe may serve as a basis for the selective targeting of other unactivated serines.
Glimmers of hope in large carnivore recoveries
Authors: Ingeman Kurt E. , Zhao Lily Z. , Wolf Christopher , Williams David R. , Ritger Amelia L. , Ripple William J. , Kopecky Kai L. , Dillon Erin M. , DiFiore Bartholomew P. , Curtis Joseph S. , Csik Samantha R. , Bui An , Stier Adrian C. 
Published: July 2022

AbstractIn the face of an accelerating extinction crisis, scientists must draw insights from successful conservation interventions to uncover promising strategies for reversing broader declines. Here, we synthesize cases of recovery from a list of 362 species of large carnivores, ecologically important species that function as terminal consumers in many ecological contexts. Large carnivores represent critical conservation targets that have experienced historical declines as a result of direct exploitation and habitat loss. We examine taxonomic and geographic variation in current extinction risk and recovery indices, identify conservation actions associated with positive outcomes, and reveal anthropogenic threats linked to ongoing declines. We find that fewer than 10% of global large carnivore populations are increasing, and only 12 species (3.3%) have experienced genuine improvement in extinction risk, mostly limited to recoveries among marine mammals. Recovery is associated with species legislation enacted at national and international levels, and with management of direct exploitation. Conversely, ongoing declines are robustly linked to threats that include habitat modification and human conflict. Applying lessons from cases of large carnivore recovery will be crucial for restoring intact ecosystems and maintaining the services they provide to humans.
Analytical method validation for assay determination of cannabidiol and tetrahydrocannabinol in hemp oil infused products by RP-HPLC
Authors: Analakkattillam Sandhyarani , Langsi Victor K. , Hanrahan John P. , Moore Eric 
Published: July 2022

AbstractA simple quantitative reverse phase high performance liquid chromatographic (RP-HPLC) method has been developed and validated for assay determination of cannabidiol and tetrahydrocannabinol in hemp oil infused products. The RP-HPLC method was developed and optimized for the mobile phase composition, flow rate, column selection and detector wavelength. An isocratic elution of samples were performed on SOLAS 100 Å C18 150 mm × 4.6 mm, 5 μm column with a mobile phase containing 75/25 acetonitrile/water v/v, with a flow rate of 1.5 mL/min by using an ultraviolet–visible (UV/Vis) detector operating at 214 nm. The RP-HPLC method was validated to meet regulatory requirements which covers specificity, accuracy, range, linearity, precision, system suitability and robustness. The validated assay test method was applied successfully to quantify cannabidiol and tetrahydrocannabinol in commercial hemp oil infused products such as tablets, soft gel capsules, plant extract oils, oral drops, tincture, and beverage enhancers. All the test results were found acceptable as per ICH guidelines, and this confirmed the feasibility of this method for its intended use in regular quality control and assay of cannabidiol and tetrahydrocannabinol in hemp oil infused products.
Enhanced osteogenic differentiation of stem cells by 3D printed PCL scaffolds coated with collagen and hydroxyapatite
Authors: Ebrahimi Zahra , Irani Shiva , Ardeshirylajimi Abdolreza , Seyedjafari Ehsan 
Published: July 2022

AbstractBone tissue engineering uses various methods and materials to find suitable scaffolds that regenerate lost bone due to disease or injury. Poly(ε-caprolactone) (PCL) can be used in 3D printing for producing biodegradable scaffolds by fused deposition modeling (FDM). However, the hydrophobic surfaces of PCL and its non-osteogenic nature reduces adhesion and cell bioactivity at the time of implantation. This work aims to enhance bone formation, osteogenic differentiation, and in vitro biocompatibility via PCL scaffolds modification with Hydroxyapatite (HA) and Collagen type I (COL). This study evaluated the osteosupportive capacity, biological behavior, and physicochemical properties of 3D-printed PCL, PCL/HA, PCL/COL, and PCL/HA/COL scaffolds. Biocompatibility and cells proliferation were investigated by seeding human adipose tissue-derived mesenchymal stem cells (hADSCs) onto the scaffolds, which were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and 6-diamidino-2-phenylindole (DAPI) staining. In addition, the bone differentiation potential of the hADSCs was assessed using calcium deposition, alkaline phosphatase (ALP) activity, and bone-related protein and genes. Although all constructed scaffolds support hADSCs proliferation and differentiation, the results showed that scaffold coating with HA and COL can boost these capacities in a synergistic manner. According to the findings, the tricomponent 3D-printed scaffold can be considered as a promising choice for bone tissue regeneration and rebuilding.
Forecast of a future leveling of the incidence trends of female breast cancer in Taiwan: an age-period-cohort analysis
Authors: Chen Yi-Chu , Su Shih-Yung , Jhuang Jing-Rong , Chiang Chun-Ju , Yang Ya-Wen , Wu Chao-Chun , Lin Li-Ju , Lee Wen-Chung 
Published: July 2022

AbstractBreast cancer is the most common cancer among women in Taiwan. The age-standardized incidence rate has doubled in just 20 years, causing considerable concern to health professionals and the general public. This study used an ensemble of age-period-cohort models to estimate breast cancer incidence trends in Taiwan from 1997 to 2016 and project trends up to 2035. The (truncated) world standard population (World Health Organization 2000) proportions (age groups: 25–29, 30–34, …, 80–84, and older than 85 years) were used to calculate age-standardized incidence rates. The age-standardized incidence rate from 1997 (60.33/100,000 population) to 2016 (128.20/100,000 population) increased rapidly. The projection is that the increase in the age-standardized incidence will subsequently slow and exhibit a plateau in 2031 (151.32/100,000 population). From 2026 to 2035, the age-specific incidence rates for women older than 55 years old (postmenopausal breast cancer) are projected to increase with larger percentage increments for older women. A future leveling of female breast cancer incidence trends in Taiwan is anticipated. The majority of the patients with breast cancer in the future will be women aged 55 years and older. Education on lifestyle recommendations and mammography screening is required to reduce the burden of breast cancer. The results should have implications for other countries which are also confronted with the same public health problem of rapidly increasing breast cancer incidences.
Identification and implication of tissue-enriched ligands in epithelial–endothelial crosstalk during pancreas development
Authors: Moulis Manon , Runser Steve Vincent Maurice , Glorieux Laura , Dauguet Nicolas , Vanderaa Christophe , Gatto Laurent , Tyteca Donatienne , Henriet Patrick , Spagnoli Francesca M. , Iber Dagmar , Pierreux Christophe E. 
Published: July 2022

AbstractDevelopment of the pancreas is driven by an intrinsic program coordinated with signals from other cell types in the epithelial environment. These intercellular communications have been so far challenging to study because of the low concentration, localized production and diversity of the signals released. Here, we combined scRNAseq data with a computational interactomic approach to identify signals involved in the reciprocal interactions between the various cell types of the developing pancreas. This in silico approach yielded 40,607 potential ligand-target interactions between the different main pancreatic cell types. Among this vast network of interactions, we focused on three ligands potentially involved in communications between epithelial and endothelial cells. BMP7 and WNT7B, expressed by pancreatic epithelial cells and predicted to target endothelial cells, and SEMA6D, involved in the reverse interaction. In situ hybridization confirmed the localized expression of Bmp7 in the pancreatic epithelial tip cells and of Wnt7b in the trunk cells. On the contrary, Sema6d was enriched in endothelial cells. Functional experiments on ex vivo cultured pancreatic explants indicated that tip cell-produced BMP7 limited development of endothelial cells. This work identified ligands with a restricted tissular and cellular distribution and highlighted the role of BMP7 in the intercellular communications contributing to vessel development and organization during pancreas organogenesis.
Decision effect of a deep-learning model to assist a head computed tomography order for pediatric traumatic brain injury
Authors: Heo Sejin , Ha Juhyung , Jung Weon , Yoo Suyoung , Song Yeejun , Kim Taerim , Cha Won Chul 
Published: July 2022

AbstractThe study aims to measure the effectiveness of an AI-based traumatic intracranial hemorrhage prediction model in the decisions of emergency physicians regarding ordering head computed tomography (CT) scans. We developed a deep-learning model for predicting traumatic intracranial hemorrhages (DEEPTICH) using a national trauma registry with 1.8 million cases. For simulation, 24 cases were selected from previous emergency department cases. For each case, physicians made decisions on ordering a head CT twice: initially without the DEEPTICH assistance, and subsequently with the DEEPTICH assistance. Of the 528 responses from 22 participants, 201 initial decisions were different from the DEEPTICH recommendations. Of these 201 initial decisions, 94 were changed after DEEPTICH assistance (46.8%). For the cases in which CT was initially not ordered, 71.4% of the decisions were changed (p < 0.001), and for the cases in which CT was initially ordered, 37.2% (p < 0.001) of the decisions were changed after DEEPTICH assistance. When using DEEPTICH, 46 (11.6%) unnecessary CTs were avoided (p < 0.001) and 10 (11.4%) traumatic intracranial hemorrhages (ICHs) that would have been otherwise missed were found (p = 0.039). We found that emergency physicians were likely to accept AI based on how they perceived its safety.
Eolian erosion of polygons in the Atacama Desert as a proxy for hyper-arid environments on Earth and beyond
Authors: Sager Christof , Airo Alessandro , Arens Felix L. , Schulze-Makuch Dirk 
Published: July 2022

AbstractPolygonal networks occur on various terrestrial and extraterrestrial surfaces holding valuable information on the pedological and climatological conditions under which they develop. However, unlike periglacial polygons that are commonly used as an environmental proxy, the information that polygons in the hyper-arid Atacama Desert can provide is little understood. To promote their use as a proxy, we investigated a polygonal network within an inactive channel that exhibits uncommonly diverse surface morphologies and mineral compositions, using geochemical and remote sensing techniques. Our findings show that the polygons belong to a continuous network of the same genetic origin. Their differences result from post-formational differential eolian erosion up to 50 cm depth, exposing indurated subsurface horizons rich in sulfate or nitrate and chloride. Their location in an ancient channel could lead to the misinterpretation of fluvial polygon erosion, however, we find no such signs but evidence for aqueous resurfacing of microtopography by fog and minimal rainwater infiltration. Our findings extend the use of polygons as proxies in the Atacama Desert, indicating saline soils and hyper-arid conditions. We conclude that this example of polygon erosion can guide future polygon research, especially regarding the use of erosional surfaces on Earth and beyond to gain valuable subsurface insights.
A simplified prediction model for end-stage kidney disease in patients with diabetes
Authors: Inoguchi Toyoshi , Okui Tasuku , Nojiri Chinatsu , Eto Erina , Hasuzawa Nao , Inoguchi Yukihiro , Ochi Kentaro , Takashi Yuichi , Hiyama Fujiyo , Nishida Daisuke , Umeda Fumio , Yamauchi Teruaki , Kawanami Daiji , Kobayashi Kunihisa , Nomura Masatoshi , Nakashima Naoki 
Published: July 2022

AbstractThis study aimed to develop a simplified model for predicting end-stage kidney disease (ESKD) in patients with diabetes. The cohort included 2549 individuals who were followed up at Kyushu University Hospital (Japan) between January 1, 2008 and December 31, 2018. The outcome was a composite of ESKD, defined as an eGFR < 15 mL min−1 [1.73 m]−2, dialysis, or renal transplantation. The mean follow-up was 5.6 $$\pm$$
±
3.7 years, and ESKD occurred in 176 (6.2%) individuals. Both a machine learning random forest model and a Cox proportional hazard model selected eGFR, proteinuria, hemoglobin A1c, serum albumin levels, and serum bilirubin levels in a descending order as the most important predictors among 20 baseline variables. A model using eGFR, proteinuria and hemoglobin A1c showed a relatively good performance in discrimination (C-statistic: 0.842) and calibration (Nam and D’Agostino $$\chi$$
χ
2 statistic: 22.4). Adding serum albumin and bilirubin levels to the model further improved it, and a model using 5 variables showed the best performance in the predictive ability (C-statistic: 0.895, $$\chi$$
χ
2 statistic: 7.7). The accuracy of this model was validated in an external cohort (n = 5153). This novel simplified prediction model may be clinically useful for predicting ESKD in patients with diabetes.