bluuebunny/crossref_metadata_2025_split huggingface dataset:
Formation of Longitudinal River Valleys and the Fixing of Drainage Divides in Response to Exhumation of Crystalline Basement
Authors: Bernard Thomas , Sinclair Hugh D. , Gailleton Boris , Fox Matthew 
Published: April 2021

AbstractVariations in rock strength act as a first‐order control on mountain landscapes. However, the transient topographic signal of basement exhumation has not been explored. We use model outputs to demonstrate the mobility of drainage divides in mountain ranges in response to the exhumation of basement rocks and the implications for the morphology of river catchments. The exhumation of harder rocks within a catchment reduces upstream channel steepness and erosion rates in contrast to neighboring catchments. The results are a shift in the orogen‐scale drainage divide toward the harder rocks, and the formation of range parallel longitudinal valleys as neighboring river networks capture the headwaters of catchments impacted by the harder lithology. Our model outputs provide a process explanation for the initiation of many longitudinal valleys in mountain ranges, and for the pinning of drainage divides on rocks of higher strength as seen the Central Pyrenees, Western Alps, or High Atlas.
The Critical Factor in Controlling the Auroral Intensity in the Cusp Region as Revealed by a Statistical Study on Midday Gap and Non‐Gap Events
Authors: Qiu Hui‐Xuan , Han De‐Sheng , Feng Hui‐Ting , Shi Run , Zhou Su , Zhang Y.‐L. 
Published: April 2021

AbstractTaking advantage of the high spatial‐resolution and global coverage of Defense Meteorological Satellite Program/Special Sensor Ultraviolet Spectrographic Imager observations, we investigated the critical interplanetary factors in controlling the cusp auroral emission by dividing the midday auroras into the gap (weak emission) and non‐gap (intense emission) events. Although the cusp auroral intensity is essentially determined by a parameter related to the IMF (interplanetary magnetic field) direction, IMF magnitude (|By|), and solar wind speed (V), we found that the cusp aurora is statistically weak during the southward IMF but intense when the V and IMF |By| are greater. Further, we confirmed that even with V > 600 km/s, the intense‐aurora event still shows a minimum occurrence near the IMF |By| = 0. However, when the IMF |By| is greater, the V becomes less significant for the intense‐aurora occurrence. These results demonstrate that the IMF |By| is critical in controlling the cusp auroral intensity, most likely by producing an electric field which is given as .
Observed Global Increases in Tropical Cyclone‐Induced Ocean Cooling and Primary Production
Authors: Da Nguyen Dac , Foltz Gregory R. , Balaguru Karthik 
Published: April 2021

AbstractTropical cyclones provide an important source of ocean mixing, bringing cold, nutrient‐rich water to the surface and triggering phytoplankton blooms. Here, we show significant increases in global tropical cyclone‐induced sea surface temperature cooling and surface chlorophyll‐a concentration of 0.05°C and 3.7 × 10−3 mg m−3 per decade over the past 20–35 years. The trends have been driven primarily by an increase in the intensity of strong tropical cyclones. The increase in chlorophyll‐a concentration has been, on average, 1.6% per decade in oligotrophic areas during the tropical cyclone season, in contrast to a decrease of 0.1% per decade during the other months. This tropical cyclone‐induced increase has partially mitigated the overall decline in primary production under climate change.
Regulator of calcineurin 1 gene isoform 4 in pancreatic ductal adenocarcinoma regulates the progression of tumor cells
Authors: Lao Mengyi , Zhang Xiaozhen , Ma Tao , Xu Jian , Yang Hanshen , Duan Yi , Ying Honggang , Zhang Xiaoyu , Guo Chengxiang , Qiu Junyu , Bai Xueli , Liang Tingbo 
Published: April 2021

AbstractTherapeutic strategies to treat pancreatic ductal adenocarcinoma (PDAC) remain unsatisfying and limited. Therefore, it is imperative to fully determine the mechanisms underlying PDAC progression. In the present study, we report a novel role of regulator of calcineurin 1, isoform 4 (RCAN1.4) in regulating PDAC progression. We demonstrated that RCAN1.4 expression was decreased significantly in PDAC tissues compared with that in para-cancerous tissues, and correlated with poor prognosis of patients with pancreatic cancer. In vitro, stable high expression of RCAN1.4 could suppress the metastasis and proliferation and angiogenesis of pancreatic tumor cells. In addition, interferon alpha inducible protein 27 (IFI27) was identified as having a functional role in RCAN1.4-mediated PDAC migration and invasion, while VEGFA play a vital role in RCAN1.4-mediated PDAC angiogenesis. Analysis of mice with subcutaneously/orthotopic implanted xenograft tumors and liver metastasis model confirmed that RCAN1.4 could modulate the growth, metastasis, and angiogenesis of tumors via IFI27/VEGFA in vivo. In conclusion, our results suggested that RCAN1.4 suppresses the growth, metastasis, and angiogenesis of PDAC, functioning partly via IFI27 and VEGFA. Importantly, our results provided possible diagnostic criteria and therapeutic targets for PDAC.
Phase 1b/2 trial of tepotinib in sorafenib pretreated advanced hepatocellular carcinoma with MET overexpression
Authors: Decaens Thomas , Barone Carlo , Assenat Eric , Wermke Martin , Fasolo Angelica , Merle Philippe , Blanc Jean-Frédéric , Grando Véronique , Iacobellis Angelo , Villa Erica , Trojan Joerg , Straub Josef , Bruns Rolf , Berghoff Karin , Scheele Juergen , Raymond Eric , Faivre Sandrine 
Published: April 2021

Abstract
Background
This Phase 1b/2 study evaluated tepotinib, a highly selective MET inhibitor, in US/European patients with sorafenib pretreated advanced hepatocellular carcinoma (aHCC) with MET overexpression.

Methods
Eligible adults had aHCC, progression after ≥4 weeks of sorafenib, and, for Phase 2 only, MET overexpression. Tepotinib was administered once daily at 300 or 500 mg in Phase 1b (‘3 + 3’ design), and at the recommended Phase 2 dose (RP2D) in Phase 2. Primary endpoints were dose-liming toxicities (DLTs; Phase 1b) and 12-week investigator-assessed progression-free survival (PFS; Phase 2).

Results
In Phase 1b (n = 17), no DLTs occurred and the RP2D was confirmed as 500 mg. In Phase 2 (n = 49), the primary endpoint was met: 12-week PFS was 63.3% (90% CI: 50.5–74.7), which was significantly greater than the predefined null hypothesis of ≤15% (one-sided binomial exact test: P < 0.0001). Median time to progression was 4 months. In Phase 2, 28.6% of patients had treatment-related Grade ≥3 adverse events, including peripheral oedema and lipase increase (both 6.1%).

Conclusions
Tepotinib was generally well tolerated and the RP2D (500 mg) showed promising efficacy and, therefore, a positive benefit–risk balance in sorafenib pretreated aHCC with MET overexpression.

Trial Registration
ClinicalTrials.gov: NCT02115373.
α-Fetoprotein mRNA in situ hybridisation is a highly specific marker of hepatocellular carcinoma: a multi-centre study
Authors: Lu Shi-Xun , Huang Yu-Hua , Liu Li-Li , Zhang Chris Zhiyi , Yang Xia , Yang Yuan-Zhong , Shao Chun-Kui , Li Jian-Ming , Xie Dan , Zhang Xuchen , Jain Dhanpat , Yun Jing-Ping 
Published: April 2021

Abstract
Background
Pathologic diagnosis of hepatocellular carcinoma (HCC) can be challenging in differentiating from benign and non-hepatocytic malignancy lesions. The aim of this study was to investigate the potential utility of α-fetoprotein (AFP) mRNA RNAscope, a sensitive and specific method, in the diagnosis of HCC.

Methods
Three independent retrospective cohorts containing 2216 patients with HCC, benign liver lesions, and non-hepatocytic tumours were examined. AFP was detected using ELISA, IHC (Immunohistochemistry), and RNAscope. Glypican3 (GPC3), hepatocyte paraffin-1 (HepPar-1), and arginase-1 (Arg-1) proteins were detected using IHC.

Results
AFP RNAscope improved the HCC detection sensitivity by 24.7–32.7% compared with IHC. In two surgical cohorts, a panel of AFP RNAscope and GPC3 provided the best diagnostic value in differentiating HCC from benign hepatocytic lesions (AUC = 0.905 and 0.811), and a panel including AFP RNAscope, GPC3, HepPar-1, and Arg-1 yielded the best AUC (0.971 and 0.977) when distinguishing HCC from non-hepatocytic malignancies. The results from the liver biopsy cohort were similar, and additional application of AFP RNAscope improved the sensitivity by 18% when distinguishing HCC from benign hepatocytic lesions.

Conclusions
AFP mRNA detected by RNAscope is highly specific for hepatocytic malignancy and may serve as a novel diagnostic biomarker for HCC.
Down-regulation of SLC25A20 promotes hepatocellular carcinoma growth and metastasis through suppression of fatty-acid oxidation
Authors: Yuan Peng , Mu Jiao , Wang Zijun , Ma Shuaijun , Da Xiuwei , Song Jian , Zhang Hongxin , Yang Le , Li Jibin , Yang Jingyue 
Published: April 2021

AbstractSolute carrier family 25 member 20 (SLC25A20) is a mitochondrial-membrane–carrier protein involved in the transport of acylcarnitines into mitochondrial matrix for oxidation. A previous-integrated-proteogenomic study had identified SLC25A20 as one of the top-three prognostic biomarkers in HCC. However, the expression and the biological function of SLC25A20 have not yet been investigated in HCC. In the present study, we found that SLC25A20 expression is frequently down-regulated in HCC cells mainly due to the up-regulation of miR-132-3p. Down-regulation of SLC25A20 is associated with a poor prognosis in patients with HCC. SLC25A20 suppressed HCC growth and metastasis, both in vitro and in vivo, by suppression of G1–S cell transition, epithelial-to-mesenchymal transition (EMT), and induction of cell apoptosis. Mechanistically, SLC25A20 down-regulation promoted HCC growth and metastasis through suppression of fatty-acid oxidation. Altogether, SLC25A20 plays a critical tumor-suppressive role in carcinogenesis of HCC; SLC25A20 may serve as a novel prognostic factor and therapeutic target for patients with HCC.
LncRNA-HOTAIR activates autophagy and promotes the imatinib resistance of gastrointestinal stromal tumor cells through a mechanism involving the miR-130a/ATG2B pathway
Authors: Zhang Jinyan , Chen Ke , Tang Yuexiao , Luan Xiaorui , Zheng Xiaoxiao , Lu Xuemei , Mao Jiayan , Hu Liqiang , Zhang Shufen , Zhang Xianning , Chen Wei 
Published: April 2021

AbstractGastrointestinal stromal tumors (GISTs) are common neoplasms of the gastrointestinal tract that can be treated successfully using C-kit target therapy and surgery; however, imatinib chemoresistance is a major barrier to success in therapy. The present study aimed to discover alternative pathways in imatinib-resistant GISTs. Long noncoding RNAs (lncRNAs) are newly discovered regulators of chemoresistance. Previously, we showed that the lncRNA HOTAIR was upregulated in recurrent GISTs. In this study, we analyzed differentially expressed lncRNAs after imatinib treatment and found that HOTAIR displayed the largest increase. The distribution of HOTAIR in GISTs was shifted from nucleus to cytoplasm after imatinib treatments. The expression of HOTAIR was validated as related to drug sensitivity through Cell Counting Kit-8 assays. Moreover, HOTAIR was associated strongly with cell autophagy and regulated drug sensitivity via autophagy. Mechanistically, HOTAIR correlated negatively with miRNA-130a in GISTs. The downregulation of miRNA-130a reversed HOTAIR-small interfering RNA-induced suppression of autophagy and imatinib sensitivity. We identified autophagy-related protein 2 homolog B (ATG2B) as a downstream target of miR-130a and HOTAIR. ATG2B downregulation reversed the effect of pEX-3-HOTAIR/miR-130a inhibitor on imatinib sensitivity. Finally, HOTAIR was shown to influence the autophagy and imatinib sensitivity of GIST cells in mouse tumor models. Our results suggested that HOTAIR targets the ATG2B inhibitor miR-130a to upregulate the level of cell autophagy so that promotes the imatinib resistance in GISTs.
Allelic and phenotypic heterogeneity in Junctophillin-3 related neurodevelopmental and movement disorders
Authors: Bourinaris Thomas , Athanasiou Alkyoni , Efthymiou Stephanie , Wiethoff Sarah , Salpietro Vincenzo , Houlden Henry 
Published: April 2021

AbstractJunctophilin-3 belongs to a triprotein junctional complex implicated in the regulation of neuronal excitability and involved in the formation of junctional membrane structures between voltage-gated ion channels and endoplasmic (ryanodine) reticular receptors. A monoallelic trinucleotide repeat expansion located within the junctophilin-3 gene (JPH3) has been implicated in a rare autosomal dominant (AD) late-onset (and progressive) disorder clinically resembling Huntington disease (HD), and known as HD-like 2 (HDL2; MIM# 606438). Although the exact molecular mechanisms underlying HDL2 has not yet been fully elucidated, toxic gain-of-function of the aberrant transcript (containing the trinucleotide repeat) and loss of expression of (full-length) junctophilin-3 have both been implicated in HDL2 pathophysiology. In this study, we identified by whole exome sequencing (WES) a JPH3 homozygous truncating variant [NM_020655.4: c.17405dup; p.(Val581Argfs*137)]. in a female individual affected with genetically undetermined neurodevelopmental anomalies (including delayed motor milestones, abnormal social communication, language difficulties and borderline cognitive impairment) and paroxysmal attacks of dystonia since her early infancy. Our study expands the JPH3-associated mutational spectrum and clinical phenotypes, implicating the loss of Junctophilin-3 in heterogeneous neurodevelopmental phenotypes and early-onset paroxysmal movement disorders.
The effect of language on performance: do gendered languages fail women in maths?
Authors: Kricheli-Katz Tamar , Regev Tali 
Published: April 2021

AbstractResearch suggests that gendered languages are associated with gender inequality. However, as languages are embedded in cultures, evidence for causal effects are harder to provide. We contribute to this ongoing debate by exploring the relationship between gendered languages and the gender gap in mathematics achievements. We provide evidence for causality by exploiting the prominent (but not exclusive) practice in gendered languages of using masculine generics to address women. In an experiment on a large representative sample of the Hebrew-speaking adult population in Israel, we show that addressing women in the feminine, compared to addressing them in the masculine, reduces the gender gap in mathematics achievements by a third. These effects are stronger among participants who acquired the Hebrew language early in childhood rather than later in life, suggesting that it is the extent of language proficiency that generates one’s sensitivity to being addressed in the masculine or in the feminine. Moreover, when women are addressed in the masculine, their efforts (in terms of time spent on the maths test) decrease and they report feeling that “science is for men” more than when addressed in the feminine. We supplement the analysis with two experiments that explore the roles of general and task-specific stereotypes in generating these effects.
A method to analyze the influence of mechanical strain on dermal collagen morphologies
Authors: Witte Maximilian , Rübhausen Michael , Jaspers Sören , Wenck Horst , Fischer Frank 
Published: April 2021

AbstractCollagen fibers and their orientation play a major role in the mechanical behavior of soft biological tissue such as skin. Here, we present a proof-of-principle study correlating mechanical properties with collagen fiber network morphologies. A dedicated multiphoton stretching device allows for mechanical deformations in combination with a simultaneous analysis of its collagen fiber network by second harmonic generation imaging (SHG). The recently introduced Fiber Image Network Evaluation (FINE) algorithm is used to obtain detailed information about the morphology with regard to fiber families in collagen network images. To demonstrate the potential of our method, we investigate an isotropic and an anisotropic ex-vivo dorsal pig skin sample under quasi-static cyclic stretching and relaxation sequences. Families of collagen fibers are found to form a partially aligned collagen network under strain. We find that the relative force uptake is accomplished in two steps. Firstly, fibers align within their fiber families and, secondly, fiber families orient in the direction of force. The maximum alignment of the collagen fiber network is found to be determined by the largest strain. Isotropic and anisotropic samples reveal a different micro structural behavior under repeated deformation leading to a similar force uptake after two stretching cycles. Our method correlates mechanical properties with morphologies in collagen fiber networks.
Depressive symptoms, anxiety, and quality of life of Japanese women at initiation of ART treatment
Authors: Kato Tsuguhiko , Sampei Makiko , Saito Kazuki , Morisaki Naho , Urayama Kevin Y. 
Published: April 2021

AbstractAssisted reproductive technology (ART) treatment accounted for 6% of total births in 2017 and is increasing which places Japan among the top worldwide in number of treatments performed. Although ART treatment patients often experience heavy physical and psychological burden, few epidemiologic studies have been conducted in Japan. We examined mental health and health-related quality of life (QOL) among women at early stages of treatment. We recruited 513 women who have initiated ART treatment, either in-vitro fertilization or intracytoplasmic sperm injection, from four medical facilities in the Tokyo area and through web-based approaches. At baseline, we collected socio-demographic information and assessed depressive symptoms, anxiety, and QOL. Descriptive analyses were performed overall and stratified by factors such as age. Mild depressive symptoms or worse, assessed with Quick Inventory of Depressive Symptoms, were observed among 54% of participants. Mean score for State-Trait Anxiety Inventory was 52 with a standard deviation of 11 for the state, and 39% were categorized as high anxiety. QOL results, assessed with SF-12, showed the same negative tendency for social functioning and role (emotional), while general health and physical functioning were consistent with the national average. Young participants appeared to suffer mentally more than older participants (p < 0.01 for depressive symptoms). Our findings suggest that patients may be at high risk of depressive symptoms, high anxiety, and low QOL even from the early stages of ART treatment.
Hybrid neural network based on novel audio feature for vehicle type identification
Authors: Chen Haoze , Zhang Zhijie 
Published: April 2021

AbstractDue to the audio information of different types of vehicle models are distinct, the vehicle information can be identified by the audio signal of vehicle accurately. In real life, in order to determine the type of vehicle, we do not need to obtain the visual information of vehicles and just need to obtain the audio information. In this paper, we extract and stitching different features from different aspects: Mel frequency cepstrum coefficients in perceptual characteristics, pitch class profile in psychoacoustic characteristics and short-term energy in acoustic characteristics. In addition, we improve the neural networks classifier by fusing the LSTM unit into the convolutional neural networks. At last, we put the novel feature to the hybrid neural networks to recognize different vehicles. The results suggest the novel feature we proposed in this paper can increase the recognition rate by 7%; destroying the training data randomly by superimposing different kinds of noise can improve the anti-noise ability in our identification system; and LSTM has great advantages in modeling time series, adding LSTM to the networks can improve the recognition rate of 3.39%.
Sweet taste of heavy water
Authors: Ben Abu Natalie , Mason Philip E. , Klein Hadar , Dubovski Nitzan , Ben Shoshan-Galeczki Yaron , Malach Einav , Pražienková Veronika , Maletínská Lenka , Tempra Carmelo , Chamorro Victor Cruces , Cvačka Josef , Behrens Maik , Niv Masha Y. , Jungwirth Pavel 
Published: April 2021

AbstractHydrogen to deuterium isotopic substitution has only a minor effect on physical and chemical properties of water and, as such, is not supposed to influence its neutral taste. Here we conclusively demonstrate that humans are, nevertheless, able to distinguish D2O from H2O by taste. Indeed, highly purified heavy water has a distinctly sweeter taste than same-purity normal water and can add to perceived sweetness of sweeteners. In contrast, mice do not prefer D2O over H2O, indicating that they are not likely to perceive heavy water as sweet. HEK 293T cells transfected with the TAS1R2/TAS1R3 heterodimer and chimeric G-proteins are activated by D2O but not by H2O. Lactisole, which is a known sweetness inhibitor acting via the TAS1R3 monomer of the TAS1R2/TAS1R3, suppresses the sweetness of D2O in human sensory tests, as well as the calcium release elicited by D2O in sweet taste receptor-expressing cells. The present multifaceted experimental study, complemented by homology modelling and molecular dynamics simulations, resolves a long-standing controversy about the taste of heavy water, shows that its sweet taste is mediated by the human TAS1R2/TAS1R3 taste receptor, and opens way to future studies of the detailed mechanism of action.
How does the composition of a PAH influence its microsolvation? A rotational spectroscopy study of the phenanthrene–water and phenanthridine–water clusters
Authors: Loru Donatella , Steber Amanda L. , Pinacho Pablo , Gruet Sébastien , Temelso Berhane , Rijs Anouk M. , Pérez Cristóbal , Schnell Melanie 
Published: April 2021

The influence of a nitrogen atom in the backbone of a PAH was revealed by the hydrated clusters of phenanthrene and phenanthridine in a rotational spectroscopy study. Background image credit: NASA, ESA, and the Hubble Heritage Team (STScI/AURA) – ESA/Hubble Collaboration.
Urinary l-erythro-β-hydroxyasparagine—a novel serine racemase inhibitor and substrate of the Zn2+-dependent d-serine dehydratase
Authors: Ito Tomokazu , Tono Mayuka , Kitaura Yasuyuki , Hemmi Hisashi , Yoshimura Tohru 
Published: April 2021

Abstract
In the present study, we identified l-erythro-β-hydroxyasparagine (l-β-EHAsn) found abundantly in human urine, as a novel substrate of Zn2+-dependent d-serine dehydratase (DSD). l-β-EHAsn is an atypical amino acid present in large amounts in urine but rarely detected in serum or most organs/tissues examined. Quantitative analyses of urinary l-β-EHAsn in young healthy volunteers revealed significant correlation between urinary l-β-EHAsn concentration and creatinine level. Further, for in-depth analyses of l-β-EHAsn, we developed a simple three-step synthetic method using trans-epoxysuccinic acid as the starting substance. In addition, our research revealed a strong inhibitory effect of l-β-EHAsn on mammalian serine racemase, responsible for producing d-serine, a co-agonist of the N-methyl-d-aspartate (NMDA) receptor involved in glutamatergic neurotransmission.