bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinguishing Direct Human‐Driven Effects on the Global Terrestrial Water Cycle
Authors: Kåresdotter Elisie , Destouni Georgia , Ghajarnia Navid , Lammers Richard B. , Kalantari Zahra 
Published: August 2022

AbstractPopulation growth is increasing the pressure on water resource availability. For useful assessment and planning for societal water availability impacts, it is imperative to disentangle the direct influences of human activities in the landscape from external climate‐driven influences on water flows and their variation and change. In this study we used the water balance model, a gridded global hydrological model, to quantify and distinguish human‐driven change components, modified by interventions such as dams, reservoirs, and water withdrawals for irrigation, industry, and households, from climate‐driven change components on four key water balance variables in the terrestrial hydrological system (evapotranspiration, runoff, soil moisture, storage change). We also analyzed emergent effect patterns in and across different parts of the world, facilitating exploration of spatial variability and regional patterns on multiple spatial scales, from pixel to global, including previously uninvestigated parts of the world. Our results show that human activities drive changes in all hydrological variables, with different magnitudes and directions depending on geographical location. The differences between model scenarios with and without human activities were largest in regions with the highest population densities. In such regions, which also have relatively large numbers of dams for irrigation, water largely tends to be removed from storage and go to feed increased runoff and evapotranspiration fluxes. Our analysis considers a more complete set of hydrological variables than previous studies and can guide further research and management planning for future hydrological and water availability trends, including in relatively data‐poor parts of the world.
EdgePhase: A Deep Learning Model for Multi‐Station Seismic Phase Picking
Authors: Feng Tian , Mohanna Saeed , Meng Lingsen 
Published: August 2022

AbstractIn this study, we build a multi‐station phase‐picking model named EdgePhase by integrating an Edge Convolutional module with a state‐of‐the‐art single‐station phase‐picking model, EQTransformer. The Edge Convolutional module, a variant of Graph Neural Network, exchanges information relevant to seismic phases between neighboring stations. In EdgePhase, seismograms are first encoded into the latent representations, then converted into enhanced representations by the Edge Convolutional module, and finally decoded into the P‐ and S‐phase probabilities. Compared to the standard EQTransformer, EdgePhase increases the precision (fraction of phase identifications that are real) and recall (fraction of phase arrivals that are identified) rate by 5% on our training and test data sets of Southern California earthquakes. To evaluate its performance in regions of different tectonic settings, we applied EdgePhase to detect the early aftershocks following the 2020 M7.0 Samos, Greece earthquake. Compared to a local earthquake catalog, EdgePhase produced 190% additional detections with an event distribution more conformative to a planar fault interface, suggesting higher fidelity in event locations. This case study indicates that EdgePhase provides a strong regional generalization capability in real‐world applications.
Stirring and Mixing in the Wake of Velasco Reef, Palau
Authors: Johnston T. M. Shaun , Rudnick Daniel L. 
Published: August 2022

AbstractOver 2 years, underwater gliders measured currents, temperature, and salinity along lines 40 km up‐ and downstream of the abrupt topography of Palau to examine topographic effects on the incident flow. The mean flow is westward and is associated with the North Equatorial Current. Salinity on isopycnals is a passive tracer. During westward flow, this tracer variance is elevated downstream in the strongest flow north of the topography at scales of 36 km (evaluated from 12 to 60 km) consistent with a wake eddy at the scale of the topography. During eastward flow, variance is elevated downstream at all measured scales. This result suggests eddies are trapped at the topography because westward eddy propagation is opposed by the incident eastward flow. This time‐mean tracer and current structure up‐ and downstream are used to estimate terms in the advection‐diffusion equation. The mean isopycnal diffusivity is about 17 times greater than background values at 36‐km scales (and 40 times greater within 20 km of the topography), while the mean diapycnal diffusivity is 100 times greater than background values for this latitude. The contrast between up‐and downstream salinity on isopycnals can reach 0.2 psu over 5–10 km, which is seen in the glider measurements and one ship‐based survey. This contrast arises due to eddies detaching from the North Equatorial Countercurrent or its recirculations. These episodes are associated with westward‐propagating, intraseasonal Rossby waves.
A state-of-the-science review and guide for measuring environmental exposure biomarkers in dried blood spots
Authors: Jacobson Tyler A. , Kler Jasdeep S. , Bae Yeunook , Chen Jiexi , Ladror Daniel T. , Iyer Ramsunder , Nunes Denise A. , Montgomery Nathan D. , Pleil Joachim D. , Funk William E. 
Published: August 2022

Abstract
Background
Dried blood spot (DBS) sampling is a simple, cost-effective, and minimally invasive alternative to venipuncture for measuring exposure biomarkers in public health and epidemiological research. DBS sampling provides advantages in field-based studies conducted in low-resource settings and in studies involving infants and children. In addition, DBS samples are routinely collected from newborns after birth (i.e., newborn dried blood spots, NDBS), with many states in the United States permitting access to archived NDBS samples for research purposes.

Objectives
We review the state of the science for analyzing exposure biomarkers in DBS samples, both archived and newly collected, and provide guidance on sample collection, storage, and blood volume requirements associated with individual DBS assays. We discuss recent progress regarding analytical methods, analytical sensitivity, and specificity, sample volume requirements, contamination considerations, estimating extracted blood volumes, assessing stability and analyte recovery, and hematocrit effects.

Methods
A systematic search of PubMed (MEDLINE), Embase (Elsevier), and CINAHL (EBSCO) was conducted in March 2022. DBS method development and application studies were divided into three main chemical classes: environmental tobacco smoke, trace elements (including lead, mercury, cadmium, and arsenic), and industrial chemicals (including endocrine-disrupting chemicals and persistent organic pollutants). DBS method development and validation studies were scored on key quality-control and performance parameters by two members of the review team.

Results
Our search identified 47 published reports related to measuring environmental exposure biomarkers in human DBS samples. A total of 28 reports (37 total studies) were on methods development and validation and 19 reports were primarily the application of previously developed DBS assays. High-performing DBS methods have been developed, validated, and applied for detecting environmental exposures to tobacco smoke, trace elements, and several important endocrine-disrupting chemicals and persistent organic pollutants. Additional work is needed for measuring cadmium, arsenic, inorganic mercury, and bisphenol A in DBS and NDBS samples.

Significance
We present an inventory and critical review of available assays for measuring environmental exposure biomarkers in DBS and NDBS samples to help facilitate this sampling medium as an emerging tool for public health (e.g., screening programs, temporal biomonitoring) and environmental epidemiology (e.g., field-based studies).
Regulated cell death (RCD) in cancer: key pathways and targeted therapies
Authors: Peng Fu , Liao Minru , Qin Rui , Zhu Shiou , Peng Cheng , Fu Leilei , Chen Yi , Han Bo 
Published: August 2022

AbstractRegulated cell death (RCD), also well-known as programmed cell death (PCD), refers to the form of cell death that can be regulated by a variety of biomacromolecules, which is distinctive from accidental cell death (ACD). Accumulating evidence has revealed that RCD subroutines are the key features of tumorigenesis, which may ultimately lead to the establishment of different potential therapeutic strategies. Hitherto, targeting the subroutines of RCD with pharmacological small-molecule compounds has been emerging as a promising therapeutic avenue, which has rapidly progressed in many types of human cancers. Thus, in this review, we focus on summarizing not only the key apoptotic and autophagy-dependent cell death signaling pathways, but the crucial pathways of other RCD subroutines, including necroptosis, pyroptosis, ferroptosis, parthanatos, entosis, NETosis and lysosome-dependent cell death (LCD) in cancer. Moreover, we further discuss the current situation of several small-molecule compounds targeting the different RCD subroutines to improve cancer treatment, such as single-target, dual or multiple-target small-molecule compounds, drug combinations, and some new emerging therapeutic strategies that would together shed new light on future directions to attack cancer cell vulnerabilities with small-molecule drugs targeting RCD for therapeutic purposes.
The overlooked role of a biotin precursor for marine bacteria - desthiobiotin as an escape route for biotin auxotrophy
Authors: Wienhausen Gerrit , Bruns Stefan , Sultana Sabiha , Dlugosch Leon , Groon Luna-Agrippina , Wilkes Heinz , Simon Meinhard 
Published: August 2022

Abstract
Biotin (vitamin B7) is involved in a wide range of essential biochemical reactions and a crucial micronutrient that is vital for many pro- and eukaryotic organisms. The few biotin measurements in the world’s oceans show that availability is subject to strong fluctuations. Numerous marine microorganisms exhibit biotin auxotrophy and therefore rely on supply by other organisms. Desthiobiotin is the primary precursor of biotin and has recently been detected at concentrations similar to biotin in seawater. The last enzymatic reaction in the biotin biosynthetic pathway converts desthiobiotin to biotin via the biotin synthase (BioB). The role of desthiobiotin as a precursor of biotin synthesis in microbial systems, however, is largely unknown. Here we demonstrate experimentally that bacteria can overcome biotin auxotrophy if they retain the bioB gene and desthiobiotin is available. A genomic search of 1068 bacteria predicts that the biotin biosynthetic potential varies greatly among different phylogenetic groups and that 20% encode solely bioB and thus can potentially overcome biotin auxotrophy. Many Actino- and Alphaproteobacteria cannot synthesize biotin de novo, but some possess solely bioB, whereas the vast majority of Gammaproteobacteria and Flavobacteriia exhibit the last four crucial biotin synthesis genes. We detected high intra- and extracellular concentrations of the precursor relative to biotin in the prototrophic bacterium, Vibrio campbellii, with extracellular desthiobiotin reaching up to 1.09 ± 0.15*106 molecules per cell during exponential growth. Our results provide evidence for the ecological role of desthiobiotin as an escape route to overcome biotin auxotrophy for bacteria in the ocean and presumably in other ecosystems.
Development of an extensive workflow for comprehensive clinical pharmacogenomic profiling: lessons from a pilot study on 100 whole exome sequencing data
Authors: Tafazoli Alireza , van der Lee Maaike , Swen Jesse J. , Zeller Anna , Wawrusiewicz-Kurylonek Natalia , Mei Hailiang , Vorderman Ruben H. P. , Konopko Krzysztof , Zankiewicz Andrzej , Miltyk Wojciech 
Published: August 2022

AbstractThis pilot study is aimed at implementing an approach for comprehensive clinical pharmacogenomics (PGx) profiling. Fifty patients with cardiovascular diseases and 50 healthy individuals underwent whole-exome sequencing. Data on 1800 PGx genes were extracted and analyzed through deep filtration separately. Theoretical drug induced phenoconversion was assessed for the patients, using sequence2script. In total, 4539 rare variants (including 115 damaging non-synonymous) were identified. Four publicly available PGx bioinformatics algorithms to assign PGx haplotypes were applied to nine selected very important pharmacogenes (VIP) and revealed a 45–70% concordance rate. To ensure availability of the results at point-of-care, actionable variants were stored in a web-hosted database and PGx-cards were developed for quick access and handed to the study subjects. While a comprehensive clinical PGx profile could be successfully extracted from WES data, available tools to interpret these data demonstrated inconsistencies that complicate clinical application.
ACSL4-dependent ferroptosis does not represent a tumor-suppressive mechanism but ACSL4 rather promotes liver cancer progression
Authors: Grube Julia , Woitok Marius Maximilian , Mohs Antje , Erschfeld Stephanie , Lynen Celina , Trautwein Christian , Otto Tobias 
Published: August 2022

AbstractFerroptosis is a novel type of programmed cell death that differs from apoptosis in that it involves iron-dependent peroxidation of membrane phospholipids. Its role in a variety of human disorders, including cancer has been hypothesized in recent years. While it may function as an endogenous tumor suppressor in a variety of cancers, its role during initiation and progression of liver cancer, particularly hepatocellular carcinoma (HCC), is yet unknown. Because HCC is most commonly found in chronically injured livers, we utilized two well-established mouse models of chronic injury-dependent HCC formation: Treatment with streptozotocin and high-fat diet as metabolic injury model, as well as treatment with diethylnitrosamine and carbon tetrachloride as toxic injury model. We used mice with hepatocyte-specific deletion of Acsl4, a key mediator of ferroptosis, to explore the significance of ferroptotic cell death in hepatocytes, the cell type of origin for HCC. Surprisingly, preventing ferroptotic cell death in hepatocytes by deleting Acsl4 does not increase the formation of HCC. Furthermore, Acsl4-deficient livers display less fibrosis and proliferation, especially in the HCC model of toxic damage. Intriguingly, in this model, the absence of ACSL4-dependent processes such as ferroptosis significantly slow down the growth of HCC. These findings suggest that during HCC formation in a chronically injured liver, ferroptotic cell death is not an endogenous tumor-suppressive mechanism. Instead, we find that ACSL4-dependent processes have an unanticipated cancer-promoting effect during HCC formation, which is most likely due to aggravated liver damage as demonstrated by increased hepatic fibrosis. Previous studies suggested that ferroptosis might have beneficial effects for patients during HCC therapy. As a result, during HCC progression and therapy, ferroptosis may have both cancer-promoting and cancer-inhibitory effects, respectively.
lncRNA CYTOR promotes aberrant glycolysis and mitochondrial respiration via HNRNPC-mediated ZEB1 stabilization in oral squamous cell carcinoma
Authors: Zhu Weiwen , Wang Jie , Liu Xiang , Xu Yanbin , Zhai Rundong , Zhang Jiayi , Wang Mengqi , Wang Mengyao , Liu Laikui 
Published: August 2022

AbstractOral squamous cell carcinoma (OSCC), the most common malignancy of the oral and maxillofacial region, severely affects human health. However, current treatments for OSCC commonly show only a ~60% 5-year survival rate of patients with distant metastases, indicating an urgent need for targeted treatments for patients with advanced metastases. Here, we report a survival-related long non-coding RNA, CYTOR, which is highly expressed in the lesions of oral cancer patients. We found that CYTOR can promote both migration and invasion in oral cancer cells as well as the epithelial–mesenchymal transition (EMT). RNA-sequencing of CYTOR-knockdown oral cancer cells revealed that CYTOR can regulate mitochondrial respiration and RNA splicing. Mechanistically, we found that nuclear-localized CYTOR interacts with HNRNPC, resulting in stabilization of ZEB1 mRNAs by inhibiting the nondegradative ubiquitination of HNRNPC. By synthesizing CYTOR-targeting small interfering RNAs (siRNAs) encapsulated in Nanoscale Metal Organic Frameworks (NMOFs), we demonstrate the targeted suppression of CYTOR to inhibit invasion and metastasis of oral cancer cells in a nude mouse model. Cumulatively, this study reveals the potential role of the CYTOR-HNRNPC-ZEB1 axis in regulating mitochondrial metabolism and glycolysis of oral cancer cells, and illustrates the effective use of lncRNA targeting in anti-metastatic cancer therapies.
KCNK3 inhibits proliferation and glucose metabolism of lung adenocarcinoma via activation of AMPK-TXNIP pathway
Authors: Lin Guofu , Lin Lanlan , Lin Hai , Chen Wenhan , Chen Luyang , Chen Xiaohui , Chen Shaohua , Lin Qinhui , Xu Yuan , Zeng Yiming 
Published: August 2022

AbstractNon-small cell lung cancer (NSCLC) is a primary histological subtype of lung cancer with increased morbidity and mortality. K+ channels have been revealed to be involved in carcinogenesis in various malignant tumors. However, TWIK-related acid-sensitive potassium channel 1 (TASK-1, also called KCNK3), a genetic member of K2P channels, remains an enigma in lung adenocarcinoma (LUAD). Herein, we investigated the pathological process of KCNK3 in proliferation and glucose metabolism of LUAD. The expressions of KCNK3 in LUAD tissues and corresponding adjacent tissues were identified by RNA sequencing, quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry. Gain and loss-of-function assays were performed to estimate the role of KCNK3 in proliferation and glucose metabolism of LUAD. Additionally, energy metabolites of LUAD cells were identified by targeted metabolomics analysis. The expressions of metabolic molecules and active biomarkers associated with AMPK-TXNIP signaling pathway were detected via western blot and immunofluorescence. KCNK3 was significantly downregulated in LUAD tissues and correlated with patients’ poor prognosis. Overexpression of KCNK3 largely regulated the process of oncogenesis and glycometabolism in LUAD in vitro and in vivo. Mechanistic studies found that KCNK3-mediated differential metabolites were mainly enriched in AMPK signaling pathway. Furthermore, rescue experiments demonstrated that KCNK3 suppressed proliferation and glucose metabolism via activation of the AMPK-TXNIP pathway in LUAD cells. In summary, our research highlighted an emerging role of KCNK3 in the proliferative activity and glycometabolism of LUAD, suggesting that KCNK3 may be an optimal predictor for prognosis and a potential therapeutic target of LUAD.
LncRNA in tumorigenesis of non-small-cell lung cancer: From bench to bedside
Authors: Hu Qin , Ma Huiyun , Chen Hongyu , Zhang Zhouwei , Xue Qun 
Published: August 2022

AbstractLung cancer has been one of the leading causes of cancer-related death worldwide, and non-small-cell lung cancer (NSCLC) accounts for the majority of lung cancer morbidity, yet the pathogenesis of NSCLC has not been fully elucidated. Recently, long-chain non-coding RNA (lncRNA) has attracted widespread attention. LncRNA is a type of non-coding RNA whose transcript length exceeds 200 nucleotides. After constant research, academics updated their understanding of lncRNA, especially its role in the biological processes of cancer cells, including epigenetic regulation, cell proliferation, and cell differentiation. Notably, examination of lncRNAs could serve as potential hallmarks for clinicopathological features, long-term prognosis, and drug sensitivity. Therefore, it is necessary to explore the functions of lncRNA in NSCLC and innovate potential strategies against NSCLC based on lncRNA-related research. Herein, we reviewed the functions of lncRNA in the occurrence, diagnosis, treatment, and prognosis of NSCLC, which not only help promote a comprehensive view of lncRNA in NSCLC, but also shed light on the potential of lncRNA-based diagnosis and treatment of NSCLC.
Zero dispersion Kerr solitons in optical microresonators
Authors: Anderson Miles H. , Weng Wenle , Lihachev Grigory , Tikan Alexey , Liu Junqiu , Kippenberg Tobias J. 
Published: August 2022

AbstractSolitons are shape preserving waveforms that are ubiquitous across nonlinear dynamical systems from BEC to hydrodynamics, and fall into two separate classes: bright solitons existing in anomalous group velocity dispersion, and switching waves forming ‘dark solitons’ in normal dispersion. Bright solitons in particular have been relevant to chip-scale microresonator frequency combs, used in applications across communications, metrology, and spectroscopy. Both have been studied, yet the existence of a structure between this dichotomy has only been theoretically predicted. We report the observation of dissipative structures embodying a hybrid between switching waves and dissipative solitons, existing in the regime of vanishing group velocity dispersion where third-order dispersion is dominant, hence termed as ‘zero-dispersion solitons’. They are observed to arise from the interlocking of two modulated switching waves, forming a stable solitary structure consisting of a quantized number of peaks. The switching waves form directly via synchronous pulse-driving of a Si3N4microresonator. The resulting comb spectrum spans 136 THz or 97% of an octave, further enhanced by higher-order dispersive wave formation. This dissipative structure expands the domain of Kerr cavity physics to the regime near to zero-dispersion and could present a superior alternative to conventional solitons for broadband comb generation.
Individuals with ventromedial frontal damage display unstable but transitive preferences during decision making
Authors: Yu Linda Q. , Dana Jason , Kable Joseph W. 
Published: August 2022

AbstractThe ventromedial frontal lobe (VMF) is important for decision-making, but the precise causal role of the VMF in the decision process has not been fully established. Previous studies have suggested that individuals with VMF damage violate transitivity, a hallmark axiom of rational decisions. However, these prior studies cannot properly distinguish whether individuals with VMF damage are truly prone to choosing irrationally from whether their preferences are simply more variable. We had individuals with focal VMF damage, individuals with other frontal damage, and healthy controls make repeated choices across three categories—artworks, chocolate bar brands, and gambles. Using proper tests of transitivity, we find that, in our study, individuals with VMF damage make rational decisions consistent with transitive preferences, even though they exhibit greater variability in their preferences. That is, the VMF is necessary for having strong and reliable preferences, but not for being a rational decision maker. VMF damage affects the variability with which value is assessed, but not the consistency with which value is sought.