bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic heterogeneity: Challenges, impacts, and methods through an associative lens
Authors: Woodward Alexa A. , Urbanowicz Ryan J. , Naj Adam C. , Moore Jason H. 
Published: August 2022

AbstractGenetic heterogeneity describes the occurrence of the same or similar phenotypes through different genetic mechanisms in different individuals. Robustly characterizing and accounting for genetic heterogeneity is crucial to pursuing the goals of precision medicine, for discovering novel disease biomarkers, and for identifying targets for treatments. Failure to account for genetic heterogeneity may lead to missed associations and incorrect inferences. Thus, it is critical to review the impact of genetic heterogeneity on the design and analysis of population level genetic studies, aspects that are often overlooked in the literature. In this review, we first contextualize our approach to genetic heterogeneity by proposing a high‐level categorization of heterogeneity into “feature,” “outcome,” and “associative” heterogeneity, drawing on perspectives from epidemiology and machine learning to illustrate distinctions between them. We highlight the unique nature of genetic heterogeneity as a heterogeneous pattern of association that warrants specific methodological considerations. We then focus on the challenges that preclude effective detection and characterization of genetic heterogeneity across a variety of epidemiological contexts. Finally, we discuss systems heterogeneity as an integrated approach to using genetic and other high‐dimensional multi‐omic data in complex disease research.
Moronic acid improves intestinal inflammation in mice with chronic colitis by inhibiting intestinal macrophage polarization
Authors: Ruan Shuiliang , Zha Li 
Published: August 2022

AbstractThis study focuses on exploring the role and mechanism of moronic acid (MOA), a small triterpenoid molecule, against inflammatory bowel disease (IBD). Intestinal macrophages were cultured in vitro, and their M1 polarization was induced by lipopolysaccharide (LPS) and interferon gamma (IFN‐γ). After intervention with MOA, the proportion of M1 macrophages was detected, and the levels of inflammatory cytokines (TNF‐α, IL‐6, and IL‐1β) were examined by ELISA. IFA staining was performed to determine the P50 and CD86 expressions, while DCFH‐DA was used to determine the reactive oxygen species (ROS) level, as well as the p‐P50 and NLRP3 protein levels. Additionally, we also used N‐acetylcysteine, a ROS inhibitor, to further explore the association between MOA and ROS‐NF‐κB signaling. In murine experimentation, colitis was induced in mice with DSS. After MOA intervention, we assessed the mucosal barrier damage, tissue ROS, as well as protein and inflammatory cytokine levels. MOA could inhibit the M1 polarization of intestinal macrophages, suppress the expressions of inflammatory cytokines, and reduce the level of ROS‐NF‐κB‐NLRP3 signaling. After inhibiting ROS through NAC treatment, the effect of MOA was evidently weakened. Clearly, MOA exerted its activity via ROS. In the murine model, MOA could lower the CD86 level in the intestinal tissues, inhibit the M1 polarization of macrophages, and reduce the tissue levels of inflammatory cytokines. This study finds that MOA can regulate ROS‐NF‐κB‐NLRP3 signaling by inhibiting ROS, thereby suppressing the M1 polarization of intestinal macrophages, which plays a protective role in IBD.
Curcumin attenuates Cr (VI)‐induced cell growth and migration by targeting autophagy‐dependent reprogrammed metabolism
Authors: Dlamini Mongameli B. , Bao Shibo , Gao Zeyun , Mei Junjie , Ge Hong , Jiang Liping , Geng Chengyan , Li Qiujuan , Shi Xiaoxia , Liu Yong , Cao Jun 
Published: August 2022

AbstractHexavalent chromium [Cr (VI)] is a well‐established carcinogen. Cr (VI)‐treated cells are phenotypically characterized by aberrant levels of growth and migration. Curcumin, a polyphenolic compound from the plant turmeric, has been found to possess antiproliferation, anti‐inflammation, and antioxidant properties. In this study, the effect of curcumin on Cr (VI)‐induced cell survival and migration and the underlying mechanism were investigated. Cell viability assay on A549 and human embryonic lung fibroblast cells showed that curcumin at the concentration of 10 µM could significantly attenuate Cr (VI)‐induced viability in both cell lines. Following Western blot assay and metabolomics assays, cotreatment with curcumin and Cr (VI) resulted in the suppression of Cr (VI)‐induced glycolysis‐, autophagy‐, and migration‐related proteins. Meanwhile, curcumin increased Cr (VI)‐reduced oxidative phosphorylation (OXPHOS)‐related proteins, COXIV and ND1. Moreover, curcumin suppressed Cr (VI)‐induced mitochondrial dysfunction, mitochondrial mass decrease, and mitochondrial membrane potential loss. Treatment with curcumin for 24 h significantly attenuated pcATG4B‐induced autophagy and the subsequent expression of glucose transporter 1, hexokinase II, and pyruvate kinase M2. Wound healing and transwell assay demonstrated that curcumin reduced Cr (VI)‐induced cell migration. Taken together, these results showed that curcumin was able to attenuate Cr (VI)‐induced cell viability and migration by targeting autophagy‐dependent reprogrammed metabolism from OXPHOS to glycolysis.
RBM3 is an outstanding cold shock protein with multiple physiological functions beyond hypothermia
Authors: Hu Yajie , Liu Yang , Quan Xin , Fan Wenxuan , Xu Bin , Li Shize 
Published: August 2022

AbstractRNA‐binding motif protein 3 (RBM3), an outstanding cold shock protein, is rapidly upregulated to ensure homeostasis and survival in a cold environment, which is an important physiological mechanism in response to cold stress. Meanwhile, RBM3 has multiple physiological functions and participates in the regulation of various cellular physiological processes, such as antiapoptosis, circadian rhythm, cell cycle, reproduction, and tumogenesis. The structure, conservation, and tissue distribution of RBM3 in human are demonstrated in this review. Herein, the multiple physiological functions of RBM3 were summarized based on recent research advances. Meanwhile, the cytoprotective mechanism of RBM3 during stress under various adverse conditions and its regulation of transcription were discussed. In addition, the neuroprotection of RBM3 and its oncogenic role and controversy in various cancers were investigated in our review.
Model‐Informed Rationale for Early Therapeutic Drug Monitoring of Colistin in Critically Ill Patients
Authors: Mathew Sumith K. , Rao Shoma V. , Prabha Ratna , Neely Michael N. , Mathew Binu Susan , Aruldhas Blessed Winston , Veeraraghavan Balaji , Kandasamy Subramani 
Published: August 2022

AbstractAdequate colistin exposure is important for microbiological clearance. This study was performed in critically ill patients >18 years old to develop a simplified nonparametric pharmacokinetic (PK) model of colistin for routine clinical use and to determine the role of dose optimization. The Non‐Parametric Adaptive Grid algorithm within the Pmetrics software package for R was used to develop a PK model from 47 patients, and external validation of the final model was performed in 13 patients. A 1‐compartment multiplicative gamma error model with 0‐order input and first‐order elimination of colistin was developed with creatinine clearance and serum albumin as covariates on elimination rate constant. An R2 for observed vs individual predicted colistin concentrations of 0.92 was obtained in the validation cohort. High interindividual variability in colistin steady‐state area under the plasma concentration–time curve (AUC) from from 120 hours to 144 hours (coefficient of variation = 80.1%) and a high interoccasion variability (median coefficient of variation of AUC from time 0 to hours predicted every 8 hours for initial 96 hours after starting colistin = 23.8) was predicted in patients who received this antibiotic for a period of over 152 hours (n = 22). With the model‐suggested dose regimen, only 20% of simulated profiles achieved AUC from time 0 to 24 hours in the range of 50 to 60 mg • h/L due to high variability in population PK. In this group of patients, steady‐state colistin concentrations were predicted to be achieved >96 hours after initiation of colistimethate sodium. This study advocates the need for early and repeated therapeutic drug monitoring and dose optimization in critically ill patients to achieve adequate therapeutic concentration of colistin.
Projected dry/wet regimes in China using SPEI under four SSP‐RCPs based on statistically downscaled CMIP6 data
Authors: Chen Xinguo , Li Yi , Yao Ning , Liu De Li , Liu Qingzhu , Song Xiaoyan , Liu Fenggui , Pulatov Bakhtiyor , Meng Qingtao , Feng Puyu 
Published: August 2022

AbstractDry/wet conditions are one of the key constituents of climate change. The understanding of dry/wet variability is vital for production and water resources management. In this research, the temporal variations of 12‐month timescale standardized precipitation evapotranspiration (SPEI) over 2021–2100 under the SSP1‐2.6, SSP2‐4.5, SSP3‐7.0 and SSP5‐8.5 scenarios in seven subregions and China's mainland were investigated over the baseline period of 1961–2000. The run theory was used to project the variations of dry/wet frequency, duration and severity at different levels during 1961–2000, 2021–2060 and 2061–2100 based on the estimated SPEI. The results showed that dry tendency would occur in northwest China. The linear trend for SSP1‐2.6, SSP2‐4.5, SSP3‐7.0 and SSP5‐8.5 were −0.056, −0.031, 0.009 and −0.072 per decade, respectively. While wet tendency would occur in the other regions over 2021–2100. The mild, moderate and severe dry/wet duration and severity over 2021–2060 and 2061–2100 would gradually decrease. Except for northwest China and Qinghai‐Tibetan Plateau, the extreme drought duration and severity would increase in the other subregions, while the extreme wet duration and severity would increase in most regions of China. The drought frequency in north China would range from 0 to 14 times and be smaller than the other regions over 2021–2060 and 2060–2100. However, the wet frequency in south China would be larger than that in the other regions. The dry/wet frequency duration and severity for the SSP5‐8.5 scenario would be the largest among the four scenarios. The projected dry/wet conditions can provide useful information for future water resources management.
Rapid glacier recession at Monte San Lorenzo (Patagonia) in response to abrupt Southern Hemisphere warming 13.0–12.0 ka BP
Authors: Martin Julian R. V. , Thorndycraft Varyl R. , Davies Bethan J. , Rodés Ángel 
Published: August 2022

AbstractMid‐latitude Patagonian glaciers are sensitive to changes in the complex coupled ocean–atmospheric climate system of the Southern Hemisphere. Here, we investigate glacier response to a period of rapid climate warming immediately post‐dating the Antarctic Cold Reversal (ACR). We analyse a sequence of 13 ice margins, four of them dated, from an outlet valley of the Monte San Lorenzo ice cap (47.3°S). We constrain glacier recession of 31.7 km over a period of ~1 kyr from 13.2  ±  0.4 to 12.1  ±  0.4 ka. The average rate of recession was 35.2 m a−1 over this 1‐kyr period, increasing from 12.75 m a−1 at the start of the record (moraines M1 to M4) to 50 m a−1 from M9 to M12. This recession occurred during a period of rapid warming when the austral westerlies shifted polewards. It is likely that ice extent stabilized during the Holocene, with ice occupying the M13 moraine during repeated Holocene neoglacials, before anthropogenic warming caused recession at a rate of 55.5 m a−1 from 1985 to 2016. We conclude that 20th century rates of recession were higher than those during post‐ACR warming, though of a similar order of magnitude.
The efficacy of the American College of Surgeons Surgical Risk Calculator in the prediction of postoperative complications in oncogeriatric patients after curative surgery for abdominal tumors
Authors: El Asmar Antoine , Hafez Karim , Fauconnier Pauline , Moreau Michel , Dal Lago Lissandra , Pepersack Thierry , Donckier Vincent , Liberale Gabriel 
Published: August 2022

AbstractBackgroundThe American College of Surgeons (ACS) has developed a Surgical Risk Calculator (SRC) to predict postoperative surgical complications. No studies have reported the performance of the ACS‐SRC in oncogeriatric patients. Our objective was to evaluate the predictive performance of the ACS‐SRC in these patients, treated with curative surgery for an abdominal malignancy.MethodsThis is a retrospective study including 136 patients who underwent elective abdominal oncological surgery, between 2017 and 2019, at our institution. Postoperative complications were classified according to the ACS‐SRC, and its predictive performance was analyzed by assessing discrimination and calibration and using receiver operating characteristics and area under the curve (AUC).ResultsDiscrimination was adequate with AUC of 0.7113 (95% confidence interval [CI]: 1.062–1.202, p = 0.0001; Brier 0.198) for serious complications and 0.7230 (95% CI: 1.101–1.756, p = 0.0057; Brier 0.099) for pneumonia; and poor for sepsis, surgical site infection (SSI), and urinary tract infection (UTI) with AUCs of 0.6636 (95% CI: 1.016–1.353, p = 0.0299; Brier 0.142), 0.6167 (95% CI: 1.003–1.266, p = 0.0450; Brier 0.175), and 0.6598 (95% CI: 1.069–2.145, p = 0.0195; Brier 0.082), respectively.ConclusionThe ACS‐SRC is an adequate predictor for serious complications and pneumonia in oncogeriatric patients treated surgically for abdominal cancer. However, the predictive power of the calculator appears to be low for sepsis, UTI, and SSI.
Transoral Laser Microsurgery in Recurrent Laryngeal Cancer: A Systematic Review and Meta‐analysis
Authors: Russo Elena , Costantino Andrea , Veneroni Maria Vittoria , Festa Bianca Maria , Pellini Raul , Campo Flaminia , Petruzzi Gerardo , Spriano Giuseppe , Mercante Giuseppe , De Virgilio Armando 
Published: August 2022

ObjectiveTo determine the oncological outcomes of salvage transoral laser microsurgery (TLM) in the treatment of patients suffering from recurrent laryngeal cancer.MethodsPubMed/MEDLINE, Cochrane Library, and Scopus databases were searched. English language, original studies investigating oncological outcomes of TLM in adult patients with recurrent laryngeal cancer were included. Data were pooled using a distribution‐free approach for estimating summary local control (LC), disease‐specific survival (DSS), and overall survival (OS) curves with random effects.ResultsTwo hundred and thirty‐five patients underwent salvage TLM after primary (chemo)radiotherapy. The mean follow‐up time was 60.8 months (95% CI: 32.7–88.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 74.2% (61.7–89.4), 53.9% (38.5–75.3), and 39.1% (25.2–60.8). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 88.4% (82.0–95.3), 67.8% (50.9–90.3), and 58.9% (42.7–81.1). Two hundred and seventy‐one patients underwent TLM after primary laser treatment. The mean follow‐up time was 70.9 months (95% CI: 36.9–104.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 72.2% (64.7–80.6), 53.2% (42.2–66.9), and 40.4% (29.6–55.2). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 92.1% (85.5–99.1), 77.0% (64.4–92.0), and 67.1% (51.6–87.3).ConclusionsTLM is a valuable treatment option for the management of locally recurrent laryngeal carcinoma if performed by experienced surgeons and following rigorous patients' selection criteria. Further studies should be conducted to define stage‐based clinical guidelines.Level of EvidenceNA Laryngoscope, 133:1425–1433, 2023
Cathodic disbonding tests operating at large cathodic potentials for long periods need current monitoring, pH control and anode isolation
Authors: Benedetti Alessandro , Castelli Filippo , Stifanese Roberto , Traverso Pierluigi , Faimali Marco , Bergo Andrea , Delucchi Marina 
Published: August 2022

AbstractMetallic structures in service in seawater are protected by coupling cathodic protection and paints, where the former may induce disbondment of the latter. A preliminary evaluation of the cathodic disbondment risk can be made by cathodic disbondment tests (CDTs). Many CDTs use cathodic potentials as large asE < −1400 mV versus saturated calomel electrode (SCE) applied up to 90 days. Only two CDT protocols require contemporary anode isolation, current and pH monitoring, without its correction. These three aspects were considered to develop a hybrid CDT; it consisted of polarizing steel panels at −1500 mV versus SCE for 12 weeks. The chemical effects related to the anodic processes were investigated. A pH acidic shift was observed and was justified by the increasing current demand due to paint damage and brucite precipitation on the panels. The necessity of anode isolating glass to prevent chlorine chemical attack against the paints, potentially affecting the disbondment result, was verified by estimating the virtual chemical attack induced by free chlorine. In conclusion, current monitoring, pH control and anode isolation are highly suggested to correctly conduct and interpret the cathodic disbondment results when CDTs requiring large electronegative potentials are applied for long periods.
Cyanate Ester Resin with High Heat‐Resistance and Degradable Diacetal Structure: Synthesis, Polymerization, and Properties
Authors: Liu Linze , Xia Yiqinq , Wang Lian , Shi Rui , Yan Shuai , Zhao Xingyu , Jin Yongzhong , Sheng Yuping 
Published: August 2022

AbstractCyanate resins are high‐performance thermosetting resins with excellent mechanical, thermal, and dielectric properties. In this work, a novel cyanate ester monomer, 3,9‐bis‐(4‐cyanato‐phenyl)‐2,4,8,10‐tetraoxa‐spiro[5.5]undecane structure (DBCE), is prepared based on a diphenol (DB) with a degradable diacetal structure. The characterization of the chemical structures and polymerization behaviors of the samples are achieved by nuclear magnetic resonance spectroscopy, fourier transform infrared spectroscopy, and differential scanning calorimetry. The obtained results confirm the successful syntheses of DB and DBCE, and the polymerization temperature of DBCE is between 160 °C to 250 °C, which is lower than that of a comparative commercial cyanate ester resin (BADCy). The thermal and dielectric properties of the curedresin (Poly‐DBCE) are explored by dynamic mechanical analysis, thermogravimetric analysis, and an Agilent impedance analyzer. The results reveal that Poly‐DBCE manifest promising heat resistance (Tg = 294 °C) and thermal stability (Td,5 = 347 °C and char yield at 800 °C = 37.6%). The dielectric constant and dielectric loss of the Poly‐DBCE at 10 MHz are 3.11 and 0.0095, respectively. Additionally, the Poly‐DBCE is completely degraded under mildly acidic conditions, and efficient recoveries of carbon fiber and glass fiber with high values are reported from their corresponding fiber‐reinforced composites.
E2F7 enhances hepatocellular carcinoma growth by preserving the SP1/SOX4/Anillin axis via repressing miRNA‐383‐5p transcription
Authors: Hao Fengjie , Wang Nan , Zhang Yifan , Xu Wen , Chen Yongjun , Fei Xiaochun , Wang Junqing 
Published: August 2022

AbstractE2F family participates in most human malignancies by activating the transcription of the cell cycle‐related genes. Whereas, as a specifical atypical member of this family, E2F7 was described as a repressor against its downstream genes and exerted oscillatory and controversial functions in cancers. Our previous study identified a molecular interaction promoting hepatocellular carcinoma (HCC) growth induced by SOX4 and Anillin. Meanwhile, we preliminarily identified SP1 as the upstream activator of SOX4. Intriguingly, we observed that the repressive E2F7 presents a remarkable high expression in HCC, and is positively correlated and involved in the same pathway with the potentially SP1/SOX4/Anillin axis. However, their exact interaction or mechanism controlling tumor progress between these genes has not been illustrated. Thus, we focused on this point in this study and attempted to improve the potential regulating axis in HCC cell proliferation and tumor growth for promoting tumor prevention and control. The expression profile of E2F7 in HCC tissues and tumor cells was detected along with the related candidate genes, through real‐time quantitative polymerase chain reaction assay, the Western blot analysis, and the immunohistochemistry assay, combined with bioinformatics analysis of the HCC information from the the Cancer Genome Altas and Gene Expression Omnibus data sets. The correlation between E2F7 and HCC patients' clinicopathologic features was explored. Gain‐of and loss‐of‐function assays were conducted both in vitro and in vivo along with the rescue experiment, for revealing the relative genes' functions in HCC progress. The ChIP and the dual‐luciferase reporter assays were performed to verify the transcriptional regulating profile between E2F7 and SP1/SOX4/Anillin axis. E2F7 was upregulated in HCC and significantly correlated with SP1/SOX4/Anillin axis. High E2F7 expression is associated with dismal clinicopathologic features and poor survival of the patients. E2F7 depletion potently impaired SP1/SOX4/Anillin expression and significantly inhibited HCC growth. Furthermore, intensive exploration demonstrated that E2F7 preserves high SP1 levels by abrogating miR‐383‐5p in a transcriptional way. Atypical E2F7 is an important repressive transcription factor commonly upregulated in the HCC environment. E2F7 facilitates HCC growth by repressing miR‐383‐5p transcription and sequentially promoting SP1/SOX4/Anillin axis. Our findings provide us with probable targets for HCC prevention and therapeutic treatment.
Spatial and Temporal Characteristics of California Commercial Fisheries from 2005 to 2019 and Potential Overlap with Offshore Wind Energy Development
Authors: Wang Yi-Hui , Walter Ryan K. , White Crow , Ruttenberg Benjamin I. 
Published: August 2022

Abstract
As climate change accelerates and fisheries management continues to evolve, California's commercial fisheries are changing. To improve the understanding of recent California fisheries dynamics, we compiled and analyzed commercial landings receipts to characterize temporal and spatial variation in landing and value of key fisheries groups within the exclusive economic zone across the state from 2005 to 2019. We found that California fisheries continue a shift first observed in the 1980s from higher-biomass, lower-value species, such as coastal pelagic species and market squid, toward lower-biomass, higher-value species, such as Dungeness crab Cancer magister and groundfish. Over the 15-year time series analyzed, total landings declined by nearly two-thirds but total value remained relatively stable, likely due to a focus on higher value species and rising prices. The northern half of the state has become much more economically valuable, accounting for over 50% of total value across the state in 2019. A case study analysis found groundfish to be the dominant fisheries in the two areas that have been identified as priorities for potential offshore wind development in central and northern California. Our results elucidate the most recent status and trends of California's commercial fisheries, over time, across space, and among different fisheries groups, providing valuable information for informing fisheries management and marine spatial planning.