bluuebunny/crossref_metadata_2025_split huggingface dataset:
O‐GlcNAcylation promotes the migratory ability of hepatocellular carcinoma cells via regulating FOXA2 stability and transcriptional activity
Authors: Huang Huang , Wu Qiong , Guo Xinyi , Huang Tianmiao , Xie Xueqin , Wang Lingyan , Liu Yangzhi , Shi Lin , Li Wenli , Zhang Jianing , Liu Yubo 
Published: April 2021

AbstractO‐GlcNAcylation is a posttranslational modification that regulates numerous nuclear and cytoplasmic proteins and is emerging as a key regulator of various biological processes, such as transcription, signal transduction, and cell motility. Although increasing evidence has shown that elevated levels of global O‐GlcNAcylation are linked to the metastasis in hepatocellular carcinoma (HCC) cells, the underlying mechanism is still ambiguous. In this study, we demonstrated that forkhead box protein A2 (FOXA2), an essential transcription factor for liver homeostasis and HCC developing, was O‐GlcNAcylated by O‐GlcNAc transferase (OGT) and regulates HCC cells migration and invasion. Opposite FOXA2 and OGT expression tendency were observed in HCC tissues, and lower FOXA2 levels predicted a poor prognosis in HCC patients. The reduction of FOXA2 in HCC cells was found to be inversely correlated with the cellular O‐GlcNAcylation and cell migratory ability. Notably, we found that FOXA2 was modified by O‐GlcNAcylation and that O‐GlcNAcylation activated the ubiquitination degradation of FOXA2 in highly metastatic HCC cells. Although this modification did not affect FOXA2 nuclear localization capability, O‐GlcNAcylation on FOXA2 was key for attenuating FOXA2‐mediated transcription. O‐GlcNAcylation decreased the transcription of FOXA2 downstream target gene E‐cadherin and it ultimately promoted O‐GlcNAcylation‐mediated HCC cell migration and invasion. The results provide insights into the role of O‐GlcNAcylation in regulating FOXA2 activity and suggest its important implications in HCC metastasis.
Roles and mechanisms of YAP/TAZ in orthodontic tooth movement
Authors: Deng Lanzhi , Chen Yilin , Guo Jiusi , Han Xianglong , Guo Yongwen 
Published: April 2021

AbstractYes‐associated protein (YAP) and transcriptional coactivator with PDZ‐binding motif (TAZ) are transcriptional coactivators encoded by paratactic homologous genes, shuttle‐crossing between cytoplasm and nucleus to regulate the gene expression and cell behavior and standing at the center place of the sophisticated regulatory networking of mechanotransduction. Orthodontic tooth movement (OTM) is a process in which extracellular mechanical stimuli are transformed into intracellular biochemical signals to regulate cellular responses and tissue remodeling. Literature studies have confirmed that YAP/TAZ plays an important role not only in embryonic development, homeostasis and tumorigenesis, but also in mechanical‐biochemical signal transduction of periodontal tissues under the mediation of various signal molecules in its upstream and downstream. Herein, we review the advances in the roles and mechanisms of YAP/TAZ in OTM to provide insights for better understanding and further study of the OTM and possible targeted clinical intervention in orthodontic treatment.
Transcriptional regulation of the basic helix‐loop‐helix factor AmeloD during tooth development
Authors: Al Thamin Shahad , Chiba Yuta , Yoshizaki Keigo , Tian Tian , Jia LingLing , Wang Xin , Saito Kan , Li Jiyao , Yamada Aya , Fukumoto Satoshi 
Published: April 2021

AbstractThe epithelial‐mesenchymal interactions are essential for the initiation and regulation of the development of teeth. Following the initiation of tooth development, numerous growth factors are secreted by the dental epithelium and mesenchyme that play critical roles in cellular differentiation. During tooth morphogenesis, the dental epithelial stem cells differentiate into several cell types, including inner enamel epithelial cells, which then differentiate into enamel matrix‐secreting ameloblasts. Recently, we reported that the novel basic‐helix‐loop‐helix transcription factor, AmeloD, is actively engaged in the development of teeth as a regulator of dental epithelial cell motility. However, the gene regulation mechanism of AmeloD is still unknown. In this study, we aimed to uncover the mechanisms regulating AmeloD expression during tooth development. By screening growth factors that are important in the early stages of tooth formation, we found that TGF‐β1 induced AmeloD expression and ameloblast differentiation in the dental epithelial cell line, SF2. TGF‐β1 phosphorylated ERK1/2 and Smad2/3 to induce AmeloD expression, whereas treatment with the MEK inhibitor, U0126, inhibited AmeloD induction. Promoter analysis of AmeloD revealed that the proximal promoter of AmeloD showed high activity in dental epithelial cell lines, which was enhanced following TGF‐β1 stimulation. These results suggested that TGF‐β1 activates AmeloD transcription via ERK1/2 phosphorylation. Our findings provide new insights into the mechanisms that govern tooth development.
Ultrastructure of antennal sensilla of Copidosomopsis nacoleiae (Eady) (Hymenoptera: Chalcidoidea: Encyrtidae), a parasitoid of Diaphania angustalis (Snellen) (Lepidoptera: Crambidae)
Authors: Zhang Yu‐Jing , Chen Dong‐Yu , Chao Xue‐Ting , Dong Zi‐Shu , Huang Zong‐You , Zheng Xia‐Lin , Lu Wen 
Published: April 2021

AbstractThe antennal sensilla of Copidosomopsis nacoleiae (Eady) (Hymenoptera: Chalcidoidea: Encyrtidae) were observed under scanning and transmission electron microscopy in this study. The antennae of C. nacoleiae are geniculate, and the flagellum is composed of five subsegments in males and six in females. Six types of sensilla were observed, including sensilla trichodea, sensilla chaetica, sensilla basiconic capitate pegs, sensilla placodea, sensilla basiconica, and Böhm's bristles. Sensilla trichodea were evenly distributed throughout the antennae. Sensilla chaetica, sensilla basiconic capitate pegs and sensilla placodea were found on the flagellomeres. Sensilla basiconica were only found on the club, and Böhm's bristles were found on the radicle and the pedicel. Sensilla trichodea, sensilla placodea, sensilla chaetica, and sensilla basiconic capitate pegs were found to be the most common sensilla of the parasitoids in the superfamily Chalcidoidea. The external and internal characteristics, types, number, distribution, and dimensions of these sensilla are described, and their possible functions are discussed in accordance with host‐detection behavior. Future studies on the host location mechanisms of C. nacoleiae will be based upon these observations.
Examining sources and pathways of phosphorus transfer in a ditch‐drained field
Authors: Mosesso Lauren R. , Buda Anthony , Collick Amy , Kennedy Casey , Folmar Gordon , Shober Amy 
Published: April 2021

AbstractUnderstanding the processes that mobilize and transport dissolved phosphorus (P) during storms is critical to managing P in flat landscapes with open ditch drainage and legacy soil P. In this study, we used routine baseflow monitoring and intensive storm sampling at a ditch‐drained site on Maryland's Lower Eastern Shore (July 2017–September 2018) to assess whether concentration–discharge (C‐Q) relationships and chemical and isotopic hydrograph separation could provide insight into the processes that mobilize and transport dissolved P in ditch drainage. Using a segmented regression model, we determined that long‐term C‐Q relationships for dissolved P differed above and below a discharge threshold of 6.4 L s–1. Intensive storm sampling revealed that small storms (n = 3) occurring at or below the discharge threshold generally exhibited complex hysteresis and dissolved P dilution patterns that were consistent with deeper (>122 cm) groundwater inputs with low dissolved P concentrations (0.04 mg L–1). In contrast, large storms occurring well above the discharge threshold (n = 4) induced rising water tables and preferential flow pathways that most likely tapped dissolved P–enriched shallow (<20 cm) soil waters (0.89 mg L–1), producing consistent clockwise hysteresis and dissolved P flushing patterns. Notably, chemical and isotope hydrograph separation during two of the largest storms revealed significant event water fractions (59–68%) that strongly suggested a role for the rapid delivery of dissolved P via preferential flow pathways. Findings highlight the need to mitigate vertical P stratification as a means for reducing dissolved P flushing from ditch‐drained landscapes with legacy P.
Permanent endoscopic gallbladder stenting versus removal of gallbladder drainage, long‐term outcomes after management of acute cholecystitis in high‐risk surgical patients for cholecystectomy: Multi‐center retrospective cohort study
Authors: Maruta Akinori , Iwashita Takuji , Iwata Keisuke , Yoshida Kensaku , Uemura Shinya , Mukai Tsuyoshi , Yasuda Ichiro , Shimizu Masahito 
Published: April 2021

AbstractBackgroundEndoscopic transpapillary gallbladder drainage (EGBD) has been reported as an effective gallbladder drainage treatment option for acute cholecystitis in high‐risk surgical patients. However, the long‐term outcomes such as cholecystitis' recurrence rate after placement of EGB stenting (EGBS) have not been well studied yet.AimsThe aim of the present study was to compare the long‐term outcome of EGBS and removal of gallbladder drainage after percutaneous transhepatic gallbladder drainage (PTGBD) or endoscopic nasogallbladder drainage (ENGBD) for acute cholecystitis in high‐risk surgical patients and clarify the usefulness of long‐term placement of EGBS.MethodsWe retrospectively studied 180 high‐risk surgical patients with acute cholecystitis between January 2010 and December 2018. The patients were divided into two groups: EGBS group (long‐term placement of EGBS) or Removal group (removal of drainage tube after PTGBD or ENGBD). Clinical outcomes, including long‐term results, were compared between the groups.ResultsThe cumulative late adverse event (AE) rates were 5.0% and 22.1% in the EGBS and Removal group (P = .002), with a median follow‐up period of 375 and 307 days in the two groups, respectively. The cumulative cholecystitis recurrence rate was 5.0% (2/40) in the EGBS group and 16% (21/131) in the Removal group (P = .024), respectively. In the multivariate analysis for late AE, only EGBS was an independent risk factor with a decreasing value.ConclusionThe permanent EGBS in high‐risk surgical patients with acute cholecystitis was considered effective in reducing the risk of late AE.
Targeted urine metabolomics with a graphical reporting tool for rapid diagnosis of inborn errors of metabolism
Authors: Steinbusch Laura K.M. , Wang Ping , Waterval Huub W.A.H. , Stassen Fons A.P.M. , Coene Karlien L.M. , Engelke Udo F.H. , Habets Daphna D.J. , Bierau Jörgen , Körver‐Keularts Irene M.L.W. 
Published: April 2021

AbstractThe current diagnostic work‐up of inborn errors of metabolism (IEM) is rapidly moving toward integrative analytical approaches. We aimed to develop an innovative, targeted urine metabolomics (TUM) screening procedure to accelerate the diagnosis of patients with IEM. Urinary samples, spiked with three stable isotope‐labeled internal standards, were analyzed for 258 diagnostic metabolites with an ultra‐high performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UHPLC‐QTOF‐MS) configuration run in positive and negative ESI modes. The software automatically annotated peaks, corrected for peak overloading, and reported peak quality and shifting. Robustness and reproducibility were satisfactory for most metabolites. Z‐scores were calculated against four age‐group‐matched control cohorts. Disease phenotypes were scored based on database metabolite matching. Graphical reports comprised a needle plot, annotating abnormal metabolites, and a heatmap showing the prioritized disease phenotypes. In the clinical validation, we analyzed samples of 289 patients covering 78 OMIM phenotypes from 12 of the 15 society for the study of inborn errors of metabolism (SSIEM) disease groups. The disease groups include disorders in the metabolism of amino acids, fatty acids, ketones, purines and pyrimidines, carbohydrates, porphyrias, neurotransmitters, vitamins, cofactors, and creatine. The reporting tool easily and correctly diagnosed most samples. Even subtle aberrant metabolite patterns as seen in mild multiple acyl‐CoA dehydrogenase deficiency (GAII) and maple syrup urine disease (MSUD) were correctly called without difficulty. Others, like creatine transporter deficiency, are illustrative of IEM that remain difficult to diagnose. We present TUM as a powerful diagnostic screening tool that merges most urinary diagnostic assays expediting the diagnostics for patients suspected of an IEM.
A generic emergency protocol for patients with inborn errors of metabolism causing fasting intolerance: A retrospective, single‐center study and the generation of www.emergencyprotocol.net
Authors: Rossi Alessandro , Hoogeveen Irene J. , Lubout Charlotte M. A. , de Boer Foekje , Fokkert‐Wilts Marieke J. , Rodenburg Iris L. , van Dam Esther , Grünert Sarah C. , Martinelli Diego , Scarpa Maurizio ,   CONNECT MetabERN Collaboration Group, Dekker Hanka , te Boekhorst Sebastiaan T. , van Spronsen Francjan J. , Derks Terry G. J. 
Published: April 2021

AbstractPatients with inborn errors of metabolism causing fasting intolerance can experience acute metabolic decompensations. Long‐term data on outcomes using emergency letters are lacking. This is a retrospective, observational, single‐center study of the use of emergency letters based on a generic emergency protocol in patients with hepatic glycogen storage diseases (GSD) or fatty acid oxidation disorders (FAOD). Data on hospital admissions, initial laboratory results, and serious adverse events were collected. Subsequently, the website www.emergencyprotocol.net was generated in the context of the CONNECT MetabERN eHealth project following multiple meetings, protocol revisions, and translations. Representing 470 emergency protocol years, 127 hospital admissions were documented in 54/128 (42%) patients who made use of emergency letters generated based on the generic emergency protocol. Hypoglycemia (here defined as glucose concentration < 3.9 mmol/L) was reported in only 15% of hospital admissions and was uncommon in patients with ketotic GSD and patients with FAOD aged >5 years. Convulsions, coma, or death was not documented. By providing basic information, emergency letters for individual patients with hepatic GSD or the main FAOD can be generated at www.emergencyprotocol.net, in nine different languages. Generic emergency protocols are safe and easy for home management by the caregivers and the first hour in‐hospital management to prevent metabolic emergencies in patients with hepatic GSD and medium‐chain Acyl CoA dehydrogenase deficiency. The website www.emergencyprotocol.net is designed to support families and healthcare providers to generate personalized emergency letters for patients with hepatic GSD and the main FAOD.
Chemogenetic manipulation of astrocytic signaling in the basolateral amygdala reduces binge‐like alcohol consumption in male mice
Authors: Nwachukwu Kala N. , Evans William A. , Sides Tori R. , Trevisani Christopher P. , Davis Ambryia , Marshall S. Alex 
Published: April 2021

AbstractBinge drinking is a common occurrence in the United States, but a high concentration of alcohol in the blood has been shown to have reinforcing and reciprocal effects on the neuroimmune system in both dependent and non‐dependent scenarios. The first part of this study examined alcohol's effects on the astrocytic response in the central amygdala and basolateral amygdala (BLA) in a non‐dependent model. C57BL/6J mice were given access to either ethanol, water, or sucrose during a “drinking in the dark” paradigm, and astrocyte number and astrogliosis were measured using immunohistochemistry. Results indicate that non‐dependent consumption increased glial fibrillary acidic protein (GFAP) density but not the number of GFAP+ cells, suggesting that non‐dependent ethanol is sufficient to elicit astrocyte activation. The second part of this study examined how astrocytes impacted behaviors and the neurochemistry related to alcohol using the chemogenetic tool, DREADDs (designer receptors exclusively activated by designer drugs). Transgenic GFAP‐hM3Dq mice were administered clozapine N‐oxide both peripherally, affecting the entire central nervous system (CNS), or directly into the BLA. In both instances, GFAP‐Gq‐signaling activation significantly reduced ethanol consumption and correlating blood ethanol concentrations. However, GFAP‐Gq‐DREADD activation throughout the CNS had more broad effects resulting in decreased locomotor activity and sucrose consumption. More targeted GFAP‐Gq‐signaling activation in the BLA only impacted ethanol consumption. Finally, a glutamate assay revealed that after GFAP‐Gq‐signaling activation glutamate concentrations in the amygdala were partially normalized to control levels. Altogether, these studies support the theory that astrocytes represent a viable target for alcohol use disorder therapies.
Work and suicide: An interdisciplinary systematic literature review
Authors: Howard Matt C. , Follmer Kayla B. , Smith Mickey B. , Tucker Raymond P. , Van Zandt Elise C. 
Published: April 2021

SummaryAlthough organizational scholars have long been interested in employees' well‐being and occupational health, less work has focused specifically on suicide behaviors among employees. This dearth of research is concerning given that individuals spend a significant portion of their waking hours at work, and suicide deaths among American workers are on the rise. To encourage the study of work and suicide with the intent of ultimately reducing mortality, we first provide a theoretical framework that incorporates two eminent theories of suicide: interpersonal‐psychological theory of suicide and psychache theory of suicide. We then report the findings of an interdisciplinary systematic literature review that offers an overview of current research related to work and suicide, including antecedent, mediating, and moderating effects. The results of our systematic literature review are presented via the lens of our theoretical framework, supporting that it is an appropriate perspective to understand the relation of work and suicide. Finally, we conclude by identifying avenues for continued research on the interplay between work and suicide, again incorporating these research directions into our theoretical framework. Together, our manuscript integrates multiple domains of research, while addressing a timely and critical public health crisis that stems, in part, from employees' workplace experiences.
Outcomes of adverse drug events reported with potentially inappropriate medications in older adults, 2004–2017
Authors: Park Sharon K. , Luu Bao Tran 
Published: April 2021

AbstractBackgroundPrescribing of potentially inappropriate medications (PIMs) in adults who are ≥65 years old have been associated with adverse drug events (ADEs).AimTo describe ADEs with PIMs in the older adults based on demographics, ADE severity level, and medication class.MethodAll ADEs reported to the U.S. Food and Drug Administration Adverse Event Reporting System between 1 January 2004 and 31 December 2017 were reviewed. Data were collected for any ADEs associated with PIMs in adults with ages ≥65 years per the Beers Criteria, including demographics, ADE severity, and ADE date. ADEs were further analysed for any death, hospitalisation, disability, and other serious outcomes associated with PIMs. Data were analysed descriptively.ResultsThe number of reported ADEs increased steadily over the 13‐year period. Of the total 68 762 ADEs reported, 80.4% were serious ADEs and more women experienced ADEs (52.0%) than men (46.4%). Age group between 65–74 had a higher number of ADE reports than other groups. Of the 55 302 serious ADEs, 2723 were deaths. The anticoagulants class had the highest percentage of ADEs with death outcomes (57.3%), followed by cardiovascular drugs. An estimated cost to manage the total number of serious ADEs was approximately USD$2 billion for the older adults over the 13‐year period.ConclusionADEs from PIMs occurred frequently among older adults and steadily increased over 13 years. Anticoagulants had the highest proportion of the reported ADEs and most of the ADEs were of serious outcomes including death, disabilities, and hospitalisations. The ADEs potentially incur substantial healthcare costs for this population.
The survival benefit of surgery for perihilar cholangiocarcinoma in octogenarians: Shinshu University experience
Authors: Yasukawa Koya , Shimizu Akira , Kubota Koji , Notake Tsuyoshi , Sugenoya Shinsuke , Hosoda Kiyotaka , Ikehara Tomohiko , Hayashi Hikaru , Kobayashi Ryoichiro , Soejima Yuji 
Published: April 2021

AbstractBackground and ObjectivesIn today's aging society, surgery is increasingly performed for older patients with perihilar cholangiocarcinoma (PHCC). This study aimed to examine survival and oncological outcomes in octogenarians with PHCC who underwent surgery.MethodsWe retrospectively examined 480 consecutive PHCC patients treated for PHCC between 1991 and 2020. Two hundred forty‐seven underwent resection. Patient and clinical characteristics, including postoperative complications, overall survival (OS), and disease‐free survival (DFS) were analyzed.ResultsThe proportion of octogenarians with PHCC undergoing surgery increased from 5.2% in 1991–2000 to 13.4% in 2016–2020. R0 resection and postoperative complication rates were comparable between octogenarians and younger patients. Five‐year OS (30.0% vs. 31.7%) and DFS (20.0% vs. 29.5%) did not significantly differ. One‐year OS was significantly better in octogenarians who underwent resection than those who did not (95.0% vs. 17.6%; p < .001). Two octogenarians who developed Clavien–Dindo grade III complications had undergone right hemihepatectomy (RH). Posthepatectomy liver failure and biliary leakage (Grade B) were also observed in octogenarians who underwent RH.ConclusionIn well‐selected octogenarians with PHCC, surgery offers short‐ and long‐term outcomes comparable with those of their younger counterparts. RH may be considered in octogenarians on an individual basis.
A Network Analysis of the Associations Between Posttraumatic Stress Symptoms and Posttraumatic Growth Among Disaster‐Exposed Chinese Young Adults
Authors: Yuan Guangzhe , Park Crystal L. , Birkeland Samuel R. , Yip Paul S. Y. , Hall Brian J. 
Published: April 2021

AbstractPosttraumatic stress symptoms (PTSS) and posttraumatic growth (PTG) have been shown to coexist following exposure to a traumatic event, but consensus about what accounts for this association is lacking. Network analysis is a novel analytic method that can explain this linkage. In a sample of 1,809 Chinese college students (66.1% female, age range: 16–35 years) who were directly exposed to a typhoon, we investigated the network structure of PTSS and PTG, along with bridge symptoms and elements, to elucidate how distress and growth coexist. The seven strongest edges found in the model included two between elements in the PTSS cluster, one between elements of PTG, and four between elements of PTSS and PTG. Eight bridge symptoms and elements emerged: intrusive thoughts, emotional cue reactivity, hypervigilance, self‐destructive or reckless behavior, nightmares, and physiological cue reactivity among PTSS, and changed priorities and stronger religious faith among PTG elements. These findings reveal connections between PTSS and PTG that explain how these constructs may coexist in individuals exposed to natural disasters. The network perspective provides a novel way to conceptualize the association between PTSS and PTG and contributes to the field's understanding of recovery after traumatic events.