bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating bile acid concentrations and non‐alcoholic fatty liver disease in Guatemala
Authors: Rivera‐Andrade Alvaro , Petrick Jessica L. , Alvarez Christian S. , Graubard Barry I. , Florio Andrea A. , Kroker‐Lobos Maria F. , Parisi Dominick , Freedman Neal D. , Lazo Mariana , Guallar Eliseo , Groopman John D. , Ramirez‐Zea Manuel , McGlynn Katherine A. 
Published: April 2022

SummaryBackgroundNon‐alcoholic fatty liver disease (NAFLD) is a major liver disease worldwide. Bile acid dysregulation may be a key feature in its pathogenesis and progression.AimsTo characterise the relationship between bile acid levels and NAFLD at the population levelMethodsWe conducted a cross‐sectional study in Guatemala in 2016 to examine the prevalence of NAFLD. Participants (n = 415) completed questionnaires, donated blood samples and had a brief medical exam. NAFLD was determined by calculation of the fatty liver index. The levels of 15 circulating bile acids were determined by LC–MS/MS. Adjusted prevalence odds ratios (PORadj) and 95% CI were calculated to examine the relationships between bile acid levels (in tertiles) and NAFLD.ResultsPersons with NAFLD had significantly higher levels of the conjugated primary bile acids glycocholic acid (GCA) (PORadj T3 vs T1 = 1.85), taurocholic acid (TCA) (PORadj T3 vs T1 = 2.45) and taurochenodeoxycholic acid (TCDCA) (PORadj T3 vs T1 = 2.10), as well as significantly higher levels the unconjugated secondary bile acid, deoxycholic acid (DCA) (PORadj T3 vs T1 = 1.78) and its conjugated form, taurodeoxycholic acid (TDCA) (PORadj T3 vs T1 = 1.81).ConclusionsThe bile acid levels of persons with and without NAFLD differed significantly. Among persons with NAFLD, higher levels of the conjugated forms of CA (i.e. GCA, TCA) and the secondary bile acids that derive from CA (i.e. DCA, TDCA) may indicate there is hepatic overproduction of CA, which may affect the liver via aberrant signalling mediated by the bile acids.
Ondansetron use in nausea and vomiting during pregnancy: A descriptive analysis of prescription patterns and patient characteristics in UK general practice
Authors: Slattery Jim , Quinten Chantal , Candore Gianmario , Pinheiro Luis , Flynn Robert , Kurz Xavier , Nordeng Hedvig 
Published: April 2022

AimsThe objective of this study was to describe ondansetron drug utilization patterns during pregnancy to treat nausea and vomiting in pregnancy (NVP). Moreover, we aimed to describe the maternal factors associated with NVP and antiemetic use.MethodsThe data consist of pregnancies with a live birth(s) within an IMRD‐UK registered GP practice. Descriptive statistics were used to investigate patterns of ondansetron use in pregnancy and to describe maternal characteristics associated with NVP and antiemetic drug utilization. We differentiate first‐ from second‐line use during pregnancy using antiemetic prescription pathways.ResultsThe dataset included 733 633 recorded complete pregnancies from 2005 to 2019. NVP diagnosis and ondansetron prescription prevalence increased from 2.7% and 0.1% in 2005 to 4.8% and 2.5% in 2019 respectively. Over the period 2015–2019, the most common oral daily dosages were 4 mg/d (8.5%), 8 mg/d (37.1%), 12 mg/d (37.5%) and between 16 and 24 mg/d (16.9%). Prescription of ondansetron was initiated during the first trimester of pregnancy in 40% of the cases and was moderately used as a first‐line therapy (2.8%), but preferred choice of second‐line therapy. Women with mental health disorders, asthma and/or prescribed folic acid were more likely to experience NVP and use antiemetics in pregnancy than their counterparts.ConclusionThis study confirms that ondansetron is increasingly used off‐label to treat NVP during pregnancy, also in the first trimester and before other prescription antiemetics have been prescribed. Several maternal comorbidities and folic acid use were more common among women experiencing NVP and using antiemetics, including ondansetron.
A GLP‐1/glucagon (GCG)/CCK2 receptors tri‐agonist provides new therapy for obesity and diabetes
Authors: Zhao Songfeng , Yan Zhiming , Du Yue , Li Zeyun , Tang Chunli , Jing Lin , Sun Lidan , Yang Qimeng , Tang Xueling , Yuan Yongliang , Han Jing , Jiang Neng 
Published: April 2022

Background and PurposeGlucagon‐like peptide‐1 (GLP‐1) and glucagon (GCG) receptor dual agonist have promising therapeutic effects in the treatment of obesity and diabetes. Moreover, GLP‐1 and cholecystokinin 2 (CCK2) dual agonists have been shown to restore pancreas function and improve glycaemic control in preclinical studies. We describe, for the first time, the beneficial effects of GLP‐1/glucagon receptor and GLP‐1/CCK2 dual agonists, which can be integrated into one peptide, resulting in significant anti‐diabetes and anti‐obesity effectiveness.Experimental ApproachThe in vitro potency of this novel peptide Xenopus (x) GLP‐1/GCG/CCK2 tri‐agonist (xGLP/GCG/gastrin) against GLP‐1, GCG, CCK1 and CCK2 receptors was determined on cells expressing the corresponding receptors by cAMP accumulation or ERK1/2 phosphorylation assays. The in vivo anti‐diabetes and anti‐obesity effects of this tri‐agonist xGLP/GCG/gastrin were studied in both db/db and diet induced obesity (DIO) mice.Key ResultsxGLP/GCG/gastrin was a potent and selective GLP‐1, GCG and CCK2 tri‐agonist. In DIO mice, the metabolic benefits of xGLP‐1/GCG/gastrin, such as reduction of body weight and hepatic lipid contents were significantly better than those of the peptide ZP3022 (GLP‐1/CCK‐2 dual agonist) and liraglutide. In a short‐term study in db/db mice, xGLP/GCG/gastrin treatment had considerable effects, increasing islet numbers, islet areas and insulin content. In a long‐term treatment study using db/db mice, xGLP‐1/GCG/gastrin showed a significantly and sustained improvement in glucose tolerance and glucose control compared with that of liraglutide, ZP3022, cotadutide (GLP‐1/GCG dual agonist) and xGLP/GCG‐15.Conclusions and ImplicationsThese results demonstrate the therapeutic potential of xGLP‐1/GCG/gastrin for the treatment of obesity and diabetes.
EBV genome variations enhance clinicopathological features of nasopharyngeal carcinoma in a non‐endemic region
Authors: Kondo Satoru , Okuno Yusuke , Murata Takayuki , Dochi Hirotomo , Wakisaka Naohiro , Mizokami Harue , Moriyama‐Kita Makiko , Kobayashi Eiji , Kano Makoto , Komori Takeshi , Hirai Nobuyuki , Ueno Takayoshi , Nakanishi Yosuke , Endo Kazuhira , Sugimoto Hisashi , Kimura Hiroshi , Yoshizaki Tomokazu 
Published: April 2022

AbstractNasopharyngeal carcinoma (NPC) is caused by infection with Epstein–Barr virus (EBV) and endemic in certain geographic regions. EBV lytic gene, BALF2, closely associates with viral reactivation and BALF2 gene variation, the H‐H‐H strain, causes NPC in endemic region, southern China. Here, we investigate whether such EBV variations also affect NPC in a non‐endemic region, Japan. Viral genome sequencing with 47 EBV isolates of Japanese NPC were performed and compared with those of other EBV‐associated diseases from Japan or NPC in Southern China. EBV genomes of Japanese NPC are different from those of other diseases in Japan or endemic NPC; Japanese NPC was not affected by the endemic strain (the BALF2 H‐H‐H) but frequently carried the type 2 EBV or the strain with intermediate risk of endemic NPC (the BALF2 H‐H‐L). Seven single nucleotide variations were specifically associated with Japanese NPC, of which six were present in both type 1 and 2 EBV genomes, suggesting the contribution of the type 2 EBV‐derived haplotype. This observation was supported by a higher viral titer and stronger viral reactivation in NPC with either type 2 or H‐H‐L strains. Our results highlight the importance of viral strains and viral reactivation in the pathogenesis of non‐endemic NPC.
Association of the collagen signature with pathological complete response in rectal cancer patients
Authors: Jiang Wei , Wang Shijie , Wan Jinliang , Zheng Jixiang , Dong Xiaoyu , Liu Zhangyuanzhu , Wang Guangxing , Xu Shuoyu , Xiao Weiwei , Gao Yuanhong , Zhuo Shuangmu , Yan Jun 
Published: April 2022

AbstractCollagen in the tumor microenvironment is recognized as a potential biomarker for predicting treatment response. This study investigated whether the collagen features are associated with pathological complete response (pCR) in locally advanced rectal cancer (LARC) patients receiving neoadjuvant chemoradiotherapy (nCRT) and develop and validate a prediction model for individualized prediction of pCR. The prediction model was developed in a primary cohort (353 consecutive patients). In total, 142 collagen features were extracted from the multiphoton image of pretreatment biopsy, and the least absolute shrinkage and selection operator (Lasso) regression was applied for feature selection and collagen signature building. A nomogram was developed using multivariable analysis. The performance of the nomogram was assessed with respect to its discrimination, calibration, and clinical utility. An independent cohort (163 consecutive patients) was used to validate the model. The collagen signature comprised four collagen features significantly associated with pCR both in the primary and validation cohorts (p < 0.001). Predictors in the individualized prediction nomogram included the collagen signature and clinicopathological predictors. The nomogram showed good discrimination with area under the ROC curve (AUC) of 0.891 in the primary cohort and good calibration. Application of the nomogram in the validation cohort still gave good discrimination (AUC = 0.908) and good calibration. Decision curve analysis demonstrated that the nomogram was clinically useful. In conclusion, the collagen signature in the tumor microenvironment of pretreatment biopsy is significantly associated with pCR. The nomogram based on the collagen signature and clinicopathological predictors could be used for individualized prediction of pCR in LARC patients before nCRT.
Perspectives from the Chair of ICMEMO
Authors: Leon Ophelia 
Published: April 2022

AbstractThe author offers a personal view on the Russian invasion of Ukraine, a sovereign nation, and observations of the self‐evident war crimes taking place, including attacks on memorial sites and the people who work to preserve the memory of past atrocities. In this perspective, Leon argues for conciliation rather than expulsion of the ICOM Russia from the ICOM community, and highlights the important work that memorial museums can do to foster peace, cooperation, and mutual understanding. The author is the chair of the International Committee of Memorial Museums in Remembrance of the Victims of Public Crimes (ICMEMO).
Using near‐ground leaf temperatures alters the projected climate change impacts on the historical range of a floristic biodiversity hotspot
Authors: Trew Brittany T. , Early Regan , Duffy James P. , Chown Steven L. , Maclean Ilya 
Published: April 2022

AbstractAimSpecies distribution models (SDMs) have been used widely to predict the responses of species to climate change. However, the climate data used to drive these models typically represents ambient air temperatures, derived from measurements taken 1–2 m above the ground. Most plant species live near the ground where temperatures can differ significantly, owing to the effects of solar radiation and reduced wind speed. Here, we investigate differences in spatio‐temporal patterns in near‐ground leaf and ambient air temperatures and the implications this has on projected changes in species richness of a suite of Fynbos plant species.LocationFynbos Biome, South Africa.MethodsFor each individual plant species (n = 83), we constructed two types of SDMs: one using ambient air temperatures and one using near‐ground leaf temperatures. Each of these models was fitted to species occurrence data for a recent time period and projected backwards into the past. Species richness projections for both time periods were then constructed using binarized projections.ResultsWe found that the impact of climate change on species richness – both the degree of suitable climate lost from the historical range and gained outside of the historical range – was greater using SDMs built with near‐ground leaf temperatures. Independent validation of the hindcast projections revealed near‐ground SDMs to be more accurate.Main ConclusionsOur study suggests that SDMs constructed using ambient air temperatures are likely overestimating the breadth of the species’ occupied thermal niche, thus underestimating the climate change‐driven risk to species where near‐ground leaf and ambient air temperatures are particularly decoupled from one another. Additionally, ambient air SDMs may be underestimating the ex‐situ refugial potential of inland mountains. Ambient air temperatures should not be considered an effective surrogate for investigating climate change impacts on species living near the ground.
Human‐mediated eco‐evolutionary processes of the herbivorous insect Hyalopterus arundiniformis during the Holocene
Authors: Liu Tongyi , Chen Jing , Jiang Liyun , Qiao Gexia 
Published: April 2022

AbstractAimPleistocene climatic fluctuations have been identified as a dominant factor in evolutionary and ecological processes underlying contemporary species distribution. In contrast, anthropogenic activity during the Holocene has been largely neglected in phylogeographic inference. Here, by integrating archaeological evidence, phylogeographic analyses and a climatic niche‐based approach, the role of Holocene human activity in determining the evolutionary trajectory of insect pests is investigated using Hyalopterus arundiniformis (HAR) as a model.LocationEurasia.MethodsWe compiled archaeological records and historical data for the host plant (i.e. peach) of HAR. Phylogeographic structure, genetic diversity and gene flow were estimated. Historical demographic dynamics were explored using coalescent‐based analyses. The origin and dispersal history were assessed using an approximate Bayesian computation (ABC) approach. The changes in climatic niche breadth during geographic expansion were evaluated via niche comparison analyses.ResultsOur results revealed that HAR originated in Southwest China and dispersed to Southeast and Northwest China, and it was then introduced to western Eurasia from Northwest China. The climatic niche shifted significantly with range expansions, and niche expansion explained the largest proportion of niche dynamics. Population size expansion occurred in the Holocene and coincided with the domestication and trans‐Eurasian trade of peach.Main conclusionsThe geographic range, effective population size and climatic niche breadth of HAR expanded following the human‐mediated dispersal of its host plant during the Holocene. Our results highlight that the expansion of Neolithic agriculture and trans‐Eurasian crop exchange along ancient communication routes may have played an important role in shaping the distribution and demographic dynamics of herbivorous insects. This study also provides essential information for pest management and biological invasions.
Inventory control under different forms of uncertainty: Ambiguity and stochastic variability
Authors: Ma Siqi , Aloysius John 
Published: April 2022

AbstractInventory decision makers routinely face ambiguity due to the psychological awareness that there is unknown information about salient events that is knowable in principle. Researchers on inventory control behavior in the face of uncertainty have primarily focused on uncertainty due to stochastic variability. However, most decision situations in the naturally occurring world involve both forms of uncertainty—ambiguity and stochastic variability. We report the results of two experiments that partial out the effects of ambiguity and stochastic variability by orthogonal manipulation of these two forms of uncertainty in a newsvendor task. Contrary to established mathematical models of decision making under uncertainty, increased ambiguity results in increased mean absolute percentage error, and a corresponding decrease in profit. We also find a systematic bias toward underordering associated with increased ambiguity, which is over and above the bias associated with increased stochastic variability. We do not see evidence for learning with repeated play, so that the effects of induced ambiguity appear to persist. Finally, based on our findings, we suggest measures that managers can use to ameliorate the effects of ambiguity.
Efficacy, safety, and economic impact of diazepam suppositories with as‐needed acetaminophen for prevention of seizure recurrence during the same fever episode in children with suspected simple febrile seizures
Authors: Tanaka Miki , Wang Qianzhi , Morikawa Yoshihiko , Tsukamoto Junya , Sammori Hiroaki , Takehira Ken , Yano Mizuki , Miyama Satoshi , Fujita Saki , Narita Kazutoshi , Kishibe Shun , Morikawa Emi Kawaguchi , Suzuki Satoko , Hataya Hiroshi 
Published: April 2022

AbstractObjectiveThis study was undertaken to evaluate the efficacy, safety, and economic impact of diazepam suppositories with as‐needed acetaminophen in comparison with as‐needed acetaminophen alone for prevention of seizure recurrence during the same fever episode in suspected pediatric simple febrile seizures (SFS).MethodsThis single‐center, prospective, observational study was conducted from July 29, 2019 to February 15, 2021 at a children's hospital. Children aged 6 months to 60 months presenting to the emergency department with suspected SFS were included. Participants receiving both diazepam suppositories and as‐needed acetaminophen were compared with those receiving as‐needed acetaminophen alone. The primary outcome was seizure recurrence during the same fever episode. The secondary outcomes included the incidence of central nervous system (CNS) pathologies, adverse events, and medical costs.ResultsOf the 316 participants, 228 (72.2%) had their first febrile seizure. Diazepam (.3–.5 mg/kg for up to two doses) was administered to 88 of 316 patients (27.8%). The outcomes were available for 306 patients. The recurrence rate was 3.5% (3/85) in the patients receiving diazepam with as‐needed acetaminophen and 12.2% (27/221) in the patients receiving as‐needed acetaminophen alone (relative risk = .29, 95% confidence interval [CI] = .09–.93, p = .03). The adjusted odds ratio of diazepam administration against recurrence was .23 (95% CI = .07–.78, p = .02). None of the patients had a CNS pathology. No severe adverse events occurred, although mild ataxia was observed significantly more often in the patients receiving diazepam and as‐needed acetaminophen (29.4% vs. 18.7%, p = .04). The median medical cost was US $199 (interquartile range [IQR] = 86–244) for the group receiving both medications and US $202 (IQR = 114–242) for the group receiving as‐needed acetaminophen alone.SignificanceCompared with as‐needed acetaminophen alone, diazepam with as‐needed acetaminophen may reduce seizure recurrence more during the same fever episode without severe adverse events or additional costs in children with suspected SFS.
Low‐income, first‐generation students' experiences of parent support in career development
Authors: Ion Irina Elena 
Published: April 2022

AbstractObjectiveThe aim of this article is to explore the lived experiences of low‐income, first‐generation students (FGSs) in career development and the role played by their families in this process.BackgroundThe literature illustrates mixed results of the parental influence on first generation students' career development. Several studies portray low family involvement in students' career plans and outcomes. In contrast, the strengths‐based literature presents the family as the main “source” of FGS assets. However, there is a dearth of strengths‐based studies regarding FGSs' career development and family role.MethodA phenomenological study was carried out using semistructured interviews with twenty Romanian low‐income FGSs.ResultsLow‐income FGS families rely on an extensive array of assets that help FGSs to navigate the academic system and to develop their careers, suggesting the role of familial capital. Despite this, several challenges jeopardize FGSs' career development.ConclusionFamilial capital is a useful concept for the analysis of career development for low‐income FGSs. Still, the extent to which students' strengths and their familial capital are sufficient for a coherent career development process is limited.ImplicationsThe strengths‐based view can inform research aimed at identifying the assets of vulnerable populations. Within academia, familial capital should be recognized as a mechanism able to reinforce the capabilities and resources of low‐income FGSs. In‐school vocational and career counseling beginning in early career‐life periods can improve career development for those who may be the first in their families to go to university.
Development and validation of a predictive risk model for frailty in elderly patients with multimorbidity
Authors: Huang Fengmei , Yang Xiaoling , Yuan Li , Wang Miye , Li Rao , Ye Ziwei , Lv Jing , He Ting 
Published: April 2022

AimsThis study aimed to investigate the influencing factors of frailty in elderly patients with multimorbidity and to develop a predictive risk model for frailty in elderly patients with multimorbidity.MethodsIn total, 3836 elderly patients with multimorbidity who were admitted to the medical wards of five grade A tertiary hospitals in Sichuan Province from March 2020 to June 2021 were selected. Based on the general data of patients with multimorbidity, the independent risk factors for frailty were obtained using logistic analysis, and a risk prediction model of frailty was developed.ResultsIndependent risk factors for frailty in patients with multimorbidity were age, types of medication, and comorbidity with chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD) and chronic cerebrovascular disease (CCVD); and the protective factors for frailty were body mass index (BMI), exercise and education level. The expression of the model was Z = −2.054 + 0.016 × age − 0.029 × BMI − 0.153 × education level‐1.059 × exercise + 0.203 × types of medication + 0.788 × comorbidity with CHF + 0.950 × comorbidity with COPD + 0.363 × comorbidity with CCVD.ConclusionAge, BMI, education level, exercise, types of medication, and comorbidity with CHF, COPD and CCVD can affect frailty risk in elderly patients with multimorbidity, which may be helpful to predict the frailty risk of elderly patients with multimorbidity. Geriatr Gerontol Int 2022; 22: 471–476.
University presidents as policy entrepreneurs: Evidence from U.S. universities engaged in prestige behaviour
Authors: Martinez Magdalena , Henkle Jason 
Published: April 2022

AbstractThis article examines how university presidents who led their institutions to achieve Carnegie “R1 Highest Research Activity” managed policy tensions created by prestige priorities and worked with groups and coalitions internally and externally. Striving to achieve R1 status requires U.S. universities to re‐calibrate their focus, resources, and messaging both internally and externally. Using four elements of policy entrepreneurship (PE), the three cases included in this article illustrate the critical role of university presidents as PE in maintaining a sustained effort over an extended period. University leaders displayed their social acuity and built teams by cultivating their social and political capital with influential constituents and groups. As PE, university presidents were deliberate and thoughtful about the language they used to define and describe policy problems and solutions. The findings expand our understanding of the role of university presidents as PE.