bluuebunny/crossref_metadata_2025_split huggingface dataset:
A chromosome level genome assembly of Propsilocerus akamusi to understand its response to heavy metal exposure
Authors: Sun Xiaoya , Liu Wenbin , Li Ruoqun , Zhao Cong , Pan Lina , Yan Chuncai 
Published: March 2021

AbstractChironomidae species are universally used for studying the impact of pollutants in aquatic systems. The nonbiting midge Propsilocerus akamusi is often found in urban streams and is suitable for use as a toxicological bioindicator. However, few studies have previously examined metal stress in this species. We sequenced the genome of this urban midge to address this question. Here, we present the first chromosome‐level genome of P. akamusi, obtained from Illumina short‐read and PacBio long‐read sequences with Hi‐C technology. The size of the very small assembled genome was 85.83 Mb with a contig N50 of 6.2 Mb and a scaffold N50 of 26.1 Mb. This assembly revealed significant expansion of haemoglobin (Hb) genes, some of which formed large tandem repeats. Transcriptomic studies for copper tolerance identified four genes in the tandem array that were highly expressed, all of which presented intron loss. This characteristic might highlight the potential role of Hb genes in copper tolerance. Additionally, detoxification genes, chemosensory genes and heat shock protein genes of this midge were identified, some of which are associated with metal stress. The high‐quality assembled genome of P. akamusi and the transcriptomic analyses provide new insight into the molecular mechanisms of heavy metal stress. Our comparison of the P. akamusi genome with other dipteran genomes provides valuable resources for understanding the evolutionary history, genetics, and ecology of this species as well as those of other midges.
Biglycan, tumor endothelial cell secreting proteoglycan, as possible biomarker for lung cancer
Authors: Morimoto Hirofumi , Hida Yasuhiro , Maishi Nako , Nishihara Hiroshi , Hatanaka Yutaka , Li Cong , Matsuno Yoshihiro , Nakamura Toru , Hirano Satoshi , Hida Kyoko 
Published: March 2021

AbstractObjectivesIn lung cancer, surgery remains the most curative treatment and limited resection is beneficial for patients with low cardiopulmonary function and low malignancy tumors. However, there are no biomarkers of low malignancy to select candidates for limited resection without compromising the outcome of treatments. Recently we identified biglycan (BGN) as a tumor endothelial cell (TEC) marker that is associated with tumor progression in various cancers. In this study, we analyzed the association between BGN expression in TECs in lung cancer and cancer progression in patients.Materials and MethodsFirst, we performed immunohistochemistry of BGN with resected lung tumor tissues of 155 patients who had undergone thoracic surgery and analyzed the correlation between BGN‐positive vessel density in primary lung tumors and clinicopathological factors. Second, we measured the BGN levels in preoperative serum of other 46 patients with lung cancer by ELISA, and analyzed the correlation between BGN expression in tumor tissues and blood BGN levels.ResultsHigh BGN expression in the TECs was significantly associated with T factor, and was a significant negative predictor. BGN levels in preoperative serum of 46 patients with lung cancer was significantly correlated with BGN expression in the TECs. Preoperative serum BGN level was significantly lower in healthy volunteers and less invasive adenocarcinoma than in invasive adenocarcinoma and other lung carcinomas. These results suggest that low BGN level in preoperative serum in patients with lung cancer might indicate low malignancy.ConclusionsBGN can be a potential biomarker for lung cancer.
A retrospective analysis of pembrolizumab plus chemotherapy versus pembrolizumab monotherapy for advanced or recurrent non‐small cell lung cancer
Authors: Isono Taisuke , Kagiyama Naho , Shibata Shun , Nakajima Hitomi , Matsui Yuma , Takano Kenji , Nishida Takashi , Hosoda Chiaki , Kawate Eriko , Kobayashi Yoichi , Ishiguro Takashi , Takaku Yotaro , Kurashima Kazuyoshi , Yanagisawa Tsutomu , Takayanagi Noboru 
Published: March 2021

AbstractBackgroundAlthough clinical trials have investigated the addition of pembrolizumab to chemotherapy for non‐small cell lung cancer, none have investigated the addition of chemotherapy to pembrolizumab.MethodsWe conducted a retrospective study of 71 NSCLC patients including 33 treated with pembrolizumab plus chemotherapy (combination therapy group) and 38 treated with pembrolizumab monotherapy (monotherapy group) from 1 May 2016 to 31 August 2020.ResultsEleven of 33 (33.3%) patients in the combination therapy group and 37 of 38 (97.4%) patients in the monotherapy group had programmed cell death ligand‐1 (PD‐L1) tumor proportion score (TPS) ≥50%. Objective response rate (ORR) and median overall survival (OS) were not significantly different between the combination therapy group and monotherapy group (54.5% vs. 47.4, p = 0.637 and 16.6 vs. 27.0 months, p = 0.463). In patients with PD‐L1 TPS ≥50%, ORR and median OS were not different between the combination therapy group and the monotherapy group (63.6% vs. 48.6%, p = 0.499 and not reached vs. 27.0 months, p = 0.976). Thirty‐three (100%) patients experienced adverse events (AEs) in the combination therapy group and 32 (84.2%) in the monotherapy group. Treatment discontinuation at 1 year due to AEs occurred more frequently in the combination therapy group (45.2%) than in the monotherapy group (21.1%).ConclusionThere was no significant difference in ORR and OS between the two groups, and treatment discontinuation was more frequent in the combination group. A randomized controlled trial is needed to evaluate the addition of chemotherapy to pembrolizumab for first‐line treatment in patients with PD‐L1 TPS ≥50%.
Ibrutinib modulates Aβ/tau pathology, neuroinflammation, and cognitive function in mouse models of Alzheimer's disease
Authors: Lee Hyun‐ju , Jeon Seong Gak , Kim Jieun , Kang Ri Jin , Kim Seong‐Min , Han Kyung‐Min , Park HyunHee , Kim Ki‐taek , Sung You Me , Nam Hye Yeon , Koh Young Ho , Song Minseok , Suk Kyoungho , Hoe Hyang‐Sook 
Published: March 2021

AbstractWe previously demonstrated that ibrutinib modulates LPS‐induced neuroinflammation in vitro and in vivo, but its effects on the pathology of Alzheimer's disease (AD) and cognitive function have not been investigated. Here, we investigated the effects of ibrutinib in two mouse models of AD. In 5xFAD mice, ibrutinib injection significantly reduced Aβ plaque levels by promoting the non‐amyloidogenic pathway of APP cleavage, decreased Aβ‐induced neuroinflammatory responses, and significantly downregulated phosphorylation of tau by reducing levels of phosphorylated cyclin‐dependent kinase‐5 (p‐CDK5). Importantly, tau‐mediated neuroinflammation and tau phosphorylation were also alleviated by ibrutinib injection in PS19 mice. In 5xFAD mice, ibrutinib improved long‐term memory and dendritic spine number, whereas in PS19 mice, ibrutinib did not alter short‐ and long‐term memory but promoted dendritic spinogenesis. Interestingly, the induction of dendritic spinogenesis by ibrutinib was dependent on the phosphorylation of phosphoinositide 3‐kinase (PI3K). Overall, our results suggest that ibrutinib modulates AD‐associated pathology and cognitive function and may be a potential therapy for AD.
Cellular aging beyond cellular senescence: Markers of senescence prior to cell cycle arrest in vitro and in vivo
Authors: Ogrodnik Mikolaj 
Published: March 2021

AbstractThe field of research on cellular senescence experienced a rapid expansion from being primarily focused on in vitro aspects of aging to the vast territories of animal and clinical research. Cellular senescence is defined by a set of markers, many of which are present and accumulate in a gradual manner prior to senescence induction or are found outside of the context of cellular senescence. These markers are now used to measure the impact of cellular senescence on aging and disease as well as outcomes of anti‐senescence interventions, many of which are at the stage of clinical trials. It is thus of primary importance to discuss their specificity as well as their role in the establishment of senescence. Here, the presence and role of senescence markers are described in cells prior to cell cycle arrest, especially in the context of replicative aging and in vivo conditions. Specifically, this review article seeks to describe the process of “cellular aging”: the progression of internal changes occurring in primary cells leading to the induction of cellular senescence and culminating in cell death. Phenotypic changes associated with aging prior to senescence induction will be characterized, as well as their effect on the induction of cell senescence and the final fate of cells reviewed. Using published datasets on assessments of senescence markers in vivo, it will be described how disparities between quantifications can be explained by the concept of cellular aging. Finally, throughout the article the applicational value of broadening cellular senescence paradigm will be discussed.
Changes in Alcohol Use and Drinking and Driving Outcomes From Before Arrest for Driving Under the Influence to After Interlock Removal
Authors: Voas Robert B. , Tippetts Anthony Scott , Romano Eduardo , Nochajski Thomas H. , Manning Amy R. , Taylor Eileen , Scherer Michael 
Published: March 2021

BackgroundHalf of the offenders convicted of impaired driving in the United States are sentenced to install alcohol ignition interlock devices (IIDs), which prevent them from starting their vehicles if they have been drinking. No research has yet explored offenders’ patterns of alcohol consumption and driving under the influence of alcohol (DUI) from the time before the arrest to the time period after the IID is installed. This study aims to fill that gap in knowledge.MethodsUsing the Timeline Follow‐back interview procedure, we assessed the daily drinking of 153 convicted DUI offenders’ self‐reported total alcohol consumption and rates of self‐reported driving after drinking over 4 phases: before DUI arrest, between arrest and IID installation, during the phase on the interlock, and after the interlock is removed. Because information about behaviors in each period was not available for every participant, comparisons were made using paired‐sample contrasts.ResultsCompared with before the arrest, total alcohol use decreased by 50% in the 4‐month phase following arrest and before IID installation, though it did not change much afterward. The frequency of drinking and driving decreased sharply after the arrest (−82%), with further decrease upon installation of the interlock (−58%, p = 0.05). The frequency of drinking and driving after the IID was removed returned to preinstallation drinking and driving status (+58%, p = 0.01).ConclusionsParticipants made significant adjustments to their drinking behavior by adhering to the traditional DUI driving restrictions in the postarrest phase. Although installation of an IID was not associated with a significant change in drinking, it further reduced the frequency of drinking and driving. Evaluations of the IID experience should take into account information on an individual's drinking and DUI behaviors not only before the IID was installed, but before the individual was arrested.
A conserved haplotype in Wagyu cattle contains RAB4A whose encoded protein regulates glucose trafficking in muscle and fat cells
Authors: Hudson N. J. , Porto‐Neto L. , Naval‐Sanchez M. , Lyons R. E. , Reverter Antonio 
Published: March 2021

SummaryThe Wagyu breed of taurine cattle possess favourable genetics for intramuscular fat (IMF) but genomic loci associated with the trait remain under characterised. Here, we report the identification of a previously unidentified genomic region possessing a particular haplotype structure in Wagyu. Through deployment of a genome‐wide haplotype detection analysis that captures regions conserved in a target population but not other populations we screened 100 individual Wagyu and contrasted them with 100 individuals from two independent comparison breeds, Charolais and Angus, using high‐density SNPs. An extreme level of Wagyu conservation was assigned to a single genomic window (spanning genomic coordinates BTA28:41 088–300 265 bp). In fact, a five‐SNP region spanning 27 096 bp is almost perfectly conserved among the 100 Wagyu individuals assayed and partially overlaps RAB4A. Focussing in, two consecutive SNPs (genomic coordinates 236 949 and 239 950) are apparently fixed within the Wagyu (BB and AA respectively), but at mixed frequencies in the other two breeds. These SNPs are located in the two introns straddling exon 7. In a separate analysis using the 1000 Bulls database, we found that, coincident with exon 7 of RAB4A first allele frequencies were highest in the high IMF Japanese Native (Wagyu) breeds (0.78) and lowest in the low IMF indicine breeds (Nelore and Brahman), with intermediate marbling breeds (Angus and Charolais) assigned intermediate rankings (0.42). RAB4A is known to encode a protein that regulates intracellular trafficking of the insulin‐regulated glucose transporter GLUT4. RAB4A can be considered an attractive new positional candidate for IMF development.
Drivers of farm commercialization in Nigeria and Tanzania
Authors: Owusu Obed , İşcan Talan B. 
Published: March 2021

AbstractWhile total factor productivity (TFP) difference between the subsistence and commercial farm types is negligible, a large number of subsistence‐based farms remain outside the market economy, and national policies have emphasized the need to bring them into the fold of commercial agriculture. Improving market access may help induce greater farm commercialization and thus greater investment in agriculture. However, there is little empirical evidence on farm‐level factors that stimulate agricultural commercialization in SSA. Using a nationally representative panel data from the Living Standards Measurement Study‐Integrated Surveys on Agriculture, this article estimates the likelihood of being a commercial versus a subsistence farmer and the likelihood of transitioning from one farm type to another based on observable characteristics in Nigeria and Tanzania. The analysis demonstrates that although a substantial proportion of farms have no market participation in a given year, there are rich transition dynamics over time. The results from the probit regression show that resource endowments (land, labor, chemical use) and farm characteristics (multicropping system; irrigation; crop types such as fruits, vegetables, and cash crops; and animal traction use) do matter for market participation and the transitioning of subsistence farms into a market economy. These variables are positively correlated with farm commercialization and increase the likelihood of market participation. Overall, policies aimed at improving farmers' access to resources and promoting sustainable smallholder agriculture could be instrumental in raising productivity in agriculture and enhancing marketable agricultural output.
Osteogenic effect of low‐intensity pulsed ultrasound and whole‐body vibration on peri‐implant bone. An experimental in vivo study
Authors: Shobara Kenta , Ogawa Toru , Shibamoto Aya , Miyashita Makiko , Ito Akiyo , Sitalaksmi Ratri M. 
Published: March 2021

AbstractObjectivesThe aims of this study were (i) to compare the osteogenic impact of low‐intensity pulsed ultrasound (LIPUS) and low‐magnitude high‐frequency (LMHF) loading achieved with whole‐body vibration (WBV) on peri‐implant bone healing and implant osseointegration in rat tibiae, and (ii) to examine their combined effect on these processes.Material and methodsTitanium implants were inserted in the bilateral tibiae of 28 Wistar rats. Rats were randomly divided into four groups: LIPUS + WBV, LIPUS, WBV, and control. LIPUS was applied to the implant placement site for 20 min/day on 5 days/week (1.5 MHz and 30 mW/cm2). WBV was applied for 15 min/day on 5 days/week (50 Hz and 0.5 g). In the LIPUS + WBV group, both stimuli were applied under the same stimulation conditions as in the LIPUS and WBV groups. After 4 weeks of treatment, peri‐implant bone healing and implant osseointegration were assessed using removal torque (RT) tests, micro‐CT analyses of relative gray (RG) value, and histomorphometrical analyses of bone‐to‐implant contact (BIC) and peri‐implant bone formation (BV/TV).ResultsThe LIPUS + WBV group had significantly greater BIC than the WBV and control groups. Although there were no significant intergroup differences in RT, RG value, and BV/TV, these variables tended to be greater in the LIPUS + WBV group than the other groups.ConclusionsThe combination of LIPUS and LMHF loading may promote osteogenic activity around the implant. However, further study of the stimulation conditions of LIPUS and LMHF loading is necessary to better understand the osteogenic effects and the relationship between the two stimuli.
Analysis of malignant melanoma risk and outcomes in solid organ transplant recipients: Assessment of transplant candidacy and the potential role of checkpoint inhibitors
Authors: Zwald Fiona , Carvajal Richard D. , Walker John , Sawinski Deirdre , Al‐Adra David 
Published: March 2021

AbstractMalignant melanoma (MM) causes tremendous morbidity and mortality in the solid organ transplant population and may arise in three different clinical scenarios: (1) pretransplant melanoma; (2) de novo melanoma post transplantation and (3) donor‐derived melanoma. This manuscript primarily addresses the first two scenarios with respect to the evaluation and management of pretransplant MM, consideration of transplant candidacy and the occurrence and management of de novo MM post transplantation. The authors outline current evidence describing risks associated with pre‐transplant melanoma to support recently established expert opinion for transplant candidacy.
Vorteile, Sicherheit und Nebenwirkungen der Tumeszenz‐Lokalanästhesie bei dermatologischen Operationen an Säuglingen
Authors: Roerden Alisa , Neunhoeffer Felix , Götz Angelika , Häfner Hans‐Martin , Kofler Lukas 
Published: March 2021

ZusammenfassungDie Tumeszenz‐Lokalanästhesie (TLA) spielt bei dermatochirurgischen Eingriffen eine wichtige Rolle. Die TLA bietet etliche Vorteile, wie lang anhaltende Betäubung, reduzierte Blutung während der Operation und Vermeidung möglicher Komplikationen einer Vollnarkose. Einfache Durchführung, günstiges Risikoprofil und breites Indikationsspektrum sind weitere Gründe dafür, dass TLA zunehmend auch bei Säuglingen eingesetzt wird. Es gibt nicht nur viele Indikationen für chirurgische Exzisionen im Säuglingsalter, wie angeborene Naevi, sondern es hat auch erhebliche Vorteile, wenn diese Exzisionen in einem frühen Alter durchgeführt werden. Dazu zählen die geringere Größe der Läsionen sowie die unproblematische Wundheilung und Geweberegeneration im Säuglingsalter. Dennoch müssen hinsichtlich der Anwendung der TLA bei Säuglingen einige Aspekte berücksichtigt werden, darunter die Dosierung, eine veränderte Plasmaproteinbindung und die Notwendigkeit einer adäquaten und lang anhaltenden Schmerzkontrolle.
Oral semaglutide improves postprandial glucose and lipid metabolism, and delays gastric emptying, in subjects with type 2 diabetes
Authors: Dahl Kirsten , Brooks Ashley , Almazedi Firas , Hoff Søren Tetens , Boschini Cristina , Bækdal Tine A. 
Published: March 2021

AbstractAimTo assess the effects of oral semaglutide on postprandial glucose and lipid metabolism, and gastric emptying, in subjects with type 2 diabetes (T2D).Materials and MethodsIn this randomized, double‐blind, single‐centre, crossover trial, subjects with T2D received once‐daily oral semaglutide (escalated to 14 mg) followed by placebo, or vice versa, over two consecutive 12‐week periods. Glucose and lipid metabolism, and gastric emptying (paracetamol absorption) were assessed before and after two types of standardized meals (standard and/or fat‐rich) at the end of each treatment period. The primary endpoint was area under the glucose 0–5‐h curve (AUC0–5h) after the standard breakfast.ResultsFifteen subjects were enrolled (mean age 58.2 years, HbA1c 6.9%, body weight 93.9 kg, diabetes duration 3.1 years; 13 [86.7%] males). Fasting concentrations of glucose were significantly lower, and C‐peptide significantly greater, with oral semaglutide versus placebo. Postprandial glucose (AUC0–5h) was significantly lower with oral semaglutide versus placebo (estimated treatment ratio, 0.71; 95% CI, 0.63, 0.81; p < .0001); glucose incremental AUC (iAUC0–5h/5h) and glucagon AUC0–5h were also significantly reduced, with similar results after the fat‐rich breakfast. Fasting concentrations of triglycerides, very low‐density lipoprotein (VLDL) and apolipoprotein B48 (ApoB48) were significantly lower with oral semaglutide versus placebo. AUC0–8h for triglycerides, VLDL and ApoB48, and triglycerides iAUC0–8h/8h, were significantly reduced after oral semaglutide versus placebo. During the first postprandial hour, gastric emptying was delayed (a 31% decrease in paracetamol AUC0–1h) with oral semaglutide versus placebo. One serious adverse event (acute myocardial infarction) occurred during oral semaglutide treatment.ConclusionOral semaglutide significantly improved fasting and postprandial glucose and lipid metabolism, and delayed gastric emptying.
Intergenerational income mobility and transmission channels in a transition economy: Evidence from China*
Authors: Yan Weibo , Deng Xiaolan 
Published: March 2021

AbstractFor a large transition economy characterized by urban–rural segmentation, regional disparity and multiple ethnicities, the information transmitted by an integrated measure of intergenerational income mobility is quite limited. Using the method of TS2SLS, this paper estimates the overall and the structure of intergenerational income mobility in recent China. After careful consideration of potential life‐cycle, attenuation and co‐residence biases, our preferred intergenerational income elasticity is 0.41 for father–children and 0.56 for mother–children, which suggests a low level of intergenerational mobility. We then focus on the structure of the mobility regarding age cohort, gender, ethnicity, region, registration type and income percentile. By investigating possible channels, our results show that (a) the role of non‐cognitive characteristics, cognitive abilities, education, occupation and party membership jointly account for nearly 63% of intergenerational transmission, (b) education and occupation are two dominant channels, and (c) non‐cognitive characteristics and cognitive abilities have direct and indirect effects on intergenerational transmission.
Soil carbon persistence governed by plant input and mineral protection at regional and global scales
Authors: Chen Leiyi , Fang Kai , Wei Bin , Qin Shuqi , Feng Xuehui , Hu Tianyu , Ji Chengjun , Yang Yuanhe 
Published: March 2021

AbstractElucidating the processes underlying the persistence of soil organic matter (SOM) is a prerequisite for projecting soil carbon feedback to climate change. However, the potential role of plant carbon input in regulating the multi‐layer SOM preservation over broad geographic scales remains unclear. Based on large‐scale soil radiocarbon (∆14C) measurements on the Tibetan Plateau, we found that plant carbon input was the major contributor to topsoil carbon destabilisation despite the significant associations of topsoil ∆14C with climatic and mineral variables as well as SOM chemical composition. By contrast, mineral protection by iron–aluminium oxides and cations became more important in preserving SOM in deep soils. These regional observations were confirmed by a global synthesis derived from the International Soil Radiocarbon Database (ISRaD). Our findings illustrate different effects of plant carbon input on SOM persistence across soil layers, providing new insights for models to better predict multi‐layer soil carbon dynamics under changing environments.