bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between Proton Pump Inhibitor Use and Biliary Tract Cancer Risk: A Swedish Population‐Based Cohort Study
Authors: Kamal Habiba , Sadr‐Azodi Omid , Engstrand Lars , Brusselaers Nele 
Published: May 2021

Background and Aims
Biliary tract cancer is a group of highly aggressive malignant disorders, yet risk factors are poorly understood. In this study, we aim to assess whether prolonged use of proton pump inhibitors (PPIs) increases the risk of incident biliary tract carcinoma in a nation‐wide population‐based cohort in Sweden.

Approach and Results
Using nation‐wide registries, we identified all adults who received maintenance PPIs (≥180 days) according to the Swedish Prescribed Drug Register from 2005 through 2012. Data on incident biliary tract cancer were retrieved from the Swedish Cancer, Death and Outpatient Registers. Risk of biliary tract cancer in persons who received PPI treatment was compared with the general population of the corresponding age, sex, and calendar year yielding standardized incidence ratios (SIRs) with 95% CIs. Of 738,881 PPI users (median follow‐up of 5.3 years), 206 (0.03%) developed gallbladder cancer and 265 (0.04%) extrahepatic and 131 (0.02%) intrahepatic bile duct cancer corresponding to SIRs of 1.58 (95% CI, 1.37‐1.81), 1.77 (95% CI, 1.56‐2.00), and 1.88 (95% CI, 1.57‐2.23), respectively. In sensitivity analyses restricted to persons without a history of gallstones or chronic liver or pancreatic diseases, SIRs were 1.36 (95% CI, 1.17‐1.57) and 1.47 (95% CI, 1.19‐1.80) for extra‐ and intrahepatic duct cancer, respectively. The risk remained higher than the corresponding general population with ≥5 years of PPIs use, ruling out confounding by indication.

Conclusions
In this study, long‐term use of PPIs was associated with an increased risk of gallbladder, intrahepatic, and extrahepatic bile duct cancer compared with the general population.
Numerical solution for Sisko nanofluid flow through stretching surface in a Darcy–Forchheimer porous medium with thermal radiation
Authors: Upreti Himanshu , Joshi Navneet , Pandey Alok K. , Rawat Sawan K. 
Published: May 2021

AbstractThe heat transfer assessments in a Sisko nanofluid flow over a stretching surface in a Darcy–Forchheimer porous medium with heat generation and thermal radiation are studied. The numerical analysis technique is used to assess the governing nonlinear equations of the model. The influence of Forchheimer number, porosity, heat generation, radiation, and material parameters is examined. The outlines of Nusselt number and skin friction coefficient corresponding to pertinent parameters are revealed. The comparison of Nusselt number outlines of working fluid and Newtonian fluid is depicted. From the analysis, it has been examined that with the increase in Forchheimer number and material parameter values, heat transfer function decreases, whereas heat transfer characteristics of Sisko nanofluid increase with heat generation and material parameters. Moreover, working fluid velocity outlines depreciate when there is an increase in porosity parameter for both shear‐thinning and shear‐thickening. The comparison of this study with previous research has been conducted.
Soil moisture influenced the variability of air temperature and oasis effect in a large inland basin of an arid region
Authors: Hao Xingming , Hao Haichao , Zhang Jingjing 
Published: May 2021

AbstractSoil moisture plays a significant role in land‐atmosphere interactions. Changing fractions of latent and sensible heat fluxes caused by soil moisture variations can affect near‐surface air temperature, thus influencing the oasis's cooling effect in arid regions. In this study, the framework for the evaporative fraction (EF) dependence on soil moisture is used to analyse the impacts of soil moisture variation on near‐surface air temperature and the oasis effect. The result showed that soil moisture's contribution rate to EF was significantly higher than that of EF to temperature. Under the interaction of temperature sensitivity to EF and EF to soil moisture, the ∂T/∂ϴ presented a similar tempo‐spatial variation with both of the above. It was most significant in oasis areas during summer (−1.676), while it was weaker in plain desert areas during the autumn (−0.071). In the study region, the effect of soil moisture variation on air temperature can reach 0.018–0.242 K for different land‐cover types in summer. The maximum variation of soil moisture in summer can alter air temperature by up to 0.386 K. The difference in temperature variability between the oasis and desert areas promoted the formation of the oasis effect. For different oasis, the multi‐year average oasis cold effect index (OCI) ranged from −1.36 to −0.26 K. In comparison, the average summer OCI ranged from −1.38 to −0.29 K. The lower bound of the cooling effect of oasis ranged from −4.97 to −1.69 K. The analysis framework and results of this study will provide a new perspective for further research on the evolution process of the oasis effect and water–heat balance in arid areas.
A feasibility study of a portable intraoperative specimen imaging X‐ray system based on carbon nanotube field emitters
Authors: Gupta Amar Prasad , Yeo Seung Jun , Mativenga Mallory , Jung Jaeik , Kim Wooseob , Lim Jongmin , Park Junyoung , Ahn Jeung Sun , Kim Seung Hoon , Chae Moon Shik , Yeon Yeong Heum , Kim Namkug , Ko Beom‐Seok , Ryu Jehwang 
Published: May 2021

AbstractsWhen breast cancer is surgically removed, a rim of normal tissue surrounding the tumor is also removed. This rim of normal tissue is called a margin and is studied by a pathologist to determine whether or not all tumor was removed. The pathologist achieves this by cutting the surgically removed tissue into thin slices and observing each slice under a microscope. This process is time‐consuming. Here, we investigate the feasibility of using a portable carbon nanotube (CNT)‐based X‐ray system for in situ detection of the presence of tumor cells in the surgical margin. Using the proposed technique, we successfully obtain X‐ray images, which clearly show cancer masses and microcalcifications. This feasibility study shows that portable CNT‐based X‐ray systems are promising candidates for next‐generation in situ pathological examinations.
Regional gene therapy for bone healing using a 3D printed scaffold in a rat femoral defect model
Authors: Kang H Paco , Ihn Hansel , Robertson Djani M , Chen Xiao , Sugiyama Osamu , Tang Amy , Hollis Roger , Skorka Tautis , Longjohn Donald , Oakes Daniel , Shah Ramille , Kohn Donald , Jakus Adam E , Lieberman Jay R 
Published: May 2021

AbstractAt the present time there are no consistently satisfactory treatment options for some challenging bone loss scenarios. We have previously reported on the properties of a novel 3D‐printed hydroxyapatite‐composite material in a pilot study, which demonstrated osteoconductive properties but was not tested in a rigorous, clinically relevant model. We therefore utilized a rat critical‐sized femoral defect model with a scaffold designed to match the dimensions of the bone defect. The scaffolds were implanted in the bone defect after being loaded with cultured rat bone marrow cells (rBMC) transduced with a lentiviral vector carrying the cDNA for BMP‐2. This experimental group was compared against 3 negative and positive control groups. The experimental group and positive control group loaded with rhBMP‐2 demonstrated statistically equivalent radiographic and histologic healing of the defect site (p > 0.9), and significantly superior to all three negative control groups (p < 0.01). However, the healed defects remained biomechanically inferior to the unoperated, contralateral femurs (p < 0.01). When combined with osteoinductive signals, the scaffolds facilitate new bone formation in the defect. However, the scaffold alone was not sufficient to promote adequate healing, suggesting that it is not substantially osteoinductive as currently structured. The combination of gene therapy with 3D‐printed scaffolds is quite promising, but additional work is required to optimize scaffold geometry, cell dosage and delivery.
Modifying the catalytic preference of alpha‐amylase toward n‐alkanes for bioremediation purposes using in silico strategies
Authors: Pinto Éderson Sales Moreira , Feltes Bruno César , Pedebos Conrado , Dorn Márcio 
Published: May 2021

AbstractSince the beginning of oil exploration, whole ecosystems have been affected by accidents and bad practices involving petroleum compounds. In this sense, bioremediation stands out as the cheapest and most eco‐friendly alternatives to reverse the damage done in oil‐impacted areas. However, more efforts must be made to engineer enzymes that could be used in the bioremediation process. Interestingly, a recent work described that α‐amylase, one of the most evolutionary conserved enzymes, was able to promiscuously degrade n‐alkanes, a class of molecules abundant in the petroleum admixture. Considering that α‐amylase is expressed in almost all known organisms, and employed in numerous biotechnological processes, using it can be a great leap toward more efficient applications of enzyme or microorganism‐consortia bioremediation approaches. In this work, we employed a strict computational approach to design new α‐amylase mutants with potentially enhanced catalytic efficiency toward n‐alkanes. Using in silico techniques, such as molecular docking, molecular dynamics, metadynamics, and residue–residue interaction networks, we generated mutants potentially more efficient for degrading n‐alkanes, L183Y, and N314A. Our results indicate that the new mutants have an increased binding rate for tetradecane, the longest n‐alkane previously tested, which can reside in the catalytic center for more extended periods. Additionally, molecular dynamics and network analysis showed that the new mutations have no negative impact on protein structure than the WT. Our results aid in solidifying this enzyme as one more tool in the petroleum bioremediation toolbox.
Effect of miR‐630 expression on esophageal cancer cell invasion and migration
Authors: Liu Xi , Wu Wei , Zhang Shixin , Tan Wenfeng , Qiu Yang , Liao Kelong , Yang Kang 
Published: May 2021

AbstractBackgroundEsophageal cancer (EC) is a common malignancy of the digestive tract, with high incidence. The objective of this study was to investigate the effect of miR‐630 expression on esophageal cancer (EC) cell invasion and migration.MethodsThe study group comprised 58 EC patients admitted to our hospital from April 2014 to 2016, and the control group comprised 60 healthy people visiting the hospital during the same period. miR‐630 levels in the peripheral blood of the two groups were compared, and the diagnostic value of miR‐630 for EC was analyzed. EC cell lines were used to evaluate the influence of miR‐630 expression on EC cell invasion and migration.ResultsmiR‐630 expression was low in EC (p < 0.050). A receiver operating characteristic curve analysis showed that miR‐630 expression had a good diagnostic value for EC (p < 0.050) and was associated with disease course, pathological stage, differentiation degree, tumor metastasis, and patient prognosis and survival (p < 0.05). The ROC curve analysis showed that when cutoff value was 5.38, the diagnostic sensitivity and specificity of miR‐630 for EC were 73.33% and 76.67%, respectively; area under the ROC curve was 0.778 (95%CI 0.695–0.861). Transfection of miR‐630 into EC cells indicated that miR‐630 overexpression can reduce EC cell invasion and migration (p < 0.05). miR‐630 expression is low in EC and has good diagnostic value for EC.ConclusionmiR‐630 overexpression can reduce EC cell invasion and migration, showing a possible key role of miR‐630 in EC diagnosis and treatment in the future.
FASCIN regulates actin assembly for spindle movement and polar body extrusion in mouse oocyte meiosis
Authors: Hu Lin‐Lin , Pan Meng‐Hao , Yang Feng‐Lian , Zong Zi‐Ao , Tang Feng , Pan Zhen‐Nan , Lu Xiang , Ren Yan‐Ping , Wang Jun‐Li , Sun Shao‐Chen 
Published: May 2021

AbstractDuring mouse oocyte meiotic maturation, actin filaments play multiple roles in meiosis such as spindle migration and cytokinesis. FASCIN is shown to be an actin‐binding and bundling protein, making actin filaments tightly packed and parallel‐aligned, and FASCIN is involved in several cellular processes like adhesion and migration. FASCIN is also a potential prognostic biomarker and therapeutic target for the treatment of metastatic disease. However, little is known about the functions of FASCIN in oocyte meiosis. In the present study, we knocked down the expression of FASCIN, and our results showed that FASCIN was essential for oocyte maturation. FASCIN was all expressed in the different stages of oocyte meiosis, and it mainly localized at the cortex of oocytes from the GV stage to the MII stage and showed a similar localization pattern with actin and DAAM1. Depletion of FASCIN affected the extrusion of the first polar body, and we also observed that some oocytes extruded from the large polar bodies. This might have resulted from the defects of actin assembly, which further affected the meiotic spindle positioning. In addition, we showed that inhibition of PKC activity decreased FASCIN expression, indicating that FASCIN might be regulated by PKC. Taken together, our results provided evidence for the important role of FASCIN on actin filaments for spindle migration and polar body extrusion in mouse oocyte meiosis.
Perivascular cell‐derived extracellular vesicles stimulate colorectal cancer revascularization after withdrawal of antiangiogenic drugs
Authors: Huang Maohua , Chen Minfeng , Qi Ming , Ye Geni , Pan Jinghua , Shi Changzheng , Yang Yunlong , Zhao Luyu , Mo Xukai , Zhang Yiran , Li Yong , Zhong Jincheng , Lu Weijin , Li Xiaobo , Zhang Jiayan , Lin Jinrong , Luo Liangping , Liu Tongzheng , Tang Patrick Ming‐Kuen , Hong An , Cao Yihai , Ye Wencai , Zhang Dongmei 
Published: May 2021

AbstractAntiangiogenic tyrosine kinase inhibitors (AA‐TKIs) have become a promising therapeutic strategy for colorectal cancer (CRC). In clinical practice, a significant proportion of cancer patients temporarily discontinue AA‐TKI treatment due to recurrent toxicities, economic burden or acquired resistance. However, AA‐TKI therapy withdrawal‐induced tumour revascularization frequently occurs, hampering the clinical application of AA‐TKIs. Here, this study demonstrates that tumour perivascular cells mediate tumour revascularization after withdrawal of AA‐TKI therapy. Pharmacological inhibition and genetic ablation of perivascular cells largely attenuate the rebound effect of CRC vascularization in the AA‐TKI cessation experimental settings. Mechanistically, tumour perivascular cell‐derived extracellular vehicles (TPC‐EVs) contain Gas6 that instigates the recruitment of endothelial progenitor cells (EPCs) for tumour revascularization via activating the Axl pathway. Gas6 silence and an Axl inhibitor markedly inhibit tumour revascularization by impairing EPC recruitment. Consequently, combination therapy of regorafenib with the Axl inhibitor improves overall survival in mice metastatic CRC model by inhibiting tumour growth. Together, these data shed new mechanistic insights into perivascular cells in off‐AA‐TKI‐induced tumour revascularization and indicate that blocking the Axl signalling may provide an attractive anticancer approach for sustaining long‐lasting angiostatic effects to improve the therapeutic outcomes of antiangiogenic drugs in CRC.
Human d‐lactate dehydrogenase deficiency by LDHD mutation in a patient with neurological manifestations and mitochondrial complex IV deficiency
Authors: Kwong Anna Ka‐Yee , Wong Sheila Suet‐Na , Rodenburg Richard J. T. , Smeitink Jan , Chan Godfrey Chi Fung , Fung Cheuk‐Wing 
Published: May 2021

AbstractBackgroundd‐lactate, one of the isomers of lactate, exists in a low concentration in healthy individuals and it can be oxidized to pyruvate catalyzed by d‐lactate dehydrogenase. Excessive amount of d‐lactate causes d‐lactate acidosis associated with neurological manifestations.Methods and ResultsWe report here a patient with developmental delay, cerebellar ataxia, and transient hepatomegaly. Enzyme analysis in the patient's skin fibroblast showed decreased mitochondrial complex IV activity. Using whole exome sequencing, we identified compound heterozygous variants in the LDHD gene, which encodes the d‐lactate dehydrogenase, consisting of a splice site variant c.469+1dupG and a missense variant c.752C>T, p.(Thr251Met) which are pathogenic and likely pathogenic respectively according to the American College of Medical Genetics and Genomics (ACMG) classification. The serum d‐lactate level was subsequently detected to be elevated (0.61 mmol/L, reference value: 0‐0.25 mmol/L).ConclusionThis is the third report on LDHD mutations associated with d‐lactate elevation and was first reported to have decreased mitochondrial complex IV activity. The study provides more information on this rare metabolic condition but the association of LDHD deficiency with the clinical presentations requires further investigations.
Uncertainty of central China summer precipitation and related natural internal variability under global warming of 1 to 3°C
Authors: Li Zhibo , Chen Wen , Chen Shangfeng , Sun Ying , Qian Danlei 
Published: May 2021

AbstractThis study examines the response of summer precipitation over central China to global warming via the 50‐member large‐ensemble simulations conducted with the Canadian Earth System Model Version 2. It is found that the model ensemble mean summer precipitation stagnates under warming of 1 to 3°C, while precipitation increases rapidly over central China after 3°C of warming. This phenomenon indicates a strong nonlinear relationship between precipitation change and global warming, and the effects due to natural internal variability are more substantial than those of CO2 forcing in the early warming stage. We further examine the factors responsible for the large uncertainty of the precipitation projection over central China under warming of 1 to 3°C. For the members producing a precipitation increase over central China, the geopotential height and sea level pressure changes show a positive North Atlantic Oscillation–like trend pattern over the North Atlantic and a southeastward propagating atmospheric teleconnection from the North Atlantic to China. The atmospheric teleconnection from the mid–high‐latitude Atlantic to China provides diverging winds in the upper troposphere, causing ascending motion, and contributes to increased precipitation over central China. Besides, an El Niño‐like trend pattern of sea surface temperature (SST) is apparent in the preceding winter, which could contribute to the formation a low‐level anticyclone trend over the western North Pacific (WNP) in the subsequent summer via modulating the SST anomalies in the Indian and Atlantic oceans. The northward water vapour transport in the western part of the anticyclone also favours increased precipitation in central China. The above processes also apply to decreased precipitation, except with opposite signs of anomalies. This study highlights the combined contributions of mid–high‐latitude teleconnection and the WNP anticyclone related to tropical Pacific SST to the uncertainty in the projection of precipitation over central China.
The drivers of extreme rainfall event timing in Australia
Authors: Dey Raktima , Bador Margot , Alexander Lisa V. , Lewis Sophie C. 
Published: May 2021

AbstractAustralia experiences some of the world's most variable rainfall. Previous studies have mostly focused on understanding rainfall variability in terms of frequency and intensity. However, understanding the timing of when extreme rainfall occurs is crucial for seasonal prediction, although it largely remains unexplored. Here we investigate the timing of extreme rainfall in Australia and the spatial variability of this timing. This study examines how some of the large‐scale drivers, such as the El Niño–Southern Oscillation (ENSO) and the Interdecadal Pacific Oscillation (IPO), determine the timing and interannual variability of the timing of extreme rainfall in Australia. Our results show that there is a clear spatial north–south delineation in the season when extreme rainfall occurs in Australia, shown by a contour diagonally extending roughly from 21°S in the west of Australia to 33°S in the east. North of this contour, extreme rainfall usually occurs in austral summer, with the smallest interannual variability in the timing of extreme rainfall in this region. In the south, extreme rainfall usually occurs in autumn/winter months; however, the timing is highly variable. In southeast Australia (SEA), extreme rainfall can fall at any time of the year, which makes seasonal prediction extremely challenging for this region. Both observation and reanalysis data show that the area where extreme rainfall occurs in summer extends further south during negative IPO years. We also find that IPO and ENSO phases, and the interaction between them, play significant roles in both determining the timing of extreme rainfall and constraining the interannual variability, especially in SEA. We focus on SEA for further analysis as this region shows the greatest shift in seasonality of extremes in response to large‐scale variability. We conclude that studying the relationship between rainfall and large‐scale drivers is important for verification and improvement of the seasonal prediction of extreme rainfall.
Comparison of methods for filling in gaps in monthly rainfall series in arid regions
Authors: Abu Romman Zeinab , Al‐Bakri Jawad , Al Kuisi Mustafa 
Published: May 2021

AbstractFull and reliable rainfall data are required for hydrological modelling, integrated water resource management, and planning. However, these data suffer from record gaps and sparse rain gage distribution, which implies that the use of an imputation method is crucial. This study aims to compare the outputs from 10 imputation methods that were used to infill missing rainfall depth data (MRD) in an arid Mediterranean region. Different statistical tests were used to assess the outputs from the imputation methods. The results showed that for MRD ranges between 5 and 20% the stepwise multiple linear regression (MLRsw) method was valid and produced the best results with a root‐mean‐square error (RSME) and mean absolute error (MAE) of less than 7 and 2 mm, respectively. This was followed by the Monte Carlo Markov chain expectation–maximization‐based multiple imputation (MI‐MCMC) method, which had an RSME and MAE of 1.01 and 0.08 mm, respectively, at 20% MRD. On the other hand, the use of satellite data for imputation (LR_GPCC estimates) was appropriate for MRD ranging between 10 and 15%, while the statistical and spatial method was suitable for MRD of less than 5%.