bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hormone therapy use and the risk of acute kidney injury in patients with prostate cancer: a population-based cohort study
Authors: Cardwell Chris R. , O’Sullivan Joe M. , Jain Suneil , Hicks Blánaid M. , Devine Paul A. , McMenamin Úna C. 
Published: March 2021

Abstract
Background
Hormone therapy is widely used in prostate cancer. However, studies have raised concerns that hormone therapy, particularly the use of gonadotropin-releasing hormone agonists, could increase the risk of acute kidney injury.

Methods
Men newly diagnosed with non-metastatic prostate cancer, from 2012 to 2017, were identified from the Scottish Cancer Registry. A matched comparison cohort of prostate cancer-free men was also identified. Hormone therapy use was determined from the Prescribing Information System in Scotland. The primary outcome was hospitalisations with acute kidney injury taken from Scottish hospital records (SMR01) up to June 2019. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for acute kidney injury by hormone therapy use.

Results
The prostate cancer cohort contained 10,751 patients followed for 41,997 person years, during which there were 618 hospitalisations with acute kidney injury. Prostate cancer patients had higher rates of acute kidney injury compared with cancer-free controls (adjusted HR = 1.47 95% CI 1.29, 1.69). However, prostate cancer patients currently using hormone therapy (adjusted HR = 1.14 95% CI 0.92, 1.41), including gonadotropin-releasing hormone (GnRH) agonists (adjusted HR = 1.13 95% CI 0.90, 1.40), did not appear to have a marked increase in acute kidney injury compared with prostate cancer patients not using hormone therapy after adjusting for potential confounders.

Conclusions
In our cohort, there was little evidence that gonadotropin-releasing hormone agonists were associated with marked increases in acute kidney injury.
MIRLET7BHG promotes hepatocellular carcinoma progression by activating hepatic stellate cells through exosomal SMO to trigger Hedgehog pathway
Authors: Xia Yunhong , Zhen Lu , Li Hongxia , Wang Shuomin , Chen Sun , Wang Chongchong , Yang Xiaoyu 
Published: March 2021

AbstractHepatocellular carcinoma (HCC), commonly caused by liver fibrosis, is a global challenge with high morbidity. Activation of hepatic stellate cells (HSCs) contributes to hepatic fibrosis. Exosomes are small vesicles that play a significant role in cell-to-cell communication. Smoothened (SMO) is the key signal transducer for Hedgehog pathway. This study was designed to study the function and underlying mechanism of SMO in HSC activation. Functional assays including 5-Ethynyl-2´-deoxyuridine, colony formation, wound healing, transwell, and sphere formation assays disclosed the function of SMO. Western blot analysis of exosome biomarkers, immunofluorescence staining assay, electron microscope, and flow cytometry revealed the existence of exosomes. Bioinformatics analyses and mechanistic assays uncovered the interplays between RNAs. Nude mice xenograft model was established to evaluate HCC tumor growth. We uncovered that SMO was an oncogene in HCC cells and was low-expressed in quiescent HSCs. Then, SMO was upregulated in HSCs cultured with HCC cells-conditioned medium. Next, it was revealed that HCC cells-derived exosomes activated HSCs by transmitting SMO to HSCs. Subsequently, we recognized that microRNA let-7b host gene (MIRLET7BHG) served as the competing endogenous RNA against miR-330-5p to upregulate SMO. In turn, SMO induced hedgehog pathway to promote GLI family zinc finger 1 (Gli1), leading to transcriptional activation of MIRLET7BHG in activated HSCs. In summary, this study demonstrated that Gli1-induced MIRLET7BHG facilitated HCC by activating HSCs through exosomal SMO to stimulate hedgehog pathway, providing a new road for HCC treatment.
Development of short and long-range magnetic order in the double perovskite based frustrated triangular lattice antiferromagnet Ba$$_{2}$$MnTeO$$_{6}$$
Authors: Khatua J. , Arh T. , Mishra Shashi B. , Luetkens H. , Zorko A. , Sana B. , Rao M. S. Ramachandra , Nanda B. R. K. , Khuntia P. 
Published: March 2021

AbstractFrustrated magnets based on oxide double perovskites offer a viable ground wherein competing magnetic interactions, macroscopic ground state degeneracy and complex interplay between emergent degrees of freedom can lead to correlated quantum phenomena with exotic excitations highly relevant for potential technological applications. By local-probe muon spin relaxation ($$\mu$$
μ
SR) and complementary thermodynamic measurements accompanied by first-principles calculations, we here demonstrate novel electronic structure and magnetic phases of Ba$$_{2}$$

2

MnTeO$$_{6}$$

6

, where Mn$$^{2+}$$

2
+

ions with S = 5/2 spins constitute a perfect triangular lattice. Magnetization results evidence the presence of strong antiferromagnetic interactions between Mn$$^{2+}$$

2
+

spins and a phase transition at $$T_{N}$$

T
N

= 20 K. Below $$T_{N}$$

T
N

, the specific heat data show antiferromagnetic magnon excitations with a gap of 1.4 K, which is due to magnetic anisotropy. $$\mu$$
μ
SR reveals the presence of static internal fields in the ordered state and short-range spin correlations high above $$T_{N}$$

T
N

. It further unveils critical slowing-down of spin dynamics at $$T_{N}$$

T
N

and the persistence of spin dynamics even in the magnetically ordered state. Theoretical studies infer that Heisenberg interactions govern the inter- and intra-layer spin-frustration in this compound. Our results establish that the combined effect of a weak third-nearest-neighbour ferromagnetic inter-layer interaction (owing to double-exchange) and intra-layer interactions stabilizes a three-dimensional magnetic ordering in this frustrated magnet.
Co-inhibitor expression on tumor infiltrating and splenic lymphocytes after dual checkpoint inhibition in a microsatellite stable model of colorectal cancer
Authors: Slovak Ryan J. , Park Hong-Jai , Kamp William M. , Ludwig Johannes M. , Kang Insoo , Kim Hyun S. 
Published: March 2021

AbstractCheckpoint inhibitors have demonstrated clinical impact in colorectal cancer with deficient mismatch repair and high microsatellite instability. However, the majority of patients have disease with stable microsatellites that responds poorly to immunotherapies. Combinations of checkpoint inhibitors are under investigation as a way of increasing immunogenicity and promoting a robust anti-tumor immune response. The purpose of this study is to quantify the immune responses induced by mono and dual checkpoint inhibition in a mismatch repair proficient model of colorectal cancer (CRC). Tumor growth rates were monitored over time and compared between groups. We utilized fluorescence-activated cell sorting to analyze CD8+ and CD4+ T cells after treatment with either single PD-1 inhibition or dual PD-1 and CTLA-4 inhibition. Additionally, we sought to quantify the expression of co-inhibitory surface molecules PD-1, LAG3, and TIM3. Dual checkpoint inhibition was associated with a significantly slower growth rate as compared to either mono PD-1 inhibition or control (p < 0.05). Neither monotherapy nor dual checkpoint inhibition significantly affected the tumoral infiltration of lymphocytes. After treatment with dual inhibitors, infiltrating CD8+ T cells demonstrated significantly less expression of PD-1 (1700 vs. 2545 and 2462; p < 0.05) and LAG3 (446.2 vs. 694.4 and 707; p < 0.05) along with significantly more expression of TIM3 (12,611 vs. 2961 and 4259; p < 0.05) versus the control and anti-PD-1 groups. These results suggest that dual therapy with anti-CTLA-4 and anti-PD-1 antibodies significantly inhibits growth of microsatellite stable CRC by suppressing immunosuppressive checkpoints. Upregulation of TIM3 represents a potential escape mechanism and a target for future combination immunotherapies in CRC.
Predicting amyloid positivity in patients with mild cognitive impairment using a radiomics approach
Authors: Kim Jun Pyo , Kim Jonghoon , Jang Hyemin , Kim Jaeho , Kang Sung Hoon , Kim Ji Sun , Lee Jongmin , Na Duk L. , Kim Hee Jin , Seo Sang Won , Park Hyunjin 
Published: March 2021

AbstractPredicting amyloid positivity in patients with mild cognitive impairment (MCI) is crucial. In the present study, we predicted amyloid positivity with structural MRI using a radiomics approach. From MR images (including T1, T2 FLAIR, and DTI sequences) of 440 MCI patients, we extracted radiomics features composed of histogram and texture features. These features were used alone or in combination with baseline non-imaging predictors such as age, sex, and ApoE genotype to predict amyloid positivity. We used a regularized regression method for feature selection and prediction. The performance of the baseline non-imaging model was at a fair level (AUC = 0.71). Among single MR-sequence models, T1 and T2 FLAIR radiomics models also showed fair performances (AUC for test = 0.71–0.74, AUC for validation = 0.68–0.70) in predicting amyloid positivity. When T1 and T2 FLAIR radiomics features were combined, the AUC for test was 0.75 and AUC for validation was 0.72 (pvs. baseline model < 0.001). The model performed best when baseline features were combined with a T1 and T2 FLAIR radiomics model (AUC for test = 0.79, AUC for validation = 0.76), which was significantly better than those of the baseline model (p < 0.001) and the T1 + T2 FLAIR radiomics model (p < 0.001). In conclusion, radiomics features showed predictive value for amyloid positivity. It can be used in combination with other predictive features and possibly improve the prediction performance.
Nuclear and cytosolic pS727-STAT3 levels correlate with overall survival of patients affected by clear cell renal cell carcinoma (ccRCC)
Authors: Arévalo Jazmine , Lorente David , Trilla Enrique , Salcedo María Teresa , Morote Juan , Meseguer Anna 
Published: March 2021

AbstractClear cell renal cell carcinoma (ccRCC) is the most frequent and aggressive subtype of renal carcinoma. So far, the basis of its oncogenesis remains unclear resulting in a deficiency of usable and reliable biomarkers for its clinical management. Previously, we showed that nuclear expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated at its serine 727 (pS727), was inversely proportional to the overall survival of ccRCC patients. Therefore, in the present study, we validated the value of pS727-STAT3 as a clinically relevant biomarker in ccRCC. This work is a retrospective study on 82 ccRCC patients treated with nephrectomy and followed-up for 10 years. Immunohistochemical expression of pS727-STAT3 was analyzed on a tissue microarray and nuclear and cytosolic levels were correlated with clinical outcome of patients. Our results showed that pS727-STAT3 levels, whether in the nucleus (p = 0.002; 95% CI 1.004–1.026) or the cytosol (p = 0.040; 95% CI 1.003–1.042), significantly correlate with patients’ survival in an independent-manner of clinicopathological features (Fuhrman grade, risk group, and tumor size). Moreover, we report that patients with high pS727-STAT3 levels who undergone adjuvant therapy exhibited a significant stabilization of the disease (~ 20 months), indicating that pS727-STAT3 can pinpoint a subset of patients susceptible to respond well to treatment. In summary, we demonstrated that high pS727-STAT3 levels (regardless of their cellular location) correlate with low overall survival of ccRCC patients, and we suggested the use of pS727-STAT3 as a prognostic biomarker to select patients for adjuvant treatment to increase their survival.
Phosphoprotein enriched in astrocytes (PEA)-15 is a novel regulator of adipose tissue expansion
Authors: Verschoor Pola J. , Greig Fiona H. , Rochford Justin J. , Levate Giovanni , Delibegovic Mirela , Thompson Dawn , Leeson-Payne Alasdair , Dekeryte Ruta , Banks Ruth , Ramos Joe W. , Nixon Graeme F. 
Published: March 2021

AbstractExcessive expansion of adipose tissue in obesity typically leads to overflow and accumulation of lipids in other tissues, causing fatty liver disease and atherosclerosis. The intracellular protein, phosphoprotein enriched in astrocytes (PEA)-15 has been linked to metabolic disease but its role in lipid storage has not been examined. To delineate the role of PEA-15 in adipose tissue, we placed PEA-15−/− mice on a high fat diet. These mice developed increased body weight and greater white adipose tissue expansion compared to high fat diet-fed wild type mice. This was due to increased adipocyte cell size in PEA-15−/− mice consistent with greater lipid storage capacity. Surprisingly, PEA-15−/− mice exhibited improvements in whole body insulin sensitivity, lower hepatic weight and decreased serum triglycerides indicating a protective phenotype. To determine effects on atherosclerosis, PEA-15−/− mice were crossed with the ApoE−/− mice on a high fat diet. Strikingly, these mice were protected from atherosclerosis and had less hepatic lipid accumulation despite increased adiposity. Therefore, we reveal for the first time that PEA-15 plays a novel role in regulating the expansion of adipose tissue. Decreasing PEA-15 expression increases the sequestering of lipids in adipose tissue, protecting other tissues in obesity, thereby improving metabolic health.
Comparing survival outcomes for cervical cancer based on the 2014 and 2018 International Federation of Gynecology and Obstetrics staging systems
Authors: Shin Wonkyo , Ham Tae Young , Park Young Ran , Lim Myong Cheol , Won Young-Joo 
Published: March 2021

AbstractThe International Federation of Gynecology and Obstetrics (FIGO) cervical cancer staging system was modified in 2018, introducing new stage IB subdivisions and new lymph node status considerations in stage IIIC. We compared cervical cancer survival outcomes according to the 2014 and 2018 FIGO staging systems. We selected 10% of cervical cancer cases (2010–2015) from the Korean national cancer registry (2010–2015) through a systematic sampling method. We collected information using a collaborative stage data collection system and evaluated the results according to both staging systems. The log-rank test was used to analyze overall survival differences. No significant difference in survival was observed between 2018 subdivisions IB1/IB2/IB3 (P = 0.069), whereas a considerable difference was observed between these subdivisions according to histological subtypes. In the 2018 FIGO staging system, stage IIIC had better survival than stage IIIA/IIIB (P < 0.001). We observed considerable heterogeneity in 2018 stage IIIC related to the corresponding stages of the 2014 staging system (stages IA1–IIIB). The size of the primary cervical mass was related to survival (P < 0.001). In conclusion, using lymph node status to define stage IIIC captured a broad range of prognoses. The inclusion of primary tumor size considerations may improve the staging accuracy of advanced cervical cancer.
Associations of pathological diagnosis and genetic abnormalities in meningiomas with the embryological origins of the meninges
Authors: Okano Atsushi , Miyawaki Satoru , Hongo Hiroki , Dofuku Shogo , Teranishi Yu , Mitsui Jun , Tanaka Michihiro , Shin Masahiro , Nakatomi Hirofumi , Saito Nobuhito 
Published: March 2021

AbstractCertain driver mutations and pathological diagnoses are associated with the anatomical site of meningioma, based on which the meninges have different embryological origins. We hypothesized that mutations and pathological diagnoses of meningiomas are associated with different embryological origins. We comprehensively evaluated associations among tumor location, pathological diagnosis (histological type), and genetic alterations including AKT1, KLF4, SMO, POLR2A, and NF2 mutations and 22q deletion in 269 meningioma cases. Based on the embryological origin of meninges, the tumor locations were as follows: neural crest, paraxial mesodermal, and dorsal mesodermal origins. Tumors originating from the dura of certain embryologic origin displayed a significantly different pathological diagnoses and genetic abnormality ratio. For instance, driver genetic mutations with AKT1, KLF4, SMO, and POLR2A, were significantly associated with the paraxial mesodermal origin (p = 1.7 × 10−10). However, meningiomas with NF2-associated mutations were significantly associated with neural crest origin (p = 3.9 × 10–12). On analysis of recurrence, no difference was observed in embryological origin. However, POLR2A mutation was a risk factor for the tumor recurrence (p = 1.7 × 10−2, Hazard Ratio 4.08, 95% Confidence Interval 1.28–13.0). Assessment of the embryological origin of the meninges may provide novel insights into the pathomechanism of meningiomas.
Properties of assembly of superparamagnetic nanoparticles in viscous liquid
Authors: Usov N. A. , Rytov R. A. , Bautin V. A. 
Published: March 2021

AbstractDetailed calculations of the specific absorption rate (SAR) of a dilute assembly of iron oxide nanoparticles with effective uniaxial anisotropy dispersed in a liquid are performed depending on the particle diameters, the alternating (ac) magnetic field amplitude H0 and the liquid viscosity. For small and moderate H0 values with respect to particle anisotropy field Hk the SAR of the assembly as a function of the particle diameter passes through a characteristic maximum and then reaches a plateau, whereas for sufficiently large amplitudes, H0 ~ Hk, the SAR increases monotonically as a function of diameter. The realization of viscous and magnetic oscillation modes for particle unit magnetization vector and director for moderate and sufficiently large H0 values, respectively, explains this behavior. It is found that the SAR of the assembly changes inversely with the viscosity only in a viscous mode, for nanoparticles of sufficiently large diameters. In the magnetic mode the SAR of the assembly is practically independent of the viscosity, since in this case the nanoparticle director only weakly oscillates around the ac magnetic field direction. The conditions for the validity of the linear response theory have been clarified by comparison with the numerical simulation data.
Vortex trapping recaptures energy in flying fruit flies
Authors: Lehmann Fritz-Olaf , Wang Hao , Engels Thomas 
Published: March 2021

AbstractFlapping flight is one of the most costly forms of locomotion in animals. To limit energetic expenditures, flying insects thus developed multiple strategies. An effective mechanism to reduce flight power expenditures is the harvesting of kinetic energy from motion of the surrounding air. We here show an unusual mechanism of energy harvesting in an insect that recaptures the rotational energy of air vortices. The mechanism requires pronounced chordwise wing bending during which the wing surface momentary traps the vortex and transfers its kinetic energy to the wing within less than a millisecond. Numerical and robotic controls show that the decrease in vortex strength is minimal without the nearby wing surface. The measured energy recycling might slightly reduce the power requirements needed for body weight support in flight, lowering the flight costs in animals flying at elevated power demands. An increase in flight efficiency improves flight during aversive manoeuvring in response to predation and long-distance migration, and thus factors that determine the worldwide abundance and distribution of insect populations.
Using carpet plots to analyze transit times of low frequency oscillations in resting state fMRI
Authors: Fitzgerald Bradley , Yao Jinxia Fiona , Talavage Thomas M. , Hocke Lia M. , Frederick Blaise deB , Tong Yunjie 
Published: March 2021

AbstractA “carpet plot” is a 2-dimensional plot (time vs. voxel) of scaled fMRI voxel intensity values. Low frequency oscillations (LFOs) can be successfully identified from BOLD fMRI and used to study characteristics of neuronal and physiological activity. Here, we evaluate the use of carpet plots paired with a developed slope-detection algorithm as a means to study LFOs in resting state fMRI (rs-fMRI) data with the help of dynamic susceptibility contrast (DSC) MRI data. Carpet plots were constructed by ordering voxels according to signal delay time for each voxel. The slope-detection algorithm was used to identify and calculate propagation times, or “transit times”, of tilted vertical edges across which a sudden signal change was observed. We aim to show that this metric has applications in understanding LFOs in fMRI data, possibly reflecting changes in blood flow speed during the scan, and for evaluating alternative blood-tracking contrast agents such as inhaled CO2. We demonstrate that the propagations of LFOs can be visualized and automatically identified in a carpet plot as tilted lines of sudden intensity change. Resting state carpet plots produce edges with transit times similar to those of DSC carpet plots. Additionally, resting state carpet plots indicate that edge transit times vary at different time points during the scan.
Biological effects of biochar and zeolite used for remediation of soil contaminated with toxic heavy metals
Authors: Głąb Tomasz , Gondek Krzysztof , Mierzwa–Hersztek Monika 
Published: March 2021

AbstractBiochar and zeolite are widely used in the remediation of soil contaminated with toxic heavy metals. However, the interaction of these amendments and their effects on grass productivity have not been comprehensively summarized. The aim of this study was to investigate the biological effects of zeolite and biochar used as soil amendments in the process of remediating soil contaminated with Cd, Pb and Zn. In a pot experiment, the following treatments were applied: zeolite, biochars produced at temperatures of 350 °C and 550 °C, mixtures of biochars and zeolite, and a control treatment without any amendments. The soil amendments were tested on two grass species: tall fescue (Festuca arundinacea Schreb.) and cocksfoot (Dactylis glomerata L.). The root morphometric parameters and aboveground production were determined in 2017 and 2018.Higher biomass production was observed in the tested grasses in the treatments with zeolite alone (0.229 kg DM m−2) or mixed with the biochars (0.239 kg DM m−2) than in control treatment (0.029 kg DM m−2). Zeolite used in contaminated soil significantly affected root biomass and root morphology parameters. Zeolite application resulted in significantly higher root biomass (2.30 mg cm−3) and root length (76.61 cm cm−3) than those in the treatments without zeolite (0.29 mg cm−3 and 6.90 cm cm−3). Biochar as a soil amendment did not affect most root morphometric parameters. The application of biochars only slightly reduced the root diameter of cocksfoot. The root diameter of tall fescue was similar in all treatments (0.075 mm) except the control (0.063 mm) and biochar 550 treatments (0.067 mm), in which slightly thinner roots were observed.