bluuebunny/crossref_metadata_2025 huggingface dataset:
L-type amino acid transporter 1 is associated with chemoresistance in breast cancer via the promotion of amino acid metabolism
Authors: Sato Miku , Harada-Shoji Narumi , Toyohara Takafumi , Soga Tomoyoshi , Itoh Masatoshi , Miyashita Minoru , Tada Hiroshi , Amari Masakazu , Anzai Naohiko , Furumoto Shozo , Abe Takaaki , Suzuki Takashi , Ishida Takanori , Sasano Hironobu
Published: January 2021

18F-FDG PET/CT has been used as an indicator of chemotherapy effects, but cancer cells can remain even when no FDG uptake is detected, indicating the importance of exploring other metabolomic pathways. Therefore, we explored the amino acid metabolism, including L-type amino acid transporter-1 (LAT1), in breast cancer tissues and clarified the role of LAT1 in therapeutic resistance and clinical outcomes of patients. We evaluated LAT1 expression before and after neoadjuvant chemotherapy and examined the correlation of glucose uptake using FDG-PET with the pathological response of patients. It revealed that LAT1 levels correlated with proliferation after chemotherapy, and amino acid and glucose metabolism were closely correlated. In addition, LAT1 was considered to be involved in treatment resistance and sensitivity only in luminal type breast cancer. Results of in vitro analyses revealed that LAT1 promoted amino acid uptake, which contributed to energy production by supplying amino acids to the TCA cycle. However, in MCF-7 cells treated with chemotherapeutic agents, oncometabolites and branched-chain amino acids also played a pivotal role in energy production and drug resistance, despite decreased glucose metabolism. In conclusion, LAT1 was involved in drug resistance and could be a novel therapeutic target against chemotherapy resistance in luminal type breast cancer.
GATA3 somatic mutations are associated with clinicopathological features and expression profile in TCGA breast cancer patients
Authors: Afzaljavan Fahimeh , Sadr Ayeh Sadat , Savas Sevtap , Pasdar Alireza
Published: January 2021

The effect of somatic mutations and the gene expression profiles on the prognosis is well documented in cancer research. This study was conducted to evaluate the association of GATA3 somatic mutations with tumor features, survival, and expression profiles in breast cancer. Clinicopathological information was compared between TCGA-BRCA patients with GATA3-mutant and non-mutant tumors in all patients as well as in ER-positive subgroup. Cox-regression method was used to evaluate the association of the GATA3 mutation status with overall survival time. Differential gene expression, functional annotation, and protein–protein interaction analyses were performed using edgeR, Metascape, DAVID, STRING and CytoNCA. GATA3-mutant and non-mutant samples had significantly different clinicopathological features (p < 0.05). While GATA3 mutation status was not associated with the overall survival in the entire cohort (padj = 0.52), the GATA3-wild type ER-positive cases had a better prognosis than mutant ones (padj = 0.04). GATA3 expression was higher in tumors than normal tissues. Several pathways were different between mutant and non-mutant groups (p < 0.05). Interleukin-6 was found as the highest scored gene in both comparisons (normal vs. mutant and normal vs. non-mutant groups) in the entire patient and in the ER-positive subgroup, suggesting the association of IL6 with breast tumorigenesis. These findings suggest that GATA3 mutations can be associated with several tumor characteristics and influence the pattern of gene expression. However, GATA3 mutation status seems to be a prognostic factor for the disease only in ER-positive patients.
LECT2 as a hepatokine links liver steatosis to inflammation via activating tissue macrophages in NASH
Authors: Takata Noboru , Ishii Kiyo-aki , Takayama Hiroaki , Nagashimada Mayumi , Kamoshita Kyoko , Tanaka Takeo , Kikuchi Akihiro , Takeshita Yumie , Matsumoto Yukako , Ota Tsuguhito , Yamamoto Yasuhiko , Yamagoe Satoshi , Seki Akihiro , Sakai Yoshio , Kaneko Shuichi , Takamura Toshinari
Published: January 2021

It remains unclear how hepatic steatosis links to inflammation. Leukocyte cell-derived chemotaxin 2 (LECT2) is a hepatokine that senses fat in the liver and is upregulated prior to weight gain. The aim of this study was to investigate the significance of LECT2 in the development of nonalcoholic steatohepatitis (NASH). In human liver biopsy samples, elevated LECT2 mRNA levels were positively correlated with body mass index (BMI) and increased in patients who have steatosis and inflammation in the liver. LECT2 mRNA levels were also positively correlated with the mRNA levels of the inflammatory genes CCR2 and TLR4. In C57BL/6J mice fed with a high-fat diet, mRNA levels of the inflammatory cytokines Tnfa and Nos2 were significantly lower in Lect2 KO mice. In flow cytometry analyses, the number of M1-like macrophages and M1/M2 ratio were significantly lower in Lect2 KO mice than in WT mice. In KUP5, mouse kupffer cell line, LECT2 selectively enhanced the LPS-induced phosphorylation of JNK, but not that of ERK and p38. Consistently, LECT2 enhanced the LPS-induced phosphorylation of MKK4 and TAB2, upstream activators of JNK. Hepatic expression of LECT2 is upregulated in association with the inflammatory signature in human liver tissues. The elevation of LECT2 shifts liver residual macrophage to the M1-like phenotype, and contributes to the development of liver inflammation. These findings shed light on the hepatokine LECT2 as a potential therapeutic target that can dissociate liver steatosis from inflammation.
Effect of silibinin capsules combined with lifestyle modification on hepatic steatosis in patients with chronic hepatitis B
Authors: Lv Duo-Duo , Wang You-Juan , Wang Meng-Lan , Chen En-Qiang , Tao Ya-Chao , Zhang Dong-Mei , Tang Hong
Published: January 2021

The coexistence of HBV infection and hepatic steatosis is a novel characteristic of liver disease. Silibinin capsules (SC) is a silybin-phospholipid complex containing silybin as the bioactive component, which exerts a remarkable biological effect on various liver diseases, including nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to investigate (1) the prevalence of hepatic steatosis in the general population and patients with chronic hepatitis B (CHB) and (2) to evaluate the effect of SC combined with therapeutic lifestyle changes (TLC) compared with TLC alone on hepatic steatosis in patients with CHB. A total of 16,451 individuals underwent transient elastography (TE) with the control attenuation parameter (CAP) measurement, among which the prevalence of hepatic steatosis was 31.1% in patients with CHB and 42.2% in the general population. The prevalence of hepatic steatosis differed between patients with CHB and the general population at an age of 40 years or older but was similar in individuals aged 39 years or younger (p < 0.05). Furthermore, in patients with CHB presenting hepatic steatosis, the post-6-month relative reduction in CAP in the SC combined with TLC group (p = 0.001) was significantly greater than in the TLC alone group (p = 0.183). The CAP distribution of different steatosis grades (S1, S2, and S3) in the SC combined with TLC group was decreased and S0 (CAP < 248 dB/m) increased significantly, but not significant in the TLC group. Thus, SC combined with TLC may effectively improve hepatic steatosis in patients with CHB.
Ketogenic diet effects on inflammatory allodynia and ongoing pain in rodents
Authors: Ruskin David N. , Sturdevant Isabella C. , Wyss Livia S. , Masino Susan A.
Published: January 2021

Ketogenic diets are very low carbohydrate, high fat, moderate protein diets used to treat medication-resistant epilepsy. Growing evidence suggests that one of the ketogenic diet’s main mechanisms of action is reducing inflammation. Here, we examined the diet’s effects on experimental inflammatory pain in rodent models. Young adult rats and mice were placed on the ketogenic diet or maintained on control diet. After 3–4 weeks on their respective diets, complete Freund’s adjuvant (CFA) was injected in one hindpaw to induce inflammation; the contralateral paw was used as the control. Tactile sensitivity (von Frey) and indicators of spontaneous pain were quantified before and after CFA injection. Ketogenic diet treatment significantly reduced tactile allodynia in both rats and mice, though with a species-specific time course. There was a strong trend to reduced spontaneous pain in rats but not mice. These data suggest that ketogenic diets or other ketogenic treatments might be useful treatments for conditions involving inflammatory pain.
Effect of postoperative corticosteroids on surgical outcome and aqueous autotaxin following combined cataract and microhook ab interno trabeculotomy
Authors: Honjo Megumi , Yamagishi Reiko , Igarashi Nozomi , Ku Chui Yong , Kurano Makoto , Yatomi Yutaka , Igarashi Koji , Aihara Makoto
Published: January 2021

To evaluate the effect of postoperative corticosteroids on surgical outcome and autotaxin (ATX) levels after microhook ab interno trabeculotomy combined with cataract surgery (μLOT-CS), prospective, consecutive non-randomized case series comparing outcomes of 30 eyes with primary open angle glaucoma was performed. The aqueous ATX, intraocular pressure (IOP) and glaucoma medications were monitored for 3 months postoperatively. An in-vivo mouse μLOT model was generated. In vitro, ATX and fibrotic changes induced by dexamethasone (Dex) treatment following scratch (S) in cultured human trabecular meshwork (hTM) cells were assessed by immunofluorescence, immunoenzymatic assay, and RT-qPCR. Postoperative ATX at 1 week and the number of antiglaucoma medications at 3 months were significantly lower in non-steroid group, and steroid use was the only variable significantly associated with postoperative medications at 3 months in multiregression analyses. In vitro, ATX activity was significantly upregulated in the Dex + S group, and αSMA was significantly upregulated in the Dex and Dex + S groups. Fibronectin and COL1A1 were significantly upregulated in the S group. μLOT-CS decreased IOP and medications in the overall cohort, and non-use of postoperative steroids resulted in a smaller number of postoperative medications. Limiting postoperative steroids in μLOT may minimize IOP elevation and postoperative fibrosis.
PTEN inhibitor bpV(HOpic) confers protection against ionizing radiation
Authors: Chauhan Ankit , Sah Dhananjay Kumar , Kumari Neeraj , Kalra Namita , Soni Ravi , Bhatt Anant Narayan
Published: January 2021

Exposure to Ionizing radiation (IR) poses a severe threat to human health. Therefore, there is an urgent need to develop potent and safe radioprotective agents for radio-nuclear emergencies. Phosphatidylinositol-3-kinase (PI3K) mediates its cytoprotective signaling against IR by phosphorylating membrane phospholipids to phosphatidylinositol 3,4,5 triphosphate, PIP3, that serve as a docking site for AKT. Phosphatase and Tensin Homolog on chromosome 10 (PTEN) antagonizes PI3K activity by dephosphorylating PIP3, thus suppressing PI3K/AKT signaling that could prevent IR induced cytotoxicity. The current study was undertaken to investigate the radioprotective potential of PTEN inhibitor (PTENi), bpV(HOpic). The cell cytotoxicity, proliferation index, and clonogenic survival assays were performed for assessing the radioprotective potential of bpV(HOpic). A safe dose of bpV(HOpic) was shown to be radioprotective in three radiosensitive tissue origin cells. Further, bpV(HOpic) significantly reduced the IR-induced apoptosis and associated pro-death signaling. A faster and better DNA repair kinetics was also observed in bpV(HOpic) pretreated cells exposed to IR. Additionally, bpV(HOpic) decreased the IR-induced oxidative stress and significantly enhanced the antioxidant defense mechanism in cells. The radioprotective effect of bpV(HOpic) was found to be AKT dependant and primarily regulated by the enhanced glycolysis and associated signaling. Furthermore, this in-vitro observation was verified in-vivo, where administration of bpV(HOpic) in C57BL/6 mice resulted in AKT activation and conferred survival advantage against IR-induced mortality. These results imply that bpV(HOpic) ameliorates IR-induced oxidative stress and cell death by inducing AKT signaling mediated antioxidant defense system and DNA repair pathways, thus strengthening its potential to be used as a radiation countermeasure.
Convective meniscus splitting of polysaccharide microparticles on various surfaces
Authors: Okeyoshi Kosuke , Yamashita Miki , Budpud Kulisara , Joshi Gargi , Kaneko Tatsuo
Published: January 2021

In contrast to convective self-assembly methods for colloidal crystals etc., “convective meniscus splitting method” was developed to fabricate three-dimensionally ordered polymeric structures. By controlling the geometry of evaporative interface of polymer solution, a deposited membrane with uniaxial orientation and layered structures can be prepared. Here it is demonstrated that xanthan gum polysaccharide microparticles with diameter ~ 1 µm can bridge a millimeter-scale gap to form such a membrane because the capillary force among the particles is more dominant than the gravitational force on the evaporative interface. This method is applicable for various substrates with a wide range of wettability (water contact angle, 11°–111°), such as glass, metals, and plastics. The specific deposition can be also confirmed between frosted glasses, functional-molecules-modified glasses, and gold-sputtered substrates. By using such a universal method, the membrane formed on a polydimethylsiloxane surface using this method will provide a new strategy to design a functional polysaccharide wall in microfluidic devices, such as mass-separators.
Individual fate and gut microbiome composition in the European wild rabbit (Oryctolagus cuniculus)
Authors: Funosas Gerard , Triadó-Margarit Xavier , Castro Francisca , Villafuerte Rafael , Delibes-Mateos Miguel , Rouco Carlos , Casamayor Emilio O.
Published: January 2021

Studies connecting microbiome composition and functional performance in wildlife have received little attention and understanding their connections with wildlife physical condition are sorely needed. We studied the variation in gut microbiota (hard fecal pellets) between allopatric subspecies of the European wild rabbit in wild populations and in captured individuals studied under captivity. We evaluated the influence of environmental and host-specific factors. The microbiome of wild rabbit populations reduced its heterogeneity under controlled conditions. None of the host-specific factors tested correlated with the microbiota composition. We only observed significant intra-group dispersion for the age factor. The most diverse microbiomes were rich in Ruminococcaceae potentially holding an enriched functional profile with dominance of cellulases and xylanases, and suggesting higher efficiency in the digestion of fiber-rich food. Conversely, low diversity gut microbiomes showed dominance of Enterobacteriaceae potentially rich in amylases. We preliminary noticed geographical variations in field populations with higher dominance of Ruminococcaceae in south-western than in north-eastern Spain. Spatial differences appeared not to be subspecies driven, since they were lost in captivity, but environmentally driven, although differences in social structure and behavior may also play a role that deserve further investigations. A marginally significant relationship between the Ruminococcaceae/Enterobacteriaceae ratio and potential life expectancy was observed in captive rabbits. We hypothesize that the gut microbiome may determine the efficiency of feeding resource exploitation, and can also be a potential proxy for life expectancy, with potential applications for the management of declining wild herbivorous populations. Such hypotheses remain to be explored in the future.
Marek’s disease virus Meq oncoprotein interacts with chicken HDAC 1 and 2 and mediates their degradation via proteasome dependent pathway
Authors: Liao Yifei , Lupiani Blanca , Izumiya Yoshihiro , Reddy Sanjay M.
Published: January 2021

Marek’s disease virus (MDV) encodes a basic-leucine zipper (BZIP) protein, Meq, which is considered the major MDV oncoprotein. It has been reported that the oncogenicity of Meq is associated with its interaction with C-terminal binding protein 1 (CtBP), which is also an interaction partner of Epstein-Barr virus encoded EBNA3A and EBNA3C oncoproteins. Since both EBNA3C and CtBP interact with histone deacetylase 1 (HDAC1) and HDAC2, we examined whether Meq shares this interaction with chicken HDAC1 (chHDAC1) and chHDAC2. Using confocal microscopy analysis, we show that Meq co-localizes with chHDAC1 and chHDAC2 in the nuclei of MDV lymphoblastoid tumor cells. In addition, immunoprecipitation assays demonstrate that Meq interacts with chHDAC1 and chHDAC2 in transfected cells and MDV lymphoblastoid tumor cells. Using deletion mutants, interaction domains were mapped to the N-terminal dimerization domain of chHDAC1 and chHDAC2, and the BZIP domain of Meq. Our results further demonstrate that this interaction mediates the degradation of chHDAC1 and chHDAC2 via the proteasome dependent pathway. In addition, our results show that Meq also induces the reduction of global ubiquitinated proteins through a proteasome dependent pathway. In conclusion, our results provide evidence that Meq interacts with chHDAC1 and chHDAC2, and induces their proteasome dependent degradation.
Avalanche effect for chemically modified dust mitigation from surfaces
Authors: Adukwu Johnny Ebaika , Yilbas Bekir Sami , Jalilov Almaz , Al-Qahtani Hussain , Sahin Ahmet Z. , Al-Sharafi Abdullah , Abubakar Abba Abdulhamid , Yakubu Mubarak , Khaled Mazen , Hassan Ghassan
Published: January 2021

Cost effective dust mitigation from surfaces is one of the challenges in various sectors. The reduction of dust adhesion on surfaces plays a vital role for dust mitigation from surfaces under the gravitational influence. Creating an avalanche effect on dusty surfaces improves the dust mitigation rate and provides an effective cleaning process. Hence, solution treatment of dust by low concentration hydrofluoric acid is considered towards reducing dust adhesion on glass surfaces. To increase the rate of dust mitigation, the avalanche influence is created by the higher density and larger size particles (5300 kg/m3and ~ 50 µm) than the average size dust particles (2800 kg/m3and 1.2 µm) via locating them in the top region of the dusty glass surfaces. Mitigation velocity of the dust particles is evaluated using a high-speed recording system and the tracker program. Findings revealed that solution treatment (curing) of the dust particles results in the formation of fluorine compounds, such as CaF2and MgF2, on dust surfaces, which suppress dust adhesion on surfaces. OSHA Globally Harmonized System lists the fluorine compounds formed as environmentally non-harmful. Avalanche's influence results in dust mitigation at a smaller tilt angle of the glass surface (~ 52°) than that of the case with none-avalanche influence (63°). Area cleaned on the glass surface, via dust mitigation, is larger as the avalanche is introduced, which becomes more apparent for the solution treated dust particles. Dust mitigation under avalanche influence improves optical transmittance of the dusty glass samples by a factor of 98%.
Precise diagnosis of three top cancers using dbGaP data
Authors: Liu Xu-Qing , Liu Xin-Sheng , Rong Jian-Ying , Gao Feng , Wu Yan-Dong , Deng Chun-Hua , Jiang Hong-Yan , Li Xiao-Feng , Chen Ye-Qin , Zhao Zhi-Guo , Liu Yu-Ting , Chen Hai-Wen , Li Jun-Liang , Huang Yu , Ji Cheng-Yao , Liu Wen-Wen , Luo Xiao-Hu , Xiao Li-Li
Published: January 2021

The challenge of decoding information about complex diseases hidden in huge number of single nucleotide polymorphism (SNP) genotypes is undertaken based on five dbGaP studies. Current genome-wide association studies have successfully identified many high-risk SNPs associated with diseases, but precise diagnostic models for complex diseases by these or more other SNP genotypes are still unavailable in the literature. We report that lung cancer, breast cancer and prostate cancer as the first three top cancers worldwide can be predicted precisely via 240–370 SNPs with accuracy up to 99% according to leave-one-out and 10-fold cross-validation. Our findings (1) confirm an early guess of Dr. Mitchell H. Gail that about 300 SNPs are needed to improve risk forecasts for breast cancer, (2) reveal an incredible fact that SNP genotypes may contain almost all information that one wants to know, and (3) show a hopeful possibility that complex diseases can be precisely diagnosed by means of SNP genotypes without using phenotypical features. In short words, information hidden in SNP genotypes can be extracted in efficient ways to make precise diagnoses for complex diseases.
Completeness of open access FluNet influenza surveillance data for Pan-America in 2005–2019
Authors: Simpson Ryan B. , Gottlieb Jordyn , Zhou Bingjie , Hartwick Meghan A. , Naumova Elena N.
Published: January 2021

For several decades, the World Health Organization has collected, maintained, and distributed invaluable country-specific disease surveillance data that allow experts to develop new analytical tools for disease tracking and forecasting. To capture the extent of available data within these sources, we proposed a completeness metric based on the effective time series length. Using FluNet records for 29 Pan-American countries from 2005 to 2019, we explored whether completeness was associated with health expenditure indicators adjusting for surveillance system heterogeneity. We observed steady improvements in completeness by 4.2–6.3% annually, especially after the A(H1N1)-2009 pandemic, when 24 countries reached > 95% completeness. Doubling in decadal health expenditure per capita was associated with ~ 7% increase in overall completeness. The proposed metric could navigate experts in assessing open access data quality and quantity for conducting credible statistical analyses, estimating disease trends, and developing outbreak forecasting systems.
Enzymatic defense of Cyperus brevifolius in hydrocarbons stress environment and changes in soil properties
Authors: Chakravarty Paramita , Deka Hemen
Published: January 2021

Hydrocarbons or crude oil contamination of soil is still a burning problem around the globe. The herbs competent that are to survive in hydrocarbons contaminated habitats have some adaptive advantages to cope up with the adverse situations prevailing in that environment. In the present study, the adaptive response of Cyperus brevifolius in the heavily polluted soil with crude oil has been investigated in terms of survivability, changes in productivity, antioxidants, phytochemicals and functional group pro files of the plant species. Besides, changes in enzymes, beneficial bacterial population and physico-chemical conditions of contaminated soil were also studied during 60 days of experimental trials. The results showed significant enhancement in activities of soil dehydrogenase, urease, alkaline phosphatase, catalase, and amylase whereas reduction in cellulase, polyphenol oxidase and peroxidase activities. There was a significant increase in nitrogen fixing, phosphate and potassium solubilizing bacterial population, improvement in physico-chemical conditions and a decrease in total oil and grease (TOG) levels. Besides there was significant variations in the productivity parameters and antioxidant profiles of Cyperus brevifolius in hydrocarbons stress condition suggesting enzymatic defense of the herb. The fourier-transform infrared (FT-IR) analysis indicated uptake and metabolism of some hydrocarbon components by the experimental plant from the hydrocarbons polluted soil.
Consistent choice of landscape urbanization level across the annual cycle in a migratory waterbird species
Authors: Chyb Amelia , Jedlikowski Jan , Włodarczyk Radosław , Minias Piotr
Published: January 2021

Rapid urbanization has a great impact on avian distribution, ecology, habitat selection, and behavior. Recent avian studies indicated that individuals remain consistent in their behavioral responses to human disturbance across short periods of time. However, there is still little information about keeping consistent behaviors in distinct locations across different stages of the annual cycle. In this study, we aimed to test for long-term consistency in habitat selection with respect to urbanization in a migratory waterbird species, the Eurasian cootFulica atra. For this purpose, we individually marked ca. 300 coots from four populations that varied in urbanization level and tracked their habitat preferences during the non-breeding season. We found that individuals from urban breeding populations selected habitats with a higher share of artificial areas during the non-breeding season, when compared to non-urban individuals. Also, a comparison of non-breeding sites selected by birds from our study populations with random sites showed that urban birds selected sites with higher urbanization level than resulting from random availability. Finally, we found a seasonal variation in habitat preferences in coots—individuals from all study populations selected more urbanized areas as the non-breeding season progressed. The results indicate that birds are able to remain consistent in habitat preferences not only at a large geographical scale, but also across different seasons. Marked between-population variation in habitat selection across the annual cycle may reflect personality differences of coots from urban and non-urban populations, and it stays in line with the personality-matching habitat choice hypothesis.
CHA2DS2-VASc score in acute ischemic stroke with atrial fibrillation: results from the Clinical Research Collaboration for Stroke in Korea
Authors: Lee Hak-Loh , Kim Joon-Tae , Lee Ji Sung , Kim Beom Joon , Park Jong-Moo , Kang Kyusik , Lee Soo Joo , Kim Jae Guk , Cha Jae-Kwan , Kim Dae-Hyun , Park Tai Hwan , Park Sang-Soon , Lee Kyung Bok , Lee Jun , Hong Keun-Sik , Cho Yong-Jin , Park Hong-Kyun , Lee Byung-Chul , Yu Kyung-Ho , Oh Mi Sun , Kim Dong-Eog , Ryu Wi-Sun , Choi Jay Chol , Kwon Jee-Hyun , Kim Wook-Joo , Shin Dong-Ick , Sohn Sung Il , Hong Jeong-Ho , Park Man-Seok , Choi Kang-Ho , Cho Ki-Hyun , Lee Juneyoung , Bae Hee-Joon
Published: January 2021

We investigated a multicenter registry to identify estimated event rates according to CHA2DS2-VASc scores in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). The additional effectiveness of antiplatelets (APs) plus oral anticoagulants (OACs) compared with OACs alone considering the CHA2DS2-VASc scores was also explored. This study retrospectively analyzed a multicenter stroke registry between Jan 2011 and Nov 2017, identifying patients with acute ischemic stroke with AF. The primary outcome event was a composite of recurrent stroke, myocardial infarction, and all-cause mortality within 1 year. A total of 7395 patients (age, 73 ± 10 years; men, 54.2%) were analyzed. The primary outcome events at one year ranged from 5.99% (95% CI 3.21–8.77) for a CHA2DS2-VASc score of 0 points to 30.45% (95% CI 24.93–35.97) for 7 or more points. After adjustments for covariates, 1-point increases in the CHA2DS2-VASc score consistently increased the risk of primary outcome events (aHR 1.10 [1.06–1.15]) at 1-year. Among OAC-treated patients at discharge (n = 5500), those treated with OAC + AP (vs. OAC alone) were more likely to experience vascular events, though among patients with a CHA2DS2-VASc score of 5 or higher, the risk of primary outcome in the OAC + AP group was comparable to that in the OAC alone group (Pint = 0.01). Our study found that there were significant associations of increasing CHA2DS2-VASc scores with the increasing risk of vascular events at 1-year in AIS with AF. Further study would be warranted.
New combination chemotherapy of cisplatin with an electron-donating compound for treatment of multiple cancers
Authors: Zhang Qinrong , Lu Qing-Bin
Published: January 2021

Cisplatin is the first and most widely used platinum-based chemotherapy drug and is the cornerstone agent in treating a broad spectrum of cancers. However, its clinical application is often limited by severe toxic side effects and drug resistance. Based on the discovered dissociative electron transfer mechanism of cisplatin, a novel combination of cisplatin with [9-(2-carboxyphenyl)-6-diethylamino-3-xanthenylidene]-diethylammonium chloride (basic violet 10, BV10) is proposed to potentiate the chemotherapeutic effect of cisplatin. Here, we show that this combination enhances the anti-cancer effect of cisplatin in both in vitro cell lines and in vivo xenograft mouse models of cisplatin-sensitive and -resistant lung, ovarian and cervical cancers while introducing minimal additional toxic side effects. Furthermore, femtosecond time-resolved laser spectroscopic measurements demonstrate that cisplatin reacts with BV10 via an electron transfer mechanism. These results indicate that the combination of cisplatin with BV10 is promising for improving the chemotherapy of cancers with various extents of cisplatin resistance.
Formation environments and mechanisms of multistage paleokarst of Ordovician carbonates in Southern North China Basin
Authors: Zhang Haitao , Xu Guangquan , Liu Mancai , Wang Minhua
Published: January 2021

With the reduction of oil and gas reserves and the increase of mining difficulty in Northern China, the carbonate rocks in Southern North China Basin are becoming a significant exploration target for carbonate reservoirs. However, the development characteristics, formation stages, formation environments and mechanisms of the carbonate reservoirs in Southern North China Basin are still unclear, which caused the failures of many oil and gas exploration wells. This study focused on addressing this unsolved issue from the Ordovician carbonate paleokarst in the Huai-Fu Basin, which is located in the southeast of Southern North China Basin and one of the key areas for oil and gas exploration. Based on petrology, mineralogy and geochemical data, pore types, distribution characteristics, and formation stages of the Ordovician paleokarst were analyzed. Then, in attempt to define the origins of porosity development, the formation environments and mechanisms were illustrated. The results of this study showed that pore types of the Ordovician carbonates in the Huai-Fu Basin are mainly composed of intragranular pores, intercrystalline (intergranular) pores, dissolution pores (vugs), fractures, channels, and caves, which are usually in fault and fold zones and paleoweathering crust. Furthermore, five stages and five formation environments of the Ordovician paleokarst were identified. Syngenetic karst, eogenetic karst, and paleoweathering crust karst were all developed in a relatively open near-surface environment, and their formations are mainly related to meteoric water dissolution. Mesogenetic karst was developed in a closed buried environment, and its formation is mainly related to the diagenesis of organic matters and thermochemical sulfate reduction in the Permian-Carboniferous strata. Hydrothermal (water) karst was developed in a deep-buried and high-temperature environment, where hydrothermal fluids (waters) migrated upward through structures such as faults and fractures to dissolve carbonate rocks and simultaneously deposited hydrothermal minerals and calcites. Lastly, a paleokarst evolution model, combined with the related porosity evolution processes, nicely revealed the Ordovician carbonate reservoir development. This study provides insights and guidance for further oil and gas exploration in the Southern North China Basin, and also advances our understanding of the genesis of carbonate paleokarst around the world.
Author Correction: Pluripotent stem cell model of Shwachman–Diamond syndrome reveals apoptotic predisposition of hemoangiogenic progenitors
Authors: Hamabata Takayuki , Umeda Katsutsugu , Kouzuki Kagehiro , Tanaka Takayuki , Daifu Tomoo , Nodomi Seishiro , Saida Satoshi , Kato Itaru , Baba Shiro , Hiramatsu Hidefumi , Osawa Mitsujiro , Niwa Akira , Saito Megumu K. , Kamikubo Yasuhiko , Adachi Souichi , Hashii Yoshiko , Shimada Akira , Watanabe Hiroyoshi , Osafune Kenji , Okita Keisuke , Nakahata Tatsutoshi , Watanabe Kenichiro , Takita Junko , Heike Toshio
Published: January 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Effects of cannabis on visual function and self-perceived visual quality
Authors: Ortiz-Peregrina Sonia , Ortiz Carolina , Casares-López Miriam , Jiménez José R. , Anera Rosario G.
Published: January 2021

Cannabis is one of the most used drugs of abuse in the world. The objective of this study was to analyze the effects of smoking cannabis on vision and to relate these to those perceived by the user. Thirty-one cannabis users participated in this study. Visual function assessment was carried out in a baseline session as well as after smoking cannabis. We evaluated static visual acuity, contrast sensitivity, stereoacuity, accommodative response, straylight, night-vision disturbances (halos) and pupil size. The participants were also divided into two groups depending on whether they perceived their vision to have worsened after smoking cannabis. A logistic regression analysis was employed to identify which visual test could best predict self-perceived visual effects. The study found that smoking cannabis has significant adverse effects on all the visual parameters analyzed (p < 0.05). Self-perceived visual quality results revealed that about two thirds of the sample think that smoking cannabis impairs their vision. Contrast sensitivity, specifically for the spatial frequency 18 cpd, was identified as the only visual parameter significantly associated with self-perceived visual quality (Odds Ratio: 1.135; p = 0.040). Smoking cannabis is associated with negative effects on visual function. Self-perceived visual quality after smoking cannabis could be related to impaired contrast sensitivity.
Operant and classical learning principles underlying mind–body interaction in pain modulation: a pilot fMRI study
Authors: Lee In-Seon , Jung Won-Mo , Lee Ye-Seul , Wallraven Christian , Chae Younbyoung
Published: January 2021

The operant conditioning has been less studied than the classical conditioning as a mechanism of placebo-like effect, and two distinct learning mechanisms have never been compared to each other in terms of their neural activities. Twenty-one participants completed cue-learning based pain rating tasks while their brain responses were measured using functional magnetic resonance imaging. After choosing (instrumental) or viewing (classical) one of three predictive cues (low- and high-pain cues with different level of certainty), they received painful stimuli according to the selected cues. Participants completed the same task during the test session, except that they received only a high pain stimulus regardless of the selected cues to identify the effects of two learning paradigms. While receiving a high pain stimulation, low-pain cue significantly reduced pain ratings compared to high-pain cue, and the overall ratings were significantly lower under operant than under classical conditioning. Operant behavior activated the temporoparietal junction significantly more than the passive behavior did, and neural activity in the primary somatosensory cortex was significantly reduced during pain in instrumental as compared with classical conditioning trials. The results suggest that pain modulation can be induced by classical and operant conditioning, and mechanisms of attention and context change are involved in instrumental learning.
Hydrodynamic particle focusing enhanced by femtosecond laser deep grooving at low Reynolds numbers
Authors: Zhang Tianlong , Namoto Misuzu , Okano Kazunori , Akita Eri , Teranishi Norihiro , Tang Tao , Anggraini Dian , Hao Yansheng , Tanaka Yo , Inglis David , Yalikun Yaxiaer , Li Ming , Hosokawa Yoichiroh
Published: January 2021

Microfluidic focusing of particles (both synthetic and biological), which enables precise control over the positions of particles in a tightly focused stream, is a prerequisite step for the downstream processing, such as detection, trapping and separation. In this study, we propose a novel hydrodynamic focusing method by taking advantage of open v-shaped microstructures on a glass substrate engraved by femtosecond pulse (fs) laser. The fs laser engraved microstructures were capable of focusing polystyrene particles and live cells in rectangular microchannels at relatively low Reynolds numbers (Re). Numerical simulations were performed to explain the mechanisms of particle focusing and experiments were carried out to investigate the effects of groove depth, groove number and flow rate on the performance of the groove-embedded microchannel for particle focusing. We found out that 10-µm polystyrene particles are directed toward the channel center under the effects of the groove-induced secondary flows in low-Re flows, e.g. Re < 1. Moreover, we achieved continuous focusing of live cells with different sizes ranging from 10 to 15 µm, i.e. human T-cell lymphoma Jurkat cells, rat adrenal pheochromocytoma PC12 cells and dog kidney MDCK cells. The glass grooves fabricated by fs laser are expected to be integrated with on-chip detection components, such as contact imaging and fluorescence lifetime-resolved imaging, for various biological and biomedical applications, where particle focusing at a relatively low flow rate is desirable.
Livestock integration into soybean systems improves long-term system stability and profits without compromising crop yields
Authors: de Albuquerque Nunes Pedro Arthur , Laca Emilio Andrés , de Faccio Carvalho Paulo César , Li Meng , de Souza Filho William , Robinson Kunrath Taise , Posselt Martins Amanda , Gaudin Amélie
Published: January 2021

Climate models project greater weather variability over the coming decades. High yielding systems that can maintain stable crop yields under variable environmental scenarios are critical to enhance food security. However, the effect of adding a trophic level (i.e. herbivores) on the long-term stability of agricultural systems is not well understood. We used a 16-year dataset from an integrated soybean-beef cattle experiment to measure the impacts of grazing on the stability of key crop, pasture, animal and whole-system outcomes. Treatments consisted of four grazing intensities (10, 20, 30 and 40 cm sward height) on mixed black oat (Avena strigosa) and Italian ryegrass (Lolium multiflorum) pastures and an ungrazed control. Stability of both human-digestible protein production and profitability increased at moderate to light grazing intensities, while over-intensification or absence of grazing decreased system stability. Grazing did not affect subsequent soybean yields but reduced the chance of crop failure and financial loss in unfavorable years. At both lighter and heavier grazing intensities, tradeoffs occurred between the stability of herbage production and animal live weight gains. We show that ecological intensification of specialized soybean systems using livestock integration can increase system stability and profitability, but the probability of win–win outcomes depends on management.
Predictors for bronchoalveolar lavage recovery failure in diffuse parenchymal lung disease
Authors: Koda Keigo , Hozumi Hironao , Yasui Hideki , Suzuki Yuzo , Karayama Masato , Furuhashi Kazuki , Enomoto Noriyuki , Fujisawa Tomoyuki , Inui Naoki , Nakamura Yutaro , Suda Takafumi
Published: January 2021

Bronchoalveolar lavage (BAL) plays a role in the diagnosis of diffuse parenchymal lung diseases (DPLD); however, poor BAL fluid (BALF) recovery results in low diagnostic reliability. BAL is relatively safe, but its indications should be carefully considered in patients with risks. Therefore, estimating the likelihood of recovery failure is helpful in clinical practice. This study aimed to clarify predictors of BALF recovery failure and to develop its simple-to-use prediction models. We detected the predictors applying a logistic regression model on clinical, physiological, and radiological data from 401 patients with DPLD (derivation cohort). The discrimination performance of the prediction models using these factors was evaluated by the c-index. In the derivation cohort, being a man, the forced expiratory volume in one second/forced vital capacity, and a BAL target site other than right middle lobe or left lingula were independent predictors. The c-indices of models 1 and 2 that we developed were 0.707 and 0.689, respectively. In a separate cohort of 234 patients (validation cohort), the c-indices of the models were 0.689 and 0.670, respectively. In conclusion, we developed and successfully validated simple-to-use prediction models useful for pulmonologists considering BAL indications or target sites, based on independent predictors for BALF recovery failure.
Author Correction: A detailed characterization of complex networks using Information Theory
Authors: Freitas Cristopher G. S. , Aquino Andre L. L. , Ramos Heitor S. , Frery Alejandro C. , Rosso Osvaldo A.
Published: January 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Rotatable central composite design versus artificial neural network for modeling biosorption of Cr6+ by the immobilized Pseudomonas alcaliphila NEWG-2
Authors: Saber WesamEldin I. A. , El-Naggar Noura El-Ahmady , El-Hersh Mohammed S. , El-khateeb Ayman Y. , Elsayed Ashraf , Eldadamony Noha M. , Ghoniem Abeer Abdulkhalek
Published: January 2021

Heavy metals, including chromium, are associated with developed industrialization and technological processes, causing imbalanced ecosystems and severe health concerns. The current study is of supreme priority because there is no previous work that dealt with the modeling of the optimization of the biosorption process by the immobilized cells. The significant parameters (immobilized bacterial cells, contact time, and initial Cr6+ concentrations), affecting Cr6+ biosorption by immobilized Pseudomonas alcaliphila, was verified, using the Plackett–Burman matrix. For modeling the maximization of Cr6+ biosorption, a comparative approach was created between rotatable central composite design (RCCD) and artificial neural network (ANN) to choose the most fitted model that accurately predicts Cr6+ removal percent by immobilized cells. Experimental data of RCCD was employed to train a feed-forward multilayered perceptron ANN algorithm. The predictive competence of the ANN model was more precise than RCCD when forecasting the best appropriate wastewater treatment. After the biosorption, a new shiny large particle on the bead surface was noticed by the scanning electron microscopy, and an additional peak of Cr6+ was appeared by the energy dispersive X-ray analysis, confirming the role of the immobilized bacteria in the biosorption of Cr6+ ions.
Functional analysis of tomato CHIP ubiquitin E3 ligase in heat tolerance
Authors: Zhang Yan , Lai Xiaodong , Yang Siqing , Ren Huan , Yuan Jingya , Jin Huanchun , Shi Chengchen , Lai Zhibing , Xia Gengshou
Published: January 2021

Plants have evolved genetic and physiological mechanisms to mitigate the adverse effects of high temperature. CARBOXYL TERMINUS OF THE HSC70-INTERACTING PROTEINS (CHIP) is a conserved chaperone-dependent ubiquitin E3 ligase that targets misfolded proteins. Here, we report functional analysis of the SlCHIP gene from tomato (Solanum lycopersicum) in heat tolerance. SlCHIP encodes a CHIP protein with three tandem tetracopeptide repeat (TPR) motifs and a C-terminal U box domain. Phylogenetic analysis of CHIP homologs from animals, spore-bearing and seed plants revealed a tree topology similar to the evolutionary tree of the organisms. Expression of SlCHIP was induced under high temperature and was also responsive to plant stress hormones. Silencing of SlCHIP in tomato reduced heat tolerance based on increased heat stress symptoms, reduced photosynthetic activity, elevated electrolyte leakage and accumulation of insoluble protein aggregates. The accumulated protein aggregates in SlCHIP-silenced plants were still highly ubiquitinated, suggesting involvement of other E3 ligases in ubiquitination. SlCHIP restored the heat tolerance of Arabidopsis chip mutant to the wild type levels. These results indicate that tomato SlCHIP plays a critical role in heat stress responses most likely by targeting degradation of misfolded proteins that are generated during heat stress.
Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer
Authors: Katsube Ryoichi , Noma Kazuhiro , Ohara Toshiaki , Nishiwaki Noriyuki , Kobayashi Teruki , Komoto Satoshi , Sato Hiroaki , Kashima Hajime , Kato Takuya , Kikuchi Satoru , Tazawa Hiroshi , Kagawa Shunsuke , Shirakawa Yasuhiro , Kobayashi Hisataka , Fujiwara Toshiyoshi
Published: January 2021

Cancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy.
AlO6 clusters’ electric storage effect in amorphous alumina supercapacitors
Authors: Fukuhara Mikio , Kuroda Tomoyuki , Hasegawa Fumihiko , Hashida Toshiyuki , Takeda Mitsuhiro , Konno Kazuya , Fujima Nobuhisa
Published: January 2021

In this study, the electric storage effect of AlO6 clusters in amorphous alumina (AAO) supercapacitors was investigated in terms of cluster morphologies under electron-beam irradiation. Based on first-principles density functional calculation, the optimised structure of AlO6 clusters around an O-vacancy is characterised by a large vacant space created by the absence of an O atom and its neighbouring Al atom. The localised electrons present near the two-atomic vacancies induce positive charges on the inside of the insulating oxide surface, ensuring the adsorption of many electrons on the surface. Electron-beam irradiation (adsorption) from 100 to 180 keV causes the lengths of the Al–O bonds of the cluster to shrink, but then return to the original length with decreasing voltage energy, indicating a rocking-chair-type charge-breathing effect accompanied by a volume expansion of approximately 4%. The I–V and I–R characteristics depicted Coulomb blockade for the switching effect of both the negative and positive potentials. The Ragone plot of the AAO supercapacitor is located at capability area of the second cell.