bluuebunny/crossref_metadata_2025_split huggingface dataset:
JmjC-KDMs KDM3A and KDM6B modulate radioresistance under hypoxic conditions in esophageal squamous cell carcinoma
Authors: Macedo-Silva Catarina , Miranda-Gonçalves Vera , Lameirinhas Ana , Lencart Joana , Pereira Alexandre , Lobo João , Guimarães Rita , Martins Ana Teresa , Henrique Rui , Bravo Isabel , Jerónimo Carmen 
Published: December 2020

AbstractEsophageal squamous cell carcinoma (ESCC), the most frequent esophageal cancer (EC) subtype, entails dismal prognosis. Hypoxia, a common feature of advanced ESCC, is involved in resistance to radiotherapy (RT). RT response in hypoxia might be modulated through epigenetic mechanisms, constituting novel targets to improve patient outcome. Post-translational methylation in histone can be partially modulated by histone lysine demethylases (KDMs), which specifically removes methyl groups in certain lysine residues. KDMs deregulation was associated with tumor aggressiveness and therapy failure. Thus, we sought to unveil the role of Jumonji C domain histone lysine demethylases (JmjC-KDMs) in ESCC radioresistance acquisition. The effectiveness of RT upon ESCC cells under hypoxic conditions was assessed by colony formation assay. KDM3A/KDM6B expression, and respective H3K9me2 and H3K27me3 target marks, were evaluated by RT-qPCR, Western blot, and immunofluorescence. Effect of JmjC-KDM inhibitor IOX1, as well asKDM3Aknockdown, in in vitro functional cell behavior and RT response was assessed in ESCC under hypoxic conditions. In vivo effect of combined IOX1 and ionizing radiation treatment was evaluated in ESCC cells using CAM assay. KDM3A, KDM6B, HIF-1α, and CAIX immunoexpression was assessed in primary ESCC and normal esophagus. Herein, we found that hypoxia promoted ESCC radioresistance through increased KDM3A/KDM6B expression, enhancing cell survival and migration and decreasing DNA damage and apoptosis, in vitro. Exposure to IOX1 reverted these features, increasing ESCC radiosensitivity and decreasing ESCC microtumors size, in vivo. KDM3A was upregulated in ESCC tissues compared to the normal esophagus, associating and colocalizing with hypoxic markers (HIF-1α and CAIX). Therefore, KDM3A upregulation in ESCC cell lines and primary tumors associated with hypoxia, playing a critical role in EC aggressiveness and radioresistance. KDM3A targeting, concomitant with conventional RT, constitutes a promising strategy to improve ESCC patients’ survival.
Effects of SGLT2 inhibitors on eGFR in type 2 diabetic patients—the role of antidiabetic and antihypertensive medications
Authors: Kitamura Koichi , Hayashi Koichi , Ito Shinsuke , Hoshina Yuiko , Sakai Masahiro , Yoshino Kaede , Endo Keita , Fujitani Shigeki , Suzuki Toshihiko 
Published: December 2020

AbstractRecent randomized trials demonstrating the beneficial effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in type 2 diabetes suggest that early reductions in eGFR upon initiation of SGLT2i therapy are associated with improved renal outcomes. Multiple concomitant medications, including antidiabetic and antihypertensive agents, are commonly used, however, which may modify the renal hemodynamic action of SGLT2is. Here we found that background treatment with metformin diminished the SGLT2i-induced reductions in eGFR after 3 months of SGLT2i therapy in patients with type 2 diabetes and hypertension (−2.29 ± 0.90 vs −5.85 ± 1.27 mL/min/1.73 m2 for metformin users (n = 126) and nonusers (n = 97), respectively). Other antidiabetic agents (DPP4 inhibitors, sulfonylureas and insulin) had no effect on the eGFR response to SGLT2is. Antihypertensive drugs, including calcium channel blockers (CCBs) and β blockers, did not affect the SGLT2i-induced changes in eGFR, whereas renin-angiotensin system inhibitors (RASis) tended to enhance this response (p = 0.059). Next, we evaluated the interaction between metformin and RASis in the eGFR responses to SGLT2is. Under no background treatment with RASis, metformin abrogated the eGFR response to SGLT2is, but this response was preserved when RASis had been given along with metformin (decreases of 0.75 ± 1.28 vs. 4.60 ± 1.15 mL/min/1.73 m2 in eGFR, p = 0.028). No interaction between metformin and insulin or between metformin and DPP4 inhibitors was observed. In conclusion, metformin blunts the SGLT2i-induced decrease in eGFR, but coadministration of RASis ameliorates this response. Furthermore, the inability of CCBs to modify the SGLT2i-induced reduction in eGFR suggests that the SGLT2i-induced renal microvascular action is mediated predominantly by postglomerular vasodilation rather than preglomerular vasoconstriction.
Activation of the NRF2 pathway in Keap1-knockdown mice attenuates progression of age-related hearing loss
Authors: Oishi Tetsuya , Matsumaru Daisuke , Ota Nao , Kitamura Hiroshi , Zhang Tianxiang , Honkura Yohei , Katori Yukio , Motohashi Hozumi 
Published: December 2020

AbstractAge-related hearing loss (AHL) is a progressive sensorineural hearing loss in elderly people. Although no prevention or treatments have been established for AHL, recent studies have demonstrated that oxidative stress is closely related to pathogenesis of AHL, suggesting that suppression of oxidative stress leads to inhibition of AHL progression. NRF2 is a master transcription factor that regulates various antioxidant proteins and cytoprotection factors. To examine whether NRF2 pathway activation prevents AHL, we used Keap1-knockdown (Keap1FA/FA) mice, in which KEAP1, a negative regulator of NRF2, is decreased, resulting in the elevation of NRF2 activity. We compared 12-month-old Keap1FA/FA mice with age-matched wild-type (WT) mice in the same breeding colony. In the Keap1FA/FA mice, the expression levels of multiple NRF2 target genes were verified to be significantly higher than the expression levels of these genes in the WT mice. Histological analysis showed that cochlear degeneration at the apical and middle turns was ameliorated in the Keap1FA/FA mice. Auditory brainstem response (ABR) thresholds in the Keap1FA/FA mice were significantly lower than those in the WT mice, in particular at low–mid frequencies. Immunohistochemical detection of oxidative stress markers suggested that oxidative stress accumulation was attenuated in the Keap1FA/FA cochlea. Thus, we concluded that NRF2 pathway activation protects the cochlea from oxidative damage during aging, in particular at the apical and middle turns. KEAP1-inhibiting drugs and phytochemicals are expected to be effective in the prevention of AHL.
Leakage detection for a transmon-based surface code
Authors: Varbanov Boris Mihailov , Battistel Francesco , Tarasinski Brian Michael , Ostroukh Viacheslav Petrovych , O’Brien Thomas Eugene , DiCarlo Leonardo , Terhal Barbara Maria 
Published: December 2020

AbstractLeakage outside of the qubit computational subspace, present in many leading experimental platforms, constitutes a threatening error for quantum error correction (QEC) for qubits. We develop a leakage-detection scheme via Hidden Markov models (HMMs) for transmon-based implementations of the surface code. By performing realistic density-matrix simulations of the distance-3 surface code (Surface-17), we observe that leakage is sharply projected and leads to an increase in the surface-code defect probability of neighboring stabilizers. Together with the analog readout of the ancilla qubits, this increase enables the accurate detection of the time and location of leakage. We restore the logical error rate below the memory break-even point by post-selecting out leakage, discarding less than half of the data for the given noise parameters. Leakage detection via HMMs opens the prospect for near-term QEC demonstrations, targeted leakage reduction and leakage-aware decoding and is applicable to other experimental platforms.
PLEKHG5 regulates autophagy, survival and MGMT expression in U251-MG glioblastoma cells
Authors: Witte Kaya Elisa , Slotta Carsten , Lütkemeyer Melanie , Kitke Angelika , Coras Roland , Simon Matthias , Kaltschmidt Christian , Kaltschmidt Barbara 
Published: December 2020

AbstractA signalling pathway involving PLEKHG5 (guanine exchange factor) for the Ras superfamily member RAB26 to transcription factor NF-κB was discovered in autophagy. PLEKHG5 was reported in glioblastoma multiforme (GBM) and correlates with patient survival. Thus, the generation of a cellular model for understanding PLEKHG5 signalling is the study purpose. We generated a CRISPR/Cas9-mediated knockout of PLEKHG5 in U251-MG glioblastoma cells and analysed resulting changes. Next, we used a mRFP-GFP-LC3+reporter for visualisation of autophagic defects and rescued the phenotype ofPLEKHG5wildtype via transduction of a constitutively active RAB26QL-plasmid. Effects of overexpressing RAB26 were investigated and correlated with the O6-methylguanine-DNA methyltransferase (MGMT) and cellular survival.PLEKHG5knockout showed changes in morphology, loss of filopodia and higher population doubling times. Accumulation of autolysosomes was resulted by decreased LAMP-1 in PLEKHG5-deficient cells. Rescue ofPLEKHG5−/−restored the downregulation of RhoA activity, showed faster response to tumour necrosis factor and better cellular fitness. MGMT expression was activated after RAB26 overexpression compared to non-transduced cells. Survival ofPLEKHG5knockout was rescued together with sensitivity to temozolomide by RAB26QL. This study provides new insights in the PLEKHG5/RAB26 signalling within U251-MG cells, which suggests potential therapeutic strategies in other glioma cells and further in primary GBM.
Novel mutant camelina and jatropha as valuable feedstocks for biodiesel production
Authors: Aslam Muhammad Mahran , Khan Asif Ali , Cheema Hafiza Masooma Naseer , Hanif Muhammad Asif , Azeem Muhammad Waqar , Azmat Muhammad Abubakkar 
Published: December 2020

AbstractNovel mutant camelina has become a crop of interest inspired by its short growing season, low harvesting costs and high oil composition. Despite those advantages, limited research has been done on novel mutant lines to determine applicability for biodiesel production. Jatropha is an extremely hardy, frugal and high oil yielding plant species. The major aim of the present study was not only to compare biodiesel production from jatropha and camelina but was also to test the efficacy of camelina mutant lines (M6 progenies) as superior feedstock. The biodiesel yield from camelina oil and jatropha oil was 96% and 92%, respectively. The gas chromatographic analysis using flame ionization detector (GC-FID) showed that mutant camelina oil biodiesel sample contain major amount of oleic acid (46.54 wt%) followed by linolenic acid (20.41 wt%) and linoleic acid (16.55 wt%). Jatropha biodiesel found to contain major amount of oleic acid (45.03 wt%) followed by linoleic acid (25.07 wt%) and palmitic acid (19.31 wt%). The fuel properties of produced biodiesel were found in good agreement with EN14214 and ASTM D6751 standards. The mutant camelina lines biodiesel have shown comparatively better fuel properties than jatropha. It has shown low saponification value (120.87–149.35), high iodine value (130.2–157.9) and better cetane number (48.53–59.35) compared to jatropha biodiesel which have high saponification value (177.39–198.9), low iodine value (109.7–123.1) and lesser cetane number (47.76–51.26). The results of the present student of utilizing novel mutant camelina lines for biodiesel production are quite promising and are helpful in turning out the outcomes of the previous studies suggesting that C. sativa biodiesel presents serious drawbacks for biodiesel applications.
Biodegradation of polycyclic aromatic hydrocarbons, phenol and sodium sulfate by Nocardia species isolated and characterized from Iranian ecosystems
Authors: Azadi Davood , Shojaei Hasan 
Published: December 2020

AbstractAnthropogenic pollutants are known to have adverse effect on ecosystem, biodiversity and human health. Bioremediation is an option that has been widely used to remediate organic contaminants and reduce the risk of these hazardous materials. Microorganisms are readily available to screen and can be rapidly characterized to be applied in many extreme environmental conditions. Actinomycetes have a great potential for the production of bioactive secondary metabolites which have biodegradation activity. This study aimed to screen and characterize Nocardia species with biodegradation potential from diverse Iranian ecosystems. The isolates were screened from 90 collected environmental samples, identified and characterized using conventional and molecular microbiological methods including the PCR amplification and sequencing analysis of 16S rRNA and rpoB genetic markers. Growth rate in presence of pollutants, chromatography, Gibbs and turbidometric methods were used to determine bioremediation ability. A total of 19 Nocardia isolates were recovered from the cultured samples (21.1%) that belonged to 10 various species. The most prevalent Nocardia species was N. farcinica; 4 isolates (21%), followed by N. cyriacigeorgica and N. cashijiensis like; 3 isolates each (15.7%) and N. asteroides and N. kroppenstedtii; 2 isolates each (10.5%). Our results showed that various Nocardia species have great potential for bioremediation purposes, although they have not received much attention of the scholars for such significant usage.
Prognostic effect of high-density lipoprotein cholesterol level in patients with atherosclerotic cardiovascular disease under statin treatment
Authors: Li Yi-Heng , Tseng Wei-Kung , Yin Wei-Hsian , Lin Fang-Ju , Wu Yen-Wen , Hsieh I-Chang , Lin Tsung-Hsien , Sheu Wayne Huey-Herng , Yeh Hung-I , Chen Jaw-Wen , Wu Chau-Chung ,   Taiwanese Secondary Prevention for Patients with AtheRosCLErotic Disease (T-SPARCLE) Registry Investigators
Published: December 2020

AbstractIn patients with atherosclerotic cardiovascular disease (ASCVD) under statin treatment, the influence of on-treatment level of high-density lipoprotein cholesterol (HDL-C) on cardiovascular (CV) events is controversial. Statin-treated patients were selected from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry, a multicenter, observational study of adult patients with ASCVD in Taiwan. Low HDL-C was defined as < 40 mg/dL for men and < 50 mg/dL for women. The primary outcome was a composite CV events including CV death, myocardial infarction (MI), stroke or cardiac arrest with resuscitation. A total of 3731 patients (mean age 65.6 years, 75.6% men) were included. Patients with on-treatment low HDL-C (44%, mean HDL-C 34.9 ± 6.8 mg/dL) were younger and with more diabetes and higher body weight. The mean follow-up time was 2.7 years. We used restricted cubic spline curves to examine the potential non-linear association between HDL-C and adverse outcomes. Decreased HDL-C levels were associated with a significantly increased risk of CV events in women (< 49 mg/dL in women) but not in men (< 42 mg/dL in men). However, the protective effect of elevated HDL-C levels was more prominent in men than in women. In ASCVD patients with statin therapy, low on-treatment HDL-C was common in Taiwan and associated with an increased risk of CV events in women. Higher HDL-C levels provided more protective effect in men than in women.
Leuconostoc mesenteroides mediates an electrogenic pathway to attenuate the accumulation of abdominal fat mass induced by high fat diet
Authors: Pham Minh Tan , Yang John Jackson , Balasubramaniam Arun , Rahim Adelia Riezka , Adi Prakoso , Do Thi Tra My , Herr Deron Raymond , Huang Chun-Ming 
Published: December 2020

AbstractAlthough several electrogenic bacteria have been identified, the physiological effect of electricity generated by bacteria on host health remains elusive. We found that probiotic Leuconostoc mesenteroides (L. mesenteroides) can metabolize linoleic acid to yield electricity via an intracellular cyclophilin A-dependent pathway. Inhibition of cyclophilin A significantly abolished bacterial electricity and lowered the adhesion of L. mesenteroides to the human gut epithelial cell line. Butyrate from L. mesenteroides in the presence of linoleic acid were detectable and mediated free fatty acid receptor 2 (Ffar2) to reduce the lipid contents in differentiating 3T3-L1 adipocytes. Oral administration of L. mesenteroides plus linoleic acid remarkably reduced high-fat-diet (HFD)-induced formation of 4-hydroxy-2-nonenal (4-HNE), a reactive oxygen species (ROS) biomarker, and decreased abdominal fat mass in mice. The reduction of 4-HNE and abdominal fat mass was reversed when cyclophilin A inhibitor-pretreated bacteria were administered to mice. Our studies present a novel mechanism of reducing abdominal fat mass by electrogenic L. mesenteroides which may yield electrons to enhance colonization and sustain high amounts of butyrate to limit ROS during adipocyte differentiation.
Enhanced image sensing with avalanche multiplication in hybrid structure of crystalline selenium photoconversion layer and CMOSFETs
Authors: Imura Shigeyuki , Mineo Keitada , Honda Yuki , Arai Toshiki , Miyakawa Kazunori , Watabe Toshihisa , Kubota Misao , Nishimoto Keisuke , Sugiyama Mutsumi , Nanba Masakazu 
Published: December 2020

AbstractThe recent improvements of complementary metal–oxide–semiconductor (CMOS) image sensors are playing an essential role in emerging high-definition video cameras, which provide viewers with a stronger sensation of reality. However, the devices suffer from decreasing sensitivity due to the shrinkage of pixels. We herein address this problem by introducing a hybrid structure comprising crystalline-selenium (c-Se)-based photoconversion layers and 8 K resolution (7472 × 4320 pixels) CMOS field-effect transistors (FETs) to amplify signals using the avalanche multiplication of photogenerated carriers. Using low-defect-level NiO as an electric field buffer and an electron blocking layer, we confirmed signal amplification by a factor of approximately 1.4 while the dark current remained low at 2.6 nA/cm2 at a reverse bias voltage of 22.6 V. Furthermore, we successfully obtained a brighter image based on the amplified signals without any notable noise degradation.
Kinetics and thermodynamics of hydrolysis of crystal violet at ambient and below ambient temperatures
Authors: Salahudeen Nurudeen , Rasheed Adamu A. 
Published: December 2020

AbstractHydrolysis reaction was carried out at varying NaOH concentrations of 0.008, 0.016 and 0.024 M, variable temperature of 6 and 21 °C, and constant initial crystal violet (CV) concentration of 2.6 × 10–5 M. Kinetic data of the reaction were generated using UV–Vis Spectrophotometer. Analysis of the reaction kinetics shows that the overall rate order of the hydrolysis reaction was 1st order. The individual rate order of the reaction with respect to NaOH and CV was temperature dependent. At 21 °C the rate order with respect to NaOH and CV were 0.24th and 0.76th, respectively. While at 6 °C the individual rate order were 0.38th and 0.62th with respect to NaOH and CV, respectively. Values of the reaction rate constant (k) at 21 and 6 °C were 7.2 and 1.9 $$\left( {\frac{{{\text{mol}}}}{{\text{L}}}} \right)^{{ - 0.9}} min^{-1}$$molL-0.9min-1, respectively. The activation energy of the reaction was determined as 60.57 kJ/mol. The reaction was an endothermic reaction having enthalpy values of 58.13 and 58.29 kJ/mol at 21 and 6 °C, respectively. The entropy and Gibbs free energy of the hydrolysis reaction at ambient temperature of 21 °C were − 64.72 J/mol K and 77.15 kJ/K, respectively. At 6 °C the entropy and Gibbs free energy of the reaction were − 64.29 J/mol K and 76.19 kJ/K, respectively.
The largest known cowrie and the iterative evolution of giant cypraeid gastropods
Authors: Dominici Stefano , Fornasiero Mariagabriella , Giusberti Luca 
Published: December 2020

AbstractBased on the fossil record, we explore the macroevolutionary relationship between species richness and gigantism in cowries (Cypraeidae), the best-studied family of gastropods, with a global diversity distribution that parallels that of tropical corals, mangroves and seagrasses. We introduce Vicetia bizzottoi sp. nov. based on a Priabonian fossil found in northeastern Italy, the largest documented cowrie found so far and the youngest of a lineage of Eocene Gisortiinae species. The Gisortiinae stratigraphic record in western Europe indicates that species selection favoured large size and armouring of the shell. Palaeoecology and per-stage species richness suggest that gigantism occurred in peripheral habitats with respect to diversity hotspots, where smaller species were favoured. The Eocene–Oligocene boundary was marked by a turnover and the Chattian global warming favoured small-sized species of derived clades. Species selection leading to gigantism is further documented in Miocene lineages of Zoila and Umbilia, in the southern hemisphere, two extant genera distributed at the periphery of modern diversity hotspots, suggesting that the negative relationship between size and diversity is a recurring pattern in the evolutionary history of cowries. This palaeontological evidence is projected onto the existing hypotheses that explain analogous biogeographic patterns in various other taxa. Likewise, body size-species richness negative relationship was possibly driven in cowries by physiological, ecological and life history constraints.
Minimally invasive versus traditional open transforaminal lumbar interbody fusion for the treatment of low-grade degenerative spondylolisthesis: a retrospective study
Authors: Qin Rongqing , Wu Tong , Liu Hongpeng , Zhou Bing , Zhou Pin , Zhang Xing 
Published: December 2020

AbstractThis was a retrospective study. We aimed to compare the clinical efficacy and safety between minimally invasive and traditional open transforaminal lumbar interbody fusion in the treatment of low-grade lumbar degenerative spondylolisthesis (LDS). 81 patients with LDS grades 1 and 2 treated in our spinal department from January 2014 to July 2016 were retrospectively analyzed. The MIS-TLIF group included 23 males and 11 females, while the TO-TLIF group included 29 males and 18 females. Follow-up points were set at 7 days, 3 months, 6 months, 12 months postoperatively and the last follow-up. Various clinical and radiological indicators were used to evaluate and compare the efficacy and safety between the two procedures. 8 cases (3 in the MIS-TLIF group and 5 in the TO-TLIF group) were loss of follow-up after discharge. And the remaining 73 patients were followed up for at least 2 years. No statistically significant difference was observed in the terms of age, sex, BMI, slippage grade, and surgical segments. The MIS-TLIF group had a longer operation and fluoroscopy time compared with the TO-TLIF group. But the MIS-TLIF group was associated with less blood loss, ambulation time, hospital stay, and time of return to work. In each group, significant improvement were observed in BP-VAS, ODI and vertebral slip ratio at any time-point of follow-up when compared with the preoperative condition. When the time-point of follow-up was less than 1 year, the MIS-TLIF group had significant advantages in the BP-VAS and ODI compared with TO-TLIF group. But no significant difference was observed in the BP-VAS and ODI at either 12 month follow-up or the last follow-up. Besides, no statistical difference was detected in vertebral slip ratio at any time-point of follow-up between the two groups. Successful intervertebral bone fusion was found in all patients and no significant difference was found in the incidence of total complications. Thus, we considered that MIS-TLIF and TO-TLIF both achieve satisfactory clinical efficacy in the treatment of low-grade single-segment LDS. But MIS-TLIF appears to be a more efficacious and safe technique with reduced tissue damage, less blood loss and quicker recovery.