bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-throughput screening identifies a novel natural product-inspired scaffold capable of inhibiting Clostridioides difficile in vitro
Authors: Pal Rusha , Dai Mingji , Seleem Mohamed N. 
Published: May 2021

AbstractClostridioides difficile is an enteric pathogen responsible for causing debilitating diarrhea, mostly in hospitalized patients. The bacterium exploits on microbial dysbiosis induced by the use of antibiotics to establish infection that ranges from mild watery diarrhea to pseudomembranous colitis. The increased prevalence of the disease accompanied by exacerbated comorbidity and the paucity of anticlostridial drugs that can tackle recurrence entails novel therapeutic options. Here, we report new lead molecules with potent anticlostridial activity from the AnalytiCon NATx library featuring natural product-inspired or natural product-derived small molecules. A high-throughput whole-cell-based screening of 5000 synthetic compounds from the AnalytiCon NATx library helped us identify 10 compounds capable of inhibiting the pathogen. Out of these 10 hits, we found 3 compounds with potent activity against C. difficile (MIC = 0.5–2 μg/ml). Interestingly, these compounds had minimal to no effect on the indigenous intestinal microbial species tested, unlike the standard-of-care antibiotics vancomycin and fidaxomicin. Further in vitro investigation revealed that the compounds were nontoxic to Caco-2 cell line. Given their potent anticlostridial activity, natural product-inspired scaffolds may suggest potential avenues that can address the unmet needs in preventing C. difficile mediated disease.
Lidocaine and bupivacaine as part of multimodal pain management in a C57BL/6J laparotomy mouse model
Authors: Durst Mattea S. , Arras Margarete , Palme Rupert , Talbot Steven R. , Jirkof Paulin 
Published: May 2021

AbstractWhile the use of local anesthesia as part of multimodal pain management is common practice in human and veterinarian surgery, these drugs are not applied routinely in rodent surgery. Several recommendations on the use of local anesthesia exist, but systematic studies on their efficacy and side effects are lacking. In the present study, male and female C57BL/6J mice were subjected to a sham vasectomy or a sham embryo transfer, respectively. We tested whether a mixture of subcutaneously injected Lidocaine and Bupivacaine in combination with systemic Paracetamol applied via drinking water results in superior pain relief when compared to treatment with local anesthesia or Paracetamol alone. We applied a combination of methods to assess behavioral, emotional, and physiological changes indicative of pain. Voluntary Paracetamol intake via drinking water reached the target dosage of 200 mg/kg in most animals. Local anesthesia did not lead to obvious side effects such as irregular wound healing or systemic disorders. No relevant sex differences were detected in our study. Sevoflurane anesthesia and surgery affected physiological and behavioral measurements. Surprisingly, Paracetamol treatment alone significantly increased the Mouse Grimace Scale. Taken together, mice treated with a combination of local anesthesia and systemic analgesia did not show fewer signs of post-surgical pain or improved recovery compared to animals treated with either local anesthesia or Paracetamol.
Low serum adiponectin level is associated with better physical health-related quality of life in chronic kidney disease
Authors: Kim Ji Hye , Han Ji Min , Kim Hyang , Lee Kyu-Beck , Chung Wookyung , Kim Yong-Soo , Park Sue K. , Chae Dong Wan , Ahn Curie , Oh Kook-Hwan , Hyun Young Youl ,   KNOW-CKD Study Group
Published: May 2021

AbstractHyperadiponectemia is paradoxically associated with renal disease progression and mortality in chronic kidney disease (CKD). Its association with health-related quality of life (HR-QOL) is unknown. This study aimed to verify the association between adiponectin and HR-QOL in Korean pre-dialysis CKD cohort. This cross-sectional study analyzed 1551 pre-dialysis CKD patients from KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into three tertiles (T1–T3) according to adiponectin levels. HR-QOL was assessed using SF-36. High physical component summary (PCS) and mental component summary (MCS) were defined as highest quartile of each score. Multivariate logistic regression was used to analyze odds ratio (OR) and 95% confidence interval (CI) for high PCS and MCS. Prevalence of high PCS were 33.3%, 27.5%, and 17.0% and that of high MCS were 31.7%, 24.8%, and 21.3% for T1, T2, and T3 (both p for trend < 0.001). The adjusted OR [95% CI] of T1 and T2 in reference to T3 were 1.56 [1.09–2.23] and 1.19 [0.85–1.68] for high PCS and 1.19 [0.85–1.68] and 0.94 [0.68–1.29] for high MCS. Serum adiponectin level was inversely associated with physical HR-QOL in Korean pre-dialysis CKD patients. This relationship was independent of various cardiovascular risk factors.
Deceleration capacity of heart rate variability as a predictor of sedation related hypotension
Authors: Tsai Feng-Fang , Liu Chih-Min , Wang Hsiu-Po , Yeh Jia-Rong , Fan Shou-Zen 
Published: May 2021

AbstractHigh risk and geriatric patients are supposed to suffer higher risks of hypotension underwent painless endoscopic procedures. This study evaluated different biomarkers associated with hypotension in off-site patients and aimed to determine the most relevant risk factors in space and monitoring limited environment. The inclusions of this observational cohort study underwent complex endoscopic procedures were sedated with age-adjusted doses of target-controlled infusion of propofol. The following pre-sedative parameters were analysed: time domain, frequency domain, and Deceleration capacity (DC) of heart rate variability, estimated cardiac output data and the index of cardiac contractility from the cardiometer. Patients were divided into hypotension group (blood pressure < 90 mmHg or a > 35% decrease) and non-hypotension group according to peri-sedative blood pressure, regression analysis is used to examine the association between factors and hypotension. Total data from 178 patients (age range: 33–94 years) were analysed. Age was not significantly different between the hypotension and non-hypotension groups (p = 0.978). Among all the factors, DC was most associated with hypotension (p = 0.05), better than cardiometer, age, and ASA status. In conclusion, DC, which can be interpreted as the indicator of parasympathetic activity and was significantly and negatively correlated with sedation-related hypotension. Pre-sedative measuring DC from routine ECG monitoring is simple and cost-effective and should be added to haemodynamic monitoring in the endoscopic room.
Genetic influence of CYP2D6 on pharmacokinetics and acute subjective effects of LSD in a pooled analysis
Authors: Vizeli Patrick , Straumann Isabelle , Holze Friederike , Schmid Yasmin , Dolder Patrick C. , Liechti Matthias E. 
Published: May 2021

AbstractLysergic acid diethylamide (LSD) is a classic psychedelic substance that is used recreationally and investigated in psychiatric research. There are no pharmacogenetic studies on LSD. In vitro metabolic studies indicate that several cytochrome P450 (CYP) isoforms (e.g., CYP2D6, CYP1A2, and CYP2C9) are involved in LSD metabolism, but in vivo data are scarce. The present study examined the influence of genetic polymorphisms of CYP genes on the pharmacokinetics and acute effects of LSD in healthy subjects. We identified common genetic variants of CYPs (CYP2D6, CYP1A2, CYP2C9, CYP2C19, and CYP2B6) in 81 healthy subjects who were pooled from four randomized, placebo-controlled, double-blind Phase 1 studies. We found that genetically determined CYP2D6 functionality significantly influenced the pharmacokinetics of LSD. Individuals with no functional CYP2D6 (i.e., poor metabolizers) had longer LSD half-lives and approximately 75% higher parent drug and main metabolite 2-oxo-3-hydroxy LSD area-under-the-curve blood plasma concentrations compared with carriers of functional CYP2D6. Non-functional CYP2D6 metabolizers also exhibited greater alterations of mind and longer subjective effect durations in response to LSD compared with functional CYP2D6 metabolizers. No effect on the pharmacokinetics or acute effects of LSD were observed with other CYPs. These findings indicate that genetic polymorphisms of CYP2D6 significantly influence the pharmacokinetic and subjective effects of LSD. Given the potential therapeutic use of psychedelics, including LSD, the role of pharmacogenetic tests prior to LSD-assisted psychotherapy needs to be further investigated.
Weather temperature and the incidence of hospitalization for cardiovascular diseases in an aging society
Authors: Yoneyama Kihei , Nakai Michikazu , Higuma Takumi , Teramoto Kanako , Watanabe Mika , Kaihara Toshiki , Sumita Yoko , Miyamoto Yoshihiro , Yasuda Satoshi , Ishibashi Yuki , Izumo Masaki , Tanabe Yasuhiro , Harada Tomoo , Ogawa Hisao , Akashi Yoshihiro J. 
Published: May 2021

AbstractWeather temperatures affect the incidence of cardiovascular diseases (CVD), but there is limited information on whether CVD hospitalizations are affected by changes in weather temperatures in a super-aging society. We aimed to examine the association of diurnal weather temperature changes with CVD hospitalizations. We included 1,067,171 consecutive patients who were admitted to acute-care hospitals in Japan between April 1, 2012 and March 31, 2015. The primary outcome was the number of CVD hospitalizations per day. The diurnal weather temperature range (DTR) was defined as the minimum weather temperature subtracted from the maximum weather temperature on the day before hospitalization. Multilevel mixed-effects linear regression models were used to estimate the association of DTR with cardiovascular hospitalizations after adjusting for weather, hospital, and patient demographics. An increased DTR was associated with a higher number of CVD hospitalizations (coefficient, 4.540 [4.310–4.765]/°C change, p < 0.001), with greater effects in those aged 75–89 (p < 0.001) and ≥ 90 years (p = 0.006) than among those aged ≤ 64 years; however, there were no sex-related differences (p = 0.166). Greater intraday weather temperature changes are associated with an increased number of CVD hospitalizations in the super-aging society of Japan, with a greater effect in older individuals.
Soil organic carbon cycling in response to simulated soil moisture variation under field conditions
Authors: Singh Shikha , Mayes Melanie A. , Shekoofa Avat , Kivlin Stephanie N. , Bansal Sangeeta , Jagadamma Sindhu 
Published: May 2021

AbstractThe combination of extended dry periods and high intensity rainfall, common in the southeastern US, leads to greater variability in soil moisture and consequently increases uncertainty to microbial processes pertinent to soil carbon (C) mineralization. However, field-based findings on soil moisture sensitivity to soil C cycling are very limited. Therefore, a field experiment was conducted in 2018 and 2019 on a soybean (Glycine maxL.) cropland in the southeastern US with three soil moisture treatments: drought (simulated using rainout-shelter from June to October in each year), rainfed (natural precipitation), and irrigated (irrigation and precipitation). Soil respiration was measured weekly from May to November in both years. Soil samples were collected multiple times each year from 0–5, 5–15, and 15–30 cm depths to determine microbial biomass C (MBC), extractable organic C (EOC), hydrolytic enzyme activities, and fungal abundance. The cumulative respiration under drought compared to other treatments was lower by 32% to 33% in 2018 and 38% to 45% in 2019. Increased MBC, EOC, and fungal abundance were observed under drought than other treatments. Specific enzyme activity indicated fewer metabolically active microbes under drought treatment compared to rainfed and irrigated treatments. Also, maintenance of enzyme pool was observed under drought condition. These results provide critical insights on microbial metabolism in response to soil moisture variation and how that influences different pools of soil C under field conditions.
Tolerance and decolorization potential of duckweed (Lemna gibba) to C.I. Basic Green 4
Authors: Singh Hanwant , Raj Shani , Kumar Deepak , Sharma Shubhangani , Bhatt Upma , kalaji Hazem M. , Wróbel Jacek , Soni Vineet 
Published: May 2021

AbstractWith growing human culture and industrialization, many pollutants are being introduced into aquatic ecosystems. In recent years, dyes have become a major water pollutant used in the manufacture of paints and other production purposes. In this research, the potential of duckweed (Lemna gibba) plant was investigated spectrophotometrically as an obvious bioagent for the biological decolorization of the organic dye C.I. Basic Green 4 (Malachite Green, BG4). Photosynthetic efficiency analysis showed that the photosynthetic apparatus of L. gibba is very tolerant to BG4. Significant induction of reactive oxygen species (ROS) scavenging enzymes was observed after 24h of biodecolorization process in L. gibba treated with 15 and 30 mg/l BG4. The experimental results showed that L. gibba has a strong ability to extract BG4 from contaminated water and the best results were obtained at 25–30°C and pH 8.0. We conclude that duckweed L. gibba can be used as a potent decolorization organism for BG4.
Soil bacterial community composition in rice–fish integrated farming systems with different planting years
Authors: Zhao Zheng , Chu Changbin , Zhou Deping , Wang Qingfeng , Wu Shuhang , Zheng Xianqing , Song Ke , Lv Weiguang 
Published: May 2021

AbstractThe high productivity and efficient nutrient utilization in rice–fish integrated farming system are well reported. However, the characteristics of soil bacterial communities and their relationship with soil nutrient availability in rice–fish field remain unclear. In this study, we selected three paddy fields, including a rice monoculture field and two rice–fish fields with different planting years, to investigate the soil bacterial community composition with Illumina MiSeq sequencing technology. The results indicated that the soil properties were significantly different among different rice farming systems. The soil bacterial community composition in the rice–fish field was significantly different from that in the rice monoculture field. Five of the top 15 phyla were observed with significant differences and Nitrospirae was the most significant one. However, no taxa observed with significance between the rice planting area and aquaculture area no matter in the 1st or 5th year of rice–fish field. RDA analysis showed that the soil bacterial community differentiation in the 5th year of rice–fish field was positively correlated with soil properties, such as AN and OM contents, EC and pH value. Although the rice yields in rice–fish field decreased, the net economic benefit of the rice–fish system enhanced obviously due to the high value of aquaculture animals.
The transcriptome analysis on urea response mechanism in the process of ergosterol synthesis by Cordyceps cicadae
Authors: Su Qihui , Zhang Zhicai , Liu Xiaocui , Wang Feng 
Published: May 2021

AbstractNitrogen source is required for the growth of Cordyceps cicadae and involved in the regulation of metabolite synthesis. In order to further investigate the regulatory effects of nitrogen sources on the ergosterol synthesis by C. cicadae. We first confirmed that urea could significantly increase the ergosterol synthesis. The transcriptome analysis showed that compared with biomass cultured in the control fermentation medium (CFM), 1340 differentially expressed genes (DEGs) were obtained by Gene Ontology (GO) annotation, and 312 DEGs were obtained by Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation from the biomass cultured in CFM + CO(NH2)2. Urea up-regulated D-3-phosphoglycerate dehydrogenase gene transcription level and down-regulated enolase and L-serine/L-threonine ammonialyase gene transcription level, increased serine synthesis, allosterically activate pyruvate kinase, to promote the synthesis of pyruvate and CH3CO ~ SCOA, the primer of ergosterol; Urea increase the genes transcription related with ergosterol synthesis by up-regulating the steroid regulatory element binding protein gene transcription levels. The transcriptome results were provided by those of qRT-PCR. Collectively, our finding provided valuable insights into the regulatory effect of nitrogen source on the ergosterol synthesis by C. cicadae.
Cost-effectiveness of a hypothetical cell or gene therapy cure for sickle cell disease
Authors: Salcedo Jonathan , Bulovic Jenniffer , Young Colin M. 
Published: May 2021

AbstractSickle cell disease (SCD) is a group of inherited genetic conditions associated with lifelong complications and increased healthcare resource utilization. Standard treatment for SCD in the US varies based on stage of the disease and observed clinical severity. In this study, we aim to evaluate the potential cost-effectiveness of a durable cell or gene therapy cure for sickle cell disease from the US healthcare sector perspective. We developed a lifetime Markov model to evaluate the cost-effectiveness of a hypothetical single-administration durable treatment (DT) for SCD provided at birth, relative to standard of care (SOC). We informed model inputs including direct healthcare costs, health state utility weights, transition probabilities, and mortality rates using a retrospective database analysis of commercially insured individuals and the medical literature. Our primary outcome of interest was the incremental cost-effectiveness ratio (ICER) of DT versus SOC evaluated at a base case willingness-to-pay (WTP) threshold of $150,000 per quality-adjusted life year (QALY). We tested the robustness of our base case findings through scenario, deterministic sensitivity (DSA), and probabilistic sensitivity analyses (PSA). In the base case analysis, treatment with DT was cost-effective with an ICER of $140,877/QALY relative to SOC for a hypothetical cohort involving 47% females. Both males (ICER of $135,574/QALY) and females (ICER of $146,511/QALY) were similarly cost-effective to treat. In univariate DSA the base case ICER was most sensitive to the costs of treating males, DT treatment cost, and the discount rate. In PSA, DT was cost-effective in 32.7%, 66.0%, and 92.6% of 10,000 simulations at WTP values of $100,000, $150,000, and $200,000 per QALY, respectively. A scenario analysis showed cost-effectiveness of DT is highly contingent on assumed lifetime durability of the cure. A hypothetical cell or gene therapy cure for SCD is likely to be cost-effective from the US healthcare sector perspective. Large upfront costs of a single administration cure are offset by significant downstream gains in health for patients treated early in life. We find cost-effectiveness outcomes do not vary substantially by gender; however, several model parameters including assumed durability and upfront cost of DT are likely to influence cost-effectiveness findings.
Statistical optimization of experimental parameters for extracellular synthesis of zinc oxide nanoparticles by a novel haloalaliphilic Alkalibacillus sp.W7
Authors: Al-Kordy Hend M. H. , Sabry Soraya A. , Mabrouk Mona E. M. 
Published: May 2021

AbstractGreen synthesis of zinc oxide nanoparticles (ZnO NPs) through simple, rapid, eco-friendly and an economical method with a new haloalkaliphilic bacterial strain (Alkalibacillus sp. W7) was investigated. Response surface methodology (RSM) based on Box-Behnken design (BP) was used to optimize the process parameters (ZnSO4.7H2O concentration, temperature, and pH) affecting the size of Alkalibacillus-ZnO NPs (Alk-ZnO NPs). The synthesized nanoparticles were characterized using UV–visible spectrum, X-ray diffraction (XRD), Scanning electron microscope-energy dispersive X-ray spectroscopy (SEM–EDX), Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and Zeta potential. The UV–Vis spectrum of ZnO NPs revealed a characteristic surface plasmon resonance (SPR) peak at 310 nm. XRD pattern confirmed the hexagonal wurtzite structure of highly pure with a crystallite size 19.5 nm. TEM proved the quasi-spherical shape nanoparticles of size ranging from 1 to 30 nm. SEM–EDX showed spherical shaped and displayed a maximum elemental distribution of zinc and oxygen. FTIR provided an evidence that the biofunctional groups of metabolites in Alkalibacillus sp.W7 supernatant acted as viable reducing, capping and stabilizing agents.
Mapping marine debris encountered by albatrosses tracked over oceanic waters
Authors: Nishizawa Bungo , Thiebot Jean-Baptiste , Sato Fumio , Tomita Naoki , Yoda Ken , Yamashita Rei , Takada Hideshige , Watanuki Yutaka 
Published: May 2021

AbstractAnthropogenic marine debris is a threat to marine organisms. Understanding how this debris spatially distributes at sea and may become associated with marine wildlife are key steps to tackle this current issue. Using bird-borne GPS- and video-loggers on 13 black-footed albatrosses Phoebastria nigripes breeding in Torishima, Japan, we examined the distribution of large floating debris in the Kuroshio Current area, western North Pacific. A total of 16 floating debris, including styrofoam (n = 4), plastic pieces (n = 3), plastic sheet (n = 1), fishery-related items (rope or netting, n = 4), and unidentified debris (n = 4), were recorded across the 9003 km covered by nine birds. The debris was concentrated in the southern area of the Kuroshio Current, where the surface current was weak, and the albatrosses were foraging. The albatrosses displayed changes in flight direction towards the debris when at a mean distance of 4.9 km, similarly to when approaching prey, and one bird was observed pecking at a plastic sheet; indicating that albatrosses actively interacted with the debris. This paper shows the usefulness of studying wide-ranging marine predators through the use of combined biologging tools, and highlights areas with increased risk of debris exposure and behavioral responses to debris items.
Dicing of composite substrate for thin film AlGaInP power LEDs by wet etching
Authors: Horng Ray-Hua , Sinha Shreekant , Tarntair Fu-Gow , Feng Hsiang-An , Tu Chia-Wei 
Published: May 2021

AbstractIn this paper, thin film AlGaInP LED chips with a 50 μm thick composite metal substrate (Copper-Invar-Copper; CIC) were obtained by the wet etching process. The pattern of the substrate was done by the backside of the AlGaInP LED/CIC. There was no delamination or cracking phenomenon of the LED epilayer which often occurs by laser or mechanical dicing. The chip area was 1140 μm × 1140 μm and the channel length was 360 μm. The structure of the CIC substrate was a sandwich structure and consisted of Cu as the top and bottom layers, with a thickness of 10 μm, respectively. The middle layer was Invar with a 30% to 70% ratio of Ni and Fe and a total thickness of 30 μm. The chip pattern was successfully obtained by the wet etching process. Concerning the device performance after etching, high-performance LED/CIC chips were obtained. They had a low leakage current, high output power and a low red shift phenomenon as operated at a high injected current. After the development and fabrication of the copper-based composite substrate for N-side up thin-film AlGaInP LED/CIC chips could be diced by wet etching. The superiority of wet etching process for the AlGaInP LED/CIC chips is over that of chips obtained by mechanical or laser dicing.