bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity in patterns of helminth infections across populations of mountain gorillas (Gorilla beringei beringei)
Authors: Petrželková Klara J. , Uwamahoro Carine , Pafčo Barbora , Červená Barbora , Samaš Peter , Mudakikwa Antoine , Muvunyi Richard , Uwingeli Prosper , Gilardi Kirsten , Nziza Julius , Noheri Jean Bosco , Eckardt Winnie , Ndagijimana Felix , Ssebide Benard , Okwirokello Ricky , Nizeyimana Fred , Syaluha Eddy Kambale , Nzayisenga Gaspard , Flores Girón Luis , Bahizi Méthode , Ntwari Adrien Emile , Lukusa Jean-Paul , Tumushime Jean Claude , Mangura Damien , Mapilanga Jeff , Kalonji Arthur , Aruho Robert , Stryková Anna , Tehlarová Zuzana , Cameira Rita , Lowenstine Linda , Šlapeta Jan , Romportl Dušan , Ferrari Nicola , Cranfield Michael , Modrý David
Published: May 2021

Conservation efforts have led to the recovery of the endangered mountain gorilla populations. Due to their limited potential for spatial expansion, population densities increased, which may alter the epidemiology of infectious diseases. Recently, clinical gastrointestinal illnesses linked to helminth infections have been recorded in both gorilla populations. To understand drivers and patterns of helminth infections we quantified strongylid and tapeworm infections across both Virunga Massif and Bwindi populations using fecal egg counts. We assessed the impact of age, sex, group size, season and spatial differences used as a proxy, which reflects observed variation in the occurrence of gastrointestinal problems, vegetation types, gorilla subpopulation growth and associated social structure on helminth infections. We revealed striking geographic differences in strongylid infections with higher egg counts mostly in areas with high occurrences of gastrointestinal disease. Increased helminth egg counts were also associated with decreasing group size in some areas. Observed spatial differences may reflect mutual effects of variations in subpopulation growth rates, gorilla social structure, and vegetation associated with altitude across mountain gorilla habitat. Helminth infection intensities in Virunga gorillas were lowest in the youngest and the oldest animals. Elucidating parasite infection patterns of endangered species with low genetic diversity is crucial for their conservation management.
Assessment of axillary node status by ultrasound after neoadjuvant chemotherapy in patients with clinically node-positive breast cancer according to breast cancer subtype
Authors: Maeshima Yurina , Sakai Takehiko , Ogiya Akiko , Takahashi Yoko , Miyagi Yumi , Kokubu Yumi , Osako Tomo , Ito Yoshinori , Takahashi Shunji , Ohno Shinji , Ueno Takayuki
Published: May 2021

The use of sentinel node biopsy (SNB) following neoadjuvant chemotherapy (NAC) for patients with cN1 breast cancer is controversial. Improvements of negative predictive value (NPV) by axillary ultrasound (AUS), which corresponds to the accurate prediction rate of node-negative status after NAC, would lead to decreased FNR of SNB following NAC. In this study, we retrospectively investigated the accurate prediction rate of NPV by AUS after NAC in patients with cytologically node-positive breast cancer treated between January 2012 and December 2016. Of 279 eligible patients, the NPV was 49.2% in all patients, but varied significantly by tumor subtype (p < 0.001) and tumor response determined by magnetic resonance imaging (MRI) (p = 0.0003). Of the 23 patients with clinically node negative (ycN0) by AUS and clinical complete response in primary lesion by MRI, the NPV was 100% in patients with HR±/HER2+ or HR−/HER2− breast cancer. In conclusion, regarding FNR reduction post-NAC, it will be of clinical value to take tumor subtype and primary tumor response using MRI into account to identify patients for SNB after NAC.
Author Correction: Considering serum alanine aminotransferase and gamma-glutamyltransferase levels together strengthen the prediction of impaired fasting glucose risk: a cross-sectional and longitudinal study
Authors: Jeong Ji Hye , Jung Susie , Kim Kyu-Nam
Published: May 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The modulatory effects of alfalfa polysaccharide on intestinal microbiota and systemic health of Salmonella serotype (ser.) Enteritidis-challenged broilers
Authors: Li Zemin , Zhang Chongyu , Li Bo , Zhang Shimin , Haj Fawaz G. , Zhang Guiguo , Lee Yunkyoung
Published: May 2021

Salmonella serotype (ser.) Enteritidis infection in broilers is a main foodborne illness that substantially threatens food security. This study aimed to examine the effects of a novel polysaccharide isolated from alfalfa (APS) on the intestinal microbiome and systemic health of S. ser. Enteritidis-infected broilers. The results indicated that broilers receiving the APS-supplemented diet had the improved (P < 0.05) growth performance and gut health than those fed no APS-supplemented diet. Supplementation with APS enhanced (P < 0.05) the richness of gut beneficial microbes such as Bacteroidetes, Barnesiella, Parabacteroides, Butyricimonas, and Prevotellaceae, while decreased (P < 0.05) the abundance of facultative anaerobic bacteria including Proteobacteria, Actinobacteria, Ruminococcaceae, Lachnospiraceae, and Burkholderiaceae in the S. ser. Enteritidis-infected broilers. The Bacteroides and Odoribacter were identified as the two core microbes across all treatments and combined with their syntrophic microbes formed the hub in co-occurrence networks linking microbiome structure to performance of broilers. Taken together, dietary APS supplementation improved the systemic health of broilers by reshaping the intestinal microbiome regardless of whether S. ser. Enteritidis infection was present. Therefore, APS can be employed as a potential functional additives to inhibit the S. ser. Enteritidis and enhance the food safety in poultry farming.
A comparative study of synthetic winged peptides for absolute protein quantification
Authors: Benesova Eliska , Vidova Veronika , Spacil Zdenek
Published: May 2021

A proper internal standard choice is critical for accurate, precise, and reproducible mass spectrometry-based proteomics assays. Synthetic isotopically labeled (SIL) proteins are currently considered the gold standard. However, they are costly and challenging to obtain. An alternative approach uses SIL peptides or SIL "winged" peptides extended at C- or/and N-terminus with an amino acid sequence or a tag cleaved during enzymatic proteolysis. However, a consensus on the design of a winged peptide for absolute quantification is missing. In this study, we used human serum albumin as a model system to compare the quantitative performance of reference SIL protein with four different designs of SIL winged peptides: (i) commercially available SIL peptides with a proprietary trypsin cleavable tag at C-terminus, (ii) SIL peptides extended with five amino acid residues at C-terminus, (iii) SIL peptides extended with three and (iv) with five amino acid residues at both C- and N-termini. Our results demonstrate properties of various SIL extended peptides designs, e.g., water solubility and efficiency of trypsin enzymatic cleavage with primary influence on quantitative performance. SIL winged peptides extended with three amino acids at both C- and N-termini demonstrated optimal quantitative performance, equivalent to the SIL protein.
Semantic and spatial congruency mould audiovisual integration depending on perceptual awareness
Authors: Delong Patrycja , Noppeney Uta
Published: May 2021

Information integration is considered a hallmark of human consciousness. Recent research has challenged this tenet by showing multisensory interactions in the absence of awareness. This psychophysics study assessed the impact of spatial and semantic correspondences on audiovisual binding in the presence and absence of visual awareness by combining forward–backward masking with spatial ventriloquism. Observers were presented with object pictures and synchronous sounds that were spatially and/or semantically congruent or incongruent. On each trial observers located the sound, identified the picture and rated the picture’s visibility. We observed a robust ventriloquist effect for subjectively visible and invisible pictures indicating that pictures that evade our perceptual awareness influence where we perceive sounds. Critically, semantic congruency enhanced these visual biases on perceived sound location only when the picture entered observers’ awareness. Our results demonstrate that crossmodal influences operating from vision to audition and vice versa are interactively controlled by spatial and semantic congruency in the presence of awareness. However, when visual processing is disrupted by masking procedures audiovisual interactions no longer depend on semantic correspondences.
COVID-19 infection data encode a dynamic reproduction number in response to policy decisions with secondary wave implications
Authors: Rowland Michael A. , Swannack Todd M. , Mayo Michael L. , Parno Matthew , Farthing Matthew , Dettwiller Ian , George Glover , England William , Reif Molly , Cegan Jeffrey , Trump Benjamin , Linkov Igor , Lafferty Brandon , Bridges Todd
Published: May 2021

The SARS-CoV-2 virus is responsible for the novel coronavirus disease 2019 (COVID-19), which has spread to populations throughout the continental United States. Most state and local governments have adopted some level of “social distancing” policy, but infections have continued to spread despite these efforts. Absent a vaccine, authorities have few other tools by which to mitigate further spread of the virus. This begs the question of how effective social policy really is at reducing new infections that, left alone, could potentially overwhelm the existing hospitalization capacity of many states. We developed a mathematical model that captures correlations between some state-level “social distancing” policies and infection kinetics for all U.S. states, and use it to illustrate the link between social policy decisions, disease dynamics, and an effective reproduction number that changes over time, for case studies of Massachusetts, New Jersey, and Washington states. In general, our findings indicate that the potential for second waves of infection, which result after reopening states without an increase to immunity, can be mitigated by a return of social distancing policies as soon as possible after the waves are detected.
A predictive model for vertebrate bone identification from collagen using proteomic mass spectrometry
Authors: Yang Heyi , Butler Erin R. , Monier Samantha A. , Teubl Jennifer , Fenyö David , Ueberheide Beatrix , Siegel Donald
Published: May 2021

Proteogenomics is an increasingly common method for species identification as it allows for rapid and inexpensive interrogation of an unknown organism’s proteome—even when the proteome is partially degraded. The proteomic method typically uses tandem mass spectrometry to survey all peptides detectable in a sample that frequently contains hundreds or thousands of proteins. Species identification is based on detection of a small numbers of species-specific peptides. Genetic analysis of proteins by mass spectrometry, however, is a developing field, and the bone proteome, typically consisting of only two proteins, pushes the limits of this technology. Nearly 20% of highly confident spectra from modern human bone samples identify non-human species when searched against a vertebrate database—as would be necessary with a fragment of unknown bone. These non-human peptides are often the result of current limitations in mass spectrometry or algorithm interpretation errors. Consequently, it is difficult to know if a “species-specific” peptide used to identify a sample is actually present in that sample. Here we evaluate the causes of peptide sequence errors and propose an unbiased, probabilistic approach to determine the likelihood that a species is correctly identified from bone without relying on species-specific peptides.
Modular barcode beads for microfluidic single cell genomics
Authors: Delley Cyrille L. , Abate Adam R.
Published: May 2021

Barcode beads allow efficient nucleic acid tagging in single cell genomics. Current barcode designs, however, are fabricated with a particular application in mind. Repurposing to novel targets, or altering to add additional targets as information is obtained is possible but the result is suboptimal. Here, we describe a modular framework that simplifies generation of multifunctional beads and allows their easy extension to new targets.
Identification of hepatic fibrosis inhibitors through morphometry analysis of a hepatic multicellular spheroids model
Authors: Song Yeonhwa , Kim Sanghwa , Heo Jinyeong , Shum David , Lee Su-Yeon , Lee Minji , Kim A-Ram , Seo Haeng Ran
Published: May 2021

A chronic, local inflammatory milieu can cause tissue fibrosis that results in epithelial-to-mesenchymal transition (EMT), endothelial-to-mesenchymal transition (EndMT), increased abundance of fibroblasts, and further acceleration of fibrosis. In this study, we aimed to identify potential mechanisms and inhibitors of fibrosis using 3D model-based phenotypic screening. We established liver fibrosis models using multicellular tumor spheroids (MCTSs) composed of hepatocellular carcinoma (HCC) and stromal cells such as fibroblasts (WI38), hepatic stellate cells (LX2), and endothelial cells (HUVEC) seeded at constant ratios. Through high-throughput screening of FDA-approved drugs, we identified retinoic acid and forskolin as candidates to attenuate the compactness of MCTSs as well as inhibit the expression of ECM-related proteins. Additionally, retinoic acid and forskolin induced reprogramming of fibroblast and cancer stem cells in the HCC microenvironment. Of interest, retinoic acid and forskolin had anti-fibrosis effects by decreasing expression of α-SMA and F-actin in LX2 cells and HUVEC cells. Moreover, when sorafenib was added along with retinoic acid and forskolin, apoptosis was increased, suggesting that anti-fibrosis drugs may improve tissue penetration to support the efficacy of anti-cancer drugs. Collectively, these findings support the potential utility of morphometric analyses of hepatic multicellular spheroid models in the development of new drugs with novel mechanisms for the treatment of hepatic fibrosis and HCCs.
Effects of elevated temperature on the corrosion resistance of silver–cobalt oxide–titanium dioxide (Ag/Co3O4/TiO2) nanocomposites coating on AISI 1020
Authors: Ibrahim Mohammed , Agboola Joseph B. , Abdulkareem Saka A. , Adedipe Oyewole , Tijani Jimoh O.
Published: May 2021

The effects of temperature on corrosion resistance of Silver–Cobalt oxide and Titanium Dioxide (Ag/Co3O4/TiO2) nanocomposite coated AISI 1020 in a high-temperature environment was investigated. The Ag, Co3O4and TiO2nanoparticles were individually produced by mixing the salt precursors with extract ofPiptadeniastrum Africanaleaf under the optimized synthesis conditions. The nanocomposite was produced by mixing Ag, Co3O4and TiO2nanoparticles (NPs) in equal proportions to constitute 75 wt% of the composite. 10 wt% epoxy resin and its hardener in the ratio (1:1) were added to serve as the binder, while 15 wt% of CNT was introduced to serve as support. The produced Ag/Co3O4/TiO2nanocomposite was coated on the surface of mild steel (AISI 1020) by the dipping method. The coated samples were heated in a muffle furnace to 35, 100, 200, and 300 °C. Microstructural evolution of the coatings was investigated using X-ray diffraction, scanning electron microscopy and energy dispersive spectrometer. The corrosion resistance of the coated and heated and un-heated steel samples was determined using the potentiodynamic polarization method. The results show that Ag/Co3O4/TiO2nanocomposite coated sample cured at 100 °C exhibited the highest corrosion resistance of 195.12 Ω.
Identification of novel source of salt tolerance in local bread wheat germplasm using morpho-physiological and biochemical attributes
Authors: Hussain Nadeem , Ghaffar Abdul , Zafar Zafar Ullah , Javed Muhammad , Shah Kausar Hussain , Noreen Sibgha , Manzoor Hamid , Iqbal Muhammad , Hassan Islam Frahat Zaky , Bano Hussan , Gul Hafiza Saima , Aamir Misbah , Khalid Ayesha , Sohail Younas , Ashraf Muhammad , Athar Habib-ur-Rehman
Published: May 2021

Salt tolerant wheat cultivars may be used as genetic resource for wheat breeding to ensure yield stability in future. The study was aimed to select salt tolerant cultivar(s) to identify novel source of salt tolerance in local wheat germplasm. Initially, 40 local wheat cultivars were screened at 150 mM NaCl stress at seedling stage. Selected salt-tolerant (three; S-24, LU-26S and Pasban-90) and salt-sensitive (four; MH-97, Kohistan-97, Inqilab-91 and Iqbal-2000) wheat cultivars were further evaluated using growth, yield, biochemical and physiological attributes. Growth and yield of selected cultivars were reduced under salt stress due to decline in plant water status, limited uptake of macronutrients (N, P and K), reduced K+/Na+ratio, photosynthetic pigments and quantum yield of PSII. Wheat plants tried to acclimate salt stress by osmotic adjustment (accumulation of total soluble sugars, proline and free amino acids). Degree of salinity tolerance in cvs. S-24 and LU-26S found to be associated with maintenance of K+/Na+ratio, osmo-protectant and photosynthetic activity and can be used as donor for salt tolerance in wheat breeding program at least in Pakistan. These cultivars can be further characterized using molecular techniques to identify QTLs/genes for salt exclusion, osmo-protectant and photosynthetic activity for molecular breeding.
Protein model accuracy estimation empowered by deep learning and inter-residue distance prediction in CASP14
Authors: Chen Xiao , Liu Jian , Guo Zhiye , Wu Tianqi , Hou Jie , Cheng Jianlin
Published: May 2021

The inter-residue contact prediction and deep learning showed the promise to improve the estimation of protein model accuracy (EMA) in the 13th Critical Assessment of Protein Structure Prediction (CASP13). To further leverage the improved inter-residue distance predictions to enhance EMA, during the 2020 CASP14 experiment, we integrated several new inter-residue distance features with the existing model quality assessment features in several deep learning methods to predict the quality of protein structural models. According to the evaluation of performance in selecting the best model from the models of CASP14 targets, our three multi-model predictors of estimating model accuracy (MULTICOM-CONSTRUCT, MULTICOM-AI, and MULTICOM-CLUSTER) achieve the averaged loss of 0.073, 0.079, and 0.081, respectively, in terms of the global distance test score (GDT-TS). The three methods are ranked first, second, and third out of all 68 CASP14 predictors. MULTICOM-DEEP, the single-model predictor of estimating model accuracy (EMA), is ranked within top 10 among all the single-model EMA methods according to GDT-TS score loss. The results demonstrate that inter-residue distance features are valuable inputs for deep learning to predict the quality of protein structural models. However, larger training datasets and better ways of leveraging inter-residue distance information are needed to fully explore its potentials.
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

Clostridioides 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

While 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

Hyperadiponectemia 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

High 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

Lysergic 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

Weather 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

The 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

With 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

The 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

Nitrogen 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

Sickle 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

Green 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

Anthropogenic 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

In 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.
Brain tumor segmentation based on deep learning and an attention mechanism using MRI multi-modalities brain images
Authors: Ranjbarzadeh Ramin , Bagherian Kasgari Abbas , Jafarzadeh Ghoushchi Saeid , Anari Shokofeh , Naseri Maryam , Bendechache Malika
Published: May 2021

Brain tumor localization and segmentation from magnetic resonance imaging (MRI) are hard and important tasks for several applications in the field of medical analysis. As each brain imaging modality gives unique and key details related to each part of the tumor, many recent approaches used four modalities T1, T1c, T2, and FLAIR. Although many of them obtained a promising segmentation result on the BRATS 2018 dataset, they suffer from a complex structure that needs more time to train and test. So, in this paper, to obtain a flexible and effective brain tumor segmentation system, first, we propose a preprocessing approach to work only on a small part of the image rather than the whole part of the image. This method leads to a decrease in computing time and overcomes the overfitting problems in a Cascade Deep Learning model. In the second step, as we are dealing with a smaller part of brain images in each slice, a simple and efficient Cascade Convolutional Neural Network (C-ConvNet/C-CNN) is proposed. This C-CNN model mines both local and global features in two different routes. Also, to improve the brain tumor segmentation accuracy compared with the state-of-the-art models, a novel Distance-Wise Attention (DWA) mechanism is introduced. The DWA mechanism considers the effect of the center location of the tumor and the brain inside the model. Comprehensive experiments are conducted on the BRATS 2018 dataset and show that the proposed model obtains competitive results: the proposed method achieves a mean whole tumor, enhancing tumor, and tumor core dice scores of 0.9203, 0.9113 and 0.8726 respectively. Other quantitative and qualitative assessments are presented and discussed.
Polymerized albumin restores impaired hemodynamics in endotoxemia and polymicrobial sepsis
Authors: Belcher Donald A. , Williams Alexander T. , Palmer Andre F. , Cabrales Pedro
Published: May 2021

Fluid resuscitation following severe inflammation-induced hypoperfusion is critical for the restoration of hemodynamics and the prevention of multiorgan dysfunction syndrome during septic shock. Fluid resuscitation with commercially available crystalloid and colloid solutions only provides transient benefits, followed by fluid extravasation and tissue edema through the inflamed endothelium. The increased molecular weight (M.W.) of polymerized human serum albumin (PolyHSA) can limit fluid extravasation, leading to restoration of hemodynamics. In this prospective study, we evaluated how fluid resuscitation with PolyHSA impacts the hemodynamic and immune response in a lipopolysaccharide (LPS) induced endotoxemia mouse model. Additionally, we evaluated fluid resuscitation with PolyHSA in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Resuscitation with PolyHSA attenuated the immune response and improved the maintenance of systemic hemodynamics and restoration of microcirculatory hemodynamics. This decrease in inflammatory immune response and maintenance of vascular wall shear stress likely contributes to the maintenance of vascular integrity following fluid resuscitation with PolyHSA. The sustained restoration of perfusion, decrease in pro-inflammatory immune response, and improved vascular integrity that results from the high M.W. of PolyHSA indicates that a PolyHSA based solution is a potential resuscitation fluid for endotoxic and septic shock.
A novel CMAQ-CNN hybrid model to forecast hourly surface-ozone concentrations 14 days in advance
Authors: Sayeed Alqamah , Choi Yunsoo , Eslami Ebrahim , Jung Jia , Lops Yannic , Salman Ahmed Khan , Lee Jae-Bum , Park Hyun-Ju , Choi Min-Hyeok
Published: May 2021

Issues regarding air quality and related health concerns have prompted this study, which develops an accurate and computationally fast, efficient hybrid modeling system that combines numerical modeling and machine learning for forecasting concentrations of surface ozone. Currently available numerical modeling systems for air quality predictions (e.g., CMAQ) can forecast 24 to 48 h in advance. In this study, we develop a modeling system based on a convolutional neural network (CNN) model that is not only fast but covers a temporal period of two weeks with a resolution as small as a single hour for 255 stations. The CNN model uses meteorology from the Weather Research and Forecasting model (processed by the Meteorology-Chemistry Interface Processor), forecasted air quality from the Community Multi-scale Air Quality Model (CMAQ), and previous 24-h concentrations of various measurable air quality parameters as inputs and predicts the following 14-day hourly surface ozone concentrations. The model achieves an average accuracy of 0.91 in terms of the index of agreement for the first day and 0.78 for the fourteenth day, while the average index of agreement for one day ahead prediction from the CMAQ is 0.77. Through this study, we intend to amalgamate the best features of numerical modeling (i.e., fine spatial resolution) and a deep neural network (i.e., computation speed and accuracy) to achieve more accurate spatio-temporal predictions of hourly ozone concentrations. Although the primary purpose of this study is the prediction of hourly ozone concentrations, the system can be extended to various other pollutants.