bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyrazoline derivatives as promising novel antischistosomal agents
Authors: Morais Cristiane S. , Mengarda Ana C. , Miguel Fábio B. , Enes Karine B. , Rodrigues Vinícius C. , Espírito-Santo Maria Cristina C. , Siyadatpanah Abolghasem , Wilairatana Polrat , Couri Mara R. C. , de Moraes Josué 
Published: December 2021

AbstractPraziquantel is the only available drug to treat schistosomiasis, a parasitic disease that currently infects more than 240 million people globally. Due to increasing concerns about resistance and inadequate efficacy there is a need for new therapeutics. In this study, a series of 17 pyrazolines (15–31) and three pyrazoles (32–34) were synthesized and evaluated for their antiparasitic properties against ex vivo adult Schistosoma mansoni worms. Of the 20 compounds tested, six had a 50% effective concentration (EC50) below 30 μM. Our best hit, pyrazoline 22, showed promising activity against adult schistosomes, with an EC50 < 10 µM. Additionally, compound 22 had low cytotoxicity, with selectivity index of 21.6 and 32.2 for monkey and human cell lines, respectively. All active pyrazolines demonstrated a negative effect on schistosome fecundity, with a marked reduction in the number of eggs. Structure–activity relationship analysis showed that the presence of the non-aromatic heterocycle and N-substitution are fundamental to the antischistosomal properties. Pharmacokinetics, drug-likeness and medicinal chemistry friendliness studies were performed, and predicted values demonstrated an excellent drug-likeness profile for pyrazolines as well as an adherence to major pharmaceutical companies’ filters. Collectively, this study demonstrates that pyrazoline derivatives are promising scaffolds in the discovery of novel antischistosomal agents.
Hypertrophy of the ligamentum flavum in lumbar spinal canal stenosis is associated with abnormal accumulation of specific lipids
Authors: Yamada Tomohiro , Horikawa Makoto , Sato Tomohito , Kahyo Tomoaki , Takanashi Yusuke , Ushirozako Hiroki , Kurosu Kenta , Al Mamun Md. , Mihara Yuki , Oe Shin , Arima Hideyuki , Banno Tomohiro , Yosida Go , Hasegawa Tomohiko , Yamato Yu , Matsuyama Yukihiro , Setou Mitsutoshi 
Published: December 2021

AbstractLigamentum flavum hypertrophy (HLF) is the most important component of lumbar spinal canal stenosis (LSCS). Analysis of hypertrophied ligamentum flavum (HLF) samples from patients with LSCS can be an important que. The current study analyzed the surgical samples of HLF samples in patients with LCSC using quantitative and qualitative high performance-liquid chromatography and mass spectrometry. We collected ligamentum flavum (LF) tissue from twelve patients with LSCS and from four patients with lumbar disk herniation (LDH). We defined LF from LSCS patients as HLF and that from LDH patients as non-hypertrophied ligamentum flavum (NHLF). Total lipids were extracted from the LF samples and evaluated for quantity and quality using liquid chromatography and mass spectrometry. The total lipid amount of the HLF group was 3.6 times higher than that of the NHLF group. Phosphatidylcholines (PCs), ceramides (Cers), O-acyl-ω-hydroxy fatty acids (OAHFAs), and triglycerides (TGs) in the HLF group were more than 32 times higher than those of the NHLF group. PC(26:0)+H+, PC(25:0)+H+, and PC(23:0)+H+ increased in all patients in the HLF group compared to the NHLF group. The thickness of the LF correlated significantly with PC(26:0)+H+ in HLF. We identified the enriched specific PCs, Cers, OAHFAs, and TGs in HLF.
Impact of the APOBEC3A/B deletion polymorphism on risk of ovarian cancer
Authors: Gansmo Liv B. , Sofiyeva Nigar , Bjørnslett Merete , Romundstad Pål , Hveem Kristian , Vatten Lars , Dørum Anne , Lønning Per E. , Knappskog Stian 
Published: December 2021

AbstractA germline 29.5-kb deletion variant removes the 3’ end of the APOBEC3A gene and a large part of APOBEC3B, creating a hybrid gene that has been linked to increased APOBEC3 activity and DNA damage in human cancers. We genotyped the APOBEC3A/B deletion in hospital-based samples of 1398 Norwegian epithelial ovarian cancer patients without detected BRCA1/2 germline mutations and compared to 1,918 healthy female controls, to assess the potential cancer risk associated with the deletion. We observed an association between APOBEC3A/B status and reduced risk for ovarian cancer (OR = 0.75; CI = 0.61–0.91; p = 0.003) applying the dominant model. Similar results were found in other models. The association was observed both in non-serous and serous cases (dominant model: OR = 0.69; CI = 0.50–0.95; p = 0.018 and OR = 0.77; CI = 0.62–0.96; p = 0.019, respectively) as well as within high-grade serous cases (dominant model: OR = 0.79; CI = 0.59–1.05). For validation purposes, we mined an available large multinational GWAS-based data set of > 18,000 cases and > 26,000 controls for SNP rs12628403, known to be in linkage disequilibrium with the APOBEC3A/B deletion. We found a non-significant trend for SNP rs12628403 being linked to reduced risk of ovarian cancer in general and similar trends for all subtypes. For clear cell cancers, the risk reduction reached significance (OR = 0.85; CI = 0.69–1.00).
Graphene oxide and fluorescent aptamer based novel biosensor for detection of 25-hydroxyvitamin D3
Authors: Gupta Ritika , Kaul Sunaina , Singh Vishal , Kumar Sandeep , Singhal Nitin Kumar 
Published: December 2021

AbstractFor maintaining the healthy metabolic status, vitamin D is a beneficial metabolite stored majorly in its pre-activated form, 25-hydroxyvitamin D3 (25(OH)D3). Due to its important role in bone strengthening, the study was planned to quantify 25(OH)D3 levels in our blood. Quantification techniques for 25(OH)D3 are costly thus requiring a need for a low cost, and sensitive detection methods. In this work, an economic, and sensitive sensor for the detection of 25(OH)D3 was developed using aptamer and graphene oxide (GO). Aptamer is an oligonucleotide, sensitive towards its target, whereas, GO with 2D nanosheets provides excellent quenching surface. Aptamer labeled with fluorescein (5’, 6-FAM) is adsorbed by π–π interaction on the GO sheets leading to quenching of the fluorescence due to Förster resonance energy transfer (FRET). However, in the presence of 25(OH)D3, a major portion of aptamer fluorescence remains unaltered, due to its association with 25(OH)D3. However, in the absence, aptamer fluorescence gets fully quenched. Fluorescence intensity quenching was monitored using fluorescence spectrophotometer and agarose gel based system. The limit of detection of 25(OH)D3 by this method was found to be 0.15 µg/mL whereas when GO-COOH was used, limit of detection was improved to 0.075 µg/mL. Therefore, this method could come up as a new sensing method in the field of vitamin D detection.
Lats2 promotes heart failure by stimulating p53-mediated apoptosis during pressure overload
Authors: Shao Dan , Zhai Peiyong , Hu Chengchen , Mukai Risa , Sciarretta Sebastiano , Del Re Dominic , Sadoshima Junichi 
Published: December 2021

AbstractThe Hippo pathway plays a wide variety of roles in response to stress in the heart. Lats2, a component of the Hippo pathway, is phosphorylated by Mst1/2 and, in turn, phosphorylates YAP, causing inactivation of YAP. Lats2 stimulates apoptosis and negatively affects hypertrophy in cardiomyocytes. However, the role of Lats2 during cardiac stress is poorly understood in vivo. Lats2 is activated in the mouse heart in response to transverse aortic constriction (TAC). We used systemic Lats2 +/- mice to elucidate the role of endogenous Lats2. Cardiac hypertrophy and dysfunction induced by 4 weeks of TAC were attenuated in Lats2 +/- mice, and interstitial fibrosis and apoptosis were suppressed. Although TAC upregulated the Bcl-2 family proapoptotic (Bax and Bak) and anti-apoptotic (Bcl-2 and Bcl-xL) molecules in non-transgenic mice, TAC-induced upregulation of Bax and Bak was alleviated and that of Bcl-2 was enhanced in Lats2 +/- mice. TAC upregulated p53, but this upregulation was abolished in Lats2 +/- mice. Lats2-induced increases in apoptosis and decreases in survival in cardiomyocytes were inhibited by Pifithrin-α, a p53 inhibitor, suggesting that Lats2 stimulates apoptosis via a p53-dependent mechanism. In summary, Lats2 is activated by pressure overload, thereby promoting heart failure by stimulating p53-dependent mechanisms of cell death.
Thoracic skeletal muscle quantification using computed tomography and prognosis of elderly ICU patients
Authors: Moon Sung Woo , Kim Song Yee , Choi Ji Soo , Leem Ah Young , Lee Su Hwan , Park Moo Suk , Kim Young Sam , Chung Kyung Soo 
Published: December 2021

AbstractIn elderly ICU patients, the prevalence of skeletal muscle loss is high. Longitudinal effect of thoracic muscles, especially in elderly ICU patients, are unclear although skeletal muscle loss is related with the short- and long-term outcomes. This study aimed to evaluate whether pectoralis muscle mass loss could be a predictor of prognosis in elderly ICU patients. We retrospectively evaluated 190 elderly (age > 70 years) patients admitted to the ICU. We measured the cross-sectional area (CSA) of the pectoralis muscle (PMCSA) at the fourth vertebral region. CT scans within two days before ICU admission were used for analysis. Mortality, prolonged mechanical ventilation, and longitudinal changes in Sequential Organ Failure Assessment (SOFA) scores were examined. PMCSA below median was significantly related with prolonged ventilation (odds ratio 2.92) and a higher SOFA scores during the ICU stay (estimated mean = 0.94). PMCSA below median was a significant risk for hospital mortality (hazards ratio 2.06). In elderly ICU patients, a low ICU admission PMCSA was associated with prolonged ventilation, higher SOFA score during the ICU stay, and higher mortality. Adding thoracic skeletal muscle CSA at the time of ICU admission into consideration in deciding the therapeutic intensity in elderly ICU patients may help in making medical decisions.
Plant age at the time of ozone exposure affects flowering patterns, biotic interactions and reproduction of wild mustard
Authors: Duque Laura , Poelman Erik H. , Steffan-Dewenter Ingolf 
Published: December 2021

AbstractExposure of plants to environmental stressors can modify their metabolism, interactions with other organisms and reproductive success. Tropospheric ozone is a source of plant stress. We investigated how an acute exposure to ozone at different times of plant development affects reproductive performance, as well as the flowering patterns and the interactions with pollinators and herbivores, of wild mustard plants. The number of open flowers was higher on plants exposed to ozone at earlier ages than on the respective controls, while plants exposed at later ages showed a tendency for decreased number of open flowers. The changes in the number of flowers provided a good explanation for the ozone-induced effects on reproductive performance and on pollinator visitation. Ozone exposure at earlier ages also led to either earlier or extended flowering periods. Moreover, ozone tended to increase herbivore abundance, with responses depending on herbivore taxa and the plant age at the time of ozone exposure. These results suggest that the effects of ozone exposure depend on the developmental stage of the plant, affecting the flowering patterns in different directions, with consequences for pollination and reproduction of annual crops and wild species.
Quantitative modeling of carcinogenesis induced by single beams or mixtures of space radiations using targeted and non-targeted effects
Authors: Shuryak Igor , Sachs Rainer K. , Brenner David J. 
Published: December 2021

AbstractIonizing radiations encountered by astronauts on deep space missions produce biological damage by two main mechanisms: (1) Targeted effects (TE) due to direct traversals of cells by ionizing tracks. (2) Non-targeted effects (NTE) caused by release of signals from directly hit cells. The combination of these mechanisms generates non-linear dose response shapes, which need to be modeled quantitatively to predict health risks from space exploration. Here we used a TE + NTE model to analyze data on APC(1638N/+) mouse tumorigenesis induced by space-relevant doses of protons, 4He, 12C, 16O, 28Si or 56Fe ions, or γ rays. A customized weighted Negative Binomial distribution was used to describe the radiation type- and dose-dependent data variability. This approach allowed detailed quantification of dose–response shapes, NTE- and TE-related model parameters, and radiation quality metrics (relative biological effectiveness, RBE, and radiation effects ratio, RER, relative to γ rays) for each radiation type. Based on the modeled responses for each radiation type, we predicted the tumor yield for a Mars-mission-relevant mixture of these radiations, using the recently-developed incremental effect additivity (IEA) synergy theory. The proposed modeling approach can enhance current knowledge about quantification of space radiation quality effects, dose response shapes, and ultimately the health risks for astronauts.
Fishing intensification as response to Late Holocene socio-ecological instability in southeastern South America
Authors: Toso Alice , Hallingstad Ellen , McGrath Krista , Fossile Thiago , Conlan Christine , Ferreira Jessica , da Rocha Bandeira Dione , Giannini Paulo César Fonseca , Gilson Simon-Pierre , de Melo Reis Bueno Lucas , Bastos Murilo Quintans Ribeiro , Borba Fernanda Mara , do Santos Adriana M. P. , Colonese André Carlo 
Published: December 2021

AbstractThe emergence of plant-based economies have dominated evolutionary models of Middle and Late Holocene pre-Columbian societies in South America. Comparatively, the use of aquatic resources and the circumstances for intensifying their exploitation have received little attention. Here we reviewed the stable carbon and nitrogen isotope composition of 390 human individuals from Middle and Late Holocene coastal sambaquis, a long-lasting shell mound culture that flourished for nearly 7000 years along the Atlantic Forest coast of Brazil. Using a newly generated faunal isotopic baseline and Bayesian Isotope Mixing Models we quantified the relative contribution of marine resources to the diet of some of these groups. Through the analysis of more than 400 radiocarbon dates we show that fishing sustained large and resilient populations during most of the Late Holocene. A sharp decline was observed in the frequency of sambaqui sites and radiocarbon dates from ca. 2200 years ago, possibly reflecting the dissolution of several nucleated groups into smaller social units, coinciding with substantial changes in coastal environments. The spread of ceramics from ca. 1200 years ago is marked by innovation and intensification of fishing practices, in a context of increasing social and ecological instability in the Late Holocene.
Toxicity of internalized polyalanine to cells depends on aggregation
Authors: Iizuka Yutaro , Owada Ryuji , Kawasaki Takayasu , Hayashi Fumio , Sonoyama Masashi , Nakamura Kazuhiro 
Published: December 2021

AbstractIn polyalanine (PA) diseases, the disease-causing transcription factors contain an expansion of alanine repeats. While aggregated proteins that are responsible for the pathogenesis of neurodegenerative disorders show cell-to-cell propagation and thereby exert toxic effects on the recipient cells, whether this is also the case with expanded PA has not been studied. It is also not known whether the internalized PA is toxic to recipient cells based on the degree of aggregation. In this study, we therefore prepared different degrees of aggregation of a peptide having 13 alanine repeats without flanking sequences of PA disease-causative proteins (13A). The aggregated 13A was spontaneously taken up by neuron-like cultured cells. Functionally, strong aggregates but not weak aggregates displayed a deficit in neuron-like differentiation in vitro. Moreover, the injection of strong but not weak 13A aggregates into the ventricle of mice during the neonatal stage led to enhanced spontaneous motor activity later in life. Thus, PA in the extracellular space has the potential to enter adjacent cells, and may exert toxicity depending on the degree of aggregation.
Generalized partially functional linear model
Authors: Xiao Weiwei , Wang Yixuan , Liu Haiyan 
Published: December 2021

AbstractIn this paper, a generalized partially functional linear regression model is proposed and the asymptotic property of the proposed estimated coefficients in the model is established. Extensive simulation experiment results are consistent with the theoretical result. Finally, two application examples of the model are given. One is sleep quality study where we studied the effects of heart rate, percentage of sleep time on total sleep in bed, wake after sleep onset and number of wakening during the night on sleep quality in 22 healthy people. The other one is mortality rate where we studied the effects of air quality index, temperature, relative humidity, GDP per capita and the number of beds per thousand people on the mortality rate across 80 major cities in China.
Economic and environmental impact assessment of sustainable future irrigation practices in the Indus Basin of Pakistan
Authors: Muzammil Muhammad , Zahid Azlan , Breuer Lutz 
Published: December 2021

AbstractPakistan’s agriculture is characterized by insecure water supply and poor irrigation practices. We investigate the economic and environmental feasibility of alternative improved irrigation technologies (IIT) by estimating the site-specific irrigation costs, groundwater anomalies, and CO2 emissions. IIT consider different energy sources including solar power in combination with changes in the irrigation method. The status quo irrigation costs are estimated to 1301 million US$ year−1, its groundwater depletion to 6.3 mm year−1 and CO2 emissions to 4.12 million t year−1, of which 96% originate from energy consumption and 4% via bicarbonate extraction from groundwater. Irrigation costs of IIT increase with all energy sources compared to the status quo, which is mainly based on diesel engine. This is because of additional variable and fixed costs for system’s operation. Of these, subsidized electricity induces lowest costs for farmers with 63% extra costs followed by solar energy with 77%. However, groundwater depletion can even be reversed with 35% rise in groundwater levels via IIT. Solar powered irrigation can break down CO2 emissions by 81% whilst other energy sources boost emissions by up to 410%. Results suggest that there is an extremely opposing development between economic and ecological preferences, requiring stakeholders to negotiate viable trade-offs.
Chemical strategies for triggering the immune response to the mycotoxin patulin
Authors: Duncan Hadyn , Mercader Josep V. , Agulló Consuelo , Gil-Sepulcre Marcos , Abad-Somovilla Antonio , Abad-Fuentes Antonio 
Published: December 2021

AbstractMycotoxins represent a major concern for human and animal health because of their harmful effects and high occurrence in food and feed. Rapid immunoanalytical methods greatly contribute to strengthening the safety of our food supply by efficiently monitoring chemical contaminants, so high-affinity and specific antibodies have been generated for almost all internationally regulated mycotoxins. The only exception is patulin, a mycotoxin mainly produced by Penicillium expansum for which such a target has not yet been achieved. Accordingly, no point-of-need tests commonly used in food immunodiagnostics are commercially available for patulin. In the present study, three functionalized derivatives conforming to generally accepted rules in hapten design were firstly tested to generate suitable antibodies for the sensitive immunodetection of patulin. However, these conventional bioconjugates were unable to elicit the desired immune response, so an alternative strategy that takes advantage of the high electrophilic reactivity of patulin was explored. Patulin was reacted with 4-bromothiophenol, and the obtained adduct was used to produce antibodies with nanomolar affinity values. These results demonstrated for the first time that targeting the adduct resulting from the reaction of patulin with a thiol-containing compound is a promising approach for developing user-friendly immunoanalytical techniques for this elusive mycotoxin.
Macroclimatic conditions as main drivers for symbiotic association patterns in lecideoid lichens along the Transantarctic Mountains, Ross Sea region, Antarctica
Authors: Wagner Monika , Brunauer Georg , Bathke Arne C. , Cary S. Craig , Fuchs Roman , Sancho Leopoldo G. , Türk Roman , Ruprecht Ulrike 
Published: December 2021

AbstractLecideoid lichens as dominant vegetation-forming organisms in the climatically harsh areas of the southern part of continental Antarctica show clear preferences in relation to environmental conditions (i.e. macroclimate). 306 lichen samples were included in the study, collected along the Ross Sea coast (78°S–85.5°S) at six climatically different sites. The species compositions as well as the associations of their two dominant symbiotic partners (myco- and photobiont) were set in context with environmental conditions along the latitudinal gradient. Diversity values were nonlinear with respect to latitude, with the highest alpha diversity in the milder areas of the McMurdo Dry Valleys (78°S) and the most southern areas (Durham Point, 85.5°S; Garden Spur, 84.5°S), and lowest in the especially arid and cold Darwin Area (~ 79.8°S). Furthermore, the specificity of mycobiont species towards their photobionts decreased under more severe climate conditions. The generalist lichen species Lecanora fuscobrunnea and Lecidea cancriformis were present in almost all habitats, but were dominant in climatically extreme areas. Carbonea vorticosa, Lecidella greenii and Rhizoplaca macleanii were confined to milder areas. In summary, the macroclimate is considered to be the main driver of species distribution, making certain species useful as bioindicators of climate conditions and, consequently, for assessing the consequences of climate change.