bluuebunny/crossref_metadata_2025_split huggingface dataset:
Introduction, adaptation and characterization of monk fruit (Siraitia grosvenorii): a non-caloric new natural sweetener
Authors: Shivani  , Thakur Babit Kumar , Mallikarjun C. P. , Mahajan Mitali , Kapoor Priya , Malhotra Jigyasa , Dhiman Rimpy , Kumar Dinesh , Pal Probir Kumar , Kumar Sanjay 
Published: March 2021

AbstractSiraitia grosvenorii, an herbaceous perennial plant, native to the southern parts of China, is commonly used as a low-calorie natural sweetener. It contains cucurbitane-type triterpene glycosides known as mogrosides. The extract from monk fruit is about 300 times sweeter than sucrose. In spite of its immense importance and International demand, Siraitia grosvenorii (Swingle) is not commercially cultivated outside China since scientific information for cultivation of this species is lacking. Planting material of monk fruit plant was not available in India. Thus, the seeds of monk fruit were introduced in India from China after following International norms. Then the experiments were conducted on different aspects such as seed germination, morphological and anatomical characterization, phenology, flowering and pollination behaviors, and dynamic of mogroside-V accumulation in fruit. The hydropriming at 40 °C for 24 h was found effective to reduce the germination time and to increase the germination rate (77.33%). The multicellular uniseriate trichomes were observed in both the leaf surfaces, however, higher trichomes density was observed in the ventral surface of males compared to females. The microscopic view revealed that the ovary was trilocular (ovary consists three chambers) having two ovules in each chamber or locule. Most of the fruits were globose or oblong type with 5–7 cm in length and 4–7 cm diameter. Mogroside-V content in fruit at 80 days after pollination was 0.69% on dry weight basis. The rate of increase of mogroside-V accumulation from 50 to 70 days was very slow, whereas a sharp increase was observed from 70 to 80 days. The higher receptivity of stigma was observed with fully open flowers. The floral diagram and formula have also been developed for both male and female flowers. Our results highlighted that monk fruit can be grown in Indian conditions.
Real-world outcomes versus clinical trial results of immunotherapy in stage IV non-small cell lung cancer (NSCLC) in the Netherlands
Authors: Cramer-van der Welle Christine M. , Verschueren Marjon V. , Tonn Merel , Peters Bas J. M. , Schramel Franz M. N. H. , Klungel Olaf H. , Groen Harry J. M. , van de Garde Ewoudt M. W. ,   The Santeon NSCLC Study Group, Kastelijn E. A. , Vermeer L. C. , van den Borne B. E. E. M. , van Putten J. W. G. , Schouwink J. H. , Smit A. A. J. 
Published: March 2021

AbstractThis study aims to assess how clinical outcomes of immunotherapy in real-world (effectiveness) correspond to outcomes in clinical trials (efficacy) and to look into factors that might explain an efficacy-effectiveness (EE) gap. All patients diagnosed with stage IV non-small cell lung cancer (NSCLC) in 2015–2018 in six Dutch large teaching hospitals (Santeon network) were identified and followed-up from date of diagnosis until death or end of data collection. Progression-free survival (PFS) and overall survival (OS) from first-line (1L) pembrolizumab and second-line (2L) nivolumab were compared with clinical trial data by calculating hazard ratios (HRs). From 1950 diagnosed patients, 1005 (52%) started with any 1L treatment, of which 83 received pembrolizumab. Nivolumab was started as 2L treatment in 141 patients. For both settings, PFS times were comparable between real-world and trials (HR 1.08 (95% CI 0.75–1.55), and HR 0.91 (95% CI 0.74–1.14), respectively). OS was significantly shorter in real-world for 1L pembrolizumab (HR 1.55; 95% CI 1.07–2.25). Receiving subsequent lines of treatment was less frequent in real-world compared to trials. There is no EE gap for PFS from immunotherapy in patients with stage IV NSCLC. However, there is a gap in OS for 1L pembrolizumab. Fewer patients proceeding to a subsequent line of treatment in real-world could partly explain this.
Network and synaptic mechanisms underlying high frequency oscillations in the rat and cat olfactory bulb under ketamine-xylazine anesthesia
Authors: Średniawa Władysław , Wróbel Jacek , Kublik Ewa , Wójcik Daniel Krzysztof , Whittington Miles Adrian , Hunt Mark Jeremy 
Published: March 2021

AbstractWake-related ketamine-dependent high frequency oscillations (HFO) can be recorded in local field potentials (LFP) from cortical and subcortical regions in rodents. The mechanisms underlying their generation and occurrence in higher mammals are unclear. Unfortunately, anesthetic doses of pure ketamine attenuate HFO, which has precluded their investigation under anesthesia. Here, we show ketamine-xylazine (KX) anesthesia is associated with a prominent 80–130 Hz rhythm in the olfactory bulb (OB) of rats, whereas 30–65 Hz gamma power is diminished. Simultaneous LFP and thermocouple recordings revealed the 80–130 Hz rhythm was dependent on nasal respiration. This rhythm persisted despite surgical excision of the piriform cortex. Silicon probes spanning the dorsoventral aspect of the OB revealed this rhythm was strongest in ventral areas and associated with microcurrent sources about the mitral layer. Pharmacological microinfusion studies revealed dependency on excitatory-inhibitory synaptic activity, but not gap junctions. Finally, a similar rhythm occurred in the OB of KX-anesthetized cats, which shared key features with our rodent studies. We conclude that the activity we report here is driven by nasal airflow, local excitatory-inhibitory interactions, and conserved in higher mammals. Additionally, KX anesthesia is a convenient model to investigate further the mechanisms underlying wake-related ketamine-dependent HFO.
Performance of preclinical models in predicting drug-induced liver injury in humans: a systematic review
Authors: Dirven Hubert , Vist Gunn E. , Bandhakavi Sricharan , Mehta Jyotsna , Fitch Seneca E. , Pound Pandora , Ram Rebecca , Kincaid Breanne , Leenaars Cathalijn H. C. , Chen Minjun , Wright Robert A. , Tsaioun Katya 
Published: March 2021

AbstractDrug-induced liver injury (DILI) causes one in three market withdrawals due to adverse drug reactions, causing preventable human suffering and massive financial loss. We applied evidence-based methods to investigate the role of preclinical studies in predicting human DILI using two anti-diabetic drugs from the same class, but with different toxicological profiles: troglitazone (withdrawn from US market due to DILI) and rosiglitazone (remains on US market). Evidence Stream 1: A systematic literature review of in vivo studies on rosiglitazone or troglitazone was conducted (PROSPERO registration CRD42018112353). Evidence Stream 2: in vitro data on troglitazone and rosiglitazone were retrieved from the US EPA ToxCast database. Evidence Stream 3: troglitazone- and rosiglitazone-related DILI cases were retrieved from WHO Vigibase. All three evidence stream analyses were conducted according to evidence-based methodologies and performed according to pre-registered protocols. Evidence Stream 1: 9288 references were identified, with 42 studies included in analysis. No reported biomarker for either drug indicated a strong hazard signal in either preclinical animal or human studies. All included studies had substantial limitations, resulting in “low” or “very low” certainty in findings. Evidence Stream 2: Troglitazone was active in twice as many in vitro assays (129) as rosiglitazone (60), indicating a strong signal for more off-target effects. Evidence Stream 3: We observed a fivefold difference in both all adverse events and liver-related adverse events reported, and an eightfold difference in fatalities for troglitazone, compared to rosiglitazone. In summary, published animal and human trials failed to predict troglitazone’s potential to cause severe liver injury in a wider patient population, while in vitro data showed marked differences in the two drugs’ off-target activities, offering a new paradigm for reducing drug attrition in late development and in the market. This investigation concludes that death and disability due to adverse drug reactions may be prevented if mechanistic information is deployed at early stages of drug development by pharmaceutical companies and is considered by regulators as a part of regulatory submissions.
Distribution and altitudinal patterns of carbon and nitrogen storage in various forest ecosystems in the central Yunnan Plateau, China
Authors: Li Jianqiang , Chen Qibo , Li Zhuang , Peng Bangxiao , Zhang Jianlong , Xing Xuexia , Zhao Binyang , Song Denghui 
Published: March 2021

AbstractThe carbon (C) pool in forest ecosystems plays a long-term and sustained role in mitigating the impacts of global warming, and the sequestration of C is closely linked to the nitrogen (N) cycle. Accurate estimates C and N storage (SC, SN) of forest can improve our understanding of C and N cycles and help develop sustainable forest management policies in the content of climate change. In this study, the SC and SN of various forest ecosystems dominated respectively by Castanopsis carlesii and Lithocarpus mairei (EB), Pinus yunnanensis (PY), Pinus armandii (PA), Keteleeria evelyniana (KE), and Quercus semecarpifolia (QS) in the central Yunnan Plateau of China, were estimated on the basis of a field inventory to determine the distribution and altitudinal patterns of SC and SN among various forest ecosystems. The results showed that (1) the forest SC ranged from 179.58 ± 20.57 t hm−1 in QS to 365.89 ± 35.03 t hm−1 in EB. Soil, living biomass and litter contributed an average of 64.73%, 31.72% and 2.86% to forest SC, respectively; (2) the forest SN ranged from 4.47 ± 0.94 t ha−1 in PY to 8.91 ± 1.83 t ha−1 in PA. Soil, plants and litter contributed an average of 86.88%, 10.27% and 2.85% to forest SN, respectively; (3) the forest SC and SN decreased apparently with increasing altitude. The result demonstrates that changes in forest types can strongly affect the forest SC and SN. This study provides baseline information for forestland managers regarding forest resource utilization and C management.
Determination of Dy substitution site in Nd2−xDyxFe14B by HAADF-STEM and illustration of magnetic anisotropy of “g” and “f” sites, before and after substitution
Authors: Haider Syed Kamran , Kang Min-Chul , Hong Jisang , Kang Young Soo , Yang Cheol-Woong , Kim Dongsoo 
Published: March 2021

AbstractNd2Fe14B and Nd2−xDyxFe14B (x = 0.25, 0.50) particles were prepared by the modified co-precipitation followed by reduction–diffusion process. Bright field scanning transmission electron microscope (BF-STEM) image revealed the formation of Nd–Fe–B trigonal prisms in [− 101] viewing zone axis, confirming the formation of Nd2Fe14B/Nd2−xDyxFe14B. Accurate site for the Dy substitution in Nd2Fe14B crystal structure was determined as “f” site by using high-angle annular dark field scanning transmission electron microscope (HAADF-STEM). It was found that all the “g” sites are occupied by the Nd, meanwhile Dy occupied only the “f” site. Anti-ferromagnetic coupling at “f” site decreased the magnetic moment values for Nd1.75Dy0.25Fe14B (23.48 μB) and Nd1.5Dy0.5Fe14B (21.03 μB) as compared to Nd2Fe14B (25.50 μB). Reduction of magnetic moment increased the squareness ratio, coercivity and energy product. Analysis of magnetic anisotropy at constant magnetic field confirmed that “f” site substitution did not change the patterns of the anisotropy. Furthermore, magnetic moment of Nd2Fe14B, Nd2−xDyxFe14B, Nd (“f” site), Nd (“g” site) and Dy (“f” site) was recorded for all angles between 0° and 180°.
Boundary condition and oceanic impacts on the atmospheric water balance in limited area climate model ensembles
Authors: Goergen Klaus , Kollet Stefan 
Published: March 2021

AbstractRegional climate models (RCMs) are indispensable in climate research, albeit often characterized by biased terrestrial precipitation and water budgets. This study identifies excess oceanic evaporation, in conjunction with the RCMs’ boundary conditions, as drivers contributing to these biases in RCMs with forced sea surface temperatures in a CORDEX RCM ensemble over Europe. The RCMs are relaxed to the prescribed lateral boundary conditions originating from a global model, effectively matching the driving model's overall atmospheric moisture flux divergence. As a consequence, excess oceanic evaporation results in positive precipitation biases over land due to forced internal recycling of moisture to maintain the overall flux divergence prescribed by the boundary conditions. This systematic behaviour is shown through an analysis of long-term atmospheric water budgets and atmospheric moisture exchange between oceanic and continental areas in a multi-model ensemble.
The effects of direct current stimulation and random noise stimulation on attention networks
Authors: Lema Alberto , Carvalho Sandra , Fregni Felipe , Gonçalves Óscar F. , Leite Jorge 
Published: March 2021

AbstractAttention is a complex cognitive process that selects specific stimuli for further processing. Previous research suggested the existence of three attentional networks: alerting, orienting and executive. However, one important topic is how to enhance the efficiency of attentional networks. In this context, understanding how this system behaves under two different modulatory conditions, namely transcranial direct current stimulation (tDCS) and transcranial Random Noise Stimulation (tRNS), will provide important insights towards the understanding of the attention network system. Twenty-seven healthy students took part on a randomized single-blinded crossover study, testing the effects that involved three modalities of unilateral stimulation (tRNS, anodal tDCS, and sham) over the DLPFC, during the performance of the attention network test (ANT) in three different conditions: standard, speed and accuracy. Results showed that tRNS was able to increase attention during more complex situations, namely by increasing alerting and decreasing conflict effect in the executive network. Under the Speed condition, tRNS increased efficiency of the alerting network, as well as under the more demanding conflict network, tRNS overall increased the performance when comparing to sham. No statistical significant effects of tDCS were observed. These results are compatible with the attention requiring the synchronization of pre-existing networks, rather the reinforcement or creation of new pathways.
Disparities in access to health care system as determinant of survival for patients with pancreatic cancer in the State of São Paulo, Brazil
Authors: de Jesus Victor Hugo Fonseca , da Costa Wilson Luiz , Claro Laura Carolina Lopez , Coimbra Felipe José Fernandez , Dettino Aldo Lourenço Abbade , Riechelmann Rachel P. , Curado Maria Paula 
Published: March 2021

AbstractLittle is known about the features and outcomes of Brazilian patients with pancreatic cancer. We sought to describe the socio-economic characteristics, patterns of health care access, and survival of patients diagnosed with malignant pancreatic tumors from 2000 to 2014 in São Paulo, Brazil. We included patients with malignant exocrine and non-classified pancreatic tumors according to the International Classifications of Disease (ICD)-O-2 and -O-3, diagnosed from 2000 to 2014, who were registered in the FOSP database. Prognostic factors for overall survival (OS) in the subgroup of patients with ductal or non-specified (adeno)carcinoma were evaluated using Cox proportional hazard model. The study population consists of 6855 patients. Median time from the first visit to diagnosis and treatment were 13 (Interquartile range [IQR] 4–30) and 24 (IQR 8–55) days, respectively. Both intervals were longer for patients treated in the public setting. Median OS was 4.9 months (95% confidence interval [95% CI] 4.7–5.2). Increasing age, male gender, lower educational level, treatment in the public setting, absence of treatment, advanced stage, and treatment from 2000 to 2004 were associated with inferior OS. From 2000–2004 to 2010–2014, no improvement in OS was seen for patients treated in the public setting. Survival of patients with malignant pancreatic tumors remains dismal. Socioeconomical variables, especially health care funding, are major determinants of survival. Further work is necessary to decrease inequalities in access to medical care for patients with pancreatic cancer in Brazil.
Nutritional, phytochemical, and in vitro anticancer potential of sugar apple (Annona squamosa) fruits
Authors: Shehata Mohamed Gamal , Abu-Serie Marwa Muhammad , Abd El-Aziz Nourhan Mohammad , El-Sohaimy Sobhy Ahmed 
Published: March 2021

AbstractIn plants, Fruits and their wastes are the main sources of bioactive compounds. Currently, Annona fruits have attracted the attention of people interested in health-promoting foods due to their phytochemical content that their activities were not studied before. This study aimed to explore the potential antioxidant, antimicrobial, and in vitro anticancer activity of two cultivars Annona squamosa (Annona b. and Annona h.) seed, peel, and pulp. We also meausred phenolic, flavonoid, sulfated polysaccharide, tannins, and triterpenoids. Polyphenol identification was determined using RP-HPLC. Results of the antioxidant activity revealed that the highest activity was observed for Annona h. seed extract using DPPH and ABTS assays with IC50 6.07 ± 0.50 and 9.58 ± 0.53 µg/ml, respectively. The antimicrobial activity against various pathogenic strains revealed that the peel extracts of both Annona b. and Annona h. exhibited the best antimicrobial activity. We also assessed the IC50 values for anticancer activity in all six Annona b. and Annona h samples against four cancer cell lines colon (Caco-2), prostate (PC3), liver (HepG-2), and breast (MCF-7) using MTT assay. Annona b. and Annona h seed extracts had the lowest IC50 values for four cancer cell lines with 7.31 ± 0.03 and 15.99 ± 1.25 for PC-3 and MCF-7, respectively. Both seed extracts, Annona b. and Annona h., showed significantly down-regulated mRNA expression of Bcl-2 and up-regulated p53 in all treated cell lines. Apoptosis was evaluated using nuclear staining, flow cytometric analysis, and immunohistochemistry of the proliferation marker (Ki-67). Additional studies are required to characterize the bioactive compounds responsible for the observed activities of Annona seed and determine its mechanism as an anticancer drug.
Enhanced ferroelectric switching speed of Si-doped HfO2 thin film tailored by oxygen deficiency
Authors: Lee Kyoungjun , Park Kunwoo , Lee Hyun-Jae , Song Myeong Seop , Lee Kyu Cheol , Namkung Jin , Lee Jun Hee , Park Jungwon , Chae Seung Chul 
Published: March 2021

AbstractInvestigations concerning oxygen deficiency will increase our understanding of those factors that govern the overall material properties. Various studies have examined the relationship between oxygen deficiency and the phase transformation from a nonpolar phase to a polar phase in HfO2 thin films. However, there are few reports on the effects of oxygen deficiencies on the switching dynamics of the ferroelectric phase itself. Herein, we report the oxygen- deficiency induced enhancement of ferroelectric switching properties of Si-doped HfO2 thin films. By controlling the annealing conditions, we controlled the oxygen deficiency concentration in the ferroelectric orthorhombic HfO2 phase. Rapid high-temperature (800 °C) annealing of the HfO2 film accelerated the characteristic switching speed compared to low-temperature (600 °C) annealing. Scanning transmission electron microscopy and electron energy-loss spectroscopy (EELS) revealed that thermal annealing increased oxygen deficiencies, and first-principles calculations demonstrated a reduction of the energy barrier of the polarization flip with increased oxygen deficiency. A Monte Carlo simulation for the variation in the energy barrier of the polarization flipping confirmed the increase of characteristic switching speed.
Hydromorphological evaluation of the river training impact on a multi-thread river system (Belá River, Carpathians, Slovakia)
Authors: Kidová Anna , Radecki-Pawlik Artur , Rusnák Miloš , Plesiński Karol 
Published: March 2021

AbstractThe paper evaluates the impact of river training works designed to address problems associated with flooding on the braided-wandering Belá River in Slovakian Carpathians. This impact was investigated after the flood event in July 2018 on 11 river reaches where the river engineering and management intervention was applied. We analyzed its impact by spatio-temporal variations in river morphology (12 channel parameters) and changes in cross-section and hydraulic parameters (flow velocity, shear stress, stream power, W/D ratio) between pre- and post-flood management periods. The research hypotheses related to decreasing geodiversity in managed river reaches, a rapid increase in flow velocity during an extreme flood in river reaches where there is no sufficient floodplain inundation due to artificially high banks built by river training works, and increasing erosive force in the channel zone thanks to river management intervention were confirmed. The intervention in the braidplain area of the Belá River resulted in an undesirable simplification of the river pattern, loss of geomorphic diversity, loss of channel–floodplain connectivity, and disturbance and restraint of hydromorphological continuity. Identification of main conflicts of the Belá River management is important for clarifying the different approaches of stakeholders in the study area and aims to provide an objective illustration of their consequences. The presented analyses could help in future management issues as well as in the more critical decision-making process in vulnerable and rare braided river systems on the present when we are losing so many natural rivers by human decisions.
Flexible annotation atlas of the mouse brain: combining and dividing brain structures of the Allen Brain Atlas while maintaining anatomical hierarchy
Authors: Takata Norio , Sato Nobuhiko , Komaki Yuji , Okano Hideyuki , Tanaka Kenji F. 
Published: March 2021

AbstractA brain atlas is necessary for analyzing structure and function in neuroimaging research. Although various annotation volumes (AVs) for the mouse brain have been proposed, it is common in magnetic resonance imaging (MRI) of the mouse brain that regions-of-interest (ROIs) for brain structures (nodes) are created arbitrarily according to each researcher’s necessity, leading to inconsistent ROIs among studies. One reason for such a situation is the fact that earlier AVs were fixed, i.e. combination and division of nodes were not implemented. This report presents a pipeline for constructing a flexible annotation atlas (FAA) of the mouse brain by leveraging public resources of the Allen Institute for Brain Science on brain structure, gene expression, and axonal projection. A mere two-step procedure with user-specified, text-based information and Python codes constructs FAA with nodes which can be combined or divided objectively while maintaining anatomical hierarchy of brain structures. Four FAAs with total node count of 4, 101, 866, and 1381 were demonstrated. Unique characteristics of FAA realized analysis of resting-state functional connectivity (FC) across the anatomical hierarchy and among cortical layers, which were thin but large brain structures. FAA can improve the consistency of whole brain ROI definition among laboratories by fulfilling various requests from researchers with its flexibility and reproducibility.