bluuebunny/crossref_metadata_2025_split huggingface dataset:
Finding Druggable Sites in Proteins using TACTICS
Authors: Evans Daniel J. , Yovanno Remy A. , Rahman Sanim , Cao David W. , Beckett Morgan Q. , Patel Milan H. , Bandak Afif F. , Lau Albert Y. 
Published: February 2021

AbstractStructure-based drug discovery efforts require knowledge of where drug-binding sites are located on target proteins. To address the challenge of finding druggable sites, we developed a machine-learning algorithm called TACTICS (Trajectory-based Analysis of Conformations To Identify Cryptic Sites), which uses an ensemble of molecular structures (such as molecular dynamics simulation data) as input. First, TACTICS uses k-means clustering to select a small number of conformations that represent the overall conformational heterogeneity of the data. Then, TACTICS uses a random forest model to identify potentially bindable residues in each selected conformation, based on protein motion and geometry. Lastly, residues in possible binding pockets are scored using fragment docking. As proof-of-principle, TACTICS was applied to the analysis of simulations of the SARS-CoV-2 main protease and methyltransferase and theYersinia pestisaryl carrier protein. Our approach recapitulates known small-molecule binding sites and predicts the locations of sites not previously observed in experimentally determined structures. The TACTICS code is available athttps://github.com/Albert-Lau-Lab/tactics_protein_analysis.
Causal approach to environmental risks of seabed mining
Authors: Kaikkonen Laura , Helle Inari , Kostamo Kirsi , Kuikka Sakari , Törnroos Anna , Nygård Henrik , Venesjärvi Riikka , Uusitalo Laura 
Published: February 2021

ABSTRACTSeabed mining is approaching the commercial mining phase across the world’s oceans. This rapid industrialization of seabed resource use is introducing new pressures to marine environments. The environmental impacts of such pressures should be carefully evaluated prior to permitting new activities, yet observational data is mostly missing. Here, we examine the environmental risks of seabed mining using a causal, probabilistic network approach. Drawing on a series of interviews with a multidisciplinary group of experts, we outline the cause-effect pathways related to seabed mining activities to inform quantitative risk assessments. The approach consists of (1) iterative model building with experts to identify the causal connections between seabed mining activities and the affected ecosystem components, and (2) quantitative probabilistic modelling to provide estimates of mortality of benthic fauna in the Baltic Sea. The model is used to evaluate alternative mining scenarios, offering a quantitative means to highlight the uncertainties around the impacts of mining. We further outline requirements for operationalizing quantitative risk assessments, highlighting the importance of a cross-disciplinary approach to risk identification. The model can be used to support permitting processes by providing a more comprehensive description of the potential environmental impacts of seabed resource use, allowing iterative updating of the model as new information becomes available.
Money stock determination process and money multiplier: case of South Korea
Authors: Ongan Serdar , Gocer Ismet 
Published: February 2021

PurposeThis study aims to re-examine the money stock determination process for South Korea under the assumption of the existence of potential asymmetric (non-linear) relations (a mechanism) between the money stock and the monetary base. Because, the true and detailed diagnosis of this mechanism is crucially important for the Bank of Korea’s (BOK)’ monetary policy, as this country has been adopting an inflation targeting policy (ITP) for a long-time.Design/methodology/approachThis paper applies the non-linear autoregressive distributed lag model by Shinet al.(2014). This model separates the original series of the monetary base into their increases (+) and decreases (−). The increases (+) and decreases (−) done by the BOK correspond to expansionary and contractionary monetary policies, respectively, in this study.FindingsThe empirical findings are two-fold. First, the money stock determination process in Korea has a non-linear (asymmetric) structure. This means that increases (+) and decreases (−) in the monetary base have asymmetric (different) impacts on money stock. Second, the BOK’s only expansionary monetary policy exhibits exogenous nature money stock determination with an almost stable money multiplier. These findings may help the BOK to take preventive precautions in its monetary policy implementations.Originality/valueThis study with its methodology may help the BOK to take preventive measures in its ongoing ITP proactively.
Covid-19, out-of-pocket medical expenses and consumption
Authors: Leightner Jonathan E. 
Published: February 2021

Purpose
Based upon estimates of the change in consumption due to a change in out-of-pocket-health expenses (dC/dOOPHE) for 43 countries, this paper aims to argue for a reevaluation of what constitutes OOPHE when determining health insurance especially in the wake of Covid-19.

Design/methodology/approach
Reiterative truncated projected least squares (RTPLS), a statistical technique designed to handle the omitted variables problem of regression analysis.

Findings
If budgets are binding than dC/dOOPHE should be 0; if OOPHE merely adds to current consumption than dC/dOOPHE should be 1. However, merely plotting consumption versus OOPHE for the 43 countries for which organization for economic cooperation and development has the required data clearly shows a dC/dOOPHE much greater than one. This paper’s estimates of dC/dOOPHE for 2000 to 2017 range from 15.6 for Switzerland (in 2016) to 225.2 for Columbia (in 2003).

Research limitations/implications
RTPLS cannot determine what part of the results are due to an increase in income causing both consumption and OOPHE to increase and what part is because of actual OOPHE far exceeding official OOPHE. However, the latter is involved.

Practical implications
As Covid-19 sickens millions while depriving millions of their normal means of generating income, what constitutes OOPHE should be expanded when determining health insurance. This paper’s results imply that even prior to Covid-19 health insurance covered much less than the optimal amount of actual OOPHE.

Originality/value
This is the first paper to use RTPLS to estimate dC/dOOPHE.
Evaluation of bioequivalence of two flurbiprofen axetil injections: A randomized, open‐label, double‐cycle, and crossover study
Authors: Wang Jin , Dong Liuhan , Wang Rui , Cai Yun 
Published: February 2021

AbstractFlurbiprofen is a non‐steroidal anti‐inflammatory drug. We evaluated the bioequivalence of a new formulation of flurbiprofen axetil for injection and the reference drug ROPION (another kind of flurbiprofen axetil injection marketed for use) in healthy Chinese subjects. This is a single‐centre, randomized, open‐label, single‐dose, two period crossover bioequivalence study. Each subject received a single intravenous injection at the dose of 50 mg under fasting. The drug was dissolved in 100 mL normal saline, and the injection was completed in 15 minutes. There was a 7‐day washout period between the two administrations. The plasma concentrations of flurbiprofen were measured by LC‐MS/MS, and descriptive statistics were used to describe the safety outcomes including adverse events (AEs) and adverse drug reactions (ADRs). Twenty‐four subjects were enrolled in this study. Mean values of primary PK parameters (Tmax, Cmax, AUC0‐t, AUC0‐∞, λz, T1/2) were similar (P > 0.05). Tmax for both products is 0.3 hours. The 90% confidence intervals (CIs) for peak concentration Cmax ranged between 96.87% and 100.42%, and the area under curve AUC0‐t and AUC0‐∞ ranged between 99.09% and 104.29% and 98.97% and 104.29%, respectively. The 90% CIs for the geometric means and ratios of primary PK endpoints of flurbiprofen axetil injection to reference drug ranged between 98.97% and 104.29%. The adverse event rate of the test product was 8.3% and no serious adverse events (SAE) occurred in this clinical study. We concluded that the test product and the reference drug were bioequivalent and the safety was high in healthy Chinese subjects.
Indian dye yielding plants: Efforts and opportunities
Authors: Aggarwal Shilpi 
Published: February 2021

AbstractThe present review article deals with the information on the dye‐yielding plants of India. Dyes are intensively coloured compounds that are applied to a substrate such as fibre, paper, cosmetics, hair, etc. to give colours and can be extracted from the roots, fruits/berries, bark, leaves, flowers, and stem/wood, fungi, and lichens by various processes of extractions. In addition to their dye‐yielding characteristics, many of these plants possess medicinal values and can be used for multiple other purposes. Plant derived‐colours have an important role in human life because of their safe and eco‐friendly nature. But due to the availability of economically cheaper synthetic dyes, the indigenous knowledge of extraction, processing, and proper utilisation has been diminished. Nowadays, the demand for natural dyes has been increased worldwide due to awareness about their beneficial properties. It has been essential that proper documentation and measure of conservation should be undertaken to preserve these natural dye‐yielding plants. This review article is an aid to a collective inquiry into Indian dye plants.
Epigenetics of ankylosing spondylitis: Recent developments
Authors: Yang Hui , Chen Yuting , Xu Wei , Shao Ming , Deng Jixiang , Xu Shanshan , Gao Xing , Guan Shiyang , Wang Jinian , Xu Shengqian , Shuai Zongwen , Pan Faming 
Published: February 2021

AbstractAnkylosing spondylitis (AS) is a chronic inflammatory autoimmune disease which mainly affects the spine, sacroiliac joint and peripheral joints. To date, the exact causes and pathogenesis of AS still remain unknown. It is considered that the pathogenesis of AS is associated with genetic, infection, environment, immunity and other factors. Among them, the role of genetic factors in the pathogenesis of AS has been studied most deeply. However, over the past few years, the function of environmental predisposition and epigenetic modification in the pathogenesis of AS has received extensive attention. This paper summarizes the recent progress in the epigenetics of AS, including abnormal epigenetic modifications at AS‐associated genomic loci, such as DNA methylation, histone modification, microRNA, and so on. In summary, the findings of this review attempt to explain the role of epigenetic modification in the occurrence and development of AS. Nevertheless, there are still unknown and complicated aspects worth exploring to deepen our understanding of the pathogenesis of AS.
Antisense‐Induced Downregulation of Clock Genes in the Shell Region of the Nucleus Accumbens Reduces Binge Drinking in Mice
Authors: Sharma Rishi , Puckett Hunter , Kemerling Micaela , Parikh Meet , Sahota Pradeep , Thakkar Mahesh 
Published: February 2021

IntroductionsBinge drinking is a deadly pattern of alcohol consumption. Evidence suggests that genetic variation in clock genes is strongly associated with alcohol misuse; however, the neuroanatomical basis for such a relationship is unknown. The shell region of the nucleus accumbens (NAcSh) is well known to play a role in binge drinking. Hence, we examined whether clock genes in the NAcSh regulate binge drinking.MethodsTo address this question, 2 experiments were performed on male C57BL/6J mice. In the first experiment, mice exposed to alcohol or sucrose under the 4‐day drinking‐in‐the‐dark (DID) paradigm were euthanized at 2 different time points on day 4 [7 hours after light (pre–binge drinking) or dark (post–binge drinking) onset]. The brains were processed for RT–PCR to examine the expression of circadian clock genes (Clock, Per1, and Per2) in the NAcSh and suprachiasmatic nucleus (SCN). In the second experiment, mice were exposed to alcohol, sucrose, or water as described above. On day 4, 1 hour prior to the onset of alcohol exposure, mice were bilaterally infused with either a mixture of circadian clock gene antisense oligodeoxynucleotides (AS‐ODNs; antisense group) or nonsense/random ODNs (R‐ODNs; control group) through surgically implanted cannulas above the NAcSh. Alcohol/sucrose/water consumption was measured for 4 hours. Blood alcohol concentration was measured to confirm binge drinking. Microinfusion sites were histologically verified using cresyl violet staining.ResultsAs compared to sucrose, mice euthanized post–binge drinking (not pre–binge drinking) on day 4 displayed a greater expression of circadian genes in the NAcSh but not in the SCN. Knockdown of clock genes in the NAcSh caused a significantly lower volume of alcohol to be consumed on day 4 than in the control treatment. No differences were found in sucrose or water consumption.ConclusionsOur results suggest that clock genes in the NAcSh play a crucial role in binge drinking.
Growth and competition between a native leguminous forb and an alien grass from the Cerrado under elevated CO2
Authors: de Oliveira Amanda Cristina Gonçalves , Rios Patrick Moreira , Pereira Eduardo Gusmão , Souza João Paulo 
Published: February 2021

AbstractThe increase in atmospheric CO2 concentration ([CO2]) due to climate change may alter the composition of communities and the functioning of ecosystems. Owing to greater nitrogen use efficiency, leguminous plants present more effective responses to increasing [CO2] than non‐legumes. The objective of this study was to evaluate the morphophysiological and growth responses of two species from the Cerrado, a native C3 herbaceous legume (Stylosanthes capitata Vogel.) and an invasive C4 grass (Melinis minutiflora P. Beauv) growing alone or in competition, in ambient (350 ppm) and high (1000 ppm) [CO2]. Competition with S. capitata reduced leaf development and dry matter production in M. minutiflora individuals, regardless of [CO2]. Stylosanthes capitata increased root system growth under high [CO2] and competition. This change allows greater soil exploitation, decreasing nutrient limitation to S. capitata development. The leguminous species S. capitata showed advantages in the competition for resources under high [CO2] concerning the invasive grass. Although invasive C4 species are initially better in the colonisation of the invaded areas, the C3 native species of Cerrado may adjust morphophysiological traits when growing at high [CO2] and develop strategies that enable it to more effectively compete for resources.
A comparative whole genome sequencing analysis identified a candidate locus for lack of operculum in cultivated gilthead seabream (Sparus aurata)
Authors: Bertolini F. , Ribani A. , Capoccioni F. , Buttazzoni L. , Utzeri V. J. , Bovo S. , Schiavo G. , Caggiano M. , Rothschild M. F. , Fontanesi L. 
Published: February 2021

SummaryThe gilthead seabream (Sparus aurata, Sparidae family) is commonly used for aquaculture. Despite its great economic value, several problems in its cultivation remain. One of the major concerns is the high frequency of morphological abnormalities occurring during the early developmental stages. Partial and/or total lack of operculum is the most frequent anomaly affecting the fish cranial region. The existence of genetic factors that can at least partially determine this defect has been hypothesized. In this work, two DNA pools of highly related fry, one composed of normal‐looking (control) fish and the other lacking an operculum (case), were constructed and whole‐genome resequencing data produced from the two were compared. The analysis revealed a 1 Mb region on chromosome 2 with higher heterozygosity in the lack of operculum DNA pool than in the control DNA pool, consistent with the enrichment, in the first DNA pool, of one or more haplotypes causing or predisposing to the defect together with other normal haplotypes. A window‐based FST analysis between the two DNA pools indicated that the same region had the highest divergence score. This region contained 2921 SNVs, 10 of which, with predicted high impacts (three splice donor and seven stop‐gained variants), were detected in novel genes that are homologous to calcium‐sensing receptor‐like genes, probably involved in bone development. Other studies are needed to clarify the genetic mechanisms involved in predisposing fry to this deformity and then to identify associated markers that could be used in breeding programs to reduce the frequency of this defect in the broodstock.
Increased TOX expression concurrent with PD‐1, Tim‐3, and CD244 in T cells from patients with non‐Hodgkin lymphoma
Authors: Huang Shuxin , Liang Chaofeng , Zhao Yujie , Deng Tairan , Tan Jiaxiong , Lu Yuhong , Liu Sichu , Li Yangqiu , Chen Shaohua 
Published: February 2021

AbstractAimTo characterize immune suppression in lymphoma, thymocyte selection‐associated high mobility group box protein (TOX) expression and co‐expression with programmed cell death receptor‐1 (PD‐1), T cell immunoglobulin mucin‐domain‐containing‐3 (Tim‐3), and CD244 in CD3+, CD4+, CD8+, and regulatory T (Treg) cells from patients with lymphomas were analyzed.MethodsTOX expression and co‐expression with PD‐1, Tim‐3, and CD244 in CD3+, CD4+, Treg, and CD8+ T cells were analyzed by multi‐color fluorescent flow cytometry using peripheral blood (PB) from 13 newly diagnosed, untreated lymphoma patients, and 11 healthy individuals.ResultsAn increased percentage of TOX+ CD3+, CD4+, and CD8+ T cells was found in PB from patients with B cell non‐Hodgkin's lymphoma (B‐NHL) in comparison with healthy controls. Moreover, TOX+PD‐1+ and TOX+Tim‐3+ double‐positive T cells increased among the CD3+, CD4+, and CD8+T cell populations in the B‐NHL group. There was apparent heterogeneity in TOX expression and co‐expression with PD‐1, Tim‐3, and CD244 in CD3+, CD4+, and CD8+ T cells in different lymphoma patients. In addition, the percentage of CD4+CD25+FoxP3+ T cells (Treg) among the CD3+ and CD4+ T cells significantly increased, and the number of TOX+ and TOX+PD‐1+ Treg cells also significantly increased in the B‐NHL group.ConclusionsHigher expression of TOX concurrent with PD‐1, Tim‐3, and CD244 in T cells from patients with B‐NHL may contribute to T cell exhaustion and impair their special anti‐tumor T cell activity. TOX may be considered a potential target for reversing T cell exhaustion and improving T cell function in hematological malignancies.
Review of systemic chemotherapy in unresectable colorectal peritoneal carcinomatosis
Authors: Nindra Udit , Shahnam Adel , Mahon Kate L. 
Published: February 2021

AbstractColorectal cancer remains the third most common malignancy in Australia with the peritoneum being the second most common metastatic site. Colorectal peritoneal carcinomatosis (CPC) can be treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy but this is only limited to a small subset of patients. Those with inoperable disease have a particularly poor prognosis. While the ideal systemic regimen has not been defined, 5‐fluorouracil‐based chemotherapy regimens appear to provide overall and progression free survival benefits. The role of targeted agents such as bevacizumab (vascular endothelial growth factor inhibitor) or cetuximab (epidermal growth factor inhibitor) in the setting of CPC is still evolving. Currently, retrospective analyses have shown promising results for the use of bevacizumab in addition to systemic chemotherapy but similar results have not been seen with cetuximab or panitumumab. However, there is significant heterogeneity in the trial data, lack of prospective randomized controlled trials and demonstrated treatment variability based on age and tumour characteristics. This review summarises the current literature in regard to treatment in the unresectable CPC setting as well as discussing issues with the current data and highlighting the need for further trials.
Psoriatic arthritis in patients with psoriasis: A clinical‐epidemiological study at a dermatology center in western Mexico
Authors: Barba‐Gómez José Fernando , Zolano‐Orozco Miroslava , Guevara‐Gutiérrez Elizabeth , Briseño‐Rodríguez Gabriela , Villanueva‐Quintero Guadalupe , Tlacuilo‐Parra Alberto , García‐Figueroa José Luis , Samano‐Tirado Gustavo , Terán‐Estrada Leobardo , Galván‐Villegas Federico , Gutiérrez‐Ureña Sergio 
Published: February 2021

AbstractBackground/ObjectivePsoriatic arthritis (PsA) is a chronic inflammatory illness. Approximately, 15% of psoriasis patients have undiagnosed PsA. In Mexico, we found no related studies. Our objective was to investigate the clinical–epidemiological characteristics of PsA in psoriasis patients in western Mexico.MethodsA cross‐sectional study including Mexican patients with clinical and histopathological diagnosis of psoriasis. Physical examination, rheumatoid factor analysis and radiographies of axial and peripheral skeleton were performed. The prevalence of PsA using the CASPAR criteria, age, sex; clinical variants of PsA, psoriasis type and the Psoriasis Area and Severity Index (PASI), were assessed. Descriptive and inferential statistics were used.ResultsOf 90 patients with psoriasis, 48 met the criteria for PsA, with a prevalence of 53%, and average age of 50 ± 15 years. Predominating were, the female sex in 29 (60%), the axial variant of PsA in 24 (50%), and psoriasis plaques in 40 (83%). The average PASI was 12 ± 11. All cases were rheumatoid factor negative. These variables were not significantly different when comparing subjects with and without PsA, except for the female sex (60% vs. 7%; P < 0.001).ConclusionsPatients with psoriasis should intentionally be evaluated jointly Dermatologists and Rheumatologists searching joint involvement given the high prevalence of PsA previously undiagnosed.
(Almost) Everything in Moderation: New Evidence on Americans' Online Media Diets
Authors: Guess Andrew M. 
Published: February 2021

AbstractDoes the internet facilitate selective exposure to politically congenial content? To answer this question, I introduce and validate large‐N behavioral data on Americans' online media consumption in both 2015 and 2016. I then construct a simple measure of media diet slant and use machine classification to identify individual articles related to news about politics. I find that most people across the political spectrum have relatively moderate media diets, about a quarter of which consist of mainstream news websites and portals. Quantifying the similarity of Democrats' and Republicans' media diets, I find nearly 65% overlap in the two groups' distributions in 2015 and roughly 50% in 2016. An exception to this picture is a small group of partisans who drive a disproportionate amount of traffic to ideologically slanted websites. If online “echo chambers” exist, they are a reality for relatively few people who may nonetheless exert disproportionate influence and visibility.