bluuebunny/crossref_metadata_2025_split huggingface dataset:
AKT-likekinase promotes cell survival during nutritional stress in trypanosomatids
Authors: Mejía Andrés Felipe Díez , Pedroza María Magdalena , Orrego Lina M. , Muñoz Sergio Andrés Pulido , Echeverry María Clara , Rojas Mauricio , Soares Maurilio José , Pérez-Victoria José María , Muskus Carlos Enrique , Robledo Sara María , Marín-Villa Marcel , Varela-Miranda Rubén E. 
Published: July 2020

AbstractTritryps are protozoan parasites that belong to the Trypanosomatidae family, which encompasses the etiologic agents of leishmaniasis, African and American trypanosomiasis. These parasites undergo different stress conditions across their life cycle, such as nutritional stress, which needs to be deadened in order to guarantee the survival of the parasite inside its vector and mammal hosts. Here we show that the lack of the serine threonine kinase PKB / AKT-likefunction, either by allosteric inhibition of its Plekstrin domain (PH) inT. cruzi, the reduction of the gene transcripts inT. bruceiby RNAi assays, or by AKT-like gene knockout inL. major, reduce the tolerance to nutritional stress of parasites that triggers apoptosis-like events, including DNA fragmentation, mitochondrial damage and loss of plasma membrane integrity. Additionally, we observed that double knockout of Akt-likeinL. majorimpairs its infective capacity. This work confirms some of the previously described functions regarding parasite survival for AKT-like kinases in theLeishmaniagenus. The present work also provides strong evidence of the probable function of Akt-likeinT. cruzi andT. bruceisurvival and infectivity.Author summaryEndemic countries for neglected tropical diseases are called to play a paramount role in the discovery of new drug candidates through the application of new drug development strategies. Rational drug design method have proven to be compatible with the development of new drug for orphan and neglected diseases since it substantially reduces the costs of discovery and development, a desirable condition for public funded initiatives. Previously we have identified a new parasite protein kinase (AKT-like) as promising new target candidate by means of computational tools and probed its biological role in trypanosomatids. Here we show that inhibition of the AKT-likekinase in trypanosomatids by different approaches (chemical inhibition, interference RNA and gene knockout) decreases the fitness and survival of the parasitesin vitro, interfering with the capacity of the parasites to react and survive stress conditions similar to those experienced by the cell in the natural life cycle. Additionally our results strongly supports the potential of a new family of compounds previously described by bioinformatics means as potential trypanocidal agents. Altogether we show that the specific inhibition of the AKT-like is a promising strategy for the further development of anti-trypanosome drugs.
VIP plasma levels associate with survival in severe COVID-19 patients, correlating with protective effects in SARS-CoV-2-infected cells
Authors: Temerozo Jairo R. , Sacramento Carolina Q. , Fintelman-Rodrigues Natalia , Pão Camila R. R. , de Freitas Caroline S. , Dias Suelen Silva Gomes , Ferreira André C. , Mattos Mayara , Soares Vinicius Cardoso , Teixeira Lívia , Azevedo-Quintanilha Isaclaudia G. , Hottz Eugenio D. , Kurtz Pedro , Bozza Fernando A. , Bozza Patrícia T. , Souza Thiago Moreno L. , Bou-Habib Dumith Chequer 
Published: July 2020

AbstractInfection by SARS-CoV-2 may elicit uncontrolled and damaging inflammatory responses. Thus, it is critical to identify compounds able to inhibit virus replication and thwart the inflammatory reaction. Here, we show that the plasma levels of the immunoregulatory neuropeptide VIP are elevated in patients with severe COVID-19, correlating with reduced inflammatory mediators and with survival on those patients. In vitro, VIP and PACAP, highly similar neuropeptides, decreased the SARS-CoV-2 genome replication in human monocytes and viral production in lung epithelial cells, also reducing cell death. Both neuropeptides inhibited the production of proinflammatory mediators in lung epithelial cells and in monocytes. VIP and PACAP prevented in monocytes the SARS-CoV-2-induced activation of NF-kB and SREBP1 and SREBP2, transcriptions factors involved in proinflammatory reactions and lipid metabolism, respectively. They also promoted CREB activation, a transcription factor with antiapoptotic activity and negative regulator of NF-kB. Specific inhibition of NF-kB and SREBP1/2 reproduced the anti-inflammatory, antiviral and cell death protection effects of VIP and PACAP. Our results support further clinical investigations of these neuropeptides against COVID-19.
The deubiquitinase (DUB) USP13 promotes Mcl-1 stabilisation in cervical cancer
Authors: Morgan Ethan L. , Patterson Molly R. , Barba-Moreno Diego , Wilson Adam , Macdonald Andrew 
Published: July 2020

AbstractUbiquitination is a critical regulator of cellular homeostasis. Aberrations in the addition or removal of ubiquitin can result in the development of cancer and key components of the ubiquitination machinery serve as oncogenes or tumour suppressors. An emerging target in the development of cancer therapeutics are the deubiquitinase (DUB) enzymes that remove ubiquitin from protein substrates. Whether this class of enzyme plays a role in cervical cancer has not been fully explored. By interrogating the cervical cancer data from the TCGA consortium, we noted that the DUB USP13 is amplified in approximately 15% of cervical cancer cases. We confirmed that USP13 expression was increased in cervical cancer cell lines, cytology samples from patients with cervical disease and in cervical cancer tissue. Depletion of USP13 inhibited cervical cancer cell proliferation. Mechanistically, USP13 bound to, deubiquitinated and stabilised Mcl-1, a pivotal member of the anti-apoptotic Bcl-2 family and the reduced Mcl-1 expression contributed to the observed proliferative defect. Importantly, the expression of USP13 and Mcl-1 proteins correlated in cervical cancer tissue. Finally, we demonstrated that depletion of USP13 expression or inhibition of USP13 enzymatic activity increased the sensitivity of cervical cancer cells to the BH3 mimetic inhibitor ABT-263. Together, our data demonstrates that USP13 is a potential oncogene in cervical cancer that functions to stabilise the pro-survival protein Mcl-1, offering a potential therapeutic target for these cancers.
Estimating maximal microbial growth rates from cultures, metagenomes, and single cells via codon usage patterns
Authors: Weissman Jake L. , Hou Shengwei , Fuhrman Jed A. 
Published: July 2020

AbstractMaximal growth rate is a basic parameter of microbial lifestyle that varies over several orders of magnitude, with doubling times ranging from a matter of minutes to multiple days. Growth rates are typically measured using laboratory culture experiments. Yet, we lack sufficient understanding of the physiology of most microbes to design appropriate culture conditions for them, severely limiting our ability to assess the global diversity of microbial growth rates. Genomic estimators of maximal growth rate provide a practical solution to survey the distribution of microbial growth potential, regardless of cultivation status. We developed an improved maximal growth rate estimator, and implement this estimator in an easy-to-use R package (gRodon), which outperforms the state-of-the-art growth estimator in multiple settings, including in a community context where we implement a novel species abundance correction for metagenomes. Additionally, we estimate maximal growth rates from over 200,000 genomes, metagenome-assembled genomes, and single-cell amplified genomes to survey growth potential across the range of prokaryotic diversity. We provide these compiled maximal growth rates in a publicly-available database (EGGO), which we use to illustrate how culture collections show a strong bias towards organisms capable of rapid growth. We demonstrate how this database can be used to propagate maximal growth rate predictions to organisms for which we lack genomic information, on the basis of 16S rRNA sequence alone. Finally, we observe a bias in growth predictions for extremely slow-growing organisms, ultimately leading us to suggest a novel evolutionary definition of oligotrophy based on the selective regime an organism occupies.SignificanceDespite the wide perception that microbes have rapid growth rates, many environments like seawater and soil are often dominated by microorganisms that can only grow very slowly. Our knowledge about growth is necessarily biased towards easily culturable organisms, which turn out to be those that tend to grow fast, because microbial growth rates have traditionally been measured using lab growth experiments. But how are potential growth rates distributed in nature? We developed a tool to predict maximum growth rate from an organism’s genome sequence (gRodon). We predicted the growth rates of over 200,000 organisms and compiled these predictions in a publicly-available database (EGGO), which illustrates how current collections of cultured microbes are strongly biased towards fast-growing organisms.
‘Walking in two worlds’: A qualitative review of income management in Cape York
Authors: Scott John , Staines Zoe , Higginson Angela , Lauchs Mark , Ryan Vanessa , Zhen Liuissa 
Published: July 2020

AbstractThe Cape York Welfare Reform (CYWR) initiative aims to reduce ‘passive dependence’ on welfare and restore ‘positive social norms’ to revitalise cultural and social networks and support economic engagement in Indigenous communities in the Cape York Region of Australia. Critics of the initiative and, in particular, its income management (IM) policies have associated it with a broader neoliberal reform agenda that delineates social ‘problems’ from their historical and structural context. This paper discusses key qualitative findings from a strategic review of CYWR, paying particular attention to the ways in which Cape York IM (CYIM) straddles both Indigenous and settler social norms, while perpetuating neoliberal conceptualisations of welfare ‘dependency’. We situate these findings within the existing literature on Australia's other IM models and also consider them in relation to subsequent government responses to the review and associated policies. We argue that CYIM represents a unique initiative, the subtle nuances of which have been largely ignored or misunderstood by critics. Further, we conclude that any extension or revision of this initiative should be considered with respect to deep and wide‐ranging consultation of the Indigenous communities subject to CYWR. However, such consultation has not been the standard practice in Australian contexts.
Royal commissions and policy influence
Authors: Mintrom Michael , O'Neill Deirdre , O'Connor Ruby 
Published: July 2020

AbstractRoyal commissions are established at the Commonwealth and state levels in Australia to investigate matters of significant public concern. These distinctive entities are highly respected both by government and the community. They are typically expected to produce reports that will have significant impact. Although a large number are created primarily to determine why specific events happened and where accountabilities lie, many are expected to generate findings and recommendations that will lead to policy change. We review common strategies that actors in and around government deploy with the purpose of shaping public policy. This leads to an exploration of the influence strategies deployed by three Australian royal commissions that achieved high levels of policy impact. Lessons are drawn for how future royal commissions might create policy legacies that deliver high public value.
Liver damage at admission is an independent prognostic factor for COVID‐19
Authors: Chen Liu Ying , Chu Hui Kuan , Bai Tao , Tu Sheng Jin , Wei Yuan , Li Zhong Lin , Hu Li Lin , Zhu Rui , Zhang Lei , Han Chao Qun , Xiao Li , He Qi , Song Jun , Liu Wei Hua , Zhu Qing Jing , Chen Hua , Yang Ling , Hou Xiao Hua 
Published: July 2020

ObjectiveAbnormal liver function is a common form of extra‐pulmonary organ damage in patients with coronavirus disease 2019 (COVID‐19). Patients with severe COVID‐19 have a higher probability and progression of liver injury than those without severe disease. We aimed to evaluate the prognosis of liver injury in patients with COVID‐19.MethodsWe retrospectively included 502 patients with laboratory‐confirmed SARS‐CoV‐2 infection. Clinical features and survival of patients with and without liver injury were compared. Cox proportional hazards models were used to determine the variables that might have an effect on survival.ResultsAmong the 502 patients enrolled, 301 patients had abnormal liver function with increased neutrophil count, C‐reactive protein, creatinine, troponin I (TnI), D‐dimer, lactose dehydrogenase and creatine kinase. Patients with abnormal liver functions had a higher mortality rate (28.9% vs 9.0%, P < 0.001), a higher ratio of male sex (65.1% vs 40.8%, P < 0.001) and a higher chance of developing systemic inflammatory response syndrome (53.5% vs 41.3%, P = 0.007). Among patients with abnormal liver functions, patients with grade 2 liver damage (with both abnormal alanine aminotransferase or aspartate aminotransferase levels and abnormal alkaline phosphatase or gamma‐glutamyl transpeptidase levels) had a higher ratio of male patients, elevated neutrophil count, procalcitonin, D‐dimer levels and mortality rate. Multivariate Cox regression analyses suggested that the grade of liver damage (hazard ratio: 1.377, 95% confidence interval: 1.000‐1.896, P = 0.049) was an independent predictor of death.ConclusionsPatients with COVID‐19 and abnormal liver functions have a higher mortality than those with normal liver functions. Liver damage is an independent prognostic factor of COVID‐19.
A Proposal for a New Universal Development Commitment
Authors: Sumner Andy , Gulrajani Nilima , Wickstead Myles , Glennie Jonathan 
Published: July 2020

AbstractMost developed countries have accepted, in principle at least, the 50‐year‐old commitment of contributing 0.7 per cent of gross national income to supporting the development of developing countries. But what if all countries made a universal development commitment, meaning a scaled contribution? We propose a new universal and scaled financial commitment to development, informed by but not necessarily identical to official development assistance. This paper: (1) sets out how a new era is emerging of higher global ambitions – for example, to end poverty; (2) proposes a new way to raise and govern international public funds; and (3) discusses the possible size and use of contributions, and the evolution in global governance and democracy that a new deal would entail. We conclude with a set of questions that the proposal raises.
Association Between Methamphetamine Use and Psychiatric Hospitalization, Chemical Restraint, and Emergency Department Length of Stay
Authors: Murphy Charles E. , Wang Ralph C. , Coralic Zlatan , Lai Andrew R. , Raven Maria 
Published: July 2020

AbstractObjectivesMethamphetamine intoxication is an increasing cause of emergency department (ED) visits in the United States, particularly in the west. In San Francisco, California, 47% of patients visiting psychiatric emergency services are intoxicated with methamphetamine. Such patients often visit the ED due to acute psychiatric symptoms, yet ED‐based research investigating the outcomes and resource utilization of these visits is limited.MethodsWe examined a retrospective cohort of ED patients requiring ED‐based psychiatric consultation from June 2017 to July 2018. We evaluated the association between methamphetamine visits and need for chemical restraint, psychiatric hospitalization, and length of stay (LOS).ResultsWe identified 2,087 ED visits with psychiatric consults. Based on urine toxicology results and discharge diagnosis, 403 visits involved methamphetamine with or without other drugs, 480 involved other drugs without methamphetamine, and 1,204 had no evidence of drug use. Methamphetamine visits were associated with increased odds of chemical restraint compared to visits without drug use (adjusted odds ratio [AOR] = 3.2, 95% CI = 2.1 to 5.2, p < 0.001), but not other drug visits (AOR = 1.2, 95% CI = 0.8 to 1.9, p = 0.4). Methamphetamine visits had lower odds of psychiatric hospitalization than other drug visits (AOR = 0.62, 95% CI = 0.41 to 0.95, p = 0.03) and longer adjusted LOS than visits without drug use (+4.3 hours, 95% CI = 4.1 to 8.3 hours, p < 0.001) but not other drug visits (+1.5 hours, 95% CI = −0.6 to 3.7 hours, p = 0.2).ConclusionsMethamphetamine ED visits were associated with increased odds of needing chemical restraint and of an increased ED LOS but not with psychiatric inpatient admission. These results indicate an opportunity to improve the efficiency of ED care for these patients.
The temporal association between incident late‐life depression and incident dementia
Authors: Heser K. , Fink A. , Reinke C. , Wagner M. , Doblhammer G. 
Published: July 2020

ObjectiveThere is an established association between depression and subsequent dementia. The present study examined temporal associations between incident late‐life depression and subsequent dementia, also considering age and sex.MethodsWe used longitudinal health claims data from the largest German health insurance provider (‘Allgemeine Ortskrankenkasse’) considering up to 9 follow‐up years in piecewise exponential models. ICD‐10 codes were used to define incident depression and dementia in individuals ≥65 years (n = 97 110).ResultsIncident depression was associated with a higher risk of subsequent dementia (incidence rate ratios (IRR) adjusted for age and sex: IRR = 1.58, 95% CI = 1.51–1.64). The strongest association was found for the shortest interval of 1 quarter (IRR = 2.04, 95% CI = 1.88–2.21), with significant associations up to an interval of roughly 3 years. The association was more pronounced and lasted for more quarters in the younger portion of this study group (ages from 65–74: IRR = 2.00, 95% CI = 1.83–2.18; 75–84: IRR = 1.64, 95% CI = 1.55–1.73; ≥85: IRR = 1.19, 95% CI = 1.08–1.31). It was stronger among men than women (men: IRR = 1.98, 95% CI = 1.84–2.14; women: IRR = 1.44, 95% CI = 1.37–1.51) with no sex‐specific temporal association.ConclusionThis large claims data study confirmed that incident late‐life depression is associated with a higher risk of dementia within the 3 years following diagnosis. Hence, incident late‐life depression should prompt further cognitive examinations and referrals to specialists. This might apply especially to younger seniors and men.
Morphology of the tongue and laryngeal entrance in the Common pheasant (Phasianus colchicus); a light and scanning electron microscopic study
Authors: Mohammad Payam Elyasi Seyed , Goodarzi Nader 
Published: July 2020

AbstractThe present work was carried out to describe morphological features of the tongue and laryngeal entrance of the Common pheasantPhasianus colchicus, using light and scanning electron microscopy. The lingual apex was taper‐shaped with a shallow median sulcus. A V‐shaped papillary crest with 15–20 caudally directed conical papillae was located between the radix and corpus linguae. The second row of papillae consisting of three caudolaterally directed conical papillae was arranged caudal to the main papillary crest. The mons laryngealis was equipped caudally with a double‐layer of large conical papillae as pharyngeal crest, and few small conical papillae were seen around the glottis. Scanning electron microscope (SEM) observation showed that the apex linguae and corpus were covered with compact filiform papillae, while the radix linguae were free of papillae. Numerous openings of salivary gland can be seen on the radix linguae and mons laryngealis at higher magnification. On histological sections, all parts of the tongue and mons laryngealis were covered with a keratinised stratified squamous epithelium. The keratinised layer became thinner rostro‐caudally. The simple alveolar salivary glands were distributed in the submucosa from the apex linguae to the radix linguae as well as the mons laryngealis. PAS staining revealed mucin‐secreting activity of this glands. According to the findings, although the tongue and laryngeal entrance of the Common pheasant is characteristics of a galliform bird, it has some features similar to passeriformes and falconiformes.
Circulating microRNA‐15b‐5p as a biomarker for asthma‐COPD overlap
Authors: Hirai Keita , Shirai Toshihiro , Shimoshikiryo Takayuki , Ueda Megumi , Gon Yasuhiro , Maruoka Shuichiro , Itoh Kunihiko 
Published: July 2020

AbstractBackgroundIt remains unclear how to characterize different subtypes of asthma and chronic obstructive pulmonary disease (COPD). We previously described serum periostin and chitinase‐3‐like protein 1 (YKL‐40) as useful markers for asthma‐COPD overlap (ACO). MicroRNAs (miRNAs) are now recognized as markers for identifying the pathophysiological features in several diseases. This study aimed to identify circulating miRNAs that could discriminate patients with ACO from patients with asthma or COPD.MethodsThis study included two independent cohorts. First, we screened 84 miRNAs for expression levels in patients with ACO (n = 6) or asthma (n = 6) using a quantitative real‐time PCR array. The miRNAs showing at least a 2‐fold difference in the discovery phase were analyzed in 30 patients each with asthma, COPD, or ACO in the replication phase. The diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve (AUROC).ResultsNine miRNAs were identified in the discovery phase. Five of these miRNAs (miR‐148a‐3p, miR‐15b‐5p, miR‐223‐3p, miR‐23a‐3p, and miR‐26b‐5p) had lower levels in ACO patients and could discriminate between ACO patients and patients with either asthma or COPD. miR‐15b‐5p was the most accurate miRNA for the discrimination of patients with ACO (AUROC, 0.71). Moreover, the combined assessment of miR‐15b‐5p, serum periostin, and YKL‐40 (AUROC, 0.80) improved diagnostic accuracy for ACO compared with the combined model of periostin and YKL‐40 (AUROC, 0.69).ConclusionsCirculating miR‐15b‐5p is a potential marker for identifying patients with ACO. By elucidating the molecular pathways controlled by miRNAs, we may better understand the pathophysiology of ACO.
Trust and well‐being: Evidence from Indonesia
Authors: Nizeyumukiza Emmanuel , Cilik Pierewan Adi , Ndayambaje Edmond , Ayriza Yulia 
Published: July 2020

AbstractThere is a growing empirical scholarship on the benefits of trust for well‐being in the literature. However, few studies have been conducted in the Indonesian context. This study is intended at investigating the association between different measures of trust and well‐being in Indonesia using national representative data from the 5th wave of the Indonesian Family Life Survey on a sample of 27,150 individuals. Multiple regression was performed to calculate the estimates of this relationship. The main findings revealed a small positive relationship of trust in neighbors with life satisfaction and a small positive relationship of trust in police with life satisfaction and happiness beyond the contribution of gender, age, level of education, marital status, personality trait, economic status, and physical and mental health. This study suggests that policies that can forge trustworthiness of neighborhoods and institutions should be developed and prioritized.