bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nicotinamide adenine dinucleotide: Biosynthesis, consumption and therapeutic role in cardiac diseases
Authors: Tannous Cynthia , Booz George W. , Altara Raffaele , Muhieddine Dina H. , Mericskay Mathias , Refaat Marwan M. , Zouein Fouad A. 
Published: August 2020

AbstractNicotinamide adenine dinucleotide (NAD) is an abundant cofactor that plays crucial roles in several cellular processes. NAD can be synthesized de novo starting with tryptophan, or from salvage pathways starting with NAD precursors like nicotinic acid (NA), nicotinamide (NAM) or nicotinamide riboside (NR), referred to as niacin/B3 vitamins, arising from dietary supply or from cellular NAD catabolism. Given the interconversion between its oxidized (NAD+) and reduced form (NADH), NAD participates in a wide range of reactions: regulation of cellular redox status, energy metabolism and mitochondrial biogenesis. Plus, NAD acts as a signalling molecule, being a cosubstrate for several enzymes such as sirtuins, poly‐ADP‐ribose‐polymerases (PARPs) and some ectoenzymes like CD38, regulating critical biological processes like gene expression, DNA repair, calcium signalling and circadian rhythms. Given the large number of mitochondria present in cardiac tissue, the heart has the highest NAD levels and is one of the most metabolically demanding organs. In several models of heart failure, myocardial NAD levels are depressed and this depression is caused by mitochondrial dysfunction, metabolic remodelling and inflammation. Emerging evidence suggests that regulating NAD homeostasis by NAD precursor supplementation has therapeutic efficiency in improving myocardial bioenergetics and function. This review provides an overview of the latest understanding of the different NAD biosynthesis pathways, as well as its role as a signalling molecule particularly in cardiac tissue. We highlight the significance of preserving NAD equilibrium in various models of heart diseases and shed light on the potential pharmacological interventions aiming to use NAD boosters as therapeutic agents.
A systematic review of mental health literacy in Pakistan
Authors: Munawar Khadeeja , Abdul Khaiyom Jamilah Hanum , Bokharey Iram Zehra , Park Miriam Sang‐Ah , Choudhry Fahad Riaz 
Published: August 2020

AbstractIndividual mental health has become a primary global concern. In Pakistan, the prevalence of mental health issues is still unclear, as not many studies have assessed the level of mental health literacy (MHL) in the country. This systematic review aims to bridge this gap by encouraging the early detection of mental disorders, lessening stigma, and improving help‐seeking behavior. Nine electronic databases were searched to identify empirical literature in this area. Only studies that evaluated MHL efficacy and those published in English were selected. Non‐peer reviewed articles and gray literature were excluded. From 613 studies retrieved, 59 studies met the inclusion criteria and were reviewed. Forty‐three of the included studies mentioned mental health outcome measures (of which only four mentioned reliability indices), 13 discussed stigma, 18 examined help‐seeking approaches to mental illness treatments, and 47 discussed mental health knowledge. Additionally, the outcome of the MHL measures had considerable heterogeneity and limited validity. Meta‐analysis was not conducted due to a lack of MHL operationalization. Besides, the measurement tools in the studies lacked consistency and standardization. This review compiled the available studies on MHL to assist researchers currently studying the various dimensions of MHL, as well as those designing new studies or investigating effective methods to increase MHL. This review highlights the need for well‐designed controlled intervention studies. Further implications for researchers, practitioners, and policymakers are mentioned.
Inter‐relationships between burnout, personality and coping features in residents within an ACGME‐I Accredited Psychiatry Residency Program
Authors: Lee Yu Wei , Kudva Kundadak Ganesh , Soh Mark , Chew Qian Hui , Sim Kang 
Published: August 2020

AbstractBackgroundBurnout during residency training is associated with various factors. Within the context of stress/coping transactional model in which one's personality can influence stress appraisal and coping, there is limited evidence examining the relationship between burnout and personality factors amongst psychiatry residents.ObjectivesWe aim to evaluate the prevalence of burnout within a cohort of psychiatry residents and its relationship with personality factors, demographic, work‐related factors and coping features.MethodsWe conducted a cross‐sectional study involving 50 out of 77 eligible residents (response rate 64.9%) and administered the Oldenberg Burnout Inventory (OLBI), NEO‐Five Factor Inventory (NEO‐FFI) and Brief COPE Inventory. Burnout was defined as crossing the thresholds for exhaustion (≥2.25) and disengagement (≥2.1) scores. We compared the burnout vs nonburnout groups and examined the relationship between burnout, personality factors and coping strategies using correlational and mediational analyses.ResultsOverall, 78% of our cohort met criteria for burnout. Burnout was correlated with hours of work per week (rs = .409, P = .008), neuroticism (OR 1.2, 95% CI 1.01‐1.43, P = .041) and avoidance coping (OR 1.61, 95% CI 1.06‐2.46, P = .025). Neuroticism was significantly correlated (all P < .001) with all coping domains (Seeking Social Support, rs = 0.40; Problem Solving, rs = 0.52; Avoidance, rs = 0.55; Positive thinking, rs = 0.41) and was a partial mediator between avoidance coping and burnout (β of indirect path = 0.168, [SE = 0.066]; P = .011).ConclusionsWe found a considerable burnout rate amongst psychiatry residents which was associated with neuroticism and avoidance coping, and suggest ways to better tackle occupational burnout during residency training.
Effects of different sources and levels of dietary chromium supplementation on performance of broiler chicks
Authors: Safwat Assem Mohamed , Elnaggar Asmaa Shawkey , Elghalid Osama Ahmed , EL‐Tahawy Waleed Salah 
Published: August 2020

AbstractThe current experiment was carried out to evaluate the effect of different dietary chromium supplementation sources, chromium oxide (Cr2O3), chromium methionine (Cr‐Met), or chromium yeast (Cr‐yeast), at different levels each (500 or 1,000 ppb) on growth performance, physiological traits, and carcass characteristics of broiler chicks. A total of 490 seven‐day‐old Arbor Acres chicks were randomly distributed into 7 experimental groups each in 10 replicates of 7 birds each. The groups were control, 500 ppb Cr2O3, 1,000 ppb Cr2O3, 500 ppb Cr‐Met, 1,000 ppb Cr‐Met, 500 ppb Cr‐yeast, and 1,000 ppb Cr‐yeast. The results showed significant superiority of the organic chromium sources (Cr‐Met or Cr‐yeast) concerning body weight and weight gain, the group supplemented with 1,000 ppb Cr‐yeast consumed the lowest feed (3,185 g) and had the best feed conversion ratio (1.60) compared to the control (1.73). The chromium treatments recorded significantly better protein and lipid profile, antioxidant status, and immunological parameters than the control group. Similarly, dietary chromium supplementation increased carcass yield and decreased intestinal pathogenic bacteria. In conclusion, supplementing broiler diets with organic chromium sources at 1,000 ppb promotes growth performance, physiological traits, and carcass characteristics; such chromium treatments enhanced the antioxidant status and immunity levels of broilers.
Drug exposure of first‐line anti‐tuberculosis drugs in China: A prospective pharmacological cohort study
Authors: Gao Yazhou , Davies Forsman Lina , Ren Weihua , Zheng Xubin , Bao Ziwei , Hu Yi , Bruchfeld Judith , Alffenaar Jan‐Willem 
Published: August 2020

AimExploring the need for optimization of drug exposure to improve tuberculosis (TB) treatment outcome is of great importance. We aimed to describe drug exposure at steady state as well as the population pharmacokinetics (PK) of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) in Chinese TB patients.MethodsA prospective multicentre PK study of RIF, INH and PZA was conducted in China between January 2015 and December 2017. Six blood samples were collected from each subject for drug concentration measurement. Nonlinear mixed effect analyses were used to develop population PK models.ResultsIn total, 217 patients were included. Positive correlations between body weight, clearance and volume of distribution were identified for RIF and PZA, whereas body weight only influenced clearance for INH. In addition, males had higher RIF clearance and thus lower RIF exposure than women. Acetylator status was significantly associated with INH clearance as INH exposure in intermediate and fast acetylators was significantly lower than in slow acetylators, especially in low‐weight bands. Simulations also showed significantly lower drug exposures in low‐weight bands for all three drugs. Patients weighing <38 kg were respectively exposed to 30.4%, 45.9% and 18.0% lower area under the concentration‐time curve of RIF, INH and PZA than those weighing ≥70 kg. Higher doses by addition of one fixed‐dose combination tablet or 150 mg INH were simulated and found to be effective in improving INH drug exposures, especially in low‐weight bands.ConclusionPK variability of first‐line anti‐TB drugs is common in Chinese TB patients. The developed population PK models can be used to optimize drug exposures in Chinese patients. Moreover, standard dosing needs to be adjusted to increase target attainment.
Pharmacologic effects of oseltamivir in immunocompromised adult patients as assessed by population PK/PD analysis and drug‐disease modelling for dosing regimen optimization
Authors: Sturm Stefan , Lemenuel‐Diot Annabelle , Patel Kashyap , Gibiansky Leonid , Bhardwaj Rajinder , Smith Patrick F. , Dang Steve , Zwanziger Elke , Nasmyth‐Miller Clare , Ravva Patanjali 
Published: August 2020

AimPharmacologic effects were analysed to determine a dose recommendation for oseltamivir in immunocompromised (IC) adults with influenza.MethodsQuantitative clinical pharmacology methods were applied to data from 160 adult IC patients (aged 18‐78 years) from two studies (NV20234, 150 patients; NV25118, 10 patients) who received oseltamivir 75‐200 mg twice daily for up to 10 days. An established population‐pharmacokinetic (PK) model with additional effects on oseltamivir and oseltamivir carboxylate (OC) clearance described the PK characteristics of oseltamivir in IC patients versus otherwise healthy (OwH) patients from previous clinical trials. Estimated PK parameters were used to evaluate exposure‐response relationships for virologic endpoints (time to cessation of viral shedding, viral load measures and treatment‐emergent resistance). A drug‐disease model characterized the viral kinetics of influenza accounting for the effect of OC on viral production.ResultsOseltamivir clearance was 32.5% lower (95% confidence interval [CI], 26.1‐38.8) and OC clearance was 33.7% lower (95% CI, 23.2‐44.1) in IC versus OwH patients. No notable exposure‐response relationships were identified for exposures higher than those achieved after conventional dose oseltamivir 75 mg, which appeared to be close to the maximum effect of oseltamivir. Simulations of the drug‐disease model predicted that initiating treatment within 48 hours of symptom onset had maximum impact, and a treatment duration of 10 days was favourable over 3‐5 days to limit viral rebound.ConclusionsOur findings support the use of conventional‐dose oseltamivir 75 mg twice daily for 10 days in the treatment of IC adult patients with influenza.
Bromodomain 4 is a potent prognostic marker associated with immune cell infiltration in breast cancer
Authors: Zhong Limei , Yang Zhiyong , Lei Da , Li Lijuan , Song Shaohua , Cao Donglin , Liu Yufeng 
Published: August 2020

AbstractBromodomain 4 (BRD4), a member of the bromodomain and extra‐terminal domain protein family, has become a promising epigenetic target in cancer and inflammatory diseases; however, the detailed biological role of BRD4 in breast cancer (BRCA) remains undetermined. We analysed the BRD4 expression levels using the Oncomine and TIMER databases and evaluated the clinical impact of BRD4 on BRCA prognosis using Kaplan‐Meier plot and PrognoScan. The correlation between BRD4 and tumour‐infiltrating immune cells was investigated using TIMER. Furthermore, the correlation between BRD4 expression levels was also analysed using TIMER in addition to the GEPIA database for immune cell gene markers. BRD4 expression was significantly higher in BRCA tissues than in normal tissues, which was significantly correlated with poor overall survival (OS). Specifically, high BRD4 expression was correlated with worse OS and progression‐free survival in patients with BRCA. In addition, BRD4 expression was correlated with levels of infiltrating monocytes (CSF1R, cor = 0.204, P = 9.19e−12), tumour‐associated macrophages (CD68, cor = 0.129, P = 1.81e−05), M1/M2 macrophages and different effector T cells (including Th1/Th2/Treg) in BRCA. These findings suggest that BRD4 could be used as a prognostic biomarker for determining prognosis and immune cell infiltration levels in BRCA.
Bayesian variable selection for non‐Gaussian responses: a marginally calibrated copula approach
Authors: Klein Nadja , Smith Michael Stanley 
Published: August 2020

AbstractWe propose a new highly flexible and tractable Bayesian approach to undertake variable selection in non‐Gaussian regression models. It uses a copula decomposition for the joint distribution of observations on the dependent variable. This allows the marginal distribution of the dependent variable to be calibrated accurately using a nonparametric or other estimator. The family of copulas employed are “implicit copulas” that are constructed from existing hierarchical Bayesian models widely used for variable selection, and we establish some of their properties. Even though the copulas are high dimensional, they can be estimated efficiently and quickly using Markov chain Monte Carlo. A simulation study shows that when the responses are non‐Gaussian, the approach selects variables more accurately than contemporary benchmarks. A real data example in the Web Appendix illustrates that accounting for even mild deviations from normality can lead to a substantial increase in accuracy. To illustrate the full potential of our approach, we extend it to spatial variable selection for fMRI. Using real data, we show our method allows for voxel‐specific marginal calibration of the magnetic resonance signal at over 6000 voxels, leading to an increase in the quality of the activation maps.
Can typical game features have unintended consequences? A study of players’ learning and reactions to challenge and failure in an educational programming game
Authors: Chase Catherine C. , Malkiewich Laura J. , Lee Alison , Slater Stefan , Choi Ahram , Xing Chenmu 
Published: August 2020

AbstractIt is difficult to motivate learners to seek out and persist at challenging learning tasks where failure is likely. However, in game environments, people seem highly motivated to engage with challenges and respond productively to failure. Many typical game features purportedly enhance intrinsic motivation and self‐efficacy, which should improve students’ reactions to challenge and failure, which should in turn enhance learning. An experimental study with early middle school students tested these assumptions by comparing a “Full” version of a typical, commercial programming game to a “Minimal” version of the same game where common game features such as narrative, performance metrics, high‐quality graphics, and sound were removed. In contrast to our hypotheses, players of the Full Game were less likely to choose coding challenges, were less tolerant of coding failures and gained less coding knowledge. Intrinsic motivation and self‐efficacy did not differ between conditions. Correlational analyses showed that failure tolerance and challenge seeking may critically affect learning from educational games. The current study offers an existence proof that some common game features can hinder players' failure tolerance, challenge‐seeking and learning, in certain game contexts. Future research should isolate the effects of individual game features, test generalizability and explore which contextual variables influence the findings.
Lacking socio‐economic status reduces subjective well‐being through perceptions of meta‐dehumanization
Authors: Sainz Mario , Martínez Rocío , Moya Miguel , Rodríguez‐Bailón Rosa , Vaes Jeroen 
Published: August 2020

Previous research has identified that both low‐ and high‐socio‐economic groups tend to be dehumanized. However, groups that have a deprived position are more willing to interiorize the negative perceptions that others have about them compared with affluent groups. In this project, we address the role of meta‐(de)humanization (the perceived humanity one thinks is ascribed or denied to one’s group) based on socio‐economic status differences and its influence in the perceived psychological well‐being. We conducted two studies: In Study 1 (correlational,N = 990), we analysed the relationship between socio‐economic status, meta‐dehumanization, and well‐being. Results indicated that lower socio‐economic status positively predicted more meta‐dehumanization and worse well‐being. Moreover, meta‐dehumanization mediated the relationship between socio‐economic status and well‐being. In Study 2 (experimental,N = 354), we manipulated socio‐economic status (low‐, middle‐, and high‐socio‐economic status conditions) to evaluate its influence on meta‐dehumanization and well‐being. Results indicated that individuals of low (vs. higher)‐socio‐economic status perceived more meta‐dehumanization and reported worse well‐being. Finally, a multicategorical mediational analysis indicated that low (vs. middle or high)‐socio‐economic status led to worse well‐being through higher perceived meta‐dehumanization. We discuss differences in perceived meta‐(de)humanization based on groups’ socio‐economic status and implications on the population’s well‐being.
Targeting IL‐5 pathway against airway hyperresponsiveness: A comparison between benralizumab and mepolizumab
Authors: Calzetta Luigino , Ritondo Beatrice Ludovica , Matera Maria Gabriella , Facciolo Francesco , Rogliani Paola 
Published: August 2020

Background and PurposeAirway hyperresponsiveness (AHR) is a central abnormality in asthma. IL‐5 may modulate AHR in animal models of asthma, but the available data is inconsistent on the impact of targeting IL‐5 pathway against AHR. The difference between targeting IL‐5 or the IL‐5 receptor, α subunit (IL‐5Rα) in modulating AHR remains to be investigated in human airways. The aim of this study was to compare the role of the anti‐IL‐5Rα benralizumab and the anti‐IL‐5 mepolizumab against AHR and to assess whether these agents influence the levels of cAMP.Experimental ApproachPassively sensitized human airways were treated with benralizumab and mepolizumab. The primary endpoint was the inhibition of AHR to histamine. The secondary endpoints were the protective effect against AHR to parasympathetic activation and mechanical stress, and the tissue modulation of cAMP.Key ResultsBenralizumab and mepolizumab significantly inhibited the AHR to histamine (maximal effect −134.14 ± 14.93% and −108.29 ± 32.16%, respectively), with benralizumab being 0.73 ± 0.10 logarithm significantly more potent than mepolizumab. Benralizumab and mepolizumab significantly inhibited the AHR to transmural stimulation and mechanical stress. Benralizumab was 0.45 ± 0.16 logarithm significantly more potent than mepolizumab against AHR to parasympathetic activation. The effect of these agents was significantly correlated with increased levels of cAMP.Conclusion and ImplicationsTargeting the IL‐5/IL‐5Rα axis is an effective strategy to prevent the AHR. Benralizumab was more potent than the mepolizumab and the concentration‐dependent beneficial effects of both these monoclonal antibodies were related to improved levels of cAMP in hyperresponsive airways.
Assessing avian diversity and community composition along a successional gradient in traditional Lacandon Maya agroforests
Authors: Falkowski Tomasz B. , Vázquez‐Pérez José Raúl , Chankin Adolfo , Campos‐Beltrán Atzin Yetlanezi , Rangel‐Salazar José L. , Cohen Jonathan B. , Diemont Stewart A.W. 
Published: August 2020

AbstractEvidence regarding the ability of agroforests to conserve biological diversity has been mixed; they tend to maintain avian communities with species richness similar to that of undisturbed forest ecosystems but generally do not completely preserve community composition. Using a combination of occupancy modeling and non‐metric multidimensional scaling on point‐count data, we assessed changes in avian community diversity and composition along a successional gradient in traditional Lacandon Maya agroforests and compared them to protected areas in the region. Bird species richness and diversity in Lacandon agroforests peaked in early secondary forest stages. These agroforests' mean Shannon–Weiner diversity was 5% higher than that of nearby protected areas, but their species richness was similar. Community composition in Lacandon agroforests changed throughout succession, with earlier stages supporting communities distinctly characterized by generalist species, while subsequent, less‐intensively managed stages tended to support more forest‐dwellers. The bird community observed in even the most mature secondary forest stages in Lacandon agroforests differed from that of undisturbed rain forest ecosystems. These results demonstrate the potential of traditional Lacandon agroforestry management to conserve avian biodiversity while ensuring food sovereignty for farmers. However, because the community composition of early‐successional stages was different than later stages, shortening fallow cycles and reducing forest cover to increase agricultural production will limit the species this system can support. This study illustrates the value of incorporating traditional agroecosystems into conservation planning as well as maintaining protected areas, because the latter serve as refugia for species that require undisturbed forest habitat in an agroecological matrix.Abstract in Spanish is available with online material.
Deficiency of pseudogene UPAT leads to hepatocellular carcinoma progression and forms a positive feedback loop with ZEB1
Authors: Xiang Leyang , Huang Xiaoting , Wang Siqi , Ou Huohui , Chen Zhanjun , Hu Zhigang , Huang Yu , Li Xianghong , Yuan Yawei , Yang Dinghua 
Published: August 2020

AbstractHepatocellular carcinoma (HCC) is a common disease worldwide. Accumulating reports have evidenced the internal connection between epithelial‐mesenchymal transition (EMT) and cancer stem cells (CSCs), as well as their significance in metastasis and post–operative recurrence. In this study, we investigated an interesting ubiquitin‐proteasome pathway associated pseudogene of AOC4, also known as UPAT, and showed that it was downregulated in 39.78% (37/93) of patients with hepatitis B virus (HBV)‐related HCC. Downregulation of UPAT was associated with multiple worse clinicopathological parameters, as well as decreased recurrence‐free survival (RFS). In vitro and in vivo assays found that overexpression of UPAT significantly suppressed cellular migration, invasion, EMT processes, and CSC properties. Mechanistic studies showed that UPAT promoted ZEB1 degradation via a ubiquitin‐proteasome pathway and, in contrast, ZEB1 transcriptionally suppressed UPAT by binding to multiple E‐box (CACCTG) elements in the promoter region. Moreover, UPAT was negatively correlated with ZEB1 protein in HCC tissues, their combined expression discriminated RFS outcomes for patients with HBV‐related HCC. These data on the UPAT‐ZEB1 circuit‐mediated pathway will further knowledge on EMT and CSCs, and may help to develop novel therapeutic approaches for the prevention of HCC metastasis.