bluuebunny/crossref_metadata_2025 huggingface dataset:
Political Development in Modern Turkey
Authors: Malysheva D.
Published: April 2021

The transformation of political system in Turkey resulted in creation of a pluralistic society, while the Justice and Development Party (AKP) – the winner of the country’s last five national elections – provides with the most relevant political model which is unique for the country with a predominant Muslim population. Turkey has made an impressive progress since Recep Tayyip Erdoğan and his populist AKP came to power in 2002. The country entered the G20, its GDP tripled, while exports increased fivefold. Turkey's role in international affairs has grown significantly. For more than a decade of Erdoğan's leadership, the government has undertaken a limited democratization process through amendments to the Constitution and steps to eliminate the military tutelage over the civil authority. Nowadays domestic political process in Turkey is characterized by the erosion of secularism and the planting of a moderate (“soft”) Islam. The ruling Turkish elite seeks to transform local society into a more conservative one. In April 2013, Erdoğan initiated discussion by Parliament to the proposed new Constitution, including the transition from a parliamentary to a presidential form of government. The major breakthrough has been reached in relations with the Kurds. In March 2013, a truce was attained with the jailed PKK (Kurdistan Workers Party) leader Abdullah öcalan. The PKK forces retreated hereupon to bases in the autonomous Iraqi Kurdistan. The Kurdish party – Peace and Democracy – is presented in the Parliament, along with the ruling AKP (which takes 50% of the seats) and the opposition Republican People's Party. At the same time Turkey has already seen societal polarization since the 2013 Gezi Park protests (“the Turkish Spring”) which grew into a nationwide protest movement. This, however, did not affect the determination of the AKP to build a model based on the market economy, parliamentary democracy and Islamic traditions. This model may be in demand in other countries with a prevailing Muslim population. Turkey’s political system can also inspire Arab neighbouring countries, where – like in Turkey – the pro-Islamic ruling parties are actively looking for alternative forms of development.
The Effect of Supplementation of Avocado Seed Flour (Persea americana Mill.) in Feed on Blood Lipids Profile and Egg Yolk Cholesterol of Japanese Quail (Corturnix-corturnix japonica)
Authors: Sujud Apriyanto Yosua , Iriyanti Ning , Tugiyanti Elly
Published: April 2021

The purpose of this research is to determine the effect of avocado seed flour (ASF) supplementation in feed on blood lipids and quail egg yolk cholesterol. The materials were 100 female quails aged 4 weeks old with ration ingredients consist of corn, bran, paddy, soybean meal, fish flour, avocado seed flour, palm oil, CaCO3, premix, lysine, and methionine. The research conducted an experiment with 4 treatments of ASF supplementation levels incorporated into basal feed, namely 0% ASF (R0), 3% ASF (R1), 6% ASF (R2), and 9% ASF (R3). The observed variables included blood cholesterol, High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), triglyceride, and egg yolk cholesterol. The data were subjected to the one-way Analysis of variance (ANOVA) in a completely randomized design, followed by HSD test when differences between treatments were observed. The result showed that ASF supplementation significantly reduced blood cholesterol levels and the egg yolk cholesterol, did not significantly affect LDL and triglyceride levels. The HDL levels and egg yolk cholesterol tend to decrease as the level of ASF increased. It is concluded that avocado seed flour (ASF) supplementation up to 9% is safe for quail feed supplementation.
Is The Desire to Take Selfies Related to Self-Esteem in High School Teens?
Authors: Windarwati Heni Dwi , Ati Niken Asih Laras , Ilmy Shofi Khaqul , Sulaksono Ari Dwi , Fitriyah Erna Tsalatsatul , Kusumawati Mira Wahyu
Published: April 2021

Selfitis is one of the phenomena that is currently popular among adolescents. Adolescents are attracted to show self-presentation, one of which is through selfies. This study aimed to identify the correlation between the obsessive desire to take selfies and high school adolescents' self-esteem. This research was a quantitative study with a cross-sectional design. The study population was high school adolescents aged 15-16 years with 797 participants recruited using a total sampling method. The instrument in this study used the Rosenberg self-esteem questionnaire to measure self-esteem and the Selfitis Behavior Scale (SBS) questionnaire to measure selfitis in adolescents. The results showed that most of the adolescents had borderline selfitis (46.3%) and high self-esteem (88.1%). Factors that were significantly related to taking selfies amongst adolescents were gender (p-value: 0.000) and socioeconomic status (p-value: 0.000). Meanwhile, gender (p-value: 0.013), socio-economic status (p-value: 0.032), family harmony (p-value: 0.000), and selfitis (p-value: 0.000) were significantly related to self-esteem in adolescents. The multivariate analysis results showed that harmony in the family was the most influential factor in adolescents' self-esteem. Adolescents with higher levels of selfitis and harmony in the family tended to have better self-esteem.
Effects of Five-Finger Relaxation Technique on Depression in Type 2 Diabetes Mellitus Patients
Authors: Dewi Rosliana , Agustina Fanny Dwi , Budhiana Johan , Fatmala Syiva Dwi
Published: April 2021

Diabetes mellitus (DM) can cause physical and psychological changes for sufferers. Psychological changes include changes in self-concept and depression. Psychological changes can be treated with nonpharmacological therapies, one of which is five-finger relaxation technique. The research aimed to reveal the effect of five-finger relaxation technique on depression experienced by type 2 DM patients. The five-finger relaxation technique is one of the generalist relaxation techniques by recalling pleasant experiences. This research is a quasi-experiment. Samples of this research were 34 respondents whom were selected using purposive sampling.  The intervention was carried out once a day for 3 consecutive days.  In order to measure depression, a valid and reliable questionnaire of Indonesian version of the Beck Depression Inventory (BDI) was employed.  Data were analyzed using the Wilcoxon Test and the Mann-Whitney Test. The results showed the was a decrease in depression in the control group (p-value of 0.008) and the intervention group (p-value of 0.000) and there were differences in depression in the control group and the intervention group (p-value of 0.000). It can be concluded that there is an effect of five-finger relaxation technique on depression in type 2 DM patients.
HYDROELECTRIC DAMS FROM MADEIRA RIVER SEASONALLY IMPACTS THE FISHERIES PRODUCTION IN THE GUAPORÉ BASIN (RONDÔNIA, BRAZIL)
Authors: De Freitas Helen Cristina PARAZZI , DORIA Carolina Rodrigues da Costa , SOUSA Raniere Garcez Costa
Published: April 2021

In the Amazon region, fisheries play an important role in the socioeconomic and cultural context and are directly affected by changes in the hydrological cycle, which can interfere with the numbers and frequencyof fish species landed. This study analyzed the variation of fishery production against the seasonality of the water level of the Guaporé River (a tributary of the Madeira River) using information contained in the records of fishery landings in the area under study. In addition, two periods pre (2000 to 2008) and post (2009 to 2019) installation of the Jirau and Santo Antônio dams in the Madeira River were considered. Fish production in the period prior to damming indicated linearity (r2 = 0.41) which was inversely proportional to the water levels of the Guaporé River, with low fish production in the flood and high production during the low water phases. However, for the period after damming, these variables showed low correlation (r2 = 0.14). Among the fish species exploited, 35.13% presented significant differences (p <0.05) between the production values for the periods before and after installation of the dams. Therefore, the results showed significant differences between the values of fishery production by species and phases of the hydrological cycle of the Guaporé River, which occurred in the periods pre and post damming of the Madeira River, which indicates that the hydroelectric dams have negatively impacted the fish stocks of this region. The information contained in this study is useful and serves as a basis for coherent decision-making, since it aids in the sustainable management and monitoring of fish stocks in the Madeira River Basin.
Heat Transfer Research in Blown-Through Non-Passable Heating Mains Channels. Part 1
Authors: Sednin V. A. , Bubyr T. V.
Published: April 2021

Abstract. To increase the efficiency of operation of heating networks located in non-passable channels, a schematic and structural solution of regenerative-utilization heat use was previously proposed and at the same time it is shown that it isdifficult to create an acceptable full-scale experimental installation or the difficulty of conducting a passive experiment on existing heating mains in non-passable channels. As an alternative solution for performing research, it is proposed to create and use a virtual experimental setup developed on the basis of the ANSYS software package, which has received wide recognition in the world. The initial results of  model verification showed that the study of heat transfer and aerodynamics in blown-through non-passable heating mains using such a solution is promising. A study has been carried out using a virtual experimental setup based on a six-factor second-order rotatble plan containing 46 points on a hypersphere with six star points. It is shown that there is no need to randomize the order of conducting and repeating the study at the points of computational experiment plan. Second-order regression equations have obtained for calculating a complex of objective functions: the required air pressure to achieve a given flow rate, the intensity of heat transfer directly from the pipes of the heating main, as well as from the walls of the channel to the blown air. The geometry of the channels of typical standard sizes of heating mains, the length of the sections, the temperature of the outside air and soil, and the air flow rate in the channel have been taken as the influencing factors in the calculations.  For the obtained regression equations, significant coefficients have been established and the transition from dimensionless to natural factors has been carried out. The adequacy of the obtained regression equations has been determined using standard statistical estimation methods based on the calculated values of the Fisher’s, Student’s and other criteria.
Приближенное представление дилогарифмами решения одной вариационной краевой задачи для круга при граничном условии Неймана
Authors: Meleshko I. N. , Lasy P. G.
Published: April 2021

It is known that boundary value problems for the Laplace  and Poisson equations are equivalent to the problem of the calculus of variations  – the minimum of an integral for which the given partial differential equation is the Euler – Lagrange equation.  For example, the problem of the minimum of the Dirichlet integral in the unit disc centered at the origin on some admissible set of functions for given values of the normal derivative on the circle is equivalent to the Neimann boundary value problem for the Laplace equation in this domain. An effective approximate dilogarithm representation of the solution of the above equivalent variational boundary value problem is constructed on the basis of the known exact solution of the Neumann Boundary value problem for a circle using a special approximate formula for the Dini integral. The approximate formula is effective in the sense that it is quite simple in numerical implementation, stable, and the error estimation, which is  uniform over a circle, allows calculations with the given accuracy. A special quadrature formula for the Dini integral has a remarkable property – its coefficients are non-negative. Quadrature formulas with non-negative coefficients occupy a special place in the theory of approximate calculations of definite integrals and its applications. Naturally, this property becomes even more significant when the coefficient are not number, but some functions. The performed numerical analysis of the approximate solution confirms its effectiveness.
Direct Method for Solving Bilinear Programming Problem
Authors: Matveyeva L. D.
Published: April 2021

The bilinear programming problem is considered, where a column, which corresponds to one of the variables, is not fixed but can be chosen from a convex set. This problem is known as the Dantzig – Wolfe problem. Earlier, a modified support method was proposed to solve the problem, using the decomposition of the problem constraints of the Dantzig – Wolfe method. The author of the paper has developed a direct exact method for solving the formulated problem. The method is based on the idea of the solving a linear programming problem with generalized direct constraints and a general concept of an adaptive solution method. The notions of support, support plan, optimal and suboptimal (e-optimal) plan are introduced which is a given approximation of the objective function to the optimal plan of the problem. Criteria for optimality and suboptimality of the support plan have been formulated and have been proved in the paper. The search for the optimal solution is based on the idea of maximizing the increment of the objective function. This approach allows more fully to take into account the main target and structure of the problem. Improving a support plan consists of two parts: replacing the plan and replacing the support. To find a suitable direction, a special derived problem is solved while taking into account the main constraints of the problem. The replacement of the support is based on the search for the optimal plan of the dual problem. The method leads to an optimal solution to the problem in a finite number of iterations (in the case of a non-degenerate value).
Particle-Transport Mechanism in Liquid/Liquid/Solid Multiphase Pipeline Flow of High-Viscosity Oil/Water/Sand
Authors: Archibong-Eso Archibong , Baba Yahaya , Aliyu Aliyu , Ribeiro Joseph , Abam Fidelis , Yeung Hoi
Published: April 2021

In this study, an investigation of sand transport in heavy-oil/water multiphase flow is performed. The study is conducted in three multiphase-flow pipeline-test facilities with internal diameters (IDs) of 1, 1, and 3 in. The pipeline orientations relative to the horizontal in the facilities are 0, +30, and 0°, respectively. Oil viscosity of 3.5 and 10.0 Pa·s with sand volume fractions from 0.010 to 0.100 vol% were used in the study. The effects of oil viscosity, upward inclination, sand volume fraction, pipe ID, and water cut on the sand-transport mechanism in pipelines are investigated. In the horizontal test section, flow patterns—namely, dispersed flow (DF), plug flow (PF), plug flow with moving sand bed (PFM), and plug flow with stationary sand bed (PFS)—were identified through flow visualization. In addition to the aforementioned, two flow patterns—stratified wavy flow with moving sand bed (SWM) and stratified wavy flow with dunes (SWD)—were observed in the inclined pipeline orientation. The pressure gradient measured decreased with a decrease in water cut until a minimum value was reached. Beyond the minimum pressure gradient, further reduction in water cut led to an increase in pressure gradient. The sand minimum transport condition (MTC) in the oil/water/sand test was largely the same for the 1-in. 30° upward inclined and the 1-in. horizontal test section. In contrast, that of the 3-in. horizontal test section was considerably higher. An improved MTC predictive correlation is proposed for multiphase heavy-oil/water/sand flow. The proposed correlation outperforms the existing models when tested on the heavy-oil/water/sand data set.
Comparison of the Calculated Drought Return Periods Using Tri-variate and Bivariate Copula Functions under Climate Change Condition
Authors: Naeini Elaheh Motevalibashi , Akhoond-Ali Ali Mohammad , Radmanesh Fereydoun , Koupai Jahangir Abedi , Soltaninia Shahrokh
Published: April 2021

Concerning the various effects of climate change on intensifying extreme weather phenomena all around the world, studying its possible consequences in the following years has attracted the attention of researchers. As the drought characteristics identified by drought indices are highly significant in investigating the possible future drought, the Copula function is employed in many studies. In this study, the two- and three-variable Copula functions were employed for calculating the return period of drought events for the historical, the near future, and the far future periods. The results of considering the two- and three-variable Copula functions were separately compared with the results of the calculated Due to the high correlation between drought characteristics, bivariate and trivariate of Copula functions were applied to evaluate the return periods of the drought. The most severe historical drought was selected as the benchmark, and the drought zoning map for the GCM models was drawn. The results showed that severe droughts can be experienced, especially in the upper area of the basin where the primary water resource is located. Also, the nature of the drought duration plays a decisive role in the results of calculating the return periods of drought events.
Pac-Man bacteria eat nanoprobes for aggregation-enhanced imaging and killing diverse microorganisms
Authors: Yang Yunmin , Chu Binbin , Cheng Jiayi , Tang Jiali , Song Bin , Wang Houyu , He Yao
Published: April 2021

Currently optical-based techniques for in vivo microbial population imaging are limited by low imaging depth and highly light-scattering tissue; and moreover, are generally effective against only one specific group of bacteria. Here, we introduce an innovative Pac-Man imaging and therapy strategy, in which different bacteria displayed like Pac-Man actively eat the glucose polymer (GP)-modified gold nanoparticles through ATP-binding cassette (ABC) transporter pathway, followed by laser irradiation-mediated aggregation in the bacterial cells. As a result, the aggregates display ~ 15.2-fold enhancement in photoacoustic signals and ~ 3.0-fold enhancement in antibacterial rate compared with non-aggregated counterparts. Significantly, the developed Pac-Man strategy allows ultrasensitive imaging of as low as ~ 105 colony-forming unit (CFU) of bacteria in vivo, which is around two orders of magnitude lower than most optical contrast agents. We further demonstrate Pac-Man strategy enables the detection of ~ 107 CFU bacteria residing within tumour or gut. This technique enables visualization and treatment of diverse bacteria, setting the crucial step forward the study of microbial ecosystem.
An Efficient Pairing-free Batch Verification Scheme for VANET
Authors: Lai Yan-Ming , Cheng Pu-Jen
Published: April 2021

An intelligent traffic system, which can flexibly allocate traffic resources, serves as a good assistant to help us improve traffic safety and efficiency of controlling traffic volume, providing instant traffic information and giving priority to ambulances. Although such system is powerful, it could be misused without prop er protection. For example, malicious drivers might forge the message of the ambulance so that they can quickly pass through intersections. In addition, because traffic information is huge and needs to be processed immediately, traditional schemes that pro cess the information one by one are not competent. For this issue, a lot of batch schemes have been proposed. Most of them adopt the algorithm of Bilinear pairing while the others tries to avoid it since pairing operations are complex. However, such pairin g - free schemes are not applicable because their calculation time will explode when there are more data waiting to be processed. In this article, we briefly describe those schemes and propose a more effective one to solve the problems mentioned above.
Decarbonisation scenarios of the U.S. electricity system and their costs
Authors: Qiu Yang , Cohen Stuart , Suh Sangwon
Published: April 2021

Decarbonising electricity is crucial for climate change mitigation, while understanding its economic implications has been a challenge. Previous analyses primarily rely on levelised cost or single-year optimization, which fail to account for the complex spatiotemporal dynamics of capacity expansion and dispatch decisions. Here, we present a regionally resolved national model that considers such dynamics and quantifies the cost of decarbonising the U.S. electricity system under a set of possible scenarios. The result shows that, compared to a business-as-usual scenario, reducing 80% CO2 emission by 2050 relative to 2005 level would incur, depending on the scenarios, $220~$490 billion additional costs (present value in 2020 US$, equivalent to ¢0.15~¢0.34 kWh-1) to the electric sector during 2020–2050, with regional costs ranging -¢0.08~¢0.51 kWh-1. When compared with the mitigated CO2, these additional costs equal to $10 and $37 per tCO2 reduced, which are well below the social cost of carbon in the literature.
LINC01268 and CTB-31O20.2 as Prognostic and Functional Protective Immune Related lncRNAs in Glioblastoma
Authors: Liu Dong-Hui , Yang Xiu , Meng Han , Zhang Gui Yun , Shen Shanghang
Published: April 2021

Glioblastoma (GBM) is the most common and deadly tumor in the central nervous system. Recent studies illuminated that long noncoding RNAs (lncRNAs) serve as competitive endogenous RNAs (ceRNAs) and play an important role in GBM by regulating immune responses. Here, GBM datasets from TCGA database were analyzed to obtain 356 significantly differentially expressed lncRNAs (DE-lncRNAs), 4951 DE-mRNAs, and 34 DE-miRNAs in GBM, respectively. For mRNAs, 369 DE-mRNAs were identified as immune-related genes in Immport database. For DE-lncRNAs, univariate analysis identified 39 DE-lncRNAs with prognostic significance, and 9 DE-lncRNAs are included in ImmLnc database. Then, combined analysis was conducted, by integrating 9 immune related DE-lncRNAs, 369 immune related DE-mRNAs and 34 DE-miRNAs, and generated a ceRNA network composed of 2 upregulated lncRNAs (LINC01268 and CTB-31O20.2), 3 downregulated miRNAs and 5 upregulated mRNAs. Then we focused on LINC01268 and CTB-31O20.2, and Kaplan-Meier survival, univariate and multivariate Cox regression analysis showed that LINC01268 and CTB-31O20.2 serve as independent protective prognostic markers in GBM. Finally, LINC01268 and CTB-31O20.2 overexpression was conducted in GBM cell U251. CCK8, transwell and scratch healing assay indicated that LINC01268 and CTB-31O20.2 inhibits GBM cell line U251 proliferation, invasion and migration. To sum up, LINC01268 and CTB-31O20.2 are independent prognostic immune related markers, and reduces cancer cell proliferation and metastasis in GBM.
Drought Mitigation in Cocoa (Theobroma Cacao L.) Through Developing Tolerant Hybrids
Authors: BABY Juby , Janakyseifudeen Minimol , Basura Suma , Venugopal Santhoshkumar Adiyodi , Joseph Jiji , sidharthan Panchami pottekkat
Published: April 2021

Background:Cocoa, being a shade loving crop cannot withstand long periods of water stress. Breeding for drought tolerance is the need of the hour due to change in climatic condition and extension of crop to non traditional area. Hybrids were produced by crossing four tolerant genotypes in all possible combination. The cross GVI 55 x M 13.12 didn’t yield any fruit due to cross incompatibility between these genotypes. Various biochemical parameters act as the true indicators to select tolerant and susceptible types. The major biochemical parameters considered after imposing stress included proline, nitrate reductase activity, superoxide dismutase content and glycine betaine. Results: The drought tolerant hybrids were having high amount of proline, superoxide dismutase enzyme and glycine betaine content. Normally, plants having drought stress shows low amount of nitrate reductase activity. However, in case of hybrids, the drought tolerant hybrids were having higher NR activity than the susceptible hybrids. The highest amount of NR was found in the control plants kept at fully irrigated conditions.Conclusions: This experiment showed the role of different biochemical enzymes and osmolytes in giving tolerance to plants during drought stress. Logistic regression analysis selected proline and nitrate reductase as the two biochemical markers for identifying efficient drought tolerant genotypes in the future breeding programmes.
Causation of potential drug to drug interactions alerts, alert overrides, and adverse drug events
Authors: Ariff Aminah Mazyin Mohamed , Nalliah Sivalingam , Hadi Hafidz Abd , Win Nay Thu , Thoulath Mohamed Imran , Aktifanus Ahmad Tantawi  Jauhari , Mutaya Subashini Muthiah , Yusof Ahmad K. M.
Published: April 2021

Background: Drug-drug interactions (DDIs) leading to adverse drug event (ADEs) are of special interest because they represent preventable medication errors. Preventable ADE can result in errors involving the manifestation of adverse patient outcomes. Given the high complexity of critically ill cardiac patients, it is important to learn how CDDSS affects outcomes in this population and the number of alerts that likely be safely suppressed. Purpose: Identify adverse DDIs that is clinically detected and review the appropriateness of the doctor’s actions to the potential DDIs (PDDIs) alert. Study Design: This is a prospective observational study conducted at critical cardiac care unit (CCU) in a selected tertiary cardiac center for a duration of six months. Methods: Physicians treating critically ill cardiac patients were presented with PDDIs data which were acquired from two commercially available CDDSS. The relationship between the decision to prescribe and factors hypothesized to affect physicians' decisions were examined. Results: Evaluation of 709 patient medication profiles were conducted, resulting in 521 assessed patient profiles having had one or more PDDIs with 87% of them were influenced by polypharmacy. Ninety-one patients (17.5%) were associated with one or more adverse DDIs. Of the total 3284 potential DDIs alerts, 95.5% of the alerts were overridden. Preventable ADE as an outcome of inappropriate override have resulted 83.1 %. (236/284) of adverse DDIs. Whereas, appropriate overrides as an outcome of clinically irrelevant ADE were 16.9 % (48/284). Conclusion: Poor preventive actions taken by the doctors caused drug related harm to the patients despite having CDDSS in place. This suggests that CDDSS is an important application to minimize the harm associated with adverse DDIs by alerting physicians of potentially unsafe situations.
Global mitigation efforts should prioritize support to the emerging emitters
Authors: Guan Dabo , Cui Can , Wang Daoping , Chemutai Vicky , Brenton Paul , Zhang Shaohui , Zhang Qiang , Davis Steven
Published: April 2021

International efforts to avoid dangerous climate change have historically focused on reducing energy-related CO2 emissions from countries with either the largest economies (e.g., the EU and the U.S.) and/or the largest populations (e.g., China and India). However, in recent years, emissions have surged among a different, much less-examined group of countries, raising concerns that a next generation of high-emitting economies will obviate current mitigation targets. Compounding the limited analyses of these emerging emitters, the long-term effects of the COVID-19 pandemic on economic activity and energy systems remain unclear. Here, we analyze the trends and drivers of emissions in each of the 59 countries where emissions 2010-2018 grew faster than the global average (excluding China and India), and then project their emissions under a range of pandemic recovery and longer-term energy scenarios. Although future emissions diverge considerably depending on responses to COVID and subsequent pathways, we find that emissions from these countries combined nonetheless reach 5.4 to 6.6 Gt CO2 by 2040 in all our scenarios—substantially in excess of emissions from these regions in published scenarios that successfully limit global warming to 2°C. Our results highlight the critical importance of ramping up mitigation efforts in countries that to this point have been largely ignored. Given the accompanying challenge of economic development and poverty reduction, this will require support from historically high-emitting countries to decelerate emissions growth, including through considerable economic support and appropriate transfer of technologies that are required for transition to low carbon growth.
AMPK blocks chromatin activation and consequent R-loop formation to protect genome stability following acute starvation
Authors: Sun Bing , Sherrin McLean , Roy Richard
Published: April 2021

During periods of starvation organisms must modify both gene expression and metabolic pathways to adjust to the energy stress. We previously reported that C. elegans that lack AMPK have transgenerational reproductive defects that result from abnormally elevated H3K4me3 levels in the germ line following recovery from acute starvation1. Here we show that H3K4me3 is dramatically increased at promoters, driving aberrant transcription elongation that results in the accumulation of R-loops in the starved AMPK mutants. DRIP-seq analysis demonstrated that a significant proportion of the genome was affected by R-loop formation with a dramatic expansion in the number of R-loops at numerous loci, most pronounced at the promoter-TSS regions of genes in the starved AMPK mutants. The R-loops are transmissible into subsequent generations, likely contributing to the transgenerational reproductive defects typical of these mutants following starvation. Strikingly, AMPK null germ lines show considerably more RAD-51 foci at sites of R-loop formation, potentially sequestering it from its critical role at meiotic breaks and/or at sites of induced DNA damage. Our study reveals a previously unforeseen role of AMPK in maintaining genome stability following starvation, where in its absence R-loops accumulate, resulting in reproductive compromise and DNA damage hypersensitivity.
Prognostic role and clinicopathological features of SMAD4 gene mutation in colorectal cancer: a systematic review and meta-analysis
Authors: Fang Tian , Liang Tingting , Wang Yizhuo , Wang Chang
Published: April 2021

Background Approximately 5.0%-24.2% of colorectal cancers (CRCs) have activating mutations in SMAD4, making it one of the frequently mutated genes in CRC. We thus carried out a comprehensive system review and meta-analysis investigating the prognostic significance and clinicopathological features of mutation of SMAD4 gene in CRC. Methods A detailed literature search was conducted in PubMed, Web of Science and Embase databases to study the relationship between mutations of SMAD4 gene and the demographic and clinicopathological characteristics in patients with CRC. The hazard ratios with 95% confidence intervals were used to evaluate the effect of SMAD4 mutations on overall survival (OS) and progression-free survival (PFS)/recurrence-free survival (RFS).Results Ten studies enrolling 4394 patients were eligible for inclusion. Data on OS were available from five studies. Comparing SMAD4-mutated CRC patients with SMAD4 wild-type CRC patients, the summary HR for OS was 1.46 (95% confidence interval [95% CI] 1.28–1.67, P=0.001), the summary HR for PFS/RFS was 1.59 (95% CI=1.14–2.22, P=0.006). In terms of clinicopathology parameters, SMAD4 mutations were associated with tumor location (odds ratio [OR]= 1.15, colon/rectum, 95% CI=1.01-1.31, P=0.042), TNM stage (OR=0.78, stage Ⅰ-Ⅲ/Ⅳ, [95% CI] 0.63-0.97, P=0.025), lymph node metastases (OR=1.42, N+/N0, 95% CI=1.20-1.67, P<0.001), mucinous differentiation (OR=2.23, 95% CI=1.85-2.70, P<0.001) and rat sarcoma viral oncogene homolog (RAS) status (OR=0.47, RAS wild-type/RAS mutation, 95% CI=0.30-0.73, P=0.001). No connection was found with age, gender, tumor grade, microsatellite instability (MSI) status and b-viral oncogene homolog B1(BRAF) status. Besides, publication bias was not observed in all studies.Conclusions This meta-analysis suggests that SMAD4 mutation was associated with OS, PFS/RFS, and clinicopathological parameters, including tumor site, disease stage, RAS status, lymph node metastases and tumor mucinous differentiation. It was indicated that SMAD4 mutations could predict the poor prognosis and aggressive clinicopathological characteristics of CRC. More large-sample cohort studies were needed to further confirm this conclusion. As SMAD4 mutation was found to be closely associated with RAS mutations, their relationship was worth further investigating.
Non-Invasive Metabolomics Biomarkers of Production Efficiency and Beef Carcass Quality Traits
Authors: Artegoitia Virginia M. , Newman J. W. , Foote A. P. , Shackelford S. D. , King D.A. , Wheeler T. L. , Lewis R. M. , Freetly H. C.
Published: April 2021

The inter-cattle growth variations stem from the interaction of many metabolic processes making animal selection difficult. We hypothesized that growth could be predicted using metabolomics. Urinary biomarkers of cattle feed efficiency were explored using mass spectrometry-based untargeted and targeted metabolomics. Feed intake and weight-gain was measured in steers (n=75) on forage-based growing rations (stage-1, 84 d) followed by high-concentrate finishing rations (stage-2, 84 d). Urine from days 0, 21, 42, 63, and 83 in each stage were analyzed from steers with the greater (n = 14) and least (n = 14) average-daily-gain (ADG) and comparable dry-matter-intake (DMI; within 0.32 SD of the mean). Steers were slaughtered after stage-2. Adjusted fat-thickness and carcass-yield-grade increased in greater-ADG-cattle selected in stage-1, but carcass traits did not differ between ADG-selected in stage-2. Overall 85 untargeted metabolites segregated greater- and least-ADG animals, with overlap across diets (both stages) and breed type, despite sampling time effects. Total 18-BAs and 5-steroids were quantified and associated with performance and carcass quality across ADG-classification depending on the stage. Stepwise logistic regression of urinary BA and steroids had >90% accuracy identifying efficient-ADG-steers. Urine metabolomics provides new insight into the physiological mechanisms and potential biomarkers for feed efficiency.
Assessment and Mitigation of Cardiovascular Risk for Prostate Cancer Patients: A review of the evidence
Authors: Davey Patrick , Alexandrou Kyriacos
Published: April 2021

Background: Cardiovascular disease (CVD) is a common co-morbidity in patients with prostate cancer. In this review, we summarise the published literature on the association of cardiovascular risk with androgen deprivation therapy (ADT) treatment and explore the potential differences between the gonadotropin-releasing hormone (GnRH) agonists and antagonists and the molecular mechanisms that may be involved. We also provide a practical outlook on the identification of underlying CV risk and explore the different stratification tools available. Results: While not definitive, the current evidence suggests that GnRH antagonists may be associated with lower rates of certain CV events vs agonists, particularly in patients with pre-existing CVD. We have reached this conclusion as the highest-grade evidence from randomised clinical trials comparing GnRH agonists verses antagonists is uniform in finding lower CV event rates with GnRH antagonists. Risk reduction strategies such as lifestyle advice, consideration of ADT modality, and co-medications may help to reduce CV risk factors and improve outcomes in prostate cancer patients receiving ADT. Conclusions: Given all the data that is currently available, identification of baseline CV risk factors may be key to risk mitigation in patients with prostate cancer receiving ADT.
The Role of Mineral Surfaces in Miller’s Experiment
Authors: Criado Joaquìn , Bizzarri Bruno Mattia , Garcìa-Ruiz Juan Manuel , Saladino Raffaele , Mauro Ernesto Di
Published: April 2021

We have designed a set of experiments to test the role of mineral surfaces on the yielding of the Miller-Urey type of experiment. Two experiments were performed in borosilicate flasks, two in a Teflon flask and a third couple in a Teflon flask with pieces of borosilicate submerged in the water. The experiments were performed in CH4, N2, and NH3 atmosphere either buffered at pH 8.7 with NH4Cl or unbuffered solutions. The Gas Chromatography-Mass Spectroscopy results show important differences in the yields, in the number of products and in their structural complexity. In particular, a dipeptide, complex dicarboxylic acids, PAHs, and a complete panel of biological nucleobases form more efficiently or exclusively in the borosilicate vessel. Our results suggest the crucial role of mineral catalysis in Miller-Urey synthesis.
Sex Differences in the Genetics of Sarcoidosis Across European and African Ancestry Populations
Authors: Xiong Ying , Kullberg Susanna , Garman Lori , Pezant Nathan , Ellinghaus David , Vasila Vasiliki , Eklund Anders , Rybicki Benjamin , Iannuzzi Michael , Schreiber Stefan , Müller-Quernheim Joachim , Montgomery Courtney , Grunewald Johan , Padyukov Leonid , Rivera Natalia V.
Published: April 2021

Background: Sex differences in the susceptibility of sarcoidosis are unknown. The study aims to identify sex-dependent genetic variations in two sarcoidosis clinical phenotypes: Löfgren's syndrome (LS) and non- Löfgren's syndrome (non-LS).Methods: A meta-analysis of genome-wide association studies was conducted in Europeans and African Americans, totaling 10,103 individuals from three population-based cohorts, Sweden (n = 3,843), Germany (n = 3,342), and the United States (n = 2,918), followed by replication look-up in the UK Biobank (n = 387,945). A genome-wide association study based on Immunochip data consisting of 141,000 single nucleotide polymorphisms (SNPs) was conducted in males and females in each cohort, respectively. The association test was based on logistic regression using the additive model in LS and non-LS independently. Additionally, gene-based analysis, expression quantitative trait loci (eQTL) assessments, and enrichment analysis were performed to discover functionally relevant mechanisms related to biological sex. Results: In LS sarcoidosis, we identified various sex-dependent genetic variations (798 SNPs in males and 703 SNPs in females). Genetic findings in sex groups were explicitly located in the extended major histocompatibility complex. In non-LS, we detected 16 SNPs in males and 38 in females, primarily localized to the MHC class II region. Additionally, the ANXA11 gene, a well-documented locus in sarcoidosis, was associated exclusively with non-LS males. Gene-based, eQTL assessment and enrichment analyses revealed distinct sex-dependent genomic loci and gene expression variation in the sex groups. Conclusions: Our findings provide new evidence of the existence of sex-dependent genetic variations underlying sarcoidosis genetic architecture. These findings suggest a sex bias in molecular mechanisms of sarcoidosis.
Differences in Rituximab Use Between Pediatric Rheumatologists and Nephrologists for the Treatment of Refractory Lupus Nephritis and Renal Flare in Childhood-Onset Sle
Authors: Gilbert Mileka , Goilav Beatrice , Hsu Joyce J. , Nietert Paul J. , Meidan Esra , Chua Annabelle , Ardoin Stacy P. , Wenderfer Scott E. , Scheven Emily von , Ruth Natasha M.
Published: April 2021

Background: Consensus treatment plans have been developed for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in childhood-onset systemic lupus erythematosus. However, patients who do not respond to initial therapy, or who develop renal flare after remission, warrant escalation of treatment. Our objective was to assess current practices of pediatric nephrologists and rheumatologists in North America in treatment of refractory proliferative LN and flare.Methods: Members of Childhood Arthritis and Rheumatology Research Alliance and the American Society for Pediatric Nephrology were surveyed in November 2015 to assess therapy choices (other than modifying steroid dosing) and level of agreement between rheumatologists and nephrologists for proliferative LN patients. Two cases were presented: 1) refractory disease after induction treatment with corticosteroid and cyclophosphamide and 2) nephritis flare after initial response to treatment. Survey respondents chose treatments for three follow up scenarios for each case that varied by severity of presentation. Treatment options included cyclophosphamide, mycophenolate mofetil, rituximab, and others, alone or in combination.Results: Treatment choices between nephrologists and rheumatologists were highly variable. A majority (>50%) consensus of either nephrologists or rheumatologists on treatment choice was only achieved in two of six total follow up scenarios for refractory LN or flare. Rheumatologists in comparison to nephrologists chose more therapy options that contained rituximab in five of six scenarios. These differences were statistically significant (p < 0.05). Conclusions: Therapy choices for pediatric rheumatologists and nephrologists in the treatment of refractory LN or LN flare were highly variable with rheumatologists more often choosing rituximab. Further investigation is necessary to delineate the reasons behind this finding. This study highlights the importance of collaborative efforts in developing consensus treatment plans for pediatric LN.
Volumetric Lattice Boltzmann Method for Wall Stresses of Image-based Pulsatile Flows
Authors: Zhang Xiaoyu , Gomez-Paz Joan , McDonough J. M. , Is Mahfuzul MD , Andreopoulos Yiannis , Yu Huidan
Published: April 2021

Image-based computational fluid dynamics (CFD) has become a new capability for determining wall stresses of pulsatile flows. However, a computational platform that directly connects image information to pulsatile wall stresses is lacking. Prevailing methods rely on manual crafting of a hodgepodge of multidisciplinary software packages, which is usually laborious and error prone. We present a new technique to compute wall stresses in image-based pulsatile flows using the lattice Boltzmann method (LBM). The novelty includes: (1) a unique image processing to extract flow domain and local wall normality, (2) a seamless connection between image extraction and CFD, (3) an en-route calculation of strain-rate tensor, and (4) GPU acceleration (not included here). We first generalize the streaming operation in the LBM and then conduct an application study for laminar and turbulent pulsatile flows in an image-based pipe (Reynolds number: 10 to 5000). The computed pulsatile velocity and shear stress are in good agreement with Womersley solutions for laminar flows and concurrent laboratory measurements for turbulent flows. This technique is being used to study (1) the hemodynamic wall stresses in inner choroid endothelium, (2) the drag force in sand flows, and (3) effects of waste streams on ion exchange kinetics in porous media.
Influence of Prior Major Bleeding on the Safety and Effectiveness of Left Atrial Appendage Closure in Non-Valvular Atrial Fibrillation Patients: A Single-Center Study
Authors: Zhao Mingzhong , Hou Cody R. , Xiong Xiaolin , Post Felix , Herold Nora , Walsleben Jens , Meng Zhaohui , Yu Jiangtao
Published: April 2021

Purpose: Left atrial appendage closure (LAAC) may present an alternative to anticoagulation in patients with non-valvular atrial fibrillation (NVAF). However, evidence regarding benefit of LAAC in patients with prior major bleeding is limited. We evaluate whether a previous bleeding factor influences the safety and effectiveness of LAAC. Methods: A total of 377 consecutive patients scheduled for LAAC were categorized into a bleeding group (n=137) and non-bleeding group (n=240). The implantation success and prevalence of severe peri-procedural complications, and efficacy/ safety endpoints during follow-up were investigated. Results: The bleeding group had more patients ≥75 years old (P=0.044), higher CHA2DS2-VASc (P=0.029) and HAS-BLED scores (P=0.001) than the non-bleeding group. Implantation success and severe peri-procedural complications were similar. During an average 2 years’ follow-up, major bleeding events (P=0.917), all-cause death (P=0.313), co-primary efficacy events (P=0.063), and the cumulative survival ratio (P=0.828) were comparable. However, the incidence of thromboembolism was lower in the bleeding group (P=0.031). The observed thromboembolism rate was reduced by 86.1% (P<0.005) and 43.9% (P<0.05) and the observed bleeding rate was decreased by 39.0% (P<0.05) and 34.8% (P<0.05) in the bleeding and non-bleeding groups, respectively. The extent of relative risk reduction in thromboembolism was significantly higher in the bleeding group (86.1% vs. 43.9%, P<0.01). Conclusion: LAAC may provide a safe and effective alternative to long-term antithrombotic therapy in NVAF patients with or without prior bleeding. The efficacy of LAAC in reducing thromboembolism instead of major bleeding seems to be higher in patients with versus without prior bleeding.
Effects of parity, frustration, and stochastic fluctuations on integrated information of consciousness for networks with two small-sized loops
Authors: Hosaka Tadaaki
Published: April 2021

Background: Integrated Information Theory (IIT) has been attracting attention as a theory of consciousness. The latest version, IIT3.0, is still at the stage of accumulating knowledge concerning fundamental networks. This paper presents an evaluation of the system-level integrated conceptual information of a major complex, ΦMax, associated with the center of consciousness for a small-scale network containing two small loops in accordance with the IIT3.0 framework. We focus on the following parameters characterizing the system model: 1) number of nodes in the loop, 2) frustration of the loop, and 3) temperature controlling the stochastic ﬂuctuation of the state transition. Speciﬁcally, assuming that the two loops are coupled systems, such as cerebral hemispheres, the eﬀect of these parameters on the values of ΦMax and conditions for major complexes formed by a single loop, rather than the entire network, is investigated.Results: Our ﬁrst ﬁnding is that parity of the number of nodes forming a loop has a strong eﬀect on the integrated conceptual information ΦMax. For loops with an even number of nodes, the number of concepts tends to decrease, and ΦMax becomes smaller. When the loop is formed with an odd number of nodes, the system without frustration and the system with two frustrated loops can have exactly the same ΦMax. It is also shown that, although counterintuitive, the value of ΦMax can be maximized in the presence of stochastic ﬂuctuations. Our second ﬁnding is that a major complex is more likely to be formed by a small number of nodes under small stochastic ﬂuctuations. In particular, this tendency is enhanced for larger numbers of nodes constituting a loop. On the other hand, the entire network can easily become a major complex under larger stochastic ﬂuctuations, and this tendency can be reinforced by frustration.Conclusions: Our results indicating that the entire network dominates and maintains a high level of consciousness in the presence of a certain degree of ﬂuctuation and frustration may qualitatively correspond to actual neural behaviors. The results of this study are expected to contribute to the veriﬁcation of the consistency of IIT with the actual nervous system in the future.