bluuebunny/crossref_metadata_2025 huggingface dataset:
Criminality in the Armed Forces of Ukraine as an object of criminological research
Authors:   Academy of the State penitentiary service, Chernihiv, Ukraine, M. S. Puzyrov
Published: July 2021

The article analyzes criminality in the Armed Forces of Ukraine as an object of criminological research. The expediency of studying criminality in the Armed Forces of Ukraine in both broad and narrow senses is found. In the first case, the analyzed type of criminality has its general criminal nature and is represented by a set of criminal offenses, the commission of which is possible both by servicemen of the Armed Forces of Ukraine and other entities. This is the so-called general criminality represented by such criminal offenses as injuries of varying severity, murders, theft, etc. In a narrow sense, criminality in the Armed Forces of Ukraine is considered as a set of relevant criminal offenses, the commission of which is possible only through the person’s presence in the status of a special entity, which in this context is a serviceman of the Armed Forces of Ukraine. In this case, it’s about criminal offenses against the established procedure for military service (military criminal offenses), provided in Section XIX of the Special Part of the Criminal Code of Ukraine. The concept of “crime prevention in the Armed Forces of Ukraine” is scientifically substantiated and defines as a set of special organizational, administrative, criminal law, criminal procedural, criminal-executive and operative-search measures of specially authorized units of the Armed Forces of Ukraine in cooperation with law enforcement agencies on prevention and cessation of criminal-illegal encroachments regarding the established order of military service, economic, violent, mercenary-violent (etc) orientation in the Armed Forces of Ukraine, which are carried out on the basis of constitutional and special-branch norms and principles concerning defined groups or individually defined persons, methods and means provided by the current legislation. Key words: Armed Forces of Ukraine, military servicemen, criminological research, criminality, determinants, prevention.
Natural hybridization between immigrant narrow–barred Spanish mackerel Scomberomorus commerson (Lacepède, 1800) and endemic West African Spanish mackerel Scomberomorus tritor (Cuvier, 1832) in the Egyptian Mediterranean coast
Authors: Bakhoum S. A.
Published: July 2021

Immigrant narrow–barred Spanish mackerel, West African Spanish mackerel and specimens with an external appearance somewhere between these putative parents were collected from Abu Qir Bay, East Alexandria, Egypt. The hybrid index results and univariate and multivariate analysis indicated a natural hybridization between these two species. The discriminant function analysis successfully classified individual fish in the data to one of the three fish groups. Squared Mahalanobis distances extracted from the groups indicated the three groups were clearly distinct from each other. Moreover, distances between the hybrid and Scomberomorus tritor were longer than those of the hybrid and S. commerson. The mean values of the condition factor for the hybri were significantly higher than those of S. commerson. Natural mortality of the hybrid was significantly lower than that of the exotic parent (S. commerson), indicating that the environmental conditions in the examined region are more suitable for the hybrid type species than for the invasive parental species.
Andrological characteristics of tropical milking criollo bulls
Authors: Pérez-Hernández Ponciano , Estrella-García Andea G. , Canseco-Sedano Rodolfo , Lopez-Ortiz Silvia , Ahuja-Del Carmen Concepción , Guerrero-Hernández Jonathan
Published: July 2021

Objective: To assess the testicular and semen characteristics in Criollo LecheroTropical (CLT) bulls in the subhumid Mexican tropics.Design/methodology/approach: Eight bulls were included in the study and distributedin two groups: G1 (n=5): young bulls and G2 (n=3): adult bulls. All bulls were managedunder grazing and were evaluated throughout one year. From each bull the followingmeasurements were taken once a month: live weight, body condition score, scrotalcircumference, and testicular width, length and volume. Semen was obtained every 3months via artificial vagina. Semen variables evaluated in each collection were: aspect,volume, mass and individual motility, and sperm concentration and morphology.
Results: Live weight and testicular measurements increased linearly during the study inbulls from both groups. All bulls had scrotal circumference larger than the minimumthreshold value for cattle and semen of high quality.Study limitations/implications: The low availability of CLT bulls prevented theinclusion of a larger number of animals in the study. This low availability of animalsmakes it necessary to establish standard values for testicular measurements and semencharacteristics in the CLT breed in order to select the best individuals as sires andcontribute to its conservation.Findings/conclusions: The CLT bulls had good scrotal circumference and semenquality since a young age and into adulthood. These traits make the CLT bulls animportant alternative for livestock breeding in the tropics.
Financial Literacy, Risk Tolerance, and Financial Management of Micro-enterprise Actors
Authors: Hirawati Heni , Sijabat Yacobo P , Giovanni Axel
Published: July 2021

Micro-enterprises have a significant role in the country’s economy. However, business owners must face various problems to develop their business. One of the problems is the limited funding for micro-enterprises due to the low financial literacy of business owners. In addition, the business owner’s tolerance for risk is also expected to affect the financial management of micro-enterprises. This study aims to determine the level of financial literacy and tolerance of business owners and the financial management of micro-enterprises. This research method uses a questionnaire distributed to micro-enterprise owners in Central Java Province and Yogyakarta Special Region. The results showed that the level of financial literacy of micro-enterprise owners was in the medium category. Micro-enterprise owners have a neutral attitude towards risk and are not individuals who dare to take risks but do not avoid risk. Financial management carried out by business owners is still in the poor category. Improvement of financial literacy, understanding of risks, and financial management of micro-enterprises still need to be done.
Expression of HOXC10 gene regulates the growth and invasion of prostate cancer cells
Authors: Song Hongmei , Ye Xuxiao , Liang Tao , Yan Dongliang , Li Zuowei
Published: July 2021

The present study was undertaken to decipher the role of HOXC10 gene in regulating the growth and metastasis of prostate cancer. The results revealed significant (p<0.05) up-regulation of HOXC10 gene in human prostate cancer tissues and cell lines. The silencing of HOXC10 transcript level significantly (p<0.05) inhibited the growth and colony formation of DU145 and 22Rv1 prostate cancer cells. The DAPI staining revealed that inhibition of DU145 and 22Rv1 prostate cancer cell viability was due to the induction of apoptosis. The transwell assay showed that HOXC10 significantly (p<0.05) inhibits the invasion of prostate cancer cells. The Western blotting revealed that HOXC10 gene exerts its effects via modulation of Ras/Raf/MEK/ERK signaling cascade. Collectively, the results point towards the therapeutic potential of HOXC10 in the treatment of prostate cancer.
Tongxinluo preserves the renal function in diabetic kidney disease via protecting the HK-2 cells from the patterns of programmed cell death
Authors: Shen Shuang , Hou Yunlong , Wu Yiling
Published: July 2021

This study was explored the renoprotective effect of Tongxinluo (a Traditional Chinese Medicine) on diabetic kidney disease and its underlying mechanism. The results revealed significant (p<0.05) up-regulation of the expression of Bcl-2 and down-regulation of NF-κB p-p65, ASC, NLRP3, caspase-1, cleaved GSDMD, IL-1β, caspase-3, Bax and the ratio of Bcl-2 and Bax in immortalized proximal tubular HK-2 cells cultured by hyperglycemia combined with hyperlipidemia. In db/db mice, Tongxinluo treatment substantially decreased the 24 hours albuminuria excretion rate and the urine albumin-creatinine ratios and renal morphologic abnormalities. Similarly, the levels of NF-κB p-p65, NLRP3, caspase-1, cleaved GSDMD, IL-1β, caspase-3, and the ratio of Bcl-2 and Bax were down-regulated by Tongxinluo treatment in the kidney samples of db/db mice (p<0.05). Taken together, according to the anti-pyroptosis and anti-apoptosis effect of Tongxinluo, it shows the potential to be effective for the treatment of diabetic kidney disease.
Experimental models for vascular endothelial dysfunction
Authors: Garg Anchal , Gupta Vardan , Tomar Ritu , Arora Mandeep Kumar
Published: July 2021

Vascular endothelial dysfunction is characterized by apoptosis of endothelial cells, an imbalance between vasoconstrictory and vasodilatory substances, the imbalance between ROS and antioxidants, vascular remodeling, loss of vascular integrity which leads to an increased risk of cardiovascular complications. To date, no therapeutic intervention is available as a promising agent. This may be due to a poor understanding of the underlying mechanism involved in vascular endothelial dysfunction in the pathogenesis. Animal models sharing identical features as that of humans are paramount to understand fundamental physiology, mechanism and to explore new targets for developing therapeutic agents. Thus, it becomes mandatory to re-explore the available animal models for a better understanding of molecular pathways involving vascular endothelial dysfunction. The purpose of this paper is to review different models for vascular endothelial dysfunction to the outlook for developing new drugs to treat vascular endothelial dysfunction.
Patrimonio rural y cambio climático
Authors: Baena Gallé José Manuel
Published: July 2021

Se analiza brevemente como las transformaciones técnicas en el sector agroganadero han provocado efectos en el cambio climático y, a su vez, el abandono de formas tradicionales de producción, con las que se relacionan múltiples ejemplos del patrimonio cultural.
DESIGN AND SIMULATION OF COCONUT TREE CLIMBING TOOL FOR COCONUT FARMERS IN LOMBOK SANGATTA BAY, EAST KUTAI
Authors: Arifin Kuswandi , Suherna Suherna , Samosir Alapson
Published: July 2021

Great potentiality of coconut cannot be separated from the method of coconut harvest which still draw a lot of problems in. Until now, coconut farmers still use climber service in coconut harvesting. The process of coconut tree climbing is usually done without tools. This is very risky for the harvesters. Since the utilization of animal service (monkeys) have already prohibited from commercial activities, human service in coconut tree climbing becomes the alternative for the farmers. For this reason, the aim of this study is to design a tool for coconut tree climbing that will help coconut harvesters in Lombok Sangatta Bay, East Kutai, by considering climber's characteristics. Furthermore, the tool is made in form of design, which then being simulated to determine the tools’ safety level, stress level and the ability which is designed by using SolidWorks 2018 software.The result for the proposed design of coconut tree climbing tool for coconut harvester in Lombok Sangatta Bay, East Kutai, is to use 20 mm x 20 mm x 2 mm of hollow profile with AISI 1020 material built, which is declared safe for 80 kg capacity. The highest score of stress is 223.04 Mpa on body holder, 4.68 mm deflection, 1.6 in factor of safety, and 17.08 kg for tool's overall weight
IMPROVEMENT OF THE WORKING SYSTEM IN MR. WASH LAUNDRY USING ERGONOMIC PARTICIPATORY METHOD
Authors: Rini Asih Setyo , Prakoso Indro
Published: July 2021

Mr. Wash laundry is one of the Small and Medium Enterprises (SME) located in Yogyakarta. This business was founded in 2015 with 2 workers. In work operations, many involve physical activities that can cause fatigue and musculoskeletal complaints, causing decreased productivity and miscommunication to consumers. Therefore, this research was conducted to improve the work system to minimize these impacts. The method in this study uses an ergonomics participator. This method involves a participatory team, namely ergonomists, owners, and workers. The result of this research is the design of an ironing table and chair using the anthropometric specifications of workers which can reduce fatigue and musculoskeletal complaints.
System-specific salmon louse infestation thresholds for salmon farms to minimize impacts on wild sea trout populations
Authors: Shephard S , Gargan P
Published: July 2021

Salmon lice Lepeophtheirus salmonis from aquaculture can cause negative impacts on sea trout Salmo trutta and other wild salmonids. Long-term records from 5 Irish rivers were used to explore relationships between annual sea trout runs and estimated total number of lice on nearby salmon farms. It was hypothesised that local environmental conditions may result in system-specific differences in realised louse pressure on sea trout. Louse count was thus tested as an absolute number and as a relative pressure, i.e. standardised by farm. When the standardised total number of mobile lice on a given salmon farm in April was above baseline level (50th percentile of observed annual values on that farm), there was a high probability of a below-average sea trout run in the local river. Absolute louse counts did not show an important effect on runs. This finding suggests that salmon farm louse production in spring can have a strong system-specific regulating effect on wild sea trout populations. Total number of lice on a farm was most strongly driven by changes in individual infestation rate, with a lesser effect of stocking density. Thresholds for number of mobile lice per farmed salmon required to maintain total louse count below the baseline varied with stocking density and among systems: greater density required lower infestation rate. Regulations relying on a generic louse threshold to trigger treatment are not sufficient to protect sea trout populations—stocking density and site characteristics must be considered to evaluate system-specific infestation pressure and impacts on wild salmonids.
ELECTROACOUSTIC MUSIC AND THE SLOVAK MUSICAL AVANT-GARDE IN THE 1960S
Authors: ČIERNA ALENA
Published: July 2021

In the 1960s, the development of music in Slovakia was marked by prominent generational and stylistic confrontations of the compositional poetries of the previous generations of composers and the just emerging one. In the composers’ community, an initiative was gaining a foothold that reassessed the practices, norms, and achievements of the previous developmental stages of Slovak music and looked for new points of departure. In certain stages of the given period, the first graduates of the Academy of Performing Arts (Ilja Zeljenka, Juraj Pospíšil, Pavol Šimai, Ladislav Kupkovič, Peter Kolman, Roman Berger, Jozef Malovec, Miroslav Bázlik, Ivan Parík, Tadeáš Salva, and others) entered the musical scene. The genesis and the formation of the Slovak musical avant-garde in the 1960s was determined by their quest for the novel possibilities of expression and the compositional techniques of the so-called New Music of Western Europe. They included experimenting with previously unknown electrogenic compositional materials and techniques of electroacoustic music. Slovak electroacoustic music, which achieved success in Slovakia and abroad already in the 1960s, emerged first on a private basis, later in the Sound Studio of the Czechoslovak Television, and, primarily, in the Experimental Studio of the Czechoslovak Radio.
PROTOLYTIC EQUILIBRIUM OF TETRA- AND PENTANITROFLUORESCEINS IN A BINARY SOLVENT ACETONITRILE – DIMETHYL SULFOXIDE (MASS RATIO 96 : 4)
Authors: Moskaeva Elena , Mosharenkova Ahina , Shekhovtsov Sergey , Mchedlov-Petrossyan Nikolay
Published: July 2021

In this paper, the acid-base and tautomeric equilibria of four nitrofluorescein dyes, 2,4,5,7-tetranitrofluorescein, 2,4,5,7,4’-pentanitrofluorescein, 2,4,5,7,5’-pentanitrofluorescein, and 2,4,5,7-tetranitrofluorescein methyl ester, were studied. As reaction media, a binary solvent acetonitrile – dimethyl sulfoxide (96 : 4 by mass) was used. The acidity scale in this solvent was established previously. The indices of the dissociation constants of the dyes were determined using the spectrophotometric method.

Interpreting the  values ​​requires an understanding of the state of tautomeric equilibria. The behavior of these compounds differs significantly from that of other fluorescein dyes, e.g., halogen derivatives. In the case of the first three compounds, i.e., for dyes with a free carboxylic group, the lactonic structure is predominant not only for the neutral form, but even for the double-charged anion. The single-charged anionic form exists as an equilibrium mixture of a colored (and fluorescent) tautomer and an almost colorless lactone. The fourth compound with esterified carboxylic group exhibits extreme stability in its anionic form. 

Evaluation of the tautomerization constants made it possible to calculate the microscopic equilibrium constants of the stepwise dissociation of dye lactones, k1L and k2L. The consideration of the difference (pk2L – pk1L) allowed estimating the effective relative permittivity of the space between the ionizing groups basing on the Bjerrum – Kirkwood – Westheimer equation. Tautomerism of anions was discussed from the point of view of stabilization of symmetric structures.
La acogida y la integración de refugiados en Portugal: recuperando las voces de los actores
Authors: Goldberg Alejandro
Published: July 2021

This paper analyzes, in an articulated way, the trajectories experienced by a group of Syrian refugees hosted in Portugal, within the framework of the European relocation program (2015-2017), and the policies adopted, as well as the programs implemented, to host and integrate them in the country. From the development of an ethnographic methodology, the perspectives of the actors themselves of these processes were recovered. Through the analysis of their narratives, it was possible to detect a series of deficits, shortcomings, and development needs not covered in terms of refugee-hosting programs and integration policies, which can be synthesized into three main ones: language (lack of effective teaching of the Portuguese language), work (lack of support tools for its search and job placement) and training (lack of training). A fourth element to consider in the analysis is that of structural obstacles, fundamentally those of bureaucratic-clientele order
Critical Temperature-Humidity Index Thresholds for Dry Cows in a Subtropical Climate
Authors: Ouellet Véronique , Toledo Izabella M. , Dado-Senn Bethany , Dahl Geoffrey E. , Laporta Jimena
Published: July 2021

The effects of heat stress on dry cows are profound and significantly contribute to lower overall welfare, productivity, and profitability of the dairy sector. Although dry cows are more thermotolerant than lactating cows due to their non-lactating state, similar environmental thresholds are currently used to estimate the degree of heat strain and cooling requirements. Records of dry cow studies conducted over 5 years in Gainesville, Florida, USA were pooled and analyzed to determine environmental thresholds at which dry cows exhibit signs of heat stress in a subtropical climate. Dry-pregnant multiparous dams were actively cooled (CL; shade of a freestall barn, fans and water soakers, n = 107) or not (HT; shade only, n = 111) during the last 7 weeks of gestation, concurrent with the entire dry period. Heat stress environmental indices, including ambient temperature, relative humidity, and temperature-humidity index (THI), and animal-based indices, including respiration rate, rectal temperature and daily dry matter intake were recorded in all studies. Simple correlations were performed between temperature-humidity index and each animal-based indicator. Differences in respiration rate, rectal temperature and dry matter intake between treatments were analyzed by multiple regression. Using segmented regression, temperature-humidity thresholds for significant changes in animal-based indicators of heat stress were estimated. Stronger significant correlations were found between the temperature-humidity index and all animal-based indices measured in HT dry cows (−0.22 ≤ r ≤ 0.35) relative to CL dry cows (−0.13 ≤ r ≤ 0.19). Although exposed to similar temperature-humidity index, rectal temperature (+0.3°C; P < 0.001) and respiration rate (+23 breaths/min; P < 0.001) were elevated in HT dry cows compared with CL cows whereas dry matter intake (−0.4 kg of dry matter/d; P = 0.003) was reduced. Temperature-humidity index thresholds at which respiration rate and rectal temperature began to change were both determined at a THI of 77 in HT dry cows. No significant temperature-humidity threshold was detected for dry matter intake. At a practical level, our results demonstrate that dry cow respiration rate and rectal temperature increased abruptly at a THI of 77 when provided only shade and managed in a subtropical climate. Therefore, in the absence of active cooling, dry cows should be closely monitored when or before THI reaches 77 to avoid further heat-stress related impairments during the dry period and the subsequent lactation and to mitigate potential carry-over effects on the offspring.
Statistical-Shape Prediction of Lower Limb Kinematics During Cycling, Squatting, Lunging, and Stepping—Are Bone Geometry Predictors Helpful?
Authors: De Roeck Joris , Duquesne Kate , Van Houcke Jan , Audenaert Emmanuel A.
Published: July 2021

Purpose: Statistical shape methods have proven to be useful tools in providing statistical predications of several clinical and biomechanical features as to analyze and describe the possible link with them. In the present study, we aimed to explore and quantify the relationship between biometric features derived from imaging data and model-derived kinematics.

Methods: Fifty-seven healthy males were gathered under strict exclusion criteria to ensure a sample representative of normal physiological conditions. MRI-based bone geometry was established and subject-specific musculoskeletal simulations in the Anybody Modeling System enabled us to derive personalized kinematics. Kinematic and shape findings were parameterized using principal component analysis. Partial least squares regression and canonical correlation analysis were then performed with the goal of predicting motion and exploring the possible association, respectively, with the given bone geometry. The relationship of hip flexion, abduction, and rotation, knee flexion, and ankle flexion with a subset of biometric features (age, length, and weight) was also investigated.

Results: In the statistical kinematic models, mean accuracy errors ranged from 1.60° (race cycling) up to 3.10° (lunge). When imposing averaged kinematic waveforms, the reconstruction errors varied between 4.59° (step up) and 6.61° (lunge). A weak, yet clinical irrelevant, correlation between the modes describing bone geometry and kinematics was observed. Partial least square regression led to a minimal error reduction up to 0.42° compared to imposing gender-specific reference curves. The relationship between motion and the subject characteristics was even less pronounced with an error reduction up to 0.21°.

Conclusion: The contribution of bone shape to model-derived joint kinematics appears to be relatively small and lack in clinical relevance.
Wholesome Coin: A pHealth Solution to Reduce High Obesity Rates in Gulf Cooperation Council Countries Using Cryptocurrency
Authors: Alsalamah Hessah A. , Nasser Shorog , Alsalamah Shada , Almohana Albatoul I. , Alanazi Areej , Alrrshaid Fay
Published: July 2021

Obesity is considered one of the leading causes of chronic and noncommunicable diseases; these include diabetes, cardiovascular disease, and cancer. The obesity prevalence is threefold higher in the Arab Gulf Cooperation Council (GCC) population than the rest of the world and leaves healthcare providers within the region with no alternative than to offer continuous and sustainable healthcare services. Obesity prevention would be more economical for governments than providing treatment. Preventing obesity is challenging because it requires motivating individuals to live a healthy lifestyle. Personal health (pHealth) has recently been actively involved in finding solutions to encourage healthy living. However, pHealth does not address the high percentage of people lacking the desire to maintain healthy living plans, which could have a negative effect on attempts aimed at reducing obesity prevalence. This study sheds light on the challenges faced by the GCC governments in reducing high obesity rates using pHealth; we propose a solution, Wholesome Coin, which incorporates advanced technologies to help governments reduce high obesity rates. Wholesome Coin has two components: one uses wearable IoT (WIoT) to help patients manage their behavior by tracking their physical activities and diet, and the other utilizes blockchain technology to help healthcare payers to incentify patients to maintain a healthy living plan by awarding digital coins that can be redeemed for real goods and services. GCC governments’ adoption of Wholesome Coin could improve the quality of life of obese patients in a seamless, secure, and self-motivated manner, resulting in a healthier tomorrow, especially amid challenging times featuring global social distance campaigns.
The Effect of Fluoride and Iron Content on the Clinkering of Alite-Ye’elimite-Ferrite (AYF) Cement Systems
Authors: Isteri Visa , Ohenoja Katja , Hanein Theodore , Kinoshita Hajime , Illikainen Mirja , Tanskanen Pekka , Fabritius Timo
Published: July 2021

Alite–ye’elimite–ferrite (AYF) cement is a more sustainable alternative to Portland cement (PC) that may offer improved mechanical, rheological, and chemical performance. Using traditional raw materials and conventional clinker processing conditions, alite (C3S) and ye’elimite (C4A3$), the major phases in PC and calcium sulfoaluminate (CSA) cements, respectively, cannot be coproduced. The typical formation temperature in the kiln for alite is >1350°C, but ye’elimite normally breaks down above 1300°C. However, with careful composition control and in the presence of fluoride, alite can be mineralized and formed at lower temperatures, thus enabling the production of AYF clinkers in a single stage. In this study, the production of AYF cement clinkers with different chemical compositions is attempted at 1250°C. The sensitivity of the fluoride content is initially assessed with a fixed target clinker composition to determine the optimal requirements. The effect of altering the target ferrite (C4AF) and alite (C3S) contents is also assessed followed by the effect of altering the target C4AF and C4A3$ contents. It is shown that AYF clinkers can be produced in a single stage through the careful control of the fluoride content in the mix; however, the formation/persistence of belite and mayenite could not be avoided under the conditions tested. It is also shown that ∼10 wt% ferrite in the target composition provides sufficient AYF clinker burnability and the amount of fluoride needs to be controlled to avoid stabilization of mayenite.
The Novel Non-coding Transcriptional Regulator Gm18840 Drives Cardiomyocyte Apoptosis in Myocardial Infarction Post Ischemia/Reperfusion
Authors: Luo Changjun , Xiong Si , Huang Yiteng , Deng Ming , Zhang Jing , Chen Jianlin , Yang Rongfeng , Ke Xiao
Published: July 2021

Background

Ischemia/reperfusion-mediated myocardial infarction (MIRI) is a major pathological factor implicated in the progression of ischemic heart disease, but the key factors dysregulated during MIRI have not been fully elucidated, especially those essential non-coding factors required for cardiovascular development.

Methods

A murine MIRI model and RNA sequencing (RNA-seq) were used to identify key lncRNAs after myocardial infarction. qRT-PCR was used to validate expression in cardiac muscle tissues and myocardial cells. The role of Gm18840 in HL-1 cell growth was determined by flow cytometry experiments in vitro. Full-length Gm18840 was identified by using a rapid amplification of cDNA ends (RACE) assay. The subcellular distribution of Gm18840 was examined by nuclear/cytoplasmic RNA fractionation and qRT-PCR. RNA pulldown and RNA immunoprecipitation (RIP)-qPCR assays were performed to identify Gm18840-interacting proteins. Chromatin isolation by RNA purification (ChIRP)-seq (chromatin isolation by RNA purification) was used to identify the genome-wide binding of Gm18840 to chromatin. The regulatory activity of Gm18840 in transcriptional regulation was examined by a luciferase reporter assay and qRT-PCR.

Results

Gm18840 was upregulated after myocardial infarction in both in vivo and in vitro MIRI models. Gm18840 was 1,471 nt in length and localized in both the cytoplasm and the nucleus of HL-1 cells. Functional studies showed that the knockdown of Gm18840 promoted the apoptosis of HL-1 cells. Gm18840 directly interacts with histones, including H2B, highlighting a potential function in transcriptional regulation. Further ChIRP-seq and RNA-seq analyses showed that Gm18840 is directly bound to the cis-regulatory regions of genes involved in developmental processes, such as Junb, Rras2, and Bcl3.

Conclusion

Gm18840, a novel transcriptional regulator, promoted the apoptosis of myocardial cells via direct transcriptional regulation of essential genes and might serve as a novel therapeutic target for MIRI.
Mechanical Overloading Induced-Activation of mTOR Signaling in Tendon Stem/Progenitor Cells Contributes to Tendinopathy Development
Authors: Nie Daibang , Zhou Yiqin , Wang Wang , Zhang Jianying , Wang James H.-C.
Published: July 2021

Despite the importance of mechanical loading in tendon homeostasis and pathophysiology, the molecular responses involved in the mechanotransduction in tendon cells remain unclear. In this study, we found that in vitro mechanical loading activated the mammalian target of rapamycin (mTOR) in rat patellar tendon stem/progenitor cells (TSCs) in a stretching magnitude-dependent manner. Application of rapamycin, a specific inhibitor of mTOR, attenuated the phosphorylation of S6 and 4E-BP1 and as such, largely inhibited the mechanical activation of mTOR. Moreover, rapamycin significantly decreased the proliferation and non-tenocyte differentiation of PTSCs as indicated by the reduced expression levels of LPL, PPARγ, SOX-9, collagen II, Runx-2, and osteocalcin genes. In the animal studies, mice subjected to intensive treadmill running (ITR) developed tendon degeneration, as evidenced by the formation of round-shaped cells, accumulation of proteoglycans, and expression of SOX-9 and collagen II proteins. However, daily injections of rapamycin in ITR mice reduced all these tendon degenerative changes. Collectively, these findings suggest that mechanical loading activates the mTOR signaling in TSCs, and rapamycin may be used to prevent tendinopathy development by blocking non-tenocyte differentiation due to mechanical over-activation of mTOR in TSCs.
LncRNA DGCR5 Isoform-1 Silencing Suppresses the Malignant Phenotype of Clear Cell Renal Cell Carcinoma via miR-211-5p/Snail Signal Axis
Authors: Zhong Guang-Xin , Luo Dan , Fan Yi-jun , Wang Jue , Liu Bing-Qiang , Xu Zhong-Hua , Zhang Xiang
Published: July 2021

Long non-coding RNAs (lncRNAs) play important roles during the initiation and progression of cancer. We identified DiGeorge Syndrome Critical Region Gene 5 (DGCR5) as a clear cell renal cell carcinoma (ccRCC) cancer- and lineage-specific lncRNA. Agarose gel electrophoresis analysis and sanger sequencing verified two main isoforms of DGCR5 in ccRCC patient tissues and cell lines. Quantitative polymerase chain reaction further demonstrated that the expression level of DGCR5 major isoform (isoform-1) was higher in ccRCC tissues than that in papillary/chromophobe RCC and other multiple solid malignant tumors. We investigate the biological functions of DGCR5 isoform-1 in ccRCC and show that DGCR5 isoform-1 exerts a tumor-promoting effect in ccRCC. DGCR5 isoform-1 is localized in cytoplasm and shares the same binding sequence to the tumor-suppressive miR-211-5p with the epithelial-to-mesenchymal transition key component SNAI. Furthermore, cellular and molecular experiments demonstrate that DGCR5 isoform-1 could sequester miR-211-5p, leading to the elevation of Snail protein and downregulation of its downstream targets and further promoting ccRCC cell proliferation and migration. Thus, our study indicates that DGCR5 isoform-1 could contribute to ccRCC progression by sponging miR-211-5p through regulating the expression of Snail protein and could serve as a reliable diagnostic biomarker in ccRCC.
Adjuvanticity of β -Glucan for Vaccine Against Trichinella spiralis
Authors: Liu Yi , Liu Xiaolei , Yang Li , Qiu Yangyuan , Pang Jianda , Hu Xiaoxiang , Dong Zijian , Liu Zengshan , Jin Xuemin
Published: July 2021

In the past 30 years, few researches focus on the efficacy of adjuvant against Trichinella spiralis infection. Identifying new, improved vaccine adjuvants for T. spiralis infection are required. β-glucan are effective and safe as adjuvant for infectious diseases. In this paper, we first observed the adjuvanticity of β-glucan as adjuvant for defensing helminth T. spiralis in vivo. We showed that IgG and IgE were elevated in the mice immunized with β-glucan combined with recombinant T. spiralis serine protease inhibitor (rTs-Serpin), which is one of the vaccine candidates. Furthermore, in vitro, the combination of β-glucan and rTs-Serpin enhanced the maturation of bone marrow dendritic cells (BMDCs) compared to rTs-Serpin alone. We showed that β-glucan + rTs-Serpin –treated BMDCs secreted higher production of IL-12 and IL-10. Moreover, β-glucan + rTs-Serpin –treated BMDCs not only promoted the population of CD4+ IFN-γ+ T cells, but also enhanced the population of CD4+ IL-4+ T cells. These findings suggested that β-glucan, as an adjuvant, have the capacity to protect against T. spiralis infection via activating both Th1 and Th2 immune response.
Genome-Wide Analysis Identifies Rag1 and Rag2 as Novel Notch1 Transcriptional Targets in Thymocytes
Authors: Dong Yang , Guo Hao , Wang Donghai , Tu Rongfu , Qing Guoliang , Liu Hudan
Published: July 2021

Recombination activating genes 1 (Rag1) and Rag2 are expressed in immature lymphocytes and essential for generating the vast repertoire of antigen receptors. Yet, the mechanisms governing the transcription of Rag1 and Rag2 remain to be fully determined, particularly in thymocytes. Combining cDNA microarray and ChIP-seq analysis, we identify Rag1 and Rag2 as novel Notch1 transcriptional targets in acute T-cell lymphoblastic leukemia (T-ALL) cells. We further demonstrate that Notch1 transcriptional complexes directly bind the Rag1 and Rag2 locus in not only T-ALL but also primary double negative (DN) T-cell progenitors. Specifically, dimeric Notch1 transcriptional complexes activate Rag1 and Rag2 through a novel cis-element bearing a sequence-paired site (SPS). In T-ALL and DN cells, dimerization-defective Notch1 causes compromised Rag1 and Rag2 expression; conversely, dimerization-competent Notch1 achieves optimal upregulation of both. Collectively, these results reveal Notch1 dimerization-mediated transcription as one of the mechanisms for activating Rag1 and Rag2 expression in both primary and transformed thymocytes. Our data suggest a new role of Notch1 dimerization in compelling efficient TCRβ rearrangements in DN progenitors during T-cell development.
New Family Members of FG Repeat Proteins and Their Unexplored Roles During Phase Separation
Authors: Shinkai Yoichi , Kuramochi Masahiro , Miyafusa Takamitsu
Published: July 2021

The condensation and compartmentalization of biomacromolecules in the cell are driven by the process of phase separation. The main effectors of phase separation are intrinsically disordered proteins, which include proteins with a phenylalanine-glycine (FG) repeat domain. Our understanding of the biological function of FG repeat proteins during phase separation has been mainly derived from recent research on a member of the nuclear pore complex proteins, nucleoporins containing FG repeat domain (FG-NUPs). FG-NUPs form meshwork structures by inter- and intra-molecular FG domain interactions, which confine the nucleo-cytoplasmic exchange. Whereas FG-NUPs localize in the nuclear membrane, other FG repeat proteins reside in the cytoplasm and the nucleoplasm, and the biological function of the FG repeat domain of these proteins is not well described. In the present review, we list the FG repeat proteins that are known to phase separate in the cell, and review their biological functions. We extract the unraveled features of FG repeat proteins as an activator of barrier formation and homotypic cell-cell interactions. Understanding the regulatory mechanisms of FG repeat proteins will provide a potential delivery tool for therapeutic reagents.
Emerging Threat of Multidrug Resistant Pathogens From Neonatal Sepsis
Authors: Zou Hua , Jia Xiaojiong , He Xiao , Su Yan , Zhou Ligang , Shen Yan , Sheng Chenglin , Liao Ang , Li Chunli , Li Qiuhong
Published: July 2021

Multidrug-resistant (MDR) pathogens are responsible for a substantial burden of morbidity and mortality from neonatal sepsis; however, data on these sepsis-related pathogens among hospitalized neonates in China are not well characterized. In this study, a total of 240 strains were isolated from four Women and Children’s hospitals in Southwest China between 2014 and 2019. Of these included pathogens, 104 (43.33%) were gram-positive bacteria, 129 (53.75%) were gram-negative bacteria, and 7 (2.92%) were fungi.Escherichia coli(E. coli, 34.01%) andKlebsiella pneumoniae(K. pneumoniae, 15.35%) were the main pathogen of neonate bacteremia. ST167 were the most prevalent STs inE. coliand ST11 inK. pneumoniae.Our study found thatE. coli(62.71%) was the predominate pathogen of early-onset sepsis, among which 64.86% were MDR. Late-onset sepsis was mainly caused byK. pneumoniae(28.31%) andE. coli(24.78%), with showing that 78.33% of these pathogens were MDR. Notably, the prevalence of EO/LO pathogens were quite different from Indian and south of China. Moreover, we found thatblaCTX-M(42.06%) was most dominant resistant genes with about a third isolates (31.09%) were positive forblaCTX-M-15. All the carbapenem-resistantK. pneumoniaewere positive for NDM-1. Moreover, late-onset sepsis and antibiotic exposure were significantly associated with MDR infection. Emerging multi-resistant pathogens of sepsis posts a serious threat to neonatal outcomes and emphasizes an urgent need to control their further spread.
Estimating Remaining Carbon Budgets Using Temperature Responses Informed by CMIP6
Authors: Rypdal Martin , Boers Niklas , Fredriksen Hege-Beate , Eiselt Kai-Uwe , Johansen Andreas , Martinsen Andreas , Falck Mentzoni Endre , Graversen Rune G. , Rypdal Kristoffer
Published: July 2021

A remaining carbon budget (RCB) estimates how much CO2 we can emit and still reach a specific temperature target. The RCB concept is attractive since it easily communicates to the public and policymakers, but RCBs are also subject to uncertainties. The expected warming levels for a given carbon budget has a wide uncertainty range, which increases with less ambitious targets, i.e., with higher CO2 emissions and temperatures. Leading causes of RCB uncertainty are the future non-CO2 emissions, Earth system feedbacks, and the spread in the climate sensitivity among climate models. The latter is investigated in this paper, using a simple carbon cycle model and emulators of the temperature responses of the Earth System Models in the Coupled Model Intercomparison Project Phase 6 (CMIP6) ensemble. Driving 41 CMIP6 emulators with 127 different emission scenarios for the 21st century, we find almost perfect linear relationship between maximum global surface air temperature and cumulative carbon emissions, allowing unambiguous estimates of RCB for each CMIP6 model. The range of these estimates over the model ensemble is a measure of the uncertainty in the RCB arising from the range in climate sensitivity over this ensemble, and it is suggested that observational constraints imposed on the transient climate response in the model ensemble can reduce uncertainty in RCB estimates.
Telemedicine Improves the Short-Term Medical Care of Acute ST-Segment Elevation Myocardial Infarction After Primary Percutaneous Coronary Intervention
Authors: Kamel Heba , Hafez Mohamed Saber , Bastawy Islam
Published: July 2021

Objectives: Telemedicine appears to be a promising tool for healthcare professionals to deliver remote care to patients with cardiovascular diseases especially during the COVID-19 pandemic. We aimed in this study to evaluate the value of telemedicine added to the short-term medical care of acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI).

Methods: Two hundred acute STEMI patients after primary PCI were randomly divided into two groups. One hundred patients in group A (study group) received a monthly videoconferencing teleconsultation using a smartphone application for 3 months starting 1 week after discharge and at least a single face-to-face (F2F) clinic visit. We reviewed in each virtual visit the symptoms of patients, adherence to healthy lifestyle measures, medications, smoking cessation, and cardiac rehabilitation. Group B (control group) included 100 patients who received at least a single F2F clinic visit in the first 3 months after discharge. Both groups were interviewed after 4 months from discharge for major adverse cardiac events (MACE), adherence to medications, smoking cessation, and cardiac rehabilitation. A survey was done to measure the satisfaction of patients with telemedicine.

Results: There was no significant difference between both groups in MACE and their adherence to aspirin, P2Y12 inhibitor, and beta-blockers. However, group A patients had better adherence to statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, smoking cessation, and cardiac rehabilitation. Sixty-one percent of patients stated that these videoconferencing teleconsultations were as good as the clinic visits, while 87% of patients were satisfied with telemedicine.

Conclusions: Telemedicine may provide additional benefit to the short-term regular care after primary PCI to STEMI patients through videoconferencing teleconsultations by increasing their adherence to medications and healthy lifestyle measures without a significant difference in the short-term MACE. These virtual visits gained a high level of satisfaction among the patients.
Genome Size Estimation and Full-Length Transcriptome of Sphingonotus tsinlingensis: Genetic Background of a Drought-Adapted Grasshopper
Authors: Zhao Lu , Wang Hang , Li Ping , Sun Kuo , Guan De-Long , Xu Sheng-Quan
Published: July 2021

Sphingonotus Fieber, 1852 (Orthoptera: Acrididae), is a grasshopper genus comprising approximately 170 species, all of which prefer dry environments such as deserts, steppes, and stony benchlands. In this study, we aimed to examine the adaptation of grasshopper species to arid environments. The genome size of Sphingonotus tsinlingensis was estimated using flow cytometry, and the first high-quality full-length transcriptome of this species was produced. The genome size of S. tsinlingensis is approximately 12.8 Gb. Based on 146.98 Gb of PacBio sequencing data, 221.47 Mb full-length transcripts were assembled. Among these, 88,693 non-redundant isoforms were identified with an N50 value of 2,726 bp, which was markedly longer than previous grasshopper transcriptome assemblies. In total, 48,502 protein-coding sequences were identified, and 37,569 were annotated using public gene function databases. Moreover, 36,488 simple tandem repeats, 12,765 long non-coding RNAs, and 414 transcription factors were identified. According to gene functions, 61 cytochrome P450 (CYP450) and 66 heat shock protein (HSP) genes, which may be associated with drought adaptation of S. tsinlingensis, were identified. We compared the transcriptomes of S. tsinlingensis and two other grasshopper species which were less tolerant to drought, namely Mongolotettix japonicus and Gomphocerus licenti. We observed the expression of CYP450 and HSP genes in S. tsinlingensis were higher. We produced the first full-length transcriptome of a Sphingonotus species that has an ultra-large genome. The assembly characteristics were better than those of all known grasshopper transcriptomes. This full-length transcriptome may thus be used to understand the genetic background and evolution of grasshoppers.
CYP2B6 Functional Variability in Drug Metabolism and Exposure Across Populations—Implication for Drug Safety, Dosing, and Individualized Therapy
Authors: Langmia Immaculate M. , Just Katja S. , Yamoune Sabrina , Brockmöller Jürgen , Masimirembwa Collen , Stingl Julia C.
Published: July 2021

Adverse drug reactions (ADRs) are one of the major causes of morbidity and mortality worldwide. It is well-known that individual genetic make-up is one of the causative factors of ADRs. Approximately 14 million single nucleotide polymorphisms (SNPs) are distributed throughout the entire human genome and every patient has a distinct genetic make-up which influences their response to drug therapy. Cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of antiretroviral, antimalarial, anticancer, and antidepressant drugs. These drug classes are commonly in use worldwide and face specific population variability in side effects and dosing. Parts of this variability may be caused by single nucleotide polymorphisms (SNPs) in theCYP2B6gene that are associated with altered protein expression and catalytic function. Population variability in theCYP2B6gene leads to changes in drug metabolism which may result in adverse drug reactions or therapeutic failure. So far more than 30 non-synonymous variants inCYP2B6gene have been reported. The occurrence of these variants show intra and interpopulation variability, thus affecting drug efficacy at individual and population level. Differences in disease conditions and affordability of drug therapy further explain why some individuals or populations are more exposed to CYP2B6 pharmacogenomics associated ADRs than others. Variabilities in drug efficacy associated with the pharmacogenomics ofCYP2B6have been reported in various populations. The aim of this review is to highlight reports from various ethnicities that emphasize on the relationship between CYP2B6 pharmacogenomics variability and the occurrence of adverse drug reactions.In vitroandin vivostudies evaluating the catalytic activity of CYP2B6 variants using various substrates will also be discussed. While implementation of pharmacogenomic testing for personalized drug therapy has made big progress, less data on pharmacogenetics of drug safety has been gained in terms of CYP2B6 substrates. Therefore, reviewing the existing evidence on population variability in CYP2B6 and ADR risk profiles suggests that, in addition to other factors, the knowledge on pharmacogenomics of CYP2B6 in patient treatment may be useful for the development of personalized medicine with regards to genotype-based prescription.