bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artocarpesin acts on human platelet aggregation through inhibition of cyclic nucleotides and MAPKs
Authors: Kwon Hyuk-Woo , Irfan Muhammad , Lee Yuan Yee , Rhee Man Hee , Shin Jung-Hae 
Published: April 2022

AbstractThe cardiovascular diseases (CVDs) are becoming a critical threat to our lives in these years. It is now widely accepted that platelets play an important role in cardiovascular disease as they have a fundamental role in thrombosis. Therefore, many drugs or natural substances have been developed to treat CVDs. Cudrania tricuspidata is a regional plant containing various constituents, such as xanthones, flavonoids, organic acids, and polysaccharides. It has been widely used in East Asia as an important ethnomedicine for the treatment of many diseases such as eczema, mumps, tuberculosis and acute arthritis. Therefore, we evaluated antiplatelet effects using artocarpesin isolated from C. tricuspidata. Confirmation of the antiplatelet function of artocarpesin was made according to the following analyzes. Artocarpesin inhibited collagen-induced human platelet aggregation, calcium mobilization, glycoprotein IIb/IIIa activation and thrombin-induced clot retraction through the regulation of associated signaling molecules. Artocarpesin increased the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and inositol 1, 4, 5-triphosphate receptor I (IP3RI). On the other hand, the phosphorylation of cytosolic phospholipase A2 (cPLA2), mitogen-activated protein kinases p38, JNK and phosphoinositide 3-kinase (PI3K)/Akt decreased. Thus, the study highlights that artocarpesin has an inhibitory effect on platelet activity and thrombus formation, showing its potential value in preventing platelet-induced cardiovascular disease.
Therapeutic synergy of Triptolide and MDM2 inhibitor against acute myeloid leukemia through modulation of p53-dependent and -independent pathways
Authors: Chen Qinwei , Deng Suqi , Deng Manman , Shi Yuanfei , Zhong Mengya , Ding Lihong , Jiang Yuelong , Zhou Yong , Carter Bing Z. , Xu Bing 
Published: April 2022

AbstractDysregulation of MDM2, a p53 negative regulator, frequently occurs in acute myeloid leukemia (AML) and is associated with unfavorable prognoses, rendering the p53-MDM2 axis an attractive target for the development of small-molecule inhibitors. MDM2 antagonists have been intensely developed but only lead to limited clinical activity, suggesting combination with additional drugs is an unmet medical need. In this study, we reported that Triptolide synergized with MDM2 inhibitor Nutlin-3a to suppress cell proliferation and induce mitochondrial-mediated apoptosis in p53 wt AML in vitro and ex vivo. More importantly, Triptolide cooperated with Nutlin-3a to delay tumor growth and abrogate leukemia burden in an AML xenograft model. In addition, we observed that Triptolide and Nutlin-3a were also cooperative in part of p53 deficient cases. Mechanistically, Nutlin-3a upregulated the transcriptional expressions of the p53 downstream targets PUMA and p21, while Triptolide declined the mRNA levels of two anti-apoptotic factors, XIAP and Mcl-1, in p53 wt cells. These effects were more notable when Triptolide and Nutlin-3a were combined. Our results revealed that Triptolide monotherapy exerted its antileukemia effect via both p53-dependent and independent ways, with the latter through perturbation of the MYC-ATF4 axis-mediated ER stress. Collectively, these data suggested that the Triptolide-Nutlin-3a combination might be a novel potential therapeutic intervention for patients with AML and it warrants further clinical evaluations.
An actualized screening of schizophrenia-associated genes
Authors: Boulenouar Houssam , Benhatchi Hadjer , Guermoudi Farah , Oumiloud Ahlem Hania , Rahoui Asma 
Published: April 2022

Abstract
Background
Schizophrenia is a psychotic disorder that impacts around 0.5% to 1.2% of the world's population. It has been well established that heredity plays an essential role in the causation of schizophrenia, with genetic heritability of up to 80%. A several new schizophrenia susceptibility genes were identified at the start of the twenty-first century. The aim of this systematic review will be to explore the association between single nucleotide polymorphisms (SNPs) and schizophrenia risk in people all over the world.

Methods
This systematic review collected available data on genetic variants associated with schizophrenia in worldwide populations. A PubMed and Science Direct search was investigated to identify all studies published until December 2020 on genetic susceptibility to schizophrenia in various populations, excluding family studies, transversal studies, cohort studies, experimental studies, and descriptive studies; those that demonstrate an association between repeat polymorphism (CNV, VNTR, etc.). All researches on genetic predispositions of schizophrenia and accepting the predetermined inclusion criteria were included in this systematic review.

Findings
Thirty-six studies focused on the schizophrenia-associated genes were retained in which a total of 44 polymorphisms among 26 susceptibility genes to schizophrenia have been associated in the world populations.

Conclusion
Despite the few number of studies published about genetic of schizophrenia, some genetic variations have been consistently correlated to schizophrenia, particularly in China, as this analysis shows. Further data, especially from genome-wide association studies, might contribute in the development of a reference for schizophrenia genetic susceptibility markers.
Safety and Efficacy of Lonapegsomatropin in Children With Growth Hormone Deficiency: enliGHten Trial 2-Year Results
Authors: Maniatis Aristides K , Casella Samuel J , Nadgir Ulhas M , Hofman Paul L , Saenger Paul , Chertock Elena D , Aghajanova Elena M , Korpal-Szczyrska Maria , Vlachopapadopoulou Elpis , Malievskiy Oleg , Chaychenko Tetyana , Cappa Marco , Song Wenjie , Mao Meng , Mygind Per Holse , Smith Alden R , Chessler Steven D , Komirenko Allison S , Beckert Michael , Shu Aimee D , Thornton Paul S 
Published: April 2022

Abstract

Purpose
The objectives of the ongoing, Phase 3, open-label extension trial enliGHten are to assess the long-term safety and efficacy of weekly administered long-acting growth hormone lonapegsomatropin in children with growth hormone deficiency.

Methods
Eligible subjects completing a prior Phase 3 lonapegsomatropin parent trial (heiGHt or fliGHt) were invited to participate. All subjects were treated with lonapegsomatropin. Subjects in the United States switched to the TransCon hGH Auto-Injector when available. Endpoints were long-term safety, annualized height velocity, pharmacodynamics [insulin-like growth factor-1 SD score (SDS) values], and patient- and caregiver-reported assessments of convenience and tolerability.

Results
Lonapegsomatropin treatment during enliGHten was associated with continued improvements in height SDS through week 104 in treatment-naïve subjects from the heiGHt trial (−2.89 to −1.37 for the lonapegsomatropin group; −3.0 to −1.52 for the daily somatropin group). Height SDS also continued to improve among switch subjects from the fliGHt trial (−1.42 at fliGHt baseline to −0.69 at week 78). After 104 weeks, the average bone age/chronological age ratio for each treatment group was 0.8 (0.1), showing only minimal advancement of bone age relative to chronological age with continued lonapegsomatropin treatment among heiGHt subjects. Fewer local tolerability reactions were reported with the TransCon hGH Auto-Injector compared with syringe/needle.

Conclusions
Treatment with lonapegsomatropin continued to be safe and well-tolerated, with no new safety signals identified. Children treated with once-weekly lonapegsomatropin showed continued improvement of height SDS through the second year of therapy without excess advancement of bone age.
Spine Volumetric BMD and Strength in Premenopausal Idiopathic Osteoporosis: Effect of Teriparatide Followed by Denosumab
Authors: Agarwal Sanchita , Shane Elizabeth , Lang Thomas , Shiau Stephanie , Kamanda-Kosseh Mafo , Bucovsky Mariana , Lappe Joan M , Stubby Julie , Recker Robert R , Hu Yizhong , Wang Zexi , Edward Guo X , Cohen Adi 
Published: April 2022

Abstract

Context
Premenopausal women with idiopathic osteoporosis (PreMenIOP) have marked deficits in bone density, microstructure, and strength.

Objective
To define effects of treatment with teriparatide followed by denosumab on lumbar spine (LS) volumetric bone mineral density (vBMD) and stiffness by finite element analysis assessed on central quantitative computed tomography (cQCT) scans.

Design, Settings, and Participants
Ancillary analysis of baseline, post-teriparatide, and post-denosumab cQCT scans from a randomized trial of 41 women allocated to teriparatide (20 mcg daily; n = 28) or placebo (n = 11). After 6 months, those on teriparatide continued for 18 months, and those on placebo switched to teriparatide for 24 months. After completing teriparatide, 33 enrolled in a Phase 2B extension with denosumab (60 mg every 6 months) for 12 months.

Main Outcome Measures
Primary outcomes were percentage change from baseline in LS trabecular vBMD and stiffness after teriparatide and between end of teriparatide and completing denosumab. Percentage change from baseline in LS trabecular vBMD and stiffness after sequential teriparatide and denosumab were secondary outcomes.

Findings
There were large increases (all Ps &lt; 0.001) in trabecular vBMD (25%), other vBMD parameters, and stiffness (21%) after teriparatide. Statistically significant increases in trabecular vBMD (10%; P &lt; 0.001) and other vBMD parameters (P = 0.03-0.001) were seen after denosumab, while stiffness increased by 7% (P = 0.068). Sequential teriparatide and denosumab led to highly significant (all Ps &lt; 0.001) increases LS trabecular vBMD (43%), other vBMD parameters (15-31%), and stiffness (21%).

Conclusions
The large and statistically significant increases in volumetric density and stiffness after sequential treatment with teriparatide followed by denosumab are encouraging and support use of this regimen in PreMenIOP.
Insulin Sensitivity and Metabolic Flexibility Parallel Plasma TCA Levels in Early Chronotype With Metabolic Syndrome
Authors: Remchak Mary-Margaret E , Heiston Emily M , Ballantyne Anna , Dotson Brielle L , Stewart Nathan R , Spaeth Andrea M , Malin Steven K 
Published: April 2022

Abstract

Context
People characterized as late chronotype have elevated type 2 diabetes and cardiovascular disease risk compared to early chronotype. It is unclear how chronotype is associated with insulin sensitivity, metabolic flexibility, or plasma TCA cycle intermediates concentration, amino acids (AA), and/or beta-oxidation.

Objective
This study examined these metabolic associations with chronotype.

Methods
The Morningness-Eveningness Questionnaire (MEQ) was used to classify adults with metabolic syndrome (ATP III criteria) as either early (n = 15 [13F], MEQ = 64.7 ± 1.4) or late (n = 19 [16F], MEQ = 45.5 ± 1.3) chronotype. Fasting bloods determined hepatic (HOMA-IR) and adipose insulin resistance (Adipose-IR) while a 120-minute euglycemic clamp (40 mU/m2/min, 5 mmoL/L) was performed to test peripheral insulin sensitivity (glucose infusion rate). Carbohydrate (CHOOX) and fat oxidation (FOX), as well as nonoxidative glucose disposal (NOGD), were also estimated (indirect calorimetry). Plasma tricarboxylic acid cycle (TCA) intermediates, AA, and acyl-carnitines were measured along with VO2max and body composition (DXA).

Results
There were no statistical differences in age, BMI, fat-free mass, VO2max, or ATP III criteria between groups. Early chronotype, however, had higher peripheral insulin sensitivity (P = 0.009) and lower HOMA-IR (P = 0.02) and Adipose-IR (P = 0.05) compared with late chronotype. Further, early chronotype had higher NOGD (P = 0.008) and greater insulin-stimulated CHOOX (P = 0.02). While fasting lactate (P = 0.01), TCA intermediates (isocitrate, α-ketoglutarate, succinate, fumarate, malate; all P ≤ 0.04) and some AA (proline, isoleucine; P = 0.003-0.05) were lower in early chronotype, other AA (threonine, histidine, arginine; all P ≤ 0.05) and most acyl-carnitines were higher (P ≤ 0.05) compared with late chronotype.

Conclusion
Greater insulin sensitivity and metabolic flexibility relates to plasma TCA concentration in early chronotype.
Deficiency of C1QL1 Reduced Murine Ovarian Follicle Reserve Through Intraovarian and Endocrine Control
Authors: Lu Xiaosheng , Ding Fei , Chen Yao , Ke Shiyun , Yuan Shaochun , Qiu Han , Xiao Luanjuan , Yu Yanhong 
Published: April 2022

AbstractOvarian aging is associated with depletion of the ovarian follicle reserve, which is the key determinant of fertility potential in females. In this study, we found that the small, secreted protein complement 1Q-like (C1QL1) is involved in the regulation of follicle depletion through intraovarian and endocrine control in a multidimensional collaborative manner. C1ql1 was detected to be conserved in the ovary and showed high transcript levels during folliculogenesis. Blockade of C1QL1 by IP and ovarian intrabursal injection of C1QL1 antiserum into prepubertal mice impaired folliculogenesis accompanied by reductions in body weight, fat mass, and intraovarian lipid accumulation. An elevation of circulating estradiol levels, reduction of hypothalamic KISS1 and GnRH expression, and a decrease in serum FSH levels were found in C1QL1-deficient mice. In C1QL1-deficient ovaries, many primordial follicles were recruited and developed into medium follicles but underwent atresia at the large follicle stages, which resulted in depletion of follicle reserve. Depletion of C1QL1 alleviated the inhibitory effect of C1QL1 on granulosa cell apoptosis and the stimulatory effect of C1QL1 on granulosa cell autophagy, which resulted in accumulation in the preantral and early antral follicles and an increase in the atretic follicles. The abnormal profile of endocrine hormones accelerated the intraovarian effect of C1QL1 deficiency and further led to depletion of ovarian reserve. Altogether, this study revealed the expression patterns and the mechanism of action of C1QL1 during folliculogenesis and demonstrated that deficiency of C1QL1 caused ovarian follicular depletion.
Provincial Administration in Crisis and Emergency Managament in Turkey
Authors: Çapar Selim , Koca Mehmet 
Published: April 2022

The unexpected and extraordinary situations such as typhoon, flood, earthquake, volcano eruption, nuclear, epidemic, chemical and biological substances threatening human health, accidents related to airline, sea or highway transportations, terrorist attacks, widespread act of force, risk of war as well as extraordinary developments in monetary and financial markets are generally considered among the causes of crisis.
Due to different factors such its geographical location, geological structure, the characteristics of the settlements and the inconvenience of the existing building stock, Turkey is often faced with disasters and state of emergencies.
The Ministry of Interior is responsible and authorized for both ensuring the public order and security in Turkey and for disaster management throughout the country. In the provinces and districts within the provincial administration system. The provincial administrators working as the representative of the central administration are responsible and authorized. The provincial executives undertake the function of “lifeguard in extraordinary situations”. Unlike the other professions, provincial executives fulfill their leadership and organizational duties both on the institutions and organizations affiliated to them, and the personnel working in these units and also on the management of crisis, disasters and emergency situations. In this study, the duties and responsibilities of provincial executives in the management of crisis and emergency situations in Turkey and the capacity of provincial executives to manage crises and emergency situations are presented.
Structure of Turkish leisure industry
Authors: Şmşek Kerem Yıldırım 
Published: April 2022

The potential of a society or the developed facilities can play a central role for improving the economy of a country. The leisure industry has been growing to be a giant industry that can contribute to Turkey’s economy which is placed in low ranks of the better life index between Organisation for Economic Co-operation and Development (OECD) countries. However, one of the most significant elements that slow down the progress in Turkey is that the professional competence framework has not been drawn leading to problems in the employment of professional specialists. The guiding element for the determination of the professional competence framework is a model that can define the industrial dimensions related with the profession.
The models and literature knowledge for the leisure industry has been found limited when the international literature is examined. In the scope of this research, four leisure models that were stated within international literature were examined and a new model that would be suitable for the Turkish leisure industry was proposed in the light of previous models. In addition, the Turkish leisure industry was discussed in detail in order to fill the deficiency within international literature about Turkish leisure industry.
​Extended English summary is in the end of Full Text PDF (TURKISH) file.
Özet

Bir toplumun sahip olduğu potansiyel ya da geliştirdiği olanaklar, ülke ekonomisinin daha iyi olması için merkezi bir rol üstlenebilir. Ekonomik Kalkınma ve İşbirliği Örgütü (OECD) ülkelerinin daha iyi yaşama indeksi sıralamasında alt sıralarda olan Türkiye için rekreasyon endüstrisi gelecekte ülke ekonomisine önemli katkılar sağlayabilecek dev bir endüstri olma yolunda ilerlemektedir. Ancak Türkiye’deki bu ilerlemeyi yavaşlatan en önemli unsurlardan biri meslek uzmanlarının istihdamında sorun yaratan mesleki yeterlilik çerçevesinin henüz çizilememiş olmasıdır. Mesleki yeterlilik çerçevesinin belirlenmesinde kılavuz unsur ise meslekle ilişkili endüstriyel boyutları tanımlayabilen model olabilir.
Uluslararası literatür incelendiğinde rekreasyon endüstrisine yönelik model ya da literatür bilgisi sınırlı durumdadır. Araştırma kapsamında uluslararası literatürde ön plana çıkmış dört rekreasyon modeli incelenmiş ve bu modeller doğrultusunda Türk rekreasyon endüstrisinin yapısına uygun bir model önerilmiştir.
PCSK9 and LRP6: potential combination targets to prevent and reduce atherosclerosis
Authors: Desita Saskia R. , Hariftyani Arisvia S. , Jannah Ayik R. , Setyobudi Assyadila K. , Oktaviono Yudi H. 
Published: April 2022

Abstract
Coronary artery disease (CAD) is a disease characterized by atherosclerosis formation which causes sudden cardiac death. The prevalence of CAD is expected to increase by 2030. Atherosclerosis started from accumulation of LDL in the blood vessels, followed by endothelial cell activation and dysfunction. PCSK9 is a gene that plays an important role in the creation of atherosclerotic plaque through induced degradation of LDLRs. Inhibition of PCSK9 gene resulted in a decrease of LDLRs degradation and reduction in LDL-C levels. LRP6, as well as its mutation, is a coreceptor that contributes to atherosclerosis through the canonical Wnt/β-catenin pathway. By employing EMPs mediated miRNA-126, third-generation antisense against miR-494-3p (3 GA-494), and recombinant Wnt mouse Wnt3a (rmWnt3a), the inhibition of LRP6 could reduce VSMCs proliferation, enhancing anti-inflammatory macrophages, and diminished bioactive lipids component, respectively. Those mechanisms lead to the stabilization and reduction of atherosclerosis plaques.
Experimental and numerical investigation of drop weight impact of aramid and UHMWPE reinforced epoxy
Authors: Hassoon Omar H. , Abed Mayyadah S. , Oleiwi Jawad K. , Tarfaoui M. 
Published: April 2022

AbstractDue to their characteristics such as weight/strength ratio and absorbed energy, the widespread use of composite materials in the last decades engorged the companies to exploit these materials invariant applications like the aerospace, automobile, and marine hull. However, there are some obstructs to the use of these materials that may constrain that. This came from the fact, that composite materials suffer from different damages modes that occur during loading and can be lead to catastrophic failure in their structure, such as intralaminar and interlaminar damage. Consequently, this motivated the researchers to study its behavior considering different damage modes and at different loading states. This work performed a finite element simulation using the Abaqus program of low-velocity drop impact for epoxy reinforced with Kevlar 49 and Ultra High Molecular Weight Polyethylene (UHMWPE) with different thicknesses and number of layers. A user-defined material VUMAT subroutine-based progressive damage model, and the Hashin failure criteria implemented in Abaqus Explicit finite element code had been utilized in this work. In Addition, the interlaminar damage models depend on the cohesive zone model (CZM). The numerical simulation results were compared with the experiments data to confirm the reliability of the numerical model.
Spectroscopic ellipsometry for low-dimensional materials and heterostructures
Authors: Yoo SeokJae , Park Q-Han 
Published: April 2022

Abstract
Discovery of low-dimensional materials has been of great interest in physics and material science. Optical permittivity is an optical fingerprint of material electronic structures, and thus it is an important parameter in the study of the properties of materials. Spectroscopic ellipsometry provides a fast, robust, and noninvasive method for obtaining the optical permittivity spectra of newly discovered materials. Atomically thin low-dimensional materials have an extremely short vertical optical path length inside them, making the spectroscopic ellipsometry of low-dimensional materials unique, compared to traditional ellipsometry. Here, we introduce the fundamentals of spectroscopic ellipsometry for two-dimensional (2D) materials and review recent progress. We also discuss technical challenges and future directions in spectroscopic ellipsometry for low-dimensional materials.
Histopathological Spectrum of Nephrectomies; a Single Centre Experience of over 14 Years
Authors: Abbas Farhat , Aalmeen Gul , Latief Muzamil , Wani Shahid , Wani Mohsin , Farooq Summyia 
Published: April 2022

Nephrectomy is conducted either as an open or a laparoscopic procedure for a variety of clinical indications. These include both neoplastic and non-neoplastic conditions, such as the non-functioning kidney. In many patients the final diagnosis is established on the histopathology of the retrieved kidney. In this study, retrospective analysis of data of last 14 years was studied pertaining to the number and indications of nephrectomy at the present study centre. Demographic and clinical details were assessed. Gross and microscopic histopathological details were recorded. Diagnosis was established on the basis of clinical features and histopathology. A total of 638 total nephrectomy specimens were received. Of these, 280 cases were of neoplastic and 358 of non-neoplastic lesions, with a male-to-female ratio of 1.21:1. The age range varied widely according to clinical manifestations. The age range in the present study was 5–84 years. Patients operated for non-neoplastic disorders were younger (mean age: 38.1 years) than those operated for neoplastic disorders (mean age: 54.4 years). Clear renal cell carcinoma (RCC) was the commonest RCC type (150 patients) followed by papillary RCC (51 cases). Nephrectomy is done due to both benign and malignant clinical indications as observed in this study. The most common indication was chronic pyelonephritis with the non-functioning kidney.