bluuebunny/crossref_metadata_2025_split huggingface dataset:
Occurrence, functionality and abundance of the TERT promoter mutations
Authors: Rachakonda Sivaramakrishna , Hoheisel Jörg D. , Kumar Rajiv 
Published: July 2021

AbstractTelomere shortening at chromosomal ends due to the constraints of the DNA replication process acts as a tumor suppressor by restricting the replicative potential in primary cells. Cancers evade that limitation primarily through the reactivation of telomerase via different mechanisms. Mutations within the promoter of the telomerase reverse transcriptase (TERT) gene represent a definite mechanism for the ribonucleic enzyme regeneration predominantly in cancers that arise from tissues with low rates of self‐renewal. The promoter mutations cause a moderate increase in TERT transcription and consequent telomerase upregulation to the levels sufficient to delay replicative senescence but not prevent bulk telomere shortening and genomic instability. Since the discovery, a staggering number of studies have resolved the discrete aspects, effects and clinical relevance of the TERT promoter mutations. The promoter mutations link transcription of TERT with oncogenic pathways, associate with markers of poor outcome and define patients with reduced survivals in several cancers. In this review, we discuss the occurrence and impact of the promoter mutations and highlight the mechanism of TERT activation. We further deliberate on the foundational question of the abundance of the TERT promoter mutations and a general dearth of functional mutations within noncoding sequences, as evident from pan‐cancer analysis of the whole‐genomes. We posit that the favorable genomic constellation within the TERT promoter may be less than a common occurrence in other noncoding functional elements. Besides, the evolutionary constraints limit the functional fraction within the human genome, hence the lack of abundant mutations outside the coding sequences.
Synthesis of rod‐shaped dipolar compounds for the study of long‐range electronic interactions
Authors: Chuang Jay , Chang Chun‐Wei , Chang Yuan Jay , Chou Po‐Ting , Wen Yuh‐Sheng , Liu Ching‐Yang , Chou Teh‐Chang , Chow Tahsin J. 
Published: July 2021

AbstractTwo series of rod‐shaped dipolar organic compounds are synthesized, each of which contains an electron donor (D), an electron acceptor (A), and a rigid hydrocarbon spacer (S). The first series of S compounds belong to the derivatives of oligo‐norbornyl (NB3 and NB4); and the second series of S the derivatives of a cage‐shaped heptacyclic tetradecane (HT2a,b and HT4a,b). The absorption/emission spectra and the oxidation/reduction potentials of D's and A's are measured, and the free energy of the photo‐excited electron transfer (PET) process is estimated according to the Marcus relationship. The degree of fluorescence quenching is found to be proportional to the corresponding free energy. The symmetry correlation between the frontier molecular orbitals of D and A is believed to play a significant role in the PET processes.
The intermediate‐conductance calcium‐activated potassium channel KCa3.1 contributes to alkalinization‐induced vascular calcification in vitro
Authors: Bai Yaling , Xu Jinsheng , Yang Shuo , Zhang Huiran , He Lei , Zhou Wei , Cheng Meijuan , Zhang Shenglei 
Published: July 2021

AbstractObjectiveIn order to find new strategies for the prevention of vascular calcification in uremic individuals especially treated by dialysis and develop novel therapeutic targets in vascular calcification, we explore the role of KCa3.1 in alkalinization‐induced VSMCs calcification in vitro.MethodRat VSMCs calcification model was established by beta‐glycerophosphate (β‐GP, 10 mM) induction. The pH of Dulbecco's modified Eagle's medium (DMEM) was adjusted every 24 h with 10 mM HCl or 10 mM NaHCO3. The mineralization was measured by Alizarin Red staining and O‐cresolphthalein complex one method. mRNA and protein expression were detected by RT‐PCR and Western blot or immunofluorescence. Ca2+ influx was measured by Elisa.ResultThe results indicated that alkalization induced an increase in Ca2+ influx to enhance VSMCs calcification. Furthermore, the increase of calcification was associated with the expression of KCa3.1 via advanced expression of osteoblastic differentiation markers alkaline phosphatase (ALP) and Runt‐related transcription factor 2 (Runx2). Blocking KCa3.1 with TRAM‐34 or shRNA vector can significantly lowered the effects of calcification in the activity of ALP and Runx2 expression.ConclusionTogether all, our studies suggested that alkalinization can promote vascular calcification by upregulating KCa3.1 channel and enhancing osteogenic/chondrogenic differentiation by upregulating Runx2. The specific inhibitor TRAM‐34 and KCa3.1‐shRNA ameliorated VSMCs calcification by downregulating KCa3.1.
CircRNA WHSC1 promotes non‐small cell lung cancer progression via sponging microRNA‐296‐3p and up‐regulating expression of AKT serine/threonine kinase 3
Authors: Shi Fengfeng , Yang Qin , Shen Dongdong , Chen Jianwei 
Published: July 2021

AbstractBackgroundLung cancer is the most commonly diagnosed cancer and leading cause of cancer death, with 80%–85% of non‐small cell lung cancer (NSCLC). Circular RNAs (circRNAs) have been shown to be promising early diagnostic and therapeutic molecular biomarkers for NSCLC. However, biological role and regulatory mechanism of circRNA WHSC1 (circWHSC1) in NSCLC are unknown. Therefore, we aim to explore the function and mechanism of circWHSC1 in NSCLC oncogenesis and progression.MethodsqRT‐PCR was used for circWHSC1 level evaluation; Kaplan‐Meier was used for survival analysis; bioinformatics, dual‐luciferase activity, and RNA pull‐down were used for evaluating competing endogenous RNA (ceRNA) network; cell viability, colony formation, apoptosis, migration, and invasion were used for cell function analysis; function gain and loss with rescue experiments were used for exploring mechanism of circWHSC1 in NSCLC development.ResultsSignificantly up‐regulated circWHSC1 and down‐regulated microRNA‐296‐3p (miR‐296‐3p) were identified in NSCLC tissues and cells. Up‐regulated circWHSC1 was associated with poor prognosis in NSCLC patients. MiR‐296‐3p was sponged by circWHSC1, and AKT serine/threonine kinase 3 (AKT3) was target of miR‐296‐3p; meanwhile, miR‐296‐3p over‐expression significantly down‐regulated AKT3 expression, and co‐transfecting anti‐miR‐296‐3p rescued circWHSC1 silence caused AKT3 down‐regulation. CircWHSC1 silence significantly inhibited colony formation, viability, invasion, and migration, while increased NSCLC cell apoptosis, which were partially rescued by anti‐miR‐296‐3p.ConclusionCircWHSC1 is an independent indicator of poor prognosis in NSCLC patients, and functions as a ceRNA of miR‐296‐3p to up‐regulate AKT3, consequently promotes NSCLC cell growth and metastasis. Targeting circWHSC1 might be a prospective strategy for diagnosis, therapeutics, and prognosis of NSCLC.
La3+and F−dual‐doped multifunctional hydroxyapatite nanoparticles: Synthesis and characterization
Authors: Erdem Umit , Turkoz Mustafa B. 
Published: July 2021

AbstractHydroxyapatite (HA) co‐doped with La3+and F−ions were synthesized by the precipitation method and sintered at 1,100°C for 1 hr. Samples were characterized by the standard experimental methods including the density, X‐Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy (SEM) to investigate their microstructure, phase formation, and bonding characteristics in detail. Moreover, the materials produced were identified using the microhardness tests. It was observed that in the most of materials, the hydroxyapatite was found to be the main phase with a minor amount of β‐tricalcium phosphate (β‐TCP). Furthermore, the presence of fluoride and small amount of β‐TCP was verified with all the characteristic FTIR bands of hydroxyapatite for the majority of samples studied. The result in SEM evaluation is that the produced HA powders have less deformed, uniformly distributed, and regularly shaped particles. Here, the material density has changed towards a less dense state with the increasing rate of La doping, but statistically significant difference was not obtained (p, .1942 > .05) with increase of the F doping. A significant difference was obtained the microhardness values between La3+and F−ions co‐doped HA materials and pure HA (p[.0053] < .05). Accordingly, this study confirmed that since the La3+and F−ions can potentially increase the efficacy of HA. According to the spectral, mechanical, and microstructure analysis result, this material can be as a good candidate product for use as an occluding material for dental application.
The diagnostic significance of circulating lncRNA ADAMTS9‐AS2 tumor biomarker in non‐small cell lung cancer among the Egyptian population
Authors: Abdul‐Maksoud Rehab S. , Rashad Nearmeen M. , Elsayed Walid S. H. , Elsayed Rasha S. , Sherif Magda M. , Abbas Ahmad , El Shabrawy Mohamed 
Published: July 2021

AbstractBackgroundLong non‐coding RNA ADAM metallopeptidase with thrombospondin type 1 motif, 9 antisense RNA 2 (ADAMTS9‐AS2) was recognized as a novel tumor suppressor and plays an important role in the initiation and progression of malignant behavior in human cancers, although its plasma expression and clinical value in patients with non‐small cell lung cancer (NSCLC) remain unknown. We aimed to analyze the diagnostic role of ADAMTS9‐AS2 and cytokeratin 19 fragmentation antigen (CYFRA 21‐1) in NSCLC.MethodsThe present study included 80 control subjects, 80 patients with benign lung lesion and 80 NSCLC patients. The expression of ADAMTS9‐AS2 in the tissue and plasma was detected by a real‐time polymerase chain reaction. Serum CYFRA 21‐1 was analyzed using an enzyme‐linked immunosorbent assay.ResultsIn comparison with benign lung lesion and controls, tissue and plasma ADAMTS9‐AS2 expression were significantly down‐regulated in NSCLC (p < 0.001). Decreased ADAMTS9‐AS2 expression was associated with TNM stages in NSCLC patients (p < 0.001). Up‐regulation of CYFRA 21‐1 was reported among NSCLC patients and it was associated with TNM staging. Tissue and plasma ADAMTS9‐AS2 expression levels were the predicting factors for NSCLC and they both correlated negatively with CYFRA 21‐1 levels. Plasma ADAMTS9‐AS2 levels had a significant positive correlation with their tumor tissue levels. Plasma ADAMTS9‐AS2 showed a higher sensitivity (95%) and specificity (99.1%) in the diagnosis of NSCLC than CYFRA 21‐1 (61.3% sensitivity and 60% specificity).ConclusionsOur results suggested that decreased plasma ADAMTS9‐AS2 expression might act as a novel non‐invasive tumor biomarker in NSCLC diagnosis. Furthermore, plasma ADAMTS9‐AS2 might predict aggressive tumor behavior.
The beginning of a new therapeutic era in acute myeloid leukemia
Authors: Récher Christian 
Published: July 2021

AbstractIn the field of AML, the early 2000s were shaped by the advent of novel molecular biology technologies including high‐throughput sequencing that improved prognostic classification, response evaluation through the quantification of minimal residual disease, and the launch of research on targeted therapies. Our knowledge of leukemogenesis, AML genetic diversity, gene‐gene interactions, clonal evolution, and treatment response assessment has also greatly improved. New classifications based on chromosomal abnormalities and gene mutations are now integrated on a routine basis. These considerable efforts contributed to the discovery and development of promising drugs which specifically target gene mutations, apoptotic pathways and cell surface antigens as well as reformulate classical cytotoxic agents. In less than 2 years, nine novels drugs have been approved for the treatment of AML patients, and many others are being intensively investigated, in particular immune therapies. There are now numerous clinical research opportunities offered to clinicians, thanks to these new treatment options. We are only at the start of a new era which should see major disruptions in the way we understand, treat, and monitor patients with AML.
A simple risk score for detecting radiological occult metastasis in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma
Authors: Sakaguchi Tatsuma , Satoi Sohei , Hashimoto Daisuke , Yamamoto Tomohisa , Yamaki So , Hirooka Satoshi , Ishida Mitsuaki , Ikeura Tsukasa , Inoue Kentaro , Sekimoto Mitsugu 
Published: July 2021

AbstractBackgroundWe advocated carbohydrate antigen (CA) 19‐9 ≥ 150 U/mL and tumor size ≥30 mm as “high‐risk markers” for predicting unresectability among patients with radiologically resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). The main aim is to establish a risk scoring system for occult abdominal metastasis (OAM) in R/BR PDAC.MethodsPredictors of OAM were investigated retrospectively in an experiment cohort from 2006 to 2018. The proposed risk scoring system was validated in another cohort from 2019 to 2020.ResultsFive hundred and thirteen eligible patients were divided into the experimental (405 patients; OAM, 22%) and validation cohorts (108 patients). Multivariate analysis identified tumor location of body/tail (odds ratio [OR] 4.45, P < .0001) and “high‐risk markers” (OR 2.07, P = .011) as independent predictors of OAM. A scoring system consisting of body/tail (yes: 1, no: 0) and “high‐risk markers” (yes: 1, no: 0) was constructed. In the validation cohort, when staging laparoscopy (SL) was performed for patients with scores 1/2, the eligibility for SL, sensitivity, and negative predictive value of OAM were 55%, 91%, and 96%, respectively.ConclusionsTumor location of body/tail and “high‐risk markers” were independent predictors of OAM, composing our simple and reproducible risk scoring system.
Aid for health, economic growth, and the emigration of medical workers
Authors: Lanati Mauro , Thiele Rainer 
Published: July 2021

AbstractDebates on the extent to which developing countries suffer from a brain drain often focus on the emigration of locally scarce health personnel. In this paper, we empirically examine how two potential determinants—aid for health and local income levels—affect the emigration rates of doctors and nurses from developing countries. Employing a standard gravity model of international migration, we show that aid for health has a negative effect on the emigration of both nurses and doctors. Our findings suggest that donors influence the emigration decisions of doctors and nurses through improvements in health infrastructure. Higher income per capita is also associated with lower emigration from developing countries for doctors and nurses alike. Given that nurses typically belong to the poorer segments of populations in the countries of origin, we can conclude that even at low initial income levels, on balance, economic growth provides an incentive to stay.
Clinical utility of methionine restriction in adenosine kinase deficiency
Authors: Almuhsen Najmah , Guay Simon‐pierre , Lefrancois Marie , Gauvin Cheryl , Al Bahlani AL Qasim , Ahmed Najma , Saint‐Martin Christine , Gagnon Tommy , Waters Paula , Braverman Nancy , Buhas D. 
Published: July 2021

AbstractAdenosine kinase (ADK) deficiency is a rare autosomal recessive inborn error of metabolism involving the methionine and purine metabolic pathways. Prior reports show that most patients present in infancy with jaundice, hypotonia, developmental delay, and mild dysmorphic features. Characteristic biochemical findings included hypoglycemic hyperinsulinism, cholestasis, elevated liver functions, methionine, S‐adenosylhomocysteine, and S‐adenosylmethionine, with normal or mildly elevated homocysteine level. Brain imaging demonstrated atrophy, hydrocephalus, and delayed myelination. There are 26 reported patients of ADK deficiency, of which 14 patients were placed on a methionine‐restricted diet. Clinical improvement with methionine restriction was not well described.Case reportWe report an infant who presented at birth with persistently elevated ammonia (100‐163 μmol/L), hypoglycemia, cholestasis, and liver dysfunction. The initial metabolic and genetic work‐up was nondiagnostic, with only a mildly increased plasma methionine level (51 [<38 μmol/L]). Iron depositions in the liver and in lip mucosa led to suspicion of gestational alloimmune liver disease. Immunoglobulin therapy and exchange transfusion treatments demonstrated transient clinical and biochemical improvements. However, subsequent episodes of acute liver failure with development of neurological abnormalities led to further evaluation. Metabolic studies showed a 25‐fold increase in plasma methionine level at 8 months of life (1022 [<38 μmol/L]) with white matter abnormalities on brain MRI. Expanded molecular testing identified the disease. Urinary purines profile showed elevations of adenosine and related metabolites. Introduction of a low‐methionine diet resulted in rapid clinical amelioration, improvement of brain MRI findings, and normalization of liver functions and methionine levels.
Divergent developmental trajectories in two siblings with neuropathic mucopolysaccharidosis type II (Hunter syndrome) receiving conventional and novel enzyme replacement therapies: A case report
Authors: Tomita Kazuyoshi , Okamoto Shungo , Seto Toshiyuki , Hamazaki Takashi , So Sairei , Yamamoto Tatsuyoshi , Tanizawa Kazunori , Sonoda Hiroyuki , Sato Yuji 
Published: July 2021

AbstractMucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X‐linked recessive lysosomal storage disease caused by a mutation in the IDS gene and characterized by systemic accumulations of glycosaminoglycans. Its somatic symptoms can be relieved by enzyme replacement therapy (ERT) with idursulfase, but because the enzyme cannot cross the blood‐brain‐barrier (BBB), it does not address the progressive neurodegeneration and subsequent central nervous system (CNS) manifestations seen in patients with neuropathic MPS‐II. However, pabinafusp alfa, a human iduronate‐2‐sulfatase (IDS) fused with a BBB‐crossing anti‐transferrin receptor antibody, has been shown to be efficacious against both the somatic and CNS symptoms of MPS II. We report two cases of MPS‐II in Japanese siblings sharing the same G140V mutation in the IDS gene, who showed markedly contrasting developmental trajectories following enzyme replacement therapy (ERT). Sibling 1 was diagnosed at 2 years of age, started undergoing conventional ERT shortly afterward, and scored a developmental quotient (DQ) of 53 on the Kyoto Scale of Psychological Development (KSPD) at 4 years of age. Sibling 2 was diagnosed prenatally and received conventional ERT from the age of 1 month through 1 year and 11 months, when he switched to pabinafusp alpha. He attained a DQ of 104 at age 3 years and 11 months, along with significant declines in heparan sulfate concentrations in the cerebrospinal fluid. This marked difference in neurocognitive development highlights the importance of early initiation of ERT with a BBB‐penetrating enzyme in patients with neuropathic MPS‐II.
Evaluation of predictors of severe‐moderate COVID‐19 infections at children: A review of 292 children
Authors: Kara Aybüke A. , Böncüoğlu Elif , Kıymet Elif , Arıkan Kamile Ö. , Şahinkaya Şahika , Düzgöl Mine , Cem Ela , Çelebi Mİray , Ağın Hasan , Bayram Süleyman N. , Özkan Behzat , Devrim İlker 
Published: July 2021

AbstractAlthough the underlying disease is associated with a severe course in adults and laboratory abnormalities have been widely reported, there are not sufficient data on the clinical course of coronavirus disease 2019 (COVID‐19) in children with pre‐existing comorbid conditions and on laboratory findings. We aimed to describe the independent risk factors for estimating the severity of the COVID‐19 in children. All children between 1 month and 18 years old who were hospitalized during the period of March 11–December 31, 2020, resulting from COVID‐19 were included in the study. Patients were categorized into mild (group 1) and moderate + severe/critically (group 2) severity based on the criteria. Demographic characteristics, comorbidities, and laboratory variables between the two groups were compared. A total of 292 children confirmed to have COVID‐19 infection were included in the study. The most common associated diseases were obesity (5.1%) and asthma bronchiale (4.1%). We observed that disease progressed more severely in patients with underlying diseases, especially obesity and asthma bronchiale (for patients with obesity odds ratio [OR] 9.1, 95% confidence interval [CI] 1.92–43.28, p = 0.005 and for patients with asthma bronchiale OR 4.1, 95% CI 1.04–16.80, p = 0.044). In group 2 patients, presence of lymphopenia and hypoalbuminemia, and also an elevation in serum levels of C‐reactive protein, procalcitonin, and uric acid were detected and these results were statistically significant (p values; p < 0.001, p = 0.046, p = 0.006, p = 0.045, p < 0.001, respectively). The strongest predictor of moderate‐severe COVID‐19 infections in the children was uric acid, with an odds ratio of 1.6 (95% CI 1.14–2.13, p = 0.005) and lymphocytes with an odds ratio of 0.7 (95% CI 0.55–0.88, p = 0.003). Although children are less susceptible to COVID‐19, the pre‐existing comorbid condition can predispose to severe disease. In addition, lymphopenia and high uric acid are indicators that COVID‐19 infection may progress more severely.
Evaluation of the relationship between pentraxin 3 (PTX3) rs2305619 (281A/G) and rs1840680 (1449A/G) polymorphisms and the clinical course of COVID‐19
Authors: Kerget Ferhan , Kerget Buğra , Kahraman Çiğdem Yüce , Araz Ömer , Akgün Metin , Uçar Elif Yılmazel , Sağlam Leyla 
Published: July 2021

AbstractMacrophage activation syndrome (MAS) is one of the main causes of morbidity and mortality in patients with coronavirus disease 2019 (COVID‐19). This study aimed to investigate the relationship between the pentraxin 3 (PTX3) gene polymorphisms rs2305619 (281A/G) and rs1840680 (1449A/G) and the development of MAS in patients with COVID‐19. The study included a total of 94 patients aged 18–45 who were diagnosed as having COVID‐19 between June and December 2020. PTX3 281A/G and 1449A/G polymorphism frequencies were evaluated. PTX3 281A/G allele and genotype frequencies did not deviate from Hardy–Weinberg (HW) equilibrium in the MAS or non‐MAS group (χ2: 0.049, df: 2, p = 0.976, χ2: 0.430, df: 2, p = 0.806). PTX3 1449A/G allele and genotype frequencies deviated significantly from HW equilibrium in the non‐MAS group (χ2: 6.794, df: 2, p = 0.033) but not in the MAS group (χ2: 2.256, df: 2, p = 0.324). The AG genotype was significantly more frequent in the non‐MAS group, while the AA genotype was significantly more frequent in the MAS group (χ2: 11.099, df: 2, p= 0.004). Analysis of the PTX3 1449A/G polymorphism showed that individuals with the GG genotype had higher serum PTX3 levels than those with the AA and AG genotypes (p = 0.001 for both). Analysis of the PTX3 1449A/G polymorphism in patients with COVID‐19 showed that those with the AG genotype were relatively more protected from MAS compared with individuals with the AA genotype. In addition, lower serum PTX3 levels are observed in patients carrying the A allele.