bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct conversion of human fibroblasts into dopaminergic neuron-like cells using small molecules and protein factors
Authors: Qin Hua , Zhao An-Dong , Sun Meng-Li , Ma Kui , Fu Xiao-Bing 
Published: November 2020

AbstractBackgroundGeneration of neurons is essential in cell replacement therapy for neurodegenerative disorders like Parkinson’s disease. Several studies have reported the generation of dopaminergic (DA) neurons from mouse and human fibroblasts by ectopic expression of transcription factors, in which genetic manipulation is associated with potential risks.MethodsThe small molecules and protein factors were selected based on their function to directly induce human fetal lung IMR-90 fibroblasts into DA neuron-like cells. Microscopical, immunocytochemical, and RT-qPCR analyses were used to characterize the morphology, phenotype, and gene expression features of the induced cells. The whole-cell patch-clamp recordings were exploited to measure the electrophysiological properties.ResultsHuman IMR-90 fibroblasts were rapidly converted into DA neuron-like cells after the chemical induction using small molecules and protein factors, with a yield of approximately 95% positive TUJ1-positive cells. The induced DA neuron-like cells were immunopositive for pan-neuronal markers MAP2, NEUN, and Synapsin 1 and DA markers TH, DDC, DAT, and NURR1. The chemical induction process did not involve a neural progenitor/stem cell intermediate stage. The induced neurons could fire single action potentials, which reflected partially the electrophysiological properties of neurons.ConclusionWe developed a chemical cocktail of small molecules and protein factors to convert human fibroblasts into DA neuron-like cells without passing through a neural progenitor/stem cell intermediate stage. The induced DA neuron-like cells from human fibroblasts might provide a cellular source for cell-based therapy of Parkinson’s disease in the future.
Intensive blood pressure lowering: a practical review
Authors: Camafort Miguel , Redón Josep , Pyun Wook Bum , Coca Antonio 
Published: November 2020

Abstract
According to the last Hypertension guideline recommendations, it may be concluded that intensive BP lowering is only advisable in a subgroup of patients where there is a clear net benefit of targeting to lower BP goals. However, taking into account the relevance of correct BP measurement, estimates of the benefits versus the harm should be based on reliable office BP measurements and home BP measurements.
There is still debate about which BP goals are optimal in reducing morbidity and mortality in uncomplicated hypertensives and in those with associated comorbidities. In recent years, trials and meta-analyses have assessed intensive BP lowering, with some success. However, a careful examination of the results shows that current data are not easily applicable to the general hypertensive population.
This article reviews the evidence on and controversies about intensive BP lowering in general and in specific clinical situations, and the importance of obtaining reliable BP readings in patients with hypertension and comorbidities.
The abundance of a transfer RNA-derived RNA fragment small RNA subpopulation is enriched in cauda spermatozoa
Authors: Stanger Simone J. , Bernstein Ilana R. , Anderson Amanda L. , Hutcheon Kate , Dun Matthew D. , Eamens Andrew L. , Nixon Brett 
Published: November 2020

AbstractThe small RNA (sRNA) landscape of mammalian spermatozoa is considerably altered as these gametic cells migrate through the segment specific microenvironments of the epididymis. More specifically, the microRNA (miRNA) species of sRNA dominates the sRNA landscape of spermatozoa of the proximal caput segment of the epididymis. However, in sperm cells sourced from the distal cauda epididymal segment, the transfer RNA (tRNA)-derived RNA fragment (tRF) sRNA species is the most abundant. Here we show that the 5′ halves of fifteen mature tRNAs were used as processing substrates for the production of a specific subpopulation of tRF sRNAs, 30 to 33 nucleotides (30–33-nt) in length. A quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) approach was used to experimentally validate the sRNA sequencing identified trend of enriched abundance of this specific 30–33-nt tRF subpopulation in cauda spermatozoa. The length, and exclusive alignment of the cauda spermatozoa enriched tRF subpopulation to the 5′ half of each processed tRNA precursor, identified ANGIOGENIN (ANG) as the endonuclease likely responsible for tRF production in the mouse epididymis: a prediction confirmed via immunoblotting assessment of ANG abundance in spermatozoa sourced from the caput, corpus and cauda epididymal segments. When taken together with our previous profiling of miRNA and Piwi-interacting RNA (piRNA) sRNA abundance in spermatozoa sourced from the three segments of physiologically normal mouse epididymides, the tRF profile reported here adds greater depth of coverage to the global sRNA landscape of the mouse epididymis; a roadmap constructed to assist with the future molecular characterization of sRNA-directed responses to a wide range of imposed environmental stressors.
Fabrication and characterization of sterically stabilized liposomes of topotecan
Authors: Patel Dasharath , Patel Niteshkumar 
Published: November 2020

AbstractBackgroundRecently, the development of drug delivery which delivers controlled drug release at the tumor sites emerged as an attractive option for enhancing anticancer therapeutics. Next-generation nanotherapeutics must not contain only the nanoscale but should find their way to the solid tumor via active or passive targeting. Surface modification by pegylated lipids is one of the approaches used to made liposomes long-circulating and passively target the tumor. Pegylation of liposomes help them to alter the pharmacokinetics of drug molecule in vivo. The successful journey of such a complex drug delivery system from bench to clinic requires in-depth understanding and characterization. In this research, we fabricated and characterized sterically stabilized liposomes of topotecan which meets the clinical need. Liposomes have been prepared using ethanol injection-solvent evaporation method followed by extrusion for size reduction. Outer medium was replaced with an isotonic sucrose solution using dialysis followed by drug loading. We characterized liposomes’ membrane phase and dynamics, drug and lipid quantification, size distribution, state of encapsulated drug, internal volume and internal pH of liposomes, presence, and thickness of grafted PEG on the liposomes surface, and in vitro leakage test.ResultsAll these studied parameters directly or indirectly provide information regarding the pharmacokinetic behavior of the formulation and the tumor-targeting property of the drugs in vivo. We encapsulated the topotecan in nanoliposomes with pegylation on the surface resulting in long-circulating stealth liposomes. Nanoliposomes remotely loaded with topotecan by transmembrane gradient method.ConclusionOur in vitro characterization of topotecan liposomes provides an explanation for the good therapeutic efficacy of tumor cells.
Multiple strictures of the small intestine demanding surgical intervention as a rare consequence of graft versus host disease – case report
Authors: Sobkowiak-Sobierajska Agnieszka , Błaszczyński Michał , Mańkowski Przemysław , Wachowiak Jacek 
Published: November 2020

Abstract

Background
Intestinal strictures are an extremely rare and life-threating complication in patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT). We describe the case of a child operated for multiple strictures of the small intestine secondary to GvHD.

Case presentation
A 7-year-old girl underwent second allo-HSCT from matched unrelated donor for post-CALR-positive-ET myelofibrosis and its relapse after the first HSCT. HSCT was complicated with grade IV acute GvHD (skin and gut). The patient was treated with CsA, with methylprednisolone, and due to corticosteroid resistance subsequently with etanercept and ECP. She required parenteral nutrition due to malabsorption symptoms and anorexia for 15 months after HSCT. On day + 457, the laparotomy was performed due to increasing symptoms of mechanical bowel obstruction. Ten critical cicatricial strictures of the small intestine were revealed. Nine segmental resections of the strictured segments and 6 intestinal anastomoses were done during one surgical procedure. The postoperative period was uncomplicated, and oral feeding was gradually implemented, achieving full coverage. Pathological examination confirmed the diagnosis of overlap syndrome of acute and chronic GvHD. Therefore, the patient started therapy with ruxolitinib which was continued till 30 months after HSCT. Corticosteroids were gradually withdrawn on day + 574. Currently, 32 months after the second HSCT, no GvHD and no gastrointestinal disturbances are observed. The patient remains in hematological and molecular remission of myelofibrosis.

Conclusions
GvHD therapy is largely based on conservative treatment, but a patient presenting with occlusive symptoms due to permanent changes in the gastrointestinal wall needs to undergo surgery to ensure its efficient functioning.
Long-Term Mental Disorders in the Accident-Exposed Population of the Southern Urals
Authors: Burtovaia E. , Kantina T. , Litvinchuk E. 
Published: November 2020

Purpose: To study late mental and behavioral disorders (ICD-10) in individuals who were accidentally exposed in the Southern Urals.
Material and methods: The research subjects are the persons who were exposed to radiation as a result of dumping of radioactive waste into the Techa River (1949–1956), who were born before 1953 and lived in the Techa River basin between 1950 and 1960. The study group consists of 425 people, women predominate (72.5 %), people with secondary special education make up 44.5 %, and pensioners amount to 89.4 %. Mean age at examination was 67.3 ± 5.3 years. Information on radiation doses included data on the absorbed dose to the stomach, which was considered as an analog of brain exposure (50 ± 3 mGy). The paper uses clinical-anamnestic, clinical-psychopathological, clinical and instrumental methods.
Results: It has been demonstrated that in the long-term period, accidentally exposed individuals have organic nonpsychotic mental disorders (72.2 %), with the predominance of organic asthenic (29.6 %) and organic cognitive (36.5 %) disorders. Among the studied individuals, only 20.9 % showed no signs of mental illness. Higher absorbed doses to the stomach (70 ± 8 mGy, p = 0.01) was determined in patients with organic cognitive disorder. Concomitant somatic pathology is present in patients with organic cognitive disorder — hypertension (90.3 %, p = 0.005), ischemic heart disease (56.7, p = 0.004), chronic brain ischemia (43.2 %, p = 0.04). Patients with organic asthenic disorder may have hypertension (94.4 %, p = 0.0002), ischemic heart disease (51.6 %, p = 0.04), chronic brain ischemia (35.7 %, p = 0.02). In the group of patients without mental pathology, the most common were hypertension (76.4 %), diseases of the musculoskeletal system (61.7 %, p = 0.03), and ischemic heart disease (37.1 %). Multiple correlation analysis showed a weak statistically significant association of organic mental disorders with chronic brain ischemia, hypertension, ischemic heart disease and the age of patients.
Conclusion: The performed study complements the current understanding of long-term mental disorders in exposed individuals, and requires further research to study the pathogenesis of cerebrovascular and cardiovascular diseases in individuals exposed to radiation.
Immune Status of a Man Long after Chronic Radiation Exposure
Authors: Akleyev A. 
Published: November 2020

Purpose: Assessment of major parameters of the system immunity in 376 Techa riverside residents affected by external γ- and internal (mainly due to 90Sr) irradiation 60–68 years after the onset of exposure.
Material and methods: The study involved 376 residents of the settlements located in the basin of the Techa River which was contaminated due to releases of liquid radioactive waste of Mayak Production Association. Red bone marrow received the largest doses that reached 4457.1 mGy, mean dose value was 1080.8 ± 38.4 mGy. Doses to the thymus and peripheral organs of the immune system in the exposed individuals were much lower; mean dose value was 65.3 ± 4.9 mGy. The study of the systemic immunity included the analysis of the parameters that characterize functional status of adaptive and innate immunity, as well as of the cytokine system.
Results: Pro-inflammatory changes of the cytokines spectrum (decrease of IL-4 in blood serum, increase of TNFα and IFNγ) were observed in exposed people with a background of involution changes.
Conclusion: Persistent reduction in the number of neutrophils in blood against normal levels of granulocyte colony-stimulating and granulocyte-macrophage colony-stimulating factors in blood serum could be indicative of certain inefficiency of hematopoietic stem cell pool. The most distinct features of immunity in exposed persons concerned the cytokine spectrum which were inflammatory in nature and on the one hand could be involved in the mechanisms of development of long-term effects of radiation and on the other could have a protective effect on the protection of the body from cells carrying sublethal abnormalities.
Neocortex (Frontal and Temporal Lobe) Discirculatory Lesions of the Chernobyl Accident Liquidators at the Remote Period (Based on Diffusion Tensor MRI Data)
Authors: Aleksanin S. , Serebryakova S. , Levashkina I. 
Published: November 2020

Purpose: To find the distinctive features of the white matter tracts’ structural changes for Chernobyl accident liquidators with ebcephalopathy at the remote period using DT-MRI methods.
Material and methods: Chernobyl accident liquidators group (41 subjects) and group of control (49 subjects), all subjects with stage II of encephalopathy, mean age of liquidators’ group 68.3 ± 6.9 years, gropup of control — 68.6 ± 5.8 years. All subjects were clinically examined to confirm encephalopathy stage, hypertension, diabetes (and prove patients of both groups have comparable level of damage of those deseases), as well as with routine MRI and DT-MRI protocols. According routine MRI results, all subjects of both groups had high level of discirculatory damages: multifocal lesions of white matter and periventricular leukoaraiosis, mixed replacement hydrocephalus.
Results: Liquidator’s group average fraction anisotropy coefficient (CFA) had shown statistically significant reduction in four frontal and temporal lobe tracts of neocortex if compare with average CFA in the group of control: superior longitudinal fasciculi (р < 0.02); front sections of corona radiata (р < 0.02); anterior horn of internal capsule (р < 0.01), inferior longitudinal fasciculi (р < 0.01).
Conclusion: Frontal and temporal lobe tracts of neocortex, responsible for cognitive processes, are the most sensible to accident liquidation negative factors. Cerebral structure changes, found for group of liquidators, are similar to elder people with encephalopathy, but are clnically more strongly marked, what proves hyoptesis of early aging of liquidators’ brain structures.
Factors Influencing the Health Condition of the Adult Population Residing in the Activity Area of Atomic Industry Enterprise
Authors: Kalinkin D. , Takhauova T. , Karpov A. , Samoilova Yu. , Plaksin M. , Semenova Yu. , Takhauov A. , Kiriakidi E. , Takhauova L. 
Published: November 2020

Purpose: Development of the basic directions of a modern strategy for protecting the health of the adult population living in the activity zone of nuclear industry enterprises (using the example of the Seversk population).
Material and methods: The object of the study was the population of the city of Seversk, formed around the Siberian Group of Chemical Enterprises. The subject of the study was demographic indicators; disability; incidence of malignant neoplasms, diseases of the circulatory system, injuries and accidents); socio-economic, behavioral and technological risk factors affecting the occurrence of major diseases.
Results: It was established that by the end of the study period (1970–2017), the studied population was in a state of natural population decline due to a decrease in the birth rate and an increase in mortality, while the mortality rate exceeded the birth rate.
During the period under review, the primary incidence of malignant neoplasia significantly increased; at the same time, the incidence of cardiovascular diseases, as well as the frequency of injuries and poisoning, decreased. Among the adult population of Seversk, behavioral factors (the habit of smoking, regular use of alcohol, a sedentary lifestyle, lack of regular physical activity) are more common than socio-economic (living conditions, financial situation) risk factors. Important risk factors are incorrect assessment by citizens of their own health and the reasons for its violation. Among Siberian Group of Chemical Enterprises workers exposed to tekhnogenic risk factor (long-term occupational exposure), there is an increased risk of cancer death of all localizations taken together, respiratory and digestive organs; bones, joints, mesothelium, soft tissues and genitals. At the same time, the risk of oncological mortality during irradiation was not exceeded in the range of small doses of (up to 100 mSv), and for any of the localization of malignant neoplasms this effect is not dose-dependent.
Conclusion: The data obtained made it possible to specify and substantiate the basic directions of the modern strategy for protecting the health of the adult population living in the activity zone of nuclear industry enterprises (using the example of the Seversk population).
Evaluation of Effects of Diagnostic Exposure Using Data from Epidemiological Registry of Ozyorsk Population Exposed to Computed Tomography
Authors: Osipov M. , Fomin E. , Sokolnikov M. 
Published: November 2020

Purpose: To assess the contribution of low doses of diagnostic radiation due to computed tomography to carcinogenic risk among population of Ozersk.
Material and methods: The study describes the results of the analysis of data from the radiation-epidemiological register created in the laboratory of radiation epidemiology of the Southern Urals Biophysics Institute of Ozersk. The register contains information on 26,626 CT examinations of Ozersk residents of all age groups, including children under 1 year old, carried out in medical departments of the Chelyabinsk region during the period from 1993 to 2018.
Results: Based on the analyzed medical and dosimetric information from the CT Register database, the chances of malignant neoplasms among patients exposed to diagnostic irradiation during computed tomography were assessed taking into account the presence of the main radiation and non-radiation factors (age, sex, occupational exposure, number of CT examinations, effective dose and DLP).
Conclusion: In a cohort of Ozersk residents who were exposed to low doses of diagnostic radiation during computed tomography, a statistically significant effect of sex and age attained to malignant neoplasm was obtained. Also, a significant relationship was found between the effective dose from diagnostic CT and the likelihood of subsequent cancer development diagnosed no earlier than 2 years after the first CT examination. At the same time, the DLP did not statistically significantly increase the chances of developing a malignant neoplasm in the study cohort for both the population and the personnel of the Mayak PA.
Registry for Chronic Radiation Sickness in a Cohort of Mayak PA Workers Exposed to Ionizing Radiation
Authors: Azizova T. , Bannikova M. , Grigor'eva E. , Zhuntova G. , Moseeva M. , Bragin E. 
Published: November 2020

Purpose: To present descriptive characteristics, and structure of the chronic radiation sickness (CRS) registry prospects of its use.
Materials and methods: A registry for CRS diagnosed in workers of the nuclear production facility Mayak Production Association (PA) throughout the follow-up period of 1948–2018 was established within a medical and dosimetry database ‘Clinic’ of the Southern Urals Biophysics Institute.
Results: The CRS registry includes 2068 cases: 1517 (73.4 %) in males and 551 (26.6 %) in females. Almost all workers (97.9 %) with CRS were hired at the Mayak PA in 1948–1954 and chronically externally and/or internally exposed to ionizing radiation. At a date of CRS diagnosis the mean cumulative red bone marrow absorbed dose of external exposure to gamma rays was 1.1 ± 0.7 Gy in males and 1.0 ± 0.6 Gy in females; the mean annual dose was 0.46 ± 0.33 Gy and 0.38 ± 0.22 Gy in males and females, respectively; maximum annual dose was 0.67 ± 0.46 Gy and 0.55 ± 0.34 Gy in males and females, respectively. The CRS frequency in the Mayak PA worker cohort significantly increased with the cumulative and mean annual RBM absorbed dose of external exposure to gamma rays. In the meantime, the CRS frequency was not associated either with a dose of external neutron exposure or with a dose of internal exposure to alpha particles from incorporated plutonium.
Conclusion: The established CRS registry providing complete high quality demographical, medical and dosimetry information, together with available biological specimens, in future will allow: the updating of dose–response and dose–time–response relationships; the estimation of latent periods, risks and dose thresholds and associated uncertainties for CRS development; certain tissue reactions in lymphoid and haematopoietic tissues; and a better understanding of their development patterns and mechanisms, taking into account non-radiation factors.
Analysis and perspectives of the level of enterprises digitalization (Lithuanian manufacturing sector case)
Authors: Bickauske Daiva , Simanaviciene Zaneta , Jakubavicius Arturas , Vilys Mantas , Mykhalchyshyna Larysa 
Published: November 2020

The impact of technological advances in all industry sectors is being felt and, thus, there is no doubt that digital transformation will have significantly affect Lithuanian manufacturing sector. In order to assess the extent to which Lithuanian processing industry companies are digitalized, an in-depth descriptive analysis of installed digital technologies in these companies was executed. The goal of this analysis – to determine whether Lithuanian companies of processing industry has been sufficiently digitalized and are ready to completely adopt the principles of Industry 4.0 in the installation of digital solutions within all segments of the value-chain creation. The research on already-applied digital tools and technologies in those companies was made during the phase of analysis. There was also an attempt to define the most digitalized processes of operation and the least or non-digitalized processes of operations in those companies. After the assessment of a current digitalization level in the company was made, there was an attempt to clarify the strengths and problematic challenges as well as the underlying reasons for its challenges. After the above-mentioned data was collected, recommendations on which additional tools and means to apply in order to encourage the process of digitalization in the companies were formulated and passed on to the companies.