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CLINICAL-METABOLIC AND HORMONAL RELATIONSHIPS BETWEEN PARATHYROID DISEASE AND OTHER NON-CANCEROUS ENDOCRINE DISORDERS IN THE CHORNOBYL NPP ACCIDENT SURVIVORS

Probl Radiac Med Radiobiol. 2021 Dec;26:410-425. doi: 10.33145/2304-8336-2021-26-410-425.

ABSTRACT

OBJECTIVE: to investigate the clinical, hormonal-metabolic and structural features of parathyroid injuries in sur-vivors exposed to ionizing radiation after the Chornobyl NPP accident in adulthood and childhood, both with theirconnections to other non-cancerous endocrine disorders, and to establish the respective interhormonal and dys-metabolic relationships.

MATERIALS AND METHODS: Clinical effects of ionizing radiation on the endocrine system in persons affected by theChornobyl NPP accident (n = 224) and their descendants (n = 146), compared with the general population sample(n = 70) were the study object. All patients underwent the ultrasound thyroid and parathyroid examination. Thegenerally recognized clinical, anthropometric (body weight, height, thigh volume, body mass index), instrumental(ultrasound examination of thyroid and parathyroid glands), laboratory (biochemical, hormonal), and statisticalmethods were applied. Parametric and nonparametric statistical methods were used in data processing. The value ofp < 0.05 was considered a statistically significant.

RESULTS: No significant difference was found in the incidence of carbohydrate metabolic disorders in the ChornobylNPP (ChNPP) accident consequences clean-up workers (ACCUW), evacuees from the NPP 30-km exclusion zone, res-idents of radiologically contaminated areas and in the control group in whom the parathyroid hyperplasia wasdetected. There was a significant increase in the incidence of arterial hypertension among ACCUW who had parathy-roid hyperplasia (76.9%) vs. the control group (51.2%). In cases of parathyoid hyperplasia the vitamin D levels weresignificantly lower than without it. Vitamin D insufficiency/deficiency was found in 94% of the surveyed subjects.The average level of parathyroid hormone in blood serum was significantly higher in the ACCUW of «iodine» period withdiagnosed parathyroid hyperplasia than in the control group: (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml,p < 0.05. Results of multivariative analysis indicated a strong association of vitamin 25(OH)D insufficiency/defi-ciency with development of thyroid disease, carbohydrate metabolic disorders, cardiovascular disease, osteo-penia/osteoporosis. parathyroid ultrasound scan was at that an effective diagnostic method for primary screeningfor parathyroid hyperplasia and regular monitoring of the treatment efficiency. When examining children bornto parents irradiated after the ChNPPA the parathyroid hyperplasia (58%) and low serum content of vitamin D(11.6 ± 3.5) nmol / l were most often found in children living on radiologically contaminated territories (RCT).A strong correlation was established between the HOMA insulin resistance index and serum content of vitamin D(r = 0.65), parathyroid hormone (r = 0.60), and free thyroxine (r = 0.68) in the group of children born to parents irra-diated after the ChNPPA, having got chronic autoimmune thyroiditis, which indicated a relationship between thy-roid function, impaired carbohydrate and fat metabolism and the state of parathyroids.

CONCLUSIONS: No difference in the incidence of carbohydrate metabolic disorders was found in the ChNPP ACCUW,evacuees from the 30-km exclusion zone, and residents of radiologically contaminated territories in whom parathy-roid hyperplasia was detected vs. the control group. Patients with parathyroid hyperplasia were found to be defi-cient in vitamin D in 94% of cases, and level of latter was significantly lower than under the normal parathyroid size.There was a significant increase in the incidence of diagnosed arterial hypertension among ACCUW who had parathy-roid hyperplasia vs. the control group: (76.9 ± 3.5)% vs. (51.2 ± 3.7)%. According to multivariate analysis a strongassociation between the vitamin 25(OH)D insufficiency/deficiency and development of thyroid disease, carbohydratemetabolic disorders, cardiovascular disease, and osteopenia/osteoporosis was established. The average level of pa-rathyroid hormone in the blood serum of the ChNPP ACCUW of the «iodine» period with diagnosed parathyroid hyper-plasia was significantly higher (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml; p <0,05) in the control group.

PMID:34965563 | DOI:10.33145/2304-8336-2021-26-410-425

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INFLUENCE OF RADIOACTIVE BACKGROUND ON SEXUAL FUNCTION IN MEN FROM DIFFERENT REGIONS OF UKRAINE

Probl Radiac Med Radiobiol. 2021 Dec;26:479-497. doi: 10.33145/2304-8336-2021-26-479-497.

ABSTRACT

OBJECTIVE: The article attempts to analyze the nature of sexual dysfunctions in patients living in areas exposed toionizing radiation as a result of the Chornobyl accident.

MATERIALS AND METHODS: A study of sexual function was carried out in 186 people (group I) living in the territoriesof Kyiv (Polisske, Chornobyl, Ivankiv, Borodianka, Vyshhorod, Makariv districts) and Zhytomyr (Malyn and Korostendistricts) regions. The control group consisted of persons who were born and lived on the territory of Ivano-Frankivsk and Chernivtsi regions (group II, n = 123). Diagnostics was carried out on an outpatient basis in accor-dance with the standards of the WHO and the Ministry of Health of Ukraine.

RESULTS: Analyzing the obtained research results, a significantly larger number of patients with sexual dysfunctionwas identified in group I (82.3 %) than in group II (44.7 %) (р < 0.01). Psychopathological disorders disturbed,respectively, 60.2 % and 41.4 % (p < 0.01). Complaints of decreased libido were presented by 25.8 % of the surveyedmen exposed to ionizing radiation, and 6.5 % of them were concerned about a sharp depression of libido. In groupII patients, this indicator was 14.6 % and 3.3 %, respectively. The integral index of «libido» of the ICEF question-naire revealed a statistically significant difference between the groups (9.23 ± 0.89 and 12.22 ± 1.26, respectively;р < 0.05). In patients exposed to ionizing radiation as a result of the Chornobyl accident, the concentration oftestosterone decreases, and the content of FSH, LH, as well as globulin, which makes sex hormones, increases.Erectile dysfunction in patients of group I was detected in 58.1 % of men, and in patients of group II – 35.0 % (р < 0.01).The difference in the integral indicators of the ICEF questionnaire between the groups was 1.3 times behind the«libido» domain. For other domains – by 1.5-1.6 times. In men living in the territories of Kyiv and Zhytomyr regions,erectile dysfunction occurs earlier and is characterized by a more severe course than in people born and lived in theterritory of Ivano-Frankivsk and Chernivtsi regions. Both in terms of low rates of normal erection (in patients ofgroups I and II, respectively 3.8 % and 13.3 %), and for high percentages of existing moderate/severe ED (respec-tively 71.0 % and 45.5 %), persons from group I are characterized by significantly worse data than persons fromgroup II (р < 0.01). Orgasm pathology was found in 40.3 % of patients in group I and in 25.2 % of patients in groupII (р < 0.01). The quality of life index according to the QoL index in the context of existing sexual disorders in groupI of patients was 4.7 ± 0.4, in patients of group II – 3.9 ± 0.2 (р < 0.05).

CONCLUSIONS: The data obtained indicate a tendency for a more significant violation of sexual functions in men whowere born and lived in territories exposed to radioactive contamination as a result of the Chornobyl accident.

PMID:34965568 | DOI:10.33145/2304-8336-2021-26-479-497

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SELECTION AND TESTING OF EXPERIMENTAL MODELS OF NORMAL AND MALIGNANT HUMAN CELLS IN VITRO AND EVALUATION OF THEIR SENSITIVITY RANGE TO THE NEUTRON/CAPTURE AND PHOTON/CAPTURE AGENTS AND PHOTOSENSITIZERS

Probl Radiac Med Radiobiol. 2021 Dec;26:260-272. doi: 10.33145/2304-8336-2021-26-260-272.

ABSTRACT

OBJECTIVE: to investigate the structural and morpho-functional changes in test systems of malignant (A-549 cellline) and normal (fibroblasts of the 6th passage) human cells during incubation with gadolinium-containing pho-ton-capture agent «Dotavist» and photosensitizer «Fotolon».

METHODS: The passaged (continuously interweaved) cell culture technique on normal human fibroblasts and malig-nant human cells; cytological, biophysical, statistical methods.

RESULTS: The cytotoxic properties of «Dotavist» gadolinium-containing photon-capturing agent and «Photolon»photosensitizer in a wide range of concentrations (5, 10, 25, 50, 100 and 200 μl/ml) were studied by the morpho-functional characteristics (growth kinetics, proliferative and mitotic activity, presence of atypical cells) in the invitro test systems of malignant (non-small cell lung cancer cell line A-549) and normal (6th passage fibroblasts)human cells. It was found that the cytotoxic properties of «Dotavist» in test systems of malignant and normal cellsare expressed under its administration in high concentrations (100 and 200 μl/ml). During incubation with«Photolon» photosensitizer the cytotoxic effect on malignant cells was determined at the lowest concentrations (5and 10 μl/ml). Photosensitizer administration in the increasing concentrations has lead to genotoxic effects.Cytotoxic effect of photosensitizer on the normal human fibroblasts was evident in the 5-200 μl/ml concentrationrange. There was a moderate decrease in mitotic activity along with increasing concentration. Genotoxic propertiesof photosensitizer were evident at 25 μl/ml concentration and above.

CONCLUSION: Study results of the effectiveness of neutron-capture and photon-capture technologies by the sensi-tivity assay in the in vitro test systems of human malignant cells (non-small cell lung cancer cell line A-549) andnormal cells (transplantable human fibroblast culture, the 6th passage) to the gadolinium-containing photon-cap-ture «Dotavist» agent and «Photolon» photosensitizer in different concentrations provide the basis for pre-clinicalstage of evaluating the effectiveness of medications used in binary technologies.

PMID:34965553 | DOI:10.33145/2304-8336-2021-26-260-272

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HEALTH IN THE SYSTEM OF VALUES OF THE POPULATION OF THE SURVEILLANCE ZONES NUCLEAR POWER PLANTSS

Probl Radiac Med Radiobiol. 2021 Dec;26:219-234. doi: 10.33145/2304-8336-2021-26-219-234.

ABSTRACT

OBJECTIVE: to determine the place of health in the system of values of the population of the surveillance zone (SZ)of nuclear power plants (NPPs) and its importance in the perception of emergency risks (ER).

MATERIALS AND METHODS: To determine the place of health in the value system, a survey of the able-bodied popula-tion of satellite cities of Rivne (RNPP) and South Ukrainian (SUNPP) nuclear power plants was conducted using non-repetitive sampling, where the sampling error does not exceed 7,0 %. The motivational and behavioral componentthat determined health in the individual hierarchy of values of the subject according to the questionnaireBerezovskaya R. A. was studied. Statistical and mathematical methods were used in the research process.

RESULTS: The array of respondents was conditionally divided into 4 groups according to their attitude to humanhealth. And the group where a person’s life position is focused exclusively on health is the most common – 77,0 %.Group IV, which wants to live without limiting itself, is 8,1 %. The component integrity of values-goals and values-means among the urban population of the SZ of both nuclear power plants is the same: the main goal in life is health,happy family life, and as a means – perseverance, diligence and health. Goal values in groups I and IV have somedifferences: in the first group of respondents the main goal in life is health, and in the fourth, where a person’s lifeguidelines exclude any restrictions – a happy family life. Values for these populations have some differences, but inboth groups health appears to be the main means to an end. There is a close correlation between the core of termi-nal values and the average indicators of the state of concern about the risk of emergencies.

CONCLUSIONS: Identified hierarchy of values: a group of stable dominant values; average status values; group of leastsignificant values. The values of the highest status among the values-goals are – health, happy family life and inte-resting work. Most respondents plan to achieve them through values such as «health», «perseverance and hardwork». There is a close correlation between the core of terminal values and the average indicators of the state ofconcern about the risk of emergencies.

PMID:34965550 | DOI:10.33145/2304-8336-2021-26-219-234

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MODIFICATION OF THE TUMOR/INDUCED BYSTANDER EFFECT BY IRRADIATION UNDER COCULTIVATION OF LYMPHOCYTES FROM PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA AND LYMPHOCYTES FROM HEALTHY DONORS

Probl Radiac Med Radiobiol. 2021 Dec;26:248-259. doi: 10.33145/2304-8336-2021-26-248-259.

ABSTRACT

OBJECTIVE: Study the tumor-induced bystander effect of blood cells from chronic lymphocytic leukemia (CLL)patients on non-transformed bystander cells (peripheral blood lymphocytes (PBL) of conditionally healthy individ-uals) and the possibility of its modification after the impact of ionizing radiation.

MATERIALS AND METHODS: We carried out cocultivation and separate cultivation of blood samples from conditionallyhealthy volunteers and patients with CLL according to our technique. Using the Comet assay, the relative level ofDNA damage was evaluated.

RESULTS: A statistically significant increase (р < 0.001) in the level of DNA damage in PBL culture of conditionallyhealthy individuals after co-cultivation with malignant cells of CLL patients was observed. After irradiation, a drop in the level of cells with a high degree of DNA damage was noted, which was connected with an increase in the frequency of cells that were delayed in division at the S stage of the cell cycle. An increase in apoptotic activity in cultures of bystander cells was observed in all variants of the experiment (р < 0.001).

CONCLUSION: The influence of irradiated blood cells of patients with CLL results in an enhancement of the tumor-induced bystander effect manifestation in the PBL of conditionally healthy individuals.

PMID:34965552 | DOI:10.33145/2304-8336-2021-26-248-259

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Clinical Pathway for Vaso-Occlusive Pain Reduces Hospital Admissions

J Healthc Qual. 2022 Jan-Feb 01;44(1):50-58. doi: 10.1097/JHQ.0000000000000292.

ABSTRACT

BACKGROUND: Vaso-occlusive pain leads to high acute care utilization among patients with sickle cell disease (SCD). Data suggest that clinical pathways (CPWs) reduce variation in the management of vaso-occlusive pain and improve clinical outcomes.

METHODS: We implemented and evaluated a CPW for vaso-occlusive pain at our institution using a before and after study design. The primary objective was to decrease acute care utilization among patients with SCD, which was assessed by the primary outcome measures of hospital length of stay (LOS), 30-day readmission rate, and total hospitalizations annually per patient. Secondary outcome measures were packed red blood cell transfusions, and acute chest syndrome incidence. Patient-controlled analgesia use and promethazine use were assessed to estimate CPW use.

RESULTS: Three hundred fourty-four admissions in 112 patients were analyzed, of which 193 admissions occurred pre-CPW and 151 admissions occurred post-CPW implementation. Post-CPW implementation, we observed a significant decrease in hospital admissions annually per patient, an increase in patient-controlled analgesia use, and a decrease in intravenous promethazine use. We observed trends toward decreased 30-day readmission rate and increased acute chest syndrome incidence, which were not statistically significant. No effect was found on hospital LOS.

CONCLUSIONS: Clinical pathway implementation at our institution reduced variation in management and decreased hospital admissions for vaso-occlusive pain.

PMID:34965539 | DOI:10.1097/JHQ.0000000000000292

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AGING OF THE CHORNOBYL CATASTROPHE SURVIVORS AND PROBLEMS OF THEIR MENTAL HEALTH SURVEY

Probl Radiac Med Radiobiol. 2021 Dec;26:162-187. doi: 10.33145/2304-8336-2021-26-162-187.

ABSTRACT

BACKGROUND: Depopulation processes in Ukraine have been affected by the Chornobyl catastrophe (ChC), but therate of demographic aging of survivors remains uncertain. Although the mental health disorders of the survivors arerecognized internationally, problems of their research remain unresolved. Thus, these areas of research are relevant.Objective is to determine the rate of demographic aging of survivors of the Chornobyl NPP (ChNPP) accident and toanalyze the state of their mental health survey, outlining solutions.

MATERIALS AND METHODS: Information and statistical sources for 1986-2019 of the Ministry of Health of Ukraine andthe State Statistics Service of Ukraine on the age of the ChC survivors are used. The results of previous own researchand other scientists using the data of the Clinical and Epidemiological Register (CER) of the State Institution«National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine»(NRCRM), the State Register of ChC survivors (SRU), and the Department of Radiation Psychoneurology, Institute ofClinical Radiology, NRCRM are integrated. Theoretical, general scientific, demographic and mathematical-statisticalresearch methods and documentary analysis are used.

RESULTS: It is shown that in 2018, compared to 1995, the number of the ChC survivors, who are under the supervi-sion of the Ministry of Health of Ukraine, decreased by almost 987 thousand. The part of people born from personsof the 1st-3rd accounting groups increased in the structure of survivors (from 13.1 % in 1995 to 13.6 %), and thisdecreased in persons living or lived in the territories subject to supervision (75.1 % and 63.1 %, respectively), butin evacuees and Chornobyl clean-up workers (liquidators) this did not change significantly. A high level of aging ofthe ChC survivors (except for the 4th group) is revealed: liquidators – 59.0 %; evacuees – 25.0 %, and residents ofradioactively contaminated territories (RCT) – 30.7 %. It has been proved that the countries of RCT differ signifi-cantly in the number of the ChC survivors and their structure. The increase in the post-accident period indicators ofthe level of aging and the average age of the RCT population indicates negative changes in age parameters and theneed to continue research to identify factors «responsible» for such changes. Long-term mental health disordersand neuropsychiatric effects in the ChC survivors have been identified – an excess of cerebrovascular pathology andneurocognitive deficits, especially in liquidators, which may indicate an accelerated aging. Radiation risks havebeen revealed for acute and chronic cerebrovascular pathology and organic mental disorders of non-psychotic andpsychotic levels. Neurophysiological and molecular-biological atypia of aging processes under an exposure to lowdoses of and low dose rate of ionizing radiation have been found. The psyche under the age of 40 years old at thetime of exposure is more vulnerable. Existing statistical and registry data underestimate the level of mental disor-ders in the population of Ukraine, including the ChC survivors by an order of magnitude.

CONCLUSIONS: The ChC survivors are aging in the country. The negative tendencies in age parameters of survival indi-cate the need to continue research to identify the factors «responsible» for such changes. Mental health disordersand neuropsychiatric effects in the ChC survivors are underestimated. It is necessary to create a national psychiatricregistry of Ukraine and long-term (lifelong) monitoring of survivors with well-planned clinical and epidemiologicalstudies of general and mental health with reliable dosimetric support based on national registries using the latest information technologies.

PMID:34965547 | DOI:10.33145/2304-8336-2021-26-162-187

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Dose-Response Relationship in Selective Serotonin and Norepinephrine Reuptake Inhibitors in the Treatment of Major Depressive Disorder: A Meta-Analysis and Network Meta-Analysis of Randomized Controlled Trials

Psychother Psychosom. 2021 Dec 29:1-10. doi: 10.1159/000520554. Online ahead of print.

ABSTRACT

INTRODUCTION: Selective serotonin and norepinephrine reuptake inhibitors (SNRI) are among the most prescribed antidepressants, and dose escalation is a frequently applied strategy after non-response to an initially prescribed dose.

OBJECTIVE: This meta-analysis aimed to find evidence of a dose-response relationship or to the contrary in direct comparisons of different SNRI doses in patients with major depressive disorder.

METHODS: A systematic literature search for RCTs comparing at least two doses of SNRIs was carried out in CENTRAL, PubMed, PsycINFO, and EMBASE. Doses were classified as high, medium, and low according to manufacturers’ product monographs and analyses at the level of SNRIs as a group and for single substances, accompanied by sensitivity network meta-analyses (Prospero CRD42018081031).

RESULTS: From 2,070 studies screened, we included 26 studies with a total of 10,242 patients. Comparisons of medium versus low and high versus medium doses resulted in clinically and statistically non-significant standardized mean differences of -0.06 (-0.16 to 0.04) and -0.06 (-0.16 to 0.03) in favor of higher doses. In the analyses of single substances, no statistically significant results emerged, and many contrasts yielded very small effect sizes. Dropouts due to side effects tended to be more frequent with higher doses. Heterogeneity was low. Network meta-analyses of direct comparisons supported the findings, as did a risk of bias analysis.

CONCLUSION: Based on the lack of positive evidence for a dose-response relationship in SNRIs as a group and in single SNRIs, we recommend prescribing medium doses. In case of insufficient response, we do not recommend increasing the dose of SNRIs.

PMID:34965534 | DOI:10.1159/000520554

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Development of Urinary Diagnostic Biomarker for IgA Nephropathy by Lectin Microarray

Am J Nephrol. 2021 Dec 29:1-11. doi: 10.1159/000520998. Online ahead of print.

ABSTRACT

INTRODUCTION: The pathogenic roles of aberrantly glycosylated IgA1 have been reported. However, it is unexplored whether the profiling of urinary glycans contributes to the diagnosis of IgAN.

METHODS: We conducted a retrospective study enrolling 493 patients who underwent renal biopsy at Okayama University Hospital between December 2010 and September 2017. We performed lectin microarray in urine samples and investigated whether c-statistics of the reference standard diagnosis model employing hematuria, proteinuria, and serum IgA were improved by adding the urinary glycan intensity.

RESULTS: Among 45 lectins, 3 lectins showed a significant improvement of the models: Amaranthus caudatus lectin (ACA) with the difference of c-statistics 0.038 (95% CI: 0.019-0.058, p < 0.001), Agaricus bisporus lectin (ABA) 0.035 (95% CI: 0.015-0.055, p < 0.001), and Maackia amurensis lectin (MAH) 0.035 (95% CI: 0.015-0.054, p < 0.001). In 3 lectins, each signal plus reference standard showed good reclassification (category-free NRI and relative IDI) and good model fitting associated with the improvement of AIC and BIC. Stratified by eGFR, the discriminatory ability of ACA plus reference standard was maintained, suggesting the robust renal function-independent diagnostic performance of ACA. By decision curve analysis, there was a 3.45% net benefit by adding urinary glycan intensity of ACA to the reference standard at the predefined threshold probability of 40%.

CONCLUSIONS: The reduction of Gal(β1-3)GalNAc (T-antigen), Sia(α2-3)Gal(β1-3)GalNAc (Sialyl T), and Sia(α2-3)Gal(β1-3)Sia(α2-6)GalNAc (disialyl-T) was suggested by binding specificities of 3 lectins. C1GALT1 and COSMC were responsible for the biosynthesis of these glycans, and they were known to be downregulated in IgAN. The urinary glycan analysis by ACA is a useful and robust noninvasive strategy for the diagnosis of IgAN.

PMID:34965524 | DOI:10.1159/000520998

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Occupational safety and health management of COVID-19 at a company in the Peruvian fishing sector

Arch Prev Riesgos Labor. 2021 Jul 15;24(3):240-251. doi: 10.12961/aprl.2021.24.03.02.

ABSTRACT

OBJECTIVE: To evaluate the occupational safety and health management of COVID-19 at a company in the Peruvian fishing sector Methods: The independent variable was occupational safety and health management, defined as the implementation of preventive and control measures in response to COVID-19. The dependent variable was defined as the number of detected COVID-19 cases and test positivity rate. We used a pre- (implementation phase) and post-test (following the implementation phase) study design. We performed a non-parametric inferential analysis to identify any significant pre- and post-test differences and any associations between the variables.

RESULTS: The company initiated a strategy to detect positive cases through the use of serological tests. During the first stage, 2329 tests were conducted, yielding a positivity rate of 71%. Once prevention and control actions were implemented, the positivity rate in August 2020 had decreased to 15.65%,, a statistically significant decrease (p<0.05), as well as its relationship to the measures implemented.

CONCLUSIONS: This occupational safety and health intervention significantly reduced the number of COVID-19 cases and positivity rate in this group of workers in the Peruvian fishing sector.

PMID:34965330 | DOI:10.12961/aprl.2021.24.03.02