bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutral Lipid Cacostasis Contributes to Disease Pathogenesis in Amyotrophic Lateral Sclerosis
Authors: Dodge James C. , Jensen Elizabeth H. , Yu Jinlong , Sardi S. Pablo , Bialas Allison R. , Taksir Tatyana V. , Bangari Dinesh S. , Shihabuddin Lamya S. 
Published: October 2020

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease characterized by motor neuron (MN) death. Lipid dysregulation manifests during disease; however, it is unclear whether lipid homeostasis is adversely affected in the in the spinal cord gray matter (GM), and if so, whether it is because of an aberrant increase in lipid synthesis. Moreover, it is unknown whether lipid dysregulation contributes to MN death. Here, we show that cholesterol ester (CE) and triacylglycerol levels are elevated several-fold in the spinal cord GM of male sporadic ALS patients. Interestingly, HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, was reduced in the spinal cord GM of ALS patients. Increased cytosolic phospholipase A2 activity and lyso-phosphatidylcholine (Lyso-PC) levels in ALS patients suggest that CE accumulation was driven by acyl group transfer from PC to cholesterol. Notably, Lyso-PC, a byproduct of CE synthesis, was toxic to human MNsin vitro. Elevations in CE, triacylglycerol, and Lyso-PC were also found in the spinal cord of SOD1G93Amice, a model of ALS. Similar to ALS patients, a compensatory downregulation of cholesterol synthesis occurred in the spinal cord of SOD1G93Amice; levels of sterol regulatory element binding protein 2, a transcriptional regulator of cholesterol synthesis, progressively declined. Remarkably, overexpressing sterol regulatory element binding protein 2 in the spinal cord of normal mice to model CE accumulation led to ALS-like lipid pathology, MN death, astrogliosis, paralysis, and reduced survival. Thus, spinal cord lipid dysregulation in ALS likely contributes to neurodegeneration and developing therapies to restore lipid homeostasis may lead to a treatment for ALS.SIGNIFICANCE STATEMENTNeurons that control muscular function progressively degenerate in patients with amyotrophic lateral sclerosis (ALS). Lipid dysregulation is a feature of ALS; however, it is unclear whether disrupted lipid homeostasis (i.e., lipid cacostasis) occurs proximal to degenerating neurons in the spinal cord, what causes it, and whether it contributes to neurodegeneration. Here we show that lipid cacostasis occurs in the spinal cord gray matter of ALS patients. Lipid accumulation was not associated with an aberrant increase in synthesis or reduced hydrolysis, as enzymatic and transcriptional regulators of lipid synthesis were downregulated during disease. Last, we demonstrated that genetic induction of lipid cacostasis in the CNS of normal mice was associated with ALS-like lipid pathology, astrogliosis, neurodegeneration, and clinical features of ALS.
Development and validation of a rapid UHPLC-MS/MS method for the determination of fenofibric acid in human plasma: Application to a pharmacokinetic study of fenofibrate tablet in Chinese subjects
Authors: Wu Xiaorong , Wang Yankai , Liang Binbin , Wu Honghai , Wu Liying , Song Jing , Liu Jianfang 
Published: October 2020

AbstractAn ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) method was developed to determine the fenofibric acid (FA) in human plasma and applied to a pharmacokinetic study of fenofibrate tablet (Lipanthyl® supra, 160 mg) on Chinese subjects which had not been reported. Bezafibrate was used as an internal standard (IS), and the plasma samples were precipitated by methanol. Multiple reaction monitoring (MRM) mode was used to quantitatively analyzed FA m/z 317.2 → 230.7 and the IS m/z 360.0 → 274.0 in the electrospray ionization (ESI) negative interface. The calibration curves were linear over the range of 50–30,000  ng/mL (r2  ≥  0.996). The intra-day and inter-day precision (coefficient of variation, CV%) was less than 2.7 and 2.5%, respectively. The accuracy (relative error, RE%) ranged from −4.5 to 6.9%. The average recovery was higher than 86.2%, and the matrix effect was between 95.32 and 110.55%. The simple, rapid, and selectivity method was successfully applied to the pharmacokinetic study of fenofibrate tablets on Chinese subjects.
Return to Work for People with Hand Injuries: Strategies and Barriers
Authors: Uys Michelle Elizabeth , Buchanan Helen , Van Niekerk Lana 
Published: October 2020

Introduction: The socio-economic burden of a hand injury in South Africa is substantial, particularly for manual labourers whose job tasks are physically demanding and require hand function. Barriers to participation in work occur on an economic, social and level, as well as on a therapist and client-specific level.Aim: This study aimed to identify the strategies and barriers encountered by occupational therapists in work-related transitions after a serious hand injury.Methods: A descriptive cross-sectional design was utilised. A questionnaire was developed for the study through a rigorous developmentdevelopment process that included piloting. The final instrument was disseminated as an online questionnaire to occupational therapists working within the field of return-to-work and hand injuries. As no data were available on the number of occupational therapists working within this field, convenience sampling was used with snowballing as a strategy to increase the number of possible respondents. Data were exported into Microsoft Excel and descriptive analyses were conducted.Results: Forty three occupational therapists completed the questionnaire. Respondents mostly focused on treating components of function (100%), addressing activities of daily living (97.67%) and issuing home programmes (97.67%) as direct intervention strategies to facilitate work-related transitions. One of the least used strategies was issuing assistive devices for work (30.23%). The least used work-specific strategies included conducting worksite visits, observing clients (or proxies) completing work tasks in the workplace and implementing work trials. Financial support and compensation were viewed as both an asset and a barrier.Conclusion: Without knowledge about the representability of the study sample, the results of this study cannot be generalised.However, the therapists who responded to the questionnaire were offering a range of strategies to address work-related transitions for people with serious hand injuries, despite the numerous barriers that exist.
THE VALUE OF BASAL EXPRESSION LEVEL OF HEMOXYGENASE-1 FOR SENSITIVITY OF HUMAN MELANOMA CELLS TO OXIDATIVE STRESS IN VITRO
Authors: Sidorova T. A. , Solomko E. Sh. , Khochenkova Yu. A. , Prokofieva A. A. , Khochenkov D. A. 
Published: October 2020

Introduction.The molecular basis of radio- and photodynamic therapy (PDT), the mechanism of action of a number of antitumor chemotherapy drugs is oxidative stress (OS). The enzyme hemoxygenase-I (НO-1), a molecular marker of OS, is a key participant in the system of protection and adaptation of tumor cells under stress.Objective.To find out whether the sensitivity of human melanoma tumor cells to OS depends on the basal and modulator-induced levels of НO-1 expressionMaterial and methods.Human melanoma cell lines were used in the study. The expression of mRNA НO-1 in cells was studied by real-time RT-PCR, the reactive oxygen species content in cells – by flow cytometry and the cytotoxicity of drugs – by MTT assay.Results.According to our data, human melanoma cells have different basal levels of HO-1 transcription: high (3.0–3.5 o. u.) in lines MelIL, MelP, medium (1.5 o. u.) in lines MeWo, MelZ, MelIbr and low (0.5 o. e.) – MelMe, A375).There is no direct correlation between the level of basal cell expression of HO-1 and their sensitivity to the OS inducer – Н2О2. The hemin-induced increase in HO-1 expression in cells is accompanied by doubled resistance to Н2О2. It was found that HO-1 repression in the presence of apigenin was registered in melanoma cells with different basal levels, but sensitization to Н2О2 (2–4 times) was observed only for cells with medium (MeWo) and low (A375) levels of basal HO-1 expression. It was found that the decrease in basal expression of HO-1 induced by apigenin is accompanied by an increase in the reactive oxygen species content in cells.Conclusions.The results of our research allow us to recommend natural flavon apigenin, a modulator of HO-1 expression, for inclusion in the chemotherapy and PDT regimens to increase the effectiveness of human melanoma treatment.
PRECLINICAL TOXICITY STUDY OF THE NEW ANTIFUNGAL DRUG AMPHAMID
Authors: Treschalin I. D. , Golibrodo V. A. , Treschalin M. I. , Tevyashova A. N. , Pereverzeva E. R. 
Published: October 2020

Introduction.Amphotericin B remains the drug of first choice in the treatment of most severe systemic fungal infections. However, it is characterized by very low solubility and high toxicity. Amphamide – semisynthetic derivative of Amphotericin B – have been prepared at the Gause Institute of New Antibiotics. It showed several advantages over amphotericin B in vivo.Objective.The aim of the study was to investigate the toxicological safety of amphamide drug formulation in chronic experiment on rats.Materials and methods.The study was performed in male and female Wistar rats. Amphamide drug formulation was injected intraperitonealy at the total doses of MTD and LD50(30 × 0,07 mg/kg or 30 × 0,17 mg/kg with 24-h interval). During the experiment body weight, hematological parameters, blood biochemical parameters, electrocardiography and urinalysis were performed. Animals were sacrificed on 1st and 30th day after the end of treatment. At necropsy, the mass coefficients of heart, liver, kidneys, spleen and thymus were calculated. The internal organs were subjected to histological evaluation.Results.It has been shown that the treatment with total dose of amphamide produces an increase of urea and creatinine level in serum, changes in urine composition and its specific gravity. Microscopic pathology observation showed dose-dependent structure abnormalities in kidneys, liver, lungs, stomach, and testes. Multiple administration of low dose of the drug produces transient toxic effects completely reversible within 30 days. When amphamide was used in a high dose, morphological signs of toxic cardiomyopathy were found.Conclusion.The results of the clinical and laboratory studies and microscopic pathology observation of kidneys demonstrate that nephrotoxicity is the main limiting type of drug toxicity. Dose dependence and reversibility within a month of toxic effects of amphamide allows us to recommend it to further advance.
EFFECT OF HLA-DR ANTIBODY CONCENTRATION ON ESTIMATION OF THE NUMBER OF CD14<sup>+</sup>HLA-DR<sup>LOW /–</sup>-CELLS IN THE BLOOD OF PATIENTS WITH B-CELL chronic lymphocytic leukemia
Authors: Ponomarev A. V. , Misyurin V. A. , Baryshnikova M. A. 
Published: October 2020

Introduction. Immunoregulatory functions of myeloid-derived suppressor cells have been extensively studied over the recent decades. Additionally, myeloid-derived suppressor cells have been investigated as a prognostic factor.Objective. To optimize the measurement of monocytic myeloid-derived suppressor cells in the peripheral blood of patients with B-cell chronic lymphocytic leukemia.Materials and methods. The number of myeloid-derived suppressor cells with CD14+HLA-DRlow/–-phenotype was determined in the peripheral blood of patients with B-cell chronic lymphocytic leukemia and healthy donors by flow cytometry. The measurement was carried out at two points, which differed in the concentration of anti-HLA-DR antibodies − 15 and 4 μl.Results. The median amount of myeloid-derived suppressor cells in the peripheral blood of B-cell chronic lymphocytic leukemia patients with 15 μl of anti-HLA-DR antibody was 1.9 %, and with 4 μl of antibody concentration – 7 %. Healthy donors had that median of 0.15 % with 15 μl of antibody and 0.3 % with 4 μl concentration.Conclusion. The number of CD14+HLA-DRlow/–-cells in the blood of patients with B-cell chronic lymphocytic leukemia is sensitive to the concentration of the HLA-DR antibody.Compliance with patient rights and principles of bioethics. The study protocol No 3 of 13.02.2020 was approved by the biomedical ethics committee of Research Institute of Experimental Diagnostics and Therapy of Tumors N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation. All patients gave written informed consent to participate in the study.
Discrimination of Small Earthquakes and Buried Single-Fired Chemical Explosions at Local Distances (&lt;150  km) in the Western United States from Comparison of Local Magnitude (ML) and Coda Duration Magnitude (MC)
Authors: Koper Keith D. , Holt Monique M. , Voyles Jonathan R. , Burlacu Relu , Pyle Moira L. , Wang Ruijia , Schmandt Brandon 
Published: October 2020

ABSTRACTSeismologists distinguish underground nuclear explosions from more commonly occurring earthquakes using moment tensor inversion, high-frequency P/S amplitude ratios, mb:Ms comparisons, and P-pP differential travel times. These methods are generally successful for large seismic events (M&gt;3–4) well recorded at regional-to-teleseismic distances (&gt;150  km); however, it is unclear whether they can be modified to work for small events (M&lt;3) well recorded only at local distances (&lt;150  km). Here, we evaluate a recently proposed, local-distance seismic source discriminant—the difference between local magnitude (ML) and coda duration magnitude (MC)—using seismograms of earthquakes and buried, single-fired chemical explosions recorded in three regions of the western United States. The quantity ML–MC was previously found to be sensitive to source depth, effectively discriminating mine blasts, induced earthquakes, and very shallow tectonic earthquakes from deeper crustal earthquakes. In this study, we report the first evaluation of ML–MC as a depth discriminant using data from buried, single-fired explosions that, unlike the seismic sources studied earlier, are good analogs for underground nuclear explosions. We find that even when using generic, uncalibrated methods of assigning magnitudes, ML–MC separates single-fired explosions and earthquakes. The area under the receiver operating characteristic curve is 0.92 for 19 explosions and 14 earthquakes in Washington, 0.90 for 22 explosions and 90 earthquakes in Wyoming, and 0.99 for three explosions and 149 earthquakes in Nevada. ML:MC comparisons have the potential to enhance discrimination based on high-frequency P/S amplitudes ratios—which perform less well at local than regional distances—because the two metrics have complementary sensitivities.
Preparedness for prevention and Mitigation guidelines of COVID -19 at Academic Medical institute
Authors: M Mohsen Dalia , E Saad Ibrahim , Alawm Khaled , Dogham Rawhia , Mohieeldin Hazem 
Published: October 2020

The (n-COVID -19) novel coronavirus 2019 has been recognized as a highly pathogenic virus that infects the human respiratory tract and has high morbidity and mortality. The n-COVID -19 is an enormous burden on health-care facilities, causing approximately 2.1% mortality so far. Countries globally are at risk of developing pneumonia due to this novel Corona Virus. The surge of coronavirus disease 2019 (COVID-19) cases reached over 100 countries with more than 100,000 cases. The disease is fast spread among human, due to the assessment of transmission methods still not clear. Infection prevention control measures are essential in medical institutes. A poor understanding of the disease among academic and non-academic employees may result in delayed treatment and the rapid spread of infection. This study aimed to investigate and assess the level of preparedness, knowledge, and perceptions of the medical institute employees about COVID-19.A cross-sectional, web-based study was conducted among academic and non-academic employees about COVID19 during the period from July to August 2020. The actual preparedness level of medical institutes can be determined by examining academic and non-academic employees' perceptions. A 33-item questioner survey instrument was developed and distributed using employees' email; it required 5 minutes to complete. A questionnaire survey concerning the perceptions of risks and countermeasures and knowledge about novel coronavirus 2019 was distributed at different Medical institutes. A chi-square test was used to investigate the level of association among variables at the significance level of p&#60;0.05.All participants completed the survey. Seventy-five valid questionnaire responses were received and analyzed. After adjusting for sex, specialty, Qualification, and years of experience, knowledge of preventive measures (K-scores) in the medical institute, institutional measures (I-scores) were found to be more indicative of the level of preparedness across the institution.As the global danger of COVID-19 continues to emerge, it is critical to improving the knowledge and perceptions of academic and non-academic employees. Educational interventions are urgently needed to reach academic and non-academic employees beyond borders. Substantial differences in emergency infection prevention and control measures, as perceived by academic and non-academic employees exist in a medical institute. Furthermore, to achieve a higher level of preparedness for prevention and mitigation for infectious diseases, Medical institutions should designate and implement effective mitigation guidelines of COVID -19 at Academic Medical institute.
Prevalence of inducible clindamycin resistance among Staphylococcus aureus isolates from a tertiary care hospital
Authors: Samal Badhuli , Padekar Hira , Dash Lona , Shastri Jayanthi 
Published: October 2020

Clindamycin is an excellent drug for skin and soft tissue Staphylococcus aureus infections, but resistance mediated by inducible macrolide-lincosamide-streptogramin B (iMLS)phenotype leads to in vivo therapeutic failure even though they may be in vitro susceptible in Kirby–Bauer disk diffusion method (KBDDM). Hence the study was undertaken to detect the prevalence of iMLS phenotype among Staphylococcus aureus isolates by double disk approximation test (D-test) in a tertiary care hospital. A total of 100 consecutive Staphylococcus species isolates were identified by standard microbiological methods and subjected to antimicrobial susceptibility testing by KBDDM. Clindamycin-resistance either in the form of iMLSB or cMLSB was determined through double disk diffusion method or D-test by using erythromycin (2 μg) and clindamycin (15μg) as per the CLSI guidelines. Out of 100 Staphylococcus species studied, 50(50%) were methicillin sensitive Staphylococcus aureus, 30(30%) were Methicillin resistant Staphylococcus aureus and 20 (20%) were Coagulase negative Staphylococci. Out of 80 Staphylococcus aureus studied, iMLSB, cMLSB and MS phenotype were 32.5%, 1.25%, 5% respectively. Inducible resistance and MS phenotype were found to be higher in MRSA as compared to MSSA (60%, 6.66% and 16%, 4% respectively). The study revealed 32.5% of Staphylococcus aureus isolates were inducible clindamycin resistant, which could be easily misidentified as clindamycin susceptible in Kirby–Bauer disk diffusion method. Therefore, clinical microbiology laboratory should routinely perform D-test in all clinically isolated Staphylococcus aureus to guide clinicians for the appropriate use of clindamycin.
ESCRITOS MÉDICOS SOBRE A INFÂNCIA NO BRASIL (1832-1882)
Authors: CINTRA MARIANA DE PAULA 
Published: October 2020

No Brasil do século XIX, e mais proeminentemente no Rio de Janeiro, médicos e estudantes de medicina produziram uma série de trabalhos que tinham como propósito disseminar os saberes acadêmicos sobre as doenças, os tratamentos, a nutrição e a higiene da criança. Segundo esses escritos, estava em construção uma ciência médica nacional preocupada em moralizar as práticas cotidianas que diziam respeito à família: o parto, a higiene, a alimentação, a limpeza dos ambientes privados, entre outros. A partir de um movimento mais amplo de primazia dos seres frágeis na medicina portuguesa do século XVIII e, mais tarde, no Brasil, a proposta deste artigo é mapear quais foram os saberes veiculados sobre o trato infantil nos primeiros cinquenta anos da Faculdade de Medicina do Rio de Janeiro, com ênfase em dois aspectos amplamente difundidos nas teses médicas do período: a prevenção e a medicação.

Palavras-chave: Medicina. Crianças. Saúde. Prevenir. Medicar.
Editorial
Authors: Fernández-Morales Flavio Humberto 
Published: October 2020

Al iniciar su segunda década de existencia, la Revista de Investigación, Desarrollo e Innovación (RIDI), ha decidido abandonar la versión impresa y mudar al formato digital. El papel, tan querido por quienes disfrutan la manipulación del texto de manera tangible, ha dejado de ser una opción viable para la divulgación de los contenidos. Ejemplo de ello, es que, por limitación de espacio, las bibliotecas universitarias ya no aceptan el canje en papel, sino que se hace de forma digital.
Igualmente, los costos ambientales y económicos asociados a la impresión y distribución de los ejemplares, se pueden reorientar a la mejora de los procesos editoriales, lo que redundará en la calidad de la revista.
En adelante, RIDI continuará difundiendo sus contenidos a través de su página web, la cual aprovecha las bondades de la plataforma Open Journal System (OJS), y en la que se encuentran disponibles todos los números de la revista.
Esperamos que este cambio redunde en beneficio de nuestros usuarios, a saber: autores, lectores y comunidad académica, al brindar mayor agilidad en la publicación de los artículos, junto a una mayor visibilidad de los contenidos.

En el presente fascículo, Vol. 11 No. 1, se incluyen catorce artículos, resultado del proceso investigativo en temáticas relacionadas con administración, educación e ingeniería, los cuales invitamos a consultar y utilizar en sus investigaciones. Asimismo, se invita a los interesados en publicar los resultados de sus trabajos de investigación, a que envíen sus manuscritos a la revista; los requisitos de forma se pueden consultar en nuestra página WEB, en las instrucciones para los autores.

Cordialmente,

FLAVIO HUMBERTO FERNÁNDEZ MORALES
Editor
Revista de Investigación, Desarrollo e Innovación
ISSN: 2027-8306 - ISSN-e: 2389-9417
Universidad Pedagógica y Tecnológica de Colombia