bluuebunny/crossref_metadata_2025_split huggingface dataset:
Features of risk analysis, assessment and control methods in pharmaceutical development
Authors: Tishkov S. V. , Blynskaya E. V. , Alekseev K. V. , Alekseev V. K. 
Published: April 2023

Quality Risk Management (QRM) is an important aspect of pharmaceutical development in the Quality-by-Design paradigm, since it determines the Design Space, critical quality attributes and critical process attributes.The purpose of this review is to systematize and analyze the main aspects of the QRM system in relation to each element of pharmaceutical development. This review article discusses the following key elements of QRM such as: risk analysis, risk control, risk communication, risk verification. For risk analysis, the advantages and disadvantages of QRM tools such as Preliminary Hazard Analysis, Failure Mode Effects Analysis, Fault Tree Analysis are presented and analyzed, Hazard Operability Analysis and Hazard Analysis and Critical Control Points. In addition, a description of the methods of mathematical planning and design of experiments for pharmaceutical development and QRM is given and their significance for these systems is determined. Elements of QRM such as root cause analysis, brainstorming, and a corrective and preventive action procedure are given as risk control and mitigation tools.In this paper, the main stages of QRM are considered and conclusions are formulated regarding the main advantages and disadvantages of the methods of identification, analysis, control, risk reporting, and the main ways for further improvement of the presented system are proposed.
The relationship of lymphoid populations (infiltration) of the primary tumor with bone marrow immune responses in patients with breast cancer
Authors: Chulkova S. V. , Sholokhova E. N. , Poddubnaya I. V. , Stylidi I. S. , Egorova A. V. , Kozlov N. A. , Tupitsyn N. N. 
Published: April 2023

Backgraund. Currently, immunotherapy is firmly established in the standard of cancer treatment. The basis for the appointment of immunotherapy are immunological tumor markers, which include lymphoid infiltration, a detailed study of which has received increasing attention in the last decade. An undoubted interest is the study of lymphoid infiltration, not only depending on the morpho-clinical parameters of breast cancer (BC), but also on the immune system of the bone marrow.Aim. To evaluate the infiltration of the primary tumor by lymphocytes depending on the morpho-clinical characteristics of BC and immune responses in the bone marrow.Materials and methods. This study included 125 patients with BC who received treatment at the “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Health of Russia. Tumor stage II was prevailed, а moderate degree of differentiation (G2) was more often noted. The luminal BC – 67 %, non-luminal – 33 %. Immunophenotyping of the primary tumor: cryostat sections, ZEISS Axioscope luminescent microscope (Zeiss AG, Germany). CD45+, CD38+, T- and B-cell infiltration were assessed. Bone marrow: CD3+, CD4+, CD8+, CD19+, CD16+, CD56+ lymphocytes and their subpopulations were studied (FACSCanto II flow cytometer, Kaluza Analysis v2.1 program (Beckman Coulter, USA)).Results. CD45+ infiltration was noted in 50.5 % of cases (severe in 30 %, moderate – 26.4 %). CD8+ cells significantly infiltrated the tumor in 21.4 % of cases. CD38+ infiltration was observed in 40 %. In the non-luminal BC, severe CD45 infiltration was observed more frequently than in the luminal (33 % vs 26 %). CD38+ infiltration is expressed in non-luminal BC (p = 0.016). CD45+ infiltration was positively correlated with earlier stages (p = 0.071) more pronounced in infiltrative ductal BC, than in lobular BC: 59.2 % vs 20 % (p = 0.05). The content of CD45RO+cells in bone marrow in the luminal BC is higher than in the non-luminal: 37.3 ± 2.3 % vs 28 ± 2.8 % (p = 0.04). The number of CD19+CD38+ cells, on the contrary, is less: 24.2 ± 2 % vs 34.8 ± 6 % (p = 0.041). Tumor-infiltrating lymphocytes highly correlated with bone marrow lymphoid populations: CD38+ cells with NK-bone marrow cells; CD4+ cells with the B-precursors; CD8+cells with the B1-lymphocytes.Conclusion. Lymphoid infiltration of BC is associated with stage, tumor size, histological type and biological subtype. Intratumoral populations CD38+, CD4+, CD3+, CD8+ cells are in a negative correlation with bone marrow lymphoid populations.
Nanoprobes based on fluorescent semiconductor nanocrystals and single-domain antibodies for highly sensitive detection of epidermal growth factor receptor in tumor cells
Authors: Nifontova G. O. , Kalenichenko D. V. , Baryshnikova M. A. , Sokolova Z. A. , Samokhvalov P. S. , Karaulov A. V. , Sukhanova A. V. , Nabiev I. R. 
Published: April 2023

Background. The development of highly oriented conjugates of quantum dots (QDs) and single-domain antibodies (sdAbs) as innovative fluorescence imaging nanoprobes that specifically recognize tumor biomarkers, in particular, epidermal growth factor receptor (EGFR), is a promising approach to improving immunohistochemical tumor typing.Aim. The study was aimed at developing fluorescent nanoprobes based on QDs and sdAbs that specifically recognize EGFR, as well as evaluating their functional characteristics (size and optical properties) and functional activity.Materials and methods. QDs were obtained using high-temperature organometallic synthesis and transferred into the aqueous phase by means of stepwise replacement of ligands on the QD surface. The QDs and sdAbs were conjugated in an oriented manner using a bifunctional cross-linking agent. Detailed characteristics of the resulting conjugates were analyzed by the dynamic light scattering and immunoassay methods. Functional activity was assessed on the model human epidermoid carcinoma cells line A431.Results. The QD–sdAb conjugates have been standardized in terms of control parameters determining their functional activity, in particular, hydrodynamic diameter and efficiency of binding with target tumor cells. They are characterized by high dispersity, homogeneity, and specific functional activity towards their molecular target.Conclusion. The results demonstrate the potential use of the designed QD–sdAb conjugates for EGRF detection in immunohistochemical typing of tumor.
Pharmaceutical development for transdermal dosage forms of nifedipine: justification of the choice and specificity of the action
Authors: Tokaev V. V. , Stepanova E. F. , Makieva M. S. , Morozov Yu. A. , Pozdnyakov D. I. , Gagloeva D. I. 
Published: April 2023

Background. Present day in medicine can be assessed as an active period of the fight against cardiovascular diseases. This group of diseases cannot be considered obsolete in any way, and even taking into account the emerging new pathology – coronavirus infection – cardiovascular diseases have consolidated their dominant position. Among the drugs used for appropriate pharmacotherapy, stands out nifedipine (1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridindicarboxylic acid dimethyl ether) – a drug that can inhibit the flow of calcium into the cardiomyocytes of vascular smooth muscle cells. The drug has been on the domestic pharmaceutical market for quite a long time, but it is still in demand. However, nifedipine has quite pronounced side effects, including those associated with its oral administration – nausea caused by irritation of the gastrointestinal tract, rarely gum hyperplasia. And at the same time, the main modern dosage form of nifedipine is tablets. Therefore, expanding the range of its dosage forms is an urgent issue. Moreover, well-chosen dosage forms reduce the side effect of the drug. This is especially true for extended versions. So pharmaceutical development in relation to the creation of original dosage forms of nifedipine is quite appropriate.Aim. Determination of the possibility of absorption of nifedipine from the proposed dosage forms – transdermal patch and transdermal gel.Materials and methods. To determine nifedipine in rat blood plasma samples, high-performance liquid chromatography was used (chromatograph “Millichrome A-02” (Institute of Chromatography “EcoNova”, LLC, Russia).Results. Chromatograms of blood plasma samples of all animals on whose skin a transdermal gel or patch was applied revealed a peak coinciding in retention time with the peak of the standard sample of nifedipine.Conclusion. The possibility of penetration of nifedipine from the patch and transdermal gel through intact animal skin has been confirmed.
A template for exempting and protecting children from COVID vaccination
Authors: Rennebohm Robert M. 
Published: April 2023

In the era of the COVID-19 pandemic, medical professionals and broader community are being heavily pushed to vaccinate against COVID. In many cases, vaccination was mandatory, usually without proper informed consent. Many citizens questioned reasonableness of the mass vaccination campaign, especially vaccination of children, and, accordingly, asked to be exempted from the compulsory vaccination.
This document is aimed to exempt and protect children from vaccination against COVID, and is intended to inform everyone involved in making vaccination decisions. Not a single child should be given any of the COVID vaccines. Naturally acquired immunity against COVID significantly exceeds the immunity induced by vaccines. The interaction between the immune system and viruses is multidimensional and involves complex and delicate adjustments in both the virus and the immune system at the individual and population level. COVID vaccines use a simplified, one-dimensional, exclusionary approach that can disrupt important components and functions of the immune system. The mass vaccination campaign against COVID causes serious damage to the immune ecosystem, it is responsible for generation of a long series of new dominant variants that become more contagious and resistant to vaccines (due to the phenomenon of immune escape) and will inevitably become more virulent. This is based on the fundamental laws of natural selection and was predictable. The organizers of the mass vaccination campaign failed to assess the complexity and sensitivity of the immune ecosystem and, thus, prolonged the COVID-19 pandemic and made it catastrophically dangerous. COVID vaccines have proven unable to prevent infection or transmission of the virus. The virus, as expected, quickly became resistant to vaccine neutralizing antibodies.
For the above-mentioned scientific reasons, the mass vaccination campaign against COVID must be stopped for the whole of humanity and especially for children.
Assessment of hematological parameters in children with COVID-19 in the Republic of Sakha (Yakutia)
Authors: Evseeva Sardana A. , Klimova Tatiana M. , Bogdashin Vladimir V. , Makarova Avgustina M. , Sleptsova Snezhana S. , Burtseva Tatiana E. , Chasnyk Vyacheslav G. 
Published: April 2023

BACKGROUND:During the coronavirus pandemic, one of the most important areas of scientific research was the study of laboratory parameters, as well as calculated indices that could be used as criteria reflecting the course of the infectious process, and could be used as predictors of severe course and adverse outcome of the disease.
AIM:Assessment of hematological parameters in children with COVID-19 in the Republic of Sakha (Yakutia).
MATERIALS AND METHODS:The article presents data from a retrospective study of 344 cases of a new coronavirus infection caused by the COVID-19 virus (ICD-10 code U07.1) in children hospitalized in the period from 03/23/202012/27/2020 in the Childrens Infectious Clinical Hospital of Yakutsk.
RESULTS:The results of the study showed that upon admission to the hospital, the proportion of children with reduced leukocyte levels exceeded the proportion of children with leukocytosis (23 versus 10%), there were reduced hemoglobin levels, changes in the content of platelets, segmented neutrophils, lymphocytes. The rate of erythrocyte sedimentation was increased in 48% of children. Neutrophilia and lymphopenia were associated with the severity of the childrens condition. The values of the ratio of neutrophils to lymphocytes in some age groups were associated with the severity of the condition of children.
CONCLUSIONS:The infectious process in children with a new coronavirus infection is accompanied by a change in the leukocyte formula, an increase in ESR and a change in the platelet content. Neutrophilia and lymphopenia are associated with the severity of the condition of children.
Calibration of mb(Pn), mb(Lg) scales and transportability of the M0:mb discriminant to new tectonic regions
Authors: Priestley Keith F. , Patton Howard J. 
Published: April 2023

Abstract
We have developed M0:mb relationships for earthquakes and explosions in central Asia using regional waveform data from the Chinese broadband, digital station, WMQ. Regional magnitude scales, mb(Pn) and mb(Lg), were established by (1) determining the attenuation rates of Pn and Lg waves, (2) calibrating the mb(Pn) against the teleseismic mb, and (3) applying Nuttli's method to determine mb from the Lg waves. Seismic moments for earthquakes and explosions were obtained by applying the Bolt and Herraiz (1983) method calibrated using CMT moments for earthquakes and regional moment estimates of the Soviet Joint Verification Experiment (JVE) explosion. The results show that M0:mb(Pn) relationships for central Asian earthquakes and explosions are in excellent agreement with the relationships for the western United States. This demonstrates that the M0:mb discriminant is transportable to other regions and supports theoretical claims (Patton and Walter, 1993) that M0:mb are directly comparable for explosions detonated in different emplacement media. Successful application depends upon correcting the mb(Pn) for the magnitude bias known to exist between the Shagan River test site and the Nevada Test Site (NTS). In general, region-specific mb bias must be accounted for whenever regional magnitude scales are calibrated against teleseismic mb, as pointed out by Douglas and Marshall (1996). Transporting M0:mb(Lg) can be problematic because attenuation rates based on coda waves or Lg waves from earthquakes may not necessarily apply to Lg waves from explosions, and vice versa. This is demonstrated for the western United States where the coda Q measured from explosion data is much lower than the coda Q from earthquake data. We show that mb(Lg) for earthquakes located close to NTS is greatly overestimated using the Q values determined from the coda of NTS explosions. This is apparently not a problem for Lg calibration in central Asia, perhaps because of differences in velocity and/or Q structures for the two regions. Other important considerations are the character of Lg propagation on short paths (&lt;400 km) for NTS explosions versus long paths (1000 km) for East Kazakh explosions and the properties of coda-wave spreading as a function of distance and velocity structures for different tectonic regions.
Regional discrimination of chemical explosions and earthquakes: A case study in Morocco
Authors: Plafcan Dan , Sandvol Eric , Seber Dogan , Barazangi Muawia , Ibenbrahim Aomar , Cherkaoui Taj-Eddine 
Published: April 2023

AbstractTo examine the limitations in the techniques for discriminating between chemical explosions and earthquakes at local and regional distances, we have applied several standard heuristics to seismic events in northwest Morocco where little a priori information was available. Although the eight Oud Zem phosphate mine explosions have similar geographic locations, total charge size, and presumably ripple-fired mechanisms, the seismic recordings are characterized by a surprising amount of diversity. Time and path independent modulations, due to the periodic source mechanism of the ripple-fired explosions, rarely unequivocally distinguish the explosions from the earthquakes. Our findings imply that more often than the current literature suggests, source inconsistencies such as differing blasting arrangements have a role in the failure of common discriminants. Furthermore, crustal seismic velocity and the attenuation structure seemed to shape the seismic signals more than the nature of the source mechanism, although site effects could not be ruled out. The 10-to 15-Hz Pg/Sg ratio test proved to be the most precise and accurate discriminant. Popular intraphase spectral and cross-spectral ratios performed considerably worse. Finally, we argue that a regional case-based approach requires extensive regional information to meet the demanding verification goals of the Comprehensive Test Ban Treaty.
A mathematical theorem useful for the direct estimation of seismic source spectra
Authors: Kim S. G. , Chen Y.-T. , Wu Z.-L. , Panza G. F. 
Published: April 2023

Abstract
In this note, we prove a mathematical theorem for the direct estimation of the source spectra of earthquakes using a single seismogram. Considering a combination of Fourier spectra, the effects of the “source term” and the “attenuation term” from a single seismogram can be separated. Using signal-processing techniques, such an approach may be expressed in terms of the estimation of the Wigner distribution.
Soil response on the Fraser delta to theMW= 5.1 Duvall, Washington, earthquake
Authors: Cassidy John F. , Rogers Garry C. , Weichert Dieter H. 
Published: April 2023

AbstractStrong-motion recordings of the 3 May 1996 MW = 5.1 Duvall, Washington, earthquake made in southwestern British Columbia provide the best constraints, to date, on soil response to seismic shaking on the Fraser delta, just south of Vancouver. A total of nine strong-motion instruments in southern B.C. triggered during this earthquake, seven of which are on or near the Fraser delta. These recordings were made at epicentral distances of 140 to 180 km. A preliminary analysis of these data clearly shows that for low frequencies (&lt;3 Hz) seismic spectral amplification (by a factor of 2 to 7) occurs on the Fraser delta relative to nearby bedrock or thin firm-soil sites. However, at higher frequencies, moderate attenuation is observed at the Fraser delta sites. The largest peak ground accelerations recorded (generally around 2 to 3 Hz) were not on the thickest delta sediments but nearer the edge of the delta. Peak amplification is more pronounced in the horizontal component of ground motion than in the vertical. The average SH/Z ratio for peak values at the Fraser delta sites is 4.5 ± 0.9 compared to 1.6 ± 0.6 for the bedrock and firm-soil sites. In addition to the strong-motion records, we also utilize five three-component broadband recordings of this earthquake made in southern B.C. (epicentral distances of 140 to 520 km), and 12 short-period vertical-component recordings (epicentral distances of 130 to 380 km) to document attenuation of peak acceleration with distance for this earthquake. The observed values are slightly lower than those predicted by the ground-motion relations proposed for the year 2000 National Building Code of Canada.
Ultrasonography as an alternative to radiographs in assessing fracture healing
Authors: Sethia Dimple , Hadhimane Amith , Rai Kirthi Kumar 
Published: April 2023

To determine whether ultrasound can assess healing of bone and check the development of callus prior to conventional radiograph thereby enabling early diagnosis of delayed union or confirmation of union. Fracture healing was evaluated with ultrasonography and radiography on specific intervals until healing was complete; in 20 fracture sites. Based on the findings of ultrasonographic and radiographic scores were assigned to classify healing.18 out of 20 fracture sites had completely healed with mature callus formation at the end of 3 months while only 2 fracture sites showed delayed healing. In patients with normal healing, colour doppler ultrasound showed neovascularisation in the 1 month of healing. With time it was noticed that the depth and width of the fractured site was reducing and becoming more isoechoic with the adjacent normal bone sites. Assessment of these parameters being more evident on the USG were statistically significant when compared with OPG. Ultrasound can be considered as a useful guide in assessing fracture healing as a replacement to conventional imaging modalities such as the OPG, particularly in the early prediction of impaired fracture healing.
La exposición de información no financiera
Authors: Werbin Eliana Mariela , Cohen Natalia Lorena , Quadro Martín Ernesto 
Published: April 2023

La exposición completa (en inglés full disclosure) es una propuesta para la integración de información financiera y no financiera, que es analizada por organismos internacionales emisores de normas contables y de marcos de presentación voluntaria que siguen el objetivo de alinear la información que se presenta a los usuarios.
El objetivo de este artículo es analizar la normativa de exposición contable de información financiera y la importancia de la presentación voluntaria de información no financiera. Se presenta un estudio de análisis cualitativo de la información de informes de sustentabilidad publicados por bancos argentinos durante el período 2006 – 2020.
A Identifikasi Karakteristik Fisik Tanaman Sorgum Bioguma untuk Perancangan Mesin Perontok Sorgum
Authors: Nurhasanah Ana 
Published: April 2023

Proses mekanisasi perontokan tanaman sorgum yang efektif dan efisien memerlukan informasi tentang sifat-sifat teknis yang meliputi sifat fisik maupun mekanik dari jenis tanaman sorgum tersebut. Penelitian ini bertujuan memperoleh beberapa sifat fisik tanaman sorgum varietas bioguma pada bagian biji, batang dan daun untuk proses mekanisasi perontokan biji dan batang tanaman sorgum. Penelitian ini menggunakan metode deskriptif dengan jumlah ulangan 3 sampai 30 tergantung dari parameter yang diukur. Semua pengambilan sampel dilakukan secara acak. Tanaman sorgum yang diuji adalah dari beberapa lahan Majalengka dan Bogor. Karakteristik biji rata-rata mempunyai ukuran 4,58 x 4,32 x 2,64 mm dengan kadar air biji 7,5%, namun untuk biji dengan kadar air biji 30% berukuran rata-rata 5,2x4,8x2,3 mm. Tingkat kekerasan (breaking point/titik pecah) batang sekitar 13 KgF dan daya tarik malai rata-rata 0,4 KgF