bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA methylation patterns suggest the involvement of DNMT3B and TET1 in osteosarcoma development
Authors: Pires Sara Ferreira , de Barros Juliana Sobral , Costa Silvia Souza , Scliar Marília Oliveira , Lengert André Helvoort , Boldrini Érica , Silva Sandra Regina Morini , Tasic Ljubica , Vidal Daniel Onofre , Krepischi Ana Cristina Victorino , Maschietto Mariana
Published: August 2022

Osteosarcomas commonly arise during the bone growth and remodeling in puberty, making it plausible to infer the involvement of epigenetic alterations in their development. We investigated DNA methylation and related genetic variants in 28 primary osteosarcomas aiming to identify deregulated driver pathways. Methylation and genomic data was obtained using the Illumina HM450K beadchips and the TruSight One sequencing panel, respectively. Aberrant DNA methylation was spread throughout the osteosarcomas genomes. We identified 3,146 differentially methylated CpGs comparing osteosarcomas and bone tissue samples, with high methylation heterogeneity, global hypomethylation and focal hypermethylation at CpG islands. Differentially methylated regions (DMR) were detected in 585 loci (319 hypomethylated and 266 hypermethylated), mapped to the promoter regions of 350 genes. These DMR-genes were enriched for biological processes related to skeletal system morphogenesis, proliferation, inflammatory response and signal transduction. Six tumor suppressor genes harbored deletions or promoter hypermethylation (DLEC1, GJB2, HIC1, MIR149, PAX6, WNT5A), and four oncogenes presented gains or hypomethylation (ASPSCR1, NOTCH4, PRDM16, RUNX3). Our analysis also revealed hypomethylation at 6p22, a region that contains several histone genes. DNMT3B gain was found to be a recurrent copy number change in osteosarcomas, providing a possible explanation for the observed phenotype of CpG island hypermethylation. While the detected open-sea hypomethylation likely contributes to the well-known osteosarcoma genomic instability, enriched CpG island hypermethylation suggests an underlying mechanism possibly driven by overexpression of DNMT3B likely resulting in silencing of tumor suppressors and DNA repair genes.
Measurements of decaying grid turbulence with various initial conditions
Authors: Zhao Yongfei , Yang Yang , Li Mingshui , Lei Yongfu , Peng Yuxuan
Published: August 2022

The uniform grid is widely used for the aim of generating the approximately homogeneous and isotropic turbulence. Although many previousstudies have investigated the influence of initial conditions of the uniform square grids, including the Reynolds number, mesh size, bar size,cross-section of bar and solidities, on the statistical characteristics ofthe grid turbulence, the influence of mesh shape has rarely been studied. Compared to the traditional uniform square grid, the present workinvestigates the influence of different mesh shapes (the uniform non-square grid) on the grid turbulence, and this change of mesh shape canbe easily achieved based on the traditional uniform square grid. Thework found that in the cases of uniform non-square grid, the distance ofturbulence needs to fully develop is shorten, the low frequency components of fluctuating velocity increase while high frequency componentsdecrease, leading to the difference of energy distribution. Meanwhile, theuse of uniform non-square grid reduces the anisotropies of decaying turbulence to a certain extent. The skewness is much closer to the theoreticalvalue 0, while the flatness almost remains unchanged. The decay exponents and power-law coefficients obtained are affected by the mesh shapeand the decay exponent could be much closer to 1. Furthermore, largerintegral length scales can be obtained at the same downstream position by using the uniform non-square grid, compared to traditional uniformsquare grid. This may better meet requirements of large-scale turbulence in some engineering communities, such as the wind engineering
Freeze-and-Mutate: Abnormal Sample Identification for DL Applications through Model Core Analysis
Authors: Wang Huiyan , Chen Ziqi , Xu Chang
Published: August 2022

Deep learning (DL) applications, representing an emerging form of new software, are gaining increasing popularity by their intelligent and adaptive services. However, their service reliability depends highly on the prediction accuracy of their internally-integrated DL models. In practice, DL models are often observed to suffer from ill predictions upon abnormal inputs (e.g., adversarial attacking samples, out-of-distribution (OOD) samples, and etc.), and this could easily lead to unexpected behaviors or even catastrophic consequences (e.g., system crash). One promising way to guard the application reliability is to reveal such abnormal inputs in time before they are fed to the DL models integrated in the concerned applications. Then remedy actions (e.g., discarding or fixing these inputs) can be done to protect applications from acting abnormally. Existing work addressed this revealing problem by either making sample distance-comparison based analysis or generating sufficient model mutants for comparative analysis. However, such treatments caused a restricted focus on samples only, while overlooking the DL models themselves, or had to analyze massive mutants, incurring non-negligible overheads to applications. In this article, we propose a novel approach, NetChopper, to conducting a core analysis on the target DL model, and then partitioning it into two parts, one associating closely with the training knowledge being the model core (expected to be important and thus stable), and the other being the remaining part (expected to be immaterial and thus changeable). Based on such partitioning, NetChopper proceeds to preserve (or freeze) the model core, but mutate the remaining part to produce only a small number of model mutants. Later, NetChopper becomes able to reveal abnormal inputs from normal ones by exploiting these model-relevant and light-weight mutants only. We experimentally evaluated NetChopper by widely-used DL subjects (e.g., MNIST+LeNet4, and CIFAR10+VGG16) and typical abnormal inputs (e.g., adversarial and OOD samples). The results reported NetChopper's promising AUROC scores in revealing the abnormal degrees of inputs, generally and stably outperforming, or comparably effective as, state-of-the-art techniques (e.g., mMutant, Surprise, and Mahalanobis), and also confirmed its high effectiveness and efficiency (with only marginal online overhead).
Topology and adenocarcinoma cell localization dataset on the labyrinthin diapeutic biomarker
Authors: Sharma Ankit , Babich Michael , Li Tianhong , Radosevich James A.
Published: August 2022

Objective:
The discovery and characterization of tumor associated antigens is increasingly important to advance the field of immuno-oncology. In this regard, labyrinthin has been implicated as a neo-antigen found on the cell surface of adenocarcinomas. Data on the 1) topology, 2) amino acid (a.a.) homology analyses and 3) cell surface localization of labyrinthin by fluorescent activated cell sorter (FACS) are studied in support of labyrinthin as a novel, pan-adenocarcinoma marker.
Results:
Bioinformatics analyses predict labyrinthin as a type II protein with calcium binding domain(s), N-myristoylation sites, and kinase II phosphorylation sites. Sequence homologies for labyrinthin (255 a.a.) were found vs. the intracellular aspartyl/asparaginyl beta-hydroxylase (ASPH; 758 a.a.) and the ASPH-gene related protein junctate (299 a.a.), which are both type II proteins. Labyrinthin was detected by FACS on only non-permeablized A549 human lung adenocarcinoma cells, but not on normal WI-38 human lung fibroblasts nor primary cultures of normal human glandular-related cells. Microscopic images of immunofluorescent labelled MCA 44-3A6 binding to A549 cells at random cell cycle stages complement the FACS results by further showing that labyrinthin persisted on the cell surfaces along with some cell internalization within 20 minutes.
An Automated System for Cephalometric Soft-tissue Landmark Detection
Authors: Elaiwat Said , Azad Mohammad , Alam Mohammad
Published: August 2022

The ability to detect cephalometric landmarks in x-ray images plays a crucial role in several medical applications, including orthodontics and maxillofacial surgery. The manual annotation of landmarks is time-consuming and prone to inaccuracy. These limitations can be overcome by building a system for automated landmark detection. Towards this goal, we propose a fully automated system for the task of soft-tissue landmark detection. The proposed method combines two different types of descriptors, Haar-like features and spatial features, to build a strong classifier using Adaboost technique. In order to evaluate the proposed method, we introduce a new dataset for soft-tissue landmark detection task along with two evaluation protocols to define detection rate. The first protocol represents the detection rate within mean radial error (MRE) while the second protocol represents the detection rate within a predefined confidence region R. Reported experiments demonstrate the superior performance of the proposed method compared to state-of-the-art.
Effects of combination treatment using arsenic trioxide and resveratrol on human breast cancer (MCF-7) cells
Authors: Hu Hongye , Zhu Xiaofang , Zhang Xiaohua , Huang Guanli
Published: August 2022

Background: Arsenic trioxide (ATO) has shown remarkable efficacy in the treatment of cancer. Resveratrol (RSV) has anti-tumor, anti-aging, and anti-inflammatory properties. We examined the anti-cancer effects of using ATO plus RSV together against human breast cancer (MCF-7) cells.Methods: MCF-7 cells were treated with ATO (0–16 μM) alone or combined with RSV (0–100 μM). Cell viability and percent apoptosis were estimated using Cell Counting Kit-8, the TUNEL assay and microscopy. mRNA and protein expression of caspase-3, caspase-7, Bax, and B-cell lymphoma (Bcl)-2 were assessed by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Chromatin immunoprecipitation (ChIP) was adopted to determine the histone acetylation of the promoter regions of caspase-3, caspase-7, Bax, and Bcl-2.Results: Combined treatment was more efficacious than treatment of ATO alone or RSV alone in suppressing the viability of MCF-7 cells. The intracellular mechanisms of cytotoxicity of ATO+RSV treatment were revealed to be a relative increase in mRNA and protein expression of caspase-3, caspase-7, and Bax, and relative decrease in Bcl-2, in MCF-7 cells. ChIP results showed that combined treatment increased the acetylation of histone H3K27 in the promoter region of caspase-3, caspase-7, and Bax, but decreased the acetylation of histone H3K27 in Bcl-2.Conclusion: Combination therapy using ATO and RSV could be employed for BC treatment.
Mentorship matters: the example of mentoring by Dr. Alberto F. García – a role model for future Colombian academic trauma and emergency surgeons
Authors: Manzano-Nunez Ramiro
Published: August 2022

Purpose Little is known about the current status of mentoring and mentorship programs in the Colombian surgical community. This report aims to present the example of Dr. Alberto Federico García's mentoring to inform Colombian surgeons interested in mentoring young individuals who desire to pursue a surgical career. To this end, this paper describes Dr. Garcia's mentees' academic trajectory since they started working with him. Methods The academic trajectory of Dr. Garcia’s mentees was descriptively analyzed. Results Since 2015, 5 young physicians worked under the mentorship of Dr. Garcia at FVL university hospital in Cali, Colombia. All the mentees had a considerable rise in their research outputs since they started working with Dr. Garcia. Overall, the mentees submitted and presented abstracts in surgical meetings and got accepted into a residency program in general surgery. Conclusion This paper depicts a consistent improvement in the academic performance of Dr. Garcia's mentees during the period they worked with him, including research output and the mentees' personal goal of getting admitted to a general surgery residency program.
Predictive Risk Model for the Development of Encephalopathy in Patients with Nutritional Pancreatic Necrosis
Authors: Mikhin V. S , Burchuladze N. Sh. , Popov A. S. , Turovets M. I. , Mikhin I. V. , Kitaeva A. V.
Published: August 2022

The objective: to develop a predictive model for assessing the risk of developing encephalopathy (EP) in patients with nutritional pancreatic necrosis.

Subjects and Methods. A single-center prospective cohort study was conducted at Faculty Surgery Clinic of Volgograd State Medical University from 2010 to 2020. Logistic regression analysis was used to build a model for predicting the risk of developing EP.

Results. A total of 429 patients were included in the study. It was determined that in the majority of patients EP manifested in the first three days after hospitalization. A statistically significant predictive model of correlation of the risk to develop EP with clinical and demographic variables showed that an increase in the severity of the patient's condition (according to the SOFA scale) by 1 point increased the risk by 1.9 times, and an increase in bilirubin levels by 1 μmol/l, and urea by 1 mmol/l increased the risk of AED by 8.0% and 28.0%, respectively. In non-alcoholic pancreatic necrosis, compared with the alcoholic genesis of the disease, and when using early (before day 3) enteral nutrition, there was a significant reduction in the risk of developing EP by 175.5% and 137% of cases. The specificity and sensitivity of the model were 78.7% and 82.8%, respectively.

Conclusions. In nurtitional pancreatic necrosis, an increase in the severity of the patient's condition, alcoholic genesis of the disease, progression of signs of liver and kidney failure significantly increased the risk of developing EP. At the same time, early enteral nutrition contributed to a significant reduction in the risk of this complication. The presented predictive model is recommended to be used in routine clinical practice.
Comparison of Effectiveness of Pressure Support and Mandatory Ventilation Modes at the End of General Combined Anesthesia
Authors: Pyzhov V. A. , Khrapov K. N. , Miroshkina V. M.
Published: August 2022

The objective: to compare effectiveness of pressure support and mandatory ventilation modes at the final stage of general anesthesia.

Subjects and Methods. 58 patients were included in the study. All patients underwent laparoscopic or open surgery under combined general anesthesia with muscle relaxants and tracheal intubation. At the end of the operation, after suturing the muscle layer, patients were randomly divided into two groups, depending on the further mode of ventilation: the mandatory mode group with dual control until extubation (n = 29) and the spontaneous breathing mode group with pressure support (n = 29). The time of awakening, the severity of post-extubation cough, hemodynamic parameters and oxygenation immediately before and 5 minutes after extubation were assessed.

Results. In the groups of patients, statistically significant differences were observed in the time of awakening (252 ± 67 sec and 426 ± 71 sec in PSV and PCV-VG Groups, respectively), extubation (287 ± 55 sec and 464 ± 67 sec in the PSV and PCV-VG groups, respectively), and transfer from the operating room (473 ± 60 sec and 687 ± 77 sec in the PSV and PCV-VG groups, respectively) (p < 0.0001). Also, patients receiving PSV respiratory support had higher saturation levels 5 minutes after extubation (p < 0.0001), and heart rate and mean arterial pressure immediately before extubation were lower than in the mandatory ventilation group (p = 0.013 and p < 0.0001, respectively). In addition, in the mode of spontaneous breathing with pressure support, a lower severity of post-extubation cough was observed (p = 0.003).

Conclusion. The use of a spontaneous breathing mode with pressure support at the end of general combined anesthesia has several advantages versus mandatory ventilation mode. These advantages include faster awakening, extubation and transfer of the patient to the ward, lower severity of post-extubation cough, as well as better gas exchange after extubation, lower intensity of hypertension and tachycardia before it.
Epidural Analgesia as a Part of Combined Anesthesia during Abdominal Oncological Surgeries (Results of the Survey among the Russian Anesthesiologists and Resuscitators)
Authors: Smolin N. S. , Khrapov K. N. , Miroshkina V. M.
Published: August 2022

The objective: to analyze the contemporary specific parameters of intraoperative management of epidural analgesia (EA) in combined anesthesia in abdominal oncological surgeries in different medical organizations of Russia.

Subjects and Methods. The data necessary for analysis and statistical processing were obtained by developing a formalized questionnaire (21 questions, some of which with the possibility of choosing several answers at the same time – multiple choice), published on the official website of the Association of Anesthesiologists-Resuscitators (https://association-ar.ru/). The survey lasted for 16 days (from May 23, 2022 to June 7, 2022). The survey results were collected using the Google Forms online service and processed using the Google Spreadsheets. Multiple choice responses were processed as absolute numbers and presented as a percentage of the total number of responses to a particular question.

Results. The total number of respondents who took part in the survey was 217 specialists from various medical organizations, mostly from the North-Western Federal District of the Russian Federation (34.1%) with more than 15 years of expertise in the specialty (44.7%). According to the survey results, the following specific features of EA during combined anesthesia practice in Russia have been identified: most participants perform EA in the sitting position (63.6%); ropivacaine is the drug of choice among local anesthetics (LA) (84.2%); as a rule, EA is initiated prior to incision (69.6%). During open surgical interventions, 44.7% use a combined EA method (continuous infusion and bolus injection – bolus-based mode), while during laparoscopic surgeries there is no preferred method (combined method – 33.1%; continuous infusion only – 35.5%; bolus injection only – 31.4%). Low concentrations of LA (0.2 ‒ 0.375%) combined with a low volume of administration (4‒10 ml for bolus, 4‒8 ml/h for infusion) are used more often both in open and laparoscopic surgeries. In most cases, achievement of effective EA is supported by lower doses of systemic opioid analgesics (65.4%). Insufficient degree of intraoperative analgesia is managed in different ways, such as using systemic opioids (68.7%), enhancing epidural analgesia (17.5%), and administration of non-opioid analgesics (13.8%).

Conclusion. At present, there is no unified approach to the method of EA in combined anesthesia. The results of the survey showed the uncertainty of experts' opinions regarding the choice of LA concentrations for EA, the rate and volume of its administration into the epidural space. Finding the optimal method of intraoperative EA in abdominal oncological surgery is the most important clinical objective in terms of reducing perioperative complications.
The Helsinki Declaration on Patient Safety in Anesthesia – Russian Experience: a Questionnaire Survey
Authors: Kabanova T. A. , Degtyarev P. A. , Shkerdina M. I. , Kostikov A. P. , Khalimov M. Ya. , Tereschenko E. V. , Babaev M. A.
Published: August 2022

The objective: to determine the quality of knowledges about the Helsinki Declaration on Patient Safety among Russian anesthesiologists and intensivists and how widely its vision and standards have been adopted in clinical practice.

Subjects and Methods. The study design involved the creation of 44-item online and offline questionnaire. The questions were divided into three blocks: personal information, data on hospitals where respondents work, and questions about implementation of the Helsinki protocol in their practice. Some of the questions required open answers. Persons with higher medical education who have completed residency and/or internship in anesthesiology and resuscitation and are working in this field in the Russian Federation were invited to participate in the survey.

Results. 140 (21.5%) respondents answered all the question of the questionnaire. Of those surveyed, 76.4% were familiar with the Helsinki Declaration on Patient Safety, but only 17.1% felt they had sufficient knowledge of the concept. 43.6% of the respondents apply the Helsinki Declaration on Patient Safety to their clinical practice, while 49.3% of the respondents had difficulty answering whether they follow the Declaration in their work or not. The study showed a satisfactory level of compliance with mandatory standards for monitoring in the perioperative period but all the EBA-recommended standards are applied in only 23% of the hospitals. 26.4% of the respondents use the Safe Surgery Checklist prepared by the World Health Organization. 58.6% of the respondents use the reporting/notification system for adverse events or critical conditions in the perioperative period.

Conclusion. The survey has shown that many of the surveyed anesthesiologists and intensivists have good knowledge of the Helsinki Declaration on Patient Safety and successfully apply it to their clinical practice but some doctors do it unconsciously, not understanding what standards they follow. Organization of additional educational programs could help physicians to improve their knowledge and raise their awareness in order to provide safer patient care. We also suggest introduction of unified checklists and national reporting systems for adverse events or critical conditions in the perioperative period.
Integrable quadratic structures in peakon models
Authors: Avan Jean , Frappat Luc , Ragoucy Eric
Published: August 2022

We propose realizations of the Poisson structures for the Lax representations of three integrable n-body peakon equations, Camassa-Holm, Degasperis-Procesi and Novikov. The Poisson structures derived from the integrability structures of the continuous equations yield quadratic forms for the r-matrix representation, with the Toda molecule classical r-matrix playing a prominent role.
We look for a linear form for the r-matrix representation. Aside from the Camassa-Holm case, where the structure is already known, the two other cases do not allow such a presentation, with the noticeable exception of the Novikov model at n=2.
Generalized Hamiltonians obtained from the canonical Sklyanin trace formula for quadratic structures are derived in the three cases.
Avaliação técnica e econômica de sistema fotovoltaico conectado à rede, para aviário de frango de corte
Authors: Justina Natã Della , Siqueira Jair Antonio Cruz , Tokura Luciene Kazue , Villa Bruna de , Tokura Willian Isao , Silveira Vander Fabio , Rodrigues Hamom Ventura
Published: August 2022

Com o mercado de frango em expansão, as empresas passaram a se preocupar com o aumento da eficiência do processo produtivo, dando espaço para a automação de aviários, para atender a demanda de mercado. Por outro lado, os sistemas de conforto automatizados utilizados na avicultura possuem grande demanda de energia elétrica, gerando um dos maiores custos da produção avícola brasileira. Diante do exposto, a utilização de sistemas renováveis de energia pode ser de grande importância para o setor avícola. Desta forma, foi objetivo do trabalho dimensionar e avaliar economicamente um sistema fotovoltaico ligado à rede para atender a demanda exigida pelos aviários de frango de corte, da cidade de Santa Izabel do Oeste - PR. Posteriormente ao dimensionamento do sistema, foi realizado o estudo da viabilidade econômica do mesmo, por meio dos valores disponibilizados pelas empresas do ramo, utilizando a técnica de payback para o estudo e avaliação da viabilidade econômica do sistema. Pelo dimensionamento da metodologia empregada  obteve-se um sistema composto com 342 módulos de 270 Wp, policristalinos, com 3 inversores de 30 kWp. A viabilidade econômica mostrou um tempo de retorno de 4 anos, com uma TIR de 30,02%. Os resultados permitiram concluir que há uma boa viabilidade técnica e econômica para instalação do sistema.
Aplicação do modelo DPSIR (Drivers – Pressures – State – Impact – Response) com foco nas respostas tecnológicas para a redução dos gases de efeito estufa
Authors: Bartu Castilho Viana Gabriela , Jesús Olortiga Asencios Yvan
Published: August 2022

As mudanças climáticas são um grande desafio da atualidade. Sabe-se que o aumento da concentração de gases de efeito estufa, especialmente o CO2, intensifica essa problemática. Esse aumento é decorrente de algumas atividades humanas, por exemplo, o consumo energético. Para entender essa relação causal, o presente estudo teve como objetivo aplicar o modelo de causa e efeito DPSIR (Drivers – Pressures – State – Impact – Response) com foco nas respostas tecnológicas que favorecem a redução da emissão do CO2 e a transformação do mesmo em produtos com valor agregado. Nesse caso, foi utilizado uma busca bibliográfica sistêmica nas bases de dados de artigos científicos. Com a aplicação do DPSIR foi possível visualizar de forma mais clara as forças motrizes que levam a emissão de CO2, pressões no meio ambiente, mudança de estados, impactos e por fim, as respostas tecnológicas. As principais abordagens tecnológicas identificadas foram a captura e armazenamento de carbono (CCS) bem como sua utilização (CCUS), sendo este último relacionado a reciclagem do CO2.  Essa reciclagem pode ocorrer por diversas rotas químicas, como a fotocatálise de CO2 que apresenta grande vantagem por não necessitar de adição energética em seu processo e a outra rota é a hidrogenação do CO2 que permite obter uma variedade de produtos com finalidades energéticas distintas. Por fim, as mudanças climáticas são um desafio sistêmico que necessita de soluções seja do âmbito público, privado ou tecnológico que combinam e cooperam entre si, nesse sentido a aplicação do modelo DPSIR pode ser uma estratégia para os tomadores de decisão.
Regulatory Mechanisms of Vanillic Acid in Cardiovascular Diseases:
A Review
Authors: Lashgari Naser-Aldin , Roudsari Nazanin M. , Momtaz Saeideh , Abdolghaffari Amir H. , Atkin Stephen L. , Sahebkar Amirhossein
Published: August 2022

Cardiovascular diseases (CVD) are the primary cause of death globally. Activation of oxidative stress and inflammatory pathways are contributory to the development of CVD. Pharmacological activities of vanillic acid have been investigated suggesting that they may have therapeutic utility clinically. Given its phenolic nature, the anti-inflammatory and antioxidant properties of vanillic acid have been shown to exert potent inhibitory activity against Adenosine Monophosphate-Activated Protein Kinase (AMPK), Nuclear Factor Kappa B (NF-κB), the Janus kinase (JAK)/signal transducer and activator of transcription (STAT), Nod‐like receptor family protein (NLRP), Toll like receptors (TLRs), Mitogen-Activated Signaling Proteins (MAPK) and Mammalian Target of Rapamycin (mTOR) signaling pathways. Vanillic acid has been shown to block pro-inflammatory cytokines and suppress inflammatory cascades. The inhibitory impact of vanillic acid on reactive oxygen species (ROS) and nitric oxygen synthase (iNOS) expression has also been demonstrated. Vanillic acid reduces oxidative-related markers such as superoxide dismutase (SOD), glutathione (GSH), Heme Oxygenase 1 (HO-1), and glutathione peroxidase (GSH-Px). Here, we review the cardioprotective effects and mechanisms of action of vanillic acid in CVD. Current potential applications of vanillic acid in CVD are discussed with respect to preclinical and clinical studies.
Determination of Traditional and Designer Benzodiazepines in Urine through
LC-MS/MS
Authors: Rossi Brian , Freni Francesca , Carelli Claudia , Moretti Matteo , Galatone Dario , Vignali Claudia , Morini Luca
Published: August 2022

Background:

The detection of new designer benzodiazepines in biological fluids and tissues, together with the traditional ones, could represent an important analytical update for laboratories performing clinical
and forensic toxicological analysis.

Objective:

A liquid chromatography tandem mass spectrometry method (LC-MS/MS) has been developed, fully
validated, and applied to a cohort of real urine samples collected from patients under withdrawal treatment and
from intoxication cases.

Methods:

100 µL urines were added to a buffer solution containing deuterated internal standards; the samples
were then extracted through a liquid/liquid procedure, dried under a nitrogen stream, and reconstituted in mobile phase. The chromatographic separation was performed in reverse phase through a C18 column with gradient elution. Mass spectrometry operated in positive polarization and multiple reaction monitoring mode.

Results:

25 molecules were optimized for instrumental analysis: 9 designer benzodiazepines and 16 traditional
compounds (parent drugs and main metabolites). Sensitivity, specificity, linearity, accuracy, imprecision, recovery, matrix effects, and carry-over have been evaluated for all molecules. Only cinazepam did not satisfy all
acceptance criteria for validation. 10 among the 50 analyzed samples tested positive for at least one of the
monitored molecules. In particular, two different samples collected from the same case provided positive results
for flubromazepam, a designer benzodiazepine.

Conclusion:

The method was proven to be useful in detecting not only traditional benzodiazepines but also new
designer ones. The identification of a New Psychoactive Substance in real samples confirmed that analytical
procedures should be updated to include as many substances as possible.
Gender Matters. Sex-related Differences in Immunotherapy Outcome in Patients with Non-small Cell Lung Cancer
Authors: Caliman Enrico , Petrella Maria Cristina , Rossi Virginia , Mazzoni Francesca , Grosso Anna Maria , Fancelli Sara , Paglialunga Luca , Comin Camilla Eva , Roviello Giandomenico , Pillozzi Serena , Antonuzzo Lorenzo
Published: August 2022

Background:

Emerging evidence identified sex as a variable regulating immune system functions and modulating response to immunotherapy in cancer patients.

Objective:

This retrospective study analysed sex-related differences in immunotherapy outcomes in a real-world population of non-small cell lung cancer (NSCLC) patients treated with immune check-point inhibitors (ICIs).

Methods:

We retrospectively investigated clinical data of 99 patients with advanced NSCLC and treated with single-agent nivolumab and pembrolizumab at Medical Oncology Unit, Careggi Universi-ty Hospital, Florence (Italy), between April 2014 to August 2019. Main clinical characteristics and clinical outcomes were analysed.

Results:

Our study showed that the efficacy of ICI treatment differed according to gender. A trend for better median progression-free survival (mPFS) was reported in males (mPFS 5.0 months, 95% Con-fidence Interval [CI] 4.0-11.0) than females (mPFS 4.5 months, 95% CI 2.0-9.0) (p=0.133), while no significant difference for overall survival (OS) between the two sex groups was observed (p=0.622). In the nivolumab cohort, we showed a statistically significant difference for a longer PFS in men compared to women (log-rank p=0.054), HR for PFS in females versus males was 1.81 (95% CI 0.97-3.37, p=0.062). Disease control rate (DCR) was achieved in 55.7% and 45.7% of men and women, respectively, while disease progression was registered in 44.3% of males and 54.3% of females (p=0.386).

Conclusions:

Gender is a variable that should be taken into account in the choice of immunotherapy. Future prospective randomized trials testing tailored sex-based immunotherapy strategies are required to validate our findings before integrating into clinical practice.
Recent Advances of α-Glucosidase Inhibitors: A Comprehensive Review
Authors: Agrawal Neetu , Sharma Manisha , Singh Shikha , Goyal Ahsas
Published: August 2022

Background:

Diabetes mellitus (DM) is a critical health issue prevailing in nearly half a billion people worldwide. It is one of the most threatening metabolic diseases. Type 2 DM is caused due to insulin resistance and accounts for 90% of diabetes cases. If it remains untreated, it can lead to major frightening complications and can cause death, which ultimately threatens mankind.

Discussion:

Various oral hypoglycaemic drugs are available today, acting on different targets by adopting different pathways However, the α-glucosidase inhibitors proved to be a novel and effective strategy to manage T2DM. These inhibitors alleviate the postprandial glycemia by aiming to inhibit intestinal α-glucosidase competitively and reversibly, thus delaying carbohydrate digestion and turning down the rate of glucose absorption. Plenty of α-glucosidase inhibitors have been discovered from synthetic routes as well as from natural sources, including plants, fungi, and bacteria.

Conclusion:

This article comprises the natural and synthetic α-glucosidase discovered from 2016-2021 and can be utilized to discover novel α-glucosidase inhibitors further. This review is an endeavor to highlight the progress in the discovery and development of α-glucosidase inhibitors which could provide a low-height flying bird’s eye view to the medicinal chemists for the development of clinically viable drugs using this information.
Hydrazides and Hydrazones: Robust Scaffolds in Neurological and Neurodegenerative
Disorders
Authors: Agrawal Neetu , Mishra Raghav , Pathak Shilpi , Goyal Ahsas , Shah Kamal
Published: August 2022

Background:

Hydrazides and hydrazones are found in a variety of bioactive compounds that
have a wide range of pharmacological applications. There have been significant advancements in this
field in recent years, with many new aspects of hydrazone chemistry and applications emerging.

Methods:

This piqued researchers' interest in synthesizing a variety of hydrazone derivatives for
various biological applications.

Results:

According to a comprehensive review of the literature, the hydrazone template possesses an
immense potential to be developed for the treatment of a variety of brain-related disorders. Thus,
researchers are expeditiously exploring the chemical compounds bearing hydrazone moiety to find lead
molecules for the development of potential agents for the treatment of neurological and neurodegenerative
disorders.

Conclusion:

In this review, the biological activities of various hydrazide and hydrazone analogues
against various neurological and neurodegenerative disorders are summarized. Furthermore, there is a
great potential for this scaffold, which medicinal chemists should look into for the development of new
prospective drug candidates.
Synthesis, Molecular Docking Studies, and In vitro Anticancer Evaluation
of Novel Tolfenamic Acid Derivatives
Authors: Tahtamouni Lubna H. , Mehihi Abbas A. , Kubba Ammar A.
Published: August 2022

Background:

Accumulating experimental evidence has demonstrated that tolfenamic acid (TA) has anticancer activity. TA has been shown to modulate the expression of several cancer-related genes involved in apoptosis and cell cycle arrest, as well as metastasis and angiogenesis.

Objective:

The current study was carried out to evaluate the anticancer activities of eight newly synthesized TA derivatives by conducting in silico molecular docking studies and in vitro biological evaluations to validate their VEGFR-2 tyrosine kinase inhibitory activities.

Methods:

The novel TA derivatives (3A–F–5) were obtained by reacting TA hydrazide with substituted aldehydes, phthalic anhydride, and succinic anhydride, respectively. Spectroscopic techniques were used to characterize the target molecules. Docking studies were performed to determine the binding patterns to the potential molecular target VEGFR-2, and these were compared with the results of the in vitro VEGFR-2 tyrosine kinase (TK) inhibition assay.

Results:

Our findings indicate that the newly synthesized compounds are cytotoxic, with compound 4 being the most potent. Additionally, all compounds inhibited VEGFR-2 TK activity, the EC50 value of compound 4 was nearly identical to that of the conventional VEGFR TK inhibitor sorafenib. SAR studies revealed that the presence of an aryl or a heteroaryl fragment attached to the hydrophilic linker (as found in compound 4) is crucial to the anticancer activity.

Conclusion:

The outcomes suggest that the isoindoline derivative (compound 4) is a good candidate for further investigation. The docking results provide evidence for a correlation between the experimental and predicted VEGFR-2 TK inhibitory activity. Moreover, ADMET studies indicate that all ligands have good pharmacokinetic properties.
Imaging of the Abdominal Wall Sinus Tract: Comparison of Computed
Tomography Sinography and X-Ray Sinography
Authors: Yan Yuchang , Du Xuechao , Sun Pengtao , Liu Sujun , Pan Zhenyu , Yang Shuo
Published: August 2022

Objective:

To clarify the comparative benefits of X-ray sinography and computed tomography (CT) sinography in assessing the abdominal wall sinus tract.

Methods:

In this cross-sectional study, patients in our hospital with an abdominal wall sinus tract who
had received both X-ray sinography and CT sinography from January 2018 to January 2021 were enrolled.
The intraoperative findings were used as the gold standard to calculate the accuracy of the two
methods. Kappa statistic was employed to evaluate the concordance between the two methods and the
intraoperative findings. Differences in diameters measured on X-ray sinography and CT sinography
images were analyzed using the Wilcoxon signed rank test.

Results:

The study sample consisted of 74 patients. The accuracy of the CT sinography in diagnosing
the extent of the sinus invasion was 85.1%, while the accuracy of the X-ray sinography was 59.5%. For
the sinus confined to the abdominal wall (Kappa: 0.783 VS 0.248), the sinus extending into the abdominal
cavity (Kappa: 0.734 VS 0.339), and the sinus with fistula formation (Kappa: 0788 VS 0.496),
the consistency of the CT sinography and surgery were significantly better than that of the X-ray sinography.
Diameters of the sinus tract measured on CT images were statistically larger than the diameters
measured on X-ray sinography (P<0.001).

Conclusion:

CT sinography has significant advantages to X-ray sinography in depicting the extent of the abdominal wall sinus tract and the presence of a fistula.
YARN Schedulers for Hadoop MapReduce Jobs: Design Goals, Issues and
Taxonomy
Authors: Kotikam Gnanendra , Selvaraj Lokesh
Published: August 2022

Objective:

Big Data processing is a demanding task, and several big data processing frameworks have emerged during recent decades. The performance of these frameworks greatly dependent on resource management models.

Methods:

YARN is one of such models which acts as a resource management layer and provides computational resources for execution engines (Spark, MapReduce, storm, etc.) through its schedulers. The most important aspect of resource management is job scheduling.

Results:

In this paper, we first present the design goal of YARN real-life schedulers (FIFO, Capacity, and Fair) for the MapReduce engine. Later, we discuss the scheduling issues of the Hadoop MapReduce cluster.

Conclusion:

Many efforts have been carried out in the literature to address issues of data locality, heterogeneity, straggling, skew mitigation, stragglers and fairness in Hadoop MapReduce scheduling. Lastly, we present the taxonomy of different scheduling algorithms available in the literature based on some factors like environment, scope, approach, objective and addressed issues.
A Patent Data Analysis of the Innovation Trends in Biological Control
Agent Formulations
Authors: Fatimi Ahmed
Published: August 2022

Background:

Biological control (i.e., biocontrol) can be defined as the use of microbial
inoculants with a direct and purposeful manipulation of natural enemies, potentially replacing
harmful pesticides, to control pests, plant pathogens, and weeds. This study concerns patent analysis
of biocontrol agent-based formulations. This form of patent analysis encapsulates information
that could be used as a reference by researchers in the fields of agriculture and plants, as well as
those interested, especially in biocontrol agents for agriculture.

Methods:

The state has been reviewed by introducing what has been patented concerning Biocontrol
Agents (BCAs). Four patent databases have been used, and different keywords and related
terms to BCAs were used, and patents were searched according to title, abstract, and claims. The
search was then filtered regarding publication year, patent families, patent classifications, inventors,
applicants, owners, and jurisdictions.

Results:

During a search, 2371 patent documents were found between 1982 and 2021. The United
States was ranked first with 694 patent documents. 2015 was the year with the maximum number
of patent documents (278). The patent classification codes reveal that most inventions are intended
for biocides, pest repellants or attractants, or plant growth regulators containing or obtained
from microorganisms, viruses, microbial fungi, etc. Moreover, they are also intended for biocidal,
pest repellant, pest attractant, or plant growth regulatory activities of chemical compounds or
preparations, such as fungicides, athropodicides, and nematocides, which are concentrated in most
patents.

Conclusion:

The knowledge clusters and expert driving factors of this patent analysis indicate
that the research and development based on the formulation of biocontrol agents are concentrated
in most patents.
Diabetes Mellitus and COVID-19
Authors: Bhadada Sanjay Kumar , Pal Rimesh
Published: August 2022

The
novel coronavirus disease (COVID-19) has scourged the world since its outbreak
in December 2019 in Wuhan, China. The disease tends to be asymptomatic or mild
in nearly 80% of the patients. However, around 5% of the patients tend to have critical
diseases complicated by acute respiratory distress syndrome (ARDS), shock, and
multiple organ failure. The disease tends to be specifically severe in patients
with advancing age and in those with underlying comorbidities. Diabetes
mellitus has emerged as distinctive comorbidity that is associated with severe
disease, acute respiratory distress syndrome, intensive care unit admission,
and mortality in COVID- 19. The impaired innate immune system, underlying
pro-inflammatory milieu, reduced expression of angiotensin-converting enzyme 2
(ACE2), and concomitant use of reninangiotensin- aldosterone system-active
drugs are some of the proposed pathophysiological links between diabetes
mellitus and COVID-19 severity. On the contrary, the presence of active
COVID-19 infection in a patient with underlying diabetes mellitus leads to the
worsening of glucose control. Although glucose control prior to hospital
admission has not been consistently associated with clinical outcomes in
diabetic patients with COVID-19, in-hospital good glycemic control is
associated with a lower rate of complications and all-cause mortality.
Gastrointestinal and Hepatobiliary Manifestations of COVID-19
Authors: Mehtani Rohit , Taneja Sunil
Published: August 2022

The
world in 2020 has witnessed the spread of a novel coronavirus, the severe acute
respiratory syndrome coronavirus-2 (SARS-CoV-2), which typically involves the
respiratory tract causing symptoms like fever, cough and shortness of breath
and, in severe cases leading to the development of acute respiratory distress syndrome
(ARDS). As the disease has evolved across the globe, a large number of patients
are being recognised with atypical symptoms, including abdominal pain, nausea,
vomiting and diarrhea. Involvement of liver in form of elevated aminotransferases
and association of increased severity of coronavirus disease of 2019 (COVID-19)
with pre-existing chronic liver disease has also been noted. The detection of
virus in saliva and faeces of patients has unveiled the possibility of
faecal-oral transmission of the virus and the risk of transmission during
endoscopic procedures. Liver transplant recipients or patients undergoing liver
transplant also need specialised care during this pandemic because of the
possible interplay of immunosuppression and SARS-CoV-2. Various drugs used in
the treatment of COVID-19 can also cause gastrointestinal symptoms or drug
induced liver injury (DILI). This review will focus on the symptomatology,
mechanism and pathological findings of SARS-CoV-2 in the liver and
gastrointestinal tract. We will also highlight safe endoscopy practices to curtail
the spread of COVID-19 and implications of the disease in liver transplant recipients.
COVID-19 and Pulmonary Diseases
Authors: Prasad Kuruswamy Thurai
Published: August 2022

The
coronavirus disease 2019 (COVID-19) primarily affects the respiratory system,
commonly manifesting as pneumonia. The clinical presentation of COVID-19 is
challenging to distinguish from community-acquired pneumonia due to other etiologies
and respiratory exacerbations of pre-existing chronic respiratory diseases. Fortunately,
the majority of patients have an asymptomatic or mild illness. However, some
patients may develop profound hypoxemia secondary to diffuse alveolar damage and
occlusion of alveolar capillaries by microthrombi. When patients with compromised
lung function due to pre-existing respiratory diseases develop this disease,
they face a setback. The management of the pre-existing illness is often suboptimal
due to COVID-19-related restrictions. Further, these patients are more likely
to develop severe manifestations of COVID-19 resulting in more severe morbidity
and mortality. Diagnosis is established by performing a reverse transcription-polymerase
chain reaction (RT-PCR) on samples from the respiratory tract. Treatment of the
mild disease is primarily supportive, while supplemental oxygen and mechanical
ventilation may be indicated for more severe cases. Several treatment options,
including antiviral agents, corticosteroids, immunomodulators, and convalescent
plasma therapy, are being investigated. Currently, there is no evidence to indicate
that the diagnosis and treatment of COVID-19 are different in those with
preexisting respiratory conditions. In the absence of an effective antiviral
agent or vaccine, disease prevention is assumed to be of paramount importance.
Social distancing and proper use of personal protective equipment are critical
in the prevention of transmission.