bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of biomarkers, immune infiltration landscape, and treatment targets of ischemia–reperfusion acute kidney injury at an early stage by bioinformatics methods
Authors: You Ruilian , Heyang Zhige , Ma Yixin , Xia Peng , Zheng Hua , Lin Jianfeng , Ji Peili , Chen Limeng
Published: June 2022

Background

Mechanisms underlying ischemia/reperfusion injury-acute kidney injury (IRI-AKI) are not fully elucidated. We conducted an integrative analysis of IRI-AKI by bioinformatics methods.

Methods

We screened gene expression profiles of the IRI-AKI at early phase from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and enrichment pathways were conducted based on gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and Gene set enrichment analysis (GSEA). Immune cell infiltration analysis was performed to reveal the change of the microenvironment cell types. We constructed protein–protein interaction (PPI), and Cytoscape with plug-ins to find hub genes and modules. We performed robust rank aggregation (RRA) to combine DEGs and analyzed the target genes for miRNA/transcription factor (TF) and drug-gene interaction networks.

Results

A total of 239 and 384 DEGs were identified in GSE87024 and GSE34351 separately, with the 73 common DEGs. Enrichment analysis revealed that the significant pathways involve mitogen-activated protein kinase (MAPK) signaling, interleukin-17, and tumor necrosis factor (TNF) signaling pathway, etc. RRA analysis detected a total of 27 common DEGs. Immune cell infiltration analysis showed the plasma cells reduced and T cells increased in IRI-AKI. We identified JUN, ATF3, FOS, EGR1, HMOX1, DDIT3, JUNB, NFKBIZ, PPP1R15A, CXCL1, ATF4, and HSPA1B as hub genes. The target genes interacted with 23 miRNAs and 116 drugs or molecular compounds such as curcumin, staurosporine, and deferoxamine.

Conclusion

Our study first focused on the early IRI-AKI adopting RRA analysis to combine DEGs in different datasets. We identified significant biomarkers and crucial pathways involved in IRI-AKI and first construct the immune landscape and detected the potential therapeutic targets of the IRI-AKI by drug-gene network.
Association between serum uric acid levels and incidence of nonalcoholic fatty liver disease in users of preventive medicine service in southern Brazil: a retrospective study
Authors: Leite Mariana F. , Haagsma Ariele B. , Machado-Júnior Paulo-André B. , Martins Grasiele L. , Olandoski Márcia , Baena Cristina P.
Published: June 2022

Background

Nonalcoholic fatty liver disease (NAFLD) is a silent disease with increasing prevalence. High levels of serum uric acid (SUA) have been associated with cardiometabolic diseases, yet the possible association between SUA levels and NAFLD is not elucidated. This article aim is to evaluate the possible association between SUA and NAFLD in a Brazilian population.

Methods

This retrospective study evaluated patients submitted to two evaluations between 2015 and 2016 at a preventive medicine service. The diagnosis of NAFLD was performed through abdominal ultrasound, and its progression was defined as favorable or unfavorable according to the degrees of steatosis. Patients with hyperthyroidism, pregnancy, viral hepatitis, use of methotrexate or anabolic steroids, significant alcohol consumption were excluded. Possible confounding factors were evaluated through a multivariate model.

Results

A total of 279 patients were included in the final sample. In the first evaluation, 20.1% were women and the mean age was 46.9 (± 7.9) years, with a mean body mass index of 27.3 (± 4.0) kg/m2. About 26.9% of the individuals were diagnosed with NAFLD, and the mean of SUA levels was 5.7 (± 1.4) mg/dL; a favorable progression of NAFLD was observed in 79.2% of the patients, and the SUA levels at baseline were not significantly associated with the NAFLD progression (p = 0.43).

Conclusions

Despite NAFLD high prevalence, SUA levels were not significantly associated with NAFLD progression in one year in this sample.
1H-NMR-based serum metabolomic study to evaluate the effect of asarone and metformin on experimentally induced diabetic hepatocellular carcinoma in rats
Authors: Das Bhrigu Kumar , K Jayalakshmi , Gadad Pramod C.
Published: June 2022

Background

The increased prevalence of hepatocellular carcinoma (HCC) in diabetic patients has focused on the need to characterize the role of altered metabolites in liver carcinogenesis. In this study, together with the serum biochemistry and histopathological observation,1H nuclear magnetic resonance (1H-NMR)-based metabolomics was carried out to study the effect of asarone and metformin in diabetic HCC rats. Intraperitoneal administration of streptozotocin (STZ; 55 mg/kg b.w.) was used to induce diabetes in male Wistar rats. Further, 2 weeks later, after confirmation of diabetes, another group received diethylnitrosamine (DEN; 200 mg/kg b.w.) to simulate the diabetic HCC condition. The combined dose ofα-andβ-asarone (50 µg/kg b.w. in the ratio of 1:1) and metformin HCl (250 mg/kg b.w.) treatment was orally given to the diabetic HCC rats for 18 weeks. The serum samples were subjected to1H-NMR-based metabolomics analysis to explore the metabolite changes at the end of the study.

Results

1H-NMR study quantitatively distinguished the metabolites, such as pyruvate, lactate, creatine, acetate, glutamine, valine, and alanine, which varied between the diabetic HCC and normal rats. Furthermore, compared to the diabetic HCC group, the administration of asarone and metformin resulted in a substantial change in metabolite levels. Histopathological examination indicated that treatment attenuates the magnitude of the toxic effect of STZ + DEN.

Conclusions

The aberrant glucose, lipid, and amino acid metabolisms were associated with developing hepatocarcinogenesis in rats during the diabetic condition. Treatment with asarone and metformin attenuated the metabolic changes due to STZ + DEN-induced diabetic HCC.
Traditional knowledge and phytochemical screening of plants used in snakebite prevention in Benin
Authors: Dossou Ayékotchami Jacques , Fandohan Adandé Belarmain , Omara Timothy , Gbenou Joachin
Published: June 2022

Background

Snake envenomation is a public health problem that has caused many deaths, disabilities and significant physical, psychological and socio-economic losses worldwide. In many rural communities, some plants have been utilized for preventing snake envenomation. The present study aims to document the knowledge of traditional medicine specialists on the plants used to prevent snakebites or repel snakes in Benin. A survey was conducted between January 2020 and September 2020 to this end. A total of 238 traditional healers and 56 hunters of different socio-cultural groups were interviewed using snowball sampling technique. Survey data were analyzed using Relative Citation Frequency. The diversity of antisnake bite plants was assessed using the Shannon diversity index, Piélou equitability, the Bray–Curtis similarity index and a Factorial Correspondence Analysis. Finally, qualitative phytochemical screening was performed on aqueous extracts following standard methods based on staining and/or precipitation reactions.

Results

A total of 74 plant species belonging to 36 families and 70 genera were identified. The most frequently encountered families were Leguminosae (27.3%), Euphorbiaceae (8.1%), Arecaceae, Asteraceae and Cucurbitaceae (4.5% each).Annona senegalensis,Securidaca longipedunculata,Piliostigma thonningii,Chenopodium ambrosioidesandCymbopogon citratuswere the most cited species. The analysis of the intra-community diversity of antisnake bite plants from socio-cultural and sociolinguistic groups showed a high diversity and strong equi-representativeness of the plants used in the prevention of snakebites in Benin. Preliminary qualitative analysis of the bioactive compounds in extracts of the most cited antisnake bite plants revealed the presence of alkaloids, flavonoids, tannins, saponosides, mucilages, reducing compounds and triterpenoids.

Conclusions

In-depth pharmacological and phytochemical studies would make it possible to rationalize on the effectiveness of the identified medicinal plants as well as provide insights of the compounds responsible for their antisnake bite activity.
Salicylic acid derivatives as potential α-glucosidase inhibitors: drug design, molecular docking and pharmacokinetic studies
Authors: Aminu Khalifa Sunusi , Uzairu Adamu , Umar Abdullahi Bello , Ibrahim Muhammad Tukur
Published: June 2022

Background

Diabetes mellitus (DM) is one of the most defying health risk in the twenty-first century promoting a high rate of morbidity and mortality that could possibly increase if no intervention is in place. However, drugs for curing DM are available but are associated with adverse side effect necessitating the pursuit for a safe antidiabetic drugs. The present study was conducted in order to develop a QSAR model that would be used to predict the activities of salicylic acid derivatives, as well as to determine the binding interactions of the compounds with α-glucosidase using molecular docking studies.

Results

Model one was selected and reported as the best model based on its fitness with the following validation keys: R2(trng set) = 0.968, R2(adj) = 0.957, Q2(cv) = 0.932, LOF = 0.085 and R2(test set) = 0.864. Five potent analogues were designed using the ligand-based method with their predicted activities been calculated and found to be higher compared to the lead compound. Furthermore, binding interactions of the designed analogues within the active site of α-glucosidase (pdb id:3L4V) illustrate a good binding affinities than kotalanol and acarbose. However, the ADMET and drug-likeness properties predicted the design analogues to be pharmacologically and orally safe by not having more than one violation of Lipinski’s (Ro5) criteria.

Conclusions

The present findings therefore showed that the salicylic acid derivatives could serve as α-glucosidase inhibitors. The compounds can be studied further for a hunts of promising drug candidates against diabetes mellitus.
A multiscale approach to targeted docetaxel formulations: combination therapy, nanotechnology, electrospinning and 3D printing—a review
Authors: Oyediran Karamot O. , Ilomuanya Margaret O. , Azubuike Chukwuemeka P. , Nurudeen Layeni
Published: June 2022

Background

Cancer remains one of the leading causes of death worldwide. Docetaxel, first marketed as ‘Taxotere’, has been approved for use as a chemotherapeutic for management of gastric, breast, neck, head, non-small cell lung cancer and prostate cancer.

Main body

Taxotere, is a docetaxel formulation solubilized in tween 80 and 13% ethanol solution. It is effective as a chemotherapeutic agent but has numerous toxic effects due to the ethanol and polysorbate. Aside from this, challenges with administration during mixing of the docetaxel with the diluent exist. Poor mixing results in gel formation while addition of the drug mix to an infusion may result in micelle formation. These challenges have necessitated remodeling of the currently available docetaxel formulation, but none has made it to clinical setting as an alternative. Efforts have also been made to develop oral docetaxel formulation to ease administration of the drug. Attempts have also been made to develop other dosage forms, notably transdermal formulations and implants to target cancer cells while avoiding systemic side effects. Formulation methods such as nanoformulation, drug coupling with other active moieties, 3D fabrication as well as electrospinning have been employed.

Conclusions

Development of novel formulations of docetaxel for different chemotherapeutic needs appears promising with some formulations currently in clinical trials. Exploring other drug formulation techniques such as the use of 2D LDH may produce novel anticancer formulations in the future.
Shift and homogenization of gut microbiome during invasion in marine fishes
Authors: Escalas Arthur , Auguet Jean-Christophe , Avouac Amandine , Belmaker Jonathan , Dailianis Thanos , Kiflawi Moshe , Pickholtz Renanel , Skouradakis Grigorios , Villéger Sébastien
Published: June 2022

Biological invasion is one of the main components of global changes in aquatic ecosystems. Unraveling how establishment in novel environments affects key biological features of animals is a key step towards understanding invasion. Gut microbiome of herbivorous animals is important for host health but has been scarcely assessed in invasive species. Here, we characterized the gut microbiome of two invasive marine herbivorous fishes (Siganus rivulatus and Siganus luridus) in their native (Red Sea) and invaded (Mediterranean Sea) ranges. The taxonomic and phylogenetic diversity of the microbiome increased as the fishes move away from the native range and its structure became increasingly different from the native microbiome. These shifts resulted in homogenization of the microbiome in the invaded range, within and between the two species. The shift in microbial diversity was associated with changes in its functions related with the metabolism of short-chain fatty acids. Altogether, our results suggest that the environmental conditions encountered by Siganidae during their expansion in Mediterranean ecosystems strongly modifies the composition of their gut microbiome along with its putative functions. Further studies should pursue to identify the precise determinants of these modifications (e.g. changes in host diet or behavior, genetic differentiation) and whether they participate in the ecological success of these species.
Expressions of resistome is linked to the key functions and stability of active rumen microbiome
Authors: Ma Tao , Zaheer Rahat , McAllister Tim A. , Guo Wei , Li Fuyong , Tu Yan , Diao Qiyu , Guan Le Luo
Published: June 2022

Background

The resistome describes the array of antibiotic resistant genes (ARGs) present within a microbial community. Recent research has documented the resistome in the rumen of ruminants and revealed that the type and abundance of ARGs could be affected by diet and/or antibiotic treatment. However, most of these studies only assessed ARGs using metagenomics, and expression of the resistome and its biological function within the microbiome remains largely unexplored.

Results

We characterized the pools of ARGs (resistome) and their activities in the rumen of 48 beef cattle belonging to three breeds (Angus, Charolais, Kinsella composite hybrid), using shotgun metagenomics and metatranscriptomics. Sixty (including 20 plasmid-associated) ARGs were expressed which accounted for about 30% of the total number of ARGs (187) identified in metagenomic datasets, with tetW and mefA exhibiting the highest level of expression. In addition, the bacterial hosts of 17 expressed ARGs were identified. The active resistome was less diverse in Kinsella composite hybrid than Angus, however, expression of ARGs did not differ among breeds. Although not associated with feed efficiency, the total abundance of expressed ARGs was positively correlated with metabolic pathways and ‘attenuation values’ (a measurement of stability) of the active rumen microbiome, suggesting that ARGs expression influences the stability and functionality of the rumen microbiome. Moreover, Ruminococcus spp., Prevotella ruminicola, Muribaculaceae spp. and Collinsella aerofaciens were all identified as hosts of expressed ARGs, possibly promoting the dominance of these carbohydrate degraders within the rumen microbiome.

Conclusions

Findings from this study provide new insight into the active rumen resistome in vivo, which may inform strategies to limit the spread of ubiquitously found ARGs from the rumen to the broader environment without negatively impacting the key functional outcomes of the rumen microbiome.
Species sensitivity distribution of dichlorvos in surface water species
Authors: Bustos Nahuel Jano , Iriel Analia , Cirelli Alicia Fernández , Cedergreen Nina
Published: June 2022

Dichlorvos is an organophosphorus insecticide frequently detected in surface waters all around the world. From an evaluation of the environmental quality concentrations (EQC) for dichlorvos in surface waters adopted by different countries, it was observed a wide variability among them. This is despite regulatory EQC-values are typically based on toxicity data and species sensitivity distribution (SSD) in all the investigated regulatory frameworks, and therefore should be similar. Hence, what is the cause of the differences between national and regional EQC-values? And, which ones will protect the aquatic fauna? These hypotheses were proposed to explain differences among SSDs based on the choice of toxicity data: (i) EQC values obtained from technical presentation (pure dichlorvos) will be higher than the estimated from dichlorvos formulation (containing other substances to improve the efficiency of the active principle), as they may include synergists; (ii) different taxa will have different sensitivities; (iii) data produced under different experimental conditions will severely affect the SSD. Regarding their capacity to protect the aquatic fauna the hypotheses were; iv) environmental concentration of dichlorvos represents a risk for aquatic organisms; and v) not all EQC-values are protective for the aquatic fauna. These were tested through a meta-analysis of toxicity data enabling the construction of SSD’s across technical and formulated dichlorvos and species of several taxa, and across literature and experimental data produced under analogous conditions. Finally, the EQC elaborated were compared with a meta-study on monitored environmental concentrations. The study suggested that technical dichlorvos increased toxicity compared to formulated products up to two-fold for arthropods. Species phylogeny affected sensitivity, but the SSD derived values used for setting regulatory concentrations were remarkably robust to the inclusion/exclusion of less sensitive species. The SSD results from the literature and experimental data were similar in the case of technical dichlorvos results. The regional differences in EQC values therefore most likely stem from political considerations on how to use SSDs to derive EQCs rather than from differences in SSDs. The experimental SSD defined a protective concentration of 6.5 ng L− 1 for 5% of the species, which is according to the European EQC, but one to two-fold lower than the limit values of the US, China, and Argentina.
A bibliometric analysis of urban food security
Authors: Frayne Bruce , Dordi Truzaar , McCordic Cameron , Sunu Naomi , Williamson Clare
Published: June 2022

The study of urban food security has evolved dramatically over the past few decades. This evolution has been punctuated, and catalyzed, by insights into the dynamic transformation of food systems in cities. The evolution of this field, as revealed by its scholarly writings, provides an important vantage point for understanding both the dynamic transformation of the urban food system as well as the lens through which that transformation has been understood. This investigation adopted a bibliometric methodology, blending quantitative and qualitative analytical techniques, to assess the dynamic evolution of the literature over time. This methodology included a quantitative analysis of the metadata for 162 publications on urban food security. The results of this analysis provided an overview of research progress, historical and evolutionary trends, geographic disparities, keyword distribution, networks of collaboration, and key thematic foci. The quantitative analysis is complemented with a qualitative examination of top publications in the field. The results present a historical narrative of the evolution of urban food security research. In particular, the results indicate that the field has diversified its foci along key distinctions in food access and supply. The findings also identify common strategies and challenges inherent to the governance of urban food systems. In summary, this investigation provides a unique vantage point for discovering the evolution of urban food security and the perspectives that have defined that evolution.
An adult with left isomerism having an interrupted inferior vena cava and persistent left superior vena cava associated with partial atrioventricular canal defect and complete heart block — a case report
Authors: Ali Mohammed Wahaj , Husain Shaikh Mohammed , Iyer Ramnath , Desai Neelam
Published: June 2022

Background

Persistent left superior vena cava is a well-recognized thoracic venous abnormality, most of which do not present with any symptoms. Its opening into the left atrium is uncommonly encountered and, if present, is noted to be associated with various other complex intracardiac malformations, which further complicates its management. Herein, we highlight a case of an adult with persistent left superior vena cava with a spectrum of other cardiac anomalies rarely encountered with it, which was effectively managed by tailored surgical intervention.

Case presentation

A 26-year-old female on meticulous evaluation was found to have left isomerism with an interrupted inferior vena cava and hemiazygos continuing as a persistent left superior vena cava. It was also associated with common atrium, partial atrioventricular canal defect, and complete heart block. This complex array of anomalies was managed surgically. Common atrium was closed with atrial neo-septation using autologous pericardial patch tailored in a way, such that the persistent left superior vena cava drained into right atrium with left atrial appendage being on right side of neo-septum. Cleft in the left atrioventricular valve was also repaired. Despite preoperative complete heart block, the patient had an uneventful postoperative recovery and was in atrial fibrillation with controlled ventricular rate, thus precluding the need for permanent pacemaker implantation.

Conclusions

A rare spectrum of adult congenital cyanotic heart disease was successfully managed with thorough preoperative evaluation and judicious intraoperative management. Surgical management should be tailored based on specific anatomy for reduction of morbidity and optimum results.
Exploring key molecular signatures of immune responses and pathways associated with tuberculosis in comorbid diabetes mellitus: a systems biology approach
Authors: Selvan G. Tamizh , Gollapalli Pavan , Shetty Praveenkumar , Kumari N. Suchetha
Published: June 2022

Background

Comorbid type 2 diabetes mellitus (T2DM) increases the risk for tuberculosis (TB) and its associated complications, although the pathological connections between T2DM and TB are unknown. The current research aims to identify shared molecular gene signatures and pathways that affirm the epidemiological association of T2DM and TB and afford clues on mechanistic basis of their association through integrative systems biology and bioinformatics approaches. Earlier research has found specific molecular markers linked to T2DM and TB, but, despite their importance, only offered a limited understanding of the genesis of this comorbidity. Our investigation used a network medicine method to find possible T2DM-TB molecular mediators.

Results

Functional annotation clustering, interaction networks, network cluster analysis, and network topology were part of our systematic investigation of T2DM-TB linked with 1603 differentially expressed genes (DEGs). The functional enrichment and gene interaction network analysis emphasized the importance of cytokine/chemokine signalling, T cell receptor signalling route, NF-kappa B signalling pathway and Jak-STAT signalling system. Furthermore, network analysis revealed significant DEGs such as ITGAM and STAT1, which may be necessary for T2DM-TB immune responses. Furthermore, these two genes are modulators in clusters C4 and C5, abundant in cytokine/chemokine signalling and Jak-STAT signalling pathways.

Conclusions

Our analyses highlight the role of ITGAM and STAT1 in T2DM-TB-associated pathways and advances our knowledge of the genetic processes driving this comorbidity.
Total thyroidectomy using intracapsular dissection: the technique, complications, and surgical outcomes
Authors: R. Sumanth K. , Panduranga Rao Santosh Uttarkar
Published: June 2022

Background

Diseases of the thyroid gland are common with a prevalence of 4–7% in the general population, the incidence being higher in endemic areas. Surgical removal is one of the most important treatments for thyroid swellings and it is very important for both the surgeon and patient to understand the surgery, its complications and the outcome. The most frequent complications of thyroid surgeries are related to the injury of recurrent laryngeal nerves or metabolic derangements related to injury of parathyroid glands. Hence intracapsular dissection may be carried out to avoid these potential complications which ensure a good surgical outcome in a select group of patients. The study aims to define the technique of thyroidectomy using intracapsular dissection and assess the complications related to this technique of thyroid surgery. This prospective observational study was carried out on 41 patients who underwent total thyroidectomy after evaluation from November 2013 to June 2016.

Results

Two patients developed transient hypocalcemia following the surgery out of 41 patients. No patients developed permanent RLN palsy or permanent hypocalcemia.

Conclusion

Thyroidectomy done using the intracapsular dissection technique is a safe and easy procedure for benign thyroid swellings. This technique aims to minimize tissue handling and dissection in the lateral thyroid groove and thereby reduce the postoperative complications related to the injury of recurrent laryngeal nerve and parathyroid glands, increasing the surgical outcomes and patient compliance. Hence, intracapsular dissection can be routinely practiced for the extirpation of benign thyroid swellings.
High-frequency audiometry, speech perception in quiet and noise, and vestibular-evoked myogenic potential in women with polycystic ovary syndrome
Authors: Apeksha Kumari , Basappa Ananya , Devananda Darshan
Published: June 2022

Purpose

The study aimed to investigate the effect of PCOS on high-frequency thresholds, speech perception in quiet and in presence of noise, and vestibular functioning in women with and without PCOS and to correlate the speech perception scores with that of the pure-tone thresholds obtained at conventional and higher frequencies.

Methods

Women with and without PCOS in the age range of 18–40 years diagnosed between January 2019 and January 2020 were participants. Conventional and high-frequency audiometry (HFA), speech perception in quiet and in noise (SPIN), and cervical vestibular-evoked myogenic potentials (cVEMP) and ocular vestibular-evoked myogenic potentials (oVEMP) were assessed for both groups.

Results

Conventional audiometry (250 Hz to 8000 Hz) showed no statistically significant difference between both groups. High-frequency audiometry (9000 Hz to 20,000 Hz) showed significantly poorer pure-tone thresholds for women with PCOS compared to women without PCOS. SPIN results showed significantly lower SPIN scores for women with PCOS for − 3dB SNR, − 6 dB SNR, and − 9dB SNR. No difference in scores was observed for quiet conditions and 0 dB SNR for women with and without PCOS. cVEMP and oVEMP responses showed reduced amplitude in women with PCOS.

Conclusion

All the women diagnosed with having PCOS should be screened for hearing loss, speech perception difficulty in quiet and in presence of noise, and vestibular system functioning. If the hearing is affected, intervention should be started early in life.
A comparison between Kalman ensemble generator and geostatistical frequency-domain electromagnetic inversion: The impacts on near-surface characterization
Authors: Narciso João , Bobe Christin , Azevedo Leonardo , Van De Vijver Ellen
Published: June 2022

The spatial distribution of the physical properties of the first meters beneath the earth’s surface is often complex due to its highly dynamic nature and small-scale heterogeneities resulting from natural and anthropogenic processes. Therefore, obtaining numerical 3D models that accurately describe the spatial distribution of these properties is often challenging yet essential for different fields such as environmental assessment and remediation, geoarchaeological conservation, and precision agriculture. Frequency-domain electromagnetic (FDEM) induction methods have proven their potential to image these properties in high (spatial) detail because FDEM measurements are sensitive to two key soil properties: electrical conductivity and magnetic susceptibility. Predicting subsurface properties from FDEM data requires solving an ill-posed and nonlinear inverse problem with multiple solutions. Recently, there has been a rapid growth of FDEM inversion methods, which may be broadly divided into probabilistic and deterministic methods. We compare two stochastic FDEM inversion approaches: the Kalman ensemble generator (KEG) and another one formulated as an iterative geostatistical FDEM inversion. Both methods are applied to a synthetic data set with spatially heterogeneous physical properties of interest, mimicking a real landfill mining site. The predicted models are compared with the reference models in terms of histogram and variogram models reproduction and in their ability to quantify spatial uncertainty. The results indicate the ability of both methods to predict the reference values. Although the KEG is computationally efficient, it struggles to reproduce the extreme values. In contrast, the geostatistical inversion approach ensures the reproduction of the imposed histograms and variogram models in the predicted models. As the prior information is included in both inversion methods in different ways, the pointwise variance models computed from all of the posterior models have different information. The synthetic data set is available to the community, so it can be used as a benchmark for other FDEM inversion methods.
A new method to estimate the total magnetization direction from the magnetic anomaly: Multiple correlation
Authors: Jian Xiange , Liu Shuang , Hu Xiangyun , Zhang Yujie , Zhu Dan , Zuo Boxin
Published: June 2022

Natural remanent magnetization diverts the direction of the total magnetization vector from the earth’s magnetic field direction. It is important to determine the magnetization direction because the processing and inversion of magnetic usually need the magnetization direction as a priori information. The conventional strategy for estimating the magnetization direction is to compute the crosscorrelation between the reduced-to-the-pole (RTP) field and one magnetic magnitude transform, which is insensitive to the magnetization direction. A new theory and method are proposed that the total magnetization direction is determined by computing the multiple correlation coefficients between the RTP field and the multiple direction-insensitive magnitudes transforms, such as the total magnitude anomaly and the normalized source strength. The linear regression between the RTP field and the direction-insensitive magnitude transforms is established. Then, the correlation is computed by the RTP field and the constructed regressor. The proposed method is tested on synthetic of single and complex models, respectively. Then, the method is applied to the field data of the Yeshan region (eastern China) and the Black Hill Norite (southern Australia). The proposed multiple correlation is an extension of the conventional crosscorrelation method that provides an accurate and robust way to estimate the magnetization direction from the total field anomaly.
VP/VS ratio anomalies in fractured rocks and implication for dolomite gas reservoir identification in the northwest Sichuan Basin
Authors: Ding Pinbo , Di Guidong , Chen Kang , Cai Jianchao , Li Xiang-Yang
Published: June 2022

The dolomite gas reservoir of the Permian Chihsia Formation has recently become the main target of hydrocarbon exploration in the northwest Sichuan Basin. Owing to its substantially low porosity and permeability, the dolomite gas reservoir has become a great challenge for geophysicists in terms of distinguishing gas-filled dolomite thin layers. We have used limestone and dolomite core samples from the Permian in the northwest Sichuan Basin to investigate the physical characteristics of the dolomite gas reservoir in a laboratory. Dolomite has a comparatively higher permeability than limestone due to its higher fracture development. X-ray CT scanning indicates that a few large pore spaces dominate the pore space in limestone that cannot provide good pore connections, whereas small pores and fractures dominate the pore spaces in dolomite. The fracture development in the dolomites provides insignificant porosity that substantially increases the permeability. The [Formula: see text] ratio estimated from well-logging data in the northwest Sichuan Basin indicates significantly lower anomalies. These low [Formula: see text] anomalies validate the rock-physics analysis from the laboratory data and indicate that the [Formula: see text] ratio could be a good indicator of gas reservoirs in dolomite layers.
Seismic interpretation of sandstone-type uranium deposits in the Songliao Basin, Northeast China
Authors: Hu Shuang , Hu Huiting , Shi Erxiu , Tang Chao , Zhang Rui , Hao Yugang
Published: June 2022

Nuclear energy is a clean energy source that can replace fossil energy on a large scale, and the nuclear energy industry has great advantages in terms of its technical maturity, economic potential, and sustainability. The stable supply of uranium ore, a type of energy mineral, is an important factor for the sustainable development of the nuclear energy industry; as a result, uranium ore has increasingly become the focus of current mineral exploration. We have used seismic attribute analysis, stratal slicing, and seismic inversion to characterize the Sifangtai Formation’s sandstone-type uranium deposit in area A of the central Songliao Basin. We conclude that seismic attribute analysis and the stratal slicing method can predict the continuous reservoir sand body in the study area, and seismic inversion can describe the spatial features of the reservoir sand body in detail. Further analysis of uranium-bearing drilling finds that uranium ore is located in the middle sand body of the lower segment of the Sifangtai Formation, in the middle of the study area, and that the predicted reservoir sand body meets the high-precision requirements for exploration. We use the combination of seismic interpretation and drilling analysis of uranium-bearing ore bodies to effectively predict the size and shape of uranium-bearing ore bodies, and this combined approach can provide guidance for uranium exploration. Furthermore, the results of this study also are significant for the prediction of sand bodies in uranium reservoirs.
Major Adverse Cardiac Events With Immune Checkpoint Inhibitors: A Pooled Analysis of Trials Sponsored by the National Cancer Institute—Cancer Therapy Evaluation Program
Authors: Naqash Abdul Rafeh , Moey Melissa Y.Y. , Cherie Tan Xiao-Wei , Laharwal Mehak , Hill Vanessa , Moka Nagabhishek , Finnigan Shanda , Murray James , Johnson Douglas B. , Moslehi Javid J. , Sharon Elad
Published: June 2022

PURPOSE

Major adverse cardiac events (MACEs) because of immune checkpoint inhibitors (ICIs) are infrequent immune-related adverse events (irAEs) that comprise a spectrum of cardiac toxicities with variable manifestations. ICI-related MACEs can lead to significant morbidity and mortality, hence the need to better define presentations of MACEs and their association with noncardiac irAEs in ICI-treated patients.

METHODS

We conducted a retrospective pooled analysis of MACE captured in the serious adverse events reporting database of the National Cancer Institute–Cancer Therapy Evaluation Program for National Cancer Institute–sponsored investigational clinical trials between June 2015 and December 2019. Patients were eligible if they had been treated with anti–programmed cell death protein-1 (anti–PD-1)/programmed cell death-ligand 1 (anti–PD-L1) alone or with additional anticancer therapies.

RESULTS

A total of 6,925 participants received anti–PD-(L)1-based therapies; 48% (n = 3,354) were treated with single-agent anti–PD-(L)1 therapy. Of 6,925 patients, 0.6% (n = 40) qualified as ICI-related MACE, with 77.5% (n = 31 of 40) being ≥ grade 3. Myocarditis accounted for 45% (n = 18 of 40) of total ICI-MACEs. Concurrent multisystem involvement with other noncardiac irAEs was seen in 65% (n = 26 of 40). Most patients with myocarditis (83%, n = 15 of 18) had one or more noncardiac irAEs associated. Incidence of MACE was higher with anti–PD-(L)1 + targeted therapies compared with anti–PD-(L)1 + anti–cytotoxic T-cell lymphocyte-4 combinations (2.1% v 0.9%, P = .08). There was a higher incidence of myocarditis with anti–PD-(L)1-based combination therapies versus single-agent anti–PD-(L)1 therapies (0.36%, n = 13 of 3,571 v 0.15%, n = 5 of 3,354, P = .08). Deaths related to myocarditis were identified in 22.5% (n = 4 of 18). All four patients who died had concurrent myositis.

CONCLUSION

Increasing patient and prescriber awareness in understanding patterns of ICI-MACE and associated noncardiac irAEs should be emphasized. Better characterization of the risk of MACE with the concurrent use of non–ICI-based anticancer therapies with anti–PD-(L)1 treatments is needed.
Circulating Tumor DNA and Late Recurrence in High-Risk Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer
Authors: Lipsyc-Sharf Marla , de Bruin Elza C. , Santos Katheryn , McEwen Robert , Stetson Daniel , Patel Ashka , Kirkner Gregory J. , Hughes Melissa E. , Tolaney Sara M. , Partridge Ann H. , Krop Ian E. , Knape Charlene , Feger Ute , Marsico Giovanni , Howarth Karen , Winer Eric P. , Lin Nancy U. , Parsons Heather A.
Published: June 2022

PURPOSE

To examine the prevalence and dynamics of circulating tumor DNA (ctDNA) and its association with metastatic recurrence in patients with high-risk early-stage hormone receptor–positive breast cancer (HR+ BC) more than 5 years from diagnosis.

METHODS

We enrolled 103 patients with high-risk stage II-III HR+ BC diagnosed more than 5 years prior without clinical evidence of recurrence. We performed whole-exome sequencing (WES) on primary tumor tissue to identify somatic mutations tracked via a personalized, tumor-informed ctDNA test to detect minimal residual disease (MRD). We collected plasma at the time of consent and at routine visits every 6-12 months. Patients were followed for clinical recurrence.

RESULTS

In total, 85 of 103 patients had sufficient tumor tissue; of them, 83 of 85 (97.6%) patients had successful whole-exome sequencing. Personalized ctDNA assays were designed targeting a median of 36 variants to test 219 plasma samples. The median time from diagnosis to first sample was 8.4 years. The median follow-up was 10.4 years from diagnosis and 2.0 years from first sample. The median number of plasma samples per patient was two. Eight patients (10%) had positive MRD testing at any time point. Six patients (7.2%) developed distant metastatic recurrence, all of whom were MRD-positive before overt clinical recurrence, with median ctDNA lead time of 12.4 months. MRD was not identified in one patient (1.2%) with local recurrence. Two of eight MRD-positive patients had not had clinical recurrence at last follow-up.

CONCLUSION

In this prospective study, in patients with high-risk HR+ BC in the late adjuvant setting, ctDNA was identified a median of 1 year before all cases of distant metastasis. Future studies will determine if ctDNA-guided intervention in patients with HR+ BC can alter clinical outcomes.
Full Laparoscopic Vascular Reconstruction for Portal Tumoral Invasion During a Right Hepatectomy Using the Caudal Approach
Authors: Rotellar Fernando , Luján Juan , Almeida Ana , Benito Alberto , Hidalgo Francisco , López-Olaondo Luis , Martí-Cruchaga Pablo , Zozaya Gabriel
Published: June 2022

Background

Laparoscopic liver surgery has progressively evolved. Consequently, liver procedures are increasingly performed laparoscopically, particularly in experienced centers. However, vascular resection and reconstruction still are considered a limitation for laparoscopy1 due to the risk of bleeding and the technical difficulty.

Methods

A 72-year-old woman with a history of colorectal cancer had a 10 cm metastasis diagnosed in the right hemiliver with tumoral invasion of the right portal branch and tumor thrombus advancing to the portal confluence. After adjuvant chemotherapy and with stable disease, surgical resection was planned.2,3 Tips to avoid portal stenosis were carefully followed.

Results

The operation was performed with a fully laparoscopic procedure. To minimize manipulation, an in situ right hepatectomy was performed.4 The right hepatic artery was dissected and ligated. The liver transection was guided with a caudal approach of the middle hepatic vein.5 The right biliary duct was then divided, achieving an excellent exposure of the portal bifurcation. The main and left portal trunks were occluded with vascular clamps, and the right portal vein was sharply divided with scissors. The stump was sutured to minimize backflow bleeding and to cover the tumor thrombus. Then, the portal opening was transversally sutured with a 5/0 running suture. The clamps were released, and the authors observed no bleeding and an adequate caliber with no stenosis. The procedure was completed in the standard fashion. The postoperative course was uneventful, and the woman was discharged on postoperative day 3. No early or late complications were observed.6

Conclusions

In selected cases, patients who require vascular resection and reconstruction during hepatectomies can benefit from the advantages of a laparoscopic approach.
Pathogenetic and diagnostic role of osteoprotegerin in the combined course of osteoarthritis and obesity
Authors: Litvynova A. , Pasiieshvili L.
Published: June 2022

In recent years, it has been proven that the formation of OA can occur against the background of impaired bone metabolism.

Bone remodeling is considered as a continuous complex process aimed at eliminating microdamages and updating the bone matrix. A key link in the regulation of this process is the system RANK / RANKL / OPG (osteoprotegerin), which provides a balance of activity of osteoblasts and osteoclasts. It blocks the interaction between RANK and RANKL by intercepting the RANKL ligand, which inhibits osteoclast development and reduces bone resorption.

Thus, these properties of OPG can be considered as one of the pathogenetic factors in patients with dystrophic joint lesions.

Objective: to investigate the content and role of osteoprotegerin in young patients with osteoarthritis, which occurs against the background of changes in body weight.

Materials and methods. The study involved 75 young patients (mean age - 30.92 ± 0.546 years) with overweight or obesity, who in the previous stages of the study was diagnosed with osteoarthritis (main group). The comparison group was represented by 50 patients with osteoarthritis and normal body weight. The age of patients was 30.95 ± 0.545 years; as in the previous group, men predominated - 64% and 36% respectively.

Benchmarks of osteoprotegerin were obtained in a study of 37 relatively healthy individuals of the same age and sex.

The level of osteoprotegerin was determined by enzyme-linked immunosorbent assay using the FineTest EH0247 reagent kit, China.

The outcomes were processed by the methods of variation statistics using the computer program STATISTICA.Results and discussion. When determining the content of OPG in the serum of patients of the main group was found to increase to 124.03 pg / ml, against control - 65.64 pg / ml. In the group of patients with isolated OA, this value was 92.29 pg / ml. Meaning that, in OA, running on the background of altered BMI, the content of OPG is likely to increase, both in relation to the norm and the results of the comparison group (p <0,001).

The formation and course of osteoarthritis is accompanied by an increase in osteoprotegerin, the content of which depends on the degree of obesity and the radiological stage of the process.

Conclusions: The course of osteoarthritis is accompanied by an increase in osteoprotegerin, which is considered a negative regulator of bone resorption.

In osteoarthritis, which occurs against the background of changes in body mass index, a direct correlation with the degree of obesity.

Changes in osteoprotegerin in patients with osteoarthritis depend on the radiological stage of joint damage and are most pronounced in individuals with stage 2 obesity and stage 2 radiological changes
Effect of an antidisbiotic agent on the biosynthesis of fatty acids of liver lipids of rats which received palm oil on the background of dysbiosis
Authors: Levitsky A. , Markov A. , Velichko V. , Selivanskaya I. , Lapinskaya A.
Published: June 2022

Background. To determine the effect of antidysbiotic agent on the biosynthesis of fatty acids of lipids in the liver of rats fed a high-fat diet (HFD) with palm oil against the background of dysbiosis.

Methods. The HFD contained 15% palm oil. In a biological experiment, white rats were used, divided into 4 groups: the 1st group received a fat-free diet (FFD), the 2nd, 3rd, and 4th received HFD. In rats of the 3rd and 4th groups, dysbiosis was reproduced using lincomycin. Rats of the 4th group from the first day of the experiment received an antidysbiotic agent (inulin + quercetin, ADA) with food. The duration of feeding is 39 days. Liver lipids were divided into 3 fractions: neutral lipids (NL), phospholipids (PL), and free fatty acids (FFA). The fatty acid composition of the fractions was determined by gas chromatography. The “activities” of fatty acid synthase, palmitic acid elongase, and stearyl-CoA- desaturase (SCD18 and SCD16) were determined.

Results. The presence of all classes of fatty acids (FA) in the liver lipids of rats treated with FFD was established.  Consumption of HFD with palm oil increased the content of NL in the liver by 6 times (gr. 2), and in group 3 by 8 times.  The introduction of ADA reduces the content of NL almost to the level of the 1st group.  The content of ω-3 polyunsaturated fatty acids (PUFA) decreases in the PL fraction in rats of the 3rd group and is restored in rats of the 4th group. In rats treated with HFD, the "activity" of synthase, SCD18 and very strongly SCD16 are reduced.

Conclusion: The negative effect of palm oil on the background of dysbiosis on the biosynthesis of fatty acids in the liver, leading to hepatic steatosis and deficiency of ω-3 PUFA, can be prevented by the use of an antidysbiotic agent.