bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Paraclinical Biomarkers and the Hitches to Assess Conversion to Secondary Progressive Multiple Sclerosis: A Systematic Review
Authors: Krajnc Nik , Bsteh Gabriel , Berger Thomas
Published: August 2021

Conversion to secondary progressive (SP) course is the decisive factor for long-term prognosis in relapsing multiple sclerosis (MS), generally considered the clinical equivalent of progressive MS-associated neuroaxonal degeneration. Evidence is accumulating that both inflammation and neurodegeneration are present along a continuum of pathologic processes in all phases of MS. While inflammation is the prominent feature in early stages, its quality changes and relative importance to disease course decreases while neurodegenerative processes prevail with ongoing disease. Consequently, anti-inflammatory disease-modifying therapies successfully used in relapsing MS are ineffective in SPMS, whereas specific treatment for the latter is increasingly a focus of MS research. Therefore, the prevention, but also the (anticipatory) diagnosis of SPMS, is of crucial importance. The problem is that currently SPMS diagnosis is exclusively based on retrospectively assessing the increase of overt physical disability usually over the past 6–12 months. This inevitably results in a delay of diagnosis of up to 3 years resulting in periods of uncertainty and, thus, making early therapy adaptation to prevent SPMS conversion impossible. Hence, there is an urgent need for reliable and objective biomarkers to prospectively predict and define SPMS conversion. Here, we review current evidence on clinical parameters, magnetic resonance imaging and optical coherence tomography measures, and serum and cerebrospinal fluid biomarkers in the context of MS-associated neurodegeneration and SPMS conversion. Ultimately, we discuss the necessity of multimodal approaches in order to approach objective definition and prediction of conversion to SPMS.
Gastric Electrical Dysarrhythmia in Probable Rapid Eye Movement Sleep Behavior Disorder
Authors: Peng Anjiao , Ji Shuming , Li Wanling , Lai Wanlin , Qiu Xiangmiao , He Shixu , Dong Bosi , Huang Cheng , Chen Lei
Published: August 2021

Background: Subjective gastrointestinal complaints have been repeatedly reported in patients with REM sleep behavior disorder (RBD), but objective evidence is scarce. We aimed to objectively investigate the gastrointestinal dysfunction in individuals with probable RBD (pRBD) using an electrogastrogram.

Methods: Thirty-two participants with pRBD and 60 age- and gender-matched healthy controls were enrolled. pRBD was diagnosed based on questionnaires and further assessed by experienced neurologists. After thorough assessment of participants' subjective gastrointestinal symptoms, preprandial and postprandial gastric activities were measured using an electrogastrogram. Dominant frequency, dominant power ratio, and the ratio of preprandial to postprandial power were analyzed.

Results: Among the gastric symptoms, hiccup (34.8 vs. 9.6%, p = 0.017) and postprandial gastric discomfort (43.5 vs. 15.4%, p = 0.017) were more frequent in participants with pRBD than in controls. The dominant frequency on the electrode overlying the gastric pyloric antrum was lower in pRBD than in healthy controls (2.9 [2.6–2.9] vs. 2.9 [2.9–3.2] cpm, p = 0.006). A reduced dominant power ratio from the same electrode was also found in individuals with pRBD (60.7 [58.0–64.5] vs. 64.2 [58.7–69.6] %, p = 0.046).

Conclusion: Patients with pRBD have a higher rate of gastric dysfunction, which presented as irregular slow wave rhythmicity on an electrogastrogram.
Intracranial Pressure and Cerebral Perfusion Pressure in Large Spontaneous Intracranial Hemorrhage and Impact of Minimally Invasive Surgery
Authors: Al-Kawaz Mais N. , Li Yunke , Thompson Richard E. , Avadhani Radhika , de Havenon Adam , Gruber Joshua , Awad Issam , Hanley Daniel F. , Ziai Wendy
Published: August 2021

Introduction: We investigated the effect of hematoma volume reduction with minimally invasive surgery (MIS) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with large spontaneous intracerebral hemorrhage (ICH).

Methods:Post-hoc analysis of the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation (MISTIE III) study, a clinical trial with blinded outcome assessments. The primary outcome was the proportion of ICP readings ≥20 and 30 mmHg, and CPP readings <70 and 60 mm Hg. Secondary outcomes included major disability (modified Rankin scale >3) and mortality at 30 and 365 days. We assessed the relationship between proportion of high ICP and low CPP events and MIS using binomial generalized linear models, and outcomes using multiple logistic regression.

Results: Of 499 patients enrolled in MISTIE III, 72 patients had guideline based ICP monitors placed, 34 in the MIS group and 38 in control (no surgery) group. Threshold ICP and CPP events ≥20/ <70 mmHg occurred in 31 (43.1%) and 52 (72.2%) patients respectively. On adjusted analyses, proportion of ICP readings ≥20 and 30 mmHg were significantly lower in the MIS group vs. control group [Odds Ratio (OR) 0.27, 95% Confidence Interval [CI] 0.11–0.63 (p = 0.002); OR = 0.18, 0.04–0.75, p = 0.02], respectively. Proportion of CPP readings <70 and 60 mm Hg were also significantly lower in MIS patients [OR 0.31, 95% CI 0.15–0.63 (p = 0.001); OR 0.30, 95% CI 0.11–0.83 (p = 0.02)], respectively. Higher proportions of CPP readings <70 and 60 mm were significantly associated with short term mortality (p = 0.04), and (p = 0.006), respectively. Long term mortality was significantly associated with higher proportion of time with ICP ≥ 20 (p = 0.04), ICP ≥ 30 (p = 0.04), and CPP <70 mmHg (p = 0.01).

Conclusion: Our results are consistent with the hypothesis that surgical reduction of ICH volume decreases proportion of high ICP and low CPP events and that these variables are associated with short- and long-term mortality.
Novel Therapies for Parkinsonian Syndromes–Recent Progress and Future Perspectives
Authors: Przewodowska Dominika , Marzec Weronika , Madetko Natalia
Published: August 2021

Background: Atypical parkinsonian syndromes are rare, fatal neurodegenerative diseases associated with abnormal protein accumulation in the brain. Examples of these syndromes include progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration. A common clinical feature in parkinsonism is a limited improvement with levodopa. So far, there are no disease-modifying treatments to address these conditions, and therapy is only limited to the alleviation of symptoms. Diagnosis is devastating for patients, as prognosis is extremely poor, and the disease tends to progress rapidly. Currently, potential causes and neuropathological mechanisms involved in these diseases are being widely investigated.

Objectives: The goal of this review is to summarize recent advances and gather emerging disease-modifying therapies that could slow the progression of atypical parkinsonian syndromes.

Methods: PubMed and Google Scholar databases were searched regarding novel perspectives for atypical parkinsonism treatment. The following medical subject headings were used: “atypical parkinsonian syndromes—therapy,” “treatment of atypical parkinsonian syndromes,” “atypical parkinsonian syndromes—clinical trial,” “therapy of tauopathy,” “alpha-synucleinopathy treatment,” “PSP therapy/treatment,” “CBD therapy/treatment,” “MSA therapy/treatment,” and “atypical parkinsonian syndromes—disease modifying.” All search results were manually reviewed prior to inclusion in this review.

Results: Neuroinflammation, mitochondrial dysfunction, microglia activation, proteasomal impairment, and oxidative stress play a role in the neurodegenerative process. Ongoing studies and clinical trials target these components in order to suppress toxic protein accumulation. Various approaches such as stem cell therapy, anti-aggregation/anti-phosphorylation agent administration, or usage of active and passive immunization appear to have promising results.

Conclusion: Presently, disease-modifying strategies for atypical parkinsonian syndromes are being actively explored, with encouraging preliminary results. This leads to an assumption that developing accurate, safe, and progression-halting treatment is not far off. Nevertheless, the further investigation remains necessary.
Food Access Worries, Food Assistance Use, Purchasing Behavior, and Food Insecurity Among New Yorkers During COVID-19
Authors: Clay Lauren A. , Rogus Stephanie
Published: August 2021

The coronavirus disease of 2019 (COVID-19) disrupted health, economy, and food systems across the United States. This cross-sectional study examined the relationship between food access worries, food assistance use, and purchasing behaviors and food insecurity during COVID-19 among residents of New York State. New Yorkers were recruited to complete a web-based survey through Qualtrics. The survey took place in the summer and fall of 2020 and asked respondents about food access worries, food assistance use, food insecurity, and food purchasing behaviors. Chi-square analysis examined the relationships between food concerns, food assistance use, purchasing behaviors, and demographic characteristics by reported food insecurity, and significant results were analyzed in a series of logistic regression models. Results showed that higher food worries, Supplemental Nutrition Assistance Program (SNAP) use, reported food assistance and delivery as food sources, and self-reported Hispanic ethnicity were associated with a higher likelihood of experiencing food insecurity. Future research is needed to assess the ongoing impacts of the pandemic on food access and food insecurity, particularly among underserved groups. Measures that provide additional money for food and improved food access can alleviate barriers to accessing enough healthy food at this time.
Dietary Protein From Different Sources Exerted a Great Impact on Lipid Metabolism and Mitochondrial Oxidative Phosphorylation in Rat Liver
Authors: Shi Xuebin , Huang Zixin , Zhou Guanghong , Li Chunbao
Published: August 2021

Associations between meat diets and human health have been widely considered. In this study, we focused on long-term effects of different sources of meat protein on liver metabolic enzymes. For 90 days, rats were fed with semisynthetic diets that differed only with protein source. Casein was used as a reference and isolated soybean, fish, chicken, pork, and beef proteins were compared. Changes in liver proteome were determined by isobaric tag for relative and absolute quantitation (iTRAQ) labeling and liquid chromatography electrospray ionization tandem mass spectrometry/mass spectrometry (LC–ESI–MS/MS). Fish and pork protein diets upregulated the gene expression involved in cholesterol synthesis and esterification, and pork protein diet also upregulated the gene expression of high-density lipoprotein receptor and low-density lipoprotein receptor. Chicken, pork, and beef protein diets upregulated the gene expression involved in cholesterol reverse transport and bile acid production, which increased the total cholesterol level in the fish protein diet group. Total cholesterol levels in liver were lower in the pork and beef protein diet groups. Triglyceride levels in liver were lower in chicken, pork, and beef protein diet groups. Peroxisomal proliferator-activated receptor-gamma coactivator-1 was upregulated by chicken, pork and beef protein diets, and promoted the degradation and metabolism of triglyceride, resulting in lower triglyceride in the three diet groups. Meat proteins at a recommended level could be more conducive to cholesterol degradation, triglyceride decomposition, and energy balance maintenance at a healthy level. The findings give a new insight into the associations between meat diet intake and human health.
Development of a Prognostic Scoring System for Hepatocellular Carcinoma Patients With Main Portal Vein Tumor Thrombus Undergoing Conventional Transarterial Chemoembolization: An Analysis of 173 Patients
Authors: Li Jing-huan , Yin Xin , Fan Wen-shuai , Zhang Lan , Chen Rong-xin , Chen Yi , Li Li-xin , Ge Ning-ling , Gan Yu-hong , Wang Yan-hong , Ren Zheng-gang
Published: August 2021

Background

Patients with hepatocellular carcinoma (HCC) with main portal vein tumor thrombus (mPVTT) have poor prognosis. Promising systemic therapies, such as target therapies, have limited benefits. The purpose of this study is to retrospectively evaluate the benefits of conventional TACE (c-TACE) and to establish a prognostic stratification of HCC patients with mPVTT.

Methods

This is a single center retrospective study conducted over 5 years (duration of performing c-TACE), on consecutive HCC patients with mPVTT receiving c-TACE. Univariable and multivariable analysis were used to explore factors independently associated with overall survival (OS). Based on Cox-regression analysis, prognostic models were developed and internally validated by bootstrap methods. Discrimination and performance were measured by Akaike information criterion, concordance index, and likelihood ratio test.

Results

A total of 173 patients were included. Median OS was 6.0 months (95%CI: 3.92~8.08). The independent variables correlated with survival were largest tumor diameter, tumor number, mPVTT extension, and AFP. In the final model, patients were assigned 2 points if largest tumor diameter ≥8 cm, or tumor number ≥2, 1point if main trunk was complete obstructed, or AFP ≥400 ng/ml. By summing up these points, patients were divided into three risk groups according to the score at the 15rd and 85th percentiles, in which median OS were 18, 7, and 3.5months, respectively (p<0.001). The model shown optimal discrimination, performance, and calibration.

Conclusions

c-TACE could provide survival benefits in HCC patients with mPVTT and the proposed prognostic stratification may help to identify good candidates for the treatment, and those for whom c-TACE may be futile.
CEUS-Based Radiomics Can Show Changes in Protein Levels in Liver Metastases After Incomplete Thermal Ablation
Authors: Bao Haiwei , Chen Ting , Zhu Junyan , Xie Haiyang , Chen Fen
Published: August 2021

Objective

To investigate the ability of contrast-enhanced ultrasound (CEUS)-based radiomics combined with machine learning to detect early protein changes after incomplete thermal ablation.

Methods

HCT-26 colorectal adenoma cells were engrafted into the livers of 80 mice, which were randomly divided into 4 groups for palliative laser ablation. Changes in heat shock protein (HSP) and apoptosis-related protein expression in the tumors were assessed. SCID mice subjected to CEUS and ultrasonography were divided into training (n=56) and test (n=24) datasets. Then, 102 features from seven feature groups were extracted. We use the least absolute shrinkage and selection operator (LASSO) feature selection method to fit the machine learning classifiers. The feature selection methods and four classifiers were combined to determine the best prediction model.

Results

The areas under the receiver-operating characteristic curves (AUCs) of the classifiers in the test dataset ranged from 0.450 to 0.932 (median: 0.721). The best score was obtained from the model in which the omics data of CEUS was analyzed in the arterial phase by random forest (RF) classification.

Conclusions

A machine learning model, in which radiomics characteristics are extracted by multimodal ultrasonography, can accurately, rapidly and noninvasively identify protein changes after ablation.
Successful Treatment of Refractory and Relapsed CNS Acute Lymphoblastic Leukemia With CD-19 CAR-T Immunotherapy: A Case Report
Authors: Htun Kyaw Thu , Gong Qiang , Ma Le , Wang Ping , Tan Ya , Wu Guangsheng , Chen Jieping
Published: August 2021

In recent decades, survival was significantly improved in B cell acute lymphoblastic leukemia (B-ALL) patients. But refractory and relapsed B-ALL still has aggressive clinical behavior and poor prognosis. Especially, the patients with central nervous system infiltration is very difficult to achieve complete remissions with routine treatment. Chimeric antigen receptor-modified T-cell therapy targeting CD-19 has shown to be a beneficial treatment approach in refractory and relapsed B cell acute lymphoblastic leukemia (r/r ALL). However, there are very few studies reporting to treatment of refractory and relapsed B cell ALL with central nervous system infiltration. Here, we reported one single case of a patient diagnosed with relapsed B cell ALL with CNS infiltration who was successfully treated by second generation CAR containing a co-stimulator CD28 or 4-1BB therapy. Long-term proliferation of CAR-T cells in peripheral blood and bone marrow was observed more than 18 months. After CAR-T treatment, the patient got toxicity of grade 1 cytokine release syndrome and achieved significantly 36 months event free survival of follow-up. It is suggested that CD-19 CAR containing CD28 or 4-1BB costimulatory may be an effective therapy in refractory and relapsed B cell ALL with central nervous system infiltration. Its toxicity is mild, and its safety is high.

Clinical Trial Registration:ClinicalTrials.gov Identifier: NCT02349698.
Characterization of the Therapeutic Effects of Novel Chimeric Antigen Receptor T Cells Targeting CD38 on Multiple Myeloma
Authors: Li Xiaorui , Feng Yaru , Shang Fengqin , Yu Zhuoying , Wang Tieshan , Zhang Jing , Song Zhiru , Wang Ping , Shi Bingjie , Wang Jianxun
Published: August 2021

Multiple myeloma (MM) is a tumor type characterized by the unregulated proliferation of clonal plasma cells in the bone marrow. Immunotherapy based on chimeric antigen receptor T cell (CAR-T) therapy has achieved exciting success in the treatment of hematological malignant tumors. CD38 is highly and evenly expressed in MM and is an attractive target for MM treatment. Here, we successfully constructed two novel second-generation CAR-T cells targeting CD38 by retroviral vector transduction. CD38 CAR-T cells could be activated effectively after stimulation with CD38-positive tumor cells and secrete cytokines such as IFN-γ and TNF-α to promote tumor cell apoptosis in in vitro experiments. Real-time fluorescence monitoring experiments, luciferase detection experiments and flow cytometry experiments revealed the efficient and specific killing abilities of CD38 CAR-T cells against CD38-positive tumor cells. The proliferation ability of CD38 CAR-T cells in vitro was higher than that of untransduced T cells. Further antitumor experiments in vivo showed that CD38 CAR-T cells could be quickly activated to secrete IFN-γ and eliminate tumors. Thus, novel CD38-targeted second-generation CAR-T cells have efficient and specific antitumor activity and may become a novel therapy for the clinical treatment of MM.
Case Report: The Formation of a Truncated PAX5 Transcript in a Case of Ph-Positive Mixed Phenotype Acute Leukemia With dic(7;9)(p11-p13;p13)
Authors: Yu Yan , Zeng Zhao , Xie Jundan , Lu Qiongyu , Cai Wenzhi , Zhang Ruixi , Pan Jinlan , Zhao Yun , Sun Aining , Qiu Huiying , Chen Suning
Published: August 2021

PAX5 plays a critical role in B-cell precursor development and is involved in various chromosomal translocations that involve the fusion of a portion of PAX5 to at least 49 different partners reported to date. Here, we identified a novel PAX5 fusion transcript in a Ph-positive mixed phenotype acute leukemia case with dic(7;9)(q13;q13), in which a translocation juxtaposes the 5’ region of PAX5 and the ubiquitin-conjugating enzyme E2D4 (UBE2D4) to generate a PAX5-UBE2D4 fusion gene. To further explore the general characteristics and function of PAX5-UBE2D4, we cloned the full-length cDNA, which was amplified from the bone marrow of the patient. Interestingly, the fusion was located in the nucleus and negatively affected PAX5 transcription activity. Importantly, the fusion promoted tumor growth in nude mice and the proliferation of NIH3T3 cells in vitro. In conclusion, the fusion resulted in partial oncogenic activity, in contrast to the tumor suppressor activity of wild-type PAX5.
Transferrin-Conjugated Erianin-Loaded Liposomes Suppress the Growth of Liver Cancer by Modulating Oxidative Stress
Authors: Yang Anhui , Sun Zhen , Liu Rui , Liu Xin , Zhang Yue , Zhou Yulin , Qiu Ye , Zhang Xinrui
Published: August 2021

Background

Liver cancer is one of the most malignant human cancers, with few treatments and a poor prognosis. Erianin (ERN) is a natural compound with multiple pharmacological activities that has been reported to have numerous excellent effects against liver cancer in experimental systems. However, its application in vivo has been limited due to its poor aqueous solubility and numerous off-target effects. This study aimed to improve the therapeutic efficacy of ERN by developing novel ERN-loaded tumor-targeting nanoparticles.

Results

In this study, ERN was loaded into liposomes by ethanol injection (LP-ERN), and the resulting LP-ERN nanoparticles were treated with transferrin to form Tf-LP-ERN to improve the solubility and enhance the tumor-targeting of ERN. LP-ERN and Tf-LP-ERN nanoparticles had smooth surfaces and a uniform particle size, with particle diameters of 62.60 nm and 88.63 nm, respectively. In HepG2 and SMMC-7721 cells, Tf-LP-ERN induced apoptosis, decreased mitochondrial membrane potentials and increased ERN uptake more effectively than free ERN and LP-ERN. In xenotransplanted mice, Tf-LP-ERN inhibited tumor growth, but had a minimal effect on body weight and organ morphology. In addition, Tf-LP-ERN nanoparticles targeted tumors more effectively than free ERN and LP-ERN nanoparticles, and in tumor tissues Tf-LP-ERN nanoparticles promoted the cleavage PARP-1, caspase-3 and caspase-9, increased the expression levels of Bax, Bad, PUMA, and reduced the expression level of Bcl-2. Moreover, in the spleen of heterotopic tumor model BALB/c mice, ERN, LP-ERN and Tf-LP-ERN nanoparticles increased the expression levels of Nrf2, HO-1, SOD-1 and SOD-2, but reduced the expression levels of P-IKKα+β and P-NF-κB, with Tf-LP-ERN nanoparticles being most effective in this regard. Tf-LP-ERN nanoparticles also regulated the expression levels of TNF-α, IL-10 and CCL11 in serum.

Conclusion

Tf-LP-ERN nanoparticles exhibited excellent anti-liver cancer activity in vivo and in vitro by inducing cellular apoptosis, exhibiting immunoregulatory actions, and targeting tumor tissues, and did so more effectively than free ERN and LP-ERN nanoparticles. These results suggest that the clinical utility of a Tf-conjugated LP ERN-delivery system for the treatment of liver cancer warrants exploration.
Immunotherapy for the Treatment of Cutaneous Squamous Cell Carcinoma
Authors: Boutros Andrea , Cecchi Federica , Tanda Enrica Teresa , Croce Elena , Gili Riccardo , Arecco Luca , Spagnolo Francesco , Queirolo Paola
Published: August 2021

Cutaneous squamous cell carcinoma (CSCC) accounts for approximately 20% of all keratinocytic tumors. In most cases, the diagnosis and treatments are made on small, low-risk lesions. However, in about 5% of cases, CSCC may present as either locally advanced or metastatic (i.e. with locoregional lymph nodes metastases or distant localizations). Prior to the introduction of immunotherapy in clinical practice, the standard treatment of advanced CSCC was not clearly defined, and up to 60% of patients received no systemic therapy. Thanks to a strong pre-clinical rationale, clinical trials led to the FDA (Food and Drug Administration) and EMA (European Medicines Agency) registration of cemiplimab, a PD-1 inhibitor that achieved encouraging results in terms of objective response, overall survival, and quality of life. Subsequently, the anti-PD-1 pembrolizumab received the approval for the treatment of advanced CSCC by the FDA only. In this review, we will focus on the definition of advanced CSCC and on the current and future therapeutic options, with a particular regard for immunotherapy.
Transcriptomic and Proteomic Study on the High-Fat Diet Combined With AOM/DSS-Induced Adenomatous Polyps in Mice
Authors: Guo Cui , Xu Yimin , Han Xinyue , Liu Xiaoqiang , Xie Runnan , Cheng Zhihong , Fu Xiaoling
Published: August 2021

Objective

To screen and identify molecular targets and bacteria genus leading to adenomatous polyps in mouse induced by high-fat diet (HFD) +AOM/DSS using omics technology.

Methods

The molecular targets of colorectal adenoma disease were obtained from the GeneCards and OMIM database. The SPF C57BL mice were randomly divided into blank (Control) and AOM/DSS+HFD colorectal adenoma model (ADH) groups. The ADH model group was intraperitoneally injected with AOM reagent. Then, mice were given with 2.5% DSS (in free drinking water) and high-fat diet to establish the mouse model. During this period, the changes of physical signs of mice in each group were observed. After the end of modeling, HE staining was used to evaluate the histopathological change of mice. The differentially expressed genes and proteins in the Control group and ADH group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. The histological results were analyzed by intersection with the intestinal adenoma molecular targets obtained from the database. Moreover, the changes of intestinal flora in the two groups were examined. The correlation between targets and differential bacteria was analyzed and verified by Parallel Reaction Monitoring (PRM) to comprehensively evaluate the mouse model of adenomatous polyp induced by AOM/DSS+HFD.

Results

The general condition and histopathological results of mice confirmed that the ADH mouse model was successfully established and tubular adenoma was formed. A total of 604 genes and 42 proteins related to intestinal adenoma were obtained by histological analysis and database intersection analysis. The intestinal microflora of ADH mice was different from that of normal mice, and the constituents and abundance of intestinal flora were similar to those of human intestinal adenoma. GATA4 and LHPP were selected as potential pathological markers of the model mice by correlation analysis of targets and intestinal flora. The results of PRM verification were highly consistent with the results of RNA-Seq transcriptome sequencing and TMT analysis.

Conclusion

The pathological results, molecular pathological markers and the changes of intestinal flora suggest that the mouse ADH model is ideal for studying the transformation of inflammatory cancer. The ADH model will be helpful for understanding the occurrence and development of human colorectal cancer at the transcriptomic and proteomic level.
CYP450 Genotype—Phenotype Concordance Using the Geneva Micrococktail in a Clinical Setting
Authors: Ing Lorenzini Kuntheavy , Desmeules Jules , Rollason Victoria , Bertin Stéphane , Besson Marie , Daali Youssef , Samer Caroline F.
Published: August 2021

Pharmacokinetic variability is a major source of differences in drug response and can be due to genetic variants and/or drug-drug interactions. Cytochromes P450 are among the most studied enzymes from a pharmacokinetic point of view. Their activity can be measured by phenotyping, and/or predicted by genotyping. Depending on the presence of drugs and/or diseases that can affect their in vivo activity, both approaches can be complementary. In 2014, the Geneva cocktail using dried blood spots was validated in healthy volunteers for CYP450 phenotyping. Since its clinical implementation, it has been used in approximately 500 patients in various clinical situations. Our study aims to report the concordance between CYP450 genotype and phenotype in real-life patients. The prospectively collected data from patients who were genotyped and/or phenotyped between January 2014 and December 2020 were reviewed. A total of 537 patients were genotyped and/or phenotyped for CYP450 during this period, and 241 underwent simultaneous genotyping and phenotyping allowing for genotype/phenotype concordance assessment. Genotyping correctly predicted poor metabolizer phenotypes for most CYPs isoenzymes studied, whereas agreement was more variable for intermediate, normal, and ultrarapid metabolizers. Discrepancies between the phenotype predicted on the basis of genotyping and the measured phenotype were not always explained by concurrent medication (phenotypic switch). Therefore genotyping and phenotyping tests are complementary approaches when aiming to individualize drug therapy. In the 537 patients, the majority of clinical situations were observed with analgesic/anesthetic drugs (n = 187), followed by antidepressants (n = 153), antineoplastics (n = 97), and immunosuppressants (n = 93). Inefficacy (or low drug levels) and adverse drug reaction (or high drug levels) were the main reasons for testing. Genotype and/or phenotype results explained or at least contributed to the clinical event in 44% of cases.
Genome-Wide Association Study of Waterlogging Tolerance in Barley (Hordeum vulgare L.) Under Controlled Field Conditions
Authors: Borrego-Benjumea Ana , Carter Adam , Zhu Min , Tucker James R. , Zhou Meixue , Badea Ana
Published: August 2021

Waterlogging is one of the main abiotic stresses severely reducing barley grain yield. Barley breeding programs focusing on waterlogging tolerance require an understanding of genetic loci and alleles in the current germplasm. In this study, 247 worldwide spring barley genotypes grown under controlled field conditions were genotyped with 35,926 SNPs with minor allele frequency (MAF) > 0.05. Significant phenotypic variation in each trait, including biomass, spikes per plant, grains per plant, kernel weight per plant, plant height and chlorophyll content, was observed. A genome-wide association study (GWAS) based on linkage disequilibrium (LD) for waterlogging tolerance was conducted. Population structure analysis divided the population into three subgroups. A mixed linkage model using both population structure and kinship matrix (Q+K) was performed. We identified 17 genomic regions containing 51 significant waterlogging-tolerance-associated markers for waterlogging tolerance response, accounting for 5.8–11.5% of the phenotypic variation, with a majority of them localized on chromosomes 1H, 2H, 4H, and 5H. Six novel QTL were identified and eight potential candidate genes mediating responses to abiotic stresses were located at QTL associated with waterlogging tolerance. To our awareness, this is the first GWAS for waterlogging tolerance in a worldwide barley collection under controlled field conditions. The marker-trait associations could be used in the marker-assisted selection of waterlogging tolerance and will facilitate barley breeding.
Deciphering the Behavioral Response of Meloidogyne incognita and Fusarium oxysporum Toward Mustard Essential Oil
Authors: Dutta Anirban , Mandal Abhishek , Kundu Aditi , Malik Monika , Chaudhary Amrendra , Khan Matiyar Rahaman , Shanmugam Veerubommu , Rao Uma , Saha Supradip , Patanjali Neeraj , Kumar Rajesh , Kumar Anil , Dash Sukanta , Singh Pradeep Kumar , Singh Anupama
Published: August 2021

Environmental concerns related to synthetic pesticides and the emphasis on the adoption of an integrated pest management concept as a cardinal principle have strengthened the focus of global research and development on botanical pesticides. A scientific understanding of the mode of action of biomolecules over a range of pests is key to the successful development of biopesticides. The present investigation focuses on the in silico protein-ligand interactions of allyl isothiocyanate (AITC), a major constituent of black mustard (Brassica nigra) essential oil (MEO) against two pests, namely, Meloidogyne incognita (Mi) and Fusarium oxysporum f. sp. lycopersici (Fol), that cause severe yield losses in agricultural crops, especially in vegetables. The in vitro bioassay results of MEO against Mi exhibited an exposure time dependent on the lethal concentration causing 50% mortality (LC50) values of 47.7, 30.3, and 20.4 μg ml−1 at 24, 48, and 72 h of exposure, respectively. The study revealed short-term nematostatic activity at lower concentrations, with nematicidal activity at higher concentrations upon prolonged exposure. Black mustard essential oil displayed excellent in vitro Fol mycelial growth inhibition, with an effective concentration to cause 50% inhibition (EC50) value of 6.42 μg ml−1. In order to decipher the mechanism of action of MEO, its major component, AITC (87.6%), which was identified by gas chromatography–mass spectrometry (GC-MS), was subjected to in silico docking and simulation studies against seven and eight putative target proteins of Mi and Fol, respectively. Allyl isothiocyanate exhibited the highest binding affinity with the binding sites of acetyl cholinesterase (AChE), followed by odorant response gene-1 (ODR1) and neuropeptide G-protein coupled receptor (nGPCR) in Mi, suggesting the possible suppression of neurotransmission and chemosensing functions. Among the target proteins of Fol, AITC was the most effective protein in blocking chitin synthase (CS), followed by 2,3-dihydroxy benzoic acid decarboxylase (6m53) and trypsinase (1try), thus inferring these as the principal molecular targets of fungal growth. Taken together, the study establishes the potential of MEO as a novel biopesticide lead, which will be utilized further to manage the Mi–Fol disease complex.
Salivary Oxytocin Is Negatively Associated With Religious Faith in Japanese Non-Abrahamic People
Authors: Yamada Junko , Nakawake Yo , Shou Qiulu , Nishina Kuniyuki , Matsunaga Masahiro , Takagishi Haruto
Published: August 2021

Spirituality and religiosity have a significant impact on one's well-being. Although previous studies have indicated that the neuropeptide hormone oxytocin is associated with spirituality/religiosity, existing findings remain inconsistent. Some studies have reported a positive relationship between oxytocin and spirituality/religiosity, while other studies have reported a negative association. Herein, we examined the association between endogenous oxytocin and spirituality/religiosity in 200 non-Abrahamic Japanese individuals (102 females, mean age ± standard deviation = 41.53 ± 10.46) by measuring the level of salivary oxytocin and spiritual/religious faith. We found that the level of salivary oxytocin was negatively associated with spiritual/religious faith. Individuals with higher levels of salivary oxytocin tend to have more negative spiritual/religious faith compared with those with low oxytocin levels (e.g., “Spirituality/religiosity makes people passive and clinging.”). Moreover, this tendency was only significant in individuals who were not interested in a specific religion. The uniqueness of spirituality/religiosity in Japan could help interpret the current findings.
Influence of Storage Period on the Geochemical Evolution of a Compressed Energy Storage System
Authors: Iloejesi Chidera O. , Beckingham Lauren E.
Published: August 2021

Subsurface porous aquifers are being considered for use as reservoirs for compressed energy storage of renewable energy. In these systems, a gas is injected during times in which production exceeds demand and extracted for energy generation during periods of peak demand or scarcity in production. Current operational subsurface energy facilities use salt caverns for storage and air as the working gas. CO2 is potentially a more favorable choice of working gas where under storage conditions CO2 has high compressibility which can improve operational efficiency. However, the interaction of CO2 and brine at the boundary of the storage zone can produce a chemically active fluid which can result in mineral dissolution and precipitation reactions and alter the properties of the storage zone. This study seeks to understand the geochemical implications of utilization of CO2 as a working gas during injection, storage and extraction flow cycles. Here, reactive transport simulations are developed based on 7 h of injection, 11 h of withdrawal and 6 h of reservoir closure, corresponding to the schedule of the Pittsfield field test, for 15 years of operational life span to assess the geochemical evolution of the reservoir. The evolution in the storage system is compared to a continuously cyclic system of 12 h injection and extraction. The result of the study on operational schedule show that mineral reactivity occurs at the inlet of the domain. Furthermore, the porosity of the inner domain is preserved during the cycling of CO2 acidified brine for both systems.
Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei of Appendiceal Origin: A Single Center Experience
Authors: Santullo Francesco , Pacelli Fabio , Abatini Carlo , Attalla El Halabieh Miriam , Fortunato Giusy , Lodoli Claudio , Giovinazzo Francesco , Rotolo Stefano , Di Giorgio Andrea
Published: August 2021

Background: Pseudomyxoma peritonei (PMP) originating from appendiceal mucinous neoplasm is a rare peritoneal malignancy characterized by the progressive intraperitoneal accumulation of mucus leading to death if left untreated. In recent years, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) offered increased survival rates. This study aims to identify the clinical, pathological, and surgical features influencing safety and survival outcomes of patients undergoing CRS and HIPEC for PMP of appendiceal origin.

Methods: A retrospective analysis of all patients undergoing CRS and HIPEC for PMP of appendiceal origin from January 2015 to May 2019 was conducted at our institution.

Results: Study population included 50 patients (74% female, 26% male). The median age at CRS was 60 (38–84). The median peritoneal cancer index (PCI) was 17. Complete cytoreductive surgery (CC 0–1) was achieved in 47 patients (94%). HIPEC chemotherapeutic regimen was based on oxaliplatin for 13 (28%) patients and mitomycin for 34 (72%) patients. We experienced a total of 19 (38%) postoperative complications, of which 14 (74%) of grade I-II and 5 (26%) of grade III-IV, according to the Clavien-Dindo classification. The median follow-up period was 27 months (12–107) from the date of cytoreductive surgery. The mean survival rate was 100 months, with a 5-year OS of 91%. The mean progression-free survival rate was 77 months (0–107), with a 5-year PFS of 63%. Multivariate analysis identified adenocarcinoma histotype and incomplete cytoreduction to significantly worsen progression-free survival, while incomplete cytoreduction was the only independent predictor of poorer overall survival.

Conclusion: Complete cytoreduction and appendiceal neoplasm histotype play a crucial role in the survival of patients affected by PMP of appendiceal origin. The rates of morbidity associated with CRS and HIPEC for PMP are acceptable.
Hematology, Biochemistry Reference Intervals, and Morphological Description of Peripheral Blood Cells for a Captive Population of Crocodylus intermedius in Colombia
Authors: Barajas-Valero Steven , Rodríguez-Almonacid Cristian , Rojas-Sereno Zulma , Moreno-Torres Carlos , Matta Nubia E.
Published: August 2021

The Orinoco crocodile (Crocodylus intermedius, Graves, 1918) is the most threatened crocodilian of South America. There is only scarce information available about the physiology of this neotropical crocodile. This study aimed to propose baseline hematological and biochemistry reference data and intervals and a morphological description of the peripheral blood cells of captive C. intermedius. Blood was collected from 318 clinically healthy individuals maintained in captivity at Villavicencio, Colombia. Eight of these individuals were sampled and resampled, and these data were compared. Reference intervals were proposed for hematological values [packed cell volume (PCV), red blood cell count, white blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, hemoglobin, and white blood cell count differential counts] and biochemistries [total solids, alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase, glucose, albumin, cholesterol, uric acid, creatinine, and lactate] including adults and juveniles, males and females' crocodiles. Blood cell morphology for the species is described. Significant differences between sex and age were observed. The intraindividual analysis concluded differences for total solids (P ≤ 0.01) and red blood cell counts (P ≤ 0.01). Some biochemical analytes showed a moderate correlation between them, such as ALT–alkaline phosphatase and ALT–uric acid. We present here novel and baseline data with special importance for the clinical diagnosis, improving the national reintroduction programs from either in situ and ex situ populations.
Three-Dimensional Kinematics of the Pelvis and Caudal Lumbar Spine in German Shepherd Dogs
Authors: Schaub Katharina I. , Kelleners Nicola , Schmidt Martin J. , Eley Nele , Fischer Martin S.
Published: August 2021

Lumbosacral vertebral motion is thought to be a factor in the development of degenerative lumbosacral stenosis in German shepherd dogs. So far, few studies exist describing natural canine lumbosacral movement in vivo. Therefore, this investigation aims to achieve a detailed in vivo analysis of bone movement of the lumbosacral region to gain a better understanding of the origin of degenerative lumbosacral stenosis using three-dimensional non-invasive in vivo analysis of canine pelvic and caudal lumbar motion (at L6 and L7). Biplanar cineradiography of the pelvis and caudal lumbar spine of four clinically sound German shepherd dogs at a walk and at a trot on a treadmill was recorded. Pelvic and intervertebral motion was virtually reconstructed and analyzed with scientific rotoscoping. The use of this technique made possible non-invasive measurement of physiological vertebral motion in dogs with high accuracy. Furthermore, the gait patterns of the dogs revealed a wide variation both between individual steps and between dogs. Pelvic motion showed a common basic pattern throughout the stride cycle. Motion at L6 and L7, except for sagittal rotation at a trot, was largely asynchronous with the stride cycle. Intervertebral motion in all dogs was small with approximately 2–3° rotation and translations of approximately 1–2 mm. The predominant motion of the pelvis was axial rotation at a walk, whereas lateral rotation was predominant at a trot. L7 showed a predominance of sagittal rotation (with up to 5.1° at a trot), whereas lateral rotation was the main component of the movement at L6 (about 2.3° in both gaits). During trotting, a coupling of various motions was detected: axial rotation of L7 and the pelvis was inverse and was coupled with craniocaudal translation of L7. In addition, a certain degree of compensation of abnormal pelvic movements during walking and trotting by the caudal lumbar spine was evident.
Summarisation, Simulation and Comparison of Nine Control Algorithms for an Active Control Mount with an Oscillating Coil Actuator
Authors: Fan Rang-Lin , Wang Pu , Han Chen , Wei Li-Jun , Liu Zi-Jian , Yuan Pei-Ju
Published: August 2021

With the further development of the automotive industry, the traditional vibration isolation method is difficult to meet the requirements for wide frequency bands under multiple operating conditions, the active control mount (ACM) is gradually paid attentions, and the control algorithm plays a decisive role. In this paper, the ACM with oscillating coil actuator (OCA) is taken as the object, and the comparative study of the control algorithms is performed to select the optimal one for ACM. Through the modelling of ACM, the design of controller and the system simulations, the force transmission rate is used to compare the vibration isolation performance of the nine control algorithms, which are least mean square (LMS) adaptive feedforward control, recursive least square (RLS) adaptive feedforward control, filtered reference signal LMS (FxLMS) adaptive control, linear quadratic regulator (LQR) optimal control, H2 control, H∞ control, proportional integral derivative (PID) feedback control, fuzzy control and fuzzy PID control. In summary, the FxLMS adaptive control algorithm has the better performance and the advantage of easier hardware implementation, and it can apply in ACMs.
Assessing Forage Potential of the Global Collection of Finger Millet (Eleusine coracana (L.) Gaertn.) Germplasm Conserved at the ICRISAT Genebank
Authors: Backiyalakshmi Chinnadurai , Babu Chakrapani , Naresh Reddy Dagunapur , Padmakumar Varijakshapanicker , Prasad Kodukula V. S. V. , Azevedo Vania Cristina Renno , Vetriventhan Mani
Published: August 2021

Finger millet is an important drought-tolerant and grain-nutrient dense food crop grown in semi-arid regions in Asia and Africa. The forage is used as a source of dry roughage for feeding livestock. In this study, the finger millet diversity panel (310 accessions and four controls) representing the global collection of the finger millet germplasm conserved at the ICRISAT genebank was assessed for forage quality and diversity in the years 2018 and 2019. Results of the study suggested that finger millet can generate stover yield ranging from 2890 to 10,779 kg ha−1. Finger millet forage contained 6.47% to 8.15% of crude protein, >90% of dry matter content, 11.47% to 14.17% of ash content, 62.36% to 67.73% of neutral detergent fiber (NDF), 33.07% to 38.37% of acid detergent fiber (ADF), 3.95% to 4.80% of acid detergent lignin (ADL), 6.18% to 6.89% of metabolizable energy (ME) and 45.21% to 49.09% of in vitro organic matter digestibility (IVOMD) with the grain yield of 810 to 3698 kg ha−1 at maturity stage. The per se performance between the races, regions, and biological status has been performed and differed significantly for important traits. The 314 accessions were grouped into five clusters based on the performance for food-feed traits. Except for crude protein, there was a positive relationship between forage quality-positive traits and grain yield, indicating that agronomic and forage quality traits could be improved simultaneously. The top 10 promising accessions for important forage quality traits and accessions with multiple forage quality traits were identified. This study provides a detailed understanding of the variability that exists in forage quality traits in crop residues and their association with agronomic traits in the finger millet germplasm. The identified top-performing accessions would be the key genetic resources for developing dual-purpose cultivars and the information from this study will be useful for future finger millet food-feed trait improvement.
Breeding Aspects of Selected Ornamental Bulbous Crops
Authors: Marasek-Ciolakowska Agnieszka , Sochacki Dariusz , Marciniak Przemysław
Published: August 2021

This article provides an overview of the origin, genetic diversity and methods and trends in breeding of selected ornamental geophytes (Lilium, Tulipa, Narcissus and Hippeastrum). The role of interspecific hybridisation and polyploidisation in assortment development is reviewed. A great variety of cultivars with traits of interest have been generated over the last century by using classical breeding. Geophyte breeders have been interested in a diversity of traits, including resistance to diseases, flower colour and shape, long lasting flowering and a long vase life. Shortening the long breeding process of many geophytes by reducing the juvenile phase and using in vitro techniques are reviewed. Currently, the breeding process has been enhanced by using modern molecular cytogenetic techniques. Genomic in situ hybridisation is frequently used, among other techniques, for genome differentiation in interspecific hybrids, and for assessment of the extent of intergenomic recombination in backcross progenies. Furthermore, several molecular marker techniques are used for verification of hybrid status, identification of genetic diversity, confirmation of the genetic fidelity of in vitro propagated plants and construction of high-density linkage maps. Recently, a myriad of new plant breeding technologies, such as cisgenetics and genome editing technologies have been used to improve the traits of ornamental geophytes, an endeavour that is discussed here. Breeding trends, cultivar novelties as well a new cultivars registered by international authorities during the last five years are presented in detail.