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Nevin Manimala Statistics

Study of the effects of long-term outcomes of autologous peripheral blood stem cell reinfusion in patients with decompensated cirrhosis

Zhonghua Gan Zang Bing Za Zhi. 2022 Mar 20;30(3):279-284. doi: 10.3760/cma.j.cn501113-20220228-00091.

ABSTRACT

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.

PMID:35462483 | DOI:10.3760/cma.j.cn501113-20220228-00091

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Nevin Manimala Statistics

Divergent Signaling Pathways May Lead to Convergence in Cancer Therapy – A Review

Cell Physiol Biochem. 2022 Apr 25;56(2):180-208. doi: 10.33594/000000512.

ABSTRACT

Cancer is a chaos of uncontrolled cell proliferation that has consistently invented new circuitry programs to operate inside the cell machinery. Globally, cancer statistics account for 65% of mortality worldwide, mainly due to the adoption of lifestyle behaviours. In 2020, FDA approved 40 new drugs, out of which 16 (40%) were approved as cancer drugs. Overall, the risk of dying from cancer decreased, but further reductions in cancer death rates can be accelerated by applying existing cancer control knowledge across all the population segments, emphasising those in the lowest socio-economic and other disadvantaged population. Various therapeutic regimes, including low-molecular-weight inhibitors, targeting oncogenic signaling pathways are under development. However, the pitfall of targeted therapies is the quick emergence of acquired drug resistance encumbered with toxic side effects. Several FDA acclaimed therapeutic legacies or biosimilars earmarked signaling pathways of rare diseases (cystic fibrosis, erythropoietic protoporphyria, neuromyelitis optica spectrum disorder, tenosynovial giant cell tumor, sickle cell disease, systemic sclerosis-associated interstitial lung disease, muscular dystrophy), neurological and psychiatric disorders, infectious diseases, heart, lung, circulatory, endocrine diseases, autoimmune conditions, cancers and blood disorders. When cancer progresses, these signals develop specific characteristics that can be targeted for anti-cancer therapy. The designer inhibitors have emerged as novel pharmaceutical interventions that aim to block the pathways in an effort to reverse the abnormal phenotype of the cancer cells. Numerous cell-signaling channels have evolved and invigorated to make off three-dimensional feedback networks. The magnitude of accessible information by pathways occupies curated information as a consortium. To fully appreciate the pivotal roles that signaling cascades play in tumor development, it is necessary to understand the involved signaling cascades in the interaction between cancer cells. The prime endeavour is to canonically curate all signaling pathways involving cell cycle, EGFR, MAPK, GPCR, PI3K/ AKT/mTOR, immune checkpoints, nuclear receptors, janus kinase, transcription activators etc., involving the manipulation of genetic and nuclear receptors. Here, we will summarize the vast amount of information describing the signals that mediate crosstalk between cancer cells and the targets related to this crosstalk.

PMID:35462471 | DOI:10.33594/000000512

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Cut-off values of neonatal lysosomal storage disease-related enzymes detected by tandem mass spectrometry

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2021 Mar 25;50(7):1-5. doi: 10.3724/zdxbyxb-2022-0095. Online ahead of print.

ABSTRACT

To establish cut-off values of lysosomal storage disease (LSD)-related enzymes by tandem mass spectrometry. A total of 26 689 newborns and 7 clinically confirmed LSD children underwent screening for LSDs (glycogen storage disease typeⅡ, Fabry disease, mucopolysaccharidosis type Ⅰ, Krabbe disease, Niemann-Pick disease A/B and Gaucher disease). The activities of LSD-related enzymes were detected by tandem mass spectrometry. The 20% of the median enzyme activity of each batch of acid β-glucocerebrosidase, acid sphingomyelinase, β-galactocerebroside, α–iduronidase and acid α-glucosidase, and the 30% of the median enzyme activity of were taken as cut-off values of corresponding enzymes. The genetic diagnosis was performed in neonates whose enzyme activity was lower than 70% of the cut-off value. The enzyme activities of 7 clinically confirmed cases were all lower than the cut-off values. Among 26 689 newborns, 142 cases (0.53%) were suspected positive for LSDs, including 25 cases of β-galactocerebroside deficiency, 1 case of α–iduronidase deficiency, 19 cases of α-galactosidase deficiency, and 97 cases of acid α-glucosidase deficiency. Eight infants were genetically diagnosed with LSDs, including 3 cases of glycogen storage disease type Ⅱ, 3 cases of Krabbe disease, and 2 cases of Fabry disease, with a positive predictive value of about 5.6%. Cut-off values ​​of the six LSD enzyme activities all showed a downward trend from March to August, and an upward trend from September to December. There was a statistically significant difference in LSD enzyme activity among different months (<0.05). The established cut-off values of LSD-related enzyme activities detected by tandem mass spectrometry can be used for screening LSDs in neonates, and the enzyme activity would be affected by temperature and humidity.

PMID:35462462 | DOI:10.3724/zdxbyxb-2022-0095

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Trends and influencing factors of perinatal birth defects in Huai’an from 2008 to 2020

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2021 Mar 25;50(7):1-9. doi: 10.3724/zdxbyxb-2021-0120. Online ahead of print.

ABSTRACT

: To analyze the incidence, trends and related factors of birth defects in Huai’an from 2008 to 2020. : The surveillance data from maternal and child health system of Huai’an from 2008 to 2020 and Huai’an Statistical Yearbook were used for analysis. Taking the annual change percentage and average annual change percentage (AAPC) as the main outcome indicators, the JoinPoint regression analysis was performed to estimate the changing trend of birth defects from 2008 to 2020. Spearman correlation analysis was used to examine the association between birth defects and birth rate, marriage rate, proportion of women with advanced maternal age. : During 2008 to 2020, a total of 3414 cases of neonatal birth defects occurred in Huai’an, with an incidence of 4.6‰ (3414/736 608). The rate of perinatal birth defects in Huai’an showed an increasing trend (AAPC=8.8%, =3.2, <0.01), and the year of 2016 was a significant changing point. Among 24 types of birth defects, the incidence of congenital heart disease rose and became the most prevalent defect, while the incidence of neural tube malformations such as anencephaly, encephalocele and spina bifida was declined. The incidence of birth defect was negatively correlated with the birth rate (=-0.751, <0.01), not correlated with marriage rate (=-0.516, >0.05), and positively correlated with the proportion of women with advanced maternal age (=0.726, <0.01). : The incidence of birth defects in Huai’an shows an increasing trend from 2008 to 2020 with congenital heart disease as the most common type of birth defect, and the increase of birth defects incidence is closely related with the increase of the proportion of women with advanced maternal age.

PMID:35462467 | DOI:10.3724/zdxbyxb-2021-0120

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Comparative efficacy of targeted structural patterns of electroencephalography neurofeedback in children with inattentive or combined attention deficit hyperactivity disorder

Brain Behav. 2022 Apr 24:e2572. doi: 10.1002/brb3.2572. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate and compare the effects of three courses of different structural patterns of electroencephalography neurofeedback on predominantly inattentive attention deficit hyperactivity disorder (ADHD-PI) and combined ADHD (ADHD-CT).

METHODS: Thirty-eight ADHD-PI and ADHD-CT children were selected and completed three courses of different structural patterns of electroencephalography neurofeedback according to their ADHD type. Before and after each course, relative power value of electroencephalography, including θ, β, α, SMR and their ratios (θ/β, θ/α), and eighteen integrated visual and auditory continuous performance test (IVA/CPT) quotients were obtained and compared. Data were analyzed by SPSS software, and p < .05 was considered statistically significant.

RESULTS: After one course, θ, three IVA/CPT quotients in both types and two comprehensive quotients in ADHD-CT changed significantly (all p < .05). After two courses, θ/α, θ/β and five IVA/CPT quotients in both types, θ and α in ADHD-PI, four comprehensive quotients, and four respond control quotients in ADHD-CT varied significantly compared to before treatment and after one course (all p < .05). After three courses, α, β, θ, θ/α, θ/β and ten IVA/CPT quotients in both types changed significantly compared to before treatment and after one course (all p < .05). In addition, six IVA/CPT quotients in both types after three courses were significantly higher than those after two courses (all p < .05).

CONCLUSION: Different structural patterns of electroencephalography neurofeedback targeted for ADHD-CT and ADHD-PI were both effective and feasible. Three courses of EEG neurofeedback were most effective.

PMID:35462456 | DOI:10.1002/brb3.2572

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Nevin Manimala Statistics

Proteomic profiling of human bone from different anatomical sites – A pilot study

Proteomics Clin Appl. 2022 Apr 24:e2100049. doi: 10.1002/prca.202100049. Online ahead of print.

ABSTRACT

PURPOSE: The study aim is a comparative proteome-based analysis of different autologous bone entities (alveolar bone (AB), iliac cortical bone (IC) and iliac spongiosa (IS)) used for alveolar onlay grafting.

EXPERIMENTAL DESIGN: Site-matched bone samples of AB, IC and IS were harvested during alveolar onlay grafting. Proteins were extracted using a detergent-based (sodium dodecyl sulfate) strategy and trypsinized. Proteome analysis was performed using liquid chromatography – tandem mass spectrometry (LC-MS/MS). MaxQuant was used for peptide-to-spectrum matching, peak detection, and quantitation. Linear models for microarray analysis (LIMMA) were used to detect differentially abundant peptides and proteins.

RESULTS: 1730 different proteins were identified across the 15 samples at a false discovery rate of 1 %. Partial least-squares discriminant analysis approved segregation of AB, IC and IS protein profiles. LIMMA statistics highlighted 66 proteins that were more abundant in AB then in IC (vs. 92 proteins were enriched in IC over AB). Gene ontology enrichment analysis revealed a matrisomal vs. an immune-related proteome fingerprint in AB vs IC.

CONCLUSION AND CLINICAL RELEVANCE: This pilot study demonstrates an ECM protein-related proteome fingerprint in AB and an immune-related proteome fingerprint in IS and IC. This article is protected by copyright. All rights reserved.

PMID:35462455 | DOI:10.1002/prca.202100049

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Production and optimization of L-asparaginase by Streptomyces koyangensis SK4 isolated from Arctic sediment

J Basic Microbiol. 2022 Apr 24. doi: 10.1002/jobm.202200116. Online ahead of print.

ABSTRACT

Actinomycetes isolated from the Arctic sediment were evaluated for the production of the enzyme L-asparaginase, an enzyme used to treat acute lymphoblastic leukemia. The most potent strain Streptomyces koyangensis SK4 was selected for L-asparaginase enzyme production by submerged fermentation. The effect of various fermentation parameters on enzyme production was analyzed statistically using the Plackett Burman design and response surface method. Effects of eight parameters including temperature, pH, incubation time, inoculum size, agitation speed, the concentration of starch, L-asparagine and yeast extract were studied on L-asparaginase production by the Arctic isolate Streptomyces koyangensis SK4. Factors such as temperature, pH, incubation time, agitation speed and L-asparagine concentration were found to be important factors influencing the L-asparaginase production. Maximum enzyme activity of 136 IU/ml was obtained at 20°C on the seventh day of incubation in the Asparagine dextrose broth maintained at pH-7.5, agitation speed-125 rpm and L-asparagine concentration of 7.5 g/L. The statistical optimization method described in this study proved effective for increasing the L-asparaginase production by Arctic actinomycetes. This article is protected by copyright. All rights reserved.

PMID:35462434 | DOI:10.1002/jobm.202200116

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Correlation of Morphological Features of Chromosomal Instability and Flow Cytometric DNA Ploidy Analysis in Aspirates of Breast Carcinoma

Acta Cytol. 2022 Apr 22:1-7. doi: 10.1159/000524053. Online ahead of print.

ABSTRACT

OBJECTIVE: Morphological indicators of chromosomal instability (CI), including multipolar mitoses, chromatin bridges (CB), strings, nuclear buds (NB), micronuclei (MN), and deoxyribonucleic acid (DNA) ploidy analysis help in prognostication of breast carcinoma. The present study was done to evaluate CI in breast carcinoma and correlate with DNA ploidy and tumor grade.

STUDY DESIGN: Fifty cases of carcinoma breast diagnosed by fine-needle aspiration cytology were included. Robinson’s grading method was used on smears to grade breast carcinoma. To assess the morphological features of CI, the best May-Grünwald Giemsa stained smear was chosen. At least 1,000 epithelial cells on oil immersion magnification (×100 objective) were counted. DNA ploidy on the aspirates was done by flow cytometry.

RESULTS: All the patients were female, diagnosed as infiltrating ductal carcinoma on cytology. Eight tumors were grade I, 32 were grade II, and 10 were grade III. MN was seen in 48 cases, NB in 45, and CB in 12 cases. Mean MN, NB, and CB scores in aneuploid (24) cases were 9.96 ± 8.42, 5.29 ± 4.71, and 1.08 ± 1.84 while 6.19 ± 6.67, 1.92 ± 1.79, and 0.11 ± 0.33 were seen in diploid (26) cases. Statistically significant positive correlation was observed between CI and DNA ploidy.

CONCLUSIONS: Morphological evaluation of CI by light microscopy on routinely stained breast aspirates is feasible, although a meticulous search is required. Cytomorphological features of CI and ploidy have a positive correlation with increasing tumor grade.

PMID:35462374 | DOI:10.1159/000524053

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Desidustat in Anemia due to Non-Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-ND)

Am J Nephrol. 2022 Apr 22:1-9. doi: 10.1159/000523961. Online ahead of print.

ABSTRACT

BACKGROUND: Desidustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is being developed to treat anemia in patients with chronic kidney disease (CKD) without dialysis dependency.

METHODS: In total, 588 patients with a clinical diagnosis of anemia due to CKD without dialysis need and with baseline hemoglobin of 7.0-10.0 g/dL (inclusive) were randomized in a 1:1 ratio to receive either desidustat 100 mg oral tablets thrice a week for 24 weeks or biosimilar darbepoetin subcutaneous injection 0.75 μg/kg once in 2 weeks for 24 weeks. The primary outcome was the change from baseline in hemoglobin to evaluation period of Weeks 16-24. Key secondary outcomes included the number of patients with hemoglobin response, changes in the hepcidin levels, changes in the vascular endothelial growth factor (VEGF) levels, and changes in the lipid and lipoprotein profiles.

RESULTS: Hemoglobin change from baseline to Weeks 16-24 was 1.95 g/dL in the desidustat group and 1.83 g/dL in the darbepoetin group (difference: 0.11 g/dL; 95% CI: -0.12, 0.34), which met prespecified non-inferiority margin (-0.75 g/dL). The hemoglobin responders were significantly higher (p = 0.0181) in the desidustat group (196 [77.78%]) compared to the darbepoetin group (176 [68.48%]). The difference of change in hepcidin from baseline to Week 12 and Week 24 (p = 0.0032 at Week 12, p = 0.0016 at Week 24) and the difference of change in low-density lipoprotein from baseline to Week 24 (p value = 0.0269) between the two groups was statistically significant. The difference of change from baseline in VEGF to Weeks 12 and 24 between the two groups was not statistically significant.

CONCLUSION: Desidustat is non-inferior to darbepoetin in the treatment of anemia due to non-dialysis dependent CKD and it is well-tolerated.

PMID:35462372 | DOI:10.1159/000523961

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Challenges in modelling the sediment retention ecosystem service to inform an ecosystem account – Examples from the Mitchell catchment in northern Australia

J Environ Manage. 2022 Apr 21;314:115102. doi: 10.1016/j.jenvman.2022.115102. Online ahead of print.

ABSTRACT

A systems analysis perspective related to soil science is necessary to achieve many of the sustainability targets articulated by the United Nations Sustainable Development Goals (SDGs). The System of Environmental-Economic Accounting – Ecosystem Accounting (SEEA-EA) framework is the international statistical standard for quantifying both the contributions that ecosystems make to the economy, and the impacts of economic activity on ecosystems. However, due to the difficulty of obtaining empirical data on ecosystem service flows, in many cases such quantification is informed by ecosystem service models. Previous research on the Mitchell catchment, Queensland Australia provided a novel opportunity to quantify the implications of using a model of hillslope erosion and sediment delivery in isolation (as represented in one of the most frequently used ecosystem service models – InVEST), by comparing such estimates against multiple lines of local empirical data, and a more comprehensive representation of locally important erosion and deposition processes through a sediment budget model. Estimates of the magnitude of hillslope erosion modelled using an approach similar to InVEST and the calibrated sediment budget differed by an order of magnitude. If an uncalibrated InVEST-type model was used to inform the relative distribution of erosion magnitude, findings suggest the incorrect erosion process would be identified as the dominant contributor to suspended sediment loads. However, the sediment budget model could only be calibrated using data on sediment sources and sinks that had been collected through sustained research effort in the catchment. A comparable level of research investment may not be available to inform ecosystem service assessments elsewhere. Findings for the Mitchell catchment demonstrate that practitioners should exercise caution when using model-derived estimates of the sediment retention ecosystem service, which have not been calibrated and validated against locally collected empirical data, to inform an ecosystem account and progress towards achieving the SDGs.

PMID:35462256 | DOI:10.1016/j.jenvman.2022.115102