Zimmermannjuul0411

Modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine + nab-paclitaxel (GemNab) regimens represent a standard treatment in advanced pancreatic cancer (aPC). DPYD and UGT1A1 variants are relevant predictors of fluoropyrimidine and irinotecan-associated adverse events (AEs). Furthermore, data about the associations between polymorphisms in ABCB and CDA genes and GemNab-related toxicities are still controversial. The present study analyzes the association between DPYD, UGT, ABCB1, CDA variants, and AEs in aPC patients (pts) treated with mFOLFIRINOX or GemNab. Blood samples collected from 104 aPC pts treated with mFOLFIRINOX and 63 with GemNab were tested for DPYD c.1679T>G, IVS14+1G>A, c.2194G>A, c.2846A>T, UGT1A1*28, CDA c.79A>C, and ABCB1 c.1236C>T, c.2677G>T/A, c.3435C>T by real-time PCR and automatic sequencing. In mFOLFIRINOX cohort, DPYD IVS14+1GA genotype was associated with G4 hematological AEs, while the UGT1A1*28 significantly correlated with the risk of thrombocytopenia (p = 0.006). In the GemNab cohort, a significant association between CDA c.79CC and high-grade nausea was observed (p = 0.002). Moreover, the presence of at least a mutant allele in ABCB1 increased the risk of overall hematological AEs (p = 0.01), both further strengthened by the presence of CDA c.79CC (p = 0.0002). DPYD IVS14+1A allele is confirmed to be associated with fluoropyrimidine life-threatening toxicities, and UGT1A1*28 is related with a higher risk of hematologic AEs following irinotecan treatment. CDA c.79C and ABCB1 c.1236T, c.2677T/A, and c.3435T mutant alleles are predictive biomarkers of GemNab-related AEs. All these variants should be considered in aPC pts candidate to mFOLFIRINOX or GemNab treatments.We evaluated the cost-effectiveness of a genotype-guided strategy among patients with acute coronary syndromes using a decision-tree model based on the Singapore healthcare payer's perspective over a 1-year time horizon. Three dual antiplatelet strategies were considered universal clopidogrel, genotype-guided, and universal ticagrelor. The prevalence of loss-of-function alleles was assumed to be 61.7% and model inputs were identified from the literature. Our primary outcome of interest was incremental cost-effectiveness ratio (ICER) compared to universal clopidogrel. Both genotype-guided (72,158 SGD/QALY) and universal ticagrelor (82,269 SGD/QALY) were considered cost-effective based on a willingness-to-pay (WTP) threshold of SGD 88,991. In our secondary analysis, the ICER for universal ticagrelor was 114,998 SGD/QALY when genotype-guided was taken as a reference. Probabilistic sensitivity analysis revealed that genotype-guided was the most cost-effective strategy when the WTP threshold was between SGD 70,000 to 100,000. Until more data are available, our study suggests that funding for a once-off CYP2C19 testing merits a consideration over 1 year of universal ticagrelor.Kiwifruit has gained increasing attention worldwide for its unique flavor and high nutritional value. Rapid softening after harvest greatly shortens its shelf-life and reduces the commercial value. Therefore, it is imperative and urgent to identify and clarify its softening mechanism. This study aimed to analyze and compare the long noncoding RNA (lncRNA) and mRNA expression patterns in ABA-treated (ABA) and room temperature (RT)-stored fruits with those in freshly harvested fruits (CK) as control. A total of 697 differentially expressed genes (DEGs) and 81 differentially expressed lncRNAs (DELs) were identified while comparing ABA with CK, and 458 DEGs and 143 DELs were detected while comparing RT with CK. The Kyoto Encyclopedia of Genes and Genomes analysis of the identified DEGs and the target genes of DELs revealed that genes involved in starch and sucrose metabolism, brassinosteroid biosynthesis, plant hormone signal transduction, and flavonoid biosynthesis accounted for a large part. The co-localization networks, including 38 DEGs and 31 DELs in ABA vs. CK, and 25 DEGs and 25 DELs in RT vs. CK, were also performed. Genes related to fruit ripening, such as genes encoding β-galactosidase, mannan endo-1,4-β-mannosidase, pectinesterase/pectinesterase inhibitor, and NAC transcription factor, were present in the co-localization network, suggesting that lncRNAs were involved in regulating kiwifruit ripening. Notably, several ethylene biosynthesis- and signaling-related genes, including one 1-aminocyclopropane-1-carboxylic acid oxidase gene and three ethylene response factor genes, were found in the co-localization network of ABA vs. CK, suggesting that the promoting effect of ABA on ethylene biosynthesis and fruit softening might be embodied by increasing the expression of these lncRNAs. These results may help understand the regulatory mechanism of lncRNAs in ripening and ABA-induced fruit softening of kiwifruit.In this paper, we solve generalized KG-oscillator interacts with a uniform magnetic field in five-dimensional space-time background produced by topological defects under a linear confining potential using the Kaluza-Klein theory. We solve this equation and analyze an analogue of the Aharonov-Bohm effect for bound states. We observe that the energy level for each radial mode depend on the global parameters characterizing the space-time, the confining potential, and the magnetic field which shows a quantum effect.

To assess the association of cerebral oxygen saturation (CrSO

) collected by near infrared spectroscopy (NIRS) during therapeutic hypothermia (TH) and rewarming with evidence of brain injury on post-rewarming MRI.

This retrospective cohort study included 49 infants, who received TH for mild to severe neonatal encephalopathy. Of those, 26 presented with brain injury assessed by a novel MRI grading system, whereas 23 had normal MRI scans.

CrSO

increased significantly from the first to the second day of TH in infants with brain injury, whereas it remained stable in patients with normal MRI.Increasing mean CrSO

values during rewarming was associated with brain injury (aOR 1.14; 95% CI 1.00-1.28), specifically with gray matter (GM) injury (aOR 1.23; 95% CI 1.02-1.49). The area under the ROC curve showed an excellent discrimination for GM involvement.

Clinically applied NIRS during TH and rewarming can assist in identifying the risk for brain injury.

Clinically applied NIRS during TH and rewarming can assist in identifying the risk for brain injury.

To assess whether prenatal exposure to marijuana (THC) results in abnormal amplitude integrated encephalograms (aEEG).

This was a (2018-2020) prospective cohort study of prenatally THC-exposed newborns. Maternal and Infant demographics, urine (UDS) and umbilical cord drug screening (UCDS) were recorded. A limited channel continuous aEEG was obtained within 48 h of birth. Statistical analysis included univariate, multivariate, and logistical regression.

A total of 30 mother/infant dyads were enrolled. 60% (18/30) of neonates had abnormal aEEGs with sleep wake cycle (SWC) disturbances (p < 0.001). UCDS Carboxy-THC pg/g levels were similar in infants with abnormal [1758 (296,2838)] and normal aEEG [1589 (332,2794)], p = 0.82.

Absence of SWCs on aEEG is associated with prenatal THC exposure. While THC UCDS levels did not correlate to aEEG results future longitudinal studies are necessary to obtain detailed history of THC use and to evaluate its association with abnormal aEEG and the neurodevelopmental outcomes.

Absence of SWCs on aEEG is associated with prenatal THC exposure. While THC UCDS levels did not correlate to aEEG results future longitudinal studies are necessary to obtain detailed history of THC use and to evaluate its association with abnormal aEEG and the neurodevelopmental outcomes.The annual frequency of tornadoes during 1950-2018 across the major tornado-impacted states were examined and modeled using anthropogenic and large-scale climate covariates in a hierarchical Bayesian inference framework. Anthropogenic factors include increases in population density and better detection systems since the mid-1990s. Large-scale climate variables include El Niño Southern Oscillation (ENSO), Southern Oscillation Index (SOI), North Atlantic Oscillation (NAO), Pacific Decadal Oscillation (PDO), Arctic Oscillation (AO), and Atlantic Multi-decadal Oscillation (AMO). The model provides a robust way of estimating the response coefficients by considering pooling of information across groups of states that belong to Tornado Alley, Dixie Alley, and Other States, thereby reducing their uncertainty. The influence of the anthropogenic factors and the large-scale climate variables are modeled in a nested framework to unravel secular trend from cyclical variability. Population density explains the long-term trend in Dixie Alley. The step-increase induced due to the installation of the Doppler Radar systems explains the long-term trend in Tornado Alley. NAO and the interplay between NAO and ENSO explained the interannual to multi-decadal variability in Tornado Alley. PDO and AMO are also contributing to this multi-time scale variability. SOI and AO explain the cyclical variability in Dixie Alley. find more This improved understanding of the variability and trends in tornadoes should be of immense value to public planners, businesses, and insurance-based risk management agencies.Patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative/Ki-67-high (ER+HER2-Ki-67high) luminal breast cancer have a worse prognosis and do not respond to hormonal treatment and chemotherapy. This study sought to identify disease-related protein networks significantly associated with this subtype, by assessing in-depth proteomes of 10 lesions of high and low Ki-67 values (HOT, five; COLD, five) microdissected from the five tumors. Weighted correlation network analysis screened by over-representative analysis identified the five modules significantly associated with the HOT lesions. Pathway enrichment analysis, together with causal network analysis, revealed pathways of ribosome-associated quality controls, heat shock response by oxidative stress and hypoxia, angiogenesis, and oxidative phosphorylation. A semi-quantitative correlation of key-protein expressions, protein co-regulation analysis, and multivariate correlation analysis suggested co-regulations via network-network interaction among the four HOT-characteristic modules. Predicted highly activated master and upstream regulators were most characteristic to ER-positive breast cancer and associated with oncogenic transformation, as well as resistance to chemotherapy and endocrine therapy. Interestingly, inhibited intervention causal networks of numerous chemical inhibitors were predicted within the top 10 lists for the WM2 and WM5 modules, suggesting involvement of potential therapeutic targets in those data-driven networks. Our findings may help develop therapeutic strategies to benefit patients.Halomonas malpeensis strain YU-PRIM-29T is a yellow pigmented, exopolysaccharide (EPS) producing halophilic bacterium isolated from the coastal region. To understand the biosynthesis pathways involved in the EPS and pigment production, whole genome analysis was performed. The complete genome sequencing and the de novo assembly were carried out using Illumina sequencing and SPAdes genome assembler (ver 3.11.1) respectively followed by detailed genome annotation. The genome consists of 3,607,821 bp distributed in 18 contigs with 3337 protein coding genes and 53% of the annotated CDS are having putative functions. Gene annotation disclosed the presence of genes involved in ABC transporter-dependent pathway of EPS biosynthesis. As the ABC transporter-dependent pathway is also implicated in the capsular polysaccharide (CPS) biosynthesis, we employed extraction protocols for both EPS (from the culture supernatants) and CPS (from the cells) and found that the secreted polysaccharide i.e., EPS was predominant. The EPS showed good emulsifying activities against the petroleum hydrocarbons and its production was dependent on the carbon source supplied.