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Additionally, autophagy did not play a role in acquired resistance to cisplatin in our novel cisplatin-resistant OSSC cell line (SCC-4cisR) obtained by pulsed stepwise exposure of SCC-4 cells to cisplatin (~14-fold change in sensitivity). There was no change in the basal levels of autophagy in the SCC-4cisR cells compared to the SCC-4 cells. Furthermore, a significant increase in cisplatin-induced autophagy was observed only in the SCC-4 cells, but not in the derived SCC-4cisR cells. Collectively, these data indicate that autophagy may not be implicated in acquired cisplatin resistance in OSCC.
To elaborate an ECG-based nomogram estimating the probability to detect cardiac involvement by cardiac magnetic resonance (CMR) in Fabry Disease (FD).

119 FD patients and 26 healthy controls underwent ECG and CMR. Test (n=88, 60%) and validation cohorts (n=57, 40%) were randomly derived. Cardiac involvement was defined as the presence of low myocardial T1 value, a CMR-surrogate of myocardial glycosphingolipid storage. ECG changes associated with low T1 value were identified in the test cohort, included in the nomogram and then tested in the validation cohort.

Sokolow-Lyon index (AUC=0.769), ratio between P-wave and PR-segment durations (Pwave/PRsegment) (AUC=0.778), QRS duration (AUC=0.703), QT (AUC=0.769) duration were independently associated with the presence of low T1 on CMR at multivariate analysis. An ECG-based nomogram including these four parameters was accurate in identifying patients with CMR evidence of glycosphingolipid storage (c-index of the derived-nomogram=0.90 in the test group; 0.81 in the validation group).

We propose a practical ECG-based nomogram accurately estimating the probability to detect low T1 values by CMR in FD patients. The application of this tool in clinical practice could improve early detection of FD cardiac involvement.
We propose a practical ECG-based nomogram accurately estimating the probability to detect low T1 values by CMR in FD patients. The application of this tool in clinical practice could improve early detection of FD cardiac involvement.Previous studies have shown MALDI-TOF MS to be a powerful tool in wine yeast identification and potential prediction of application. However, it is also established that substrate composition influences protein expression, but the degree to which this may affect MALDI-TOF spectra (and analytical results thereof) has not been fully explored. To further inform assay optimisation, the influence on MALDI-TOF spectra was determined using eight Saccharomyces strains of diverse origins cultivated on grape juices from Pinot Noir and Chardonnay varieties, synthetic grape juice, and laboratory-grade artificial culture media (YPD broth and agar). Our results demonstrated significant influences of culture media on strain MALDI-TOF spectra. Yeast culture on YPD agar is recommended for taxonomic studies, with YPD broth culture of S. cerevisiae offering improved intra-subspecific differentiation Furthermore, our data supported a correlation between MALDI spectra and the potential industrial application of individual yeast strains.
To compare OGTT-derived estimates of β-cell function between youth and adults with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes after treatment discontinuation in RISE.

Youth (n=89) and adults (n=132) were randomized to 3months glargine followed by 9months metformin (G/M) or 12months metformin (MET). Insulin sensitivity and β-cell responses were estimated from 3-hour OGTTs over 21months. Linear mixed models tested for differences by time and age group within each treatment arm.

After treatment withdrawal, HbA1c increased in both youth and adults with a larger net increase in G/M youth vs. adults at 21months. Among youth, β-cell function decreased starting at 12months in G/M and 15months in MET. Among adults, β-cell function remained relatively stable although insulin secretion rates decreased in G/M at 21months. At 21months vs. baseline β-cell function declined to a greater extent in youth vs. adults in both the G/M and MET treatment arms.

After treatment withdrawal youth demonstrated progressive decline in β-cell function after stopping treatment with either G/M or MET. In contrast, β-cell function in adults remained stable despite an increase in HbA1c over time. ClinicalTrials.gov Identifier NCT01779375 and NCT01779362 at clinical trials.gov.
After treatment withdrawal youth demonstrated progressive decline in β-cell function after stopping treatment with either G/M or MET. Dihydroethidium cell line In contrast, β-cell function in adults remained stable despite an increase in HbA1c over time. ClinicalTrials.gov Identifier NCT01779375 and NCT01779362 at clinical trials.gov.The brain is organized into anatomically distinct structures consisting of a variety of projection neurons. While such evolutionarily conserved neural circuit organization underlies the innate ability of animals to swiftly adapt to environments, they can cause biased cognition and behavior. Although recent studies have begun to address the causal importance of projection-neuron types as distinct computational units, it remains unclear how projection types are functionally organized in encoding variables during cognitive tasks. This review focuses on the neural computation of decision making in the prefrontal cortex and discusses what decision variables are encoded by single neurons, neuronal populations, and projection type, alongside how specific projection types constrain decision making. We focus particularly on "over-representations" of distinct decision variables in the prefrontal cortex that reflect the biological and subjective significance of the variables for the decision makers. We suggest that task-specific over-representation in the prefrontal cortex involves the refinement of the given decision making, while generalized over-representation of fundamental decision variables is associated with suboptimal decision biases, including pathological ones such as those in patients with psychiatric disorders. Such over-representation of the fundamental decision variables in the prefrontal cortex appear to be tightly constrained by afferent and efferent connections that can be optogenetically intervened on. These ideas may provide critical insights into potential therapeutic targets for psychiatric disorders, including addiction and depression.
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