Effort discounts reward-based control allocation: A neurodynamic perspective.

The amount of cognitive and neural resources allocated to a task is largely determined by the reward we can expect. However, it remains under-appreciated how this reward-expectation-based control allocation is modulated by effort expenditure. The present event-related potential study investigated this issue through the lens of neural dynamics. Thirty-four participants completed an effort-based monetary incentive delay task while their EEG was recorded. Effort demand was manipulated by adding no (low effort) or much (high effort) noise to the target. Behaviorally, participants exhibited reward-related speeding regardless of effort expenditure, as revealed by faster RTs for reward than neutral trials. Our ERP results demonstrated a widespread facilitatory influence of reward expectation on neural dynamics extending from cue evaluation as indexed by the cue-P3, to control preparation as indexed by the contingent negative variation (CNV), and finally to control engagement as indexed by the target-P3. Critically, the neural facilitation was discounted by effort expenditure during both the control-preparation and control-engagement stages instead of the cue-evaluation stage. Overall, this study provides neurodynamic evidence that control allocation is determined by reward and effort via a cost-benefit analysis.

A prospective phase II randomized study of docetaxel combined with lobaplatin versus TPF regimen induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced head and neck squamous cell carcinoma.

PURPOSE: To compare the toxicity and clinical efficacy of TL (docetaxel + lobaplatin) induction chemotherapy combined with lobaplatin concurrent chemoradiotherapy and TPF (docetaxel + cisplatin + 5-fluorouracil) induction chemotherapy combined with cisplatin concurrent chemoradiotherapy in the treatment of locally advanced head and neck squamous cell carcinoma. METHODS AND PATIENTS: In total, 128 patients with locally advanced head and neck cancer were prospectively enrolled between August 2016 and April 2021. They were randomly divided into trial group and control group, all using chronological dosage mode. The trial group used TL regimen induction chemotherapy combined with lobaplatin concurrent chemoradiotherapy; the control group used TPF regimen induction chemotherapy and cisplatin concurrent chemotherapy. The endpoints were adverse events and survival rates at 1, 3 and 5 years. RESULTS: Median follow-up was 42 months (20-71 months). (1) Adverse events: During induction chemotherapy, compared with TPF group, grade 3-4 leukocytes and neutrophils, diarrhea, 1-2 hyperbilirubinemia, nausea / vomiting, oral mucositis, fatigue, anorexia, hyponatremia were significantly lower in TL group (p<0. 05): 6% vs. 35%, 14% vs. 53%, 0% vs. 6%, 15% vs. 40%, 9% vs. 56%, 0% vs. 10%, 3% vs. 13%, 2% vs. 23%, 15% vs. 74%. During chemoradiotherapy, the incidence of hyponatremia, hypokalaemia and grade 1-2 nausea was significantly lower in the TL group (p<0. 05), with 24% vs. 69%, 20% vs. 65% and 24% vs. 44%, respectively. However, more grade 3-4 thrombocytopenia were observed in the TL group (15% vs. 3%, p<0. 05). (2) There was no significant difference in the recent objective response rate (ORR) between patients with TL group and TPF group (p=0.961). (3) There was no statistical difference in 1, 3 and 5 years OS between TL group and TPF group, respectively, (71.0% vs. 67.5%, p=0.573), (56.6% vs. 56.9%, p=0.814), (52.5% vs. 52.9%, p=0.841); 1, 3 and 5 years PFS are: (63.4% vs. 64.0%, p=0.883), (51.1% vs. 54.0%, p=0.705) and (47.3% vs. 45.9%, p=0.887), None of them were significantly different. Multivariate analysis of COX regression showed that T stage (p=0.01) and surgery (p=0.046) were independent factors affecting PFS and OS, respectively. OS subgroup analysis shows that people receiving the TL regimen in postoperative and nodal stage N1 and N2 patients tended to survive longer than those receiving the TPF regimen. CONCLUSION: Patients with postoperative, N1 or N2 stage locally advanced head and neck squamous cell carcinoma (HNSCC) may have more significant clinical benefits when treated with TL regimen. TL regimen has advantages in reducing toxic side effects and can be used as one of the first-line treatment options. TRIAL REGISTRATION: ClinicalTrials.gov (No. NCT03117257).

Distinct neural dynamics underlying risk and ambiguity during valued-based decision making.

Uncertainty can be fractioned into risk and ambiguity psychologically and neurobiologically. However, whether and how risk and ambiguity are dissociated in terms of neural dynamics during value-based decision making remain elusive. The present event-related potential (ERP) study addressed these issues by asking participants to perform a wheel-of-fortune task either during a risky context (Experiment 1; N = 30) where outcome probability was known or during an ambiguous context (Experiment 2; N = 30) where outcome probability was unknown. Results revealed that the cue-P3 was more enhanced for risk versus ambiguity during the anticipatory phase, whereas the RewP was more increased for ambiguity than risk during the consummatory phase. Moreover, the SPN and the fb-P3 components were further modulated by the levels of risk and ambiguity, respectively. These findings demonstrate a neural dissociation between risk and ambiguity, which unfolds from the anticipatory phase to the consummatory phase.

Neural dynamics of effort-modulated reward processing.

Previous studies have established that effort can either decrease reward value as a cost or increase reward value as an augmenter, which is referred to as the effort paradox. The present event-related potential study investigated the neural dynamics underlying the modulation of reward processing by effort expenditure. Thirty-two participants completed a modified monetary incentive delay task in a high-effort context and a low-effort context to earn monetary rewards while their EEG was recorded during effort anticipation, effort execution, and effort completion, respectively. Results revealed the multiphase nature of the effort-reward relationship, which unfolds over time. During effort anticipation, effort discounts reward value as reflected by a reduced contingent negative variation for high- versus low-effort trials. During effort exertion, the target-P3 reward effect was accrued by effort expenditure. Finally, effort also provides its own value following effort completion, as revealed by an enhanced stimulus-preceding negativity for high-effort relative to low-effort trials. These findings provide new insights into the relationship between effort expenditure and reward processing and are helpful to mitigate the effort paradox.

Decomposing the effort paradox in reward processing: Time matters.

Effort expenditure not only discounts reward value prospectively but also accrues reward value retrospectively. To decompose the effort paradox in reward processing, the current event-related potential study investigated the neural dynamics underlying effects of effort expenditure on subsequent reward processing. Participants exerted one of two levels of effort to obtain an opportunity of winning a high or low amount of monetary reward, and we focused on electrophysiological activity during the anticipatory and consummatory phases of reward processing. During the anticipatory phase, the stimulus-preceding negativity was enhanced when potential high rewards were anticipated, but this reward effect disappeared following high-effort expenditure. During the consummatory phase, feedback-related ERPs were increased for high relative to low rewards, and this reward effect was enlarged following effort expenditure during the early stage (200-300 ms) as indexed by the reward positivity but not the late stage (400-600 ms) as indexed by the P3. Our findings provide a strong support for the psychological contrast theory and indicate that time matters in decomposing the effort paradox for reward processing such that effort expenditure reduces reward sensitivity during the anticipatory phase but enhances reward sensitivity during the consummatory phase.

miR-223-3p regulating the occurrence and development of liver cancer cells by targeting FAT1 gene.

Objective: To explore the mechanism of miR-223-3p regulating the occurrence and development of liver cancer cells by targeting FAT1 gene. Methods: Bioinformatics analysis was used to analyze the differentially expressed genes in liver cancer tissue chips. Forty-eight cases of liver cancer tissues and corresponding adjacent tissues were selected, and qRT-PCR was used to detect the expression of miR-223-3p and FAT1mRNA in tissues. Wound healing assay was used to detect the migration ability of liver cancer cells. Transwell assay was used to detect cells invasion ability. Dual-luciferase assay was used to detect the targeting relationship between miR-223-3p and FAT1. Western blot was used to detect the protein expression of EMT-related markers, E-cadherin and Vimentin. Results: FAT1 was highly expressed in liver cancer tissues and cells, while miR-223-3p was lowly expressed. Silencing FAT1 could inhibite the proliferation, migration, invasion and EMT of liver cancer cells. miR-223-3p targeted down-regulated the expression of FAT1, and inhibited the proliferation, migration, invasion and EMT of liver cancer cells by targeting FAT1. Conclusion: miR-223-3p regulates the occurrence and development of liver cancer cells by targeted down-regulating the expression of FAT1.

Meta-Analysis of Laparoscopic versus Open Hepatectomy for Live Liver Donors.

OBJECTIVE: To document the safety and efficacy of laparoscopic living donor hepatectomy in comparison with open liver resection for living donor liver transplantation. METHODS: Medline database, EMASE and Cochrane library were searched for original studies comparing laparoscopic living donor hepatectomy (LLDH) and open living donor hepatectomy (OLDH) by January 2015. Meta-analysis was performed to evaluate donors' perioperative outcomes. RESULTS: Nine studies met selection criteria, involving 1346 donors of whom 318 underwent LLDH and 1028 underwent OLDH. The Meta analysis demonstrated that LLDH group had less operative blood loss [patients 1346; WMD: -56.09 mL; 95%CI: -100.28-(-11.90) mL; P = 0.01], shorter hospital stay [patients 737; WMD: -1.75 d; 95%CI: -3.01-(-0.48) d; P = 0.007] but longer operative time (patients 1346; WMD: 41.05 min; 95%CI: 1.91-80.19 min; P = 0.04), compared with OLDH group. There were no significant difference in other outcomes between LLDH and OLDH groups, including overall complication, bile leakage, postoperative bleeding, pulmonary complication, wound complication, time to dietary intake and period of analgesic use. CONCLUSIONS: LLDH appears to be a safe and effective option for LDLT. It improves donors' perioperative outcomes as compared with OLDH.

Measuring Particulate Emissions of Light Duty Passenger Vehicles Using Integrated Particle Size Distribution (IPSD).

The California Air Resources Board (ARB) adopted the low emission vehicle (LEV) III particulate matter (PM) standards in January 2012, which require, among other limits, vehicles to meet 1 mg/mi over the federal test procedure (FTP). One possible alternative measurement approach evaluated to support the implementation of the LEV III standards is integrated particle size distribution (IPSD), which reports real-time PM mass using size distribution and effective density. The IPSD method was evaluated using TSI's engine exhaust particle sizer (EEPS, 5.6-560 nm) and gravimetric filter data from more than 250 tests and 34 vehicles at ARB's Haagen-Smit Laboratory (HSL). IPSD mass was persistently lower than gravimetric mass by 56-75% over the FTP tests and by 81-84% over the supplemental FTP (US06) tests. Strong covariance between the methods suggests test-to-test variability originates from actual vehicle emission differences rather than measurement accuracy, where IPSD offered no statistical improvement over gravimetric measurement variability.

Primary gas- and particle-phase emissions and secondary organic aerosol production from gasoline and diesel off-road engines.

Dilution and smog chamber experiments were performed to characterize the primary emissions and secondary organic aerosol (SOA) formation from gasoline and diesel small off-road engines (SOREs). These engines are high emitters of primary gas- and particle-phase pollutants relative to their fuel consumption. Two- and 4-stroke gasoline SOREs emit much more (up to 3 orders of magnitude more) nonmethane organic gases (NMOGs), primary PM and organic carbon than newer on-road gasoline vehicles (per kg of fuel burned). The primary emissions from a diesel transportation refrigeration unit were similar to those of older, uncontrolled diesel engines used in on-road vehicles (e.g., premodel year 2007 heavy-duty diesel trucks). Two-strokes emitted the largest fractional (and absolute) amount of SOA precursors compared to diesel and 4-stroke gasoline SOREs; however, 35-80% of the NMOG emissions from the engines could not be speciated using traditional gas chromatography or high-performance liquid chromatography. After 3 h of photo-oxidation in a smog chamber, dilute emissions from both 2- and 4-stroke gasoline SOREs produced large amounts of semivolatile SOA. The effective SOA yield (defined as the ratio of SOA mass to estimated mass of reacted precursors) was 2-4% for 2- and 4-stroke SOREs, which is comparable to yields from dilute exhaust from older passenger cars and unburned gasoline. This suggests that much of the SOA production was due to unburned fuel and/or lubrication oil. The total PM contribution of different mobile source categories to the ambient PM burden was calculated by combining primary emission, SOA production and fuel consumption data. Relative to their fuel consumption, SOREs are disproportionately high total PM sources; however, the vastly greater fuel consumption of on-road vehicles renders them (on-road vehicles) the dominant mobile source of ambient PM in the Los Angeles area.

A combination of increased Rho kinase activity and N-terminal pro-B-type natriuretic peptide predicts worse cardiovascular outcome in patients with acute coronary syndrome.

BACKGROUND: Recent experimental evidence suggests that the Rho/Rho-kinase (ROCK) system may play an important role in the pathogenesis of acute coronary syndrome (ACS) but there are little clinical data. This study examined if ROCK activity is increased in patients with acute coronary syndrome and if ROCK activity predicts long-term cardiovascular event. METHOD: Blood samples were collected from 188 patients within 12h after admission for ACS (53% men; aged 70 ± 13) and from 61 control subject. The main outcome measures were all cause mortality, readmission with ACS or congestive heart failure (CHF) from presentation within around 2 years (mean:14.4 ± 7.2 months; range: 0.5 to 26 months). RESULTS: ROCK activity increased in ST elevation myocardial infarction (STEMI, n=90) (3.33 ± 0.93), non-STEMI (NSTEMI, n=68) (3.37 ± 1.04) and unstable angina (UA, n=30) (2.53 ± 0.59) groups when compared with disease controls (n=31) (2.06 ± 0.38, all p<0.001) and healthy controls (n=30) (1.54 ± 0.43, all p<0.001). There were 24 deaths, 34 readmissions with ACS and 15 admissions with CHF within 2 years. Patients with a high N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high ROCK activity on admission had a five-fold risk of a cardiovascular event (RR: 5.156; 95% CI: 2.180-12.191) when compared to those with low NT-proBNP and low ROCK activity. CONCLUSION: ROCK activity was increased in patients with ACS, particularly in those with myocardial infarction. The combined usage of both ROCK activity and NT-proBNP might identify a subset of ACS patients at particularly high risk.

Quality of life after percutaneous coronary intervention in the elderly with acute coronary syndrome.

BACKGROUND: Health-related quality of life (HRQoL) is an important but often neglected outcome measure in acute coronary syndrome (ACS) management. The prevalence of elderly presenting with ACS and undergoing percutaneous coronary intervention (PCI) is rising. We aimed to explore the impact of PCI on health status in elderly ACS patients. METHODS: We prospectively enrolled 624 patients admitted to our institution with ACS from February 2006 to May 2008. Short Form (SF)-36 health survey was used to assess HRQoL at baseline and 6 months. Baseline characteristics and HRQoL were compared for patients treated with PCI within 30 days of index ACS admission vs. medical therapy across 3 age groups (<60, 60-79 and ≥80 years). RESULTS: PCI was performed in 73.6%, 55.7% and 21.3% in patients aged <60, 60-79 and older than 80 years, respectively (p<0.01). Elderly patients were more likely to be female (16.9 vs. 35.4 vs. 54.6%, p<0.01) and had more co-morbidities (p<0.01). Older patients were less likely to undergo angiography (84.8 vs. 65.2 vs. 24.8%, p<0.01). Baseline HRQoL decreased with advancing age (p<0.01). However, elderly patients who underwent PCI experienced the most improvement in physical health than younger age groups. PCI was an independent predictor (Odds Ratio = 1.79, 95% CI: 1.10-2.92) of better physical health status at 6 months. CONCLUSION: Elderly ACS patients who underwent PCI experienced the most improvement in physical health compared to younger patients. Our findings suggest that age per se should not deter against revascularization because of potential benefits in HRQOL.

Correlation between ECT2 gene expression and methylation change of ECT2 promoter region in pancreatic cancer.

BACKGROUND: Pancreatic cancer is closely related to epigenetic abnormality. The epithelial cell transforming sequence 2 gene (ECT2) plays a critical role in Rho activation during cytokinesis, and thus may play a role in the pathogenesis of pancreatic cancer. In this study, we investigated the relationships between aberrant expression and epigenetic changes of the ECT2 gene in pancreatic cancer. METHODS: Four cell lines (PANC-1, Colo357, T3M-4 and PancTuI) and pancreatic ductal adenocarcinoma (PDAC) tissues were used for mRNA detection. After restriction isoschizomer endonucleases (MspI/HpaII) were used to digest the DNA sequence (5'-CCGG-3'), PCR was made to amplify the product. And RT-PCR was applied to determine the expression of the gene. RESULTS: The mRNA expression of the ECT2 gene was higher in pancreatic tumor tissue than in normal tissue. The gene was also expressed in the 4 PDAC cell lines. The methylation states of the upstream regions of the ECT2 gene were almost identical in normal, tumor pancreatic tissues, and the 4 PDAC cell lines. Some of the 5'-CCGG-3' areas in the upstream region of ECT2 were methylated, while others were unmethylated. CONCLUSIONS: The oncogene ECT2 is overexpressed in pancreatic tumor tissues as verified by RT-PCR detection. The methylation status of DNA in promoter areas is involved in the gene expression, along with other factors, in pancreatic cancer.

Epigenetic changes of pituitary tumor-derived transforming gene 1 in pancreatic cancer.

BACKGROUND: Pancreatic cancer is a devastating disease with abnormal genetic changes. The pituitary tumor-derived transforming gene (PTTG) is considered to be implicated in the tumorigenesis of cancers when the gene is epigenetically transformed. In this study, we investigated the relationships between aberrant expression and epigenetic changes of the PTTG1 gene in pancreatic cancer. METHODS: We chose 4 cell lines (PANC-1, Colo357, T3M-4 and PancTuI) and pancreatic ductal adenocarcinoma (PDAC) tissues. After using restriction isoschizomer endonucleases (MspI/HpaII) to digest the DNA sequence (5'-CCGG-3'), we performed PCR reaction to amplify the product. And RT-PCR was applied to determine the gene expression. RESULTS: The mRNA expression of the PTTG1 gene was higher in pancreatic tumor than in normal tissue. The gene was also expressed in the 4 PDAC cell lines. The methylation states of the upstream regions of the PTTG1 gene were almost identical in normal, tumor pancreatic tissues and the 4 PDAC cell lines. Some (5'-CCGG-3') areas in the upstream region of PTTG1 were methylated, while some others were unmethylated. CONCLUSIONS: The oncogene PTTG1 was overexpressed in pancreatic tumor tissues and verified by RT-PCR detection. The methylation status of DNA in promoter areas was involved in the gene expression with the help of other factors in pancreatic cancer.