Mitochondrial GSNOR Alleviates Cardiac Dysfunction via ANT1 Denitrosylation.

BACKGROUND: The cardiac-protective role of GSNOR (S-nitrosoglutathione reductase) in the cytoplasm, as a denitrosylase enzyme of S-nitrosylation, has been reported in cardiac remodeling, but whether GSNOR is localized in other organelles and exerts novel effects remains unknown. We aimed to elucidate the effects of mitochondrial GSNOR, a novel subcellular localization of GSNOR, on cardiac remodeling and heart failure (HF). METHODS: GSNOR subcellular localization was observed by cellular fractionation assay, immunofluorescent staining, and colloidal gold particle staining. Overexpression of GSNOR in mitochondria was achieved by mitochondria-targeting sequence-directed adeno-associated virus 9. Cardiac-specific knockout of GSNOR mice was used to examine the role of GSNOR in HF. S-nitrosylation sites of ANT1 (adenine nucleotide translocase 1) were identified using biotin-switch and liquid chromatography-tandem mass spectrometry. RESULTS: GSNOR expression was suppressed in cardiac tissues of patients with HF. Consistently, cardiac-specific knockout mice showed aggravated pathological remodeling induced by transverse aortic constriction. We found that GSNOR is also localized in mitochondria. In the angiotensin II-induced hypertrophic cardiomyocytes, mitochondrial GSNOR levels significantly decreased along with mitochondrial functional impairment. Restoration of mitochondrial GSNOR levels in cardiac-specific knockout mice significantly improved mitochondrial function and cardiac performance in transverse aortic constriction-induced HF mice. Mechanistically, we identified ANT1 as a direct target of GSNOR. A decrease in mitochondrial GSNOR under HF leads to an elevation of S-nitrosylation ANT1 at cysteine 160 (C160). In accordance with these findings, overexpression of either mitochondrial GSNOR or ANT1 C160A, non-nitrosylated mutant, significantly improved mitochondrial function, maintained the mitochondrial membrane potential, and upregulated mitophagy. CONCLUSIONS: We identified a novel species of GSNOR localized in mitochondria and found mitochondrial GSNOR plays an essential role in maintaining mitochondrial homeostasis through ANT1 denitrosylation, which provides a potential novel therapeutic target for HF.

Clinical value of echocardiography combined with serum Cav-1, NFATc1, and PAI-1 in the diagnosis of Kawasaki disease complicated with coronary artery lesions.

To analyze the clinical value of echocardiography combined with serum lacuna protein-1 (Cav-1), activated T cell nuclear factor C1 (NFATc1), and plasminogen activator inhibitor-1 (PAI-1) in the diagnosis of Kawasaki disease (KD) complicated with coronary artery lesions (CAL). A total of 200 children with KD treated in our hospital from January 2019 to October 2021 were grouped as the KD alone group (n = 56) and the KD complicated with CAL group (n = 144) according to the results of coronary angiography. The levels of Cav-1, NFATc1, and PAI-1 were detected by enzyme-linked immunosorbent assay. Echocardiography was performed and the internal diameters of left and right coronary arteries were compared between the two groups. The area under the curve (AUC), sensitivity, and specificity of echocardiography combined with serum Cav-1, NFATc1, and PAI-1 in the diagnosis of KD complicated with CAL were analyzed with receiver operating characteristic (ROC) curve. Coronary angiography, as the gold standard, showed that the sensitivity of echocardiography in diagnosing KD with CAL was 88.19% (127/144), the specificity was 66.07% (37/56), and the accuracy was 82.00% (164/200). ROC curve analysis revealed that the AUC of KD complicated with CAL diagnosed by echocardiography, Cav-1, NFATc1, and PAI-1 was 0.819, 0.715, 0.688, and 0.663, respectively, and the AUC of combined diagnosis of the four was 0.896. The combination of echocardiography, Cav-1, NFATc1, and PAI-1 has high value in diagnosing KD complicated with CAL, which can be widely used in clinical practice.

Effect of 1 H-NMR serum lipoproteins on immunotherapy response in advanced triple-negative breast cancer patients.

We previously reported the results of a phase II trial of anti-PD-1 antibody plus anti-vascular endothelial growth factor receptor 2 inhibitors and eribulin in heavily pretreated advanced triple-negative breast cancer with a favorable objective response rate (ORR) of 37.0% (NCT04303741). Here we report updated survival outcomes and serum metabolite changes of the study. Proton nuclear magnetic resonance spectroscopy was used to detect metabolite dynamics and explore biomarkers for response. We found that treatment-sensitive patients had higher very low-density lipoprotein-related metabolite expression at baseline. A lipid proteomics model consisting of six metabolites predicted ORR and progression-free survival at 6 months with area under the receiver operating characteristic curves of 0.88 and 0.87, respectively. Serum asparagine and sarcosine concentrations were significantly higher after treatment in treatment-resistant patients. In conclusion, we constructed a model consisting of six metabolites to identify patients who benefit more from the triplet treatment, and asparagine and sarcosine may be associated with treatment resistance.

Neoadjuvant checkpoint blockade in combination with Chemotherapy in patients with tripe-negative breast cancer: exploratory analysis of real-world, multicenter data.

PURPOSE: Despite the poor prognosis of triple-negative breast cancer (TNBC), it has been demonstrated that neoadjuvant immunotherapy in combination with chemotherapy can improve the pathologic complete response (pCR) rate and/or long-term outcome of TNBC. However, there have been no real-world studies reporting on the effectiveness of neoadjuvant checkpoint inhibitors in early TNBC. METHODS: Between November 2019 and December 2021, 63 early TNBC patients treated with anti-PD-1 antibodies (pembrolizumab or camrelizumab) or anti-PD-L1 antibody (atezolizumab) in combination with chemotherapy at seven institutions were included. PCR1 defined as ypT0/Tis and ypN0 was the primary endpoint. Secondary endpoints included pCR2 defined as ypT0/Tis, overall response rate (ORR), disease-free survival (DFS), drug-related adverse events (AEs) and biomarkers. RESULTS: Among the patients in the current study, 34.9% of patients were able to achieve pCR1, and 47.6% of patients had achieved pCR2. The ORR was 82.5%. 33 patients with non-pCR2 tumors were found to have a median DFS of 20.7 months (95% CI 16.3 months-not reached). The DFS of patients with pCR2 and non-pCR2 after neoadjuvant therapy was significantly different (HR = 0.28, 95% CI 0.10-0.79; P = 0.038). The most common AEs were nausea (63.4%), fatigue (42.7%), leucopenia (30.0%) and elevated transaminase (11.7%). CONCLUSION: It is possible to achieve a meaningful pCR rate and DFS by combining neoadjuvant checkpoint blockade with chemotherapy in patients with high-risk TNBC. Compared to clinical trials, however, there was a slightly lower pCR rate in this multicentered real-world study.

Diagnostic performance of diffusion-weighted imaging versus 18F-FDG PET/CT in differentiating pulmonary lesions: an updated meta-analysis of comparative studies.

OBJECTIVE: To compare the diagnostic accuracy of diffusion-weighted imaging (DWI) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for differentiating pulmonary nodules and masses. METHODS: We systematically searched six databases, including PubMed, EMBASE, the Cochrane Library, and three Chinese databases, to identify studies that used both DWI and PET/CT to differentiate pulmonary nodules. The diagnostic performance of DWI and PET/CT was compared and pooled sensitivity and specificity were calculated along with 95% confidence intervals (CIs). The Quality Assessment of Diagnostic Accuracy Studies 2 was used to assess the quality of the included studies, and STATA 16.0 software was utilized to perform statistical analysis. RESULTS: Overall, 10 studies that enrolled a total of 871 patients with 948 pulmonary nodules were included in this meta-analysis. DWI had greater pooled sensitivity (0.85 [95% CI 0.77-0.90]) and specificity (0.91 [95% CI 0.82-0.96]) than PET/CT (sensitivity, 0.82 [95% CI 0.70-0.90]); specificity, (0.81, [95% CI 0.72-0.87]). The area under the curve of DWI and PET/CT were 0.94 (95% CI 0.91-0.96) and 0.87 (95% CI 0.84-0.90) (Z = 1.58, P > 0.05), respectively. The diagnostic odds ratio of DWI (54.46, [95% CI 17.98-164.99]) was superior to that of PET/CT (15.77, [95% CI 8.19-30.37]). The Deeks' funnel plot asymmetry test showed no publication bias. The Spearman correlation coefficient test revealed no significant threshold effect. Lesion diameter and reference standard could be potential causes for the heterogeneity of both DWI and PET/CT studies, and quantitative or semi-quantitative parameters used would be a potential source of bias for PET/CT studies. CONCLUSION: As a radiation-free technique, DWI may have similar performance compare with PET/CT in differentiating malignant pulmonary nodules or masses from benign ones.

Recoverable Flexible Perovskite Solar Cells for Next-Generation Portable Power Sources.

Flexible perovskite solar cells (FPSCs) with excellent recoverability show a wide range of potential applications in portable power sources. The recoverability of FPSCs requires outstanding bendability of each functional layer, including the flexible substrates, electrodes, perovskite light absorbers, and charge transport materials. This review highlights the recent progress and practical applications of high-recoverability FPSCs, and illustrates the routes toward improvement of the recoverability and environmental stability through the choice of flexible substrates and the preparation of high-quality perovskite films, as well as the optimization of charge-selective contacts. In addition, we explore the intrinsic properties of each functional layer from the physical perspective and analyze how to select suitable functional layers. Additionally, some effective strategies are summarized, including material modification engineering of selective contacts, additives and interface engineering of interlayers, which can release mechanical stress and increase the power-conversion efficiency (PCE) and recoverability of the FPSCs. The challenges of making high-performance FPSCs with long-term stability and high recoverability are discussed. Finally, future applications and perspectives for FPSCs are discussed, aiming to promote more extensive commercialization processes for lightweight and durable FPSCs.

Neural mechanisms of the mood effects on third-party responses to injustice after unfair experiences.

Behavioral decision theory argues that humans can adjust their third-party responses (e.g., punishment and compensation) to injustice by integrating unfair experiences. Typically, the mood plays an important role in such a decision-making process. However, the underlying neurocognitive bases remain largely unclear. We first employ a modified third-party justice game in which an allocator split an amount of money between oneself and a receiver. The participants can reapportion the money as observers by choosing from the following three costly options: compensate the receiver, accept the current allocation, or punish the allocator. Then, a second-party pseudo interaction is conducted where participants receive more (i.e., advantageous unfair experience) or less (i.e., disadvantageous unfair experience) than others. Finally, participants perform the third-party justice game again after unfair experiences. Here, we use functional near-infrared spectroscopy (fNIRS) to measure participants' brain activities during third-party responses to injustice. We find participants compensate more to the receiver after advantageous unfair experience, which involved enhanced positive emotion, weakened sense of unfairness, and is linked with increased activity in the right dorsolateral prefrontal cortex (rDLPFC). In contrast, participants punish more on the allocator after disadvantageous unfair experience, which might primarily stem from their negative emotional responses, strong sense of unfairness, and is associated with significantly decreased activity in the rDLPFC. Our results suggest that third-party compensation and punishment involved differential psychological and neural bases. Our findings highlight the crucial roles of second-party unfair experiences and the corresponding mood responses in third-party responses to unfairness, and unravel the intermediate neural architecture.

Gamma-band neural coupling during conceptual alignment.

Conceptual alignment is a prerequisite for mutual understanding. However, little is known about the neurophysiological brain-to-brain underpinning during conceptual alignment for mutual understanding. Here, we recorded multi-channel electroencephalogram (EEG) simultaneously from two participants in Experiment 1 and adopted the dual-tACS techniques in Experiment 2 to investigate the underlying brain-to-brain EEG coupling during conceptual alignment and the possible enhancement effect. Our results showed that 1) higher phase-locking value (PLV), a sensitive measure for quantifying neural coupling strength between EEG signals, at the gamma frequency band (28-40 Hz), was observed in the left temporoparietal site (left TP) area between successful versus unsuccessful conceptual alignment. The left TP gamma coupling strength correlated with the accuracy of conceptual alignment and differentiated whether subjects belonged to the SUCCESS or FAILURE groups in our study. 2) In-phase gamma-band transcranial alternating current stimulation (tACS) over the left TP area increased the accuracy of subjects in the SUCCESS group but not the FAILURE group. 3) The effect of perspective-taking on the accuracy was mediated by the gamma coupling strength within the left TP area. Our results support the role of gamma-band coupling between brains for interpersonal conceptual alignment. We provide dynamic interpersonal neurophysiological insights into the formation of successful communication.

Intravoxel Incoherent Motion Diffusion-Weighted Imaging for Predicting and Monitoring the Response of Anti-Angiogenic Treatment in the Orthotopic Nude Mouse Model of Lung Adenocarcinoma.

BACKGROUND: The treatment efficacy of angiogenesis inhibitor could be underestimated at an early stage based on tumor volume changes. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can quantitatively assess tumors at the cellular level, but it is unclear whether it can provide useful information for assessing treatment response of anti-angiogenic treatment for lung adenocarcinoma. PURPOSE: To determine the use of IVIM-DWI for non-invasive monitoring of the early response to anti-angiogenic treatment in the orthotopic transplantation of lung adenocarcinoma model. STUDY TYPE: Prospective. POPULATION: Thirty-seven nude mice were randomized into two groups: treatment group (received bevacizumab + cisplatin, N = 20) and control group (received saline, N = 17). FIELD STRENGTH/SEQUENCE: Single-shot turbo spin-echo (TSE) IVIM-DWI, TSE T2-weighted imaging at 3.0 T. ASSESSMENT: Tumor volume, IVIM parameters (apparent diffusion coefficient [ADC], diffusivity [D], perfusion fraction [f], and pseudo-diffusion coefficient [D*]) were measured before and 2 hours, 3, 7, 10 and 14 days after treatment. Regions of interest were manually drawn along the inner edge of the tumor by two radiologists with 5 and 10-year experience in magnetic resonance imaging. Pathological examinations (hematoxylin and eosin stain, cluster of differentiation 34) were performed. STATISTICAL TESTS: Kolmogorov-Smirnov test, repeated-measure two-way analysis of variance test, Mann-Whitney U test, Pearson correlation analysis, receiver operating characteristic curve. P < 0.05 was considered statistically significant. RESULTS: The tumor volume of the two groups was significantly different only on day 14 (control group vs. treatment group, 43.15 ± 18.28 mm3 vs. 28.41 ± 1.71 mm3 ). ADC2h , ADC10d , D2h , D7d , D10d , and D14d were significantly higher, while f10d and f14d were significantly lower in the treatment group compared to those of the control group. Both the △ADC2h (r = -0.631) and △D2h (r = -0.700) showed moderate correlations with the relative tumor volume on day 14. DATA CONCLUSION: IVIM has the potential to predict and monitor the early response to anti-angiogenic treatment, earlier than size changes, for lung adenocarcinoma. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 4.

Evaluation of peripheral nerve acute crush injury in rabbits: comparison among diffusion kurtosis imaging, diffusion tensor imaging and electromyography.

OBJECTIVE: Diffusion kurtosis imaging (DKI) has been proven to provide additional value for assessing many central nervous system diseases compared with conventional diffusion tensor imaging (DTI); however, whether it has the same value in peripheral nerve injury is unclear. This study aimed to investigate the performance of DKI, DTI, and electromyography (EMG) in evaluating peripheral nerve crush injury (PNCI) in rabbits. MATERIALS AND METHODS: A total of 27 New Zealand white rabbits were selected to establish a PNCI model. Longitudinal DTI, DKI, and EMG were evaluated before surgery and 1 day, 3 days, 1 week, 2 weeks, 4 weeks, 6 weeks, and 8 weeks after surgery. At each time point, two rabbits were randomly selected for pathological examination. RESULTS: The results showed that fractional anisotropy (FA) derived from both DKI and DTI demonstrated a significant difference between injured and control nerves at all time points (all P < 0.005) mean kurtosis of the injured nerve was lower than that on the control side after 2-8 weeks (all P < 0.05). No statistically significant difference was found in radial kurtosis, axial kurtosis, and apparent diffusion coefficient at almost every time point. The difference in compound muscle action potential (CMAP) of the bilateral gastrocnemius at each time point was statistically significant (all P < 0.001). CONCLUSIONS: CMAP was a sensitive and reliable method to assess acute PNCI without being affected by perineural edema. DKI may not be superior to DTI in evaluating peripheral nerves, DTI with a shorter scanning time was preferred as an effective choice for evaluating acute peripheral nerve traumatic injury.

Biomarkers of response to camrelizumab combined with apatinib: an analysis from a phase II trial in advanced triple-negative breast cancer patients.

PURPOSE: We recently reported results of a phase II trial that camrelizumab plus apatinib induced an objective response rate (ORR) at 43.3% in advanced triple-negative breast cancer (TNBC). This study presents analysis of potential biomarkers. METHODS: TILs, CD8+ T cells and PD-1/PD-L1 expression were evaluated in tumor samples by immunohistochemistry. 59 Cytokines/chemokines, growth factors, or checkpoint-related proteins, blood immune cell subpopulations were analyzed in blood samples by multiplexed bead immunoassays or flow cytometry. Correlation between biomarkers and clinical outcomes including ORR, progression-free survival (PFS), and overall survival (OS) was analyzed. RESULTS: 28 Patients had biopsies and blood collected. Baseline TILs were significantly associated with longer PFS (P = 0.035). An increase of tumor-infiltrating CD8+ T cells > 15% during therapy was associated with higher ORR (P = 0.040). Patients with lower baseline plasma levels of HGF or IL-8 were more likely to respond to treatment (P = 0.005 or 0.001, respectively), and showed a longer PFS and OS. Patients with a decrease of IL-8, or an increase of TIM-3 or CD152 during treatment responded more to treatment (P = 0.008, 0.040, or 0.014, respectively). Responders had a higher baseline CD4+ T cells and B cell proportions in blood than non-responders (P = 0.002 and 0.030, respectively). CONCLUSION: Higher baseline TILs or a greater increase of tumor-infiltrating CD8+ T cells during therapy, lower baseline plasma HGF/IL-8, a decrease of plasma IL-8, an increase of plasma TIM-3/CD152 during therapy, higher baseline CD4+ T cells or B cells proportion in blood are potential biomarkers for combinational anti-angiogenesis and immunotherapy in advanced TNBC patients.

Neoadjuvant everolimus plus letrozole versus fluorouracil, epirubicin and cyclophosphamide for ER-positive, HER2-negative breast cancer: a randomized pilot trial.

BACKGROUND: Here we evaluated the feasibility, efficacy, tolerability, and treatment-mediated immune modulation of neoadjuvant everolimus plus letrozole versus chemotherapy in treating postmenopausal patients with ER-positive, HER2-negative breast cancer. METHODS: Postmenopausal women with ER-positive, HER2-negative breast cancer who had a primary tumor > 2 cm or positive axillary lymph node(s) proofed by biopsy were randomly (1,1) enrolled to receive neoadjuvant everolimus plus letrozole for 18 weeks or fluorouracil, epirubicin plus cyclophosphamide (FEC) for 6 cycles before surgery. Primary outcome was feasibility of the trial. Secondary outcome included ultrasound response rate, pathological complete response rate, breast-conserving surgery rate, toxicities, treatment-mediated immune modulation and biomarkers. RESULTS: Forty patients were randomized. Completion rate was 90.0% in the neoadjuvant endocrine therapy (NET) arm but 70.0% in the neoadjuvant chemotherapy (NAC) arm. The ultrasound response rate was 65.0% in NET arm and 40.0% in FEC arm, respectively. In terms of the adverse events, clearly favored NET arm. Everolimus plus letrozole increased the ratio of peripheral Tregs to CD4+ T cells and tumor PD-L1 expression, and decreased Ki67 index and tumor-infiltrating Tregs, and patients with a greater increase of tumor-specific CTLs showed more sensitive to NET. CONCLUSION: This pilot trial showed that neoadjuvant everolimus plus letrozole might achieve a favorable ultrasound response rate with low toxicities in treating postmenopausal ER-positive, HER2-negative breast cancer patients. Everolimus plus letrozole might have positive antitumoral immunity effects. Further large randomized controlled trials are needed to confirm our findings. TRAIL REGISTRATION: A Trial of Neoadjuvant Everolimus Plus Letrozole Versus FEC in Women With ER-positive, HER2-negative Breast Cancer, registered on 07/04/2016 and first posted on 18/04/2016, NCT02742051 .

Sufentanil EC50 for endotracheal intubation with aerosol inhalation of carbonated lidocaine by ultrasonic atomizer.

BACKGROUND: Nebulized lidocaine reduced stress response for endotracheal intubation. However, the impact of novel lidocaine aerosol inhalation for intubation by ultrasonic atomizer was unclear. Hence, we designed aerosol inhalation of lidocaine by ultrasonic atomizer, to seek whether the dosage of sufentanil for intubation could be less or not. METHODS: Intravenous injection of sufentanil started at 0.5 µg/kg, and sufentanil dosage was increased/decreased (step-size 0.05 µg/kg for sufentanil) using Dixon's up and down method. The observation was terminated after 8 reflexes. RESULTS: The EC50 and EC95 of sufentanil with lidocaine by ultrasonic atomizer for intubation were found to be 0.232 µg/kg (95% CI: 0.187-0.270 µg/kg) and 0.447 µg/kg (95% CI: 0.364-0.703 µg/kg). 55.88% out of 34 patients showed hemodynamic index change < 20% of baseline during intubation. CONCLUSION: Aerosol inhalation of lidocaine by ultrasonic atomizer reduced the dosage of sufentanil for endotracheal intubation. Lidocaine inhalation by ultrasonic atomizer for airway anesthesia with minimal dosage of sufentanil could be recommended, particularly in patients who need more stable hemodynamic changes or spontaneous respiration. TRIAL REGISTRATION: Chinese Registry of Central Trial, ChiCTR-IOR-17014198 . Registered 28 December 2017.

Neural alignment during face-to-face spontaneous deception: Does gender make a difference?

This study investigated the gender differences in deception and their neural basis in the perspective of two-person neuroscience. Both male and female dyads were asked to perform a face-to-face spontaneous sender-receiver deception task, while their neural activities in the prefrontal cortex (PFC) and right temporal parietal junction (rTPJ) were recorded simultaneously using functional near-infrared spectroscopy (fNIRS)-based hyperscanning. Male and female dyads displayed similar deception rate, successful deception rate, and eye contact in deception trials. Moreover, eye contact in deception trials was positively correlated with the success rate of deception in both genders. The fNIRS data showed that the interpersonal neural synchronization (INS) in PFC was significantly enhanced only in female dyads when performed the deception task, while INS in rTPJ was increased only in male dyads. Such INS was correlated with the success rate of deception in both dyads. Granger causality analysis showed that no significant directionality between time series of PFC (or rTPJ) in each dyad, which could indicate that sender and receiver played equally important role during deception task. Finally, enhanced INS in PFC in female dyads mediated the contribution of eye contact to the success rate of deception. All findings in this study suggest that differential patterns of INS are recruited when male and female dyads perform the face-to-face deception task. To our knowledge, this is the first interbrain evidence for gender difference of successful deception, which could make us a deeper understanding of spontaneous face-to-face deception.

Extensive Microsurgical Reconstruction of Chest Wall Defects for Locally Advanced Breast Cancer: A 10-Year Single-Unit Experience.

BACKGROUND: Despite improvements in the early detection of breast cancer, locally advanced breast cancer (LABC) involving the chest wall exists in developing countries. Surgical resection remains a controversial management option. This study aims to demonstrate the value of chest wall reconstructive techniques for large LABC defects and report long-term outcomes. MATERIALS AND METHODS: We report a 10-years single-unit experience in the reconstruction of large defects (>300 cm). From 2007 to 2017, all LABC cases managed with large surgical resection with immediate microsurgical chest wall reconstruction were included in this study. Herein, we present the demographics, comorbidities, clinicopathological LABC characteristics, surgical techniques (free flap choice, recipient vessels), and outcomes (survival, complication, cosmesis, and patient satisfaction). RESULTS: Of the 104 LABC cases, free deep inferior epigastric artery perforator flap was performed in 41 (39.4%) cases, free anterolateral thigh flap in 5 (4.8%), free deep inferior epigastric artery perforator combined with pedicled transverse rectus abdominis myocutaneous (TRAM) flap in 23 (22.1%), free muscle-sparing transverse rectus abdominis muscle flap in 30 (28.9%), and free transverse upper gracilis flap in 5 (4.8%). Complications were low. Over a median follow-up of 49.5 months, the 3-year local recurrence rate and distant metastasis-free survival were 13.9% and 84.9%, respectively. In addition, the 3-year disease-free survival and overall survival were 84.2% and 92.0%, respectively. The rate of excellent and good ratings by the esthetic assessment panel was 83.0%, and the patient satisfaction rate was 90.0%. CONCLUSION: Wide resection and microvascular free tissue transfer is oncologically safe in LABC with huge tumors and provides versatile solutions for the reconstruction of extensive chest wall defects. With favorable long-term survival and cosmetic outcomes, surgical resection of LABC combined with flap reconstruction may offer a practical approach in difficult and complicated cases. IMPLICATIONS FOR PRACTICE: In this retrospective review, it was demonstrated that wide resection followed by distinct chest wall reconstructive free flaps transfer is oncologically safe in LABC with huge tumors and provides useful solutions for the reconstruction of extensive chest wall defects.

Interplay between prior knowledge and communication mode on teaching effectiveness: Interpersonal neural synchronization as a neural marker.

Teacher-student interaction allows students to combine prior knowledge with new information to develop new knowledge. It is widely understood that both communication mode and students' knowledge state contribute to the teaching effectiveness (i.e., higher students' scores), but the nature of the interplay of these factors and the underlying neural mechanism remain unknown. In the current study, we manipulated the communication modes (face-to-face [FTF] communication mode/computer-mediated communication [CMC] mode) and prior knowledge states (with vs. without) when teacher-student dyads participated in a teaching task. Using functional near-infrared spectroscopy, the brain activities of both the teacher and student in the dyads were recorded simultaneously. After teaching, perceived teacher-student interaction and teaching effectiveness were assessed. The behavioral results demonstrated that, during teaching with prior knowledge, FTF communication improved students' academic performance, as compared with CMC. Conversely, no such effect was found for teaching without prior knowledge. Accordingly, higher task-related interpersonal neural synchronization (INS) in the left prefrontal cortex (PFC) was found in the FTF teaching condition with prior knowledge. Such INS mediated the relationship between perceived interaction and students' test scores. Furthermore, the cumulative INS in the left PFC could predict the teaching effectiveness early in the teaching process (around 25-35 s into the teaching task) only in FTF teaching with prior knowledge. These findings provide insight into how the interplay between the communication mode and students' knowledge state affects teaching effectiveness. Moreover, our findings suggest that INS could be a possible neuromarker for dynamic evaluation of teacher-student interaction and teaching effectiveness.

Dynamic interpersonal neural synchronization underlying pain-induced cooperation in females.

Individuals in pain are motivated to be cooperative in social interaction. Yet, there has been little research on how pain dynamically affects cooperation at a neural level. The present study investigated the cooperative behavior under acute physical pain by asking dyads to complete three blocks of button-press cooperative task, while neural activities were recorded simultaneously on each subject by the fNIRS-based hyperscanning. Results showed that individuals in pain improved their cooperation rate across task blocks. Accordingly, increased interpersonal neural synchronization (INS) was found at the left prefrontal cortex in second block, whereas increased INS was found at the right prefrontal cortex and the right parietal cortex in third block compared to the first block. Moreover, the change of INS in right parietal cortex was positively correlated with subjective pain rating in the pain treatment group. In addition, dynamic interpersonal neural networks were identified in painful condition with increasing frontoparietal networks across time. By uncovering dissociative neural processes involved in how pain affects cooperation in social interaction, the present work provides the first interbrain evidence to highlight the sociality of pain on social interaction in perspective of motivational aspect of pain.

Development and validation of nomograms predicting survival in Chinese patients with triple negative breast cancer.

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive and heterogeneous disease. Nomograms predicting outcomes of TNBC are needed for risk management. METHODS: Nomograms were based on an analysis of 296 non-metastatic TNBC patients treated at Sun Yat-sen Memorial Hospital from 2002 to 2014. The end points were disease-free survival (DFS) and overall survival (OS). Predictive accuracy and discriminative ability were evaluated by concordance index (C-index), area under the curve (AUC) and calibration curve, and compared with the American Joint Committee on Cancer (AJCC) staging system, PREDICT and CancerMath. Models were subjected to bootstrap internal validation and external validation using independent cohorts of 191 patients from the second Xiangya Hospital and Peking University Shenzhen Hospital between 2007 and 2012. RESULTS: On multivariable analysis of training cohort, independent prognostic factors were stromal tumor-infiltrating lymphocytes (TILs), tumor size, node status, and Ki67 index, which were then selected into the nomograms. The calibration curves for probability of DFS and OS showed optimal agreement between nomogram prediction and actual observation. The C-index of nomograms was significantly higher than that of the seventh and eighth AJCC staging system for predicting DFS (training: 0.743 vs 0.666 (P = 0.003) and 0.664 (P = 0.024); validation: 0.784 vs 0.632 (P = 0.02) and 0.607 (P = 0.002)) and OS (training: 0.791 vs 0.683 (P = 0.004) and 0.677 (P < 0.001); validation: 0.783 vs 0.656 (P = 0.006) and 0.606 (P = 0.001)). Our nomograms had larger AUCs compared with PREDICT and CancerMath. In addition, the nomograms showed good performance in stratifying different risk groups of patients both in the training and validation cohorts. CONCLUSION: We have developed novel and practical nomograms that can provide individual prediction of DFS and OS for TNBC based on stromal TILs, tumor size, node status, and Ki67 index. Our nomograms may help clinicians in risk consulting and selection of long term survivors.

Characteristics of and risk factors for death in elderly patients with acute kidney injury: a multicentre retrospective study in China.

PURPOSE OF THE STUDY: The incidence of acute kidney injury (AKI) with a poor prognosis in the elderly has been increasing each year. This study aimed to investigate the clinical characteristics of and risk factors for death from AKI in the elderly and help improve prognosis. STUDY DESIGN: This study was a retrospective cohort study based on data from adult patients (≥18 years old) admitted to 15 hospitals in China between 1 January 2009 and 31 December 2011. The characteristics of AKI in the elderly were compared with those in younger patients. RESULTS: In elderly patients with AKI, rates of hypertension, cardiovascular disease and multiple organ dysfunction syndrome (MODS) were higher than in younger patients (44.2% vs 31.2%, 16.1% vs 4.6% and 20.9% vs 16.9%, respectively), the length of ICU stay was longer (3.8 days vs 2.7 days, P=0.019) and renal biopsy (1.0% vs 7.13%, P<0.001) and dialysis (9.6% vs 19.2%, P<0.001) were performed less. Hospital-acquired (HA) AKI was more common than community-acquired (CA) AKI (60.3% vs 39.7%), while the most common cause of AKI was pre-renal (53.5%). Multiple logistic regression analysis showed that age (OR 1.041, 95% CI 1.023 to 1.059), cardiovascular disease (OR 1.980, 95% CI 1.402 to 2.797), cancer (OR 2.302, 95% CI 1.654 to 3.203), MODS (OR 3.023, 95% CI 1.627 to 5.620) and mechanical ventilation (OR 2.408, 95% CI 1.187 to 4.887) were significant risk factors for death. CONCLUSIONS: HA-AKI and pre-renal AKI were more common in the elderly. Age, cardiovascular disease, cancer, MODS and mechanical ventilation were independent risk factors for death in the elderly with AKI.

Development of nomograms to predict axillary lymph node status in breast cancer patients.

BACKGROUND: Prediction of axillary lymph node (ALN) status preoperatively is critical in the management of breast cancer patients. This study aims to develop a new set of nomograms to accurately predict ALN status. METHODS: We searched the National Cancer Database to identify eligible female breast cancer patients with profiles containing critical information. Patients diagnosed in 2010-2011 and 2012-2013 were designated the training (n = 99,618) and validation (n = 101,834) cohorts, respectively. We used binary logistic regression to investigate risk factors for ALN status and to develop a new set of nomograms to determine the probability of having any positive ALNs and N2-3 disease. We used ROC analysis and calibration plots to assess the discriminative ability and accuracy of the nomograms, respectively. RESULTS: In the training cohort, we identified age, quadrant of the tumor, tumor size, histology, ER, PR, HER2, tumor grade and lymphovascular invasion as significant predictors of ALNs status. Nomogram-A was developed to predict the probability of having any positive ALNs (P_any) in the full population with a C-index of 0.788 and 0.786 in the training and validation cohorts, respectively. In patients with positive ALNs, Nomogram-B was developed to predict the conditional probability of having N2-3 disease (P_con) with a C-index of 0.680 and 0.677 in the training and validation cohorts, respectively. The absolute probability of having N2-3 disease can be estimated by P_any*P_con. Both of the nomograms were well-calibrated. CONCLUSIONS: We developed a set of nomograms to predict the ALN status in breast cancer patients.