SCREENES: Enhancing non-uniform sampling reconstruction for symmetrical NMR spectroscopy.

BACKGROUND: Symmetrical NMR spectroscopy, such as Total Correlation Spectroscopy (TOCSY) and other homonuclear spectroscopy, displays symmetry in chemical shift but are generally not symmetrical in terms of intensity, which constitutes a pivotal branch of multidimensional NMR spectroscopy and offers a robust tool for elucidating the structures and dynamics of complex samples, particularly in the context of biological macromolecules. Non-Uniform Sampling (NUS) stands as a critical technique for accelerating multidimensional NMR experiments. However, symmetrical NMR spectroscopy inherently presents dynamic peak intensities, where cross peaks tend to be substantially weaker compared to diagonal peaks. Recovering these weaker cross peaks from NUS data poses a significant challenge, often resulting in compromised data quality. RESULTS: We enhance the reconstruction quality of NUS symmetrical NMR spectroscopy based on the assumption that the asymmetry in intensity is mild. Regarding the sampling schedule, we employ the symmetrical sampling structure integrated with Poisson sampling schedule to enhance the efficiency of data acquisition. In term of the reconstruction algorithm, we propose the new method by incorporating hard and soft symmetrical constraints into our recently developed L1-norm-based Compressed Sensing (CS) method known as Sparse Complex-valued REconstruction Enabled by Newton method (SCREEN). Additionally, we propose a two-step reconstruction strategy that separately addresses diagonal and cross peaks. In this two-step strategy, cross peaks are effectively reconstructed by excluding the stronger diagonal peaks. Extensive experimental results validate the effectiveness of our proposed methodology. SIGNIFICANCE: This method enhances the overall quality of the reconstructed NUS symmetrical NMR spectra, especially in terms of cross peaks, thereby enriching the interpretation of spectral information. Furthermore, it boosts the robustness towards regularization parameters, facilitating a user-friendly experience.

AttentionViz: A Global View of Transformer Attention.

Transformer models are revolutionizing machine learning, but their inner workings remain mysterious. In this work, we present a new visualization technique designed to help researchers understand the self-attention mechanism in transformers that allows these models to learn rich, contextual relationships between elements of a sequence. The main idea behind our method is to visualize a joint embedding of the query and key vectors used by transformer models to compute attention. Unlike previous attention visualization techniques, our approach enables the analysis of global patterns across multiple input sequences. We create an interactive visualization tool, AttentionViz (demo: http://attentionviz.com), based on these joint query-key embeddings, and use it to study attention mechanisms in both language and vision transformers. We demonstrate the utility of our approach in improving model understanding and offering new insights about query-key interactions through several application scenarios and expert feedback.

TIL-Derived CAR T Cells Improve Immune Cell Infiltration and Survival in the Treatment of CD19-Humanized Mouse Colorectal Cancer.

Chimeric antigen receptor-engineered T cells (CAR Ts) targeting CD19 have shown unprecedented prognosis in treating hematological cancers. However, the lack of a tumor-specific antigen as the target and an inhospitable tumor environment limit the clinical application of CAR T in solid tumors. Tumor-infiltrating T lymphocytes (TIL) exhibit diverse T cell receptor clonality and superior tumor-homing abilities. Therefore, in our study, human CD19-target TIL CAR-Ts armed with CD3ζ and 4-1BB signaling domains were constructed. Mouse colorectal cancer CT26 cells expressing human CD19 (hCD19+-CT26) were developed to assess the anti-tumor activity of TIL CAR-T cells, both in vitro and in vivo. Compared with splenic CAR T adoptive transfer, TIL CAR-T administration showed superior tumor suppression ability in hCD19+-CT26 tumor-bearing mice. Furthermore, more T cells were found at the tumor site and had lower exhaustion-related inhibitory receptor (T cell immunoglobulin and mucin domain-containing protein 3, Tim3) expression and higher immune memory molecule (CD62L) expression. Overall, we provided an artificial tumor-specific antigen in solid tumors and demonstrated that combined CAR-expressing TIL-Ts (TIL CAR-Ts) exhibited strong anti-tumor activity, with improved T cell infiltration and immune memory. Our humanized tumor antigen presented platform of mice suggests that TIL CAR-T-based adoptive therapy could be a promising strategy for solid cancer treatment.

GRIN-toolbox: A versatile and light toolbox for NMR inversion.

NMR technique serves as a powerful analytical tool with diverse applications in fields such as chemistry, biology, and material science. However, the effectiveness of NMR heavily relies on data post-processing which is often modeled as regularized inverse problem. Recently, we proposed the Generally Regularized INversion (GRIN) algorithm and demonstrated its effectiveness in NMR data processing. GRIN has been integrated as a friendly graphic user interface-based toolbox which was not detailed in the original paper. In this paper, to make GRIN more practically accessible to NMR practitioners, we focus on introducing the usage of GRIN-Toolbox with processing examples and the corresponding processing graphic interfaces, and the user manual is attached as Supplementary Material. GRIN-Toolbox is versatile and lightweight, where various kinds of data processing tasks can be completed with one click, including but not limited to diffusion-ordered spectroscopy processing, magnetic resonance imaging under-sampling reconstruction, Laplace (diffusion or relaxation) NMR inversion, spectrum denoising, etc. In addition, GRIN-Toolbox could be extended to more applications with user-designed inversion models and freely available at https://github.com/EricLin1993/GRIN.

[LncRNA RUNX1-IT1 regulating malignant pleomorphic adenoma via mir-195/CyclinD1].

PURPOSE: To investigate the regulation of long non-coding RNA (LncRNA) RUNX1-IT1 on microrna (mir-195)/CyclinD1 (CyclinD1) in malignant pleomorphic adenoma (MPA). METHODS: The MPA tissues and para-carcinoma tissues were collected and the expression levels of LncRNA RUNX1-IT1, miR-195 and CyclinD1 mRNA were detected, the correlation and clinical pathology of MPA was analyzed and compared. MPA cell line SM-AP1 was cultured and transfected with negative control(NC) siRNA, LncRNA RUNX1-IT1siRNA, miR-NC and miR-195 inhibitor. Cell proliferation level A490 and expression levels of miR-195 and CyclinD1 were detected. LncRNA RUNX1-IT1 targeting miR-195 and miR-195 targeting CyclinD1 were analyzed by dual luciferase reporter gene assay. SPSS 21.0 software package was used for data analysis. RESULTS: The expression level of LncRNA RUNX1-IT1 and CyclinD1 in MPA were higher than those in para tumor tissues, and the expression level of miR-195 was lower than that in para tumor tissues(P＜0.05). LncRNA RUNX1-IT1was negatively correlated with miR-195, positively correlated with CyclinD1, and miR-195 was negatively correlated with CyclinD1. The expression of LncRNA RUNX1-IT1 and CyclinD1 in MPA tissue with tumor diameter≥3 cm, recurrence and distant metastasis increased(P＜0.05), while the expression of miR-195 decreased(P＜0.05). After knockdown of LncRNA RUNX1-IT1, A490 level and CyclinD1 expression level decreased, while miR-195 expression level increased(P＜0.05). miR-195 decreased the fluorescence activity of LncRNA RUNX1-IT1 and CyclinD1 reporter genes(P＜0.05). After miR-195 was inhibited, the effect of LncRNA RUNX1-IT1 knockdown on decreasing A490 level and CyclinD1 expression level weakened(P＜0.05). CONCLUSIONS: LncRNA RUNx1-IT1 may participate in the development of MPA by regulating the expression of miR-195/CyclinD1.

Generalizability and quality control of deep learning-based 2D echocardiography segmentation models in a large clinical dataset.

Use of machine learning (ML) for automated annotation of heart structures from echocardiographic videos is an active research area, but understanding of comparative, generalizable performance among models is lacking. This study aimed to (1) assess the generalizability of five state-of-the-art ML-based echocardiography segmentation models within a large Geisinger clinical dataset, and (2) test the hypothesis that a quality control (QC) method based on segmentation uncertainty can further improve segmentation results. Five models were applied to 47,431 echocardiography studies that were independent from any training samples. Chamber volume and mass from model segmentations were compared to clinically-reported values. The median absolute errors (MAE) in left ventricular (LV) volumes and ejection fraction exhibited by all five models were comparable to reported inter-observer errors (IOE). MAE for left atrial volume and LV mass were similarly favorable to respective IOE for models trained for those tasks. A single model consistently exhibited the lowest MAE in all five clinically-reported measures. We leveraged the tenfold cross-validation training scheme of this best-performing model to quantify segmentation uncertainty. We observed that removing segmentations with high uncertainty from 14 to 71% studies reduced volume/mass MAE by 6-10%. The addition of convexity filters improved specificity, efficiently removing < 10% studies with large MAE (16-40%). In conclusion, five previously published echocardiography segmentation models generalized to a large, independent clinical dataset-segmenting one or multiple cardiac structures with overall accuracy comparable to manual analyses-with variable performance. Convexity-reinforced uncertainty QC efficiently improved segmentation performance and may further facilitate the translation of such models.

Scarless Epicanthoplasty and Concomitant Double Eyelidplasty in Chinese Eyelids.

BACKGROUND: The presence of mild or moderate medial epicanthus is typical in Asian patients. Numerous epicanthoplasty techniques have been described previously. However, these methods usually leave obvious scars in the medial canthal area. The aim of this report is to introduce a novel epicanthoplasty technique and a concomitant double eyelidplasty which avoid leaving scars in the medial canthal region. METHODS: From July 2013 to July 2015, 252 patients received epicanthoplasty and concomitant double eyelidplasty with this new technique. The medial epicanthus was corrected through the medial end of the eyelid crease incision. One hundred eighteen of these patients were followed up for 3-24 months (8 months in average). The preoperative and postoperative interepicanthal distances were measured at pre, 3 and 6 months post-operation. The aesthetic results were evaluated with patient visual analog scale (VAS) scores. RESULTS: The average intercanthal distance significantly decreased 3 months after the operation (32.7 ± 2.3 mm vs 36.5 ± 2.6 mm, p < 0.05, paired t test). Little retraction was noticed at 6 months after the operation (33.0 ± 2.4 vs 32.7 ± 2.3 mm, p < 0.05, paired t test). The mean patient VAS score associated with satisfaction of overall outcome was 4.2 at 6 months after operation (range 2.5-5.0). CONCLUSION: This new method provides an effective way to correct the medial epicanthus without leaving any scar in the medial canthal region. Patients with mild to moderate medial epicanthus are good candidates for this procedure. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

New Design for Axillary Dual-Plane Endoscopic Breast Augmentation for Asians: the Feasibility of Two Types of Dual-Plane Implant Pockets in 70 Patients as Measured by the BREAST-Q.

BACKGROUND: The design methods for dual-plane implant pockets for axillary endoscopic breast augmentation vary among different countries. We applied a modified approach for an Asian population. METHODS: Seventy patients with micromastia underwent our modified approach between 2011 and 2014. Breasts were divided into two types according to the soft-tissue pinch thickness of the lower pole: type I (thickness >2 cm; Group I) and type II (thickness ≤2 cm; Group II). The levels at which the pectoralis major (PM) was severed were 6-6.5 cm and 3-4 cm below the nipple for type I and II pockets, respectively. Then, dissection of the retromammary space was continued from the severance level downward to the new inframammary fold for type I pockets, whereas no dissection was made for type II pockets. All patients completed the pre- and post-operative BREAST-Q augmentation modules. RESULTS: During a mean follow-up of 10 months (range, 6-12 months), patients reported higher satisfaction with breasts after surgery than before surgery (satisfaction scores of 64.9 ± 5.6 vs. 14.7 ± 11.0). The mean satisfaction score for the overall outcome was 91.3 ± 17.3. However, there was no significant difference in physical well-being (87.1 ± 10.4 vs. 85.2 ± 11.7). No complications such as severe capsular contracture or displacement occurred. CONCLUSION: Distinguishing the need for a type I or II dual-plane pocket can lead to good outcomes and optimal soft-tissue coverage. The higher satisfaction and quality of life reported by our patients indicate that our new design is feasible and safe for most Asians with a medium build. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.