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Natural scenes sparsely activate neurons in the primary visual cortex (V1). However, how sparsely active neurons reliably represent complex natural images and how the information is optimally decoded from these representations have not been revealed. Using two-photon calcium imaging, we recorded visual responses to natural images from several hundred V1 neurons and reconstructed the images from neural activity in anesthetized and awake mice. A single natural image is linearly decodable from a surprisingly small number of highly responsive neurons, and the remaining neurons even degrade the decoding. Furthermore, these neurons reliably represent the image across trials, regardless of trial-to-trial response variability. Based on our results, diverse, partially overlapping receptive fields ensure sparse and reliable representation. We suggest that information is reliably represented while the corresponding neuronal patterns change across trials and collecting only the activity of highly responsive neurons is an optimal decoding strategy for the downstream neurons. Natural scenes sparsely activate V1 neurons. Here, the authors show that a small number of active cells reliably represent visual contents of a natural image across trials regardless of response variability, due to the diverse and partially overlapping representations of individual cells.

Implantable neural microelectrodes that can record extracellular biopotentials from small, targeted groups of neurons are critical for neuroscience research and emerging clinical applications including brain-controlled prosthetic devices. The crucial material-dependent problem is developing microelectrodes that record neural activity from the same neurons for years with high fidelity and reliability. Here, we report the development of an integrated composite electrode consisting of a carbon-fibre core, a poly( p -xylylene)-based thin-film coating that acts as a dielectric barrier and that is functionalized to control intrinsic biological processes, and a poly(thiophene)-based recording pad. The resulting implants are an order of magnitude smaller than traditional recording electrodes, and more mechanically compliant with brain tissue. They were found to elicit much reduced chronic reactive tissue responses and enabled single-neuron recording in acute and early chronic experiments in rats. This technology, taking advantage of new composites, makes possible highly selective and stealthy neural interface devices towards realizing long-lasting implants. Implantable neural microelectrodes are critical to neuroscience research and emerging clinical applications including brain-controlled prostheses. A composite electrode consisting of a carbon fibre core, an insulating polymer coating and a polythiophene-based recording pad has now been developed that shows reduced chronic reactive tissue response in rats compared with existing architectures, owing to its smaller size and improved mechanical compliance with brain tissue.

A minicolumn is the smallest anatomical module in the cortical architecture, but it is still in debate whether it serves as functional units for cortical processing. In the rodent primary visual cortex (V1), neurons with different preferred orientations are mixed horizontally in a salt and pepper manner, but vertical functional organization was not examined. In this study, we found that neurons with similar orientation preference are weakly but significantly clustered vertically in a short length and horizontally in the scale of a minicolumn. Interestingly, the vertical clustering is found only in a part of minicolumns, and others are composed of neurons with a variety of orientation preferences. Thus, the mouse V1 is a mixture of vertical clusters of neurons with various degrees of orientation similarity, which may be the compromise between the brain size and keeping the vertical clusters of similarly tuned neurons at least in a subset of clusters. Primary visual cortical neurons display mostly a salt and pepper arrangement of orientation preferences along the horizontal cortical axis. Here the authors show that a significant subset of minicolumns, one-cell wide arrays of cells arranged along the vertical axis, show similar orientation tuning preferences.

In 1990, Okuda et al. reported the first isolation and characterization of oenothein B, a unique ellagitannin dimer with a macrocyclic structure, from the Oenothera erythrosepala leaves. Since then, a variety of macrocyclic analogs, including trimeric–heptameric oligomers have been isolated from various medicinal plants belonging to Onagraceae, Lythraceae, and Myrtaceae. Among notable in vitro and in vivo biological activities reported for oenothein B are antioxidant, anti-inflammatory, enzyme inhibitory, antitumor, antimicrobial, and immunomodulatory activities. Oenothein B and related oligomers, and/or plant extracts containing them have thus attracted increasing interest as promising targets for the development of chemopreventive agents of life-related diseases associated with oxygen stress in human health. In order to better understand the significance of this type of ellagitannin in medicinal plants, this review summarizes (1) the structural characteristics of oenothein B and related dimers; (2) the oxidative metabolites of oenothein B up to heptameric oligomers; (3) the distribution of oenotheins and other macrocyclic analogs in the plant kingdom; and (4) the pharmacological activities hitherto documented for oenothein B, including those recently found by our laboratory.

Implantable neural interfaces are important tools to accelerate neuroscience research and translate clinical neurotechnologies. The promise of a bidirectional communication link between the nervous system of humans and computers is compelling, yet important materials challenges must be first addressed to improve the reliability of implantable neural interfaces. This perspective highlights recent progress and challenges related to arguably two of the most common failure modes for implantable neural interfaces: (1) compromised barrier layers and packaging leading to failure of electronic components; (2) encapsulation and rejection of the implant due to injurious tissue–biomaterials interactions, which erode the quality and bandwidth of signals across the biology–technology interface. Innovative materials and device design concepts could address these failure modes to improve device performance and broaden the translational prospects of neural interfaces. A brief overview of contemporary neural interfaces is presented and followed by recent progress in chemistry, materials, and fabrication techniques to improve in vivo reliability, including novel barrier materials and harmonizing the various incongruences of the tissue–device interface. Challenges and opportunities related to the clinical translation of neural interfaces are also discussed.

We used a neuromusculoskeletal model of bipedal walking to examine the effects of foot–ground friction conditions and gait patterns on slip- and trip-induced falls. We developed three two-dimensional neuro-musculoskeletal models in a self-organized manner representing young adults, elderly non-fallers, and elderly fallers. We simulated walking under different foot-ground friction conditions. The static friction coefficient between the foot and the ground was varied from 0.05 to 2.0. Under low friction conditions, the three gait models demonstrated slip-induced falls. The elderly faller model experienced the most slip. This is because the RCOF was higher in the elderly faller model due to its short stride length but much smaller foot clearance. Under high friction conditions, only the elderly faller model demonstrated trip-induced falls. Based on the analysis using the margin of stability, the forward postural stability of the model gradually decreased under high-friction conditions, with the toe of the swing foot contacting the ground and subsequently falling forward. These results imply that there is an optimal coefficient of friction for the ground to prevent slip- and trip-induced falls by people with less stable gaits, which may provide new insights into the design of shoes and floor surfaces for the elderly.

The use of immune checkpoint inhibitors to treat urothelial carcinoma (UC) is increasing rapidly without clear guidance for validated risk stratification. This multicenter retrospective study collected clinicopathological information on 463 patients, and 11 predefined variables were analyzed to develop a multivariate model predicting overall survival (OS). The model was validated using an independent dataset of 292 patients. Patient characteristics and outcomes were well balanced between the discovery and validation cohorts, which had median OS times of 10.2 and 12.5 mo, respectively. The final validated multivariate model was defined by risk scores based on the hazard ratios (HRs) of independent prognostic factors including performance status, site of metastasis, hemoglobin levels, and the neutrophil‐to‐lymphocyte ratio. The median OS times (95% confidence intervals [CIs]) for the low‐, intermediate‐, and high‐risk groups (discovery cohort) were not yet reached (NYR) (NYR–19.1), 6.8 mo (5.8‐8.9), and 2.3 mo (1.2‐2.6), respectively. The HRs (95% CI) for OS in the low‐ and intermediate‐risk groups vs the high‐risk group were 0.07 (0.04‐0.11) and 0.23 (0.15‐0.37), respectively. The objective response rates for in the low‐, intermediate‐, and high‐risk groups were 48.3%, 28.8%, and 10.5%, respectively. These differential outcomes were well reproduced in the validation cohort and in patients who received pembrolizumab after perioperative or first‐line chemotherapy (N = 584). In conclusion, the present study developed and validated a simple prognostic model predicting the oncological outcomes of pembrolizumab‐treated patients with chemoresistant UC. The model provides useful information for external validation, patient counseling, and clinical trial design. A multicenter study using real‐world data of patients who received pembrolizumab treatment for chemoresistant urothelial cancer reports a prognostication model based on 4 risk factors (Eastern Cooperative Oncology Group performance status, site of metastasis, low hemoglobin, and high lymphocyte‐to‐neutrophil ratio). The model was developed using data from the first 463 patients and externally validated by an independent cohort of 292 patients with high concordance and reproducibility.

Cereblon (CRBN) is a target for immunomodulatory drugs. This study investigated the prognostic value of the expression of CRBN‐pathway genes on the clinical relevance of lenalidomide (Len) treatment and evaluated the levels of CRBN‐binding proteins and mutations in these genes after Len treatment. Forty‐eight primary multiple myeloma cells were collected prior to treatment with Len and dexamethasone (Ld) and 25 paired samples were obtained post‐Ld therapy. These tumor cells were used to determine the expression and mutated forms of the CRBN‐pathway genes. Following normalization with CRBN levels, there was a significantly reduced IKZF1/CRBN ratio in samples that responded poorly to Ld therapy. Moreover, patients with low ratios of IKZF1/CRBN showed a significantly shorter progression‐free survival (PFS) and overall survival (OS) than those with higher ratios. However, patients with high ratios of KPNA2/CRBN showed a significantly shorter PFS and OS than patients with lower ratios. Of the 25 paired samples analyzed, most samples showed a reduction in the expression of CRBN and an increase in IKZF1 gene expression. No mutations were observed in CRBN, IKZF1, or CUL4A genes in the post‐Ld samples. In conclusion, a decreased expression of IKZF1 and increased expression of KPNA2 compared to that of CRBN mRNA predicts poor outcomes of Ld therapy. This study investigated the prognostic value of the expression of cereblon (CRBN)‐pathway genes on the clinical relevance of lenalidomide treatment and evaluated the levels of CRBN‐binding proteins, mutations in these genes, and the methylation status of the CRBN promoter sequence. In conclusion, a decreased expression of IKZF1 and increased expression of KPNA2 compared to that of CRBN mRNA predicts poor outcomes of lenalidomide and dexamethasone therapy.

We conducted a multicenter, retrospective study to determine the anatomical distribution and prognostic factors of gastrointestinal (GI) follicular lymphoma (FL). This study included 125 patients with stage I and II1 GI–FL. Of the 125 patients, the small intestine was examined in 70 patients, with double‐balloon endoscopy and/or capsule endoscopy. The most frequently involved GI–FL site was the duodenal second portion (DSP) (81%), followed by the jejunum (40%); 85% of patients with involvement of the DSP also had jejunal or ileal lesions. The absence of abdominal symptoms and macroscopic appearance of multiple nodules were significantly present in the DSP‐positive group. During a median follow up of 40 months, six patients showed disease progression. Patients with involvement of the DSP had better progression‐free survival (PFS) than those without such involvement (P = 0.001). A multivariate analysis revealed that male sex, the presence of abdominal symptoms, and negative involvement of the DSP were independently associated with poor PFS. In conclusion, most patients with GI–FL have duodenal lesions associated with multiple jejunal or ileal lesions. Gastrointestinal follicular lymphomas involving the DSP might be a distinct entity showing a favorable clinical course. (Cancer Sci 2011; 102: 1532–1536)