Sentinel lymph node identification using NIR-II ultrabright Raman nanotags on preclinical models.

Surface-enhanced Raman spectroscopy (SERS) nanotags have garnered much attention as promising bioimaging contrast agent with ultrahigh sensitivity, but their clinical translation faces challenges including biological and laser safety. As breast sentinel lymph node (SLN) imaging agents, SERS nanotags used by local injection and only accumulation in SLNs, which were removed during surgery, greatly reduce biological safety concerns. But their clinical translation lacks pilot demonstration on large animals close to humans. The laser safety requires irradiance below the maximum permissible exposure threshold, which is currently not achievable in most SERS applications. Here we report the invention of the core-shell SERS nanotags with ultrahigh brightness (1 pM limit of detection) at the second near-infrared (NIR-II) window for SLN identification on pre-clinical animal models including rabbits and non-human primate. We for the first time realize the intraoperative SERS-guided SLN navigation under a clinically safe laser (1.73 J/cm2) and identify multiple axillary SLNs on a non-human primate. No evidence of biosafety issues was observed in systematic examinations of these nanotags. Our study unveils the potential of NIR-II SERS nanotags as appropriate SLN tracers, making significant advances toward the accurate positioning of lesions using the SERS-based tracer technique.

Spatial Attention Modulates Neuronal Interactions between Simple and Complex Cells in V1.

Visual perception is profoundly modulated by spatial attention, which can selectively prioritize goal-related information. Previous studies found spatial attention facilitated the efficacy of neuronal communication between visual cortices with hierarchical organizations. In the primary visual cortex (V1), there is also a hierarchical connection between simple (S) and complex (C) cells. We wonder whether and how spatial attention modulates neuronal communication within V1, especially for neuronal pairs with heterogeneous visual input. We simultaneously recorded the pairs' activity from macaque monkeys when they performed a spatial-attention-involved task, then applied likelihood-based Granger causality analysis to explore attentional modulation of neuronal interactions. First, a significant attention-related decrease in Granger causality was found in S-C pairs, which primarily displayed in the S-to-C feedforward connection. Second, the interaction strength of the feedforward connection was significantly higher than that of the feedback under attend toward (AT) conditions. Although information flow did not alter as the attentional focus shifted, the strength of communications between target- and distractor-stimuli-covered neurons differed only when attending to complex cells' receptive fields (RFs). Furthermore, pairs' communications depended on the attentional modulation of neurons' firing rates. Our findings demonstrate spatial attention does not induce specific information flow but rather amplifies directed communication within V1.

Modulation of Spike Count Correlations Between Macaque Primary Visual Cortex Neurons by Difficulty of Attentional Task.

Studies have shown that spatial attention remarkably affects the trial-to-trial response variability shared between neurons. Difficulty in the attentional task adjusts how much concentration we maintain on what is currently important and what is filtered as irrelevant sensory information. However, how task difficulty mediates the interactions between neurons with separated receptive fields (RFs) that are attended to or attended away is still not clear. We examined spike count correlations between single-unit activities recorded simultaneously in the primary visual cortex (V1) while monkeys performed a spatial attention task with two levels of difficulty. Moreover, the RFs of the two neurons recorded were non-overlapping to allow us to study fluctuations in the correlated responses between competing visual inputs when the focus of attention was allocated to the RF of one neuron. While increasing difficulty in the spatial attention task, spike count correlations were either decreased to become negative between neuronal pairs, implying competition among them, with one neuron (or none) exhibiting attentional enhancement of firing rate, or increased to become positive, suggesting inter-neuronal cooperation, with one of the pair showing attentional suppression of spiking responses. Besides, the modulation of spike count correlations by task difficulty was independent of the attended locations. These findings provide evidence that task difficulty affects the functional interactions between different neuronal pools in V1 when selective attention resolves the spatial competition.

Feature-based attention elicited by precueing in an orientation discrimination task.

Specific visual features can be attended to and processed with a higher priority by our brain, termed feature-based attention (FBA). Two potential mechanisms for FBA have been suggested: goal-driven attentional mediating and stimulus-driven feature priming. Some researchers argued that several reported top-down FBA effects might also involve the influence of feature priming. To clarify this confusion, we used an orientation discrimination task in which the target was tilted randomly from the horizontal or vertical axis and presented at one of four iso-eccentric positions. The target's orientation was precued from trial to trial by an oriented line (Experiment 1) or by a symbolic arrow presented peripherally (Experiment 2) or centrally (Experiments 3/4). The cue could be either valid or invalid according to the congruency of its indicating orientation with the target's nearest cardinal axis. Our results demonstrate that the discrimination speed was significantly faster following a valid than an invalid cue (validity effect) in the session with 80% cue validity when both response accuracy and speed were emphasized. Moreover, this validity effect could also be observed in the session with 50% cue validity using the line cue (Experiment 1), even though its magnitude was significantly reduced, which illustrates the impact of feature priming. However, we did not find the validity effect in the session with 50% cue validity using the symbolic cue (Experiments 2/3). These modulations on the magnitude of the validity effect should be ascribed to top-down attentional mediating that is independent of spatial attention (illustrated by Experiment 3). Importantly, when response accuracy was stressed over speed in Experiment 4, the accuracy was significantly higher following a valid than an invalid cue in the session with 80% cue validity but not in the session with 50% cue validity. Our findings indicate that both top-down attentional mediating and feature priming are important mechanisms for FBA.

Body mass index is associated with Barrett esophagus and cardiac mucosal metaplasia.

A positive association between body mass index (BMI) and risk of esophageal adenocarcinoma has been reported. Barrett esophagus (BE) is a precursor lesion for esophageal adenocarcinoma. Cardiac mucosa (CM) and BE are both reflux-induced metaplastic columnar epithelia in the esophagus. We investigated the association between BMI and BE/CM in a case-control study. A total of 174 BE patients, 333 CM patients, and 274 controls were included in this study. Multivariate logistic regression methods were used to estimate odds ratios (OR) for BE or CM associated with BMI. Linear regression analysis was employed to examine the relationship between length of columnar lined esophagus (CLE) and BMI. A dose-dependent relationship was found between BMI and BE (P=.0004). The multivariate-adjusted OR for BE was 3.3 (95% confidence interval [CI], 1.6-6.7) when obese individuals (BMI >or=30 kg/m(2)) were compared to lean individuals (BMI < 22 kg/m(2)). Similarly, a dose-dependent relationship was found between BMI and CM (P=.03). The multivariate-adjusted OR for CM comparing obese to lean persons was 1.8 (95% CI, 1.04-3.10). The length of CLE was positively related to BMI (P=.04). In conclusion, BMI is associated with BE and CM and appears to act early in the sequence of events leading from gastroesophageal reflux disease to metaplasia (CM and BE) to dysplasia and finally to adenocarcinoma.

A proposed explanation for female predominance in alveolar soft part sarcoma. Noninactivation of X; autosome translocation fusion gene?

BACKGROUND: Alveolar soft-part sarcoma (ASPS) is a rare malignant soft tissue tumor with both clinically and morphologically distinct features. It often involves the extremities of adolescents and young adults and shows a predilection for females. Recently, ASPS was found to have a nonreciprocal der(17)t(X;17) translocation with the corresponding fusion gene located in chromosome 17. Because females have an extra X-chromosome, their likelihood of developing an X;autosome translocation is theoretically double that of males, and thus, this extra X-chromosome is a likely explanation for female predominance of ASPS. METHODS: The authors used data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry program, which included 87 ASPS cases (33 males and 54 females), and published ASPS cases, which included 317 cases (121 males and 196 females), to test our hypothesis. The authors compared the observed proportion of female cases with that expected under the two X-chromosomes-double-risk hypothesis including the consideration of X-inactivation status. RESULTS: The hypothesis that the fusion gene is not subject to X-inactivation is supported by data (P = 0.6, 0.24, and 0.20 for SEER cases, published cases, and their combination, respectively). In contrast, the competing hypothesis that the fusion gene is subject to X-inactivation is rejected (P = 0.007, < 0.00001, and < 0.00001 for SEER cases, published cases, and their combination, respectively). CONCLUSIONS: Therefore, the authors found a statistical association between the female predominance observed in ASPS and female possession of an extra X-chromosome/noninactivation of the ASPS X;autosome translocation fusion gene.

T-cell lymphoma in HIV-infected patients.

Linkage of AIDS and cancer registries has indicated an increase in T-cell lymphomas among individuals infected with the HIV. The characteristics of T-cell versus B-cell lymphoma in HIV-infected patients are not well described. Retrospectively, 11 cases of T-cell lymphoma were identified from the AIDS-Lymphoma Registry at the University of Southern California. These patients were compared with 418 consecutive HIV-seropositive patients with B-cell lymphoma diagnosed and treated within the same time period. T-cell lymphomas comprised 3% of all AIDS lymphomas. Pathologic types included peripheral T-cell lymphoma in 5; anaplastic large cell lymphoma in 3; and angioimmunoblastic, enteropathy type, and human T-cell lymphotropic virus-I-related adult T-cell lymphoma/leukemia in 1 case each. No differences in demographic characteristics, history of prior opportunistic infection, or immunologic characteristics were observed between T-cell and B-cell cases. Extranodal involvement of the skin (36% vs. 2%, P < 0.001) and bone marrow (45% vs. 15%, P = 0.019) was significantly more common in T-cell lymphomas. The median survival of patients with T-cell lymphomas was not significantly different from that of B-cell lymphoma patients (10.6 vs. 6.6 months, P = 0.13). T-cell lymphomas in HIV-infected patients represent a spectrum of pathologic types. T-cell lymphomas differ from B-cell cases in terms of a higher propensity for skin and bone marrow involvement. The median survival of patients with T-cell lymphoma is comparable to that of patients with B-cell AIDS-related lymphoma.

Systemic mastocytosis with associated clonal hematological non-mast-cell lineage disease: analysis of clinicopathologic features and activating c-kit mutations.

The majority of patients with systemic mastocytosis with associated clonal, hematological non-mast cell lineage disease (SM-AHNMD) have a myeloid stem cell malignancy including myelodysplastic syndromes (MDS), myelodysplastic/myeloproliferative disorders, acute myeloid leukemia (AML), or chronic myeloproliferative disease. The clinicopathologic features of SM-AHNMD have not been fully characterized. We describe seven cases of this entity: 3 with MDS, 3 with AML, and 1 with chronic myelomonocytic leukemia. In the majority of cases, SM was diagnosed concurrently with the myeloid malignancy and aberrant mast cell morphology was observed. The commonly described c-kit enzymatic site mutation Asp816Val was detected only in 2 cases, while 3 patients carried the Asp816His mutation. Among the 3 cases with AML, 2 patients carried the translocation t(8;21). On the basis of our results and other reported cases, there appears to be a specific association between SM and AML with t(8;21). Concurrent occurrence of SM may define a subset of patients with de novo AML and other myeloid malignancies who have an adverse prognosis. As clinically effective tyrosine kinase inhibitors that inhibit enzymatic-type c-kit mutations are being developed, detection of mast cell proliferation associated with myeloid malignancy may have important therapeutic implications.