A deep learning diagnostic platform for diffuse large B-cell lymphoma with high accuracy across multiple hospitals

Diagnostic histopathology is a gold standard for diagnosing hematopoietic malignancies. Pathologic diagnosis requires labor-intensive reading of a large number of tissue slides with high diagnostic accuracy equal or close to 100 percent to guide treatment options, but this requirement is difficult to meet. Although artificial intelligence (AI) helps to reduce the labor of reading pathologic slides, diagnostic accuracy has not reached a clinically usable level. Establishment of an AI model often demands big datasets and an ability to handle large variations in sample preparation and image collection. Here, we establish a highly accurate deep learning platform, consisting of multiple convolutional neural networks, to classify pathologic images by using smaller datasets. We analyze human diffuse large B-cell lymphoma (DLBCL) and non-DLBCL pathologic images from three hospitals separately using AI models, and obtain a diagnostic rate of close to 100 percent (100% for hospital A, 99.71% for hospital B and 100% for hospital C). The technical variability introduced by slide preparation and image collection reduces AI model performance in cross-hospital tests, but the 100% diagnostic accuracy is maintained after its elimination. It is now clinically practical to utilize deep learning models for diagnosis of DLBCL and ultimately other human hematopoietic malignancies

The Association between Sampling and Survival in Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy and Pancreaticoduodenectomy

Adequate sampling is essential to an accurate pathologic evaluation of pancreatectomy specimens resected for pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT). However, limited data are available for the association between the sampling and survival in these patients. We examined the association of the entire submission of the tumor (ESOT) and the entire submission of the pancreas (ESOP) with disease-free survival (DFS) and overall survival (OS), as well as their correlations with clinicopathologic features, for 627 patients with PDAC who received NAT and pancreaticoduodenectomy. We demonstrated that both ESOT and ESOP were associated with lower ypT, less frequent perineural invasion, and better tumor response (p \u3c 0.05). ESOP was also associated with a smaller tumor size (p \u3c 0.001), more lymph nodes (p \u3c 0.001), a lower ypN stage (p \u3c 0.001), better differentiation (p = 0.02), and less frequent lymphovascular invasion (p = 0.009). However, since ESOP and ESOT were primarily conducted for cases with no grossly identifiable tumor or minimal residual carcinoma in initial sections, potential bias cannot be excluded. Both ESOT and ESOP were associated with less frequent recurrence/metastasis and better DFS and OS (p \u3c 0.05) in the overall study population. ESOP was associated with better DFS and better OS in patients with ypT0/ypT1 or ypN0 tumors and better OS in patients with complete or near-complete response (p \u3c 0.05). ESOT was associated with better OS in patients with ypT0/ypT1 or ypN0 tumors (p \u3c 0.05). Both ESOT and ESOP were independent prognostic factors for OS according to multivariate survival analyses. Therefore, accurate pathologic evaluation using ESOP and ESOT is associated with the prognosis in PDAC patients with complete or near-complete pathologic response and ypT0/ypT1 tumor after NAT

Control and Characterization of Individual Grains and Grain Boundaries in Graphene Grown by Chemical Vapor Deposition

The strong interest in graphene has motivated the scalable production of high quality graphene and graphene devices. Since large-scale graphene films synthesized to date are typically polycrystalline, it is important to characterize and control grain boundaries, generally believed to degrade graphene quality. Here we study single-crystal graphene grains synthesized by ambient CVD on polycrystalline Cu, and show how individual boundaries between coalescing grains affect graphene's electronic properties. The graphene grains show no definite epitaxial relationship with the Cu substrate, and can cross Cu grain boundaries. The edges of these grains are found to be predominantly parallel to zigzag directions. We show that grain boundaries give a significant Raman "D" peak, impede electrical transport, and induce prominent weak localization indicative of intervalley scattering in graphene. Finally, we demonstrate an approach using pre-patterned growth seeds to control graphene nucleation, opening a route towards scalable fabrication of single-crystal graphene devices without grain boundaries.Comment: New version with additional data. Accepted by Nature Material

Rectal Melanoma: Rare Cancer with Grave Prognosis

Malignant melanoma of the rectum is an exceedingly rare type of cancer with an aggressive presentation, comprising up to 4% of all anorectal cancers. Presentation of this cancer tends to occur in individuals in their late 80s, with nonspecific symptoms such as anal pain or rectal bleeding. Diagnosing rectal melanoma, especially in early stages, is difficult due to its amelanotic presentation and lack of pigmentation, which results in poor remission rates and prognosis. Furthermore, surgical treatment is difficult as these types of malignant melanomas tend to spread along submucosal planes; thus, complete resections are impractical, especially if caught later. In this case report, we present the radiological and pathological features as seen in a 76-year-old man diagnosed with rectal melanoma. Based on his presentation of a heterogeneous bulky anorectal mass with extensive local invasion, initial impressions were colorectal carcinoma. However, surgical pathology found the mass to be a c-KIT+ melanoma, with positive SOX10, Melan-A, HMB-45, and CD117 biomarkers. While the patient was treated with imatinib, the melanoma was too widespread and aggressive, leading to progression and ultimately death

Diagnosis and differential diagnosis of hepatic graft versus host disease (GVHD).

Graft versus host disease (GVHD) is a common complication following allogeneic hematopoietic cell transplantation (HCT) that typically manifests as injury to the skin, gastrointestinal mucosa, and liver. In some cases, hepatic GVHD may be histologically indistinguishable from other disorders such as infection and drug-induced liver injury (DILI). Additionally, clinical signs and symptoms are frequently confounded by the superimposed effects of pretransplant chemoradiotherapy, immunotherapy (IT) (targeted to the underlying malignancy), GVHD prophylaxis, and infection. Thus, careful attention to and correlation with clinical findings, laboratory values, and histologic features is essential for diagnosis. This review, aimed at the practicing pathologist, will discuss current clinical and histologic criteria for GVHD, the approach to diagnosis of hepatic GVHD, and features helpful for distinguishing it from other entities in the differential diagnosis

Release and elementary mechanisms of nitric oxide in hair cells

The enzyme nitric oxide (NO) synthase, that produces the signaling molecule NO, has been identified in several cell types in the inner ear. However, it is unclear whether a measurable quantity of NO is released in the inner ear to confer specific functions. Indeed, the functional significance of NO and the elementary cellular mechanism thereof are most uncertain. Here, we demonstrate that the sensory epithelia of the frog saccule release NO and explore its release mechanisms by using self-referencing NO-selective electrodes. Additionally, we investigated the functional effects of NO on electrical properties of hair cells and determined their underlying cellular mechanism. We show detectable amounts of NO are released by hair cells (>50 nM). Furthermore, a hair-cell efferent modulator acetylcholine produces at least a threefold increase in NO release. NO not only attenuated the baseline membrane oscillations but it also increased the magnitude of current required to generate the characteristic membrane potential oscillations. This resulted in a rightward shift in the frequency-current relationship and altered the excitability of hair cells. Our data suggest that these effects ensue because NO reduces whole cell Ca(2+) current and drastically decreases the open probability of single-channel events of the L-type and non L-type Ca(2+) channels in hair cells, an effect that is mediated through direct nitrosylation of the channel and activation of protein kinase G. Finally, NO increases the magnitude of Ca(2+)-activated K(+) currents via direct NO nitrosylation. We conclude that NO-mediated inhibition serves as a component of efferent nerve modulation of hair cells

Characteristics of karst groundwater flow systems of typical faulted basins in Yimeng Mountain area: A case study of Laiwu Basin

China Geological Survey has organized and implemented 1:50 000 standard map hydrogeological survey with an area of more than 40000 square kilometers in Yimeng Mountain area. And it carried out a large amount of water prospecting and well drilling demonstration work in villages and towns with serious water shortage, obtained rich geological data and gained a new understanding of groundwater flow systems. Under the influence of Mesozoic and Cenozoic structures, the faults and folds, extensional detachment and magmatic intrusion occurred in Yimeng Mountain area, formed a series of graben-semi graben basins characterized by overlapping in the south and faulting in the north, and finally formed today's typical "basin-mountain" karst hydrogeological structure and the relatively independent karst groundwater system, which taking basin as unit. In order to study the development characteristics of groundwater flow system in Yimeng Mountain area, Laiwu Basin was selected as a typical study area. On the basis of the field geological survey, through comprehensively analyze the geomorphic units, the three-dimensional spatial distribution of water bearing rock groups, groundwater level, hydrochemistry, and water isotope results on the north and south sides of the basin, this paper comprehensively discusses the characteristics of multistage karst groundwater flow systems with typical "basin-mountain" structure in Yimeng Mountain area. The results show that, the karst groundwater in Laiwu Basin presents a "centripetal" runoff from the outer periphery to the center of the basin. Affected by human activities, controlled by geological structure and aquifer distribution, the characteristics of groundwater flow systems between the north and south sides of the basin are different. There are mainly intermediate and local groundwater flow systems in the south of the basin, while a single local groundwater flow system is developed in the north of the basin, however, it occupies nearly 1/2 of the groundwater sources that have been explored and demonstrated. In addition, it is found that at the lowest erosion base level of Dawen River, the voids separated by regional detachment structure and hydrothermal mixing, together with rock layer, interlayer fissures and bedding dissolution voids, form a three-dimensional karst groundwater network, which influence the circulation path and depth of karst water. Guided by this understanding, the completion rate of exploration production combined wells has reached 86%, which strengthens the combination of theory and practice of groundwater flow system theory in hydrogeological work in bedrock mountainous areas in North China

BCG as an Innovative Option for HCC Treatment: Repurposing and Mechanistic Insights.

This study investigates Bacillus Calmette-Guérin (BCG) as a potential treatment for hepatocellular carcinoma (HCC), a condition often associated with unfavorable treatment outcomes. Exploiting BCGs recognized immune-boosting properties, preclinical trials are conducted using HCC mice, with a single subcutaneous dose of BCG administered post-tumor formation. Results indicate that BCG treatment effectively diminishes tumor burden and extends survival in both male and female HCC mice. Positive influences on hepatic fibrosis and metabolism are observed, leading to a reduction in lipid levels. Spatial analysis underscores BCGs tumor-specific effects, inducing the enrichment of metabolic pathways and inhibiting various cancer-related pathways. Furthermore, BCG promotes immune cell infiltration, including CD4+, CD8+ T cells, and M1 macrophages, in both v-akt murine thymoma viral oncogene homolog 1(AKT)/neutoblastoma RAS viral oncogene homolog (RAS) and β-catenin positive HCC models. Interestingly, blocking T cells, trained immunity, and Interferon-γ (IFN-γ) function reverses BCGs anti-HCC effects. In conclusion, BCG emerges as a promising treatment option for HCC, characterized by a favorable safety profile and efficacy in inhibiting fibrosis, improving metabolism, and engaging both trained immunity and T cells in therapeutic mechanisms