Deep learning at the edge enables real-time streaming ptychographic imaging.

Coherent imaging techniques provide an unparalleled multi-scale view of materials across scientific and technological fields, from structural materials to quantum devices, from integrated circuits to biological cells. Driven by the construction of brighter sources and high-rate detectors, coherent imaging methods like ptychography are poised to revolutionize nanoscale materials characterization. However, these advancements are accompanied by significant increase in data and compute needs, which precludes real-time imaging, feedback and decision-making capabilities with conventional approaches. Here, we demonstrate a workflow that leverages artificial intelligence at the edge and high-performance computing to enable real-time inversion on X-ray ptychography data streamed directly from a detector at up to 2 kHz. The proposed AI-enabled workflow eliminates the oversampling constraints, allowing low-dose imaging using orders of magnitude less data than required by traditional methods.

Long-term safety and efficacy of filgotinib treatment for rheumatoid arthritis in Japanese patients naïve to MTX treatment (FINCH 3).

OBJECTIVES: To evaluate the long-term safety and efficacy of filgotinib (FIL) for Japanese patients with rheumatoid arthritis (RA) and limited/no prior methotrexate (MTX) exposure. We present a Japanese population subanalysis of a global randomised-controlled trial at Week 52 and interim long-term extension (LTE) to Week 48 through June 2020. METHODS: Patients were randomised to FIL 200 mg plus MTX, FIL 100 mg plus MTX, FIL 200 mg, or MTX for 52 weeks. At completion, eligible patients could enrol in the LTE. Those receiving FIL continued; those receiving MTX were rerandomised (blinded) to FIL 200 or 100 mg upon discontinuation of MTX. After a 4-week washout period, MTX could be re-added. RESULTS: Adverse event rates at Week 52 and in the LTE to Week 48 were comparable across treatment groups. Week 52 American College of Rheumatology 20% improvement (ACR20) rates were 83% (19/23), 82% (9/11), 75% (9/12), and 76% (19/25) for FIL 200 mg plus MTX, FIL 100 mg plus MTX, FIL 200 mg, and MTX, respectively. Through LTE Week 48, ACR20 rates were maintained. CONCLUSIONS: In the 56 Japanese patients treated with FIL, efficacy was maintained through Week 52 and beyond, with no increases in the incidence of adverse events.

Primary ALK-Negative TP63-Rearranged Anaplastic Large Cell Lymphoma in the Bladder: Potential for Misdiagnosis.

A 76-year-old gentleman presented with persistent lower urinary tract symptoms. Multiple biopsies, radiological correlation and ancillary studies were required to achieve a diagnosis. The main differential diagnoses lies between urothelial carcinoma and anaplastic large cell lymphoma (ALCL), both of which are known to be positive for p63 and GATA3. An accurate diagnosis is crucial as the management is significantly different. To avoid misdiagnosis a comprehensive immunohistochemistry panel is necessary. Primary bladder lymphomas are rare. Our case represents the first case of primary ALK-negative TP63-rearranged ALCL. We reviewed the literature and discussed the potential pitfalls for misdiagnosis.

Relationships between Size Distribution, Morphological Characteristics, and Viscosity of Cellulose Nanofibril Dispersions.

Rheological parameters of cellulose nanofibril dispersions (CNF) are relevant and commonly used as quality control for producing of this type of material. These parameters are affected by morphological features and size distribution of the nanofibrils. Understanding the effect of size distribution is essential for analyzing the rheological properties, viscosity control, performance of CNFs, and potential dispersion applications. This study aims at comprehending how the morphological characteristics of the CNFs and their size distribution affect the rheological behavior of dispersions. The CNF dispersions were fractionated by size, obtaining six fractions of each, which were analyzed for their morphology and rheology (viscosity, intrinsic viscosity). In the dilute region, the viscosity and intrinsic viscosity behavior of CNF dispersions are linear concerning the size distribution present in the dispersion. In the semi-dilute region, the size of the fibrils and the fiber aggregates have a relevant effect on the viscosity behavior of CNF dispersions, which are satisfactorily related (R2 = 0.997) using the rule of logarithmic additivity of the dispersion viscosities of size fractions.

Scalable and accurate multi-GPU-based image reconstruction of large-scale ptychography data.

While the advances in synchrotron light sources, together with the development of focusing optics and detectors, allow nanoscale ptychographic imaging of materials and biological specimens, the corresponding experiments can yield terabyte-scale volumes of data that can impose a heavy burden on the computing platform. Although graphics processing units (GPUs) provide high performance for such large-scale ptychography datasets, a single GPU is typically insufficient for analysis and reconstruction. Several works have considered leveraging multiple GPUs to accelerate the ptychographic reconstruction. However, most of these works utilize only the Message Passing Interface to handle the communications between GPUs. This approach poses inefficiency for a hardware configuration that has multiple GPUs in a single node, especially while reconstructing a single large projection, since it provides no optimizations to handle the heterogeneous GPU interconnections containing both low-speed (e.g., PCIe) and high-speed links (e.g., NVLink). In this paper, we provide an optimized intranode multi-GPU implementation that can efficiently solve large-scale ptychographic reconstruction problems. We focus on the maximum likelihood reconstruction problem using a conjugate gradient (CG) method for the solution and propose a novel hybrid parallelization model to address the performance bottlenecks in the CG solver. Accordingly, we have developed a tool, called PtyGer (Ptychographic GPU(multiple)-based reconstruction), implementing our hybrid parallelization model design. A comprehensive evaluation verifies that PtyGer can fully preserve the original algorithm's accuracy while achieving outstanding intranode GPU scalability.

Efficacy and safety of filgotinib alone and in combination with methotrexate in Japanese patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: Subpopulation analyses of 24-week data of a global phase 3 study (FINCH 3).

OBJECTIVES: To evaluate the efficacy and safety of filgotinib for Japanese patients with rheumatoid arthritis (RA) and limited or no prior methotrexate (MTX) exposure. METHODS: Data up to 24 weeks were analysed for 71 Japanese patients from a 52-week global Phase 3 study. Patients with RA and limited or no prior MTX exposure were randomised in a 2:1:1:2 ratio to filgotinib 200 mg plus MTX, filgotinib 100 mg plus MTX, filgotinib 200 mg, or MTX. Maximum MTX dose was 15 mg/week. Primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at Week 24. RESULTS: Week 24 ACR20 rates in Japanese patients were 82.6%, 90.9%, 83.3%, and 80.0% for filgotinib 200 mg plus MTX, filgotinib 100 mg plus MTX, filgotinib 200 mg, and MTX, respectively. Greater ACR20 rates with filgotinib vs MTX occurred at Week 2. Greater proportions receiving filgotinib vs MTX achieved DAS28-CRP <2.6 at Weeks 12 and 24. Adverse event rates were comparable across treatments and between the Japanese and overall populations. CONCLUSIONS: While Week 24 ACR20 rates were similar, filgotinib provided faster responses and higher remission rates vs MTX. In Japanese patients with RA and limited or no prior MTX exposure, filgotinib was generally well tolerated.

Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: the phase 3, randomised controlled FINCH 3 trial.

OBJECTIVES: To investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure. METHODS: This 52-week, phase 3, multicentre, double-blind clinical trial (NCT02886728) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24. RESULTS: The primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX (p<0.001). A significantly greater proportion treated with FIL100+ MTX compared with MTX achieved an ACR20 response (80%, p=0.017) at week 24. Significant improvement in Health Assessment Questionnaire-Disability Index was seen at week 24; least-squares mean change from baseline was -1.0 and -0.94 with FIL200+MTX and FIL100+MTX, respectively, versus -0.81 with MTX (p<0.001, p=0.008, respectively). Significantly higher proportions receiving FIL200+MTX (54%) and FIL100+MTX (43%) achieved DAS28(CRP) <2.6 versus MTX (29%) (p<0.001 for both) at week 24. Hierarchical testing stopped for comparison of ACR20 for FIL200 monotherapy (78%) versus MTX (71%) at week 24 (p=0.058). Adverse event rates through week 52 were comparable between all treatments. CONCLUSIONS: FIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX.

Iron Pill-Induced Gastritis in the Paediatric Population.

Iron is the most common trace mineral in the body. The effects of iatrogenic iron pill-induced gastritis (IPIG) at therapeutic levels are underreported and underappreciated in the paediatric population. Herein, we report a case of an 11-year-old boy presenting with increasing epigastric pain and refusing oral intake secondary to iron pill tablets. We report only the second confirmed case of a paediatric patient with IPIG in the peer-reviewed literature.

HPV-Related Multiphenotypic Sinonasal Carcinoma: A Unique Case.

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC), originally known as HPV-related carcinoma with adenoid cystic carcinoma-like features, is a recently described neoplasm that presents only in the sinonasal tract, displays features of both a surface-derived carcinoma and a salivary gland carcinoma, and is associated with high-risk HPV, specifically HPV type 33. Majority of the cases display high-grade histologic features, but HMSC paradoxically behaves in a relatively indolent fashion. Distinguishing HMSC from other histologic mimickers is essential as the management and prognosis are significantly different. In this article, we present a unique case of HMSC and review the literature.

Joint ptycho-tomography reconstruction through alternating direction method of multipliers.

We present the extension of ptychography for three-dimensional object reconstruction in a tomography setting. We describe the alternating direction method of multipliers (ADMM) as a generic reconstruction framework to efficiently solve the nonlinear optimization problem. In this framework, the ADMM breaks the joint reconstruction problem into two well-defined subproblems: ptychographic phase retrieval and tomographic reconstruction. In this paper, we use the gradient descent algorithm to solve both problems and demonstrate the efficiency of the proposed approach through numerical simulations. Further, we show that the proposed joint approach relaxes existing requirements for lateral probe overlap in conventional ptychography. Thus, it can allow more flexible data acquisition.

Cutaneous tumoural melanosis: a presentation of complete regression of cutaneous melanoma.

Partial regression is common in cutaneous melanoma; however, complete regression manifesting as tumoural melanosis is rare, conceptually challenging and under-reported. In this study we report on clinical, histological and molecular findings in four cases of completely regressed cutaneous melanoma with nodal or brain metastasis, followed by a comprehensive review of the literature. Our series included three women and one man with an average age of 60 years, and clinical presentation with hyper-pigmented cutaneous lesions. The main histological findings were expansile aggregates of melanophages with complete absence of malignant melanocytes on microscopic and immunohistochemical examination of the entire primary skin lesions, as well as substantial reduction in the number of junctional melanocytes in the overlying epidermis. NRAS mutant/BRAF wild type metastatic deposits were identified in three patients, with one patient having a BRAF V600E mutant metastatic tumour. Tumoural melanosis likely represents a partially effective immunological response to melanoma, with complete eradication of cutaneous disease and less effective systemic results. Patients with tumoural melanosis should be managed as potential completely regressed cutaneous melanoma, with comprehensive physical examination, imaging work up and close follow up.

Histological Features of Flagellate Erythema.

Flagellate erythema is a distinctive eruption characterized by "whip-like" linear or curvilinear streaks and plaques, occurring mainly on the trunk. It has classically been described in 2 disparate clinical settings: chemotherapy with bleomycin and ingestion of mushrooms (most commonly Shiitake mushrooms). Most of the literature comprises single case reports, often with minimal histological description of rather nonspecific features. We describe in detail the histological features of 3 cases of flagellate erythema (2 related to bleomycin therapy and one related to ingestion of mushrooms) and review the findings described in the literature to define the spectrum of histological changes encountered in this eruption. Our 3 cases showed mild epidermal changes, with spongiosis and variable interface inflammation. All 3 showed a relatively prominent dermal lymphohistiocytic infiltrate, with features suggestive of a lymphocytic vasculopathy extending to at least the mid-reticular dermis. Eosinophils were a prominent component of the inflammatory infiltrate in 2 cases. Our review of the literature identified a total of 45 publications, representing reports of 46 patients, containing histological information. As well as bleomycin- and mushroom-related cases, similar eruptions have been reported in the context of connective tissue disease and other drugs. Although cases related to connective tissue disease show features of the underlying condition, cases secondary to drugs or mushrooms predominantly show features compatible with common patterns of exanthematous/morbilliform drug reaction. In particular, subtle spongiosis and/or interface dermatitis combined with a dermal lymphocytic infiltrate that includes increased numbers of eosinophils is a common finding. Features of a lymphocytic vasculopathy may be seen in a subset of these cases.

Rotation-as-fast-axis scanning-probe x-ray tomography: the importance of angular diversity for fly-scan modes.

We investigate the effects of angular diversity on image-reconstruction quality of scanning-probe x-ray tomography for both fly- and step-mode data collection. We propose probe-coverage maps as a tool for both visualizing and quantifying the distribution of probe interactions with the object. We show that data sampling with more angular diversity yields better tomographic image reconstruction as long as it does not come at the cost of not covering some voxels in the object. Therefore, for fly-mode data collection, rotation-as-fast-axis (RAFA) trajectories are superior to raster or other non-RAFA trajectories because they allow for the increasing of angular diversity without sacrificing spatial coverage uniformity. In contrast, for step-mode data collection and a fixed measurement budget, increasing angular diversity can come at the cost of not covering some voxels, and may not be desired. This study has implications for how scanning-probe microscopes should be collecting data in order to make the most of limited resources.

Atypical Features Resembling Poorly Differentiated Thyroid Carcinoma Presenting Entirely within a Follicular Adenoma.

Poorly differentiated thyroid carcinoma (PDTC) is rare and is usually widely invasive at presentation. Here we present an unusual case with a component meeting diagnostic criteria for PDTC by Turin consensus proposal arising within a follicular adenoma. A 44-year-old female was found to have an incidental right thyroid nodule that was suggestive of follicular neoplasm on FNA. Histological examination of hemithyroidectomy revealed an 11 mm focus with insular growth pattern, alteration in cell morphology, and high mitotic count meeting criteria for PDTC. In addition there were several regions showing trabecular architecture with increased mitotic activity but not meeting criteria for PDTC. The literature for such cases is sparse but suggests much better prognosis than conventional invasive PDTC, although a biological potential for aggressive behaviour may be possible.