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Abstract Background In a recent post hoc analysis of multinational clinical trial data, dupilumab treatment for patients with moderate or severe atopic dermatitis (AD) reduced all‐cause and AD‐related hospitalisations. Objectives We studied the impact of dupilumab on health care resource utilisation (HCRU) and AD medication by comparing use during the 6 months either side of starting dupilumab (index) in a real‐world setting. Methods This observational, retrospective, cohort study used Japanese hospital claims data (1 April 2018 to 28 February 2019). A total of 357 patients (mean [range] age 45 [15–92] years; 65.5% male) with ≥1 AD diagnosis and ≥1 dupilumab prescription were included. Outcome variables included AD treatments and HCRU during the 6 months pre‐ and post‐index. Results The number of all‐cause hospitalisations decreased by 43.1% (from 51 in the 6 months before to 29 in the 6 months after dupilumab initiation), with a 96.0% reduction in skin/subcutaneous tissue disease‐related hospitalisations (25 to 1). Use of nonsteroidal systemic immunosuppressants, phototherapy and systemic corticosteroids decreased (by 59.8%, 59.5% and 30.6%, respectively) after dupilumab initiation. At 180 days after dupilumab initiation, 86.8% of patients were still taking dupilumab. Conclusions Overall, these results suggest that dupilumab can reduce skin/soft tissue‐related hospitalisations and use of various other AD medications in a real‐world setting.

Abstract Data science health research promises tremendous benefits for African populations, but its implementation is fraught with substantial ethical governance risks that could thwart the delivery of these anticipated benefits. We discuss emerging efforts to build ethical governance frameworks for data science health research in Africa and the opportunities to advance these through investments by African governments and institutions, international funding organizations and collaborations for research and capacity development.

Objectives: Extramammary Paget’s disease (EMPD) is a neoplastic skin disease of unknown etiology. EMPD is frequently associated with forkhead box A1 (FOXA1) expression, which correlates with the expression of estrogen receptor alpha (ER). FOXA1 regulates the transcriptional activity of ER and may function cooperatively in the tumorigenesis of breast cancer. Methods: We performed immunohistochemical staining for FOXA1 and ER using tissue samples from 16 patients with EMPD. Results: The nuclei of Paget cells isolated from each of the 16 patients with EMPD (100%) were strongly FOXA1-positive, and the FOXA1 staining intensity was similar across all samples. ER staining was detected in the nuclei of Paget cells originating from seven patients with EMPD (44%), and the ER staining intensity varied between these patients. Conclusions: In the present study, we confirmed that EMPD was frequently associated with FOXA1 expression. However, ER expression varied between patients and did not always coincide with FOXA1 expression. No clear relationship was observed between ER expression, the intensity of ER staining, or EMPD metastasis and prognosis. However, the results indicate that hormone-dependent cancer therapy may be effective in patients with ER-positive EMPD.

Abstract The extravillous trophoblast cell lineage is a key feature of placentation and successful pregnancy. Knowledge of transcriptional regulation driving extravillous trophoblast cell development is limited. Here, we map the transcriptome and epigenome landscape as well as chromatin interactions of human trophoblast stem cells and their transition into extravillous trophoblast cells. We show that integrating chromatin accessibility, long-range chromatin interactions, transcriptomic, and transcription factor binding motif enrichment enables identification of transcription factors and regulatory mechanisms critical for extravillous trophoblast cell development. We elucidate functional roles for TFAP2C, SNAI1, and EPAS1 in the regulation of extravillous trophoblast cell development. EPAS1 is identified as an upstream regulator of key extravillous trophoblast cell transcription factors, including ASCL2 and SNAI1 and together with its target genes, is linked to pregnancy loss and birth weight. Collectively, we reveal activation of a dynamic regulatory network and provide a framework for understanding extravillous trophoblast cell specification in trophoblast cell lineage development and human placentation.

Abstract Background The transferrin receptor (TfR) encoded by TFRC gene is the main cellular iron importer. TfR is highly expressed in many cancers and is expected to be a promising new target for cancer therapy; however, its role in nasopharyngeal carcinoma (NPC) remains unknown. Methods The TfR levels were investigated in NPC tissues and cell lines using immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. Knockdown of TFRC using two siRNA to investigate the effects on intracellular iron level and biological functions, including proliferation by CKK-8 assay, colony formation, cell apoptosis and cell cycle by flow cytometry, migration and invasion, and tumor growth in vivo by nude mouse xenografts. RNA sequencing was performed to find possible mechanism after TFRC knockdown on NPC cells and further verified by western blotting. Results TfR was overexpressed in NPC cell lines and tissues. Knockdown of TFRC inhibited cell proliferation concomitant with increased apoptosis and cell cycle arrest, and it decreased intracellular iron, colony formation, migration, invasion, and epithelial-mesenchymal transition in HK1-EBV cells. Western blotting showed that TFRC knockdown suppressed the levels of the iron storage protein FTH1, anti-apoptotic marker BCL-xL, and epithelial-mesenchymal transition markers. We confirmed in vivo that TFRC knockdown also inhibited NPC tumor growth and decreased Ki67 expression in tumor tissues of nude mouse xenografts. RNA sequencing and western blotting revealed that TFRC silencing inhibited the PI3K/Akt/mTOR signaling pathway. Conclusions These results indicated that TfR was overexpressed in NPC, and TFRC knockdown inhibited NPC progression by suppressing the PI3K/Akt/mTOR signaling pathway. Thus, TfR may serve as a novel biomarker and therapeutic target for NPC.

This study proposes a novel approach that utilizes Convolutional Neural Networks (CNNs) and Support Vector Machines (SVMs) to tackle a critical challenge: detecting defects in wrapped film products. With their delicate and reflective film wound around a core material, these products present formidable hurdles for conventional visual inspection systems. The complex task of identifying defects, such as unwound or protruding areas, remains a daunting endeavor. Despite the power of commercial image recognition systems, they struggle to capture anomalies within wrap film products. Our research methodology achieved a 90% defect detection accuracy, establishing its practical significance compared with existing methods. We introduce a pioneering methodology centered on covariance vectors extracted from latent variables, a product of a Variational Autoencoder (VAE). These covariance vectors serve as feature vectors for training a specialized One-Class SVM (OCSVM), a key component of our approach. Unlike conventional practices, our OCSVM does not require images containing defects for training; it uses defect-free images, thus circumventing the challenge of acquiring sufficient defect samples. We compare our methodology against feature vectors derived from the fully connected layers of established CNN models, AlexNet and VGG19, offering a comprehensive benchmarking perspective. Our research represents a significant advancement in defect detection technology. By harnessing the latent variable covariance vectors from a VAE encoder, our approach provides a unique solution to the challenges faced by commercial image recognition systems. These advancements in our study have the potential to revolutionize quality control mechanisms within manufacturing industries, offering a brighter future for product integrity and customer satisfaction.

Chronic constipation is a common gastrointestinal disorder, and its management is critical. However, it is extremely difficult to assess its subjective symptoms when patients are unable to report them due to cognitive or physical disabilities, especially in cases of patients with incurable geriatric, pediatric, palliative, psychiatric, or neurological diseases. We had previously established a protocol for observing and assessing rectal fecal retention using ultrasonography and for classifying cases into three categories based on the rectal findings: no fecal retention, fecal retention without hard stools, and fecal retention with hard stools. However, although the detection of rectal fecal retention using ultrasonography would be expected to lead to better therapeutic management, there is no standard algorithm for selecting specific treatments and defecation care options based on ultrasonographic findings. Therefore, we organized an expert consensus meeting of multidisciplinary professionals to develop such an algorithm based on rectal ultrasonography findings for patients with constipation in both residential and hospital settings.