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Primary diffuse large B-cell lymphoma (DLBCL) of the female genital tract is a rare case. It is hard to diagnose DLBCL of the uterine cervix before surgery because it is often misdiagnosed as cervical myoma or cervical squamous cell carcinoma. Here, we report a case of cervical DLBCL misdiagnosed as a cervical myoma. A 48-year-old premenopausal woman was referred to the gynecology department due to abnormal uterine bleeding with a normal Papanicolaou smear. The initial diagnosis according to ultrasound and computed tomography was a cervical myoma. She had undergone a hysterectomy with bilateral salpingectomy. The final diagnosis was cervical DLBCL and she was referred to the department of hematology for treatment with Rituximab combined chemotherapy. After six courses of chemotherapy, complete remission was reached. At a 2-year follow-up, the patient is alive without interval change.

We assessed the diagnostic accuracy of the age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) for predicting mortality and disease severity in pediatric patients with suspected or confirmed infection. We conducted a systematic search of PubMed, EMBASE, the Cochrane Library, and Web of Science. Eleven studies with a total of 172,569 patients were included in the meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio of the age-adjusted qSOFA for predicting mortality and disease severity were 0.69 (95% confidence interval [CI] 0.53–0.81), 0.71 (95% CI 0.36–0.91), and 6.57 (95% CI 4.46–9.67), respectively. The area under the summary receiver-operating characteristic curve was 0.733. The pooled sensitivity and specificity for predicting mortality were 0.73 (95% CI 0.66–0.79) and 0.63 (95% CI 0.21–0.92), respectively. The pooled sensitivity and specificity for predicting disease severity were 0.73 (95% CI 0.21–0.97) and 0.72 (95% CI 0.11–0.98), respectively. The performance of the age-adjusted qSOFA for predicting mortality and disease severity was better in emergency department patients than in intensive care unit patients. The age-adjusted qSOFA has moderate predictive power and can help in rapidly identifying at-risk children, but its utility may be limited by its insufficient sensitivity.

Monocyte/macrophage lineage cells are highly plastic and can differentiate into various cells under different environmental stimuli. Bone-resorbing osteoclasts are derived from the monocyte/macrophage lineage in response to receptor activator of NF-κB ligand (RANKL). However, the epigenetic signature contributing to the fate commitment of monocyte/macrophage lineage differentiation into human osteoclasts is largely unknown. In this study, we identified RANKL-responsive human osteoclast-specific superenhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) by integrating data obtained from ChIP-seq, ATAC-seq, nuclear RNA-seq and PRO-seq analyses. RANKL induced the formation of 200 SEs, which are large clusters of enhancers, while suppressing 148 SEs in macrophages. RANKL-responsive SEs were strongly correlated with genes in the osteoclastogenic program and were selectively increased in human osteoclasts but marginally presented in osteoblasts, CD4+ T cells, and CD34+ cells. In addition to the major transcription factors identified in osteoclasts, we found that BATF binding motifs were highly enriched in RANKL-responsive SEs. The depletion of BATF1/3 inhibited RANKL-induced osteoclast differentiation. Furthermore, we found increased chromatin accessibility in SE regions, where RNA polymerase II was significantly recruited to induce the extragenic transcription of SE-eRNAs, in human osteoclasts. Knocking down SE-eRNAs in the vicinity of the NFATc1 gene diminished the expression of NFATc1, a major regulator of osteoclasts, and osteoclast differentiation. Inhibiting BET proteins suppressed the formation of some RANKL-responsive SEs and NFATc1-associated SEs, and the expression of SE-eRNA:NFATc1. Moreover, SE-eRNA:NFATc1 was highly expressed in the synovial macrophages of rheumatoid arthritis patients exhibiting high-osteoclastogenic potential. Our genome-wide analysis revealed RANKL-inducible SEs and SE-eRNAs as osteoclast-specific signatures, which may contribute to the development of osteoclast-specific therapeutic interventions.

We compared the clinical course of pregnant women with coronavirus disease 2019 (COVID-19) before and after the emergence of the omicron variant and based on vaccination status. We retrospectively reviewed the electronic medical charts of 224 patients and 82 deliveries from November 1, 2020, to March 7, 2022; of these, 42% were diagnosed during the omicron dominance period. Disease severity and morbidity of COVID-19 were significantly decreased during the omicron era. The vaccination rates among the patients were higher after omicron emergence (31.9%) than before (6.9%). Overall, 4.1% and 25% of patients had severe symptoms, and 2.6% and 16.2% required oxygen therapy in the vaccination and non-vaccination groups, respectively. Overall, patients had a more favorable clinical course in the omicron era; moreover, vaccinated patients were better protected than non-vaccinated patients, indicating the importance of vaccination against COVID-19.

This study examines female–male differences in English writing outcomes for Taiwanese primary school learners enrolled in a Content and Language Integrated Learning (CLIL) program. Narrative and expository writing samples of 212 primary school students (Male = 103, Female = 109) in Taiwan were collected and scored using several measures including spelling accuracy, correct word sequences, lexical diversity, total t-units, and a holistic rubric for ideas. Students’ topic interest was also measured through a Likert-scale survey. The findings revealed differences between females and males and the two genres of writing. While there were statistical differences attributed to gender and topic interest variables for some writing measures, further analysis revealed that these effects were minimal in terms of practical significance. The paper raises questions about the relationship between female–male writing differences and CLIL and provides suggestions for future research to broaden our understanding and support diversity in the CLIL classroom.

Lexical stress plays a critical role in multisyllabic word reading in English. However, assignment of English lexical stress, which is neither fixed nor marked in writing, can pose significant challenges for English learners and has not been well-understood. The present study aims to fill the research gap by studying sensitivity to lexical stress cues and its contribution to their word reading performance among young English-language learners whose first language is Korean. The fundamental differences in prosodic systems between Korean and English provide theoretical significance of studying how bilingual children having no lexical stress in their first language process English lexical stress. This study focuses on two major cues to English lexical stress: morphological and orthographic cues. Findings revealed that the participants are sensitive to the two stress cues, with better performance with orthographic cues to stress assignment. However, no statistically significant correlations were found among variables on stress cue sensitivity with those on reading.

Osteoclasts are bone-resorbing cells that play an essential role in homeostatic bone remodeling and pathological bone erosion. Macrophage colony stimulating factor (M-CSF) is abundant in rheumatoid arthritis (RA). However, the role of M-CSF in arthritic bone erosion is not completely understood. Here, we show that M-CSF can promote osteoclastogenesis by triggering the proteolysis of c-FMS, a receptor for M-CSF, leading to the generation of FMS intracellular domain (FICD) fragments. Increased levels of FICD fragments positively regulated osteoclastogenesis but had no effect on inflammatory responses. Moreover, myeloid cell-specific FICD expression in mice resulted in significantly increased osteoclast-mediated bone resorption in an inflammatory arthritis model. The FICD formed a complex with DAP5, and the FICD/DAP5 axis promoted osteoclast differentiation by activating the MNK1/2/EIF4E pathway and enhancing NFATc1 protein expression. Moreover, targeting the MNK1/2 pathway diminished arthritic bone erosion. These results identified a novel role of c-FMS proteolysis in osteoclastogenesis and the pathogenesis of arthritic bone erosion.

Endoscopic photodynamic therapy (PDT) has attracted much attention as a minimally invasive, minimally toxic treatment. PDT can selectively destroy cancer cells by reactive oxygen generated through chemical reaction of photosensitizers that absorb incident light with a certain wavelength. However, the efficacy of PDT is limited due to shallow light penetration mainly caused by Rayleigh scattering in biological tissue. We previously demonstrated that the air bubbles temporarily induced by ultrasound (US) act as a Mie scattering medium, thus increasing light penetration, called US-assisted light penetration increase. For endoscopic applications of the proposed method, the endoscopic probe for US-assisted PDT should be developed; it should be as small as possible while being able to deliver laser for treatment and provide high acoustic energy for air bubble generation in the laser pathway. Satisfying those requirements is very challenging. In this paper, we report a recently developed endoscopic probe for US-assisted PDT that meets the requirements. The probe consists of two 3 MHz US transducers placed side by side and tilted at an angle of 25° and an optical fiber for laser delivery. The probe size was measured at 60.5 mm $\times \,\, 14$ mm $\times \,\,14$ mm suitable for endoscopic applications. In the experiment, it was shown that the probe could increase the laser intensity by 28%, compared to the laser only illumination. Even this increase is higher than the previous measurement using a commercial ring-shaped 1.1 MHz HIFU transducer with outer and inner diameters of 64 mm and 22.6 mm.

New bone anabolic agents for the effective treatment of bone metabolic diseases like osteoporosis are of high clinical demand. In the present study, we reveal the function of salt-inducible kinase 1 (SIK1) in regulating osteoblast differentiation. Gene knockdown of SIK1 but not of SIK2 or SIK3 expression in primary preosteoblasts increased osteoblast differentiation and bone matrix mineralization. SIK1 also regulated the proliferation of osteoblastic precursor cells in osteogenesis. This negative control of osteoblasts required the catalytic activity of SIK1. SIK1 phosphorylated CREB regulated transcription coactivator 1 (CRTC1), preventing CRTC1 from enhancing CREB transcriptional activity for the expression of osteogenic genes like Id1. Furthermore, SIK1 knockout (KO) mice had higher bone mass, osteoblast number, and bone formation rate versus littermate wild-type (WT) mice. Preosteoblasts from SIK1 KO mice showed more osteoblastogenic potential than did WT cells, whereas osteoclast generation among KO and WT precursors was indifferent. In addition, bone morphogenic protein 2 (BMP2) suppressed both SIK1 expression as well as SIK1 activity by protein kinase A (PKA)–dependent mechanisms to stimulate osteogenesis. Taken together, our results indicate that SIK1 is a key negative regulator of preosteoblast proliferation and osteoblast differentiation and that the repression of SIK1 is crucial for BMP2 signaling for osteogenesis. Therefore, we propose SIK1 to be a useful therapeutic target for the development of bone anabolic strategies.

Bone destruction induced by breast cancer metastasis causes severe complications, including death, in breast cancer patients. Communication between cancer cells and skeletal cells in metastatic bone microenvironments is a principal element that drives tumor progression and osteolysis. Tumor-derived factors play fundamental roles in this form of communication. To identify soluble factors released from cancer cells in bone metastasis, we established a highly bone-metastatic subline of MDA-MB-231 breast cancer cells. This subline (mtMDA) showed a markedly elevated ability to secrete S100A4 protein, which directly stimulated osteoclast formation via surface receptor RAGE. Recombinant S100A4 stimulated osteoclastogenesis in vitro and bone loss in vivo. Conditioned medium from mtMDA cells in which S100A4 was knocked down had a reduced ability to stimulate osteoclasts. Furthermore, the S100A4 knockdown cells elicited less bone destruction in mice than the control knockdown cells. In addition, administration of an anti-S100A4 monoclonal antibody (mAb) that we developed attenuated the stimulation of osteoclastogenesis and bone loss by mtMDA in mice. Taken together, our results suggest that S100A4 released from breast cancer cells is an important player in the osteolysis caused by breast cancer bone metastasis.

Photoacoustic (PA) imaging has attracted much attention as a new biomedical imaging modality due to its ultrasonic spatial resolution, optical contrast resolution, and deeper imaging depth than oth...

Despite a dramatic increase in Asian-White biracial individuals in the US, there is still a lack of research on this population. Using phenomenology, the purpose of this study was to delve into the lived experiences of Asian-White interracial couples and their experiences raising their biracial children. A total of 10 couples participated, and they reported on their perception of their children’s racial/ethnic identity, their children’s understanding of race, the types of racial and cultural socialization practices in which they engaged, cultural differences within their family, and differential treatment based on their children’s appearance.

Background Prostate cancers frequently metastasize to bone, where the best microenvironment for distant colonization is provided. Since osteotropic metastasis of prostate cancer is a critical determinant of patients’ survival, searches for preventive measures are ongoing in the field. Therefore, it is important to dissect the mechanisms of each step of bone metastasis, including the epithelial-mesenchymal transition (EMT) and cross-talk between metastatic niches and cancer cells. Methods In this study, we established a highly bone-metastatic subline of human prostate cancer cells by selecting bone-homing population of PC3 cells after cardiac injection of eight-week-old male BALB/c-nude mice. Then we assessed the proliferation, EMT characteristics, and migration properties of the subline (mtPC3) cells in comparison with the parental PC3 cells. To investigate the role of S100A4, we performed gene knock-down by lentiviral transduction, or treated cells with recombinant S100A4 protein or a S100A4-neutralizing antibody. The effect of cancer cells on osteoclastogenesis was evaluated after treatment of pre-osteoclasts with conditioned medium (CM) from cancer cells. Results The mtPC3 cells secreted a markedly high level of S100A4 protein and showed elevated cell proliferation and mesenchymal properties. The increased proliferation and EMT traits of mtPC3 cells was inhibited by S100A4 knock-down, but was not affected by exogenous S100A4. Furthermore, S100A4 released from mtPC3 cells stimulated osteoclast development via the cell surface receptor RAGE. Down-regulation or neutralization of S100A4 in the CM of mtPC3 cells attenuated cancer-induced osteoclastogenesis. Conclusion Altogether, our results suggest that intracellular S100A4 promotes cell proliferation and EMT characteristics in tumor cells, and that secreted S100A4 activates osteoclastogenesis, contributing to osteolytic bone metastasis. Thus, S100A4 upregulation in cancer cells highly metastatic to bone might be a key element in regulating bone metastasis.

Additional file 3: Supplementary Fig. 3. The uncropped full-length western blotting images of figures.

Title of my work is 'Playing with Remine.' Playing means playing or interacting with each other. There are two reasons why I design this work. Currently, I'm designing my website using interactive pictures and videos which visitors can play with them by clicking. Because I unsatisfied with traditional way to communicare with audiences only through the art piece of the artist is onesided communication. If you click my character on the website, you can meet Kim Hae-min(me) sitting in the room. Kim Hae-min doesn't has any attention to visiotors and doing her own habits. But if visitors matches certain conditions which attracts Kim Hae-min she beings to interreact with visitors. After that text messages pops up and visitors can choice questions to ask they want. Kim Hae-min's response depends on which question you choose. The response can be kind, ignoring the questions, explain the work, or talk about society. In other words, it is a reactive character with various events. Motivation of this project is also my personal experience. I've felt that there's actually not a lot of communication between people, and how can I be honest, comfortable and funny? In other way i also plan to expand this work to installation project. The audience passes by and sees Kim Hae-min. The audience enters the installation space and asks questions to the character. And then, if you don't agree or if you have conflicting values, you move on to the mini-game format. 'Battle with Remine' I'm thinking of trying this piece with interactive projection mapping. In the mini-game, I'm going to put various devices to solve the conflicts between me and visitors.

Bone is a dynamic tissue and is constantly being remodeled by bone cells. Metabolic reprogramming plays a critical role in the activation of these bone cells and skeletal metabolism, which fulfills the energy demand for bone remodeling. Among various metabolic pathways, the importance of lipid metabolism in bone cells has long been appreciated. More recent studies also establish the link between bone loss and lipid-altering conditions—such as atherosclerotic vascular disease, hyperlipidemia, and obesity—and uncover the detrimental effect of fat accumulation on skeletal homeostasis and increased risk of fracture. Targeting lipid metabolism with statin, a lipid-lowering drug, has been shown to improve bone density and quality in metabolic bone diseases. However, the molecular mechanisms of lipid-mediated regulation in osteoclasts are not completely understood. Thus, a better understanding of lipid metabolism in osteoclasts can be used to harness bone cell activity to treat pathological bone disorders. This review summarizes the recent developments of the contribution of lipid metabolism to the function and phenotype of osteoclasts.

Exosomes, which are released from all cells and take part in cell-to-cell communication, have been utilized as drug delivery vehicles in many recent studies. Immunotherapy is an emerging technology which uses patients' innate immune systems. In immunotherapy, immune cells are stimulated through antibodies, the other immune cells and genetic modifications for the purposes of, for instance, cancer therapy. In this study, tumor-derived re-assembled exosome (R-Exo) was simultaneously utilized as both a drug delivery carrier and an immunostimulatory agent. A chlorin e6 photosensitizer was loaded into tumor-derived exosomes during exosomal re-assembly. After this modification, R-Exo retains its original average size and has the same membrane proteins, which allows for targeting of tumor cells. Chlorin e6-loaded R-Exo (Ce6-R-Exo) can be visualized by photoacoustic imaging and can efficiently generate reactive oxygen species inside tumor cells under laser irradiation. In addition, Ce6-R-Exo increased the release of cytokines from immune cells, which indicates that these modified exosomes can be used as an immunotherapeutic agent. In conclusion, we developed a novel strategy that enables photoacoustic imaging-guided photodynamic and immune-combination therapy for the treatment of cancer with tumor-derived Ce6-R-Exo.

As a minimally invasive method, sentinel lymph node biopsy (SLNB) in conjunction with guidance methods is the standard method to determine cancer metastasis in breast. The desired guidance methods for SLNB should be capable of precise SLN localization for accurate diagnosis of micro-metastases at an early stage of cancer progression and thus facilitate reducing the number of SLN biopsies for minimal surgical complications. For this, high sensitivity to the administered dyes, high spatial and contrast resolutions, deep imaging depth, and real-time imaging capability are pivotal requirements. Currently, various methods have been used for SLNB guidance, each with their own advantages and disadvantages, but no methods meet the requirements. In this review, we discuss the conventional SLNB guidance methods in this perspective. In addition, we focus on the role of the PA imaging modality on real-time SLN identification and biopsy guidance. In particular, PA-based hybrid imaging methods for precise SLN identification and efficient biopsy guidance are introduced, and their unique features, advantages, and disadvantages are discussed.

Light is an attractive tool for high spatial- and contrast-resolution imaging, highly sensitive molecular imaging, and target-selective therapy, and it does not exhibit the risks associated with ionizing radiation. The main limitation of using light in clinical applications is its superficial imaging and therapeutic depth caused by high optical scattering in biological media. Here, we demonstrate that the scattering and thus defocusing of the incident light can be alleviated when simultaneously delivered ultrasound generates air bubbles in the pathway of the incident light, thus increasing the light penetration. The bubbles are temporally induced by ultrasound with an intensity that is sufficiently low to avoid tissue damage and act as a Mie scattering medium in which light is scattered predominantly in the forward direction. The change in the optical scattering property caused by the ultrasound is undone after cessation of the insonification. From the results, it is expected that this proposed method will open a new route for overcoming the limitations of current optical imaging and therapeutic techniques.

Interpersonal romantic relationships are heavily influenced by societal norms and beliefs. These beliefs can place a great deal of stress on a relationship’s capacity for self-efficacy and behavior...

Osteoclasts (OCs), cells specialized for bone resorption, are generated from monocyte/macrophage precursors by a differentiation process governed by RANKL. Here, we show that DCTN1, a key component of the dynactin complex, plays important roles in OC differentiation. The expression of DCTN1 was upregulated by RANKL. The inhibition of DCTN1 expression by gene knockdown suppressed OC formation, bone resorption, and the induction of NFATc1 and c-Fos, critical transcription factors for osteoclastogenesis. More importantly, the activation of Cdc42 by RANKL was inhibited upon DCTN1 silencing. The forced expression of constitutively active Cdc42 restored the OC differentiation of precursors with DCTN1 deletion. In addition, PAK2 was found to be activated by RANKL and to function downstream of Cdc42. The DCTN1-Cdc42 axis also inhibited apoptosis and caspase-3 activation. Furthermore, the anti-osteoclastogenic effect of DCTN1 knockdown was verified in an animal model of bone erosion. Intriguingly, DCTN1 overexpression was also detrimental to OC differentiation, suggesting that DCTN1 should be regulated at the appropriate level for effective osteoclastogenesis. Collectively, our results reveal that DCTN1 participates in the activation of Cdc42/PAK2 signaling and the inhibition of apoptosis during osteoclastogenesis., Bone remodeling: Regulatory protein identified A critical mechanism for maintaining bone health uncovered by scientists in South Korea could provide insights into bone disease development. Bone remodeling is a lifetime process of bone generation that ensures bones remain healthy. Osteoclasts (OC), cells that break down bone, differentiate from white blood cell populations. Disruption to OC formation and function plays a critical role in bone diseases, yet the regulatory mechanisms in OC generation are unclear. Hong-Hee Kim at Seoul National University and co-workers investigated the role of a protein called DCTN1, which is involved in skeletal assembly processes. The team found that inhibiting DCTN1 suppressed the expression of key proteins needed for OC formation in cell cultures and mouse models. Overexpressing DCTN1 was equally damaging, suggesting the protein plays a key regulatory role.