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Purpose Varus alignment is known as one of the major causes of medial compartment osteoarthritis (OA). Medial meniscus extrusion also plays a critical role in the in the development of OA. However, studies on the exact relationship between alignment parameters and medial meniscus extrusion are limited. Therefore, this study aimed to investigate this relationship in patients with knee OA. Methods Based on a retrospective analysis of the outpatient magnetic resonance imaging (MRI) database, 190 knees were identified to be examined using weight-bearing, whole-leg radiographs and MRIs within 3 months from the first consultation. Subsequently, various parameters of lower leg alignment were measured, which affected the knee varus in radiographs. Finally, a statistical analysis was performed to assess the relationships between the OA grade, distance of medial meniscus extrusion (MME), and alignment parameters; hip–knee–ankle angle (HKAA), percentage of mechanical axis (% MA), medial proximal tibial angle (MPTA), and joint line convergence angle (JLCA). The subjects were divided according to the presence or absence of MME (Group A: MME distance below 3 mm, Group B: MME distance 3 mm and above) to assess the differences in each alignment parameter correlated with MME distance between the groups. Results MME distance significantly increased with OA grade progression. HKAA, % MA, MPTA, and JLCA significantly correlated with medial meniscus extrusion distance ( r  = − 0.21, − 0.23, − 0.16, 0.3, respectively). Multiple regression analysis of each significant alignment combined with age, sex, and body mass index revealed that HKAA, % MA, MPTA, and JLCA were significant independent factors of MME distance ( P  = 0.008, 0.0026, 0.011, 0.0001, respectively). These significant findings were reinforced in group B. In contrast, the correlation between alignment parameters and medial meniscus extrusion distance was not significant in group A. Conclusion Varus alignment factors are related to MME distance especially in extruded meniscus knees, as the OA grade progressed. Therefore, the coexistence of varus alignment and MME can be the risk factors for OA progression. As the low MPTA was an independent alignment factor for generating varus alignment, patients with osteoarthritis of the knee with both, low MPTA and MME could be the appropriate candidates for early intervention by high tibial osteotomy. Level of evidence III.

In a prospective study involving 50 patients with severe aortic stenosis and anemia, 94% had angiodysplasia, of whom 69% had lesions in the small intestine. After TAVR, the number and size of angiodysplastic lesions were reduced.

Background Controlling metastasis is essential for improving the prognosis of patients with gastric cancer (GC). Here, we aimed to identify a molecule required for GC metastasis and to investigate its potential utility as a target for the development of therapeutic antibodies (Abs). Methods Transcriptome and bioinformatics analyses of human GC cell lines identified the neuronal pentraxin receptor ( NPTXR ) as a candidate molecule. NPTXR function was probed by modulating its expression in GC cells and assessing the effects on intracellular signaling and malignant behaviors in vitro and in mouse xenograft models. We also generated anti-NPTXR Abs and Nptxr −/− mice, and assessed the clinical significance of NPTXR expression in GC specimens. Results NPTXR mRNA expression in clinical specimens was associated with disease progression and was significantly higher in tissues from GC patients with distant metastasis compared with those without. NPTXR regulated expression of genes involved in metastatic behaviors as well as activation of the PI3K–AKT–mTOR, FAK–JNK, and YAP signaling pathways. NPTXR silencing promoted caspase-mediated apoptosis and attenuated GC cell proliferation, cell cycle progression, migration, invasion, adhesion, stem cell-like properties, and resistance to 5-fluorouracil in vitro, and also inhibited the tumorigenicity of GC cells in vivo. Anti- NPTXR Abs inhibited GC peritoneal metastasis in mice. Nptxr −/− mice showed no abnormalities in reproduction, development, metabolism, or motor function. Conclusions NPTXR plays an essential role in controlling the malignant behavior of GC cells in vitro and in vivo. NPTXR -targeting Abs may thus have utility as novel diagnostic tools and/or treatment modalities for GC.

Body cooling is recommended for patients with heat stroke and heat exhaustion. However, differences in the outcomes of patients who do or do not receive active cooling therapy have not been determined. The best available evidence supporting active cooling is based on a case series without comparison groups; thus, the effectiveness of this method in improving patient prognoses cannot be appropriately quantified. Therefore, we compared the outcomes of heat stroke patients receiving active cooling with those of patients receiving rehydration-only therapy. This prospective observational multicenter registry-based study of heat stroke and heat exhaustion patients was conducted in Japan from 2010 to 2019. The patients were stratified into the “severe” group or the “mild-to-moderate” group, per clinical findings on admission. After conducting multivariate logistic regression analyses, we compared the prognoses between patients who received “active cooling + rehydration” and patients who received “rehydration only,” with in-hospital death as the endpoint. Sex, age, onset situation (i.e., exertional or non-exertional), core body temperature, liver damage, renal dysfunction, and disseminated intravascular coagulation were considered potential covariates. Among those who received active cooling and rehydration-only therapy, the in-hospital mortality rates were 21.5% and 35.5%, respectively, for severe patients (n = 231) and 3.9% and 5.7%, respectively, for mild-to-moderate patients (n = 578). Rehydration-only therapy was associated with a higher in-hospital mortality in patients with severe heat illness (adjusted odds ratio [aOR], 3.29; 95% confidence interval [CI], 1.21–8.90), whereas the cooling methods were not associated with lower in-hospital mortality in patients with mild-to-moderate heat illness (aOR, 2.22; 95% CI, 0.92–5.84). Active cooling was associated with lower in-hospital mortality only in the severe group. Our results indicated that active cooling should be recommended as an adjunct to rehydration-only therapy for patients with severe heat illness.

RNA editing by adenosine deaminase acting on RNA (ADAR) enzymes plays a role in cancer progression. However, its clinical significance in metastatic colorectal cancer (CRC) remains unclear. This study aimed to evaluate whether ADAR1 expression predicts prognosis and treatment response in colorectal cancer (CRC) with synchronous liver metastasis. This study included 40 patients with stage IV CRC and synchronous liver metastases. ADAR1 expression in tumor tissues was evaluated using immunohistochemistry. Expression levels were quantified using the immunoreactive score, and associations with clinicopathological features, overall survival (OS), and chemotherapy response were examined. High ADAR1 expression was significantly associated with multiple liver metastases ( P  = 0.0206), lymph node metastasis ( P = 0.0241), and reduced response to chemotherapy ( P  = 0.0224). Significantly shorter OS was observed in patients with high ADAR1 expression in the nucleus ( P  = 0.0458). ADAR1 expression was an independent prognostic factor comparable to the presence of extrahepatic metastases. Low ADAR1 expression was correlated with a higher likelihood of achieving a response to chemotherapy. ADAR1 expression can reflect tumor aggressiveness and chemotherapy resistance in patients with CRC and synchronous liver metastasis. ADAR1 has considerable potential as a dual-purpose biomarker for stratifying patients based on prognosis and optimizing treatment intensity.

Objective Trifluridine/tipiracil (FTD/TPI) is one of the options for late-line treatment of colorectal cancer (CRC). However, the specific patient populations that would particularly benefit from it remain unclear. This study attempted to identify predictive markers of chemotherapy efficacy with trifluridine/tipiracil (FTD/TPI), focusing on the RNA-editing enzyme adenosine deaminase acting on RNA 1 (ADAR1) expression and neutrophil–lymphocyte ratio (NLR). Methods To assess the effectiveness of FTD/TPI in CRC patients, we retrospectively analyzed 72 CRC patients at Okayama University Hospital from 2014 to 2022. Results Adding bevacizumab to FTD/TPI resulted in a more prolonged progression-free survival (PFS), consistent with the SUNLIGHT study findings ( p  = 0.0028). Among the participants, those with a high NLR had a shorter PFS ( p  = 0.0395). Moreover, high ADAR1 expression was associated with longer PFS (p  = 0.0151). In multivariate analysis, low ADAR1 (HR = 3.43, p  = 0.01) and absence of bevacizumab (HR = 4.25, p  = 0.01) were identified as factors shortening PFS. The high ADAR1 group demonstrated fewer cases of progressive disease and a higher proportion of stable disease than the low ADAR1 group ( p  = 0.0288). Low NLR and high ADAR1 were predictive markers of prolonged PFS in the bevacizumab-treated group ( p  = 0.0036). Conclusion Low NLR and high ADAR1 were predictive markers for a positive response to the FTD/TPI plus bevacizumab regimen associated with prolonged PFS. The FTD/TPI plus bevacizumab regimen should be proactively implemented in the low NLR and high ADAR1 subgroups.

Creating impressive video content such as movies and advertisements is a very important yet challenging task in business that requires both a sense of creativity and a lot of experience. Even professionals cannot necessarily invoke the impressions and emotions that they have aimed at. Many video advertisements are created and then disappear without giving a large impact on viewers. This paper presents a large-scale dataset of television (TV) advertisements that consists of 14,490 videos. The impressions of each video such as the recognition rate and interestingness rate are from the results of questionnaires answered by 620 participants. We also present a baseline for predicting the impression effects of TV advertisements by using visual and audio information, metadata such as broadcasting pattern, business category, the popularity of the casts, and text information including texts appearing on videos and narrations in audios. We predict four impressions of the viewers: 1) how much participants remember the video afterward, 2) how much they feel like buying the product/service, 3) how much they become interested in the product/service, and 4) how much they like the content of the advertisement itself. By combining images, audio, metadata, cast data, and text data, our baseline method is able to predict such impressions with a correlation of 0.69-0.82, much better than using a single-modal feature such as visual data or audio data only. This paper also gives some possible applications such as estimating the importance scores of each key frame, which gives us informative insights about how to make the advertisement content more impressive.

BackgroundThe expression of solute carrier (SLC) 7 family genes is reportedly associated with several malignancies. Here, we focused on SLC7A9 and investigated its expression, function, and clinical significance in esophageal squamous cell carcinoma (ESCC). MethodsSLC7A9 transcription levels were evaluated in 13 ESCC cell lines, and polymerase chain reaction (PCR) array analysis was conducted to detect coordinately expressed genes with SLC7A9. SLC7A9 contributions to proliferation, invasion, and migration were evaluated in ESCC cells subjected to siRNA-mediated gene knockdown and pCMV6-entry plasmid-mediated overexpression. SLC7A9 expression was detected in 189 ESCC tissues by quantitative reverse-transcription (qRT)-PCR and correlated with clinicopathological parameters.ResultsThe expression levels of SLC7A9 varied widely in ESCC cell lines and correlated with FGFBP1 expression. Knockdown of SLC7A9 significantly suppressed the proliferation, invasion, and migration of the ESCC cell lines. Moreover, overexpression of SLC7A9 enhanced cell proliferation and migration. In analyses of clinical specimens, SLC7A9 mRNA was overexpressed in the ESCC tissues compared with the adjacent normal esophageal tissues. High mRNA expression was significantly associated with high levels of squamous cell carcinoma-related antigen and carcinoembryonic antigen, advanced disease stage, and lymph node metastasis. High SLC7A9 expression was also significantly associated with poor disease-specific and disease-free survival, and lymph node recurrence after radical surgery, but not with the other recurrence patterns. On multivariate analysis, high SLC7A9 expression was an independent predictor of lymph node recurrence.ConclusionsSLC7A9 influences the malignant behavior of ESCC cells. Tumor SLC7A9 expression may serve as a novel biomarker for predicting lymph node metastasis and recurrence in ESCC patients.

Summer-type hypersensitivity pneumonitis commonly occurs in Japan during the warm and humid season, when the causative Trichosporon asahii flourish. The assessment of anti-T. asahii antibodies in patients with hypersensitivity pneumonitis without any obvious causative antigen may be useful even outside Japan.