Search

Abstract Background In 2023, the concept of metabolic dysfunction‐associated steatotic liver disease (MASLD) was introduced as an alternative to non‐alcoholic fatty liver disease (NAFLD). We aimed to assess the quantity and quality of skeletal muscle using each of these diagnostic classifications. Methods This cross‐sectional study included 18 154 participants (11 551 [63.6%] men and 6603 [36.4%] women, mean age 53.0 ± 8.8). The participants were classified into four categories: neither steatotic liver disease (SLD), NAFLD only, MASLD only or both SLDs. An appendicular skeletal muscle mass adjusted for body mass index of

Abstract Due to scarcity of anomaly situations in the early manufacturing stage, an unsupervised anomaly detection (UAD) approach is widely adopted which only uses normal samples for training. This approach is based on the assumption that the trained UAD model will accurately reconstruct normal patterns but struggles with unseen anomalies. To enhance the UAD performance, reconstruction-by-inpainting based methods have recently been investigated, especially on the masking strategy of suspected defective regions. However, there are still issues to overcome: (1) time-consuming inference due to multiple masking, (2) output inconsistency by random masking, and (3) inaccurate reconstruction of normal patterns for large masked areas. Motivated by this, this study proposes a novel reconstruction-by-inpainting method, dubbed Excision And Recovery (EAR), that features single deterministic masking based on the ImageNet pre-trained DINO-ViT and visual obfuscation for hint-providing. Experimental results on the MVTec AD dataset show that deterministic masking by pre-trained attention effectively cuts out suspected defective regions and resolves the aforementioned issues 1 and 2. Also, hint-providing by mosaicing proves to enhance the performance than emptying those regions by binary masking, thereby overcomes issue 3. The proposed approach achieves a high performance without any change of the model structure. Promising results are shown through laboratory tests with public industrial datasets. To suggest EAR be possibly adopted in various industries as a practically deployable solution, future steps include evaluating its applicability in relevant manufacturing environments.

BackgroundMyosteatosis, ectopic fat accumulation in skeletal muscle, is a crucial component of sarcopenia, linked to various cardiometabolic diseases. This study aimed to analyze the association between dyslipidemia and myosteatosis using abdominal computed tomography (CT) in a large population.MethodsThis study included 11,823 patients not taking lipid-lowering medications with abdominal CT taken between 2012 and 2013. Total abdominal muscle area (TAMA), measured at the L3 level, was segmented into skeletal muscle area (SMA) and intramuscular adipose tissue. SMA was further classified into normal attenuation muscle area (NAMA: good quality muscle) and low attenuation muscle area (poor quality muscle). NAMA divided by TAMA (NAMA/TAMA) represents good quality muscle. Atherosclerotic dyslipidemia was defined as high-density lipoprotein cholesterol (HDL-C) less than 40 mg/dL in men and 50 mg/dL in women, low-density lipoprotein cholesterol (LDL-C) greater than 160 mg/dL, triglycerides (TG) greater than 150 mg/dL, small dense LDL-C (sdLDL-C) greater than 50.0 mg/dL, or apolipoprotein B/A1 (apoB/A1) greater than 0.08.ResultsThe adjusted odds ratios (ORs) of dyslipidemia according to the HDL-C and sdLDL definitions were greater in both sexes in the lower quartiles (Q1~3) of NAMA/TAMA compared with Q4. As per other definitions, the ORs were significantly increased in only women for LDL-C and only men for TG and ApoB/A1. In men, all lipid parameters were significantly associated with NAMA/TAMA, while TG and ApoB/A1 did not show significant association in women.ConclusionMyosteatosis measured in abdominal CT was significantly associated with a higher risk of dyslipidemia. Myosteatosis may be an important risk factor for dyslipidemia and ensuing cardiometabolic diseases.

Lung cancer represents a significant global health concern and stands as the leading cause of cancer-related mortality worldwide. The identification of specific genomic alterations such as EGFR and KRAS in lung cancer has paved the way for the development of targeted therapies. While targeted therapies for lung cancer exhibiting EGFR, MET and ALK mutations have been well-established, the options for RET mutations remain limited. Importantly, RET mutations have been found to be mutually exclusive from other genomic mutations and to be related with high incidences of brain metastasis. Given these facts, it is imperative to explore the development of RET-targeting therapies and to elucidate the mechanisms underlying metastasis in RET-expressing lung cancer cells. In this study, we investigated PLM-101, a novel dual-target inhibitor of RET/YES1, which exhibits notable anti-cancer activities against CCDC6-RET-positive cancer cells and anti-metastatic effects against YES1-positive cancer cells. Our findings shed light on the significance of the YES1-Cortactin-actin remodeling pathway in the metastasis of lung cancer cells, establishing YES1 as a promising target for suppression of metastasis. This paper unveils a novel inhibitor that effectively targets both RET and YES1, thereby demonstrating its potential to impede the growth and metastasis of RET rearrangement lung cancer.

Acute myeloid leukemia (AML) is a prevalent form of leukemia in adults. As its survival rate is low, there is an urgent need for new therapeutic options. In AML, FMS-like tyrosine kinase 3 (FLT3) mutations are common and have negative outcomes. However, current FLT3-targeting agents, Midostaurin and Gilteritinib, face two significant issues, specifically the emergence of acquired resistance and drug-related adverse events leading to treatment failure. Rearranged during transfection (RET), meanwhile, is a proto-oncogene linked to various types of cancer, but its role in AML has been limited. A previous study showed that activation of RET kinase enhances FLT3 protein stability, leading to the promotion of AML cell proliferation. However, no drugs are currently available that target both FLT3 and RET. This study introduces PLM-101, a new therapeutic option derived from the traditional Chinese medicine indigo naturalis with potent in vitro and in vivo anti-leukemic activities. PLM-101 potently inhibits FLT3 kinase and induces its autophagic degradation via RET inhibition, providing a superior mechanism to that of FLT3 single-targeting agents. Single- and repeated-dose toxicity tests conducted in the present study showed no significant drug-related adverse effects. This study is the first to present a new FLT3/RET dual-targeting inhibitor, PLM-101, that shows potent anti-leukemic activity and fewer adverse effects. PLM-101, therefore, should be considered for use as a potential therapeutic agent for AML.

IntroductionType 2 diabetes mellitus (T2DM) is a chronic, progressive disease requiring lifelong treatment, and durable medication is essential for maintaining stable glycemic control. This study aimed to evaluate the long-term efficacy of dulaglutide in participants who have continued the drug for more than one year.MethodsWe conducted a retrospective study on 605 participants, who used dulaglutide for over one year between 2016 and 2020. Changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose, and bodyweight from baseline to last prescription day were assessed. Adherence was evaluated by the proportion of days covered (PDC), and a PDC value ≥ 0.80 was considered adherent.ResultsThe mean age was 54.0 ± 11.1 years, and 46.1% were female. The mean baseline HbA1c, bodyweight, and duration of diabetes were 8.8% (72.7 mmol/mol), 75.6 kg, and 12.2 years, respectively. During the mean follow-up of 33.1 months, HbA1c and bodyweight decreased by 1.28% (14 mmol/mol, P < 0.001) and by 3.19 kg (P < 0.001), respectively. The participants were highly adherent with PDC ≥ 0.80 in 92.4% of the participants.ConclusionIn T2DM patients, long-term dulaglutide treatment was effective in maintaining HbA1c and weight reduction. Dulaglutide could be a favorable option of long-term treatment in real-world clinical practice.

Abstract Background Alopecia refers to a condition developed by gradual reduction of hair loss by various abnormal causes such as endocrine system, genetic factors, and stress. Stromal vascular fraction (SVF) isolated from the fat is one of the latest innovative solutions in the field of regeneration therapy. We focused on presenting effectiveness of clinical cases to improve AGA through transplantation of autologous SVF into the scalp. Objective To confirm the efficacy of the autologous SVF usage to the patients with AGA. Methods Nine patients (age range 43–64 years; 4 men, grade IV to V and 5 women, grade I to III), who are suffering from androgenic alopecia (AGA), were treated with single transplantation of autologous SVF in the upper scalp. Autologous SVF was isolated and characterized prior to the injection of live 7–9 × 106 cells into the patients’ treatment site. The hair loss improvement effect was assessed by three test criteria: hair skin quality, hair thickness and hair density 3 and 6 months after post-injection compared to pre-injection status. Results Hair density of SVF-treated side was significantly increased after 3 and 6 months of transplantation compared to non-treated side (P = 0.01 and P = 0.009 per each). And significant improvement in the score of the keratin on the scalp was seen in the injected area as compared to the non-injected area 6 months after transplantation (P = 0.032). Although thickness increase was observed at 3 and 6 months after transplantation, there was no statistical significance (P = 0.142 and 0.155, respectively). Conclusions One transplantation of autologous SVF for the AGA patients, hair density and score for the keratin were significantly increased within 6 months. This study shows that SVF is a very effective way to treat hair loss and most of subjects are satisfied with the result after treatment.

This study employed a critical inquiry paradigm to explore the significance of equity and social justice in teaching qualitative methodologies and methods to graduate students. Graduate students of multiple minoritized identities and a faculty member conducted a two-year inquiry into the research apprenticeship experience, including the stages of student-led conceptualization, data collection, analysis, international conference presentation, and publication. The study investigated the experiences of the faculty and students as well as the responsibilities of the institution against the backdrop of historical and contemporary pandemics. Consequently, we problematized hidden curriculum and unconscious assumptions to suggest research course design sequencing improvements. The findings emphasize the impact of these experiences on qualitative research teaching and learning practices and institutional responsibility to graduate student research apprenticeships. The Graduate Research Apprenticeship Nested Design Pathway is presented as a tool that institutions worldwide can adapt and implement to serve the complex needs of their students.

Eosinophilic gastrointestinal disorder (EGID) is an uncommon disease that is accompanied by intestinal eosinophil infiltration without a secondary cause of eosinophilia. Eosinophilic enteritis is a secondary portion of EGID that can present a range of gastrointestinal symptoms according to the affected depth of the intestinal layer. The subserosal type of eosinophilic enteritis presenting as ascites is relatively rarer than the mucosal type. In general, eosinophilic enteritis occurs in patients with food allergies, but its mechanism is unclear. The authors experienced a 29-year-old female patient with a large amount of ascites with diarrhea and abdominal pain. The patient was diagnosed with an influenza A infection one week earlier. Peripheral eosinophilia (absolute eosinophil count: 6,351 cells/mm3) and eosinophilic ascites (97% of white blood cells in the ascites are eosinophil) were present. Abdominal CT revealed a large amount of ascites and edematous changes in the ileum and ascending colon wall. A diagnosis of eosinophilic enteritis was confirmed as eosinophilic ascites by paracentesis, with eosinophil infiltration of the bowel wall by an endoscopic biopsy. The patient's symptoms improved rapidly after using steroids. To the best of the author’s knowledge, this is the first report of eosinophilic enteritis with massive ascites after an influenza A virus infection in a Korean adult.

Paclitaxel is used in the treatment of cancer especially in breast, stomach and ovarian cancer. However, peripheral neuropathic pain (PNP) induction is the most common devastating side effect of paclitaxel treatment. The objective of this study was to evaluate the PNP related behavioral changes in rats following oral administration of a novel oral paclitaxel formulation DHP107 (Liporaxel) in comparison with another popular intravenous paclitaxel preparation (Taxol). The rats were equally divided in to three groups namely, NC group (normal control): was treated with saline in a matched volume, LPX group (Liporaxel were administered orally) and TAX group (Taxol was administered intravenously). Less pain like behaviors were observed in LPX group in comparison with TAX group evidenced by significant higher level of hot plate paw withdrawal threshold (PWT), von Frey filament PWT and mechanical PWT than TAX group. Reduced lipid peroxidation and elevated antioxidant activities in serum, dorsal root ganglion (DRG) and sciatic nerve (SN) in LPX group than TAX group. In addition, cell apoptosis and expression of pain and neuropathy related proteins activation in LPX group was found lowered and myelin sheath thickness was higher in DRG and SN but not significantly different from the TAX group. Therefore, oral DHP107 could be a promising chemotherapeutic agent due to inducing less PNP. [ J Adv Biotechnol Exp Ther 2019; 2(2.000): 55-64]

Abstract Background The incidence of tongue squamous cell carcinoma (TSCC) in young patients has recently increased, and these TSCCs are believed to be etiologically distinct from those in older patients, who have longer exposure to risk factors such as tobacco and alcohol. The prognosis of TSCCs in young patients remains controversial. Methods We retrospectively reviewed the records of 117 patients (2001–2011) who were diagnosed with squamous cell carcinoma of the oral tongue. Patients were divided into two age groups, older (ages over 40) and younger (ages 40 and younger). Data were compared between the two groups, and survival rates were analyzed. Results The results show that there are significant differences in overall, disease-free, and distant metastasis-free survival rates between the two groups. Five-year overall survival rates were 70% in older patients and 42% in young patients (p = 0.033). Five-year disease-free survival rates were 73% in older patients and 40% in young patients (p = 0.011), and 5-year distant metastasis-free survival rates were 97% in older patients and 62% in young patients (p = 0.033). Multivariate analysis revealed that histologic grade was the only independent risk factor for overall survival in both groups of patients (p = 0.002, HR = 2.287). The analysis also demonstrated that age was the critical risk factor for distant metastasis (p = 0.046, HR = 9.687). Conclusion In this study, young (ages 40 and younger) patients with squamous cell carcinoma of the oral tongue had a higher rate of distant metastasis and a worse prognosis. Accordingly, we propose the necessity of an extensive therapeutic regimen that should be used in all young patients with TSCC.

Background: Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinical-radiological entity, characterized by mild encephalitis or encephalopathy associated with a reversible lesion of the corpus callosum, which commonly involves the splenium. MERS with autoimmune thyroid disease has rarely been reported. Case Report: A 37-year-old man with Grave’s disease presented to our institution, with symptoms of confused mentality, visual hallucinations, headache, and fever. Because there was no other etiology for changed mentality, headache, and fever, except for elevated antithyroid antibodies (antimicrosomal antibodies, anti-thyroglobulin antibody, and thyrotropin binding inhibitor immunoglobulin) in the blood and mild pleocytosis in the CSF study, we diagnosed the case as steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT). A hyperintense signal on T2-weighted images, a hypointense signal on T1-weighted images, and a non-enhancing lesion in the splenium of corpus callosum on initial magnetic resonance imaging (MRI) disappeared on follow-up MRI, which was compatible with the criteria of MERS. Conclusion: Although MRI images in autoimmune thyroid disease have usually been unremarkable, we report a case of MERS in SREAT.

BackgroundTransverse abdominis plane (TAP) block can be recommended as a multimodal method to reduce postoperative pain in laparoscopic abdominal surgery. However, it is unclear whether TAP block following local anesthetic infiltration is effective. We planned this study to evaluate the effectiveness of the latter technique in laparoscopic totally extraperitoneal hernia repair (TEP).MethodsWe randomly divided patients into two groups: the control group (n = 37) and TAP group (n = 37). Following the induction of general anesthesia, as a preemptive method, all of the patients were subjected to local anesthetic infiltration at the trocar sites, and the TAP group was subjected to ultrasound-guided bilateral TAP block with 30 ml of 0.375% ropivacaine in addition before TEP. Pain was assessed in the recovery room and post-surgery at 4, 8, and 24 h. Additionally, during the postoperative 24 h, the total injected dose of analgesics and incidence of nausea were recorded.Results:On arrival in the recovery room, the pain score of the TAP group (4.33 ± 1.83) was found to be significantly lower than that of the control group (5.73 ± 2.04). However, the pain score was not significantly different between the TAP group and control group at 4, 8, and 24 h post-surgery. The total amounts of analgesics used in the TAP group were significantly less than in the control group. No significant difference was found in the incidence of nausea between the two groups.ConclusionsTAP block following local infiltration had a clinical advantage only in the recovery room.

Purpose: Bariatric surgery is an efficient procedure for the remission of type 2 diabetes (T2DM) from morbid obesity. However, in Asian countries, the mean body mass index (BMI) of T2DM patients is about 25 kg/m2. Various data on patients undergoing gastric bypass surgery suggest that the control of T2DM after surgery occurs rapidly. We hypothesized that even in nonobese patients with T2DM, the levels of incretin and insulin changed along with the improvement of T2DM as a consequence of the gastric bypass. Materials and methods: From March to December 2011, 12 nonobese patients (mean BMI; 26.2 kg/m2) with poorly-controlled [mean glycated hemoglobin (HbA1C); 9.5%] diabetes underwent gastric bypass surgery. Values related to diabetes, including incretin [gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1)] levels were measured before and 1 month after surgery. All values were measured in response to a 75 g oral glucose tolerance test (OGTT). Results: On average, the BMI decreased by 2.1 ± 0.7 kg/m2. Mean HbA1C level decreased by 1.6 ± 2%. Oral glucose-stimulated insulin levels increased and GLP-1 levels also increased significantly. Oral glucose-stimulated GIP levels decreased sharply. Conclusion: Soon after gastric bypass in nonobese T2DM patients, control of T2DM is achieved. The incretin release after oral glucose is improved. This could be a consequence of changes of the enteroinsular axis, particularly in the incretins.

Duodenal adenocarcinoma is a rare cancer, contributing

Category: Bunion Introduction/Purpose: A severe hallux valgus deformity in rheumatoid patient is usually treated with the 1st MTP fusion, since the high success rate with low percentage of recurrence leads to higher patient satisfaction. However the large 1st inter- metatarsal angle, sometimes, is not decreased after the fusion, and the patient may suffer the persistent bunion pain. We tried to solve this problem by performing the 1st MTP fusion and the 1st proximal metatarsal osteotomy in one stage. We report our surgical technique with the outcome analysis of the patients. Methods: Six patients with the severe rheumatoid hallux valgus deformity were followed for more than 12 months after the combined 1st MTP fusion and 1st proximal metatarsal osteotomy. All were women. The mean age of patients was 51.3 years, and the mean follow up period was 2 years and 1 month. Inclusion criterion was a rheumatoid hallux valgus deformity of more than 18 degrees of the 1st intermetatarsal angle. The MTP fusion was fixed with threaded Steinmann pins and the proximal metatarsal osteotomy was fixed with Kirschner wires through the single curvilinear skin incision. Clinically American Orthopaedic Foot and Ankle Society (AOFAS) hallux MP-IP scale, and patient’s satisfaction after the surgery were analyzed. Radiographically the union of the fusion and the osteotomy was investigated. Results: Clinically the AOFAS scale improved from the preoperative 51.2 points to the postoperative 84.3 points. All patients were satisfied with the results. There were no wound problem or nonunion of fusion/osteotomy. Conclusion: The combined 1st MTP fusion and 1st proximal metatarsal osteotomy was an effective and safe procedure for the severe rheumatoid hallux valgus deformity with the large 1st inter-metatarsal angle.

This study employed a critical inquiry paradigm to explore the significance of equity and social justice in teaching qualitative methodologies and methods to graduate students. Graduate students of multiple minoritized identities and a faculty member conducted a two-year inquiry into the research apprenticeship experience, including the stages of student-led conceptualization, data collection, analysis, international conference presentation, and publication. The study investigated the experiences of the faculty and students as well as the responsibilities of the institution against the backdrop of historical and contemporary pandemics. Consequently, we problematized hidden curriculum and unconscious assumptions to suggest research course design sequencing improvements. The findings emphasize the impact of these experiences on qualitative research teaching and learning practices and institutional responsibility to graduate student research apprenticeships. The Graduate Research Apprenticeship Nested Design Pathway is presented as a tool that institutions worldwide can adapt and implement to serve the complex needs of their students. [ABSTRACT FROM AUTHOR]

Context: Ectopic fat deposition in skeletal muscle, termed myosteatosis, is a key factor in developing insulin resistance. Objective: This work aimed to evaluate the association between insulin resistance and myosteatosis in a large Asian population. Methods: A total of 18 251 participants who had abdominal computed tomography were included in this cross-sectional study. Patients were categorized into 4 groups according to quartiles of Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). The total abdominal muscle area (TAMA) at the L3 vertebral level was segmented into normal-attenuation muscle area (NAMA), low-attenuation muscle area (LAMA), and intermuscular adipose tissue (IMAT). The absolute values of TAMA, NAMA, LAMA, and IMAT and the ratios of NAMA/BMI, LAMA/BMI, and NAMA/TAMA were used as myosteatosis indices. Results: The absolute values of TAMA, NAMA, LAMA, and IMAT appeared to increase with higher HOMA-IR levels, and LAMA/BMI showed a similar upward trend. Meanwhile, the NAMA/BMI and NAMA/TAMA index showed downward trends. As HOMA-IR levels increased, the odds ratios (ORs) of the highest quartile of NAMA/BMI and NAMA/TAMA index decreased and that of LAMA/BMI increased. Compared with the lowest HOMA-IR group, the adjusted ORs (95% CI) in the highest HOMA-IR group for the lowest NAMA/TAMA quartile were 0.414 (0.3640.471) in men and 0.464 (0.384-0.562) in women. HOMA-IR showed a negative correlation with NAMA/BMI (r = -0.233 for men and r = -0.265 for women), and NAMA/TAMA index (r = -0.211 for men and r = -0.214 for women), and a positive correlation with LAMA/BMI (r = 0.160 for men and r = 0.119 for women); P was less than .001 for all. Conclusion: In this study, a higher HOMA-IR level was significantly associated with a high risk of myosteatosis. [ABSTRACT FROM AUTHOR]