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In clinical practice, urethral diseases are not as frequent as conditions affecting other components of the urinary system. Radiological imaging tests, such as retrograde urethrography, CT, MRI, and PET/CT, along with patient history, are crucial for accurately assessing relatively rare urethral lesions. This article aimed to provide a comprehensive overview of urethral lesions, from traumatic changes to neoplasms, and discuss the multimodal imaging findings of various urethral lesions that radiologists should know. To this end, the normal imaging anatomy of the urethra and a step-by-step approach that can be used in clinical practice have been presented to help in the systematic understanding of urethral lesions., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Triple-negative breast cancer (TNBC) lacks the expression of hormone and HER2 receptors and is highly malignant with no effective therapeutic targets. In TNBC, the cancer stem-like cell (CSC) population is considered to be the main cause of resistance to treatment. Thus, the therapeutic targeting of this population could substantially improve patient survival. Here, we identify the RNA-binding protein ZCCHC24 as enriched in the mesenchymal-like TNBC population. ZCCHC24 promotes the expression of a set of genes related to tumorigenicity and treatment resistance by directly binding to the cis-element "UGUWHWWA" in their mRNAs, thereby stabilizing them. One of the ZCCHC24 targets, ZEB1, is a transcription factor that promotes the expression of cancer stemness genes and reciprocally induces ZCCHC24 expression. ZCCHC24 knockdown by siRNAs shows a therapeutic effect and reduces the mesenchymal-like cell population in TNBC patient-derived xenografts. ZCCHC24 knockdown also has additive effects with the BET inhibitor JQ1 in suppressing tumor growth in TNBC patient-derived xenografts., (© 2024. The Author(s).)

An 83-year-old woman presented with disturbance of consciousness and hand tremor. She had taken lithium carbonate 300 mg/day for bipolar disorder and magnesium oxide 660 mg/day for constipation. Blood tests revealed lithium poisoning, hypermagnesemia and acute kidney injury. Computed tomography showed colonic obstruction caused by cancer of the descending colon. In the outpatient section, her blood pressure decreased to 89/54 mmHg, and her heart rate dropped to 40 bpm. We considered that the obstructive ileus induced intravascular dehydration, which led to toxic serum concentrations of lithium and magnesium, triggering the emergence of severe arrythmia induced by sinus dysfunction. The patient was treated with fluid resuscitation and hemodialysis, followed by endoscopic stent replacement for the descending colon cancer obstruction. These treatments improved her general condition and alleviated the lithium poisoning, hypermagnesemia and colonic obstruction. Such a case is considered extremely rare., Competing Interests: We have no conflict of interest to declare., (© The Author(s) 2024. Published by Oxford University Press.)

Increasing pieces of evidence have suggested that astrocyte function has a strong influence on neuronal activity and plasticity, both in physiological and pathophysiological situations. In epilepsy, astrocytes have been shown to respond to epileptic neuronal seizures; however, whether they can act as a trigger for seizures has not been determined. Here, using the copper implantation method, spontaneous neuronal hyperactivity episodes were reliably induced during the week following implantation. With near 24-h continuous recording for over 1 week of the local field potential with in vivo electrophysiology and astrocyte cytosolic Ca 2+ with the fiber photometry method, spontaneous occurrences of seizure episodes were captured. Approximately 1 day after the implantation, isolated aberrant astrocyte Ca 2+ events were often observed before they were accompanied by neuronal hyperactivity, suggesting the role of astrocytes in epileptogenesis. Within a single developed episode, astrocyte Ca 2+ increase preceded the neuronal hyperactivity by ~20 s, suggesting that actions originating from astrocytes could be the trigger for the occurrence of epileptic seizures. Astrocyte-specific stimulation by channelrhodopsin-2 or deep-brain direct current stimulation was capable of inducing neuronal hyperactivity. Injection of an astrocyte-specific metabolic inhibitor, fluorocitrate, was able to significantly reduce the magnitude of spontaneously occurring neuronal hyperactivity. These results suggest that astrocytes have a role in triggering individual seizures and the reciprocal astrocyte-neuron interactions likely amplify and exacerbate seizures. Therefore, future epilepsy treatment could be targeted at astrocytes to achieve epilepsy control., (© 2024 The Authors. GLIA published by Wiley Periodicals LLC.)

Background: Fine bubble (FB) bathing has shown benefits on a mouse model of atopic dermatitis (AD). However, its efficacy in dogs with AD remains to be evaluated., Objective: This study aimed to assess the clinical effectiveness of FB bathing in dogs with AD., Animals: Seventeen dogs with AD whose clinical presentation showed a Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) score of <40., Materials and Methods: The dogs were randomly assigned to either the FB bathing group or the shampoo group. The treatments were administered once a week as per the instructions, in a trial totalling 4 weeks. Evaluations were conducted on Day (D)0 and D28 to assess the outcomes of the trial. The severity of AD was measured using the CADESI-04 and the pruritus Visual Analog Scale (PVAS). The skin barrier function parameters, transepidermal water loss (TEWL) and stratum corneum hydration were measured before and after the treatment., Results: Both treatment groups demonstrated a decreasing trend in CADESI-04 scores, yet the FB group exhibited significant improvement in comparison to the shampoo group after 1 month of trial. There were no significant changes in PVAS scores in either group. No significant difference was found in skin barrier function parameters between the two treatments, although TEWL slightly decreased in the FB group and slightly increased in the shampoo group after treatment., Conclusions and Clinical Relevance: These results suggested that FB treatment provides benefits for dogs with AD and offers an alternative topical treatment option with a lesser impact on skin barrier function compared to frequent shampooing., (© 2024 Vet Derm Tokyo Dermatological and Laboratory Service for Animals. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of ESVD and ACVD.)

Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer; therefore, new therapeutic approaches are required to improve the prognosis of LSCC. Although immunotherapies targeting B7 family molecules were explored as treatments for several cancer types, the expression and significance of B7-H3 in the tumor microenvironment (TME) and its relationship with other immune checkpoint molecules have not yet been investigated in detail. We used high-throughput quantitative multiplex immunohistochemistry to examine B7-H3 expression in the TME. We investigated the relationship between B7-H3 expression and prognosis as well as changes in the TME with B7-H3 expression using 110 surgically resected pathological specimens retrospectively. We examined the correlation between B7-H3 and programmed cell death-ligand 1 (PD-L1) expression in single cells. High B7-H3 expression in tumor cells was associated with a better prognosis and a significant increase in the number of CD163 + PD-L1 + macrophages. Quantitative analysis revealed that there is a positive correlation between B7-H3 and PD-L1 expression in tumor and stromal cells, as well as in intratumoral tumor-infiltrating lymphocytes and tumor-associated macrophages in the same cells. CD68 + , CD163 + , and CK + cells with PD-L1 + phenotypes had higher B7-H3 expression compared to PD-L1 - cells. Our findings demonstrate a correlation between B7-H3 and PD-L1 expression in the same cells, indicating that therapies targeting B7-H3 could provide additional efficacy in patients refractory to PD-L1-targeting therapies.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. New therapeutic strategies are needed for the treatment of refractory DLBCL. 4-Hydroxy-2-nonenal (4-HNE) is a cytotoxic lipid peroxidation marker, which alters intracellular signaling and induces genetic mutations. Lipid peroxidation is associated with nonapoptotic cell death, called ferroptosis. However, the relationship between 4-HNE accumulation and feroptotic regulators in DLBCL has not been fully evaluated. Here, we aimed to evaluate the accumulation of lipid peroxide and the expression of ferroptosis suppressor protein 1 (FSP1) in DLBCL using immunohistochemistry. We found a significant increase in the expression of FSP1 in cases with nuclear 4-HNE accumulation (P = .021). Both nuclear and cytoplasmic 4-HNE accumulation and FSP1 positivity were independent predictors of worse prognosis. In vitro exposure to 4-HNE resulted in its concentration- and time-dependent intracellular accumulation and increased expression of FSP1. Furthermore, short-term (0.25 and 1.0 μM) or long-term (0.25 μM) exposure to 4-HNE induced resistance to not only apoptosis but also ferroptosis. Taken together, regulation of FSP1 through 4-HNE accumulation may attenuate resistance to cell death in treatment-resistant DLBCL and might help develop novel therapeutic strategies for refractory DLBCL., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

A woman in her 70s, initially suspected of having fibroadenoma due to a well-defined mass in her breast, underwent regular mammography and ultrasound screenings. Over several years, no appreciable alterations in the mass were observed, maintaining the fibroadenoma diagnosis. However, in the fourth year, an ultrasound indicated slight enlargement and peripheral irregularities in the mass, even though the mammography images at that time showed no alterations. Interestingly, mammography images over time showed the gradual disappearance of previously observed arterial calcification around the mass. Pathological examination eventually identified the mass as invasive ductal carcinoma. Although the patient had breast tissue arterial calcification typical of atherosclerosis, none was present around the tumor-associated arteries. This case highlights the importance of monitoring arterial calcification changes in mammography, suggesting that they are crucial indicators in breast cancer diagnosis, beyond observing size and shape alterations.

Objectives: The aim is to evaluate the prevention and development of cervical cancer in systemic lupus erythematosus (SLE) patients in Japan and its background based on a questionnaire survey., Methods: The questionnaire was handed to 460 adult female SLE patients at 12 medical institutions. The participants were grouped by age, and data related to their human papillomavirus vaccination status, age at first coitus, cervical cancer screening, and diagnosis of cervical cancer were analysed., Results: A total of 320 responses were received. Patients aged 35-54 years included a higher proportion of patients whose age at first coitus was <20 years. This group also showed a higher rate of cervical cancer/dysplasia. Only nine patients had a human papillomavirus vaccination history. Adequate frequency of cervical cancer screening was slightly higher (52.1%) among SLE patients than in the Japanese general population. However, 23% of the patients had never undergone examination, primarily because of a feeling of troublesome. The incidence of cervical cancer was significantly higher among SLE patients. One reason for this may be associated with the use of immunosuppressants, although the difference was not significant., Conclusions: SLE patients are at a higher risk of cervical cancer and dysplasia. Rheumatologists should proactively recommend vaccination and screening examinations for SLE female patients., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In normal intestines, a fetal/regenerative/revival cell state can be induced upon inflammation. This plasticity in cell fate is also one of the current topics in human colorectal cancer (CRC). To dissect the underlying mechanisms, we generated human CRC organoids with naturally selected genetic mutation profiles and exposed them to two different conditions by modulating the extracellular matrix (ECM). Among tested mutation profiles, a fetal/regenerative/revival state was induced following YAP activation via a collagen type I-enriched microenvironment. Mechanistically, YAP transcription was promoted by activating AP-1 and TEAD-dependent transcription and suppressing intestinal lineage-determining transcription via mechanotransduction. The phenotypic conversion was also involved in chemoresistance, which could be potentially resolved by targeting the underlying YAP regulatory elements, a potential target of CRC treatment., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: Cardiac amyloidosis is a fatal disease of severe heart failure caused by the accumulation of amyloid in the myocardium. This disease is often advanced by the time cardiac symptoms appear; therefore, early detection and treatment are critical for a good prognosis. Recently, it has been suggested that cardiac amyloidosis is implicated in several orthopedic diseases, including carpal tunnel syndrome (CTS), which is often reported to precede cardiac dysfunction. Shoulder disease has also been suggested to be associated with cardiac amyloidosis; however, there have been no reports investigating the rate of amyloid deposition in shoulder specimens and the simultaneous prevalence of cardiac amyloidosis. Herein, we investigated the prevalence of intraoperative specimen amyloid deposition and cardiac amyloidosis in shoulder disease and CTS to determine the usefulness of shoulder specimen screening as a predictor of cardiac amyloidosis development., Methods: A total of 41 patients undergoing arthroscopic shoulder surgery and 33 patients undergoing CTS surgery were enrolled in this study. The shoulder group included rotator cuff tears, contracture of the shoulder, synovitis, and calcific tendonitis. In the shoulder group, a small sample of synovium and the long head of the biceps brachii tendon were harvested, while the transverse carpal ligament was harvested from the CTS group. The intraoperative specimens were pathologically examined for amyloid deposition, and patients with amyloid deposition were examined for the presence of cardiac amyloidosis by cardiac evaluation., Results: In the shoulder group, three cases (7.3%) of transthyretin amyloid deposition were found, all of which involved rotator cuff tears. None of these three cases with amyloid deposition were associated with cardiac amyloidosis. When examining the specimens, the amyloid deposition rate in the long head of the biceps brachii tendon was higher than that in the synovium. In the CTS group, 12 cases (36.4%) of transthyretin amyloid deposition were observed. Of these cases, seven underwent cardiac evaluation and two were identified with cardiac amyloidosis., Conclusion: While the prevalence of amyloid deposition and cardiac amyloidosis in the CTS group was consistent with previous reports, the shoulder group showed a lower deposition rate and no concomitant cardiac amyloidosis. Therefore, it remains debatable whether investigating amyloid deposition in samples obtained from shoulder surgery is beneficial for the early detection of cardiac amyloidosis., (© 2023 The Authors.)

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) is useful for preoperatively diagnosing various pancreatic tumors. Although there is a risk of complications, such as pancreatitis, this procedure achieves the crucial need of reducing unnecessary invasive surgery for benign lesions. Herein, we reported a surgically resected case of pancreatic hamartoma in the pancreatic head whose retrospective analysis revealed that the specimens obtained via EUS-FNAB contained hamartoma fragments. Pancreatic hamartoma is an extremely rare benign disease that is exceptionally difficult to diagnose before surgical resection owing to its rarity and lack of established imaging findings. To the best of our knowledge, the preoperative diagnosis of pancreatic hamartoma via EUS-FNAB specimens has not been reported to date. Herein, postoperative EUS-FNAB evaluation revealed a collection of pancreatic hamartoma lesions, although the initial diagnosis was pancreatic tissue with focal atrophy and fibrosis. Diagnosis using EUS-FNAB can be challenging owing to the very small sample size. If mature acini and ducts with fibrous stroma without islets are observed in the EUS-FNAB specimen, pancreatic hamartoma should be considered as a differential diagnosis. Thus, careful follow-up or reexamination of EUS-FNAB should be considered instead of surgery if a benign lesion is suspected preoperatively., (© 2023 Wiley Periodicals LLC.)

Accumulation of 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation, has various favorable and unfavorable effects on cancer cells; however, the clinicopathological significance of its accumulation in hepatocellular carcinoma (HCC) and its metabolic pathway remain unknown. This study analyzed 4-HNE accumulation and its clinicopathological significance in HCC. Of the 221 cases, 160 showed relatively low accumulation of 4-HNE in HCC tissues, which was an independent prognostic predictor. No correlation was found between 4-HNE accumulation and the expression of the antioxidant enzymes glutathione peroxidase 4, ferroptosis suppressor protein 1, and guanosine triphosphate cyclohydrolase 1. Therefore, we hypothesized that 4-HNE metabolism is up-regulated in HCC. A database search was focused on the transcriptional regulation of aldo-keto reductases, alcohol dehydrogenases, and glutathione-S-transferases, which are the metabolic enzymes of 4-HNE, and seven candidate transcription factor genes were selected. Among the candidate genes, the knockdown of SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4) increased 4-HNE accumulation. Immunohistochemical analysis revealed an inverse correlation between 4-HNE accumulation and SMARCA4 expression. These results suggest that SMARCA4 regulates 4-HNE metabolism in HCC. Therefore, targeting SMARCA4 provides a basis for a new therapeutic strategy for HCC via 4-HNE accumulation and increased cytotoxicity.

Comprehensive screenings to clarify indirect cell-cell interactions, such as those in the tumor microenvironment, especially comprehensive assessments of supporting cells' effects, are challenging. Therefore, in this study, indirect CRISPR screening for drug resistance with cell-cell interactions was invented. The photoconvertible fluorescent protein Dendra2 was inducted to supporting cells and explored the drug resistance responsible factors of supporting cells with CRISPR screenings. Random mutated supporting cells co-cultured with leukemic cells induced drug resistance with cell-cell interactions. Supporting cells responsible for drug resistance were isolated with green-to-red photoconversion, and 39 candidate genes were identified. Knocking out C9orf89, MAGI2, MLPH, or RHBDD2 in supporting cells reduced the ratio of apoptosis of cancer cells. In addition, the low expression of RHBDD2 in supporting cells, specifically fibroblasts, of clinical pancreatic cancer showed a shortened prognosis, and a negative correlation with CXCL12 was observed. Indirect CRISPR screening was established to isolate the responsible elements of cell-cell interactions. This screening method could reveal unknown mechanisms in all kinds of cell-cell interactions by revealing live phenotype-inducible cells, and it could be a platform for discovering new targets of drugs for conventional chemotherapies., (© 2023. The Author(s).)

Purpose: To retrospectively compare the clinical and pathological characteristics of breast masses and non-mass lesions that underwent ultrasound (US)-guided 16-gauge spring-loaded core needle biopsy (CNB) or 12-gauge spring-loaded vacuum-assisted biopsy (VAB)., Methods: We retrospectively compared the results from US-guided diagnostic breast biopsy performed with a 16-gauge CNB (Magnum™) or a 12-gauge VAB (Celero ® ). The patients' backgrounds and pathological features for each device were examined., Results: In 453 patients with 500 lesions, 373 lesions underwent CNB and 127 underwent VAB. The positive biopsy rate (positive predictive value 3) was significantly higher for VAB (92/127; 72.4%) than for CNB (231/373; 61.9%) (P = 0.032). Non-mass lesions were biopsied more frequently with VAB (57/127; 47.4%) than with CNB (27/378; 7.14%) (P = 0.000). The upgrade rate from high-risk to malignant lesions was significantly higher for CNB (5/19; 26.3%) than for VAB (1/8; 12.5%) (P = 0.043). There were five (1.34%) specimen failures with CNB and one (0.78%) with VAB, 18 (4.82%) re-biopsies with CNB and three (2.36%) with VAB, and 11/21 (52.4%) upgrades from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) with CNB and 11/30 (36.7%) with VAB. Although these rates tended to be higher with CNB than with VAB, the difference was not significant., Conclusion: Although VAB had a significantly higher rate of non-mass lesion biopsies, the upgrade rate from high-risk to malignant lesions was significantly lower for VAB than for CNB. US-guided 12-gauge spring-loaded VAB may be more appropriate for biopsy of non-mass lesions., (© 2023. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

We investigated whether 18 F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography images restored via deep learning (DL) improved image quality and affected axillary lymph node (ALN) metastasis diagnosis in patients with breast cancer. Using a five-point scale, two readers compared the image quality of DL-PET and conventional PET (cPET) in 53 consecutive patients from September 2020 to October 2021. Visually analyzed ipsilateral ALNs were rated on a three-point scale. The standard uptake values SUV max and SUV peak were calculated for breast cancer regions of interest. For "depiction of primary lesion", reader 2 scored DL-PET significantly higher than cPET. For "noise", "clarity of mammary gland", and "overall image quality", both readers scored DL-PET significantly higher than cPET. The SUV max and SUV peak for primary lesions and normal breasts were significantly higher in DL-PET than in cPET ( p < 0.001). Considering the ALN metastasis scores 1 and 2 as negative and 3 as positive, the McNemar test revealed no significant difference between cPET and DL-PET scores for either reader ( p = 0.250, 0.625). DL-PET improved visual image quality for breast cancer compared with cPET. SUV max and SUV peak were significantly higher in DL-PET than in cPET. DL-PET and cPET exhibited comparable diagnostic abilities for ALN metastasis.