Phase 1 trial of 4-1BB-based adoptive T-cell therapy targeting human telomerase reverse transcriptase in patients with advanced refractory solid tumors.

BACKGROUND AIMS: Human telomerase reverse transcriptase (hTERT) is an attractive target for anti-cancer therapies. We developed an effective method for generating hTERT-specific CD8+ T cells (hTERT-induced natural T cells [TERTiNTs]) using peripheral blood mononuclear cells (PBMCs) from patients with solid cancers and investigated their feasibility and safety. METHODS: This was a single-center phase 1 trial using a 3 + 3 dose escalation design to evaluate six dose levels of TERTiNTs. PBMCs from each patient were screened using an hTERT peptide panel to select those that stimulated CD8+ T cells. The four most stimulatory peptides were used to produce autologous CD8+ T cells from patients refractory or intolerant to standard therapies. Eligible patients received a single intravenous infusion of TERTiNTs at different dose levels (4 × 108 cells/m2, 8 × 108 cells/m2 and 16 × 108 cells/m2). Pre-conditioning chemotherapy, including cyclophosphamide alone or in combination with fludarabine, was administered to induce lymphodepletion. RESULTS: From January 2014 to October 2019, a total of 24 patients with a median of three prior lines of therapy were enrolled. The most common adverse events were lymphopenia (79.2%), nausea (58.3%) and neutropenia (54.2%), mostly caused by pre-conditioning chemotherapy. The TERTiNT infusion was well tolerated, and dose-limiting toxicities were not observed. None of the patients showed objective responses. Seven patients (30.4%) achieved stable disease with a median progression-free survival of 3.9 months (range, 3.2-11.3). At the highest dose level (16 × 108 cells/m2), four of five patients showed disease stabilization. CONCLUSIONS: The generation of TERTiNTs was feasible and safe and provided an interesting disease control rate in heavily pre-treated cancer patients.

Cross-Activation of Regulatory T Cells by Self Antigens Limits Self-Reactive and Activated CD8+ T Cell Responses.

The interaction between regulatory T (Treg) cells and self-reactive T cells is a crucial mechanism for maintaining immune tolerance. In this study, we investigated the cross-activation of Treg cells by self-antigens and its impact on self-reactive CD8+ T cell responses, with a focus on the P53 signaling pathway. We discovered that major histocompatibility complex (MHC) I-restricted self-peptides not only activated CD8+ T cells but also induced the delayed proliferation of Treg cells. Following HLA-A*0201-restricted Melan-A-specific (pMelan) CD8+ T cells, we observed the direct expansion of Treg cells and concurrent suppression of pMelan+CD8+ T cell proliferation upon stimulation with Melan-A peptide. Transcriptome analysis revealed no significant alterations in specific signaling pathways in pMelan+CD8+ T cells that were co-cultured with activated Treg cells. However, there was a noticeable upregulation of genes involved in P53 accumulation, a critical regulator of cell survival and apoptosis. Consistent with such observation, the blockade of P53 induced a continuous proliferation of pMelan+CD8+ T cells. The concurrent stimulation of Treg cells through self-reactive TCRs by self-antigens provides insights into the immune system's ability to control activated self-reactive CD8+ T cells as part of peripheral tolerance, highlighting the intricate interplay between Treg cells and CD8+ T cells and implicating therapeutic interventions in autoimmune diseases and cancer immunotherapy.

Seminal Plasma-Derived Extracellular-Vesicle Fractions from HIV-Infected Men Exhibit Unique MicroRNA Signatures and Induce a Proinflammatory Response in Cells Isolated from the Female Reproductive Tract.

The continuing spread of HIV/AIDS is predominantly fueled by sexual exposure to HIV-contaminated semen. Seminal plasma (SP), the liquid portion of semen, harbors a variety of factors that may favor HIV transmission by facilitating viral entry into host cells, eliciting the production of proinflammatory cytokines, and enhancing the translocation of HIV across the genital epithelium. One important and abundant class of factors in SP is extracellular vesicles (EVs), which, in general, are important intercellular signal transducers. Although numerous studies have characterized blood plasma-derived EVs from both uninfected and HIV-infected individuals, little is known about the properties of EVs from the semen of HIV-infected individuals. We report here that fractionated SP enriched for EVs from HIV-infected men induces potent transcriptional responses in epithelial and stromal cells that interface with the luminal contents of the female reproductive tract. Semen EV fractions from acutely infected individuals induced a more proinflammatory signature than those from uninfected individuals. This was not associated with any observable differences in the surface phenotypes of the vesicles. However, microRNA (miRNA) expression profiling analysis revealed that EV fractions from infected individuals exhibit a broader and more diverse profile than those from uninfected individuals. Taken together, our data suggest that SP EVs from HIV-infected individuals exhibit unique miRNA signatures and exert potent proinflammatory transcriptional changes in cells of the female reproductive tract, which may facilitate HIV transmission.IMPORTANCE Seminal plasma (SP), the major vehicle for HIV, can modulate HIV transmission risk through a variety of mechanisms. Extracellular vesicles (EVs) are extremely abundant in semen, and because they play a key role in intercellular communication pathways and immune regulation, they may impact the likelihood of HIV transmission. However, little is known about the properties and signaling effects of SP-derived EVs in the context of HIV transmission. Here, we conduct a phenotypic, transcriptomic, and functional characterization of SP and SP-derived EVs from uninfected and HIV-infected men. We find that both SP and its associated EVs elicit potent proinflammatory transcriptional responses in cells that line the genital tract. EVs from HIV-infected men exhibit a more diverse repertoire of miRNAs than EVs from uninfected men. Our findings suggest that EVs from the semen of HIV-infected men may significantly impact the likelihood of HIV transmission through multiple mechanisms.

RELT negatively regulates the early phase of the T-cell response in mice.

RELT (tumor necrosis factor receptor superfamily member 19-like, TNFRSF19L) is a TNFR superfamily member that is primarily expressed in immune cells and lymphoid tissues, but whose immunological function is not well-defined. Here, we show that RELT is expressed by naive T cells and DCs, and their activation or maturation decreases RELT expression. Using RELT knockout (RELT-/- ) mice, we demonstrate that RELT deficiency selectively promotes the homeostatic proliferation of CD4+ T cells but not CD8+ T cells, and enhances anti-tumor CD8+ T-cell responses. We also demonstrate, using an adoptive transfer model in which RELT is knocked-out in either the transferred transgenic CD8+ T cells or the recipient melanoma-bearing mice, that RELT on multiple immune cells limits the hyper-response of tumor-specific CD8+ T cells. Hyper-responsiveness of RELT-deficient T cells was induced by promoting their proliferation. Taken together, our findings suggest that RELT acts as a negative regulator that controls the early phase of T-cell activation probably by promoting T-cell apoptosis.

In vivo 4-1BB deficiency in myeloid cells enhances peripheral T cell proliferation by increasing IL-15.

4-1BB signals are considered positive regulators of T cell responses against viruses and tumors, but recent studies suggest that they have more complex roles in modulating T cell responses. Although dual roles of 4-1BB signaling in T cell responses have been suggested, the underlying mechanisms are still not fully understood. In this study, we tested whether 4-1BB expression affected T cell responses differently when expressed in myeloid versus lymphoid cells in vivo. By assessing the proliferation of 4-1BB(+/+) and 4-1BB(-/-) T cells in lymphocyte-deficient RAG2(-/-) and RAG2(-/-)4-1BB(-/-) mice, we were able to compare the effects on T cell responses of 4-1BB expression on myeloid versus T cells. Surprisingly, adoptively transferred T cells were more responsive in tumor-bearing RAG2(-/-)4-1BB(-/-) mice than in RAG2(-/-) mice, and this enhanced T cell proliferation was further enhanced if the T cells were 4-1BB deficient. Dendritic cells (DCs) rather than NK or tissue cells were the myeloid lineage cells primarily responsible for the enhanced T cell proliferation. However, individual 4-1BB(-/-) DCs were less effective in T cell priming in vivo than 4-1BB(+/+) DCs; instead, more DCs in the secondary lymphoid organs of RAG2(-/-)4-1BB(-/-) mice appeared to induce the enhanced T cell proliferation by producing and transpresenting more IL-15. Therefore, we conclude that in vivo 4-1BB signaling of myeloid cells negatively regulates peripheral T cell responses by limiting the differentiation of DCs and their accumulation in secondary lymphoid organs.

Authentic GITR Signaling Fails To Induce Tumor Regression unless Foxp3+ Regulatory T Cells Are Depleted.

The glucocorticoid-induced TNFR family-related protein (GITR, TNFRSF18, CD357) is expressed on effector and regulatory T (Treg) cells. Previous studies demonstrated that GITR triggering by anti-GITR mAb enhanced T and B cell-mediated immune responses. GITR-deficient T cells, however, also proliferate more than normal T cells, and this effect is unexplained. Because the activities of mAbs are controlled by their Fc regions, the true effect of GITR signaling needs to be determined by examining its interaction with authentic ligand. Therefore, we generated a pentamerized form of the GITRL extracellular domain (pGITRL) for ligation to GITR and compared its effect on T cells with that of anti-GITR mAb. The pGITRL was more effective than anti-GITR mAb in enhancing the proliferation of effector and regulatory cells in vitro and in vivo. Nonetheless, the growth of MC38 adenocarcinoma cells in vivo was only suppressed for initial 15 d by pGITRL, whereas it was suppressed indefinitely by anti-GITR mAb. Detailed analysis revealed that pGITRL induced extensive proliferation of Foxp3(+)CD4(+) Treg cells and led to the accumulation of activated Treg cells in tumor tissue and draining lymph nodes. Because GITR signaling could not neutralize the suppressive activity of activated Treg cells, pGITRL seems to lose its adjuvant effect when sufficient activated Treg cells have accumulated in the lymph nodes and tumor tissue. Indeed, the antitumor effects of pGITRL were markedly enhanced by depleting CD4(+) cells. These results suggest that GITR signaling has stimulatory effects on effector T cells and inhibitory effects through Treg cells.

CRIg signals induce anti-intracellular bacterial phagosome activity in a chloride intracellular channel 3-dependent manner.

Macrophages provide a first line of defense against bacterial infection by engulfing and killing invading bacteria, but intracellular bacteria such as Listeria monocytogenes (LM) can survive in macrophages by various mechanisms of evasion. Complement receptor of the immunoglobulin (CRIg), a C3b receptor, binds to C3b on opsonized bacteria and facilitates clearance of the bacteria by promoting their uptake. We found that CRIg signaling induced by agonistic anti-CRIg mAb enhanced the killing of intracellular LM by macrophages, and that this occurred in LM-containing phagosomes. Chloride intra-cellular channel 3 CLIC3, an intracellular chloride channel protein, was essential for CRIg-mediated LM killing by directly interacting with the cytoplasmic domain of CRIg, and the two proteins colocalized on the membranes of LM-containing vacuoles. CLIC3(-/-) mice were as susceptible to LM as CRIg(-/-) mice. These findings identify a mechanism embedded in the process by which macrophages take up opsonized bacteria that prevents the bacteria from evading cell-mediated killing.

4-1BB signal stimulates the activation, expansion, and effector functions of γδ T cells in mice and humans.

We show here that the expression of 4-1BB is rapidly induced in γδ T cells following antigenic stimulation in both mice and humans, and ligation of the newly acquired 4-1BB with an agonistic anti-4-1BB augments cell division and cytokine production. We further demonstrate that γδ rather than αß T cells protect mice from Listeria monocytogenes (LM) infection and 4-1BB stimulation enhances the γδ T-cell activities in the acute phase of LM infection. IFN-γ produced from γδ T cells was the major soluble factor regulating LM infection. Vγ1(+) T cells were expanded in LM-infected mice and 4-1BB signal triggered an exclusive expansion of Vγ1(+) T cells and induced IFN-γ in these Vγ1(+) T cells. Similarly, 4-1BB was induced on human γδ T cells and shown to be fully functional. Combination treatment with human γδ T cells and anti-hu4-1BB effectively protected against LM infection in human γδ T cell-transferred NOD-SCID mice. Taken together, these data provide evidence that the 4-1BB signal is an important regulator of γδ T cells and induces robust host defense against LM infection.

Evaluation of ChatGPT and Google Bard Using Prompt Engineering in Cancer Screening Algorithms.

Large language models (LLMs) such as ChatGPT and Bard have emerged as powerful tools in medicine, showcasing strong results in tasks such as radiology report translations and research paper drafting. While their implementation in clinical practice holds promise, their response accuracy remains variable. This study aimed to evaluate the accuracy of ChatGPT and Bard in clinical decision-making based on the American College of Radiology Appropriateness Criteria for various cancers. Both LLMs were evaluated in terms of their responses to open-ended (OE) and select-all-that-apply (SATA) prompts. Furthermore, the study incorporated prompt engineering (PE) techniques to enhance the accuracy of LLM outputs. The results revealed similar performances between ChatGPT and Bard on OE prompts, with ChatGPT exhibiting marginally higher accuracy in SATA scenarios. The introduction of PE also marginally improved LLM outputs in OE prompts but did not enhance SATA responses. The results highlight the potential of LLMs in aiding clinical decision-making processes, especially when guided by optimally engineered prompts. Future studies in diverse clinical situations are imperative to better understand the impact of LLMs in radiology.

4-1BB triggering ameliorates experimental autoimmune encephalomyelitis by modulating the balance between Th17 and regulatory T cells.

Agonistic anti-4-1BB Ab is known to ameliorate experimental autoimmune encephalomyelitis. 4-1BB triggering typically leads to the expansion of CD8(+) T cells, which produce abundant IFN-γ, and this in turn results in IDO-dependent suppression of autoimmune responses. However, because neutralization of IFN-γ or depletion of CD8(+) T cell only partially abrogates the effect of 4-1BB triggering, we sought to identify an additional mechanism of 4-1BB-triggered suppression of autoimmune responses using IFN-γ- or IFN-γR-deficient mice. 4-1BB triggering inhibited the generation of Th17 cells that is responsible for experimental autoimmune encephalomyelitis induction and progression, and increased Foxp3(+)CD4(+) regulatory T (Treg) cells, particularly among CD4(+) T cells. This was not due to a direct effect of 4-1BB signaling on CD4(+) T cell differentiation: 4-1BB signaling not only reduced Th17 cells and increased Treg cells in wild-type mice, which could be due to IFN-γ production by the CD8(+) T cells, but also did so in IFN-γ-deficient mice, in that case by downregulating IL-6 production. These results show that although secondary suppressive mechanisms evoked by 4-1BB triggering are usually masked by the strong effects of IFN-γ, 4-1BB signaling seems to modulate autoimmune responses by a number of mechanisms, and modulation of the Th17 versus Treg cell balance is one of those mechanisms.

Short-term clinical outcomes for 100 consecutive cases of laparoscopic pylorus-preserving pancreatoduodenectomy: improvement with surgical experience.

BACKGROUND: Few reports describe the use of laparoscopic pylorus-preserving pancreaticoduodenectomy (LPPPD) in centers with experience using this technique. In addition, the clinical outcomes of this procedure remain undetermined. METHODS: In the current study, 100 patients with benign or malignant lesions in the pancreatic head underwent LPPPD between May 2007 and December 2011. The overall clinical outcomes and changes in these outcomes during the surgeon learning period were analyzed to assess the feasibility and safety of this procedure. RESULTS: Pathologic examination of the pancreas confirmed intraductal papillary mucinous neoplasms in 37 patients, solid pseudopapillary tumors in 17 patients, neuroendocrine tumors in 15 patients, serous cystic neoplasms in seven patients, pancreatic ductal adenocarcinomas in seven patients, ampulla of Vater tumors and duodenal gastrointestinal stromal tumors in five patients, and other disease in seven patients. The median operative time was 7.9 h, which decreased with accumulating experience of the surgeon using this procedure, from 9.8 h for the first 33 cases to 6.6 h for the last 34 cases. Complications developed in 25% of the patients, including six cases (6%) with significant pancreatic fistula [International Study Group on Pancreatic Fistula (ISGPF) grade B]. The complication rate decreased from 33.3% for the first 33 cases to 17.6% for the last 34 cases. The mean hospital stay was 14 days, which also decreased from 20.4 days for the first 33 cases to 11.5 days for the last 34 cases. For the 12 patients in the study cohort with invasive malignant disease, the median tumor size was 2.8 cm, and the median number of lymph nodes harvested was 13. All the patients had margin-negative R0 resections. CONCLUSION: The LPPPD procedure is technically safe and feasible, with an acceptable rate of morbidity and other clinical outcomes for benign and malignant diseases. Clinical outcomes can be improved once a learning curve has been overcome.

A novel ultrasonic inspection method of the heat exchangers based on circumferential waves and deep neural networks.

The heat exchanger (HE) is an important component of almost every energy generation system. Periodic inspection of the HEs is particularly important to keep high efficiency of the entire system. In this paper, a novel ultrasonic water immersion inspection method is presented based on circumferential wave (CW) propagation to detect defective HE. Thin patch-type piezoelectric elements with multiple resonance frequencies were adopted for the ultrasonic inspection of narrow-spaced HE in an immersion test. Water-filled HE was used to simulate defective HE because water is the most reliable indicator of the defect. The HE will leak water no matter what the defect pattern is. Furthermore, continuous wavelet transform (CWT) was used to investigate the received CW, and inverse CWT was applied to separate frequency bands corresponding to the thickness and lateral resonance modes of the piezoelectric element. Different arrangements of intact and leaky HE were tested with several pairs of thin piezoelectric patch probes in various instrumental setups. Also, direct waveforms in the water without HE were used as reference signals, to indicate instrumental gain and probe sensitivity. Moreover, all filtered CW corresponding to resonance modes together with the direct waveforms in the water were used to train the deep neural networks (DNNs). As a result, an automatic HE state classification method was obtained, and the accuracy of the applied DNN was estimated as 99.99%.

Screening adequacy of unstained thyroid fine needle aspiration samples using a deep learning-based classifier.

Fine needle aspiration (FNA) biopsy of thyroid nodules is a safe, cost-effective, and accurate diagnostic method for detecting thyroid cancer. However, about 10% of initial FNA biopsy samples from patients are non-diagnostic and require repeated FNA, which delays the diagnosis and appropriate care. On-site evaluation of the FNA sample can be performed to filter out non-diagnostic FNA samples. Unfortunately, it involves a time-consuming staining process, and a cytopathologist has to be present at the time of FNA. To bypass the staining process and expert interpretation of FNA specimens at the clinics, we developed a deep learning-based ensemble model termed FNA-Net that allows in situ screening of adequacy of unstained thyroid FNA samples smeared on a glass slide which can decrease the non-diagnostic rate in thyroid FNA. FNA-Net combines two deep learning models, a patch-based whole slide image classifier and Faster R-CNN, to detect follicular clusters with high precision. Then, FNA-Net classifies sample slides to be non-diagnostic if the total number of detected follicular clusters is less than a predetermined threshold. With bootstrapped sampling, FNA-Net achieved a 0.81 F1 score and 0.84 AUC in the precision-recall curve for detecting the non-diagnostic slides whose follicular clusters are less than six. We expect that FNA-Net can dramatically reduce the diagnostic cost associated with FNA biopsy and improve the quality of patient care.

Ultrasonic tomography imaging enhancement approach based on deep convolutional neural networks.

Abstract: The containment liner plate (CLP) is a thin layer of carbon steel material applied as a base for concrete structures protecting nuclear material. The structural health monitoring of the CLP is critical to ensure the safety of nuclear power plants. Hidden defects in the CLP can be identified utilizing ultrasonic tomographic imaging techniques such as the reconstruction algorithm for the probabilistic inspection of damage (RAPID) methodology. However, Lamb waves have a multimodal dispersion feature, which makes the selection of a single mode more difficult. Thus, sensitivity analysis was utilized since it allows for the determination of each mode's level of sensitivity as a function of frequency; the S0 mode was chosen after examining the sensitivity. Even though proper Lamb wave mode was selected, the tomographic image had blurred zones. Blurring reduces the precision of an ultrasonic image and makes it more difficult to distinguish the dimensions of the flaw. To enhance the tomographic image of the CLP, deep learning architecture such as U-Net was utilized for the segmentation of the experimental ultrasonic tomographic image, which includes an encoder and decoder part for better visualization of the tomographic image. Nevertheless, collecting enough ultrasonic images to train the U-Net model was not economically feasible, and only a small number of the CLP specimens can be tested. Thus, it was necessary to utilize transfer learning and get the values of the parameters from a pre-trained model with a much larger dataset as a starting point for a new task, rather than training a new model from scratch. Through these deep learning approaches, we were able to eliminate the blurred section of the ultrasonic tomography, leading to images with clear edges of defects and no blurred zones.

Determination of cystic duct patency using hepatobiliary MRI with gadoxetate disodium: is T1 precontrast imaging necessary?

PURPOSE: To determine the need for precontrast T1-weighted imaging in determining cystic duct patency using hepatobiliary phase imaging with gadoxetate disodium-enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: MRI exams using gadoxetate disodium from October 4, 2008 to April 14, 2010 were reviewed in a retrospective fashion. Two reviewers independently reviewed only the 20-minute T1-weighted delayed postcontrast images to determine the presence of excreted contrast in the gallbladder lumen. Contrast was deemed present if hyperintense signal material was seen in the antidependent portion of the gallbladder lumen. The actual presence of contrast in the gallbladder was determined by directly comparing the pre- and postcontrast T1-weighted images using consensus review. RESULTS: In all, 187 cases were included. Three (1.6%) were deemed indeterminate due to complete homogeneous opacification of the gallbladder. All three cases were identified as indeterminate by both reviewers. Of the remaining 184 cases, 136 filled (74%) and 48 did not fill (26%). Both reviewers correctly identified 136/136 cases of gallbladder filling. Reviewer A identified 47/48 cases of nonfilling and reviewer B identified 46/48 cases of nonfilling. Sensitivity and specificity were 100% and 98% for reviewer A and 100% and 96% for reviewer B, respectively. CONCLUSION: The presence of excreted contrast in the gallbladder lumen can be determined using gadoxetate disodium-enhanced MRI without precontrast T1-weighted imaging.

Formation of Ag nanostrings induced by lyotropic liquid-crystalline phospholipid multilayer.

Morphological variation of the Ag nanoparticles embedded in a lyotropic phospholipid (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, DOPE) membrane during hydration was investigated. Hydration at 5 °C resulted in transformation of the Ag nanoparticles into a bundle of Ag nanostrings as the Ag nanoparticles conformed to the H(II) phase of the DOPE molecules. Above 30 °C, the nanoparticles quickly coarsened into large polygonal-shaped particles since high mobility of the lipid molecules overwhelmed the tendency for the Ag nanoparticles to order. The result provided an insight into the long-term stability of nanoparticles trapped in different lipid membranes depending on the structural ordering of the molecules.

Peripheral 4-1BB signaling negatively regulates NK cell development through IFN-gamma.

Stimulation of 4-1BB (CD137) was shown to produce strong anticancer effects in vivo. In contrast, 4-1BB-deficient (4-1BB(-/-)) B6 mice are remarkably resistant to tumor growth. We set out to determine the mechanisms involved in these seemingly contradictory observations. We found that the therapeutic effects of 4-1BB triggering were mainly dependent on CD8(+) T cells and partially on NK cells, whereas CD8(+) T and NK cells were equally needed to suppress tumor growth in 4-1BB(-/-) mice. Cellular analysis showed that the frequency and number of NK cells in the spleen and bone marrow were decreased by 4-1BB triggering but were increased in the absence of 4-1BB signaling in tumor-challenged mice. The 4-1BB-mediated downregulation of NK cell development was primarily dependent on IFN-gamma, which was produced by peripheral CD8(+) T and NK cells. The suppression of NK cell development by 4-1BB-mediated IFN-gamma production occurred in the bone marrow. As 4-1BB signaling increased in the periphery, more CD8(+) T cells but fewer NK cells contributed to the antitumor immunity. As 4-1BB signaling decreased, more NK cells participated in the antitumor immunity. We conclude that 4-1BB signaling results in a shift of the dominant type of immune cell in antitumor immunity from the innate NK cell to the adaptive CD8(+) T cell and that the level of IFN-gamma is critical for this 4-1BB-mediated shift.

Defect Detection and Characterization in Concrete Based on FEM and Ultrasonic Techniques.

In order to estimate the crack depth in concrete using time-of-flight, finite element analysis and experiments were performed on non-cracked concrete blocks and 45 mm and 70 mm vertical cracks. As a result of measuring the time-of-flight change by changing the positions of the transmitter and receiver, it was confirmed that the finite element analysis results agreed with the experimental results, and high accuracy was confirmed by various formulas for calculating the depth of defects using the obtained experimental measurements for comparison. In addition to the verification of the simulation and experimental theory, research was conducted through actual field cases, and methodologies for crack detection and depth evaluation for concrete structures were presented, and furthermore, the expected effects of improving the soundness and safety of structures were shown.

Ultrasonographic evaluation of patients with abnormal liver function tests in the emergency department.

Ultrasonography is often the initial modality used to evaluate patients found to have abnormal liver function tests (LFTs) in the emergency department. While an assessment for biliary ductal dilatation and obstruction remains one of the main questions to answer, radiologists should also be aware of the ultrasonographic appearance of other conditions that can cause abnormal LFTs. This may be crucial for the management and disposition of patients in the emergency department. This article reviews the ultrasonographic features of diseases that may cause abnormal LFTs.

Pelvic ultrasonography of the postpartum uterus in patients presenting to the emergency room with vaginal bleeding and pelvic pain.

Pelvic pain and vaginal bleeding are common symptoms in postpartum women presenting to the emergency room (ER). Pelvic ultrasonography plays a crucial role in evaluating symptomatic postpartum patients by allowing a rapid diagnosis and treatment initiation. The main goal of imaging is to distinguish between causes of pelvic pain and vaginal bleeding that may be managed conservatively and those requiring emergent intervention. This pictural essay focuses on the ultrasonographic features of common postpartum conditions for which patients may present to the ER with vaginal bleeding and pelvic pain, including retained products of conception, endometritis, uterine arteriovenous malformation, uterine artery pseudoaneurysm, ovarian vein thrombosis, bladder flap hematoma, and uterine dehiscence/rupture.