The association between arterial stiffness and socioeconomic status: a cross-sectional study using estimated pulse wave velocity.

BACKGROUND: The impact of socioeconomic status (SES) on arterial stiffness remains unclear. This study aimed to explore the association between both personal and household income, as well as education level, and estimated pulse wave velocity (ePWV). METHODS: A total of 13,539 participants (mean age 52.9 ± 16.7 years; 57.1% women) from the Korean National Health and Nutrition Survey database were analyzed. For SES variables, information on personal and household income and education level was collected using standardized questionnaires. RESULTS: The ePWV did not show significant differences across groups categorized by individual income levels (P = 0.183). However, there was a noticeable trend of decreasing ePWV with increasing household income levels (P < 0.001). Additionally, ePWV demonstrated a significant negative correlation with higher education levels, indicating that ePWV decreased in groups with higher educational attainment (P < 0.001). In multiple linear regression analyses, both household income (ß = -0.055; P < 0.001) and education level (ß = -0.076; P < 0.001) were negatively associated with ePWV, even after adjusting for potential confounders. CONCLUSIONS: Lower household income and lower education levels were associated with higher ePWV, providing further evidence of the influence of SES on arterial stiffness.

Development and validation of a machine learning-based model for post-sepsis frailty.

Background: The development of post-sepsis frailty is a common and significant problem, but it is a challenge to predict. Methods: Data for deep learning were extracted from a national multicentre prospective observational cohort of patients with sepsis in Korea between September 2019 and December 2021. The primary outcome was frailty at survival discharge, defined as a clinical frailty score on the Clinical Frailty Scale ≥5. We developed a deep learning model for predicting frailty after sepsis by 10 variables routinely collected at the recognition of sepsis. With cross-validation, we trained and tuned six machine learning models, including four conventional and two neural network models. Moreover, we computed the importance of each predictor variable in the model. We measured the performance of these models using a temporal validation data set. Results: A total of 8518 patients were included in the analysis; 5463 (64.1%) were frail, and 3055 (35.9%) were non-frail at discharge. The Extreme Gradient Boosting (XGB) achieved the highest area under the receiver operating characteristic curve (AUC) (0.8175) and accuracy (0.7414). To confirm the generalisation performance of artificial intelligence in predicting frailty at discharge, we conducted external validation with the COVID-19 data set. The XGB still showed a good performance with an AUC of 0.7668. The machine learning model could predict frailty despite the disparity in data distribution. Conclusion: The machine learning-based model developed for predicting frailty after sepsis achieved high performance with limited baseline clinical parameters.

Cisplatin induces kidney damage through the down-regulation of Prx I by autophagic degradation.

In this study, we investigated the potential role of PrxI in cis-diamminedichloroplatinum (cisplatin)-induced renal damage in mice. The anticancer drug cisplatin is a chemotherapeutic agent that is widely used to treat solid tumors. Cisplatin-induced nephrotoxicity is a serious dose-limiting side effect, primarily caused by oxidative stress. The oxidative stress further damages DNA, membranes, and mitochondria, and increases endoplasmic reticulum (ER) stress. Cisplatin produces reactive oxygen species (ROS) through Cytochrome P450 2E1 (CYP2E1) and localizes to the surface of the ER, where CYP2E1 is located. Among the six Prx isoforms, Prx I was selectively degraded in cisplatin-treated kidneys during severe renal function damage. Prx I degradation is blocked in mouse proximal tubular cells treated with 3-methyladenine, an autophagy inhibitor, and in MEF lacking ATG7. Moreover, increased ROS levels on the ER surface due to CYP2E1 overexpression further accelerated Prx I degradation. These results suggest that Prx I degradation is largely mediated through autophagy, which is promoted by cisplatin-induced ER stress. Ablation of Prx I exacerbated cisplatin-induced nephrotoxicity and significantly increased the abundance of oxidative stress, ER stress, and inflammatory markers in the kidney, indicating that Prx I plays a protective role against cisplatin-induced nephrotoxicity.

Development of a Versatile High-through-put Oligonucleotide LC-MS Method to Accelerate Drug Discovery.

Liquid chromatography-mass spectrometry (LC-MS) is an effective tool for high-throughput quantification of oligonucleotides that is crucial for understanding their biological roles and developing diagnostic tests. This paper presents a high-throughput LC-MS/MS method that may be versatilely applied for a wide range of oligonucleotides, making it a valuable tool for rapid screening and discovery. The method is demonstrated using an in-house synthesized MALAT-1 Antisense oligonucleotide (ASO) as a test case. Biological samples were purified using a reversed liquid-liquid extraction process automated by a liquid handling workstation and analyzed with ion-pairing LC-MS/MS. The assay was evaluated for sensitivity (LLOQ = 2 nM), specificity, precision, accuracy, recovery, matrix effect, and stability in rat cerebrospinal fluid (CSF) and plasma. Besides some existing considerations such as column selection, ion-pairing reagent, and sample purification, our work focused on the following four subtopics: 1) selecting the appropriate Multiple Reaction Monitoring (MRM) transition to maximize sensitivity for trace-level ASO in biological samples; 2) utilizing a generic risk-free internal standard (tenofovir) to avoid crosstalk interference from the oligo internal standard commonly utilized in the LC-MS assay; 3) automating the sample preparation process to increase precision and throughput; and 4) comparing liquid-liquid extraction (LLE) and solid-phase extraction (SPE) as sample purification methods in oligo method development. The study quantified the concentration of MALAT-1 ASO in rat CSF and plasma after intrathecal injection and used the difference between the two matrices to evaluate the injection technique. The results provide a solid foundation for further internal oligonucleotide discovery and development.

Automated Idiopathic Normal-Pressure Hydrocephalus Diagnosis via Artificial Intelligence-Based 3D T1 MRI Volumetric Analysis.

BACKGROUND AND PURPOSE: Idiopathic normal pressure hydrocephalus (iNPH) is reversible dementia, that is underdiagnosed. The purpose of this study was to develop an automated diagnostic method for iNPH using artificial intelligence techniques with a T1-weighted MRI scan. MATERIALS AND METHODS: We quantified iNPH, Parkinson's disease, Alzheimer's disease, and healthy control patients on T1-weighted 3D brain MRI scans using 452 scans for training and 110 scans for testing. Automatic component measurement algorithms were developed for Evans' index, Sylvian fissure enlargement, high-convexity tightness, callosal angle, and normalized lateral ventricle volume. XGBoost models were trained for both automated measurements and manual labels for iNPH prediction. RESULTS: A total of 452 patients (200 men; mean age ± standard deviation, 73.2 ± 6.5 years) were included in the training set. Of the 452 patients, 111 (24.6%) had iNPH. We obtained AUC values of 0.956 for automatically measured high-convexity tightness and 0.830 for Sylvian fissure enlargement. Intra-class correlation values of 0.824 for the callosal angle and 0.924 for Evans' index were measured. Using the decision tree of the XGBoost model, the model trained on manual labels obtained an average cross-validation AUC of 0.988 on the training set and 0.938 on the unseen test set, while the fully automated model obtained a cross-validation AUC of 0.983 and an unseen test AUC of 0.936. CONCLUSION: We demonstrated a machine-learning algorithm capable of diagnosing iNPH from a 3D T1-weighted MRI scan that is robust to the failure. We propose a method to scan large numbers of 3D T1-weighted MRI scans with minimal human intervention, making possible large-scale iNPH screening. ABBREVIATIONS: iNPH = idiopathic normal-pressure hydrocephalus; PD = Parkinson's disease; AD = Alzheimer's disease; HC = healthy control; CSF = cerebrospinal fluid; DESH = disproportionately enlarged subarachnoid space hydrocephalus; 3D = three-dimensional.

Safety and efficacy of HK-660S in patients with primary sclerosing cholangitis: A randomized double-blind phase 2a trial.

Background/Aims: A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC. Methods: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, participants were assigned in a 2:1 ratio to receive either 100 mg of HK-660S or a placebo twice daily for 12 weeks. The primary outcomes were the reduction in serum alkaline phosphatase (ALP) levels and the percentage of participants showing improvements in PSC severity, as determined by magnetic resonance cholangiopancreatography (MRCP) with the Anali score. Secondary endpoints included changes in liver stiffness and adverse events. Results: The analysis included 21 patients, 15 receiving HK-660S, and six receiving a placebo. Improvements in the Anali score were observed in 13.3% of the HK-660S group, with no improvements in the placebo group. HK-660S treatment resulted in a 15.2% reduction in mean ALP levels, compared to a 6.6% reduction in the placebo group. A stratified ad-hoc analysis based on baseline ALP levels showed a statistically significant response in the HK-660S group among those with ALP levels greater than twice the upper limit of normal, with a 50% responder rate (p = 0.05). Additionally, 26.7% of the HK-660S group showed improvements in the enhanced liver fibrosis score, with no improvements in the placebo group. HK-660S was generally well-tolerated. Conclusions: HK-660S is well-tolerated among patients with PSC and may improve bile duct strictures, decrease serum ALP levels, and reduce liver fibrosis. (cris.nih.go.kr, Number KCT0006590).

Identification of molecular subtypes of dementia by using blood-proteins interaction-aware graph propagational network.

Plasma protein biomarkers have been considered promising tools for diagnosing dementia subtypes due to their low variability, cost-effectiveness, and minimal invasiveness in diagnostic procedures. Machine learning (ML) methods have been applied to enhance accuracy of the biomarker discovery. However, previous ML-based studies often overlook interactions between proteins, which are crucial in complex disorders like dementia. While protein-protein interactions (PPIs) have been used in network models, these models often fail to fully capture the diverse properties of PPIs due to their local awareness. This drawback increases the chance of neglecting critical components and magnifying the impact of noisy interactions. In this study, we propose a novel graph-based ML model for dementia subtype diagnosis, the graph propagational network (GPN). By propagating the independent effect of plasma proteins on PPI network, the GPN extracts the globally interactive effects between proteins. Experimental results showed that the interactive effect between proteins yielded to further clarify the differences between dementia subtype groups and contributed to the performance improvement where the GPN outperformed existing methods by 10.4% on average.

Analysis of the waitlist performance and post-transplant outcomes of lung transplant in elderly recipients in Korea: A nationwide cohort study.

BACKGROUND: There is a lack of information on the waitlist performance and post-transplant outcomes of lung transplants in elderly recipients in Korea. METHODS: We retrospectively reviewed and analyzed data from the Korean Network for Organ Sharing database between March 2010 and August 2023. RESULTS: In total, 2574 patients were listed for lung transplantation during the study period, with 511 (19.9%) of them being over 65 years of age. Among these, 188 patients (36.8%) underwent transplantation, while 184 patients (36%) passed away without undergoing transplantation at the time of data extraction. The most prevalent underlying disease on the waitlist was idiopathic pulmonary fibrosis, accounting for 68.1%. The 1-year survival rate was significantly lower in the elderly compared to that in the nonelderly (65.4 vs. 75.4%; p = .004). In the multivariate Cox analysis, elderly (hazard ratio [HR], 1.49; 95% CI, 1.14-1.97; p = .004) and a high urgent status at registration (HR, 1.83; 95% CI, 1.40-2.40; p < .001) were significantly associated with post-transplant 1-year mortality. Kaplan-Meier curves demonstrated a significant difference in post-transplant mortality based on the urgency status at enrollment (χ2 = 8.302, p = .016). Even with the same highly urgent condition at the time of transplantation, different prognoses were observed depending on the condition at listing (χ2 = 9.056, p = .029). CONCLUSION: The elderly exhibited worse transplant outcomes than nonelderly adults, with a highly urgent status at registration identified as a significant risk factor. Unprepared, highly urgent transplantation was associated with poor outcomes.

Increased needle passes for comparable diagnostic yield in endoscopic ultrasound-guided tissue acquisition for pancreatic stiff lesions measured by elastography.

BACKGROUND/OBJECTIVES: Pancreatic cancer is characterized by tissue stiffness due to the high concentration of cancer-associated fibroblasts and extracellular matrix. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is performed to diagnose pancreatic cancer but yields false-negative results attributed to inadequate specimens. EUS-elastography is a real-time assessment method to pancreatic tissue stiffness. This study aims to investigate the correlation between diagnostic yield and the number of needle passes based on the stiffness measured by elastography. METHODS: Patients who underwent EUS-TA for pancreatic solid mass were retrospectively reviewed and included in this study. The number of needle passes during EUS-TA was determined based on macroscopic on-site evaluation. Tissue stiffness measurements were taken using EUS-elastography. The primary study outcome was the diagnostic yield. The secondary outcome included the number of needle passes required for a diagnosis. RESULTS: A total of 652 patients were included. The average stiffness differed depending on the location of the tumor, and high-stiffness group had more malignant lesions. Although the diagnostic yield was not significantly different between groups, the number of needle passes was significantly higher in the high-stiffness group (3.6 ± 1.0 vs. 3.2 ± 0.9, p < 0.001). CONCLUSIONS: The higher the stiffness of the pancreatic mass in EUS-elastography, the more needle passes are required to achieve a comparable diagnostic yield.

Bacteria, Fungi, and Scalp Psoriasis: Understanding the Role of the Microbiome in Disease Severity.

Background: Psoriasis is a chronic skin condition affected by genetic and environmental factors. Changes in the skin microbiome may affect the immune system and skin barrier functions, thereby contributing to the development and progression of psoriasis. The scalp, which is a common site for psoriasis, is often resistant to therapy. Although several studies have investigated the scalp microbiome, analyses focusing on both bacteria and fungi remain scarce. Methods: We examined the scalp microbiomes of 11 patients with psoriasis complicated with scalp lesions and categorized them according to their Psoriasis Area Severity Index (PASI) scores. The bacterial and fungal data were analyzed using QIIME2 pipeline version 2021.04 and the UNITE database version 8.3, respectively. Results: The Shannon indices for mild (2 patients), moderate (4 patients), and severe (5 patients) groups were 0.97, 1.38, and 1.88, respectively. A significant correlation was observed between increased mycobiome diversity and disease severity (p = 4.07 × 10-5, Spearman's correlation: 0.9269). Compared with the mild and moderate groups, the severe group exhibited a higher abundance of Malassezia globosa. Pseudomonas and Staphylococcus were, respectively, more prevalent in the moderate and severe groups than in the mild group. Conclusions: This study highlights the potential role of increased fungal diversity and specific microbial compositions in the severity of scalp psoriasis, suggesting a possible avenue for targeted therapeutic interventions.

Transcriptomic profiling of intermediate cell carcinoma of the liver.

BACKGROUND: Intermediate cell carcinoma (Int-CA) is a rare and enigmatic primary liver cancer characterized by uniform tumor cells exhibiting mixed features of both HCC and intrahepatic cholangiocarcinoma. Despite the unique pathological features of int-CA, its molecular characteristics remain unclear yet. METHODS: RNA sequencing and whole genome sequencing profiling were performed on int-CA tumors and compared with those of HCC and intrahepatic cholangiocarcinoma. RESULTS: Int-CAs unveiled a distinct and intermediate transcriptomic feature that is strikingly different from both HCC and intrahepatic cholangiocarcinoma. The marked abundance of splicing events leading to intron retention emerged as a signature feature of int-CA, along with a prominent expression of Notch signaling. Further exploration revealed that METTL16 was suppressed within int-CA, showing a DNA copy number-dependent transcriptional deregulation. Notably, experimental investigations confirmed that METTL16 suppression facilitated invasive tumor characteristics through the activation of the Notch signaling cascade. CONCLUSIONS: Our results provide a molecular landscape of int-CA featured by METTL16 suppression and frequent intron retention events, which may play pivotal roles in the acquisition of the aggressive phenotype of Int-CA.

Structural Perspectives on Metal Dependent Roles of Ferric Uptake Regulator (Fur).

Iron is crucial for the metabolism and growth of most prokaryotic cells. The ferric uptake regulator (Fur) protein plays a central role in regulating iron homeostasis and metabolic processes in bacteria. It ensures the proper utilization of iron and the maintenance of cellular functions in response to environmental cues. Fur proteins are composed of an N-terminal DNA-binding domain (DBD) and a C-terminal dimerization domain (DD), typically existing as dimers in solution. Fur proteins have conserved metal-binding sites named S1, S2, and S3. Among them, site S2 serves as a regulatory site, and metal binding at S2 results in conformational changes. Additionally, as a transcriptional regulator, Fur specifically binds to a consensus DNA sequence called the Fur box. To elucidate the structural and functional properties of Fur proteins, various structures of metal- or DNA-bound Fur proteins or apo-Fur proteins have been determined. In this review, we focus on the structural properties of Fur proteins according to their ligand-bound state and the drug development strategies targeting Fur proteins. This information provides valuable insights for drug discovery.

Astrocyte-derived dominance winning reverses chronic stress-induced depressive behaviors.

Individuals with low social status are at heightened risk of major depressive disorder (MDD), and MDD also influences social status. While the interrelationship between MDD and social status is well-defined, the behavioral causality between these two phenotypes remains unexplored. Here, we investigated the behavioral relationships between depressive and dominance behaviors in male mice exposed to chronic restraint stress and the role of medial prefrontal cortex (mPFC) astrocytes in these behaviors. Chronic restraint stress induced both depressive and submissive behaviors. Chemogenetic mPFC astrocyte activation significantly enhanced dominance in chronic stress-induced submissive mice by increasing the persistence of defensive behavior, although it did not affect depressive behaviors. Notably, repetitive winning experiences following mPFC astrocyte stimulation exerted anti-depressive effects in chronic restraint stress-induced depressive mice. These data indicate that mPFC astrocyte-derived winning experience renders anti-depressive effects, and may offer a new strategy for treating depression caused by low status in social hierarchies by targeting mPFC astrocytes.

Comparing Diagnostic Accuracy of Radiologists versus GPT-4V and Gemini Pro Vision Using Image Inputs from Diagnosis Please Cases.

Background The diagnostic abilities of multimodal large language models (LLMs) using direct image inputs and the impact of the temperature parameter of LLMs remain unexplored. Purpose To investigate the ability of GPT-4V and Gemini Pro Vision in generating differential diagnoses at different temperatures compared with radiologists using Radiology Diagnosis Please cases. Materials and Methods This retrospective study included Diagnosis Please cases published from January 2008 to October 2023. Input images included original images and captures of the textual patient history and figure legends (without imaging findings) from PDF files of each case. The LLMs were tasked with providing three differential diagnoses, repeated five times at temperatures 0, 0.5, and 1. Eight subspecialty-trained radiologists solved cases. An experienced radiologist compared generated and final diagnoses, considering the result correct if the generated diagnoses included the final diagnosis after five repetitions. Accuracy was assessed across models, temperatures, and radiology subspecialties, with statistical significance set at P < .007 after Bonferroni correction for multiple comparisons across the LLMs at the three temperatures and with radiologists. Results A total of 190 cases were included in neuroradiology (n = 53), multisystem (n = 27), gastrointestinal (n = 25), genitourinary (n = 23), musculoskeletal (n = 17), chest (n = 16), cardiovascular (n = 12), pediatric (n = 12), and breast (n = 5) subspecialties. Overall accuracy improved with increasing temperature settings (0, 0.5, 1) for both GPT-4V (41% [78 of 190 cases], 45% [86 of 190 cases], 49% [93 of 190 cases], respectively) and Gemini Pro Vision (29% [55 of 190 cases], 36% [69 of 190 cases], 39% [74 of 190 cases], respectively), although there was no evidence of a statistically significant difference after Bonferroni adjustment (GPT-4V, P = .12; Gemini Pro Vision, P = .04). The overall accuracy of radiologists (61% [115 of 190 cases]) was higher than that of Gemini Pro Vision at temperature 1 (T1) (P < .001), while no statistically significant difference was observed between radiologists and GPT-4V at T1 after Bonferroni adjustment (P = .02). Radiologists (range, 45%-88%) outperformed the LLMs at T1 (range, 24%-75%) in most subspecialties. Conclusion Using direct radiologic image inputs, GPT-4V and Gemini Pro Vision showed improved diagnostic accuracy with increasing temperature settings. Although GPT-4V slightly underperformed compared with radiologists, it nonetheless demonstrated promising potential as a supportive tool in diagnostic decision-making. © RSNA, 2024 See also the editorial by Nishino and Ballard in this issue.

Association between Age-Adjusted Endothelial Activation and Stress Index and Intensive Care Unit Mortality in Patients with Severe COVID-19.

BACKGROUND: Endothelial activation and stress index (EASIX) reflects endothelial dysfunction or damage. Because endothelial dysfunction is one of the key mechanisms, a few studies have shown the clinical usefulness of original and age-adjusted EASIX (age-EASIX) in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical utility of age-EASIX in predicting intensive care unit (ICU) mortality in critically ill patients with COVID-19 in South Korea. METHODS: Secondary analysis was performed using clinical data retrospectively collected from 22 nationwide hospitals in South Korea between January 1, 2020, and August 31, 2021. Patients were at least 19 years old and admitted to the ICU for severe COVID-19, demanding at least high-flow nasal cannula oxygen therapy. EASIX [lactate dehydrogenase (U/L)×creatinine (mg/dL)/platelet count (109 cells/L)] and age-EASIX (EASIX×age) were calculated and log2-transformed. RESULTS: The mean age of 908 critically ill patients with COVID-19 was 67.4 years with 59.7% male sex. The mean log2 age-EASIX was 7.38±1.45. Non-survivors (n=222, 24.4%) in the ICU had a significantly higher log2 age-EASIX than of survivors (8.2±1.52 vs. 7.1±1.32, p<0.001). log2 age-EASIX was significantly associated with ICU mortality (odds ratio, 1.541; 95% confidence interval, 1.322 to 1.796; p<0.001) and had a better area under the receiver operating characteristic curve than of the sequential organ failure assessment (SOFA) score in predicting ICU mortality (0.730 vs. 0.660, p=0.001). CONCLUSION: Age-EASIX is significantly associated with ICU mortality and has better discriminatory ability than the SOFA score in predicting ICU mortality.

Aggressive hydration with lactated Ringer's solution versus plasma solution for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (ALPS study): protocol for a multicentre, double-blind, randomised controlled trial.

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) plays an indispensable role in treating pancreato-biliary diseases but carries a risk of post-ERCP pancreatitis (PEP). Despite advances in the prevention strategies, prevention of PEP remains imperfect, necessitating more refined hydration methods. This study investigates the effectiveness of lactated Ringer's solution versus plasma solution in preventing PEP. METHOD AND ANALYSIS: This multicentre, double-blind, randomised controlled trial, will be initiated by the investigator-sponsor, and conducted in three tertiary centres in South Korea. The aim of this study is to assess the effectiveness of hydration in preventing PEP in patients with naïve papillae. It will target patients with naïve papillae, focusing on those at medium to high risk of PEP. Patients aged ≤18 years and those with serious comorbidities, acute/chronic pancreatitis and various other medical conditions will be excluded. Eligible participants will be randomly assigned into two arms in equal numbers: (1) PEP prevention using lactated Ringer's solution and (2) PEP prevention using plasma solution. The primary outcome of this study will be the occurrence of PEP, and secondary outcomes will be additional risk factors and potential adverse events related to ERCP. With a total enrolment of 844 patients, the study will be able to detect significant differences between the intervention arms. ETHICS AND DISSEMINATION: Ethical approval is obtained from each institution (Asan Medical Centre, 2023-0382; Seoul National University Hospital, H-2302-05-1404; Samsung Medical Centre, SMC 2023-02-001-009). All participants provided informed consent following clear explanation of the study procedures. The results of the study will be disseminated in peer-reviewed journals and research conferences. TRIAL REGISTRATION NUMBER: NCT05832047. PROTOCOL VERSION: Ver 4.1 (2023).

Navigating the Modern Landscape of Sepsis: Advances in Diagnosis and Treatment.

Sepsis poses a significant threat to human health due to its high morbidity and mortality rates worldwide. Traditional diagnostic methods for identifying sepsis or its causative organisms are time-consuming and contribute to a high mortality rate. Biomarkers have been developed to overcome these limitations and are currently used for sepsis diagnosis, prognosis prediction, and treatment response assessment. Over the past few decades, more than 250 biomarkers have been identified, a few of which have been used in clinical decision-making. Consistent with the limitations of diagnosing sepsis, there is currently no specific treatment for sepsis. Currently, the general treatment for sepsis is conservative and includes timely antibiotic use and hemodynamic support. When planning sepsis-specific treatment, it is important to select the most suitable patient, considering the heterogeneous nature of sepsis. This comprehensive review summarizes current and evolving biomarkers and therapeutic approaches for sepsis.

Cortical volumetric changes after cochlear implantation in postlingually deaf adults: correlation with speech perception abilities.

This study aims to analyse the volumetric changes in brain MRI after cochlear implantation (CI), focusing on the speech perception in postlingually deaf adults. We conducted a prospective cohort study with 16 patients who had bilateral hearing loss and received unilateral CI. Based on the surgical side, patients were categorized into left and right CI groups. Volumetric T1-weighted brain MRI were obtained before and one year after the surgery. To overcome the artifact caused by the internal device in post-CI scan, image reconstruction method was newly devised and applied using the contralateral hemisphere of the pre-CI MRI data, to run FreeSurfer. We conducted within-subject template estimation for unbiased longitudinal image analysis, based on the linear mixed effect models. When analyzing the contralateral cerebral hemisphere before and after CI, a substantial increase in superior frontal gyrus and superior temporal gyrus (STG) volumes was observed in the left CI group. A positive correlation was observed in the STG and post-CI word recognition score in both groups. As far as we know, this is the first study attempting longitudinal brain volumetry based on post-CI MRI scans. We demonstrate that better auditory performance after CI is associated with structural restoration in central auditory structures.

Optimizing angular range in digital breast tomosynthesis: A phantom study investigating lesion detection across varied breast density and thickness.

PURPOSE: To determine the optimal angular range (AR) for digital breast tomosynthesis (DBT) systems that provides highest lesion visibility across various breast densities and thicknesses. METHOD: A modular DBT phantom, consisting of tissue-equivalent adipose and glandular modules, along with a module embedded with test objects (speckles, masses, fibers), was used to create combinations simulating different breast thicknesses, densities, and lesion locations. A prototype DBT system operated at four ARs (AR±7.5°, AR±12.5°, AR±19°, and AR±25°) to acquire 11 projection images for each combination, with separate fixed doses for thin and thick combinations. Three blinded radiologists independently assessed lesion visibility in reconstructed images; assessments were averaged and compared using linear mixed models. RESULTS: Speckle visibility was highest with AR±7.5° or AR±12.5°, decreasing with wider ARs in all density and thickness combinations. The difference between AR±7.5° and AR±12.5° was not statistically significant, except for the tube-side speckles in thin-fatty combinations (5.83 [AR±7.5°] vs. 5.39 [AR±12.5°], P = 0.019). Mass visibility was not affected by AR in thick combinations, while AR±12.5° exhibited the highest mass visibility for both thin-fatty and thin-dense combinations (P = 0.032 and 0.007, respectively). Different ARs provided highest fiber visibility for different combinations; however, AR±12.5° consistently provided highest or comparable visibility. AR±12.5° showed highest overall lesion visibility for all density and thickness combinations. CONCLUSIONS: AR±12.5° exhibited the highest overall lesion visibility across various phantom thicknesses and densities using a projection number of 11.