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Oluwaseun Ikotun, Esther Wan Ching Lee The University of Manchester, Faculty of Biology, Medicine and Health, Manchester, UKCorrespondence: Oluwaseun IkotunThe University of Manchester, Faculty of Biology, Medicine and Health, Manchester, UKEmail oluwaseun.ikotun@student.manchester.ac.uk We read with great interest the work by Shahid1 et al with regards to gap year medical residents displaying higher levels of emotional intelligence when compared to their peers. As UK-based medical students, we appreciate the benefits of a gap year before engaging with medical education proposed in this study. However, we believe there are certain considerations that need to be addressed to better understand how clinicians of the future may use emotional intelligence to better patient outcomes. View the original paper by Shahid and colleagues

Oluwaseun Ikotun, Esther Wan Ching Lee The University of Manchester, Faculty of Biology, Medicine and Health, Manchester, UKCorrespondence: Oluwaseun IkotunThe University of Manchester, Faculty of Biology, Medicine and Health, Manchester, UKEmail oluwaseun.ikotun@student.manchester.ac.uk We read with interest the original work by Sobczak1 et al investigating the experiences of Polish patients, whom suffer with obesity, when interacting with healthcare professionals. As UK-based medical students and future clinicians we appreciate that as a society, improvements can be made in both our attitudes and our care of individuals with high body mass index (BMI). Therefore, we would like to offer our comments and address certain topics arising from the study. View the original paper by Sobczak and colleagues

Oluwaseun Ikotun, Esther Wan Ching Lee, Michael Glover The University of Manchester, Faculty of Biology, Medicine and Health, Manchester, UKCorrespondence: Oluwaseun IkotunThe University of Manchester, Faculty of Biology, Medicine and Health, Manchester, UKEmail oluwaseun.ikotun@student.manchester.ac.uk We read with great interest the study by Jalali et al1 with respect to the relationship between sleep quality and academic achievement amongst healthcare students. Given the increasing societal understanding of the effect of sleep deprivation on mental health combined with the intensity of undergraduate training we found this to be a thought stimulating discussion as final year medical students. However, we believe certain factors could be improved to further the impact of this study and potential well-being of undergraduate students. View the original paper by Jalali and colleagues

Objective: The aim of this study was to analyze the origins of prostatic arteries (PAs) in the Korean population and compare them with those reported in the literature., Materials and Methods: From April 2018 to February 2024, 108 male (mean age ± standard deviation: 71.6 ± 9.7 years) with lower urinary tract symptoms (n = 102) or refractory hematuria (n = 6) underwent prostatic artery embolization (PAE). Computed tomography and angiography images were retrospectively reviewed. The branching pattern of the internal iliac artery (IIA) was classified according to the Yamaki system. The origin of the PA was categorized using the de Assis definition, and the incidence of each type was recorded. A systematic literature review was conducted and the most common types of PA were investigated., Results: PAE was successfully implemented on 211 of the 216 pelvic sidewalls. PA cannulation failed in five sidewalls due to a steno-occlusive state. The most common IIA type was type A, in which the IIA was divided into the superior gluteal artery and gluteal-pudendal trunk (77%). Of 226 PAs analyzed, including 15 in 211 sidewalls exhibiting dual PAs, the most common PA origin was the internal pudendal artery (type IV, 35%), followed by the superior vesical (type I, 25%) and obturator (type III, 21%) arteries. Anterior division of IIA (type II) was less common (10%). Type V (uncommon origins) occurred in 8% of cases, including five distal internal pudendal arteries, four quadfurcations, three inferior gluteal arteries, three trifurcations, two medial femoral circumflex arteries, and two rectal arteries. Two of the five patients with surgically or endovascularly altered anatomy were successfully treated via PAs originating from the medial femoral circumflex arteries. Globally, type I is the most common PA type., Conclusion: In the Korean population, the most common IIA pattern and PA origin were types A and IV, respectively., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Korean Society of Radiology.)

Despite the high incidence of dry mouth in postmenopausal women, its underlying mechanisms and therapeutic interventions remain underexplored. Using ovariectomized (OVX) mouse models, here this study identifies ferroptosis, an iron-dependent regulated cell death, as a central mechanism driving postmenopausal salivary gland (SG) dysfunction. In the OVX-SGs, TGFβ signaling pathway is enhanced with the aberrant TGFβ2 expression in SG mesenchymal cells. Intriguingly, TGFβ2 treatment reduces iron-storing ferritin levels, leading to lipid peroxidation and ferroptotic death in SG epithelial organoids (SGOs). Mechanistically, TGFβ2 promotes the autophagy-mediated ferritin degradation, so-called ferritinophagy. A notable overexpression of the type III TGFβ receptor (TβRIII) is found in the OVX-SGs and TGFβ2-treated SGOs, while the silencing of TβRIII mitigates the ferroptosis-mediated deleterious effects of TGFβ2 on SGOs. Finally, administration of ferroptosis inhibitor, Liproxstatin-1 (Lip-1), improves saliva secretion in OVX mice. Present findings collectively suggest a link between TGFβ signaling, ferroptosis, and SG injury, offering new therapeutic avenues for postmenopausal xerostomia., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: The co-design of health technology enables patient-centeredness and can help reduce barriers to technology use., Objective: The study objectives were to identify what remote patient monitoring (RPM) technology has been co-designed for inpatients and how effective it is, to identify and describe the co-design approaches used to develop RPM technologies and in which contexts they emerge, and to identify and describe barriers and facilitators of the co-design process., Methods: We conducted a systematic review of co-designed RPM technologies for inpatients or for the immediate postdischarge period and assessed (1) their effectiveness in improving health outcomes, (2) the co-design approaches used, and (3) barriers and facilitators to the co-design process. Eligible records included those involving stakeholders co-designing RPM technology for use in the inpatient setting or during the immediate postdischarge period. Searches were limited to the English language within the last 10 years. We searched MEDLINE, Embase, CINAHL, PsycInfo, and Science Citation Index (Web of Science) in April 2023. We used the Joanna Briggs Institute critical appraisal checklist for quasi-experimental studies and qualitative research. Findings are presented narratively., Results: We screened 3334 reports, and 17 projects met the eligibility criteria. Interventions were designed for pre- and postsurgical monitoring (n=6), intensive care monitoring (n=2), posttransplant monitoring (n=3), rehabilitation (n=4), acute inpatients (n=1), and postpartum care (n=1). No projects evaluated the efficacy of their co-designed RPM technology. Three pilot studies reported clinical outcomes; their risk of bias was low to moderate. Pilot evaluations (11/17) also focused on nonclinical outcomes such as usability, usefulness, feasibility, and satisfaction. Common co-design approaches included needs assessment or ideation (16/17), prototyping (15/17), and pilot testing (11/17). The most commonly reported challenge to the co-design process was the generalizability of findings, closely followed by time and resource constraints and participant bias. Stakeholders' perceived value was the most frequently reported enabler of co-design. Other enablers included continued stakeholder engagement and methodological factors (ie, the use of flexible mixed method approaches and prototyping)., Conclusions: Co-design methods can help enhance interventions' relevance, usability, and adoption. While included studies measured usability, satisfaction, and acceptability-critical factors for successful implementation and uptake-we could not determine the clinical effectiveness of co-designed RPM technologies. A stronger commitment to clinical evaluation is needed. Studies' use of diverse co-design approaches can foster stakeholder inclusivity, but greater standardization in co-design terminology is needed to improve the quality and consistency of co-design research., (©Jennifer Sumner, Si Ying Tan, Yuchen Wang, Camille Hui Sze Keck, Eunice Wei Xin Lee, Emily Hwee Hoon Chew, Alexander Wenjun Yip. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 15.10.2024.)

Background & Aims: Noninvasive variceal risk stratification systems have not been validated in patients with hepatocellular carcinoma (HCC), which presents logistical barriers for patients in the setting of systemic HCC therapy. We aimed to develop and validate a noninvasive algorithm for the prediction of varices in patients with unresectable HCC., Methods: We performed a retrospective cohort study in 21 centers in the United States including adult patients with unresectable HCC and Child-Pugh A5-B7 cirrhosis diagnosed between 2007 and 2019. We included patients who completed an esophagogastroduodonoscopy (EGD) within 12 months of index imaging but before HCC treatment. We divided the cohort into a 70:30 training set and validation set, with the goal of maximizing negative predictive value (NPV) to avoid EGD in low-risk patients., Results: We included 707 patients (median age, 64.6 years; 80.6% male; 74.0% White). Median time from HCC diagnosis to EGD was 47 (interquartile range, 114) days, with 25.0% of patients having high-risk varices. A model using clinical variables alone achieved an NPV of 86.3% in the validation cohort, whereas a model integrating clinical and imaging variables had an NPV 97.4% in validation. The clinical and imaging model would avoid EGDs in more than half of low-risk patients while misclassifying 7.7% of high-risk patients., Conclusions: A model incorporating clinical and imaging data can accurately predict the absence of high-risk varices in patients with HCC and avoid EGD in many low-risk patients before the initiation of systemic therapy, thus expediting their care and avoiding treatment delays., (Copyright © 2024. Published by Elsevier Inc.)

Postbiotics have various functional effects, such as antioxidant, anti-inflammatory, and anti-obesity. Levilactobacillus brevis BK3, the subject of this study, was derived from lactic acid bacteria isolated from Kimchi, a traditional Korean fermented food. The antioxidant activity of BK3 was confirmed through the measurements of 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and total antioxidant capacity (TAC). The wrinkle improvement effect was validated by assessing elastase inhibitory activity and collagenase inhibitory activity. The intracellular activity was confirmed using human keratinocytes (HaCaT) and human fibroblasts (HFF-1). BK3 protects skin cells from oxidative stress induced by H 2 O 2 and reduces intracellular reactive oxygen species (ROS) production. In addition, the expressions of the antioxidant genes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were upregulated. Meanwhile, matrix metalloproteinase-1 (MMP-1) and collagen type I alpha 1 (COL1A1), involved in collagen degradation and synthesis, were significantly regulated. These results suggest the possibility of utilizing BK3 as a functional ingredient with antioxidant and wrinkle-improving effects.

The COVID-19 pandemic caused by SARS-CoV-2 becomes a serious threat to global health and requires the development of effective antiviral therapies. Current therapies that target viral proteins have limited efficacy with side effects. In this study, we investigated the antiviral activity of MIT-001, a small molecule reactive oxygen species (ROS) scavenger targeting mitochondria, against SARS-CoV-2 and other zoonotic viruses in vitro. The antiviral activity of MIT-001 was quantified by RT-qPCR and plaque assay. We also evaluated the functional analysis of MIT-001 by JC-1 staining to measure mitochondrial depolarization, total RNA sequencing to investigate gene expression changes, and immunoblot to quantify protein expression levels. The results showed that MIT-001 effectively inhibited the replication of B.1.617.2 and BA.1 strains, Zika virus, Seoul virus, and Vaccinia virus. Treatment with MIT-001 restored the expression of heme oxygenase-1 (HMOX1) and NAD(P)H: quinone oxidoreductase 1 (NqO1) genes, anti-oxidant enzymes reduced by SARS-CoV-2, to normal levels. The presence of MIT-001 also alleviated mitochondrial depolarization caused by SARS-CoV-2 infection. These findings highlight the potential of MIT-001 as a broad-spectrum antiviral compound that targets for zoonotic RNA and DNA viruses, providing a promising therapeutic approach to combat viral infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Contact tracing technology has been adopted in many countries to aid in identifying, evaluating, and handling individuals who have had contact with those infected with COVID-19. Singapore was among the countries that actively implemented the government-led contact tracing program known as TraceTogether. Despite the benefits the contact tracing program could provide to individuals and the community, privacy issues were a significant barrier to individuals' acceptance of the program., Objective: Building on the privacy calculus model, this study investigates how the perceptions of the 2 key groups (ie, government and community members) involved in the digital contact tracing factor into individuals' privacy calculus of digital contact tracing., Methods: Using a mixed method approach, we conducted (1) a 2-wave survey (n=674) and (2) in-depth interviews (n=12) with TraceTogether users in Singapore. Using structural equation modeling, this study investigated how trust in the government and the sense of community exhibited by individuals during the early stage of implementation (time 1) predicted privacy concerns, perceived benefits, and future use intentions, measured after the program was fully implemented (time 2). Expanding on the survey results, this study conducted one-on-one interviews to gain in-depth insights into the privacy considerations involved in digital contact tracing., Results: The results from the survey showed that trust in the government increased perceived benefits while decreasing privacy concerns regarding the use of TraceTogether. Furthermore, individuals who felt a connection to community members by participating in the program (ie, the sense of community) were more inclined to believe in its benefits. The sense of community also played a moderating role in the influence of government trust on perceived benefits. Follow-up in-depth interviews highlighted that having a sense of control over information and transparency in the government's data management were crucial factors in privacy considerations. The interviews also highlighted surveillance as the most prevalent aspect of privacy concerns regarding TraceTogether use. In addition, our findings revealed that trust in the government, particularly the perceived transparency of government actions, was most strongly associated with concerns regarding the secondary use of data., Conclusions: Using a mixed method approach involving a 2-wave survey and in-depth interview data, we expanded our understanding of privacy decisions and the privacy calculus in the context of digital contact tracing. The opposite influences of privacy concerns and perceived benefit on use intention suggest that the privacy calculus in TraceTogether might be viewed as a rational process of weighing between privacy risks and use benefits to make an uptake decision. However, our study demonstrated that existing perceptions toward the provider and the government in the contact tracing context, as well as the perception of the community triggered by TraceTogether use, may bias user appraisals of privacy risks and the benefits of contact tracing., (©Hyunjin Kang, Jeong Kyu Lee, Edmund WJ Lee, Cindy Toh. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 07.03.2024.)

This study investigated the effects of supplementation of low-temperature probiotics isolated from the intestines of olive flounder on the growth performance, digestibility, and regulation of intestinal microbiota and the expression of genes related to growth, immunity, and apoptosis in olive flounder. Bacteria showing high growth at approximately 15-20 °C, which is the temperature of olive flounder culture, were isolated and confirmed to be Pseudomonas species through 16S rRNA gene sequence analysis. Whole-genome sequencing revealed that the strain has a 6,195,122 bp single circular chromosome and a guanine-cytosine content of 59.9%. In the feeding trial, supplementation with 1 × 10 8  CFU/g of the isolate strain positively modulated growth performances, digestive enzyme activity, and gut microbiota composition of olive flounder. RT-qPCR for the comparison of growth, immunity, and apoptosis-related gene expression levels showed no significant differences between the groups. Therefore, the isolated host-associated low-temperature probiotics improved the growth performance of olive flounder by causing positive changes in digestive activity and intestinal microbial composition without affecting host gene expression., (© 2024. The Author(s).)

Two novel strains of Rummeliibacillus sp. and Microbacterium sp. were identified from the intestine of olive flounder ( Paralichthys olivaceus ) and characterized in vitro as potential probiotics. Feeds without probiotic and with a 50:50 mixture of these two strains (1 × 10 8 CFU/g feed) were denoted as the control and Pro diets, respectively. Three randomly selected tanks (20 flounders/tank, ~11.4 g each) were used for each diet replication. After 8 weeks of feeding, the growth and feed utilization of the flounder in the Pro group improved ( p < 0.05) compared to the control. Among four immune parameters, only myeloperoxidase activity was elevated in the Pro group. Serum biochemistry, intestinal microbial richness (Chao1), and diversity (Shannon index) remained unchanged ( p ≥ 0.05), but phylogenetic diversity was enriched in the Pro fish intestine. Significantly lower Firmicutes and higher Proteobacteria were found in the Pro diet; the genus abundance in the control and Pro was as follows: Staphylococcus > Lactobacillus > Corynebacterium and Lactobacillus > Staphylococcus > Corynebacterium , respectively. Microbial linear discriminant scores and a cladogram analysis showed significant modulation. Therefore, the combination of two host-associated probiotics improved the growth and intestinal microbial population of flounder and could be supplemented in the Korean flounder industry.

Arachidonic and adrenic acids in the membrane play key roles in ferroptosis. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism and contributes to ferroptosis resistance. A metabolic drug screen reveals that darapladib, an inhibitor of Lp-PLA2, synergistically induces ferroptosis in the presence of GPX4 inhibitors. We show that darapladib is able to enhance ferroptosis under lipoprotein-deficient or serum-free conditions. Furthermore, we find that Lp-PLA2 is located in the membrane and cytoplasm and suppresses ferroptosis, suggesting a critical role for intracellular Lp-PLA2. Lipidomic analyses show that darapladib treatment or deletion of PLA2G7, which encodes Lp-PLA2, generally enriches phosphatidylethanolamine species and reduces lysophosphatidylethanolamine species. Moreover, combination treatment of darapladib with the GPX4 inhibitor PACMA31 efficiently inhibits tumour growth in a xenograft model. Our study suggests that inhibition of Lp-PLA2 is a potential therapeutic strategy to enhance ferroptosis in cancer treatment., (© 2023. Springer Nature Limited.)

Ferroptosis, a type of cell death induced by lipid peroxidation, has emerged as a novel anti-cancer strategy. Cancer cells frequently acquire resistance to ferroptosis. However, the underlying mechanisms are poorly understood. To address this issue, we conducted a thorough investigation of the genomic and transcriptomic data derived from hundreds of human cancer cell lines and primary tissue samples, with a particular focus on non-small cell lung carcinoma (NSCLC). It was observed that mutations in Kelch-like ECH-associated protein 1 (KEAP1) and subsequent nuclear factor erythroid 2-related factor 2 (NRF2, also known as NFE2L2) activation are strongly associated with ferroptosis resistance in NSCLC. Additionally, AIFM2 gene, which encodes ferroptosis suppressor protein 1 (FSP1), was identified as the gene most significantly correlated with ferroptosis resistance, followed by multiple NRF2 targets. We found that inhibition of NRF2 alone was not sufficient to reduce FSP1 protein levels and promote ferroptosis, whereas FSP1 inhibition effectively sensitized KEAP1-mutant NSCLC cells to ferroptosis. Furthermore, we found that combined inhibition of FSP1 and NRF2 induced ferroptosis more intensely. Our findings imply that FSP1 is a crucial suppressor of ferroptosis whose expression is partially dependent on NRF2 and that synergistically targeting both FSP1 and NRF2 may be a promising strategy for overcoming ferroptosis resistance in cancer., (© 2023. The Author(s).)

Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease that can progress to nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis, and hepatocellular carcinoma (HCC). NAFLD ranges from simple steatosis (or nonalcoholic fatty liver [NAFL]) to NASH as a progressive form of NAFL, which is characterized by steatosis, lobular inflammation, and hepatocellular ballooning with or without fibrosis. Because of the complex pathophysiological mechanism and the heterogeneity of NAFLD, including its wide spectrum of clinical and histological characteristics, no specific therapeutic drugs have been approved for NAFLD. The heterogeneity of NAFLD is closely associated with cellular plasticity, which describes the ability of cells to acquire new identities or change their phenotypes in response to environmental stimuli. The liver consists of parenchymal cells including hepatocytes and cholangiocytes and nonparenchymal cells including Kupffer cells, hepatic stellate cells, and endothelial cells, all of which have specialized functions. This heterogeneous cell population has cellular plasticity to adapt to environmental changes. During NAFLD progression, these cells can exert diverse and complex responses at multiple levels following exposure to a variety of stimuli, including fatty acids, inflammation, and oxidative stress. Therefore, this review provides insights into NAFLD heterogeneity by addressing the cellular plasticity and metabolic adaptation of hepatocytes, cholangiocytes, hepatic stellate cells, and Kupffer cells during NAFLD progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as potential conflicts of interest., (Copyright © 2023 Park, Choi, Kim, Yang, An, Lee, Han, Lee, Kim, Bae and Oh.)

Background: The impact of renal function on hepatic encephalopathy (HE) following transjugular intrahepatic portosystemic shunt (TIPS) placement for refractory ascites is poorly understood. We investigated the role of renal function on HE following TIPS placement., Methods: A retrospective study was performed for patients undergoing TIPS for refractory ascites from 2007-2019. Patients were stratified by GFR at time of TIPS placement and by whether they were on hemodialysis (HD). Chronic kidney disease (CKD) stage 3 or higher was defined as pre-TIPS GFR < 60 for at least 3 months. Logistic regression analyses were used to identify the role of GFR and CKD at time of TIPS placement on HE within 60 days post TIPS placement., Results: Among 201 TIPS patients for refractory ascites (61% male; mean age 59.1), 78 (39%) patients were in CKD, and 16 (21%) were on HD. Mean GFR at time of TIPS placement was 62.7 ± 28.2 for all non-HD patients ( n = 185). Compared with the GFR ≥ 90 group, GFR < 30 or HD (OR, 3.56; 95%CI, 1.19-10.7; p = 0.023) and CKD (OR, 2.52; 95%CI, 1.40-4.53; p = 0.002) at time of TIPS placement were significant predictors of post-TIPS placement HE within 60 days. GFRs between 30-60 and 60-90 were not significant predictors., Conclusions: In TIPS patients for recurrent ascites, patients with acutely impaired renal function or chronic renal dysfunction were at an increased risk for HE after TIPS.

Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. This process contributes to cellular and tissue damage in various human diseases, such as cardiovascular diseases, neurodegeneration, liver disease, and cancer. Although polyunsaturated fatty acids (PUFAs) in membrane phospholipids are preferentially oxidized, saturated/monounsaturated fatty acids (SFAs/MUFAs) also influence lipid peroxidation and ferroptosis. In this review, we first explain how cells differentially synthesize SFA/MUFAs and PUFAs and how they control fatty acid pools via fatty acid uptake and β-oxidation, impacting ferroptosis. Furthermore, we discuss how fatty acids are stored in different lipids, such as diacyl or ether phospholipids with different head groups; triglycerides; and cholesterols. Moreover, we explain how these fatty acids are released from these molecules. In summary, we provide an integrated view of the diverse and dynamic metabolic processes in the context of ferroptosis by revisiting lipidomic studies. Thus, this review contributes to the development of therapeutic strategies for ferroptosis-related diseases., (© 2023. The Author(s).)

Gastrointestinal (GI) cancers are among the leading causes of cancer-related mortality and have traditionally been treated using a combination of surgical resection and chemoradiotherapy (CRT). While the introduction of immunotherapies over the last decade have dramatically changed the treatment landscape for some GI malignancies, including esophageal, gastric, and colorectal cancer, treatment resistance remains a major unaddressed obstacle for many patients. There has thus been emerging interest in determining the optimal treatment strategy for the delivery of immunotherapy in combination with traditional therapies. In this regard, a growing number of preclinical and clinical studies have suggested that combining radiation therapy (RT) with immunotherapy may work synergistically to improve treatment response through amplification of the abscopal effect. In this review, we discuss the rationale for RT in combination with immunotherapy. We further discuss how this knowledge may lead to a paradigm shift in the application of RT and highlight remaining issues pertaining to the delivery of combination therapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-105/coif). GYY serves as the Editor-in-Chief of Journal of Gastrointestinal Oncology. The other authors have no conflicts of interest to declare., (2023 Journal of Gastrointestinal Oncology. All rights reserved.)

Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Mitochondrial uncoupling protein 1 (UCP1) is activated in BAT during cold stress and dissipates mitochondrial proton motive force generated by the electron transport chain to generate heat. However, other mitochondrial factors required for brown adipocyte respiration and thermogenesis under cold stress are largely unknown. Here, we show LETM1 domain-containing protein 1 (LETMD1) is a BAT-enriched and cold-induced protein required for cold-stimulated respiration and thermogenesis of BAT. Proximity labeling studies reveal that LETMD1 is a mitochondrial matrix protein. Letmd1 knockout male mice display aberrant BAT mitochondria and fail to carry out adaptive thermogenesis under cold stress. Letmd1 knockout BAT is deficient in oxidative phosphorylation (OXPHOS) complex proteins and has impaired mitochondrial respiration. In addition, BAT-specific Letmd1 deficient mice exhibit phenotypes identical to those observed in Letmd1 knockout mice. Collectively, we demonstrate that the BAT-enriched mitochondrial matrix protein LETMD1 plays a tissue-autonomous role that is essential for BAT mitochondrial function and thermogenesis., (© 2023. The Author(s).)

Background: Although non-target puncture (NPT)-related complications are well known to clinicians performing TIPS, there is no NTP-focused study to assess the true clinical sequalae of NTP-related complications. In this study, the aim was to evaluate the incidence, safety, clinical outcomes and complications related to NTPs during the portal access of TIPS procedures., Methods: A retrospective review of 369 TIPS procedures from October 2007 to September 2019 was performed. We identified inadvertent NTPs, including biliary, hepatic artery, lymphatic and capsular punctures. Next, the medical records and images were reviewed and analyzed to assess the safety and clinical outcomes of these cohorts., Results: A total of 71 NTPs were identified in 56 patients (15.18% of 369 patients). Of 369 TIPS patients, there were (1) 28 biliary punctures (7.6%), (2) 16 extracapsular punctures (4.3%), (3) 15 lymphatic punctures (4.1%) and (4) 12 hepatic artery punctures (3.3%). The overall complication rate was 2.2% (8/369). Based on the Clavien-Dindo classification, three patients (0.8%) had a minor complication. In addition, five patients (1.4%) experienced grade II-V major complications, such as symptomatic hemoperitoneum, arterio-biliary fistula or hemorrhagic shock leading to death. Mortality (0.5%) was only caused by extracapsular puncture combined with other NTP., Conclusions: NTPs during the portal access of TIPS procedures are associated with low complication risk. However, when extracapsular punctures are combined with other NTPs, a more severe complication, including mortality, can occur. Nevertheless, all patients with NTP should be closely monitored at a higher level of care after TIPS placement.

Aims/hypothesis: Non-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes may more easily progress towards severe forms of non-alcoholic steatohepatitis (NASH) and cirrhosis. Although the Wnt effector transcription factor 7-like 2 (TCF7L2) is closely associated with type 2 diabetes risk, the role of TCF7L2 in NAFLD development remains unclear. Here, we investigated how changes in TCF7L2 expression in the liver affects hepatic lipid metabolism based on the major risk factors of NAFLD development., Methods: Tcf7l2 was selectively ablated in the liver of C57BL/6N mice by inducing the albumin (Alb) promoter to recombine Tcf7l2 alleles floxed at exon 5 (liver-specific Tcf7l2-knockout [KO] mice: Alb-Cre;Tcf7l2 f/f ). Alb-Cre;Tcf7l2 f/f and their wild-type (Tcf7l2 f/f ) littermates were fed a high-fat diet (HFD) or a high-carbohydrate diet (HCD) for 22 weeks to reproduce NAFLD/NASH. Mice were refed a standard chow diet or an HCD to stimulate de novo lipogenesis (DNL) or fed an HFD to provide exogenous fatty acids. We analysed glucose and insulin sensitivity, metabolic respiration, mRNA expression profiles, hepatic triglyceride (TG), hepatic DNL, selected hepatic metabolites, selected plasma metabolites and liver histology., Results: Alb-Cre;Tcf7l2 f/f essentially exhibited increased lipogenic genes, but there were no changes in hepatic lipid content in mice fed a normal chow diet. However, following 22 weeks of diet-induced NAFLD/NASH conditions, liver steatosis was exacerbated owing to preferential metabolism of carbohydrate over fat. Indeed, hepatic Tcf7l2 deficiency enhanced liver lipid content in a manner that was dependent on the duration and amount of exposure to carbohydrates, owing to cell-autonomous increases in hepatic DNL. Mechanistically, TCF7L2 regulated the transcriptional activity of Mlxipl (also known as ChREBP) by modulating O-GlcNAcylation and protein content of carbohydrate response element binding protein (ChREBP), and targeted Srebf1 (also called SREBP1) via miRNA (miR)-33-5p in hepatocytes. Eventually, restoring TCF7L2 expression at the physiological level in the liver of Alb-Cre;Tcf7l2 f/f mice alleviated liver steatosis without altering body composition under both acute and chronic HCD conditions., Conclusions/interpretation: In mice, loss of hepatic Tcf7l2 contributes to liver steatosis by inducing preferential metabolism of carbohydrates via DNL activation. Therefore, TCF7L2 could be a promising regulator of the NAFLD associated with high-carbohydrate diets and diabetes since TCF7L2 deficiency may lead to development of NAFLD by promoting utilisation of excess glucose pools through activating DNL., Data Availability: RNA-sequencing data have been deposited into the NCBI GEO under the accession number GSE162449 ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE162449 )., (© 2023. The Author(s).)

Purpose: To investigate the safety and efficacy of percutaneous cholecystoduodenal stent (CDS) placement to prevent recurrence of acute cholecystitis in patients who were unfit for cholecystectomy., Methods: Between April 2016 and January 2022, 46 patients [median age (range) = 81 (37-99) years; men = 15] with acute cholecystitis who were unfit for surgery underwent percutaneous cholecystostomy followed by a CDS placement in two institutions. Plastic stents of three different materials were used [polyethylene, polyurethane (PU), and polycarbonate (PCB)-based PU]. Clinical outcomes, including technical and clinical success rates and early (<30 days) and delayed adverse events, were retrospectively assessed by stent type., Results: CDS placement was technically successful in 39 patients. Clinical success, defined as cholecystostomy catheter removal, was achieved in 35 of 39 patients. Immediate complications, such as acute pancreatitis and peritonitis, occurred in two patients. Two patients experienced recurrent cholecystitis during a 113-day follow-up (range, 3-1,723). Three-stent groups had significantly different delayed complications on Fisher's exact test ( P = 0.021). The Bonferroni post-hoc analysis showed the PCB-PU group tended to have fewer complications than the PU group ( P = 0.060)., Conclusion: CDS placement is applicable in treating acute cholecystitis patients who were initially unfit for surgery, but further investigation is needed. Although it was not statistically significant, a PCB-PU stent can be suitable for this use because it tends to have fewer delayed complications and is equipped with a drawstring and side holes.

Raptor plays a critical role in mTORC1 signaling. High expression of Raptor is associated with resistance of cancer cells to PI3K/mTOR inhibitors. Here, we found that OTUB1-stabilized Raptor in a non-canonical manner. Using biochemical assays, we found that the tyrosine 26 residue (Y26) of OTUB1 played a critical role in the interaction between OTUB1 and Raptor. Furthermore, non-receptor tyrosine kinases (Src and SRMS kinases) induced phosphorylation of OTUB1 at Y26, which stabilized Raptor. Interestingly, phosphorylation of OTUB1 at Y26 did not affect the stability of other OTUB1-targeted substrates. However, dephosphorylation of OTUB1 destabilized Raptor and sensitized cancer cells to anti-cancer drugs via mitochondrial reactive oxygen species-mediated mitochondrial dysfunction. Furthermore, we detected high levels of phospho-OTUB1 and Raptor in samples of patients with renal clear carcinoma. Our results suggested that regulation of OTUB1 phosphorylation may be an effective and selective therapeutic target for treating cancers via down-regulation of Raptor., (© 2022. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Host-associated probiotics (HAPs) are bacteria originally isolated from rearing water or the host's gastrointestinal tract in order to enhance the host's growth and health. This study investigated the HAP potential of Bacillus sp. PM8313, isolated from wild red sea bream ( Pagrus major ), through characterization and feeding trials. Results based on in vitro tests showed that PM8313 is safe, confirming its hemolytic, cytotoxic, and antibiotic resistance. In addition, PM8313 showed advantages as a probiotic with high viability in the gastrointestinal model and a high cell adhesion rate. Whole-genome sequencing demonstrated that PM8313 has a 4,615,871 bp single circular chromosome and a guanine-cytosine content of 45.25%. It also showed the absence of genes encoding virulence factors, such as cytotoxin, enterotoxin, hemolysin, sphingomyelinase, and phospholipase. In the feeding trial, a supplemental diet of 1 × 10 8  CFU/g PM8313 positively altered the weight gain, digestive enzyme activity, and intestinal microbiota composition of red sea bream. Analysis of nonspecific immune parameters and immune-related gene expression, and a challenge test showed that PM8313 supplementation increases immunity and pathogenic bacteria resistance. Our findings suggest that PM8313 should be considered for application as a novel HAP to red sea bream aquaculture., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Ischemic stroke is the leading cause of immortal disability and death worldwide. For treatment in the acute phase, it is necessary to control excessive reactive oxygen species (ROS) damage during ischemia/reperfusion (I/R). Microglia are well known to be closely associated with excessive ROS response in the early stage of I/R. However, the precise roles of microglia associated with mitigating ROS damage, and molecular markers of heterogenetic microglia in the I/R damaged brain has not been clarified. Here, we identified a new type of microglia associated with stroke in the I/R injured brain. Single-cell RNA sequencing (scRNA-seq) was used to assess transcriptional changes of microglia and immune cells in the contralateral (CL) and ipsilateral (IL) hemispheres after transient middle cerebral artery occlusion (tMCAO) surgery to mimic ischemic stroke. We classified a unique type of microglia with enhanced antioxidant function and markers similar to those of disease-associated microglia (DAM), designated them as stroke-associated microglia (SAM). The representative antioxidant enzyme, Peroxiredoxin-1 (Prdx1), was predominantly expressed in SAM and mediated ROS defense genes, including Txn1, Srx1, Mt1, and Mt2. In the Prdx1 -/- I/R damaged brain, we observed significantly increased infarction, as assessed by TTC staining, and FACS analysis detected severe microglial cell death. Importantly, scRNA transcriptomics data showed that the SAM population was specifically decreased in Prdx1 -/- mice and that these mice exhibited decreased ROS damage resistance. Inflammatory responses which were detected by ELISA and qPCR, were also increased in Prdx1 -/- IL hemispheres. Finally, Prdx1-dependent antioxidative SAM were found to be essential for increasing the transcription levels of stroke-protective molecules, such as osteopontin and ferritin. A novel microglia type (SAM) is specifically activated in response to stroke I/R injury, and that Prdx1 expression is required for the activation and enhanced antioxidant function of SAM., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Proteins related to DNA replication have been proposed as cancer biomarkers and targets for anticancer agents. Among them, minichromosome maintenance (MCM) proteins, often overexpressed in various cancer cells, are recognized both as notable biomarkers for cancer diagnosis and as targets for cancer treatment. Here, we investigated the activity of cedrol, a single compound isolated from Juniperus chinensis , in reducing the expression of MCM proteins in human lung carcinoma A549 cells. Remarkably, cedrol also strongly inhibited the expression of all other MCM protein family members in A549 cells. Moreover, cedrol treatment reduced cell viability in A549 cells, accompanied by cell cycle arrest at the G1 phase, and enhanced apoptosis. Taken together, this study broadens our understanding of how cedrol executes its anticancer activity while demonstrating that cedrol has potential application in the treatment of human lung cancer as an inhibitor of MCM proteins.

A 56-day feeding trial was conducted to determine the effect of dietary supplementation with Bacillus sp. isolated from the intestines of red sea bream on the growth performance, immunity, and gut microbiome composition of red sea bream. Three diets (a control diet and two treatments) were formulated without Bacillus sp. PM8313 or β-glucan (control, CD), 1 × 10 8 CFU g -1 PM8313 (BSD), and 1 × 10 8 CFU g -1 PM8313 + 0.1% β-glucan (BGSD). At the end of the experiment, the weight, specific growth rate, feed conversion ratio, and protein efficiency ratio of the fish in the BSD and BGSD diet groups were significantly improved than those of the control group (P < 0.05). Additionally, amylase and trypsin activities were significantly higher (P < 0.05) in both groups compared to the control. Superoxide dismutase and lysozyme activity, which are serum non-specific immune responses, only increased in the BGSD group. The two treatment groups exhibited a marked difference in the intestinal microbiota composition compared to the control group. Furthermore, the treatment groups exhibited an upregulation of IL-6 and NF-κb, coupled with high survival rates when challenged with Edwardsiella tarda . Therefore, dietary supplementation with PM8313 improved the growth performance, digestive enzyme activity, non-specific immunity, and pathogen resistance of red sea bream, in addition to affecting the composition of its intestinal microflora., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jang, Jeon, Lee, Park, Lee, Noh, Hur, Lee, Lee, Lee, Kim, Lee and Hasan.)

The aim of the present study is to investigate the preventive effect of water extract of Mori Ramulus (MRWE) on oxidative stress-mediated cellular damages in rat skeletal L6 myoblasts. Our results demonstrated that MRWE pretreatment markedly improved cell survival and suppressed cell cycle arrest at the G2/M phase and apoptosis in hydrogen peroxide (H 2 O 2 )-treated L6 cells. H 2 O 2 -triggered DNA damage was also notably reduced by MRWE, which since it was correlated with protection of reactive oxygen species (ROS) production. Additionally, H 2 O 2 stimulated cytosolic release of cytochrome c and up-regulation of Bax/Bcl-2 ratio, whereas MRWE suppressed these changes following by H 2 O 2 . Moreover, MRWE inhibited the cleavage of poly(ADP-ribose) polymerase as well as the activity of caspase-3 by H 2 O 2 . Furthermore, MRWE enhanced H 2 O 2 -mediated expression of nuclear factor erythroid 2-associated factor 2 (Nrf2) and its representative downstream enzyme, heme oxygenase-1 (HO-1). However, the protective effects of MRWE on H 2 O 2 -induced ROS production, cell cycle arrest and apoptosis were significantly attenuated by HO-1 inhibitor. In conclusion, our present results suggests that MRWE could protect L6 myoblasts from H 2 O 2 -induced cellular injury by inhibiting ROS generation along with Nrf2-mediated activation of HO-1, indicating this finding may expand the scope of application of Mori Ramulus in medicine., Competing Interests: Conflict of interestThe authors declare that they have no conflicts of interest., (© The Author(s) under exclusive licence to Korean Society of Toxicology 2022.)

Background: This study was conducted to examine the effectiveness of a community-based primary care program focused on hypertension and diabetes in Korea., Methods: We selected patients and doctors who participated in the community-based primary care program as study subjects from Aug 2015 to Jan 2016. Patients and physicians completed a survey, and medical records were reviewed to obtain information regarding clinical variables. Change in the baseline recognition of diseases, motivation for changing health behavior, medical services utilization, doctor-patient relationship were assessed after participation in the program., Results: Both patients and physicians indicated there was improvement in recognition of disease, motivation for changing health behavior, medical services utilization, and doctor-patient relationship (All of recognition scores were above the median point). Patient health behavior such as exercise, smoking, drinking and diet and clinical variables (blood pressure and blood glucose and cholesterol level) also showed significant improvement., Conclusion: The community-based primary care program was found to be helpful in improving hypertension and diabetes patients' overall outcomes and their healthcare providers' behavior., Competing Interests: Conflict of interest The authors declare that there is no conflict of interests., (Copyright © 2022 Kim et al. Published by Tehran University of Medical Sciences.)

The Nile tilapia Oreochromis niloticus , Atlantic salmon Salmo salar , rainbow trout Oncorhynchus mykiss , olive flounder Paralichthys olivaceus , common carp Cyprinus carpio , grass carp Ctenopharyngodon idella and rohu carp Labeo rohita are farmed commercially worldwide. Production of these important finfishes is rapidly expanding, and intensive culture practices can lead to stress in fish, often reducing resistance to infectious diseases. Antibiotics and other drugs are routinely used for the treatment of diseases and sometimes applied preventatively to combat microbial pathogens. This strategy is responsible for the emergence and spread of antimicrobial resistance, mass killing of environmental/beneficial bacteria, and residual effects in humans. As an alternative, the administration of probiotics has gained acceptance for disease control in aquaculture. Probiotics have been found to improve growth, feed utilization, immunological status, disease resistance, and to promote transcriptomic profiles and internal microbial balance of host organisms. The present review discusses the effects of single and multi-strain probiotics on growth, immunity, heamato-biochemical parameters, and disease resistance of the above-mentioned finfishes. The application and outcome of probiotics in the field or open pond system, gaps in existing knowledge, and issues worthy of further research are also highlighted.

This study was performed to investigate the effect of microbial supplementation diet on the survival rate and microbiota composition of artificially produced eel larvae. Microorganisms supplemented in the diet were isolated from wild glass eel intestines and identified as Bacillus sp. through 16S rRNA sequencing analysis. In vitro tests confirmed that the strain had no hemolytic activity and virulence genes. Microbial supplemental feeding significantly increased the survival rate of artificially produced eel larvae for 30 days post-hatchling compared with that of the control group. It also caused changes in the α-diversity, β-diversity, and relative abundance of the bacterial communities. Analysis via phylogenetic investigation of communities by reconstruction of unobserved states predicted that these microbial community changes would significantly increase the carbohydrate metabolism, membrane transport, and cellular community pathway of the microbial supplementation group. Therefore, microbial supplementation feeding for eel aquaculture could increase the viability of artificially produced eel larvae and alter the microbial composition to induce metabolic changes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jang, Kim, Lee, Kim, Ryu, Shin, Lee, Lee and Lee.)

Cold atmospheric plasma (CAP) that generates reactive oxygen species (ROS) has received considerable scientific attentions as a new type of anticancer. In particular, an indirect treatment method of inducing cancer cell death through plasma-activated medium (PAM), rather than direct plasma treatment has been well established. Although various cell death pathways such as apoptosis, necroptosis, and autophagy have been suggested to be involved in PAM-induced cell death, the involvement of ferroptosis, another type of cell death regulated by lipid ROS is largely unknown. This study reports, that PAM promotes cell death via ferroptosis in human lung cancer cells, and PAM increases intracellular and lipid ROS, thereby resulting in mitochondrial dysfunction. The treatment of cells with N-acetylcysteine, an ROS scavenging agent, or ferrostatin-1, a ferroptosis inhibitor, protects cells against PAM-induced cell death. Interestingly, ferroptosis suppressor protein 1 (FSP1) is downregulated upon PAM treatment. Furthermore, the treatment of cells with iFSP1, an inhibitor of FSP1, further enhances PAM-induced ferroptosis. Finally, this study demonstrates that PAM inhibits tumor growth in a xenograft model with an increase in 4-hydroxynoneal and PTGS2, a byproduct of lipid peroxidation, and a decrease in FSP1 expression. This study will provide new insights into the underlying mechanism and therapeutic strategies of PAM-mediated cancer treatment., (© 2022. The Author(s).)

Background: Recently, the South Korean government has adopted a primary-care-based chronic disease management program as a national task. This study aimed to evaluate this program by focusing on hypertension patients and examine the effect of this program on their health., Methods: Overall, 863 subjects who responded to a survey and 1,716 subjects in administrative data were included. Effects of the program were evaluated based on intermediate outcomes (motivation for self-management, changes in health behavior, medical service utilization, duration of consultation with physicians, and medication compliance) and outcomes (disease management, service satisfaction, and physician-patient relationship, change of blood pressure). Furthermore, we compared study participants' baseline systolic and diastolic blood pressure with corresponding measurements obtained at examinations conducted at 3 and 6 months after baseline measurements., Results: Patients' motivation for self-management of hypertension, health behaviors (smoking, drinking, and exercise), regular clinic visit, and medication compliance were improved after participating in the program. Furthermore, patients' blood pressure levels were decreased while their satisfaction with physician-patient relationships was increased., Conclusion: Primary-care-based chronic disease management program is effective for managing hypertension. Therefore, it is essential to reinforce the role of community-based primary care to improve the health of patients with hypertension., Competing Interests: Conflict of interest None declared., (Copyright © 2022 Lee et al. Published by Tehran University of Medical Sciences.)

Background: To evaluate the techniques, efficacy, and safety for treating vascularly inaccessible abdominal visceral pseudoaneurysms by direct puncture and embolization., Methods: A retrospective study of 5 consecutive patients who underwent percutaneous direct puncture embolization for intra-abdominal pseudoaneurysms in our institution between January 2009 and December 2016. Technical aspects, success, clinical outcome, and complications were discussed., Results: Four patients (80%) were men, and the mean age of all five patients was 57.2 years (range, 47-72 years). The mean diameter of the pseudoaneurysms was 2.5 cm (range, 1.9-3.4 cm). All the pseudoaneurysms were punctured under the imaging guidance of fluoroscopy, ultrasound, or computed tomography. Coils and glue were used in four of the patients, the remaining one with coil only. The mean injected glue volume was 1.5 (range, 0.8-2) mL. The overall technical and clinical success rate was 100% without major complications or mortality., Conclusion: Our single-center experience and the literature review demonstrate that percutaneous direct puncture embolization is feasible and effective to serve as an alternative for treating abdominal vascular pseudoaneurysms when the traditional endovascular embolization fails. In this approach, fluoroscopy is the most needed guidance technique., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Despite the proliferation of eHealth interventions, such as web portals, for health information dissemination or the use of mobile apps and wearables for health monitoring, research has shown that underserved groups do not benefit proportionately from these eHealth interventions. This is largely because of usability issues and the lack of attention to the broader structural, physical, and psychosocial barriers to technology adoption and use. The objective of this paper is to draw lessons from a decade of experience in designing different user-centered eHealth interventions (eg, web portals and health apps) to inform future work in leveraging technology to address health disparities. We draw these lessons from a series of interventions from the work we have done over 15 years in the Viswanath laboratory at the Dana-Farber Cancer Institute and Harvard TH Chan School of Public Health, focusing on three projects that used web portals and health apps targeted toward underserved groups. The projects were the following: Click to Connect, which was a community-based eHealth intervention that aimed to improve internet skills and health literacy among underserved groups by providing home access to high-speed internet, computer, and internet training classes, as well as a dedicated health web portal with ongoing technical support; PLANET MassCONECT, which was a knowledge translation project that built capacity among community-based organizations in Boston, Lawrence, and Worcester in Massachusetts to adopt evidence-based health promotion programs; and Smartphone App for Public Health, which was a mobile health research that facilitated both participatory (eg, surveys) and passive data (eg, geolocations and web-browsing behaviors) collection for the purpose of understanding tobacco message exposure in individuals' built environment. Through our work, we distilled five key principles for researchers aiming to design eHealth interventions for underserved groups. They are as follows: develop a strategic road map to address communication inequalities (ie, a concrete action plan to identify the barriers faced by underserved groups and customize specific solutions to each of them), engage multiple stakeholders from the beginning for the long haul, design with usability-readability and navigability-in mind, build privacy safeguards into eHealth interventions and communicate privacy-utility tradeoffs in simplicity, and strive for an optimal balance between open science aspirations and protection of underserved groups., (©Edmund WJ Lee, Rachel F McCloud, Kasisomayajula Viswanath. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 07.01.2022.)

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

Rationale and Objectives: Patients with hepatic metastases from colorectal cancer have a poor prognosis in the salvage setting. This study assessed the survival benefit of adding transarterial 90 Y radioembolization in the salvage setting to systemic therapy., Materials and Methods: In this retrospective, matched-pair study, 21 patients who underwent radioembolization plus systemic therapy were matched with a cohort of 173 patients who received systemic chemotherapy alone in the salvage setting, defined as progression on at least two different regimens of systemic chemotherapy. Patients were matched one-to-one on Eastern Cooperative Oncology Group Performance Status, presence of extrahepatic disease, and presence of tumor KRAS mutation. Radioembolization patients underwent treatment using standard dosimetry to either a hepatic lobe or the whole liver. Survival data was analyzed using Kaplan-Meier analysis., Results: Patients who underwent radioembolization plus systemic therapy vs. those who had systemic therapy alone had similar demographics and exposure to prior systemic chemotherapies. Median survival from the date of primary diagnosis was 38 (95% CI 26 to 50) v 25 (95% CI 15 to 35) months in radioembolization with systemic therapy vs. systemic therapy alone (p = 0.17). Median survival from the date of hepatic metastases was 31 (95% CI 23.8 to 38.2) v 20 months (95% CI 10.2 to 29.8) in radioembolization with systemic therapy vs. systemic therapy alone (p = 0.03)., Conclusion: The addition of radioembolization to systemic therapy in patients with metastatic colorectal cancer to the liver may improve survival in the salvage setting., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Online supplemental material is available for this article .

Competing Interests: Conflict of interest The authors declare that there is no conflict of interest

Background: The prevalence of osteoporosis is increasing with the aging of the population and the socioeconomic burden. The purpose of this study was to determine the socioeconomic burden of osteoporosis in Korea. Methods: The prevalence of osteoporosis was analyzed using 2017 National Patients Sample and Korea National Health and Nutrition Examination Survey data. Direct costs were divided into healthcare and non-healthcare costs, and indirect costs were calculated by assessing the cost of loss of productivity for labor loss due to disease. Results: The prevalence of osteoporosis diagnosis was 1.91% in total, which was 13 times higher in women than in men (3.57% vs. 0.26%). The socioeconomic cost of osteoporosis was 299.1 million USD based on main diagnosis, and the cost was 13 times higher in women than in men (277.6 vs. 21.5 million USD). The total cost based on main and secondary diagnosis was 981.8 million USD. Similarly, the cost was seven times higher in women than in men (862.4 vs. 119.4 million USD). Conclusions: Osteoporosis increases the socioeconomic burden of disease, and it is significantly higher in women than in men. The policy support for the implementation of prevention and management programs would be necessary to reduce the burden of osteoporosis.

Introduction: The outcomes of transjugular intrahepatic portosystemic shunt (TIPS) placement in patients with hepatic encephalopathy (HE) are controversial. We studied the relationship of pre-TIPS HE in patients undergoing TIPS for refractory ascites on all-cause mortality and development of post-TIPS HE., Methods: A single-center retrospective comparison study was performed for patients undergoing TIPS for refractory ascites. Survival by history of pre-TIPS HE was demonstrated with Kaplan-Meier curves. Univariate and multivariate logistic regression analyses were performed to identify the predictors of post-TIPS clinical outcomes for patients with and without pre-TIPS HE., Results: We identified 202 TIPS recipients (61% male, mean ± SD; age 59.1 ± 10.2 years; mean model for end-stage liver disease score 17.3 ± 6.9). Pre-TIPS HE did not predispose patients for increased all-cause mortality, increased risk of experiencing HE within 60 days, or increased risk of hospital admission for HE within 6 months. A multivariate analysis demonstrated that total bilirubin (odds ratio [OR] 1.03; P = 0.016) and blood urea nitrogen (OR 1.15; P = 0.002) were predictors for all-cause mortality within 6 months post-TIPS. Age ≥65 years (OR 3.92; P = 0.004), creatinine (OR 2.22; P = 0.014), and Child-Pugh score (OR 1.53; P = 0.006) were predictors for HE within 60 days post-TIPS. Predictors of intensive care admission for HE within 6 months post-TIPS included age ≥65 years (OR 8.84; P = 0.018), history of any admission for HE within 6 months pre-TIPS (OR 8.42; P = 0.017), and creatinine (OR 2.22; P = 0.015)., Discussion: If controlled, pre-TIPS HE does not adversely impact patient survival or clinical outcomes, such as development of HE within 60 days of TIPS or hospital admission for HE within 6 months. Patients may be able to undergo TIPS for refractory ascites despite a history of HE., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: The purpose of this study is to describe a single institution's experience using Oncozene (OZ) microspheres for transarterial chemoembolization (OZ-TACE) of hepatocellular carcinoma (HCC), and to compare tolerability, safety, short-term radiographic tumor response, progression-free survival (PFS), and overall survival (OS) of these procedures to TACE (LC-TACE) performed with LC beads (LC). Methods: A retrospective, matched cohort study of patients undergoing DEB-TACE (drug-eluting bead transarterial chemoembolization) with OZ or LC was performed. The cohort comprised 23 patients undergoing 29 TACE with 75 or 100 μm OZ and 24 patients undergoing 29 TACE with 100-300 μm LC. Outcome measures were changes in liver function tests, complications, treatment tolerability, short-term radiographic tumor response according to modified RECIST criteria for HCC, PFS, and 1-year OS. The Mann-Whitney U test, Fisher exact test, and log rank test were used to compare the groups. Results: The BCLC or Child-Pugh scores were similar between the OZ and LC group. However, the two groups differed with respect to the etiology of background cirrhosis ( p = 0.02). All other initial demographic and tumor characteristics were similar between the two groups. OZ-TACE used less doxorubicin per treatment compared to LC-TACE (median 50 vs. 75 mg; p = 0.0005). Rates of pain, nausea, and postembolization syndrome were similar, irrespective of the embolic agent used. OZ-TACE resulted in an overall complication rate comparable to LC-TACE (20.7% vs. 10.3%; p = 0.47). LC-TACE resulted in a higher percent increase in total bilirubin on post-procedure day 1 (median 18.8 vs. 0%; p = 0.05), but this difference resolved at 1 month. Both OZ-TACE and LC-TACE resulted in similar complete (31% vs. 24%) and objective (66% vs. 79%) target lesion response rates on 1-month post-TACE imaging. Both OZ-TACE and LC-TACE had similar median progression-free survival (283 vs. 209 days; p = 0.14) and 1-year overall survival rates (85% vs. 76%; p = 0.30). Conclusion: With a significantly reduced dose of doxorubicin, TACE performed with Oncozene microspheres in a heterogeneous patient population is well-tolerated, safe, and produces a similar radiological response and survival rate when compared to LC Bead TACE.

Introduction: The purpose of this study was to investigate the rates of complications and diagnostic yield of transjugular liver biopsy (TJLB) in deceased donor liver transplant (DDLT) recipients., Methods: From January 2009 to December 2019, 1,055 TJLBs were performed in 603 adult DDLT recipients with a mean age of 54 (±12 years). Data were retrospectively reviewed to determine the diagnostic efficacy and incidence of major and minor complications in the 3-day and 1-month period after TJLB. In addition, data were stratified according to platelet count and international normalized ratio to determine the safety of TJLB in patients with varying degrees of coagulopathy., Results: TJLB yielded diagnostic rate of 98.1% (1,035/1,055), with an overall complication rate of 8.3% (88/1,055). Major complications accounted for 0.85% (9/1,055), and minor complications occurred in 7.48% (79/1,055). When patients were stratified by platelet count (0-50, 51-100, 101-200, 201-300, and >300 × 103 platelets/μL), no significant difference was noted in complication rates (9.5%, 8.6%, 7.6%, 8.5%, and 10.7%, respectively). When grouped by international normalized ratio (0-1, 1.1-2.0, 2.1-3.0, and >3.0), there was no statistical difference in complication rates (8.3%, 8.5%, 7.7%, and 0%, respectively)., Discussion: TJLB is a safe, adequate, and effective method to investigate hepatic disorders in DDLT recipients with severe coagulopathy., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)