Repeat it without me: Crowdsourcing the T1 mapping common ground via the ISMRM reproducibility challenge.

PURPOSE: T1 mapping is a widely used quantitative MRI technique, but its tissue-specific values remain inconsistent across protocols, sites, and vendors. The ISMRM Reproducible Research and Quantitative MR study groups jointly launched a challenge to assess the reproducibility of a well-established inversion-recovery T1 mapping technique, using acquisition details from a seminal T1 mapping paper on a standardized phantom and in human brains. METHODS: The challenge used the acquisition protocol from Barral et al. (2010). Researchers collected T1 mapping data on the ISMRM/NIST phantom and/or in human brains. Data submission, pipeline development, and analysis were conducted using open-source platforms. Intersubmission and intrasubmission comparisons were performed. RESULTS: Eighteen submissions (39 phantom and 56 human datasets) on scanners by three MRI vendors were collected at 3 T (except one, at 0.35 T). The mean coefficient of variation was 6.1% for intersubmission phantom measurements, and 2.9% for intrasubmission measurements. For humans, the intersubmission/intrasubmission coefficient of variation was 5.9/3.2% in the genu and 16/6.9% in the cortex. An interactive dashboard for data visualization was also developed: https://rrsg2020.dashboards.neurolibre.org. CONCLUSION: The T1 intersubmission variability was twice as high as the intrasubmission variability in both phantoms and human brains, indicating that the acquisition details in the original paper were insufficient to reproduce a quantitative MRI protocol. This study reports the inherent uncertainty in T1 measures across independent research groups, bringing us one step closer to a practical clinical baseline of T1 variations in vivo.

Epidemiology of Respiratory Viruses in Korean Children Before and After the COVID-19 Pandemic: A Prospective Study From National Surveillance System.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic led to a decrease in the seasonal incidence of many respiratory viruses worldwide due to the impact of nonpharmaceutical interventions (NPIs). However, as NPI measures were relaxed, respiratory viral infections re-emerged. We aimed to characterize the epidemiology of respiratory viruses in Korean children during post-COVID-19 pandemic years compared to that before the pandemic. METHODS: A nationwide prospective ongoing surveillance study has been conducted for detection of respiratory viruses between January 2017 and June 2023. We included data on adenovirus (AdV), human bocavirus (HBoV), human coronavirus (HCoV), human metapneumovirus (HMPV), human rhinovirus (HRV), influenza virus (IFV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV), which were detected in children and adolescents younger than 20 years. We analyzed the weekly detection frequency of individual viruses and the age distribution of the affected children. The study period was divided into prepandemic (2017-2019) and postpandemic (2021-2023) periods. RESULTS: A total of 19,589 and 14,068 samples were collected in the pre- and postpandemic periods, respectively. The overall detection rate of any virus throughout the study period was 63.1%, with the lowest occurring in the 2nd half of 2020 (50.6%) and the highest occurring in the 2nd half of 2021 (72.3%). Enveloped viruses (HCoV, HMPV, IFV, PIV, and RSV) almost disappeared, but nonenveloped viruses (AdV, HBoV, and HRV) were detected even during the peak of the COVID-19 pandemic. The codetection rate increased from 15.0% prepandemic to 19.1% postpandemic (P < 0.001). During the postpandemic period, a large out-of-season PIV and HMPV epidemic occurred, but the usual seasonality began to be restored in 2023. The mean age of children with each virus detected in 2023 was significantly greater than that in prepandemic years (P = 0.003 and 0.007 for AdV and HCoV, respectively; P < 0.001 for others). The mean age of children with IFV increased in 2022 (11.1 ± 5.2 years) from prepandemic years (7.9 ± 4.6 years) but decreased to 8.7 ± 4.1 years in 2023. CONCLUSION: With the relaxation of NPI measures, several seasonal respiratory viruses cocirculated with unusual seasonal epidemic patterns and were associated with increasing age of infected children.

The A2ml1-Knockout mouse as an animal model for non-syndromic otitis media.

BACKGROUND: Inflammation and infection of the middle ear, known as otitis media (OM), is a leading cause of hearing loss and the most frequently diagnosed disease in children worldwide. Traditionally, mouse models for OM rely on inducing acute infection through inoculation of the middle ear, e.g. with the human otopathogen non-typeable Haemophilus influenzae (NTHi), and with very few genetic models with spontaneous or chronic OM. A2ML1 variants, including loss-of-function variants, were associated with susceptibility to OM in humans, but no animal model has been reported for A2ml1-related OM. Here, we report our middle ear findings in a mouse line with a CRISPR-induced knockout (KO) of A2ml1. METHODS: Mice were X-rayed prior to harvest to determine if there are craniofacial or skeletal abnormalities. Tissue from mouse middle ears, as well as other upper respiratory mucosal tissues, were harvested. The harvested middle ear bullae were examined under microscope and submitted for histologic preparation to study phenotypic indications of OM. RNA samples isolated from middle ear tissue were assayed for expression of genes correlated with A2ML1 expression in humans. RESULTS: Data from a total of 119 mice (35 wildtype, 40 heterozygous, 44 homozygous) are presented here, with each analyses being performed on subsets of these mice. There were no significant craniofacial differences by genotype (n = 22). Findings in mice with the A2ml1-KO indicated an increased incidence of OM (n=29; odds ratio = 11; CI: 1.1, 573.6; Fisher exact two-sided p = 0.02) with tympanic membrane perforations or thickening, as well as cases of middle ear effusion, inflammatory cells, or fluid from histologic sections. Dsp was upregulated in the middle ear tissues of homozygous mice (Wilcoxon test p = 0.001). CONCLUSION: Thus far, our results in this A2ml1-KO mouse line indicate spontaneous occurrence of OM and dysregulation of Dsp in the middle ear as a potential disease mechanism for A2ml1-related OM.

Minimum clinically important difference and substantial clinical benefit in patients with chronic temporomandibular disorders.

BACKGROUND: Research on temporomandibular disorder (TMD) responsiveness is scarce and limited regarding patients' representativeness. OBJECTIVE(S): This study aimed to estimate minimum clinically important difference (MCID) and substantial clinical benefit (SCB) among a large and diverse patient population regarding sex and age. METHODS: In this study, 162 patients participated from five hospitals. MCID and SCB in pain, functional disability and quality of life were examined with anchor-based methods. Patients' global impression of change was used as the anchor. Area under the curve (AUC) values were determined for testing accuracy. Changes from baseline and coefficient of variation by responsiveness status were calculated to explain the results of accuracy. RESULTS: SCB was estimated to be 2.18 for the numeric rating scale (NRS) for pain (AUC: 0.80 [95% CI: 0.72-0.88]) in all patients and 2.50 in women (AUC: 0.81 [95% CI: 0.71-0.89]). The estimated SCB of NRS for discomfort (1.50) and Jaw Functional Limitation Scale for mastication (1.35) had wide CIs for AUCs. Likewise, the estimated MCIDs of NRS for pain (0.80) and NRS for discomfort (1.50) had wide CIs for AUCs. Among non-responders who did not achieve the MCID of NRS for pain, the coefficient of variation was very high for all outcomes other than the NRS for pain. CONCLUSION: This study investigated the responsiveness of patients with TMD using a large and diverse patient sample. SCB in pain decrease can be used to assess the responsiveness of patients with TMD. Composite outcomes should be developed to estimate MCID.

The Mediating Role of Anxiety/Depression Between Auditory Verbal Hallucinations and the Level of Insight in Schizophrenia.

OBJECTIVE: Auditory verbal hallucination (AVH) is a prominent symptom of schizophrenia causing profound distress. The influence of AVHs on insight appears to be intricate and contingent on other accompanying symptoms. This study investigated the relationship and possible mediators between AVHs and the degree of insight. METHODS: One hundred patients with schizophrenia participated in the study. Scales were used to evaluate the hallucinatory experience, the level of insight and other psychopathology. Complex relationships between variables were envisaged as a path model, whose initial structure was constructed via Gaussian Graphical Model. The validity of the final model was verified by Structural Equation Modeling. Separate analyses were performed for self-reported and clinician-rated data to enhance the model's robustness. RESULTS: The greater the severity of the physical aspects of AVHs, the lower the level of insight observed. Conversely, higher emotional distress was associated with increased insight. These relationships were only evident in the self-reported results and were not reflected in the clinician-rated results. The path model suggested that the Positive and Negative Syndrome Scale (PANSS) anxiety/depression factor was an important mediator that linked the found association. Notably, the PANSS negative symptom had the opposite effect on the PANSS anxiety/depression factor and insight, making it difficult to define its overall effect. CONCLUSION: The findings of this study provided one possible route for the positive influence of AVH experience in gaining insight. The mediating role of anxiety/depression modified by negative symptoms emerged as a valuable concept for clarifying this intricate relationship.

Extracellular signals induce dynamic ER remodeling through αTAT1-dependent microtubule acetylation.

Dynamic changes in the endoplasmic reticulum (ER) morphology are central to maintaining cellular homeostasis. Microtubules (MT) facilitate the continuous remodeling of the ER network into sheets and tubules by coordinating with many ER-shaping protein complexes, although how this process is controlled by extracellular signals remains unknown. Here we report that TAK1, a kinase responsive to various growth factors and cytokines including TGF-ß and TNF-α, triggers ER tubulation by activating αTAT1, an MT-acetylating enzyme that enhances ER-sliding. We show that this TAK1/αTAT1-dependent ER remodeling promotes cell survival by actively downregulating BOK, an ER membrane-associated proapoptotic effector. While BOK is normally protected from degradation when complexed with IP3R, it is rapidly degraded upon their dissociation during the ER sheets-to-tubules conversion. These findings demonstrate a distinct mechanism of ligand-induced ER remodeling and suggest that the TAK1/αTAT1 pathway may be a key target in ER stress and dysfunction.

Phosphoproteomic profiling identifies DNMT1 as a key substrate of beta IV spectrin-dependent ERK/MAPK signaling in suppressing angiogenesis.

ßIV-spectrin is a membrane-associated cytoskeletal protein that maintains the structural stability of cell membranes and integral proteins such as ion channels and transporters. Its biological functions are best characterized in the brain and heart, although recently we discovered a fundamental new role in the vascular system. Using cellular and genetic mouse models, we reported that ßIV-spectrin acts as a critical regulator of developmental and tumor-associated angiogenesis. ßIV-spectrin was shown to selectively express in proliferating endothelial cells (EC) and suppress VEGF/VEGFR2 signaling by enhancing receptor internalization and degradation. Here we examined how these events impact the downstream kinase signaling cascades and target substrates. Based on quantitative phosphoproteomics, we found that ßIV-spectrin significantly affects the phosphorylation of epigenetic regulatory enzymes in the nucleus, among which DNA methyltransferase 1 (DNMT1) was determined as a top substrate. Biochemical and immunofluorescence results showed that ßIV-spectrin inhibits DNMT1 function by activating ERK/MAPK, which in turn phosphorylates DNMT1 at S717 to impede its nuclear localization. Given that DNMT1 controls the DNA methylation patterns genome-wide, and is crucial for vascular development, our findings suggest that epigenetic regulation is a key mechanism by which ßIV-spectrin suppresses angiogenesis.

Antimicrobial activity of ceftazidime-avibactam against KPC-2-producing Enterobacterales: a cross-combination and dose-escalation titration study with relebactam and vaborbactam.

With the introduction of ceftazidime-avibactam worldwide, the antimicrobial activity of new ß-lactam/ß-lactamase inhibitors (BL/BLIs) needs to be investigated. From January 2020 to June 2023, Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales were collected. With a broth microdilution test of new BL/BLIs, cross-activity test with nine combinations of BLs and new BLIs and dose-escalation titration test for non-susceptible isolates were conducted to investigate inhibitory activities of new BLIs. A total of 188 isolates was collected and most isolates (186/188, 98.9%) carried the KPC-2 gene exclusively, while two isolates (1.1%) co-harbored NDM-1. Among the 186 KPC-2-producing isolates, 184 (98.9%) were susceptible to ceftazidime-avibactam, 173 (93.0%) to imipenem-relebactam, and 184 (98.9%) to meropenem-vaborbactam. All isolates non-susceptible to imipenem-relebactam or meropenem-vaborbactam became susceptible when avibactam replaced relebactam or vaborbactam, with 7 of 11 (63.6%) imipenem-relebactam non-susceptible isolates and both (100.0%) of the meropenem-vaborbactam non-susceptible isolates. When the minimum inhibitory concentrations (MICs) of BLs were compared using log2 scales, combinations with avibactam showed statistically significant efficacy in lowering MICs compared to relebactam and vaborbactam (all P < 0.05). In the dose-escalation test of new BLIs, increasing dose of all new BLIs corresponded to increased susceptibility to BLs. Ceftazidime-avibactam exhibited excellent susceptibility against KPC-2-producing Enterobacterales unless co-harboring metallo-ß-lactamase. The cross-combination test against non-susceptible isolates suggests that the inhibitory activity of avibactam was superior to those of relebactam or vaborbactam. Increasing the dose of new BLIs produced increased susceptibility to BLs, suggesting that high-concentration regimen need to be developed. IMPORTANCE: This study investigated 188 Klebsiella pneumoniae carbapenemase (KPC)-2-producing Enterobacterales collected from January 2020 to June 2023 in a tertiary care hospital of Korea. Most isolates were susceptible to ceftazidime-avibactam (98.9%) and meropenem-vaborbactam (98.9%), while susceptibility to imipenem-relebactam was lower (93.0%). The cross-combination test using nine combinations of the individual ß-lactams (BLs) and new ß-lactamase inhibitors (BLIs) showed that the inhibitory activity of avibactam was significantly superior to relebactam or vaborbactam when the Log2 MIC of BLs were compared for each combination with BLIs (all P < 0.05). The dose-escalation test of new BLIs demonstrated that increasing doses of new BLIs corresponded to increased susceptibility to BLs. Taken together, this study illustrates the excellent activity of ceftazidime-avibactam against KPC-2-producing Enterobacterales and suggests further investigation into high-concentration regimens for potentially non-susceptible clinical isolates.

Long-term skeletodental changes with early and late treatment using modified C-palatal plates in hyperdivergent Class II adolescents.

OBJECTIVES: To compare skeletodental changes between early and late treatment groups using modified C-palatal plates (MCPP) and long-term retention outcomes in hyperdivergent Class II adolescents. MATERIALS AND METHODS: Seventy-one hyperdivergent Class II patients were divided into four groups according to treatment modality and treatment timing: group 1, early treatment with MCPP (n = 16; 9.9 ± 0.9 years); group 2, late treatment with MCPP (n = 19; 12.3 ± 0.8 years); group 3, early treatment with headgear (HG; n = 18; 9.6 ± 0.8 years); and group 4, late treatment with HG (n = 18; 12.1 ± 1.2 years). Lateral cephalograms were taken and skeletal and dental variables were measured. For statistical analysis, paired t-tests, independent t-tests, and multiple regression were performed. RESULTS: The early MCPP group showed a more significant decrease in mandibular plane angle than the late MCPP group did, and vertical control was more efficient in the early group than in the late group. In the MCPP groups, both FMA and SN-GoGn were increased with late treatment but decreased with early treatment, and the difference was statistically significant (P < .01). The early-treatment MCPP group had a significant decrease in SN-GoGn of 0.6° compared with an increase of 1.7° in the early treatment HG group (P < .01). Posttreatment stability of both the early and late MCPP groups was maintained in long-term retention. CONCLUSIONS: Early MCPP showed more significant vertical control than late MCPP. However, there was no difference in long-term stability between early and late groups.

Performance evaluation of the SMG HHV-6 Q Real-Time PCR Kit for quantitative detection and differentiation of human herpesvirus 6A and 6B.

The aim of this study was to compare the performance of the newly developed SMG HHV-6 Q Real-Time PCR Kit (SMG assay) with the RealStar HHV-6 PCR Kit (RealStar assay). The analytical sensitivity and specificity, linearity, and precision of the SMG assay were evaluated. The clinical performance of the SMG assay was assessed and compared with that of the RealStar assay using 207 clinical specimens (HHV-6A positive, n = 51; HHV-6B positive, n = 64; HHV-6A/B negative, n = 92). The limit of detection of the SMG assay was 2.92 log10 copies/mL for HHV-6A DNA and 2.88 log10 copies/mL for HHV-6B DNA. The linear range was determined to be 3.40-9.00 log10 copies/mL for both viruses. Intra- and inter-assay variability were below 5% at concentrations ranging from 4 to 9 log10 copies/mL. No cross-reactivity was observed with the 25 microorganisms included in the specificity panel. The clinical sensitivity and specificity of the SMG and RealStar assays compared to in-house polymerase chain reaction and sequencing were as follows: SMG assay, 98.0% and 100% for HHV-6A DNA, respectively, and 96.9% and 100% for HHV-6B DNA, respectively; RealStar assay, 98.0% and 100% for HHV-6A DNA, respectively, and 90.6% and 100% for HHV-6B DNA, respectively. The correlation coefficients between viral loads measured by the two assays were 0.948 and 0.975, with mean differences of 0.62 and 0.32 log10 copies/mL for HHV-6A and HHV-6B DNA, respectively. These results demonstrate that the SMG assay is a sensitive and reliable tool for the quantitative detection and differentiation of HHV-6A and HHV-6B DNA.IMPORTANCEQuantitative real-time PCR (qPCR) that can distinguish between HHV-6A and HHV-6B DNA is recommended for diagnosis of active infection. The SMG HHV-6 Q Real-Time PCR Kit (SMG assay) is a newly developed qPCR assay that can differentiate between HHV-6A and HHV-6B DNA; however, little is known about its performance. In this study, we assessed the performance of the SMG assay and compared it with that of a commercially available qPCR assay, the RealStar HHV-6 PCR Kit (RealStar assay). The SMG assay demonstrated excellent analytical sensitivity and specificity, precision, and linearity. Furthermore, the viral loads measured by the SMG assay were highly correlated with those measured by the RealStar assay. Our results suggest that the SMG assay is a useful diagnostic tool for quantitative detection and differentiation of HHV-6A and HHV-6B DNA.

Reliability of Artificial Intelligence-based Cone Beam Computed Tomography Integration with Digital Dental Images.

This study aimed to introduce cone-beam computed tomography (CBCT) digitization and integration of digital dental images (DDI) based on artificial intelligence (AI)-based registration (ABR) and to evaluate the reliability and reproducibility using this method compared with those of surface-based registration (SBR). This retrospective study consisted of CBCT images and DDI of 17 patients who had undergone computer-aided bimaxillary orthognathic surgery. The digitization of CBCT images and their integration with DDI were repeated using an AI-based program. CBCT images and DDI were integrated using a point-to-point registration. In contrast, with the SBR method, the three landmarks were identified manually on the CBCT and DDI, which were integrated with the iterative closest points method. After two repeated integrations of each method, the three-dimensional coordinate values of the first maxillary molars and central incisors and their differences were obtained. Intraclass coefficient (ICC) testing was performed to evaluate intra-observer reliability with each method's coordinates and compare their reliability between the ABR and SBR. The intra-observer reliability showed significant and almost perfect ICC in each method. There was no significance in the mean difference between the first and second registrations in each ABR and SBR and between both methods; however, their ranges were narrower with ABR than with the SBR method. This study shows that AI-based digitization and integration are reliable and reproducible.

Experimental evidence for anti-metastatic actions of apigenin: a mini review.

Cancer metastasis is responsible for the majority of cancer-related deaths. Accordingly, to reduce metastasis remains a vital challenge in clinical practice, and phytochemicals have taken an attention as anti-metastatic agents. Apigenin, a plant flavone, showed anti-cancer effects against in various animal models, moreover its potentials inhibiting tumor metastasis have been reported. Herein, we analyzed the overall features at what apigenin inhibited metastasis and its action modes. We searched for articles in MEDLINE (Pubmed), EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) through March 2023. Total 6 animal studies presented anti-metastatic effects of apigenin using 5 difference experimental models, while the mechanisms involved modulations of epithelial-mesenchymal transition (EMT), matrix metalloproteinases (MMPs), angiogenesis, and various metastasis-related signaling pathways. This review provides an overall potential of apigenin as a candidate reducing the risk of cancer metastasis.

Deep learning-based image reconstruction for the multi-arterial phase images: improvement of the image quality to assess the small hypervascular hepatic tumor on gadoxetic acid-enhanced liver MRI.

PURPOSE: To evaluated the impact of a deep learning (DL)-based image reconstruction on multi-arterial-phase magnetic resonance imaging (MA-MRI) for small hypervascular hepatic masses in patients who underwent gadoxetic acid-enhanced liver MRI. METHODS: We retrospectively enrolled 55 adult patients (aged ≥ 18 years) with small hepatic hypervascular mass (≤ 3 cm) between December 2022 and February 2023. All patients underwent MA-MRI, subsequently reconstructed with a DL-based application. Qualitative assessment with Linkert scale including motion artifact (MA), liver edge (LE), hepatic vessel clarity (HVC) and image quality (IQ) was performed. Quantitative image analysis including signal to noise ratio (SNR), contrast to noise ratio (CNR) and noise was performed. RESULTS: On both arterial phases (APs), all qualitative parameters were significantly improved after DL-based image reconstruction. (LE on 1st AP, 1.22 vs 1.61; LE on 2nd AP, 1.21 vs 1.65; HVC on 1st AP, 1.24 vs 1.39; HVC on 2nd AP, 1.24 vs 1.44; IQ on 1st AP, 1.17 vs 1.45; IQ on 2nd AP, 1.17 vs 1.47, all p values < 0.05). The SNR, CNR and noise were significantly improved after DL-based image reconstruction. (SNR on AP1, 279.08 vs 176.14; SNR on AP2, 334.34 vs 199.24; CNR on AP1, 106.09 vs 64.14; CNR on AP2, 129.66 vs 73.73; noise on AP1, 1.51 vs 2.33; noise on AP2, 1.45 vs 2.28, all p values < 0.05). CONCLUSIONS: Gadoxetic acid-enhanced MA-MRI with DL-based image reconstruction improved the qualitative and quantitative parameters. Despite the short acquisition time, high-quality MA-MRI is now achievable.

Communication: Evaluation of the Humasis COVID-19 Antigen Rapid Diagnostic Test for the Diagnosis of SARS-CoV-2 Infection.

OBJECTIVE: We assessed the performance of the Humasis COVID-19 AgHS Test (Humasis, Korea), a novel antigen rapid diagnostic test (Ag-RDT) based on lateral flow immunoassay. METHODS: 85 SARS-CoV-2-positive and 155 SARS-CoV-2-negative nasopharyngeal swab specimens confirmed by rRT-PCR were tested using the Humasis and PBCheck Ag-RDTs. The analytical specificity of the Humasis Ag-RDT was evaluated using 27 strains of human respiratory pathogens. RESULTS: The overall sensitivity and specificity were 72.9% and 99.4% for the Humasis Ag-RDT and 64.7% and 100% for the PBCheck Ag-RDT, respectively. The sensitivity for specimens with Ct≤25 was 100% for both Ag-RDTs. The Humasis Ag-RDT showed no cross-reactivity with other respiratory pathogens. CONCLUSION: Our data suggests that the Humasis Ag-RDT can be a useful diagnostic tool for the detection of SARS-CoV-2 infection.

Improving the Three-Dimensional Printability of Potato Starch Loaded onto Food Ink.

This study focuses on improving the 3D printability of pea protein with the help of food inks designed for jet-type 3D printers. Initially, the food ink base was formulated using nanocellulose-alginate with a gradient of native potato starch and its 3D printability was evaluated. The 3D-printed structures using only candidates for the food ink base formulated with or without potato starch exhibited dimensional accuracy exceeding 95% on both the X and Y axes. However, the accuracy of stacking on the Z-axis was significantly affected by the ink composition. Food ink with 1% potato starch closely matched the CAD design, with an accuracy of approximately 99% on the Z-axis. Potato starch enhanced the stacking of 3D-printed structures by improving the electrostatic repulsion, viscoelasticity, and thixotropic behavior of the food ink base. The 3D printability of pea protein was evaluated using the selected food ink base, showing a 46% improvement in dimensional accuracy on the Z-axis compared to the control group printed with a food ink base lacking potato starch. These findings suggest that starch can serve as an additive support for high-resolution 3D jet-type printing of food ink material.

Efficacy of Moxibustion for Cancer-Related Fatigue in Patients with Breast Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Breast cancer is the most commonly diagnosed cancer worldwide, and most patients experience fatigue. However, there are no effective treatments for cancer-related fatigue (CRF). Several randomized controlled trials (RCTs) have suggested that moxibustion improves CRF. We conducted a systematic review and meta-analysis to compare the differences in fatigue scale scores, quality of life, and clinical efficacy in patients with breast cancer who developed CRF and did versus did not receive moxibustion. METHODS: RCTs were searched in 7 databases using a standardized search method from database inception to March 2023, and RCTs that met the inclusion criteria were selected. RESULTS: Among 1337 initially identified RCTs, 10 RCTs involving 744 participants were selected for this study. The meta-analysis involved assessment of the revised Piper Fatigue Scale scores, Cancer Fatigue Scale scores, Karnofsky Performance Scale scores, Athens Insomnia Scale scores, clinical efficacy, and Qi deficiency syndrome scale scores. Compared with the control, moxibustion was associated with significantly better Piper Fatigue Scale scores (P < 0.0001), quality of life [Karnofsky Performance Scale scores (P < 0.0001)], clinical efficacy (P = 0.0007), and Qi deficiency syndrome scale scores (P = 0.02). CONCLUSIONS: Moxibustion improves CRF in patients with breast cancer. The efficacy of moxibustion should be further examined by high-quality studies in various countries with patients subdivided by their breast cancer treatment status. REGISTRATION: PROSPERO ID: CRD42023451292.

Glycosaminoglycan modifications of betaglycan regulate ectodomain shedding to fine-tune TGF-ß signaling responses in ovarian cancer.

In pathologies including cancer, aberrant Transforming Growth Factor-ß (TGF-ß) signaling exerts profound tumor intrinsic and extrinsic consequences. Intense clinical endeavors are underway to target this pathway. Central to the success of these interventions is pinpointing factors that decisively modulate the TGF-ß responses. Betaglycan/type III TGF-ß receptor (TßRIII), is an established co-receptor for the TGF-ß superfamily known to bind directly to TGF-ßs 1-3 and inhibin A/B. Betaglycan can be membrane-bound and also undergo ectodomain cleavage to produce soluble-betaglycan that can sequester its ligands. Its extracellular domain undergoes heparan sulfate and chondroitin sulfate glycosaminoglycan modifications, transforming betaglycan into a proteoglycan. We report the unexpected discovery that the heparan sulfate glycosaminoglycan chains on betaglycan are critical for the ectodomain shedding. In the absence of such glycosaminoglycan chains betaglycan is not shed, a feature indispensable for the ability of betaglycan to suppress TGF-ß signaling and the cells' responses to exogenous TGF-ß ligands. Using unbiased transcriptomics, we identified TIMP3 as a key inhibitor of betaglycan shedding thereby influencing TGF-ß signaling. Our results bear significant clinical relevance as modified betaglycan is present in the ascites of patients with ovarian cancer and can serve as a marker for predicting patient outcomes and TGF-ß signaling responses. These studies are the first to demonstrate a unique reliance on the glycosaminoglycan chains of betaglycan for shedding and influence on TGF-ß signaling responses. Dysregulated shedding of TGF-ß receptors plays a vital role in determining the response and availability of TGF-ßs', which is crucial for prognostic predictions and understanding of TGF-ß signaling dynamics.

Survival benefit of concurrent chemoradiotherapy for advanced ampulla of Vater cancer.

BACKGROUND: Currently, there is no standard adjuvant therapy for patients with resected ampulla of Vater (AoV) cancer. AIM: To evaluate the effectiveness of adjuvant concurrent chemoradiotherapy (CCRT) in patients with advanced AoV cancer who underwent curative resection. METHODS: This single-centered, retrospective study included 29 patients with advanced AoV cancer who underwent pancreaticoduodenectomy between 2006 and 2018. The impact of CCRT on advanced AoV cancer was analyzed. RESULTS: The 1-, 3-, and 5-yr recurrence-free survival (RFS) rates for patients with advanced AoV cancer were 82.8%, 48.3%, and 40.8%, respectively, and the overall survival (OS) rates were 89.7%, 62.1%, and 51.7%, respectively. Lymphovascular invasion was found to be a significant risk factor for RFS and OS in patients with advanced AoV cancer in the univariate analysis, whereas T stage and lymph node metastasis were significantly associated with OS in the multivariate analysis. Compared to the patients who did not receive adjuvant CCRT, those who received adjuvant CCRT did not show statistically significant improvements in the RFS and OS, although they had a significantly lower average age and significantly higher platelet-to-lymphocyte ratio. CONCLUSION: Adjuvant CCRT did not improve survival outcomes in patients with advanced AoV cancer. These findings contribute to existing knowledge on the effectiveness of CCRT in this patient population and provide important insights for clinical decision-making.

No Significant Differences in Presepsin Levels According to the Causative Microorganism of Bloodstream Infection.

BACKGROUND: CD14 recognizes lipopolysaccharide (LPS), and presepsin is a fragment of soluble CD14. Still, it remains uncertain whether Gram-negative bacteria induce higher presepsin levels than other microorganisms. To address this question, this study aimed to analyze presepsin levels based on microorganisms isolated in blood cultures. MATERIALS AND METHODS: This study was a single-center study comprising suspected sepsis patients enrolled from July 2020 to September 2020. A total of 95 patients with a single isolate confirmed in blood culture were analyzed to evaluate if there are any differences in presepsin levels according to microbial isolates. Plasma presepsin level was measured using PATHFAST assay kit and analyzer (LSI Medience Corporation, Tokyo, Japan). RESULTS: There were 26 Gram-positive bacteremia, 65 Gram-negative bacteremia, and 3 fungemia patients with median presepsin levels of 869, 1,439, and 11,951 pg/mL, respectively. Besides, one case of algaemia demonstrated a presepsin level of 1,231 pg/mL. Our results showed no statistically significant difference in presepsin levels among patients with Gram-positive bacteremia, Gram-negative bacteremia, and fungemia. Furthermore, presepsin levels did not differ significantly among bloodstream infections caused by bacteria that were isolated from at least three different patients. In particular, Gram-positive bacteria such as Staphylococcus aureus and Enterococcus faecalis were able to induce presepsin levels comparable to those induced by Gram-negative bacteria. CONCLUSION: We demonstrated that there were no significant differences in plasma presepsin levels according to microbial isolates in blood culture. The major cause of the variability in presepsin levels during bloodstream infection might be the immunogenicity of each microorganism rather than the presence of LPS in the microorganism.