Prospects for Light Dark Matter Searches at Large-Volume Neutrino Detectors.

We propose a new approach to search for light dark matter (DM), with keV-GeV mass, via inelastic nucleus scattering at large-volume neutrino detectors such as Borexino, DUNE, Super-K, Hyper-K, and JUNO. The approach uses inelastic nuclear scattering of cosmic-ray boosted DM, enabling a low-background search for DM in these experiments. Large neutrino detectors, with higher thresholds than dark matter detectors, can be used, since the nuclear deexcitation lines are O(10)  MeV.

Complement C5a Receptor Signaling in Macrophages Enhances Trained Immunity Through mTOR Pathway Activation.

Complement C5a receptor (C5aR) signaling in immune cells has various functions, inducing inflammatory or anti-inflammatory responses based on the type of ligand present. The Co1 peptide (SFHQLPARSRPLP) has been reported to activate C5aR signaling in dendritic cells. We investigated the effect of C5aR signaling via the Co1 peptide on macrophages.

Coronavirus nucleocapsid-based vaccine provides partial protection against hetero-species coronavirus in murine models.

Most coronavirus vaccines focus on the spike (S) antigen, but the frequent mutations in S raise concerns about the vaccine efficacy against new variants. Although additional antigens with conserved sequences are have been tested, the extent to which these vaccines can provide immunity against different coronavirus species remains unclear. In this study, we assessed the potential of nucleocapsid (N) as a coronavirus vaccine antigen.

S2 Peptide-Conjugated SARS-CoV-2 Virus-like Particles Provide Broad Protection against SARS-CoV-2 Variants of Concern.

Approved COVID-19 vaccines primarily induce neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. However, the emergence of variants of concern with RBD mutations poses challenges to vaccine efficacy. This study aimed to design a next-generation vaccine that provides broader protection against diverse coronaviruses, focusing on glycan-free S2 peptides as vaccine candidates to overcome the low immunogenicity of the S2 domain due to the N-linked glycans on the S antigen stalk, which can mask S2 antibody responses.

Pancreatic volume and endocrine function changes following pancreaticoduodenectomy for peri-ampullary neoplasms: A retrospective single-center study utilizing pancreas volumetry.

Backgrounds/aims: We evaluated long-term pancreatic functional outcomes, including pancreatic volumetry after pancreaticoduodenectomy (PD) for peri-ampullary neoplasm.

Methods: We retrospectively reviewed 353 patients with a 12-month follow-up who underwent elective pancreaticoduodenectomies for peri-ampullary neoplasms at a single university hospital between January 2011 and December 2020. Perioperative and postoperative outcomes, long-term pancreatic endocrine functions, and pancreatic volume changes 12 month postoperatively were evaluated.

A Composite Blood Biomarker Including AKR1B10 and Cytokeratin 18 for Progressive Types of Nonalcoholic Fatty Liver Disease.

Backgruound: We aimed to evaluate whether composite blood biomarkers including aldo-keto reductase family 1 member B10 (AKR1B10) and cytokeratin 18 (CK-18; a nonalcoholic steatohepatitis [NASH] marker) have clinically applicable performance for the diagnosis of NASH, advanced liver fibrosis, and high-risk NASH (NASH+significant fibrosis).

Methods: A total of 116 subjects including healthy control subjects and patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) were analyzed to assess composite blood-based and imaging-based biomarkers either singly or in combination.

Results: A composite blood biomarker comprised of AKR1B10, CK-18, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) showed excellent performance for the diagnosis of, NASH, advanced fibrosis, and high-risk NASH, with area under the receiver operating characteristic curve values of 0.

Novel S2 subunit-specific antibody with broad neutralizing activity against SARS-CoV-2 variants of concern.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), had a major impact on both the global health and economy. Numerous virus-neutralizing antibodies were developed against the S1 subunit of SARS-CoV-2 spike (S) protein to block viral binding to host cells and were authorized for control of the COVID-19 pandemic. However, frequent mutations in the S1 subunit of SARS-CoV-2 enabled the emergence of immune evasive variants.

C5aR dendritic cells fine-tune the Peyer's patch microenvironment to induce antigen-specific CD8 T cells.

The mucosal delivery route is considered ideal for immunization. However, induction of antigen-specific mucosal immunity is difficult due to the tolerogenic environment. Therefore, developing an immunogenic mucosal dendritic cell (DC)-targeting strategy is required.

Liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma: A multicenter study.

Background: Patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) are not traditionally considered eligible for liver transplantation (LT) due to poor outcomes.

Aim: To compare outcomes between living donor LT (LDLT) patients with hepatocellular carcinoma (HCC) and LT patients with cHCC-CC and to identify risk factors for tumor recurrence and death after LT in cHCC-CC patients.

Methods: Data for pathologically diagnosed cHCC-CC patients ( = 111) who underwent LT from 2000 to 2018 were collected for a nine-center retrospective review.

Pre-existing Immunity to Endemic Human Coronaviruses Does Not Affect the Immune Response to SARS-CoV-2 Spike in a Murine Vaccination Model.

Endemic human coronaviruses (HCoVs) have been evidenced to be cross-reactive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a correlation exists between the immunological memory to HCoVs and coronavirus disease 2019 (COVID-19) severity, there is little experimental evidence for the effects of HCoV memory on the efficacy of COVID-19 vaccines. Here, we investigated the Ag-specific immune response to COVID-19 vaccines in the presence or absence of immunological memory against HCoV spike Ags in a mouse model.

Influenza viral matrix 1 protein aggravates viral pathogenicity by inducing TLR4-mediated reactive oxygen species production and apoptotic cell death.

Influenza virus is one of the most challenging viruses threating human health. Since infection with influenza virus triggers inflammatory responses and induces cell death, the molecular and cellular mechanisms by which the virus-infected cells undergo apoptotic and necrotic cell death have been widely studied. However, most of the studies have focused on the molecular events occurring in the cytosol and there is limited information on the physiological correlation between virus-induced cell death and the viral pathogenesis in vivo.

The Impact of the Multiple Bile Ducts on Postoperative Biliary Complications In Patients Undergoing Living Donor Liver Transplantation.

Background: We aimed to investigate the correlation between bile duct number and biliary complications in patients who underwent donor liver transplantation (LDLT).

Methods: We reviewed all patients who underwent LDLT in our hospital between July 2008 and December 2020. The patients were divided into 2 groups according to the number of bile ducts in the living donor graft (single duct [SD] or multiple ducts [MD]).

Overactivated NRF2 induces pseudohypoxia in hepatocellular carcinoma by stabilizing HIF-1α.

Hypoxia-inducible factor-1α (HIF-1α) is highly expressed/activated in most hypoxic tumors including hepatocellular carcinoma (HCC). Another key transcription factor, nuclear factor erythroid 2-related factor 2 (NRF2), is also constitutively overactivated in HCC. In an attempt to determine whether HIF-1α and NRF2 could play complementary roles in HCC growth and progression, we investigated the crosstalk between these two transcription factors and underlying molecular mechanisms in cultured HCC cells and experimentally induced hepatocarcinogenesis as well as clinical settings.

Pseudomonas stutzeri PM101005 inhaled with atmospheric particulate matter induces lung damage through inflammatory responses.

Atmospheric particulate matter (PM) contains a mixture of chemical and biological elements that pose threat to human health by increasing susceptibility to respiratory diseases. Although the identification of the microorganisms composing the PM has been assessed, their immunological impacts are still questionable. Here, we examined the mechanisms responsible for the pathogenicity of Pseudomonas stutzeri PM101005 (PMPS), a bacterium isolated from fine dust, in lung epithelial cells, alveolar cells, and macrophages.

Solutions to the MiniBooNE Anomaly from New Physics in Charged Meson Decays.

We point out that production of new bosons by charged meson decays can greatly enhance the sensitivity of beam-focused accelerator-based experiments to new physics signals. This enhancement arises since the charged mesons are focused and their three-body decays do not suffer from helicity suppression in the same way as their usual two-body decays. As a realistic application, we attempt to explain the MiniBooNE low energy excess utilizing this overlooked mechanism, uniquely realizing dark-sector interpretations as plausible solutions to the excess.

Plasma Aldo-Keto Reductase Family 1 Member B10 as a Biomarker Performs Well in the Diagnosis of Nonalcoholic Steatohepatitis and Fibrosis.

We found several blood biomarkers through computational secretome analyses, including aldo-keto reductase family 1 member B10 (AKR1B10), which reflected the progression of nonalcoholic fatty liver disease (NAFLD). After confirming that hepatic AKR1B10 reflected the progression of NAFLD in a subgroup with NAFLD, we evaluated the diagnostic accuracy of plasma AKR1B10 and other biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) and fibrosis in replication cohort. We enrolled healthy control subjects and patients with biopsy-proven NAFLD ( = 102) and evaluated the performance of various diagnostic markers.

Extracellular nucleoprotein exacerbates influenza virus pathogenesis by activating Toll-like receptor 4 and the NLRP3 inflammasome.

Host immune responses, such as those initiated by pattern recognition receptor (PRR) activation, are important for viral clearance and pathogenesis. However, little is known about the interactions of viral proteins with surface PRRs or, more importantly, the association of innate immune activation with viral pathogenesis. In this study, we showed that internal influenza virus proteins were released from infected cells.

Automated pancreas segmentation and volumetry using deep neural network on computed tomography.

Pancreas segmentation is necessary for observing lesions, analyzing anatomical structures, and predicting patient prognosis. Therefore, various studies have designed segmentation models based on convolutional neural networks for pancreas segmentation. However, the deep learning approach is limited by a lack of data, and studies conducted on a large computed tomography dataset are scarce.

Effect of stent graft fixation types on pararenal aortic diameter and renal function after endovascular aortic repair.

Background: This study aims to identify pararenal aortic diameter changes following endovascular aortic repair and to investigate the effects of suprarenal fixation on renal function.

Methods: Between May 2006 and January 2019, a total of 168 patients (135 males, 33 females; mean age: 75.2±8.

The impact of Model for End-Stage Liver Disease score on deceased donor liver transplant outcomes in low volume liver transplantation center: a retrospective and single-center study.

Purpose: In June 2016, the Model for End-Stage Liver Disease (MELD) score was employed in South Korea instead of the Child-Turcotte-Pugh (CTP) score. This study compared the outcomes of deceased donor liver transplantation (DDLT) before and after the MELD system application.

Methods: This retrospective study reviewed 48 patients who underwent DDLT for end-stage liver disease at a single tertiary referral center between January 2014 and December 2018.

The impact of fine particulate matter (PM) on various beneficial functions of human endometrial stem cells through its key regulator SERPINB2.

Fine particulate matter (PM) has a small diameter but a large surface area; thus, it may have broad toxic effects that subsequently damage many tissues of the human body. Interestingly, many studies have suggested that the recent decline in female fertility could be associated with increased PM exposure. However, the precise mechanisms underlying the negative effects of PM exposure on female fertility are still a matter of debate.

Inhibition of O-GlcNAcylation protects from Shiga toxin-mediated cell injury and lethality in host.

Shiga toxins (Stxs) produced by enterohemorrhagic Escherichia coli (EHEC) are the major virulence factors responsible for hemorrhagic colitis, which can lead to life-threatening systemic complications including acute renal failure (hemolytic uremic syndrome) and neuropathy. Here, we report that O-GlcNAcylation, a type of post-translational modification, was acutely increased upon induction of endoplasmic reticulum (ER) stress in host cells by Stxs. Suppression of the abnormal Stx-mediated increase in O-GlcNAcylation effectively inhibited apoptotic and inflammatory responses in Stx-susceptible cells.