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Literature circles [LC] are student-centered discussion groups that use various roles to make reading meaningful, comprehensible and enjoyable. The current research investigated the questioning effects and students' perceptions of integrating EFL [English-as-a-foreign-language] literature circles through student-led Facebook Groups. Findings indicated that although low cognitive level thinking questions were raised more often than higher-order thinking questions, the chi-square test indicated changes in questioning types. In other words, changes in student-generated higher-order thinking questions were observed. The qualitative data indicated that students benefited from the guided structure of LC, positive group dynamics, and increased reading engagement. Nevertheless, accountability, formalistic interaction and time allocation for reading tasks should also be taken into consideration in the designing of online literature circles.

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

Dravet syndrome (DS) is a genetic disorder caused by a deficit in the Nav1.1 channel, leading to drug-resistant epilepsy. The Nav1.1 channel plays a crucial role in microglial cell activation, and microglia are recognized as key mediators of seizures. In this study, we explored the role of microglia in DS-related epileptogenesis using a knock-in mouse model (Scn1aE1099X/+) that mimics a subset of DS patients. In these DS mice, we observed a significant downregulation of the Nav1.1 channel in microglia. This channel deficit led microglia to adopt a pro-inflammatory state in their quiescent phase. In the LPS-activated state, microglia predominantly exhibited an intermediate morphology rather than the expected fully activated form. The reduced expression of pro-inflammatory cytokines was detected in microglia following treatment with LPS. Notably, we found a significant decrease in the phagocytic ability of microglia in DS mice. Electrophysiological studies revealed an increased immature synaptic activity in the dentate gyrus in DS mice. The impaired microglial phagocytosis of damaged cells, combined with reduced cytokine secretion, may result in an excess of immature synaptic connections, neuronal hyperexcitation, and the formation of abnormal neural circuits in the hippocampus of Scn1aE1099X/+ mice. These changes could potentially contribute to mechanisms relevant to epileptogenesis in DS. [ABSTRACT FROM AUTHOR]

Background/Objectives: Marine turtles are globally threatened and face daily anthropogenic threats, including pollution. Water pollution from emerging contaminants such as antimicrobials is a major and current environmental concern. Methods: This study investigated the phenotypic antimicrobial resistance and heavy metal resistance genes of 47 Vibrio isolates from different stages of sea turtles (oceanic stage vs neritic stage) from the Taiwanese coast. Results: The results show that a high proportion (48.9%; 23/47) of the Vibrio species isolated from sea turtles in our study had a multiple antimicrobial resistance (MAR) pattern. It was found that Vibrio spp. isolates with a MAR pattern and those with a MAR index value greater than 0.2 were both more likely to be observed in neritic-stage sea turtles. Furthermore, isolates from neritic-stage sea turtles exhibited greater resistance to the majority of antimicrobials tested (with the exception of beta-lactams and macrolides) than isolates from the oceanic-stage groups. Isolates from neritic sea turtles were found to be more resistant to nitrofurans and aminoglycosides than isolates from oceanic sea turtles. Furthermore, isolates with a MAR pattern (p = 0.010) and those with a MAR index value greater than 0.2 (p = 0.027) were both found to be significantly positively associated with the mercury reductase (merA) gene. Conclusions: The findings of our study indicate that co-selection of heavy metals and antimicrobial resistance may occur in aquatic bacteria in the coastal foraging habitats of sea turtles in Taiwan. [ABSTRACT FROM AUTHOR]

In recent years, English instruction has emphasized the importance of listening comprehension; however, playing CDs in class is still the most widely used approach to practicing English listening skills in Taiwan. It is obvious that this training approach cannot satisfy individual needs, thus reducing the effect of promoting English listening comprehension performance. Thus, the study proposes a novel video-annotated listening review mechanism (VALRM) with two review modes -- the delayed and immediate review modes to enhance learners' listening comprehension performance. This study examines the effects of learners in the experimental group using the VALRM and those in the control group using Youtube with self-determined listening review mechanism (SDLRM) on English listening comprehension performance. Analytical results show that the learners with the VALRM support achieved significantly better listening comprehension performance than those of using the SDLRM. More importantly, the experimental results confirm that the learners in the experimental group had significantly better listening comprehension abilities even though removing the VALRM support than those of the control group removing the SDLRM support. Additionally, the interview results show most of the interviewees agreed that using the VALRM is more effective in promoting English listening learning performance than using the SDLRM because they could find out the unclear parts and replay them easily and efficiently. The main contribution of this study is to present an effective computer-assisted English listening learning tool based on the two review modes provided by the proposed VALRM in an autonomous learning environment.

Original citation: J Clin Invest. 2023;133(3):1-19. https://doi.org/10.n72/JCI157272. Citation for this corrigendum: J Clin Invest. 2023;133(9):171350. https://doi.org/10.1172/JCI171350. Yen-Po Tsao, [1,2,3] Fang-Yu Tseng, [4] Chih-Wei Chao, [1,4] Ming-Han Chen, [2] Yi-Chen Yeh, [...]

Signaling driven by nucleic acid sensors participates in interferonopathy-mediated autoimmune diseases. NLRP12, a pyrin-containing NLR protein, is a negative regulator of innate immune activation and type I interferon (IFN-I) production. Peripheral blood mononuclear cells (PBMCs) derived from systemic lupus erythematosus (SLE) patients expressed lower levels of NLRP12, with an inverse correlation with IFNA expression and high disease activity. NLRP12 expression was transcriptionally suppressed by runt-related transcription factor 1-dependent (RUNX1-dependent) epigenetic regulation under IFN-I treatment, which enhanced a negative feedback loop between low NLRP12 expression and IFN-I production. Reduced NLRP12 protein levels in SLE monocytes was linked to spontaneous activation of innate immune signaling and hyperresponsiveness to nucleic acid stimulations. Pristane-treated [Nlrp12.sup.-/-] mice exhibited augmented inflammation and immune responses; and substantial lymphoid hypertrophy was characterized in NLRP12deficient lupus-prone mice. NLRP12 deficiency mediated the increase of autoantibody production, intensive glomerular IgG deposition, monocyte recruitment, and the deterioration of kidney function. These were bound in an IFN-I signature- dependent manner in the mouse models. Collectively, we reveal a remarkable link between low NLRP12 expression and lupus progression, which suggests the impact of NLRP12 on homeostasis and immune resilience., Introduction Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with unknown etiology involving immune intolerance of endogenous nuclear materials, increased levels of auto-reactive B cells, and chronic inflammation, leading [...]

Background: Gastric cancer (GC) is a leading malignant disease in numerous countries, including Taiwan with limited therapeutic options. Animal viruses including oncolytic avian reovirus (ARV) have the possibility to avoid pre-existing immunity in humans, while being safe and immunostimulatory. Here, we provide a novel insight into oncolytic ARV and UV-ARV-sensitized patient's peripheral blood mononuclear cells (P-PBMCs) and tumor infiltrating lymphocytes (TILs) killing primary GC (PGC) cells through the surface TLR3 and TRAIL/DR4/DR5 immunogenic apoptosis pathway. Methods: We conducted a comprehensive study to reveal whether ARV- or UV-inactivated ARV (UV-ARV)-modulated P-PBMCs or TILs killing ARV- and UV-ARV-sensitized AGS cells and PGC cells derived from clinical patients and to investigate the regulation of surface TLR3 receptor and upstream signaling pathways. Apoptosis analysis by flow cytometry and Western blot, suppression of signal pathway by specific inhibitors, in situ proximity ligation assay (PLA), time-resolved flurometry and lactate dehydrogenase (LDH) cytotoxicity assays, and an in vitro co-culture model were established to study the interplay between ARV- and UV-ARV-sensitized P-PBMCs and TILs to kill PGC cells and their upstream pathways. Results: Our results reveal that increased levels of DR4 and DR5 were observed in ARV and UV-ARV sensitized PGC cells through the TLR3/p38/p53 signaling pathway. Importantly, we found that the σC protein of ARV or UV-ARV interacted with surface TLR3 of CD8+ TILs, thereby triggering the TLR3/NF-κB/IFN-γ/TRAIL signaling pathway which induces immunogenic apoptosis of PGC cells. This study sheds further light on the molecular basis behind ARV oncolysis and facilitates the ARV or UV-ARV as a cancer therapeutic. Conclusions: The study provides novel insights into ARV- or UV-ARV-sensitized P-PBMCs and CD8+ TILs to kill PGC cells through the immunogenic apoptosis pathway. We conclude that P-PBMCs can easily be obtained from GC patients and provide a rich source as TILs to kill PGC cells. [ABSTRACT FROM AUTHOR]