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International students, particularly international English as a Second Language (ESL) students who come to the United States with relatively lower levels of English oral language proficiency, are often reluctant to participate in academic discussions. In a graduate-level TESOL program with a majority of international ESL students, a video recording, sharing, and discussion platform, "Flip," was utilized in the program's teaching innovation. "Flip" is widely adopted by educators of all grade levels worldwide, as it enables educators to create a less formal online space to meet the holistic needs of international ESL students, including both academic and social needs. The article explains the teaching context of the practice, four stages of course integration with "Flip," reasons for the integration, reflections, and future pedagogical directions. Incorporating "Flip" in this program promotes linguistic benefits, teacher identity and skill development, a community of belonging, and increased equity in assessment. Practical pedagogical considerations are also provided at the end of the article.

Abnormal expression of long non-coding RNAs (lncRNAs) is associated with the dysfunctions of human trophoblast cells and the occurrence of miscarriage (abnormal early embryo loss). BBC3/PUMA (BCL2 binding component 3) plays significant roles in regulation of cell apoptosis. However, whether specific lncRNAs might regulate BBC3 in trophoblast cells and further induce apoptosis and miscarriage remains completely unclear. Through screening, we identified a novel lnc-HZ12, which was significantly highly expressed in villous tissues of recurrent miscarriage (RM) patients relative to their healthy control (HC) group. Lnc-HZ12 suppressed chaperone-mediated autophagy (CMA) degradation of BBC3, promoted trophoblast cell apoptosis, and was associated with miscarriage. In mechanism, lnc-HZ12 downregulated the expression levels of chaperone molecules HSPA8 and LAMP2A in trophoblast cells. Meanwhile, lnc-HZ12 (mainly lnc-HZ12-SO2 region in F2 fragment) and HSPA8 competitively bound with the 169RVLYNL174 patch on BBC3, which prevented BBC3 from interactions with HSPA8 and impaired the formation of BBC3-HSPA8-LAMP2A complex for CMA degradation of BBC3. Thus, lnc-HZ12 upregulated the BBC3-CASP9-CASP3 pathway and induced trophoblast cell apoptosis. In villous tissues, lnc-HZ12 was highly expressed, CMA degradation of BBC3 was suppressed, and the apoptosis levels were higher in RM vs HC villous tissues, all of which were associated with miscarriage. Interestingly, knockdown of murine Bbc3 could efficiently suppress placental apoptosis and alleviate miscarriage in a mouse miscarriage model. Taken together, our results indicated that lnc-HZ12 and BBC3 played important roles in trophoblast cell apoptosis and miscarriage and might act as attractive targets for miscarriage treatment. Abbreviation: 7-AAD: 7-aminoactinomycin D; BaP: benzopyrene; BBC3/PUMA: BCL2 binding component 3; ChIP: chromatin immunoprecipitation; CHX: cycloheximide; CMA: chaperone-mediated autophagy; CQ: chloroquine; DMSO: dimethyl sulfoxide; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HC: healthy control; HSPA8: heat shock protein family A (Hsp70) member 8; IP: immunoprecipitation; LAMP2A: lysosomal associated membrane protein 2; LncRNA: long non-coding RNA; mRNA: messenger RNA; MT: mutant-type; NC: negative control; NSO: nonspecific oligonucleotide; PARP1: poly(ADP-ribose) polymerase 1; RIP: RNA immunoprecipitation; RM: recurrent miscarriage; TBP: TATA-box binding protein; WT: wild-type. [ABSTRACT FROM AUTHOR]

Macrophages have been recognized as pivotal players in the progression of MASLD/MASH. However, the molecular mechanisms underlying their multifaceted functions in the disease remain to be further clarified. In the current study, we developed a new mouse model with YAP activation in macrophages to delineate the effect and mechanism of YAP signaling in the pathogenesis of MASLD/MASH. Genetically modified mice, featuring specific depletion of both Mst1 and Mst2 in macrophages/monocytes, were generated and exposed to a high‐fat diet for 12 weeks to induce MASLD. Following this period, livers were collected for histopathological examination, and liver non‐parenchymal cells were isolated and subjected to various analyses, including single‐cell RNA‐sequencing, immunofluorescence and immunoblotting and qRT‐PCR to investigate the impact of YAP signaling on the progression of MASLD. Our data revealed that Mst1/2 depletion in liver macrophages enhanced liver inflammation and fibrosis in MASLD. Using single‐cell RNA‐sequencing, we showed that YAP activation via Mst1/2 depletion upregulated the expressions of both pro‐inflammatory genes and genes associated with resolution/tissue repair. We observed that YAP activation increases Kupffer cell populations (i.e., Kupffer‐2 and Kupffer‐3) which are importantly implicated in the pathogenesis of MASLD/MASH. Our data indicate that YAP activation via Mst1/2 deletion enhances both the pro‐inflammatory and tissue repairing functions of Kupffer‐1 and ‐2 cells at least in part through C1q. These YAP‐regulatory mechanisms control the plasticity of liver macrophages in the context of MASLD/MASH. Our findings provide important evidence supporting the critical regulatory role of YAP signaling in liver macrophage plasticity and the progression of MASLD. Therefore, targeting the Hippo‐YAP pathway may present a promising therapeutic strategy for the treatment of MASH. [ABSTRACT FROM AUTHOR]

Summary: T/myeloid mixed phenotype acute leukaemia (MPAL) is a rare aggressive acute leukaemia with poorly understood pathogenesis. Herein, we report two cases of T/myeloid MPAL harbouring BCL11B‐associated structural variants that activate TLX3 (TLX3::BCL11B‐TLX3‐activation) by genome sequencing and transcriptomic analyses. Both patients were young males with extramedullary involvement. Cooperative gene alterations characteristic of T/myeloid MPAL and T‐lymphoblastic leukaemia (T‐ALL) were detected. Both patients achieved initial remission following lineage‐matched ALL‐based therapy with one patient requiring a lineage‐switched myeloid‐based therapy. Our study is the first to demonstrate the clinicopathological and genomic features of TLX3::BCL11B‐TLX3‐activated T/myeloid MPAL and provide insights into leukaemogenesis. [ABSTRACT FROM AUTHOR]

Introduction: The mechanism of relapsed CD19(−) B‐ALL after anti‐CD19 immunotherapy (Kymriah [CART‐19] and blinatumomab) is under active investigation. Our study aims to assess LILRB1 as a novel B‐cell marker for detecting CD19(−) B‐lymphoblasts and to analyze the clinicopathologic/genetic features of such disease to provide biological insight into relapse. Methods: Six patients (3 males/3 females, median age of 14 years) with relapsed CD19(−) B‐ALL were analyzed for cytogenetic/genetic profile and immunophenotype. Results: CD19(−) B‐ALL emerged after an interval of 5.8 months following anti‐CD19 therapy. Five of six patients had B‐cell aplasia, indicative of a persistent effect of CART or blinatumomab at relapse. Importantly, LILRB1 was variably expressed on CD19(−) and CD19(+) B lymphoblasts, strong on CD34(+) lymphoblasts and dim/partial on CD34(−) lymphoblasts. Three of six patients with paired B‐ALL samples (pre‐ and post‐anti‐CD19 therapy) carried complex and different cytogenetic abnormalities, either as completely different or sharing a subset of cytogenetic abnormalities. Conclusion: LILRB1 can be used as a novel B‐cell marker to identify CD19(−) B lymphoblasts. The emergence of CD19(−) B‐ALL appears to be associated with complex cytogenetic evolutions. The mechanism of CD19(−) B‐ALL relapse under anti‐CD19 immune pressure remains to be explored by comprehensive molecular studies. [ABSTRACT FROM AUTHOR]

Genomic imprinting is an epigenetic regulation in mammals in which a small subset of genes is monoallelically expressed dependent on their parental origin. A large imprinted domain, SGCE/PEG10 locus, is located on human chromosome 7q21s and mouse proximal chromosome 6. However, genomic imprinting of bovine SGCE/PEG10 cluster has not been systematically studied. In this study, we investigated allele expression of 14 genes of the SGCE/PEG10 locus in bovine somatic tissues and term placenta using a single nucleotide polymorphism (SNP)‐based sequencing method. In addition to SGCE and PEG10, two conserved paternally expressed genes in human and mice, five other genes (TFPI2, GNG11, ASB4, PON1, and PON3) were paternally expressed. Three genes, BET1, COL1A2, and CASD1, exhibited tissue‐specific monoallelic expression. CALCR showed monoallelic expression in tissues but biallelic expression in the placenta. Three genes, GNGT1, PPP1R9A, and PON2, showed biallelic expression in cattle. Five differentially methylated regions (DMRs) were found to be associated with the allelic expression of TFPI2, COL1A2, SGCE/PEG10, PON3, and ASB4 genes, respectively. The SGCE/PEG10 DMR is a maternally hypermethylated germline DMR, but TFPI2, COL1A2, PON3, and ASB4 DMRs are secondary DMRs. In summary, we identified five novel bovine imprinted genes (GNG11, BET1, COL1A2, CASD1, and PON1) and four secondary DMRs at the SGCE/PEG10 locus. [ABSTRACT FROM AUTHOR]

Objective: To describe cases of Kaposi's sarcoma‐associated herpesvirus (KSHV)‐associated multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL) in patients with HIV from a large, safety‐net hospital system in Dallas, Texas, USA. Methods: We conducted a retrospective review of patients with HIV‐associated PEL and/or MCD. Results: Twelve patients with PEL and 10 patients with MCD were identified. All patients were male and 17 of 20 were men who have sex with men; 66.7% of PEL patients and 50% of MCD patients had concurrent KS at the time of diagnosis; 42% of patients with PEL and 20% of patients with MCD died during the follow‐up period. We noted improved survival in our cohort compared to previous studies, particularly in our PEL patients with a median survival of 11.4 months compared to 3–6‐month median survival historically. Median follow‐up time for MCD patients was 17.5 months. This improved survival is despite suboptimal antiretroviral therapy (ART) adherence at diagnosis, with only 50% of patients on ART at the time of MCD/PEL diagnosis. Conclusion: These data highlight the importance of early recognition of PEL and MCD, and the larger‐scale efforts needed to better understand the pathogenetic drivers of clinical outcomes in patients affected by KSHV‐related diseases. [ABSTRACT FROM AUTHOR]

The article explores a specific type of paroxysmal nocturnal haemoglobinuria (PNH) known as ahemolytic PNH or white cell PNH. Unlike typical PNH, this subtype does not exhibit signs of hemolysis but is characterized by bone marrow failure and thrombophilia. The document suggests that this subtype may be caused by a PIGA mutation in a committed progenitor cell rather than a stem cell. The authors recommend considering screening for ahemolytic PNH in cases of thromboembolic events and bone marrow failure without hemolysis. [Extracted from the article]

Fibrin-associated large B-cell lymphoma (FA-LBCL) is a rare subtype of Epstein-Barr virus (EBV)-associated lymphoma, recognized as an independent entity per the 5th edition of the WHO classification of hematolymphoid neoplasms. It is usually associated with longstanding chronic inflammation and arises within fibrinous material in confined anatomic spaces. We report the clinicopathologic manifestations of two patients of FA-LBCL involving the adrenal gland and kidney. Both tumors were diagnosed after presenting as cystic masses on imaging studies. These lymphomas were non-invasive, with microscopic aggregates of large B-lymphoma cells along/within cystic wall and admixed with fibrinous material and without prominent inflammation. By immunohistochemistry and in-situ hybridization, lymphoma cells were positive for CD45, PAX5, CD79a, MUM1, BCL2, PD-L1, and EBV/EBER (Epstein-Barr virus encoded small RNA) with a high proliferation index. Both patients remain in remission after management with complete surgical resection and additional chemo-immunotherapy in one patient. Considering its rarity, scant tumor cells, and varied clinical presentations, FA-LBCL may pose diagnostic challenges, especially when presenting as extensively necrotic cystic lesions, needing multidisciplinary collaboration in formulating management. [ABSTRACT FROM AUTHOR]

Human trophoblast cells are crucial for healthy pregnancy. However, whether the defective homologous recombination (HR) repair of dsDNA break (DSB) in trophoblast cells may induce miscarriage is completely unknown. Moreover, the abundance of BRCA1 (a crucial protein for HR repair), its recruitment to DSB foci, and its epigenetic regulatory mechanisms, are also fully unexplored. In this work, it is identified that a novel lnc‐HZ10, which is highly experssed in villous tissues of recurrent miscarriage (RM) vs their healthy control group, suppresses HR repair of DSB in trophoblast cell. Lnc‐HZ10 and AhR (aryl hydrocarbon receptor) form a positive feedback loop. AhR acts as a transcription factor to promote lnc‐HZ10 transcription. Meanwhile, lnc‐HZ10 also increases AhR levels by suppressing its CUL4B‐mediated ubiquitination degradation. Subsequently, AhR suppresses BRCA1 transcription; and lnc‐HZ10 (mainly 1‐447 nt) interacts with γ‐H2AX; and thus, impairs its interactions with BRCA1. BPDE exposure may trigger this loop to suppress HR repair in trophoblast cells, possibly inducing miscarriage. Knockdown of murine Ahr efficiently recovers HR repair in placental tissues and alleviates miscarriage in a mouse miscarriage model. Therefore, it is suggested that AhR/lnc‐HZ10/BRCA1 axis may be a promising target for alleviation of unexplained miscarriage. [ABSTRACT FROM AUTHOR]

Objectives Our study aimed to develop a machine learning (ML) model to accurately classify acute promyelocytic leukemia (APL) from other types of acute myeloid leukemia (other AML) using multicolor flow cytometry (MFC) data. Multicolor flow cytometry is used to determine immunophenotypes that serve as disease signatures for diagnosis. Methods We used a data set of MFC files from 27 patients with APL and 41 patients with other AML, including those with uncommon immunophenotypes. Our ML pipeline involved training a graph neural network (GNN) to output graph-level labels and identifying the most crucial MFC parameters and cells for predictions using an input perturbation method. Results The top-performing GNN achieved 100% accuracy on the training/validation and test sets on classifying APL from other AML and used MFC parameters similarly to expert pathologists. Pipeline performance is amenable to use in a clinical decision support system, and our deep learning architecture readily enables prediction explanations. Conclusions Our ML pipeline shows robust performance on predicting APL and could be used to screen for APL using MFC data. It also allowed for intuitive interrogation of the model's predictions by clinicians. [ABSTRACT FROM AUTHOR]