Notes

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Therapeutic resistance occurs in most patients with multiple myeloma (MM). One of the key mechanisms for MM drug resistance comes from the interaction between MM cells and adipocytes that inhibits drug-induced apoptosis in MM cells; MM cells reprogram adipocytes to morph into different characterizations, including exosomes, which are important for tumor-stroma cellular communication. However, the mechanism by which exosomes mediate the cellular machinery of the vicious cycle between MM cells and adipocytes remains unclear.

Adipocytes were either isolated from bone marrow aspirates of healthy donors or MM patients or derived from mesenchymal stem cells. Co-culturing normal adipocytes with MM cells was used to generate MM-associated adipocytes. Exosomes were collected from the culture medium of adipocytes. Annexin V-binding and TUNEL assays were performed to assess MM cell apoptosis. Methyltransferase activity assay and dot blotting were used to access the m
A methylation activity of methyltransferase likeLncRNA package into adipocyte exosomes through METTL7A-mediated LncRNA m
A methylation. Exposure of adipocytes to MM cells enhances METTL7A activity in m
A methylation through EZH2-mediated protein methylation.

This study elucidates an unexplored mechanism of how adipocyte-rich microenvironment exacerbates MM therapeutic resistance and indicates a potential strategy to improve therapeutic efficacy by blocking this vicious exosome-mediated cycle.
This study elucidates an unexplored mechanism of how adipocyte-rich microenvironment exacerbates MM therapeutic resistance and indicates a potential strategy to improve therapeutic efficacy by blocking this vicious exosome-mediated cycle.
Breastfeeding offers many medical and neurodevelopmental advantages for birthing parents and infants; however, the majority of parents stop breastfeeding before it is recommended. Professional lactation support by the International Board Certified Lactation Consultants (IBCLCs) increases breastfeeding rates; however, many communities lack access to IBCLCs. Black and Latinx parents have lower breastfeeding rates, and limited access to professional lactation support may contribute to this disparity. Virtual "telelactation" consults that use two-way video have the potential to increase access to IBCLCs among disadvantaged populations. We present a protocol for the digital Tele-MILC trial, which uses mixed methods to evaluate the impact of telelactation services on breastfeeding outcomes. The objective of this pragmatic, parallel design randomized controlled trial is to assess the impact of telelactation on breastfeeding duration and exclusivity and explore how acceptability of and experiences with telelactatioe qualitative data on the experiences of different subgroups of parents with the telelactation intervention, including barriers to use, satisfaction, and strengths and limitations of this delivery model.

This is the first randomized study evaluating the impact of telelactation on breastfeeding outcomes. It will inform the design and implementation of future digital trials among pregnant and postpartum people, including Black and Latinx populations which are historically underrepresented in clinical trials.

ClinicalTrials.gov NCT04856163. Registered on April 23, 2021.
ClinicalTrials.gov NCT04856163. Registered on April 23, 2021.
Direct analogs of chemically modified bases that carry important epigenetic information, such as 5-methylcytosine (m5C)/5-methyldeoxycytosine (5mC), 5-hydroxymethylcytosine (hm5C)/5-hydroxymethyldeoxycytosine (5hmC), and N
-methyladenosine (m6A)/N
-methyldeoxyadenosine (6mA), are detected in both RNA and DNA, respectively. The modified base N
-acetylcytosine (ac4C) is well studied in RNAs, but its presence and epigenetic roles in cellular DNA have not been explored.

Here, we demonstrate the existence of N
-acetyldeoxycytosine (4acC) in genomic DNA of Arabidopsis with multiple detection methods. Genome-wide profiling of 4acC modification reveals that 4acC peaks are mostly distributed in euchromatin regions and present in nearly half of the expressed protein-coding genes in Arabidopsis. 4acC is mainly located around transcription start sites and positively correlates with gene expression levels. Imbalance of 5mC does not directly affect 4acC modification. We also characterize the associations of 4acC with 5mC and histone modifications that cooperatively regulate gene expression. Moreover, 4acC is also detected in genomic DNA of rice, maize, mouse, and human by mass spectrometry.

Our findings reveal 4acC as a hitherto unknown DNA modification in higher eukaryotes. We identify potential interactions of this mark with other epigenetic marks in gene expression regulation.
Our findings reveal 4acC as a hitherto unknown DNA modification in higher eukaryotes. We identify potential interactions of this mark with other epigenetic marks in gene expression regulation.
B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy has obtained promising results in relapsed or refractory multiple myeloma (R/R MM), while some patients do not response, or relapse in short term after treatment. Combining with anti-CD38 might solve the problem of targeting BCMA alone. We aimed to assess the efficacy and safety of BCMA and CD38 (BCMA-CD38) bispecific CAR-T cells in R/R MM patients.

We did a single-center, single-arm clinical study at the Second Affiliated Hospital of Yangtze University in China. Patients meeting with the inclusion criteria were administered with fludarabine and cyclophosphamide before CAR-T cells infusion. Response and adverse events were assessed after infusion. This study was registered with the Chinese Clinical Trial Registration Center (ChiCTR1900026286).

First, we found BCMA-CD38 CAR-T cells exhibited enhanced killing effect on BCMA+CD38+ cells in vitro, compared to BCMA CAR-T and CD38 CAR-T cells. We further demonstrated its anti-tus grades of CRS, of which five patients (31.3%) got serious CRS (Grade ≥ 3). The CAR+ cellexpansion levels were associated with the severity of CRS. Transient clonal isotype switch was observed after CAR-T infusion.

Our results confirm that BCMA-CD38 CAR-T cells therapy is feasible in treating R/R MM patients, with high response rate, low recurrence rate and manageable CRS, which will be a promising treatment option for R/R MM.

ChiCTR1900026286, registered on September 29, 2019, retrospectively registered, URL https//www.chictr.org.cn/showproj.aspx?proj=43805.
ChiCTR1900026286, registered on September 29, 2019, retrospectively registered, URL https//www.chictr.org.cn/showproj.aspx?proj=43805.
Constructing gene coexpression networks is a powerful approach for analyzing high-throughput gene expression data towards module identification, gene function prediction, and disease-gene prioritization. While optimal workflows for constructing coexpression networks, including good choices for data pre-processing, normalization, and network transformation, have been developed for microarray-based expression data, such well-tested choices do not exist for RNA-seq data. Almost all studies that compare data processing and normalization methods for RNA-seq focus on the end goal of determining differential gene expression.

Here, we present a comprehensive benchmarking and analysis of 36 different workflows, each with a unique set of normalization and network transformation methods, for constructing coexpression networks from RNA-seq datasets. We test these workflows on both large, homogenous datasets and small, heterogeneous datasets from various labs. We analyze the workflows in terms of aggregate performanceanalysis based on the experimental factors of their RNA-seq dataset.
Excess weight gain in young adulthood is associated with future weight gain and increased risk of chronic disease. Although multimodal, technology-based weight-loss interventions have the potential to promote weight loss among young adults, many interventions have limited personalization, and few have been deployed and evaluated for longer than a year. Selleck ALC-0159 We aim to assess the effects of a highly personalized, 2-year intervention that uses popular mobile and social technologies to promote weight loss among young adults.

The Social Mobile Approaches to Reducing Weight (SMART) 2.0 Study is a 24-month parallel-group randomized controlled trial that will include 642 overweight or obese participants, aged 18-35 years, from universities and community colleges in San Diego, CA. All participants receive a wearable activity tracker, connected scale, and corresponding app. Participants randomized to one intervention group receive evidence-based information about weight loss and behavior change techniques via personaliz improvement. We further hypothesize that differences in secondary outcomes will favor the intervention groups. There is a critical need to advance understanding of the effectiveness of multimodal, technology-based weight-loss interventions that have the potential for long-term effects and widespread dissemination among young adults. Our findings should inform the implementation of low-cost and scalable interventions for weight loss and risk-reducing health behaviors.

ClinicalTrials.gov NCT03907462 . Registered on April 9, 2019.
ClinicalTrials.gov NCT03907462 . Registered on April 9, 2019.
Lymph node metastasis is the main cause of poor prognosis of head and neck squamous carcinoma (HNSCC) patients. N6-methyladenosine (m6A) RNA modification is an emerging epigenetic regulatory mechanism for gene expression, and as a novel m6A reader protein, IGF2BP2 has been implicated in tumor progression and metastasis. However, not much is currently known about the functional roles of IGF2BP2 in HNSCC, and whether IGF2BP2 regulates lymphatic metastasis through m6A modification in HNSCC remains to be determined.

The expression and overall survival (OS) probability of m6A-related regulators in HNSCC were analyzed with The Cancer Genome Atlas (TCGA) dataset and GEPIA website tool, respectively. The expression levels of IGF2BP2 were measured in HNSCC tissues and normal adjacent tissues. To study the effects of IGF2BP2 on HNSCC cell metastasis in vitro and in vivo, gain- and loss- of function methods were employed. RIP, MeRIP, luciferase reporter and mRNA stability assays were performed to explore the epigenecovers the oncogenic role and potential mechanism of IGF2BP2, which serves as a m6A reader, in controlling lymphatic metastasis and EMT in HNSCC, suggesting that IGF2BP2 may act as a therapeutic target and prognostic biomarker for HNSCC patients with metastasis.
Collectively, our study uncovers the oncogenic role and potential mechanism of IGF2BP2, which serves as a m6A reader, in controlling lymphatic metastasis and EMT in HNSCC, suggesting that IGF2BP2 may act as a therapeutic target and prognostic biomarker for HNSCC patients with metastasis.
The Syrian conflict has endured for a decade, causing one of the most significant humanitarian crises since World War II. The conflict has inflicted massive damage to civil infrastructure, and not even the health care sector has been spared. On the contrary, health care has been targeted, and as a result, many health professionals have left the country. Despite the life-threatening condition, many health professionals continued to work inside Syria even in the middle of the acute crisis. This qualitative study aims to determine the factors that have motivated Syrian health professionals to work in a conflict-affected country.

The research is based on 20 semi-structured interviews of Syrian health care workers. Interviews were conducted in 2016-2017 in Gaziantep, Turkey. A thematic inductive content analysis examined the motivational factors Syrian health care workers expressed for their work in the conflict area.

Motivating factors for health care workers were intrinsic and extrinsic. Intrinsic reasons included humanitarian principles and medical ethics.
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