High Levels of DEK Autoantibodies in Sera of Patients With Polyarticular Juvenile Idiopathic Arthritis and With Early Disease Flares Following Cessation of Antiâ Tumor Necrosis Factor Therapy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142962/1/art40404_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142962/2/art40404-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142962/3/art40404.pd

Protective effect of ligustrazine on oxidative stress and apoptosis following testicular torsion in rats

Abstract Testicular torsion is a common urologic emergency and one of the causes of infertility in males. It has been reported that ligustrazine may decrease oxidative stress and reduce ischemia–reperfusion injury. This study aims to investigate the protective effect of ligustrazine in ischemia–reperfusion injury after testicular torsion-detorsion. First, 40 rats were randomly and equally divided into TMP (Ligustrazine) group, the Testicular torsion (T/D) group, the Sham (Sham operation) group, and Control group. The left testis of rats in the TMP and T/D group was rotated for 2 h. The TMP group was intraperitoneally injected with ligustrazine solution and the T/D and the Sham groups were injected with normal saline. The left testes of four groups were obtained for assay on the 4th day after the operation. Average level of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) were higher in Sham and Control groups than T/D group and TMP group. Conversely, average level of malondialdehyde (MDA) and reactive oxygen species (ROS) was lower in Sham and Control groups than T/D group and TMP group. In contrast with the T/D group, SOD, GPX, and CAT enzymatic activities increased, whereas MDA and ROS content decreased in the TMP group (P < 0.05). Microscopic observation showed that the testicular tissue of the Sham and Control groups were basically normal. The TMP and T/D groups had significant testicular tissue damage, whereas the TMP group had less damage and apoptosis than the T/D group. The apoptotic index of germ cells in the TMP group (13.05 ± 4.41) was lower than the T/D group (30.23 ± 11.31) (P < 0.05) and higher (P < 0.05) than the Sham group (0.56 ± 0.29). So we found that Ligustrazine lowered ischemia–reperfusion injury after testicular torsion-detorsion by decreasing the reactive oxygen species and suppressing apoptosis

Factors associated with adherence to post-treatment follow-up among a cohort of women with acetic acid/Lugol’s iodine positive lesions of the cervix in Cameroon: A retrospective cohort study

Background: Women treated for cervical precancerous lesions have up to a 30 % increased risk of developing cervical cancer compared to women in the general population. The aim of this study was to identify predictors for adherence to follow-up among women treated for precancerous lesions of the cervix in Cameroon. Materials and Methods: The study design was a retrospective cohort analysis of a five-year follow-up for women in Cameroon who were initially treated for cervical precancer lesions in 2013. Logistic regression models were used to determine factors associated with adherence to post-treatment follow-up. Statistical significance was set at p < 0.05. Results: Of the 344 women treated in 2013, 154 (44.77 %) never returned for a single post-treatment follow-up in five years. Marital status was the only variable statistically significantly associated with 5-year post-treatment follow-up adherence. women who had ever been married were 0.36 times (0.14 0.93)); p = 0. 0.035] less likely to adhere to post-treatment follow-up compared to women who have never been married. Although age was not statistically significant, women in the age group 30–49 years had some significance and they were 60 % [aOR, 95 %CI: 0.40 (0.18 0.89); p = 0.024] less likely to adhere to post-treatment follow-up when compared to women who were<30 years. Conclusion: Only about half of the women treated for cervical precancer in this cohort returned for post-treatment follow-up. Conducting needs assessments among these populations that are less likely to adhere to follow-up will allow us to implement and test strategies to improve adherence to follow-up

RNA-seq analysis identifies transcriptomic profiles associated with anal cancer recurrence among people living with HIV

AbstractBackground Chemoradiation therapy (CRT) is the standard of care for squamous cell carcinoma of the anus (SCCA), the most common type of anal cancer. However, approximately one fourth of patients still relapse after CRT.Methods We used RNA-sequencing technology to characterize coding and non-coding transcripts in tumor tissues from CRT-treated SCCA patients and compare them between 9 non-recurrent and 3 recurrent cases. RNA was extracted from FFPE tissues. Library preparations for RNA-sequencing were created using SMARTer Stranded Total RNA-Seq Kit. All libraries were pooled and sequenced on a NovaSeq 6000. Function and pathway enrichment analysis was performed with Metascape and enrichment of gene ontology (GO) was performed with Gene Set Enrichment Analysis (GSEA).Results There were 449 differentially expressed genes (DEGs) observed (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between the two groups. We identified a core of upregulated genes (IL4, CD40LG, ICAM2, HLA-I (HLA-A, HLA-C) and HLA-II (HLA-DQA1, HLA-DRB5) in the non-recurrent SCCA tissue enriching to the gene ontology term ‘allograft rejection’, which suggests a CD4+ T cell driven immune response. Conversely, in the recurrent tissues, keratin (KRT1, 10, 12, 20) and hedgehog signaling pathway (PTCH2) genes involved in ‘Epidermis Development,’, were significantly upregulated. We identified miR-4316, that inhibit tumor proliferation and migration by repressing vascular endothelial growth factors, as being upregulated in non-recurrent SCCA. On the contrary, lncRNA-SOX21-AS1, implicated in the progression of many other cancers, was also found to be more common in our recurrent compared to non-recurrent SCCA.Conclusions Our study identified key host factors which may drive the recurrence of SCCA and warrants further studies to understand the mechanism and evaluate their potential use in personalized treatment.Key MessageOur study used RNA sequencing (RNA-seq) to identify pivotal factors in coding and non-coding transcripts which differentiate between patients at risk for recurrent anal cancer after treatment. There were 449 differentially expressed genes (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between 9 non-recurrent and 3 recurrent squamous cell carcinoma of anus (SCCA) tissues. The enrichment of genes related to allograft rejection was observed in the non-recurrent SCCA tissues, while the enrichment of genes related to epidermis development was positively linked with recurrent SCCA tissues

Variations in Genes Encoding Human Papillomavirus Binding Receptors and Susceptibility to Cervical Precancer.

BACKGROUND: Cervical cancer oncogenesis starts with human papillomavirus (HPV) cell entry after binding to host cell surface receptors; however, the mechanism is not fully known. We examined polymorphisms in receptor genes hypothesized to be necessary for HPV cell entry and assessed their associations with clinical progression to precancer. METHODS: African American women (N = 1,728) from the MACS/WIHS Combined Cohort Study were included. Two case-control study designs were used-cases with histology-based precancer (CIN3+) and controls without; and cases with cytology-based precancer [high-grade squamous intraepithelial lesions (HSIL)] and controls without. SNPs in candidate genes (SDC1, SDC2, SDC3, SDC4, GPC1, GPC2, GPC3, GPC4, GPC5, GPC6, and ITGA6) were genotyped using an Illumina Omni2.5-quad beadchip. Logistic regression was used to assess the associations in all participants and by HPV genotypes, after adjusting for age, human immunodeficiency virus serostatus, CD4 T cells, and three principal components for ancestry. RESULTS: Minor alleles in SNPs rs77122854 (SDC3), rs73971695, rs79336862 (ITGA6), rs57528020, rs201337456, rs11987725 (SDC2), rs115880588, rs115738853, and rs9301825 (GPC5) were associated with increased odds of both CIN3+ and HSIL, whereas, rs35927186 (GPC5) was found to decrease the odds for both outcomes (P value ≤ 0.01). Among those infected with Alpha-9 HPV types, rs722377 (SDC3), rs16860468, rs2356798 (ITGA6), rs11987725 (SDC2), and rs3848051 (GPC5) were associated with increased odds of both precancer outcomes. CONCLUSIONS: Polymorphisms in genes that encode binding receptors for HPV cell entry may play a role in cervical precancer progression. IMPACT: Our findings are hypothesis generating and support further exploration of mechanisms of HPV entry genes that may help prevent progression to cervical precancer

A44: High Levels of DEK Autoantibodies May Predict Early Flare Following Cessation of Anti‐TNF Therapy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106772/1/art38460.pd

Patients with Asian-type DEL can safely be transfused using RhD-positive blood

Red blood cells (RBCs) of the Asian-type DEL phenotype express few RhD proteins and are typed as serologic RhD-negative (D-) in routine testing. RhD-positive (D+) RBC transfusion for Asian-type DEL patients has been proposed but has not been generally adopted due to a lack of direct evidence regarding its safety and underlying mechanism. We performed a single-arm multicenter clinical trial to document the outcome of D+ RBC transfusion in Asian-type DEL patients; none of the recipients (0/42; 95% confidence interval, 0%-8.40%) developed alloanti-D after a median follow-up of 226 days. We conducted a large retrospective study to detect alloanti-D immunization in 4,045 serologic D- pregnant women throughout China; alloanti-D was found only in true D- individuals (2.63%, 79/3,009), but not in those with Asian-type DEL (0/1,032). We further retrospectively examined 127 serologic D- pregnant women who had developed alloanti-D and found none with Asian-type DEL (0/127). Finally, we analyzed RHD transcripts from Asian-type DEL erythroblasts and examined antigen epitopes expressed by various RHD transcripts in vitro, finding a low abundance of full-length RHD transcripts (0.18% of the total) expressing RhD antigens carrying the entire repertoire of epitopes, which could explain the immune tolerance against D+ RBCs. Our results provide multiple lines of evidence that individuals with Asian-type DEL cannot produce alloanti-D when exposed to D+ RBCs following transfusion or pregnancy. Therefore, we recommend considering D+ RBC transfusion and discontinuing anti-D prophylaxis in Asian-type DEL patients, including pregnant women. This clinical trial is registered at www.clinicaltrials.gov as NCT03727230

A44: High Levels of DEK Autoantibodies May Predict Early Flare Following Cessation of Anti-TNF Therapy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106772/1/art38460.pd

NTIRE 2022 Challenge on Efficient Super-Resolution: Methods and Results

This paper reviews the NTIRE 2022 challenge on efficient single image super-resolution with focus on the proposed solutions and results. The task of the challenge was to super-resolve an input image with a magnification factor of $\times$4 based on pairs of low and corresponding high resolution images. The aim was to design a network for single image super-resolution that achieved improvement of efficiency measured according to several metrics including runtime, parameters, FLOPs, activations, and memory consumption while at least maintaining the PSNR of 29.00dB on DIV2K validation set. IMDN is set as the baseline for efficiency measurement. The challenge had 3 tracks including the main track (runtime), sub-track one (model complexity), and sub-track two (overall performance). In the main track, the practical runtime performance of the submissions was evaluated. The rank of the teams were determined directly by the absolute value of the average runtime on the validation set and test set. In sub-track one, the number of parameters and FLOPs were considered. And the individual rankings of the two metrics were summed up to determine a final ranking in this track. In sub-track two, all of the five metrics mentioned in the description of the challenge including runtime, parameter count, FLOPs, activations, and memory consumption were considered. Similar to sub-track one, the rankings of five metrics were summed up to determine a final ranking. The challenge had 303 registered participants, and 43 teams made valid submissions. They gauge the state-of-the-art in efficient single image super-resolution.Comment: Validation code of the baseline model is available at https://github.com/ofsoundof/IMDN. Validation of all submitted models is available at https://github.com/ofsoundof/NTIRE2022_ES