bluuebunny/crossref_metadata_2025 huggingface dataset:
Nrf2−/− regulated lung DNA demethylation and CYP2E1 DNA methylation under PM2.5 exposure
Authors: Wu Mengjie , Jiang Menghui , Ding Hao , Tang Siying , Li Daochuan , Pi Jingbo , Zhang Rong , Chen Wen , Chen Rui , Zheng Yuxin , Piao Jinmei
Published: March 2023

Cytochrome P450 (CYP450) can mediate fine particulate matter (PM2.5) exposure leading to lung injury. Nuclear factor E2-related factor 2 (Nrf2) can regulate CYP450 expression; however, the mechanism by which Nrf2−/− (KO) regulates CYP450 expression via methylation of its promoter after PM2.5 exposure remains unclear. Here, Nrf2−/− (KO) mice and wild-type (WT) were placed in a PM2.5 exposure chamber (PM) or a filtered air chamber (FA) for 12 weeks using the real-ambient exposure system. The CYP2E1 expression trends were opposite between the WT and KO mice following PM2.5 exposure. After exposure to PM2.5,CYP2E1 mRNA and protein levels were increased in WT mice but decreased in KO mice, and CYP1A1 expression was increased after exposure to PM2.5 in both WT and KO mice. CYP2S1 expression decreased after exposure to PM2.5 in both the WT and KO groups. We studied the effect of PM2.5 exposure on CYP450 promoter methylation and global methylation levels in WT and KO mice. In WT and KO mice in the PM2.5 exposure chamber, among the methylation sites examined in the CYP2E1 promoter, the CpG2 methylation level showed an opposite trend with CYP2E1 mRNA expression. The same relationship was evident between CpG3 unit methylation in the CYP1A1 promoter and CYP1A1 mRNA expression, and between CpG1 unit methylation in the CYP2S1 promoter and CYP2S1 mRNA expression. This data suggests that methylation of these CpG units regulates the expression of the corresponding gene. After exposure to PM2.5, the expression of the DNA methylation markers ten-eleven translocation 3 (TET3) and 5-hydroxymethylcytosine (5hmC) was decreased in the WT group but significantly increased in the KO group. In summary, the changes in CYP2E1, CYP1A1, and CYP2S1 expression in the PM2.5 exposure chamber of WT and Nrf2−/− mice might be related to the specific methylation patterns in their promoter CpG units. After exposure to PM2.5, Nrf2 might regulate CYP2E1 expression by affecting CpG2 unit methylation and induce DNA demethylation via TET3 expression. Our study revealed the underlying mechanism for Nrf2 to regulate epigenetics after lung exposure to PM2.5.
Texas Senate Bill 8 significantly reduced travel to abortion clinics in Texas
Authors: Andersen Martin S. , Marsicano Christopher , Pineda Torres Mayra , Slusky David
Published: March 2023

The Dobbs v. Jackson decision by the United States Supreme Court has rescinded the constitutional guarantee of abortion across the United States. As a result, at least 13 states have banned abortion access with unknown effects. Using “Texas” SB8 law that similarly restricted abortions in Texas, we provide insight into how individuals respond to these restrictions using aggregated and anonymized human mobility data. We find that “Texas” SB 8 law reduced mobility near abortion clinics in Texas by people who live in Texas and those who live outside the state. We also find that mobility from Texas to abortion clinics in other states increased, with notable increases in Missouri and Arkansas, two states that subsequently enacted post-Dobbs bans. These results highlight the importance of out-of-state abortion services for women living in highly restrictive states.
Rodent models of postherpetic neuralgia: How far have we reached?
Authors: Ou Mingxi , Chen Jiamin , Yang Shaomin , Xiao Lizu , Xiong Donglin , Wu Songbin
Published: March 2023

Background

Induced by varicella zoster virus (VZV), postherpetic neuralgia (PHN) is one of the common complications of herpes zoster (HZ) with refractory pain. Animal models play pivotal roles in disclosing the pain mechanisms and developing effective treatments. However, only a few rodent models focus on the VZV-associated pain and PHN.

Objective

To summarize the establishment and characteristics of popular PHN rodent models, thus offer bases for the selection and improvement of PHN models.

Design

In this review, we retrospect two promising PHN rodent models, VZV-induced PHN model and HSV1-induced PHN model in terms of pain-related evaluations, their contributions to PHN pathogenesis and pharmacology.

Results

Significant difference of two PHN models is the probability of virus proliferation; 2) Most commonly used pain evaluation of PHN model is mechanical allodynia, but pain-induced anxiety and other behaviours are worth noting; 3) From current PHN models, pain mechanisms involve changes in virus gene and host gene expression, neuroimmune–glia interactions and ion channels; 4) antiviral drugs and classical analgesics serve more on the acute stage of herpetic pain.

Conclusions

Different PHN models assessed by various pain evaluations combine to fulfil more comprehensive understanding of PHN.
Abundance of ACVR1B transcript is elevated during septic conditions: Perspectives obtained from a hands-on reductionist investigation
Authors: Preechanukul Anucha , Yimthin Thatcha , Tandhavanant Sarunporn , Brummaier Tobias , Chomkatekaew Chalita , Das Sukanta , Syed Ahamed Kabeer Basirudeen , Toufiq Mohammed , Rinchai Darawan , West T. Eoin , Chaussabel Damien , Chantratita Narisara , Garand Mathieu
Published: March 2023

Sepsis is a complex heterogeneous condition, and the current lack of effective risk and outcome predictors hinders the improvement of its management. Using a reductionist approach leveraging publicly available transcriptomic data, we describe a knowledge gap for the role of ACVR1B (activin A receptor type 1B) in sepsis. ACVR1B, a member of the transforming growth factor-beta (TGF-beta) superfamily, was selected based on the following: 1) induction upon in vitro exposure of neutrophils from healthy subjects with the serum of septic patients (GSE49755), and 2) absence or minimal overlap between ACVR1B, sepsis, inflammation, or neutrophil in published literature. Moreover, ACVR1B expression is upregulated in septic melioidosis, a widespread cause of fatal sepsis in the tropics. Key biological concepts extracted from a series of PubMed queries established indirect links between ACVR1B and “cancer”, “TGF-beta superfamily”, “cell proliferation”, “inhibitors of activin”, and “apoptosis”. We confirmed our observations by measuring ACVR1B transcript abundance in buffy coat samples obtained from healthy individuals (n=3) exposed to septic plasma (n = 26 melioidosis sepsis cases)ex vivo. Based on our re-investigation of publicly available transcriptomic data and newly generated ex vivo data, we provide perspective on the role of ACVR1B during sepsis. Additional experiments for addressing this knowledge gap are discussed.
Case report: Myocarditis in congenital STAT1 gain-of function
Authors: Staels Frederik , Roosens Willem , Giovannozzi Simone , Moens Leen , Bogaert Jan , Iglesias-Herrero Cecilia , Gijsbers Rik , Bossuyt Xavier , Frans Glynis , Liston Adrian , Humblet-Baron Stephanie , Meyts Isabelle , Van Aelst Lucas , Schrijvers Rik
Published: March 2023

Autosomal dominant Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations result in an inborn error of immunity characterized by chronic mucocutaneous candidiasis, recurrent viral and bacterial infections, and diverse autoimmune manifestations. Current treatment consists of chronic antifungal therapy, antibiotics for concomitant infections, and immunosuppressive therapy in case of autoimmune diseases. More recently, treatment with Janus kinases 1 and 2 (JAK1/2) inhibitors have shown promising yet variable results. We describe a STAT1 GOF patient with an incidental finding of elevated cardiac troponins, leading to a diagnosis of a longstanding, slowly progressive idiopathic myocarditis, attributed to STAT1 GOF. Treatment with a JAK-inhibitor (baricitinib) mitigated cardiac inflammation on MRI but was unable to alter fibrosis, possibly due to the diagnostic and therapeutic delay, which finally led to fatal arrhythmia. Our case illustrates that myocarditis could be part of the heterogeneous disease spectrum of STAT1 GOF. Given the insidious presentation in our case, a low threshold for cardiac evaluation in STAT1 GOF patients seems warranted.
Optimisation and Validation of a conventional ELISA and cut-offs for detecting and quantifying anti-SARS-CoV-2 Spike, RBD, and Nucleoprotein IgG, IgM, and IgA antibodies in Uganda
Authors: Oluka Gerald Kevin , Namubiru Patricia , Kato Laban , Ankunda Violet , Gombe Ben , Cotten Matthew ,   The COVID-19 Immunoprofiling Team, Musenero Monica , Kaleebu Pontiano , Fox Julie , Serwanga Jennifer
Published: March 2023

There is an urgent need for better immunoassays to measure antibody responses as part of immune-surveillance activities and to profile immunological responses to emerging SARS-CoV-2 variants. We optimised and validated an in-house conventional ELISA to identify and quantify SARS-CoV-2 spike- (S-), receptor binding domain- (RBD-), and nucleoprotein- (N-) directed IgG, IgM, and IgA binding antibodies in the Ugandan population and similar settings. Pre- and post-pandemic specimens were used to compare the utility of mean ± 2SD, mean ± 3SD, 4-fold above blanks, bootstrapping, and receiver operating characteristic (ROC) analyses in determining optimal cut-off optical densities at 450 nm (OD) for discriminating between antibody positives and negatives. “Limits of detection” (LOD) and “limits of quantitation” (LOQ) were validated alongside the assay’s uniformity, accuracy, inter-assay and inter-operator precision, and parallelism. With spike-directed sensitivity and specificity of 95.33 and 94.15%, respectively, and nucleoprotein sensitivity and specificity of 82.69 and 79.71%, ROC was chosen as the best method for determining cutoffs. Accuracy measurements were within the expected CV range of 25%. Serum and plasma OD values were highly correlated (r = 0.93, p=0.0001). ROC-derived cut-offs for S-, RBD-, and N-directed IgG, IgM, and IgA were 0.432, 0.356, 0.201 (S), 0.214, 0.350, 0.303 (RBD), and 0.395, 0.229, 0.188 (N). The sensitivity and specificity of the S-IgG cut-off were equivalent to the WHO 20/B770-02 S-IgG reference standard at 100% level. Spike negative IgG, IgM, and IgA ODs corresponded to median antibody concentrations of 1.49, 3.16, and 0 BAU/mL, respectively, consistent with WHO low titre estimates. Anti-spike IgG, IgM, and IgA cut-offs were equivalent to 18.94, 20.06, and 55.08 BAU/mL. For the first time, we provide validated parameters and cut-off criteria for the in-house detection of subclinical SARS-CoV-2 infection and vaccine-elicited binding antibodies in the context of Sub-Saharan Africa and populations with comparable risk factors.
The current landscape of CAR T-cell therapy for solid tumors: Mechanisms, research progress, challenges, and counterstrategies
Authors: Daei Sorkhabi Amin , Mohamed Khosroshahi Leila , Sarkesh Aila , Mardi Amirhossein , Aghebati-Maleki Ali , Aghebati-Maleki Leili , Baradaran Behzad
Published: March 2023

The successful outcomes of chimeric antigen receptor (CAR) T-cell therapy in treating hematologic cancers have increased the previously unprecedented excitement to use this innovative approach in treating various forms of human cancers. Although researchers have put a lot of work into maximizing the effectiveness of these cells in the context of solid tumors, few studies have discussed challenges and potential strategies to overcome them. Restricted trafficking and infiltration into the tumor site, hypoxic and immunosuppressive tumor microenvironment (TME), antigen escape and heterogeneity, CAR T-cell exhaustion, and severe life-threatening toxicities are a few of the major obstacles facing CAR T-cells. CAR designs will need to go beyond the traditional architectures in order to get over these limitations and broaden their applicability to a larger range of malignancies. To enhance the safety, effectiveness, and applicability of this treatment modality, researchers are addressing the present challenges with a wide variety of engineering strategies as well as integrating several therapeutic tactics. In this study, we reviewed the antigens that CAR T-cells have been clinically trained to recognize, as well as counterstrategies to overcome the limitations of CAR T-cell therapy, such as recent advances in CAR T-cell engineering and the use of several therapies in combination to optimize their clinical efficacy in solid tumors.
The role of immunometabolism in macrophage polarization and its impact on acute lung injury/acute respiratory distress syndrome
Authors: Wang Lian , Wang Dongguang , Zhang Tianli , Ma Yao , Tong Xiang , Fan Hong
Published: March 2023

Lung macrophages constitute the first line of defense against airborne particles and microbes and are key to maintaining pulmonary immune homeostasis. There is increasing evidence suggesting that macrophages also participate in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), including the modulation of inflammatory responses and the repair of damaged lung tissues. The diversity of their functions may be attributed to their polarized states. Classically activated or inflammatory (M1) macrophages and alternatively activated or anti-inflammatory (M2) macrophages are the two main polarized macrophage phenotypes. The precise regulatory mechanism of macrophage polarization is a complex process that is not completely understood. A growing body of literature on immunometabolism has demonstrated the essential role of immunometabolism and its metabolic intermediates in macrophage polarization. In this review, we summarize macrophage polarization phenotypes, the role of immunometabolism, and its metabolic intermediates in macrophage polarization and ALI/ARDS, which may represent a new target and therapeutic direction.
Exploration of the common genetic landscape of COVID-19 and male infertility
Authors: Chen Yinwei , Sun Taotao , Liu Kang , Yuan Penghui , Liu Chang
Published: March 2023

Background

COVID-19 has spread widely across continents since 2019, causing serious damage to human health. Accumulative research uncovered that SARS-CoV-2 poses a great threat to male fertility, and male infertility (MI) is a common comorbidity for the COVID-19 pandemic. The aim of the study was to explore the cross-talk molecular mechanisms between COVID-19 and MI.

Materials and methods

A total of four transcriptome data regarding COVID-19 and MI were downloaded from the Gene Expression Omnibus (GEO) repository, and were divided for two purposes (initial analysis and external validation). Differentially expressed genes (DEGs) analysis, GO and pathway annotation, protein-protein interaction (PPI) network, connectivity ranking, ROC analysis, immune infiltration, and translational and post-translational interaction were performed to gain hub COVID-19-related DEGs (CORGs). Moreover, we recorded medical information of COVID-19 patients with MI and matched healthy controls, and harvested their sperm samples in the university hospital. Expressions of hub CORGs were detected through the qRT-PCR technique.

Results

We identified 460 overlapped CORGs in both the COVID-19 DEGs and MI DEGs. CORGs were significantly enriched in DNA damage and repair-associated, cell cycle-associated, ubiquitination-associated, and coronavirus-associated signaling. Module assessment of PPI network revealed that enriched GO functions were closely related to cell cycle and DNA metabolism processes. Pharmacologic agent prediction displayed protein-drug interactions of ascorbic acid, biotin, caffeine, and L-cysteine with CORGs. After connectivity ranking and external validation, three hub CORGs (ENTPD6, CIB1, and EIF3B) showed good diagnostic performance (area under the curve > 0.75). Subsequently, three types of immune cells (CD8+ T cells, monocytes, and macrophages M0) were dominantly enriched, and 24 transcription factor-CORGs interactions and 13 miRNA-CORGs interactions were constructed in the network. Finally, qRT-PCR analysis confirmed that there were significant differences in the expression of hub CORGs (CIB1 and EIF3B) between the patient and control groups.

Conclusion

The present study identified and validated hub CORGs in COVID-19 and MI, and systematically explored molecular interactions and regulatory features in various biological processes. Our data provide new insights into the novel biomarkers and potential therapeutic targets of COVID-19-associated MI.
Abscopal effect triggered by radiation sequential mono-immunotherapy resulted in a complete remission of PMMR sigmoid colon cancer
Authors: Zhou Pu , Wang Yan , Qin Si , Han Yan , Yang Yumeng , Zhao Liang , Zhou Quan , Zhuo Wenlei
Published: March 2023

Background

Radiation therapy combined with immune checkpoint inhibitors (ICIs) has recently turned into an appealing and promising approach to enhance the anti-tumor immunity and efficacy of immunological drugs in many tumors. Abscopal effect induced by radiation is a phenomenon that often leads to an efficient immunity response. In this study, we investigated whether the combination of the immunogenic effects derived from radiotherapy sequential ICIs-based therapy could increase the incidence of abscopal effects, and improve the survival rates.

Case presentation

We described a clinical case regarding a 35-year-old male patient who was admitted to our hospital with a diagnosis of adenocarcinoma of the sigmoid colon and synchronous multiple liver metastases following a surgical resection. The molecular pathological examination showed immune-desert phenotype and proficient mismatch repair (pMMR). The patient was treated with adjuvant chemotherapy after surgery, however, after 7 months, multiple metastasis in the pelvic lymph nodes were diagnosed. Unfortunately, the tumor progressed despite multiple cycles of chemotherapy combined with cetuximab or bevacizumab. Within the follow-up treatment, the patient was administered with only 50Gy/25F of radiation dose to treat the anastomotic lesions. Subsequently, mono-sindilizumab was used as systemic therapy, leading to a rapid reduction of all pelvic lesions and complete clinical remission. So far, the patient survived for more than 20 months under continuous mono-sindilizumab treatment and is still in complete remission.

Conclusion

A localized radiotherapy combined with a sindilizumab-based systemic therapy may overcome the immune resistance of pMMR metastatic colorectal cancer (mCRC), thus obtaining greater efficacy of the therapy. Its mechanism may be related to the abscopal effect obtained by the synergistic use of radiation and sindilizumab, which should be further investigated in the future.
Disruption of endosomal trafficking with EGA alters TLR9 cytokine response in human plasmacytoid dendritic cells
Authors: Wiest Matthew J. , Gu Chao , Ham Hyoungjun , Gorvel Laurent , Keddis Mira T. , Griffing Leroy W. , Joo HyeMee , Gorvel Jean-Pierre , Billadeau Daniel D. , Oh SangKon
Published: March 2023

Plasmacytoid dendritic cells (pDCs) exhibit bifurcated cytokine responses to TLR9 agonists, an IRF7-mediated type 1 IFN response or a pro-inflammatory cytokine response via the activation of NF-κB. This bifurcated response has been hypothesized to result from either distinct signaling endosomes or endo-lysosomal trafficking delay of TLR9 agonists allowing for autocrine signaling to affect outcomes. Utilizing the late endosome trafficking inhibitor, EGA, we assessed the bifurcated cytokine responses of pDCs to TLR9 stimulation. EGA treatment of pDCs diminished both IFNα and pro-inflammatory cytokine expression induced by CpG DNAs (D- and K-type), CpG-DNAs complexed with DOTAP, and genomic DNAs complexed with LL37. Mechanistically, EGA suppressed phosphorylation of IKKα/β, STAT1, Akt, and p38, and decreased colocalization of CpG oligodeoxynucleotides with LAMP+ endo-lysosomes. EGA also diminished type 1 IFN expression by pDCs from systemic lupus erythematosus patients. Therefore, our findings help understand mechanisms for the bifurcated cytokine responses by pDCs and support future examination of the potential benefit of EGA in treating type 1 IFN-associated inflammatory diseases in the future.
Insights into the role of nucleotide methylation in metabolic-associated fatty liver disease
Authors: Zhang Ni , Tian Xinchen , Yan Tinghao , Wang Haochen , Zhang Dengtian , Lin Cong , Liu Qingbin , Jiang Shulong
Published: March 2023

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease characterized by fatty infiltration of the liver. In recent years, the MAFLD incidence rate has risen and emerged as a serious public health concern. MAFLD typically progresses from the initial hepatocyte steatosis to steatohepatitis and then gradually advances to liver fibrosis, which may ultimately lead to cirrhosis and carcinogenesis. However, the potential evolutionary mechanisms still need to be clarified. Recent studies have shown that nucleotide methylation, which was directly associated with MAFLD’s inflammatory grading, lipid synthesis, and oxidative stress, plays a crucial role in the occurrence and progression of MAFLD. In this review, we highlight the regulatory function and associated mechanisms of nucleotide methylation modification in the progress of MAFLD, with a particular emphasis on its regulatory role in the inflammation of MAFLD, including the regulation of inflammation-related immune and metabolic microenvironment. Additionally, we summarize the potential value of nucleotide methylation in the diagnosis and treatment of MAFLD, intending to provide references for the future investigation of MAFLD.
Comprehensive analysis, immune, and cordycepin regulation for SOX9 expression in pan-cancers and the matched healthy tissues
Authors: Liu Shuguang , Yang Lisha , Fu Jiewen , Li Ting , Zhou Baixu , Wang Kai , Wei Chunli , Fu Junjiang
Published: March 2023

SRY-box transcription factor 9 (SOX9) (OMIM 608160) is a transcription factor. The expression of SOX9 in pan-cancers and the regulation by small molecules in cancer cell lines are unclear. In the current study, we comprehensively analyzed the expression of SOX9 in normal tissues, tumor tissues and their matched healthy tissues in pan-cancers. The study examined the correlation between immunomodulators and immune cell infiltrations in normal and tumor tissues. Cordycepin (CD), an adenosine analog for SOX9 expression regulation, was also conducted on cancer cells. The results found that SOX9 protein is expressed in a variety of organs, including high expression in 13 organs and no expression in only two organs; in 44 tissues, there was high expression in 31 tissues, medium expression in four tissues, low expression in two tissues, and no expression in the other seven tissues. In pan-cancers with 33 cancer types, SOX9 expression was significantly increased in fifteen cancers, including CESC, COAD, ESCA, GBM, KIRP, LGG, LIHC, LUSC, OV, PAAD, READ, STAD, THYM, UCES, and UCS, but significantly decreased in only two cancers (SKCM and TGCT) compared with the matched healthy tissues. It suggests that SOX9 expression is upregulated in the most cancer types (15/33) as a proto-oncogene. The fact that the decrease of SOX9 expression in SKCM and the increase of SOX9 in the cell lines of melanoma inhibit tumorigenicity in both mouse and human ex vivo models demonstrates that SOX9 could also be a tumor suppressor. Further analyzing the prognostic values for SOX9 expression in cancer individuals revealed that OS is long in ACC and short in LGG, CESC, and THYM, suggesting that high SOX9 expression is positively correlated with the worst OS in LGG, CESC, and THYM, which could be used as a prognostic maker. In addition, CD inhibited both protein and mRNA expressions of SOX9 in a dose-dependent manner in 22RV1, PC3, and H1975 cells, indicating CD’s anticancer roles likely via SOX9 inhibition. Moreover, SOX9 might play an important role in tumor genesis and development by participating in immune infiltration. Altogether, SOX9 could be a biomarker for diagnostics and prognostics for pan-cancers and an emerging target for the development of anticancer drugs.
Mechanism of HIFs in osteoarthritis
Authors: Zhang Xin-An , Kong Hui
Published: March 2023

Osteoarthritis (OA) is a common disabling disease which has a high incidence rate in the elderly. Studies have found that many factors are involved in the pathogenesis of OA. Hypoxia-inducible factors (HIFs) are core regulators that induce hypoxia genes, repair the cellular oxygen environment, and play an important role in the treatment of OA. For example, HIF-1α can maintain the stability of the articular cartilage matrix, HIF-2α is able to cause chondrocyte apoptosis and intensify in-flammatory response, and HIF-3α may be the target gene of HIF-1α and HIF-2α, thereby playing a negative regulatory role. This review examines the mechanism of HIFs in cartilage extracellular matrix degradation, apoptosis, inflammatory reaction, autophagy and then further expounds on the roles of HIFs in OA, consequently providing theoretical support for the pathogenesis of OA and a new target for OA treatment.
Improving dengue diagnosis and case confirmation in children by combining rapid diagnostic tests, clinical, and laboratory variables
Authors: Coronel-Ruiz Carolina , Velandia-Romero Myriam L. , Calvo Eliana , Camacho-Ortega Sigrid , Parra-Alvarez Shirly , Beltrán Edgar O. , Calderón-Pelaez María Angélica , Porras-Ramírez Alexandra , Cortés-Muñoz Fabián , Rojas-Hernandez Juan Pablo , Velasco-Alvarez Syrley , Pinzón-Junca Alfredo , Castellanos Jaime E.
Published: March 2023

Background

Dengue is the most widely distributed arboviral disease in tropical and subtropical countries. Most suspected cases are diagnosed according to the clinical criteria, and early diagnosis is difficult. Moreover, in underdeveloped countries, several factors continue to challenge the diagnosis and surveillance of dengue cases. This study aimed to design a diagnostic algorithm using rapid diagnostic tests (RDTs), ELISA tests, and clinical and hematological variables to confirm dengue cases in febrile patients in Colombia.

Methods

Altogether, 505 samples were collected. Serum samples were evaluated by RDTs (IgM and IgG antibodies and NS1 antigen), capture IgM and IgG ELISAs, and endpoint hemi-nested RT-PCR assay (qualitative). We statistically analyzed the performance of individual tests to determine the most useful ones to confirm dengue cases accurately.

Results

Individual results for IgM, IgG, and NS1 RDTs yielded lower sensitivity and specificity values than the reference standard. High sensitivity and specificity were obtained after combining IgM and NS1 ELISA results (96.3% and 96.4%) and NS1 RDT plus IgM ELISA results (90.3% and 96.2%), respectively. Adjusted odds ratios (aORs) were calculated for clinical variables and laboratory tests to differentiate dengue from other febrile illnesses (OFI). This approach showed that myalgia, abdominal tenderness, and platelet count were identified with higher sensitivity to confirm dengue cases. IgM RDT and NS1 RDT differentiated dengue cases from OFI. A positive IgM RDT or a positive NS1 RDT combined with specific signs or symptoms confirmed 81.6% of dengue cases. A combination of clinical findings and a positive NS1 RDT or positive ELISA IgM confirmed 90.6% of the cases.

Conclusion

Our findings showed that clinical diagnoses in pediatric population alone cannot confirm true dengue cases and needs to be complemented by laboratory diagnostic tests. We also demonstrate the usefulness of combining clinical criteria with RDTs, suggesting that their implementation with the IgM ELISA test improves dengue case confirmation.
Effects of microRNAs on angiogenesis in diabetic wounds
Authors: Lyttle Bailey D. , Vaughn Alyssa E. , Bardill James R. , Apte Anisha , Gallagher Lauren T. , Zgheib Carlos , Liechty Kenneth W.
Published: March 2023

Diabetes mellitus is a morbid condition affecting a growing number of the world population, and approximately one third of diabetic patients are afflicted with diabetic foot ulcers (DFU), which are chronic non-healing wounds that frequently progress to require amputation. The treatments currently used for DFU focus on reducing pressure on the wound, staving off infection, and maintaining a moist environment, but the impaired wound healing that occurs in diabetes is a constant obstacle that must be faced. Aberrant angiogenesis is a major contributor to poor wound healing in diabetes and surgical intervention is often necessary to establish peripheral blood flow necessary for healing wounds. Over recent years, microRNAs (miRNAs) have been implicated in the dysregulation of angiogenesis in multiple pathologies including diabetes. This review explores the pathways of angiogenesis that become dysregulated in diabetes, focusing on miRNAs that have been identified and the mechanisms by which they affect angiogenesis.
Laparoscopic myomectomy – The importance of surgical techniques
Authors: Dumitrașcu Mihai Cristian , Nenciu Cătălin-George , Nenciu Adina-Elena , Călinoiu Amalia , Neacșu Adrian , Cîrstoiu Monica , Șandru Florica
Published: March 2023

Laparoscopy is a routine procedure for benign gynecological tumors. Although the laparoscopic approach for myomas is a common procedure, it can be challenging. To improve outcomes, research regarding port access, suture type, morcellation, and complication management remains ongoing. Myomectomy is the main surgical option for patients seeking uterus-sparing procedures to maintain future fertility. The laparoscopic technique is the most important in these cases, given that possible complications can impact fertility and pregnancy outcomes. Herein, we reviewed and collated the available data regarding different suture techniques, including advantages, difficulties, and possible long-term impacts.
EREG is a risk factor for the prognosis of patients with cervical cancer
Authors: Li Tianye , Feng Ruijing , Chen Bingxin , Zhou Jianwei
Published: March 2023

Background

Cervical cancer continues to threaten women's health worldwide. Identifying critical oncogenic molecules is important to drug development and prognosis prediction for patients with cervical cancer. Recent studies have demonstrated that epiregulin (EREG) is upregulated in various cancer types, which contributes to cancer progression by triggering the EGFR signaling pathway. However, the role of EREG is still unclear.

Methods

In this study, we first conducted a comprehensive biological analysis to investigate the expression of EREG in cervical cancer. Then, we investigated the correlations between EREG expression level and clinicopathological features. In addition, we validated the effects of EREG expression on the proliferation and apoptosis of cervical cancer cells.

Results

Based on the public database, we found that the expression of EREG was higher in advanced cervical cancer samples. Survival analysis showed that EREG was a risk factor for the prognosis of cervical cancer. In vitro experiments demonstrated that EREG knockdown undermined proliferation and promoted apoptosis in cancer cells.

Conclusion

EREG plays a vital role in the progression of cervical cancer, which contributes to hyperactive cell proliferation and decreased cell apoptosis. It might be a valuable target for prognosis prediction and drug development for cervical cancer in the future.
Diversity of the genus Cryobacterium and proposal of 19 novel species isolated from glaciers
Authors: Liu Qing , Yang Lei-Lei , Xin Yu-Hua
Published: March 2023

The bacterial genus Cryobacterium includes at present 14 species that live in cryospheric environments. In this study, we analyzed 101 genomes of Cryobacterium with pure cultures obtained from GenBank. They could be classified into 44 species based on average nucleotide identity (ANI) analysis, showing the diversity of Cryobacterium. Among these, 19 strains in our laboratory were isolated from the glacier samples in China. The pairwise ANI values of these 19 strains and known species were <95%, indicating that they represented 19 novel species. The comparative genomic analysis showed significant differences in gene content between the two groups with a maximum growth temperature (Tmax) of ≤ 20°C and a Tmax of >20°C. A comprehensive and robust phylogenetic tree, including 14 known species and 19 novel species, was constructed and showed five phylogenetic branches based on 265 concatenated single-copy gene sequences. The Tmax parameter had a strong phylogenetic signal, indicating that the temperature adaptation of Cryobacterium was largely through vertical transfer rather than horizontal gene transfer and was affected by selection. Furthermore, using polyphasic taxonomy combined with phylogenomic analysis, we proposed 19 novel species of the genus Cryobacterium by the following 19 names: Cryobacterium serini sp. nov., Cryobacterium lactosi sp. nov., Cryobacterium gelidum sp. nov., Cryobacterium suzukii sp. nov., Cryobacterium fucosi sp. nov., Cryobacterium frigoriphilum sp. nov., Cryobacterium cryoconiti sp. nov., Cryobacterium lyxosi sp. nov., Cryobacterium sinapicolor sp. nov., Cryobacterium sandaracinum sp. nov., Cryobacterium cheniae sp. nov., Cryobacterium shii sp. nov., Cryobacterium glucosi sp. nov., Cryobacterium algoritolerans sp. nov., Cryobacterium mannosilyticum sp. nov., Cryobacterium adonitolivorans sp. nov., Cryobacterium algoricola sp. nov., Cryobacterium tagatosivorans sp. nov., and Cryobacterium glaciale sp. nov. Overall, the taxonomy and genomic analysis can improve our knowledge of phenotypic diversity, genetic diversity, and evolutionary characteristics of Cryobacterium.
Efficient traceless modification of the P1 bacteriophage genome through homologous recombination with enrichment in double recombinants: A new perspective on the functional annotation of uncharacterized phage genes
Authors: Bednarek Agnieszka , Giermasińska-Buczek Katarzyna , Łobocka Małgorzata
Published: March 2023

The advent of high-throughput omic technologies has caused unprecedented progress in research on bacteriophages, the most abundant and still the least explored entities on earth. Despite the growing number of phage genomes sequenced and the rejuvenation of interest in phage therapy, the progress in the functional analysis of phage genes is slow. Simple and efficient techniques of phage genome targeted mutagenesis that would allow one to knock out particular genes precisely without polar effects in order to study the effect of these knock-outs on phage functions are lacking. Even in the case of model phages, the functions of approximately half of their genes are unknown. P1 is an enterobacterial temperate myophage of clinical significance, which lysogenizes cells as a plasmid. It has a long history of studies, serves as a model in basic research, is a gene transfer vector, and is a source of genetic tools. Its gene products have structural homologs in several other phages. In this perspective article, we describe a simple and efficient procedure of traceless P1 genome modification that could also serve to acquire targeted mutations in the genomes of certain other temperate phages and speed up functional annotations of phage genes.
Structural analysis and molecular dynamics simulation studies of HIV-1 antisense protein predict its potential role in HIV replication and pathogenesis
Authors: Sathiyamani Balakumaran , Daniel Evangeline Ann , Ansar Samdani , Esakialraj Bennett Henzeler , Hassan Sameer , Revanasiddappa Prasanna D. , Keshavamurthy Amrutha , Roy Sujata , Vetrivel Umashankar , Hanna Luke Elizabeth
Published: March 2023

The functional significance of the HIV-1 Antisense Protein (ASP) has been a paradox since its discovery. The expression of this protein in HIV-1-infected cells and its involvement in autophagy, transcriptional regulation, and viral latency have sporadically been reported in various studies. Yet, the definite role of this protein in HIV-1 infection remains unclear. Deciphering the 3D structure of HIV-1 ASP would throw light on its potential role in HIV lifecycle and host-virus interaction. Hence, using extensive molecular modeling and dynamics simulation for 200 ns, we predicted the plausible 3D-structures of ASP from two reference strains of HIV-1 namely, Indie-C1 (subtype-C) and NL4-3 (subtype-B) so as to derive its functional implication through structural domain analysis. In spite of sequence and structural differences in subtype B and C ASP, both structures appear to share common domains like the Von Willebrand Factor Domain-A (VWFA), Integrin subunit alpha-X (ITGSX), and ETV6-Transcriptional repressor, thereby reiterating the potential role of HIV-1 ASP in transcriptional repression and autophagy, as reported in earlier studies. Gromos-based cluster analysis of the centroid structures also reassured the accuracy of the prediction. This is the first study to elucidate a highly plausible structure for HIV-1 ASP which could serve as a feeder for further experimental validation studies.
The effects of GPER on age-associated memory impairment induced by decreased estrogen levels
Authors: Luo Wenyu , Yan Yudie , Cao Yunpeng , Zhang Yanbo , Zhang Zhen
Published: March 2023

Estrogen, as a pleiotropic endocrine hormone, not only regulates the physiological functions of peripheral tissues but also exerts vital neuroregulatory effects in the central nervous system (CNS), such as the development of neurons and the formation of neural network connections, wherein rapid estrogen-mediated reactions positively stimulate spinogenesis and regulate synaptic plasticity and synaptic transmission to facilitate cognitive and memory performance. These fast non-genomic effects can be initiated by membrane-bound estrogen receptors (ERs), three best known of which are ERα, ERβ, and G protein-coupled estrogen receptor (GPER). To date, the effects of ERα and ERβ have been well studied in age-associated memory impairment, whereas there is still a lack of attention to the role of GPER in age-associated memory impairment, and there are still disputes about whether GPER indeed functions as an ER to enhance learning and memory. In this review, we provide a systematic overview of the role of GPER in age-associated memory impairment based on its expression, distribution, and signaling pathways, which might bring some inspiration for translational drugs targeting GPER for age-related diseases and update knowledge on the role of estrogen and its receptor system in the brain.
Identification of a peptide ligand for human ALDH3A1 through peptide phage display: Prediction and characterization of protein interaction sites and inhibition of ALDH3A1 enzymatic activity
Authors: Voulgaridou Georgia-Persephoni , Theologidis Vasileios , Xanthis Vasileios , Papagiannaki Eleni , Tsochantaridis Ilias , Fadouloglou Vasiliki E. , Pappa Aglaia
Published: March 2023

Aldehyde dehydrogenase 3A1 (ALDH3A1) by oxidizing medium chain aldehydes to their corresponding carboxylic acids, is involved in the detoxification of toxic byproducts and is considered to play an important role in antioxidant cellular defense. ALDH3A1 has been implicated in various other functions such as cell proliferation, cell cycle regulation, and DNA damage response. Recently, it has been identified as a putative biomarker of prostate, gastric, and lung cancer stem cell phenotype. Although ALDH3A1 has multifaceted functions in both normal and cancer homeostasis, its modes of action are currently unknown. To this end, we utilized a random 12-mer peptide phage display library to identify efficiently human ALDH3A1-interacting peptides. One prevailing peptide (P1) was systematically demonstrated to interact with the protein of interest, which was further validated in vitro by peptide ELISA. Bioinformatic analysis indicated two putative P1 binding sites on the protein surface implying biomedical potential and potent inhibitory activity of the P1 peptide on hALDH3A1 activity was demonstrated by enzymatic studies. Furthermore, in search of potential hALDH3A1 interacting players, a BLASTp search demonstrated that no protein in the database includes the full-length amino acid sequence of P1, but identified a list of proteins containing parts of the P1 sequence, which may prove potential hALDH3A1 interacting partners. Among them, Protein Kinase C Binding Protein 1 and General Transcription Factor II-I are candidates of high interest due to their cellular localization and function. To conclude, this study identifies a novel peptide with potential biomedical applications and further suggests a list of protein candidates be explored as possible hALDH3A1-interacting partners in future studies.
Optical character recognition on engineering drawings to achieve automation in production quality control
Authors: Villena Toro Javier , Wiberg Anton , Tarkian Mehdi
Published: March 2023

Introduction: Digitization is a crucial step towards achieving automation in production quality control for mechanical products. Engineering drawings are essential carriers of information for production, but their complexity poses a challenge for computer vision. To enable automated quality control, seamless data transfer between analog drawings and CAD/CAM software is necessary.

Methods: This paper focuses on autonomous text detection and recognition in engineering drawings. The methodology is divided into five stages. First, image processing techniques are used to classify and identify key elements in the drawing. The output is divided into three elements: information blocks and tables, feature control frames, and the rest of the image. For each element, an OCR pipeline is proposed. The last stage is output generation of the information in table format.

Results: The proposed tool, called eDOCr, achieved a precision and recall of 90% in detection, an F1-score of 94% in recognition, and a character error rate of 8%. The tool enables seamless integration between engineering drawings and quality control.

Discussion: Most OCR algorithms have limitations when applied to mechanical drawings due to their inherent complexity, including measurements, orientation, tolerances, and special symbols such as geometric dimensioning and tolerancing (GD&T). The eDOCr tool overcomes these limitations and provides a solution for automated quality control.

Conclusion: The eDOCr tool provides an effective solution for automated text detection and recognition in engineering drawings. The tool's success demonstrates that automated quality control for mechanical products can be achieved through digitization. The tool is shared with the research community through Github.
Modularity and neuronal heterogeneity: Two properties that influence in vitro neuropharmacological experiments
Authors: Brofiga Martina , Poggio Fabio , Callegari Francesca , Tedesco Mariateresa , Massobrio Paolo
Published: March 2023

Introduction

The goal of this work is to prove the relevance of the experimental model (in vitro neuronal networks in this study) when drug-delivery testing is performed.

Methods

We used dissociated cortical and hippocampal neurons coupled to Micro-Electrode Arrays (MEAs) arranged in different configurations characterized by modularity (i.e., the presence of interconnected sub-networks) and heterogeneity (i.e., the co-existence of neurons coming from brain districts). We delivered increasing concentrations of bicuculline (BIC), a neuromodulator acting on the GABAergic system, and we extracted the IC50 values (i.e., the effective concentration yielding a reduction in the response by 50%) of the mean firing rate for each configuration.

Results

We found significant lower values of the IC50 computed for modular cortical-hippocampal ensembles than isolated cortical or hippocampal ones.

Discussion

Although tested with a specific neuromodulator, this work aims at proving the relevance of ad hoc experimental models to perform neuropharmacological experiments to avoid errors of overestimation/underestimation leading to biased information in the characterization of the effects of a drug on neuronal networks.
MCP-1 levels in astrocyte-derived exosomes are changed in preclinical stage of Alzheimer's disease
Authors: Wang Ting , Yao Yunxia , Han Chao , Li Taoran , Du Wenying , Xue Jinhua , Han Ying , Cai Yanning
Published: March 2023

Background

Alzheimer's disease (AD) is the most common form of dementia in older adults. There is accumulating evidence that inflammatory processes play a critical role in AD pathogenesis. In this study, we investigated whether inflammatory factors in plasma and astrocyte-derived exosomes (ADEs) from plasma are differentially expressed in the early stages of AD and their potential role in pathological processes in the AD continuum.

Method

We included 39 normal controls (NCs), 43 participants with subjective cognitive decline (SCD), and 43 participants with amnestic mild cognitive impairment (aMCI)/AD. IL-6, IL-8, and MCP-1 in plasma and ADEs from plasma were evaluated using a commercial multiplex Luminex-based kit.

Results

Pairwise comparisons between the groups showed no significant differences in plasma levels of IL-6, IL-8, or MCP-1. However, ADEs in the SCD group showed an increase in MCP-1 levels compared to the NC group. To differentiate the preclinical group, discriminant analysis was performed using sex, age, years of education, and genotype. This revealed a difference between the SCD and NC groups (area under the curve: 0.664). A Spearman correlation analysis of MCP-1 in plasma and ADEs showed no or weak correlation in the SCD (R = 0.150, p = 0.350) and aMCI/AD (R = 0.310, p = 0.041) groups, while a positive correlation in the NC group (R = 0.360, p = 0.026).

Conclusion

Plasma IL-6, IL-8, and MCP-1 levels were not significantly different. However, the concentration of MCP-1 in ADEs is slightly altered during the preclinical phase of AD, which could be a potential role of the central neuron system (CNS) immune response in the AD continuum.

Clinical trial registration

www.ClinicalTrials.gov, identifier: NCT03370744.
Absence of susceptibility vessel sign and hyperdense vessel sign in patients with cancer-related stroke
Authors: Beyeler Morin , Grunder Lorenz , Göcmen Jayan , Steinauer Fabienne , Belachew Nebiyat F. , Kielkopf Moritz , Clénin Leander , Mueller Madlaine , Silimon Norbert , Kurmann Christoph , Meinel Thomas , Bücke Philipp , Seiffge David , Dobrocky Tomas , Piechowiak Eike I. , Pilgram-Pastor Sara , Mattle Heinrich P. , Navi Babak B. , Arnold Marcel , Fischer Urs , Pabst Thomas , Gralla Jan , Berger Martin D. , Jung Simon , Kaesmacher Johannes
Published: March 2023

Background and aim

Identification of paraneoplastic hypercoagulability in stroke patients helps to guide investigations and prevent stroke recurrence. A previous study demonstrated an association between the absence of the susceptibility vessel sign (SVS) on brain MRI and active cancer in patients treated with mechanical thrombectomy. The present study aimed to confirm this finding and assess an association between the absence of the hyperdense vessel sign (HVS) on head CT and active cancer in all stroke patients.

Methods

SVS and HVS status on baseline imaging were retrospectively assessed in all consecutive stroke patients treated at a comprehensive stroke center between 2015 and 2020. Active cancer, known at the time of stroke or diagnosed within 1 year after stroke (occult cancer), was identified. Adjusted odds ratios (aOR) and their 95% confidence interval (CI) for the association between the thrombus imaging characteristics and cancer were calculated using multivariable logistic regression.

Results

Of the 2,256 patients with thrombus imaging characteristics available at baseline, 161 had an active cancer (7.1%), of which 36 were occult at the time of index stroke (1.6% of the total). The absence of SVS was associated with active cancer (aOR 3.14, 95% CI 1.45–6.80). No significance was reached for the subgroup of occult cancer (aOR 3.20, 95% CI 0.73–13.94). No association was found between the absence of HVS and active cancer (aOR 1.07, 95% CI 0.54–2.11).

Conclusion

The absence of SVS but not HVS could help to identify paraneoplastic hypercoagulability in stroke patients with active cancer and guide patient care.