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Abstract Background In the literature, reported cases of Acquired hemophilia A (AHA) induced by COVID-19 vaccination occurred after Adenoviral Vector Deoxyribonucleic Acid (DNA)- and SARS-CoV-2 Messenger Ribonucleic acid (mRNA)-Based vaccines. Here, and to the best of our knowledge, we report the first case of AHA occurring after an inactivated Sinovac-coronavac COVID-19 vaccine. Case presentation A 69-year-old Tunisian male patient consulted for severe left leg pain limiting physical mobility due to a 5*6 cm large ecchymosis located at the left inner thigh, having spontaneously appeared 5 days prior consultation and without notion of trauma. The patient had no known personal medical history. He had received the second dose of CoronaVac-SinoVac vaccine 30 days prior to consultation. Further physical examination revealed the presence of two other ecchymoses: one at the inner face of the right forearm, starting at the wrist reaching the elbow and the other at the left flank of the abdomen. Diagnosis of AHA was based on clinical presentation and confirmed with prolonged a PTT, Factor VIII deficiency and the presence of an FVIII inhibitor. The patient was successfully treated with corticosteroids and low dose Rituximab. Conclusion Clinicians should consider AHA in front of prolonged aPTT with or without spontaneous bleedings even after inactivated virus COVID-19.

This is the first study to determine the clinical importance of circulating bacterial DNA in patients with renal cell carcinoma (RCC). We performed 16S rRNA metagenomic analysis of serum extracellular vesicles (EVs) from 88 patients with RCC and 10 healthy donors and identified three abundant bacterial DNA: Bacteroidia, TM7-1, and Sphingomonadales. Combining characteristic bacterial DNA information (three bacteria-derived DNA), a BTS index was created to diagnose patients with RCC. The BTS index showed high sensitivity not only in the discovery cohort, but also in the validation cohort, suggesting that it was useful as a screening test. Furthermore, in nivolumab treatment of RCC, patients with higher levels of Bacteroidia DNA in serum EVs had significantly poorer progression-free and overall survival than did those with lower levels. This study showed that circulating Bacteria-derived DNA could be used as a biomarker for RCC.

Osteoarthritis is the most prevalent form of arthritis in the world and it is becoming a major public health problem. Osteoarthritic chondrocytes undergo morphological and biochemical changes that lead to de-differentiation. The involvement of signaling pathways, such as the Wnt pathway, during cartilage pathology has been reported. Wnt signaling regulates critical biological processes. Wnt signals are transduced through at least three intracellular signaling pathways including the canonical Wnt/β-catenin pathway, the Wnt/Ca2 + pathway and the Wnt/planar cell polarity pathway. We investigated the involvement of the Wnt canonical and non-canonical pathways in human articular chondrocyte de-differentiation in vitro. Human articular chondrocytes were cultured through four passages with no treatment, or with sFRP3 treatment, an inhibitor of Wnt pathways, or with DKK1 treatment, an inhibitor of the canonical pathway. Chondrocyte-secreted markers and Wnt pathway components were analyzed using western blotting and qPCR. Inhibition of the Wnt pathway showed that the canonical Wnt signaling probably is responsible for inhibition of collagen II expression, activation of metalloproteinase 13 expression and regulation of Wnt7a and c-jun expression during chondrocyte de-differentiation in vitro. Our results also suggest that expressions of eNOS, Wnt5a and cyclinE1 are regulated by non-canonical Wnt signaling. [ABSTRACT FROM AUTHOR]

Osteoarthritis is the most prevalent form of arthritis in the world. Certain signaling pathways, such as the wnt pathway, are involved in cartilage pathology. Osteoarthritic chondrocytes undergo morphological and biochemical changes that lead to chondrocyte de-differentiation. We investigated whether the Wnt pathway is involved in de-differentiation of human articular chondrocytes in vitro. Human articular chondrocytes were cultured for four passages in the presence or absence of IL-1 in monolayer or micromass culture. Changes in cell morphology were monitored by light microscopy. Protein and gene expression of chondrocyte markers and Wnt pathway components were determined by Western blotting and qPCR after culture. After culturing for four passages, chondrocytes exhibited a fibroblast-like morphology. Collagen type II and aggrecan protein and gene expression decreased, while collagen type I, matrix metalloproteinase 13, and nitric oxide synthase expressions increased. Wnt molecule expression profiles changed; Wnt5a protein expression, the Wnt target gene, c-jun, and in Wnt pathway regulator, sFRP4 increased. Treatment with IL-1 caused chondrocyte morphology to become more filament-like. This change in morphology was accompanied by extinction of col II expression and increased col I, MMP13 and eNOS expression. Changes in expression of the Wnt pathway components also were observed. Wnt7a decreased significantly, while Wnt5a, LRP5, β-catenin and c-jun expressions increased. Culture of human articular chondrocytes with or without IL-1 not only induced chondrocyte de-differentiation, but also changed the expression profiles of Wnt components, which suggests that the Wnt pathway is involved in chondrocyte de-differentiation in vitro. [ABSTRACT FROM AUTHOR]

Bacterial flora are present in various parts of the human body, including the intestine, and are thought to be involved in the etiology of various diseases such as multiple sclerosis, intestinal diseases, cancer, and uterine diseases. In recent years, the presence of bacterial 16S rRNA genes has been revealed in blood, which was previously thought to be a sterile environment, and characteristic blood microbiomes have been detected in various diseases. However, the mechanism and the origin of the bacterial information are unknown. In this study, we performed 16S rRNA metagenomic analysis of bacterial DNA in serum extracellular vesicles from five healthy donors and seven patients with renal cell carcinoma and detected Cutibacterium acnes DNA as a characteristic bacterial DNA in the serum extracellular vesicles of patients with renal cell carcinoma. In addition, C. acnes DNA was significantly reduced in postoperative serum extracellular vesicles from patients with renal cell carcinoma compared with that in preoperative serum extracellular vesicles from these patients and was also detected in tumor tissue and extracellular vesicles from tumor tissue-associated microbiota, suggesting an association between C. acnes extracellular vesicles and renal cell carcinoma. C. acnes extracellular vesicles were taken up by renal carcinoma cells to enhance their proliferative potential. C. acnes extracellular vesicles also exhibited tumor-promoting activity in a mouse model of renal cancer allografts with enhanced angiogenesis. These results suggest that extracellular vesicles released by C. acnes localized in renal cell carcinoma tissues act in a tumor-promoting manner., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Although esophageal achalasia has been historically treated by Heller myotomy, endoscopic esophageal dilatations are nowadays often the first-line treatment in children. The aim was to assess whether performing an endoscopic dilatation before a Heller myotomy is associated with higher risks of esophageal perforation in children., Methods: A retrospective multicentric study was performed, including children that underwent a Heller myotomy (2000-2022, 10 centers). Two groups were compared based on the history of previous dilatation before myotomy. Outcomes esophageal perforation (intra-operative or secondary) and post-operative complications requiring surgery (Clavien-Dindo III). Statistics Comparisons using contingency tables or Kruskal-Wallis when appropriate. Statistical significance: p-value < 0.05., Results: A Heller myotomy was performed in 77 children (median age: 11.8 years), with prior endoscopic dilatation in 53% (n = 41). A laparoscopic approach was used in 90%, with associated fundoplication in 95%. Esophageal perforation occurred in 19% of children (n = 15), including 12 patients with intra-operative mucosal tear and 3 with post-operative complications related to an unnoticed esophageal perforation. Previous endoscopic dilatation did not increase the risk of esophageal perforation (22% vs 17%, OR: 1.4, 95%CI: 0.43-4.69). Post-operative complications occurred in 8% (n = 6), with similar rates regardless of prior endoscopic dilatation. Intra-operative mucosal tear was the only risk factor for post-operative complications, increasing the risk of complications from 5 to 25% (OR: 6.89, 95%CI: 1.38-31.87)., Conclusions: Prior endoscopic dilatations did not increase the risk of esophageal perforation or postoperative complications of Heller myotomy in this cohort of children with achalasia. Mucosal tear was identified as a risk factor for post-operative complications., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Bone-modifying agents (BMA) are extensively used in treating patients with prostate cancer with bone metastases. However, this increases the risk of medication-related osteonecrosis of the jaw (MRONJ). The safety of long-term BMA administration in clinical practice remains unclear. We aimed to determine the cumulative incidence and risk factors of MRONJ. One hundred and seventy-nine patients with prostate cancer with bone metastases treated with BMA at our institution since 2008 were included in this study. Twenty-seven patients (15%) had MRONJ during the follow-up period (median, 19 months; interquartile range, 9-43 months). The 2-year, 5-year, and 10-year cumulative MRONJ incidence rates were 18%, 27%, and 61%, respectively. Multivariate analysis identified denosumab use as a risk factor for MRONJ, compared with zoledronic acid use (HR 4.64, 95% CI 1.93-11.1). Additionally, BMA use at longer than one-month intervals was associated with a lower risk of MRONJ (HR 0.08, 95% CI 0.01-0.64). Furthermore, six or more bone metastases (HR 3.65, 95% CI 1.13-11.7) and diabetes mellitus (HR 5.07, 95% CI 1.68-15.2) were risk factors for stage 2 or more severe MRONJ. MRONJ should be considered during long-term BMA administration in prostate cancer patients with bone metastases., (© 2024. The Author(s).)

The amalgamation of Virtual Reality (VR) and Artificial Intelligence (AI) results in the development of many promising applications that are helpful for society in many aspects. This research was done to study the effect of immersive and non-immersive applications on user's psychological parameters. In this paper, an intelligent, interactive, and immersive digital application was designed, and the various psychological parameters of users while using the application were analyzed through the brain computer interactive device, Emotiv. The impact of these robust and immersive applications on the emotions of human beings was analyzed. According to the observations, the stress and relaxation levels are getting minimally affected, whereas the engagement levels are high for an immersive application rather than a non-immersive application. Hence, it can be concluded that immersive applications put users "in" the application environment and provide a near-realistic experience by blurring the line between the real and virtual worlds. Deeper immersion results from the increased sensation of presence, which in turn is helpful in increasing motivation and emotional investment.•This paper demonstrates the implementation of the A* algorithm within the Unity 3D Game Engine to develop an intelligent digital application, fostering interactivity and depth.•This paper explores the integration of VR technology to transform the digital application into an immersive and interactive experience, enhancing user engagement and realism.•This paper investigates the utilization of the Emotiv Insight device to analyze cognitive parameters within both non-immersive AI-based and immersive AI & VR-based applications, providing insights into user experiences., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Introduction: Tumor Growth Factor-β (TGF-β) is a multifunctional cytokine that plays a crucial role in various biological processes. TGF-β is also involved in various pathologies including breast cancer (BC). BC is strongly dependent on hormone receptors such as Estrogen receptors (ERa, ERb) and Progesterone Receptor (PR)., Aim: To audit the potential cross-talk between TGF-β and the molecular distribution of hormone receptors (ERs and PR)., Methods: The current study analyzes the expression patterns of SMAD3, ERα, ERβ and PR in 40 breast tumor tissues using qRT-PCR. Furthermore, the Ki-67 and HER2/neu status have been detected by Immunohistochemistry., Results: Our results show a decrease in the SMAD3 expression in 27 of the 40 cases while its expression is increased in the remaining 13 cases (p=0.003). The over-expression of SMAD3 is associated with high tumor grades. Moreover, there is a significant positive correlation between SMAD3+ with a high proliferative index and metastases (p=0.001 and p=0.01respectevely). The SMAD3 expression relative to (ERα, ERβ) subgroups shows a significant association of SMAD3+ with the (ERα+, ERβ+) subgroups (p=0.009). The same is true for PR, our results show a significant association of SMAD3+ with PR+ (p=0.02). Moreover, analysis of the expression of molecular subgroups (SMAD3+, ERα+, ERβ+) and (SMAD3+, PR+) compared to clinical and pathological information shows a significant association with high grade tumors, a high proliferation index (p=0.02, p= 0.01 respectively) and lymph node infiltration., Conclusion: It is concluded that SMAD3 can promote cell proliferation and metastases in (ERα+, ERβ+) and PR+ breast cancer.

Domestic chickens may live in environments which restrict wing muscle usage. Notably, reduced wing activity and accompanying muscle weakness are hypothesized risk factors for keel bone fractures and deviations. We used radio-frequency identification (RFID) to measure duration spent at elevated resources (feeders, nest-boxes), ultrasonography to measure muscle thickness (breast and lower leg) changes, radiography and palpation to determine fractures and deviations, respectively, following no, partial (one-sided wing sling) and full (cage) immobilization in white- and brown-feathered birds. We hypothesized partially immobilized hens would reduce elevated resource usage and that both immobilization groups would show decreased pectoralis thickness (disuse) and increased prevalence of fractures and deviations. Elevated nest-box usage was 42% lower following five weeks of partial immobilization for brown-feathered hens but no change in resource usage in white-feathered birds was observed. Fully immobilized, white-feathered hens showed a 17% reduction in pectoralis thickness, while the brown-feathered counterparts showed no change. Lastly, fractures and deviations were not affected in either strain or form of wing immobilization; however, overall low numbers of birds presented with these issues. Altogether, this study shows a profound difference between white- and brown-feathered hens in response to wing immobilization and associated muscle physiology., (© 2023 The Authors.)

Rheumatoid arthritis (RA) is a systemic autoimmune disease during which fibroblast-like synoviocytes (FLS) contribute to both joint inflammation and destruction. FLS represent the core component of the synovial membrane. Following inflammation of this membrane, an effusion of cell-rich synovial fluid (SF) fills the joint cavity. Unlikely, SF has been shown to contain fibroblasts with some shared phenotypic traits with the synovial membrane FLS. These cells are called SF-FLS and their origin is still unclear. They are either brought into the synovium via migration through blood vessels, or they could originate within the synovium and exist in projections of the synovial membrane. SF-FLS function and phenotype are poorly documented compared to recently well-characterized synovial membrane FLS subsets. Furthermore, no study has yet reported a SF-FLS single-cell profiling analysis. This review will discuss the origin and cellular characteristics of SF-FLS in patients with RA. In addition, recent advances on the involvement of SF-FLS in the pathogenesis of RA will be summarized. Current knowledge on possible relationships between SF-FLS and other types of fibroblasts, including synovial membrane FLS, circulating fibrocytes, and pre- inflammatory mesenchymal (PRIME) cells will also be addressed. Finally, recent therapeutic strategies employed to specifically target SF-FLS in RA will be discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mahmoud, Kaabachi, Sassi, Tarhouni, Rekik, Jemmali, Sehli, Kallel-Sellami, Cheour and Laadhar.)

Purpose : Fibroblast-like synoviocytes (FLS) represent one of the principal effectors of joint damage in rheumatoid arthritis (RA). Recent discovery of the circulating fibrocyte, a potential precursor of FLS, has raised issues regarding the characterization of fibrocytes with respect to their morphology and their biological role. In this study, we evaluated the morphology of fibrocytes in vitro and their ability to produce different extracellular matrix (ECM) components in comparison with two populations of RA FLS: synovial fluid FLS (fd-FLS) and intimal lining FLS (td-FLS). We also studied the expression of ECM regulators and a set of cytokine receptors involved in the pathogenesis of RA. Materials and Methods : Fibrocytes were cultured from peripheral blood of patients with RA. FLS were cultured from synovial fluids and tissues. ECM proteins (collagen I (col I) and fibronectin), Matrix metalloproteinases (MMP) (MMP3, and MMP9), ECM regulators (β catenin, TCF4, and c-fos), and cytokine receptors (CXCR1, CXCR2, CXCR3, IL1RI, IL1RII, and IL6Rα) were analyzed using qRT-PCR and/or western blot. Results : Our results demonstrated that fibronectin and MMP3 levels were higher in FLS compared to fibrocytes. Although MMP9 was expressed in the three cell types, its level was greater in fibrocytes than in td/fd FLS. The three cell types expressed CXCR3, IL1RI, IL1RII, and IL6Rα, while the expression of CXCR1 and CXCR2 was restricted to fibrocytes. Conclusion : Our results demonstrated that fibrocytes express ECM molecules and cytokines receptors. The observed differences between fibrocytes and FLS may be due to their distinct functions or differentiation state during RA. Abbreviations: RA : Rheumatoid Arthritis FLS : fibroblast-like synoviocytes td : tissue derived fd : fluid derived SF : Synovial Fluid Wnt : Wingless MMP : Matrix Metalloproteinase CIA : murine collagen induced arthritis ECM : Extracellular matrix col I : Collagen ITCF/LEF: T-cell factor/lymphoid enhancer-binding factor AP1 : Activator Protein 1.

Background: Tissue derived fibroblast-like synoviocytes (td-FLS) are key actors in pannus formation and contribute to joint destruction and inflammation during rheumatoid arthritis (RA). Several members of the Wnt family, including Wnt5a, may contribute to RA td-FLS activation and can potentially serve as therapeutic targets., Objective: The present work aimed to investigate the expression of Wnt5a signaling elements in RA td-FLS and their potential precursors (fluid derived (fd) FLS and fibrocytes). We also studied the role of Wnt5a in RA td-FLS pro-inflammatory activity and whether the inhibitor SFRP5 could restore Wnt5a-induced synovial dysfunction in vitro ., Materials and Methods: The levels of Wnt5a, SFRP5, Wnt5a receptors/coreceptors and Wnt5a pro-inflammatory targets were determined in cultured RA td-FLS, fd-FLS and fibrocytes using qPCR under basal conditions. The expression of pro-inflammatory molecules was assessed after RA td-FLS stimulation with Wnt5a and SFRP5 at different time points., Results: Our data showed that td-FLS, fd-FLS and fibrocytes from patients with RA expressed similar levels of Wnt5a and a set of Wnt5a receptors/coreceptors. We also demonstrated that Wnt5a stimulated the expression of the pro-inflammatory targets, especially IL1β, IL8 and IL6 in RA td-FLS. Wnt5a-induced inflammation was enhanced in the presence of SFRP5. Furthermore, Wnt5a alone and in conjunction with SFRP5 inhibited the gene expression of TCF4 and the protein levels of the canonical coreceptor LRP5., Conclusion: Wnt5a pro-inflammatory effect is not inhibited but enhanced by SFRP5 in RA td-FLS. This research highlights the importance of carefully evaluating changes in Wnt5a response in the presence of SFRP5., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mahmoud, Kaabachi, Sassi, Mokhtar, Moalla, Ammar, Jemmali, Rekik, Tarhouni, Kallel-Sellami, Cheour and Laadhar.)

Background: The etiology of prostate cancer (PCa) is multiple and complex. Among the causes recently cited are chronic infections engendered by microorganisms that often go unnoticed. A typical illustration of such a case is infection due to mollicutes bacteria. Generally known by their lurking nature, urogenital mollicutes are the most incriminated in PCa. This study was thus carried out in an attempt to establish the presence of these mollicutes by PCR in biopsies of confirmed PCa patients and to evaluate their prevalence., Methods: A total of 105 Formalin-Fixed Paraffin-Embedded prostate tissues collected from 50 patients suffering from PCa and 55 with benign prostate hyperplasia were subjected to PCR amplification targeting species-specific genes of 5 urogenital mollicutes species, Mycoplasma genitalium, M. hominis, M. fermentans, Ureaplasma parvum, and U. urealyticum. PCR products were then sequenced to confirm species identification. Results significance was statistically assessed using Chi-square and Odds ratio tests., Results: PCR amplification showed no positive results for M. genitalium, M. hominis, and M. fermentans in all tested patients. Strikingly, Ureaplasma spp. were detected among 30% (15/50) of PCa patients. Nucleotide sequencing further confirmed the identified ureaplasma species, which were distributed as follows: 7 individuals with only U. parvum, 5 with only U. urealyticum, and 3 co-infection cases. Association of the two ureaplasma species with PCa cases proved statistically significant (P < 0.05), and found to represent a risk factor. Of note, Ureaplasma spp. were mostly identified in patients aged 60 and above with prostatic specific antigen (PSA) level > 4 ng/ml and an invasive malignant prostate tumor (Gleason score 8-10)., Conclusions: This study uncovered a significant association of Ureaplasma spp. with PCa arguing in favour of their potential involvement in this condition. Yet, this finding, though statistically supported, warrants a thorough investigation at a much larger scale.

Several infectious diseases and pandemics have so far emerged. Pandemics are by nature rapidly evolving. In this context, COVID-19 cases, seen recently in a growing number of countries around the world, have been increasing exponentially. So, researchers and responsible actors should take quick decisions to mitigate the spread of such diseases. To do so, several computer science solutions, including ontologies, have been proposed to cope with these issues and save humanity. The ontology is the key formalism which allows modelling knowledge along with its semantics in a formal way. Indeed, the ontology provides unambiguous definitions of a discourse's domain terms in a machine understandable way. Particularly, biomedical ontologies have ever been developed to capture and represent pandemics and infectious diseases. In this context, this paper aims to scrutinize and study these state-of-the-art ontologies., (© 2021 The Author(s). Published by Elsevier B.V.)

Introduction: Hepatic pulmonary fusion (HPF) occurring with right diaphragmatic hernia is rare. Some sporadic reports exist in the literature. It may range from just fibrovascular communication to complete parenchymal fusion which may be complex to divide. Patients and methods: We report a case of a 1-day old newborn male presented with respiratory distress relevant to a right diaphragmatic hernia. Results: The patient was operated after initial stabilization. During surgery, a 10-cm wide posterolateral defect was found. The herniated liver was only partially reducible because of HPF. This rare condition was treated by the division of the fusion and diaphragm repair using a vicryl patch. Conclusion: Through our case and a review of the literature, we will discuss the different alternatives in the treatment of HPF.

Enterobacterial components in the joints of patients are believed to contribute to a perpetuating inflammation leading to a reactive arthritis (ReA), a condition in which microbial agents cannot be recovered from the joint. At present, it is unclear whether nucleic acids from Shigella spp. are playing a pathogenic role in causing not only ReA but also other forms of arthritis. Quantitative real-time polymerase chain reaction assay (qPCR) is the method of choice for the identification of bacteria within the synovium. The aim of our study was to detect the presence of Shigella spp. nucleic acids in the synovial tissue (ST) of Tunisian arthritis patients. We investigated 57 ST samples from rheumatoid arthritis (RA) n = 38, undifferentiated oligoarthritis (UOA) n = 12, and spondyloarthritis (SpA) n = 7 patients; 5 ST samples from healthy individuals were used as controls. Shigella spp. DNA and mRNA transcripts encoding the virulence gene A (VirA) were examined using an optimized qPCR with newly designed primers and probes. Using qPCR, Shigella spp. DNA was found in 37/57 (65%) ST samples (24/38, i.e., 63.2% of RA, 8/12, i.e., 67% of UOA, and 5/7, i.e., 71.4% of SpA patients). Paired DNA and mRNA were extracted from 39 ST samples, whose VirA cDNA was found in 29/39 (74.4%) patients. qPCR did not yield any nucleic acids in the five healthy control ST samples. The qPCR assay was sensitive and showed a good intra- and inter-run reproducibility. These preliminary findings generated by an optimized, highly sensitive PCR assay underline a potential role of past gastrointestinal infections. In Tunisian patients, a bacterial etiology involving Shigella spp. in the manifestation of arthritic disorders including RA might be more common than expected.