Understanding the Role of Female Genital Tract Microbiome in Recurrent Implantation Failure.

The realization of the role of the microbiome of the female reproductive tract in health and disease has opened numerous possibilities for the scientific examination of the intertwining role between the human host and its microbiota. The imbalance in the composition of the microbial communities of the vagina and uterus is now recognized as a risk factor for many complications in pregnancy and according to the data from numerous studies, it is possible for this imbalance to play a crucial role in creating a hostile endometrial environment, and therefore, contributing to the etiology of recurrent implantation failure. Nevertheless, our current understanding of these complicated biological phenomena is far from complete, and in the future, there needs to be a systematic and thorough investigation of the diagnosis and therapy of this condition. This will enable scientists who engage in the field of assisted reproduction technologies to accurately identify and cure women in whom dysbiosis hinders the achievement of a healthy pregnancy.

Astrocytic Calcium Signaling Toolkit (astroCaST): efficient analysis of dynamic astrocytic calcium events.

The Astrocytic Calcium Signaling Toolkit (astroCaST) is a novel solution to a longstanding challenge in neuroscience research: the specialized analysis of astrocytic calcium events within fluorescence time-series imaging. Distinct from existing neuron-centric tools, astroCaST is adept at detecting and clustering astrocytic calcium events based on their unique spatiotemporal characteristics, thus filling a gap in astrocytic research methodologies. This toolkit not only facilitates the detection of such events but also extends its utility to provide comprehensive end-to-end analysis. This feature is absent in most tools targeting astrocytic activity. AstroCaST's development was motivated by the critical need for dedicated software that supports researchers in transitioning from raw video data to insightful experimental conclusions, efficiently managing large-scale datasets without compromising computational speed. It offers a user-friendly interface that caters to both novice and expert users, incorporating both a graphical user interface (GUI) for detailed explorations and a command-line interface (CLI) for extensive analyses. Expected outcomes from utilizing astroCaST include the ability to process and analyze a significantly larger volume of data. This enables a more profound and comprehensive analysis than previously possible, addressing the demands of large-scale astrocytic studies. In summary, astroCaST aims to advance astrocytic calcium imaging analysis, offering a tailored, efficient, and comprehensive toolset that enhances our understanding of astrocytic functions and their implications in neuroscience.

Prenatal Identification of a Missense Mutation of the L1CAM Gene Associated With Hydrocephalus Using Next-Generation Sequencing.

We present the case of a 35-year-old pregnant woman who visited our department for a routine ultrasonography screening scan for fetus anatomy during the 22nd week of gestation. Our report revealed a male fetus with marked hydrocephalus and severe intrauterine growth retardation. After extensive counseling, the couple decided to proceed with an invasive diagnosis via amniocentesis. The cytogenetic analysis showed findings related to clinical history and ultrasound findings related to the presence of a nucleotide change in c.578T>C with an amino acid change in p.Leu198Pro of the L1CAM gene. The result was reported as a hemizygote missense L1CAM gene variant of unknown significance. After extensive parental counseling, the couple decided on pregnancy termination. We report the present case of L1CAM mutation in p.Leu198Pro to add to the limited knowledge regarding the clinical presentation of mutations of the L1CAM gene with emphasis on prenatal diagnosis.

Pregnant women and measles: we need to be vigilant during outbreaks.

A number of countries including the UK are currently experiencing large outbreaks of measles affecting mainly young children but also adolescents and young adults. Women of childbearing age are a particular group of concern because the 1988 Wakefield Lancet paper, which falsely asserted a connection between the MMR vaccine and autism, was associated with a large and sharp decline in childhood MMR uptake over several years. This has left large cohorts of non-immune adolescents and young adults (born between 1998 and 2004), including young women who are now of childbearing age and remain susceptible to measles as well as rubella. Pregnant mothers are at higher risk of serious complications, such as pneumonia, with adverse pregnancy complications including fetal loss, premature birth, and neonatal death. Measles infection may also result in subacute sclerosing panencephalitis (SSPE), a very rare but very severe and invariably fatal neurodegenerative complication that typically manifests many years after acute measles infection but can have a short-onset latency with a fulminant course in pregnant women. Here, we summarise the epidemiology of measles infection, factors associated with the current measles outbreaks, as well as the risks and outcomes of measles, including SSPE, in pregnancy. We propose an algorithm for clinical management of measles infection in pregnancy. We also highlight the importance of early liaison with local health protection teams for risk assessment, diagnosis and management of suspected measles in pregnancy and close contacts as well as susceptible pregnant women exposed to a person with measles in the community.

Validation of Perioperative Troponin Levels for Predicting Postoperative Mortality and Long-Term Survival in Patients Undergoing Surgery for Hepatobiliary and Pancreatic Cancer.

Background: Hepatopancreato and biliary (HPB) tumors represent some of the leading cancer-related causes of death worldwide, with the majority of patients undergoing surgery in the context of a multimodal treatment strategy. Consequently, the implementation of an accurate risk stratification tool is crucial to facilitate informed consent, along with clinical decision making, and to compare surgical outcomes among different healthcare providers for either service evaluation or clinical audit. Perioperative troponin levels have been proposed as a feasible and easy-to-use tool in order to evaluate the risk of postoperative myocardial injury and 30-day mortality. The purpose of the present study is to validate the perioperative troponin levels as a prognostic factor regarding postoperative myocardial injury and 30-day mortality in Greek adult patients undergoing HPB surgery. Method: In total, 195 patients undergoing surgery performed by a single surgical team in a single tertiary hospital (2020-2022) were included. Perioperative levels of troponin before surgery and at 24 and 48 h postoperatively were assessed. Model accuracy was assessed by observed-to-expected (O:E) ratios, and area under the receiver operating characteristic curve (AUC). Survival at one year postoperatively was compared between patients with high and normal TnT levels at 24 h postoperatively. Results: Thirteen patients (6.6%) died within 30 days of surgery. TnT levels at 24 h postoperatively were associated with excellent discrimination and provided the best-performing calibration. Patients with normal TnT levels at 24 h postoperatively were associated with higher long-term survival compared to those with high TnT levels. Conclusions: TnT at 24 h postoperatively is an efficient risk assessment tool that should be implemented in the perioperative pathway of patients undergoing surgery for HPB cancer.

Expression of the O-Linked N-Acetylglucosamine-containing Epitope H (O-GlcNAcH) in Human Uterine Cervical Mucosa.

BACKGROUND/AIM: Epitope H contains an O-linked N-acetylglucosamine (O-GlcNAcH) residue in a specific conformation or environment, recognized by a site-specific monoclonal mouse IgM antibody H. O-GlcNAcH occurs in several normal and pathological cells and in several polypeptides, including keratin-8 and vimentin, on the latter in cells under stress. MATERIALS AND METHODS: In this work, we studied the distribution of O-GlcNAcH on cells of endocervical mucosa in 60 specimens of endocervical curettings, 10 of which contained 15 inflamed polyps. RESULTS: In our results, expression of O-GlcNAcH was weak in the mucosa with <5% mucin-secreting cells and up to 30% of the polyps staining positively. All non-ciliated, non-mucin-secreting cells, normal and hyperplastic 'reserve' cells, as well as the cells of immature squamous metaplasia, showed strong diffuse cytoplasmic staining for O-GlcNAcH. In mature squamous epithelium, fewer than 5% of basal cells and all the intermediate and superficial cells showed cytoplasmic staining for O-GlcNAcH, whereas parabasal cells were negative. All ciliated cells showed patchy or diffuse cytoplasmic staining. Nuclear staining for O-GlcNAcH was weak with fewer than 5% of hyperplastic 'reserve' and ciliated cells staining positively. Moreover, mucosal fibroblasts were negative, whereas all stromal cells of the polyps showed strong cytoplasmic staining for O-GlcNAcH. CONCLUSION: O-GlcNAcH is: a) differentially expressed among the cellular elements of mucosa and polyps, b) upregulated in mucin-secreting cells of polyps, c) induced in stromal cells of inflamed polyps, and d) can be used as a marker to differentiate between 'reserve' (positive) and parabasal (negative) cells, which have similar morphology using conventional cytological stains.

Central Pancreatectomy: Balancing between the Favorable Functional Results and the Increased Associated Morbidity.

Introduction Central pancreatectomy (CP) represents an organ-preserving type of pancreatic resection. The procedure has been associated with improved long-term functional results, but increased postoperative morbidity rates, compared with the more radical resection types. The purpose of the present study was to present the outcomes of three consecutive CPs performed in our department. Materials and Methods Between January 2021 and January 2022, three patients (A, B, and C) were submitted to a CP in our department. Relevant patient data including data of the detailed preoperative assessment, operations notes, and recovery charts were prospectively collected and reviewed for all subjects. A scheduled follow-up, at the outpatient clinic, was conducted to assess the long-term functional results. Results The postoperative course of patient A, a 56-year-old male, was complicated by a grade C postoperative pancreatic fistula that required a reoperation. Patient B, a 66-year-old female, developed a biochemical leak that resolved spontaneously while patient C, a 64-year-old male, had a completely uneventful recovery. The length of hospital stay for the three patients was 24, 12, and 8 days, respectively. Regarding the long-term results, patient B was lost to follow-up while both patient A and C were followed up, as outpatients, 21 and 10 months after the operation. During follow-up, in patient A, we did not record the presence of symptoms consistent with pancreatic exocrine insufficiency, the hemoglobin A1C (HbA1C) levels were 7.1% while no additional medications were needed to be prescribed to maintain the glycemic control following surgery. In patient C, a significant weight loss was recorded (body mass index reduction of 11 kg/m 2 ) without however the presence of malabsorption-specific symptoms. The HbA1C levels were 7.7% and optimal glycemic control was achieved with oral antiglycemic agents alone. Conclusion CP should be regarded as a type of pancreatic resection with certain and very limited oncological indications. An approach of balancing the advantages out of the superior postoperative functional results with the drawbacks of the increased procedure-associated morbidity could highlight the patient group that could potentially experience benefits out of this limited type of resection.

Protocol to dissect and dissociate the mouse brainstem for single-cell RNA-seq applications.

Processing dissociated cells for transcriptomics is challenging when targeting small brain structures, like brainstem nuclei, where cell yield may be low. Here, we present a protocol for dissecting, dissociating, and cryopreserving mouse brainstem that allows asynchronous sample collection and downstream processing of cells obtained from brainstem tissue in neonatal mice. Although we demonstrate this protocol with the isolated preBötzinger complex and downstream SmartSeq3 cDNA library preparation, it could be readily adapted for other brainstem areas and library preparation approaches.

Microvessel Density (MVD) in Patients with Osteosarcoma: A Systematic Review and Meta-Analysis.

A meta-analysis was designed and conducted to estimate the effect of tumoral microvessel density (MVD) on the survival of patients with osteosarcoma. There was no difference between high and low MVD regarding the overall (OS) and disease-free (DFS) survival. Low MVD tumors displayed a lower DFS at the third year of follow-up. Although primary metastases did not affect the mean MVD measurements, tumors with a good chemotherapy response had a higher MVD value. Although no significant differences between tumoral MVD, OS and DFS were found, good adjuvant therapy responders had a significant higher vascularization pattern.

Redefining biomaterial biocompatibility: challenges for artificial intelligence and text mining.

The surge in 'Big data' has significantly influenced biomaterials research and development, with vast data volumes emerging from clinical trials, scientific literature, electronic health records, and other sources. Biocompatibility is essential in developing safe medical devices and biomaterials to perform as intended without provoking adverse reactions. Therefore, establishing an artificial intelligence (AI)-driven biocompatibility definition has become decisive for automating data extraction and profiling safety effectiveness. This definition should both reflect the attributes related to biocompatibility and be compatible with computational data-mining methods. Here, we discuss the need for a comprehensive and contemporary definition of biocompatibility and the challenges in developing one. We also identify the key elements that comprise biocompatibility, and propose an integrated biocompatibility definition that enables data-mining approaches.

Pneumomediastinum: Experience with 87 Patients.

OBJECTIVE: The aim of the present series was first to present our experience in the management of 37 patients with spontaneous pneumomediastinum (SPM), and further to indicate the necessity of identifying true SPM cases as they are currently inadequately defined. METHODS: This is a single-center, retrospective study, conducted in a university hospital. Consecutive adult patients with pneumomediastinum (PM) between January 2009 and March 2020 were involved in the series. The data about age, gender, symptoms, signs, treatment, length of hospital stay (LOS), and in-hospital mortality were evaluated. RESULTS: In total, 87 cases with pneumomediastinum (37 with spontaneous and 50 with secondary PM) were analyzed. Patients in both groups were of similar ages (P=0.4). Sufferers with secondary PM were more likely to have: an associated pneumothorax (19% vs 58%, P<0.05), a chest tube placed (18.9% vs 58%, P<0.05), an associated pleural effusion (0% vs 18%, P<0.05). They presented with a longer LOS (3.9 vs 5.3 days, P<0.05), and were more likely to die (0% vs 10%, P<0.05). Additionally they showed a higher prevalence of radiologic subcutaneous emphysema (49% vs 74%, P<0.05). CONCLUSION: Spontaneous pneumomediastinum is an onset of clinical importance with a low mortality rate, short LOS and good longterm prognosis. It often presents with chest pain, dyspnea and/or subcutaneous emphysema. However, secondary causes of mediastinal air must be ruled out, due to their potential devastating outcome if not diagnosed promptly. A consensus aimed at an update of the classification guidelines is more than indispensable.

Revisiting ameloblastin; addressing the EMT-ECM axis above and beyond oral biology.

Ameloblastin (AMBN) is best characterized for its role in dental enamel formation, regulating cell differentiation and mineralization, and cell matrix adhesion. However, AMBN has also been detected in mesenchymal stem cells in addition to bone, blood, and adipose tissue. Using immunofluorescence in a pilot scheme, we identified that AMBN is expressed in different parts of the gastrointestinal (GI) tract. AMBN mRNA and protein detection in several tissues along the length of the GI tract suggests a role for AMBN in the structure and tissue integrity of the extracellular matrix (ECM). Intracellular AMBN expression in subsets of cells indicates a potential alternative role in signaling processes. Of note, our previous functional AMBN promoter analyses had shown that it contains epithelial-mesenchymal transition (EMT) regulatory elements. ΑΜΒΝ is herein presented as a paradigm shift of the possible associations and the spatiotemporal regulation of the ECM regulating the EMT and vice versa, using the example of AMBN expression beyond oral biology.

Multi-omics approach reveals dysregulated genes during hESCs neuronal differentiation exposure to paracetamol.

Prenatal paracetamol exposure has been associated with neurodevelopmental outcomes in childhood. Pharmacoepigenetic studies show differences in cord blood DNA methylation between unexposed and paracetamol-exposed neonates, however, causality and impact of long-term prenatal paracetamol exposure on brain development remain unclear. Using a multi-omics approach, we investigated the effects of paracetamol on an in vitro model of early human neurodevelopment. We exposed human embryonic stem cells undergoing neuronal differentiation with paracetamol concentrations corresponding to maternal therapeutic doses. Single-cell RNA-seq and ATAC-seq integration identified paracetamol-induced chromatin opening changes linked to gene expression. Differentially methylated and/or expressed genes were involved in neurotransmission and cell fate determination trajectories. Some genes involved in neuronal injury and development-specific pathways, such as KCNE3, overlapped with differentially methylated genes previously identified in cord blood associated with prenatal paracetamol exposure. Our data suggest that paracetamol may play a causal role in impaired neurodevelopment.

From Classic Whipple to Pylorus Preserving Pancreaticoduodenectomy and Ultimately to Pylorus Resecting - Stomach Preserving Pancreaticoduodenectomy: A Review.

Pancreaticoduodenectomy is the procedure of choice for benign or malignant tumors of the periampullary region. The preservation of the pylorus has been established as the mostly utilized approach during pancreaticoduodenectomy among the majority of specialized, in the surgical treatment of pancreatic cancer, centers worldwide. The factors that influenced this predilection are the shorter operation times, the less intraoperative blood loss, the decreased technical difficulty, and the quite similar short- and long-term outcomes compared to the classic Whipple. However, there is a notable trend in the literature highlighting the increased incidence of delayed gastric emptying following pylorus preserving pancreaticoduodenectomy. Among other factors, pylorus dysfunction attributable to the surgical maneuvers has been implemented in the etiology of this complication. In an attempt to overcome this limitation of the pylorus preserving pancreaticoduodenectomy, pylorus resecting pancreaticoduodenectomy with the preservation of the stomach was proposed. In theory, pylorus resecting pancreaticoduodenectomy could maintain the advantages of organ sparing surgery, but at the same time guarantee a more seamless gastric emptying. Only three RCTs, to date, aimed to evaluate the approach with only one reporting results in favor of the pylorus resecting pancreaticoduodenectomy in regard to the incidence of delayed gastric emptying. Further well-designed prospective randomized studies are needed for an accurate assessment of the true role of each of these surgical alternatives on the treatment of pancreatic cancer.

Bladder Cancer during Pregnancy: A Review of the Literature.

Bladder malignancy represents the fourth most common cancer in men and the eighth in women in the western world. Women under 75 years of age have a risk of 0.5-1% of developing bladder cancer. The diagnosis usually occurs between 65 and 70 years of age, whereas the mortality rate for women varies from 0.5 to 4 per 100,000 every year. Nulliparous women present a greater risk than women who have given birth. The risk is further decreased when parity increases. Theoretically, hormonal changes occurring during pregnancy play a protective role. Smoking and occupational exposure to specific chemicals are the most common risk factors of bladder cancer. Other risk factors such as chronic urinary tract inflammation, cyclophosphamide, radiotherapy, and familial correlation have been reported. The aim of this review is to highlight a rare combination, which is the co-existence of bladder malignancy and pregnancy. We present thirteen different cases of women who were diagnosed with malignant bladder tumors during their pregnancy. A review of the literature was conducted, focusing on the unspecific symptoms, possible diagnostic tools, and suitable treatment modalities. The management of bladder cancer in pregnancy is a challenging process. The fragile balance between the possible complications of pregnancy and maternal health is yet to be discussed.

Microvessel density in patients with gastrointestinal stromal tumors: A systematic review and meta-analysis.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are considered the most common mesenchymal tumors of the gastrointestinal tract. Microvessel density (MVD) constitutes a direct method of vascularity quantification and has been associated with survival rates in multiple malignancies. AIM: To appraise the effect of MVD on the survival of patients with GIST. METHODS: This study adhered to Systematic reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Electronic scholar databases and grey literature repositories were systematically screened. The Fixed Effects or Random Effects models were used according to the Cochran Q test. RESULTS: In total, 6 eligible studies were identified. The pooled hazard ratio (HR) for disease free survival (DFS) was 8.52 (95%CI: 1.69-42.84, P = 0.009). The odds ratios of disease-free survival between high and low MVD groups at 12 and 60 mo did not reach statistical significance. Significant superiority of the low MVD group in terms of DFS was documented at 36 and 120 mo (OR: 8.46, P < 0.0001 and OR: 22.71, P = 0.0003, respectively) as well as at metastases rate (OR: 0.11, P = 0.0003). CONCLUSION: MVD significantly correlates with the HR of DFS and overall survival rates at 36 and 120 mo. Further prospective studies of higher methodological quality are required.

An artificial intelligence prediction model based on extracellular matrix proteins for the prognostic prediction and immunotherapeutic evaluation of ovarian serous adenocarcinoma.

Background: Ovarian Serous Adenocarcinoma is a malignant tumor originating from epithelial cells and one of the most common causes of death from gynecological cancers. The objective of this study was to develop a prediction model based on extracellular matrix proteins, using artificial intelligence techniques. The model aimed to aid healthcare professionals to predict the overall survival of patients with ovarian cancer (OC) and determine the efficacy of immunotherapy. Methods: The Cancer Genome Atlas Ovarian Cancer (TCGA-OV) data collection was used as the study dataset, whereas the TCGA-Pancancer dataset was used for validation. The prognostic importance of 1068 known extracellular matrix proteins for OC were determined by the Random Forest algorithm and the Lasso algorithm establishing the ECM risk score. Based on the gene expression data, the differences in mRNA abundance, tumour mutation burden (TMB) and tumour microenvironment (TME) between the high- and low-risk groups were assessed. Results: Combining multiple artificial intelligence algorithms we were able to identify 15 key extracellular matrix genes, namely, AMBN, CXCL11, PI3, CSPG5, TGFBI, TLL1, HMCN2, ESM1, IL12A, MMP17, CLEC5A, FREM2, ANGPTL4, PRSS1, FGF23, and confirm the validity of this ECM risk score for overall survival prediction. Several other parameters were identified as independent prognostic factors for OC by multivariate COX analysis. The analysis showed that thyroglobulin (TG) targeted immunotherapy was more effective in the high ECM risk score group, while the low ECM risk score group was more sensitive to the RYR2 gene-related immunotherapy. Additionally, the patients with low ECM risk scores had higher immune checkpoint gene expression and immunophenoscore levels and responded better to immunotherapy. Conclusion: The ECM risk score is an accurate tool to assess the patient's sensitivity to immunotherapy and forecast OC prognosis.

BILE: A Literature Review Based Novel Clinical Classification and Treatment Algorithm of Iatrogenic Bile Duct Injuries.

PURPOSES: The management of patients with iatrogenic bile duct injuries (IBDI) is a challenging field, often with dismal medico legal projections. Attempts to classify IBDI have been made repeatedly and the final results were either analytical and extensive but not useful in everyday clinical practice systems, or simple and user friendly but with limited clinical correspondence approaches. The purpose of the present review is to propose a novel, clinical classification system of IBDI by reviewing the relevant literature. METHODS: A systematic literature review was conducted by performing bibliographic searches in the available electronic databases, including PubMed, Scopus, and the Cochrane Library. RESULTS: Based on the literature results, we propose a five (5) stage (A, B, C, D and E) classification system for IBDI (BILE Classification). Each stage is correlated with the recommended and most appropriate treatment. Although the proposed classification scheme is clinically oriented, the anatomical correspondence of each IBDI stage has been incorporated as well, using the Strasberg classification. CONCLUSIONS: BILE classification represents a novel, simple, and dynamic in nature classification system of IBDI. The proposed classification focuses on the clinical consequences of IBDI and provides an action map that can appropriately guide the treatment plan.