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BACKGROUND: Lactic acid (LA) can promote the malignant progression of tumors through the crosstalk with the tumor microenvironment (TME). However, the function of long non-coding RNAs (lncRNAs) related to LA metabolism in Wilms tumor (WT) remains unclear. METHODS: Gene expression data and clinical data of WT patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Through the ESTIMATE algorithm and Pearson correlation analysis, lncRNAs related to tumor immunity and LA metabolism were screened. Subsequently, Cox regression analysis and Lasso Cox regression analysis were used to construct a model. Furthermore, candidate genes were identified and a competitive endogenous RNA (ceRNA) network was conducted to explore the specific mechanism of characteristic genes. Finally, based on the strong clinical relevance of UNC5B-AS1, its expression and function were experimentally verified. RESULTS: The immune score and stromal score were found to be closely related to the prognosis of WT. Eventually, a prognostic model (TME-LA-LM) consisting of 6 lncRNAs was successfully identified. The model demonstrated favorable predictive ability and accuracy, with significant variation in immune infiltration and drug susceptibility observed between risk groups. Additionally, the study revealed the involvement of 2 candidate genes and 5 microRNAs (miRNAs) in the tumor's development. Notably, UNC5B-AS1 was highly expressed and found to promote the proliferation and migration of tumor cells. CONCLUSION: This study, for the first time, elucidated the prognostic signatures of WT using lncRNAs related to TME and LA metabolism. The fundings of this research offer valuable insights for future studies on immunotherapy, personalized chemotherapy and mechanism research.

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BACKGROUND: Although progress has been made in accurate diagnosis and targeted treatments, breast cancer (BC) patients with metastasis still present a grim prognosis. With the continuous emergence and development of new personalized and precision medicine targeting specific tumor biomarkers, there is an urgent need to find new metastatic and prognostic biomarkers for BC patients. METHODS: We were dedicated to identifying genes linked to metastasis and prognosis in breast cancer through a combination of in silico analysis and experimental validation. RESULTS: A total of 25 overlap differentially expressed genes were identified. Ten hub genes (namely MRPL13, CTR9, TCEB1, RPLP0, TIMM8B, METTL1, GOLT1B, PLK2, PARL and MANBA) were identified and confirmed. MRPL13, TCEB1 and GOLT1B were shown to be associated with the worse overall survival (OS) and were optionally chosen for further verification by western blot. Only MRPL13 was found associated with cell invasion, and the expression of MRPL13 in metastatic BC was significantly higher than in primary BC. CONCLUSION: We proposed MRPL13 could be a potential novel biomarker for the metastasis and prognosis of breast cancer.

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Homeodomain-only protein homeobox (HOPX) mainly exerts its transcriptional repression by physically sequestering the serum co-repressor and recruiting histone deacetylase (HDAC), possessing important potential as a prognostic gene in acute myeloid leukemia (AML). HDACs play crucial roles in cell growth, gene regulation, and metabolism, and they are also important factors in promoting AML progression. Therefore, this project attempts to investigate whether HOPX affects AML progression by interacting with HDAC2 protein. Bioinformatics analysis was employed to identify potential prognostic genes in AML. Flow cytometry and MTT assays were performed to analyze the cellular biological functions of the AML prognostic marker HOPX. The interaction network of HOPX was analyzed using the Search Tool for the Retrieval of Interacting Genes database, and the interaction between HOPX and HDAC2 was observed using endogenous and exogenous immunoprecipitation. HOPX is highly expressed in AML cells. Further research uncovered that low expression of HOPX can repress the proliferation activity, anti-apoptotic ability, and differentiation blockage of AML cells. Moreover, mechanistically, HOPX induced AML differentiation blockage and malignant progression through interaction with HDAC. HOPX can serve as a prognostic marker for AML and can interact with HDAC2 to induce AML differentiation blockage and malignant progression.

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Introduction. Eighty percent of children with primitive nephrotic syndrome (NS) will have at least one relapse in their life. Specific risk factors could be associated with a higher incidence of relapses and a worse prognosis. This study aims to deepen the demographic and onset-related risk factors in children with known diagnosis of primitive NS attending the Pediatric Nephrology Unit of the University Hospital of Padua. Methods. Observational, descriptive study of all children (1-11 years old) with a known diagnosis of Primitive NS who attended our Pediatric Nephrology Unit between 1 January 2002 and 31 March 2023. Results. 49 patients were involved. 79.5% had at least one episode of NS relapse during their lifetime. 69.4% were classified as frequently relapsing or steroid-dependent NS. The relapse risk factor "non-Western ethnicity" was related to a worse prognosis and steroid-dependent NS classification (p = 0.041). The onset-related risk factor "thrombocytosis" appears to be related to a better prognosis (p = 0.03). Conclusion. The relapse risk factors "non-Western ethnicity" and "thrombocytosis" are characterized by worse and better prognosis, respectively. This evidence could support the follow-up of primitive NS in pediatric age.

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This study gives an insight into certain systemic conditions and factors such as nutrition, age, hematological disorders, hypertension, smoking, obesity, and metabolic syndrome that have a notable effect on the periodontium. The review highlights the importance of taking these factors into consideration in periodontal therapy and their impact on the prognosis of periodontal therapies. The other systemic factors are discussed in detail elsewhere in the special issue.

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This study provided an overview of the knowledge on the main sleep-related disorders and conditions affecting the prognosis of dental treatment: sleep bruxism (SB), obstructive sleep apnea (OSA), and gastroesophageal reflux disease (GERD). Current scientific evidence seems to suggest that these phenomena (ie, SB, OSA, GERD) belong to a circle of mutually relating sleep disorders and conditions where dental practitioners can play a key role in diagnosis and treatment.

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This article explores the intersection of various systemic conditions with orthodontic treatment. Renal diseases, including chronic kidney disease and renal transplant, present challenges such as delayed tooth eruption and gingival overgrowth, necessitating careful orthodontic planning and collaboration with physicians. Liver diseases, particularly hepatitis, heighten the risk of periodontal disease and mandate strict infection control measures during orthodontic procedures. Ehlers-Danlos syndrome poses challenges related to collagen fragility, rapid tooth movement, and orthodontic relapse. Autoimmune diseases like diabetes mellitus and juvenile idiopathic arthritis require tailored orthodontic approaches considering oral complications and joint involvement.

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This review delves into the effects of autoimmune conditions like rheumatoid arthritis, inflammatory disorders such as irritable bowel syndrome, cardiovascular disease, diabetes, infectious ailments like human immunodeficiency virus, and their medications on periodontal therapy outcomes. It also explores the influence of hormones. Understanding these systemic factors is crucial for optimizing periodontal health and treatment efficacy. The review underscores the necessity of considering these variables in periodontal care. Other vital systemic factors are addressed elsewhere in this special edition.

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Clinicians who place and restore implants are always concerned about the success and longevity of the same. There are several local and systemic factors that affect osseointegration and the health of the peri-implant tissues. In this study, we review the systemic factors that can affect implant survival, osseointegration, and long-term success. The study highlights the importance of delineating, and taking into consideration these systemic factors from the planning phase to the restorative phase of dental implants. A thorough medical history, including prescription and over-the-counter medications, is vital, as there may be numerous factors that could directly or indirectly influence the prognosis of dental implants.

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Stress is a process that activates neuronal, metabolic, and neuroendocrine mechanisms. The individual's response may be determined by variables such as genetic factors, environmental conditions, sex, and age, among others. These responses are critical for survival, and the involvement of the hypothalamic-pituitary-adrenal axis is necessary for adaptation, which through counter-regulatory mechanisms seeks to restore homeostasis. Dentists are aware that there are variations in people's response to treatment, and there are many patients in whom dental treatment generates an important source of stress, which in many cases leads to treatment avoidance behavior.

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Many psychological factors may have a significant bearing on an individual's oral health and success of dental treatments. Overall, these factors may result in the avoidance of dental visits, emergency-based dental appointments, noncompliant dental behavior, the utilization of multiple oral health care providers, and poor oral health. These factors may affect the quality of life of individuals and may lead to patient dissatisfaction, poor prognosis, and failure of dental treatment. Multiple psychological factors may affect the dentist and the patient. Those factors may alter the prognosis for successful dental treatment. Physician empathy is fundamental in developing long-term physician-patient trust.

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Genetics plays a significant role in determining an individual's susceptibility to dental diseases, the response to dental treatments, and the overall prognosis of dental interventions. Here, the authors explore the various genetic factors affecting the prognosis of dental treatments focusing on dental caries, orthodontic treatment, oral cancer, prosthodontic treatment, periodontal disease, developmental disorders, pharmacogenetics, and genetic predisposition to faster wound healing. Understanding the genetic underpinnings of dental health can help personalize treatment plans, predict outcomes, and improve the overall quality of dental care.

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This article explores the various challenges systemic conditions can pose before and during orthodontic treatment. Cardiovascular conditions like infective endocarditis require antibiotic prophylaxis before certain orthodontic procedures are started. Patients with bleeding disorders require special considerations in regards to viral infection risk and maintenance of excellent atraumatic oral hygiene. Orthodontists play an important role in early identification of signs and symptoms of eating disorders and should deal with these patients sensitively. Congenital disorders, craniofacial anomalies, and nutritional deficiencies require special considerations and should be addressed appropriately before orthodontic treatment is started.

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The successful outcome of endodontic treatment is dependent on the immune response and the reparative potential of the individual. Alteration in the host immune response is a common characteristic shared by both apical periodontitis and systemic diseases. Although infection-induced periapical lesions occur in a localized environment, numerous epidemiologic studies in the last few decades have investigated the potential association between endodontic disease pathogenesis and systemic diseases. The goal of this review is to identify common systematic factors and discuss the effect they may or may not have on the prognosis and outcome of endodontic therapy.

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This article gives valuable insight into the effect of selected groups of medications on dental treatment outcome and prognosis. The review emphasizes the importance of thorough medical history, which may have an impact on the prognosis of dental treatment. We discuss drugs acting on the central nervous system, gastrointestinal tract, respiratory tract, endocrine system, and bone metabolism among others. Other pertinent drugs are discussed elsewhere in this special issue.

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The field of restorative and prosthetic dentistry focuses on restoring lost tooth structures and replacing missing teeth and lost tissue to restore or improve esthetics and oral health. Many systemic factors such as metabolic, bone, autoimmune, cardiovascular, and endocrine disorders can affect healing procedures, and bone density and impact oral health. Hence patients suffering from systemic disease when treated for prosthodontic rehabilitation can have negative prognostic outcomes. The commonest prosthodontic treatments that can be affected include dental implants, fixed prostheses, and removable prostheses. Understanding and managing these systemic factors play a key role in the success of prosthodontic treatment.

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Breast cancer is the first cancer in women in terms of incidence and mortality. In Morocco, it is a public health problem. Its prognosis is strongly linked to the stage at which it is diagnosed. It is a pathology for which diagnosis means are highly developed today, ranging from early detection to the demonstration of infra-clinical lesions, which has markedly improved the prognosis in developed countries. This work aims to identify the factors that lead patients to consult at an advanced stage in our daily practice. It is a retrospective study carried out from January 2018 to December 2018 including 525 patients with breast cancer followed in the medical oncology department of the Mohammed VI University Hospital in Marrakech. The average age was 54. The average time for consultation was 10.3 months. 63% of patients were from rural areas. Delayed diagnosis affected women above 35 years of age (80%). The most common method of detection was self-examination in 74% of cases. Inflammation (2.66%), ulceration (1.14%), signs of metastases (17.14%), and isolated breast nodes (79.4%) were other reasons for consultation. 82.2% of patients were locally advanced at the time of diagnosis. The time for treatment in our study was 3.7 weeks. In our practice, it is the conjunction of ignorance, poverty, socio-cultural habits, and difficult geographical access that are the essential factors in the late diagnosis of breast cancer.

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The dysregulation of alternative splicing (AS) is increasingly recognized as a pivotal player in the pathogenesis, progression, and treatment resistance of B-cell acute lymphoblastic leukemia (B-ALL). Despite its significance, the clinical implications of AS events in B-ALL remain largely unexplored. This study developed a prognostic model based on 18 AS events (18-AS), derived from a meticulous integration of bioinformatics methodologies and advanced machine learning algorithms. The 18-AS signature observed in B-ALL distinctly categorized patients into different groups with significant differences in immune infiltration, V(D)J rearrangement, drug sensitivity, and immunotherapy outcomes. Patients classified within the high 18-AS group exhibited lower immune infiltration scores, poorer chemo- and immune-therapy responses, and worse overall survival, underscoring the model's potential in refining therapeutic strategies. To validate the clinical applicability of the 18-AS, we established an SF-AS regulatory network and identified candidate drugs. More importantly, we conducted in vitro cell proliferation assays to confirm our analysis, demonstrating that the High-18AS cell line (SUP-B15) exhibited significantly enhanced sensitivity to Dasatinib, Dovitinib, and Midostaurin compared to the Low-18AS cell line (REH). These findings reveal AS events as novel prognostic biomarkers and therapeutic targets, advancing personalized treatment strategies in B-ALL management.

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Background: The stress hyperglycemia ratio (SHR) has emerged as a potential prognostic indicator for various critical illnesses. However, its role in determining outcomes in patients with atrial fibrillation (AF) within the intensive care unit (ICU) remains unclear. This study aimed to elucidate the association between SHR and all-cause mortality in this clinical setting. Methods: We conducted a retrospective cohort study utilizing data from a large, retrospective database. Critically ill patients with documented AF were stratified based on quartiles of SHR. The primary outcome was 365-day all-cause mortality, with secondary outcomes including 90-day and 28-day mortality. COX proportional hazards models adjusted for confounders and Kaplan-Meier curve analyses were used to explore the relationship between SHR and mortality. Results: 2,679 patients with critical AF were enrolled in the final study. Among the patients studied, those in the highest SHR quartiles exhibited an increased risk of 365-day all-cause mortality (HR:1.32, 95%CI=1.06-1.65). Notably, in subgroup analyses, the prognostic value of SHR was particularly pronounced in patients with hypertension. Sensitivity analyses confirmed the persistence of these findings after excluding cohorts with malignant tumors, and heart failure. Conclusions: Our research discerns a positive association between SHR and all-cause mortality in critically ill patients with AF, highlighting the significance of acute glycemic dysregulation on patient outcomes. Longer follow-up is still needed in the future to study the association between SHR and all-cause mortality in critically ill patients with AF.

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