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Background: The various systems of diagnosis and classification of mental disorders underline the need to evaluate the interference caused by the different disorders in a person's daily life. The Maladjustment Inventory (MI) evaluates the impairment in the individual's functioning in a brief and self-applied way, through six items. The objective of this research was to explore the psychometric properties of the MI scores through two studies, one with a Spanish clinical sample (Study 1) and another with a Spanish university students' sample (Study 2). Methods: The total sample was made up of 928 participants (81.1% women, n = 495 clinical sample). Descriptive analyses, exploration of internal structure and reliability, exploratory and confirmatory factor analyses, relationship with other variables (quality of life, anxiety, depression, neuroticism and extraversion), and percentiles and T-scores were performed. Results: The results showed good psychometric properties of the MI, with a good fit model for one factor solution in both samples, Cronbach's alpha coefficient of 0.84–88, and evidence of validity based on the relationship with other variables. Conclusion: The good psychometric properties of the MI, together with its brevity, make it a recommended instrument for the evaluation of interference in both clinical and research contexts. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Methods Results Conclusion Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults and the 5‐year survival remains low.We analyzed the gene expression profiles of the complement and coagulation cascades pathway (CCCP) in 998 bone marrow (BM) and 122 peripheral blood (PB) samples of ALL patients and healthy individuals obtained from the TCGA database and evaluated their clinical significance in terms of being diagnostic and prognostic biomarkers.We identified 18 CCCP genes (SERPINA1, C5AR1, F5, CD55, PLAUR, C3AR1, THBD, CD59, PLAU, VWF, CFD, F13A1, C1QA, C1QB, C1QC, A2M, SERPINE1 and CR2) differentially expressed in the BM samples of ALL patients compared to healthy individuals. The expression levels of CD55, F13A1 and CR2 in BM were linked with the overall survival of ALL patients. While in PB only 11 CCCP genes (e.g., SERPINA1, C5AR1, F5, PLAUR, C3AR1, THBD, CFD, F13A1, C1QA, SERPINE1, and CR2) were differentially expressed and F13A1 was significantly associated with ALL patient survival. Machine learning enabled us to predict ALL using the CCCP genes and the accuracy can reach 0.9701 and 0.9167 using the BM and PB, respectively. Furthermore, using single‐cell RNA sequencing, we found that the differential expression of CCCP genes was found with diversity in the BM‐derived immune cells of ALL patients.Our findings suggest that the CCCP genes may play a key role in the progression of ALL and can be used as potential therapeutic targets and diagnostic markers. [ABSTRACT FROM AUTHOR]

Summary: Aberrant alternative splicing (AS) contributes to leukemogenesis, but reports on the clinical and biological implications of aberrant AS in acute myeloid leukaemia (AML) remain limited. Here, we used RNA‐seq to analyse AS in AML cells from 341 patients, comparing them to healthy CD34+ haematopoietic stem cells (HSCs). Our findings highlight distinct AS patterns in the nuclear transcription factor Y subunit alpha (NFYA) gene, with two main isoforms: NFYA‐L (Long) and NFYA‐S (Short), differing in exon 3 inclusion. Patients with lower NFYA‐L but higher NFYA‐S expression, termed NFYA‐S predominance, displayed more favourable characteristics and better outcomes following intensive chemotherapy, regardless of age and European LeukemiaNet risk classification, compared to those with higher NFYA‐L but lower NFYA‐S expression, termed NFYA‐L predominance. The prognostic effects were validated using The Cancer Genome Atlas cohort. Transcriptome analysis revealed upregulated cell cycle genes in NFYA‐S predominant cases, resembling those of active HSCs, demonstrating relative chemosensitivity. Conversely, NFYA‐L predominant cases, as observed in KMT2A‐rearranged leukaemia, were associated with relative chemoresistance. NFYA‐S overexpression in OCI‐AML3 cells promoted cell proliferation, S‐phase entry and increased cytarabine sensitivity, suggesting its clinical and therapeutic relevance in AML. Our study underscores NFYA AS as a potential prognostic biomarker in AML. [ABSTRACT FROM AUTHOR]

The study by Dang and colleagues in this issue is a timely reminder of the need for careful consideration when it comes to the inclusion of putative new diagnoses in the diagnostic and statistical manual of mental disorders (DSM). The authors conclude that findings from their systematic review and meta‐analysis of recent literature bearing on the DSM‐5 other specified feeding and eating disorders (OSFED) category "support the conceptualization of atypical AN, PD and NES as clinically significant EDs with similar severity to full‐threshold EDs." This commentary attempts to provide some additional context, historical context in particular, that the author believes may be helpful when considering the potential implications of Dang and colleagues' findings. This is achieved through reference to the construct, well‐known in the sociology and feminist literature, of medicalization and by highlighting certain issues relevant to the determination of "clinical significance." I hope that readers approaching Dang and colleagues' research from the currently dominant, medical‐model perspective might be persuaded of the importance of considering alternative perspectives when interpreting findings from research of this kind. [ABSTRACT FROM AUTHOR]

Background: This study investigated the role of cyclin-dependent kinase 9 (CDK9) expression levels and prognosis in acute myeloid leukemia (AML) by examining its expression at the time of initial diagnosis. Methods: Bone marrow samples from 60 AML patients were collected for the observation group, with 20 normal human bone marrow samples serving as controls. Clinical and pathological data were gathered from the AML patients. Real-time quantitative PCR (RT-qPCR) was employed to measure CDK9 expression levels in both groups, and the association between CDK9 expression, clinical characteristics, and prognosis in AML patients was analyzed. Kaplan-Meier curves were used to assess the impact of CDK9 on overall survival (OS) in AML, while Cox regression analysis was performed to identify prognostic factors in AML patients. Results: The expression of CDK9 was significantly elevated in AML patients, compared to the control group (p < 0.05). High CDK9 expression was associated with increased white blood cell (WBC) count, poor treatment response, and worse prognosis compared to low expression (p < 0.05). Additionally, patients with high CDK9 expression exhibited significantly shortened OS compared to those with low expression (p < 0.05). High CDK9 expression emerged as an independent risk factor influencing prognosis in AML. Conclusions: CDK9 is markedly upregulated in AML patients, suggesting its potential utility as both a prognostic indicator and a therapeutic target, particularly for patients with unfavorable clinical and pathological characteristics and poor prognosis. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease, which is characterized by the selective loss of the upper and lower motor neurons. The pathogenesis of ALS remains to be elucidated and has been connected to genetic, environmental and immune conditions. Evidence from clinical and experimental studies has suggested that the immune system played an important role in ALS pathophysiology. Autoantibodies are essential components of the immune system. Several autoantibodies directed at antigens associated with ALS pathogenesis have been identified in the serum and/or cerebrospinal fluid of ALS patients. The aim of this review is to summarize the presence and clinical significance of autoantibodies in ALS. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the expression level of upstream stimulator 1 (USF1) in the bone marrow of newly diagnosed acute myeloid leukemia (AML) patients and investigate its clinical and prognostic significance. Methods: Bone marrow samples from 60 newly diagnosed AML patients constituted the observation group, while 20 samples from healthy individuals formed the control group. Real-time quantitative PCR (qRT-PCR) was used to measure the USF1 expression in both groups and to analyze its correlation with clinicopathological features and prognosis in AML patients. Kaplan-Meier curves were utilized to assess the impact of USF1 on the overall survival (OS) in AML patients. The prognostic factors of AML were examined by using Cox regression analysis. Results: A univariate analysis revealed a significantly higher USF1 expression in the AML patients compared to the control group (p < 0.001), with no difference in the clinicopathological features between the low-expression group and the control group. However, there was a significant difference between the high-expression group and the control group (p < 0.01). Moreover, the OS of the high USF1 expression group was notably shorter than of the low USF1 expression group (p < 0.0001). A multivariate analysis identified high USF1 expression and age ≥ 60 years as independent risk factors for a poor AML prognosis. Conclusions: High expression of USF1 is linked to a worse prognosis and shorter survival time in AML patients. USF1 may serve as an indicator of prognosis and survival in AML patients and could be a potential target for AML treatment. [ABSTRACT FROM AUTHOR]

Abstract Background The various systems of diagnosis and classification of mental disorders underline the need to evaluate the interference caused by the different disorders in a person’s daily life. The Maladjustment Inventory (MI) evaluates the impairment in the individual’s functioning in a brief and self-applied way, through six items. The objective of this research was to explore the psychometric properties of the MI scores through two studies, one with a Spanish clinical sample (Study 1) and another with a Spanish university students’ sample (Study 2). Methods The total sample was made up of 928 participants (81.1% women, n = 495 clinical sample). Descriptive analyses, exploration of internal structure and reliability, exploratory and confirmatory factor analyses, relationship with other variables (quality of life, anxiety, depression, neuroticism and extraversion), and percentiles and T-scores were performed. Results The results showed good psychometric properties of the MI, with a good fit model for one factor solution in both samples, Cronbach’s alpha coefficient of 0.84–88, and evidence of validity based on the relationship with other variables. Conclusion The good psychometric properties of the MI, together with its brevity, make it a recommended instrument for the evaluation of interference in both clinical and research contexts.

The statistical significance of a clinical trial analysis result is determined by a mathematical calculation and probability based on null hypothesis significance testing. However, statistical significance does not always align with meaningful clinical effects; thus, assigning clinical relevance to statistical significance is unreasonable. A statistical result incorporating a clinically meaningful difference is a better approach to present statistical significance. Thus, the minimal clinically important difference (MCID), which requires integrating minimum clinically relevant changes from the early stages of research design, has been introduced. As a follow-up to the previous statistical round article on P values, confidence intervals, and effect sizes, in this article, we present hands-on examples of MCID and various effect sizes and discuss the terms statistical significance and clinical relevance, including cautions regarding their use.

Objective: The present umbrella review aims to collate and summarize the findings from previous meta-analyses on the Triglyceride and Glucose (TyG) Index, providing insights to clinicians, researchers, and policymakers regarding the usefulness of this biomarker in various clinical settings. Methods: A comprehensive search was conducted in PubMed, Scopus, and Web of Science up to April 14, 2024, without language restrictions. The AMSTAR2 checklist assessed the methodological quality of the included meta-analyses. Statistical analyses were performed using Comprehensive Meta-Analysis (CMA) software. Results: A total of 32 studies were finally included. The results revealed significant associations between the TyG index and various health outcomes. For kidney outcomes, a high TyG index was significantly associated with an increased risk of contrast-induced nephropathy (CIN) (OR = 2.24, 95% CI: 1.82–2.77) and chronic kidney disease (CKD) (RR = 1.46, 95% CI: 1.32–1.63). High TyG index was significantly associated with an increased risk of type 2 diabetes mellitus (T2DM) (RR = 3.53, 95% CI: 2.74–4.54), gestational diabetes mellitus (GDM) (OR = 2.41, 95% CI: 1.48–3.91), and diabetic retinopathy (DR) (OR = 2.34, 95% CI: 1.31–4.19). Regarding metabolic diseases, the TyG index was significantly higher in patients with obstructive sleep apnea (OSA) (SMD = 0.86, 95% CI: 0.57–1.15), metabolic syndrome (MD = 0.83, 95% CI: 0.74–0.93), and non-alcoholic fatty liver disease (NAFLD) (OR = 2.36, 95% CI: 1.88–2.97) compared to those without these conditions. In cerebrovascular diseases, a higher TyG index was significantly associated with an increased risk of dementia (OR = 1.14, 95% CI: 1.12–1.16), cognitive impairment (OR = 2.31, 95% CI: 1.38–3.86), and ischemic stroke (OR = 1.37, 95% CI: 1.22–1.54). For cardiovascular outcomes, the TyG index showed significant associations with an increased risk of heart failure (HF) (HR = 1.21, 95% CI: 1.12–1.30), atrial fibrillation (AF) (SMD = 1.22, 95% CI: 0.57–1.87), and hypertension (HTN) (RR = 1.52, 95% CI: 1.25–1.85). Conclusion: The TyG index is a promising biomarker for screening and predicting various medical conditions, particularly those related to insulin resistance and metabolic disorders. However, the heterogeneity and methodological quality of the included studies suggest the need for further high-quality research to confirm these findings and refine the clinical utility of the TyG index. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to assess the expression levels of NAP1L5 in individuals diagnosed with acute myeloid leukemia (AML) and to investigate its clinical and prognostic significance in those with primary AML. Methods: Between June 2021 and June 2023, the Department of Hematology at the First Affiliated Hospital of Bengbu Medical University collected 100 bone marrow specimens from primary AML patients and 30 from individuals with idiopathic thrombocytopenic purpura (ITP) for this medical research study. The researchers gathered comprehensive clinical data from patients diagnosed with acute myeloid leukemia (AML). Quantitative realtime polymerase chain reaction (qRT-PCR) was utilized to measure the mRNA levels of NAP1L5 in both the experimental and the control group. The investigation involved analyzing the association between NAP1L5 expression related to AML, clinical features, and overall prognosis. The study employed the Kaplan-Meier method to evaluate the impact of NAP1L5 expression on the overall survival time (OS) in AML patients, while the Cox hazard regression model was used to identify significant prognostic factors. Results: NAP1L5 was found to be significantly more expressed in individuals with AML compared to those with ITP. Patients diagnosed with AML and exhibiting elevated NAP1L5 expression levels correlated with older age, ineffective response to chemotherapy, and a more unfavorable prognosis compared to those with lower NAP1L5 expression. Additionally, the group with high expression demonstrated a noticeably decreased overall survival (OS), compared to the group with low expression. Furthermore, a significant association was observed between the elevated NAP1L5 expression levels and an unfavorable clinical outcome in patients diagnosed with AML. Conclusions: The initial exploration of the elevated expression of NAP1L5 in AML and its clinical significance offers potential targets for AML treatment and prognostic evaluation. [ABSTRACT FROM AUTHOR]

Allergic Rhinitis (AR), a prevalent condition in otorhinolaryngology, is mediated by Type 1 hypersensitivity through IgE, characterized by Type 2 inflammatory response and eosinophil infiltration in the nasal mucosa. Since AR disease exhibits significant heterogeneity in symptom severity, an objective assessment of AR severity may facilitate better individualized treatment. To explore the changes in peripheral blood IL-9, Th9, and BAFF levels of allergic rhinitis (AR) in patients and the clinical significance associated with it. A retrospective study selected 80 AR patients admitted from January 2022 to October 2022 as the case group, dividing them into mild and moderate-to-severe groups based on symptom scores. Concurrently, 50 patients without AR, who were treated for nasal bone fractures or underwent septoplasty, were selected as the group for comparison. Alterations in the expression levels of peripheral blood IL-9, Th9, and BAFF were analyzed and compared among the different groups. The diagnostic value of serum BAFF for the severity of AR was analyzed using the receiver operating characteristic (ROC) curve. Noticeable variations were observed in clinical variables among the three groups such as, total IgE levels, peripheral blood eosinophil count and proportion, TNSS, and VAS (P< 0.05), while no statistically significant differences were observed in other variables (P> 0.05). The comparison of IL-9, Th9, and BAFF among the three groups revealed statistically significant differences (P< 0.05). Analysis using multivariate logistic regression revealed that IL-9 (OR = 2.365), Th9 (OR = 2.186), BAFF (OR = 2.307) were influencing factors of moderate-to-severe AR (P< 0.05). The ROC curve indicated that the AUC for the diagnosis of moderate-to-severe AR by IL-9, Th9, BAFF were 0.770, 0.734, 0.761, respectively, and the combined detection AUC was 0.888, an area under the curve higher than individual testing. Changes in peripheral blood IL-9, Th9, and BAFF levels in AR patients may function as indicators to assess the level of severity in diagnostic procedures. [ABSTRACT FROM AUTHOR]

Introduction: Glioma, a prevalent and deadly brain tumor, is marked by significant cellular heterogeneity and metabolic alterations. However, the comprehensive cell-of-origin and metabolic landscape in high-grade (Glioblastoma Multiforme, WHO grade IV) and low-grade (Oligoastrocytoma, WHO grade II) gliomas remains elusive. Methods: In this study, we undertook single-cell transcriptome sequencing of these glioma grades to elucidate their cellular and metabolic distinctions. Following the identification of cell types, we compared metabolic pathway activities and gene expressions between high-grade and low-grade gliomas. Results: Notably, astrocytes and oligodendrocyte progenitor cells (OPCs) exhibited the most substantial differences in both metabolic pathways and gene expression, indicative of their distinct origins. The comprehensive analysis identified the most altered metabolic pathways (MCPs) and genes across all cell types, which were further validated against TCGA and CGGA datasets for clinical relevance. Discussion: Crucially, the metabolic enzyme phosphodiesterase 8B (PDE8B) was found to be exclusively expressed and progressively downregulated in astrocytes and OPCs in higher-grade gliomas. This decreased expression identifies PDE8B as a metabolism-related oncogene in IDH-mutant glioma, marking its dual role as both a protective marker for glioma grading and prognosis and as a facilitator in glioma progression. [ABSTRACT FROM AUTHOR]

In the dynamic landscape of modern healthcare, the ability to anticipate and diagnose diseases, particularly in cases where early treatment significantly impacts outcomes, is paramount. Cancer, a complex and heterogeneous disease, underscores the critical importance of early diagnosis for patient survival. The integration of metabolomics information has emerged as a crucial tool, complementing the genotype-phenotype landscape and providing insights into active metabolic mechanisms and disease-induced dysregulated pathways. This review explores a decade of developments in the search for biomarkers validated within the realm of cancer studies. By critically assessing a diverse array of research articles, clinical trials, and studies, this review aims to present an overview of the methodologies employed and the progress achieved in identifying and validating biomarkers in metabolomics results for various cancer types. Through an exploration of more than 800 studies, this review has allowed to establish a general idea about state-of-art in the search of biomarkers in metabolomics studies involving cancer which include certain level of results validation. The potential for metabolites as diagnostic markers to reach the clinic and make a real difference in patient health is substantial, but challenges remain to be explored. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of clinical significance reporting in contemporary comparative effectiveness research (CER). Background: In CER, a statistically significant difference between study groups may or may not be clinically significant. Misinterpreting statistically significant results could lead to inappropriate recommendations that increase health care costs and treatment toxicity. Methods: CER studies from 2022 issues of the Annals of Surgery, Journal of the American Medical Association, Journal of Clinical Oncology, Journal of Surgical Research, and Journal of the American College of Surgeons were systematically reviewed by 2 different investigators. The primary outcome of interest was whether the authors specified what they considered to be a clinically significant difference in the “Methods.” Results: Of 307 reviewed studies, 162 were clinical trials and 145 were observational studies. Authors specified what they considered to be a clinically significant difference in 26 studies (8.5%). Clinical significance was defined using clinically validated standards in 25 studies and subjectively in 1 study. Seven studies (2.3%) recommended a change in clinical decision-making, all with primary outcomes achieving statistical significance. Five (71.4%) of these studies did not have clinical significance defined in their methods. In randomized controlled trials with statistically significant results, sample size was inversely correlated with effect size (r = −0.30, P = 0.038). Conclusions: In contemporary CER, most authors do not specify what they consider to be a clinically significant difference in study outcome. Most studies recommending a change in clinical decision-making did so based on statistical significance alone, and clinical significance was usually defined with clinically validated standards. [ABSTRACT FROM AUTHOR]

Low back pain (LBP) and neck pain predominate as the primary causes of disability. Cell‐ and platelet‐rich plasma (PRP) products are potential therapies with clinical trials and reviews promoting their efficacy. Nonetheless, they frequently disregard the clinical significance of reported improvements. In this systematic review, the effectuated improvements in pain, disability, quality of life (QoL), and radiographic images are comprehensively described and scored on their clinical significance. An electronic database literature search was conducted on July 2023 for in‐human assessment of cell or PRP products to alleviate discogenic pain. Papers were screened on quantitative pain, disability, QoL, radiographic improvements, and safety outcomes. Risk of bias was assessed through MINORS and Cochrane Source of Bias tools. Reported outcomes were obtained, calculated, and assessed to meet minimal clinically important difference (MCID) standards. From 7623 screened papers, a total of 80 articles met the eligibility criteria, presenting 68 specific studies. These presented at least 1974 treated patients. Overall, cell/PRP injections could alleviate pain and disability, resulting in MCID for pain and disability in up to a 2‐year follow‐up, similar to those observed in patients undergoing spinal fusion. Included trials predominantly presented high levels of bias, involved heterogeneous study designs, and only a minimal number of randomized controlled trials. Nonetheless, a clear clinically significant impact was observed for cell‐ and PRP‐treated cohorts with overall good safety profiles. These results highlight a strong therapeutic potential but also underline the need for future cost‐effectiveness assessments to determine the benefits of cell/PRP treatments. [ABSTRACT FROM AUTHOR]

Background: Although it has been shown that cyclin dependent kinase inhibitor 2A (CDKN2A) plays a significant role in a number of malignancies, its clinicopathological value and function in small cell lung cancer (SCLC) is unclear and warrants additional research. Methods: The clinical significance of CDKN2A expression in SCLC was examined by multiple methods, including comprehensive integration of mRNA level by high throughput data, Kaplan–Meier survival analysis for prognostic value, and validation of its protein expression using in-house immunohistochemistry. Results: The expression of CDKN2A mRNA in 357 cases of SCLC was evidently higher than that in the control group (n = 525) combing the data from 20 research centers worldwide. The standardized mean difference (SMD) was 3.07, and the area under the curve (AUC) of summary receiver operating characteristic curve (sROC) was 0.97 for the overexpression of CDKN2A. ACC, COAD, KICH, KIRC, PCPG, PRAD, UCEC, UVM patients with higher CDKN2A expression had considerably worse overall survival rates than those with lower CDKN2A expression with the hazard ratio (HR) > 1. Conclusion: CDKN2A upregulation extensively enhances the carcinogenesis and progression of SCLC. [ABSTRACT FROM AUTHOR]

ObjectiveClaudin18.2 has been established as a putative therapeutic target in human solid malignancies. The aim of this study is to determine claudin18.2 expression as a clinicopathological and prognostic factor in human solid tumors through a systematic review and meta-analysis. Articles were systematically reviewed for studies that included the correlation between claudin18.2 expression and clinicopathological features and prognosis in solid tumors. Meta-analysis was conducted to estimate either odds ratio and 95% confidence intervals (CIs) of clinicopathological factors or hazard ratio and 95% CIs of survival outcomes for claudin18.2 expression in all available solid tumors.Results21 studies including 5,331 patients were identified. Overall proportion of claudin18.2 positivity was 29.7%. Analyses of clinicopathological features demonstrated that claudin18.2 positivity correlated with male predominance, lower T stage, more frequent MUC5AC positivity when all primary tumors included. In subgroup analysis, gastric cancer showed significant correlation between high claudin18.2 expression and frequent EBV infection, male predominance and lower T stage. In lung cancer, claudin18.2 expression was associated with favorable overall survival. However, analyses of survival outcomes in all solid tumors showed that claudin18.2 expression was not associated with overall survival and pooled disease-free survival, tumor-specific survival, progression-free survival and relapse-free survival.ConclusionsOur study emphasizes evaluation of claudin18.2 expression as a potential prognostic factor in lung adenocarcinoma and further exploration in other solid tumors as well.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023468651.

Signal transducer and activator of transcription 4 (STAT4) is a member of the STAT family, which is a group of transcription factors that regulate cytokine signaling. Genetic polymorphisms in STAT4 strongly influence immune responses and disease outcomes, especially in cancer and autoimmune diseases. Several studies have indicated that certain STAT4 gene variants are associated with alterations in STAT4 expression and/or activity and that there is a close relationship between STAT4 polymorphisms and drug efficacy. However, the underlying mechanisms are complex, and the roles of these polymorphisms in disease acquisition, progression, and severity are of widespread concern. Therefore, we provide an overview of the clinical significance of polymorphisms in STAT4 and the mechanisms by which these STAT4 variants are involved in various diseases.

Far upstream element-binding protein 1 (FUBP1) is a single-stranded nucleic acid-binding protein that binds to the Far Upstream Element (FUSE) sequence and is involved in important biological processes, including DNA transcription, RNA biogenesis, and translation. Recent studies have highlighted the significance of aberrant expression or mutations in FUBP1 in the development of various tumors, with FUBP1 overexpression often indicating oncogenic roles in different tumor types. However, it is worth noting that recent research has discovered its tumor-suppressive role in cancer, which is not yet fully understood and appears to be tissue- or context-dependent. This review summarizes the association between FUBP1 and diverse cancers and discusses the functions of FUBP1 in cancer. In addition, this review proposes potential clinical implications and outlines future research directions to pave the way for the development of targeted therapeutic strategies focusing on FUBP1.

ObjectiveThe objective of this study is to assess the prognostic value of Ki67 and p16 proteins in laryngeal cancer.Materials and methodsThis retrospective cohort analysis comprised 260 patients diagnosed with laryngeal cancer. Immunohistochemistry (IHC) was employed to assess the expression levels of p16 and Ki67, and their correlation with the survival time of laryngeal cancer patients was analyzed.ResultsThe Ki67 index level exhibited a significant association with the prognosis of laryngeal cancer. Patients with higher Ki67 index levels demonstrated shorter survival times, more severe pathological classification, and higher tumor stages (P < 0.05). Conversely, no significant differences in prognostic characteristics of laryngeal cancer were observed in the p16 (-/+) population (P > 0.05). The median survival times for patients with Ki67 index levels of 0-35%, 36-70%, and 70-100% were 3.54 years, 2.10 years, and 1.92 years, respectively. After adjusting for age, smoking, alcohol consumption, pathological classification, surgical intervention, recurrence, and metastasis, the risk of death for patients with Ki67 index levels of 70-100% was 2.0504 times higher than that of patients with Ki67 index levels of 0-35% (95% CI: 1.2997-3.2345, P = 0.0020).ConclusionThe Ki67 index level is strongly associated with survival time and the risk of death in laryngeal cancer, making it a valuable prognostic indicator. However, the prognostic value of p16 levels in laryngeal cancer is limited. These findings provide important insights for prognosis evaluation and treatment decision-making in patients with laryngeal cancer.

ObjectiveThis study strives to the variation and significance of microRNA-21 (miR-21) in children with congenital heart disease (CHD)-related pulmonary artery hypertension (PAH).MethodsChildren with CHD (n = 179) were selected as subjects, including 101 children without PAH and 78 children with PAH. All children underwent general data collection, laboratory examination, echocardiography and cardiac catheterization. After detection of serum miR-21 expression, the predictive value and the impacts of serum miR-21 for PAH and postoperative critical illness were analyzed.ResultsSerum creatine kinase isoenzyme (CK-MB), B-type natriuretic peptide (BNP) and miR-21 were elevated, but ejection fraction (EF) and cardiac index (CI) were decreased in the CHD-PAH group. Serum miR-21 assisted in predicting PAH in CHD children, with the area under curve (AUC) of 0.801 (95% CI of 0.735∼0.857), a cut-off value of 2.56, sensitivity of 73.08, and specificity of 72.28%. Serum miR-21 in children with CHD-PAH was correlated with clinicopathological indicators such as systolic pulmonary artery pressure, mean pulmonary arterial pressure, BNP and CI. Serum miR-21 helped predict the development of postoperative critical illness in children with CHD-PAH, with an AUC of 0.859 (95% CI: 0.762–0.927, cut-off value: 4.55, sensitivity: 69.57%, specificity: 92.73%). Increased serum miR-21 was an independent risk factor of postoperative critical illness in children with CHD-PAH.ConclusionSerum miR-21 was upregulated in children with CHD-PAH, which may serve as a predictive biomarker for the onset of PAH and postoperative critical illness in CHD children.

Recently, topics related to targeted gene therapy and diagnosis have become increasingly important in disease research. The progression of many diseases is associated with specific gene signaling pathways. Therefore, the identification of precise gene targets in various diseases is crucial for the development of effective treatments. Laminin subunit beta 3 (LAMB3), a component of laminin 5, functions as an adhesive protein in the extracellular matrix and plays a vital role in regulating cell proliferation, migration, and cell cycle in certain diseases. Previous studies have indicated that LAMB3 is highly expressed in numerous tumorous and non-tumorous conditions, including renal fibrosis; squamous cell carcinoma of the skin, thyroid, lung, pancreatic, ovarian, colorectalr, gastric, breast, cervical, nasopharyngeal, bladder, prostate cancers; and cholangiocarcinoma. Conversely, it is underexpressed in other conditions, such as hepatocellular carcinoma, epidermolysis bullosa, and amelogenesis imperfecta. Consequently, LAMB3 may serve as a molecular diagnostic and therapeutic target for various diseases through its involvement in critical gene signaling pathways. This paper reviews the research status of LAMB3 and its role in related diseases.

Abstract Background Neurospecific Enolase (NSE), a multifunctional protein, is present in various tissues of the body and plays an important role in many disease processes, such as infection, inflammation, tumours, injury, and immunity. In recent years, the application of NSE in respiratory diseases has become increasingly widespread and a research hotspot. Objective This study aims to explore the relationship between NSE and childhood pneumonia, providing assistance for the diagnosis and assessment of pneumonia. Methods Using prospective research and case-control methods, We selected 129 children with pneumonia hospitalised in Weifang People’s Hospital from September 2020 to April 2022 as the case group. Among them were 67 cases of Mycoplasma pneumoniae pneumonia (MP+), 62 cases of non-Mycoplasma pneumoniae pneumonia (MP -), and 21 cases of severe pneumonia. At the same time, 136 children who underwent outpatient health examinations were selected as the control group. The levels of NSE, ESR, CRP in cases group and NSE in control group were measured separately. Result The NSE levels in the MP + group were 17.86 (14.29–22.54) ng/mL, while those in the MP- group were 17.89 (14.10–21.66) ng/mL, both of which were higher than the control group’s NSE levels of 13.26(12.18,14.44) ng/mL (H = 46.92, P = 0.000). There was no statistically significant difference in NSE levels between the MP + and MP - groups (P > 0.05). The NSE level in the severe pneumonia group was 27.38 (13.95–34.06) ng/mL, higher than that in the mild pneumonia group, which was 17.68 (14.27–21.04) ng/mL, (P = 0.024). The AUC values for diagnosing pneumonia are NSE0.714, CRP0.539, and ESR0.535, with NSE having the highest diagnostic value. Conclusion Serum NSE can serve as an inflammatory indicator for paediatric pneumonia, which has important clinical guidance significance for the diagnosis, condition evaluation, and prognosis of paediatric pneumonia.

Abstract Background The minimal important difference is a valuable metric in ascertaining the clinical relevance of a treatment, offering valuable guidance in patient management. There is a lack of available evidence concerning this metric in the context of outcomes related to female urinary incontinence, which might negatively impact clinical decision-making. Objectives To summarize the minimal important difference of patient-reported outcome measures associated with urinary incontinence, calculated according to both distribution- and anchor-based methods. Methods This is a systematic review conducted according to the PRISMA guidelines. The search strategy including the main terms for urinary incontinence and minimal important difference were used in five different databases (Medline, Embase, CINAHL, Web of Science, and Scopus) in 09 June 2021 and were updated in January 09, 2024 with no limits for date, language or publication status. Studies that provided minimal important difference (distribution- or anchor-based methods) for patient-reported outcome measures related to female urinary incontinence outcomes were included. The study selection and data extraction were performed independently by two different researchers. Only studies that reported the minimal important difference according to anchor-based methods were assessed by credibility and certainty of the evidence. When possible, absolute minimal important differences were calculated for each study separately according to the mean change of the group of participants that slightly improved. Results Twelve studies were included. Thirteen questionnaires with their respective minimal important differences reported according to distribution (effect size, standard error of measurement, standardized response mean) and anchor-based methods were found. Most of the measures for anchor methods did not consider the smallest difference identified by the participants to calculate the minimal important difference. All reports related to anchor-based methods presented low credibility and very low certainty of the evidence. We pooled 20 different estimates of minimal important differences using data from primary studies, considering different anchors and questionnaires. Conclusions There is a high variability around the minimal important difference related to patient-reported outcome measures for urinary incontinence outcomes according to the method of analysis, questionnaires, and anchors used, however, the credibility and certainty of the evidence to support these is still limited.

As widely noted in the literature and by international bodies such as the American Statistical Association, severe misinterpretations of P-values, confidence intervals, and statistical significance are sadly common in public health. This scenario poses serious risks concerning terminal decisions such as the approval or rejection of therapies. Cognitive distortions about statistics likely stem from poor teaching in schools and universities, overly simplified interpretations, and – as we suggest – the reckless use of calculation software with predefined standardized procedures. In light of this, we present a framework to recalibrate the role of frequentist-inferential statistics within clinical and epidemiological research. In particular, we stress that statistics is only a set of rules and numbers that make sense only when properly placed within a well-defined scientific context beforehand. Practical examples are discussed for educational purposes. Alongside this, we propose some tools to better evaluate statistical outcomes, such as multiple compatibility or surprisal intervals or tuples of various point hypotheses. Lastly, we emphasize that every conclusion must be informed by different kinds of scientific evidence (e.g., biochemical, clinical, statistical, etc.) and must be based on a careful examination of costs, risks, and benefits.

Background: Neurospecific Enolase (NSE), a multifunctional protein, is present in various tissues of the body and plays an important role in many disease processes, such as infection, inflammation, tumours, injury, and immunity. In recent years, the application of NSE in respiratory diseases has become increasingly widespread and a research hotspot. Objective: This study aims to explore the relationship between NSE and childhood pneumonia, providing assistance for the diagnosis and assessment of pneumonia. Methods: Using prospective research and case-control methods, We selected 129 children with pneumonia hospitalised in Weifang People's Hospital from September 2020 to April 2022 as the case group. Among them were 67 cases of Mycoplasma pneumoniae pneumonia (MP+), 62 cases of non-Mycoplasma pneumoniae pneumonia (MP -), and 21 cases of severe pneumonia. At the same time, 136 children who underwent outpatient health examinations were selected as the control group. The levels of NSE, ESR, CRP in cases group and NSE in control group were measured separately. Result: The NSE levels in the MP + group were 17.86 (14.29–22.54) ng/mL, while those in the MP- group were 17.89 (14.10–21.66) ng/mL, both of which were higher than the control group's NSE levels of 13.26(12.18,14.44) ng/mL (H = 46.92, P = 0.000). There was no statistically significant difference in NSE levels between the MP + and MP - groups (P > 0.05). The NSE level in the severe pneumonia group was 27.38 (13.95–34.06) ng/mL, higher than that in the mild pneumonia group, which was 17.68 (14.27–21.04) ng/mL, (P = 0.024). The AUC values for diagnosing pneumonia are NSE0.714, CRP0.539, and ESR0.535, with NSE having the highest diagnostic value. Conclusion: Serum NSE can serve as an inflammatory indicator for paediatric pneumonia, which has important clinical guidance significance for the diagnosis, condition evaluation, and prognosis of paediatric pneumonia. [ABSTRACT FROM AUTHOR]

ObjectiveMethodsResultsConclusionIn light of the increasing importance of immunotherapy in bladder cancer treatment, this study is aim to investigate the expression and clinical significance of programmed cell surface death-1 (PD-1) in bladder cancer patients without lymph node metastasis, and to compare and analyze the difference of PD-1 in draining lymph nodes and tumor tissues.The expression of PD-1 on T cells and the proportion of positive PD-1 + T cells of IFN-γ and CD105a were detected by flow cytometry, and the correlation between PD-1 expression and clinical parameters was analyzed.The percentage of PD-1 positive cells in drainage lymph nodes was higher than that in tumor tissues (P < 0.001). PD-1 positive cells accounted for the highest proportion in CD3 + T cells. The proportion of IFN-γ-positive PD-1 + T cells in draining lymph nodes was significantly higher than that in tumor tissues (P < 0.001), while there was no significant difference in CD105a positive PD-1 + T cells between tumor tissues and draining lymph nodes. Pathological grade, tumor size and stage were positively correlated with PD-1 expression level in the lymph nodes.The high expression of PD-1 in patients with bladder cancer without lymph node metastasis, especially in draining lymph nodes, suggests that PD-1 may play a key role in the regulation of tumor immune microenvironment. The correlation between PD-1 and clinical parameters indicates its potential prognostic value. These findings provide important clinical implications for PD-1 targeted therapy, but further prospective studies are needed to determine the application value of PD-1 in therapeutic strategies. [ABSTRACT FROM AUTHOR]

Genetic testing, including whole genome, whole exome, and other next‐generation sequencing technologies, has evolved vastly in the past decade. With this, the number of identified genes and genetic variants is constantly increasing. Although a variety of databases and online tools exist that summarize, categorize, and classify genes, a clear guideline of which information is needed when reporting a gene and what to do when identifying a new gene is lacking. This includes the correct nomenclature, descriptive information about genetic loci and genetic variation, aliases, and correlated phenotypes. This tutorial is meant to serve as an introduction to reporting genes in a paper and provides an overview of available databases and tools to obtain all necessary information on the genes of interest. [ABSTRACT FROM AUTHOR]

Background and Objectives: Facial vascular anatomy plays a pivotal role in both physiological context and in surgical intervention. While data exist on the individual course of the facial artery and vein, to date, the spatial relationship of the vasculature has been ill studied. The aim of this study was to assess the course of facial arteries, veins and branches one relative to another. Materials and Methods: In a total of 90 halved viscerocrania, the facial vessels were injected with colored latex. Dissection was carried out, the relation of the facial vessels was studied, and the distance at the lower margin of the mandible was measured. Furthermore, branches including the labial and angular vessels were assessed. Results: At the base of the mandible, the facial artery was located anterior to the facial vein in all cases at a mean distance of 6.2 mm (range 0–15 mm), with three cases of both vessels adjacent. An angular vein was present in all cases, while an angular artery was only present in 34.4% of cases. Conclusions: The main trunk of the facial artery and vein yields a rather independent course, with the facial artery always located anterior to the vein, while their branches, especially the labial vessels, demonstrate a closer relationship. [ABSTRACT FROM AUTHOR]

Accessory bones around the elbow are scarce, with a reported mean incidence rate of 0.77%. The rarest one is the os supratrochleare anterius, with only a handful of documented cases in the literature. Despite their scarcity, various types of ossicles have been documented, posing diagnostic challenges and potential misinterpretation on X-rays. Herein, we report a case of an accidentally found os supratrochleare anterius in a 43-year-old pig farmer presenting with symptoms of tennis elbow. After conservative treatment with nonsteroidal anti-inflammatory drugs and physiotherapy, he made a full recovery within 2 weeks. This report emphasizes the rarity of the ossupra trochleare anterius, the importance of accurate diagnosis, and the need for continued research and awareness of this anatomical variation. [ABSTRACT FROM AUTHOR]

Background: The minimal important difference is a valuable metric in ascertaining the clinical relevance of a treatment, offering valuable guidance in patient management. There is a lack of available evidence concerning this metric in the context of outcomes related to female urinary incontinence, which might negatively impact clinical decision-making. Objectives: To summarize the minimal important difference of patient-reported outcome measures associated with urinary incontinence, calculated according to both distribution- and anchor-based methods. Methods: This is a systematic review conducted according to the PRISMA guidelines. The search strategy including the main terms for urinary incontinence and minimal important difference were used in five different databases (Medline, Embase, CINAHL, Web of Science, and Scopus) in 09 June 2021 and were updated in January 09, 2024 with no limits for date, language or publication status. Studies that provided minimal important difference (distribution- or anchor-based methods) for patient-reported outcome measures related to female urinary incontinence outcomes were included. The study selection and data extraction were performed independently by two different researchers. Only studies that reported the minimal important difference according to anchor-based methods were assessed by credibility and certainty of the evidence. When possible, absolute minimal important differences were calculated for each study separately according to the mean change of the group of participants that slightly improved. Results: Twelve studies were included. Thirteen questionnaires with their respective minimal important differences reported according to distribution (effect size, standard error of measurement, standardized response mean) and anchor-based methods were found. Most of the measures for anchor methods did not consider the smallest difference identified by the participants to calculate the minimal important difference. All reports related to anchor-based methods presented low credibility and very low certainty of the evidence. We pooled 20 different estimates of minimal important differences using data from primary studies, considering different anchors and questionnaires. Conclusions: There is a high variability around the minimal important difference related to patient-reported outcome measures for urinary incontinence outcomes according to the method of analysis, questionnaires, and anchors used, however, the credibility and certainty of the evidence to support these is still limited. [ABSTRACT FROM AUTHOR]

Background: A vast number of researchers have discovered high levels of human epidermal growth factor receptor-2 (HER2) expression in urothelial carcinoma (UC), but they do not use a uniform scoring system. Based on the 2021 edition of clinical pathological expert consensus on HER-2 testing in UC in China, we investigated the expression level and clinical significance of HER2 in high-grade UC. Furthermore, we looked at the prognosis of patients with locally advanced/metastatic UC after combining HER2 targeting antibody-drug conjugates (ADC) medication disitamab vedotin (DV) with programmed cell death protein 1 (PD-1) inhibitor tislelizumab. Patients and methods: From 2019 to 2022, we collected paraffin specimens of UC from the Department of Urology at the Provincial Hospital Affiliated to Shandong First Medical University. HER2 expression-related factors were investigated. Patients with advanced UC who have failed systemic chemotherapy at least once and had received immune checkpoint inhibitor (ICI) medication during second-line treatment were selected and treated with DV in combination with tislelizumab. We assessed the therapy's efficacy and safety. Results: 185 patients with high-grade UC were included in this investigation. 127 patients (68.7%) were HER2 positive (IHC 2+/3+) according to the 2021 Clinical pathological expert consensus on HER2 testing in UC in China. The clinical stage of UC differed statistically significantly between the HER2-and HER2+ groups (p = 0.019). Sixteen advanced UC patients were treated with DV and tislelizumab for a median of 14 months. The disease control rate was 87.5%, while the objective response rate (ORR) was 62.5%. The ORR of HER2+ individuals was higher than that of HER2-individuals (70.0% vs. 50.0%). The median progression-free survival or overall survival was not reached. In this study, the incidence of treatment-related adverse events was 68.8% (11/16), with all of them being grade 1 or 2 adverse reactions. Conclusion: HER2 protein expressed at a high percentage in UC, and 68.7% patients expressed HER2 positive (IHC 2+/3+). HER2+ expression is positively correlated with higher clinical stage of UC. HER2 targeted ADC drug disitamab vedotin combining with PD-1 inhibitor tislelizumab has shown efficacy, safety and controllable adverse reactions in the treatment of advanced UC. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is a common malignant tumor in female. In recent years, with the change of fertility pattern and lifestyle, the incidence of breast cancer is increasing year by year, seriously endangering the health and life of women. MRI is suitable for follow-up evaluation of the course of neoadjuvant chemotherapy in LABC, but there are few related studies and reports. Based on the above background, it is necessary to further evaluate the value of functional magnetic resonance imaging in neoadjuvant chemotherapy in patients with triple negative breast cancer, so as to lay a theoretical foundation for the popularization and application of this detection method. Based on this, this study was to explore the value, diagnostic efficacy and clinical importance of functional magnetic resonance imaging in evaluating the efficacy of neoadjuvant chemotherapy in patients with triple negative breast cancer. Methods: A total of 62 patients with triple-negative breast cancer who received neoadjuvant chemotherapy in our hospital from September 2017 to September 2022 were selected. To compare the differences of functional magnetic resonance imaging (fMRI) between effective and ineffective patients with neoadjuvant chemotherapy, the related data were statistically analyzed. Results: There was no significant difference between the mode of tumor withdrawal and the pathological complete remission of tumor tissue (P>0.05). There was no significant difference in anti-Trop-2 antibody-drug conjugates (ADC) data before and after chemotherapy between over-expressed patients with human epidermal growth factor receptor-2 (HER-2) and non-over-expressed patients with HER-2 (P>0.05). The levels of ADC and D ADC in pathological complete remission patients after chemotherapy were significantly higher than those in non-pathological complete remission patients (P<0.05). Using the DADC value as the evaluation parameter, the pathological response of tumor tissue was classified as the "gold standard" to draw the ROC curve, the area under curve (AUC) was 0.673, the cut-off of DADC to evaluate the significant response of tumor tissue after chemotherapy was 1.418, the sensitivity of evaluating the efficacy was 71.9%, and the specificity was 55.0%. Conclusion: Functional magnetic resonance imaging (fMRI) has diagnostic value for neoadjuvant chemotherapy in patients with triple negative breast cancer. According to the change of ADC value, the curative effect can be predicted early and the treatment strategy can be adjusted in time. [ABSTRACT FROM AUTHOR]

Introduction: Quantitative research and quality improvement (QI) both seek to improve care provided to patients. However, clinicians often blur the lines between how to appropriately analyze data from these methodologies. Clinicians may inappropriately use statistical analyses for QI initiatives, rather than using run and statistical process control (SPC) charts to analyze improvements in outcomes. Objective: The purpose of this article was to address the analytic methods used for QI initiatives in the clinical setting in an effort to show clinicians how to identify meaningful improvements in clinical practice. Methods: In this article, we provide an example comparing the same evidence-based practice/QI initiative (chlorhexidine gluconate bathing in a medical intensive care unit) using a quasi-experimental pretest/posttest research design with statistical analyses completed with t tests with analyses using run and SPC charts to show the data trended over time. Using a pretest/posttest design, chlorhexidine gluconate bathing compliance improved from 63%to 65%, a nonsignificant change, P = .075. These same data plotted on run and SPC charts, however, show a shift and a trend, indicating clinically significant improvements per QI methodologies. Conclusion: The example in this article highlights the pitfall of relying only on statistical analyses and P values to determine the importance of a clinical project, and provides a practical example for how run or SPC charts can be used to identify improvements over time. [ABSTRACT FROM AUTHOR]

Shiga toxin-producing Escherichia coli (STEC) infection can cause a broad spectrum of symptoms spanning from asymptomatic shedding to mild and bloody diarrhea (BD) and even life-threatening hemolytic-uremic syndrome (HUS). As a member of the serine protease autotransporters of Enterobacteriaceae (SPATE) family, EspP has the ability to degrade human coagulation factor V, leading to mucosal bleeding, and also plays a role in bacteria adhesion to the surface of host cells. Here, we investigated the prevalence and genetic diversity of espP among clinical STEC isolates from patients with mild diarrhea, BD, and HUS, as well as from asymptomatic individuals, and assessed the presence of espP and its subtypes in correlation to disease severity. We found that 130 out of 239 (54.4%) clinical STEC strains were espP positive, and the presence of espP was significantly associated with BD, HUS, and O157:H7 serotype. Eighteen unique espP genotypes (GTs) were identified and categorized into four espP subtypes, i.e., espPα (119, 91.5%), espPγ (5, 3.8%), espPδ (4, 3.1%), and espPε (2, 1.5%). espPα was widely distributed, especially in strains from patients with BD and HUS, and correlated with serotype O157:H7. Serogroup O26, O145, O121, and O103 strains carried espPα only. Ten GTs were identified in espPα, and espPα/GT2 was significantly associated with severe disease, i.e., BD and HUS. Additionally, espP was strongly linked to the presence of eae gene, and the coexistence of espPα and stx2/stx2a + stx2c was closely related to HUS status. To sum up, our data demonstrated a high prevalence and genetic diversity of the espP gene in clinical STEC strains in Sweden and revealed an association between the presence of espP, espP subtypes, and disease severity. espP, particularly the espPα subtype, was prone to be present in more virulent STEC strains, e.g., "top-six" serotypes strains. [ABSTRACT FROM AUTHOR]

With the global spread of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS), the pursuit of potent treatments has ascended as a paramount concern in global healthcare. Traditional Chinese medicine (TCM) has been used for thousands of years in China and other East Asian countries and it offers remedies for an extensive array of ailments, including HIV and AIDS. This review focuses on the clinical significance of single herbs and composite tonics in TCM with antiviral activity against HIV. Initially, the anti-HIV activity of single herbs was analyzed in detail. Many herbs have been shown to have significant anti-HIV activity. The active ingredients of these herbs exhibit their anti-HIV effects through various mechanisms, such as inhibiting viral replication, preventing viral binding to host cells, and interfering with the viral lifecycle. Furthermore, we delved into the clinical significance of HIV-associated formulations provided as a result of Chinese compound prescription. These combinations of herbal ingredients are designed to amplify therapeutic efficacy and minimize adverse effects. Clinical trials have demonstrated the therapeutic benefits of these prescriptions for individuals infected with HIV. The intricate composition of these prescriptions potentially augments their anti-HIV activity through synergistic effects. Additionally, this review underscores the clinical importance of TCM in the context of HIV treatment. While numerous herbs and prescriptions exhibit anti-HIV activity, their safety and efficacy in clinical applications warrant further investigation. When combined with contemporary antiretroviral drugs, TCM may serve as an adjunctive therapy, assisting in reducing side effects, and enhancing patients' quality of life. To optimally harness these natural resources, further exploration is imperative to ascertain their efficacy, safety, and optimal utilization, thereby offering a broader spectrum of therapeutic options for HIV-afflicted individuals.

ABSTRACT Redundant carbapenemase-producing (RCP) bacteria, which carry double or multiple carbapenemases, represent a new and concerning phenomenon. The objective of this study is to conduct a comprehensive analysis of the epidemiology and genetic mechanisms of RCP strains to support targeted surveillance and control measures. A retrospective analysis was conducted using surveillance data from 277 articles. Statistical analysis was performed to determine and evaluate species prevalence, proportions of carbapenemases, antibiotic susceptibility profiles, sample information, and patient outcomes. Complete plasmid sequencing data were utilized to investigate potential antimicrobial resistance or virulence advantages that strains may gain from acquiring redundant carbapenemases. RCP bacteria are widely distributed globally, and their prevalence is increasing over time. Several countries, including China, India, Iran, Turkey, and South Korea, have reported more than 100 RCP strains. The most commonly reported RCP species are Klebsiella pneumoniae and Acinetobacter baumannii, which exhibit varying proportions of carbapenemase combinations. Certain species-carbapenemase combinations, such as K. pneumoniae carrying New Delhi metallo-β-lactamase (NDM) + oxacillinase (OXA) (56.76%) and K. pneumoniae carbapenemase (KPC) + Verona integron-encoded metallo-β-lactamase (VIM) (50.00%) carbapenemases, are associated with high mortality rates. In patients with RCP strains isolated from the bloodstream and respiratory system, the mortality rates are 58.70% and 69.23%, respectively. Analysis of plasmids from RCP strains suggests that they may acquire additional antibiotic resistance phenotypes and virulence factors. Carbapenem-resistant bacteria carrying redundant carbapenemases pose a significant global health threat. This study provides valuable insights into the epidemiology and genetic mechanisms of these bacteria, supporting the development of effective control and prevention strategies to mitigate their transmission.IMPORTANCEThis study examined the global distribution patterns of 1,780 bacteria with double or multiple carbapenemases from 277 articles and assessed their clinical impact. The presence of multiple carbapenemases increases the chances of co-resistance to other classes of antibiotics and more virulence factors, further complicating the clinical management of infections.

Abstract Low back pain (LBP) and neck pain predominate as the primary causes of disability. Cell‐ and platelet‐rich plasma (PRP) products are potential therapies with clinical trials and reviews promoting their efficacy. Nonetheless, they frequently disregard the clinical significance of reported improvements. In this systematic review, the effectuated improvements in pain, disability, quality of life (QoL), and radiographic images are comprehensively described and scored on their clinical significance. An electronic database literature search was conducted on July 2023 for in‐human assessment of cell or PRP products to alleviate discogenic pain. Papers were screened on quantitative pain, disability, QoL, radiographic improvements, and safety outcomes. Risk of bias was assessed through MINORS and Cochrane Source of Bias tools. Reported outcomes were obtained, calculated, and assessed to meet minimal clinically important difference (MCID) standards. From 7623 screened papers, a total of 80 articles met the eligibility criteria, presenting 68 specific studies. These presented at least 1974 treated patients. Overall, cell/PRP injections could alleviate pain and disability, resulting in MCID for pain and disability in up to a 2‐year follow‐up, similar to those observed in patients undergoing spinal fusion. Included trials predominantly presented high levels of bias, involved heterogeneous study designs, and only a minimal number of randomized controlled trials. Nonetheless, a clear clinically significant impact was observed for cell‐ and PRP‐treated cohorts with overall good safety profiles. These results highlight a strong therapeutic potential but also underline the need for future cost‐effectiveness assessments to determine the benefits of cell/PRP treatments.

Abstract Background Reliable species identification of cultured isolates is essential in clinical bacteriology. We established a new study algorithm named NOVA – Novel Organism Verification and Analysis to systematically analyze bacterial isolates that cannot be characterized by conventional identification procedures MALDI-TOF MS and partial 16 S rRNA gene sequencing using Whole Genome Sequencing (WGS). Results We identified a total of 35 bacterial strains that represent potentially novel species. Corynebacterium sp. (n = 6) and Schaalia sp. (n = 5) were the predominant genera. Two strains each were identified within the genera Anaerococcus, Clostridium, Desulfovibrio, and Peptoniphilus, and one new species was detected within Citrobacter, Dermabacter, Helcococcus, Lancefieldella, Neisseria, Ochrobactrum (Brucella), Paenibacillus, Pantoea, Porphyromonas, Pseudoclavibacter, Pseudomonas, Psychrobacter, Pusillimonas, Rothia, Sneathia, and Tessaracoccus. Twenty-seven of 35 strains were isolated from deep tissue specimens or blood cultures. Seven out of 35 isolated strains identified were clinically relevant. In addition, 26 bacterial strains that could only be identified at the species level using WGS analysis, were mainly organisms that have been identified/classified very recently. Conclusion Our new algorithm proved to be a powerful tool for detection and identification of novel bacterial organisms. Publicly available clinical and genomic data may help to better understand their clinical and ecological role. Our identification of 35 novel strains, 7 of which appear to be clinically relevant, shows the wide range of undescribed pathogens yet to define.

Background: Reliable species identification of cultured isolates is essential in clinical bacteriology. We established a new study algorithm named NOVA – Novel Organism Verification and Analysis to systematically analyze bacterial isolates that cannot be characterized by conventional identification procedures MALDI-TOF MS and partial 16 S rRNA gene sequencing using Whole Genome Sequencing (WGS). Results: We identified a total of 35 bacterial strains that represent potentially novel species. Corynebacterium sp. (n = 6) and Schaalia sp. (n = 5) were the predominant genera. Two strains each were identified within the genera Anaerococcus, Clostridium, Desulfovibrio, and Peptoniphilus, and one new species was detected within Citrobacter, Dermabacter, Helcococcus, Lancefieldella, Neisseria, Ochrobactrum (Brucella), Paenibacillus, Pantoea, Porphyromonas, Pseudoclavibacter, Pseudomonas, Psychrobacter, Pusillimonas, Rothia, Sneathia, and Tessaracoccus. Twenty-seven of 35 strains were isolated from deep tissue specimens or blood cultures. Seven out of 35 isolated strains identified were clinically relevant. In addition, 26 bacterial strains that could only be identified at the species level using WGS analysis, were mainly organisms that have been identified/classified very recently. Conclusion: Our new algorithm proved to be a powerful tool for detection and identification of novel bacterial organisms. Publicly available clinical and genomic data may help to better understand their clinical and ecological role. Our identification of 35 novel strains, 7 of which appear to be clinically relevant, shows the wide range of undescribed pathogens yet to define. [ABSTRACT FROM AUTHOR]

Aim/Background: The Cytochrome P450 (CYP) enzyme family, consisting of 57 distinct genes, plays a pivotal role in various biological processes. These genes encode enzymes with multifaceted functions, impacting vital processes like arachidonic acid metabolism, xenobiotic detoxification, eicosanoids production, and drug metabolism. Moreover, CYP enzymes are indispensable for the synthesis of bile acids, steroids, and numerous metabolic pathways. They also participate in the hydroxylation of retinoic acid, illustrating their remarkable versatility. While some CYP enzymes still have undiscovered functions, their role continues to captivate researchers across diverse domains. Additionally, mutations in CYP genes can give rise to inborn metabolic disorders, leading to clinically significant diseases, underscoring the importance of CYP enzymes in maintaining metabolic equilibrium and overall well-being. Beyond their initial association with hepatic drug detoxification, recent research has unveiled a broader spectrum of enzymatic processes undertaken by cytochrome P450. The complexity of CYP enzymes is progressively unfolding, emphasizing their clinical significance and opening new avenues for drug development, precision medicine, and patient care. methodology: This abstract presents a comprehensive overview of the literature on cytochrome P450 enzymes and their diverse functions. The information was gathered from a wide range of sources, including scientific articles, textbooks, and research publications. The analysis covers the genetic basis of CYP enzymes, their roles in various metabolic pathways, and the clinical implications of CYP gene mutations. Additionally, the abstract highlights the recent advances in our understanding of CYP enzymes and their expanding role in maintaining human life. Results: The results of this study showcase the remarkable diversity of functions performed by cytochrome P450 enzymes. They are intricately involved in processes critical to human health, ranging from drug metabolism to the synthesis of vital biomolecules. The study underlines the clinical significance of CYP enzymes, as mutations in these genes can lead to severe metabolic disorders and diseases. Furthermore, it emphasizes the evolving understanding of CYP enzyme complexity and its implications for drug development, precision medicine, and patient care. Conclusion: In conclusion, this abstract sheds light on the exceptional versatility and clinical importance of cytochrome P450 enzymes. Their diverse functions have far-reaching consequences for human health, making them a focal point of research in pharmacology and medicine. The evolving understanding of CYP enzyme complexity paves the way for future advancements in drug development and personalized patient care, offering new possibilities for enhancing the well-being of individuals and populations. This research underscores the significance of CYP enzymes and their potential to revolutionize the fields of medicine and pharmacology. [ABSTRACT FROM AUTHOR]

Background: Posterior glenohumeral instability is an increasingly recognized cause of shoulder pain and dysfunction among young, active populations. Outcomes after posterior stabilization procedures are commonly assessed using patient-reported outcome measures including the Single Assessment Numeric Evaluation (SANE), the Rowe instability score, the American Shoulder and Elbow Surgeons (ASES) score, and the visual analog scale (VAS) for pain. The clinical significance thresholds for these measures after arthroscopic posterior labral repair (aPLR), however, remain undefined. Purpose: We aimed to define the minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient acceptable symptomatic state (PASS) for the SANE, Rowe score, and ASES score as well as the VAS pain after aPLR. Additionally, we sought to determine preoperative factors predictive of reaching, as well as failing to reach, clinical significance. Study Design: Case-control study; Level of evidence, 3. Methods: This study was a retrospective analysis of patient-reported outcome scores collected from patients who underwent aPLR between January 2011 and December 2018. To determine the clinically significant threshold that corresponded to achieving a meaningful outcome, the MCID, SCB, and PASS were calculated for the SANE, Rowe score, ASES score, and VAS pain utilizing either an anchor- or distribution-based method. Additionally, univariate and multivariate logistic regression analyses were performed to determine the factors associated with achieving, or not achieving, the MCID, SCB, and PASS. Results: A total of 73 patients with a mean follow-up of 82.55 ± 24.20 months were available for final analysis. MCID, SCB, and PASS values for the VAS pain were 1.10, 6, and 3, respectively; for the ASES score were 7.8, 34, and 80, respectively; for the SANE were 10.15, 33, and 85, respectively; and for the Rowe score were 11.3, 60, and 90, respectively. To meet the MCID, male sex (odds ratio [OR], 1.1639; P =.0293) was found to be a positive predictor for the VAS pain, and a lower preoperative SANE score (OR, 0.9939; P =.0003) was found to be a negative predictor for the SANE. Dominant arm involvement was associated with lower odds of achieving the PASS for the ASES score (OR, 0.7834; P =.0259) and VAS pain (OR, 0.7887; P =.0436). Patients who reported a history of shoulder trauma were more likely to reach the PASS for the SANE (OR, 1.3501; P =.0089), Rowe score (OR, 1.3938; P =.0052), and VAS pain (OR, 1.3507; P =.0104) as well as the SCB for the ASES score (OR, 1.2642; P =.0469) and SANE (OR, 1.2554; P =.0444). A higher preoperative VAS pain score was associated with higher odds of achieving the SCB for both the VAS pain (OR, 1.1653; P =.0110) and Rowe score (OR, 1.1282; P =.0175). Lastly, concomitant biceps tenodesis was associated with greater odds of achieving the SCB for the ASES score (OR, 1.3490; P =.0130) and reaching the PASS for the SANE (OR, 1.3825; P =.0038) and Rowe score (OR, 1.4040; P =.0035). Conclusion: To our knowledge, this study is the first to define the MCID, SCB, and PASS for the ASES score, Rowe score, SANE, and VAS pain in patients undergoing aPLR. Furthermore, we found that patients who reported a history of shoulder trauma and those who underwent concomitant biceps tenodesis demonstrated a greater likelihood of achieving clinical significance. Dominant arm involvement was associated with lower odds of achieving clinical significance. [ABSTRACT FROM AUTHOR]

This paper examines the application of super-superiority margins in study power calculations. Unlike traditional power calculations, which primarily aim to reject the null hypothesis by any margin, a super-superiority margin establishes a clinically significant threshold. Despite potential benefits, this approach, akin to a non-inferiority calculation but in an opposing direction, is rarely used. Implementing a super-superiority margin separates the notion of the likely difference between two groups (the effect size) from the minimum clinically significant difference, without which inconsistent positions could be held. However, these are often used interchangeably. In an audit of 30 recent randomized controlled trial power calculations, four studies utilized the minimal acceptable difference, and nine utilized the expected difference. In the other studies, this was unclarified. In the post hoc scenario, this approach can shed light on the value of undertaking further studies, which is not apparent from the standard power calculation. The acceptance and rejection of the alternate hypothesis for super-superiority, non-inferiority, equivalence, and standard superiority studies have been compared. When a fixed minimal acceptable difference is applied, a study result will be in one of seven logical positions with regards to the simultaneous application of these hypotheses. The trend for increased trial size and the mirror approach of non-inferiority studies implies that newer interventions may be becoming less effective. Powering for superiority could counter this and ensure that a pre-trial evaluation of clinical significance has taken place, which is necessary to con- firm that interventions are beneficial. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a global health concern, being a leading cause of cancer-related mortality among males. Early detection and accurate prognosis are crucial for effective management. This study delves into the diagnostic and prognostic potential of 28S rRNA-derived fragments (rRFs) in PCa. Total RNA extracted from 89 PCa and 53 benign prostate hyperplasia (BPH) tissue specimens. After 3'-end polyadenylation, we performed reverse transcription to create first-strand cDNA. Using an in-house quantitative real-time PCR (qPCR) assay, we quantified 28S rRF levels. Post-treatment biochemical relapse served as the clinical endpoint event for survival analysis, which we validated internally through bootstrap analysis. Our results revealed downregulated 28S rRF levels in PCa compared to BPH patients. Additionally, we observed a significant positive correlation between 28S rRF levels and higher Gleason scores and tumor stages. Furthermore, PCa patients with elevated 28S rRF expression had a significantly higher risk of post-treatment disease relapse independently of clinicopathological data. In conclusion, our study demonstrates, for the first time, the prognostic value of 28S rRF in prostate adenocarcinoma. Elevated 28S rRF levels independently predict short-term PCa relapse and enhance risk stratification. This establishes 28S rRF as a potential novel molecular marker for PCa prognosis. [ABSTRACT FROM AUTHOR]

We will first have an historical survey of cognitive impairment in schizophrenia, with special reference to Emil Kraepelin and Eugen Bleuler. We will then consider the types of cognitive schizophrenia-wise deficits, the assessment of cognitive impairment, the clinical significance of cognitive impairment, the neurocognitive predictors of functionality, psychopharmacology and cognitive function. We will finally state that partial compliance is the main cause of high dropout rates. [ABSTRACT FROM AUTHOR]

Objective: This study aims to analyze the clinical significance and mechanism of nuclear factor erythroid 2-related factor 2 (NRF2) and glutathione peroxidase 4 (GPX4) in primary hepatic carcinoma (PHC). Methods: The expression of NRF2 and GPX4 in peripheral blood of patients with PHC was determined to analyze the diagnostic value of the two combined for PHC. The prognostic significance of NRF2 and GPX4 was evaluated by 3-year followup. Human liver epithelial cells THLE-2 and human hepatocellular carcinoma cells HepG2 were purchased, and the expression of NRF2 and GPX4 in the cells was determined. NRF2 and GPX4 aberrant expression vectors were constructed and transfected into HepG2, and changes in cell proliferation and invasion capabilities were observed. Results: The expression of NRF2 and GPX4 in patients with PHC was higher than that in patients with LC or VH (p < 0.05), and the two indicators combined was excellent in diagnosing PHC. Moreover, patients with high expression of NRF2 and GPX4 had a higher risk of death (p < 0.05). In in vitro experiments, both NRF2 and GPX4 expression was elevated in HepG2 (p < 0.05). HepG2 activity was enhanced by increasing the expression of the two, vice versa (p < 0.05). Conclusion: NRF2 and GPX4 combined is excellent in diagnosing PHC, and promotes the malignant development of PHC. [ABSTRACT FROM AUTHOR]

Aim To find out if weight loss nutraceuticals can result in clinically significant weight loss. Methods Bibliographic databases such as MEDLINE, Embase, the Cochrane Library and Web of Science, reference lists of eligible studies and review articles and conference proceedings were searched for randomised clinical trials of nutraceuticals for weight loss. Studies not meeting our eligibility criteria were discarded. A mean difference of 5% between-group weight loss was considered clinically significant. PROSPERO protocol identifier: CRD42021238650 Results We found that out of 196 sources of nutraceutical products, Portulaca oleracea, Garcinia cambogia, green tea, carnitine, Irvingia, pyruvate, chitosan, chromium, Gymnema sylvestre, turmeric and conjugated linoleic acid supplements had at least one reported clinical significance. None of them were consistent in showing this result and none had a meta-analysis to approve their clinical significance. Conclusion Current randomised trials and meta-analyses studying single sourced weight loss nutraceuticals don't strongly support their use for weight loss. P. oleracea, G. cambogia, green tea, carnitine, Irvingia, pyruvate, chitosan, chromium, G. sylvestre, turmeric and conjugated linoleic acid should further be studied to identify and develop potent bioactive agents which may result in better clinical results. [ABSTRACT FROM AUTHOR]

Objective. This study aimed to investigate the associations between osteoporosis, biochemical indexes, bone mineral density (BMD), and cardiovascular disease. Methods. A cross-sectional study design was used to examine the relationships between these parameters. Logistic regression and correlation analyses were conducted to assess the associations between elevated levels of triglyceride, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), homocysteine, and the presence of osteoporosis. Additionally, correlations betweenBMDand biochemical indexes were analyzed. The incidence of cardiovascular disease and its correlation with BMD were evaluated. Receiver operating characteristic (ROC) analysis was performed to determine the utility of BMD in identifying cardiovascular disease. Results. The results revealed that elevated triglyceride, total cholesterol, and LDL levels were positively associated with osteoporosis, while higher HDL levels and homocysteine were negatively associated. Correlation analysis demonstrated negative correlations between triglyceride levels and BMD, and positive correlations between total cholesterol and HDL levels with BMD. LDL levels showed a weak negative correlation, and homocysteine levels exhibited a strong negative correlation with BMD. The osteoporosis group had lowerBMDand a higher incidence of cardiovascular disease compared to the non-osteoporosis group. Logistic regression analysis confirmed the correlation between lower BMD and increased risk of cardiovascular disease. Conclusion. This study provides evidence supporting the associations between osteoporosis, biochemical indexes, BMD, and cardiovascular disease. Aberrations in lipid profiles and homocysteine levels may contribute to osteoporosis development. Lower BMD, particularly in individuals with osteoporosis, appears to increase the risk of cardiovascular disease. BMD shows promise as a diagnostic tool for identifying individuals at risk of cardiovascular disease. Further research is needed to elucidate the underlying mechanisms and establish the clinical implications of these relationships. Future longitudinal studies are necessary to determine causality and long-term prognostic implications. [ABSTRACT FROM AUTHOR]