Clinical Significance Research Articles

The epigenetic determinants for systemic juvenile idiopathic arthritis phenotyping and treatment response

BackgroundDetermining the role of epigenetics in systemic juvenile idiopathic arthritis (SJIA) provides an opportunity to explore previously unrecognized disease pathways and new therapeutic targets.AimWe aimed to identify the clinical significance of microRNAs (miRNA-26a, miRNA-223) in SJIA.Materials and methodsThis cross-sectional study was conducted on a group of children with SJIA attending to pediatric rheumatology clinic, at Mansoura University Children’s Hospital (MUCH) from December 2021 to November 2022. Patient demographics, and clinical, and laboratory data were collected with the measurement of microRNAs by quantitative real-time PCR. The Mann–Whitney, Kruskal–Wallis, and Spearman correlation tests were used for variable comparison and correlations, besides the receiver operating characteristic (ROC) curve for microRNAs disease activity and treatment non-response discrimination.ResultsForty patients were included in the study. On comparison of miRNA-26a, and miRNA-223 levels to the clinical, assessment measures, and laboratory features, miRNA-26a was statistically higher in cases with systemic manifestations versus those without. Similarly, it was higher in children who did not fulfill the Wallace criteria for inactive disease and the American College of Rheumatology (ACR) 70 criteria for treatment response. Meanwhile, miRNA-223 was not statistically different between cases regarding the studied parameters. The best cut-off value for systemic juvenile arthritis disease activity score-10 (sJADAS-10) and the ability of miRNA-26a, and miRNA-223 to discriminate disease activity and treatment non-response were determined by the (ROC) curve.ConclusionThe significant association of miRNA-26a with SJIA features points out that this molecule may be preferentially assessed in SJIA disease activity and treatment non-response discrimination.

Morphological Measurement and Clinical Significance of Abnormal Development of Distal Femur with Hemophilia Knee Arthritis: A Consideration on the Renewal of Total Knee Prosthesis.

The knee joint of hemophiliacs may face the result of local morphological changes due to long-term irritation of synovitis. This study aims to elucidate the morphological characteristics of distal femur in hemophilic arthritis (HA) and compare the compatibility of three types of prostheses with the anteroposterior (AP) and mediolateral (ML) dimensions of the femoral osteotomy surface. This study retrospectively and randomly selected 50 patients with HA registered for treatment at our hospital from June 2016 to August 2022 as the study subjects, with an equal number of male osteoarthritis (OA) patients and healthy male individuals set as the control group. This study used medical digitalization software to simulate osteotomies on the distal femur during total knee arthroplasties (TKA) for 50 patients with HA, OA patients, and the healthy population, respectively, and measure the morphological parameters to compare with three commonly used femoral components of TKA in clinical practice. The differences between the femur resection of anteroposterior and mediolateral (FRAP, FRML) osteotomy surface and the prosthesis's BOX-AP/ML were compared in three prostheses. One-way ANOVA and multiple Kruskal-Wallis H test were used for the normal or non-normal distribution data, and pairwise comparisons between groups were conducted using the Bonferroni method, and the linear correlation analysis was utilized to assess the relationship between section femoral morphological data and prosthesis parameters. In HA patients, the morphological characteristics of the distal femur were shown as shorter than femur AP (FAP), medial and lateral condyle anterior-posterior dimension (FMCAP, FLCAP), notch width (NW), posterolateral condyle height (PLCH), posteromedial condyle width (PMCW), and posterior condylar axis length (PCAL) dimension. They had comparatively smaller femur section aspect ratios (p < 0.005). They showed longer posterolateral condyle width (PLCW), anterior condyle mediolateral dimension (FRACML), anterolateral condyle height (ALCH), and femur resection anterior condylar mediolateral (FRACML) dimension (p < 0.005). They showed larger distal femur aspect ratio and resection aspect ratio (FAR, FRAR, p < 0.005). All selected prostheses showed ML undercoverage under similar AP dimensions, and ML undersizing of Attune systems was more obvious in three femoral prostheses. The distal femur morphological change of HA patient is shown as smaller AP dimension, narrow posterior condyle spacing, lower and shallower trochlear, thinner anterior condyle, wider and lower intercondylar notch and higher posterior-lateral condyle. The selected prostheses showed ML undercoverage under similar AP dimensions. This typical morphological tendency of the distal femur seems to warrant consideration in the process of knee joint prosthesis upgrading.

Clinical Significance of Hyperhomocysteinemia in Free Flap Failure: A Case Report

AbstractFailure of a microvascular free flap remains rare, yet multiple failures can occur, particularly in the presence of hypercoagulable conditions. This case series highlights our experience with a rare hypercoagulable state: hyperhomocysteinemia.We present two cases of patients with hyperhomocysteinemia in this report. High-dose heparinization was administered to both patients, resulting in successful salvage of one flap and failure of the other. Notably, one patient had a history of prior free flap failures. However, after correcting hyperhomocysteinemia, subsequent free flaps were successful.In cases of detected complications, a coagulability study is warranted, and adjustments to anticoagulation treatment may be necessary. Furthermore, when a history of flap failures is evident, screening for hyperhomocysteinemia may be warranted, with correction made prior to reconstruction.

The clinical significance of endoplasmic reticulum stress related genes in non-small cell lung cancer and analysis of single nucleotide polymorphism for CAV1

In recent years, protein homeostasis imbalance caused by endoplasmic reticulum stress has become a major hallmark of cancer. Studies have shown that endoplasmic reticulum stress is closely related to the occurrence, development, and drug resistance of non-small cell lung cancer, however, the role of various endoplasmic reticulum stress-related genes in non-small cell lung cancer is still unclear. In this study, we established an endoplasmic reticulum stress scores based on the Cancer Genome Atlas for non-small cell lung cancer to reflect patient features and predict prognosis. Survival analysis showed significant differences in overall survival among non-small cell lung cancer patients with different endoplasmic reticulum stress scores. In addition, endoplasmic reticulum stress scores was significantly correlated with the clinical features of non-small cell lung cancer patients, and can be served as an independent prognostic indicator. A nomogram based on endoplasmic reticulum stress scores indicated a certain clinical net benefit, while ssGSEA analysis demonstrated that there was a certain immunosuppressive microenvironment in high endoplasmic reticulum stress scores. Gene Set Enrichment Analysis showed that scores was associated with cancer pathways and metabolism. Finally, weighted gene co-expression network analysis displayed that CAV1 was closely related to the occurrence of non-small cell lung cancer. Therefore, in order to further analyze the role of this gene, Chinese non-smoking females were selected as the research subjects to investigate the relationship between CAV1 rs3779514 and susceptibility and prognosis of non-small cell lung cancer. The results showed that the mutation of rs3779514 significantly reduced the risk of non-small cell lung cancer in Chinese non-smoking females, but no prognostic effect was found. In summary, we proposed an endoplasmic reticulum stress scores, which was an independent prognostic factor and indicated immune characteristics in the microenvironment of non-small cell lung cancer. We also validated the relationship between single nucleotide polymorphism locus of core genes and susceptibility to non-small cell lung cancer.

Effects of E-Cigarettes on the Lung and Systemic Metabolome in People with HIV

The popularity of e-cigarettes (vaping) has soared, creating a public health crisis among teens and young adults. Chronic vaping can induce gut inflammation and reduce intestinal barrier function through the production of the proinflammatory molecule hydrogen sulfide (H2S). This is particularly concerning for people with HIV (PWH) as they already face impaired immune function and are at a higher risk for metabolic dysregulation, diabetes, and chronic liver disease. Furthermore, PWH experience unhealthy behaviors, making it crucial to understand the systemic metabolic dysregulation and pathophysiological mechanisms associated with vaping in this population. Here, we employed liquid chromatography–mass spectrometry (LC-MS)-based metabolomics to investigate the upper respiratory, circulation, and gut metabolic profiles of PWH who vape (n = 7) and smoke combustible tobacco/marijuana (n = 6) compared to control participants who did not vape or smoke (n = 10). This hypothesis-generating exploratory study revealed systemic alterations in purine, neurotransmitter, and vitamin B metabolisms and tissue-specific changes in inflammatory pathways and cryptic sulfur cycling associated with vaping and combustible tobacco/marijuana smoking in PWH. In addition, this study provides the first link between microbial-derived metabolite 2,3-dihydroxypropane-1-sulfonate (DHPS) and vaping/smoking (tobacco and marijuana)-induced metabolic dyshomeostasis in the gut. These findings highlight the importance of identifying the full biological and clinical significance of the physiological changes and risks associated with vaping.

A European Consensus on the Consistent Use of the Term "Keratinocyte Cancer".

Keratinocyte-derived skin cancers comprise basal cell carcinoma, squamous cell carcinoma, its precursor actinic keratosis, and Bowen's disease. Historically, this group of neoplasms has been subsumed under the term non-melanoma skin cancer. However, the term non-melanoma skin cancer can be misleading and lacks precision. Therefore, more precise and reasonable terminology, valuing the relevance of keratinocyte-derived cancer, appears pertinent to meet its clinical and scientific significance. A group of experienced dermato-oncologists initiated a consensus approach to promote the use of the term "keratinocyte cancer" instead of "non-melanoma skin cancer" when referring to carcinomas and their precursors that are derived from keratinocytes. The vote among members of the consensus group indicated unanimous agreement on the consistent use of the term "keratinocyte cancer" instead of "non-melanoma skin cancer". International delegates also voted in favour of the revised terminology. The more precise and, by means of etiopathogenesis, correct term "keratinocyte cancer" should be consistently used for malignancies originated from keratinocytes. This is expected to have a positive impact on patient-physician communication and gives better justice to this important group of keratinocyte-derived cancers.

The clinical meaning and significance of OVEMP morphology.

While some OVEMP recordings are morphologically straightforward, some are poor in appearance, which can create a challenge, as they often require a "second look" by another experienced assessor. Even OVEMPs in normal subjects are sometimes poorly formed, but we wondered if the morphological assessment of the OVEMP response might provide some additional diagnostic information. A single experienced assessor evaluated the OVEMP recordings of 60 patients referred sequentially to a tertiary care centre, and categorized them as "easy to assess" (i.e. obvious to a minimally trained assessor) or "difficult to assess", often requiring a second look by another experienced assessor. In 48 patients, the results were easy to assess (regardless of the actual clinical results) while 12 were classified as "difficult". This figure reflected the rate of morphologically poor responses we found in our population of normative data. Our clinical concern is that many centres have given up relying on OVEMP assessment because the morphology of the wave may be challenging to interpret. OVEMP assessment often calls for a "second look", requiring a collaboration between two experienced assessors. It seems that this feature may not be diagnostically useful and poor OVEMP morphology may present a challenge in interpretation, but this should not be used as a reason to defer OVEMP testing.

12 Concordance Analysis of Tissue and Circulating Tumor DNA (ctDNA) in Renal Cell Carcinoma (RCC): Insights from a Multimodal Real-World Database

Abstract Background Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) has emerged as a powerful complement to tissue NGS, offering a noninvasive and serially conductible test. Its application holds promise in enhancing the assessment of spatial and temporal molecular tumor heterogeneity, thus providing valuable insights into cancer progression and treatment response. In this study, we explore the mutational landscape of renal cell carcinoma (RCC) patients through comprehensive profiling of mutations in ctDNA and matched tissue samples, aiming to elucidate the concordance and clinical significance of molecular alterations detected in both circulating and tissue-derived DNA. Methods From the Tempus multimodal database, we retrospectively analyzed de-identified NGS data from patients with RCC that had dual tissue (Tempus xT, 648 genes) and ctDNA testing (Tempus xF, 105 genes). Patients with matched samples (collected +/- 90 days of one another) were included. We evaluated socio-demographic and clinical characteristics and select pathogenic somatic short variants (PSSV) and copy number variants [(amplifications and deletions, two copy number losses (CNL)]. Concordance analyses were restricted to the 105 genes tested on the ctDNA panel and further restricted to short variants, with the exception of amplifications and CNL detected by both xF and xT. Analysis was further stratified by metastatic status (n=260, metastatic, n=120 non-metastatic) prior to collection of both xT and xF. Results Among all patients (n=393), the median age was 61 years, and 71% were male. The patient cohort comprised a diverse population based on race, with 75% white, 12% African American, 4.8% Asian and 8% others. The median time from tissue to blood collection was 21 days (IQR, 7, 39). 67% (n=265) and 68% (n=266) had metastatic disease at the time of tissue and blood collection, respectively. The most common tissue sites were kidney (49%, n=189), bone (11%, n=43), lung (9%, n=34), lymph node (8%, n=29), liver (6%, n=23), and brain/CNS (4%, n=17). Genes harboring the most common PSSV in tissue included VHL (59% n=232), PBRM1 (31%, n=123), SETD2 (23%, n=91), TP53 (14%, n=54), BAP1 (12%, n=46) and TERT (11%, n=45). Genes with common PSSV in ctDNA included TP53 (23%, n=91), VHL (18%, n=69), BAP1 (6%, n=23), PBRM1 (5%, n=21), PTEN (4%, n=15), KRAS (4%, n=14) and NF2 (4%, n=14). The combination of tissue and ctDNA testing increased the detection of mutations (Table 1). There was higher concordance between somatic alterations in select genes among patients with metastases vs. non-metastases, including BAP1 (55.9% vs. 9.1%), TP53 (36.8% vs. 9.1%), VHL (32.3% vs. 12.5%), ARID1A (25% vs. 16.7%), and ATM (25% vs. 0%). Table 1: Detection of genetic mutations in tissue and ctDNA testing Conclusions The analysis conducted in this study highlights the complementary nature of ctDNA profiling alongside tissue-based NGS in RCC, demonstrating an increased detection of mutations. Particularly, we observed a higher concordance between ctDNA and tissue profiling in individuals with metastatic disease, suggesting the potential utility of ctDNA analysis in advanced stages of RCC. Further research is warranted to elucidate how longitudinal ctDNA analysis can delineate biomarkers of response and resistance at both the mutation and ctDNA fraction levels. Understanding these dynamics could offer valuable insights into disease progression and guide personalized treatment strategies for RCC patients. DOD CDMRP Funding: no

Compliance with Headgear Evaluated by Force- and Temperature-Sensitive Monitoring Device: A Case-Control Study

The aim was to objectively assess compliance in patients prescribed headgear and evaluate the impact of monitoring awareness, treatment duration, gender, and age on compliance levels. A total of 22 patients with Class II malocclusion wore the headgear integrated with the force and temperature sensitive Smartgear monitoring system (Smartgear, Swissorthodontics AG, Cham, Switzerland). Patients were instructed to wear the headgear for 13 h daily over a 3-month period. Randomly, 11 patients were informed that they monitored and 11 were not informed. Data were organized using Microsoft Excel and analyzed using R for statistical estimates, graphs, and hypothesis testing. Smartgear recorded an average daily compliance of 6.7 h. No statistically significant differences were found in cooperation between study group and control group over the 3 months of treatment, regardless of gender and age. However, there was slight greater cooperation in the first month than in the other months, and patients ≤10 years of age had almost 2 h more cooperation than their older counterparts. Moreover, the informed group exhibited an average of 1.1 more hours of cooperation per day than the uninformed group, which may carry clinical significance. This cooperation primarily occurred at night and was found to be statistically significant. Compliance among young patients typically remained lower than the prescribed level, regardless of their gender and psychological maturity. Although an awareness of monitoring does not seem to improve compliance, implementing such systems could still offer dentists a valuable means of obtaining objective information about their patients’ adherence.

Serum Levels and Clinical Significance of NSE, BDNF and CNTF in Patients with Cancer-associated Ischemic Stroke Complicated with Post-stroke Depression

Background: The incidence of post-stroke depression (PSD) may be higher in patients with cancer-associated ischemic stroke (CAIS). The pathogenesis of PSD is mainly related to the emotional injury of stroke and the inability of neurons to effectively repair. This study aims to explore the clinical significance of serum neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) expression levels in CAIS patients. Methods: Clinical data of 106 patients with CAIS admitted to Jinhua Guangfu Oncology Hospital from January 2012 to December 2022 were retrospectively analyzed. Serum levels of NSE, BDNF and CNTF were measured in all patients after admission. Depression screening was performed by Hamilton Depression Scale-17 (HAMD-17) three months after intravenous thrombolysis. Patients with HAMD-17 score &gt;7 were included in the PSD group (n = 44), and patients with HAMD-17 score ≤7 were included in the non-PSD group (n = 62). The general data and serum levels of NSE, BDNF and CNTF were compared between the two groups. According to HAMD-17 scores, patients in PSD group were further divided into mild depression group (8–16 points), moderate depression group (17–23 points) and severe depression group (≥24 points), and the serum levels of NSE, BDNF and CNTF were compared among the three groups. Pearson's correlation test was used to analyze the correlation between HAMD-17 scores and serum NSE, BDNF and CNTF levels in PSD patients. Logistic regression model was used to determine the influencing factors of PSD in CAIS patients. Receiver operating characteristic (ROC) curve was plotted to analyze the predictive efficacy of serum NSE, BDNF, CNTF and their combination on PSD. Results: Among 106 CAIS patients, the incidence of PSD was 41.51% (44 cases), including 19 patients with mild PSD (43.18%), 14 patients with moderate PSD (31.82%), and 11 patients with severe PSD (25.00%). There were statistically significant differences in negative life events and complications after thrombolytic therapy between PSD and non-PSD patients (p &lt; 0.05). The serum NSE level in PSD group was significantly higher than that in non-PSD group, and the serum BDNF and CNTF levels were notably lower than those in non-PSD group (all p &lt; 0.001). The serum levels of NSE, BDNF and CNTF in patients with different severity of PSD were statistically significant (all p &lt; 0.001). HAMD-17 scores in PSD patients were positively correlated with serum NSE levels (r = 0.676, p &lt; 0.001) and negatively correlated with serum BDNF and CNTF levels (r = –0.661, p &lt; 0.001; r = –0.401, p = 0.007, respectively). By binary logistic regression analysis, the levels of serum NSE, BDNF and CNTF were independent influencing factors for PSD in CAIS patients, among which NSE was a risk factor (odds ratio (OR) &gt;1, p &lt; 0.05), BDNF and CNTF were protective factors (OR &lt;1, p &lt; 0.05). Conclusion: This study reveals for the first time that the levels of serum NSE, BDNF and CNTF are closely related to the occurrence and development of PSD in CAIS patients. In clinical CAIS patients with abnormal changes in the above indicators, in addition to anti-tumor treatment and improvement of neurological deficit symptoms, attention should also be paid to the symptoms of psychological disorders.

Non-random distribution of Plasmodium Species infections and associated clinical features in children in the lake Victoria region, Kenya, 2012–2018

BackgroundWhile Plasmodium falciparum (Pf) stands out as the most lethal malaria parasite species in humans, the impact of other species should not be dismissed. Moreover, there is a notable lack of understanding of mixed-species infections and their clinical implications.MethodsWe conducted eight school-based cross-sectional malariometric surveys in the Lake Victoria region of western Kenya between January–February 2012 and September–October 2018. In each survey, a minimum of 100 children aged 3 to 15 years were randomly chosen from a school in Ungoye village on the mainland and as well as from each school selected in every catchment area on Mfangano island. Plasmodium infection was determined by microscopy and nested polymerase chain reaction (PCR). The multiple-kind lottery (MKL) model calculated the expected distribution of Plasmodium infections in the population and compared it to observed values using a chi-squared test (χ2).ResultsThe Plasmodium prevalence was 25.9% (2521/9724) by microscopy and 51.1% (4969/9724) by PCR. Among all infections detected by PCR, Pf, P. malariae (Pm), and P. ovale (Po) mono-infections were 58.6%, 3.1%, and 1.8%, respectively. Pf/Pm, Pf/Po, Pm/Po, and Pf/Pm/Po co-infections were 23.5%, 4.3%, 0.1%, and 8.6%, respectively. MKL modelling revealed non-random distributions, with frequencies of Pf/Pm and Pf/Pm/Po co-infections being significantly higher than expected (χ2 = 3385.60, p < 0.001). Pf co-infections with Pm and Po were associated with a decreased risk of fever (aOR 0.64, 95% CI 0.46–0.83; p = 0.01) and increased risks of splenomegaly (aOR 12.79, 95% CI 9.69–16.9; p < 0.001) and anaemia (aOR 2.57, 95% CI 2.09–3.15; p < 0.001), compared to single-species infections.ConclusionThis study sheds light on the potential interaction between Pf and Pm and/or Po. Given the clinical significance of mixed-species infections, improved diagnostics, and case management of Pm and Po are urgently needed.

ASO Visual Abstract: Clinical Significance of SIRPα Expression on Tumor-Associated Macrophages in Patients with Lung Squamous Cell Carcinoma.

ASO Visual Abstract: Clinical Significance of SIRPα Expression on Tumor-Associated Macrophages in Patients with Lung Squamous Cell Carcinoma.

Biomechanical Comparison of Three Locking Compression Plate Constructs from Three Manufacturers under Cyclic Torsional Loading in a Fracture Gap Model.

The aim of the study was to compare the stiffness and cyclic fatigue of locking compression plate constructs from three manufacturers, DePuy Synthes (DPS), Knight Benedikt (KB), and Provet Veterinary Instrumentation (Vi), under cyclic torsion. The constructs of DPS, KB, and Vi were assembled by fixing a 10-hole 3.5-mm stainless steel locking compression plate 1 mm away from a validated bone model with a fracture gap of 47 mm. The corresponding drill guides and locking screws were used. Three groups of six constructs were tested in cyclic torsion until failure. There was no significant difference in initial stiffness between DPS constructs (28.83 ± 0.84 N·m/rad) and KB constructs (28.38 ± 0.81 N·m/rad), and between KB constructs and Vi constructs (27.48 ± 0.37 N·m/rad), but the DPS constructs were significantly stiffer than the Vi constructs. The DPS constructs sustained the significantly highest number of cycles (24,833 ± 2,317 cycles) compared with KB constructs (16,167 ± 1,472 cycles) and Vi constructs (19,833 ± 4,792 cycles), but the difference between KB and Vi constructs was not significant. All constructs failed by screw damage at the shaft between the plate and the bone model. DPS constructs showed superior initial torsional stiffness and cyclic fatigue life than Vi constructs, whereas KB and Vi constructs shared comparable results. Further investigation is required to assess the clinical significance of these biomechanical differences.

Adult-Onset Case of Female Idiopathic Hypogonadotropic Hypogonadism and Ataxia: Genetic Background

Adult-onset cases of idiopathic hypogonadotropic hypogonadism (IHH) are characterized by partial or normal puberty development until adolescence and by the impairment of the hypothalamic–pituitary–gonadal (HPG) axis in adulthood. WDR11 and DCC genes are known to be involved in axonal development, particularly of hypothalamic GnRH neurons, and ciliogenesis. We report a female case of adult-onset hypogonadism and cerebellar ataxia, in which we identified two gene mutations. A panel of 48 genes was set up to search for variants in the causative genes of CHH. The variants found were analyzed following the American College of Medical Genetics and Genomics (ACMG) criteria to define their pathogenicity. We identified a missense heterozygous variant in the WDR11 gene NM_018117.12:c.2306T&gt;G (p.Met769Arg) and a mutation in a second gene DCC resulting in amino acid substitutions NM_005215.4:c.3533C&gt;T (p.Ser1178Phe). These variants were classified as being of uncertain clinical significance. We assume that there is a link between the variants found and the impairment of the gonadotrophic and neurological phenotype of the patient. Therefore, we propose the genetic test to identify the best therapeutic approach to identify infertility in female patients with IHH; we believe it is necessary to test WDR11 and DCC genes in larger populations with the same condition to introduce it in future protocols of assessment.

Assessing Relative Linguistic Impairment With Model-Based Item Selection.

A picture naming test is presented that reveals impairment to specific mechanisms involved in the naming process, using accuracy scores on curated item sets. A series of psychometric validation experiments are reported. Using a computational model that enables estimation of item difficulty at the lexical and sublexical stages of word retrieval, two complimentary sets of items were constructed that challenge the respective psycholinguistic levels of representation. The difference in accuracy between these item sets yields the relative linguistic impairment (RLI) score. In a cohort of 91 people with chronic left-hemisphere stroke who enrolled in a clinical trial for anomia, we assessed psychometric properties of the RLI score and then used the new scale to make predictions about other language behaviors, lesion distributions, and functional activation during naming. RLI scores had adequate psychometric properties for clinical significance. RLI scores contained predictive information about spontaneous speech fluency, over and above accuracy. A dissociation was observed between performance on the RLI item sets and performance on the subtests of an independent language battery. Sublexical RLI was significantly associated with apraxia of speech and with lesions encompassing perisylvian regions, while lexical RLI was associated with lesions to deep white matter. The RLI construct was reflected in functional brain activity during naming, independent of overall accuracy, with a respective shift of activation between dorsal and ventral networks responsible for different aspects of word retrieval. The RLI assessment satisfies the psychometric requirements to serve as a useful clinical measure.

The Search for Consistency in Residual Symptoms in Major Depressive Disorder: A Narrative Review

Residual symptoms are prevalent in major depressive disorder (MDD), encompassing a wide spectrum of symptoms such as sleep disturbances, changes in weight and appetite, cognitive impairment, and anxiety. These symptoms consistently impair daily functioning, diminish quality of life, and forecast disease relapse. Despite their clinical significance, residual symptoms lack a unified definition, potentially leading to confusion with treatment-emergent symptoms and ambiguity across studies, thereby hindering the generalizability of research findings. While some research identifies insomnia and mood disturbances as critical indicators, other studies emphasize different symptoms or find no significant correlation. Inconsistencies in defining residual symptoms, as well as methodological differences across studies, contribute to these conflicting results. While clinicians focus on alleviating negative symptoms to improve functional status, patients often prioritize achieving positive affect and overall well-being as essential components of successful treatment. It necessitates a comprehensive approach to patient care in depression. This review explores the phenomenon of residual symptoms in MDD, focusing on the ambiguity in definitions, clinical characteristics, and their impact on long-term outcomes. The lack of a standardized regulatory or academic definition for residual symptoms leads to varied interpretations among clinicians, underscoring the need for standardized terminology to guide effective treatment strategies and future research.

Comprehensive analysis of CXCL10 and MIP-3a reveals their potential clinical application in hepatocellular carcinoma

Chemokines play a crucial role in the pathogenesis of patients with hepatocellular carcinoma (HCC). The expression levels of interferon-γ-induced protein-10 (CXCL10) and macrophage inflammatory protein-3α (MIP-3a) were investigated to clarify their clinical significance in HCC.The protein levels of CXCL10 and MIP-3a in the serum of 105 HBV-associated HCC patients, 50 patients with liver cirrhosis (LC), 50 patients with chronic hepatitis B (CHB) and 50 healthy donors (HC) were detected by liquid chip technology (Luminex) or ELISA. In addition, their mRNA levels were also determined in liver cancer and adjacent cancer tissue (paracancer; ParaCa) from 65 HCC patients. The online database UALCAN was used to analyze the association between CXCL10 and pathological manifestations of liver cancer. In addition, the diagnostic value of CXCL10/MIP-3a and AFP in HCC patients was determined by analyzing the Receiver Operating Characteristic Curve (ROC).The protein concentrations of CXCL10 and MIP-3a were significantly higher in the HCC group than in the LC, CHB and HC groups. CXCL10 in sera and liver cancer tissues is significantly positively correlated with ALT, but no significance between CXCL10 in ParaCa tissues and sera-ALT. Their mRNA is significantly higher in cancer tissues than in ParaCa tissues. The areas under the ROC curve of CXCL10, MIP-3a, CXCL10 and MIP-3a combined and AFP were 0.9169, 0.9261, 0.9299 and 0.7880, respectively. Elevated chemokines CXCL10 and MIP-3a in HCC patients may be associated with the clinical manifestation of HCC and could be a potential molecular marker for prognostic evaluation or a therapeutic target for HCC.

The clinical value of noninvasive left ventricular myocardial work in the diagnosis of myocardial ischemia in coronary heart disease: a comparative study with coronary flow reserve fraction.

The prompt and precise identification of hemodynamically significant coronary artery lesions remains an ongoing challenge. This study investigated the diagnostic value of non-invasive global left ventricular myocardial work indices by echocardiography in functional status of coronary artery disease (CAD) patients with myocardial ischemia using fractional flow reserve (FFR) as the gold standard. A total of 77 consecutive patients with clinically suspected CAD were prospectively enrolled. All participants sequentially underwent echocardiography, invasive coronary angiography (ICA) and FFR measurement. According to the results of ICA, patients were divided into myocardial ischemia group (FFR ≤ 0.8, n = 27) and non-myocardial ischemia group (FFR > 0.8, n = 50). Myocardial work indices including global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), global positive work (GPW), global negative work (GNW), global systolic constructive work (GSCW) and global systolic wasted work (GSWW) were obtained by using the non-invasive left ventricular pressure strain loop (PSL) technique. Compared with the non-myocardial ischemia group, GWI, GCW, GPW and GSCW were significantly decreased in the myocardial ischemia group at either the 18-segment level or the 12-segment level (P < 0.001). At the 18-segment level, GWI < 1783.6 mmHg%, GCW < 1945.4 mmHg%, GPW < 1788.7 mmHg% and GSCW < 1916.5 mmHg% were optimal cut-off value to detect myocardial ischemia with an FFR ≤ 0.8. Global left ventricular myocardial work indices by echocardiography exhibited a good diagnostic value in patients with CAD and may have a good clinical significance for the screening of suspected myocardial ischemia.

Expression Levels and Clinical Significance of WEE1 and mTOR in Triple-Negative Breast Cancer

Expression Levels and Clinical Significance of WEE1 and mTOR in Triple-Negative Breast Cancer

A comprehensive morphometric analysis of superior and inferior mesenteric arteries using cadaveric dissection and MDCT angiography

BackgroundSuperior mesenteric artery (SMA) and inferior mesenteric artery (IMA) are vital vascular structures supplying the majority of the intestinal tract. Despite their clinical significance, comprehensive morphometric studies combining traditional cadaveric dissection with modern imaging techniques are scarce in literature. This study aimed to provide a detailed morphometric analysis of the SMA and IMA using both cadaveric dissection and multi-detector computed tomography (MDCT) angiography. MethodsThe study utilized a dual approach, combining cadaveric dissection (30 formalin-fixed cadavers) and MDCT angiography (images from 50 patients). Measurements including stem lengths, diameters at origin, and distances from the aortic bifurcation were taken, along with assessment of vertebral levels of origin and branching patterns. Data from both components were analyzed using descriptive statistics. ResultsKey findings for SMA include: Mean stem length: 3.19 ± 0.72 cm (cadaveric) vs. 2.53 ± 0.53 cm (MDCT); Mean diameter at origin: 0.93 ± 0.22 cm (cadaveric) vs. 0.57 ± 0.10 cm (MDCT); Most common vertebral level of origin: Upper border of L1 (78 % of cases); Branching pattern variations observed in 23.3 % of cadaveric specimens, which included the origin of the inferior pancreaticoduodenal artery from the first jejunal artery, a common trunk for right colic and ileocolic arteries, and absence of middle colic artery. For IMA: Mean stem length: 3.61 ± 1.29 cm (cadaveric) vs. 3.41 ± 0.69 cm (MDCT); Mean diameter at origin: 0.50 ± 0.11 cm (cadaveric) vs. 0.26 ± 0.05 cm (MDCT); Most common vertebral level of origin: Upper border of L3 (40 % of cases). No variations observed in branching pattern. ConclusionsThe detailed measurements, frequency of variations, and comparison between traditional and modern assessment techniques offer a nuanced understanding of mesenteric vascular anatomy. This study bridges the gap between classical anatomical knowledge and contemporary imaging capabilities, potentially improving surgical planning, interventional procedures, and radiological interpretation.