Clinical Sample Of Patients Research Articles

TDO2 modulates liver cancer cell migration and invasion via the Wnt5a pathway.

Liver cancer is a malignant cancer phenotype for which there currently remains a lack of reliable biomarkers and therapeutic targets for disease management. Tryptophan 2,3‑dioxygenase(TDO2), a heme‑containing polyoxygenase enzyme, is primarily expressed in cells of the liver and nervous systems. In the present study, through the combination of cancer bioinformatics and analysis of clinical patient samples, it was shown that TDO2 expression in liver cancer tissue samples was significantly higher than that in normal tissues, and liver cancer patients with high TDO2 expression had a poor prognosis. Mechanistic studies on liver cancer cells showed that TDO2 promoted cancer cell migration and invasion via signal transduction through the Wnt5a pathway. Such regulation impacted the expression of cancer‑associated biomarkers, such as matrix metalloprotease 7 (MMP7) and the cell adhesion receptor CD44. Treatment with a calcium channel blocker (azelnidipine) reduced TDO2 levels and inhibited liver cancer cell migration and invasion. A mouse xenograft cancer model showed that TDO2 promoted tumorigenesis. Furthermore, azelnidipine treatment to downregulate TDO2 also decreased liver cancer development in this mouse cancer model. TDO2 is thus not only a useful liver cancer biomarker but a potential drug target for management of liver cancer.

The Effectiveness of Eye Movement Desensitization for Post-traumatic Stress Disorder in Indonesia: A Randomized Controlled Trial.

ObjectivePost-traumatic stress disorder (PTSD) may affect individuals exposed to adversity. Eye Movement Desensitization and Reprocessing (EMDR) is an evidence-based trauma-focused psychotherapy for PTSD. There is still some debate whether the eye movements (EMs) are an effective component of EMDR. The primary aim of this study was to investigate the effectiveness of Eye Movement Desensitization (EMD) treatment in reducing PTSD symptoms compared to a retrieval-only active control condition. We also investigated whether PTSD symptom reduction was associated with reductions in depression and anxiety, and improvements in quality of life.MethodologyAdult PTSD patients (n = 91) were recruited at public psychological services in Jakarta, Bandung and Cimahi, Indonesia. PTSD was diagnosed with the Structured Clinical Interview for DSM-5 disorders (SCID-5). Participants were randomized into: EMD (n = 47) or retrieval-only (n = 44). EMD consisted of clinical history and treatment planning, preparation, assessment, EMs, closure, whereas retrieval-only consisted of the same elements except EMs. Data were collected at baseline (T0), 1-week post-treatment (T1), 1-month follow-up (T2), and 3-months follow-up (T3). Outcome measures included the PTSD Checklist for DSM-5 (PCL-5), Hopkins Symptoms Checklist-25 (HSCL-25), and the World Health Organization Quality of Life–BREF (WHOQoL–BREF). Data were analyzed with linear mixed model analysis in R Statistics.ResultsAlthough there were main effects of time indicating reductions for both EMD and retrieval-only in PCL-5 and HSCL-25 scores, and improvements in WHOQoL-BREF scores at T1, T2, and T3, no significant differences in PCL-5, HSCL-25, and WHOQoL-BREF total scores between the EMD and retrieval-only groups at T1, T2, and T3 were found (all group x time interaction p’s > 0.005).ConclusionWithin a clinical sample of PTSD patients in Indonesia, both EMD and retrieval-only was associated with reductions in symptoms of PTSD, anxiety and depression, and improvements in quality of life, although EMs did not add to the efficacy of the treatments. Further research to examine the underlying mechanisms of EMDR’s effective treatment elements in clinical samples is needed.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [ISRCTN55239132].

Lifestyle Prescription for Depression with a Focus on Nature Exposure and Screen Time: A Narrative Review.

Recent lifestyles changes have favored increased time in contact with screens and a parallel reduction in contact with natural environments. There is growing awareness that nature exposure and screen time are related to depression. So far, the roles of how these environmental lifestyles affect depressive symptoms and disorders have not been reviewed simultaneously. The aim of this review was to gather the literature regarding the role of nature exposure and screen time in depression. An emphasis was made on clinical samples of patients with well-defined depression and the different methodological approaches used in the field. A second goal was to suggest an agenda for clinical practice and research. Studies were included if they assessed depressive symptoms in patients with a clinical diagnosis of depression. An overview of the published literature was conducted using three scientific databases up to December 2021. Several interventions involving nature exposure have shown positive effects on depressive symptoms and mood-related measures. The most consistent finding suggests that walks in natural environments may decrease depressive symptoms in patients with clinical depression. Less researched interventions, such as psychotherapy delivered in a forest or access to natural environments via virtual reality, may also be effective. In contrast, fewer observational studies and no experimental research on screen time have been conducted in patients with clinical depression. Thus, recommendations for practice and research are also discussed. Scarce research, diverse interventions, and several methodological shortcomings prevent us from drawing conclusions in this area. More high-quality experimental research is needed to establish interventions with proven efficacy in clinical depression. At this stage, it is too early to formulate practice guidelines and advise the prescription of these lifestyles to individuals with depression. The present findings may serve as a basis to develop strategies based on nature exposure and screen time targeting clinical depression.

Risk Factors for Ciprofloxacin and Gentamycin Resistance among Gram Positive and Gram Negative Bacteria Isolated from Community-Acquired Urinary Tract Infections in Benghazi City

Urinary tract infections (UTIs) are a severe public health problem caused by a range of pathogens. The aims of the study were to investigate the prevalence of urinary tract infection and to see the pattern of Ciprofloxacin and Gentamycin susceptibility against uropathogens in Benghazi city. The study took place between 2021 April and October 2021. In-vitro antibacterial activity and resistance patterns of these two well-known antibiotics were studied and compared using the disk diffusion method. Laboratory reports and clinical data of patients with a positive urine culture (≥105 CFU/mL) were included in the study. Ciprofloxacin and gentamycin were tested against fourteen common bacterial pathogens, isolated from clinical samples of patients from Benghazi city Libya. A total of isolates were detected in 264 (75.4%) samples. Out of these, 75.4% were female and 24.6% were male. The majority of the study participants were in the age range of between 36-53 years (33.7%). The Increased bacterial resistance to ciprofloxacin has been shown. Most strains of E. coli and Staph aureus were resistant to ciprofloxacin and sensitive to gentamycin thereby showing that gentamycin is more effective than ciprofloxacin. This study showed that E. coli followed by staph aureus and K. pneumonia were the predominant uropathogen of UTIs in this geographical area. Most of the uropathogens were susceptible to Ciprofloxacin. The results showed that there is an alarming subject of resistance to Gentamicin against UTI patients in this area. Clinicians should be aware of the existing data and treat patients according to susceptibility patterns.

Assessing Mental Pain as a Predictive Factor of Suicide Risk in a Clinical Sample of Patients with Psychiatric Disorders.

According to contemporary suicidology, mental pain represents one of the main suicide risk factors, along with more traditional constructs such as depression, anxiety and hopelessness. This work aims to investigate the relationship between the levels of mental pain and the risk to carry out suicide or suicide attempt in the short term in order to understand if a measurement of mental pain can be used as a screening tool for prevention. For this purpose, 105 outpatients with psychiatric diagnosis were recruited at the university hospital of Varese during a check-up visit and were assessed by using psychometric scales of mental pain levels, hopelessness, anxiety and depression. Clinical and sociodemographic variables of the sample were also collected. A period of 18 months following the recruitment was observed to evaluate any suicides or attempted suicides. Subjects numbering 11 out of 105 committed an attempted suicide. From statistical analyses, high values of the Beck Depression Inventory (BDI-II), Mental Pain Questionnaire (OMMP) and Hamilton Rating Scale for Depression (HAM-D) scales showed a significant association with the risk of carrying out a suicide attempt and, among these, OMMP and BDI-II showed characteristics of good applicability and predictivity proving suitable to be used as potential tools for screening and primary prevention of suicidal behavior.

Failed Performance on the Test of Memory Malingering and Misdiagnosis in Individuals with Early-Onset Dysexecutive Alzheimer's Disease.

Individuals with early-onset dysexecutive Alzheimer's disease (dAD) have high rates of failed performance validity testing (PVT), which can lead to symptom misinterpretation and misdiagnosis. The aim of this retrospective study is to evaluate rates of failure on a common PVT, the test of memory malingering (TOMM), in a sample of clinical patients with biomarker-confirmed early-onset dAD who completed neuropsychological testing. We identified seventeen patients with an average age of symptom onset at 52.25years old. Nearly fifty percent of patients performed below recommended cut-offs on Trials 1 and 2 of the TOMM. Four of six patients who completed outside neuropsychological testing were misdiagnosed with alternative etiologies to explain their symptomatology, with two of these patients' performances deemed unreliable based on the TOMM. Low scores on the TOMM should be interpreted in light of contextual and optimally biological information and do not necessarily rule out a neurodegenerative etiology.

The role of gender in a large international OCD sample: A Report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) Network

IntroductionObsessive-compulsive disorder (OCD) is characterized by a range of phenotypic expressions. Gender may be a relevant factor in mediating the disorder's heterogeneity. The aim of the present report was to explore a large multisite clinical sample of OCD patients, hypothesizing existing demographic, geographical and clinical differences between male and female patients with OCD. MethodsSocio-demographic and clinical variables of 491 adult OCD outpatients recruited in the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network were investigated with a retrospective analysis on a previously gathered set of data from eleven countries worldwide. Patients were assessed through structured clinical interviews, the Yale- Brown Obsessive-Compulsive Scale (Y-BOCS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Self-rating Depression Scale (SDS). ResultsAmong females, adult onset (>18 years old) was significantly over-represented (67% vs. 33%, p < 0.005), and females showed a significantly older age at illness onset compared with males (20.85 ± 10.76 vs. 17.71 ± 8.96 years, p < 0.005). Females also had a significantly lower education level than males (13.09 ± 4.02 vs. 13.98 ± 3.85 years; p < 0.05), a significantly higher rate of being married (50.8% vs. 33.5%; p < 0.001) and a higher rate of living with a partner (47.5% vs. 37.6%; p < 0.001) than males. Nonetheless, no significant gender differences emerged in terms of the severity of OCD symptoms nor in the severity of comorbid depressive symptoms. No predictive effect of gender was found for Y-BOCS, MADRS and SDS severity. Discussion/Conclusions.Our findings showed significant differences between genders in OCD. A sexually dimorphic pattern of genetic susceptibility may have a crucial role to OCD clinical heterogeneity, potentially requiring different specific therapeutic strategies. Further research is warranted to validate gender as an important determinant of the heterogeneity in OCD.

Molecularly Imprinted Polymer Nanoparticles Enable Rapid, Reliable, and Robust Point-of-Care Thermal Detection of SARS-CoV-2.

Rapid antigen tests are currently used for population screening of COVID-19. However, they lack sensitivity and utilize antibodies as receptors, which can only function in narrow temperature and pH ranges. Consequently, molecularly imprinted polymer nanoparticles (nanoMIPs) are synthetized with a fast (2 h) and scalable process using merely a tiny SARS-CoV-2 fragment (∼10 amino acids). The nanoMIPs rival the affinity of SARS-CoV-2 antibodies under standard testing conditions and surpass them at elevated temperatures or in acidic media. Therefore, nanoMIP sensors possess clear advantages over antibody-based assays as they can function in various challenging media. A thermal assay is developed with nanoMIPs electrografted onto screen-printed electrodes to accurately quantify SARS-CoV-2 antigens. Heat transfer-based measurements demonstrate superior detection limits compared to commercial rapid antigen tests and most antigen tests from the literature for both the alpha (∼9.9 fg mL–1) and delta (∼6.1 fg mL–1) variants of the spike protein. A prototype assay is developed, which can rapidly (∼15 min) validate clinical patient samples with excellent sensitivity and specificity. The straightforward epitope imprinting method and high robustness of nanoMIPs produce a SARS-CoV-2 sensor with significant commercial potential for population screening, in addition to the possibility of measurements in diagnostically challenging environments.

A Selective β-Catenin-Metadherin/CEACAM1-CCL3 Axis Mediates Metastatic Heterogeneity upon Tumor-Macrophage Interaction.

Tumor heterogeneity plays a key role in cancer relapse and metastasis, however, the distinct cellular behaviors and kinetics of interactions among different cancer cell subclones and the tumor microenvironment are poorly understood. By profiling an isogenic model that resembles spontaneous human ovarian cancer metastasis with an highly metastatic (HM) and non‐metastatic (NM) tumor cell pair, one finds an upregulation of Wnt/β‐catenin signaling uniquely in HM. Using humanized immunocompetent mice, one shows for the first time that activated β‐catenin acts nonautonomously to modulate the immune microenvironment by enhancing infiltrating tumor‐associated macrophages (TAM) at the metastatic site. Single‐cell time‐lapse microscopy further reveals that upon contact with macrophages, a significant subset of HM, but not NM, becomes polyploid, a phenotype pivotal for tumor aggressiveness and therapy resistance. Moreover, HM, but not NM, polarizes macrophages to a TAM phenotype. Mechanistically, β‐catenin upregulates cancer cell surface metadherin, which communicates through CEACAM1 expressed on macrophages to produce CCL3. Tumor xenografts in humanized mice and clinical patient samples both corroborate the relevance of enhanced metastasis, TAM activation, and polyploidy in vivo. The results thus suggest that targeting the β‐catenin‐metadherin/CEACAM1‐CCL3 positive feedback cascade holds great therapeutic potential to disrupt polyploidization of the cancer subclones that drive metastasis.

Antimicrobial susceptibility of Citrobacter Koseri isolated on clinical samples of hospitalized patients

The genus Citrobacter includes 13 species and is often found in water, food, land and certain animals. It is part of the normal flora of a small proportion of healthy humans; however, the rates of colonization increase in patients in long-term care institutions and hospitals. Citrobacter koseri is an aerobic Gram-negative bacillus, ubiquitous in nature, opportunistic, that is frequently found in genitourinary and gastrointestinal tracts of animals and humans as a saprophyte flora. Citrobacter koseri is one of the most important pathogens, eventually causing epidemics difficult to control. Therefore, the objective of this article is to carry out a microbiological characterization of this pathogen. A transversal descriptive study was conducted in the Surgical Clinical Hospital Lucía Íñiguez Landín of Holguín, which covered the period from January to December 2019. The study universe consisted of all enterobacteriaceae isolated in clinical samples of adult patients admitted during this period and the sample was formed by 219 strains of Citrobacter koseri. Out of the total number of cases, 70 belonged to the intensive care service for a 32.0%. Out of the total number of samples, 139 were isolated in pus samples for a 63.5%. The strains were more resistant to ciprofloxacin, cefuroxime, ampicillin, aztreonam, ceftazidime and to gentamicin. Citrobacter koseri is able to develop multidrug resistance to known antibiotics, acts as opportunistic and can colonize people in community, consequently its dissemination should be controlled.

A New Functional Magnetic Resonance Imaging Localizer for Preoperative Language Mapping Using a Sentence Completion Task: Validity, Choice of Baseline Condition, and Test-Retest Reliability.

To avoid post-neurosurgical language deficits, intraoperative mapping of the language function in the brain can be complemented with preoperative mapping with functional magnetic resonance imaging (fMRI). The validity of an fMRI “language localizer” paradigm crucially depends on the choice of an optimal language task and baseline condition. This study presents a new fMRI “language localizer” in Russian using overt sentence completion, a task that comprehensively engages the language function by involving both production and comprehension at the word and sentence level. The paradigm was validated in 18 neurologically healthy volunteers who participated in two scanning sessions, for estimating test–retest reliability. For the first time, two baseline conditions for the sentence completion task were compared. At the group level, the paradigm significantly activated both anterior and posterior language-related regions. Individual-level analysis showed that activation was elicited most consistently in the inferior frontal regions, followed by posterior temporal regions and the angular gyrus. Test–retest reliability of activation location, as measured by Dice coefficients, was moderate and thus comparable to previous studies. Test–retest reliability was higher in the frontal than temporo-parietal region and with the most liberal statistical thresholding compared to two more conservative thresholding methods. Lateralization indices were expectedly left-hemispheric, with greater lateralization in the frontal than temporo-parietal region, and showed moderate test-retest reliability. Finally, the pseudoword baseline elicited more extensive and more reliable activation, although the syllable baseline appears more feasible for future clinical use. Overall, the study demonstrated the validity and reliability of the sentence completion task for mapping the language function in the brain. The paradigm needs further validation in a clinical sample of neurosurgical patients. Additionally, the study contributes to general evidence on test–retest reliability of fMRI.

Phenotype of Gambling Disorder Patients with Lotteries as a Preferred Form of Gambling

Lottery gambling can become an addictive behavior which can significantly interfere with daily functioning. The objectives of this work were to estimate the prevalence of lottery gambling, to assess the profile related to this gambling type in a large clinical sample of patients who met criteria for gambling disorder (GD), and to compare this profile with the other two non-strategic forms of gambling (slot-machines and bingo). Sample included n = 3,531 patients consecutively attended for treatment-seeking due to gambling-related problems. All the participants met criteria for GD and were into the range of 18 to 85 years old. Sociodemographic variables, GD severity, psychopathological state, and personality traits were assessed. Statistical comparisons between the groups defined by the patients’ gambling preference (lotteries versus other gambling activities) were conducted, with chi-square test and analysis of variance. The prevalence of lotteries as the only gambling activity was 2.5%, 8.9% for lottery gambling as primary activity with other secondary gambling types, and 20.6% for lotteries as primary or secondary gambling activity. Lottery gambling and bingo gambling were more prevalent among women (bingo included the highest percentage of women). Compared to slot machine gambling, lotteries and bingo grouped older patients and those with later age of onset of the gambling-related problems. Bingo gambling showed the highest psychological distress and the most dysfunctional personality traits. This study shows the high frequency of lottery gambling among treatment-seeking for GD patients, and it provides empirical evidence about the profile associated with this gambling activity compared to other non-strategic gambling forms. The likelihood of lottery gambling is higher for women, patients married or living with a stable partner, and those within higher social position indexes.

A Highly Sensitive CRISPR-Empowered Surface Plasmon Resonance Sensor for Diagnosis of Inherited Diseases with Femtomolar-Level Real-Time Quantification.

The clustered regularly interspaced short palindromic repeats (CRISPR) molecular system has emerged as a promising technology for the detection of nucleic acids. Herein, the development of a surface plasmon resonance (SPR) sensor that is functionalized with a layer of locally grown graphdiyne film, achieving excellent sensing performance when coupled with catalytically deactivated CRISPR‐associated protein 9 (dCas9), is reported. dCas9 protein is immobilized on the sensor surface and complexed with a specific single‐guide RNA, enabling the amplification‐free detection of target sequences within genomic DNA. The sensor, termed CRISPR‐SPR‐Chip, is used to successfully analyze recombinant plasmids with only three‐base mutations with a limit of detection as low as 1.3 fM. Real‐time monitoring CRISPR‐SPR‐Chip is used to analyze clinical samples of patients with Duchenne muscular dystrophy with two exon deletions, which are detected without any pre‐amplification step, yielding significantly positive results within 5 min. The ability of this novel CRISPR‐empowered SPR (CRISPR‐eSPR) sensing platform to rapidly, precisely, sensitively, and specifically detect a target gene sequence provides a new on‐chip optic approach for clinical gene analysis.

Development of the motivation to use substance questionnaire

BackgroundThe use of a substance is always accompanied by a motivation that pushes the subject to use and abuse the substance. This work reports the validation data of the MUS (Motivation to Use Substance), which measures and evaluates the motivation to use substances based on the dimension of resistance, confidence, pleasure, and relaxation. MethodsThe validation process involved 605 subjects belonging to a clinical sample of patients who used substances. The sample was divided into two groups: on the first, consisting of 342 subjects, an exploratory analysis was carried out, and on the second, consisting of 263 subjects, a confirmatory analysis was carried out. For concurrent and convergent validation, the SCL-90 test (Symptom Check List-90) was administered for the measurement of addiction-related psychiatric symptoms, and the ASI (Addiction Severity Index) test was administered for the measurement of the severity of the addiction. Results and ConclusionsThe MUS was found to be a robust test of construct validity, convergent, and concurrent. The results highlight gender and age differences for some of the MUS scales. Ultimately, MUS can be considered an excellent tool for structuring treatment programs for addiction services.

Risky alcohol use among patients dispensed opioid medications: A clinical community pharmacy study

BackgroundIncluded among the significant risk factors for opioid overdose is concomitant use of other central nervous system depressants, particularly alcohol. Given the continued expansion of community pharmacy in the continuum of care, it is imperative to characterize alcohol use among pharmacy patients dispensed opioids in order to establish a foundation for identification and intervention in these settings. MethodsThis secondary analysis utilized data from a one-time, cross-sectional health assessment conducted among patients dispensed opioid medications in 19 community pharmacies in Indiana and Ohio. Adult, English speaking, patients not receiving cancer care who were dispensed opioid medications were asked to self-report alcohol and substance use, behavioral and physical health, and demographic information. Descriptive and logistic regression analyses were employed to characterize alcohol use/risky alcohol use and patient characteristics associated therewith. ResultsThe analytical sample included 1494 individuals. Participants were on average 49 years of age (Standard Deviation=14.9)—with 6% being persons of color (n = 89). Weekly drinking was reported by 18.1% (n = 204) and daily drinking was reported by 6.8% (n = 77) of the study sample, with a total of 143 (9.6%) participants reporting moderate/high risk drinking.Males (Adjusted Odds Ratio [AOR]=1.94, 95% CI=1.3,2.9), those with higher pain interference (AOR=1.44, 95% CI=1.0,2.0), overdose history (AOR=1.93, 95% CI=1.1,3.5), sedative use (AOR=2.11, 95% CI=1.3,3.5), and tobacco use (AOR=2.41, 95% CI=1.6,3.7) had increased likelihood of moderate/high risk alcohol use (all p < 0.05). ConclusionsMedication labeling and clinical guidelines clearly indicate that patients should abstain from concomitant use of opioids and alcohol. This study has identified rates and associated risk factors of risky alcohol use among a clinical sample of community pharmacy patients dispensed opioid medications. Continuing this line of research and potential clinical service development has the ability to improve patient safety through addressing a significant gap within the current opioid epidemic.

More is more: Evidence for the incremental value of the SCID-II/SCID-5-PD specific factors over and above a general personality disorder factor.

Currently, 3 competing conceptualizations of personality dysfunction can be distinguished: the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) categorical model delineating 10 distinct types of personality disorders (PDs); the alternative model for PDs (DSM-5 Section III), which assesses personality functioning and traits separately; and the International Classification of Diseases, 11th Version conceptualization, which provides 1 single code for the presence of a PD (which is based on problems in functioning) as well as codes that specify the level of the disorder (mild/moderate/severe), and prominent trait domains or patterns (5 domains and 1 pattern). The current study aims to assess the incremental value of the DSM-5 PDs over and above a global personality dysfunction factor, using expert ratings obtained with the Structured Clinical Interview for DSM-IV PDs and the Structured Clinical Interview for DSM-5 PDs interview in a large sample of clinical patients (N = 3,851). All estimated bifactor models provided adequate fit to the data. We found a surprisingly low explained common variance for the g-factor (<40%), indicating that ignoring the specific PD factors would lead to a substantial loss of information. The strongest specific PDs in terms of explained common variance were the avoidant, schizotypal, and schizoid PD factors and the conduct disorder criteria set if included. Correlations between our factors and external variables were relatively low, except for the Severity Indices of Personality Problems, which aims to measure personality functioning. Our findings suggest that specific PDs still have an important role to play in the assessment of personality pathology. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

First-in-Class: Cervical cancer diagnosis based on a urine test with fluorescent cysteine probe

In vitro diagnosis is key in diagnosing diseases and has recently become easily available. In vitro diagnostic techniques have been applied to various areas including the patient-tailored treatment development, disease progress tracking, and the cohort management. In this study, we developed the world's first in vitro cervical cancer diagnosis technology based on a urine test and verified its effectiveness with clinical urine samples of patients. In clinical practices, a Pap smear screening is used to detect cervical cancer, but it has limitations in its efficacy and from the uncomfortable sensation that women feel during the process. In this study, a new promising diagnostic method for cervical cancer was introduced using the molecular probe NPO-B, which selectively responds to cysteine (Cys) among amino acids in urine and exhibits fluorescence turn-on properties. The fluorescence signal of urine samples collected from about 1500 well characterized patients were analyzed and compared with the healthy control, and the results verified that cervical cancer could be diagnosed at a high true-positive ratio (74%). Our fluorescence-based cervical cancer diagnosis has advantages in terms that it only requires a simple fluorescence measuring device, a small amount of urine sample (200 μL), and a short diagnosis time (40 min). A noble way of spotting the cervical cancer with urine was introduced for the first time and is expected to be adopted to wider clinical practices including in vitro cervical cancer diagnosis or medical check-up requiring Cys sensing.

Comparison of analytical sensitivity and efficiency for SARS-CoV-2 primer sets by TaqMan-based and SYBR Green-based RT-qPCR

The pandemic of coronavirus disease 2019 (COVID-19) continues to threaten public health. For developing countries where vaccines are still in shortage, cheaper alternative molecular methods for SARS-CoV-2 identification can be crucial to prevent the next wave. Therefore, 14 primer sets recommended by the World Health Organization (WHO) was evaluated on testing both clinical patient and environmental samples with the gold standard diagnosis method, TaqMan-based RT-qPCR, and a cheaper alternative method, SYBR Green-based RT-qPCR. Using suitable primer sets, such as ORF1ab, 2019_nCoV_N1 and 2019_nCoV_N3, the performance of the SYBR Green approach was comparable or better than the TaqMan approach, even when considering the newly dominating or emerging variants, including Delta, Eta, Kappa, Lambda, Mu, and Omicron. ORF1ab and 2019_nCoV_N3 were the best combination for sensitive and reliable SARS-CoV-2 molecular diagnostics due to their high sensitivity, specificity, and broad accessibility.Key points• With suitable primer sets, the SYBR Green method performs better than the TaqMan one.• With suitable primer sets, both methods should still detect the new variants well.• ORF1ab and 2019_nCoV_N3 were the best combination for SARS-CoV-2 detection.

Evaluation of the Prognostic Relevance of Differential Claudin Gene Expression Highlights Claudin-4 as Being Suppressed by TGFβ1 Inhibitor in Colorectal Cancer.

Background: Claudins (CLDNs) are a family of closely related transmembrane proteins that have been linked to oncogenic transformation and metastasis across a range of cancers, suggesting that they may be valuable diagnostic and/or prognostic biomarkers that can be used to evaluate patient outcomes. However, CLDN expression patterns associated with colorectal cancer (CRC) remain to be defined. Methods: The mRNA levels of 21 different CLDN family genes were assessed across 20 tumor types using the Oncomine database. Correlations between these genes and patient clinical outcomes, immune cell infiltration, clinicopathological staging, lymph node metastasis, and mutational status were analyzed using the GEPIA, UALCAN, Human Protein Atlas, Tumor Immune Estimation Resource, STRING, Genenetwork, cBioportal, and DAVID databases in an effort to clarify the potential functional roles of different CLDN protein in CRC. Molecular docking analyses were used to probe potential interactions between CLDN4 and TGFβ1. Levels of CLDN4 and CLDN11 mRNA expression in clinical CRC patient samples and in the HT29 and HCT116 cell lines were assessed via qPCR. CLDN4 expression levels in these 2 cell lines were additionally assessed following TGFβ1 inhibitor treatment. Results: These analyses revealed that COAD and READ tissues exhibited the upregulation of CLDN1, CLDN2, CLDN3, CLDN4, CLDN7, and CLDN12 as well as the downregulation of CLDN5 and CLDN11 relative to control tissues. Higher CLDN11 and CLDN14 expression as well as lower CLDN23 mRNA levels were associated with poorer overall survival (OS) outcomes. Moreover, CLDN2 and CLDN3 or CLDN11 mRNA levels were significantly associated with lymph node metastatic progression in COAD or READ lower in COAD and READ tissues. A positive correlation between the expression of CLDN11 and predicted macrophage, dendritic cell, and CD4+ T cell infiltration was identified in CRC, with CLDN12 expression further being positively correlated with CD4+ T cell infiltration whereas a negative correlation was observed between such infiltration and the expression of CLDN3 and CLDN15. A positive correlation between CLDN1, CLDN16, and neutrophil infiltration was additionally detected, whereas neutrophil levels were negatively correlated with the expression of CLDN3 and CLDN15. Molecular docking suggested that CLDN4 was able to directly bind via hydrogen bond with TGFβ1. Relative to paracancerous tissues, clinical CRC tumor tissue samples exhibited CLDN4 and CLDN11 upregulation and downregulation, respectively. LY364947 was able to suppress the expression of CLDN4 in both the HT29 and HCT116 cell lines. Conclusion: Together, these results suggest that the expression of different CLDN family genes is closely associated with CRC tumor clinicopathological staging and immune cell infiltration. Moreover, CLDN4 expression is closely associated with TGFβ1 in CRC, suggesting that it and other CLDN family members may represent viable targets for antitumor therapeutic intervention.

Education-Based Cutoffs for Cognitive Screening of Alzheimer’s Disease

Introduction: The educational background and size of the elderly population are undergoing significant changes in Finland during the 2020s. A similar process is likely to occur also in several European countries. For cognitive screening of early Alzheimer’s disease (AD), using outdated norms and cutoff scores may negatively affect clinical accuracy. The aim of the present study was to examine the effects of education, age, and gender on the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery (CERAD-nb) in a large register-based, clinical sample of patients with mild AD and nondemented at-risk persons from the general population (controls) and to examine whether corrected cutoff scores would increase the accuracy of differentiation between the 2 groups. Methods: CERAD-nb scores were obtained from AD patients (n = 389, 58% women, mean age 74.0 years) and from controls (n = 1,980, 52% women, mean age 68.5 years). The differences in CERAD-nb performance were evaluated by univariate GLM. Differentiation between the 2 groups was evaluated using a receiver operating characteristic (ROC) curve, where a larger area under the ROC curve represents better discrimination. Youden’s J was calculated for the overall performance and accuracy of each of the measures. Results: Of the demographic factors, education was the strongest predictor of CERAD-nb performance, explaining more variation than age or gender in both the AD patients and the controls. Education corrected cutoff scores had better diagnostic accuracy in discriminating between the AD patients and controls than existing uncorrected scores. The highest level of discrimination between the 2 groups overall was found for two CERAD-nb total scores. Conclusions: Education-corrected cutoff scores were superior to uncorrected scores in differentiating between controls and AD patients especially for the highest level of education and should therefore be used in clinical cognitive screening, also as the proportion of the educated elderly is increasing substantially during the 2020s. Our results also indicate that total scores of the CERAD-nb are better at discriminating AD patients from controls than any single subtest score. A digital tool for calculating the total scores and comparing education-based cutoffs would increase the efficiency and usability of the test.