CS Diagnostics

Loop-mediated isothermal amplification (LAMP) is widely used for rapid nucleic acid detection but is limited by primer-driven nonspecific amplification that produces false positives. We developed TrueLAMP, a colorimetric LAMP formulation containing an inhibitor that suppresses nonspecific amplification while preserving target-dependent reactions. Using SARS-CoV-2 as a model, TrueLAMP was evaluated across multiple primer sets. TrueLAMP eliminated amplification in no-template controls while maintaining robust target amplification, achieving 100% specificity across all no-template controls and, using the Lamb primer set as a representative benchmark, a limit of detection of 250 copies per reaction with 95% detection probability. Stable endpoint colorimetric signals were maintained over extended incubation periods, enabling flexible readout without time-critical monitoring. TrueLAMP is compatible with readily available equipment, including convection ovens and temperature-controlled smart mugs, supporting simplified and decentralized molecular testing workflows.

Myocarditis and inflammatory cardiomyopathy are inflammatory diseases of the heart muscle that can have both infectious and non-infectious causes. They can be caused by an unresolved viral infection or other infection, or they can be autoimmune, toxic, or allergic in nature. The specific identification of the pathogen and/or confirmation of inflammation can only be achieved through direct tissue analysis using endomyocardial biopsy (EMB), as neither detection of the virus nor assessment of the quality and intensity of the inflammation is possible using non-invasive methods. Accordingly, the removal and analysis of an EMB is considered the diagnostic gold standard in international guidelines and statements. The sudden onset of atypical angina pectoris and initially exertion-dependent dyspnea, as well as arrhythmias, pericardial effusion, and progressive symptoms of heart failure, indicate an acute inflammatory process of the myocardium. In addition, nonspecific symptoms such as fatigue and reduced physical performance may also occur. Diagnostic evaluation includes an electrocardiogram (ECG), cardiac imaging, and laboratory tests. The analysis of the EMB is crucial for a definitive diagnosis and thus for the initiation of an etiology-based, specific and personalized therapy. This includes histological and immunohistochemical inflammation diagnostics as well as molecular virological diagnostics. These enable both the detection of viruses and the assessment of transcriptional virus activity. New analyses using metagenomic next generation sequencing (NGS) techniques provide insights of enormous diagnostic and therapeutic relevance. This applies both to the spectrum of detectable pathogens and to the possibility of confirming transcriptional viral activity. In addition, gene expression profiling enables the differentiation of specific forms of myocardial inflammation (e.g., giant cell myocarditis, cardiac sarcoidosis, and eosinophilic myocarditis) and reduces the influence of "sampling errors" in focal inflammatory processes. The treatment of heart failure or ventricular arrhythmias is always symptomatic according to general evidence-based guidelines. In severe cases, mechanical circulatory support or even a heart transplant may be necessary. Patients with histologically confirmed myocardial inflammation or intramyocardial viral infection can be offered specific, causal, and personalized therapy. These patients can be successfully treated with immunosuppressive or antiviral therapy, which significantly improves the prognosis of the disease.

Abstract Objectives/Scope A comprehensive data collection and analysis plan was applied to a Permian Basin Devon Energy Bone Spring pad (the Devon Project) comprising 3 new wells and 2 recently drilled parent wells as shown in Figure 1. The goal of this ‘science pad’ was to characterize and quantify fracture growth between wells having stratigraphic and structural variation to further optimize well spacing, landing depths, and completion design. Methods, Procedures, Process To understand hydraulic fracture propagation and drainage behavior a suite of diagnostic tests were applied: Toe-stage conventional Diagnostic Fracture Injection Tests (DFITs) and repeat DFIT Flow-back (DFIT-FB) tests on the same toe ports,Post-frac stage fall-off analysis including a Pressure-Transient-Analysis (PTA) technique to estimate treating well perforation cluster efficiency,Fracture Driven Interaction (FDI) statistics and modeling including Sealed Wellbore Pressure Monitoring (SWPM),Post completion sequential flow-back interference testing,Parent well production diagnostics. Results, Observations, Conclusions Repeat testing of the toe-port with conventional DFITs and DFIT-FB presented a unique opportunity to compare results using different testing and analysis techniques in exactly the same location. DFIT execution was again shown to be critical to achieve the best results. DFIT-FB interpretation was challenging in this setting with low net pressure, Pnet, and net stress, Ps (defined in the nomenclature section). PTA diagnostics and modeling workflows were applied to select frac stages having sufficient post-frac stage fall-off data. This analysis provides greater clarity and quantification of well friction, perforation friction, near-well tortuosity, and Far-field Fracture Extension Pressure (FFEP). Results from the suite of diagnostic tests applied on this pad presented an important example of ‘the whole is greater than the sum of the parts’. Individual tests results, taken alone, may have been interpreted as misruns, inconclusive, or contradictory. However, taken in concert, results provided a clear picture of ‘unconventional’ fracture growth and likely depletion gaps that will be used by Devon for further testing of well spacing and fracture designs to optimize development. Novel/Additive Information Pressure data acquisition is known to be inexpensive and non-disruptive in most completion operations. However, this project demonstrated the value of more data and repeat testing to help define the range of outcomes and to distinguish when data may be indicating representative vs outlier behavior. Pre-planning and investment in higher resolution pressure gauges located on all wells-of-interest to capture uninterrupted pressure measurements is recommended.

Chronic exposure to arsenic, lead, and mercury can impair liver function, but their combined impact on hepatocellular (AST, ALT) and cholestatic (ALP) liver enzymes remains poorly defined. We analyzed data from 58,864 German outpatients without known toxic exposure to evaluate independent and synergistic effects of these metals on liver enzymes. Blood levels of arsenic, lead, and mercury were measured, and associations with AST, ALT, and ALP were assessed using multivariable models adjusted for age and sex, including interaction terms. Mercury showed the strongest positive correlation with ALT (p<0.001), indicating a pronounced hepatocellular effect. Arsenic was associated with increased AST and ALT and decreased ALP (p<0.001 for all), suggesting both hepatocellular and cholestatic involvement. Lead demonstrated weaker but significant positive associations with all enzymes (p<0.001). Co-exposure analyses revealed that arsenic plus mercury modestly but significantly increased ALT, arsenic plus lead elevated AST, and high combined arsenic and mercury exposure reduced ALP. Our findings provide new evidence that background exposure to toxic metals, even below occupational thresholds, may subtly impair liver function. Mercury emerged as the most potent hepatotoxin. These results highlight the need to reconsider current environmental safety standards, especially regarding combined exposures.

Abstract: The imposter phenomenon refers to an intense, persistent feeling of inferiority and undeserved success by often high-achieving individuals and is associated with negative psychological consequences. Previous research has shown that the imposter phenomenon is closely related to perfectionism. However, some recent findings suggest that this relationship is not consistent across different dimensions of perfectionism, specifically perfectionistic strivings (PS) and perfectionistic concerns (PC). We conducted a meta-analysis of studies reporting these correlations to provide mean estimates of the disparate relationships. Twenty-six records providing 91 unique effect sizes were included. The mean reliability-adjusted correlation with the imposter phenomenon was significantly smaller for PS ( z = .159, 95% CI [.051, .268]) than for PC ( z = .747, 95% CI [.632, .863]). Partial correlations revealed that PS showed no unique relationship with the imposter phenomenon ( z = −.069, 95% CI [−.179, .041]), whereas the unique relationship for PC was strong ( z = .783, 95% CI [.547, 1.020]).

IntroductionCervical dystonia (CD) is a chronic movement disorder characterized by motor symptoms and a spectrum of non-motor features, including cognitive difficulties, which may affect quality of life. To date, no biomarker exists to identify or monitor cognitive impairment in CD. Growth differentiation factor 15 (GDF15) has been associated with cognitive decline in several neurodegenerative diseases and movement disorders, providing a rationale for its investigation in CD. This study aimed to evaluate whether plasma GDF15 concentrations are associated with cognitive performance in individuals with CD and to assess examine the potential of GDF15 as a biomarker of cognitive decline in CD.MethodsPlasma GDF15 levels were measured in patients with CD before and after botulinum toxin (BoNT) treatment and compared with healthy controls. Correlations between GDF15 concentration, cognitive performance (MoCA total and domain scores), and clinical characteristics—including age, disease duration, and TWSTRS motor severity—were analyzed using Spearman's and Pearson's coefficients.ResultsGDF15 concentrations were significantly higher in individuals with CD compared with healthy controls. However, GDF15 levels showed no association with age, disease duration, symptom severity, or treatment response, and remained stable following botulinum toxin administration. No correlations were found between GDF15 and global cognitive performance, with the exception of a correlation with the visuospatial MoCA sub score.DiscussionWhile GDF15 concentrations were elevated in CD, they did not demonstrate consistent relationships with clinical features or cognitive outcomes. These findings suggest that GDF15 cannot currently be considered a reliable biomarker of cognitive impairment in CD. Given the limited sample size, this study should be regarded as preliminary.

Abstract Estragole and anethole are the major flavoring and aroma components of the essential oils extracted from basil ( Ocimum basilicum L.), anise ( Pimpinella anisum ), star anise ( Illicium verum ), and fennel ( Foeniculum vulgare ). Besides, they also exhibit bioactivities, such as antioxidation, antimicrobial, immunomodulation, inti-inflammation, and anti-diabetes. These properties make them being faced with substantial applications in the industries of food, cosmetics, pharmaceutics, and agriculture. Commercial estragole and anethole are currently obtained from extraction from their original plants, which suffers from unstable quality and resources. Microbial synthesis is a promising alternative approach to sustainably obtain estragole and anethole, but has not been achieved. In this study, we modularly redesigned the synthetic pathways based on the Escherichia coli chassis. Firstly, a p -coumaryl alcohol over-accumulator (436.28 mg/L) was engineered to facilitate the validation of the undemonstrated downstream module. De novo biosynthesis of estragole and anethole was achieved by stepwise analysis and BioBricks assembly. The intracellular availability of S -adenosyl-L-methionine (SAM) was revealed to be the key limiting factor, and was enhanced by deregulating the synthesis. Finally, the productions of estragole and anethole were improved by 246.88% and 202.44% compared with the initial strains. This study represents the first synthesis of estragole and anethole in microbial chassis, and the demonstration of microbial synthesis of propenyl phenols. Besides, it provided an alternative sustainable approach to obtain flavoring and aroma chemicals.

BackgroundThis exploratory study investigates differences among patients enrolled in a clinical study based on referral type (self‐referred, doctor‐referred, or other), considering demographics, family history of Alzheimer's disease (AD) and other causes of symptoms, life circumstances, and clinical care factors.MethodPatients (n =608) were classified into three referral groups: self‐referred, doctor‐referred, and other. Data on demographics, family history of AD and other causes of symptoms, life circumstances, and clinical care factors were available. Descriptive analysis compared baseline characteristics across groups using Fisher’s exact test to derive p ‐values. Multivariable logistic regression analysis identified factors associated with referral type (self‐ and doctor‐referred).ResultResults indicate notable variations in patient characteristics and clinical factors between referral groups. In the group comparisons, there were no significant differences in age, gender, race, and number of previous visits between doctor‐referred and self‐referred patients. Self‐referred patients generally had higher socioeconomic status compared to doctor‐referred patients. Significant differences were observed in referral duration, with shorter referral durations for doctor‐referred patients compared to self‐referred patients (p <0.0005). Additionally, the type of doctors previously seen by the patient significantly differed between the two groups (p <0.0005). A higher number of self‐referred patients presented in primary care first than directly to specialists. 59% of patients (n =359) indicated a family history of AD and/or dementia. Logistic regression showed that this did not have a significant impact on the referral type. The three factors that did have a significant impact on the referral type were socioeconomic status, level of education and type of doctor seen previously (p <0.05).ConclusionUnderstanding differences in patient characteristics based on referral types can provide insights into removing barriers to diagnosis and improving equitable diagnostic access. Current results explore the role of the patient's social environment, such as level of education, and how it can influence actionability on self‐presentation to medical care. Furthermore, doctor referred patients seem to have more access to the healthcare system, with shorter times between doctor visits. Future studies should focus on potential solutions for implementation of measures that improve access to timely and accurate diagnosis.