Clinical Testing Research Articles

Parkinson’s Disease: Biomarkers for Diagnosis and Disease Progression

Parkinson’s disease (PD) is a progressive neurological disease that causes both motor and nonmotor symptoms. While our understanding of putative mechanisms has advanced significantly, it remains challenging to verify biomarkers with sufficient evidence for regular clinical use. Clinical symptoms are the primary basis for diagnosing the disease, which can be mild in the early stages and overlap with other neurological disorders. As a result, clinical testing and medical records are mostly relied upon for diagnosis, posing substantial challenges during both the initial diagnosis and the continuous disease monitoring. Recent biochemical, neuroimaging, and genetic biomarkers have helped us understand the pathophysiology of Parkinson’s disease. This comprehensive study focuses on these biomarkers, which were chosen based on their relevance, methodological excellence, and contribution to the field. Biochemical biomarkers, including α-synuclein and glial fibrillary acidic protein (GFAP), can predict disease severity and progression. The dopaminergic system is widely used as a neuroimaging biomarker to diagnose PD. Numerous genes and genome wide association study (GWAS) sites have been related to the development of PD. Recent research on the SNCA gene and leucine-rich repeat protein kinase 2 (LRRK2) has shown promising results. By evaluating current studies, this review intends to uncover gaps in biomarker validation and use, while also highlighting promising improvements. It emphasizes the need for dependable and reproducible indicators in improving PD diagnosis and prognosis. These biomarkers may open up new avenues for early diagnosis, disease progression tracking, and the development of personalized treatment programs.

Diagnosis and typing of leukemia using a single peripheral blood cell through deep learning

AbstractLeukemia is highly heterogeneous, meaning that different types of leukemia require different treatments and have different prognoses. Current clinical diagnostic and typing tests are complex and time‐consuming. In particular, all of these tests rely on bone marrow aspiration, which is invasive and leads to poor patient compliance, exacerbating treatment delays. Morphological analysis of peripheral blood cells (PBC) is still primarily used to distinguish between benign and malignant hematologic disorders, but it remains a challenge to diagnose and type these diseases solely by direct observation of peripheral blood(PB) smears by human experts. In this study, we apply a segmentation‐based enhanced residual network that uses progressive multigranularity training with jigsaw patches. It is trained on a self‐built annotated dataset of 21,208 images from 237 patients, including five types of benign white blood cells(WBCs) and eight types of leukemic cells. The network is not only able to discriminate between benign and malignant cells, but also to typify leukemia using a single peripheral blood cell. The network effectively differentiated acute promyelocytic leukemia (APL) from other types of acute myeloid leukemia (non‐APL), achieving a precision rate of 89.34%, a recall rate of 97.37%, and an F1 score of 93.18% for APL. In contrast, for non‐APL cases, the model achieved a precision rate of 92.86%, but a recall rate of 74.63% and an F1 score of 82.75%. In addition, the model discriminates acute lymphoblastic leukemia(ALL) with the Ph chromosome from those without. This approach could improve patient compliance and enable faster and more accurate typing of leukemias for early diagnosis and treatment to improve survival.

Novel Approach to Fat Reduction: A Phase I Study Evaluating Safety and Tolerability of STP705 in Abdominoplasty

Background: RNAi therapeutics are a rapidly developing technology with broad medical applications predicated on reducing the expression of genes with key links to disease pathogenesis. The TGF-β1/Smad3 and COX-2 signaling pathways are strongly implicated in obesity and type 2 diabetes. Reducing the expression of TGF-β1 and COX-2 may have benefits in fat reduction procedures. The aim of this study was to assess the safety and tolerability of STP705 (a TGF-β1/COX-2 siRNA complex in a polypeptide nanoparticle vehicle) injections in persons undergoing abdominoplasty. A secondary aim was to make initial histologic observations on the efficacy of STP705 injections in inducing adipocyte apoptosis for the purpose of focal fat reduction. Methods: The study treatment consisted of 3 rounds of treatment with 7 subcutaneous abdominal injections of STP705 or placebo. Eight female subjects aged 18-65 years received 120 μg, 240 μg, or 360 μg STP705 in 0.5 or 1.0 ml doses (per injection) or an equivalent amount of placebo injected randomly across seven 1 cm2 areas. Treatments were administered 28 days apart with follow-ups occurring at 2 and 7 days’ post-procedure. Tissue samples from each of the 7 injection sites were harvested from total abdominoplasty excisional specimens obtained 28 days after the final injection. Safety assessments were conducted, including physical examination, clinical laboratory tests, electrocardiograms, evaluation of local skin reactions (LSRs), and collection of adverse events (AEs). Lipolytic and inflammatory effects of STP705 were assessed by blinded histologic analysis of harvested tissue samples. Results: There were no clinically significant changes in clinical labs, vital signs, or ECGs. The incidence of LSRs was low throughout the study. There were 3 moderate AEs deemed likely to be related to STP705 injection; none required intervention, and all resolved without dose modification. Histology revealed marginally dose-dependent tissue response with adipocyte destruction and fat remodeling. Conclusion: In general, STP705 was well tolerated at all concentrations and volumes studied. STP705 demonstrated excellent safety, and initial histologic analysis is suggestive of its efficacy in adipocyte destruction. The lack of cutaneous side effects with STP705 injection is an advantage over current treatments for similar indications.

Effects of Noise Exposure on Peripheral Auditory Function, Binaural Envelope Coding, and Speech Perception in Student Musicians With Normal Hearing

Objectives: Musicians face an increased risk of hearing loss due to prolonged and repetitive exposure to high-noise levels. Detecting early signs of hearing loss, which are subtle and often elusive to traditional clinical tests like pure-tone audiometry, is essential. The objective of this study was to investigate the impact of noise exposure on the electrophysiological and perceptual aspects of subclinical hearing damage in young musicians with normal audiometric thresholds. Design: The study included 33 musicians and 33 nonmusicians, all aged between 21 and 35 years, with normal audiometric thresholds. Participants underwent a comprehensive test battery, which encompassed standard and extended high-frequency (EHF) pure-tone audiometry (0.25 to 16 kHz), a Noise Exposure Structured Interview, auditory brainstem responses (ABRs) to clicks at various presentation rates and levels, thresholds for detecting interaural envelope time difference, and a spatial release from masking (SRM) paradigm in which the target speech was presented in the presence of either colocated or spatially separated time-reversed two-talker babble. Results: The results indicated the musician group reported greater lifetime noise exposure than the nonmusician group, but the Noise Exposure Structured Interview scores were neither correlated with the ABR results nor with the speech perception outcomes. The ABR analyses indicated diminished level-dependent growth and increased rate-dependent decline in wave I amplitudes among musicians compared with nonmusicians. The student musicians exhibited better binaural envelope processing skills than nonmusicians, emphasizing their perceptual advantages in auditory processing associated with musicianship. Speech perception results indicated no significant differences in SRM between student musicians and nonmusicians. However, in both groups, individuals with poorer EHF hearing exhibited reduced SRM compared with those with normal EHF hearing, underscoring the importance of assessing and addressing EHF hearing. Conclusions: Student musicians exhibit peripheral neural deficits; however, no clear relation was found between these neural deficits and their perceptual skills. Notably, reduced EHF thresholds were clearly related to reduced SRM, which poses a challenge for speech perception in complex multi-talker environments, affecting both musicians and nonmusicians alike.

Enhancing variant of uncertain significance (VUS) interpretation in neurogenetics: collaborative experiences from a tertiary care centre

BackgroundThe findings of variants of uncertain significance (VUS) on a clinical genetic testing report pose a challenge for attending healthcare professionals (HCPs) in patient care. Here, we describe the outcomes...

Improving the primary care clinical testing process in southwest Scotland: a systems-based approach

IntroductionAcross all healthcare environments, inadequately specified patient test requests are commonly encountered and can lead to wasted clinician time and healthcare resources, in addition to either missed or unnecessary testing...

Validation of a Set of Clinical Criteria for the Diagnosis of Secondary Progressive Multiple Sclerosis

Background/Objectives: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by progressive impairment of neuronal transmission due to focal demyelination. The most common form is RRMS (relapsing-remitting multiple sclerosis), which, under the influence of certain factors, can progress to SPMS (secondary progressive multiple sclerosis). Our study aimed to validate the criteria proposed by a working group of the Romanian Society of Neurology versus the criteria proposed by a group of experts from Spain, Karolinska, and Croatia concerning the progression from RRMS to SPMS. Methods: This was done by gathering epidemiological data (age, gender) and by applying clinical tests such as the 9HPT (9-hole peg test), 25FWT (25-foot walk test), and EDSS (expanded disability status scale) tests and the SDMT test (symbol digit modalities test). The present research is a cohort study that included a number of 120 patients diagnosed with MS according to the McDonald Diagnostic Criteria 2017. The study was carried out between January 2023 and April 2024, including patients hospitalized in the Neurology Clinic of the Clinical Rehabilitation Hospital from Iasi, Romania. The data were collected at baseline (T0) and at a 12-month interval (T1). Results: The statistical analysis was conducted using Kaiser–Meyer–Olkin analysis, which indicated a value of 0.683, thus validating the clinical tests used. The correlation matrix and the linear regression for all the tests showed highly significant statistical results. Furthermore, the ROC curve analysis of the criteria suggested by the working group of the Romanian Society of Neurology demonstrated that the EDSS, 9HPT, and 25FWT are highly sensitive in diagnosing SPMS, an opinion that is shared with the Spanish experts, but not with the Karolinska expert panel. Using the criteria given by the Croatian expert group in the ROC curve analysis showed that only the EDSS was strongly significant for the progression to the SPMS phase. Conclusions: In conclusion, all clinical methods used demonstrated that they are valid and can contribute to identifying patients with an increased risk of progression. The model proposed by the Romanian Society of Neurology working group is similar to other countries’ expert opinions and can be used to detect the risk of disease progression and establish a more tailored therapeutic management of SPMS.

The fabrication of phosphotungstate@UIO-Au/reduced graphene oxidation for electrochemical ultrasensitive detection of alpha-fetoprotein.

As an early multi-purpose tumor marker of hepatocellular carcinoma, alpha-fetoprotein (AFP) plays a vital role in early diagnosis and treatment. To achieve the early and accurate determination of AFP, the POMOF was fabricated by embedding H3PW12O40 (PW12) into UIO-66-NH2, further immobilized on reduced GO (rGO) and fabricated an innovative POMOF nanocomposite (PW@UIO-Au/rGO) as an electrochemical immunosensor (ECI-sensor). The PW@UIO-Au/rGO achieved 17-fold signal enhancement owing to their synergistic effect, enabling PW@UIO-Au/rGO exhibit high oxidase-like catalytic activity, facilitating their sensing performance. Under optimal experimental conditions, the proposed PW@UIO-Au/rGO ECI-sensor presented excellent sensing performance over a wide range from 0.01 ng mL-1 to 500 ng mL-1 with ultra-low detection of 4.0 pg mL-1. Notably, sensing results in real serum samples were verified by the clinical enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immunoassay (ECL) methods with excellent accuracy and consistency, indicating the excellent environmental tolerance of the proposed ECI-sensor. This work provided a promising strategy for designing feasible ultra-sensitive probe for sensing AFP in clinical test.

Pre-symptomatic scintigraphic and genetic cascade screening in cardiac transthyretin amyloidosis.

While early diagnosis is crucial, as new treatments can significantly slow the progression of the disease, there is growing evidence on the application of novel imaging techniques for detecting transthyretin amyloidosis (ATTR) in pre-symptomatic stages. This study aimed to evaluate the utility of pre-symptomatic scintigraphic imaging cascade screening for early detection of ATTR. During the period from 2020 to 2024, we conducted a prospective study that enrolled 100 consecutive adults. The study utilized a multimodal cascade screening approach to assess asymptomatic relatives of individuals with ATTR (ClinicalTrials.gov Identifier: NCT05814380). The analysis incorporated clinical data, genetic testing, echocardiography, scintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT) with [99mTc]Tc-DPD, regardless of the predicted age of disease onset. Overall, scintigraphy identified cardiac amyloidosis (CA) in 8.2% of relatives, while 20.5% carried a pathogenic transthyretin variant without radiotracer uptake, with Phe53Leu being predominant. Notably, no relatives of wild-type ATTR patients exhibited CA on scintigraphy or carried a transthyretin variant. Additionally, newly-diagnosed relatives with ATTR CA presented elevated high-sensitivity troponin levels and exhibited a higher incidence of pathological electrocardiographic Q waves, greater thickness of the intraventricular septum and left ventricular posterior wall, a notable decline in lateral wall and intraventricular septal E' tissue velocities measured by TDI, and the "5-5-5" sign (p < 0.05). The presented findings demonstrate that implementing a systematic screening protocol, which integrates genetic and scintigraphic testing, facilitates the early detection of ATTR. Crucially, a significant proportion of asymptomatic relatives of patients with hereditary ATTR may suffer from underlying CA. ClinicalTrials.gov Identifier: NCT05814380.

Four heterozygous de novo variants in ASXL3 identified with Bainbridge–Ropers syndrome and further dissecting published genotype–phenotype spectrum

Bainbridge–Ropers syndrome (BRPS) is a recently described neurodevelopmental genetic disorder associated with de novo truncating variants in additional sex combs like 3 (ASXL3) on chromosome 18q12.1. Trio-based exome sequencing was conducted on patients admitted to the Children’s Hospital Affiliated to Shandong University and diagnosed with unexplained intellectual disabilities or developmental delay between June 2022 and January 2024. De novo truncation of ASXL3 was identified in four patients, and the pathogenic variants and their de novo status were validated using Sanger sequencing. Comprehensive clinical phenotype–genotype information of all previously reported patients with BRPS was collected and summarized. The common clinical manifestations observed in the four patients included language and intellectual disabilities or psychomotor retardation. Genetic analysis revealed that patient 1 carried a de novo heterozygous variant, c.1667_1668del (p.Thr556Arpfs*3), whereas patient 2 had a novel heterozygous frameshift variant of ASXL3, c.3324del (p.Lys1109Serfs*34). These two variants have not been documented to date. Additionally, patients 3 and 4 exhibited a de novo variant, c.4678C &amp;gt; T (p.Arg1560Ter). Based on the combined assessment of clinical phenotypes and genetic testing results, it was postulated that all four children presented with BRPS syndrome caused by pathogenic variations in ASXL3. The present study complements the range of ASXL3 mutational and phenotypic spectra in the population, highlighting subtle distinctions in clinical manifestations between Chinese patients and other racial groups. The reporting of additional cases will contribute to further elucidating the function of ASXL3 and establishing a solid foundation for clinical diagnosis and treatment.

EXPRESS: Individual control of input rate improves recall of spoken discourse by adult users of cochlear implants: An exploratory study.

Although cochlear implants (CI) successfully replace the sense of hearing, they do not restore natural hearing. Still, CI users adapt to this novel signal, reaching meaningful levels of speech recognition in clinical tests that focus on repetition of words and short sentences. However, many patients who score above average in clinical speech perception tests complain that everyday speech interactions are both difficult and cognitively draining. In part this difficulty may be due to the naturally rapid pace of everyday discourse. We report a study in which 12 CI users aged 23 to 77, recalled multi-sentence discourse presented without interruption, or in the condition of interest, when passages were paused at major linguistic boundaries, with participants given control of when to initiate the next segment. Comprehension of the discourse structure was based on a formalized representational system that organizes discourse elements hierarchically to index the relative importance of different elements to the overall understanding of the discourse. Results showed (a) better recall when CI users were allowed to control the discourse pace, (b) an overall effect of aging, with older CI users recalling discourse less accurately, (c) better recall for passages with higher average inter-word predictability, (d) a "semantic hierarchy effect" reflected by better recall of main ideas versus minor details, (e) an attenuation of the semantic hierarchy effect for low predictability passages. Results underscore the benefits of extra processing time in addressing CI listening challenges and highlight the limited ecological validity of single-word or single-sentence speech recognition tests.

Abstract B039: Clinical liquid biopsy testing for detecting actionable genomic alterations in children and young adults with advanced solid tumors

Abstract Introduction: Given the paucity of data regarding circulating tumor DNA (ctDNA) as a modality to guide diagnosis and treatment for children with solid tumors, we conducted a prospective study to determine the frequency of diagnostic and targetable genomic variants identified by clinical ctDNA testing. Methods: GAIN is a prospective, multi-center molecular profiling study that was amended to include clinical ctDNA testing starting in January 2022. Patients were eligible if they were &amp;lt;30 years old with a refractory, recurrent, newly diagnosed with 2-year EFS &amp;lt;50%, or rare solid tumor and had measurable or evaluable disease. Paired tumor and blood samples underwent next generation sequencing (NGS) in CLIA-certified laboratories, with return of results to clinicians. Serial ctDNA samples were analyzed by F1LCDx (FoundationOne® Liquid Companion Diagnostic), an FDA-approved clinical ctDNA test that includes hybrid capture sequencing of a 300+ gene panel, comprehensive multi-omics ctDNA tumor fraction (TF) assessment, tumor mutational burden, and microsatellite instability status. We analyzed comprehensive NGS tissue-based and F1LCDx sequencing data for each participant to compare findings from each sample. The detection of alterations was stratified by ctDNA burden as assessed by ctDNA TF. We calculated the prevalence of ctDNA in our cohort, overall and by disease type. Chart review provided additional patient characteristic, diagnostic, therapeutic, and disease assessment data. The clinical impact of ctDNA results was qualitatively described. Results: The cohort included 35 patients, with a total of 70 F1LCDx samples (range 1-6 samples per patient). There were 16 unique tumor types represented, most commonly osteosarcoma (n = 8), neuroblastoma (n = 8), and Ewing sarcoma (n = 4). 77% of patients had metastatic disease at time of first ctDNA sample collection. 51% of patients had detectable ctDNA TF in at least one sample. Overall, 60% of patients had at least one actionable genomic alteration (range 0-14 variants per patient) identified in liquid biopsy samples, including 3 patients with actionable variants identified with undetectable ctDNA TF. We observed case vignettes in which ctDNA results informed clinical decisions, including disease assessment and treatment guidance. An illustrative example was the identification of ALK variants in relapse blood samples of two patients with neuroblastoma that were not identified in baseline tissue, which were targeted in both instances. Data collection and analyses as described in the methods are ongoing. Conclusion: In this prospective cohort of children and young adults with advanced solid tumors, ctDNA was detectable across a wide range of diagnoses and 60% of patients had at least one diagnostic or potentially targetable alteration identified. These data demonstrate that liquid biopsy yields actionable genomic variants, particularly when ctDNA burden is elevated. We will determine the association of these variants with those identified in tissue samples and their clinical implications in ongoing analyses. Citation Format: Holly J Roberts, Hannah Comeau, Steven G Dubois, Katerina Hoskova, Douglas I Lin, Brian D Crompton, Katherine A Janeway, David S Shulman. Clinical liquid biopsy testing for detecting actionable genomic alterations in children and young adults with advanced solid tumors [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B039.

The screening and management of skin diseases in remote African regions: a narrative review.

Skin diseases in remote African regions are often exacerbated due to a lack of resources and expertise with little current research addressing the challenges that patients and healthcare systems experience. Although skin diseases in remote African regions are prevalent and pose a substantial health burden, they remain neglected and understudied. This review aims to explore current challenges in the diagnosis and management of skin diseases in African regions and focus on the need for enhanced understanding and improved healthcare strategies. We reviewed papers that were retrieved from PubMed, Google Scholar, and other relevant academic search sites to analyze the prevalence, screening techniques, as well as management strategies and obstacles associated with dermatological diseases in remote African regions. Current literature suggests there is indeed a high prevalence of skin diseases where other infections are predominant. Further, different factors, such as socioeconomic status and environmental conditions, make it challenging for optimal screening and treatment of skin diseases in remote African regions. Common screening methods for skin diseases involve clinical examination and laboratory tests, while management includes pharmacotherapy, surgery, and counseling approaches. Overall, access to medications and adequate healthcare services remains limited. Early diagnosis and management of skin diseases in remote African regions have significant challenges, including a lack of funding for dermatology, education, and research. Future promising strategies such as teledermatology, point-of-care diagnostic technologies, and task shifting show promise in improving access to care. However, there is a need for sustained efforts to address the underlying socioeconomic factors and improve healthcare delivery in remote African regions.

Abstract A040: Using mitochondrial abundance in tumor-derived extracellular vesicles for pancreatic cancer screening

Abstract Pancreatic cancer, marked by a high mortality rate and rising incidence, often goes undetected until advanced stages, complicating treatment. Tumor-derived extracellular vesicles (EVs) have emerged as promising cancer biomarkers due to their cargo from parent cells. However, current detection methods are often time-consuming, expensive, and complex. To overcome these challenges, we developed a screening assay for pancreatic cancer that uses the mitochondrial DNA to nuclear DNA ratio in tumor-derived EVs as a distinguishing feature. This assay combines immunoprecipitation with qPCR quantification for direct detection of tumor-derived EVs from serum, utilizing DNA-isolation-free techniques and duplexing probes for qPCR, thus saving at least 3 hours. Clinical sample testing demonstrated the assay's potential as a translational tool for cancer screening, showing a weak correlation with prognosis biomarkers and sufficient discriminatory power between healthy controls, pancreatitis, and pancreatic cancer cases. Citation Format: Dali Sun. Using mitochondrial abundance in tumor-derived extracellular vesicles for pancreatic cancer screening [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A040.

Early Changes in the Locus Coeruleus in Mild Cognitive Impairment with Lewy Bodies.

Although neuromelanin-sensitive magnetic resonance imaging (NM-MRI) has been used to evaluate early neurodegeneration in Parkinson's disease, studies concentrating on the locus coeruleus (LC) in pre-dementia stages of dementia with Lewy bodies (DLB) are lacking. The aims were to evaluate NM-MRI signal changes in the LC in patients with mild cognitive impairment with Lewy bodies (MCI-LB) compared to healthy controls (HC) and to identify the cognitive correlates of the changes. We also aimed to test the hypothesis of a caudal-rostral α-synuclein pathology spread using NM-MRI of the different LC subparts. A total of 38 MCI-LB patients and 59 HCs underwent clinical and cognitive testing and NM-MRI of the LC. We calculated the contrast ratio of NM-MRI signal (LC-CR) in the whole LC as well as in its caudal, middle, and rostral MRI slices, and we compared the LC-CR values between the MCI-LB and HC groups. Linear regression analyses were performed to assess the relationship between the LC-CR and cognitive outcomes. The MCI-LB group exhibited a significant reduction in the right LC-CR compared to HCs (P = 0.021). The right LC-CR decrease was associated with impaired visuospatial memory in the MCI-LB group. Only the caudal part of the LC exhibited significant LC-CR decreases in MCI-LB patients compared to HCs on both sides (P < 0.0001). This is the first study that focuses on LC-CRs in MCI-LB patients and analyzes the LC subparts, offering new insights into the LC integrity alterations in the initial stages of DLB and their clinical correlates. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Impact of proxymetacaine on the dynamics of cyclopentolate in White 6- to 7-year-olds.

This study compared the efficacy of cyclopentolate hydrochloride at 10-, 20- and 30-min post-instillation in White 6- to 7-year-olds, with and without prior instillation of proxymetacaine hydrochloride. The primary aim was to determine if accurate autorefraction values can be obtained sooner than the current standard of 30-min post-cycloplegia. The secondary aim was to investigate whether proxymetacaine hydrochloride enhances the efficiency of cyclopentolate. Participants were 112 White 6- to 7-year-olds from the Child Eye Health Study. The right eye received 0.5% proxymetacaine hydrochloride and 1.0% cyclopentolate hydrochloride, and the left eye received only 1.0% cyclopentolate hydrochloride. Non-cycloplegic and cycloplegic refractive error (at 0, 10, 20 and 30 min) was measured using a binocular, open-field autorefractometer. Data were analysed through paired t-tests, concordance analysis, linear regression, equivalence testing and Bland-Altman analysis, using the 95% limits of agreement. Mean spherical equivalent refraction (SER) (SD) in the right eye at 0-, 10-, 20- and 30-min post-instillation was 0.62 (1.45) D, 1.52 (1.80) D, 1.64 (1.81) D and 1.72 (1.80) D, respectively. Mean left eye SER (SD) were 0.68 (1.24) D, 1.42 (1.66) D, 1.56 (1.66) D and 1.68 (1.72) D, respectively. Bland-Altman analysis showed a high level of agreement, and equivalence testing confirmed that there was no clinically significant difference in SER at 20 and 30 min in both eyes (within ±0.50 D), with mean differences of 0.08 (0.23) D in the right eye and 0.13 (0.30) D in the left eye (p = 0.21). However, SER at 10 and 30 min were equivalent in the right eye only. Accurate autorefraction values can be obtained 20-min post-instillation of 1.0% cyclopentolate in white children aged 6-7 years, potentially reducing clinical testing times. Proxymetacaine pre-instillation allows for reliable measurements as early as 10-min post-instillation of cyclopentolate. Further research is needed to validate these findings in non-White populations and to determine the safe discharge time post-proxymetacaine instillation.

Advances in research on the relationship between mitochondrial function and colorectal cancer: a bibliometric study from 2013 to 2023

The study provides a thorough examination of literature from 2013 to 2023, delving into the intricate relationship between mitochondrial function and colorectal cancer (CRC). It offers a concise overview of the current landscape and emerging trends in this rapidly evolving research area. The findings indicate a consistent rise in annual publications, reflecting growing interest and significant potential in the field. China emerges as the leading contributor, followed by the United States and India. However, despite China’s dominance in output, its average citation rate is lower than that of the US, which leads in citations per publication, highlighting a noticeable disparity. In the realm of research institutions, Shanghai Jiao Tong University and China Medical University are identified as major contributors, yet the potential for inter-institutional collaboration remains largely untapped, suggesting avenues for future synergy. Internationally, China-US collaborations are particularly robust, fostering cross-border knowledge exchange. Hyun Jin Won and Li Wei are recognized as prolific authors, while Ahmedin Jemal is an influential co-cited scholar, noted for his seminal contributions. Keyword analysis reveals research focus areas, such as the complex CRC tumor microenvironment, molecular mechanisms of oxidative stress, and key multidrug resistance pathways. It also highlights the promising potential of mitochondria-targeted therapies and nanomolecular technologies in clinical practice, signaling their growing significance in addressing complex health challenges. The study underscores the imperative to validate complex mitochondrial mechanisms and signaling pathways in CRC, with a particular emphasis on translating these insights into drug targets for clinical trials. Advancing this research is expected to refine and enhance CRC treatment strategies. Additionally, it highlights the urgency of validating mitochondrial complexities in CRC, advocating for collaborative efforts to link these mechanisms with tailored therapeutic interventions for clinical testing. This integrated approach promises significant advancements in developing effective, targeted CRC treatments, ultimately improving patient outcomes.

Abstract 4134551: Outstanding Research Award in Pediatric Cardiology: Cardiomyopathy-Associated Pathogenic Variants in Pediatric Myocarditis: A Study from the Pediatric Cardiomyopathy Registry

Background: Recent studies have demonstrated that patients with myocarditis (MC) may have a higher burden of cardiomyopathy (CM)-associated gene variants than the general population. However, data in children is limited. The Pediatric Cardiomyopathy Registry (PCMR), a large multi-center registry of children with CM, includes patients with dilated CM (DCM) secondary to myocarditis (MC). Hypothesis: We hypothesized patients with DCM secondary to MC in the PCMR have a higher burden of CM-associated gene variants than healthy controls, and clinical genetic testing in this population is rare. Aims: We aimed to: (1) calculate the prevalence of pathogenic (P) or likely pathogenic (LP) CM-associated variants in patients with DCM secondary to MC and compare to the prevalence in heart-healthy controls and (2) report the rate of clinical genetic testing in this population. Methods: The PCMR was queried to identify patients with DCM secondary to MC who underwent exome sequencing as part of a prior prospective study at 14 sites in North America. Controls from the Indiana University Biobank were matched 4:1 with cases based on genomic similarity. A curated gene list was comprised of 46 genes associated with CM. A second gene list included 102 genes associated with CM or MC in the ClinVar database. The prevalence of variants was compared using Chi-Square or Fisher’s exact tests. Results: A total of 32 patients were identified with DCM secondary to MC. Median enrollment age was 1.5 years (IQR 0.4-10.3) and 53% were female. There was no family history in 88%. The prevalence of P/LP variants from the curated list was 34.4% in cases compared to 4.7% in controls (p&lt;0.001). The prevalence of P/LP variants from the ClinVar list was 31.3% in cases compared to 6.3% in controls (p&lt;0.001). Variants were identified in 8 genes: ABCC9, ANKRD1, MYH6, MYH7, MYPN, PLN, TPM1 and TTN. No P/LP variants were found in desmosomal genes. The prevalence of variants was higher but not significantly different in older children compared to infants (45.0% vs 16.6%, p=0.1). The prevalence of variants in MC was similar to previously reported rates in all causes of DCM (34.4% vs 28.8%, p=0.5). Only 22% of cases received clinical genetic testing. Conclusion: Approximately 1 in 3 children with DCM secondary to MC carry a CM-associated P/LP variant, which is significantly higher than the prevalence in healthy controls. Given the high prevalence, routine genetic testing should be considered in this population.

Training, practice, and career considerations in forensic psychology: results from a field survey of clinical and non-clinical professionals in the United States

The current field survey describes the identities, training, practices, and careers of 351 U.S. forensic psychologists. Findings are presented for clinical forensic psychologists (n = 323) with additional consideration for those working in institutions (n = 119), private practice (n = 107), or both (n = 90), and separately for non-clinical forensic psychologists (n = 35). The sample was predominantly middle-aged, White, and female. Participants reported various training paths to the field, and professional settings and activities in the field. Student loan debt was common and significant in clinical Forensic psychologists. Income was generally high, with trends in higher incomes for private practice, board certification, urban areas, and certain geographic regions. Gendered income disparities were common, particularly among those later in their careers and in private practice, with relative parity only observed among early-career clinical forensic psychologists in institutions. Career satisfaction was generally high, with some important barriers noted. Overall, the limited representation of those with historically marginalized cultural identities restricted further consideration and understanding of these important factors in the field. Additional data and discussion are provided for these and other areas of demographics and lived experiences, training and related financial considerations, professional practices (including settings, activities, and clinical test use), and career considerations (including income, benefits, retirement planning, and satisfaction). Together, these data and related discussions offer important insights for prospective and current trainees entering the field, professionals seeking to navigate and advance their careers, and field leaders aiming to contribute to the ongoing development of forensic psychology.

Smartcard: an integrated approach for contaminant monitoring, from field to laboratory.

Effective food safety monitoring requires a multi-step approach from farm to fork, involving different methods, ranging from convenient screening devices to sophisticated laboratory confirmatory testing. However, sample transportation to routine laboratories is time-consuming and expensive. Simplified on-site sampling followed by laboratory analysis offers a potential solution. Dried blood spot (DBS) cards ensure stability and ease of sample transportation and are used in clinical testing. However, the applicability of such an approach could be broader and include the storage of dried extract from more complex (solid) matrices. Therefore, a simplified approach is presented here, using DBS cards for on-site sampling and subsequent laboratory confirmation for food contaminants. To achieve this, an analytical tool (Smartcard) was designed using 3D-printing technology. As a proof of concept, the approach was applied to detect the pesticide fipronil, which is widely used in ornamental flower production to limit pests and on poultry farms. The Smartcard can securely store the sample extracts on a DBS card (dried extract spot (DExS) card), incorporate the lateral flow immunoassay (LFIA) and immediately provide an estimate of contamination levels. After simplified in-syringe extraction of the sample, the LFIA allows direct screening of fipronil (half maximum inhibitory concentration of 6.5µg/l with calibration standards), and the same sample extract can be directly applied to the DExS card for storage and transport to the laboratory, where analyte re-extraction and instrumental analysis is performed using ultra high-pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) detecting fipronil down to 0.8µg/kg.