Sensitive Screening Research Articles

Neuropsychiatric Profiles and Cerebral Amyloid Burden in Adults without Dementia

Plain Language SummaryThis study examines how patients’ and their caregivers’ report of neuropsychiatric symptoms are associated with amyloid burden, of the primary markers of risk for amyloid burden, in older adults without dementia. Amyloid burden was measured using a PET-CT scan, and neuropsychological symptoms were measured with a self-reported and an informant-reported questionnaire. We found that neuropsychiatric symptoms were associated with amyloid burden in older adults without dementia, and these relationships were stronger in older adults with greater cognitive and functional impairment. In particular, caregivers’ report of anxiety, depression, and irritability and patients’ report of cognitive concerns were associated with greater amyloid burden. Neuropsychiatric symptoms, observed by both the patient and the informant, may be promising first identifiers of the neuropathology associated with Alzheimer’s disease and related dementias. Although neuropsychiatric symptoms have been characterized in persons with dementia, we do not yet have a clear understanding of how neuropsychiatric symptoms appear in non-dementia stages or which instruments may be the most sensitive screening tools for neuropsychiatric symptoms in older adults without dementia. These older adults without dementia may exist in a window of opportunity for behavioral and pharmacologic interventions that may prevent or slow clinical progression.

Primary sclerosing cholangitis-Diagnosis and treatment 2024

The etiology of primary sclerosing cholangitis (PSC) remains unclear, which explains in part the lack of acausal treatment. The differential diagnostic distinction from the even rarer immunoglobulin 4 (IgG4)-associated cholangitis (IAC) is becoming increasingly more successful. Advances in the understanding of different clinical courses, improvements in noninvasive diagnostics through modern magnetic resonance imaging (MRI) and the introduction of liver elastography have led to the development of improved prognostic models. The evidence for recommendations on medicinal (e.g., ursodeoxycholic acid) or endoscopic treatment (e.g., balloon dilatation and/or stent insertion) for PSC is still low. In contrast, the long-term results of liver transplantation in PSC patients are constantly improving. Due to the lack of highly sensitive and specific screening methods the early recognition of cholangiocellular carcinoma (CCC) as the most important complication is rarely successful. The continuous improvement of endoscopic retrograde cholangiopancreatography (ERCP) and direct cholangioscopy in combination with molecular biological and fluorescence in situ hybridization (FISH) analyses of bile duct tissue samples are promising for refined diagnostics. Due to the significantly increased risk of colorectal cancer, an annual colonoscopy is recommended in the presence of inflammatory bowel disease. Improvement of the early diagnostics of PSC and successful testing of new treatment strategies raise hope for acontinuous improvement in the medical support of these complex patients.

Prevalence and Correlates of Depression Among Pregnant Women at King Abdulaziz Medical City: A Tertiary Hospital in Riyadh, Saudi Arabia.

Women have a higher likelihood of experiencing depression during pregnancy due to the significant physiological and mental changes that occur during this critical period. The frequency of antenatal depression varies globally according to socioeconomic, healthcare, and cultural influences. The objective of this study is to investigate the prevalence of depression among pregnant women in Riyadh, Saudi Arabia. Women who were pregnant and who had undergone screening for depression were included in this cohort study that was conducted at King Abdulaziz Medical City (KAMC). Using a non-probability convenience sample technique, data was obtained from the hospital record system. Statistical significance was determined using Fisher's exact test and student's t-test, which analyzed demographic, clinical, demographic,and obstetric information. Significance was determined by a P-value that was lower than 0.05. Among 367 people surveyed, the prevalence of depression was 2.5%. This is much lower than rates seen both globally and in Saudi Arabia. The majority were married and non-smokerswith a high post-delivery BMI. A significant association was observed between depression and previous psychiatric diagnoses, while no significant relationships were found with gestational age, complications, chronic illnesses, or referral sources. The research shows that the rate of perinatal depression among women in Riyadh is much lower than theaverage, highlighting the critical role of cultural factors and the need for validated, culturally sensitive screening tools. Recommendations for future research include longitudinal studies and the development of culturally tailored interventions to enhance the detection and management of depression during pregnancy, integrating mental health care into routine antenatal services.

Bone scan findings of Paget’s disease of bone in patients with VCP Multisystem Proteinopathy 1

Multisystem Proteinopathy 1 (MSP1) disease is a rare genetic disorder caused by mutations in the Valosin-Containing Protein (VCP) gene with clinical features of inclusion body myopathy (IBM), frontotemporal dementia (FTD), and Paget’s disease of bone (PDB). We performed bone scan imaging in twelve patients (6 females, 6 males) with confirmed VCP gene mutation six (50%) of which has myopathy alone, four (33%) with both PDB and myopathy, and two (15%) were presymptomatic carriers. We aim to characterize the PDB in diagnosed individuals, and potentially identify PDB in the myopathy and presymptomatic groups. Interestingly, two patients with previously undiagnosed PDB had positive diagnostic findings on the bone scan and subsequent radiograph imaging. Among the individuals with PDB, increased radiotracer uptake of the affected bones were of typical distribution as seen in conventional PDB and those reported in other MSP1 cohorts which are the thoracic spine and ribs (75%), pelvis (75%), shoulder (75%) and calvarium (15%). Overall, we show that technetium-99m bone scans done at regular intervals are a sensitive screening tool in patients with MSP1 associated VCP variants at risk for PDB. However, diagnostic confirmation should be coupled with clinical history, biochemical analysis, and skeletal radiographs to facilitate early treatment and prevention complications, acknowledging its limited specificity.

Sensitive bioluminescence imaging of cryptococcosis in Galleria mellonella improves antifungal screening under in vivo conditions

ABSTRACT Cryptococcus neoformans is an environmental yeast that primarily affects immunocompromised individuals, causing respiratory infections and life-threatening meningoencephalitis. Treatment is complicated by limited antifungal options, with concerns such as adverse effects, dose-limiting toxicity, blood–brain barrier permeability, and resistance development, emphasizing the critical need to optimize and expand current treatment options against invasive cryptococcosis. Galleria mellonella larvae have been introduced as an ethical intermediate for in vivo testing, bridging the gap between in vitro antifungal screening and mouse studies. However, current infection readouts in G. mellonella are indirect, insensitive, or invasive, which hampers the full potential of the model. To address the absence of a reliable non-invasive method for tracking infection, we longitudinally quantified the cryptococcal burden in G. mellonella using bioluminescence imaging (BLI). After infection with firefly luciferase-expressing C. neoformans, the resulting bioluminescence signal was quantitatively validated using colony-forming unit analysis. Longitudinal comparison of BLI to health and survival analysis revealed increased sensitivity of BLI in discriminating cryptococcal burden during early infection. Furthermore, BLI improved the detection of treatment efficacy using first-line antifungals, thereby benchmarking this model for antifungal testing. In conclusion, we introduced BLI as a real-time, quantitative readout of cryptococcal burden in G. mellonella over time, enabling more sensitive and reliable antifungal screening.

Outer-Surface Functionalized Solid-State Nanochannels for Enhanced Sensing Properties: Progress and Perspective.

Solid-state nanochannel-based sensing systems have been established as vigorous tools for sensing plentiful biomarkers due to their label-free, highly sensitive, and high-throughput screening. However, research on solid-state nanochannels has predominantly centered on the functional groups modified on the inner wall, neglecting investigations into the outer surface. Actually, the outer surface, as a part of the nanochannels, also plays a key role in regulating ionic current. When the target nears the entrance of the nanochannel and prepares to pass through, it would also interact with functional groups located on the nanochannel's outer surface, leading to subsequent alterations in the ionic current. Recently, the probes on the outer surface have experimentally demonstrated their ability to independently regulate ionic current, unveiling advantages in in situ target detection, especially for targets larger than the diameter of the nanochannels that cannot pass through them. Here, we review the progress over the past decade in nanochannels featuring diverse outer-surface functionalization aimed at enhanced sensing performance, including charge modification, wettability adjustment, and probe immobilization. In addition, we present the promises and challenges posed by outer-surface functionalized nanochannels and discuss possible directions for their future deployments.

Highly Sensitive and Rapid Screening Technique for the Detection of Organophosphate Pesticides and Copper Compounds Using Bifunctional Recombinant TrxA-PvCarE1.

Enabling the detection of organophosphate pesticide (OP) residues through enzyme inhibition-based technology is crucial for ensuring food safety and human health. However, the use of acetylcholinesterase, the primary target enzyme for OPs, isolated from animals in practical production poses challenges in terms of sensitivity and batch stability. To address this issue, we identified a highly sensitive and reproducible biorecognition element, TrxA-PvCarE1, derived from red kidney beans and successfully overexpressed it in Escherichia coli. The resulting recombinant TrxA-PvCarE1 exhibited remarkable sensitivity toward 10 OPs, surpassing that of commercial acetylcholinesterase. Additionally, this approach demonstrated the capability to simultaneously detect copper compounds with high sensitivity, expanding the range of pesticides detectable using the traditional enzyme inhibition method. Spiking recovery tests conducted on cowpea and carrot samples verified the suitability of the TrxA-PvCarE1-based technique for real-life sample analysis. In summary, this study highlights a promising comprehensive candidate for the rapid detection of pesticide residues.

Economic evaluation for medical artificial intelligence: accuracy vs. cost-effectiveness in a diabetic retinopathy screening case

Artificial intelligence (AI) models have shown great accuracy in health screening. However, for real-world implementation, high accuracy may not guarantee cost-effectiveness. Improving AI’s sensitivity finds more high-risk patients but may raise medical costs while increasing specificity reduces unnecessary referrals but may weaken detection capability. To evaluate the trade-off between AI model performance and the long-running cost-effectiveness, we conducted a cost-effectiveness analysis in a nationwide diabetic retinopathy (DR) screening program in China, comprising 251,535 participants with diabetes over 30 years. We tested a validated AI model in 1100 different diagnostic performances (presented as sensitivity/specificity pairs) and modeled annual screening scenarios. The status quo was defined as the scenario with the most accurate AI performance. The incremental cost-effectiveness ratio (ICER) was calculated for other scenarios against the status quo as cost-effectiveness metrics. Compared to the status quo (sensitivity/specificity: 93.3%/87.7%), six scenarios were cost-saving and seven were cost-effective. To achieve cost-saving or cost-effective, the AI model should reach a minimum sensitivity of 88.2% and specificity of 80.4%. The most cost-effective AI model exhibited higher sensitivity (96.3%) and lower specificity (80.4%) than the status quo. In settings with higher DR prevalence and willingness-to-pay levels, the AI needed higher sensitivity for optimal cost-effectiveness. Urban regions and younger patient groups also required higher sensitivity in AI-based screening. In real-world DR screening, the most accurate AI model may not be the most cost-effective. Cost-effectiveness should be independently evaluated, which is most likely to be affected by the AI’s sensitivity.

Performance of aldosterone-to-renin ratio before washout of antihypertensive drugs in screening of primary aldosteronism.

The aim of this study is to evaluate performance of aldosterone-to-renin ratio (ARR) before washout of antihypertensive drugs as a screening test for primary aldosteronism (PA). This retrospective analysis included consecutive patients suspected of having secondary hypertension during a period from January 2017 to May 2022 at authors' institute. For inclusion in the final analysis, ARR must be available prior to as well as after discontinuation of antihypertensives. Patients with ARR ≥2.4(ng/dL)/(μIU/mL) after washout proceeded to confirmatory tests. Diagnosis of PA was established based on positive result of the confirmatory test. Diagnostic accuracy of ARR prior to the washout in predicting PA are shown as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The analysis included a total of 1306 patients [median age of 50.2 (41.0-59.0) years, 64.0% male]. Confirmatory tests showed PA in 215(16.5%) patients and essential hypertension (EH) in the remaining 1091(83.5%) patients. In comparison to the second screening test, the first screening test (before washout of antihypertensives) yielded lower plasma aldosterone and higher renin, and consequently lower ARR in both the PA and EH groups. At a cutoff of 0.7(ng/dL)/(μIU/ml), ARR before washout had 96.3% sensitivity, 61.2% specificity, 0.33 PPV and 0.99 NPV. At a lower cutoff of 0.5(ng/dL)/(μIU/ml), the sensitivity, specificity, PPV and NPV are 97.7%, 52.0%, 0.29 and 0.99. ARR prior to washout of antihypertensives is a sensitive screening test for PA. Washout of antihypertensives could be omitted and further investigation for PA is not warranted if ARR was ≤ 0.7(ng/dL)/(μIU/ml) before washout.

Dual-FRET aptasensor for rapid screening of Ochratoxin A in food samples

Simple, low cost, and sensitive OTA screening method is important for food safety control. The discovery of the OTA aptamer enabled the development of various aptasensors, but the structural change caused by target binding is not appreciable enough, thus limiting the sensitivity. The introduction of various nanomateirals could amplify the structure change, but such aptasensors are difficult to be standardized, thus is not suitable for screening analysis. Herein, we proposed a full DNA-based dual-FRET aptasensor, in which the aptamer was rigidified to amplify the OTA-induced structure change. Meanwhile, a dual FRET strategy was employed to increase the OTA detection sensitivity. Upon both experimental and theoretical selection, aptamer OBA33 was selected, leading to a detection limit of 2.1 nM that is lower than the limit set by Chinese National Food Safety Standard (12 nM), thus is appealing for screening of potential OTA-positive cases in a large number of rice samples. To facilitate rapid screening analysis, a mini 3D-printed sensor device was constructed by integrating LED excitation, cellphone camera image taking, and RGB extraction. Due to the technological maturity of DNA production, the proposed aptasensor could be easily standardized for fast OTA screening analysis (15 min).

Development of a Real-Time PCR Assay for the Early Detection of the Eucalyptus Pathogen Quambalaria eucalypti

Quambalaria eucalypti is a fungal pathogen that causes leaf spot, shoot blight, and stem canker on Eucalyptus spp. Early diagnosis of the disease is difficult, although the symptoms are clear in its advanced phase. To enable a rapid and sensitive screening of asymptomatic or latently infected plant material for Q. eucalypti, a SYBR green-based real-time PCR assay targeting the partial histone-H3 region was developed. The assay demonstrated specificity for Q. eucalypti, not showing cross-reactivity with other Quambalaria species or the other eucalyptus fungal pathogens tested. The primers developed in this study ensured high analytical sensitivity, allowing the detection of Q. eucalypti DNA concentrations as low as 10 fg DNA from asymptomatic plants. The robustness and efficacy of the assay was demonstrated by interlaboratory comparisons with similar results. This newly developed quantitative PCR assay can be used for more comprehensive epidemiological investigations, testing the plant material in known Q. eucalypti distribution areas for early management strategies, or collecting data for resistance breeding programs.

“I Wish I Had That!”: A Qualitative Analysis of Psychosocial Treatment Preferences Among Young Adults With Recent Concussion and Anxiety

ObjectiveTo assess psychosocial treatment preferences and factors that may affect treatment participation among young adults with a recent concussion and co-occurring anxiety. DesignIn-depth, semi-structured individual qualitative interviews, followed by thematic analysis using a hybrid deductive-inductive approach. SettingAcademic medical center in the US Northeast. ParticipantsSeventeen young adults (18-24y) who sustained a concussion within the past 3-10 weeks and reported at least mild anxiety (≥5 on the Generalized Anxiety Disorder-7 questionnaire). InterventionsNot applicable. Main Outcome MeasuresPrimary outcomes include preferences for program content (eg, topics and skills), delivery modality, format, and barriers and facilitators to participation. ResultsWe identified 4 domains characterizing participants’ perceptions of and preferences for treatment. (1) Program content: Participants preferred a program early after injury that included psychoeducation and coping skills (eg, activity pacing, deep breathing, mindfulness). (2) Therapeutic processes: Participants preferred a person-centered approach in which clinicians normalized anxiety postconcussion and reassured them of recovery. (3) Program logistics: Participants endorsed that a brief, virtual program would be acceptable. They preferred access to program components through multiple modalities (eg, audio, video) and accommodations to manage concussion symptoms. (4) Barriers and facilitators to participation: Barriers included acute concussion symptoms (eg, screen sensitivity), time constraints, and forgetting sessions. Facilitators included a program that is flexible (format, scheduling), personalized (self-chosen mode for reminders, measure of accountability), and accessible (ie, advertising through health care professionals or social media). ConclusionsParticipants need psychosocial support that normalizes their experiences and provides education and coping tools. Treatments should be accessible, flexible, and person centered. Psychosocial treatments meeting these preferences may help optimize the recovery of young adults with recent concussion and anxiety.

Factors related to changes in severity among adult and older adult patients at an internal medicine department clinic: an embedded mixed-method study

The changes in aging plus the pathology of diseases can influence the changes in severity levels. This study aimed to examine the changes in levels of severity in patients while waiting to see a doctor. The study was conducted at an outpatient clinic in northeastern Thailand with a total of 421 patients who were assessed twice for levels of severity using the Emergency Severity Index. The 38 triage nurses screened patients, and 18 were interviewed when severity level changes were observed. Data were collected April 1–30, 2021. Quantitative data were analyzed by Chi-square test, Fisher's exact test, and logistic regression. Qualitative data were analyzed by content analysis. Most patients were female, between 18 and 59 years old. Most patients did not change their level of severity. However, increasing levels of severity were found in older adults. Factors related to the changes in severity levels were age group, chronic disease, chief complaint, educational level, the duration of travel to the outpatient clinic, type of vehicle, aging process and comorbidity, pathology of diseases, reassessment interval, nurse's experience, bypassing the patient triage process, patient's self-preparation, management of triage nurses, and assignment of direct healthcare staff until the end of the treatment. Increased severity was more frequently found in older adults, so closely monitored during waiting times at a clinic is needed. Setting rescreening as a policy and having sensitive screening guidelines and tools specific to older adults would contribute to early detection and immediate treatment of deteriorating symptoms and illness to help reduce complications and morbidity.Trial registration: https://osf.io/fp3j2.

Uncovering receptor-ligand interactions using a high-avidity CRISPR activation screening platform.

The majority of clinically approved drugs target proteins that are secreted or cell surface bound. However, further advances in this area have been hindered by the challenging nature of receptor deorphanization, as there are still many secreted and cell-bound proteins with unknown binding partners. Here, we developed an advanced screening platform that combines CRISPR-CAS9 guide-mediated gene activation (CRISPRa) and high-avidity bead-based selection. The CRISPRa platform incorporates serial enrichment and flow cytometry-based monitoring, resulting in substantially improved screening sensitivity for well-known yet weak interactions of the checkpoint inhibitor family. Our approach has successfully revealed that siglec-4 exerts regulatory control over T cell activation through a low affinity trans-interaction with the costimulatory receptor 4-1BB. Our highly efficient screening platform holds great promise for identifying extracellular interactions of uncharacterized receptor-ligand partners, which is essential to develop next-generation therapeutics, including additional immune checkpoint inhibitors.

Rapid antibiotic screening based on E. coli apoptosis using a potentiometric sensor array

Phenotypic antimicrobial susceptibility testing enables reliable antibiotic screening but requires multiple strategies to identify each phenotypic change induced by different bactericidal mechanisms. Bacteria apoptosis with typical phenotypic features has never been explored for antibiotic screening. Herein, we developed an antibiotic screening method based on the measurement of antibiotic-induced phosphatidylserine (PS) exposure of apoptotic bacteria. Phosphatidylserine externalization of E. coli that can be widely used as an apoptosis marker for antibiotics with different antibacterial mechanisms was explored. A positively charged PS-binding peptide was immobilized on magnetic beads (MBs) to recognize and capture apoptotic E. coli with PS externalization. Apoptotic E. coli binding led to the charge or charge density change of MBs-peptide, resulting in a potential change on a magneto-controlled polymeric membrane potentiometric sensor. Based on the detection of apoptotic E. coli killed by antibiotics, antibiotic screening for different classes of antibiotics and silver nanoparticles was achieved within 1.5 h using a potentiometric sensor array. This approach enables sensitive, general, and time-saving antibiotic screening, and may open up a new path for antibiotic susceptibility testing.

Screening State of Play: The Biosecurity Practices of Synthetic DNA Providers.

Synthetic DNA technology is rapidly emerging as a key driver of innovation in the fields of medicine, biotechnology, and more. But it also poses significant risk, particularly in lowering barriers to the production of dangerous pathogens and toxins. At present, oversight of this technology is voluntarily coordinated among synthetic DNA providers and stakeholders, and detailed understanding of security processes, infrastructures, and insights from these providers is imperative to understand how to best mitigate the inherent risks of this technology. In this study, we aimed to determine the trends, outliers, strengths, and gaps in current DNA provider security practices through a broad survey of the gene synthesis field. We interviewed synthetic DNA providers and stakeholders about their customer and sequence screening procedures. Respondents were divided into groups based on membership in the International Gene Synthesis Consortium, nationality, whether they were a new or established company, and whether they synthesize de novo DNA or not. We then performed meta-analysis and intergroup analysis to elucidate larger trends and points of variance. In total, we interviewed 18 companies. We found that synthetic DNA providers and stakeholders tend to operate under a "zero-trust model" for screenings and utilize common governmental and private resources to navigate international import/export policies. Major variabilities were identified in the sensitivity of screening, monitoring and evaluation practices, screening pipelines, and approaches to synthetic oligonucleotide screening. In addition, we identified a significant vulnerability of lacking awareness among providers of formal law enforcement reporting procedures. Collectively, we observed significant heterogeneity in security practice throughout the field, reflective of the current lack of codified oversight for DNA synthesis. The results presented in this study provide insight into the specifics, strengths, and shortcomings of current DNA provider security practices, and are important considerations for the biosecurity community in ongoing deliberations of if, when, and how to approach oversight of synthetic DNA technology.

Analytical and clinical validation of a multiplex PCR assay for detection of Neisseria gonorrhoeae and Chlamydia trachomatis including simultaneous LGV serotyping on an automated high-throughput PCR system.

For effective infection control measures for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), a reliable tool for screening and diagnosis is essential. Here, we aimed to establish and validate a multiplex PCR assay on an automated system using a dual-target approach for the detection of CT/NG and differentiation between lymphogranuloma venereum (LGV) and non-LGV from genital and extra-genital specimens. Published primer/probe sets (CT: pmpH, cryptic plasmid; NG: porA, opa) were modified for the cobas 5800/6800/8800. Standards quantified by digital PCR were used to determine linearity and lower limit of detection (LLoD; eSwab, urine). For clinical validation, prospective samples (n = 319) were compared with a CE-marked in vitro diagnostics (CE-IVD) assay. LLoDs ranged from 21.8 to 244 digital copies (dcp)/mL and 10.8 to 277 dcp/mL in swab and urine, respectively. A simple linear regression analysis yielded slopes ranging from -4.338 to -2.834 and Pearson correlation coefficients from 0.956 to 0.994. Inter- and intra-run variability was <0.5 and <1 cycle threshold (ct), respectively. No cross-reactivity was observed (n = 42). Clinical validation showed a sensitivity of 94.74% (95% confidence interval (CI): 87.23%-97.93%) and 95.51% (95% CI: 89.01%-98.24%), a specificity of 99.59% (95% CI: 97.71%-99.98%) and 99.57% (95% CI: 97.58%-99.98%), positive predictive values of 89.91% (estimated prevalence: 3.7%; 95% CI: 80.91%-95.6%) and 88.61% (estimated prevalence: 3.4%; 95% CI: 80.18%-94.34%), and negative predictive values of 99.81% (95% CI: 98.14%-100%) and 99.85% (95% CI: 98.14%-100%) for the detection of CT and NG, respectively. In conclusion, we established a dual-target, internally controlled PCR on an automated system for the detectiwon of CT/NG from genital and extra-genital specimens. Depending on local regulations, the assay can be used as a screening or a confirmatory/typing assay.IMPORTANCEChlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) represent a major global health burden, with the World Health Organization estimating that >128 million and >82 million people, respectively, were newly infected in 2020. For effective infection control measures, a reliable tool for sensitive diagnosis and screening of CT/NG is essential. We established a multiplex PCR assay for the detection of CT/NG and simultaneous discrimination between lymphogranuloma venereum (LGV) and non-LGV strains, which has been validated for genital and extra-genital specimens on a fully automated system. To increase assay sensitivity, a dual-target approach has been chosen for both pathogens. This strategy reduces false-positive results in oropharyngeal swabs due to the detection of commensal N. species that may harbor NG DNA fragments targeted in the PCR due to horizontal gene transmission following previous infection. In sum, the established assay provides a powerful tool for use as either a screening/diagnostic or a typing/confirmatory assay.

Unveiling Epigenetic Vulnerabilities in Triple-Negative Breast Cancer through 3D Organoid Drug Screening.

Triple-negative breast cancer (TNBC) poses a therapeutic challenge due to its aggressive nature and lack of targeted therapies. Epigenetic modifications contribute to TNBC tumorigenesis and drug resistance, offering potential therapeutic targets. Recent advancements in three-dimensional (3D) organoid cultures, enabling precise drug screening, hold immense promise for identifying novel compounds targeting TNBC. In this study, we established two patient-derived TNBC organoids and implemented a high-throughput drug screening system using these organoids and two TNBC cell lines. Screening a library of 169 epigenetic compounds, we found that organoid-based systems offer remarkable precision in drug response assessment compared to cell-based models. The top 30 compounds showing the highest drug sensitivity in the initial screening were further assessed in a secondary screen. Four compounds, panobinostat, pacritinib, TAK-901, and JIB-04, targeting histone deacetylase, JAK/STAT, histone demethylases, and aurora kinase pathways, respectively, exhibited potent anti-tumor activity in TNBC organoids, surpassing the effect of paclitaxel. Our study highlights the potential of these novel epigenetic drugs as effective therapeutic agents for TNBC and demonstrates the valuable role of patient-derived organoids in advancing drug discovery.

Grading Acanthosis Nigricans Using a Smartphone and Color Analysis: A Novel Noninvasive Method to Screen for Impaired Glucose Tolerance and Type 2 Diabetes.

The objective of this study was to develop ANcam, a novel method for identifying acanthosis nigricans (AN) using a smartphone camera and computer-aided color analysis for noninvasive screening of people with impaired glucose tolerance (IGT). Adult and juvenile participants with or without diagnosed type 2 diabetes were recruited in Trinidad and Tobago. After obtaining informed consent, participants' history, demographics, anthropometrics, and A1C were collected and recorded. Three subject matter experts independently graded pictures of the posterior neck and upper back using the ANcam smartphone application and Burke methods. A correlation matrix investigated 25 color channels for association with hyperpigmentation, and the diagnostic thresholds were determined with a receiver operating characteristic curve analysis. For the 227 participants with captured images and A1C values, the cyan/magenta/yellow/black (CMYK) model color channel CMYK_K was best correlated with IGT at an A1C cutoff of 5.7% (39 mmol/mol) (R = 0.45, P <0.001). With high predictive accuracy (area under the curve = 0.854), the cutoff of 7.67 CMYK_K units was chosen, with a sensitivity of 81.1% and a specificity of 70.3%. ANcam had low interrater variance (F = 1.99, P = 0.137) compared with Burke grading (F = 105.71, P <0.001). ANcam detected hyperpigmentation on the neck at double the self-reported frequency. Elevated BMI was 2.9 (95% CI 1.9-4.3) times more likely, elevated blood pressure was 1.7 (95% CI 1.2-2.4) times more likely, and greater waist-to-hip ratio was 2.3 (95% CI 1.4-3.6) times more likely with AN present. ANcam offers a sensitive, reproducible, and user-friendly IGT screening tool to any smartphone user that performs well with most skin tones and lighting conditions.

Clinical trial and performance evaluation of the Wantai HBsAg (CMIA) diagnostic kit for screening blood donors in China

In China, according to the ‘Technical Operating Procedures for Blood Stations (2019 Edition),’ blood stations are authorized to utilize Chemiluminescence Immunoassay (CLIA) to detect pathogen markers linked with transfusion-transmissible infections. However, currently, there is no approved CLIA reagent for the screening of blood-borne diseases in China, specifically for the detection of Hepatitis B surface antigen. The objective of this research project is to conduct a comprehensive evaluation of the performance of the Wantai Chemiluminescent Microparticle Hepatitis B surface antigen reagent. This study evaluates the performance of the Wantai Chemiluminescent Microparticle Immunoassay (CMIA) on the Wan200 + analyzer in screening for Hepatitis B Surface Antigen (HBsAg) in blood samples. The clinical trial component of this evaluation is included as part of the documentation submitted to the National Medical Products Administration (NMPA) of China for the approval of blood screening reagents. The evaluation plan of this study encompasses two main components: clinical trials and performance assessment. We adopted a controlled trial design, utilizing the WanTai Chemiluminescent Microparticle Immunoassay (CMIA) on the Wan200 + analyzer and the Enzyme-Linked Immunosorbent Assay (ELISA) to screen for Hepatitis B Surface Antigen (HBsAg) in routine blood donor samples and reference serum panel samples. To ensure the accuracy of the screening, we additionally employed Abbott's ELISA reagents and HBV DNA for validation. The assessment primarily focused on key performance indicators such as sensitivity, specificity, and analytical sensitivity. Moreover, this clinical trial data has been included as part of the submission to China's National Medical Products Administration (NMPA). In the clinical trials of this study, a total of 10,470 blood donor samples underwent simultaneous testing using both CMIA and ELISA methods. Across two clinical trials, there was remarkable concordance between CMIA and the two ELISA reagents, with Kappa values exceeding 0.82. Among the 269 samples that were double-reactive in the enzyme immunoassay (ELISA) tests, CMIA exhibited a 100% reactivity detection rate. However, CMIA produced 14 and 6 false-positive results in the respective clinical trials, resulting in specificities of 99.73% and 99.89%. In contrast, the specificities for Wantai ELISA and Xin Chuang ELISA were both greater than 99.94%.When testing samples in the gray zone serum plates, CMIA's detection limit significantly exceeded that of the two ELISA assays. CMIA had a detection cutoff of 0.05 IU/mL, while the two ELISA reagents had cutoffs of 0.1 IU/mL and 0.09 IU/mL, respectively. CMIA's detection limits for the adr and adw subtypes were 0.05 IU/mL, and for the ay subtype, it was 0.1 U/mL. The detection limit for 10 HBV mutant samples was 0.5 U/mL. In 165 cases where ELISA tested negative but HBV DNA tested positive, CMIA detected 5 HBsAg-positive samples. This study evaluated the performance of the Wantai CMIA in screening for HBsAg among blood donors. The results demonstrate outstanding performance of CMIA in both clinical trials and performance assessments, detecting all true positive samples with a sensitivity of 100%. It exhibits excellent concordance with the two ELISA assays. Of particular note is its superiority in early detection of HBsAg in the screening of early-stage hepatitis B infections, reducing the window period compared to ELISA. CMIA achieves a specificity exceeding 99.73% for negative blood donors, aligning with the European Union's standards for blood screening assay specificity. In summary, Wantai's CMIA displays high sensitivity and specificity in blood donor screening, making it suitable for screening blood donors in China.