Specific Screening Research Articles

Evaluation of the mindray CL900i CLIA HIV Ag/Ab combo assay for sensitive and specific HIV screening compared to established methods.

Architect-HIV Ag/Ab combo chemiluminescence assay is globally recognized for its sensitivity but has a notable false-positive rate. In this study,we aim to evaluate the performance of a new cost-effective screening alternative, the chemiluminescence Ag/Ab combo assay (CL-900i-HIV) from Mindray, China. We selected 195 archived samples categorized according to the INNO-LIA™ HIV I/II, the gold standard confirmatory assay. These samples included true positive (n = 38; positive by Architect-HIV & INNO-LIA-HIV), true negative (n = 101; negative by Architect-HIV & INNO-LIA-HIV), false positive (n = 20; positive by Architect-HIV & negative by INNO-LIA-HIV), and indeterminate results (n = 26). We tested all samples using the Mindray CL-900i-HIV and all positive Architect-HIV samples (n = 80) were confirmed by PCR. Compared to INNO-LIA™ HIVI/II line immunoassay confirmatory assay, Mindray CL-900i-HIV demonstrated a sensitivity of 100% (95% CI 90.7-100), specificity of 100% (95% CI 97.0-100), overall percent agreement (OPA) of 100% (95% CI 97.7-100.0), and perfect agreement with the INNO-LIA confirmatory assay (κ = 1.00). Additionally, Mindray's CL-900i-HIV exhibited a significantly lower false-positive rate (8.75%) compared to Architect-HIV's (55%). Mindray CL900i demonstrated high sensitivity and very low false-positive rate, thus, has the potential to serve as an excellent, cost-effective surrogate for HIV screening, overcoming the limitations of existing automated assays.

Sustainable Development Strategies and Good Agricultural Practices for Enhancing Agricultural Productivity: Insights and Applicability in Developing Contexts—The Case of Angola

In general, agricultural productivity in Angola is low due to the limited awareness among stakeholders regarding sustainable development strategies (DSs) and good agricultural practices (GAPs) that could be adjusted to local crops, soil types, and climatic conditions. A structured approach was followed to develop a systematic literature review (SLR) that can address this gap by examining how DSs and GAPs may be adapted for Angola’s context to encourage sustainable agricultural development. Key steps included the selection and exclusion of literature from primary scientific databases based on specific screening indicators such as the publication date, language, relevance to DSs and GAPs, and geographic focus on developing or developed nations with comparable agricultural challenges. The initial search resulted in 11,392 articles, of which 4257 met the primary selection criteria. After further screening for relevance and availability, 98 articles were shortlisted, and 15 studies were ultimately included for in-depth analysis. This strict screening process ensured the inclusion of studies most applicable to Angola’s agricultural context. The key research findings indicate that certain DSs and GAPs have high adaptability potential for Angola. The findings emphasise practices such as drip irrigation and inorganic fertilisation, which are widely implemented in both developed and developing countries due to their efficiency in resource-limited environments. Additional strategies, such as water management systems, organic composting, and agroforestry practices, demonstrate significant potential to enhance soil fertility, water efficiency, and crop resilience against climate variability. By identifying these practices and strategies, this study provides a basic framework for policymakers in Angola to develop targeted implementation guidelines, fostering sustainable agricultural growth and resilience in the face of climatic challenges. Thus, this review contributes to the scientific and practical understanding of sustainable agriculture in developing countries, offering critical insights that support Angola’s efforts to achieve greater self-sufficiency and economic stability through sustainable agricultural practices.

Pregnant women and healthcare workers' perceptions on tuberculosis and screening: a cross-sectional study in Indonesia.

There is a scarcity of studies regarding the obstacles in tuberculosis (TB) screening in pregnant women. This study aimed to assess the perceptions of TB as a disease and TB screening among pregnant women and healthcare workers, describe pregnant women's perceptions on specific TB screening methods and explore associations between the perceptions of TB with the intention to have TB screening by pregnant women. A cross-sectional study was conducted at six primary healthcare centres in Yogyakarta Municipality, Indonesia among 240 pregnant women and 126 healthcare workers interviewed with a structured questionnaire about their perceptions. Perceptions were analysed as percentages and associated factors were tested by multivariable logistic regression. Most pregnant women and healthcare workers supported TB screening in pregnant women based on their perceptions of the susceptibility to or severity of TB and the benefits and risks of TB screening. Women who perceived the high susceptibility of TB disease and the benefits of TB screening were significantly more likely to have high intentions to accept TB screening in the future. Pregnant women's perceptions of TB and TB screening influenced their intention to be screened; however, appropriate testing methods for universal TB screening in pregnant women in areas with a high prevalence of TB require further studies.

Rapid parallel reconstruction and specificity screening of hundreds of T cell receptors.

The ability to screen the reactivity of T cell receptors (TCRs) is essential to understanding how antigen-specific T cells drive productive or dysfunctional immune responses during infections, cancer and autoimmune diseases. Methods to profile large numbers of TCRs are critical for characterizing immune responses sustained by diverse T cell clones. Here we provide a medium-throughput approach to reconstruct dozens to hundreds of TCRs in parallel, which can be simultaneously screened against primary human tissues and broad curated panels of antigenic targets. Using Gibson assembly and miniaturized lentiviral transduction, individual TCRs are rapidly cloned and expressed in T cells; before screening, TCR cell lines undergo combinatorial labeling with dilutions of three fluorescent dyes, which allows retrieval of the identity of individual T cell effectors when they are organized and tested in pools using flow cytometry. Upon incubation with target cells, we measure the upregulation of CD137 on T cells as a readout of TCR activation. This approach is scalable and simultaneously captures the reactivity of pooled TCR cell lines, whose activation can be deconvoluted in real time, thus providing a path for screening the reactivity of dozens of TCRs against broad panels of synthetic antigens or against cellular targets, such as human tumor cells. We applied this pipeline to systematically deconvolute the antitumoral and antiviral reactivity and antigenic specificity of TCRs from human tumor-infiltrating lymphocytes. This protocol takes ~2 months, from experimental design to data analysis, and requires standard expertise in cloning, cell culture and flow cytometry.

Family GH157 enzyme exhibits broad linkage tolerance and a dual endo/exo- β -glucanase activity on β-glucans

The structural and chemical diversity of β-glucans is reflected on the variety of essential biological roles tackled by these polysaccharides. This natural heterogeneity requires an elaborate assortment of enzymatic mechanisms to assemble, degrade or modify, as well as to extract their full biotechnological potential. Recent metagenomic efforts have provided an unprecedented growth in potential new biocatalysts, most of which remain unconfirmed or uncharacterized. Here we report the first biochemical and structural characterization of two bacterial β-glucanases from the recently created glycoside hydrolase family 157 (LaGH157 and BcGH157) and investigate their molecular basis for substrate hydrolysis. Structural analysis by X-ray crystallography revealed that GH157 enzymes belong to clan GH-A, possessing a (β/α)8-barrel fold catalytic domain, two β-sandwich accessory domains and two conserved catalytic glutamates residues, with relative positions compatible with a retaining mechanism of hydrolysis. Specificity screening and enzyme kinetics suggest that the enzymes prefer mixed-linkage glucans over β-1,3-glucans. Activity screening showed that both enzymes exhibit pH optimum at 6.5 and temperature optimum for LaGH157 and BcGH157 at 25 °C and 48 °C, respectively. Product analysis with HPAEC-PAD and LC-MS revealed that both enzymes are endo-1,3(4)-β-glucanases, capable of cleaving β-1,3 and β-1,4-linked glucoses, when preceded by a β-1,3 linkage. Moreover, BcGH157 needs a minimum of 4 subsites occupied for hydrolysis to occur, while LaGH157 only requires 3 subsites. Additionally, LaGH157 possesses exohydrolytic activity on β-1,3 and branching β-1,6 linkages. This unusual bifunctional endo-1,3(4)/exo-1,3–1,6 activity constitutes an expansion on our understanding of β-glucan deconstruction, with the potential to inspire future applications.

Wane-and-wax mechanism of nitrogenous disinfection byproducts with constant Cl/N peak under UV/chlorine treatment: Implication for new drinking water disinfection strategy

Nitrogenous disinfection byproducts (N-DBPs) are notorious for their serious health risks, yet nitrate (NO3-) mediates N-DBPs generation during UV/chlorine treatment remains unexplored. This study investigated the interaction of chlorine and NO3- on N-DBPs formation and developed a specific fragment-based screening method using UPLC-QTOF-MS to explore the underlying mechanism. Results showed that the chlorine-to-nitrogen (Cl/NO3--N) molar ratio significantly affects dichloroacetonitrile (DCAN) and dichloroacetamide (DCAM) generation, with peak concentrations at a Cl/NO3--N molar ratio of around 15. NO3- promotes the production of HO•, which positively correlates with DCAN and DCAM concentrations, also peaking at this ratio. Utilizing our developed method, three key hydroxyl-substituted intermediates that circumvent the previously reported “limiting-steps” in DCAN formation were identified. This reaction proceeds via a stepwise mechanism involving hydroxylation and chlorine substitution to produce hydroxyl-phenylacetonitrile and hydroxyl-chlorine-phenylacetonitrile. The conversion rate of hydroxyl-chlorine-phenylacetonitrile to DCAN was 8.6 times higher at Cl/NO3--N molar ratio of 15 compared to conditions without NO3-, attributed to the weakened bond strength of the side chain, as supported by density functional theory calculations. This study provides novel insights into the mechanistic pathways of DCAN and DCAM formation, critical for developing more effective drinking water disinfection technologies to control N-DBPs.

Variation in nutritional therapy practices: results of a survey on nutritional management of severe inflammatory bowel disease.

The optimal nutritional management during a severe flare of inflammatory bowel disease is uncertain. The goal of this study was to describe variations in nutritional practices between different countries, professions and types of hospitals, as well as between ulcerative colitis (UC) and Crohn's disease (CD). In this cross-sectional study, a novel questionnaire was distributed in the ECCO Congress 2022 and via ECCO country representatives. The survey was completed by 313 participants. In total, 68% of the respondents were physicians. No specific nutritional screening tool was used by 45% of respondents. Almost a quarter of respondents reported less than 25% of patients being assessed by a dietitian in the first 3 days of a flare. The most common form of nutritional therapy was oral nutritional supplements (ONS) with easy-to-digest food. Total parenteral nutrition (TPN) was used by 10% of respondents for UC patients and 7% for CD. Energy intake, stool frequency and inflammatory biomarkers were the most common factors in determining when to change nutritional therapy. There were significant differences between different countries and health care professions for all the outcomes (P < 0.05). Nutritional management did not generally vary according to hospital type (university vs. general). During the first 3 days of a flare, a diet consisting exclusively of ONS was significantly more frequently used for CD than UC (P = 0.018). Otherwise, similar nutritional therapy strategies were reported for CD and UC, including using TPN to a similar extent. There is significant variation in nutritional management practices. Country is the main determinant of differences in practice.

Delirium and Cognitive Screening in National Hip Fracture Registries: Scoping Review Protocol

Background Delirium and cognitive impairment are common in hip fracture populations and are associated with significant adverse patient outcomes. National hip fracture registries facilitate improvements in patient outcomes and care quality, such as reduced mortality and the development of specialist multidisciplinary services. However, there is substantial variation in the data collected and reported in relation to delirium and cognition, which impedes international comparison and may reduce quality of care. Objective This scoping review aims to identify delirium and cognition data items currently collected by hip fracture registries internationally, to identify associated registry guidance that exists for the administration of delirium and cognitive screening tools, and report outcomes of these data items across the most recently published annual reports of identified hip fracture registries. Methods This scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews (PRISMA-ScR). We will search the following databases: Medline Ovid; Embase; CINAHL EBSCOHost. Relevant websites such as the Fragility Fracture Network (FFN) will also be searched. Study selection and review will be carried out independently by two researchers, with discrepancies resolved by a third researcher. Data extraction and synthesis will be conducted by one reviewer and checked for accuracy and omissions by another. The scoping review findings will be informed and validated through engagement with the FFN Hip Fracture Audit Special Interest Group. Conclusion By identifying existing heterogeneity in delirium and cognitive screening tool use and administration, it is hoped that administration and specific screening tool use will become standardised to optimise comparability across countries and ensure that high quality and reliable data are included across international registry reports.

Multicenter Validation of the English Version of the Dépistage Cognitif de Québec: a Cognitive Screening Tool for Atypical Dementias.

Early detection of atypical dementia remains difficult partly because of the absence of specific cognitive screening tools. This creates undue delays in diagnosis and management. The Dépistage Cognitif de Québec (DCQ; dcqtest.org) was developed in French and later validated in participants with atypical syndromes. We report the validation of the English version. This multicentre prospective validation study was conducted in 10 centers across Canada and the United States on 260 English-speaking participants aged over 50. We translated and modified the original French DCQ to add targeted stimuli to the Visusopatial Index and social cognition vignettes to the Behavioral Index. A backward translation was performed and equivalence between languages was assessed by administering both tests to 30 bilingual participants. Mean DCQ total score (out of 100) was 95.0 (SD = 3.6). Spearman's correlation coefficient showed a strong and significant correlation (r = 0.49, p < .001) with the Montreal Cognitive Assessment. Test-retest reliability was good (Spearman's coefficient = 0.72, p < .001) and interrater reliability, excellent (intraclass correlation = 0.97, p < .001). Normative data shown in percentiles were stratified by age and education for a population-based sample of 260 English-speaking controls aged between 50 and 87years old. Similar to the French version, the English DCQ proved to be a valid cognitive screening test. The original version was very sensitive to detect atypical dementias such as primary progressive aphasias, Alzheimer's disease' variants and syndromes along the frontotemporolobar degeneration spectrum. This 20-min test can be administered à la carte and offers an alternative to detailed comprehensive neuropsychological evaluations.

Risk Factors for Developing Community-Acquired Hand Infections at a Large-Volume Urban Safety Net Hospital.

Hand infections represent a significant burden for both health care systems and their patients. Epidemiological understanding of community-acquired hand infections is limited. This study examined a cohort of hand infection patients at a large urban safety net hospital for characteristics that were associated with protective and/or risk factors for hand infections. We performed a retrospective chart review for all patients who required hand surgery consultation in the emergency department during a 1-year period (2021-2022). County-level population characteristics were obtained through the county-level data sources. We then performed a risk ratio (RR) analysis for demographic and socioeconomic characteristics. A total of 125 patients were included in the study cohort. Cisgender male (RR, 4.654; P < 0.001), Black (RR, 6.062; P < 0.001) and American Indian/Alaska Native (RR, 3.293; P = 0.041) patients were found to be overrepresented in our cohort when compared to county proportions, indicating an association with increased risk of hand infections. Patients between 35 and 49 years of age were also found to have an increased risk (RR, 1.679; P = 0.005). Age over 65 years, retirement, and employment were found to be protective factors (RR, 0.341 [P = 0.001]; RR, 0.397 [P = 0.043]; RR, 0.197 [P < 0.001]). In contrast, unemployment and unstable housing (unhoused or shelter) were found to have strong harmful risk for necessitating hand infection consults (RR, 7.587 [P < 0.001]; RR, 235.715 [P < 0.001]; RR, 29.990 [P < 0.001]). There are clear risk factors at play for hand infection incidence. We found that housing status, employment, race, gender, and age were some of the most important contributors for incidence. This information can assist clinicians and public officials in developing more specific screening algorithms and prevention tools to reduce systematic burden. Further studies are required to elucidate specific etiologies associated with hand infection risk.

Peculiarities of the dynamics of tuberculosis incidence in children in Ukraine

OBJECTIVE. To analyze the dynamics of the epidemiological situation with tuberculosis (TB) in children in Ukraine, taking into account the adverse effects of the coronavirus disease (COVID-19) pandemic and large-scale war. MATERIALS AND METHODS. The epidemiological and statistical indicators of TB incidence in Ukraine were analyzed. RESULTS. During 2022-2023, there was a negative trend in the incidence of TB – an increase in the incidence among all age groups. Among the children with TB, an accretion in the percentage of the most vulnerable contingents – children younger than 1 year old and adolescents (15-17 years old) – has been observed. Simultaneously there were a decrease in the number of children with small, limited forms of TB and an increase in the percentage of patients with bacterial excretion in all age groups. CONCLUSIONS. During the previous 2 years, for obvious reasons, the situation with TB detection, treatment and follow-up has deteriorated significantly. During the war, all children in Ukraine belong to the high-risk group for infection with Mycobacterium tuberculosis and TB disease and need (at the earliest opportunity) a specific screening examination for TB.

Pre-clinical study of IR808 dye for cervical cancer in vitro and in vivo imaging.

There is an urgent need for improved methods for early screening and rapid diagnosis of cervical cancer since current conventional screening methods are plagued by operator subjectivity and unnecessary biopsies. IR808 is a tumour-targeting near-infrared (NIR) fluorescent dye that permits NIR imaging without the requirement of chemical conjugation. Our study investigates an IR808-based strategy for real-time monitoring of the cervix in vivo and rapid assessment of cervical specimens in vitro. We investigated the uptake of IR808 in vitro using normal cervical epithelial cells and three cervical cancer cell lines. The biodistribution of IR808 was examined in vivo via intravenous injection into tumour-bearing mice. Additionally, in vitro tissues were stained with IR808 to simulate the identification of cervical tumors in the clinical setting. Biocompatibility of the dye in both cellular and animal models was also examined. IR808 exhibited significant tumour-to-background ratios in fluorescence molecular imaging of in vivo tumors in nude mice. The application of NIR fluorescent dye IR808 in specific imaging screening, safe and non-invasive real-time monitoring, and rapid identification of cervical tumors from tissue specimens is expected to improve current screening methods for cervical cancer.

Pediatric oncology nutritional practices in high-income countries: A survey from the International Society of Paediatric Oncology (SIOP).

Optimal nutrition in pediatric oncology can influence cancer-related outcomes. To establish an understanding of nutrition practice and perceptions of best practice, we queried nutrition providers practicing in pediatric oncology care centers in high-income countries. An electronic, multidisciplinary, cross-sectional survey of nutrition practices was conducted among pediatric oncology nutrition practitioners. Final analysis included 110 surveys from 71 unique institutions and included practitioners from Europe, the United States, Canada, Australia/New Zealand, South America, and the Middle East/Asia. The majority of institutions (97%) reported having dietitians; 72% had designated oncology dietitians. Approximately half of the practitioners (47%) reported feeling their institutions were inadequately staffed. The majority (78%) of institutions completed nutrition risk screening, but there was no consensus on specific screening practices. Half (50%) of the institutions that screened for nutrition risk did so in both inpatient and outpatient settings. The majority (80%) of institutions completed a nutrition assessment close to the time of diagnosis. Those that did not cite lack of staff and/or lack of time, lack of standardized approach, and consult only level of nutritional care as primary barriers. The most common topic of nutrition education provided to patients/families was nutrition-related symptom management (68%). While most institutions reported having pediatric oncology dietitians, we found a lack of standardized practice and perceived inadequate staffing. In addition, what providers perceived to be best practice did not always align with day-to-day clinical practice. Ongoing efforts are needed to develop evidence-based guidelines, including staffing recommendations, to support specialized care in this population.

CFTR Exon 10 deleterious mutations in patients with congenital bilateral absence of vas deferens in a cohort of Pakistani patients.

Congenital bilateral absence of vas deferens (CBAVD) is a urological syndrome of Wolffian ducts and is responsible for male infertility and obstructive azoospermia. This study is designed to explore the integrity of exon 10 of CFTR and its role in male infertility in a cohort of CBVAD patients in Pakistan. Genomic DNA was extracted from 17 male patients with CBAVD having clinical symptoms, and 10 healthy controls via phenol-chloroform method. Exon 10 of the CFTR gene was amplified, using PCR with specific primers and DNA screening was done by Sanger sequencing. Sequencing results were analyzed using freeware Serial Cloner, SnapGene, BioEdit and FinchTV. Furthermore, bioinformatics tools were used to analyze the mutations and their impact on the protein function and stability. We have identified 4 mutations on exon 10 of CFTR in 6 out of 17 patients. Two of the mutations were missense variants V456A, K464E, and the other two were silent mutations G437G, S431S. The identified variant V456A was present in 4 of the studied patients. Whereas, the presence of K464E in our patients further weighs on the crucial importance for its strategic location to influence the gene function at post-transcriptional and protein level. Furthermore, Polyphen-2 and SIFT analyze the mutations as harmful and deleterious. The recurrence of V456A and tactically conserved locality of K464E are evidence of their potential role in CBAVD patients and in male infertility. The data can contribute in developing genetic testing and treatment of CBAVD.

Investigating the pattern of prostate specific antigen screening among E-cigarette smokers within the behavioral risk factor surveillance system

Introduction and objectivesE-cigarettes use has recently increased, even among older individuals quitting smoking. Though past studies suggest tobacco smokers may avoid cancer screening, the relationship between e-cigarette uses and preventive health behaviors like prostate specific antigen screening is uncertain. We assessed the relationship between self-reported e-cigarette smoking and prostate specific antigen screening utilization among US adults with a history of e-cigarette use. Materials and methodsWe included men aged 50–69 years, who provided responses regarding PSA screening receipt and smoking status, from Behavioral Risk Factor Surveillance System 2020 and 2022 surveys. Primary outcome was PSA screening receipt. Multivariable regression model was performed to investigate the association between smoking status (never-smokers, current or former e-cigarette smokers, current or former tobacco smokers) and PSA screening. ResultsWe included a weighted population of 8.1 million men aged 50–69. 2.3 million (28.3%) received PSA screening. 3.9 million (48.2%) were never-smokers. 1.3 million (16.6%) were from e-cigarettes smokers group, and 2.9 million (35.2%) were from tobacco smokers group. E-cigarettes smokers were less likely to receive PSA screening within last 2 years (0.76 [0.66–0.88]) than never-smokers. No significant difference in PSA screening was detected between never-smokers and tobacco smokers (0.91 [0.82–1.02]). E-cigarette smokers were less likely to receive PSA screening within the selected time frame (0.84 [0.72–0.97]) than tobacco smokers. When examining potential mediation by primary care visits, e-cigarette smokers were less likely to have had a check-up visit in past 2 years than tobacco smokers (0.77 [0.65–0.92]). ConclusionsE-cigarette smokers were less likely to undergo PSA screening than never-smokers and tobacco smokers, possibly due to reduced use of primary care services.

Compartmentalized CRISPR Reactions (CCR) for High-Throughput Screening of Guide RNA Potency and Specificity.

CRISPR ribonucleoproteins (RNPs) use a variable segment in their guide RNA (gRNA) called a spacer to determine the DNA sequence at which the effector protein will exhibit nuclease activity and generate target-specific genetic mutations. However, nuclease activity with different gRNAs can vary considerably in a spacer sequence-dependent manner that can be difficult to predict. While computational tools are helpful in predicting a CRISPR effector's activity and/or potential for off-target mutagenesis with different gRNAs, individual gRNAs must still be validated in vitro prior to their use. Here, the study presents compartmentalized CRISPR reactions (CCR) for screening large numbers of spacer/target/off-target combinations simultaneously in vitro for both CRISPR effector activity and specificity by confining the complete CRISPR reaction of gRNA transcription, RNP formation, and CRISPR target cleavage within individual water-in-oil microemulsions. With CCR, large numbers of the candidate gRNAs (output by computational design tools) can be immediately validated in parallel, and the study shows that CCR can be used to screen hundreds of thousands of extended gRNA (x-gRNAs) variants that can completely block cleavage at off-target sequences while maintaining high levels of on-target activity. It is expected that CCR can help to streamline the gRNA generation and validation processes for applications in biological and biomedical research.

Validation of Metallothionein Immunohistochemistry as a Highly Sensitive Screening Test for Wilson Disease

Wilson’s disease (WD) is a rare autosomal recessive condition with protean clinical manifestations that results from biallelic ATP7B mutations. However, non-destructive tissue tests to be applied clinically to tissue specimens are not widely available to effectively assess patients for possible WD. Previously, we showed that metallothionein (MTH) immunohistochemistry has a high sensitivity and specificity for WD diagnosis and, thus, represents a potentially powerful diagnostic tool that can be used in routine histologic sections. We sought to validate this finding in a large cohort of bona fide WD patients and to correlate metallothionein expression with other histologic features.We identified 91 cases of WD, which included 28 needle biopsies and 64 explants from 14 centers worldwide. Histologic features were evaluated, and a histopathological pattern was assigned to each case. All cases were evaluated with Masson trichrome and MTH immunohistochemistry (clone UC1MT, Abcam) using previously published technique. Liver tissues from chronic cholestatic diseases (n= 42) were used as controls.The median age of the cohort was 28.5 years. Out of 91 total cases, 83 were positive for MTH immunostain. In the controls, all 42 cases were negative for MTH immunostain. The sensitivity and specificity of MTH immunostain for WD were 91.20% and 100%, respectively.MTH immunohistochemistry is a highly sensitive and specific cost-effective screening tool for WD. It can be used for patients across age groups, varied histologic patterns, and fibrosis stages. This marker could prove to be a valuable tool in the evaluation of patients with possible WD.

Development and Validation of an Algorithm to Predict Stillbirth Gestational Age in Medicaid Billing Records

Abstract Introduction With Medicaid covering half of US pregnancies, Medicaid Analytic eXtract (MAX) provides a valuable data source to enrich understanding about stillbirth etiologies. Objective We developed and validated a claims-based algorithm to predict GA at stillbirth. Method We linked the stillbirths identified in MAX 1999-2013 to Florida Fetal Death Records (FDRs) to obtain clinical estimates of GA (N=825). We tested several algorithms including using a fixed median GA, median GA at the time of specific prenatal screening tests, and expanded versions considering additional predictors of stillbirth within including linear regression and random forest models. We estimated the proportion of pregnancies with differences of ± 1, 2, 3 and 4 weeks between the predicted and FDR GA and the model mean square error (MSE). We validated the selected algorithms in two external samples. Results The best performing algorithm was a random forest model (MSE of 12.67 weeks2) with 84% of GAs within ± 4 weeks. Assigning a fixed GA of 28 weeks resulted in an MSE of 60.21 weeks2 and proportions of GA within ± 4 weeks of 32%. We observed consistent results in the external samples. Discussion Our prediction algorithm for stillbirths can facilitate pregnancy research in the Medicaid population.

Mass Screening for Primary Open-Angle Glaucoma: Is It Really Relevant?

Glaucoma, one of the leading causes of blindness worldwide, poses a significant public health challenge. Despite advancements in diagnostic technologies, early detection remains a challenge. This study assesses the relevance of glaucoma screening in a population-based context. Conducted in October 2023, this retrospective study involved 434 employees at two pharmaceutical laboratory sites. The average age was 44 years, with a female-to-male ratio of 0.7. A family history of glaucoma was reported in 74 participants (17%). Intraocular pressure (IOP) measurements showed that 20 participants (4.6%) had IOP above 21 mmHg, while the average IOP in the studied population was 15.5 mmHg. Glaucomatous damage to the optic nerve head was observed in 65 cases (15%). A total of 71 employees (16.5%), including 70% women, were re-examined in a hospital setting, where they underwent comprehensive ophthalmological examinations. Among them, 13 participants (18%) were diagnosed with glaucoma, representing 2.9% of the initially screened employees. This study highlights the ongoing challenge of preventing irreversible blindness due to glaucoma. Although the diagnostic approach used was effective for early detection among employees, the overall value of mass glaucoma screening remains debated. This debate is due to the disease's low prevalence, the lack of highly sensitive and specific screening tests, economic considerations, and the impact on the quality of life of those screened. Further studies are needed to evaluate the clinical effectiveness and economic efficiency of various screening strategies.

Acrolein scavengers and detoxification: From high-throughput screening of flavonoids to mechanistic study of epigallocatechin gallate

Acrolein (ACR) is a widespread, highly toxic substance that poses significant health risks. Flavonoids have been recognized as effective ACR scavengers, offering a possible way to reduce these risks. However, the lack of specific high-throughput screening methods has limited the identification of ACR scavengers, and their actual detoxifying capacity on ACR remains unknown. To address this, we developed a high-throughput screening platform to assess the ACR scavenging capacity of 322 flavonoids. Our results showed that 80.7 % of the flavonoids could scavenge ACR, but only 34.4 % exhibited detoxifying effects in an ACR-injured QSG7701 cell model. Some flavonoids even increased toxicity. Structure-activity relationship (SAR) analysis indicated that galloyl and pyrogallol units enhance scavenging but worsen ACR-induced cytotoxicity. Further investigation revealed that epigallocatechin gallate (EGCG) could exacerbate ACR-induced redox disorder, leading to cell apoptosis. Our findings provide crucial data on the scavenging and detoxifying capacities of 322 flavonoids, highlighting that ACR scavengers might not mitigate ACR-induced toxicity and could pose additional safety risks.