Screening Results Research Articles

Newborn congenital cytomegalovirus screening and hearing outcomes: a systematic review of current literature.

The purpose of this review is to summarize the very recent literature surrounding hearing outcomes of children with congenital cytomegalovirus (cCMV) detected through systematic screening programs. There are several different approaches to cCMV screening including forms of targeted vs. universal screening of newborns as well as maternally-derived prenatal testing. However, many studies fail to document hearing-related outcomes both in the newborn period and further into childhood when late-onset sensorineural hearing loss (SNHL) can occur. This systematic review included studies of neonates screened for cCMV reporting hearing outcomes for at least one point in time. Hearing targeted screening appeared the most widely reported for detection of unilateral and bilateral SNHL in those with cCMV. A few studies examined these clinical findings in relation to antiviral treatment. Congenital CMV is an important and common cause of childhood hearing loss. Newborn screening programs may expand opportunities for early diagnosis and treatment of the infection and its sequelae.

GeneRaMeN enables integration, comparison, and meta-analysis of multiple ranked gene lists to identify consensus, unique, and correlated genes.

High-throughput experiments often produce ranked gene outputs, with forward genetic screening being a notable example. While there are various tools for analyzing individual datasets, those that perform comparative and meta-analytical examination of such ranked gene lists remain scarce. Here, we introduce Gene Rank Meta Analyzer (GeneRaMeN), an R Shiny tool utilizing rank statistics to facilitate the identification of consensus, unique, and correlated genes across multiple hit lists. We focused on two key topics to showcase GeneRaMeN: virus host factors and cancer dependencies. Using GeneRaMeN 'Rank Aggregation', we integrated 24 published and new flavivirus genetic screening datasets, including dengue, Japanese encephalitis, and Zika viruses. This meta-analysis yielded a consensus list of flavivirus host factors, elucidating the significant influence of cell line selection on screening outcomes. Similar analysis on 13 SARS-CoV-2 CRISPR screening datasets highlighted the pivotal role of meta-analysis in revealing redundant biological pathways exploited by the virus to enter human cells. Such redundancy was further underscored using GeneRaMeN's 'Rank Correlation', where a strong negative correlation was observed for host factors implicated in one entry pathway versus the alternate route. Utilizing GeneRaMeN's 'Rank Uniqueness', we analyzed human coronaviruses 229E, OC43, and SARS-CoV-2 datasets, identifying host factors uniquely associated with a defined subset of the screening datasets. Similar analyses were performed on over 1000 Cancer Dependency Map (DepMap) datasets spanning 19 human cancer types to reveal unique cancer vulnerabilities for each organ/tissue. GeneRaMeN, an efficient tool to integrate and maximize the usability of genetic screening datasets, is freely accessible via https://ysolab.shinyapps.io/GeneRaMeN.

Shall We Screen Lung Cancer with Volume Computed Tomography in Austria? A Cost-Effectiveness Modelling Study.

This study assessed the cost-effectiveness of a lung cancer screening (LCS) program using low-dose computed tomography (LDCT) in Austria. An existing decision tree with an integrated Markov model was used to analyze the cost-effectiveness of LCS versus no screening from a healthcare payer perspective over a lifetime horizon. A simulation was conducted to model annual LCS for an asymptomatic high-risk population cohort aged 50-74 with a smoking history using the Dutch-Belgian Lung Cancer Screening Study (NEderlands-Leuvens Longkanker ScreeningsONderzoek, NELSON) screening outcomes. The principal measure utilized to assess cost-effectiveness was the incremental cost-effectiveness ratio (ICER). Sensitivity and scenario analyses were employed to determine uncertainties surrounding the key model inputs. At an uptake rate of 50%, 300,277 eligible individuals would participate in the LCS program, yielding 56,122 incremental quality-adjusted life years (QALYs) and 84,049 life years gained compared to no screening, with an ICER of EUR 24,627 per QALY gained or EUR 16,444 per life-year saved. Additionally, LCS led to the detection of 25,893 additional early-stage lung cancers and averted 11,906 premature lung cancer deaths. It was estimated that LCS would incur EUR 945 million additional screening costs and EUR 386 million additional treatment costs. These estimates were robust in sensitivity analyses. Implementation of annual LCS with LDCT for a high-risk population, using the NELSON screening outcomes, is cost-effective in Austria, at a threshold of EUR 50,000 per QALY.

Population health outcomes of blood-based screening for colorectal cancer in comparison to current screening modalities: insights from a discrete-event simulation model incorporating longitudinal adherence

Aim Insufficient adherence to colorectal cancer (CRC) screening impedes individual and population health benefits, with about one-third of individuals non-adherent to available screening options. The impact of poor adherence is inadequately considered in most health economics models, limiting the evaluation of real-world population-level screening outcomes. This study introduces the CAN-SCREEN (Colorectal cANcer SCReening Economics and adherENce) model, utilizing real-world adherence scenarios to assess the effectiveness of a blood-based test (BBT) compared to existing strategies. Materials and methods The CAN-SCREEN model evaluates various CRC screening strategies per 1,000 screened individuals for ages 45–75. Adherence is modeled in two ways: (1) full adherence and (2) longitudinally declining adherence. BBT performance is based on recent pivotal trial data while existing strategies are informed using literature. The full adherence model is calibrated using previously published Cancer Intervention and Surveillance Modeling Network (CISNET) models. Outcomes, including life-years gained (LYG), CRC cases averted, CRC deaths averted, and colonoscopies, are compared to no screening. Results Longitudinal adherence modeling reveals differences in the relative ordering of health outcomes and resource utilization, as measured by the number of colonoscopies performed per 1,000, between screening modalities. BBT outperforms the fecal immunochemical test (FIT) and the multitarget stool DNA (mtsDNA) test with more CRC deaths averted (13) compared to FIT and mtsDNA (7, 11), more CRC cases averted (27 vs. 16, 22) and higher LYG (214 vs. 157, 199). BBT yields fewer CRC deaths averted compared to colonoscopy (13, 15) but requires fewer colonoscopies (1,053 vs. 1,928). Limitations Due to limited data, the CAN-SCREEN model with longitudinal adherence leverages evidence-informed assumptions for the natural history and real-world longitudinal adherence to screening. Conclusions The CAN-SCREEN model demonstrates that amongst non-invasive CRC screening strategies, those with higher adherence yield more favorable health outcomes as measured by CRC deaths averted, CRC cases averted, and LYG.

The effect of the US Child Tax Credit advance payments in 2021 on adolescent mental health: Changes in depression symptoms and suicidality

ObjectiveChild poverty is associated with poor adolescent mental health. Changes to the Child Tax Credit (CTC) in 2021 in the U.S. were historic and introduced a new model of distributing the credit in advance of tax filing, providing families with stable, supplemental monthly income. This policy shift offers a unique opportunity to examine the mental health effects for adolescents. MethodsWe use electronic health record data from a large pediatric primary care network in Columbus, Ohio, which collected adolescent depression screening scores in real time as the CTC advance payments were introduced. We utilized differences in age of eligibility for the CTC to examine the changes in the probability of depression screening outcomes (positive depression screen, any depression symptom, any suicidal ideation), for adolescents eligible for the credit (turned 18 first quarter of 2022), relative to those not eligible (turned 18 last quarter of 2021) (n = 1,423). ResultsWe did not observe a significant association between the policy change and study outcomes in the overall sample. However, the percentage of adolescents with a positive depression screen significantly declined for Non-Hispanic Black (13.4 percentage point reduction, p = 0.01) and publicly insured (9.7 percentage point reduction, p = 0.04) adolescents. ConclusionsOur findings suggest reductions in depression symptoms for subgroups of adolescents who were age-eligible for the CTC compared to their counterparts who were not eligible. The CTC advance payments were a brief experiment in universal basic income and may offer a policy solution for addressing both poverty and a growing adolescent mental health crisis.

Lean-and-Green Fractional Factorial Screening of 3D-Printed ABS Mechanical Properties Using a Gibbs Sampler and a Neutrosophic Profiler

The use of acrylonitrile butadiene styrene (ABS) in additive manufacturing applications constitutes an elucidating example of a promising match of a sustainable material to a sustainable production process. Lean-and-green datacentric-based techniques may enhance the sustainability of product-making and process-improvement efforts. The mechanical properties—the yield strength and the ultimate compression strength—of 3D-printed ABS product specimens are profiled by considering as many as eleven controlling factors at the process/product design stage. A fractional-factorial trial planner is used to sustainably suppress by three orders of magnitude the experimental needs for materials, machine time, and work hours. A Gibbs sampler and a neutrosophic profiler are employed to treat the complex production process by taking into account potential data uncertainty complications due to multiple distributions and indeterminacy issues due to inconsistencies owing to mechanical testing conditions. The small-data multifactorial screening outcomes appeared to steadily converge to three factors (the layer height, the infill pattern angle, and the outline overlap) with a couple of extra factors (the number of top/bottom layers and the infill density) to supplement the linear modeling effort and provide adequate predictions for maximizing the responses of the two examined mechanical properties. The performance of the optimal 3D-printed ABS specimens exhibited sustainably acceptable discrepancies, which were estimated at 3.5% for the confirmed mean yield strength of 51.70 MPa and at 5.5% for the confirmed mean ultimate compression strength of 53.58 MPa. The verified predictors that were optimally determined from this study were (1) the layer thickness—set at 0.1 mm; (2) the infill angle—set at 0°; (3) the outline overlap—set at 80%; (4) the number of top/bottom layers—set at 5; and (5) the infill density—set at 100%. The multifactorial datacentric approach composed of a fractional-factorial trial planner, a Gibbs sampler, and a neutrosophic profiler may be further tested on more intricate materials and composites while introducing additional product/process characteristics.

Screening for Hepatocellular Carcinoma and Survival in Patients With Cirrhosis After Hepatitis C Virus Cure

The risk of hepatocellular carcinoma (HCC) declines over time after hepatitis C virus (HCV) cure by direct-acting antiviral (DAA) therapies. Liver society guidelines recommend continuing HCC screening for these patients, but data on screening outcomes are lacking. To evaluate the association of HCC screening after HCV cure with overall survival. This cohort study evaluated patients with HCV cirrhosis who achieved DAA-induced HCV cure in the Veterans Affairs health care system between January 2014 and December 2022. Data analysis occurred from October 2023 to January 2024. The percentage of time spent up to date with recommended HCC screening was calculated by year of follow-up and during the 4 years preceding HCC diagnosis (the detectable asymptomatic phase). The primary outcome was overall survival after HCC diagnosis and was compared by percentage of time spent up to date with screening using Kaplan-Meier analyses and Cox proportional hazards regression. Early-stage HCC at diagnosis and curative treatment were secondary outcomes assessed using logistic regression. A total of 16 902 individuals were included (median [IQR] age, 64.0 [60.5-67.4] years; 16 426 male [97.2%]), of whom 1622 developed HCC. The cumulative incidence of HCC declined from 2.4% (409 of 16 902 individuals) to 1.0% (27 of 2833 individuals) from year 1 to year 7 of follow-up. Being up to date with screening for at least 50% of time during the 4 years preceding HCC diagnosis was associated with improved overall survival (log-rank test of equality over strata P = .002). In multivariate analysis, each 10% increase in follow-up spent up to date with screening was associated with a 3.2% decrease in the hazard of death (hazard ratio, 0.97; 95% CI, 0.95-0.99). There was a statistically significant interaction between time since HCV cure and screening, with no association observed among those who received a diagnosis of HCC more than 5 years after HCV cure. Each 10% of time spent up to date with screening was associated with a 10.1% increased likelihood of diagnosis with early-stage HCC (95% CI, 6.3%-14.0%) and a 6.8% increased likelihood of curative treatment (95% CI, 2.8%-11.0%). In this cohort study of persons with HCV-related cirrhosis who achieved HCV cure and subsequently developed HCC, remaining up to date with screening was associated with improved overall survival, supporting the screening of eligible individuals.

Conformation, virtual cocrystal screening, synthesis and determination of dipyridamole

Drug development necessitates substantial investments in both human and material resources. In the advanced stages of development, significant solubility challenges frequently emerge, critically influencing a drug's applicability and efficacy. Crystal engineering, particularly through the application of cocrystal technology, presents a novel strategy to address these solubility issues without compromising the drug's effectiveness. However, the success rate of cocrystals formation remains relatively low. This article evaluates the impact of widely used virtual cocrystal screening methods on prediction outcomes, especially in the context of conformational diversity. The study describes the effects of eight dipyridamole (DIP) conformations and 130 cocrystal formers (CCFs) using molecular complementarity and molecular electrostatic potential methods, while the hydrogen bond propensity method did not account for conformations variations. Findings indicate that different DIP conformations lead to variable prediction outcomes in virtual cocrystal screening. Thus, it is crucial consider the conformational states of APIs and CCFs in virtual screenings to enhance prediction accuracy. By comparing virtual screening results with experimental results, this study demonstrated that incorporating conformational considerations can improve cocrystal success rates, minimize experimental workload, and contribute to energy-conservation and emission-reduction. Additionally, this research provides the true positives and true negatives data of DIP's cocrystal, laying the groundwork for further studies.

Cancer screening attendance rates in transgender and gender-diverse patients: a systematic review and meta-analysis

ObjectivesTo examine disparities in attendance rates at cancer screening services between transgender and gender-diverse (TGD) people in comparison with their cisgender (CG) counterparts, and to determine whether these differences were...

Enhancing Cervical Cancer Screening with 7-Type HPV mRNA E6/E7 Testing on Self-Collected Samples: Multicentric Insights from Mexico.

Cervical cancer remains a significant public health issue, particularly in regions with low screening uptake. This study evaluates the effectiveness of self-sampling and the 7-type HPV mRNA E6/E7 test in improving cervical cancer screening outcomes among a referral population in Mexico. A cohort of 418 Mexican women aged 25 to 65, referred for colposcopy and biopsy due to abnormal cytology results (ASC-US+), participated in this study. Self-samples were analyzed using both the 14-type HPV DNA test and the 7-type HPV mRNA E6/E7 test. The study assessed the sensitivity, specificity, positive predictive value (PPV), and the necessity of colposcopies to detect CIN3+ lesions. Participant acceptability of self-sampling was also evaluated through a questionnaire. The 7-type HPV mRNA E6/E7 test demonstrated equivalent sensitivity but significantly higher specificity (77.0%) and PPV for CIN3+ detection compared to the 14-type HPV DNA test (specificity: 45.8%, p < 0.001). The use of the HPV mRNA test as a triage tool reduced the number of colposcopies needed per CIN3+ case detected from 16.6 to 7.6 (p < 0.001). Self-sampling was highly accepted among participants, with the majority reporting confidence in performing the procedure, minimal discomfort, and willingness to undertake self-sampling at home. Self-sampling combined with the 7-type HPV mRNA E6/E7 testing offers a promising strategy to enhance cervical cancer screening by improving accessibility and ensuring precise diagnostics. Implementing these app roaches could lead to a significant reduction in cervical cancer morbidity and mortality, especially in underserved populations. Future research should focus on the long-term impact of integrating these methods into national screening programs and explore the cost-effectiveness of widespread implementation.

Universal eye screening: perinatal risk factors and ocular abnormalities in 1795 newborns not meeting retinopathy of prematurity criteria.

This prospective cohort study aimed to investigate the ocular outcomes of universal eye screening in newborns and assess the relationship between different perinatal risk factors and various ocular abnormalities in infants who do not meet the criteria for retinopathy of prematurity (ROP) screening. An universal eye screening questionnaire was utilised to screen newborn babies who did not meet the ROP screening criteria within 72 h of birth at a public and private hospital between June 2016 and April 2018. The questionnaire covered demographic characteristics, neonatal history, and eye examination findings. A trained retina specialist conducted comprehensive anterior and posterior segment examinations utilising a binocular indirect ophthalmoscope. Out of the 1795 newborns screened, 55.2% were male, and 44.8% were female. The most prevalent ocular abnormality observed was retinal haemorrhage (RH), with a prevalence of 10.64% (95% CI: 9.25-12.16%). The prevalence of non-RH abnormality was 7.5% (95% CI: 6.34-8.84%). The retinal haemorrhages were associated with normal vaginal deliveries (OR: 9.91; 95% CI: 6.71-14.64, p-value < 0.001), while non-RH abnormalities were associated with pre-term babies (OR: 4.87; 95% CI: 3.03-7.83, p < 0.001), consanguinity (OR: 2.20; 95% CI: 1.28-3.8, p < 0.001), low birth weight (OR: 0.22; 95% CI: 0.14-0.34, p < 0.001) and systemic abnormalities (OR: 3.08; 95% CI: 1.94-4.91, p < 0.001). Sight-threatening ocular pathology in newborns may be linked to perinatal risk factors such as preterm birth, low birth weight, consanguinity, and systemic abnormalities. Accordingly, it may be prudent to consider specialized ocular screening protocols for neonates within this high-risk cohort in future prospective studies.

Eye care following pre-school vision screening: Data from the Growing Up in New Zealand study.

This study aimed to determine adherence with follow-up from the New Zealand pre-school vision screening programme. The study also examined associations between pre-school vision screening outcomes and cognitive measures assessed at the 54-month follow-up in the Growing Up in New Zealand study cohort. A cross-sectional retrospective record review of pre-school vision screening outcomes and hospital ophthalmology records with linkage to Growing Up in New Zealand cohort study data. Of 176 children referred from vision screening, 21.6% did not attend a referral appointment. Of 138 children who attended a referral appointment, 21.0% did not attend one or more follow-up appointments. Ethnic differences were observed in attendance at referral appointments (attended Māori 13%, Pacific 22.5%, European/Other 64.5%; not attended Māori 26.3%, Pacific 28.9%, European/Other 44.7%; P = 0.04) and follow-up appointments (attended Māori 11.9%, Pacific 15.6%, European/Other 72.5%; not attended Māori 17.2%, Pacific 48.3%, European/Other 34.5%; P = 0.001). Vision screening outcome was significantly associated with letter naming fluency scores (P = 0.01) but not name and numbers scores (P = 0.05). Non-attendance at referral and follow-up appointments limits the efficacy of vision screening, particularly for children of Māori and Pacific ethnicity. Children referred from vision screening achieve lower scores on letter naming fluency, a key predictor of reading ability in later childhood. Equity-based improvements are required to ensure that all children referred from vision screening receive appropriate follow-up eye care.

Screening for Retinopathy of Prematurity in Neonatal Intensive Care Unit in Ain Shams University Hospital

Abstract Purpose to evaluate the Retinopathy of prematurity prevalence and screening outcome in a tertiary hospital in Cairo, Egypt. Also, to assess the risk factors for its development and to suggest modifications to the international guidelines for screening for Retinopathy of prematurity to fit the Egyptian population. Methods A prospective observational study was carried out in Neonatal Intensive Care Unit (NICU) in Ain Shams University Hospital. In this study 159 premature infants born in the period between 1 September 2018 to 1 September 2021 were screened for Retinopathy of Prematurity (ROP). Screening was based on the most inclusive criteria reported to date. All premature infants with gestational age (GA) of ≤ 34 weeks or birth weight (BW) of ≤ 2000 grams were included. Infants were also included if GA &amp;gt; 34 weeks or BW &amp;gt; 2000 grams, but multiple co-morbidities existed. The prevalence of retinopathy of prematurity and plus disease and their correlation with risk factors of interest were studied. Results The gestational age of the included infants ranged from 27 to 36 weeks, with a mean (SD) of 31.87 (± 1.81) weeks. Infants had birth weight ranging from 640 to 3900 grams, with a mean (SD) of 1784.71 (± 560.30) grams. The prevalence of ROP changes more than stage 0 in the screened infants was 25.8% (41 infants) with 7.3% of cases (11 infants) showing plus disease and 6.3% of cases (10 infants) showing severe changes that needed treatment. Of those, 2 cases (20%) fell outside the British Guideline’s criteria for Screening. there was a highly significant (p &amp;lt; 0.0001) correlation between appearance of Retinopathy of prematurity changes more than stage 0 and low gestational age, low birth weight of the screened infants, receiving mechanical ventilation, respiratory distress syndrome stage, presence of Necrotizing enterocolitis, Intraventricular haemorrhage and blood transfusion. On the other hand, no significant correlation was found between appearance of Retinopathy of prematurity changes more than stage 0 and gender (p = 0.911), presence of PDA (p = 0.187), or sepsis (p = 0.998). Conclusion Retinopathy of prematurity is a significant problem in the premature infants in Cairo, Egypt. Extremely premature infants with lower birth weight are more prone to develop this disease. However, cases with higher gestational age and birth weight than mentioned in the British guidelines screening criteria especially with multiple comorbidities showed severe Retinopathy of prematurity changes that needed intervention, which implies the need to develop a screening guideline for the Egyptian population.

Molecular autopsy in Chinese sudden cardiac death in the young.

Inherited cardiovascular conditions are significant causes of sudden cardiac death in the young (SCDY), making their investigation using molecular autopsy and prevention a public health priority. However, the molecular autopsy data in Chinese population is lacking. The 5-year result (2017-2021) of molecular autopsy services provided for victims of SCDY (age 1-40 years) was reviewed. The outcome of family cascade genetic screening and clinical evaluation was reviewed. A literature review of case series reporting results of molecular autopsy on SCDY in 2016-2023 was conducted. Among the 41 decedents, 11 were found to carry 13 sudden cardiac death (SCD)-causative genetic variants. Likely pathogenic (LP) variants were identified in the DSP, TPM1, TTN, and SCN5A genes. Cascade genetic testing identified four family members with LP variants. One family member with familial TPM1 variant was found to have hypertrophic cardiomyopathy upon clinical evaluation. This study provided insight into the genetic profile of molecular autopsy in a Chinese cohort of SCDY. The detection of important SCD-causative variants through molecular autopsy has facilitated family cascade screening by targeted genetic testing and clinical evaluation of at-risk family members. A literature review of the current landscape of molecular autopsy in the investigation of SCDY was conducted.

Reduction of Z alpha-1 antitrypsin polymers in human iPSC-hepatocytes and mice by LRRK2 inhibitors.

Alpha-1 antitrypsin deficiency (A1ATD) is a life-threatening condition caused by inheritance of the SERPINA1 'Z' genetic variant (PiZ) driving AAT protein misfolding in hepatocytes. There remain no approved medicines for this disease. Here, we report the results of a small molecule screen performed in patient derived iPSC-hepatocytes that identified Leucine-rich repeat kinase-2 (LRRK2) as a potentially new therapeutic target. Of the commercially available LRRK2 inhibitors tested, we identified CZC-25146, a candidate with favorable pharmacokinetic properties, as being capable of reducing polymer load, increasing normal AAT secretion, and reducing inflammatory cytokines in both cells and PiZ mice. Mechanistically, this effect was achieved through induction of autophagy. Our findings support the use of CZC-25146 and LRRK2 inhibitors in hepatic proteinopathy research and their further investigation as novel therapeutic candidates for A1ATD.

Donor-derived Mycoplasma and Ureaplasma infections in lung transplant recipients: A prospective study of donor and recipient respiratory tract screening and recipient outcomes

Mycoplasma hominis and Ureaplasma species are urogenital mollicutes that can cause serious donor-derived infections in lung transplant recipients. Best practices for mollicute screening remain unknown. We conducted a single-center prospective study analyzing lung transplants performed from October 5, 2020, to September 25, 2021, whereby donor and recipient bronchoalveolar lavage (BAL) samples obtained at time of transplant underwent mollicute screening via culture and polymerase chain reaction (PCR). Of 115 total lung transplants performed, 99 (86%) donors underwent combined mollicute BAL culture and PCR testing. The study cohort included these 99 donors and their matched recipients. In total, 18 (18%) of 99 donors screened positive via culture or PCR. Among recipients, 92 (93%) of 99 had perioperative BAL screening performed, and only 3 (3%) had positive results. After transplant, 9 (9%) recipients developed mollicute infection. Sensitivity of donor screening in predicting recipient mollicute infection was 67% (6/9) via culture and 56% (5/9) via PCR. Positive predictive value for donor culture was 75% (6/8), compared with 33% (5/15) for PCR. Donor screening via culture predicted all serious recipient mollicute infections and had better positive predictive value than PCR; however, neither screening test predicted all mollicute infections. Independent of screening results, clinicians should remain suspicious for posttransplant mollicute infection.

Screening Outcomes of Mammography with AI in Dense Breasts: A Comparative Study with Supplemental Screening US.

Background Comparative performance between artificial intelligence (AI) and breast US for women with dense breasts undergoing screening mammography remains unclear. Purpose To compare the performance of mammography alone, mammography with AI, and mammography plus supplemental US for screening women with dense breasts, and to investigate the characteristics of the detected cancers. Materials and Methods A retrospective database search identified consecutive asymptomatic women (≥40 years of age) with dense breasts who underwent mammography plus supplemental whole-breast handheld US from January 2017 to December 2018 at a primary health care center. Sequential reading for mammography alone and mammography with the aid of an AI system was conducted by five breast radiologists, and their recall decisions were recorded. Results of the combined mammography and US examinations were collected from the database. A dedicated breast radiologist reviewed marks for mammography alone or with AI to confirm lesion identification. The reference standard was histologic examination and 1-year follow-up data. The cancer detection rate (CDR) per 1000 screening examinations, sensitivity, specificity, and abnormal interpretation rate (AIR) of mammography alone, mammography with AI, and mammography plus US were compared. Results Among 5707 asymptomatic women (mean age, 52.4 years ± 7.9 [SD]), 33 (0.6%) had cancer (median lesion size, 0.7 cm). Mammography with AI had a higher specificity (95.3% [95% CI: 94.7, 95.8], P = .003) and lower AIR (5.0% [95% CI: 4.5, 5.6], P = .004) than mammography alone (94.3% [95% CI: 93.6, 94.8] and 6.0% [95% CI: 5.4, 6.7], respectively). Mammography plus US had a higher CDR (5.6 vs 3.5 per 1000 examinations, P = .002) and sensitivity (97.0% vs 60.6%, P = .002) but lower specificity (77.6% vs 95.3%, P < .001) and higher AIR (22.9% vs 5.0%, P < .001) than mammography with AI. Supplemental US alone helped detect 12 cancers, mostly stage 0 and I (92%, 11 of 12). Conclusion Although AI improved the specificity of mammography interpretation, mammography plus supplemental US helped detect more node-negative early breast cancers that were undetected using mammography with AI. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Whitman and Destounis in this issue.

The Uptake of Partner Participation in Sequential Preconception Carrier Screening

Introduction: Carrier screening that is performed in the preconception period allows for couples at risk for having children affected with certain single gene (Mendelian) conditions to be identified. This is the most optimal timeframe to perform such screening. Most obstetric providers utilize a sequential process in which the patient first undergoes screening and their partner is only offered testing if the initial results reveal that the first is a carrier for one or more autosomal recessive (AR) deleterious variants. If the partner fails to undergo screening, the couple cannot obtain meaningful and actionable risk information for future or current pregnancies. In this study, we sought to assess the frequency of completed carrier screening risk assessment among individuals and couples who were undergoing preconception screening at two prenatal screening programs staffed by genetic counselors and geneticists. Materials and Methods: We reviewed the screening outcomes for individuals and couples who presented for preconception carrier screening from January 1, 2020 through December 30, 2021 at Insight Medical Genetics and the clinical genetics program at Northwestern Medicine. All individuals received pretest genetic counseling prior to screening and posttest counseling after results were available. We evaluated individuals who were found to be a carrier of at least one deleterious variant and whether the partner of that person underwent carrier screening, and, if so, which type of screening. Results: 548 patients who identified as women underwent preconception carrier screening during the study period, along with 3 men presenting for initial screening. These screens consisted of a panel containing primarily autosomal recessive conditions with a few X-linked conditions. 247 individuals (45.1%) were positive for at least one pathogenic variant; of these, 244 (98.8%) were variants in genes associated with autosomal recessive conditions. A total of 219 partners (88.7%) underwent carrier screening, including the 3 female partners of the men who initiated carrier screening. Of note, 4 of the patients who underwent carrier screening reported not having a partner at the time of screening; accordingly, the partners who underwent screening represent 89.8% of individuals eligible for partner screening following an initial positive result. Of the 219 partners who underwent carrier screening, 201 (91.8%) chose a carrier screening panel of 150+ conditions, while 18 chose a more limited panel that included the gene(s) of relevance based on their partner’s results, with or without additional genes relevant to their learned/self-identified ethnicity or race. Conclusions: Approximately 10% of couples presenting for preconception genetic counseling and carrier screening found to be at potential risk for a child with an autosomal recessive condition did not obtain the requisite information to fully assess their risk of having an affected child. It is possible that the frequency of couples who do not obtain complete and actionable screening information is even higher when carrier screening is provided without the assistance of certified genetic counselors or geneticists. Recently, cell free DNA-based maternal screening has been introduced that assesses the risk for a limited number of genetic conditions in the fetus that may not require assessment of the partner. Nonetheless, providers must communicate to their patients that meaningful risk information can only be obtained when the partner undergoes screening in cases where the initial member of the couple is found to be a carrier of at least one autosomal recessive condition. Laboratories and professional societies need to develop effective educational outreach to patients and providers alike to improve the screening process for couples who want to determine if they are at risk to have a child with an inherited condition.

Contextual and individual inequalities in breast cancer screening participation and outcomes in Turin (North-West Italy)

Breast cancer incidence and screening participation exhibit an unequal distribution in the population. This study aims to investigate the impact of socioeconomic position (SEP) on three breast screening indicators (participation, recall, and cancer detection rates) among women aged 50–69 in the city of Turin between 2010 and 2019. The study also aims to determine whether contextual factors (deprivation index) or individual factors (educational level) have a greater influence. The data used in this study are sourced from the Turin Breast Screening Program (TBSP) and the Turin Longitudinal Study (TLS). To test the hypothesis and account for the hierarchical structure of the data, multilevel models were used. Both contextual and individual SEP were found to be associated with screening participation. Participation increased with higher levels of deprivation (odds ratio for most deprived: 1.13; 95% CI 1.11–1.16) and decreased with higher educational levels (OR for low educated: 1.37; 95% CI 1.34–1.40). Contextual SEP did not show any association with recall or cancer detection rates, but individual SEP had an impact. Women with lower educational levels had a statistically significant 19% lower odds of being recalled and a statistically significant 20% lower odds of being diagnosed with cancer. Additionally, immigrant women were less likely to participate in screening, be recalled, or receive a cancer diagnosis. Educational level consistently influenced the analyzed screening indicators, while contextual deprivation appeared to have less importance. It is likely that women living in less deprived areas and with higher education have greater access to opportunistic screening.

Control of 3' splice site selection by the yeast splicing factor Fyv6.

Pre-mRNA splicing is catalyzed in two steps: 5' splice site (SS) cleavage and exon ligation. A number of proteins transiently associate with spliceosomes to specifically impact these steps (1st and 2nd step factors). We recently identified Fyv6 (FAM192A in humans) as a 2nd step factor in S. cerevisiae; however, we did not determine how widespread Fyv6's impact is on the transcriptome. To answer this question, we have used RNA-seq to analyze changes in splicing. These results show that loss of Fyv6 results in activation of non-consensus, branch point (BP) proximal 3' SS transcriptome-wide. To identify the molecular basis of these observations, we determined a high-resolution cryo-EM structure of a yeast product complex spliceosome containing Fyv6 at 2.3 Å. The structure reveals that Fyv6 is the only 2nd step factor that contacts the Prp22 ATPase and that Fyv6 binding is mutually exclusive with that of the 1st step factor Yju2. We then use this structure to dissect Fyv6 functional domains and interpret results of a genetic screen for fyv6Δ suppressor mutations. The combined transcriptomic, structural, and genetic studies allow us to propose a model in which Yju2/Fyv6 exchange facilitates exon ligation and Fyv6 promotes usage of consensus, BP distal 3' SS.