Abdominal aortic aneurysm repair in Sweden vs. Finland: benefits of population-wide screening.

BACKGROUND AND AIMS: In 2006, screening of 65-year-old men for abdominal aortic aneurysm (AAA) was started in Sweden. Decline in aneurysm-related mortality has been reported since, but aneurysm incidence has been diminishing globally. Neighbouring Finland with similar population structure and health care system has no AAA screening programme. The aim of this study was to compare incidence and results of AAA repair in Sweden and Finland to differentiate the effect of screening from other changes in the epidemiology and treatment of AAA. METHODS: All repairs for intact AAA (iAAA) or ruptured AAA (rAAA) from 1998 to 2017 were identified from national registers, and mortality data for these patients were collected. RESULTS: A total of 15 927 operations for iAAA were performed in Sweden and 6933 in Finland. In Sweden, the yearly operation volume increased after introduction of screening. Both countries showed a decrease in number of rAAA operations, but the decrease was more pronounced in Sweden. Sweden had a higher proportion of all AAA repairs because of rupture in the start of the study but by the end, the proportions were similar in both countries. Long-term survival improved for 65-79-old men in Sweden after start of screening. CONCLUSIONS: This study reveals improvements in results of AAA repair in Sweden. A decrease in rAAA repair and increase in iAAA repair were evident after AAA screening was started in 2006 and resulted in better outcomes. These changes are likely the result of AAA screening as they cannot be seen in neighbouring Finland that is lacking an AAA screening programme.

Negative results from DNA-based population screening for adult-onset diseases: the recipients' experience.

DNA-based population screening for adult-onset diseases holds promise for advancing personalized medicine and improving public health. Yet as most individuals pursuing such screening receive negative results, the return of results process must ensure that negative results and their implications are clearly understood. We explored the experiences of adults who received negative results from such screening as part of the Electronic Medical Records and Genomics consortium Phase 3 project (eMERGE-3) at Columbia University. In addition to a laboratory report and a standard counseling letter explaining the negative results, participants were randomized to receive (or not) a vignette explaining the results. A diverse cohort of 437 adult participants completed both baseline and post-result surveys. Many participants reported motivations that did not match the screening goals and included hope for diagnosis and family disease risk. A quarter of participants reported not feeling confident explaining their results to others (n = 105, 24%), and those who did not receive the vignette were less confident than those who did (29% versus 19% respectively; p-value = 0.02). Open-text responses about personal and family members' reactions to the results suggested that some perceived an exaggerated benefit from the negative result and might forgo more appropriate genetic testing. Our findings highlight the complexity of returning negative results and raise concerns that participants might forgo more suitable genetic testing. Future research is needed to compare the efficacy of different forms of ancillary materials on individuals' comprehension of negative results.

A Genomic Counseling Model for Population-Based Sequencing: A Pre-Post Intervention Study.

BACKGROUND: Novel uses of genome sequencing (GS) present an opportunity for return of results to healthy individuals, prompting the need for scalable genetic counseling strategies. We evaluate the effectiveness of a genomic counseling model (GCM) and explore preferences for GS findings in the general population. METHODS: Participants (N=466) completed GS and our GCM (digital genomics platform and group-based webinar), and indicated results preferences. Surveys were administered pre- (T0) and post- (T1) GCM. Change in knowledge and decisional conflict (DC) were evaluated using paired-sample T and Wilcoxon tests. Factors influencing knowledge and results preferences were evaluated using linear and logistic regression models. RESULTS: Participants were 56% female, 58% white, and 53% ≥40 years of age. Mean knowledge scores increased (Limitations: 3.73 to 5.63; benefits: 3.73 to 5.48, p<0.0001) and DC decreased (-21.9, p<0.0001) at T1 versus T0. Eighty-six percent of participants wished to learn all GS findings at T1 vs 78% at T0 (p<0.0001). Older age, negative/mixed attitudes toward genetics, and greater DC were associated with change in preferences post-intervention. CONCLUSION: In a population-based cohort undergoing GS interested in learning GS findings, our GCM increased knowledge and reduced DC, illustrating the GCM's potential effectiveness for GS counseling in the general population.

Non-invasive prenatal testing: Assessing the availability and accessibility of information available to the pregnant population within the Republic of Ireland.

OBJECTIVE: While non-invasive prenatal testing (NIPT) has been widely adopted throughout Europe, Australia, and the USA, population level access to NIPT varies considerably. Ireland has no national screening programme for fetal anomalies, although NIPT is available from out-of-country providers. We aimed to describe the availability of NIPT in Ireland and the quality of information available online from NIPT providers. METHODS: Information available online from NIPT providers in the Republic of Ireland was analysed by examining all healthcare facilities websites and reviewing private health insurance directories. Data on information provided by NIPT providers was collected by two independent researchers from April to May 2023. RESULTS: Four of the 19 maternity hospitals/units in Ireland had information on NIPT on their websites, with three including an explanation of NIPT, testing accuracy, and associated fees (€380-480). Twenty private clinics led by obstetric consultants advertised NIPT online, of which seventeen clinics included an explanation of NIPT, testing accuracy, and associated fees (€380-€650). Twenty-nine other providers, which included ultrasound clinics, direct-to-consumer laboratory testing, and General Practitioners, advertised NIPT with 18 of these providers including an explanation of NIPT, testing accuracy, and associated fees (€179-€630). CONCLUSION: While there is apparent demand for NIPT and it is available in Ireland, there is disparity between providers on the type and quality of information available. Difficulty obtaining accessible information, the associated financial costs and location of providers advertising NIPT are likely to be barriers to accessing NIPT. A national screening programme for aneuploidy should be considered to ensure both equitable access to and reliable information about prenatal screening.

Body fluid multiomics in 3PM-guided ischemic stroke management: health risk assessment, targeted protection against health-to-disease transition, and cost-effective personalized approach are envisaged.

Because of its rapid progression and frequently poor prognosis, stroke is the third major cause of death in Europe and the first one in China. Many independent studies demonstrated sufficient space for prevention interventions in the primary care of ischemic stroke defined as the most cost-effective protection of vulnerable subpopulations against health-to-disease transition. Although several studies identified molecular patterns specific for IS in body fluids, none of these approaches has yet been incorporated into IS treatment guidelines. The advantages and disadvantages of individual body fluids are thoroughly analyzed throughout the paper. For example, multiomics based on a minimally invasive approach utilizing blood and its components is recommended for real-time monitoring, due to the particularly high level of dynamics of the blood as a body system. On the other hand, tear fluid as a more stable system is recommended for a non-invasive and patient-friendly holistic approach appropriate for health risk assessment and innovative screening programs in cost-effective IS management. This article details aspects essential to promote the practical implementation of highlighted achievements in 3PM-guided IS management. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00376-2.

Chatbot for the Return of Positive Genetic Screening Results for Hereditary Cancer Syndromes: a Prompt Engineering Study.

Background: The growing demand for genomic testing and limited access to experts necessitate innovative service models. While chatbots have shown promise in supporting genomic services like pre-test counseling, their use in returning positive genetic results, especially using the more recent large language models (LLMs) remains unexplored. Objective: This study reports the prompt engineering process and intrinsic evaluation of the LLM component of a chatbot designed to support returning positive population-wide genomic screening results. Methods: We used a three-step prompt engineering process, including Retrieval-Augmented Generation (RAG) and few-shot techniques to develop an open-response chatbot. This was then evaluated using two hypothetical scenarios, with experts rating its performance using a 5-point Likert scale across eight criteria: tone, clarity, program accuracy, domain accuracy, robustness, efficiency, boundaries, and usability. Results: The chatbot achieved an overall score of 3.88 out of 5 across all criteria and scenarios. The highest ratings were in Tone (4.25), Usability (4.25), and Boundary management (4.0), followed by Efficiency (3.88), Clarity and Robustness (3.81), and Domain Accuracy (3.63). The lowest-rated criterion was Program Accuracy, which scored 3.25. Discussion: The LLM handled open-ended queries and maintained boundaries, while the lower Program Accuracy rating indicates areas for improvement. Future work will focus on refining prompts, expanding evaluations, and exploring optimal hybrid chatbot designs that integrate LLM components with rule-based chatbot components to enhance genomic service delivery.

Our Journey from Individual Efforts to Nationwide Support: Implementing Newborn Screening for Spinal Muscular Atrophy in Serbia.

Innovative treatments for spinal muscular atrophy (SMA) yield the utmost advantages only within the presymptomatic phase, underlining the significance of newborn screening (NBS). We aimed to establish statewide NBS for SMA in Serbia. Our stepwise implementation process involved technical validation of a screening assay, collaboration with patient organizations and medical professionals, a feasibility study, and negotiation with public health representatives. Over 12,000 newborns were tested during the 17-month feasibility study, revealing two unrelated SMA infants and one older sibling. All three children received therapeutic interventions during the presymptomatic phase and have shown no signs of SMA. No false-negative results were found among the negative test results. As frontrunners in this field in Serbia, we established screening and diagnostic algorithms and follow-up protocols and raised awareness among stakeholders about the importance of early disease detection, leading to the incorporation of NBS for SMA into the national program on 15 September 2023. Since then, 54,393 newborns have been tested, identifying six SMA cases and enabling timely treatment. Our study demonstrates that effective collaborations between academia, non-profit organizations, and industry are crucial in bringing innovative healthcare initiatives to fruition, and highlights the potential of NBS to revolutionize healthcare outcomes for presymptomatic SMA infants and their families.

Preferences for Peer Support Amongst Families Engaged in Paediatric Screening Programmes: The Perspectives of Parents Involved in Screening for Type 1 Diabetes in Children Aged 3-13.

INTRODUCTION: This work describes a secondary analysis of a qualitative data set originally used to understand parent participants' preferences for the design and implementation of a screening programme for paediatric Type 1 diabetes (T1D). From this, their spontaneous preferences for peer support emerged, described here in the context of existing peer support programmes for the newly diagnosed alongside suggestions for their incorporation into screening programmes for T1D and a range of other conditions. METHODS: Data were collected from semi-structured interviews conducted with parents of children aged 3-13 years to explore their expectations, perceptions and preferences of a T1D paediatric screening programme. A secondary analysis of interviews from participants who spontaneously raised preferences for peer support was used to populate a novel framework informed by NHS England's key principles for the same, namely, Shared experiences and reciprocated support, Accessibility and inclusivity and Person-centred and integrated peer support. RESULTS: Parents in 29 of 33 interviews spontaneously described the potential value of peer support if receiving a result indicating a positive (presymptomatic T1D result) from a screening programme. Specifically, the value of 'Shared experiences and reciprocated support' in terms of emotional support and reassurance, and access to more directly interpretable and relevant information related to the condition; 'Accessibility and inclusivity' relating to access to a community of similar individuals, whether in person or online; 'Person-centred and integrated peer-support' and the need for support reflecting the changing need of the child and the integration of peer support with clinical care. CONCLUSIONS: The needs of peer support described by parents involved in T1D paediatric screening appear to be shared with those of families with children diagnosed with a range of life-altering conditions. Although the needs of peer support for paediatric screening may differ across conditions, our findings are a valuable starting point for its design both in T1D and other examples of similar population screening programmes. PATIENT OR PUBLIC CONTRIBUTION: Patients and the public have been involved throughout the design of the ELSA study and have worked with us to inform the study process. They contributed to the design and content of patient-facing materials, the content of our topic guides and the analysis and interpretation of our findings.

Simulated arbitration of discordance between radiologists and artificial intelligence interpretation of breast cancer screening mammograms.

Artificial intelligence (AI) algorithms have been retrospectively evaluated as replacement for one radiologist in screening mammography double-reading; however, methods for resolving discordance between radiologists and AI in the absence of 'real-world' arbitration may underestimate cancer detection rate (CDR) and recall. In 108,970 consecutive screens from a population screening program (BreastScreen WA, Western Australia), 20,120 were radiologist/AI discordant without real-world arbitration. Recall probabilities were randomly assigned for these screens in 1000 simulations. Recall thresholds for screen-detected and interval cancers (sensitivity) and no cancer (false-positive proportion, FPP) were varied to calculate mean CDR and recall rate for the entire cohort. Assuming 100% sensitivity, the maximum CDR was 7.30 per 1000 screens. To achieve >95% probability that the mean CDR exceeded the screening program CDR (6.97 per 1000), interval cancer sensitivities ≥63% (at 100% screen-detected sensitivity) and ≥91% (at 80% screen-detected sensitivity) were required. Mean recall rate was relatively constant across sensitivity assumptions, but varied by FPP. FPP > 6.5% resulted in recall rates that exceeded the program estimate (3.38%). CDR improvements depend on a majority of interval cancers being detected in radiologist/AI discordant screens. Such improvements are likely to increase recall, requiring careful monitoring where AI is deployed for screen-reading.

Primary Care Providers' Experiences With an Active Elective Genetic Testing Program.

Elective genetic testing (EGT) programs that provide pharmacogenomic information to guide medication management and screen for medically actionable disease predispositions are emerging in a number of health systems. Primary care providers (PCPs) are at the forefront of test initiation, patient education, and management of EGT results. However, little research has examined the experiences of PCPs in health systems offering clinical EGT. We conducted semi-structured interviews, a sub-study of the larger mixed-methods Imagenetics Initiative, with 16 PCPs at a health system in the Midwest with a clinical EGT program supported by provider education, automated clinical decision support, and enhanced access to genetic specialists. The purpose of these interviews was to understand perceptions about the benefits and barriers of implementing EGT in clinical practice. Thematic analysis indicated that EGT is conceptualized similar to traditional diagnostic services. PCPs were generally favorable toward EGT; however, targeted education did not dispel misconceptions about the goals, results, and limitations of EGT. Most PCPs endorsed the potential utility of EGT. Pharmacogenomic profiling was seen as having more immediate impact for patients than screening for monogenic disease risks. PCPs reported that they weighed discussions about EGT against time limitations and the need to prioritize patients' existing health concerns. Regardless of their education levels and familiarity with genetics, PCPs desired additional educational resources and greater access to genetic specialists. Our study provides unique insight into PCPs' experiences with clinical EGT in health systems that have adopted EGT and highlights the practical challenges and potential opportunities of EGT integration.

Routine transabdominal cervical length screening in mid-pregnancy for the prevention of preterm birth: Is it good enough to use as a screening test?

BACKGROUND: Preterm birth (PTB) is a major pregnancy complication. There is evidence that a short cervical length in mid-pregnancy may predict women at increased risk of PTB. AIMS: To evaluate the utility of population-based, transabdominal cervical length (TACL) measurement screening in mid-pregnancy for PTB prediction in women. MATERIALS AND METHODS: A transabdominal approach was initially performed, with a transvaginal (TVCL) approach offered when the TACL was <35 mm, could not be accurately measured, or the pregnancy had risk factors for PTB. TACL was compared to the directly related TVCL, when both were performed at the same assessment. Women with risk factors of PTB were included when they had both TACL and TVCL measurements performed at the same visit. RESULTS: Data were provided for 9355 singleton pregnancies from 13 participating imaging centres. A transabdominal approach was used in 9006 (96.3%), including 682 (7.3%) TVCL combined with TACL. There were 349 (3.7%) women who had TVCL only. The median TACL was longer (40 mm) than the TVCL (38 mm). In 682 paired TACL and TVCL measurements, TACL <35 mm correctly identified 96.2% of pregnancies with TVCL <25 mm, compared with 65.4% of cases when using a TACL <30 mm. A TVCL <25 mm occurred in 59 (0.6%) women. A TACL <35 mm was associated with birth <37 weeks of gestation in 12.1% of women and birth <32 weeks of gestation in 3.9%. CONCLUSIONS: Universal TACL is a feasible option for population screening of cervical length in a low-risk population, progressing to TVCL if the TACL is <35 mm or the cervix cannot be transabdominally accurately measured.

Factors associated with private or public breast cancer screening attendance in Queensland, Australia: A retrospective cross-sectional study.

This study aimed to estimate participation in private breast screening in Queensland, Australia, where public-funded screening is implemented, and to identify factors associated with the screening setting, using an online survey (999 female respondents aged 40-74). Screening-specific and socio-demographic factors were collected. Multivariable logistic regression was used to identify factors associated with screening setting (public vs private) and screening recency (<2 vs ≥2 years). Participation estimates were 53.2% (95% confidence interval, CI: 50.0%-56.3%) and 10.9% (9.0%-13.0%) for national screening program and private screening, respectively. In the screening setting model, participation in private screening was significantly associated with longer time since last screening (>4 versus <2 years, odds ratio (OR) = 7.3, 95%CI: 4.1-12.9, p < 0.001), having symptoms (OR = 9.5, 5.8-15.5, p < 0.001), younger age (40-49 versus 50-74 years, OR = 1.8, 1.1-3.0, p = 0.018) and having children <18 years in household (OR = 2.4, 1.5-3.9, p < 0.001). In the screening recency model, only screening setting was statistically significant and private screening was associated with screening recency ≥2 years (OR = 4.0, 2.8-5.7, p < 0.001). Around one in nine women screen outside of the BreastScreen Queensland program. Clinical and socio-demographic factors associated with participation in private screening were identified, providing knowledge relevant to the program's endeavours to improve screening participation.

Frequency and characteristics of errors by artificial intelligence (AI) in reading screening mammography: a systematic review.

PURPOSE: Artificial intelligence (AI) for reading breast screening mammograms could potentially replace (some) human-reading and improve screening effectiveness. This systematic review aims to identify and quantify the types of AI errors to better understand the consequences of implementing this technology. METHODS: Electronic databases were searched for external validation studies of the accuracy of AI algorithms in real-world screening mammograms. Descriptive synthesis was performed on error types and frequency. False negative proportions (FNP) and false positive proportions (FPP) were pooled within AI positivity thresholds using random-effects meta-analysis. RESULTS: Seven retrospective studies (447,676 examinations; published 2019-2022) met inclusion criteria. Five studies reported AI error as false negatives or false positives. Pooled FPP decreased incrementally with increasing positivity threshold (71.83% [95% CI 69.67, 73.90] at Transpara 3 to 10.77% [95% CI 8.34, 13.79] at Transpara 9). Pooled FNP increased incrementally from 0.02% [95% CI 0.01, 0.03] (Transpara 3) to 0.12% [95% CI 0.06, 0.26] (Transpara 9), consistent with a trade-off with FPP. Heterogeneity within thresholds reflected algorithm version and completeness of the reference standard. Other forms of AI error were reported rarely (location error and technical error in one study each). CONCLUSION: AI errors are largely interpreted in the framework of test accuracy. FP and FN errors show expected variability not only by positivity threshold, but also by algorithm version and study quality. Reporting of other forms of AI errors is sparse, despite their potential implications for adoption of the technology. Considering broader types of AI error would add nuance to reporting that can inform inferences about AI's utility.

Testing outside of the National Bowel and Breast Cancer Screening Programs in Queensland, Australia.

Setting: Bowel and breast cancer testing outside of the national programs is not routinely recorded in Australia, limiting our ability to monitor and estimate true screening coverage. Objective: This study makes preliminary estimates of the proportion of eligible participants who test for bowel and breast cancer outside of national programs using a large convenience sample of 31,065 cancer risk calculator respondents. Methods: Logistic regression was applied to assess difference in cancer testing both within and outside respective programs between demographic groups. Results: Almost one-third (9456 respondents) were aged between 50 and 74 years and eligible to participate in the National Bowel Cancer Screening Program (NBCSP) with 8073 female respondents additionally qualifying for the national BreastScreen program. Out of 4166 respondents who reported not to participate in the NBCSP, over 2000 (48.4%) reported 'screening' outside the NBCSP. For breast cancer the rate of self-reported screening outside BreastScreen was even higher, with 2442 (73.8%) of 3308 respondents who did not participate in BreastScreen reporting undergoing testing elsewhere. Interestingly, outer regional or remote residence was associated with lower participation within the NBCSP (OR = 0.92; p = 0.05) and higher testing outside of BreastScreen (OR = 1.21; p < 0.05) screening programs. Conclusion: Findings provide preliminary support for the need to better understand the volume of cancer testing taking place outside the national programs and to address reporting gaps within the health system.

Association between serum Klotho levels and hypothyroidism in older adults: NHANES 2007-2012.

Whether Klotho plays any role in hypothyroidism is unknown. This study aimed to determine the relationship between serum Klotho levels and hypothyroidism in older adults. From the 2007 to 2012 National Health and Nutrition Examination Survey (NHANES), 1444 older adults aged 65-79 were included in this cross-sectional study. Hypothyroidism was diagnosed using participants' reports of current medications and TSH tests. Klotho was measured using an enzyme-linked immunosorbent assay. The relationship between serum Klotho levels and hypothyroidism in older people was analyzed by one-way analysis of variance, multiple linear regression models, subgroup analyses, interaction tests, smoothed curve fitting, and threshold effects. A total of 209 (14.47%) participants were identified as having hypothyroidism. Serum Klotho (ln transformation) is independently and significantly negatively associated with the risk of hypothyroidism after complete adjustment for confounders (OR = 0.49, 95% CI 0.31-0.80; P = 0.0039). The results remained stable based on subgroup analyses and interaction tests. However, we observed an inverted U-shaped curve between the two using a smoothed curve fitting in the subgroups of 70 < age ≤ 75 years and females, with inflection points of 6.26 and 6.17, respectively. The results of our study indicate that serum Klotho levels negatively correlate with hypothyroidism among older adults.

Newborn Screening Today and Tomorrow: A Brief Report from the International Primary Immunodeficiencies Congress.

This article presents the report of the session on "Newborn Screening for Primary Immunodeficiencies-Now What?" organised during the International Primary Immunodeficiency Congress (IPIC) held in November 2023. This clinical conference was organised by the International Patient Organisation for Primary Immunodeficiencies (IPOPI), the global patient organisation advocating for primary immunodeficiencies (PIDs) in patients. The session aimed at exploring the advances in newborn screening (NBS) for severe combined immunodeficiency, starting with the common practice and inserting the discussion into the wider perspective of genomics whilst taking into consideration the ethical aspects of screening as well as incorporating families and the public into the discussions, so as to ensure that NBS for treatable rare disorders continues to be one of the major public health advances of the 20th century.

Implementing an Early Detection Program for Autism Spectrum Disorders in the Polish Primary Healthcare Setting-Possible Obstacles and Experiences from Online ASD Screening.

A screening questionnaire for autism symptoms is not yet available in Poland, and there are no recommendations regarding screening for developmental disorders in Polish primary healthcare. The aim of this study was to assess the opinions of parents and physicians on the legitimacy and necessity of screening for autism spectrum disorders, potential barriers to the implementation of the screening program, and the evaluation and presentation of the process of online ASD screening, which was part of the validation program for the Polish version of one of the screening tools. This study involved 418 parents whose children were screened online and 95 primary care physicians who expressed their opinions in prepared surveys. The results indicate that both parents and doctors perceive the need to screen children for ASD in the general population without a clear preference as to the screening method (online or in person). Moreover, online screening is considered by respondents as a satisfactory diagnostic method. Therefore, online screening may prove to be at least a partial method of solving numerous obstacles indicated by participants' systemic difficulties including time constraints, the lack of experienced specialists in the field of developmental disorders and organizational difficulties of healthcare systems.

Distribution and Mechanism of Japanese Brome (Bromus japonicus) Resistance to ALS-Inhibiting Herbicides in China.

Bromus japonicus is a common monocot weed that occurs in major winter wheat fields in the Huang-Huai-Hai region of China. Pyroxsulam is a highly efficient and safe acetolactate synthase (ALS)-inhibiting herbicide that is widely used to control common weeds in wheat fields. However, B. japonicus populations in China have evolved resistance to pyroxsulam by different mutations in the ALS gene. To understand the resistance distribution, target-site resistance mechanisms, and cross-resistance patterns, 208 B. japonicus populations were collected from eight provinces. In the resistant population screening experiment, 59 populations from six provinces showed different resistance levels to pyroxsulam compared with the susceptible population, of which 17 B. japonicus populations with moderate or high levels of resistance to pyroxsulam were mainly from the Hebei (4), Shandong (4) and Shanxi (9) Provinces. Some resistant populations were selected to investigate the target site-resistance mechanism to the ALS-inhibiting herbicide pyroxsulam. Three pairs of primers were designed to amplify the ALS sequence, which was assembled into the complete ALS sequence with a length of 1932 bp. DNA sequencing of ALS revealed that four different ALS mutations (Pro-197-Ser, Pro-197-Thr, Pro-197-Phe and Asp-376-Glu) were found in 17 moderately or highly resistant populations. Subsequently, five resistant populations, QM21-41 with Pro-197-Ser, QM20-8 with Pro-197-Thr and Pro-197-Phe, and QM21-72, QM21-76 and QM21-79 with Asp-376-Glu mutations in ALS genes, were selected to characterize their cross-resistance patterns to ALS inhibitors. The QM21-41, QM20-8, QM21-72, QM21-76 and QM21-79 populations showed broad-spectrum cross-resistance to pyroxsulam, mesosulfuron-methyl and flucarbazone-sodium. This study is the first to report evolving cross-resistance to ALS-inhibiting herbicides due to Pro-197-Phe mutations in B. japonicus.

Population-based BRCA germline mutation screening in the Han Chinese identifies individuals at risk of BRCA mutation-related cancer: experience from a clinical diagnostic center from greater Shanghai area.

BACKGROUND: Deleterious BRCA1/2 (BRCA) mutation raises the risk for BRCA mutation-related malignancies, including breast, ovarian, prostate, and pancreatic cancer. Germline variation of BRCA exhibits substantial ethnical diversity. However, there is limited research on the Chinese Han population, constraining the development of strategies for BRCA mutation screening in this large ethnic group. METHODS: We profile the BRCA mutational spectrum, including single nucleotide variation, insertion/deletion, and large genomic rearrangements in 2,080 apparently healthy Chinese Han individuals and 522 patients with BRCA mutation-related cancer, to determine the BRCA genetic background of the Chinese Han population, especially of the East Han. Incident cancer events were monitored in 1,005 participants from the healthy group, comprising 11 BRCA pathogenic/likely pathogenic (PLP) variant carriers and 994 PLP-free individuals, including 3 LGR carriers. RESULTS: Healthy Chinese Han individuals demonstrated a distinct BRCA mutational spectrum compared to cancer patients, with a 0.53% (1 in 189) prevalence of pathogenic/likely pathogenic (PLP) variant, alongside a 3 in 2,080 occurrence of LGR. BRCA1 c. 5470_5477del demonstrated high prevalence (0.44%) in the North Han Chinese and penetrance for breast cancer. None of the 3 LGR carriers developed cancer during the follow-up. We calculated a relative risk of 135.55 (95% CI 25.07 to 732.88) for the development of BRCA mutation-related cancers in the BRCA PLP variant carriers (mean age 42.91 years, median follow-up 10 months) compared to PLP-free individuals (mean age 48.47 years, median follow-up 16 months). CONCLUSION: The unique BRCA mutational profile in the Chinese Han highlights the potential for standardized population-based BRCA variant screening to enhance BRCA mutation-related cancer prevention and treatment.

The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation.

Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is over US$891 billion per year. Within three decades (1990-2019), the incidence increased by 70%, deaths by 43%, prevalence by 102%, and DALYs by 143%. Of over 100 million people affected by stroke, about 76% are ischemic stroke (IS) patients recorded worldwide. Contextually, ischemic stroke moves into particular focus of multi-professional groups including researchers, healthcare industry, economists, and policy-makers. Risk factors of ischemic stroke demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) and secondary (clinically manifested collateral disorders contributing to stroke risks) care. These risks are interrelated. For example, sedentary lifestyle and toxic environment both cause mitochondrial stress, systemic low-grade inflammation and accelerated ageing; inflammageing is a low-grade inflammation associated with accelerated ageing and poor stroke outcomes. Stress overload, decreased mitochondrial bioenergetics and hypomagnesaemia are associated with systemic vasospasm and ischemic lesions in heart and brain of all age groups including teenagers. Imbalanced dietary patterns poor in folate but rich in red and processed meat, refined grains, and sugary beverages are associated with hyperhomocysteinaemia, systemic inflammation, small vessel disease, and increased IS risks. Ongoing 3PM research towards vulnerable groups in the population promoted by the European Association for Predictive, Preventive and Personalised Medicine (EPMA) demonstrates promising results for the holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as a vital biosensor and AI-based multi-professional data interpretation as reported here by the EPMA expert group. Collected data demonstrate that IS-relevant risks and corresponding molecular pathways are interrelated. For examples, there is an evident overlap between molecular patterns involved in IS and diabetic retinopathy as an early indicator of IS risk in diabetic patients. Just to exemplify some of them such as the 5-aminolevulinic acid/pathway, which are also characteristic for an altered mitophagy patterns, insomnia, stress regulation and modulation of microbiota-gut-brain crosstalk. Further, ceramides are considered mediators of oxidative stress and inflammation in cardiometabolic disease, negatively affecting mitochondrial respiratory chain function and fission/fusion activity, altered sleep-wake behaviour, vascular stiffness and remodelling. Xanthine/pathway regulation is involved in mitochondrial homeostasis and stress-driven anxiety-like behaviour as well as molecular mechanisms of arterial stiffness. In order to assess individual health risks, an application of machine learning (AI tool) is essential for an accurate data interpretation performed by the multiparametric analysis. Aspects presented in the paper include the needs of young populations and elderly, personalised risk assessment in primary and secondary care, cost-efficacy, application of innovative technologies and screening programmes, advanced education measures for professionals and general population-all are essential pillars for the paradigm change from reactive medical services to 3PM in the overall IS management promoted by the EPMA.