OBJECTIVE: To examine user uptake and experience with a clinical chatbot that automates hereditary cancer risk triage by collecting personal and family cancer history in routine women's health care settings. METHODS: We conducted a multicenter, retrospective observational study of patients who used a web-based chatbot before routine care appointments to assess their risk for hereditary breast and ovarian cancer, Lynch syndrome, and adenomatous polyposis syndromes. Outcome measures included uptake and completion of the risk-assessment and educational section of the chatbot interaction and identification of hereditary cancer risk as evaluated against National Comprehensive Cancer Network criteria. RESULTS: Of the 95,166 patients invited, 61,070 (64.2%) engaged with the clinical chatbot. The vast majority completed the cancer risk assessment (89.4%), and most completed the genetic testing education section (71.4%), indicating high acceptability among those who opted to engage. The mean duration of use was 15.4 minutes (SD 2 hours, 56.2 minutes) when gaps of inactivity longer than 5 minutes were excluded. A personal history of cancer was reported by 19.1% (10,849/56,656) and a family history of cancer was reported by 66.7% (36,469/54,652) of patients who provided the relevant information. One in four patients (14,850/54,547) screened with the chatbot before routine care appointments met National Comprehensive Cancer Network criteria for genetic testing. Among those who were tested, 5.6% (73/1,313) had a disease-causing pathogenic variant. CONCLUSION: A chatbot digital health tool can help identify patients at high risk for hereditary cancer syndromes before routine care appointments. This scalable intervention can effectively provide cancer risk assessment, engage patients with educational information, and facilitate a path toward preventive genetic testing. FUNDING SOURCE: Implementation of the chatbot in clinics was funded by industry support from commercial genetic testing laboratories Ambry, Invitae, and Progenity.

Research assessing the impact of inappropriate sexual behaviour (ISB) on staff working in dementia care is circumscribed, yet studies from comparable settings indicate that ISB appears uniquely challenging, particularly to personal and cultural values. This study explored staff experiences of ISB exhibited by older adults with a dementia. Fourteen staff working within an in-patient setting were interviewed. Participants’ experiences of ISB appeared underpinned by complex social and psychological processes. Shock, embarrassment and incomprehension were prominent when ISB was initially encountered. Knowledge of dementia, familiarity with patients and social norms were important in contextualising ISB and staff often minimised its impact by construing a lack of capacity. Feelings about ISB appeared equivocal and findings suggest that the effect of ISB should be routinely considered in preparing staff who work within dementia care.

Genetic testing can provide definitive molecular diagnoses and guide clinical management decisions from preconception through adulthood. Innovative solutions for scaling clinical genomics services are necessary if they are to transition from a niche specialty to a routine part of patient care. The expertise of specialists, like genetic counselors and medical geneticists, has traditionally been relied upon to facilitate testing and follow‐up, and while ideal, this approach is limited in its ability to integrate genetics into primary care. As individuals, payors, and providers increasingly realize the value of genetics in mainstream medicine, several implementation challenges need to be overcome. These include electronic health record integration, patient and provider education, tools to stay abreast of guidelines, and simplification of the test ordering process. Currently, no single platform offers a holistic view of genetic testing that streamlines the entire process across specialties that begins with identifying at‐risk patients in mainstream care settings, providing pretest education, facilitating consent and test ordering, and following up as a “genetic companion” for ongoing management. We describe our vision for using software that includes clinical‐grade chatbots and decision support tools, with direct access to genetic counselors and pharmacists within a modular, integrated, end‐to‐end testing journey.

The primary literature on human genetic diseases with high penetrance includes descriptions of large numbers of pathogenic variants that can be essential for clinical diagnosis. Variant databases such as ClinVar and HGMD collect pathogenic variants by manual curation of either voluntary submissions or the published literature. AVADA (Automatically curated VAriant DAtabase) represents the first automated tool designed to construct a comprehensive database of highly penetrant genetic variants directly from full-text articles about human genetic disease. 2 AVADA was able to automatically curate almost 60% of the pathogenic variants deposited in 24 HGMD, over 4 times more than approaches parsing only PubMed abstracts. AVADA also 25 contains more than 60,000 pathogenic variants that are in HGMD, but not in ClinVar. Despite 26 being fully automated, 9 of AVADA's top 10 yielding journals are shared with HGMD's top 10, 27 and its mutation type distribution strongly resembles that of both HGMD and ClinVar. We demonstrate the utility of AVADA in clinical practice on a cohort of 245 patients with already diagnosed genetic diseases. Out of 260 causative variants originally reported for these patients, AVADA contained 38 variants described in the literature prior to publication of the patient cohort, compared to 43 using HGMD, 20 using ClinVar and only 13 (wholly subsumed by AVADA's) using an automated abstracts-only based approach. The database of automatically curated variants will be made available upon publication at http://bejerano.stanford.edu/AVADA. 35

Purpose The incidence of colorectal cancer (CRC) in Ghana has increased eightfold since the 1960s. In 2011, national guidelines were set forth recommending all patients aged 50–70 years old undergo annual CRC screening with fecal occult blood testing (FOBT), but adherence to these guidelines is poor and screening rates remain low for unclear reasons. Methods We performed semi-structured interviews with 28 Ghanaians including physicians ( n = 14) and patients ( n = 14) from the Komfo Anokye Teaching Hospital in Kumasi, Ghana, to better understand the factors driving screening adherence and perceived barriers identified in an earlier quantitative study. Results Participants reported sociocultural factors such as reliance on alternative medicine or religion, lack of education, and financial burden as community-level barriers to CRC screening. At the system level, screening was limited by insufficient access to FOBT as well as a perceived lack of national prioritization. This was described as inadequate efforts from the Ministry of Health regarding national education as well as lack of incorporation of CRC screening into the National Health Insurance Scheme. Conclusion Several community- and system-level barriers exist to widespread screening of CRC in Ghana. A multi-level approach will be required to improve rates of CRC screening and ultimately reduce the burden of CRC in Ghana.

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Protein arylation has attracted much attention for developing new classes of bioconjugates with improved properties. Here, we have systematically evaluated 2-sulfonylpyrimidines as covalent warheads for the mild, chemoselective and metal free cysteine S-arylation. 2-sulfonylpyrimidines react rapidly with cysteine, resulting in stable S-heteroarylated adducts at neutral pH. Fine tuning the heterocyclic core and exocyclic leaving group allowed predictable SNAr reactivity with model tripeptide glutathione in vitro, covering 9 orders of magnitude. We achieved extremely fast chemo- and regio- specific arylation of a mutant p53 protein, and confirmed arylation sites by protein X-ray crystallography. Hence, we report the first example of a protein site specifically S-arylated with iodo-aromatic motifs. Overall, this study provides the most comprehensive structure-reactivity relationship to date on heteroaryl sulfones, and highlights 2-sulfonylpyrimidine as a synthetically tractable and protein compatible covalent motif for targeting reactive cysteines, expanding the arsenal of tunable warheads for modern covalent ligand discovery.