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The COVID-19 pandemic highlighted the need for advance care planning (ACP) as a way to help mitigate the various care concerns that accompanied the healthcare crisis. However, unique obstacles to typical ACP practice necessitated the need for guidance and innovation to help facilitate these vital conversations. The aim of this systematic review was to identify the various ACP barriers and facilitators that arose during the pandemic and determine how ACP practice was affected across different contexts and among different populations. This systematic review (PROSPERO registration number: CRD42022359092), which adheres to the PRISMA guidelines for reporting systematic reviews, examined studies on ACP in the context of the COVID-19 pandemic. The review involved searches of five databases, including MEDLINE and Embase. Of the 843 identified studies, 115 met the inclusion criteria. The extracted ACP barriers and facilitators were codified and quantified. The most frequently occurring ACP barrier codes were: Social distancing measures and visitation restrictions, Uncertainty surrounding the COVID-19 prognosis, and Technological/Telehealth barriers. The most frequently occurring ACP facilitator codes were the following: Telehealth/virtual ACP platforms, Training for clinicians, and Care team collaboration. Identifying the ACP barriers and facilitators is essential for developing effective, resilient ACP promotion strategies and improving its delivery, accessibility, and acceptability.

Our ability to taste bitterness affects our food choices and alcohol consumption. Alleles in the taste 2 receptor member TAS2R38 have been linked to the ability to perceive bitterness in bitter-tasting compounds and in many foods, and people with these bitterness sensitivity alleles have been shown to be less likely to consume alcohol, presumably because of alcohol's bitter taste. In a survey of 519 participants, almost all of whom regularly consumed alcohol, we observed that genetic variants in TAS2R38 were significantly associated with both increased alcohol consumption and the ability to perceive bitterness in several foods and a bitter chemical. In total, we assayed 39 variants in 25 genes that have been implicated in the genetics of taste perception, and no other variants predicted alcohol consumption. Perception of bitterness in broccoli and a preference for black coffee were also positively associated with alcohol consumption. As the consumption of alcohol is a social activity there may be incentive to appreciate its bitter aspects, and increased perception of bitterness could therefore be associated with consumption of some bitter beverages. As this study's respondents were predominantly frequent consumers of alcohol, these findings may be consistent with previous studies that have seen that increased experience in the consumption of wine is associated with an increased perception of PROP bitterness. Further work elucidating the complex relationship between the genetics of bitter perception and alcohol consumption will better describe these connections.

Almost one third of the three million people in China suffering severe deafness are children, and 50% of these cases are believed to have genetic components to their etiology. Newborn hearing genetic screening can complement Universal Neonatal Hearing Screening for the diagnosis of congenital hearing loss as well as identifying children at risk for late-onset and progressive hearing impairment. The aim of this joint academic and Ministry of Health project was to prototype a cost effective newborn genetic screen in a community health setting on a city-wide level, and to ascertain the prevalence of variation at loci that have been associated with non-syndromic hearing loss. With the participation of 143 local hospitals in the city of Wuhan, China we screened 142,417 neonates born between May 2014 and Dec. 2015. The variants GJB2 c.235delC, SLC26A4 c.919-2A>G, and mitochondrial variants m.1555A>G and m.1494C>T were assayed using real time PCR. Newborns found to carry a variant were re-assayed by sequencing in duplicate. Within a subset of 707 newborns we assayed using real-time PCR and ARMS-PCR to compare cost, sensitivity and operating procedure. The most frequent hearing loss associated allele detected in this population was the 235delC variant in GJB2 gene. In total, 4289 (3.01%) newborns were found to carry at least one allele of either GJB2 c.235delC, SLC26A4 c.919-2A>G or two assayed MT-RNR1 variants. There was complete accordance between the real-time PCR and the ARMS PCR, though the real-time PCR had a much lower failure rate. Real-time PCR had a lower cost and operating time than ARMS PCR. Ongoing collaboration with the participating hospitals will determine the specificity and sensitivity of the association of the variants with hearing loss at birth and arising in early childhood, allowing an estimation of the benefits of newborn hearing genetic screening in a large-scale community setting.

The morphology of breast tumors is complicated and diagnosis can be difficult. We present here a novel diagnostic model which we validate on both array-based and RNA sequencing platforms which reliably distinguishes this tumor type across multiple cohorts. We also examine how this molecular classification predicts sensitivity to common chemotherapeutics in cell-line based assays. A total of 1845 invasive breast cancer cases in six cohorts were collected, split into discovery and validation cohorts, and a classifier was created and compared to pathological diagnosis, grade and survival. In the validation cohorts the concordance of predicted diagnosis with a pathological diagnosis was 92%, and 97% when inconclusively classified cases were excluded. Tumor-derived cell lines were classified with the model as having predominantly ductal or lobular-like molecular physiologies, and sensitivity of these lines to relevant compounds was analyzed. A diagnostic tool can be created that reliably distinguishes lobular from ductal carcinoma and allows the classification of cell lines on the basis of molecular profiles associated with these tumor types. This tool may assist in improved diagnosis and aid in explorations of the response of lobular type breast tumor models to different compounds.

There is considerable variability between individuals in susceptibility to infection by human immunodeficiency virus (HIV). Many social, clinical and genetic factors are known to contribute to the likelihood of HIV transmission, but there is little consensus on the relative importance and potential interaction of these factors. Additionally, recent studies of several variants in chemokine receptors have identified alleles that may be predictive of HIV transmission and disease progression; however the strengths and directions of the associations of these genetic markers with HIV transmission have markedly varied between studies. To better identify factors that predict HIV transmission in a Chinese population, 180 cohabiting serodiscordant couples were enrolled for study by the Henan Center for Disease Prevention and Control, and transmission and progression of HIV infection were regularly measured. We found that anti-retroviral therapy, education level, and condom use were the most significant factors in determining likelihood of HIV transmission in this study. We also assessed ten variants in three genes (CXCL12, CCR2, and CCR5) that have been shown to influence HIV transmission. We found two tightly linked variants in CCR2 and CCR5, rs1799864 and rs1800024, have a significant positive association with transmission as recessive models (OR>10, P value=0.011). Mixed effects models showed that these genetic variants both retained significance when assessed with either treatment or condom use. These markers of transmission susceptibility may therefore serve to help stratify individuals by risk for HIV transmission.

Background: Genetic variations, including mitochondrial mutations, are important contributors to hearing loss, especially in children, and newborn genetic screens for hearing loss mutations are becoming increasingly common. Mitochondrial mutations have been linked with ototoxic responses to common antibiotics, therefore understanding the association of these mutations with hearing loss is of special importance. To address the usefulness of screening for these mutations in a clinical setting, we formed a collaboration of clinicians and geneticists to analyse the association of mitochondrial mutations with non-syndromic hearing loss, including the effect of ethnicity, audiological test methods and aminoglycoside exposure., Methods: This survey identified 122 variants in 43 studies that have been assessed for an association with hearing loss, and meta-analysis was performed on clinically relevant subsets. RNA folding and conservation analysis further explored possible relevance of these variants., Results: Among all studies, eight variants were found to have significant associations with hearing loss. A partially overlapping set of six variants had significant association with hearing loss when aminoglycoside exposure was assessed. Five of these variants predictive of sensitivity to aminoglycoside spatially co-localise in an RNA folding model. There was little effect of the audiological test method used to assess hearing loss on the association with the variants., Conclusions: Our results found a small set of studied variants had reproducible association with hearing loss, which will help clarify mutations useful in genetic screens for hearing loss. Several of the aminoglycoside exposure-associated mutations may co-localise on folded 12S rRNA, suggesting a functional association between these loci and aminoglycoside-induced hearing loss., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)