Artificial intelligence (AI) has shown promise for diagnosing prostate cancer in biopsies. However, results have been limited to individual studies, lacking validation in multinational settings. Competitions have been shown to be accelerators for medical imaging innovations, but their impact is hindered by lack of reproducibility and independent validation. With this in mind, we organized the PANDA challenge—the largest histopathology competition to date, joined by 1,290 developers—to catalyze development of reproducible AI algorithms for Gleason grading using 10,616 digitized prostate biopsies. We validated that a diverse set of submitted algorithms reached pathologist-level performance on independent cross-continental cohorts, fully blinded to the algorithm developers. On United States and European external validation sets, the algorithms achieved agreements of 0.862 (quadratically weighted κ, 95% confidence interval (CI), 0.840–0.884) and 0.868 (95% CI, 0.835–0.900) with expert uropathologists. Successful generalization across different patient populations, laboratories and reference standards, achieved by a variety of algorithmic approaches, warrants evaluating AI-based Gleason grading in prospective clinical trials.

The ecology and genetic diversity of model yeast Saccharomyces cerevisiae prior to human domestication remain poorly understood. Taiwan is regarded as part of this yeast's geographic birthplace where the most divergent natural lineage was discovered. Here, we extensively sampled the broad-leaf forests across this continental island to probe the ancestral species diversity. We found that S. cerevisiae is distributed ubiquitously at low abundance in the forests. Whole-genome sequencing of 121 isolates revealed nine distinct lineages that diverged from Asian lineages during the Pleistocene, when a transient continental shelf land bridge connected Taiwan to other major landmasses. Three lineages are endemic to Taiwan and six are widespread in Asia, making this region a focal biodiversity hotspot. Both ancient and recent admixture events were detected between natural lineages and a genetic ancestry component associated with isolates from fruits was detected in most admixed isolates. Collectively, Taiwanese isolates harbor genetic diversity comparable to that of the whole Asia continent, and different lineages have coexisted at a fine spatial scale even on the same tree. Patterns of variations within each lineage revealed that S. cerevisiae is highly clonal and predominantly reproduces asexually in nature. We identified different selection patterns shaping the coding sequences of natural lineages and found fewer gene family expansion and contractions which contrast with domesticated lineages. This study establishes that S. cerevisiae has rich natural diversity sheltered from human influences, making it a powerful model system in microbial ecology.

The emergence of carbapenemase-producing Klebsiella pneumoniae (CPKP) has become a great concern worldwide. In this study, 994 non-duplicate, carbapenem non-susceptible Klebsiella pneumonia isolates were collected in Taiwan from 2011 to 2013 for detection of the carbapenemase genes, assessment of antimicrobial susceptibility and molecular epidemiology studies. Of these 994 isolates, 183 (18.4%) had carbapenemase genes: 157 (15.8%) KPC (145 KPC-2 and 12 KPC-17), 16 (1.6%) IMP-8, 9 (0.9%) VIM-1, and 1 (0.1%) NDM-1. KPC had the highest prevalence rate among the carbapenemases and represented a major epidemic clone circulating in Taiwan. The ST512 and ST258 KPC-2 KPs were first identified in Taiwan and were grouped into a small cluster in the PFGE profile. In addition, the genetic structure encompassing the bla KPC gene of the ST512 and ST258 isolates showed a different pattern from that of other KPC isolates. ST11 may be a major sequence type circulating in Taiwan, although a specific minor clone has begun to be observed. This is the first report of ST258 and ST512 KPC-2 KP isolates in Taiwan, whether ST258 and ST512 will become the next endemic problems in Taiwan should be closely monitored.

The early-diverging eudicot family Berberidaceae is composed of a morphologically diverse assemblage of disjunctly distributed genera long praised for their great horticultural and medicinal values. However, despite century-long studies, generic delimitation of Berberidaceae remains controversial and its tribal classification has never been formally proposed under a rigorous phylogenetic context. Currently, the number of accepted genera in Berberidaceae ranges consecutively from 13 to 19, depending on whether to define Berberis, Jeffersonia, and Podophyllum broadly, or to segregate these three genera further and recognize Alloberberis, Mahonia, and Moranothamnus, Plagiorhegma, and Dysosma, Diphylleia, and Sinopodophyllum, respectively. To resolve Berberidaceae’s taxonomic disputes, we newly assembled 23 plastomes and, together with 85 plastomes from the GenBank, completed the generic sampling of the family. With 4 problematic and 14 redundant plastome sequences excluded, robust phylogenomic relationships were reconstructed based on 93 plastomes representing all 19 genera of Berberidaceae and three outgroups. Maximum likelihood phylogenomic relationships corroborated with divergence time estimation support the recognition of three subfamilies Berberidoideae, Nandinoideae, and Podophylloideae, with tribes Berberideae and Ranzanieae, Leonticeae and Nandineae, and Podophylleae, Achlydeae, Bongardieae tr. nov., Epimedieae, and Jeffersonieae tr. nov. in the former three subfamilies, respectively. By applying specifically stated criteria, our phylogenomic data also support the classification of 19 genera, recognizing Alloberberis, Mahonia, and Moranothamnus, Plagiorhegma, and Diphylleia, Dysosma, and Sinopodophyllum that are morphologically and evolutionarily distinct from Berberis, Jeffersonia, and Podophyllum, respectively. Comparison of plastome structures across Berberidaceae confirms inverted repeat expansion in the tribe Berberideae and reveals substantial length variation in accD gene caused by repeated sequences in Berberidoideae. Comparison of plastome tree with previous studies and nuclear ribosomal DNA (nrDNA) phylogeny also reveals considerable conflicts at different phylogenetic levels, suggesting that incomplete lineage sorting and/or hybridization had occurred throughout the evolutionary history of Berberidaceae and that Alloberberis and Moranothamnus could have resulted from reciprocal hybridization between Berberis and Mahonia in ancient times prior to the radiations of the latter two genera.

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