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Training therapists is both expensive and time-consuming. Degree-based training can require tens of thousands of dollars and hundreds of hours of expert instruction. Counseling skills practice often involves role-plays, standardized patients, or practice with real clients. Performance-based feedback is critical for skill development and expertise, but trainee therapists often receive minimal and subjective feedback, which is distal to their skill practice. In this study, we developed and evaluated a patient-like neural conversational agent, which provides real-time feedback to trainees via chat-based interaction. The text-based conversational agent was trained on an archive of 2354 psychotherapy transcripts and provided specific feedback on the use of basic interviewing and counseling skills (ie, open questions and reflections-summary statements of what a client has said). A total of 151 nontherapists were randomized to either (1) immediate feedback on their use of open questions and reflections during practice session with ClientBot or (2) initial education and encouragement on the skills. Participants in the ClientBot condition used 91% (21.4/11.2) more reflections during practice with feedback (P<.001) and 76% (14.1/8) more reflections after feedback was removed (P<.001) relative to the control group. The treatment group used more open questions during training but not after feedback was removed, suggesting that certain skills may not improve with performance-based feedback. Finally, after feedback was removed, the ClientBot group used 31% (32.5/24.7) more listening skills overall (P<.001). This proof-of-concept study demonstrates that practice and feedback can improve trainee use of basic counseling skills.

Cancer has become the second leading cause of death globally. Most cancer cases are due to genetic mutations, which affect metabolism and result in facial changes. In this study, we aimed to identify the facial features of patients with cancer using the deep learning technique. Images of faces of patients with cancer were collected to build the cancer face image data set. A face image data set of people without cancer was built by randomly selecting images from the publicly available MegaAge data set according to the sex and age distribution of the cancer face image data set. Each face image was preprocessed to obtain an upright centered face chip, following which the background was filtered out to exclude the effects of nonrelative factors. A residual neural network was constructed to classify cancer and noncancer cases. Transfer learning, minibatches, few epochs, L2 regulation, and random dropout training strategies were used to prevent overfitting. Moreover, guided gradient-weighted class activation mapping was used to reveal the relevant features. A total of 8124 face images of patients with cancer (men: n=3851, 47.4%; women: n=4273, 52.6%) were collected from January 2018 to January 2019. The ages of the patients ranged from 1 year to 70 years (median age 52 years). The average faces of both male and female patients with cancer displayed more obvious facial adiposity than the average faces of people without cancer, which was supported by a landmark comparison. When testing the data set, the training process was terminated after 5 epochs. The area under the receiver operating characteristic curve was 0.94, and the accuracy rate was 0.82. The main relative feature of cancer cases was facial skin, while the relative features of noncancer cases were extracted from the complementary face region. In this study, we built a face data set of patients with cancer and constructed a deep learning model to classify the faces of people with and those without cancer. We found that facial skin and adiposity were closely related to the presence of cancer.

Histopathology image evaluation is indispensable for cancer diagnoses and subtype classification. Standard artificial intelligence methods for histopathology image analyses have focused on optimizing specialized models for each diagnostic task 1 , 2 . Although such methods have achieved some success, they often have limited generalizability to images generated by different digitization protocols or samples collected from different populations 3 . Here, to address this challenge, we devised the Clinical Histopathology Imaging Evaluation Foundation (CHIEF) model, a general-purpose weakly supervised machine learning framework to extract pathology imaging features for systematic cancer evaluation. CHIEF leverages two complementary pretraining methods to extract diverse pathology representations: unsupervised pretraining for tile-level feature identification and weakly supervised pretraining for whole-slide pattern recognition. We developed CHIEF using 60,530 whole-slide images spanning 19 anatomical sites. Through pretraining on 44 terabytes of high-resolution pathology imaging datasets, CHIEF extracted microscopic representations useful for cancer cell detection, tumour origin identification, molecular profile characterization and prognostic prediction. We successfully validated CHIEF using 19,491 whole-slide images from 32 independent slide sets collected from 24 hospitals and cohorts internationally. Overall, CHIEF outperformed the state-of-the-art deep learning methods by up to 36.1%, showing its ability to address domain shifts observed in samples from diverse populations and processed by different slide preparation methods. CHIEF provides a generalizable foundation for efficient digital pathology evaluation for patients with cancer. A study describes the development of a generalizable foundation machine learning framework to extract pathology imaging features for cancer diagnosis and prognosis prediction.

Deep learning methods are a class of machine learning techniques capable of identifying highly complex patterns in large datasets. Here, we provide a perspective and primer on deep learning applications for genome analysis. We discuss successful applications in the fields of regulatory genomics, variant calling and pathogenicity scores. We include general guidance for how to effectively use deep learning methods as well as a practical guide to tools and resources. This primer is accompanied by an interactive online tutorial. This perspective presents a primer on deep learning applications for the genomics field. It includes a general guide for how to use deep learning and describes the current tools and resources that are available to the community.

Proteins are essential to life, and understanding their structure can facilitate a mechanistic understanding of their function. Through an enormous experimental effort 1 , 2 , 3 – 4 , the structures of around 100,000 unique proteins have been determined 5 , but this represents a small fraction of the billions of known protein sequences 6 , 7 . Structural coverage is bottlenecked by the months to years of painstaking effort required to determine a single protein structure. Accurate computational approaches are needed to address this gap and to enable large-scale structural bioinformatics. Predicting the three-dimensional structure that a protein will adopt based solely on its amino acid sequence—the structure prediction component of the ‘protein folding problem’ 8 —has been an important open research problem for more than 50 years 9 . Despite recent progress 10 , 11 , 12 , 13 – 14 , existing methods fall far short of atomic accuracy, especially when no homologous structure is available. Here we provide the first computational method that can regularly predict protein structures with atomic accuracy even in cases in which no similar structure is known. We validated an entirely redesigned version of our neural network-based model, AlphaFold, in the challenging 14th Critical Assessment of protein Structure Prediction (CASP14) 15 , demonstrating accuracy competitive with experimental structures in a majority of cases and greatly outperforming other methods. Underpinning the latest version of AlphaFold is a novel machine learning approach that incorporates physical and biological knowledge about protein structure, leveraging multi-sequence alignments, into the design of the deep learning algorithm. AlphaFold predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture.

Artificial intelligence (AI) systems for computer-aided diagnosis and image-based screening are being adopted worldwide by medical institutions. In such a context, generating fair and unbiased classifiers becomes of paramount importance. The research community of medical image computing is making great efforts in developing more accurate algorithms to assist medical doctors in the difficult task of disease diagnosis. However, little attention is paid to the way databases are collected and how this may influence the performance of AI systems. Our study sheds light on the importance of gender balance in medical imaging datasets used to train AI systems for computer-assisted diagnosis. We provide empirical evidence supported by a large-scale study, based on three deep neural network architectures and two well-known publicly available X-ray image datasets used to diagnose various thoracic diseases under different gender imbalance conditions. We found a consistent decrease in performance for underrepresented genders when a minimum balance is not fulfilled. This raises the alarm for national agencies in charge of regulating and approving computer-assisted diagnosis systems, which should include explicit gender balance and diversity recommendations. We also establish an open problem for the academic medical image computing community which needs to be addressed by novel algorithms endowed with robustness to gender imbalance.

Protein structures can provide invaluable information, both for reasoning about biological processes and for enabling interventions such as structure-based drug development or targeted mutagenesis. After decades of effort, 17% of the total residues in human protein sequences are covered by an experimentally determined structure 1 . Here we markedly expand the structural coverage of the proteome by applying the state-of-the-art machine learning method, AlphaFold 2 , at a scale that covers almost the entire human proteome (98.5% of human proteins). The resulting dataset covers 58% of residues with a confident prediction, of which a subset (36% of all residues) have very high confidence. We introduce several metrics developed by building on the AlphaFold model and use them to interpret the dataset, identifying strong multi-domain predictions as well as regions that are likely to be disordered. Finally, we provide some case studies to illustrate how high-quality predictions could be used to generate biological hypotheses. We are making our predictions freely available to the community and anticipate that routine large-scale and high-accuracy structure prediction will become an important tool that will allow new questions to be addressed from a structural perspective. AlphaFold is used to predict the structures of almost all of the proteins in the human proteome—the availability of high-confidence predicted structures could enable new avenues of investigation from a structural perspective.

The introduction of AlphaFold 2 1 has spurred a revolution in modelling the structure of proteins and their interactions, enabling a huge range of applications in protein modelling and design 2 , 3 , 4 , 5 – 6 . Here we describe our AlphaFold 3 model with a substantially updated diffusion-based architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues. The new AlphaFold model demonstrates substantially improved accuracy over many previous specialized tools: far greater accuracy for protein–ligand interactions compared with state-of-the-art docking tools, much higher accuracy for protein–nucleic acid interactions compared with nucleic-acid-specific predictors and substantially higher antibody–antigen prediction accuracy compared with AlphaFold-Multimer v.2.3 7 , 8 . Together, these results show that high-accuracy modelling across biomolecular space is possible within a single unified deep-learning framework. AlphaFold 3 has a substantially updated architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues with greatly improved accuracy over many previous specialized tools.

Machine-assisted pathological recognition has been focused on supervised learning (SL) that suffers from a significant annotation bottleneck. We propose a semi-supervised learning (SSL) method based on the mean teacher architecture using 13,111 whole slide images of colorectal cancer from 8803 subjects from 13 independent centers. SSL (~3150 labeled, ~40,950 unlabeled; ~6300 labeled, ~37,800 unlabeled patches) performs significantly better than the SL. No significant difference is found between SSL (~6300 labeled, ~37,800 unlabeled) and SL (~44,100 labeled) at patch-level diagnoses (area under the curve (AUC): 0.980 ± 0.014 vs. 0.987 ± 0.008, P value = 0.134) and patient-level diagnoses (AUC: 0.974 ± 0.013 vs. 0.980 ± 0.010, P value = 0.117), which is close to human pathologists (average AUC: 0.969). The evaluation on 15,000 lung and 294,912 lymph node images also confirm SSL can achieve similar performance as that of SL with massive annotations. SSL dramatically reduces the annotations, which has great potential to effectively build expert-level pathological artificial intelligence platforms in practice. Machine-assisted recognition of colorectal cancer has been mainly focused on supervised deep learning that suffers from a significant bottleneck of requiring massive amounts of labeled data. Here, the authors propose a semi-supervised model based on the mean teacher architecture that provides pathological predictions at both patch- and patient-levels.

Google’s deep-learning program for determining the 3D shapes of proteins stands to transform biology, say scientists. Google’s deep-learning program for determining the 3D shapes of proteins stands to transform biology, say scientists.