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1. Advances in Materials and Structures for Ingestible Electromechanical Medical Devices

   https://doi.org/10.1002/anie.201806470  

   Bettinger, Christopher J. ( October 2018 , Angewandte Chemie International Edition)

   Ingestible biomedical devices that diagnose, prevent, or treat diseases has been a dream of engineers and clinicians for decades. The increasing apparent importance of gut health on overall well‐being and the prevalence of many gastrointestinal diseases have renewed focus on this emerging class of medical devices. Several prominent examples of commercially successful ingestible medical devices exist. However, many technical challenges remain before ingestible medical devices can achieve their full clinical potential. This Minireview summarizes recent discoveries in this interdisciplinary topic including novel materials, advanced materials processing techniques, and select examples of integrated ingestible electromechanical systems. After a brief historical perspective, these topics will be reviewed with a dedicated focus on advanced functional materials and fabrication strategies in the context of clinical translation and potential regulatory considerations. Future perspectives, challenges, and opportunities related to ingestible medical devices will also be summarized.

    

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2. Prediction of short-term antidepressant response using probabilistic graphical models with replication across multiple drugs and treatment settings

   https://doi.org/10.1038/s41386-020-00943-x  

   Athreya, Arjun P. ; Brückl, Tanja ; Binder, Elisabeth B. ; John Rush, A. ; Biernacka, Joanna ; Frye, Mark A. ; Neavin, Drew ; Skime, Michelle ; Monrad, Ditlev ; Iyer, Ravishankar K. ; et al ( June 2021 , Neuropsychopharmacology)

   null (Ed.)

   Abstract Heterogeneity in the clinical presentation of major depressive disorder and response to antidepressants limits clinicians’ ability to accurately predict a specific patient’s eventual response to therapy. Validated depressive symptom profiles may be an important tool for identifying poor outcomes early in the course of treatment. To derive these symptom profiles, we first examined data from 947 depressed subjects treated with selective serotonin reuptake inhibitors (SSRIs) to delineate the heterogeneity of antidepressant response using probabilistic graphical models (PGMs). We then used unsupervised machine learning to identify specific depressive symptoms and thresholds of improvement that were predictive of antidepressant response by 4 weeks for a patient to achieve remission, response, or nonresponse by 8 weeks. Four depressive symptoms (depressed mood, guilt feelings and delusion, work and activities and psychic anxiety) and specific thresholds of change in each at 4 weeks predicted eventual outcome at 8 weeks to SSRI therapy with an average accuracy of 77% ( p  = 5.5E-08). The same four symptoms and prognostic thresholds derived from patients treated with SSRIs correctly predicted outcomes in 72% ( p  = 1.25E-05) of 1996 patients treated with other antidepressants in both inpatient and outpatient settings in independent publicly-available datasets. These predictive accuracies were higher than the accuracy of 53% for predicting SSRI response achieved using approaches that (i) incorporated only baseline clinical and sociodemographic factors, or (ii) used 4-week nonresponse status to predict likely outcomes at 8 weeks. The present findings suggest that PGMs providing interpretable predictions have the potential to enhance clinical treatment of depression and reduce the time burden associated with trials of ineffective antidepressants. Prospective trials examining this approach are forthcoming. 

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3. Physiologic signatures within six hours of hospitalization identify acute illness phenotypes

   https://doi.org/10.1371/journal.pdig.0000110  

   Ren, Yuanfang ; Loftus, Tyler J. ; Li, Yanjun ; Guan, Ziyuan ; Ruppert, Matthew M. ; Datta, Shounak ; Upchurch, Gilbert R. ; Tighe, Patrick J. ; Rashidi, Parisa ; Shickel, Benjamin ; et al ( October 2022 , PLOS Digital Health)

   Keim-Malpass, Jessica (Ed.)

   During the early stages of hospital admission, clinicians use limited information to make decisions as patient acuity evolves. We hypothesized that clustering analysis of vital signs measured within six hours of hospital admission would reveal distinct patient phenotypes with unique pathophysiological signatures and clinical outcomes. We created a longitudinal electronic health record dataset for 75,762 adult patient admissions to a tertiary care center in 2014–2016 lasting six hours or longer. Physiotypes were derived via unsupervised machine learning in a training cohort of 41,502 patients applying consensus k -means clustering to six vital signs measured within six hours of admission. Reproducibility and correlation with clinical biomarkers and outcomes were assessed in validation cohort of 17,415 patients and testing cohort of 16,845 patients. Training, validation, and testing cohorts had similar age (54–55 years) and sex (55% female), distributions. There were four distinct clusters. Physiotype A had physiologic signals consistent with early vasoplegia, hypothermia, and low-grade inflammation and favorable short-and long-term clinical outcomes despite early, severe illness. Physiotype B exhibited early tachycardia, tachypnea, and hypoxemia followed by the highest incidence of prolonged respiratory insufficiency, sepsis, acute kidney injury, and short- and long-term mortality. Physiotype C had minimal early physiological derangement and favorable clinical outcomes. Physiotype D had the greatest prevalence of chronic cardiovascular and kidney disease, presented with severely elevated blood pressure, and had good short-term outcomes but suffered increased 3-year mortality. Comparing sequential organ failure assessment (SOFA) scores across physiotypes demonstrated that clustering did not simply recapitulate previously established acuity assessments. In a heterogeneous cohort of hospitalized patients, unsupervised machine learning techniques applied to routine, early vital sign data identified physiotypes with unique disease categories and distinct clinical outcomes. This approach has the potential to augment understanding of pathophysiology by distilling thousands of disease states into a few physiological signatures. 

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4. ProKnow: Process knowledge for safety constrained and explainable question generation for mental health diagnostic assistance

   https://doi.org/10.3389/fdata.2022.1056728  

   Roy, Kaushik ; Gaur, Manas ; Soltani, Misagh ; Rawte, Vipula ; Kalyan, Ashwin ; Sheth, Amit ( January 2023 , Frontiers in Big Data)

   Virtual Mental Health Assistants (VMHAs) are utilized in health care to provide patient services such as counseling and suggestive care. They are not used for patient diagnostic assistance because they cannot adhere to safety constraints and specialized clinical process knowledge ( ProKnow ) used to obtain clinical diagnoses. In this work, we define ProKnow as an ordered set of information that maps to evidence-based guidelines or categories of conceptual understanding to experts in a domain. We also introduce a new dataset of diagnostic conversations guided by safety constraints and ProKnow that healthcare professionals use ( ProKnow - data ). We develop a method for natural language question generation (NLG) that collects diagnostic information from the patient interactively ( ProKnow - algo ). We demonstrate the limitations of using state-of-the-art large-scale language models (LMs) on this dataset. ProKnow - algo incorporates the process knowledge through explicitly modeling safety, knowledge capture, and explainability. As computational metrics for evaluation do not directly translate to clinical settings, we involve expert clinicians in designing evaluation metrics that test four properties: safety, logical coherence, and knowledge capture for explainability while minimizing the standard cross entropy loss to preserve distribution semantics-based similarity to the ground truth. LMs with ProKnow - algo generated 89% safer questions in the depression and anxiety domain (tested property: safety ). Further, without ProKnow - algo generations question did not adhere to clinical process knowledge in ProKnow - data (tested property: knowledge capture ). In comparison, ProKnow - algo -based generations yield a 96% reduction in our metrics to measure knowledge capture. The explainability of the generated question is assessed by computing similarity with concepts in depression and anxiety knowledge bases. Overall, irrespective of the type of LMs, ProKnow - algo achieved an averaged 82% improvement over simple pre-trained LMs on safety, explainability, and process-guided question generation. For reproducibility, we will make ProKnow - data and the code repository of ProKnow - algo publicly available upon acceptance. 

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5. Childbirth Computational Models: Characteristics and Applications

   https://doi.org/10.1115/1.4049226  

   Chen, Sheng ; Grimm, Michele J. ( May 2021 , Journal of Biomechanical Engineering)

   null (Ed.)

   Abstract The biomechanical process of childbirth is necessary to usher in new lives—but it can also result in trauma. This physically intense process can put both the mother and the child at risk of injuries and complications that have life-long impact. Computational models, as a powerful tool to simulate and explore complex phenomena, have been used to improve our understanding of childbirth processes and related injuries since the 1990s. The goal of this paper is to review and summarize the breadth and current state of the computational models of childbirth in the literature—focusing on those that investigate the mechanical process and effects. We first summarize the state of critical characteristics that have been included in computational models of childbirth (i.e., maternal anatomy, fetal anatomy, cardinal movements, and maternal soft tissue mechanical behavior). We then delve into the findings of the past studies of birth processes and mechanical injuries in an effort to bridge the gap between the theoretical, numerical assessment and the empirical, clinical observations and practices. These findings are from applications of childbirth computational models in four areas: (1) the process of childbirth itself, (2) maternal injuries, (3) fetal injuries, and (4) protective measures employed by clinicians during delivery. Finally, we identify some of the challenges that computational models still face and suggest future directions through which more biofidelic simulations of childbirth might be achieved, with the goal that advancing models may provide more efficient and accurate, patient-specific assessment to support future clinical decision-making. 

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