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The low cost, simplicity, and ease of use of paper microfluidic devices have made them valuable medical diagnostics for applications from pregnancy testing to COVID-19 screening. Meanwhile, the increasing complexity of paper-based microfluidic devices is driving the need to produce new tools and methodologies that enable more robust biological diagnostics and potential therapeutic applications. A new design framework is being used to facilitate both research and fabrication of paper-based microfluidic biological devices to accelerate the investigative process and reduce material utilization and manpower. In this work we present a methodology for this framework to dynamically place and route microfluidic components in a nondiscrete design space where fluid volume usage, surface area utilization, and the timing required to perform specified biological assays are accounted for and optimized while also accelerating the development of potentially lifesaving new devices.

Background Atopic dermatitis (AD) is a chronic, inflammatory skin disease that affects as many as 12.5% of children aged 0-17 years and 3% of the adult population. In the United States, 31.6 million children and adults are estimated to be living with AD. Objective Therapeutic patient education (TPE) has proven its value in the management of chronic diseases for which adherence to therapy is suboptimal. This article explores experts' opinions and treatment practices to determine if TPE is a recommended and effective method for treating AD. Methods Forty-two (51%) of 82 Councilors and Associates of the International Eczema Council (IEC), an international group with expertise in AD, responded to an electronic survey on TPE and AD. Results Most respondents (97.5%) agreed that TPE should play an important role in the management of AD. Many respondents (82.9%) believed that all patients with AD, regardless of disease severity, could benefit from TPE. Limitations The International Eczema Council survey lacks specific information on AD severity. Conclusions Publications have shown the positive effect of TPE on the course of the disease, the prevention of complications, and the autonomy and quality of patient life. Survey respondents agreed that TPE can improve the quality of patient care and patient satisfaction with care.

Breakthrough invasive fungal infections (IFI) have emerged as a significant problem in patients receiving systemic antifungals; however, consensus criteria for defining breakthrough IFI are missing. This position paper establishes broadly applicable definitions of breakthrough IFI for clinical research. Representatives of the Mycoses Study Group Education and Research Consortium (MSG-ERC) and the European Confederation of Medical Mycology (ECMM) reviewed the relevant English literature for definitions applied and published through 2018. A draft proposal for definitions was developed, and circulated to all members of the two organizations for comment and suggestions. The authors addressed comments received, and circulated the updated document for approval. Breakthrough IFI was defined as any IFI occurring during exposure to an antifungal drug, including fungi outside the spectrum of activity of an antifungal. The time of breakthrough IFI was defined as the first attributable clinical sign or symptom, mycological finding or radiological feature. The period defining breakthrough IFI depends on pharmacokinetic properties and extends at least until one dosing interval after drug discontinuation. Persistent IFI describes IFI that is unchanged/stable since treatment initiation with ongoing need for antifungal therapy. It is distinct from refractory IFI, defined as progression of disease and therefore similar to non-response to treatment. Relapsed IFI occurs after treatment, and is caused by the same pathogen at the same site, although dissemination can occur. These proposed definitions are intended to support the design of future clinical trials and epidemiological research in clinical mycology, with the ultimate goal of increasing the comparability of clinical trial results.

PURPOSE:Overactive bladder syndrome is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence in the absence of urinary tract infection or another obvious pathological condition. Electronic questionnaires have been used in a few specialties with the hope of improving treatment outcomes and patient satisfaction. However, they have not been widely used in the urological field. When treating overactive bladder, the main outcome is to improve patient quality of life. The primary objective of this study was to evaluate whether electronic questionnaires would be equally accepted as or preferred to paper questionnaires. The secondary objective was to look at the preference in relation to patient age, education and iPad® tablet familiarity. MATERIALS AND METHODS:We prospectively evaluated the iList® electronic questionnaire application using a friendly iPad tablet in patients with overactive bladder who presented to the urology clinic at our institution. Each of the 80patients who were recruited randomly completed the validated OABSS (Overactive Bladder Symptom Score) and the PPBC (Patient Perception of Bladder Condition) questionnaires in paper and electronic format on the tablet. Variables potentially associated with the outcomes of interest included demographic data, questionnaire method preference, patient response rate and iPad familiarity. We used the 2-sided Z-test to determine whether the proportion of patients who considered the tablet to be the same, better or much better than paper was significantly greater than 50%. The 2-sided chi-square test was applied to assess whether the intervention effect significantly differed among the demographic subgroups. RESULTS:A total of 80 patients 21 to 87 years old were enrolled in the study from November 2015 to August 2016. Of the patients 53% were female and 49% were 65 years or younger. The incidence of those who considered the tablet to be the same or better than paper was 82.5% (95% CI 74.2-90.8, p

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The Liver Imaging and Reporting Data System (LI-RADS) is a comprehensive system for standardizing the terminology, technique, interpretation, reporting, and data collection of liver imaging with the overarching goal of improving communication, clinical care, education, and research relating to patients at risk for or diagnosed with hepatocellular carcinoma (HCC). In 2018, the American Association for the Study of Liver Diseases (AASLD) integrated LI-RADS into its clinical practice guidance for the imaging-based diagnosis of HCC. The harmonization between the AASLD and LI-RADS diagnostic imaging criteria required minor modifications to the recently released LI-RADS v2017 guidelines, necessitating a LI-RADS v2018 update. This article provides an overview of the key changes included in LI-RADS v2018 as well as a look at the LI-RADS v2018 diagnostic algorithm and criteria, technical recommendations, and management suggestions. Substantive changes in LI-RADS v2018 are the removal of the requirement for visibility on antecedent surveillance ultrasound for LI-RADS 5 (LR-5) categorization of 10-19 mm observations with nonrim arterial phase hyper-enhancement and nonperipheral “washout”, and adoption of the Organ Procurement and Transplantation Network definition of threshold growth (≥ 50% size increase of a mass in ≤ 6 months). Nomenclatural changes in LI-RADS v2018 are the removal of -us and -g as LR-5 qualifiers.

© 2016 American Chemical Society. Developing efficient photoreversible color switching systems for constructing rewritable paper is of significant practical interest owing to the potential environmental benefits including forest conservation, pollution reduction, and resource sustainability. Here we report that the color change associated with the redox chemistry of nanoparticles of Prussian blue and its analogues could be integrated with the photocatalytic activity of TiO2nanoparticles to construct a class of new photoreversible color switching systems, which can be conveniently utilized for fabricating ink-free, light printable rewritable paper with various working colors. The current system also addresses the phase separation issue of the previous organic dye-based color switching system so that it can be conveniently applied to the surface of conventional paper to produce an ink-free light printable rewritable paper that has the same feel and appearance as the conventional paper. With its additional advantages such as excellent scalability and outstanding rewriting performance (reversibility >80 times, legible time >5 days, and resolution >5 μm), this novel system can serve as an eco-friendly alternative to regular paper in meeting the increasing global needs for environment protection and resource sustainability.

This paper introduces a novel software framework to support automated development of paper-based microfluidic devices. Compared to existing lab-on-a-chip technologies, paper-based microfluidics differs in terms of substrate technologies and point-of-care usage across a wide variety environmental conditions. This paper addresses the contexts in which the software can address these challenges and presents several initial case studies that demonstrate the capabilities of the framework to produce workable and usable paper microfluidic devices.

Background Chronic kidney disease (CKD) is characterized by dysbiosis, elevated levels of uremic toxins, systemic inflammation, and increased markers of oxidative stress. These factors lead to an increased risk of cardiovascular disease (CVD) which is common among CKD patients. Supplementation with high amylose maize resistant starch type 2 (RS-2) can change the composition of the gut microbiota, and reduce markers of inflammation and oxidative stress in patients with end-stage renal disease. However, the impact of RS-2 supplementation has not been extensively studied in CKD patients not on dialysis. Aerobic exercise training lowers certain markers of inflammation in CKD patients. Whether combining aerobic training along with RS-2 supplementation has an additive effect on the aforementioned biomarkers in predialysis CKD patients has not been previously investigated. Methods The study is being conducted as a 16-week, double-blind, placebo controlled, parallel arm, randomized controlled trial. Sixty stage 3–4 CKD patients (ages of 30–75 years) are being randomized to one of four groups: RS-2 & usual care, RS-2 & aerobic exercise, placebo (cornstarch) & usual care and placebo & exercise. Patients attend four testing sessions: Two baseline (BL) sessions with follow up visits 8 (wk8) and 16 weeks (wk16) later. Fasting blood samples, resting brachial and central blood pressures, and arterial stiffness are collected at BL, wk8 and wk16. A stool sample is collected for analysis of microbial composition and peak oxygen uptake is assessed at BL and wk16. Blood samples will be assayed for p-cresyl sulphate and indoxyl sulphate, c-reactive protein, tumor necrosis factor α, interleukin 6, interleukin 10, monocyte chemoattractant protein 1, malondialdehyde, 8-isoprostanes F2a, endothelin-1 and nitrate/nitrite. Following BL, subjects are randomized to their group. Individuals randomized to conditions involving exercise will attend three supervised moderate intensity (55–65% peak oxygen uptake) aerobic training sessions (treadmills, bikes or elliptical machine) per week for 16 weeks. Discussion This study has the potential to yield information about the effect of RS-2 supplementation on key biomarkers believed to impact upon the development of CVD in patients with CKD. We are examining whether there is an additive effect of exercise training and RS-2 supplementation on these key variables. Trial registration Clinicaltrials.gov Trial registration#NCT03689569. 9/28/2018, retrospectively registered.

The International League Against Epilepsy (ILAE) Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for diagnosis of patients, but it is also critical for epilepsy research, development of antiepileptic therapies, and communication around the world. The new classification originates from a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It presents three levels, starting with seizure type, where it assumes that the patient is having epileptic seizures as defined by the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type, the next step is diagnosis of epilepsy type, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and also an unknown epilepsy group. The third level is that of epilepsy syndrome, where a specific syndromic diagnosis can be made. The new classification incorporates etiology along each stage, emphasizing the need to consider etiology at each step of diagnosis, as it often carries significant treatment implications. Etiology is broken into six subgroups, selected because of their potential therapeutic consequences. New terminology is introduced such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self-limited and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the 21st century.

Author(s): Barrett, J Christian; Alweis, Richard; Frank, Michael; O'Connor, Alec; McConville, John F; Adams, Nancy Day; Arfons, Lisa; Bernard, Sheilah; Bradley, Thomas; Buckley, John D; Cohen, Ellen; Cornett, Patricia; Elkins, Stephanie; Kopelman, Richard; Luther, Vera P; Petrusky, Jiselle; McNeill, Diana B; Omar, Bassam; Palapiano, Nancy; Roth, Teresa; Satko, Scott; Fried, Ethan D; Muchmore, Elaine A

With the recent explosion of genome sequencing data, there are now millions of uncharacterized proteins. If a scientist becomes interested in one of these proteins, it can be very difficult to find information as to its likely function. Often a protein whose sequence is similar, and which is likely to have a similar function, has been studied already, but this information is not available in any database. To help find articles about similar proteins, PaperBLAST searches the full text of scientific articles for protein identifiers or gene identifiers, and it links these articles to protein sequences. Then, given a protein of interest, it can quickly find similar proteins in its database by using standard software (BLAST), and it can show snippets of text from relevant papers. We hope that PaperBLAST will make it easier for biologists to predict proteins’ functions., Large-scale genome sequencing has identified millions of protein-coding genes whose function is unknown. Many of these proteins are similar to characterized proteins from other organisms, but much of this information is missing from annotation databases and is hidden in the scientific literature. To make this information accessible, PaperBLAST uses EuropePMC to search the full text of scientific articles for references to genes. PaperBLAST also takes advantage of curated resources (Swiss-Prot, GeneRIF, and EcoCyc) that link protein sequences to scientific articles. PaperBLAST’s database includes over 700,000 scientific articles that mention over 400,000 different proteins. Given a protein of interest, PaperBLAST quickly finds similar proteins that are discussed in the literature and presents snippets of text from relevant articles or from the curators. PaperBLAST is available at http://papers.genomics.lbl.gov/. IMPORTANCE With the recent explosion of genome sequencing data, there are now millions of uncharacterized proteins. If a scientist becomes interested in one of these proteins, it can be very difficult to find information as to its likely function. Often a protein whose sequence is similar, and which is likely to have a similar function, has been studied already, but this information is not available in any database. To help find articles about similar proteins, PaperBLAST searches the full text of scientific articles for protein identifiers or gene identifiers, and it links these articles to protein sequences. Then, given a protein of interest, it can quickly find similar proteins in its database by using standard software (BLAST), and it can show snippets of text from relevant papers. We hope that PaperBLAST will make it easier for biologists to predict proteins’ functions.

Introduction: A proper understanding of study design is essential to creating successful studies. This is also important when reading or peer reviewing publications. In this article, we aimed to identify and summarize key papers that would be helpful for faculty members interested in learning more about study design in medical education research. Methods: The online discussions of the 2016-2017 Academic Life in Emergency Medicine Faculty Incubator program included a robust and vigorous discussion about education study design, which highlighted a number of papers on that topic. We augmented this list of papers with further suggestions by expert mentors. Via this process, we created a list of 29 papers in total on the topic of medical education study design. After gathering these papers, our authorship group engaged in a modified Delphi approach to build consensus on the papers that were most valuable for the understanding of proper study design in medical education. Results: We selected the top five most highly rated papers on the topic domain of study design as determined by our study group. We subsequently summarized these papers with respect to their relevance to junior faculty members and to faculty developers. Conclusion: This article summarizes five key papers addressing study design in medical education with discussions and applications for junior faculty members and faculty developers. These papers provide a basis upon which junior faculty members might build for developing and analyzing studies.

Introduction: Modern learners have immediate, unlimited access to a wide variety of onlineresources. To appeal to this current generation of learners, educators must embrace the useof technology. However, educators must balance newer, novel technologies with traditionalmethods to achieve the best learning outcomes. Therefore, we aimed to review several papersuseful for faculty members wishing to incorporate technology into instructional design. Methods: We identified a broad list of papers relevant to teaching and lea rning with technologywithin the online discussions of the Academic Life in Emergency Medicine (ALiEM) FacultyIncubator. This list was augmented with suggestions by a guest expert (BT) and an open callon Twitter (tagged with the #meded and #FOAMed hashtags) yielding 24 papers. We thenconducted a modified three-round Delphi process within the autho rship group, including juniorand senior faculty members, to identify the most impactful papers. Results: We pared the list of 24 papers to five that were most highly rate d. Two were researchpapers and three were commentaries or editorials. The authorship group reviewed andsummarized these papers with specific consideration to their val ue to junior educators andfaculty developers. Conclusion: This is a key reading list for junior faculty members and faculty developersinterested in teaching with technology. The commentary contextualizes the importance of thesepapers for medical educators, to optimize use of technology in their teaching or incorporate intofaculty development.

Introduction: Competency-based medical education (CBME) presents a paradigm shift in medicaltraining. This outcome-based education movement has triggered substantive changes across the globe.Since this transition is only beginning, many faculty members may not have experience with CBMEnor a solid foundation in the grounding literature. We identify and summarize key papers to help facultymembers learn more about CBME. Methods: Based on the online discussions of the 2016-2017 ALiEM Faculty Incubator program, a seriesof papers on the topic of CBME was developed. Augmenting this list with suggestions by a guest expertand by an open call on Twitter for other important papers, we were able to generate a list of 21 papers intotal. Subsequently, we used a modified Delphi study methodology to narrow the list to key papers thatdescribe the importance and significance for educators interested in learning about CBME. To determinethe most impactful papers, the mixed junior and senior faculty authorship group used three-round votingmethodology based upon the Delphi method. Results: Summaries of the five most highly rated papers on the topic of CBME, as determined by thismodified Delphi approach, are presented in this paper. Major themes include a definition of core CBMEthemes, CBME principles to consider in the design of curricula, a history of the development of the CBMEmovement, and a rationale for changes to accreditation with CBME. The application of the study findingsto junior faculty and faculty developers is discussed. Conclusion: We present five key papers on CBME that junior faculty members and faculty expertsidentified as essential to faculty development. These papers are a mix of foundational and explanatorypapers that may provide a basis from which junior faculty members may build upon as they help toimplement CBME programs.

The first scientific publication on 'general adaption syndrome', or as we know today 'biologic stress' has been published in Nature in 1936 by the 29-year old Hans Selye. His results in that short publication that contained no references or illustrations, were based on experiments in rats that were exposed to severe insults/ stressors, but his idea about a 'nonspecific bodily response' originated from his observations of sick patients whom he had seen as a medical student and young clinician. Autopsy of stressed rats revealed three major, grossly visible changes: hyperemia and enlargement of the adrenals, atrophy of the thymus and lymph nodes as well as hemorrhagic gastric erosions/ulcers (the "stress triad"). Based on this and additional observations, he concluded that the key master organ in stress reactions is the adrenal cortex (although he also accepted the limited and short lasting effect of catecholamines released from the adrenal medulla) which stimulated by an increased secretion of ACTH, secreted by the anterior pituitary gland. He thus identified the first molecular mediators of the stress reaction, i.e., steroids released from the adrenal cortex that we call today glucocorticoids, based on his classification and naming of steroids. At the end of a very productive life in experimental medicine, Selye recognized that under both unpleasant and demanding stressors as well as positive, rewarding stimuli adrenal cortex releases the same glucocorticoids and only certain brain structures may distinguish the stimuli under distress and eustress - terms he introduced in 1974, that also contained his last definition of stress: the nonspecific response of the body on any demand on it. After brief description of the history of stress research, the rest of this review is focused on one element of stress triad, i.e., gastroduodenal ulceration, especially its pathogenesis, prevention and treatment. Following a short description of acute gastroprotection, discovered by one of Selye's students, we discuss new molecular mediators of gastroduodenal ulceration like dopamine and new drugs that either only heal (very potently, on molar basis) or prevent and heal ulcers like sucralfate derivatives and the relatively new peptide BPC-157. We conclude that despite the extensive and multidisciplinary research on stress during the last 80 years, a lot of basic and clinical research is needed to better understand the manifestations, central and peripheral molecular regulators of stress response, especially the modes of prevention/management of distress or its transformation into eustress and the treatment of stress-related diseases.

A quantitative analysis supports the argument that very low acceptance rates of conference papers are more likely to impede publication of bold and innovative research results than to indicate the chosen papers' prestige and elite status.

Arch Toxicol (2014) 88:171–172 DOI 10.1007/s00204-013-1176-4 LETTER TO THE EDITOR Letter from Ralph J Cicerone regarding Edward Calabrese’s paper published online first on August 4th: “how the US national academy of sciences misled the world community on cancer risk assessment: new findings challenge historical foundations of the linear dose response.” [DOI 10.1007/s00204‑013‑1105‑6, Review Article] R. J. Cicerone · K. D. Crowley Received: 18 November 2013 / Accepted: 21 November 2013 / Published online: 6 December 2013 © Springer-Verlag Berlin Heidelberg 2013 Dear Dr. Hengstler We write to express disappointment with the inappropri- ate title and unsubstantiated content of Edward Calabrese’s paper published online on 4 August: “How the US National Academy of Sciences misled the world community on can- cer risk assessment: new findings challenge historical foun- dations of the linear dose response” (Calabrese 2013). Professor Calabrese accuses 1946 Nobel Laureate Her- man Muller and his colleague Curt Stern of a pattern of deception in their treatment of experiments by another scientist. Calabrese further accuses Muller of inappropri- ately influencing fellow members of the National Research Council’s Committee on Biological Effects of Atomic Radiation (BEAR) (NRC 1956) about the genetic effects of ionizing radiation in humans. Calabrese uses correspondence between Muller and Stern concerning experiments on germ cell mutations in male fruit flies, along with subsequent scientific publications by both scientists, to make unsubstantiated insinuations about Mul- ler and Stern’s motivations: For example, that Muller was “…[p]rotecting his reputation by ensuring that his mislead- ing comments would not be discovered while still aggres- sively pushing acceptance of the linearity agenda” (p. 2). And “In the absence of new data, Stern decided upon a new strategy to ‘save’ the single-hit linearity dose response” (p. R. J. Cicerone Chair, National Research Council, US National Academy of Sciences, Washington, DC, USA K. D. Crowley (*) Nuclear and Radiation Studies Board, National Research Council, US National Academy of Sciences, 500 Fifth St, NW, Washington, DC 20001, USA e-mail: kcrowley@nas.edu 3). Calabrese also makes ad hominem remarks about Mul- ler to support his accusations: For example, “… it was well known that Muller would try to win arguments by exaggera- tion and overstatement” (p. 3). It seems clear from Calabrese’s factual descriptions that Muller and Stern were trying to make sense of experiments that yielded unexpected results. It is not surprising that they would question these results and seek to have them repli- cated. Calabrese clearly disagrees with Stern and Muller’s scientific judgments, but he is able to marshal only circum- stantial evidence to support his accusations that they sought to suppress the experiments. In the end, the experiments were published (Caspari and Stern 1948) and served to spur-on additional scientific investigations. Calabrese also asserts that Muller “[m]ade deceptive statements during his Noble (sic) Prize Lecture … that were intended to promote the acceptance of the linear dose–response model for risk assessment for ionizing radi- ation” (p. 1). This assertion is based on statements made by Muller in his lecture in support of the linearity hypothesis even though he had received the manuscript containing the experimental results some 5 weeks earlier. Given Muller and Stern’s reluctance to accept the results of these experi- ments without replication, Muller’s decision not to men- tion them is certainly not surprising. It is unfair to call his behavior deceptive. Calabrese provides no evidence that Muller inappropri- ately influenced the BEAR committee or that the NAS or the BEAR committee misled anyone. The BEAR commit- tee considered a large body of scientific work and exercised its own considerable scientific judgment in reaching a con- sensus conclusion that “the genetic harm [from radiation] is proportional to the total dose” (NRC 1956, p. 23). Moreo- ver, the BEAR committee noted that this conclusion was generally accepted by the genetics community (ibid).

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An automated sensor has been developed for use during paper manufacture that can measure flexural rigidity (bending stiffness). Based on laser ultrasonic technology, this sensor provides continuous noncontact on‐machine measurements on paper having area densities from 35 to 205 g/m2, moving at commercial manufacturing speeds, at any angle in the plane of the sheet. It was demonstrated on a high speed printing paper grade machine during commercial production. For that demonstration, the sensor was integrated into an existing scanning sensor system. Cross‐direction profiles of flexural rigidity had the expected shape, and compared well with traditional bending stiffness measurements on samples collected for that comparison.

The rarity of severe complications of this disease in children makes randomized clinical trials in immune thrombocytopenia (ITP) unfeasible. Therefore, the current management recommendations for ITP are largely dependent on clinical expertise and observations. As part of its discussions during the Intercontinental Cooperative ITP Study Group Expert Meeting in Basel, the Management working group recommended that the decision to treat an ITP patient be individualized and based mainly on bleeding symptoms and not on the actual platelet count number and should be supported by bleeding scores using a validated assessment tool. The group stressed the need to develop a uniform validated bleeding score system and to explore new measures to evaluate bleeding risk in thrombocytopenic patients-the role of rituximab as a splenectomy-sparing agent in resistant disease was also discussed. Given the apparently high recurrence rate to rituximab therapy in children and the drug's possible toxicity, the group felt that until more data are available, a conservative approach may be considered, reserving rituximab for patients who failed splenectomy. More studies of the effectiveness and side effects of drugs to treat refractory patients, such as TPO mimetics, cyclosporine, mycophenolate mofetil, and cytotoxic agents are required, as are long-term data on post-splenectomy complications. In the patient with either acute or chronic ITP, using a more personalized approach to treatment based on bleeding symptoms rather than platelet count should result in less toxicity and empower both physicians and families to focus on quality-of-life.

An automated, non‐contact, non‐destructive sensor has been developed for measurement of sheet flexural and shear rigidity in paper manufacturing. It was tested on a pilot web handler at web speeds up to 25.4 m/s. A model equation was fitted to the frequency dependence of the phase velocity of Ao mode Lamb waves. Ultrasound was generated in paper with a pulsed Nd:YAG laser and detected with a Mach‐Zehnder interferometer coupled with a scanning mirror/timing system to compensate for paper motion.

Recent years have shown a gradual shift in the content of biomedical publications that is freely accessible, from titles and abstracts to full text. This has enabled new forms of automatic text analysis and has given rise to some interesting questions: How informative is the abstract compared to the full-text? What important information in the full-text is not present in the abstract? What should a good summary contain that is not already in the abstract? Do authors and peers see an article differently? We answer these questions by comparing the information content of the abstract to that in citances—sentences containing citations to that article. We contrast the important points of an article as judged by its authors versus as seen by peers. Focusing on the area of molecular interactions, we perform manual and automatic analysis, and we find that the set of all citances to a target article not only covers most information (entities, functions, experimental methods, and other biological concepts) found in its abstract, but also contains 20% more concepts. We further present a detailed summary of the differences across information types, and we examine the effects other citations and time have on the content of citances.

Over the last year, the coronavirus disease 2019 (COVID-19) pandemic has resulted in profound disruptions across the globe, with school closures, social isolation, job loss, illness, and death affecting the lives of children and families in myriad ways. In an Editors' Note in our June 2020 issue, 1 our senior editorial team described this Journal's role in advancing knowledge in child and adolescent mental health during the pandemic and outlined areas we identified as important for science and practice in our field. Since then, the Journal has published articles on the impacts of the pandemic on child and adolescent mental health and service systems, 2-5 which are available in a special collection accessible through the Journal's website. 6 Alongside many opinion papers, the pace of publication of empirical research in this area is rapidly expanding, covering important issues such as increased frequency of mental health symptoms among children and adolescents 3,5,7-10 and changes in patterns of clinical service use such as emergency department visits. 11-14 As the Senior Editors prepared that Editors’ Note, they were acutely aware that the priorities that they identified were broad and generated by only a small group of scientists and clinicians. Although this had the advantage of enabling us to get this information out to readers quickly, we decided that a more systematic approach to developing recommendations for research priorities would be of greater long-term value. We were particularly influenced by the efforts of the partnership between the UK Academy of Medical Scientists and a UK mental health research charity (MQ: Transforming Mental Health) to detail COVID-19−related research priorities for “Mental Health Science” that was published online by Holmes et al. in The Lancet Psychiatry in April 2020. 15 Consistent with its focus on mental health research across the lifespan, several recommendations highlighted child development and children's mental health. However, a more detailed assessment of research priorities related to child and adolescent mental health was beyond the scope of that paper. Furthermore, the publication of that position paper preceded the death of George Floyd at the hands of Minneapolis police on May 25, 2020, which re-energized efforts to acknowledge and to address racism and healthcare disparities in the United States and many other countries. To build upon the JAACAP Editors’ Note 1 and the work of Holmes et al., 15 we conducted an international survey of professionals—practitioners and researchers—working on child and adolescent development and pediatric mental health to identify concerns about the impact of the pandemic on children, adolescents, and their families, as well as what is helping families navigate these impacts, and the specific research topics that are of greatest importance.

SignificanceAutomated understanding of human embryonic stem cell (hESC) videos is essential for the quantified analysis and classification of various states of hESCs and their health for diverse applications in regenerative medicine.AimThis paper aims to develop an ensemble method and bagging of deep learning classifiers as a model for hESC classification on a video dataset collected using a phase contrast microscope.ApproachThe paper describes a deep learning-based random network (RandNet) with an autoencoded feature extractor for the classification of hESCs into six different classes, namely, (1)cell clusters, (2)debris, (3)unattached cells, (4)attached cells, (5)dynamically blebbing cells, and (6)apoptotically blebbing cells. The approach uses unlabeled data to pre-train the autoencoder network and fine-tunes it using the available annotated data.ResultsThe proposed approach achieves a classification accuracy of 97.23 ± 0.94 % and outperforms the state-of-the-art methods. Additionally, the approach has a very low training cost compared with the other deep-learning-based approaches, and it can be used as a tool for annotating new videos, saving enormous hours of manual labor.ConclusionsRandNet is an efficient and effective method that uses a combination of subnetworks trained using both labeled and unlabeled data to classify hESC images.

Motivation Recent technological developments have facilitated an expansion of microbiome–metabolome studies, in which samples are assayed using both genomic and metabolomic technologies to characterize the abundances of microbial taxa and metabolites. A common goal of these studies is to identify microbial species or genes that contribute to differences in metabolite levels across samples. Previous work indicated that integrating these datasets with reference knowledge on microbial metabolic capacities may enable more precise and confident inference of microbe–metabolite links. Results We present MIMOSA2, an R package and web application for model-based integrative analysis of microbiome–metabolome datasets. MIMOSA2 uses genomic and metabolic reference databases to construct a community metabolic model based on microbiome data and uses this model to predict differences in metabolite levels across samples. These predictions are compared with metabolomics data to identify putative microbiome-governed metabolites and taxonomic contributors to metabolite variation. MIMOSA2 supports various input data types and customization with user-defined metabolic pathways. We establish MIMOSA2’s ability to identify ground truth microbial mechanisms in simulation datasets, compare its results with experimentally inferred mechanisms in honeybee microbiota, and demonstrate its application in two human studies of inflammatory bowel disease. Overall, MIMOSA2 combines reference databases, a validated statistical framework, and a user-friendly interface to facilitate modeling and evaluating relationships between members of the microbiota and their metabolic products. Availability and implementation MIMOSA2 is implemented in R under the GNU General Public License v3.0 and is freely available as a web server at http://elbo-spice.cs.tau.ac.il/shiny/MIMOSA2shiny/ and as an R package from http://www.borensteinlab.com/software_MIMOSA2.html. Supplementary information Supplementary data are available at Bioinformatics online.

Background Papers on COVID-19 are being published at a high rate and concern many different topics. Innovative tools are needed to aid researchers to find patterns in this vast amount of literature to identify subsets of interest in an automated fashion. Objective We present a new online software resource with a friendly user interface that allows users to query and interact with visual representations of relationships between publications. Methods We publicly released an application called PLATIPUS (Publication Literature Analysis and Text Interaction Platform for User Studies) that allows researchers to interact with literature supplied by COVIDScholar via a visual analytics platform. This tool contains standard filtering capabilities based on authors, journals, high-level categories, and various research-specific details via natural language processing and dozens of customizable visualizations that dynamically update from a researcher’s query. Results PLATIPUS is available online and currently links to over 100,000 publications and is still growing. This application has the potential to transform how COVID-19 researchers use public literature to enable their research. Conclusions The PLATIPUS application provides the end user with a variety of ways to search, filter, and visualize over 100,00 COVID-19 publications.

Background Economic, social, and psychologic stressors are associated with an increased risk for abusive injuries in children. Prolonged physical proximity between adults and children under conditions of severe external stress, such as witnessed during the COVID-19 pandemic with “shelter-in-place orders”, may be associated with additional increased risk for child physical abuse. We hypothesized that child physical abuse rates and associated severity of injury would increase during the early months of the pandemic as compared to the prior benchmark period. Methods We conducted a nine-center retrospective review of suspected child physical abuse admissions across the Western Pediatric Surgery Research Consortium. Cases were identified for the period of April 1-June 30, 2020 (COVID-19) and compared to the identical period in 2019. We collected patient demographics, injury characteristics, and outcome data. Results There were no significant differences in child physical abuse cases between the time periods in the consortium as a whole or at individual hospitals. There were no differences between the study periods with regard to patient characteristics, injury types or severity, resource utilization, disposition, or mortality. Conclusions Apparent rates of new injuries related to child physical abuse did not increase early in the COVID-19 pandemic. While this may suggest that pediatric physical abuse was not impacted by pandemic restrictions and stresses, it is possible that under-reporting, under-detection, or delays in presentation of abusive injuries increased during the pandemic. Long-term follow-up of subsequent rates and severity of child abuse is needed to assess for unrecognized injuries that may have occurred.

COVID-19 has disproportionally affected underrepresented minorities (URM) and low-income immigrants in the United States. The aim of the study is to examine the underlying vulnerabilities of Mexican immigrants in New York City (NYC) and Los Angeles (LA), its correspondence with area-level COVID-19 morbidity and mortality, and to document the role of trusted and culturally sensitive services offered during the pandemic through the Ventanillas de Salud (i.e. VDS, Health Windows) program. The study uses a mixed-methods approach including a cross-sectional survey of Mexican immigrants in LA and NYC collected in the Mexican Consulates at the onset of the pandemic, complemented with a georeferencing analysis and key informant interviews. Data suggested an increased vulnerability to COVID-19 given participants reported health status, health care profile and place of residence, which coincided with the georeferencing analysis. The key informant interviews confirmed the vulnerability of this population and the supporting role of VDS in helping immigrants navigate health systems and disseminate health information. Mexican immigrants had an increased vulnerability to COVID-19 at the individual, geographic and systemic levels. Trusted and culturally sensitive services are needed to overcome some of the barriers and risk factors that increase the vulnerability of URM and immigrant populations to COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s10903-021-01283-8.

Scientific findings and policy guidelines recommend integrating HIV and drug addiction prevention and care into community-based settings. Systematic capacity-building efforts are warranted to provide technical support for community health workers and improve their confidence in the integrated service provision. An intervention trial was conducted between 2018 and 2019 with 120 community health workers (CHW) from 60 communes in Vietnam's four provinces. The 60 intervention CHW received in-person training to enhance their HIV/addiction-related service knowledge and skills. Online support groups were established between trained CHW and local HIV and addiction specialists. The intervention outcomes were assessed using mixed-effects regression models with the data collected at baseline and every 3 months for 1 year. Adjusted analyses showed that intervention CHW reported a significant increase in the interaction with other treatment providers than the control group at 6 months and remained at the 12-month follow-up. The difference in the improvement of confidence in HIV/addiction-related service delivery between the intervention and control groups was significant at 6-month but became insignificant at the 12-month. Male CHW were more confident in providing services than female CHW at baseline, and gender differences in the changing patterns were observed over time. This capacity-building intervention demonstrated promising outcomes on CHW inter-agency collaborations and confidence in service delivery. Gender divides in healthcare professionals should be attended to in future studies.Los hallazgos científicos y los protocolos recomiendan integrar la prevención del VIH y la adicción a las drogas en entornos comunitarios. Se implementan esfuerzos sistemáticos de creación de capacidad para brindar apoyo técnico a los trabajadores de salud comunitarios y mejorar su confianza en la prestación de servicios integrados. Se realizó una prueba de intervención entre 2018 y 2019 con 120 trabajadores de salud comunitarios (TSC) de 60 comunas en las cuatro provincias de Vietnam. Los 60 TSC de intervención recibieron capacitación en persona para mejorar sus conocimientos y habilidades de servicios relacionados con VIH / adicción. Se establecieron grupos de apoyo en línea entre TSC capacitados y especialistas locales en VIH y adicciones. Los resultados de la intervención se evaluaron mediante modelos de regresión de efectos mixtos con los datos recopilados al inicio del estudio y cada tres meses durante un año. Los análisis ajustados mostraron que la intervención CHW informó un aumento significativo en la interacción con proveedores de tratamiento diferentes al grupo de control a los seis meses que se mantuvo en el seguimiento a los 12 meses. La diferencia en el aumento de la confianza en la prestación de servicios relacionados con VIH / adicción entre los grupos de intervención y control fue significativa a los 6 meses, pero se volvió insignificante a los 12 meses. Los TSC masculinos tenían más confianza en la prestación de servicios que las femeninas al inicio del estudio, y se observaron diferencias de género en el cambio de patrones a lo largo del tiempo. Esta intervención de creación de capacidad demostró resultados prometedores en las colaboraciones interinstitucionales de los TSC y la confianza en la prestación de servicios. Las brechas de género en los profesionales de la salud deben ser atendidas en estudios futuros.

Objective To characterize the prevalence of brain ischemia and cerebral small vessel disease in a cohort of patients with Fabry disease (FD) seen at an academic medical center. Background FD is an inherited X-linked lysosomal storage disorder with central nervous system involvement. Limited data are available in the literature on the cerebrovascular neuroimaging findings in FD, and the reported prevalence of stroke symptoms and cerebral small vessel disease has varied widely. Design/methods Brain MRI was performed in 21 patients with FD followed at University of California Irvine Medical Center. Stroke symptoms were assessed and quantification of cerebral microvascular disease was performed using small vessel disease (SVD) score. Lacunes and deep white matter hyperintensities were scored on a four-point scale of 0 (absent) and 1–3 to account for increasing severity; microbleeds were scored 0 (absent) or 1 (present). The total SVD score is the sum of the three components and ranges from 0 to 7. Results Nearly 43% (9/21) of our FD cohort (aged 32–81 years, mean = 50) had a SVD score of one or higher, all of whom were aged 50 or more years. The most common MRI-defined SVD was white matter hyperintensities (9/9, 100%), followed by microbleeds (6/9, 66%), and lacunes (3/9, 33%). The three patients with previous strokes had some of the highest SVD scores reported in the cohort (scores 3–5). Conclusions In this cohort, the prevalence of SVD (43%) was three times higher than prevalence of stroke symptoms. SVD score was highest in the those who had experienced a stroke. These findings emphasize the importance of routine MRI screening of patients with FD in order to identify and treat high risk patients.

Background: Evidence to support use of cardiac resynchronization therapy (CRT) among patients with both heart failure (HF) and atrial fibrillation (AF) is largely limited to retrospective or post hoc subanalyses. Data from a prospectively enrolled and contemporary cohort are needed. Objective: We aim to better characterize the changes from baseline in HF patients with concomitant AF subsequently implanted with a 2-lead CRT-DX system capable of sensing in the atrium, aggregating diagnostics, and delivering CRT therapy. The primary objective of this study is to evaluate the percentage of all HF subjects with an improvement in a clinical composite score from pre-CRT implant to 12 months. Methods: The study is a US-based, prospective, observational multicenter clinical trial conducted at up to 50 sites and enrolling approximately 400 subjects with a follow-up period of 1 year. Multiple subject assessments, atrial rhythm status, and device interrogation will be collected at follow-up visits occurring at 3, 6, and 12months postimplant. Results: A Clinical Events Committee will adjudicate subject HF events, arrhythmia events, death events, and all device-classified ventricular tachycardia and ventricular fibrillation episodes with treatment that are collected throughout the follow-up period. Their decisions are based on independent physician review of the data from sites and device interrogation. Conclusion: The BIO-AffectDX study aims to provide further insight into the expected outcomes from CRT treatment in patients with HF and AF.

Objective. To measure the sagittal alignment of the tibial tubercle through the sagittal tibial tubercle–trochlear groove (sTTTG) distance in patients with and without patellar chondral lesions. Design. Patients treated with patellofemoral cartilage restoration or repair procedures were retrospectively reviewed (group 1; N = 17). A control group of patients (group 2; N = 20) undergoing partial meniscectomy with normal patellar cartilage was included. An asymptomatic patellar chondrosis group (group 3; N = 15) was identified as patients undergoing partial meniscectomy with patellar cartilage wear. The sTTTG was measured on the preoperative axial T2 magnetic resonance imaging (MRI) sequence. The first point was the nadir of the anterior trochlear cartilage, and the second point was the anterior tibial tubercle. A line was drawn between these points, perpendicular to the posterior condylar axis. Comparisons were made between the 3 groups using analysis of variance testing with Bonferroni corrections. Significance was defined as P < 0.05. Results. The mean sTTTG was significantly more posterior in group 1 (5.9 ± 5.5 mm posterior to the trochlear groove) relative to group 2 (0.8 ± 5.3 mm posterior; P = 0.018). The mean value for group 3 (2.7 ± 5.3 mm posterior) fell between group 1 and 3 but was not significantly different from group 1 ( P = 0.31) or group 2 ( P = 0.89). There were no significant differences with regards to sulcus angle, Caton-Deschamps Index, TTTG, or knee flexion angle on the MRI scan. Conclusions. A more posteriorly positioned tibial tubercle was observed in patients with patellar cartilage lesions relative to those with intact patellar cartilage. Intermediate positioning was observed in patients with asymptomatic patellar chondral wear. Level of Evidence. Level 3 diagnostic study.

Background: Heterogeneity in Acute Respiratory Distress Syndrome (ARDS), as a consequence of its non-specific definition, has led to a multitude of negative randomised controlled trials (RCTs). Investigators have sought to identify heterogeneity of treatment effect (HTE) in RCTs using clustering algorithms. We evaluated the proficiency of several commonly-used machine-learning algorithms to identify clusters where HTE may be detected. Methods: Five unsupervised: Latent class analysis (LCA), K-means, partition around medoids, hierarchical, and spectral clustering; and four supervised algorithms: model-based recursive partitioning, Causal Forest (CF), and X-learner with Random Forest (XL-RF) and Bayesian Additive Regression Trees were individually applied to three prior ARDS RCTs. Clinical data and research protein biomarkers were used as partitioning variables, with the latter excluded for secondary analyses. For a clustering schema, HTE was evaluated based on the interaction term of treatment group and cluster with day-90 mortality as the dependent variable. Findings: No single algorithm identified clusters with significant HTE in all three trials. LCA, XL-RF, and CF identified HTE most frequently (2/3 RCTs). Important partitioning variables in the unsupervised approaches were consistent across algorithms and RCTs. In supervised models, important partitioning variables varied between algorithms and across RCTs. In algorithms where clusters demonstrated HTE in the same trial, patients frequently interchanged clusters from treatment-benefit to treatment-harm clusters across algorithms. LCA aside, results from all other algorithms were subject to significant alteration in cluster composition and HTE with random seed change. Removing research biomarkers as partitioning variables greatly reduced the chances of detecting HTE across all algorithms. Interpretation: Machine-learning algorithms were inconsistent in their abilities to identify clusters with significant HTE. Protein biomarkers were essential in identifying clusters with HTE. Investigations using machine-learning approaches to identify clusters to seek HTE require cautious interpretation. Funding: NIGMS R35 GM142992 (PS), NHLBI R35 HL140026 (CSC); NIGMS R01 GM123193, Department of Defense W81XWH-21-1-0009, NIA R21 AG068720, NIDA R01 DA051464 (MMC)

There is a need for real-time and predictive data on alcohol use both broadly and specific to HIV. However, substance use and HIV data often suffer from lag times in reporting as they are typically measured from surveys, clinical case visits and other methods requiring extensive time for collection and analysis. Social big data might help to address this problem and be used to provide near real-time assessments of people's alcohol use and/or alcohol. This manuscript describes three types of social data sources (i.e., social media data, internet search data, and wearable device data) that might be used in surveillance of alcohol and HIV, and then discusses the implications and potential of implementing them as additional tools for public health surveillance.

Population growth and climate change will impact food security and potentially exacerbate the environmental toll that agriculture has taken on our planet. These existential concerns demand that a passionate, interdisciplinary, and diverse community of plant science professionals is trained during the 21st century. Furthermore, societal trends that question the importance of science and expert knowledge highlight the need to better communicate the value of rigorous fundamental scientific exploration. Engaging students and the general public in the wonder of plants, and science in general, requires renewed efforts that take advantage of advances in technology and new models of funding and knowledge dissemination. In November 2018, funded by the National Science Foundation through the Arabidopsis Research and Training for the 21st century (ART 21) research coordination network, a symposium and workshop were held that included a diverse panel of students, scientists, educators, and administrators from across the US. The purpose of the workshop was to re‐envision how outreach programs are funded, evaluated, acknowledged, and shared within the plant science community. One key objective was to generate a roadmap for future efforts. We hope that this document will serve as such, by providing a comprehensive resource for students and young faculty interested in developing effective outreach programs. We also anticipate that this document will guide the formation of community partnerships to scale up currently successful outreach programs, and lead to the design of future programs that effectively engage with a more diverse student body and citizenry.

Significance Prostate cancer is the most common cancer among men. An accurate diagnosis of its severity at detection plays a major role in improving their survival. Recently, machine learning models using biomarkers identified from Raman micro-spectroscopy discriminated intraductal carcinoma of the prostate (IDC-P) from cancer tissue with a ≥85 % detection accuracy and differentiated high-grade prostatic intraepithelial neoplasia (HGPIN) from IDC-P with a ≥97.8 % accuracy. Aim To improve the classification performance of machine learning models identifying different types of prostate cancer tissue using a new dimensional reduction technique. Approach A radial basis function (RBF) kernel support vector machine (SVM) model was trained on Raman spectra of prostate tissue from a 272-patient cohort (Centre hospitalier de l'Universite de Montreal, CHUM) and tested on two independent cohorts of 76 patients [University Health Network (UHN)] and 135 patients (Centre hospitalier universitaire de Quebec-Universite Laval, CHUQc-UL). Two types of engineered features were used. Individual intensity features, i.e., Raman signal intensity measured at particular wavelengths and novel Raman spectra fitted peak features consisting of peak heights and widths. Results Combining engineered features improved classification performance for the three aforementioned classification tasks. The improvements for IDC-P/cancer classification for the UHN and CHUQc-UL testing sets in accuracy, sensitivity, specificity, and area under the curve (AUC) are (numbers in parenthesis are associated with the CHUQc-UL testing set): +4 % (+8 % ), +7 % (+9 % ), +2 % (6%), +9 (+9) with respect to the current best models. Discrimination between HGPIN and IDC-P was also improved in both testing cohorts: +2.2 % (+1.7 % ), +4.5 % (+3.6 % ), +0 % (+0 % ), +2.3 (+0). While no global improvements were obtained for the normal versus cancer classification task [+0 % (-2 % ), +0 % (-3 % ), +2 % (-2 % ), +4 (+3)], the AUC was improved in both testing sets. Conclusions Combining individual intensity features and novel Raman fitted peak features, improved the classification performance on two independent and multicenter testing sets in comparison to using only individual intensity features.

We evaluated mental health and substance use during the COVID-19 pandemic in 196 participants from the Miami Adult Studies on HIV (MASH) Cohort. A survey was administered between July-August of 2020, including validated measures of resilience and anxiety, a scale to measure COVID-19-related worry, and self-reported substance use. Compared to HIV-uninfected participants (n = 80), those living with HIV (n = 116) reported fewer anxiety symptoms, less COVID-19-related worry, and higher resilience. Those with more anxiety symptoms and lower resilience engaged in more frequent alcohol consumption, binge drinking, and cocaine use. Alcohol misuse was more common among HIV-uninfected participants. Cocaine use was reported by 21% fewer participants during the pandemic compared with 7.3 ± 1.5 months earlier. Possibly due to their experiences with HIV, PLWH responded with higher resilience and reduced worry and anxiety to the adversities brought by the COVID-19 pandemic.

Significance: Early detection of oral cancer is vital for high-risk patients, and machine learning-based automatic classification is ideal for disease screening. However, current datasets collected from high-risk populations are unbalanced and often have detrimental effects on the performance of classification. Aim: To reduce the class bias caused by data imbalance. Approach: We collected 3851 polarized white light cheek mucosa images using our customized oral cancer screening device. We use weight balancing, data augmentation, undersampling, focal loss, and ensemble methods to improve the neural network performance of oral cancer image classification with the imbalanced multi-class datasets captured from high-risk populations during oral cancer screening in low-resource settings. Results: By applying both data-level and algorithm-level approaches to the deep learning training process, the performance of the minority classes, which were difficult to distinguish at the beginning, has been improved. The accuracy of “premalignancy” class is also increased, which is ideal for screening applications. Conclusions: Experimental results show that the class bias induced by imbalanced oral cancer image datasets could be reduced using both data- and algorithm-level methods. Our study may provide an important basis for helping understand the influence of unbalanced datasets on oral cancer deep learning classifiers and how to mitigate.

Purpose We examined prostate cancer patients’ participation in research and associated factors by race/ethnicity in a multiethnic sample. Methods Men with a new diagnosis of prostate cancer were identified through the California Cancer Registry. Patients completed a cross-sectional telephone interview in English, Spanish, Cantonese or Mandarin. Multivariable logistic regression models, stratified by race/ethnicity, estimated the associations of patient demographic and health characteristics with participation in (1) any research, (2) behavioral research, and (3) biological/clinical research. Results We included 855 prostate cancer patients: African American (19%), Asian American (15%), Latino (24%), and White (42%). In the overall model of participation in any research, African American men (Odds Ratio (OR) = 2.54, 95% CI 1.63–3.94), and those with two or more comorbidities (OR = 2.20, 95% CI 1.27–3.80) were more likely to report participation. Men 65 years old and older (OR = 0.65, 95% CI 0.47–0.91), those who were married or living with a partner (OR = 0.67, 95% CI 0.45–0.98), and those who completed the interview in Spanish (OR = 0.36, 95% CI 0.15–0.85) were less likely to report participating in any research. Stratified analyses identified racial/ethnic-specific sociodemographic characteristics associated with lower research participation, including Spanish or Chinese language, older age, and lower education. Conclusion African American prostate cancer patients reported higher research participation than all other groups. However, recruitment efforts are still needed to overcome barriers to participation for Spanish and Chinese speakers, and barriers among older adults and those with lower education levels.

Author(s): Hoshino, Shinsuke; Jain, Sonia; Shimizu, Chisato; Roberts, Samantha; He, Feng; Daniels, Lori; Kahn, Andrew; Gordon, John; Burns, Jane; Tremoulet, Adriana | Abstract: Background: Myocardial histology from autopsies of young adults with giant coronary artery aneurysms following Kawasaki disease (KD) shows bridging fibrosis beyond the territories supplied by the aneurysmal arteries. The etiology of this fibrosis is unknown, but persistent, low-level myocardial inflammation and microcirculatory ischemia are both possible contributing factors. To investigate the possibility of subclinical myocardial inflammation or fibrosis, we measured validated biomarkers in young adults with a remote history of KD. Methods: We measured plasma calprotectin, galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and serum procollagen type 1C-terminal propeptide (P1CP) in 91 otherwise healthy young adults with a remote history of KD and in 88 age-similar, healthy controls. KD subjects were stratified by coronary artery aneurysm (CAA) status and history of remote myocardial infarction (MI). Results: After correction for multiple testing, calprotectin, Gal-3, and GDF-15 levels were significantly higher in subjects with persistent CAA (nn=n26) compared with KD subjects with remodeled CAA (nn=n20, pn=n0.005, 0.001, 0.0036, respectively). In a multivariable regression model with CA status as the main predictor and adjusting for sex, MI history, and interval from KD onset, CA status was a significant predictor (Persistent CAA vs KD Normal CA) of calprotectin, Gal-3, GDF-15 and sST2 levels (pn=n0.004, l0.001, 0.007, and 0.049, respectively). Conclusions: These results suggest that ongoing inflammation and fibrosis may be occurring in individuals with persistent CAA. Longitudinal follow-up is needed to clarify the clinical significance of these elevated biomarker levels in this patient population that requires life-long monitoring.

Background Reduced uterine artery compliance is associated with adverse pregnancy outcomes (APOs) and may indicate underlying maternal cardiovascular pathology. We investigated associations between second trimester uterine artery Doppler (UAD) parameters and incident maternal hypertension 2–7 years after delivery. Methods A cohort of 10,038 nulliparous US participants was recruited early in pregnancy. A subgroup of 3739, without baseline hypertension and with complete follow-up visits 2–7 years after delivery, were included in this analysis. We investigated UAD indicators of compliance including: 1) early diastolic notch; 2) resistance index (RI); and 3) pulsatility index (PI). We defined hypertension as systolic blood pressure ≥130 mmHg, diastolic ≥80 mmHg, or antihypertensive medication use. We calculated odds ratios (OR) and 95 % confidence intervals (95%CI) for associations between UAD parameters and hypertension, adjusting for age, obesity, race/ethnicity, insurance, smoking, and APOs. Results A total of 187 (5 %) participants developed hypertension after the index pregnancy. Presence of early diastolic notch on UAD was not associated with incident hypertension. Increased RI and PI correlated with higher odds of hypertension (RI: adjusted OR 1.15 [95 % CI 1.03–1.30]; PI: adjusted OR 1.03 [95%CI 1.01–1.05] for each 0.1 unit increase). Maximum RI above 0.84 or maximum PI above 2.3 more than doubled the odds of incident hypertension (RI: adjusted OR 2.49, 95%CI 1.45–4.26; PI: adjusted OR 2.36, 95%CI 1.45–3.86). Conclusion Higher resistance and pulsatility indices measured on second trimester UAD were associated with increased odds of incident hypertension 2–7 years later, and may be biomarkers of higher maternal cardiovascular risk., Graphical abstract Image 1

Objective Electronic health records (EHRs) are widely adopted, but the time demands of EHR use on ophthalmology trainees are not well understood. This study evaluated ophthalmology trainee time spent on clinical activities in an outpatient clinic undergoing EHR implementation. Design Prospective, manual time-motion observations of ophthalmology trainees in 2018. Participants Eleven ophthalmology residents and fellows observed during 156 patient encounters. Methods Prospective time-motion study of ophthalmology trainees 2 weeks before and 6 weeks after EHR implementation in an academic ophthalmology department. Manual time-motion observations were conducted for 11 ophthalmology trainees in 6 subspecialty clinics during 156 patient encounters. Time spent documenting, examining, and talking with patients were recorded. Factors influencing time requirements were evaluated using linear mixed effects models. Main Outcome Measures Total time spent by ophthalmology residents and fellows per patient, time spent on documentation, examination, and talking with patients. Results Seven ophthalmology residents and four ophthalmology fellows with mean (standard deviation) postgraduate year of 3.7 (1.2) were observed during 156 patient encounters. Using paper charts, mean total time spent on each patient was 11.6 (6.5) minutes, with 5.4 (3.5) minutes spent documenting (48%). After EHR implementation, mean total time spent on each patient was 11.8 (6.9) minutes, with 6.8 (4.7) minutes spent documenting (57%). Total time expenditure per patient did not significantly change after EHR implementation (+0.17 minutes, 95% confidence interval [CI] for difference in means: –2.78, 2.45; p = 0.90). Documentation time did not change significantly after EHR implementation in absolute terms (+1.42 minutes, 95% CI: –3.13, 0.29; p = 0.10), but was significantly greater as a proportion of total time (48% on paper to 57% on EHR; +9%, 95% CI: 2.17, 15.83; p = 0.011). Conclusion Total time spent per patient and absolute time spent on documentation was not significantly different whether ophthalmology trainees used paper charts or the recently implemented EHR. Percentage of total time spent on documentation increased significantly with early EHR use. Evaluating EHR impact on ophthalmology trainees may improve understanding of how trainees learn to use the EHR and may shed light on strategies to address trainee burnout.

Background Adverse mental and emotional health outcomes are increasingly recognized as a public health challenge associated with the COVID-19 pandemic. Objective The goal of this study was to examine the association of COVID-19 risk misperceptions with self-reported household isolation, a potential risk factor for social isolation and loneliness. Methods We analyzed data from the Franklin Templeton-Gallup Economics of Recovery Study (July to December 2020) of 24,649 US adults. We also analyzed data from the Gallup Panel (March 2020 to February 2021), which included 123,516 observations about loneliness. The primary outcome was self-reported household isolation, which we defined as a respondent having no contact or very little contact with people outside their household, analogous to quarantining. Results From July to December 2020, 53% to 57% of respondents reported living in household isolation. Most participants reported beliefs about COVID-19 health risks that were inaccurate, and overestimation of health risk was most common. For example, while deaths in persons younger than 55 years old accounted for 7% of total US deaths, respondents estimated that this population represented 43% of deaths. Overestimating COVID-19 health risks was associated with increased self-reported household isolation, with percentage differences ranging from 5.6 to 11.8 (P Conclusions Pandemic-related harms to emotional and mental well-being may be attenuated by reducing risk overestimation and household isolation preferences that exceed public health guidelines.

ZUMA-1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi-cel), an autologous CD19-directed chimaeric antigen receptor (CAR)-T cell therapy, in refractory large B-cell lymphoma. To reduce treatment-related toxicity, several exploratory safety management cohorts were added to ZUMA-1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end-points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days -5 through -3), 2×106 CAR-T cells/kg (day 0) and once-daily oral dexamethasone [10mg, day 0 (before axi-cel) through day 2]. Forty patients received axi-cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty-eight per cent of patients did not experience CRS or NEs within 72h of axi-cel. With a median follow-up of 8·9months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population.

This observational cross-sectional study of 152 people with HIV (PWH) examined the effects of age and estimated duration of HIV infection (EDI) on depressive and anxiety symptoms. All participants were cisgender men and completed the Profile of Moods State (POMS), a self-report inventory of current (i.e., past week) mood states. Overall, study results confirmed higher levels of anxiety and depression in PWH compared to individuals without HIV. Age group (

Prostate cancer (PCa) in Black Americans (BA) is diagnosed at an earlier median age and a more advanced stage than PCa in White Americans (WA). Tumor-adjacent stroma (TAS) plays a critical role in tumorigenesis of prostate cancer. We examined RNA expression in both tumor and TAS of BA compared to WA. After evaluating the geographical ancestry of each sample, preliminary analysis of our own RNA-seq data of 7 BA and 7 WA TAS revealed 1706 downregulated and 1844 upregulated genes in BA relative to WA PCa patients (p adj < 0.05). An assessment of published RNA-seq data of clinically matched tumor-enriched tissues from 15 BA and 30 WA patients revealed 932 upregulated and 476 downregulated genes in BA relative to WA (p adj < 0.05). When TAS and tumor epithelial cohorts were compared for the top 2500 statistically significant genes, immune responses were downregulated in BA vs WA TAS, while T cell-exhaustion pathways and the immune checkpoint gene CTLA4 were upregulated in BA vs WA tumors. We found fewer activated dendritic cells in tumor and more CD8 T-cells in TAS of BA versus WA PCa patients. Further characterization of these differences in the immune response of PCa patients of distinct geographical ancestry could help to improve diagnostics, prognostics, and therapy.

In this proof-of-concept work, we have developed a 3D-CNN architecture that is guided by the tumor mask for classifying several patient-outcomes in breast cancer from the respective 3D dynamic contrast-enhanced MRI (DCE-MRI) images. The tumor masks on DCE-MRI images were generated using pre- and post-contrast images and validated by experienced radiologists. We show that our proposed mask-guided classification has a higher accuracy than that from either the full image without tumor masks (including background) or the masked voxels only. We have used two patient outcomes for this study: (1) recurrence of cancer after 5 years of imaging and (2) HER2 status, for comparing accuracies of different models. By looking at the activation maps, we conclude that an image-based prediction model using 3D-CNN could be improved by even a conservatively generated mask, rather than overly trusting an unguided, blind 3D-CNN. A blind CNN may classify accurately enough, while its attention may really be focused on a remote region within 3D images. On the other hand, only using a conservatively segmented region may not be as good for classification as using full images but forcing the model's attention toward the known regions of interest.

Significance: Oral cancer is among the most common cancers globally, especially in low- and middle-income countries. Early detection is the most effective way to reduce the mortality rate. Deep learning-based cancer image classification models usually need to be hosted on a computing server. However, internet connection is unreliable for screening in low-resource settings. Aim: To develop a mobile-based dual-mode image classification method and customized Android application for point-of-care oral cancer detection. Approach: The dataset used in our study was captured among 5025 patients with our customized dual-modality mobile oral screening devices. We trained an efficient network MobileNet with focal loss and converted the model into TensorFlow Lite format. The finalized lite format model is ∼16.3 MB and ideal for smartphone platform operation. We have developed an Android smartphone application in an easy-to-use format that implements the mobile-based dual-modality image classification approach to distinguish oral potentially malignant and malignant images from normal/benign images. Results: We investigated the accuracy and running speed on a cost-effective smartphone computing platform. It takes ∼300 ms to process one image pair with the Moto G5 Android smartphone. We tested the proposed method on a standalone dataset and achieved 81% accuracy for distinguishing normal/benign lesions from clinically suspicious lesions, using a gold standard of clinical impression based on the review of images by oral specialists. Conclusions: Our study demonstrates the effectiveness of a mobile-based approach for oral cancer screening in low-resource settings.

A cantilevered liquid-nitrogen-cooled silicon mirror is described that will achieve diffraction-limited performance even under extreme power density. This mirror will serve as a robust first optic for the high-brightness undulator beamlines at the upgraded Advanced Light Source., This paper presents a novel cantilevered liquid-nitro­gen-cooled silicon mirror design for the first optic in a new soft X-ray beamline that is being developed as part of the Advanced Light Source Upgrade (ALS-U) (Lawrence Berkeley National Laboratory, USA). The beamline is optimized for photon energies between 400 and 1400 eV with full polarization control. Calculations indicate that, without correction, this design will achieve a Strehl ratio greater than 0.85 for the entire energy and polarization ranges of the beamline. With a correction achieved by moving the focus 7.5 mm upstream, the minimum Strehl ratio is 0.99. This design is currently the baseline plan for all new ALS-U insertion device beamlines.