Understanding Breast Cancer Images in Art History as a Form of Health Communication.

Can art and visual images meant for public consumption (museums, galleries, social media platforms) serve as a critical form of health communication for breast cancer patients? For their clinicians? For the population at large? Art history research methods are applied to a range of breast cancer images in western art in order to understand what the images communicate to us about patient experience, agency, and inequity in health care at the time of their construction. The following is a selective look at western art as it reflects and informs our understanding of breast cancer over time.

Kinome and phosphoproteome reprogramming underlies the aberrant immune responses in critically ill COVID-19 patients.

SARS-CoV-2 infection triggers extensive host immune reactions, leading to severe diseases in certain individuals. However, the molecular basis underlying the excessive yet non-productive immune responses in severe COVID-19 remains incompletely understood. In this study, we conducted a comprehensive analysis of the peripheral blood mononuclear cell (PBMC) proteome and phosphoproteome in sepsis patients positive or negative for SARS-CoV-2 infection, as well as healthy subjects, using quantitative mass spectrometry. Our findings demonstrate dynamic changes in the COVID-19 PBMC proteome and phosphoproteome during disease progression, with distinctive protein or phosphoprotein signatures capable of distinguishing longitudinal disease states. Furthermore, SARS-CoV-2 infection induces a global reprogramming of the kinome and phosphoproteome, resulting in defective adaptive immune response mediated by the B and T lymphocytes, compromised innate immune responses involving the SIGLEC and SLAM family of immunoreceptors, and excessive cytokine-JAK-STAT signaling. In addition to uncovering host proteome and phosphoproteome aberrations caused by SARS-CoV-2, our work recapitulates several reported therapeutic targets for COVID-19 and identified numerous new candidates, including the kinases PKG1, CK2, ROCK1/2, GRK2, SYK, JAK2/3, TYK2, DNA-PK, PKCδ, and the cytokine IL-12.

Complete mitochondrial genome of Gnathostoma binucleatum.

This report describes the mitochondrial genome of the parasite Gnathostoma binucleatum (G. binucleatum), which was obtained from naturally infected freshwater fish in Sinaloa, Mexico (22°46'00.1″N 105°40'21.8″W). G. binucleatum is responsible for human gnathostomiasis and is endemic to Mexico. It belongs to the Spirurida order of the Secernentea class of Nematoda.

Interpreting Sequence-Levenshtein distance for determining error type and frequency between two embedded sequences of equal length.

Levenshtein distance is a commonly used edit distance metric, typically applied in language processing, and to a lesser extent, in molecular biology analysis. Biological nucleic acid sequences are often embedded in longer sequences and are subject to insertion and deletion errors that introduce frameshift during sequencing. These frameshift errors are due to string context and should not be counted as true biological errors. Sequence-Levenshtein distance is a modification to Levenshtein distance that is permissive of frameshift error without additional penalty. However, in a biological context Levenshtein distance needs to accommodate both frameshift and weighted errors, which Sequence-Levenshtein distance cannot do. Errors are weighted when they are associated with a numerical cost that corresponds to their frequency of appearance. Here, we describe a modification that allows the use of Levenshtein distance and Sequence-Levenshtein distance to appropriately accommodate penalty-free frameshift between embedded sequences and correctly weight specific error types.

Senolytic and senomorphic secondary metabolites as therapeutic agents in Drosophila melanogaster models of Parkinson's disease.

Drosophila melanogaster is a valuable model organism for a wide range of biological exploration. The well-known advantages of D. melanogaster include its relatively simple biology, the ease with which it is genetically modified, the relatively low financial and time costs associated with their short gestation and life cycles, and the large number of offspring they produce per generation. D. melanogaster has facilitated the discovery of many significant insights into the pathology of Parkinson's disease (PD) and has served as an excellent preclinical model of PD-related therapeutic discovery. In this review, we provide an overview of the major D. melanogaster models of PD, each of which provide unique insights into PD-relevant pathology and therapeutic targets. These models are discussed in the context of their past, current, and future potential use for studying the utility of secondary metabolites as therapeutic agents in PD. Over the last decade, senolytics have garnered an exponential interest in their ability to mitigate a broad spectrum of diseases, including PD. Therefore, an emphasis is placed on the senolytic and senomorphic properties of secondary metabolites. It is expected that D. melanogaster will continue to be critical in the effort to understand and improve treatment of PD, including their involvement in translational studies focused on secondary metabolites.

Factors that contribute to trait mindfulness level among hospitalized patients with major depressive disorder.

Mindfulness training among patients with major depressive disorder (MDD) reduces symptoms, prevents relapse, improves prognosis, and is more efficient for those with a high level of trait mindfulness. Upon hospital admission, 126 MDD patients completed the Beck Depression Inventory (BDI), World Health Organization Quality of Life Brief, Five-Factor Mindfulness Questionnaire (FFMQ), and the Rumination Response Scale (RRS). The 65 patients that scored less than the median of all subjects on the FFMQ were placed into the low mindfulness level (LML) group. The other 61 patients were placed in the high mindfulness level (HML) group. All facet scores were statistically different between the mental health assessment scores of the HML and LML groups except for RRS brooding and FFMQ nonjudgement. Trait mindfulness level exhibited a negative and bidirectional association with MDD severity primarily through the facets of description and aware actions. Trait mindfulness was also related positively with age primarily through the facets of nonreactivity and nonjudgement. Being married is positively associated with trait mindfulness levels primarily through the facet of observation and by an associated increase in perceived quality of life. Mindfulness training prior to MDD diagnosis also associates positively with trait mindfulness level. Hospitalized MDD patients should have their trait mindfulness levels characterized to predict treatment efficiency, help establish a prognosis, and identify mindfulness-related therapeutic targets.

Disparities in Emergency Medical Services Care Delivery in the United States: A Scoping Review.

BACKGROUND: Emergency medical services (EMS) often serve as the first medical contact for ill or injured patients, representing a critical access point to the health care delivery continuum. While a growing body of literature suggests inequities in care within hospitals and emergency departments, limited research has comprehensively explored disparities related to patient demographic characteristics in prehospital care. OBJECTIVE: We aimed to summarize the existing literature on disparities in prehospital care delivery for patients identifying as members of an underrepresented race, ethnicity, sex, gender, or sexual orientation group. METHODS: We conducted a scoping review of peer-reviewed and non-peer-reviewed (gray) literature. We searched PubMed, CINAHL, Web of Science, Proquest Dissertations, Scopus, Google, and professional websites for studies set in the U.S. between 1960 and 2021. Each abstract and full-text article was screened by two reviewers. Studies written in English that addressed the underrepresented groups of interest and investigated EMS-related encounters were included. Studies were excluded if a disparity was noted incidentally but was not a stated objective or discussed. Data extraction was conducted using a standardized electronic form. Results were summarized qualitatively using an inductive approach. RESULTS: One hundred forty-five full-text articles from the peer-reviewed literature and two articles from the gray literature met inclusion criteria: 25 studies investigated sex/gender, 61 studies investigated race/ethnicity, and 58 studies investigated both. One study investigated sexual orientation. The most common health conditions evaluated were out-of-hospital cardiac arrest (n = 50), acute coronary syndrome (n = 36), and stroke (n = 31). The phases of EMS care investigated included access (n = 55), pre-arrival care (n = 46), diagnosis/treatment (n = 42), and response/transport (n = 40), with several studies covering multiple phases. Disparities were identified related to all phases of EMS care for underrepresented groups, including symptom recognition, pain management, and stroke identification. The gray literature identified public perceptions of EMS clinicians' cultural competency and the ability to appropriately care for transgender patients in the prehospital setting. CONCLUSIONS: Existing research highlights health disparities in EMS care delivery throughout multiple health outcomes and phases of EMS care. Future research is needed to identify structured mechanisms to eliminate disparities, address clinician bias, and provide high-quality equitable care for all patient populations.

Auctioning approaches for ecosystem services - Evidence and applications.

Auctions have attracted growing attention as bidding mechanisms for soliciting or allocating payments for a wide range of ecosystem services (ES). This paper reviews the latest scientific knowledge on ES auctioning approaches. Using systematically selected academic articles, we trace and discuss the development of ES auction literature across space, time, target ecosystem, and mechanism type. We integrate previous attempts to organize this body of work to produce a composite factor map of entry points to more specialized sub-literatures engaging with current issues in auction design and implementation. The results show that most academic work focuses on reverse auctions, where landowners bid their willingness to accept contracts to protect or promote ES provisioning, but we also locate several forward (i.e. beneficiaries bid their willingness to pay for ES) and mixed mechanisms. We critically analyze major advantages and challenges for each approach, emphasizing issues related to transaction costs and accessibility for participants and agencies. Overall, our findings suggest that ES auctions have a robust track record but remain administratively and logistically challenging. Further investment in open-source tools, shared infrastructure, and other efforts to make auctions more accessible to researchers, agencies, and participants alike is strongly indicated.

Don Lindberg's home library and leadership traits.

This chapter introduces the importance and some of the multidisciplinary diversity in Donald A.B. Lindberg M.D.'s home library. The latter collection minimally suggests his varied interests, which often inspired a multidisciplinary approach to tackling problems and managing the U.S. National Library of Medicine (NLM). Dr. Lindberg converted the ideas he picked up from reading into administering projects as well as to set aspirational goals for NLM and for himself. The chapter suggests Dr. Lindberg's home library was an enduring reservoir of knowledge, judgment, planning, and creativity. The chapter also discusses two of Dr. Lindberg's leadership traits: the cultivation of discovery and project development in educational administration and the need for leaders to determine and act in the greater public interest. The chapter suggests the latter two traits defined Dr. Lindberg's NLM leadership.

Neuroglial Senescence, α-Synucleinopathy, and the Therapeutic Potential of Senolytics in Parkinson's Disease.

Parkinson's disease (PD) is the most common movement disorder and the second most prevalent neurodegenerative disease after Alzheimer's disease. Despite decades of research, there is still no cure for PD and the complicated intricacies of the pathology are still being worked out. Much of the research on PD has focused on neurons, since the disease is characterized by neurodegeneration. However, neuroglia has become recognized as key players in the health and disease of the central nervous system. This review provides a current perspective on the interactive roles that α-synuclein and neuroglial senescence have in PD. The self-amplifying and cyclical nature of oxidative stress, neuroinflammation, α-synucleinopathy, neuroglial senescence, neuroglial chronic activation and neurodegeneration will be discussed. Finally, the compelling role that senolytics could play as a therapeutic avenue for PD is explored and encouraged.

Novel Genetic Signatures Associated With Sporadic Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a complex polygenetic neurodegenerative disorder. Establishing a diagnosis for ALS is a challenging and lengthy process. By the time a diagnosis is made, the lifespan prognosis is only about two to 5 years. Genetic testing can be critical in assessing a patient's risk for ALS, provided they have one of the known familial genes. However, the vast majority of ALS cases are sporadic and have no known associated genetic signatures. Our analysis of the whole genome sequencing data from ALS patients and healthy controls from the Answer ALS Consortium has uncovered twenty-three novel mutations in twenty-two protein-coding genes associated with sporadic ALS cases. The results show the majority of patients with the sporadic form of ALS have at least one or more mutation(s) in the 22 genes we have identified with probabilities of developing ALS ranging from 25-99%, depending on the number of mutations a patient has among the identified genes. Moreover, we have identified a subset of the ALS cohort that has >17 mutations in the 22 identified. In this case, a patient with this mutation profile has a 99% chance of developing ALS and could be classified as being at high risk for the disease. These genetic biomarkers can be used as an early ALS disease diagnostic tool with a rapid and non-invasive technique.

A cohort study of duplicate faecal immunochemical testing in patients at risk of colorectal cancer from North-West England.

OBJECTIVES: We sought to investigate if duplicate faecal immunochemical testing (FIT) sampling improves the negative and positive predictive value of patients thought to be at risk of colorectal cancer (CRC). Specifically, we aimed to investigate whether the proportion of FIT-negative CRC missed by a single FIT test in symptomatic patients could be reduced by duplicate FIT testing. DESIGN: A retrospective service evaluation cohort study of the diagnostic accuracy of duplicate FIT testing. SETTING: Patients referred from primary care with suspected CRC to four secondary care trusts in North-West England. PARTICIPANTS: 28 622 patients over 18-years-old with lower gastrointestinal symptoms suggestive of CRC who completed two FIT samples. PRIMARY AND SECONDARY OUTCOME MEASURES: The performance of duplicate FIT for detecting CRC at a threshold of 10 µgHb/g. RESULTS: The sensitivity if either test was >10 µgHb/g was 0.978 (0.955-0.989), specificity was 0.662 (0.657-0.668), positive predictive value 0.031 (0.028-0.035) and negative predictive value 1.00 (0.999-1.00). Despite two-thirds of patients (18952) being negative following two tests, at this threshold only seven CRC were missed over a 26-month period. All seven patients had other high-risk features which should have prompted investigation. CONCLUSIONS: This study suggests that in routine NHS practice, a duplicate FIT sample strategy together with clinical evaluation for evidence of anaemia and weight loss is superior to a single FIT sample alone and would allow symptomatic patients to be managed in primary care without the need for urgent referral to secondary care for urgent colonic imaging.

3GOLD: optimized Levenshtein distance for clustering third-generation sequencing data.

BACKGROUND: Third-generation sequencing offers some advantages over next-generation sequencing predecessors, but with the caveat of harboring a much higher error rate. Clustering-related sequences is an essential task in modern biology. To accurately cluster sequences rich in errors, error type and frequency need to be accounted for. Levenshtein distance is a well-established mathematical algorithm for measuring the edit distance between words and can specifically weight insertions, deletions and substitutions. However, there are drawbacks to using Levenshtein distance in a biological context and hence has rarely been used for this purpose. We present novel modifications to the Levenshtein distance algorithm to optimize it for clustering error-rich biological sequencing data. RESULTS: We successfully introduced a bidirectional frameshift allowance with end-user determined accommodation caps combined with weighted error discrimination. Furthermore, our modifications dramatically improved the computational speed of Levenstein distance. For simulated ONT MinION and PacBio Sequel datasets, the average clustering sensitivity for 3GOLD was 41.45% (S.D. 10.39) higher than Sequence-Levenstein distance, 52.14% (S.D. 9.43) higher than Levenshtein distance, 55.93% (S.D. 8.67) higher than Starcode, 42.68% (S.D. 8.09) higher than CD-HIT-EST and 61.49% (S.D. 7.81) higher than DNACLUST. For biological ONT MinION data, 3GOLD clustering sensitivity was 27.99% higher than Sequence-Levenstein distance, 52.76% higher than Levenshtein distance, 56.39% higher than Starcode, 48% higher than CD-HIT-EST and 70.4% higher than DNACLUST. CONCLUSION: Our modifications to Levenshtein distance have improved its speed and accuracy compared to the classic Levenshtein distance, Sequence-Levenshtein distance and other commonly used clustering approaches on simulated and biological third-generation sequenced datasets. Our clustering approach is appropriate for datasets of unknown cluster centroids, such as those generated with unique molecular identifiers as well as known centroids such as barcoded datasets. A strength of our approach is high accuracy in resolving small clusters and mitigating the number of singletons.

Sophocles' Philoctetes and Moral Injury in the COVID-19 Pandemic.

Strong emotional responses of health-care professionals to the unusual stress of providing care during the COVID-19 pandemic may be consistent with the experience of moral injury. This term, originally used to explain the feelings of guilt, shame, and righteous anger resulting from trauma experienced by US soldiers who felt betrayed by their leaders in combat, has recently been applied to the experiences of health-care workers who know the right thing to do but lack the autonomy, latitude, or authority to do it. Ancient Greek tragedy, which often explores stories about moral challenges, can provide a fruitful context for communicating about this kind of traumatic experience. Sophocles' Philoctetes is particularly relevant for health care since it describes the psychological pain of a would-be caregiver who is ordered by a superior to deny care to someone suffering with chronic pain, providing a clear example of betrayal through failed leadership and lack of authority to do the right thing. A more detailed reading of Sophocles' Philoctetes demonstrates that it also describes the kind of moral distress that results from being forced to respond to an unsolvable ethical dilemma when there is no clear right thing to do or when doing the right thing requires violating personal moral values.

Section Four: Memoirs, Resources, and Insights About Donald A.B. Lindberg M.D.

Section four provides additional insights into Donald A.B. Lindberg M.D.'s life, character, interests, and passions. It includes 20 memoirs, a few of his photographs, a Resource Guide, and an essay about the influence of his home library and leadership traits. Section four's 20 memoirs are brief, more colloquial, and sometimes personal. The memoirs discuss Dr. Lindberg's interactions with family, lifelong friends, biomedical informatics colleagues, and U.S. National Library of Medicine (NLM) peers. The Resource Guide, photos, and essay yield other insights and assist readers who wish to learn more about Dr. Lindberg.