A Drastic Shift in Lipid Adducts in Colon Cancer Detected by MALDI-IMS Exposes Alterations in Specific K+ Channels

Even though colorectal cancer (CRC) is one of the most preventable cancers, it is one of the deadliest, and recent data show that the incidence in people <50 years has unexpectedly increased. While new techniques for CRC molecular classification are emerging, no molecular feature is as yet firmly associated with prognosis. Imaging mass spectrometry (IMS) lipidomic analyses have demonstrated the specificity of the lipid fingerprint in differentiating pathological from healthy tissues. During IMS lipidomic analysis, the formation of ionic adducts is common. Of particular interest is the [Na+]/[K+] adduct ratio, which already functions as a biomarker for homeostatic alterations. Herein, we show a drastic shift of the [Na+]/[K+] adduct ratio in adenomatous colon mucosa compared to healthy mucosa, suggesting a robust increase in K+ levels. Interrogating public databases, a strong association was found between poor diagnosis and voltage-gated potassium channel subunit beta-2 (KCNAB2) overexpression. We found this overexpression in three CRC molecular subtypes defined by the CRC Subtyping Consortium, making KCNAB2 an interesting pharmacological target. Consistently, its pharmacological inhibition resulted in a dramatic halt in commercial CRC cell proliferation. Identification of potential pharmacologic targets using lipid adduct information emphasizes the great potential of IMS lipidomic techniques in the clinical field.This study was supported in part by the Institute of Health Carlos III (CP12/03338 and PI16/02200), Basque Government (IT1162-19), and the EC (European Regional Development Fund, ERDF, CP12/03338). A.M.B. and J.B-E. hold predoctoral fellowships of the Govern Balear (Direcció General d’Innovació i Recerca, FPI/2160/2018 and FPI/1787/2015, respectively), co-funded by the ESF (European Social Fund). K.P.-R. contract was supported by the Govern Balear (Servei d’Ocupació de les IIles Balears and Garantia Juvenil, JQ-SP 18/17), co-funded by the ESF. G.B.-C. and D.H.L.’s contracts were supported by the Institute of Health Carlos III, co-funded by ERDF (Miguel Servet II program, CPII17/00005 and PI16/02200, respectively). We are grateful to SGiker Lipidomic Service (UPV/EHU, MICINN, GV/EG, ESF) for the expert advice and technical and human support in MALDI-IMS analysis. The publication fee in this Open Access journal is fully supported by the Liberi Call of the IdISBa

Cancer Patient and Provider Responses to Companion Scales Assessing Experiences With LGBTQI-Affirming Healthcare

Background: Sexual and gender minority (SGM) persons are at a higher risk for some cancers and may have poorer health outcomes as a result of ongoing minority stress, social stigma, and cisnormative, heteronormative healthcare environments. This study compared patient and provider experiences of affirming environmental and behavioral cues and also examined provider-reported knowledge, attitudes, behaviors, and clinical preparedness in caring for SGM patients among a convenience sample. Methods: National convenience samples of oncology providers (n = 107) and patients (n = 88) were recruited separately via snowball sampling. No incentives were provided. After reverse coding of appropriate items for unidirectional analysis, lower scores on items indicated greater knowledge, more affirming attitudes or behaviors, and greater confidence in clinical preparedness to care for SGM patients. Pearson chi-square tests compared dichotomous variables and independent samples t-tests compared continuous variables. Other results were reported using descriptive frequencies. Results: Both patient and provider samples were predominantly female sex assigned at birth, cisgender, and heterosexual. Providers were more likely than patients to report affirming cues in clinic, as well as the ability for patients to easily document their name in use and pronouns. Providers were more likely to report asking about patient values and preferences of care versus patients’ recollection of being asked. Patients were more likely to report understanding why they were asked about both sex assigned at birth and gender identity compared to providers’ perceptions that patients would understand being asked about both. Patients were also more likely to report comfort with providers asking about sex assigned at birth and gender identity compared to providers’ perceptions of patient comfort. SGM providers had greater knowledge of SGM patient social determinants of health and cancer risks; felt more prepared to care for gay patients; were more likely to endorse the importance of knowing patient sexual orientation and gender identity; and were more likely to indicate a responsibility to learn about SGM patient needs and champion positive system changes for SGM patients compared to heterosexual/cisgender peers. Overall, providers wished for more SGM-specific training. Conclusion: Differences between patient and provider reports of affirming environments as well as differences between SGM and heterosexual/cisgender provider care support the need for expanded professional training specific to SGM cancer care

Cancer patient and provider responses to companion scales assessing experiences with LGBTQI-affirming healthcare

BackgroundSexual and gender minority (SGM) persons are at a higher risk for some cancers and may have poorer health outcomes as a result of ongoing minority stress, social stigma, and cisnormative, heteronormative healthcare environments. This study compared patient and provider experiences of affirming environmental and behavioral cues and also examined provider-reported knowledge, attitudes, behaviors, and clinical preparedness in caring for SGM patients among a convenience sample.MethodsNational convenience samples of oncology providers (n = 107) and patients (n = 88) were recruited separately via snowball sampling. No incentives were provided. After reverse coding of appropriate items for unidirectional analysis, lower scores on items indicated greater knowledge, more affirming attitudes or behaviors, and greater confidence in clinical preparedness to care for SGM patients. Pearson chi-square tests compared dichotomous variables and independent samples t-tests compared continuous variables. Other results were reported using descriptive frequencies.ResultsBoth patient and provider samples were predominantly female sex assigned at birth, cisgender, and heterosexual. Providers were more likely than patients to report affirming cues in clinic, as well as the ability for patients to easily document their name in use and pronouns. Providers were more likely to report asking about patient values and preferences of care versus patients’ recollection of being asked. Patients were more likely to report understanding why they were asked about both sex assigned at birth and gender identity compared to providers’ perceptions that patients would understand being asked about both. Patients were also more likely to report comfort with providers asking about sex assigned at birth and gender identity compared to providers’ perceptions of patient comfort. SGM providers had greater knowledge of SGM patient social determinants of health and cancer risks; felt more prepared to care for gay patients; were more likely to endorse the importance of knowing patient sexual orientation and gender identity; and were more likely to indicate a responsibility to learn about SGM patient needs and champion positive system changes for SGM patients compared to heterosexual/cisgender peers. Overall, providers wished for more SGM-specific training.ConclusionDifferences between patient and provider reports of affirming environments as well as differences between SGM and heterosexual/cisgender provider care support the need for expanded professional training specific to SGM cancer care

Arachidonic acid pathway alterations in cerebrospinal fluid of dogs with naturally occurring spinal cord injury

BACKGROUND: Canine intervertebral disc πherniation causes a naturally-occurring spinal cord injury (SCI) that bears critical similarities to human SCI with respect to both injury pathomechanisms and treatment. As such, it has tremendous potential to enhance our understanding of injury biology and the preclinical evaluation of novel therapies. Currently, there is limited understanding of the role of arachidonic acid metabolites in canine SCI. RESULTS: The CSF concentrations of PLA2 and PGE2 were higher in SCI dogs compared to control dogs (p = 0.0370 and 0.0273, respectively), but CSF LCT4 concentration in SCI dogs was significantly lower than that in control dogs (p < 0.0001). Prostaglandin E2 concentration in the CSF was significantly and positively associated with increased severity of SCI at the time of sampling (p = 0.041) and recovery 42 days post-injury (p = 0.006), as measured by ordinal behavioral scores. CONCLUSION: Arachidonic acid metabolism is altered in dogs with SCI, and these data suggest that these AA metabolites reflect injury severity and recovery, paralleling data from other model systems

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Common and Differential Traits of the Membrane Lipidome of Colon Cancer Cell Lines and their Secreted Vesicles: Impact on Studies Using Cell Lines

Colorectal cancer (CRC) is the fourth leading cause of cancer death in the world. Despite the screening programs, its incidence in the population below the 50s is increasing. Therefore, new stratification protocols based on multiparametric approaches are highly needed. In this scenario, the lipidome is emerging as a powerful tool to classify tumors, including CRC, wherein it has proven to be highly sensitive to cell malignization. Hence, the possibility to describe the lipidome at the level of lipid species has renewed the interest to investigate the role of specific lipid species in pathologic mechanisms, being commercial cell lines, a model still heavily used for this purpose. Herein, we characterize the membrane lipidome of five commercial colon cell lines and their extracellular vesicles (EVs). The results demonstrate that both cell and EVs lipidome was able to segregate cells according to their malignancy. Furthermore, all CRC lines shared a specific and strikingly homogenous impact on ether lipid species. Finally, this study also cautions about the need of being aware of the singularities of each cell line at the level of lipid species. Altogether, this study firmly lays the groundwork of using the lipidome as a solid source of tumor biomarkers

Detecting chemical misconceptions in first-year biochemistry degree undergraduates

Students possess some ideas about physical-chemical transformations that are at odds with the established chemical theory. If we want the conceptual framework to be learnt in a robust, sound way, then these misconceptions have to be challenged and, eventually, demolished scientifically [1-4].Biochemistry is a science that needs strong chemical foundations. Hence, students who are struggling with fundamental concepts from chemistry will be ill-equipped to analyse processes that are more sophisticated [5]. The first goal is to detect what these wrong ideas are. Once misconceptions are identified, a teaching-learning strategy can be conceived to address the problem [6-8].We have used a validated questionnaire composed of 25 questions, divided into five key conceptual categories related to physical-chemical phenomena [9-14]. The survey was conducted with first-year Biochemistry undergraduates reading a course on General Chemistry during the first term of the 2014/15 academic year, at the University of Extremadura, Spain.We present herein the methodology, results, analysis and conclusions drawn from this study

Decreasing Overutilization of Echocardiograms and Abdominal Imaging in the Evaluation of Children with Fungemia

Objective: Pediatric fungemia is associated with a low risk of fungal endocarditis and renal infections. The majority of current guidelines do not recommend routine abdominal imaging/echocardiograms in the evaluation of fungemia, but such imaging has been routinely ordered for patients on the pediatric gastroenterology service at our institution. Our goals were to assess the financial impact of this deviation from current clinical guidelines and redefine the standard work to reduce overutilization of abdominal ultrasounds and echocardiograms. Specifically, our goal was to reduce imaging by 50% by 18 months. Methods: Root cause analysis showed a lack of familiarity with current evidence. Using this data, countermeasures were implemented, including practitioner education of guidelines and creation of a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Balancing measures were missed episodes of fungal endocarditis and renal infection. Results: During the period January 1, 2016 to November 19, 2017, 18 of 21 episodes of fungemia in our pediatric institution occurred in patients admitted to the pediatric gastroenterology service. Abdominal imaging and echocardiograms were done 100% of the time, with no positive findings and an estimated cost of approximately $58,000. Post-intervention from November 20, 2017 to April 3, 2019, 7 of 13 episodes of fungemia occurred on this service. Frequency of abdominal imaging and echocardiograms decreased to 43% and 57%, respectively. No episodes of fungal endocarditis or renal infection were identified. Conclusion: Overutilization of abdominal imaging and echocardiograms in pediatric fungemia evaluation can be safely decreased

Together-Equitable-Accessible-Meaningful (TEAM) Training to Improve Cancer Care for Sexual and Gender Minorities (SGM): Outcomes from a Pilot Study

To alleviate health disparities experienced by sexual and gender minority (SGM) patients, cancer care professionals need further education on the needs of SGM cancer patients and their loved ones and caregivers. The Together-Equitable-Accessible-Meaningful (TEAM) Training to Improve Cancer Care for SGM Patients (TEAM SGM) was developed and piloted to address this need. This study reports healthcare professional learner outcomes from the TEAM SGM pilot intervention. The TEAM SGM Training pilot consisted of 2.5 h of content from the original online self-paced TEAM Training plus 12 1-h Zoom sessions on specialized topics in addition to readings and activities. Participants (n = 28), representing seven cancer service organizations from six states in the USA, were recruited through newsletter listservs and social media. All participants (n = 28) completed the pre-test and twenty-two participants completed the post-test. Using five factors confirmed in a separate Confirmatory Factor Analysis, paired t-tests of TEAM SGM participant pre- and post-test data were conducted. Statistically significant improvements were found in four of five factors: Environmental Cues (t(21) = 2.56, p =.018), Knowledge (t(21) = 2.15, p =.043), Clinical Preparedness (t(7) = 3.89, p =.006), Clinical Behaviors (t(21) = 2.48, p =.022). The Attitudes factor was not significantly improved from pre-intervention to post-intervention likely due to strong affirming attitudes toward SGM patients at baseline. TEAM SGM is a feasible, effective training to build capacity in SGM-affirming care for cancer care providers