bluuebunny/crossref_metadata_2025 huggingface dataset:
14154 Facilitating Community/Campus Research Teams and Projects: Community Health Small Grants Program
Authors: Croisant Sharon A. , Prochaska John , Singleton Chantele , Bohn Krista , Hallberg Lance , Wiseman Lori , Hanley Eleanor , Sommer Lesley
Published: March 2021

ABSTRACT IMPACT: The UTMB Institute for Translational Sciences (ITS) seeks to advance the field of community engagement and facilitate competency in community-engaged and community-based participatory research as a means of expanding team science to integrate community involvement and to assist investigators in building relationships that enable them to contribute to community initiatives. OBJECTIVES/GOALS: The UTMB ITS recently implemented a new Community Health Small Grants program to promote and enhance community-campus partnerships. Our goal is to better translate science from discovery to clinical practice and public health through community-engaged research, education, and dissemination. METHODS/STUDY POPULATION: Applications were solicited from community and academic research partners. Community partners may include existing collaborative groups, community health centers, health departments, nonprofits, schools, social services agencies, practice-based research networks, or Community Advisory Boards. Academic partners may include faculty and/or students. The PI may be a community or academic partner. While this Grants Program will transition to the ITS Pilot Project Program, it will utilize a separate review process and scoring rubric focused on immediate and future community benefit, project feasibility, organizational fit, and other factors unique to community-based partnership projects. RESULTS/ANTICIPATED RESULTS: We received an enthusiastic response to our RFA, based upon a long-standing program of a sister CTSA hub. Proposals received include target populations representative of our most vulnerable’‘ children, the elderly, those lacking access to health care, and those for whom language is a barrier. One addresses the Institution’s and the CEC’s need to conduct community needs assessments to enable the implementation of evidence-based programs driven by data and metrics identified and developed by our communities. Each awarded proposal demonstrates a significant and sometimes critical need for the project. Partnerships are anticipated to have significant impacts on the community and its population. DISCUSSION/SIGNIFICANCE OF FINDINGS: We generate, test, and disseminate team science, education and best practices through stakeholder involvement. Our Community Health Small Grants program aims to involve community in our scientific teams and to involve academics in community-derived projects as well as foster relationships and trust.
56326 Heart to Heart: An Interdisciplinary Community Collaboration to Address Health Disparities Through Cardiovascular Disease Risk Assessments in Underserved Urban Neighborhoods
Authors: Bales Michael E. , Zhu Jifeng , Aboharb Farid , Dusaj Neville , Shtayer Lior , Balaji Venkatesh , Keeler Allegra , Ganzer Christine A. , Ryon Krista A. ,   the H2H Consortium, Ehrmann Brett J. , Imperato-McGinley Julianne
Published: March 2021

ABSTRACT IMPACT: Leveraging partnerships with faith-based institutions and community centers in at-risk NYC neighborhoods, the H2H Program breaks down barriers to engaging with the medical establishment and addresses the increasing burden of diabetes and CVD risk factors in the most vulnerable individuals. OBJECTIVES/GOALS: Screening for modifiable risk factors is critical for cardiovascular disease (CVD) risk reduction. Low-income, urban communities often encounter barriers to care. Community-academic outreach partnerships are vital in addressing such disparities and promoting health equity and culturally targeted interventions among high-risk populations. METHODS/STUDY POPULATION: In 2010, the Weill Cornell Clinical and Translational Science Center along with Weill Cornell Medicine (WCM) and Hunter-Bellevue School of Nursing (HBSON) launched Heart to Heart (H2H), a community outreach program partnering with faith-based centers to offer free health screenings and education to some of New York City’s (NYC) most vulnerable communities. Participants work with undergraduate, nursing, medical and dietician students to complete a demographics and health questionnaire followed by vital signs and point-of-care blood testing. Participants then receive personalized health education, nutrition and lifestyle counseling by student volunteers, precepted by WCM Primary Care and HBSON faculty. Participants are provided information on local free or low-cost clinics as necessary for follow-up. RESULTS/ANTICIPATED RESULTS: To date H2H held 125 events and 5,952 screenings. Mean age of the participants was 54.3 (SD 39.6) and 3,682 (63.1%) were female. 74.2% identified as non-white. 42.1% were uninsured. 32.3% reported annual income of less than $20k. 18.3% of participants reported not having seen a doctor in the past year. 40.7% reported preexisting hypertension, of which 74.5% were on medication and 78% with sub-optimal control. 15.7% had been previously diagnosed with diabetes, of which 75.8% were on medication and 41.4% with sub-optimal control (HbA1c <7). 37.7% had been diagnosed with dyslipidemia previously, of which 47.4% were on medication and 62.1% with sub-optimal control. Screenings revealed, 56.9% had undiagnosed hypertensive blood pressures, 4.7% had an elevated HbA1c >6.5, and 49.2% had dyslipidemia. DISCUSSION/SIGNIFICANCE OF FINDINGS: H2H screening revealed significant cardiovascular health disparities, many of which were poorly controlled or newly discovered. Cross-institutional academic partnerships can empower communities with knowledge of their health status and help facilitate access to medical care to further address health risk factors.
35336 Effect of Nuclear Soluble Adenylyl Cyclase (sAC) on Melanoma Treatment Response
Authors: Bang Jakyung , Drozdz Marek M. , Dong Lauren , Merghoub Taha , Zippin Jonathan H.
Published: March 2021

ABSTRACT IMPACT: Our data identify a novel candidate for combination strategy in melanoma treatment, and can inform clinicians in their decision-making process regarding therapeutic intervention for melanoma patients. OBJECTIVES/GOALS: Soluble adenylyl cyclase (sAC) is a novel source of cyclic AMP (cAMP). In melanoma, nuclear sAC localization has an established diagnostic utility and we newly found that nuclear sAC functions as a tumor suppressor by inhibiting Hippo pathway, which affects treatment response. Here, we examine the effect of nuclear sAC on melanoma treatment response. METHODS/STUDY POPULATION: We developed a doxycycline inducible system for increasing sAC activity only in the nucleus. We assessed whether nuclear sAC activity affects treatment response, using BRAFV600 human melanoma cell lines. Using a clonogenic assay, we examined how nuclear sAC activity affects growth inhibition in the presence of a BRAF inhibitor, vemurafenib. Our findings will be confirmed in vivo using tumor xenografts. After tumor formation in NSG mice, mice will be randomized to be fed normal or doxycycline chow for nuclear sAC induction, then subdivided to receive vehicle or vemurafenib to examine the effect of nuclear sAC activity on treatment response in vivo. We will also compare melanoma biopsies collected before and after treatment with BRAF inhibitors to assess how nuclear sAC staining affects tumor morphology in vivo. RESULTS/ANTICIPATED RESULTS: So far, nuclear sAC activity has rendered SkMel178 and M263 cell lines more susceptible to vemurafenib. Cell viability was inversely correlated both with vemurafenib and with doxycycline concentration. Cell viability after vemurafenib treatment was dramatically reduced when nuclear sAC was activated. It appears that nuclear sAC enhances the sensitivity of BRAF mutant melanomas to vemurafenib in vitro. We anticipate that xenografts of these cells in mice will be more susceptible to vemurafenib when nuclear sAC is activated. We also anticipate that positive nuclear sAC staining will correlate with a favorable response to therapy. DISCUSSION/SIGNIFICANCE OF FINDINGS: Targeted therapy with BRAF inhibitors is used in late-stage melanomas, but its use is limited as patients invariably acquire resistance. Here, we identified nuclear sAC activation as a novel candidate for combination strategy. Our data will also inform clinicians how best to integrate this biomarker into their decision-making regarding therapy.
60558 Non-Suicidal Self Injury in Military Veterans with PTSD: An Ecological Momentary Assessment Study
Authors: Kachadourian Lorig , Sullivan Tami , Pietrzak Robert
Published: March 2021

ABSTRACT IMPACT: This study will help determine whether ecological momentary assessment is feasible in assessing changes in negative affect and the occurrence of non-suicidal self-injury (NSSI) in military Veterans with post-traumatic stress disorder; if so it will allow for further examination of correlates of NSSI which will inform treatment efforts. OBJECTIVES/GOALS: Given the advantages of ecological momentary assessment (EMA), and the lack of research on non-suicidal self-injury (NSSI) in military populations, the goal of the current pilot study is to determine the feasibility of using EMA to assess daily changes in post-traumatic stress disorder (PTSD) symptoms, negative affect and NSSI in veterans with PTSD. METHODS/STUDY POPULATION: Twenty military veterans with post-traumatic stress disorder (PTSD) who have engaged in non-suicidal self-injury (NSSI) in the previous 12 months will be recruited. Participants will complete assessments 4 times per day for 28 days at randomly scheduled times. Assessments will measure PTSD symptoms, negative emotions, and NSSI urges and behaviors. At the conclusion of the 28-day study period, participants will complete measures that ask about their experiences in the study, (e.g., the acceptability of the daily surveys and the accessibility of the web-based surveys). Feasibility will be determined with regard to the success of recruiting eligible participants and compliance with daily survey completion. Variability in PTSD symptoms, negative affect, and NSSI urges and behaviors also will be determined. RESULTS/ANTICIPATED RESULTS: It is anticipated that this study will successfully recruit 20 veterans with PTSD with a history of engaging in NSSI within the previous 12 months. It is also anticipated that daily survey completion rates will be approximately 90% based on previous research using EMA with veterans with PTSD and that participants will indicate satisfaction with the procedures of the study. It is anticipated that participants will demonstrate variability in PTSD symptoms, indicated by changes in the number of symptoms endorsed and the intensity of those symptoms experienced. Finally, it is anticipated that participants will demonstrate variability in negative emotions (fear, hostility, guilt, and sadness).

DISCUSSION/SIGNIFICANCE OF FINDINGS: Findings from this study will support the use of EMA in a subsequent large-scale investigation examining time-varying symptoms of PTSD and negative affect as antecedents to NSSI. Information from this large-scale study will in turn be used to inform treatments that may to decrease NSSI in veterans by targeting specific symptoms and negative emotions.
42956 Patterns and impact of long-term glucocorticoid use on RA patients at risk for major adverse cardiac events
Authors: Wallace Beth I. , Gao Yuqing , Roul Punyasha , Cohen-Mekelberg Shirley , England Bryant , Mikuls Ted , Clauw Daniel J. , Hayward Rodney , Waljee Akbar K.
Published: March 2021

ABSTRACT IMPACT: Glucocorticoid steroids are commonly used despite known dose-dependent cardiovascular toxicity, yet little is known about a) how patients with other cardiovascular risk factors use glucocorticoids, and b) how risks of glucocorticoid treatment might vary depending on a patient’s baseline cardiovascular risk. OBJECTIVES/GOALS: Up to one-third of RA patients use long-term glucocorticoids (GCs) despite a known, dose-dependent association with increased risk of major adverse cardiovascular events (MACE). We aim to evaluate patterns of GC use among RA patients with other MACE risk factors (i.e. diabetes, smoking), and examine how GC use may potentiate these risk factors. METHODS/STUDY POPULATION: We used claims data from Veterans Health Administration to identify 6,090 RA patients with ≥1 rheumatology clinic visit during 2013-2017. We used logistic regression to evaluate associations between incident MACE between 2013-2018, recent long-term GC use, and 5 MACE risk factors: hypertension, diabetes, hyperlipidemia, smoking, and prior MACE. We included two-way interaction terms between GC use and each risk factor. We used a claims-based algorithm to define MACE as any of acute MI, ischemic stroke, TIA, sudden death, or coronary revascularization, between index date and 12/31/2018. We defined index date as first rheumatology visit after meeting RA diagnostic criteria, and recent long-term GC use as ≥90 days’ supply dispensed over 2 years prior to index date. RESULTS/ANTICIPATED RESULTS: Among 2,884 eligible patients,1,553 (54%) had MACE risk factors, and 97 (3%) had prior MACE (Table 1). Overall, 16% of patients recently used long-term GC, compared to 17% of patients with MACE risk factors, and 22% of patients with prior MACE. Incident MACE occurred in 308 (11%) patients, 24% of whom had recent long-term GC use. Recent long-term GC use was independently associated with increased incident MACE (Table 2). While no interaction term was statistically significant overall, differences in odds of incident MACE were seen across levels of recent GC use for several risk factors, particularly diabetes (OR 2.10, 95% CI [0.93-4.77]), tobacco use (OR 2.88, 95% CI [1.16-7.14]) and prior MACE (OR 2.41, 95% CI [0.73-7.95]). DISCUSSION/SIGNIFICANCE OF FINDINGS: Long-term GC use is common among RA patients with MACE risk factors. In this cohort, 25% of patients with incident MACE had recently used long-term GC. Long-term GC use may potentiate effects of comorbidities like diabetes and smoking, disproportionately increasing MACE risk in certain patients.
19751 Identifying Barriers to Diabetes Technology in Low-Income, Type 1 Patients
Authors: Donahue Emily , Uniyal Apurva , Church Terry David
Published: March 2021

ABSTRACT IMPACT: This research will aid clinical and policy solutions on lessening the vast health disparities and overall access issues for low-income, type 1 diabetes patients. OBJECTIVES/GOALS: Identify key barriers to accessing continuous glucose monitors (CGMS) and care options for low-socioeconomic status (SES) patients on public insurance. Low-SES patients with type 1 diabetes (T1D) have lower utilization rates of effective diabetes management technologies and worse clinical outcomes. METHODS/STUDY POPULATION: A literature review was conducted to understand the current research landscape for T1D and lead to the identification of potential barriers which included socioeconomic status, low-income, health literacy, and racial/ethnic minority. Clinicaltrials.gov was searched using the keyword ‘type 1 diabetes’ in conjunction with the identified barriers (as well as the keyword ‘barrier’). A follow up review of each state’s Medicaid programs was conducted to analyze cost and access options for CGMs and the overall financial burden of the disease on low-SES T1D patients. States that offered CGM coverage were further analyzed to determine reimbursement rates and actual out-of-pocket cost for patients. RESULTS/ANTICIPATED RESULTS: Of 285 trials identified from Clinicaltrial.gov searches, only seven relevant trials examined barriers and T1D for low-SES patients. Additionally, many of these studies, both in and outside of the clinical trial space, seldom distinguished between type 1 and type 2 diabetes’‘ an important distinction given that T1D has a higher financial burden and a quicker onset of complications. Currently, 39 states offer various insurance coverage through their Medicaid programs, but have clinical restrictions and requirements such as pediatric coverage only or minimum blood glucose requirement checks. Additionally, there is vast variability in reimbursement rates between states ($0-$800). DISCUSSION/SIGNIFICANCE OF FINDINGS: Study results indicate less effective diabetes management for low-SES T1D patients and a need for more intersectional clinical trial research. Differences in state’s Medicaid CGM coverage, expressed in disparate clinical outcomes for these T1D patients, belies financial incentives to health improvements, as annual US T1D costs are $14.4 billion.
67702 At-Home Screening Tool for Anosmia
Authors: Gupta Shruti , Kallogjeri Dorina , Piccirillo Jay F
Published: March 2021

ABSTRACT IMPACT: By developing and validating a simple and cost-effective at-home screening tool for loss of smell, we can efficiently detect infection with COVID-19, neuropsychiatric disease such as Alzheimer’s, and post-operative smell loss. OBJECTIVES/GOALS: To develop and validate a feasible and cost-effective screening tool for olfactory dysfunction (OD) using common household items. METHODS/STUDY POPULATION: The study has two phases. In the Development phase, 120 participants with self-reported smell changes will complete a survey with a list of 45 household items to smell. Item reduction to develop the NASAL Short Smell Test will occur by measuring content validity, factor analysis, and internal consistency. In the Validation phase, 200 participants with self-reported smell changes will take the NASAL Short Smell Test at baseline and again at three weeks. In both phases, the validated University of Pennsylvania Smell Identification Test (UPSIT) will be used as the gold standard. Measures of performance as well as test-retest reliability and sensitivity to change will be measured. RESULTS/ANTICIPATED RESULTS: We anticipate that the majority of participants will have at least half of the items in their household and will report ability to smell for each. Measures of sensitivity, specificity, likelihood ratios, and UPSIT score correlations will allow us to evaluate performance of each item. Item reduction will allow us to create the NASAL Short Smell Test, in which a handful of common items will be used to create a screening tool for smell loss. The Validation phase will allow us to measure discriminative performance of this tool as well as test-retest reliability and sensitivity to change, which we expect to be at least comparable to the validated UPSIT. DISCUSSION/SIGNIFICANCE OF FINDINGS: Current tools for diagnosis of OD are costly, time-consuming, and often require a clinician to evaluate. The validation of the simple at-home NASAL Short Smell Test to screen for OD will allow us to detect infection with COVID-19, neuropsychiatric disease, or post-operative smell loss quickly and efficiently.
Professional experiences of formal healthcare providers in the provision of medical assistance in dying (MAiD): A scoping review
Authors: Ward Valerie , Freeman Shannon , Callander Taylor , Xiong Beibei
Published: March 2021

Objective

This scoping review describes the existing literature which examines the breadth of healthcare providers’ (HCP's) experiences with the provision of medical assistance in dying (MAiD).

Method

This study employed a scoping review methodology: (1) identify research articles, (2) identify relevant studies, (3) select studies based on inclusion/exclusion criteria, (4) chart the data, and (5) summarize the results.

Results

In total, 30 papers were identified pertaining to HCP's experiences of providing MAiD. Fifty-three percent of the papers were from Europe (n = 16) and 40% of studies were from the USA or Canada (n = 12). The most common participant populations were physicians (n = 17) and nurses (n = 12). This scoping review found that HCPs experienced a variety of emotional responses to providing or providing support to MAiD. Some HCPs experienced positive emotions through helping patients at the end of the patient's life. Still other HCPs experienced very intense and negative emotions such as immense internal moral conflict. HCPs from various professions were involved in various aspects of MAiD provision such as responding to initial requests for MAiD, supporting patients and families, nursing support during MAiD, and the administration of medications to end of life.

Significance of results

This review consolidates many of the experiences of HCPs in relation to the provision of MAiD. Specifically, this review elucidates many of the emotions that HCPs experience through participation in MAiD. In addition to describing the emotional experiences, this review highlights some of the roles that HCPs participate in with relation to MAiD. Finally, this review accentuates the importance of team supports and self-care for all team members in the provision of MAiD regardless of their degree of involvement.
Prolonged atrazine exposure beginning in utero and adult uterine morphology in mice
Authors: Griffiths Meaghan J. , Winship Amy L. , Stringer Jessica M. , Swindells Elyse O. , Harper Alesia P. , Finger Bethany J. , Hutt Karla J. , Green Mark P.
Published: March 2021

Through drinking water, humans are commonly exposed to atrazine, a herbicide that acts as an endocrine and metabolic disruptor. It interferes with steroidogenesis, including promoting oestrogen production and altering cell metabolism. However, its precise impact on uterine development remains unknown. This study aimed to determine the effect of prolonged atrazine exposure on the uterus. Pregnant mice (n = 5/group) received 5 mg/kg body weight/day atrazine or DMSO in drinking water from gestational day 9.5 until weaning. Offspring continued to be exposed until 3 or 6 months of age (n = 5–9/group), when uteri were collected for morphological and molecular analyses and steroid quantification. Endometrial hyperplasia and leiomyoma were evident in the uteri of atrazine-exposed mice. Uterine oestrogen concentration, oestrogen receptor expression, and localisation were similar between groups, at both ages (P > 0.1). The expression and localisation of key epithelial-to-mesenchymal transition (EMT) genes and proteins, critical for tumourigenesis, remained unchanged between treatments, at both ages (P > 0.1). Hence, oestrogen-mediated changes to established EMT markers do not appear to underlie abnormal uterine morphology evident in atrazine exposure mice. This is the first report of abnormal uterine morphology following prolonged atrazine exposure starting in utero, it is likely that the abnormalities identified would negatively affect female fertility, although mechanisms remain unknown and require further study.
Die soziale Integration von Schülerinnen und Schülern mit sozialer Unsicherheit
Authors: Weber Simone , Nicolay Philipp , Huber Christian
Published: March 2021

Zusammenfassung. Der vorliegende Beitrag untersucht den Zusammenhang zwischen sozialer Integration und sozialer Unsicherheit. Ausgehend von dem mehrdimensionalen Modell sozialer Integration ( Koster, Nakken, Pijl & van Houten, 2009 ) wird diese differenziert anhand der Dimensionen Beziehungen, Kontakte, Akzeptanz durch Mitschülerinnen und Mitschüler und eigene Wahrnehmung analysiert. Hierfür wurden Daten von N = 617 Kindern aus insgesamt 28 Schulklassen der dritten und vierten Jahrgangsstufe geprüft. Die Ergebnisse der Mehrebenenanalysen zeigen einen signifikanten negativen Zusammenhang zwischen sozialer Unsicherheit und sozialer Integration in drei der vier Dimensionen (Beziehungen, eigene Wahrnehmung und Akzeptanz). Die Ergebnisse für die einzelnen Dimensionen werden diskutiert und es werden Implikationen für die Forschung und pädagogische Praxis abgeleitet.
Potential Predictability of the Tropical Cyclone Frequency Over the Western North Pacific With 50‐km AGCM Ensemble Experiments
Authors: Ogata Tomomichi , Taguchi Bunmei , Yamamoto Ayako , Nonaka Masami
Published: March 2021

The potential predictability determined by sea surface temperature (SST) of the frequency distribution of tropical cyclones (TCs) is studied using ensemble simulations with a 50‐km resolution atmospheric general circulation model (AGCM). In this experiment, the interannual variability of the TC frequency over the western North Pacific (WNP) is primarily determined by SST, as the simulated ensemble mean signal is dominant over the ensemble spread and effectively follows the observed TC frequency in June‐July‐August (JJA). In contrast, the correlation between the observed and simulated TC frequency variability is less significant in September‐October‐November (SON). To explore the TC frequency‐SST linkage, the relationship between the TC frequency variability over the WNP and climate modes determined by SST indices is investigated. Through a correlation analysis, we found that El Niño Modoki is the major driver of the TC frequency variability over the WNP in JJA. Partial correlation analysis further reveals that internal atmospheric dynamics are important for the TC frequency variability over the WNP in SON. These results suggest that the tropical climate mode is responsible for the seasonal predictability of the TC frequency variability over the WNP and that the prediction skill is seasonally dependent with a high (low) skill in JJA (SON).
Soil Carbon Isotope Values and Paleoprecipitation Reconstruction
Authors: Stein Rebekah A. , Sheldon Nathan D. , Smith Selena Y.
Published: March 2021

Anthropogenic climate change has significant impacts at the ecosystem scale including widespread drought, flooding, and other natural disasters related to precipitation extremes. To contextualize modern climate change, scientists often look to ancient climate changes, such as shifts in ancient precipitation ranges. Previous studies have used fossil leaf organic geochemistry and paleosol inorganic chemistry as paleoprecipitation proxies, but have largely ignored the organic soil layer, which acts as a bridge between aboveground biomass and belowground inorganic carbon accumulation, as a potential recorder of precipitation. We investigate the relationship between stable carbon isotope values in soil organic matter (δ13CSOM) and a variety of seasonal and annual climate parameters in modern ecosystems and find a statistically significant relationship between δ13CSOM values and mean annual precipitation (MAP). After testing the relationship between actual and reconstructed precipitation values in modern systems, we test this potential paleoprecipitation proxy in the geologic record by comparing precipitation values reconstructed using δ13CSOM to other reconstructed paleoprecipitation estimates from the same paleosols. This study provides a promising new proxy that can be applied to ecosystems post‐Devonian (∼420 Ma) to the Miocene (∼23 Ma), and in mixed C3/C4 ecosystems in the geologic record with additional paleobotanical and palynological information. It also extends paleoprecipitation reconstruction to more weakly developed paleosol types, such as those lacking B‐ horizons, than previous inorganic proxies and is calibrated for wetter environments.
The Gaps in Environmental Networks Across Latin America
Authors: Wheeling Kate
Published: March 2021

Despite its notable influence on global carbon and water cycles, Latin America accounts for a relatively small share of FLUXNET sites, which limits the representativeness of the network in the region.
Correction: Treating the patient and not just the cancer: therapeutic burden in prostate cancer
Authors: Spratt Daniel E. , Shore Neal , Sartor Oliver , Rathkopf Dana , Olivier Kara
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41391-021-00358-9
5-Aminosalicylic acid inhibits stem cell function in human adenoma-derived cells: implications for chemoprophylaxis in colorectal tumorigenesis
Authors: Dixon Steven William , Collard Tracey Jane , Mortensson Eleanor May Harrisdotter , Legge Danny Nigel , Chambers Adam Christian , Greenhough Alexander , Creed Tom Julian , Williams Ann Caroline
Published: March 2021

Background

Most colorectal cancers (CRC) arise sporadically from precursor lesions: colonic polyps. Polyp resection prevents progression to CRC. Risk of future polyps is proportional to the number and size of polyps detected at screening, allowing identification of high-risk individuals who may benefit from effective chemoprophylaxis. We aimed to investigate the potential of 5-aminosalicylic acid (5-ASA), a medication used in the treatment of ulcerative colitis, as a possible preventative agent for sporadic CRC.

Methods

Human colorectal adenoma (PC/AA/C1, S/AN/C1 and S/RG/C2), transformed adenoma PC/AA/C1/SB10 and carcinoma cell lines (LS174T and SW620) were treated with 5-ASA. The effect on growth in two- and three-dimensional (3D) culture, β-catenin transcriptional activity and on cancer stemness properties of the cells were investigated.

Results

5-ASA was shown, in vitro, to inhibit the growth of adenoma cells and suppress β-catenin transcriptional activity. Downregulation of β-catenin was found to repress expression of stem cell marker LGR5 (leucine-rich G protein-coupled receptor-5) and functionally suppress stemness in human adenoma and carcinoma cells using 3D models of tumorigenesis.

Conclusions

5-ASA can suppress the cancer stem phenotype in adenoma-derived cells. Affordable and well-tolerated, 5-ASA is an outstanding candidate as a chemoprophylactic medication to reduce the risk of colorectal polyps and CRC in those at high risk.
Necroptosis, pyroptosis and apoptosis: an intricate game of cell death
Authors: Bertheloot Damien , Latz Eicke , Franklin Bernardo S.
Published: March 2021

Cell death is a fundamental physiological process in all living organisms. Its roles extend from embryonic development, organ maintenance, and aging to the coordination of immune responses and autoimmunity. In recent years, our understanding of the mechanisms orchestrating cellular death and its consequences on immunity and homeostasis has increased substantially. Different modalities of what has become known as ‘programmed cell death’ have been described, and some key players in these processes have been identified. We have learned more about the intricacies that fine tune the activity of common players and ultimately shape the different types of cell death. These studies have highlighted the complex mechanisms tipping the balance between different cell fates. Here, we summarize the latest discoveries in the three most well understood modalities of cell death, namely, apoptosis, necroptosis, and pyroptosis, highlighting common and unique pathways and their effect on the surrounding cells and the organism as a whole.
Short-term effects of controlled mating and selection on the genetic variance of honeybee populations
Authors: Du Manuel , Bernstein Richard , Hoppe Andreas , Bienefeld Kaspar
Published: March 2021

Directional selection in a population yields reduced genetic variance due to the Bulmer effect. While this effect has been thoroughly investigated in mammals, it is poorly studied in social insects with biological peculiarities such as haplo-diploidy or the collective expression of traits. In addition to the natural adaptation to climate change, parasites, and pesticides, honeybees increasingly experience artificial selection pressure through modern breeding programs. Besides selection, many honeybee breeding schemes introduce controlled mating. We investigated which individual effects selection and controlled mating have on genetic variance. We derived formulas to describe short-term changes of genetic variance in honeybee populations and conducted computer simulations to confirm them. Thereby, we found that the changes in genetic variance depend on whether the variance is measured between queens (inheritance criterion), worker groups (selection criterion), or both (performance criterion). All three criteria showed reduced genetic variance under selection. In the selection and performance criteria, our formulas and simulations showed an increased genetic variance through controlled mating. This newly described effect counterbalanced and occasionally outweighed the Bulmer effect. It could not be observed in the inheritance criterion. A good understanding of the different notions of genetic variance in honeybees, therefore, appears crucial to interpreting population parameters correctly.
Unusual polarimetric properties for interstellar comet 2I/Borisov
Authors: Bagnulo S. , Cellino A. , Kolokolova L. , Nežič R. , Santana-Ros T. , Borisov G. , Christou A. A. , Bendjoya Ph. , Devogèle M.
Published: March 2021

So far, only two interstellar objects have been observed within our Solar System. While the first one, 1I/‘Oumuamua, had asteroidal characteristics, the second one, 2I/Borisov, showed clear evidence of cometary activity. We performed polarimetric observations of comet 2I/Borisov using the European Southern Observatory Very Large Telescope to derive the physical characteristics of its coma dust particles. Here we show that the polarization of 2I/Borisov is higher than what is typically measured for Solar System comets. This feature distinguishes 2I/Borisov from dynamically evolved objects such as Jupiter-family and all short- and long-period comets in our Solar System. The only object with similar polarimetric properties as 2I/Borisov is comet C/1995 O1 (Hale-Bopp), an object that is believed to have approached the Sun only once before its apparition in 1997. Unlike Hale-Bopp and many other comets, though, comet 2I/Borisov shows a polarimetrically homogeneous coma, suggesting that it is an even more pristine object.
Single-atom level determination of 3-dimensional surface atomic structure via neural network-assisted atomic electron tomography
Authors: Lee Juhyeok , Jeong Chaehwa , Yang Yongsoo
Published: March 2021

Functional properties of nanomaterials strongly depend on their surface atomic structures, but they often become largely different from their bulk structures, exhibiting surface reconstructions and relaxations. However, most of the surface characterization methods are either limited to 2D measurements or not reaching to true 3D atomic-scale resolution, and single-atom level determination of the 3D surface atomic structure for general 3D nanomaterials still remains elusive. Here we demonstrate the measurement of 3D atomic structure at 15 pm precision using a Pt nanoparticle as a model system. Aided by a deep learning-based missing data retrieval combined with atomic electron tomography, the surface atomic structure was reliably measured. We found that <$$100$$
100
> and <$$111$$
111
> facets contribute differently to the surface strain, resulting in anisotropic strain distribution as well as compressive support boundary effect. The capability of single-atom level surface characterization will not only deepen our understanding of the functional properties of nanomaterials but also open a new door for fine tailoring of their performance.
Beam image-shift accelerated data acquisition for near-atomic resolution single-particle cryo-electron tomography
Authors: Bouvette Jonathan , Liu Hsuan-Fu , Du Xiaochen , Zhou Ye , Sikkema Andrew P. , da Fonseca Rezende e Mello Juliana , Klemm Bradley P. , Huang Rick , Schaaper Roel M. , Borgnia Mario J. , Bartesaghi Alberto
Published: March 2021

Tomographic reconstruction of cryopreserved specimens imaged in an electron microscope followed by extraction and averaging of sub-volumes has been successfully used to derive atomic models of macromolecules in their biological environment. Eliminating biochemical isolation steps required by other techniques, this method opens up the cell to in-situ structural studies. However, the need to compensate for errors in targeting introduced during mechanical navigation of the specimen significantly slows down tomographic data collection thus limiting its practical value. Here, we introduce protocols for tilt-series acquisition and processing that accelerate data collection speed by up to an order of magnitude and improve map resolution compared to existing approaches. We achieve this by using beam-image shift to multiply the number of areas imaged at each stage position, by integrating geometrical constraints during imaging to achieve high precision targeting, and by performing per-tilt astigmatic CTF estimation and data-driven exposure weighting to improve final map resolution. We validated our beam image-shift electron cryo-tomography (BISECT) approach by determining the structure of a low molecular weight target (~300 kDa) at 3.6 Å resolution where density for individual side chains is clearly resolved.
A domestic cat whole exome sequencing resource for trait discovery
Authors: Rodney Alana R. , Buckley Reuben M. , Fulton Robert S. , Fronick Catrina , Richmond Todd , Helps Christopher R. , Pantke Peter , Trent Dianne J. , Vernau Karen M. , Munday John S. , Lewin Andrew C. , Middleton Rondo , Lyons Leslie A. , Warren Wesley C.
Published: March 2021

Over 94 million domestic cats are susceptible to cancers and other common and rare diseases. Whole exome sequencing (WES) is a proven strategy to study these disease-causing variants. Presented is a 35.7 Mb exome capture design based on the annotated Felis_catus_9.0 genome assembly, covering 201,683 regions of the cat genome. Whole exome sequencing was conducted on 41 cats with known and unknown genetic diseases and traits, of which ten cats had matching whole genome sequence (WGS) data available, used to validate WES performance. At 80 × mean exome depth of coverage, 96.4% of on-target base coverage had a sequencing depth > 20-fold, while over 98% of single nucleotide variants (SNVs) identified by WGS were also identified by WES. Platform-specific SNVs were restricted to sex chromosomes and a small number of olfactory receptor genes. Within the 41 cats, we identified 31 previously known causal variants and discovered new gene candidate variants, including novel missense variance for polycystic kidney disease and atrichia in the Peterbald cat. These results show the utility of WES to identify novel gene candidate alleles for diseases and traits for the first time in a feline model.
Insights into the role of deep-sea squids of the genus Histioteuthis (Histioteuthidae) in the life cycle of ascaridoid parasites in the Central Mediterranean Sea waters
Authors: Palomba Marialetizia , Mattiucci Simonetta , Crocetta Fabio , Osca David , Santoro Mario
Published: March 2021

Ascaridoid nematodes comprise a wide range of heteroxenous parasites infecting top fish predators and marine mammals as definitive hosts, with crustaceans, squids, and fishes acting as intermediate/paratenic hosts. Limited data exist on the species and role of several intermediate and paratenic hosts in the life cycle of these parasites. In the aim of adding knowledge on the role of squid species in their life cycle, we have here investigated the larval ascaridoid nematodes collected from the deep-sea umbrella squid Histioteuthis bonnelli and the reverse jewel squid Histioteuthis reversa captured in the Central Mediterranean Sea (Tyrrhenian Sea). Morphological study and sequence analysis of the internal transcribed spacer (ITS) regions of the ribosomal DNA (rDNA) and the mitochondrial cytochrome c oxidase subunit 2 (mtDNA cox2) gene locus revealed the occurrence of Anisakis physeteris and of an unidentified species of the genus Lappetascaris. Sequence analysis revealed that specimens of Lappetascaris from both squid species matched at 100% sequences previously deposited in GenBank from larval ascaridoids collected in octopuses of the genus Eledone of the Mediterranean Sea. The Bayesian inference tree topology obtained from the analysis of the fragments amplified showed that Lappetascaris specimens were included in a major clade comprising Hysterothylacium species collected in fishes of the families Xiphiidae and Istiophoridae. As regards the site of infection in the squid host species, A. physeteris larvae predominated (60.7%) in the gonads, while those of Lappetascaris (76.3%) were found infecting the mantle musculature. The overall high values of parasitic load suggest both squid species as transmitting hosts of third stage larvae of Lappetascaris to top predator fishes, as well as the umbrella squid as an intermediate/paratenic host in the life cycle of A. physeteris in the Mediterranean Sea.
Detection of magnetic tracers with Mx atomic magnetometer for application to blood velocimetry
Authors: Soheilian Asieh , Tehranchi Mohammad Mehdi , Ranjbaran Maliheh
Published: March 2021

In the new generation of blood velocimeter systems, considerable attention has been paid to atomic magnetometers due to their high resolution and high sensitivity for detection of magnetic tracers. Passing the magnetic tracers adjacent to the atomic magnetometer produces a spike-like signal, the shape of which depends on the position of the tracer, as well as its velocity and orientation. The present study aimed to evaluate the effect of abrupt variations in the instantaneous velocity of the magnetic tracer on the magnetometer response compare to constant velocity. Modeling the magnetic tracer as a dipole moment indicated that the velocity dependence of the magnetic field and local magnetic field gradient associated with moving magnetic tracer cause the spike-like signal to go out of symmetry in the case of variable velocity. Based on the experimental results, any instantaneous variation in tracer velocity leads to shrinkage in the signal width. The behavior has been studied for both magnetic microwire with variable instantaneous velocity and magnetic droplets in stenosis artery phantom. In addition, the position of the tracer could be detected by following the shrinkage behavior which may occur on the peak, valley, or both. These advantageous outcomes can be applied for high sensitivity diagnosis of arterial stenosis.
Novel wideband circularly polarized DRA with squint-free radiation characteristics
Authors: Abedian Mohammad , Khalily Mohsen , Singh Vikrant , Xiao Pei , Tafazolli Rahim , Kishk Ahmed A.
Published: March 2021

A new single-fed circularly polarized dielectric resonator antenna (CP-DRA) without beam squint is presented. The DRA comprises an S-shaped dielectric resonator (SDR) with a metalized edge and two rectangular dielectric resonators (RDRs) blocks. Horizontal extension section is applied as an extension of the SDR, and a vertical-section is placed in parallel to the metallic edge. A vertical coaxial probe is used to excite the SDR and the vertical RDR blocks through an S-shaped metal element and a small rectangular metal strip. The two added RDRs that form an L-shaped DR improve the radiation characteristics and compensate for the beam squint errors. A wideband CP performance is achieved due to the excitation of several orthogonal modes such as$$TE_{\delta 11}^x$$TEδ11x,$$TE_{1\delta 1}^y$$TE1δ1y,$$TE_{121}^z$$TE121z,$$TE_{112}^y$$TE112y,$$TE_{131}^x$$TE131x, and$$TE_{311}^y$$TE311y. The experimental results demonstrate an impedance bandwidth of approximately$$66.8\%$$66.8%(3.71–7.45 GHz) and a 3-dB axial-ratio (AR) bandwidth of about$$54.8\%$$54.8%(3.72–6.53 GHz) with a stable broadside beam achieving a measured peak gain of about$$4.64 \, {\text{dBic}}$$4.64dBic. Furthermore, a 100% correction in beam squint value from$$\theta = 41^\circ$$θ=41∘to$$\theta = 0^\circ$$θ=0∘with respect to the antenna boresight is achieved.
OCT angiography metrics predict intradialytic hypotension episodes in chronic hemodialysis patients: a pilot, prospective study
Authors: Coppolino Giuseppe , Carnevali Adriano , Gatti Valentina , Battaglia Caterina , Randazzo Giorgio , Figlia Irma , Patella Gemma , Fuiano Giorgio , Andreucci Michele , Giannaccare Giuseppe , Scorcia Vincenzo , Bolignano Davide
Published: March 2021

In chronic hemodialysis (HD) patients, intradialytic hypotension (IDH) is a complication that increases mortality risk. We run a pilot study to analyzing possible relationships between optical coherence tomography angiography (OCT-A) metrics and IDH with the aim of evaluating if OCT-A could represent a useful tool to stratify the hypotensive risk in dialysis patients. A total of 35 eyes (35 patients) were analyzed. OCT-A was performed before and after a single dialysis session. We performed OCT-A 3 × 3 mm and 6 × 6 mm scanning area focused on the fovea centralis. Patients were then followed up to 30 days (10 HD sessions) and a total of 73 IDHs were recorded, with 12 patients (60%) experiencing at least one IDH. Different OCT-A parameters were reduced after dialysis: central choroid thickness (CCT), 6 × 6 mm foveal whole vessel density (VD) of superficial capillary plexus (SPC) and 6 × 6 mm foveal VD of deep capillary plexus (DCP). At logistic regression analysis, IDH was positively associated with baseline foveal VD of SCP and DCP, while an inverse association was found with the choroid. In Kaplan–Meier analyses of patients categorized according to the ROC-derived optimal thresholds, CCT, the 3 × 3 foveal VD of SCP, the 3 × 3 mm and 6 × 6 mm foveal VD of DCP and the 6 × 6 mm foveal VD of SCP were strongly associated with a higher risk of IDH over the 30-days follow-up. In HD patients, a single OCT-A measurement may represent a non-invasive, rapid tool to evaluate the compliance of vascular bed to HD stress and to stratify the risk of IDH in the short term.
Resonant nano-dimer metasurface for ultra-thin a-Si:H solar cells
Authors: Elshorbagy Mahmoud H. , Sánchez Pablo A. , Cuadrado Alexander , Alda Javier , Esteban Óscar
Published: March 2021

Low-cost hydrogenated amorphous silicon solar cells (a-Si:H) can perform better and be more competitive by including nanostructures. An optimized nano-dimer structure embedded in close contact with the back electrode of an aSi:H ultra-thin solar cells can enhance the deliverable short-circuit current up to 27.5 %. This enhancement is the result of an increase in the absorption at the active layer, that is the product of an efficient scattering from the nanostructure. From our calculations, the nano-dimer structure must be made out of a high-index of refraction material, like GaP. The evaluation of the scattering and absorption cross section of the structure supports the calculated enhancement in short-circuit current, that is always accompanied by a decrease in the total reflectance of the cell, which is reduced by about 50 %.
An integrated self-powered 3D printed sample concentrator for highly sensitive molecular detection of HIV in whole blood at the point of care
Authors: Kadimisetty Karteek , Yin Kun , Roche Aoife M. , Yi Yanjie , Bushman Frederic D. , Collman Ronald G. , Gross Robert , Feng Liang , Liu Changchun
Published: March 2021

A self-powered, integrated sample concentrator (SPISC) was developed for plasma separation, pathogen lysis, nucleic acid trapping and enrichment at the point of care.
Synthesis of dendritic mesoporous organosilica nanoparticles under a mild acidic condition with homogeneous wall structure and near-neutral surface
Authors: Luo Jiangqi , Zhang Min , Yang Yannan , Yu Chengzhong
Published: March 2021

Dendritic mesoporous organosilica nanoparticles with a molecularly homogeneous wall structure and near-neutral charged surface are synthesized, showing superior anti-fouling property.
Heterogenisation of polyoxometalates and other metal-based complexes in metal–organic frameworks: from synthesis to characterisation and applications in catalysis
Authors: Mialane P. , Mellot-Draznieks C. , Gairola P. , Duguet M. , Benseghir Y. , Oms O. , Dolbecq A.
Published: March 2021

This review provides a thorough overview of composites with molecular catalysts (polyoxometalates, or organometallic or coordination complexes) immobilised into MOFs via non-covalent interactions.
Electrochemical upgrading of depolymerized lignin: a review of model compound studies
Authors: Garedew Mahlet , Lam Chun Ho , Petitjean Laurene , Huang Shuquan , Song Bing , Lin Fang , Jackson James E. , Saffron Christopher M. , Anastas Paul T.
Published: March 2021

This review addresses advancements and challenges in the use of electrochemical methods as a means of upgrading lignin-derived model compounds to value-added products.