bluuebunny/crossref_metadata_2025 huggingface dataset:
Rectal Hypersensitivity in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis
Authors: Roberts Christopher , Albusoda Ahmed , Farmer Adam D , Aziz Qasim
Published: June 2021

Abdominal pain is a key symptom of inflammatory bowel disease (IBD), particularly in active IBD, but also occurs in patients with quiescent disease suggesting that mechanisms other than active inflammation may be responsible. Putative hypothesis to explain chronic abdominal pain in patients with quiescent IBD includes crossover with irritable bowel syndrome where rectal hypersensitivity is common and has pathophysiological implications. In contrast, in IBD, the role of rectal hypersensitivity has not been established. We aimed to determine if rectal hypersensitivity was more common in IBD compared to a healthy control population. We searched MEDLINE and EMBASE databases (1970–2018). Prospective studies that measured pain/discomfort thresholds to mechanical rectal stimuli in IBD and healthy controls were included. Data were pooled for meta-analysis and effect sizes were calculated with 95% confidence intervals (CIs). Our search strategy identified 222 citations of which 8 met the inclusion criteria, covering 133 individuals with IBD (67 men), aged between 10 and 77 compared to 99 healthy controls (55 men), aged between 10 and 67. The prevalence of rectal hypersensitivity in IBD compared to healthy controls was similar with an effect size of 0.59 (95% CIs: −0.27 to 1.44, P = .16, I2 = 87.3%). Subgroup analysis did show a significant effect size for patients compared to healthy controls with active disease (1.32) but not for quiescent disease (−0.02). These results suggest that reduced rectal pain thresholds to experimental stimulation are not seen in IBD populations except during active flares of the disease. Further research is required to understand the pathophysiology of chronic abdominal pain in quiescent IBD populations with and without chronic abdominal pain to identify appropriate management strategies.
The efficacy of adjuvant chemotherapy with capecitabine and cisplatin after surgery in locally advanced esophageal squamous cell carcinoma: a multicenter randomized phase III trial
Authors: Shim Young Mog , Yun Jeonghee , Im Young-Hyuck , Lee Genehee , Kang Danbee , Cho Juhee , Kim Kwhanmien , Park Seung-Il , Na Kook Joo , Kim Sung-bae , Zo Jae Ill
Published: June 2021

There is limited evidence for the effectiveness of adjuvant chemotherapy in esophageal squamous cell carcinoma (ESCC). This study aimed to assess whether adjuvant capecitabine and cisplatin improve survival compared to surgery alone among patients with locally advanced ESCC. This is a multicenter randomized controlled trial. Patients were eligible if they underwent curative resection for ESCC staged T2–4 or N1 and M0 according to the TNM cancer staging system sixth edition. The intervention group received four cycles of adjuvant chemotherapy (capecitabine: 1,000 mg/m 2 b.i.d for 14 days, and intravenous cisplatin: 75 mg/m2 at day 1, every 3 weeks). A total of 136 patients were randomly assigned to either the adjuvant chemotherapy group (n = 68) or surgery-alone group (n = 68). Seven patients who rejected chemotherapy after randomization were excluded from the final analysis. The cumulative incidence of recurrence within 18 months after surgery was significantly lower in the adjuvant chemotherapy group than in the surgery-alone group (hazard ratio [HR]: 0.49; 95% confidence interval (CI): 0.25–0.95]. However, the 5- and 10-year disease-free survival did not differ between treatment groups (HR: 0.84; 95% CI: 0.53–1.34 and HR: 0.76; 95% CI: 0.50–1.18, respectively). Adjuvant chemotherapy after curative resection in patients with locally advanced ESCC reduced early recurrence but had no statistically significant increase in the long-term disease-free survival. Due to the limited sample size of this study, additional randomized controlled trials with larger sample sizes are necessary.
Hybrid cardiac imaging-guided optimal management of right anomalous coronary artery origin from the opposite sinus with interarterial course (R-ACAOS): a case report
Authors: Jin Cai De , Kim Moo Hyun , Jin Xuan , Park Kyungil
Published: June 2021

Background

Determining the optimal management of right anomalous coronary artery from the opposite sinus (R-ACAOS) with an interarterial course (IAC) in middle-aged adults remains elusive. Hybrid cardiac imaging combining non-invasive and invasive approaches to identify high-risk anatomic features, as well as functional testing to assess potential ischaemic status by dynamic compression, can guide therapeutic decisions.

Case summary

A 65-year-old female was newly diagnosed with R-ACAOS with IAC, accompanied by suspected angina and two syncope episodes. She was initially considered as non-specific chest pain based on negative treadmill test (TMT) taken 10 years earlier. An anomaly of R-ACAOS with IAC travelling between the aorta and pulmonary artery was detected by coronary computed tomography angiography with a severe stenosis at the ostium, but with little evidence of atherosclerotic plaque. Exercise test (TMT) and single-photon emission computed tomography (SPECT) results were negative. Invasive imaging revealed a luminal area stenosis of 45% at the ostial right coronary artery, and a slit-like orifice anatomical feature, with a minimal lumen area of 5.81 mm2 at diastole determined by intravascular ultrasound. Based on hybrid cardiac imaging results and previous data from a case series, conservative management was recommended with strenuous exercise restrictions. The patient fared well during 12 months of follow-up after discharge.

Discussion

Hybrid cardiac imaging-guided conservative management including exercise restriction appears justifiable in such middle-aged adults with R-ACAOS accompanied by suspected angina in absence of ischaemia in stress-induced tests (TMT or SPECT), despite high-risk anatomical features of an IAC and slit-like orifice being present.
Outcomes after catheter ablation of ventricular tachycardia without implantable cardioverter-defibrillator in selected patients with arrhythmogenic right ventricular cardiomyopathy
Authors: Gandjbakhch Estelle , Laredo Mikael , Berruezo Antonio , Gourraud Jean-Basptiste , Sellal Jean-Marc , Martins Raphael , Sacher Frederic , Pison Laurent , Pruvot Etienne , Jáuregui Beatriz , Frontera Antonio , Kumar Saurabh , Wong Tom , DellaBella Paolo , Maury Philippe
Published: June 2021

Aims

The roles of implantable cardioverter-defibrillators (ICDs) and radiofrequency catheter ablation (RCA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and well-tolerated monomorphic ventricular tachycardia (MVT) are debated. In this multicentre retrospective study, we aimed at reporting the outcome of selected patients with ARVC after RCA without a back-up ICD.

Methods and results

Patients with ARVC who underwent RCA of well-tolerated MVT at 10 tertiary centres across 5 countries, without an ICD before and 3 months after RCA, without syncope or electrical storm, and with left ventricular ejection fraction ≥50% were included. In total, 65 ARVC patients [mean age 44.5 ± 13.2 years, 78% males] underwent RCA of MVT between 2003 and 2016. Clinical presentation was palpitations in 51 (80%) patients. One (2%) patient had >1 clinical MVT. At the ablative procedure, clinical MVTs (mean rate 185 ± 32 b.p.m.) were inducible in 50 (81%) patients. Epicardial ablation was performed in 19 (29%) patients. Complete acute success was achieved in 47 (72%) patients. After a median follow-up of 52.4 months (range 12.3–171.4), there was no death or aborted cardiac arrest, and VT recurred in 19 (29%) patients. Survival without VT recurrence was estimated at 88%, 80%, and 68%, 12, 36, and 60 months after RCA, respectively, and was significantly associated with the approach and the procedural outcome.

Conclusion 

In patients with ARVC, well-tolerated MVT without a back-up ICD did not lead to fatal arrhythmic event after RCA despite VT recurrences in some. Our data suggest that RCA may be an alternative to ICD in selected ARVC patients.
Genome assemblies of three closely related leaf beetle species (Galerucella spp.)
Authors: Yang Xuyue , Slotte Tanja , Dainat Jacques , Hambäck Peter A
Published: June 2021

Galerucella (Coleoptera: Chrysomelidae) is a leaf beetle genus that has been extensively used for ecological and evolutionary studies. It has also been used as biological control agent against invading purple loosestrife in North America, with large effects on biodiversity. Here, we report genome assembly and annotation of three closely related Galerucella species: G. calmariensis, G. pusilla, and G. tenella. The three assemblies have a genome size ranging from 460 to 588 Mbp, with N50 from 31,588 to 79,674 kbp, containing 29,202 to 40,929 scaffolds. Using an ab initio evidence-driven approach, 30,302 to 33,794 protein-coding genes were identified and functionally annotated. These draft genomes will contribute to the understanding of host-parasitoid interactions, evolutionary comparisons of leaf beetle species and future population genomics studies.
Anti-obesity public health advertisements increase risk factors for the development of eating disorders
Authors: Bristow Claire , Allen Kelly-Ann , Simmonds Janette , Snell Tristan , McLean Louise
Published: June 2021

Although overweight and obesity are increasing in prevalence, eating disorders such as anorexia nervosa, bulimia nervosa and binge-eating disorder are simultaneously on the rise. It is important to address the burden of disease of overweight and obesity on the population, yet there is concern that some of these efforts may be encouraging unhealthy weight control behaviours (UWCB). Using an online survey, 137 participants were exposed to four anti-obesity public health advertisements presented in random order. Weight satisfaction, shape satisfaction, desire to control weight, desire to control shape and desire to engage in UWCB were measured on a 100-point visual analogue scale. A significant effect of the experimental condition was found after exposure to Image 1 with a decrease in weight satisfaction, and increased desire to control body weight, body shape and engage in UWCB. Mean scores for UWCB also increased, on average, across all four image conditions. Public health advertisements targeting obesity risk encouraging unhealthy weight control and subsequent disordered eating behaviours. Those responsible for the implementation of such advertisements must consider very carefully the potential to cause unintended harm.
Resource partitioning between fisheries and endangered sharks in a tropical marine food web
Authors: Márquez-Velásquez Viviana , Navia Andrés F , Rosa Ricardo S , Guimarães Paulo R , Raimundo Rafael L G
Published: June 2021

Fisheries can act as top predators and affect marine biodiversity and ecosystem functioning via their target species. We studied a coastal food web in the Pacific Ocean that is modular and encompasses 360 species and small- and large-scale fisheries. Small-scale fisheries (SSF), two hammerhead sharks, one stingray, and one flatfish species are network hubs, interacting with multiple species among and within trophic levels (TLs) and modules. SSF and endangered hammerhead sharks act as hyper-hubs, which are network hubs preying on other network hubs and likely imposing widespread top-down effects. Hyper-hubs have two consequences to network structure. First, they show low dietary overlap, connecting the network in complementary ways. Second, they have overlapping indirect interactions, suggesting they can strongly affect each other. Simulations assuming distinct fishery regulations and species extinctions of different TLs and topological roles did not change network structure but redefined hub identity. We hypothesize that competition shapes resource partitioning between fisheries and hammerhead sharks. Our findings suggest that ecosystem-level strategies informed by network approaches can optimize investments to conserve marine ecosystems and ensure food security over coastal areas in the developing world.
Multidecadal daily resolved growth increments reveal climate effect on the growth of a highly migratory shark in the North Atlantic
Authors: Zhou Can
Published: June 2021

Substantial progress has been made in identifying large-scale climate effect on somatic growth through the use of ageing-based methods in aquatic environments, yet their annual/seasonal temporal resolution seems too coarse for such a fast process. Temporal resolution is a missing dimension in our understanding of climate effects on growth. Here, an alternative source of high temporal resolution growth increments embedded within a multidecadal traditional tag-recapture database was analysed to identify climate signals in the somatic growth of blue sharks Prionace glauca in the North Atlantic. Results indicate the growth response of P. glauca to the NAO occurred at a daily scale with a time-lag. Non-parametric modelling reveals an optimal response curve around the historical average of the NAO, and a significant negative response for large positive NAO anomalies. Growth predictions show that the last four decades are mostly associated with negative responses compared to the historical average. The temporal resolution of this study is unprecedented among current ageing-based studies with a comparable temporal coverage. Integrating high temporal resolution into long-term climate effect studies can open new avenues for research on identifying climate effect on growth and provide detailed clues to its mechanisms of action.
Mortality amenable to healthcare in Latin American cities: a cross-sectional study examining between-country variation in amenable mortality and the role of urban metrics
Authors: Mullachery Pricila H , Rodriguez Daniel A , Miranda J Jaime , López-Olmedo Nancy , Martinez-Folgar Kevin , Barreto Mauricio L , Diez Roux Ana V , Bilal Usama
Published: June 2021

Background

This study examined the variation in city-level amenable mortality, i.e. mortality due to conditions that can be mitigated in the presence of timely and effective healthcare, in 363 Latin American cities and measured associations between amenable-mortality rates and urban metrics.

Methods

We used death records from 363 cities with populations of >100 000 people in nine Latin American countries from 2010 to 2016. We calculated sex-specific age-adjusted amenable-mortality rates per 100 000. We fitted multilevel linear models with cities nested within countries and estimated associations between amenable mortality and urban metrics, including population size and growth, fragmentation of urban development and socio-economic status.

Results

Cities in Mexico, Colombia and Brazil had the highest rates of amenable mortality. Overall, >70% of the variability in amenable mortality was due to between-country heterogeneity. But for preventable amenable mortality, those for which the healthcare system can prevent new cases, most of the variability in rates occurred between cities within countries. Population size and fragmentation of urban development were associated with amenable mortality. Higher fragmentation of urban development was associated with lower amenable mortality in small cities and higher amenable mortality in large cities. Population growth and higher city-level socio-economic status were associated with lower amenable mortality.

Conclusions

Most of the variability in amenable mortality in Latin American cities was due to between-county heterogeneity. However, urban metrics such as population size and growth, fragmentation of urban development and city-level socio-economic status may have a role in the distribution of amenable mortality across cities within countries.
Real-World Clinical Performance Evaluation of a Fourth-Generation HIV Antigen/Antibody Differentiation Test
Authors: Krasowski Matthew D , Wier Dustin , Smith Susan , Riedel Alexander , Lauseker-Hao Yi , Kelner Michael , Wang Sihe
Published: June 2021

Background

HIV testing is still an important component of routine sexual health screening, assessment of at-risk individuals and as part of the care of pregnant women. To prevent further transmission of infection, it is important that HIV tests are highly sensitive and that positive cases are not missed. HIV serologic antigen/antibody tests are commonly used as they are capable of detecting recent and established infection.

Methods

In this study we assessed the performance of the Elecsys HIV Duo assay (Elecsys assay) against the Abbott Architect assay in 10 121 samples from US and non-US adult, pediatric, and pregnant populations including low-risk, high-risk, and known positive cohorts. Congruent repeatedly reactive and/or discrepant samples followed a confirmatory algorithm consisting of an antigen/antibody differentiation assay and a nucleic acid test, as per the study protocol.

Results

The overall sensitivity of the Elecsys assay was 100.00% (95% CI 99.81–100.00 [1977/1977]), and the specificity was 99.84% (95% CI 99.73–99.91 [8129/8142]). The Elecsys assay detected all positive samples within the study, including all 50 antigen-only positive samples and samples from different HIV subtypes, including group O, group M subtypes, HIV-2 positives, and HIV-1 and HIV-2 dual positives.

Conclusions

The Elecsys HIV Duo assay was highly sensitive for diagnosis of HIV in a range of clinical samples from the United States and outside the United States and is suitable for routine use.
Relationship between hip joint medial space ratio and collapse of femoral head in non-traumatic osteonecrosis: a retrospective study
Authors: Lin Tianye , Li Keda , Chen Weijian , Yang Peng , Zhuang Zhikun , Zhang Ying , He Wei , Zhang Qingwen , Wei Qiushi
Published: June 2021

To retrospectively analyze the medial space ratio (MSR) of the hip joint to evaluate its efficacy in predicting osteonecrosis of femoral head (ONFH)-induced collapse and its impacts on the mechanical environment of necrotic femoral head. In this retrospective analysis of traditional Chinese medicine, non-traumatic ONFH (NONFH) patients from January 2008 to December 2013 were selected. The patients were divided into collapse group and non-collapse group based on whether the femoral head collapsed. The anatomical parameters including center–edge (CE) angle, sharp angle, acetabular depth ratio and MSR were evaluated. Receiver operating characteristic curves were estimated to evaluate the sensitivity and specificity of MSR and CE angle in collapse prediction. The results showed that 135 patients (151 hips) were included in this study. The differences in CE angle and MSR between collapse group and non-collapse group were statistically significant. The mean survival time of the hips of patients with MSR <20.35 was greater (P < 0.001) than that of patients with MSR >20.35. The ONFH patients with MSR >20.35 were prone to stress concentration. We could conclude that the hip joint MSR and CE angle strongly correlated with the collapse of NONFH. The specificity of MSR is higher than that of CE angle. When MSR is >20.35, the collapse rate of ONFH will increase significantly.
Spectropolarimetry and photometry of the early afterglow of the gamma-ray burst GRB 191221B
Authors: Buckley D A H , Bagnulo S , Britto R J , Mao J , Kann D A , Cooper J , Lipunov V , Hewitt D M , Razzaque S , Kuin N P M , Monageng I M , Covino S , Jakobsson P , van der Horst A J , Wiersema K , Böttcher M , Campana S , D’Elia V , Gorbovskoy E S , Gorbunov I , Groenewald D N , Hartmann D H , Kornilov V G , Mundell C G , Podesta R , Thomas J K , Tyurina N , Vlasenko D , van Soelen B , Xu D
Published: June 2021

We report on results of spectropolarimetry of the afterglow of the long gamma-ray burst GRB 191221B, obtained with SALT/RSS and VLT/FORS2, as well as photometry from two telescopes in the MASTER Global Robotic Network, at the MASTER-SAAO (South Africa) and MASTER-OAFA (Argentina) stations. Prompt optical emission was detected by MASTER-SAAO 38 s after the alert, which dimmed from a magnitude (white-light) of ∼10–16.2 mag over a period of ∼10 ks, followed by a plateau phase lasting ∼10 ks and then a decline to ∼18 mag after 80 ks. The light curve shows complex structure, with four or five distinct breaks in the power-law decline rate. SALT/RSS linear spectropolarimetry of the afterglow began ∼2.9 h after the burst, during the early part of the plateau phase of the light curve. Absorption lines seen at ∼6010 and 5490 Å are identified with the Mg ii 2799 Å line from the host galaxy at z = 1.15 and an intervening system located at z = 0.96. The mean linear polarization measured over 3400–8000 Å was ∼1.5 per cent and the mean equatorial position angle (θ) was ∼65°. VLT/FORS2 spectropolarimetry was obtained ∼10 h post-burst, during a period of slow decline (α = −0.44), and the polarization was measured to be p = 1.2 per cent and θ = 60°. Two observations with the MeerKAT radio telescope, taken 30 and 444 d after the GRB trigger, detected radio emission from the host galaxy only. We interpret the light curve and polarization of this long GRB in terms of a slow-cooling forward shock.
Feminist Philosophy of Social Science
Authors: Crasnow Sharon
Published: June 2021

This chapter offers a preliminary investigation of some of the ways that feminist philosophers have and might continue to learn from, interact with, and ultimately contribute to discussions about key issues in the social sciences. It begins with a brief history of feminist engagement with the social sciences. In next turns to consideration of two areas in which feminist work has made a difference: methodology and concept critique. Feminist standpoint methodology, as used primarily by feminist sociologists, has been influential in both of these areas. The success of standpoint theory as a feminist methodology has motivated philosophical exploration of its relationship to feminist epistemology. Another area in which feminist approaches have had an impact is feminist critique of concepts. The way the objects of inquiry are conceptualized has an impact on what research questions can be answered. Concepts that are inadequate to capturing the lived experience of women may call for revision or replacement. Standpoint theory has been influential in this area as well. The chapter concludes by considering some questions raised by standpoint theory about the identity of knowers and how intersectionality may serve as an analytical tool to aid in addressing that question.
Feminism and Early Modern Philosophy
Authors: Boyle Deborah
Published: June 2021

This chapter offers an account of the history and central issues in feminist philosophical engagements with early modern philosophy. The chapter describes a “first wave” of feminist scholarship on early modern philosophy, beginning around the 1990s, that involved examining the work of canonical male philosophers from a feminist perspective, as well as a “second wave” that focuses on the early modern women philosophers themselves. Projects involved in this second wave include (1) explaining why and how these works dropped out of view in the first place; (2) finding, editing, translating (when necessary), and publishing neglected or lost writings; (3) contextualizing, analyzing, and critiquing these works; and (4) theorizing about and experimenting with ways to integrate these works into narratives of the history of philosophy. The chapter ends with discussion of an emerging “third wave” of opportunities for publishing, presenting at conferences, and teaching about these women philosophers.
Borders and Migration
Authors: Wilcox Shelley
Published: June 2021

Feminist philosophical approaches to migration justice typically employ nonideal methodologies and relational normative frameworks to theorize the complex relationships among intersecting social identities, structural injustice, and global migration. This chapter discusses three such feminist approaches. The first investigates the connections between structural injustice and migration policy, focusing on immigrant admissions and refugee determination. The second explores the feminization of labor migration, with an emphasis on global care chains. Finally, the third feminist approach employs intersectional methodologies to argue that specific US immigration policies work to the detriment of migrant women, particularly women of color.
Pragmatism
Authors: McKenna Erin , Hamington Maurice
Published: June 2021

This chapter offers an account of central issues and themes in feminist philosophical engagements with the uniquely American intellectual tradition often referred to as American pragmatism. After introducing pragmatism, the foundational feminist work and influence of Jane Addams is presented, followed by a discussion of other noteworthy contributors to feminist pragmatism. Significant themes in feminist pragmatism including race and identity, epistemology, care ethics, utopian thinking, and environmentalism are explored. The chapter addresses the extent to which feminist work has changed or entered the mainstream of the American pragmatism, as well as current and future directions of feminist pragmatism. In addition to offering a history of the development of feminist pragmatism, the chapter considers how feminism is a resource for pragmatism and how pragmatism is a resource for feminist philosophy.
Black Feminist Philosophy and the Politics of Refusal
Authors: Karera Axelle
Published: June 2021

This chapter discusses the meaning, possibility, and contributions of Black feminist philosophy. The chapter discusses a politics of refusal that characterizes Black women’s theorizing and develops it as a framework for understanding how Black feminist philosophy is more than mere corrective and subversion of mainstream philosophy. As a framework, Black feminist philosophical “politics of refusal” depicts how Black feminist philosophers doing philosophy for Black women and girls refuse to sell themselves short, refuse institutionally imposed intellectual trajectories, and refuse to respond to philosophy’s call to order in their attempts to lay down uncompromisingly Black feminist research agendas in philosophy. The chapter offers an overview of important contributions to the field and discusses how a politics of refusal operates as critique and knowledge production within the field.
Public health activism amid the Covid-19 pandemic: the case of the Alliance of Health Workers
Authors: Macaraan Willard Enrique R
Published: June 2021

In an editorial, the editors note how crucial the role is of public health activism in enforcing efficient and effective public health management. The government is the lead institution in any national response to the pandemic and to ensure transparency on its end, it is important for any network of health organizations and associations not to shy away from embracing an activist role. In this correspondence, the author explores the case of the Alliance of Health Workers, a union of government and private health workers, and its advocacy towards an empowered status of healthcare professionals in the Philippines.
Retracted: Economic viability in free-range chicken production
Authors: Lourençoni Dian , Faustino Amelia Carvalho , Turco Sílvia Helena Nogueira , Bonfim Otoniel Cajuí , Carolina Luana , Silva Rocha E , De Sá Silva Lins Ana Carolina
Published: June 2021

Despite the lack of large-scale farming of free-range chickens in Brazil, their production generates income in the countryside and prevents exodus of rural families in agricultural regions. The objective of this study is to evaluate the economic viability of free-range broiler production in different facilities. The experiment was conducted in two different sheds (masonry shed-SM and wooden shed-SW) located in the Plural Space of the Universidade Federal do Vale São Francisco, municipality of Juazeiro, BA. Here, 200 heavy red French free-range chickens were distributed in the two sheds and were raised from the 1st to the 88th day (slaughter). Assuming that the minimum age for slaughter is 85 days, the results indicated that at least 205 birds in SM and 217 birds in SW were necessary for the producer to earn the minimum per capita monthly wage in Brazil (2020); at least 411 birds in CG and 600 birds in GM were found to be necessary to achieve maximum productivity at the end of the production cycle. The maximum profitability in the slaughter of the chickens was achieved at an age of 60 days.
Determining the effect of the WNT/b‐catenin pathway on the ischemic blood‐brain barrier in vitro and in vivo
Authors: Page Shyanne , Villalba Heidi , Al‐Ahmad Abraham
Published: June 2021

The blood‐brain barrier (BBB) is a selectively permeable barrier made up of tight junctions formed by endothelial cells that separates the circulating blood from the brain extracellular fluid. The primary function of the BBB is to limit the movement of xenobiotics from the blood to the brain. In the event of an ischemic stroke, the BBB opens allowing water and ions to enter the brain, leading to excitotoxicity and edema formation. Targeting such opening of the barrier following ischemic stroke has become a focus in current stroke studies. It has been shown that the Wnt/b‐catenin pathway is important for barrier formation during embryonic development, therefore, we hypothesized that activation of this pathway following ischemic stroke would attenuate barrier dysfunction. Brain microvascular endothelial cells (BMECs) derived from iPSCs were cultured and placed in ischemic stress for 6hrs, followed by an 18‐hour period of re‐oxygenation. Wnt small molecule activators (CHIR99021 and SB‐216763) and inhibitors (XAV939, IWP‐4, IWR‐1) were introduced at different time points of differentiation, during ischemia, and during re‐oxygenation. Transendothelial Electrical Resistance (TEER) and permeability were performed to assess barrier integrity following re‐oxygenation. For in vivo studies, C57BL mice were subjected to one‐hour ischemia by MCAO. At the time of re‐oxygenation, mice were dosed with CHIR99021 (IP; 30mg/kg). 24‐hours post‐MCAO, TTC staining on brains was performed to determine infarct size and edema ratio. The results of the in vitro studies have shown that activation of the Wnt pathway during re‐oxygenation results in increased barrier function, suggesting that the Wnt pathway is a potential target for post‐stroke therapy.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A zebrafish FASD model for congenital heart defects
Authors: Marrs James , Sarmah Swapnalee
Published: June 2021

Mothers who drink during pregnancy expose their developing babies to ethanol, and excessive drinking often produces devastating birth defects collectively termed fetal alcohol spectrum disorder (FASD). These defects include craniofacial defects, cognitive impairment, sensorimotor disabilities and organ deformities, including various congenital heart defects (CHDs), particularly septal and conotruncal defects. Genesis mechanisms for FASD‐associated CHDs are not well understood. Using a zebrafish model, experiments tested whether alcohol interferes with different heart development events or the multiple cardiac precursors that may contribute to CHD genesis. These experiments showed that ethanol affects various cardiac regulatory networks in multiple steps of cardiogenesis (specification, myocardial migration, differentiation, looping, chamber morphogenesis, and endocardial cushion formation). Retinoic acid and folic acid co‐treatment with ethanol had differential rescue effects on FASD‐induced cardiac defects. Early (first heart field) and late‐added (second heart field and cardiac neural crest precursors) cardiac precursors were reduced by ethanol exposure. Experiments showed dysregulation of BMP, Notch and other signaling pathways during atrioventricular valve formation produced persistent valve defects. Together, these results show that embryonic ethanol exposure disrupts critical cardiac morphogenic events and reduce cardiac precursor contributions to the growing heart. Additional mechanistic studies are needed to identify key events that can be targeted therapeutically.

Support or Funding Information

NIH/NIAAA AA0022396 and AA026711

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Gait and Mobility Session: Teaching the Neurology and Neuroanatomy of Spinal Cord Injuries
Authors: Vogel Kristine S. , Palm Michael
Published: June 2021

Medical student knowledge of key ascending and descending pathways (dorsal column/medial lemniscal, spinothalamic, lateral corticospinal) is essential to their ability to identify and assess spinal cord injuries (SCI). In addition, evaluation of gait is an important component of the neurological examination. To incorporate these clinical and neuroanatomical concepts into an interactive session, which is part of an integrated nine‐week neuroscience/neurology/psychiatry module, we combined a gait observation and analysis activity, a review of spinal cord anatomy and lesions, and a question and answer interview with the patient. Before the session, students watched a short, high‐resolution video of the patient, who has a Brown‐Sequard syndrome lesion, navigating stairs and level ground, with and without his cane. They were required to submit at least three observations on the patient's gait and mobility, but were not provided with specific prompts, nor given any information about the location or nature of the lesion. Analysis of over 750 student responses from four years of the module is ongoing, and includes tabulation of lesion localization (e.g. right or left side, upper motor neuron vs. lower motor neuron, cerebral cortex vs. cerebellum vs. spinal cord), aspects of mobility (e.g. use of cane, placement of feet on stairs, turning, balance), and gait descriptors (e.g. circumduction, foot drop, wide‐based). For example, in 2015, 83/213 students correctly identified the side with lower extremity weakness/stiffness, 17/213 identified the incorrect side, and the remainder (113/213) did not indicate the side on which weakness was observed. 66/213 students compared the patient's gait with and without his cane, and 62/213 noted the patient's foot placement while ascending or descending stairs. These classifications of student observations, combined with in‐class analysis and discussion of the video guided by neurology faculty, provide insight into the development of medical student observation skills and familiarity with the neurological examination and terminology. Moreover, the question and answer session with the patient (who is a physician) adds depth to the narrative, and encourages empathy for the mobility challenges faced by individuals who have SCI.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Pathology consultation in the gross anatomy laboratory–rationale and process
Authors: Husain Mujtaba
Published: June 2021

The gross anatomy laboratory is a rich environment for learners to be exposed to a variety of pathology. In the course of dissection, students and anatomy faculty frequently encounter challenges in determining whether a finding is a normal variant or pathologic process that may or may have not led to the demise of their cadaver donors. The presence of a practicing pathologist faculty is an excellent adjunct to the learning environment, as they provide much needed context to help determine if a finding is normal or abnormal. The pathologist faculty guide the students in forming a differential diagnosis for the cause of death (COD), develop the rationale and indication for tissue biopsy and correlate histopathological with dissection and medical imaging findings. The pathologist also assist the learners in prioritizing all of the pathologic abnormalities as they relate to the COD (terminal, intermediate, and primary diagnoses) simulating a death certificate. Finally, the pathologist faculty facilitates the preparation of a clinico‐pathologic conference style format for student presentations. This mode of education provides an excellent opportunity to link the fundamentals of normal anatomy, learned traditionally in the first year of medical school, to the pathophysiology introduced in the second year of a four‐year curriculum. The process of pathology consultation in the gross anatomy laboratory will be discussed with respect to common scenarios, resources required, and successful communication strategies between the students and the pathology consultant

Support or Funding Information

None.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Integrating anatomy teaching into the clinical medicine clerkship
Authors: Pasarica Magdalena
Published: June 2021

Anatomy concepts are highly relevant for clinical teaching in the medical curriculum with many opportunities for implementation and integration. We will discuss here the most clinical relevant anatomical concepts that are relevant to a 3rd year Family Medicine clerkship experience. First, procedures are very important and common in the practice of family medicine. A baseline understanding of anatomy is necessary for procedure training. For example, at our institution, we teach join injections by using models and ultrasound to identify anatomic landmarks and then utilize cadavers for teaching the particular skill of injecting the joint. We also teach Intrauterine device insertion and cervical cytology, and for this we use models to teach the anatomy and to practice the skill. Second, interpreting radiographic studies is essential for any physician. For example, interpreting a chest x‐ray or a CT scan or an ultrasound requires a preliminary discussion of the normal anatomy, followed by pathology with integration of the clinical finding. Third, identifying abnormal pathology during clinical examination requires the knowledge of normal anatomy and pathology. For example, an abnormal musculoskeletal exam requires the knowledge of normal anatomy. As we use these pedagogies in our institutions, we learn about their advantages and disadvantages. One advantage is that the students have the opportunity to apply anatomy concepts in a clinically‐relevant real‐world scenario as they practice their skills, not only to improve their competency, but also their confidence in practicing these skills in the clinical education year and residency training. The disadvantages are that groups have to be small for maximal benefit, and also there are expensive resources to be used in addition to the requirement of knowledgeable facilitators. Other institutions interested in integrating anatomy in teaching pathology and clinical medicine in an active way could benefit from this approach.

Support or Funding Information

none

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterization of the Role of Shroom3 in Nephron Formation
Authors: Kitala Patricia , Cunanan Joanna , Bridgewater Darren
Published: June 2021

During kidney development the proper formation of the nephron, the functional unit of the kidney, is essential for normal kidney function. Nephrogenesis is the process in which nephron progenitors undergo cell shape changes and mesenchymal‐to‐epithelial transition to form mature nephrons. These cell shape changes are essential for the proper development of the nephron and for proper nephron function. Shroom3 is an actin‐binding protein that regulates epithelial cell shape. It regulates this morphogenesis by binding to F actin and interacting with Rho‐kinase. This leads to the phosphorylation of non‐muscle myosin II activating a signal pathway that causes contraction of the actomysoin network. This contraction causes the cell to form “pie” shaped cells, a process that is essential for tubule formation. Kidneys from shroom3 null mice have numerous abnormal nephrons with collapsing glomeruli at embryonic day E18.5, supporting a role for shroom3 in nephron formation. We hypothesize that Shroom3 is required for mesenchyme cells to cluster and form cell aggregates, pretubular aggregates, and renal vesicles. To support a role for Shroom3 in nephrogenesis we first localized Shroom3 expression. Shroom3 was highly expressed in the aggregating mesenchyme, renal vesicle, and parietal and visceral epithelial cells of the developing glomeruli. In contrast to wild‐type Shroom3 mice, E13.5 kidney histology of Shroom3 mutants demonstrated an increased distance of mesenchymal cells from the neighbouring ureteric bud tip cells (WT 3.85μm ± 0.30, MUT 14.80 μm ±1.22, n=9). These abnormalities were further observed by immunofluorescence (IF) using Six2 and Pax2, specific markers of the mesenchyme aggregates. In E13.5, the IF demonstrated an increased length in the cap mesenchyme (WT 179.6μm ± 24.96, MUT 306.4μm ± 33.30, n=9), and a lack of cap mesenchyme cell aggregation in Shroom3 mutants (WT 8804μm2 ±1250, MUT 12353 μm2 ±1504, n=9). In addition, E18.5 mutants displayed significantly less Six2+ cells in comparison to wild‐types (WT 149 ± 13.3, MUT 79.5 ± 7.47). The analysis for renal vesicles in Shroom3 mutants at E13.5 and E18.5 demonstrated abnormally forming renal vesicles that were few in number when compared to wild‐type (WT 3 ±0.58, MUT 1 ± 0, n=9). Taken together, our findings establish, for the first time, that Shroom3 is essential for the early stages of nephron formation, and suggest these early changes lead to improper migration and clustering of cap mesenchyme cells resulting in abnormal nephrons observed in null mice.

Support or Funding Information

CIHR, NSERC, KFOC

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Metabolic Coordination of Tumor Suppression
Authors: Finley Lydia
Published: June 2021

Increasing evidence demonstrates that intracellular metabolic pathways can be critical drivers of tumor progression. Metabolites provide the biomass required for cancer cell proliferation and contribute to antioxidant defenses that promote survival and metastatic dissemination. Moreover, oncogenic mutations in several metabolic enzymes lead to accumulation of pathological levels of metabolites that interfere with histone and DNA demethylation and impose a block to differentiation. Thus, while the ability of metabolites to contribute directly to malignant progression is well established, whether metabolites can contribute to the cell fate changes that occur during tumor suppression remains an open question. To study the role of metabolism during tumor suppression, we took advantage of a mouse model of pancreatic ductal adenocarcinoma driven by mutant Kras and inducible suppression of p53 to enable temporal control of tumor suppression. Using cell lines derived from these tumors, we found that p53 restoration is accompanied by metabolic alterations that can be uncoupled from changes in cell cycle progression. Recapitulating these metabolic alterations with pharmacologic or genetic interventions in malignant cells is sufficient to phenocopy the effects of p53 restoration on differentiation and tumor progression. These results suggest that p53‐driven metabolic rewiring directly contributes to the cell fate changes that occur during tumor suppression.

Support or Funding Information

This work was supported by the Searle Scholars Program, the Damon Runyon Cancer Research Foundation (DFS‐23‐17) and The Starr Foundation (I11‐0039).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Proteomic Approaches to Better Understand Transcriptional Regulation
Authors: Myers Sam
Published: June 2021

Cellular differentiation is often driven by gradients of multiple, simultaneous extracellular cues that must be transduced across the membrane, interpreted, and integrated to enact appropriate transcriptional responses. These processes are typically studied by measuring either a small number of proteins or post‐translationally modified sites, or the resultant changes in mRNA levels. While powerful, these approaches overlook hundreds of dynamic signaling events, changes to protein complex composition, and the subcellular localization of regulatory proteins. Here, we will show the interdisciplinary tools and approaches being developed to better understand the principles and mechanisms underlying how signal transduction orchestrates changes in gene expression.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Chlorolipids: Mediators and Outcome Predictors of Sepsis
Authors: Pike Daniel , Hartman Celine , Palladino Elisa , Albert Carolyn , Ford David
Published: June 2021

Sepsis is a serious cause of morbidity and mortality worldwide. Sepsis is the life‐threatening organ dysfunction caused by the dysregulation of the inflammatory response to an infection. One aspect of this immune response is the systemic activation of neutrophils. Intended to combat microbes through phagocytosis, production of reactive oxygen species, and the release of antimicrobial enzymes through degranulation, neutrophil defense mechanisms can also damage host tissue. Neutrophil myeloperoxidase (MPO) catalyzes the production of hypochlorous acid (HOCl). In addition to microbial targets, HOCl can attack the vinyl ether bond of host membrane plasmalogens, releasing 2‐chlorofatty aldehyde (2‐ClFALD), which is oxidized to 2‐chlorofatty acid (2‐ClFA). Collectively, these plasmalogen oxidation products are members of the chlorolipid family. Human plasma levels of the chlorolipid, 2‐ClFA, predict 30‐day mortality and acute respiratory distress syndrome (ARDS) in sepsis patients. Similarly, septic rats have time‐dependent increases in the plasma, lung, kidney, and intestine levels of 2‐ClFA. For these studies rat sepsis was caused by intraperitoneal injections of 15mL of cecal slurry (isolated from donor rats)/kg body weight. In vitro studies using a click chemistry analog of 2‐ClFA have shown 2‐ClFA localizes to the Weibel‐Palade bodies of human coronary artery endothelial cells and induce the release of their contents. Release of von Willebrand factor, angiopoietin‐2, and P‐ and E‐selectin surface expression were caused by 2‐ClFA exposure to endothelial cells from several vascular beds including human coronary artery endothelial cells and human lung microvascular endothelial cells. The release of these molecules elicits endothelial activation/dysfunction including neutrophil and platelet adherence as well as loss of the endothelial permeability barrier. Additionally, 2‐ClFA induces human neutrophils to release their DNA as neutrophil extracellular traps (NETs) in the process known as NETosis, also implicated in organ failure in sepsis. These in vitro studies with human endothelial cells and human neutrophils suggest 2‐ClFA may mediate the microvascular failure associated with sepsis including endothelial dysfunction and microvascular plugging by NETs. Overall, these studies indicate the importance of chlorolipids in sepsis as prognostic biomarkers of human sepsis outcomes and potential mediators of multi‐organ failure associated with sepsis mortality.

Support or Funding Information

Ford, PI, Multi‐PI R01 grant (GM115553), Chlorinated lipids in sepsis, NIH Ford, PI, Multi‐PI R01 grant (GM129508), Neutrophil‐dependent mediators of sepsis, NIH Pike, PI, F30 Fellowship grant (F30HL142193), Plasmalogen‐Derived Chlorinated Lipids: Mediators of Acute Lung Injury in Sepsis, NIH

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.