bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome-Wide Association Study for Inflammatory Bowel Disease Reveals Novel Candidate Susceptibility Genes in Specific Colon Subsites and Tissue Categories
Authors: Díez-Obrero Virginia , Moratalla-Navarro Ferran , Ibáñez-Sanz Gemma , Guardiola Jordi , Rodríguez-Moranta Francisco , Obón-Santacana Mireia , Díez-Villanueva Anna , Dampier Christopher Heaton , Devall Matthew , Carreras-Torres Robert , Casey Graham , Moreno Victor
Published: July 2021

Background and Aims

Genome-wide association studies [GWAS] for inflammatory bowel disease [IBD] have identified 240 risk variants. However, the benefit of understanding the genetic architecture of IBD remains to be exploited. Transcriptome-wide association studies [TWAS] associate gene expression with genetic susceptibility to disease, providing functional insight into risk loci. In this study, we integrate relevant datasets for IBD and perform a TWAS to nominate novel genes implicated in IBD genetic susceptibility.

Methods

We applied elastic net regression to generate gene expression prediction models for the University of Barcelona and University of Virginia RNA sequencing project [BarcUVa-Seq] and correlated expression and disease association research [CEDAR] datasets. Together with Genotype-Tissue Expression project [GTEx] data, and GWAS results from about 60 000 individuals, we employed Summary-PrediXcan and Summary-MultiXcan for single and joint analyses of TWAS results, respectively.

Results

BarcUVa-Seq TWAS revealed 39 novel genes whose expression in the colon is associated with IBD genetic susceptibility. They included expression markers for specific colon cell types. TWAS meta-analysis including all tissues/cell types provided 186 novel candidate susceptibility genes. Additionally, we identified 78 novel susceptibility genes whose expression is associated with IBD exclusively in immune (N = 19), epithelial (N = 25), mesenchymal (N = 22) and neural (N = 12) tissue categories. Associated genes were involved in relevant molecular pathways, including pathways related to known IBD therapeutics, such as tumour necrosis factor signalling.

Conclusion

These findings provide insight into tissue-specific molecular processes underlying IBD genetic susceptibility. Associated genes could be candidate targets for new therapeutics and should be prioritized in functional studies.
Wells and Geneva decision rules to predict pulmonary embolism: can we use them in Covid-19 patients?
Authors: Silva BV , Jorge C , Rigueira J , Rodrigues T , Silverio Antonio P , Morais P , Pereira S , Alves Da Silva P , Brito J , Placido R , G Almeida A , J Pinto F
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

 Pulmonary embolism (PE) is a recognized complication of SARS-COV2 infection due to hypercoagulability. Before the COVID era, the need for computed tomography pulmonary angiography (CTPA) to rule out PE was determined by clinical probability, based on Wells and Geneva scores, in association with D-dimer measurements. However, patients with SARS-COV2 infection have a pro-thrombotic and pro-inflammatory state which may compromise the usefulness of these algorithms to select patients for CTPA. 

Purpose

 To evaluate the accuracy of the Wells and Geneva scores to predict PE in patients with SARS-COV2 infection.

Methods

 Retrospective study of consecutive outpatients with SARS-COV2 infection proved by positive PCR who underwent CTPA due to suspected PE. The Wells and Geneva scores were calculated and the area under the curve (AUC) of the receiver operating characteristic curve was measured.

Results

 We enrolled 235 patients (61% males, mean age 69.10 ± 16.69 years) and the incidence of pulmonary embolism was 15% (35 patients). In patients with PE, emboli were located mainly in segmental arteries (60%) and bilaterally (46%). Patients with PE were older (mean age 75.06 ± 2.23 vs. 68.06 ± 1.21 years, p = 0.022), and did not differ in sex or risk factors for thromboembolic diseases from the non-PE group. Patients with PE had higher D-dimer levels (median 15.41 mg/dl, IQR 1.17 – 20.00) compared to patients without PE (median 5.99 mg/dl, IQR 0.47 – 2.82, p < 0.001).

 There was no statically significant difference between the average Wells score in patients with PE and without PE (1.04 and 0.89 respectively, p = 0.733) and the AUC demonstrated that the Wells score had no discriminatory power (AUC = 0.52). Within patients with PE, 19 patients had a Wells score of zero. Regarding the Geneva score, there was also no difference between the average score in patients with and without PE (4.20 vs 3.93 respectively, p = 0.420). AUC for Geneva score was 0.54.

Clinical probability combined with D-dimer measurement had a 100% sensitivity for both Wells and Geneva scores, but a specificity of 10% and 11%, respectively. 

Conclusion

 PE diagnosis may be challenging in patients with SARS-COV2 infection since both conditions may have similar signs and symptoms and may be associated with increased D-dimers. According to our results, traditional clinical prediction scores have little discriminatory power in these patients and a higher D-dimer cut-off should be considered to better select patients for CTPA to minimize radiation exposure and contrast-related complications in COVID-19 patients.
Anomalous origin of the right coronary artery with interarterial course: red flag or innocent bystander?
Authors: Albuquerque F , De Araujo Goncalves P , Marques H , Ferreira A , Freitas P , Lopes P , Goncalves M , Dores H , Cardim N
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Anomalous origin of the right coronary artery (right ACAOS) with interarterial course (IAC) has been associated with increased risk of sudden cardiac death (SCD). Widespread use of coronary computed tomographic angiography (CCTA) has led to increasing recognition of this condition, even among healthy individuals. This study sought to examine the prevalence, anatomical characteristics and outcomes of right ACAOS with IAC in patients undergoing CCTA for all-indications.

Methods

We conducted a retrospective analysis of consecutive patients referred for CCTA at one tertiary hospital between January 2012 and December 2020. Right ACAOS patients with IAC were analyzed for cardiac symptoms (anginal chest pain, syncope, aborted SCD) and long-term outcomes were evaluated for myocardial infarction, ischemic test results, revascularization procedures and all-cause or cardiovascular (CV) mortality. CCTAs were reviewed for proposed high-risk features (ie., take-off angle, length and severity of proximal narrowing, intramural course, interarterial length) and concomitant coronary artery disease (CAD). Association between high-risk features was analyzed. Long-term outcomes were evaluated.

Results

Among 10,928 patients referred for CCTA during the study period, we identified 28 patients (0.3% prevalence) with right ACAOS and IAC. Mean age was 55 ± 17 years, 64% were male and 11 (39.3%) presented cardiac symptoms. During a median follow-up of 44.1 ± 31.8 months, there were no CV deaths and only 1 patient (3.65%) underwent surgical revascularization. Baseline characteristics and CCTA findings are presented in figure 1.

Conclusion

Right ACAOS and IAC is an uncommon finding, with an observed prevalence of 0.3%. CCTA provides excellent anatomical characterization of anomalous vessels, including suggested high-risk features. In a population of asymptomatic patients who survived this condition well into adulthood, the risk of events was very low and medical follow up might be a reasonable option.
Prognostic value of myocardial MIBG scintigraphy in acute ischemic stroke
Authors: Bourgeois S , Peeters I , Vanderschueren G , Nous A , De Keyser J , Nakajima K , Poel E , Verberne HJ , De Raedt S
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background Autonomic dysfunction is a common complication of acute ischemic stroke and has been associated with poor functional outcome and increased mortality. We investigated the potential relation between the myocardial washout rate (WOR) of 123I-meta-iodobenzylguanidine (123I-mIBG), as a measure of cardiac sympathetic activity, and functional outcome in acute ischemic stroke. 

Methods 38 patients with ischemic stroke (11 females, 72 years old [61-81)), underwent myocardial 123I-mIBG scintigraphy within the first week after stroke onset. Early (10 minutes post-injection (pi)) and late (4 hours pi) planar scans of the thoracic region were made. Regions of interest (ROI) were drawn over the mediastinum and the heart, and heart-to-mediastinum ratio (HMR) was calculated. Myocardial WOR was calculated as follows: (ROI heart early – ROI heart late)/ (ROI heart early) x 100%. Counts were corrected for background and counts in ROI heart late were corrected for decay. Patients were divided in 2 groups: those with a good functional outcome, defined as modified Rankin Scale (mRS) ≤ 2 at 3 months after stroke (i.e., patient is functionally independent), and those with a poor functional outcome, defined as a mRS > 2. 

Results Median WOR was 27,4 % (IQR 10,4-43,6). In univariate analysis, poor functional outcome after stroke was associated with age, stroke severity on admission (measured by the National Institutes of Health Stroke Scale (NIHSS)), beta-blocker use before and during hospitalization, WOR and late HMR. In subsequent multivariate analysis WOR (OR 1.087; 95% CI 1.003-1.177, p = 0.042) was an independent predictor of poor stroke outcome even after adjustment for age and NIHSS.

Conclusions In patients with acute ischemic stroke, myocardial washout of 123I-mIBG predicts stroke outcome, even after adjustment for age and stroke severity on admission.
Prognostic value of myocardial perfusion imaging in kidney transplant recipients: a systematic review and meta-analysis
Authors: Jolink FEJ , Kelderman JR , Monroy Gonzalez AG , Benjamens S , Slart RHJA , Pol RA
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Kidney transplant recipients are at risk for major adverse cardiac events (MACE) and cardiovascular mortality. We aimed to assess the prognostic value of myocardial perfusion imaging (MPI) single-photon emission computed tomography (SPECT), in patients evaluated for transplantation, for MACE and cardiovascular mortality after kidney transplantation.

Methods

We performed a systematic literature search in PubMed, EMBASE, Web of Science, OvidSP, The Cochrane Library and Google Scholar. We retrieved studies investigating the prognostic value of MPI for MACE and mortality in kidney transplant recipients. After risk of bias assessment using QUIPS, a meta-analysis was conducted.

Results

Out of 1379 records, 14 studies (7 prospective and 7 retrospective) using MPI SPECT were included in the meta-analysis with a total of 4643 MPI procedures. No studies were excluded after QUIPS assessment. Median follow-up duration of patients ranged from 1 to 8 years. Kidney transplant recipients with perfusion defects on MPI showed an increased risk for MACE (RR 2.76, 95%-CI 1.73-4.42), cardiovascular mortality (RR 3.15, 95%-CI 1.94-5.13) and all-cause mortality (RR 2.12, 95%-CI 1.76-2.54) compared to recipients with normal MPI findings. Significant heterogeneity existed across the included studies investigating MACE.

Conclusions

Our results showed that MPI SPECT may identify patients at increased risk for MACE and mortality after kidney transplantation.
Value of coronary artery calcium score in reporting SPECT versus PET myocardial perfusion imaging
Authors: Van Dijk JD , Mouden M , Van Dalen JA , Jager PL
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Although it is well known that coronary artery calcium score (CACS) adds value to reporting myocardial perfusion imaging (MPI) SPECT, its added value to reporting PET MPI is not clear.

Purpose

Hence, our aim was determine the value of adding CACS in the assessment of PET MPI and SPECT MPI and compare the value between both modalities in a low-risk population.

Methods

We retrospectively included 412 patients, half of them underwent SPECT with CACS and half underwent Rubidium-82 PET with CACS. We created comparable groups using propensity matching, where the PET group was 1:1 matched to a comparable SPECT group, obtained from a large cohort of 4018. Next, we created two types of image sets for the 412 included patients: MPI-only and MPI + CACS. Two experienced physicians interpreted the 824 images as normal, equivocal or abnormal for  ischemia or irreversible defects and were blinded for the used modality. In addition, annualized event rates, defined as the occurrence of all-cause death, non-fatal myocardial infarction or revascularization therapy (PCI or CABG), were compared between the PET and SPECT groups using a follow-up period of 30 months.

Results

The percentage of scans interpreted as normal was 8% higher with PET-only than with SPECT-only (89 vs 80%, respectively, p = 0.014). Adding CACS to SPECT increased the percentage of scans interpreted as normal from 80% to 86% (p = 0.014), whereas this effect was absent for PET (p = 0.77). Adding CACS reduced the frequency of equivocal scans from 12% and 6% to 0% for both SPECT and PET, respectively. Furthermore, adding CACS resulted in 5% more abnormal interpreted scans for both PET (4.9 to 10%, p = 0.003) and SPECT (8.7 to 14%, p = 0.04). The annualized event rate was 2.7% for the SPECT and 3.5% for the PET group (p = 0.58). The annualized event rates for images interpreted as normal were comparable between all four types of image sets and varied between 0.7-2.0% (p > 0.084). The annualized event rate for equivocal and abnormal scans was higher for PET-only (23%) compared to SPECT-only (4.8%, p < 0.001). Moreover, the event rate for equivocal and abnormal SPECT + CACS  (8.6%) was also higher than for SPECT-only (4.8%, p = 0.04), whereas this difference was absent for PET (p = 0.07).

Conclusion

Adding CACS increases the percentage of scans interpreted as normal for SPECT MPI while the event rate remained unchanged. Adding CACS to PET did not influence the percentage of scans interpreted as normal, limiting the effect of adding CACS to PET in a low-risk population.
Macrophage depletion impairs adequate cardiac repair in mouse models of myocardial infarction with variable transmurality - insights from multimodality molecular imaging
Authors: Hess A , Langer LBN , Ross TL , Bengel FM , Thackeray JT
Published: July 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft (DFG)

Introduction

Balanced myocardial tissue inflammation following acute myocardial infarction (MI) is needed for optimal cardiac repair. Macrophages contribute to wound healing, but may also be deleterious.

Purpose

We investigated the impact of macrophage depletion on early cardiac inflammation and later functional outcome in two models of MI with variable transmurality.

Methods

C57BL/6N mice received clodronate-liposomes for macrophage depletion (n = 49) or control PBS-liposomes (n = 23). After 24h, mice underwent permanent occlusion (PO) or transient ischemia-reperfusion (I/R, 60min) of the left coronary artery or sham surgery. Cardiac inflammation was assessed on MI + 1d, 3d, and 7d by CXCR4-targeted PET/CT using 68Ga-pentixafor. 99mTc-sestamibi SPECT/CT and cardiac magnetic resonance (CMR) calculated infarct sizes and left ventricular (LV) function at 1wk and 6wks. 18F-NaF PET/CT measured tissue microcalcification at 4wks. Imaging signals were validated by ex vivo autoradiography and immunohistochemistry.

Results

Clodronate macrophage depletion did not affect infarct size compared to PBS, but perfusion defects at 6wks were significantly larger after PO compared to I/R (%LV, 32 ± 11 vs 14 ± 10, p = 0.01). In both models, infarct CXCR4 expression was higher after macrophage depletion vs PBS at all timepoints (%injected dose (ID)/g; d3: PO: 1.4 ± 0.2 vs 0.9 ± 0.1; I/R: 1.4 ± 0.2 vs 1.0 ± 0.02; p < 0.05), and confirmed by ex vivo autoradiography. Immunostaining demonstrated fewer macrophages and higher neutrophil content within the myocardium after macrophage depletion vs PBS at 1d, 3d, and 7d post-MI. Acute LV rupture after PO was more frequent in macrophage-depleted than PBS mice (37% vs 17%). Conversely, surviving PO mice showed a similarly impaired ejection fraction (EF) after macrophage depletion vs PBS at 6wks (%, 32 ± 9 vs 32 ± 11, p = 0.84). No acute LV rupture was observed after I/R, but macrophage depletion led to worse EF (%, 42 ± 11 vs 54 ± 3, p = 0.1). Macrophage-depleted mice exhibited a dense intracavity thrombus adherent to the infarct wall after either injury, as visualized on CMR at 1wk. 18F-NaF PET identified active calcification localized to the thrombus region 4wks after MI, which was colocalized to CT opaque regions at 6wks.

Conclusion

Macrophage depletion impairs cardiac repair via several mechanisms including neutrophil-dominated inflammation, LV thrombus formation and tissue calcification. This observation underscores the requirement of macrophages for effective healing and may explain adverse response to broad anti-inflammatory therapy in myocardial ischemia.
Level 1 of Entrustable Professional Activities in adult echocardiography: a position statement from the EACVI regarding the training and competence requirements for selecting and interpreting echocardiographic examinations
Authors: Stankovic Ivan , Muraru Denisa , Fox Kevin , Di Salvo Giovanni , Hasselberg Nina E , Breithardt Ole-A , Hansen Tina B , Neskovic Aleksandar N , Gargani Luna , Cosyns Bernard , Edvardsen Thor ,   Reviewers: This document was reviewed by members of the 2020-2022 EACVI Scientific Documents Committee: Daniele Andreini, Magnus Báck, Philippe B. Bertrand, Marc Dweck, Niall Keenan, Julien Magne, Leyla Elif Sade; and by the Chair of the 2020-2022 EACVI Scientific Documents Committee: Erwan Donal.
Published: July 2021

The goal of Level 1 training in echocardiography is to enable the trainee to select echocardiography appropriately for the evaluation of a specific clinical question, and then to interpret the report. It is not the goal of Level 1 training to teach how to perform the examination itself—that is the goal of higher levels of training. However, understanding the principles, indications, and findings of this crucial technique is valuable to many medical professionals including outside cardiology. This should be seen as part of a general understanding of cardiac imaging modalities. The purpose of this position statement is to define the scope and outline the general requirements for Level 1 training and competence in echocardiography. Moreover, the document aims to make a clear distinction between Level 1 competence in echocardiography and focus cardiac ultrasound (FoCUS).
‘Cyber Due Diligence’: A Patchwork of Protective Obligations in International Law
Authors: Coco Antonio , de Souza Dias Talita
Published: July 2021

With a long history in international law, the concept of due diligence has recently gained traction in the cyber context, as a promising avenue to hold states accountable for harmful cyber operations originating from, or transiting through, their territory, in the absence of attribution. Nonetheless, confusion surrounds the nature, content and scope of due diligence. It remains unclear whether it is a general principle of international law, a self-standing obligation or a standard of conduct, and whether there is a specific rule requiring diligent behaviour in cyberspace. This has created an ‘all-or-nothing’ discourse: either states have agreed to a rule or principle of ‘cyber due diligence’, or no obligation to behave diligently would exist in cyberspace. We propose to shift the debate from label to substance, asking whether states have duties to protect other states and individuals from cyber harms. By revisiting traditional cases, as well as surveying recent state practice, we contend that – whether or not there is consensus on ‘cyber due diligence’ – a patchwork of different protective obligations already applies, by default, in cyberspace. At their core is a flexible standard of diligent behaviour requiring states to take reasonable steps to prevent, halt and/or redress a range of online harms.
The effects of small-scale convection in the shallow lithosphere of the North Atlantic
Authors: Likerman Jeremías , Zlotnik Sergio , Li Chun-Feng
Published: July 2021

Curie point depth can be used as a proxy for plate temperatures. Data from the North Atlantic (10°–50°N) are used here to determine if the observed oscillations and patterns in Curie depths could be a subproduct of small-scale thermal instabilities arising at the bottom of the lithospheric plates. Our numerical models suggest that small-scale convection (SSC) cells could produce thermal perturbations at isotherms as low as the Curie point. These results are compatible with North Atlantic observations in terms of wavelengths (150–300 km), amplitudes (∼4 km) and orientations of the instabilities. Observed Curie-point depth oscillations before the onset (70 to 90 Myr) of SSC could also be linked to other different processes. We suggest that, in the case of the North Atlantic lithosphere, the spreading rate variation and the melt and upwelling could be intricately linked and cause a different pattern of SSC.
Bayesian seismic inversion: a fast sampling Langevin dynamics Markov chain Monte Carlo method
Authors: Izzatullah Muhammad , van Leeuwen Tristan , Peter Daniel
Published: July 2021

In this study, we aim to solve the seismic inversion in the Bayesian framework by generating samples from the posterior distribution. This distribution incorporates the uncertainties in the seismic data, forward model, and prior information about the subsurface model parameters; thus, we obtain more information through sampling than through a point estimate (e.g. maximum a posteriori method). Based on the numerical cost of solving the forward problem and the dimensions of the subsurface model parameters and observed data, sampling with Markov chain Monte Carlo (MCMC) algorithms can be prohibitively expensive. Herein, we consider the promising Langevin dynamics MCMC algorithm. However, this algorithm has two central challenges: (1) the step size requires prior tuning to achieve optimal performance and (2) the Metropolis–Hastings acceptance step is computationally demanding. We approach these challenges by proposing an adaptive step-size rule and considering the suppression of the Metropolis–Hastings acceptance step. We highlight the proposed method’s potential through several numerical examples and rigorously validate it via qualitative and quantitative evaluation of the sample quality based on the kernelized Stein discrepancy (KSD) and other MCMC diagnostics such as trace and autocorrelation function plots. We conclude that, by suppressing the Metropolis–Hastings step, the proposed method provides fast sampling at efficient computational costs for large-scale seismic Bayesian inference; however, this inflates the second statistical moment (variance) due to asymptotic bias. Nevertheless, the proposed method reliably recovers important aspects of the posterior, including means, variances, skewness and 1-D and 2-D marginals. With larger computational budget, exact MCMC methods (i.e. with a Metropolis–Hastings step) should be favoured. The results thus obtained can be considered a feasibility study for promoting the approximate Langevin dynamics MCMC method for Bayesian seismic inversion on limited computational resources.
Actions during the COVID-19 pandemic to protect the most vulnerable population: what is the potency amid chaos?
Authors: Oliveira Monique , Braga Maria Fernanda , Bueno Alessandra , de Sousa Douglas Pereira , Pigozi Pamela Lamarca , Moryia Rubens , Akerman Marco
Published: July 2021

By 30 May 2021, Brazil had 16 471 600 COVID-19 cases and 461 142 deaths, ranking second in the world in number of deaths and third in number of cases. Preliminary research results in Brazil and around the world show the impact of COVID-19 on more vulnerable communities. However, despite the adverse circumstances of their territories, leaders have mobilized to face the challenges. Between April and June 2020, the authors of this article interviewed informants in eight Brazilian state capitals, addressing the five points of discussion (intersectoriality, sustainability, empowerment and public participation, equity and the life cycle perspective) recently presented by EUPHA-HP, IUHPE and UNESCO Chair Global Health & Education. Official actions and documents from the Ministry of Health and Municipal Health Departments (SMS) of each capital were also analyzed. No records were found of official actions aimed at COVID-19 that addressed the territories’ specificities. In total, 15 promotional actions by the communities were identified. The selection of local actors to take on specific responsibilities during the pandemic is highlighted as a relevant action. This action alone weaves together at least three of the five HP principles (equity, life cycles and empowerment). We consider that previous forms of political empowerment, such as the recognition of territories and educational initiatives, have contributed to the subjects who are leading these inventive initiatives. However, although there is scope for promotional actions, there are infrastructural limitations that only public policies could mitigate. Such actions would demand deliberate coordination between the government and social movements, which is absent in the current context of national governance.
Effects of the digital divide on the prevention of food risk in Taiwan
Authors: Chiu Yu-Chan , Li Fang-Ying
Published: July 2021

Given the frequent occurrence of various food incidents, food safety is a significant public health concern worldwide. Health information plays an important role in risk prevention. As its reach continues to broaden, the Internet is emerging as a major source of health information for the public, although some social groups continue to have limited access. This study investigates the relation between the digital divide and practices for preventing food incidents in Taiwan. Using a nationally representative survey of 2098 adults, the results of our multinomial logistic regression and bootstrapped mediation analysis indicate the existence of second- and third-level digital divides. The association between socioeconomic status and Internet use time and digital skills results in disparities in food risk prevention behaviors and is partially mediated by online food safety information acquisition. Our findings reveal that the digital divide exacerbates health inequalities in food risk prevention. In addition to providing useful food safety information online, communication interventions should address the digital inequality by delivering food safety information through alternative networks for disadvantaged members of the public.
From APC to the genetics of hereditary and familial colon cancer syndromes
Authors: Olkinuora Alisa P , Peltomäki Päivi T , Aaltonen Lauri A , Rajamäki Kristiina
Published: July 2021

Hereditary colorectal cancer (CRC) syndromes attributable to high penetrance mutations represent 9–26% of young-onset CRC cases. The clinical significance of many of these mutations is understood well enough to be used in diagnostics and as an aid in patient care. However, despite the advances made in the field, a significant proportion of familial and early-onset cases remains molecularly uncharacterized and extensive work is still needed to fully understand the genetic nature of CRC susceptibility. With the emergence of next-generation sequencing and associated methods, several predisposition loci have been unraveled, but validation is incomplete. Individuals with cancer-predisposing mutations are currently enrolled in life-long surveillance, but with the development of new treatments, such as cancer vaccinations, this might change in the not so distant future for at least some individuals. For individuals without a known cause for their disease susceptibility, prevention and therapy options are less precise. Herein, we review the progress achieved in the last three decades with a focus on how CRC predisposition genes were discovered. Furthermore, we discuss the clinical implications of these discoveries and anticipate what to expect in the next decade.
Preoperative radio-guided localization of lung nodules with I-125 seeds: experience with 32 patients at a single institution
Authors: Fra-Fernández Sara , Gorospe-Sarasúa Luis , Ajuria-Illarramendi Odile , Serrano-Carvajal Percy Enrique , Muñoz-Molina Gemma María , Cabañero-Sánchez Alberto , Rioja-Martin Maria Eugenia , Moreno-Mata Nicolás
Published: July 2021

OBJECTIVES

Videothoracoscopic visualization and/or palpation of pulmonary nodules may be difficult due to their location, small size or limited solid component. The purpose of this study is to present our experience with computed tomography (CT)-guided preoperative localization of pulmonary nodules by percutaneous marking with radio-labelled iodine-125 seeds.

METHODS

A total of 34 pulmonary nodules were marked under CT with the placement of 33 radio-labelled iodine-125 seeds in 32 consecutive patients.

RESULTS

All patients underwent biportal video-assisted thoracic surgery (VATS) and in no case was conversion to thoracotomy necessary. A total of 88.2% of the lung nodules were successfully resected. In the remaining 11.8%, migration of the seed to the pleural cavity occurred, although these nodules were still resected during VATS. Of all the patients with pneumothorax after the marking procedure, only one required chest tube placement (3.1%). No major postoperative complications were observed.

CONCLUSIONS

Preoperative marking of pulmonary nodules with I-125 seeds under CT guidance is a feasible and safe technique that allows their intraoperative identification and resection.
The feasibility of mitral valve device foldoplasty: anin vivostudy to evaluate durable retention
Authors: Wamala Isaac , Saeed Mossab Y , Hammer Peter E , Bautista-Salinas Daniel , Gauvreau Kimberlee , Ghelani Sunil J , Vasilyev Nikolay V , del Nido Pedro J
Published: July 2021

OBJECTIVES

We have previously shown in experimental settings that a leaflet foldoplasty device reduces redundant leaflet area to re-establish mitral valve (MV) coaptation. The current study investigates the in vivo device retention and functional durability following foldoplasty.

METHODS

The prototype is of superelastic nitinol formed into a 3-dimensional shape. It is unfolded to engage a specified area of leaflet tissue and then folded to exclude this tissue from the coaptation surface. Design modifications were made and tested in benchtop studies to determine the optimal design for durable retention within the leaflet. To evaluate in vivo performance, posterior leaflet chordae were severed in Yorkshire pigs to produce complete posterior leaflet prolapse and severe mitral regurgitation. Design modifications were then used for MV repair. Five animals that underwent repair using the optimal design were observed for 2 weeks postoperative to evaluate the functional result and implant retention.

RESULTS

Device position and orientation were maintained at 2 weeks while preserving the functional MV repair in all 5 animals. Coaptation height was 5.5 ± 1.5 mm, which was not significantly different from a baseline of 4.9 ± 0.8 mm. The degree of leaflet excursion was 41.0 ± 16.0 compared to a baseline of 58.7 ± 27.5.

CONCLUSIONS

Device foldoplasty is a new concept for MV repair based on the reduction of redundant leaflet tissue area. This study demonstrates the feasibility of safe maintenance of this repair without early dislodgement or embolization.
Hospital pharmacy outpatient medication dispensing and counselling practices in North-Western Nigeria: an observational study
Authors: Abdu-Aguye Samirah N , Labaran Kamilu S , Danjuma Nuhu M , Mohammed Shafiu
Published: July 2021

Objective

To describe outpatient medication dispensing and counselling processes in pharmacies located in eight hospitals in North-Western Nigeria.

Methods

An observational study was conducted from January to March 2020 in 19 hospital pharmacies located in the eight hospitals. Two types of observations were carried out, structured observations to describe the content of patient medication counselling encounters and general observations of other activities. Quantitative data were generated from the structured observations, whereas qualitative data were collected from field notes and informal discussions with dispensers. Data collected during the structured observations were descriptively analysed, whereas other data collected during the general observation periods were grouped and organized into categories.

Key findings

A total of 782 patient counselling encounters were observed during the structured observations. The most frequent types of information provided by the dispensers during these encounters included dose (98%) and route of administration (85%). Information about the name(s), indication(s), side effect(s) of medication as well as the importance of adherence were provided in less than 5% of these cases. Dispensers also made attempts to verify ownership of prescriptions to be dispensed in only 35% of these cases. Other issues observed included lack of interventions by dispensing staff during these processes. A total of 100 dispensing errors were observed, and provision of incomplete information (usually about duration of medicines use) was the most common type of dispensing error seen.

Conclusions

Several problems were observed with the medication dispensing and counselling processes for outpatients in the hospital pharmacies observed. Interventions aimed at improving these processes are required if patients are to use their medicines correctly and safely.
The Inflammatory Cytokine Profile Associated With Liver Damage Is Broader and Stronger in Patients With Chronic Hepatitis B Compared to Patients With Acute Hepatitis B
Authors: Johnson Valiente Alexandra , Liem Kin Seng , Schwarz Kathleen B , Rosenthal Philip , Murray Karen F , Mogul Douglas , Teckman Jeffery , Rodriguez-Baez Norberto , Schwarzenberg Sarah Jane , Feld Jordan J , Wong David K , Lewis-Ximenez Lia L , Lauer Georg , Hansen Bettina E , Ling Simon C , Janssen Harry L A , Gehring Adam J
Published: July 2021

Liver damage in hepatitis B is immune driven and correlates with inflammatory markers in patient serum. There is no comparison of these markers to determine if inflammatory profiles are distinct to different types of liver damage across patients at different stages of disease. We measured 25 inflammatory markers in patients with acute hepatitis B and chronic hepatitis B with hepatitis B e antigen seroconversion and chronic patients stopping nucleoside analogue therapy. Myeloid markers dominated the inflammatory profile in all stages of hepatitis B. More inflammatory markers were detectable in chronic patients, including elevated concentrations of cytotoxic effectors Fas ligand, TRAIL, and TNF-α.
Evaluation of Three Anti-SARS-CoV-2 Serologic Immunoassays for Post-Vaccine Response
Authors: Di Meo Ashley , Miller Jessica J , Fabros Anselmo , Brinc Davor , Hall Victoria , Pinzon Natalia , Ierullo Matthew , Ku Terrance , Ferreira Victor H , Kumar Deepali , Pasic Maria D , Kulasingam Vathany
Published: July 2021

Background

In North America, both messenger RNA (mRNA) vaccines, Pfizer-BioNTech BNT162b2, and Moderna mRNA-1273, each utilizing a 2-dose regimen, have started to be administered to individuals.

Methods

We evaluated the quantitative serologic antibody response following administration of either a single dose or both doses of an mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in a cohort of 98 participants (88 healthcare workers [HCW] and 10 solid organ transplant [SOT] recipients). Antibody levels were compared across 3 immunoassays: Elecsys Anti-SARS-CoV-2 S (Roche Diagnostics), SARS-CoV-2 TrimericS IgG (DiaSorin), and SARS-CoV-2 IgG II Quant (Abbott).

Results

Among HCW, sensitivity ranged from 100% (Roche), 99% (Abbott) and 98% (DiaSorin). The SARS-CoV-2 IgG II Quant and SARS-CoV-2 TrimericS IgG assays showed good agreement with a Pearson correlation coefficient of R = 0.95. Pearson correlation coefficients of R = 0.82 and 0.83 were obtained for Elecsys Anti-SARS-CoV-2 S vs SARS-CoV-2 TrimericS IgG and SARS-CoV-2 IgG II Quant vs Elecsys Anti-SARS-CoV-2 S, respectively. Significant differences in antibody levels between HCW and SOT recipients were observed. A decrease in antibody levels from time of vaccine administration to blood draw was evident. Among those with a second dose, an increase in antibody levels with increased time between administration of the first and second dose was observed.

Conclusions

The absolute values generated from each of the assay platforms are not interchangeable. Antibody levels differed with increased time between vaccine administration and with increased time between administration of the first and second dose. Further, significant differences in antibody levels between HCW and SOT recipients were observed.
Typographic Histories: Three Decades of Research
Authors: Farias Priscila L , Aynsley Jeremy
Published: July 2021

This Virtual Special Issue includes twelve articles published in the Journal of Design History between 1988 to 2020 that focus on typographic histories. The selected articles address different aspects of the subject, ranging from designing letterforms and manufacturing typefaces to putting those letterforms to use—through typesetting and letterpress printing, typewriting, collage, lithography and photocopying. To provide a context for this selection of articles this Introduction begins by characterizing the place of typographic histories within the Journal of Design History and the broader field of design history. It then considers the methods, models and approaches available that offer a framework for understanding and interpreting typographic practices and objects. Recognizing that the historiography of typography has a trajectory that predates design history by many years, reference is made to other disciplines that have contributed to this longer history. We then give a brief overview of the various kinds of archives and collections where the materials, methods and objects of typography are held and can be studied. The Introduction concludes by detailing the contribution of the selected articles, grouping them and drawing out themes that become apparent by placing them together. Finally, the article offers suggestions for future research and scholarship.
Pig pigmentation: testing Gloger’s rule
Authors: Newell Caroline , Walker Hannah , Caro Tim
Published: July 2021

Comparative studies indicate that several mammalian clades obey Gloger’s rule in that they exhibit darker coloration in humid warm climates, although the mechanisms responsible for this association still are poorly understood. We surveyed external appearances of a single species, the feral pig (Sus scrofa), shot at 48 hunting lodges across North America and matched these to potential abiotic drivers, namely: relative humidity, temperature, precipitation, and ultraviolet (UV) radiation, and to biotic factors of habitat shade and predation pressure. We found that darker animals occupy locations of greater precipitation and warmer temperatures, as expected from Gloger’s rule. The recent range expansion of S. scrofa implies selection for pelage coloration has occurred very rapidly. Separating pelage coloration into eumelanin- and phaeomelanin-based pigmentation, we found more pronounced eumelanin-based pelage in areas of higher rainfall and temperatures and UV radiation, whereas pelage phaeomelanin is related to cool dry climates with lower UV radiation. This implies that humidity or UV protection but not crypsis are the mechanisms underlying Gloger’s rule in this species and the factors driving eumelanin and phaeomelanin expression in mammalian pelage are different, reinforcing new interpretations of this venerable rule.
Gastro-cutaneous fistula treated with trionic (cell alginate activate packing)
Authors: Mahmutaj Dafina , Braha Bedri , Krasniqi Jehona
Published: July 2021

Gastrocutaneous fistulae are traditionally treated with to parenteral nutrition or surgical management. We are presenting a case of a 56-year-old man who underwent a surgical closure of a gastrocutaneous fistula with a trionic (cell alginate activate packing). The fistula recurred on postoperative day 14, after the Bilroth II operation.

For the first 8 days after filling the fistula with trionic, we applied total parenteral nutrition. Later, the patient started taking liquid foods through the mouth. The leak of the fistulous liquid was conspicuously reduced, and on the 20th day, it ceased completely.
An AMUSING look at the host of the periodic nuclear transient ASASSN-14ko reveals a second AGN
Authors: Tucker M A , Shappee B J , Hinkle J T , Neustadt J M M , Eracleous M , Kochanek C S , Prieto J L , Payne A V , Galbany L , Anderson J P , Auchettl K , Auge C , Holoien Thomas W-S
Published: July 2021

We present Multi-Unit Spectroscopic Explorer (MUSE) integral-field spectroscopy of ESO 253−G003, which hosts a known active galactic nucleus (AGN) and the periodic nuclear transient ASASSN-14ko, observed as part of the All-weather MUse Supernova Integral-field of Nearby Galaxies survey. The MUSE observations reveal that the inner region hosts two AGN separated by $1.4\pm 0.1~\rm {kpc}$ (≈1${_{.}^{\prime\prime}}$7). The brighter nucleus has asymmetric broad permitted emission-line profiles and is associated with the archival AGN designation. The fainter nucleus does not have a broad emission-line component but exhibits other AGN characteristics, including $\hbox{$v_{\rm {FWHM}}$} \approx 700~\hbox{km~s$^{-1}$}$ forbidden line emission, $\rm{\log _{10}(\rm{[O\,\small {III}]}/\rm{H\beta})} \approx 1.1$, and high-excitation potential emission lines, such as [Fe vii] λ6086 and He ii λ4686. The host galaxy exhibits a disturbed morphology with large kpc-scale tidal features, potential outflows from both nuclei, and a likely superbubble. A circular relativistic disc model cannot reproduce the asymmetric broad emission-line profiles in the brighter nucleus, but two non-axisymmetric disc models provide good fits to the broad emission-line profiles: an elliptical disc model and a circular disc + spiral arm model. Implications for the periodic nuclear transient ASASSN-14ko are discussed.
Structure and morphology of the MATLAS dwarf galaxies and their central nuclei
Authors: Poulain Mélina , Marleau Francine R , Habas Rebecca , Duc Pierre-Alain , Sánchez-Janssen Rubén , Durrell Patrick R , Paudel Sanjaya , Ahad Syeda Lammim , Chougule Abhishek , Müller Oliver , Lim Sungsoon , Bílek Michal , Fensch Jérémy
Published: July 2021

We present a photometric study of the dwarf galaxy population in the low to moderate density environments of the MATLAS (Mass Assembly of early-Type gaLAxies with their fine Structures) deep imaging survey. The sample consists of 2210 dwarfs, including 508 nucleated. We define a nucleus as a compact source that is close to the galaxy photocentre (within 0.5 $R_\mathrm{ e}$) which is also the brightest such source within the galaxy’s effective radius. The morphological analysis is performed using a 2D surface brightness profile modelling on the g-band images of both the galaxies and nuclei. Our study reveals that, for similar luminosities, the MATLAS dwarfs show ranges in the distribution of structural properties comparable to cluster (Virgo and Fornax) dwarfs and a range of sizes comparable to the Local Group and Local Volume dwarfs. Colour measurements using the r- and i-band images indicate that the dwarfs in low and moderate density environments are as red as cluster dwarfs on average. The observed similarities between dwarf ellipticals in vastly different environments imply that dEs are not uniquely the product of morphological transformation due to ram-pressure stripping and galaxy harassment in high density environments. We measure that the dwarf nuclei are located predominantly in massive, bright and round dwarfs and observe fewer nuclei in dwarfs with a faint centre and a small size. The colour of the galaxy nucleus shows no clear relation to the colour of the dwarf, in agreement with the migration and wet migration nucleus formation scenarios. The catalogues of the MATLAS dwarfs photometric and structural properties are provided.
Towards a robust estimation of orientation parameters between ICRF and Gaia celestial reference frames
Authors: Malkin Zinovy
Published: July 2021

An analysis of the source position differences between very long baseline interferometry-based ICRF and Gaia-celestial reference frame catalogues is a key step in assessing their systematic errors and determining their mutual orientation. One of the main factors that limits the accuracy of determination of the orientation parameters between two frames is the impact of outliers. To mitigate this effect, a new method is proposed based on pixelization data over the equal-area cells, followed by median filtering of the data in each cell. After this, a new data set is formed, consisting of data points near-uniformly distributed over the sphere. The vector spherical harmonics decomposition is then applied to this data to finally compute the orientation parameters between ICRF and Gaia frames. To validate the proposed approach, a comparison was made of the ICRF3-SX and Gaia DR2 catalogues using several methods for outliers removal. The results of this work showed that the proposed method is practically insensitive to outliers and thus provides much more robust results of catalogues comparison than the methods used so far. This conclusion was confirmed by analogous test comparison of the Gaia DR2 and OCARS catalogues.
Testing the chemical homogeneity of chemically tagged dissolved birth clusters
Authors: Cheng Chloe M , Price-Jones Natalie , Bovy Jo
Published: July 2021

Chemically tagging stars back to common formation sites in the Milky Way and establishing a high level of chemical homogeneity in these chemically tagged birth clusters is crucial for understanding the chemical and dynamical history of the Galactic disc. We constrain the intrinsic abundance scatter in 17 newly chemically tagged dissolved birth clusters found in the APOGEE survey by modelling APOGEE spectra as a one-dimensional function of initial stellar mass, performing forward modelling of the observed stellar spectra, then comparing the data and simulations using Approximate Bayesian Computation. We exemplify this method with the well-known open clusters M67, NGC 6819, and NGC 6791. We study 15 elements measured by APOGEE and find that, in general, we are able to obtain very strong constraints on the intrinsic abundance scatter of most elements in the chemically tagged birth clusters, with upper limits of ≲0.02 dex for C, ≲0.03 dex for O, Mn, and Fe, ≲0.04 dex for Si and Ni, and ≲0.05 dex for N, Mg, and Ca. While we find some evidence for a small amount of chemical inhomogeneity in the remaining elements (i.e. Na, Al, S, K, Ti, and V), we are still able to obtain similar or stronger limits compared to those found for open clusters, consistent with previous findings. By strongly constraining their level of chemical homogeneity, we can strengthen the statement that these groups of stars represent birth clusters, with promising implications for future chemical tagging studies.