bluuebunny/crossref_metadata_2025 huggingface dataset:
Frontal cortical functional connectivity is impacted by anaesthesia in macaques
Authors: Giacometti Camille , Dureux Audrey , Autran-Clavagnier Delphine , Wilson Charles R E , Sallet Jérôme , Dirheimer Manon , Procyk Emmanuel , Hadj-Bouziane Fadila , Amiez Céline
Published: November 2021

A critical aspect of neuroscience is to establish whether and how brain networks evolved across primates. To date, most comparative studies have used resting-state functional magnetic resonance imaging (rs-fMRI) in anaesthetized nonhuman primates and in awake humans. However, anaesthesia strongly affects rs-fMRI signals. The present study investigated the impact of the awareness state (anaesthesia vs. awake) within the same group of macaque monkeys on the rs-fMRI functional connectivity organization of a well-characterized network in the human brain, the cingulo-frontal lateral network. Results in awake macaques show that rostral seeds in the cingulate sulcus exhibited stronger correlation strength with rostral compared to caudal lateral frontal cortical areas, while more caudal seeds displayed stronger correlation strength with caudal compared to anterior lateral frontal cortical areas. Critically, this inverse rostro-caudal functional gradient was abolished under anaesthesia. This study demonstrated a similar functional connectivity (FC) organization of the cingulo-frontal cortical network in awake macaque to that previously uncovered in the human brain pointing toward a preserved FC organization from macaque to human. However, it can only be observed in awake state suggesting that this network is sensitive to anaesthesia and warranting significant caution when comparing FC patterns across species under different states.
Electrophysiological evidence for a common magnitude representation of spatiotemporal information in working memory
Authors: Cui Minghui , Peng Chunhua , Huang Mei , Chen Youguo
Published: November 2021

Spatiotemporal interference has attracted increasing attention because it provides a window for studying the neural representation of magnitude in the brain. We aimed to identify the neural basis of spatiotemporal interference using a Kappa effect task in which two circles were presented in sequence with two time intervals and three space distances. Participants reproduced the time intervals while ignoring the space distance when electroencephalogram signals were recorded synchronously. The behavior results showed that production time increased with time interval and space distance. Offset of the time intervals elicited typical P2 and P3b components. Larger parietal P2 and P3b amplitudes were elicited by the combination of longer time intervals and longer space distances. The parietal P2 and P3b amplitudes were positively correlated with the production time, and the corresponding neural source was located in the parietal cortex. The results suggest that the parietal P2 and P3b index updates a common representation of spatiotemporal information in working memory, which provides electrophysiological evidence for the mechanisms underlying spatiotemporal interferences. Our study supports a theory of magnitude, in which different dimensions can be integrated into a common magnitude representation in a generalized magnitude system that is localized at the parietal cortex.
Pyopneumopericarditis from a gastropericardial fistula: a case report
Authors: Lee John , Ramkumar Satish , Ha Phil , Raghunath Ajay , Dundon Benjamin
Published: November 2021

Background

Pyopneumopericarditis is a very rare diagnosis that requires prompt recognition and urgent treatment. It denotes the presence of pus and air in the pericardium with associated inflammation of the fibrous pericardial sac.

Case summary

A 49-year-old gentleman was admitted with pyopneumoperciarditis on a background of a previous uncomplicated Roux-en-Y gastric bypass surgery performed 7 years prior. He underwent emergency surgery for an omental patch repair of an ulcer perforation involving the diaphragm and pericardium. His inpatient stay was complicated by persistent seropurulent output from the pericardial drain, loculated pleural effusion, and deconditioning.

Discussion

Management is extrapolated from the literature regarding purulent pericarditis. This condition albeit rare, requires swift recognition as without treatment mortality approaches 100%. Colchicine is an important adjunctive therapy postoperatively to prevent constrictive physiology.
Four-dimensional echocardiography and left ventricular systolic strain measured via two-dimensional speckle-tracking for Danon disease: a case series
Authors: Changsheng Ma , Fan Jiali , Bingyuan Zhou , Jiawei Zhou , Li Wang , Lin Fan , Yuping Liao , Caiming Zhao
Published: November 2021

Background

Danon disease is an X-linked multisystemic disorder characterized by skeletal myopathy, cardiomyopathy, and intellectual disability.

Case summary

Herein, we describe two patients affected by Danon disease from the same family, a father (Patient 1) and his daughter (Patient 2). In Patient 1, a short PR interval with pre-excitation was evident. In Patient 2, over a 24-h period 2369 atrial premature beats and rare isolated ventricular ectopics were detected. Both patients exhibited left ventricular hypertrophy with non-compaction myocardium, and the left ventricular ejection fraction was impaired in Patient 1 and normal in Patient 2. In Patient 2, the total left ventricular strain value was reduced, and layer-specific strain revealed that subepicardial strain impaired more than in other layers. Late gadolinium enhancement was detected both in left and right ventricles in Patient 2, and cardiac fibrosis was more apparent in the subepicardium of left ventricular free wall. Four-dimensional (4D) echocardiography revealed that left atrial reservoir strain and left ventricular total longitudinal strain were induced.

Discussion

Novel 4D echocardiography and left ventricular systolic strain may play important role in diagnosis and myocardial functional evaluation in Danon disease.
Immunomodulation in antiphospholipid-antibody-associated endocarditis: a case report and review of the literature
Authors: Haertel Franz , Kretzschmar Daniel , Schulze P Christian , Neumann Thomas
Published: November 2021

Background

Non-infectious endocarditis is a rare complication in patients with systemic lupus erythematosus or antiphospholipid syndrome (APS). The mitral valve is mainly affected, usually showing vegetations on the ventricular and atrial side of the valve.

Case summary

A 27-year-old female patient with a known APS was referred to our hospital with night sweats, weight loss, reduction in performance, and dizziness. A floating structure associated to the mitral valve was identified in a transoesophageal echocardiogram with typical changes, in accordance with a non-infectious endocarditis (Libman–Sacks). Only a trace of mitral regurgitation was present and a mass on the posterior mitral valve leaflet. Laboratory findings showed antibody and inflammatory marker measurements either negative or within normal range. The patient received therapeutic oral anticoagulation using a vitamin K antagonist and a combined immunosuppression consisting of hydroxychloroquine and prednisolone. The symptoms of the patient resolved within 3 months after starting the initial treatment. The follow-up echocardiogram showed an almost normal mitral valve function with only a slight regional thickening of the posterior mitral leaflet and no stenosis. Following a 7-year period of observation being on a medical regimen of hydroxychloroquine and a vitamin K antagonist, no evidence of clinical and/or echocardiographic recurrence was detected.

Discussion

This case report represents a successful medical management of non-infectious endocarditis using immunosuppressive and anticoagulation therapies without significant residual lesions. Although optimal management of non-bacterial endocarditis remains in the area of uncertainty, this combination therapy deems promising.
Case report of heart transplantation for giant cell myocarditis in a patient with common variable immunodeficiency
Authors: Franzon Thomas A , Kovalszki Anna , Rabah Raja , Nicklas John M
Published: November 2021

Background

Solid-organ transplantation in patients with common variable immunodeficiency (CVID) is controversial due to the risk for severe and recurrent infections. Determining transplantation candidacy in CVID patients is further complicated by the presence of CVID-related non-infectious complications that can reduce overall survival and also recur in the transplanted organ. Data regarding solid organ transplantation in patients with CVID are limited, particularly in heart transplantation.

Case summary

A 32-year-old female with CVID presented with new heart failure after 3 months of dyspnoea on exertion. Her echocardiogram showed severe global systolic dysfunction with an ejection fraction of approximately 10%, and her right heart catheterization revealed severe biventricular pressure overload and severely reduced cardiac output. Endomyocardial biopsy revealed giant cells and mononuclear infiltrate consistent with giant cell myocarditis (GCM). Despite medical management, she developed progressive cardiogenic shock and underwent uncomplicated orthotopic heart transplantation on hospital Day 38. After 2 years of follow-up, she has had no major infectious complications and continues to have normal graft function with no recurrence of GCM.

Conclusion

We report a case of successful heart transplantation for GCM in a patient with CVID, with no major infectious complications after 2 years of follow-up. CVID should not be considered an absolute contraindication for heart transplantation.
Abiraterone-induced refractory hypokalaemia and torsades de pointes in a patient with metastatic castration-resistant prostate carcinoma: a case report
Authors: Riad Mariam , Allison Jeffery Scott , Nayyal Shahla , Hritani AbdulWahab
Published: November 2021

Background

Abiraterone, an androgen deprivation therapy, has been used in the treatment of metastatic castration-resistant prostate cancer (mCRPC). It has been associated with increased risks of hypokalaemia and cardiac disorders. We report a case of torsades de pointes (TdP) associated with abiraterone use and refractory hypokalaemia in a man with mCRPC.

Case summary

A 78-year-old man with mCRPC presented to the emergency room for generalized weakness. Laboratory results revealed a potassium level of 2.2 mmol/L (3.5–5.0), magnesium level of 2.4 mg/dL (1.6–2.5), and normal kidney and hepatic functions. Initial electrocardiogram showed atrial fibrillation with rapid ventricular rate of 106 b.p.m., frequent premature ventricular contractions, and a QTc of 634 ms. The patient had multiple episodes of TdP, became pulseless and underwent advanced cardiac life support, including defibrillation. Despite a total of 220 mEq of intravenous potassium chloride, his potassium level only improved to 2.8 mmol/L. He received spironolactone and amiloride to promote urinary potassium reabsorption in addition to hydrocortisone, in an effort to reduce abiraterone’s effect on increasing mineralocorticoid synthesis.

Discussion

Abiraterone has been widely used in mCRPC since its approval by the Food and Drug Adminstration in 2011. Regulatory guidelines and standardized close QTc and electrolyte monitoring in patients may help prevent fatal arrhythmias associated with abiraterone.
An m-Health intervention to improve education, self-management, and outcomes in patients admitted for acute decompensated heart failure: barriers to effective implementation
Authors: Zisis Georgios , Carrington Melinda J , Oldenburg Brian , Whitmore Kristyn , Lay Maria , Huynh Quan , Neil Christopher , Ball Jocasta , Marwick Thomas H
Published: November 2021

Aims

Effective and efficient education and patient engagement are fundamental to improve health outcomes in heart failure (HF). The use of artificial intelligence (AI) to enable more effective delivery of education is becoming more widespread for a range of chronic conditions. We sought to determine whether an avatar-based HF-app could improve outcomes by enhancing HF knowledge and improving patient quality of life and self-care behaviour.

Methods and results

In a randomized controlled trial of patients admitted for acute decompensated HF (ADHF), patients at high risk (≥33%) for 30-day hospital readmission and/or death were randomized to usual care or training with the HF-app. From August 2019 up until December 2020, 200 patients admitted to the hospital for ADHF were enrolled in the Risk-HF study. Of the 72 at high-risk, 36 (25 men; median age 81.5 years; 9.5 years of education; 15 in NYHA Class III at discharge) were randomized into the intervention arm and were offered education involving an HF-app. Whilst 26 (72%) could not use the HF-app, younger patients [odds ratio (OR) 0.89, 95% confidence interval (CI) 0.82–0.97; P < 0.01] and those with a higher education level (OR 1.58, 95% CI 1.09–2.28; P = 0.03) were more likely to enrol. Of those enrolled, only 2 of 10 patients engaged and completed ≥70% of the program, and 6 of the remaining 8 who did not engage were readmitted.

Conclusions

Although AI-based education is promising in chronic conditions, our study provides a note of caution about the barriers to enrolment in critically ill, post-acute, and elderly patients.
Can machine learning bring cardiovascular risk assessment to the next level? A methodological study using FOURIER trial data
Authors: Rousset Adrien , Dellamonica David , Menuet Romuald , Lira Pineda Armando , Sabatine Marc S , Giugliano Robert P , Trichelair Paul , Zaslavskiy Mikhail , Ricci Lea
Published: November 2021

Aims

Through this proof of concept, we studied the potential added value of machine learning (ML) methods in building cardiovascular risk scores from structured data and the conditions under which they outperform linear statistical models.

Methods and results

Relying on extensive cardiovascular clinical data from FOURIER, a randomized clinical trial to test for evolocumab efficacy, we compared linear models, neural networks, random forest, and gradient boosting machines for predicting the risk of major adverse cardiovascular events. To study the relative strengths of each method, we extended the comparison to restricted subsets of the full FOURIER dataset, limiting either the number of available patients or the number of their characteristics. When using all the 428 covariates available in the dataset, ML methods significantly (c-index 0.67, P-value 2e−5) outperformed linear models built from the same variables (c-index 0.62), as well as a reference cardiovascular risk score based on only 10 variables (c-index 0.60). We showed that gradient boosting—the best performing model in our setting—requires fewer patients and significantly outperforms linear models when using large numbers of variables. On the other hand, we illustrate how linear models suffer from being trained on too many variables, thus requiring a more careful prior selection. These ML methods proved to consistently improve risk assessment, to be interpretable despite their complexity and to help identify the minimal set of covariates necessary to achieve top performance.

Conclusion

In the field of secondary cardiovascular events prevention, given the increased availability of extensive electronic health records, ML methods could open the door to more powerful tools for patient risk stratification and treatment allocation strategies.
High-intensity statin treatment is associated with reduced plaque structural stress and remodelling of artery geometry and plaque architecture
Authors: Gu Sophie Z , Costopoulos Charis , Huang Yuan , Bourantas Christos , Woolf Adam , Sun Chang , Teng Zhongzhao , Losdat Sylvain , Räber Lorenz , Samady Habib , Bennett Martin R
Published: November 2021

Aims

Plaque structural stress (PSS) is a major cause of atherosclerotic plaque rupture and major adverse cardiovascular events (MACE). We examined the predictors of changes in peak and mean PSS (ΔPSSpeak, ΔPSSmean) in three studies of patients receiving either standard medical or high-intensity statin (HIS) treatment.

Methods and results

We examined changes in PSS, plaque size, and composition between 7348 co-registered baseline and follow-up virtual-histology intravascular ultrasound images in patients receiving standard medical treatment (controls, n = 18) or HIS (atorvastatin 80 mg, n = 20, or rosuvastatin 40 mg, n = 22). The relationship between changes in PSSpeak and plaque burden (PB) differed significantly between HIS and control groups (P < 0.001). Notably, PSSpeak increased significantly in control lesions with PB >60% (P = 0.04), but not with HIS treatment. However, ΔPSSpeak correlated poorly with changes in lumen and plaque area or PB, plaque composition, or lipid lowering. In contrast, ΔPSSpeak correlated significantly with changes in lumen curvature, irregularity, and roughness (P < 0.05), all of which were reduced in HIS patients. ΔPSSmean correlated with changes in lumen area, PA, PB, and circumferential calcification, and was unchanged with either treatment.

Conclusion

Our observational study shows that PSSpeak changes over time were associated with baseline disease severity and treatment. The PSSpeak increase seen in advanced lesions with standard treatment was associated with remodelling artery geometry and plaque architecture, but this was not seen after HIS treatment. Smoothing plaques by reducing plaque/lumen roughness, irregularity, and curvature represents a novel mechanism whereby HIS may reduce PSS and, thus may protect against plaque rupture and MACE.
Intrahousehold Resource Allocation and Individual Poverty: Assessing Collective Model Predictions using Direct Evidence on Sharing
Authors: Bargain Olivier , Lacroix Guy , Tiberti Luca
Published: November 2021

Welfare analyses conducted by policy practitioners around the world usually rely on equivalised or per capita expenditures and ignore the extent of within-household inequality. Recent advances in the estimation of collective models suggest ways to retrieve the complete sharing process within families using homogeneity assumptions (typically preference stability upon exclusive goods across individuals or household types) and the observation of exclusive goods. So far, the prediction of these models has not been validated, essentially because intrahousehold allocation is seldom observed. We provide such a validation by leveraging a unique dataset from Bangladesh, which contains information on the fully individualised expenditures of each family member. We also test the core assumption (efficiency) and homogeneity assumptions used for identification. It turns out that the collective model predicts individual resources reasonably well when using clothing, i.e., one of the rare goods commonly assignable to males, females and children in standard expenditure surveys. It also allows for identifying poor individuals in non-poor households, while the traditional approach understates poverty among the poorest individuals.
Can External Threats Foster a European Union Identity? Evidence from Russia’s Invasion of Ukraine
Authors: Gehring Kai
Published: November 2021

Can external threats strengthen group identity? A growing body of research in economics emphasises the importance of cultural attributes such as identity for trust and cooperation. However, where these attributes come from is not well understood. This paper examines reactions to the Russian invasion of Ukraine in 2014, looking at European Union member states. Comparing low-threat to high-threat states in a difference-in-differences design, I find a sizeable and persistent positive effect on EU identity. It is associated with higher trust in EU institutions and support for common policies. Lower-level identities remain unaffected, and proximity to Russia and Russian minority size are driving high-threat status.
Influence of residual primary entry following the tear-oriented strategy for acute type A aortic dissection
Authors: Kawahito Koji , Aizawa Kei , Kimura Naoyuki , Yamaguchi Atsushi , Adachi Hideo
Published: November 2021

OBJECTIVES

Although a tear-oriented strategy has contributed to improving short-term surgical outcomes of acute type A aortic dissection (ATAAD), long-term clinical influences of residual entry tear in the downstream aorta have not been fully investigated. The goal of this study was to assess the long-term surgical outcomes of ATAAD with or without a residual entry tear in the downstream aorta.

METHODS

Medical records of 1107 patients with ATAAD who underwent emergency surgery between 1990 and 2018 were retrospectively reviewed. A tear-oriented paradigm was adopted for the baseline strategy. The 837 patients in whom the entry tears were resected comprised the resected group, and the 270 patients with a residual entry tear comprised the residual group. Of these patients, 252 in each group were analysed using propensity score matching, and long-term outcomes were compared with or without residual entry.

RESULTS

Hospital deaths were lower in the resected group (3.2% vs 8.3%; P = 0.020). The survival rate was not significantly different between the groups: It was 83.8% and 68.5% in the resected group and 80.2% and 66.5% in the residual group at 5 and 10 years, respectively (P = 0.600). However, residual entry in the downstream aorta affected the distal aortic event-free survival rate (90.4% and 80.6% in the resected group and 82.3% and 67.4% in the residual group at 5 and 10 years, respectively; P = 0.003). Furthermore, multivariable risk analysis of 1107 patients confirmed that a residual entry in the downstream aorta was a risk factor for distal aortic events.

CONCLUSIONS

The tear-oriented strategy remains the gold standard for high-risk patients; however, the extensive operation might be considered for stable patients to reduce long-term aortic events.
Acromegaly and cardiovascular outcomes: a cohort study
Authors: Hong Sangmo , Kim Kyung-Soo , Han Kyungdo , Park Cheol-Young
Published: November 2021

Aims

Cardiovascular disease is a common complication in acromegaly. We investigated the risk of cardiovascular disease and mortality in patients with acromegaly in a large-scale population using nationwide data in Korea.

Methods and results

We performed a nationwide, retrospective, observational, cohort study of patients with acromegaly (n = 1874) and age- and sex-matched subjects without acromegaly (n = 9370) for a mean follow-up of 7.5 ± 3.2 years. The study outcomes were myocardial infarction, stroke, atrial fibrillation, congestive heart failure, and all-cause death. All outcomes were analysed by Cox proportional hazards regression analysis while controlling for age, sex, household income, place, Type 2 diabetes, hypertension, and dyslipidaemia. The incidence (per 1000 person-years) of atrial fibrillation (3.06 vs. 1.70; P = 0.001), congestive heart failure (3.11 vs. 1.63; P < 0.001), and all-cause mortality (6.31 vs. 4.03; P < 0.001) in patients with acromegaly was higher than in controls. However, the incidence of myocardial infarction and stroke did not differ between groups. After adjustment for covariates, the risk for atrial fibrillation [hazard ratio (HR): 1.59; 95% confidence interval (CI): 1.09–2.31], congestive heart failure (HR: 1.54; 95% CI: 1.06–2.25), and all-cause mortality (HR: 1.31; 95% CI: 1.01–1.69) was significantly higher in patients with acromegaly. In time lag sensitivity analysis, a higher risk for atrial fibrillation was observed only in the first 4 years after diagnosis in acromegaly patients compared with controls (HR: 3.05; 95% CI: 1.94–4.79).

Conclusion

Patients with acromegaly were at higher risk for atrial fibrillation, congestive heart failure, and all-cause death. The risk of atrial fibrillation had a time-dependent association with acromegaly.
Profile of patients with type 2 diabetes and glycated haemoglobin ≥ 10% followed in general practice
Authors: Fortin Frédéric , Vorilhon Philippe , Laporte Catherine , Boirie Yves , Ruivard Marc , Riquelme Marie , Pereira Bruno , Tanguy Gilles
Published: November 2021

Objective

To determine whether profiles of patients with unbalanced type 2 diabetes (T2DM) and glycated haemoglobin (HbA1c) ≥ 10% could be identified on the basis of socio-demographic, behavioural, clinical, and biological characteristics.

Methods

Retrospective, cross-sectional, factorial analysis study of patients with T2DM treated for at least 1 year, with HbA1c ≥ 10%. Patients were recruited via medical analysis laboratories, France. Patients were followed up in general practice with possible recourse to specialist consultations. Data were collected by means of self-administered questionnaires sent by post.

Results

A total of 104 patients were included: 69 men and 35 women, with a median age of 66 ± 12 years, body mass index 30.7 ± 6.2kg/m2 and 47% in a vulnerable socio-economic situation. Fifty patients (48%) were followed exclusively by their general practitioners and only 30% had no compliance problems. Creatinuria was measured at least once during the year in 92% of patients, but microalbuminuria was measured in only 20%. Age, socio-economic precariousness, insulin treatment, and follow-up by several health professionals had a negative influence on quality of life (QoL). Two patient profiles were defined by factor analysis: (i) young, rural, smoker, socially isolated, precarious patient with poor compliance and QoL; and (ii) elderly, urban, regular physical activity, in a couple, without precariousness and with satisfactory QoL.

Conclusions

Analysis of the characteristics of patients with T2DM and glycaemic imbalance reveals profiles that are useful in clinical practice for a personalized approach to treatment and active prevention of diabetes complications.
Taxonomic and functional characterization of the rumen microbiome of Japanese Black cattle revealed by 16S rRNA gene amplicon and metagenome shotgun sequencing
Authors: Sato Yoshiaki , Takebe Hiroaki , Tominaga Kento , Oishi Kazato , Kumagai Hajime , Yoshida Takashi , Hirooka Hiroyuki
Published: November 2021

This study aimed to determine the taxonomic and functional characteristics of the Japanese Black (JB) steer rumen microbiome. The rumen microbiomes of six JB steers (age 14.7 ± 1.44 months) and six JB sires × Holstein dams crossbred (F1) steers (age 11.1 ± 0.39 months), fed the same diet, were evaluated. Based on 16S rRNA gene sequencing, the beta diversity revealed differences in microbial community structures between the JB and F1 rumen. Shotgun sequencing showed that Fibrobacter succinogenes and two Ruminococcus spp., which are related to cellulose degradation were relatively more abundant in the JB steer rumen than in the F1 rumen. Furthermore, the 16S rRNA gene copy number of F. succinogenes was significantly higher in the JB steer rumen than in the F1 rumen according to quantitative real-time polymerase chain reaction analysis. Genes encoding the enzymes that accelerate cellulose degradation and those associated with hemicellulose degradation were enriched in the JB steer rumen. Although Prevotella spp. were predominant both in the JB and F1 rumen, the genes encoding carbohydrate-active enzymes of Prevotella spp. may differ between JB and F1.
Pesticide-induced disturbances of bee gut microbiotas
Authors: Hotchkiss Michelle Z , Poulain Alexandre J , Forrest Jessica R K
Published: November 2021

Social bee gut microbiotas play key roles in host health and performance. Worryingly, a growing body of literature shows that pesticide exposure can disturb these microbiotas. Most studies examine changes in taxonomic composition in Western honey bee (Apis mellifera) gut microbiotas caused by insecticide exposure. Core bee gut microbiota taxa shift in abundance after exposure but are rarely eliminated, with declines in Bifidobacteriales and Lactobacillus near melliventris abundance being the most common shifts. Pesticide concentration, exposure duration, season and concurrent stressors all influence whether and how bee gut microbiotas are disturbed. Also, the mechanism of disturbance—i.e. whether a pesticide directly affects microbial growth or indirectly affects the microbiota by altering host health—likely affects disturbance consistency. Despite growing interest in this topic, important questions remain unanswered. Specifically, metabolic shifts in bee gut microbiotas remain largely uninvestigated, as do effects of pesticide-disturbed gut microbiotas on bee host performance. Furthermore, few bee species have been studied other than A. mellifera, and few herbicides and fungicides have been examined. We call for these knowledge gaps to be addressed so that we may obtain a comprehensive picture of how pesticides alter bee gut microbiotas, and of the functional consequences of these changes.
Wing hearts in four-wingedUltrabithorax-mutant flies—the role of Hox genes in wing heart specification
Authors: Tögel Markus , Pass Günther , Paululat Achim
Published: November 2021

Wings are probably the most advanced evolutionary novelty in insects. In the fruit fly Drosophila melanogaster, proper development of wings requires the activity of so-called wing hearts located in the scutellum of the thorax. Immediately after the imaginal ecdysis, these accessory circulatory organs remove hemolymph and apoptotic epidermal cells from the premature wings through their pumping action. This clearing process is essential for the formation of functional wing blades. Mutant flies that lack intact wing hearts are flightless and display malformed wings. The embryonic wing heart progenitors originate from two adjacent parasegments corresponding to the later second and third thoracic segments. However, adult dipterian flies harbor only one pair of wings and only one pair of associated wing hearts in the second thoracic segment. Here we show that the specification of WHPs depends on the regulatory activity of the Hox gene Ultrabithorax. Furthermore, we analyzed the development of wing hearts in the famous four-winged Ultrabithorax (Ubx) mutant, which was first discovered by Ed Lewis in the 1970s. In these flies, the third thoracic segment is homeotically transformed into a second thoracic segment resulting in a second pair of wings instead of the club-shaped halteres. We show that a second pair of functional wing hearts is formed in the transformed third thoracic segment and that all wing hearts originate from the wild-type population of wing heart progenitor cells.
Multiple epistatic DNA variants in a single gene affect gene expression in trans
Authors: Lutz Sheila , Van Dyke Krisna , Feraru Matthew A , Albert Frank W
Published: November 2021

DNA variants that alter gene expression in trans are important sources of phenotypic variation. Nevertheless, the identity of trans-acting variants remains poorly understood. Single causal variants in several genes have been reported to affect the expression of numerous distant genes in trans. Whether these simple molecular architectures are representative of trans-acting variation is unknown. Here, we studied the large RAS signaling regulator gene IRA2, which contains variants with extensive trans-acting effects on gene expression in the yeast Saccharomyces cerevisiae. We used systematic CRISPR-based genome engineering and a sensitive phenotyping strategy to dissect causal variants to the nucleotide level. In contrast to the simple molecular architectures known so far, IRA2 contained at least seven causal nonsynonymous variants. The effects of these variants were modulated by nonadditive, epistatic interactions. Two variants at the 5′-end affected gene expression and growth only when combined with a third variant that also had no effect in isolation. Our findings indicate that the molecular basis of trans-acting genetic variation may be considerably more complex than previously appreciated.
Replication Note: What is Political Incivility?
Authors: Stryker Robin , Conway Bethany Anne , Bauldry Shawn , Kaul Vasundhara
Published: November 2021

Because political incivility is so consequential and those consequences depend on observers’ perceptions, we must know what Americans perceive as uncivil. Stryker, Conway, and Danielson (2016) conducted one of the first studies addressing this using confirmatory factor analysis on 23 types of potential incivility, but the authors used a local sample representing undergraduates at one southwestern university. Using 20 of their 23 measures and replicating their analyses on a national sample of more than 2000 respondents representing U.S. whites, Blacks, and Latinx, this study finds the same conceptual structure for perceived political incivility with very similar response patterns as Stryker et al. (2016). Perceived political incivility is an overarching construct with three analytically distinct, inter-correlated dimensions: insulting utterances, deception, and behaviors that tend to shut down ongoing and inclusive discussion.
Target-Based Small Molecule Drug Discovery Towards Novel Therapeutics for Inflammatory Bowel Diseases
Authors: Li Yi , Chen Jianping , Bolinger Andrew A , Chen Haiying , Liu Zhiqing , Cong Yingzi , Brasier Allan R , Pinchuk Irina V , Tian Bing , Zhou Jia
Published: November 2021

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a class of severe and chronic diseases of the gastrointestinal (GI) tract with recurrent symptoms and significant morbidity. Long-term persistence of chronic inflammation in IBD is a major contributing factor to neoplastic transformation and the development of colitis-associated colorectal cancer. Conversely, persistence of transmural inflammation in CD is associated with formation of fibrosing strictures, resulting in substantial morbidity. The recent introduction of biological response modifiers as IBD therapies, such as antibodies neutralizing tumor necrosis factor (TNF)-α, have replaced nonselective anti-inflammatory corticosteroids in disease management. However, a large proportion (~40%) of patients with the treatment of anti-TNF-α antibodies are discontinued or withdrawn from therapy because of (1) primary nonresponse, (2) secondary loss of response, (3) opportunistic infection, or (4) onset of cancer. Therefore, the development of novel and effective therapeutics targeting specific signaling pathways in the pathogenesis of IBD is urgently needed. In this comprehensive review, we summarize the recent advances in drug discovery of new small molecules in preclinical or clinical development for treating IBD that target biologically relevant pathways in mucosal inflammation. These include intracellular enzymes (Janus kinases, receptor interacting protein, phosphodiesterase 4, IκB kinase), integrins, G protein-coupled receptors (S1P, CCR9, CXCR4, CB2) and inflammasome mediators (NLRP3), etc. We will also discuss emerging evidence of a distinct mechanism of action, bromodomain-containing protein 4, an epigenetic regulator of pathways involved in the activation, communication, and trafficking of immune cells. We highlight their chemotypes, mode of actions, structure-activity relationships, characterizations, and their in vitro/in vivo activities and therapeutic potential. The perspectives on the relevant challenges, new opportunities, and future directions in this field are also discussed.
Characterization of Mycophenolate Mofetil Gastrointestinal Toxicity and Risk Factors for Severe Disease and Poor Prognosis
Authors: Bhattacharya Sumona , Stoleru Gianna , Patel Preet , Abutaleb Ameer , Stashek Kristen , Cross Raymond K
Published: November 2021

Lay Summary

Authors performed a chart review to identify cases of mycophenolate mofetil gastrointestinal toxicity at our institution. In this cohort, friability was associated with severe disease; and nausea and erythema were associated with poor prognosis.
Treatment of Fistulizing Perianal Crohn’s Disease by Autologous Microfat Enriched With Adipose-Derived Regenerative Cells
Authors: Sørensen Karam Matlub , Jensen Charlotte Harken , Sheikh Søren Paludan , Qvist Niels , Sørensen Jens Ahm
Published: November 2021

In this pilot study, short-term efficacy and safety of fat graft enriched with Adipose-Derived Regenerative Cells (ADRC) in the treatment of Crohn’s high anal fistula was evaluated. Clinical fistula healing was achievable in 75% of cases, by a single treatment.
On ℓp-Gaussian–Grothendieck Problem
Authors: Chen Wei-Kuo , Sen Arnab
Published: November 2021

For $p\geq 1$ and $(g_{ij})_{1\leq i,j\leq n}$ being a matrix of i.i.d. standard Gaussian entries, we study the $n$-limit of the $\ell _p$-Gaussian–Grothendieck problem defined as $$\begin{align*} & \max\Bigl\{\sum_{i,j=1}^n g_{ij}x_ix_j: x\in \mathbb{R}^n,\sum_{i=1}^n |x_i|^p=1\Bigr\}. \end{align*}$$The case $p=2$ corresponds to the top eigenvalue of the Gaussian orthogonal ensemble; when $p=\infty $, the maximum value is essentially the ground state energy of the Sherrington–Kirkpatrick mean-field spin glass model and its limit can be expressed by the famous Parisi formula. In the present work, we focus on the cases $1\leq p<2$ and $2<p<\infty .$ For the former, we compute the limit of the $\ell _p$-Gaussian–Grothendieck problem and investigate the structure of the set of all near optimizers along with stability estimates. In the latter case, we show that this problem admits a Parisi-type variational representation and the corresponding optimizer is weakly delocalized in the sense that its entries vanish uniformly in a polynomial order of $n^{-1}$.
Rapid SARS-CoV-2 Inactivation in a Simulated Hospital Room Using a Mobile and Autonomous Robot Emitting Ultraviolet-C Light
Authors: Lorca-Oró Cristina , Vila Jordi , Pleguezuelos Patricia , Vergara-Alert Júlia , Rodon Jordi , Majó Natàlia , López Sergio , Segalés Joaquim , Saldaña-Buesa Francesc , Visa-Boladeras Maria , Veà-Baró Andreu , Campistol Josep Maria , Abad Xavier
Published: November 2021

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since 2019 has made mask-wearing, physical distancing, hygiene, and disinfection complementary measures to control virus transmission. Especially for health facilities, we evaluated the efficacy of an UV-C autonomous robot to inactivate SARS-CoV-2 desiccated on potentially contaminated surfaces. ASSUM (autonomous sanitary sterilization ultraviolet machine) robot was used in an experimental box simulating a hospital intensive care unit room. Desiccated SARS-CoV-2 samples were exposed to UV-C in 2 independent runs of 5, 12, and 20 minutes. Residual virus was eluted from surfaces and viral titration was carried out in Vero E6 cells. ASSUM inactivated SARS-CoV-2 by ≥ 99.91% to ≥ 99.99% titer reduction with 12 minutes or longer of UV-C exposure and onwards and a minimum distance of 100cm between the device and the SARS-CoV-2 desiccated samples. This study demonstrates that ASSUM UV-C device is able to inactivate SARS-CoV-2 within a few minutes.
Environmental Thermal Stress Induces Neuronal Cell Death and Developmental Malformations in Reptiles
Authors: Sanger Thomas J , Harding Laura , Kyrkos Judith , Turnquist Alexandrea J , Epperlein Lilian , Nunez Sylvia A , Lachance Dryden , Dhindsa Seerat , Stroud James T , Diaz Raul E , Czesny Beata
Published: November 2021

Synopsis

Every stage of organismal life history is being challenged by global warming. Many species are already experiencing temperatures approaching their physiological limits; this is particularly true for ectothermic species, such as lizards. Embryos are markedly sensitive to thermal insult. Here, we demonstrate that temperatures currently experienced in natural nesting areas can modify gene expression levels and induce neural and craniofacial malformations in embryos of the lizard Anolis sagrei. Developmental abnormalities ranged from minor changes in facial structure to significant disruption of anterior face and forebrain. The first several days of postoviposition development are particularly sensitive to this thermal insult. These results raise new concern over the viability of ectothermic species under contemporary climate change. Herein, we propose and test a novel developmental hypothesis that describes the cellular and developmental origins of those malformations: cell death in the developing forebrain and abnormal facial induction due to disrupted Hedgehog signaling. Based on similarities in the embryonic response to thermal stress among distantly related species, we propose that this developmental hypothesis represents a common embryonic response to thermal insult among amniote embryos. Our results emphasize the importance of adopting a broad, multidisciplinary approach that includes both lab and field perspectives when trying to understand the future impacts of anthropogenic change on animal development.
Key requirements of a video-call system in a critical care department as discovered during the rapid development of a solution to address COVID-19 visitor restrictions
Authors: Conroy Irial , Murray Aoife , Kirrane Frank , Cullen Leonie , Anglim Paul , O’Keeffe Derek
Published: November 2021

The COVID-19 pandemic necessitated stringent visitor restrictions in critical care departments worldwide, creating challenges in keeping family members connected to patients and clinical staff. Previous studies have examined how hospitals addressed this challenge by repurposing existing tele-ICU systems or by using personal smartphones as a workaround and have analyzed clinical and family feedback. This case report addresses the experience of rapidly implementing a video-call system in the critical care department of a tertiary referral hospital that had no prior video-call system in place, detailing the key requirements in that setting. The 24 requirements were identified via interviews and surveys to both clinical and technical professionals. The top requirements identified were sound and video quality, usability for clinical staff, call control by staff, and patient privacy. From tailoring a video-call solution for this setting, we learned that video-endpoint selection is a key design decision. The initial proposal was to use wireless tablets, but the selection of a large wired video-endpoint allowed us to better address the requirements in the critical care setting. This was based on several characteristics of the large wired video-endpoint, including: high-fidelity video and sound, with directional noise-cancelling; large touch-screen setup for minimal-click navigation; wired as well as wireless connectivity.
Evaluation of reticulorumen temperature boluses for the diagnosis of subclinical cases of bovine respiratory disease in feedlot cattle
Authors: Flattot Emilie A-L , Batterham Tony R , Timsit Edouard , White Brad J , McMeniman Joe P , Ward Michael P , González Luciano A
Published: November 2021

Bovine respiratory disease (BRD) is the most important and costly health issue of the feedlot industry worldwide. Remote monitoring of reticulorumen temperature has been suggested as a potential tool to improve the diagnostic accuracy of BRD. The present study aimed to evaluate 1) the difference and degree of reticulorumen hyperthermia episodes between healthy and subclinical BRD feedlot steers, and 2) determine the correlation between reticulorumen hyperthermia and lung pathology, performance, and carcass traits. Mixed-breed feedlot steers (n = 148) with a mean arrival weight of 321 ± 3.34 kg were administered a reticulorumen bolus at feedlot entry and monitored for visual and audible signs of BRD until slaughter when lungs were examined and scored for lesions indicative of BRD. Post-slaughter animals with no record of BRD treatment were assigned to one of three case definitions. Healthy steers had no visual or audible signs of BRD (i.e., CIS=1), and total lung consolidation score < 5% or pleurisy score < 3 at slaughter. Subclinical BRD cases had a CIS of 1, and a lung consolidation score ≥ 5% or a pleurisy score of 3 at slaughter. Mild CIS cases had at least one CIS of 2, and a lung consolidation score < 5% and a pleurisy score < 3 at slaughter. Subclinical BRD and mild CIS cases had longer total duration of reticulorumen hyperthermia, more episodes and longer average episode duration above 40.0 °C compared to healthy steers (P < 0.05). A moderate positive correlation was found between lung consolidation and total duration (r = 0.27, P < 0.001), episode duration (r = 0.29, P < 0.001), and number of episodes (r = 0.20, P < 0.05). Pleurisy score was also found to be moderately and positively correlated with total duration (r = 0.23, P < 0.01), episode duration (r = 0.37, P < 0.001), and number of episodes (r = 0.26, P < 0.01). Moderate negative correlations were found between reticulorumen hyperthermia and carcass traits including hot standard carcass weight (HSCW) (−0.22 ≤ r ≤ −0.23, P < 0.05) and P8-fat depth (−0.18 ≤ r ≤ −0.32, P < 0.05). Subclinical BRD reduced carcass weight by 22 kg and average daily gain (ADG) by 0.44 kg/day compared to healthy steers (P < 0.05), but mild CIS cases had no effect on performance (P > 0.05). The reticulorumen bolus technology appears promising for detection of subclinical BRD cases in feedlot cattle as defined by lung pathology at slaughter.
Technical note: overcoming host contamination in bovine vaginal metagenomic samples with nanopore adaptive sequencing
Authors: Ong Chian Teng , Ross Elizabeth M , Boe-Hansen Gry B , Turni Conny , Hayes Ben J , Tabor Ala E
Published: November 2021

Animal metagenomic studies, in which host-associated microbiomes are profiled, are an increasingly important contribution to our understanding of the physiological functions, health and susceptibility to diseases of livestock. One of the major challenges in these studies is host DNA contamination, which limits the sequencing capacity for metagenomic content and reduces the accuracy of metagenomic profiling. This is the first study comparing the effectiveness of different sequencing methods for profiling bovine vaginal metagenomic samples. We compared the new method of Oxford Nanopore Technologies (ONT) adaptive sequencing, which can be used to target or eliminate defined genetic sequences, to standard ONT sequencing, Illumina 16S rDNA amplicon sequencing, and Illumina shotgun sequencing. The efficiency of each method in recovering the metagenomic data and recalling the metagenomic profiles was assessed. ONT adaptive sequencing yielded a higher amount of metagenomic data than the other methods per 1 Gb of sequence data. The increased sequencing efficiency of ONT adaptive sequencing consequently reduced the amount of raw data needed to provide sufficient coverage for the metagenomic samples with high host-to-microbe DNA ratio. Additionally, the long reads generated by ONT adaptive sequencing retained the continuity of read information, which benefited the in-depth annotations for both taxonomical and functional profiles of the metagenome. The different methods resulted in the identification of different taxa. Genera Clostridium, which was identified at low abundances and categorized under Order “Unclassified Clostridiales” when using the 16S rDNA amplicon sequencing method, was identified to be the dominant genera in the sample when sequenced with the three other methods. Additionally, higher numbers of annotated genes were identified with ONT adaptive sequencing, which also produced high coverage on most of the commonly annotated genes. This study illustrates the advantages of ONT adaptive sequencing in improving the amount of metagenomic data derived from microbiome samples with high host-to-microbe DNA ratio and the advantage of long reads in preserving intact information for accurate annotations.