bluuebunny/crossref_metadata_2025 huggingface dataset:
The usage CZT SPECT to assess myocardial blood flow and flow reserve in myocardial infarction with non-obstructive coronary arteries patients
Authors: Maltseva A , Mochula A , Vorobyeva D , Gulya M , Ryabov V , Zavadovsky K
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background. Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) is currently of interest in terms of a small amount of data related to myocardial perfusion, myocardial blood flow (MBF) and myocardial flow reserve (MFR).

Purpose. To assess the severity of myocardial perfusion, MBF and MFR impairment in MINOCA patients in comparison to those with MI with obstructive coronary artery disease (MICAD) and non-obstructive stable coronary artery disease (SCAD).

Methods. The study group comprised 40 patients (29 men, mean age 62.9 ± 10.7 years). 28 patients were admitted to the hospital due to the acute coronary syndrome. At admission all patients underwent invasive coronary angiography (ICA) and cardiac biomarkers – Creatine phosphokinase-MB (CPK-MB) and Troponin I (TnI) measurement. Two groups of patients were created based on ICA results: 1) MINOCA: with coronary artery stenosis <50%, n = 11; 2) MICAD: with coronary artery stenosis ≥50%, n = 17. SCAD patients group without obstructive atherosclerosis was retrospectively selected from the hospital database. All patients underwent dynamic SPECT on Cadmium-Zinc-Telluride (CZT) gamma camera with the assessment of semi-quantitative indexes of myocardial perfusion (SSS, SRS, SDS) and quantitative parameters (rest MBF (rMBF), stress MBF (sMBF) and MFR).

Results. After 24 hours cardiospecific biomarkers levels in MINOCA group were significantly (p < 0.05) lower compared to MICAD group: CPK-MB 21.5 (13.7;45.0) vs. 94.4 (53.1;217.0) U/L; TnI 0.5 (0.1;3.3) vs. 9.8 (2.0;23.0) ng/ml. Standard myocardial perfusion indexes differed significantly (p < 0.05) among all three groups (except SDS between the first and second groups): MINOCA: SSS 5.0 (3.0;6.0), SDS 2.0 (1.0;3.0); MICAD: SSS 9.0 (5.0;13.0), SDS 3.0 (2,0;5.0); SCAD: SSS 1.5 (0.5;2.0), SDS 0.0 (0.0;2.0). Moreover, sMBF and MFR differed significantly in all three groups of patients: MINOCA: sMBF 1.2 (0.8;1.7) ml/min/g, MFR 2.0 (1.2;2.4); MICAD: sMBF 0.7 (0.6;1.0) ml/min/g, MFR 1.2 (1.1;1.5); control group: sMBF 2.2 (2.1;2.3) ml/min/g, MFR 2.6 (2.5;2.8). In 7/11 (64%) of MINOCA patients the value of sMBF was ≤1.5 ml/min/g. In the MICAD group 16/17 (94%) had sMBF ≤1.5 ml/min/g and all SCAD patients had sMBF >1.5 ml/min/g. In 4/11 (36%) of MINOCA patients MFR values were less than 2; in MICAD group MFR < 2 was observed in 15/17 (88%) patients.

Conclusion. MINOCA patients have more severe myocardial perfusion abnormalities, lower MBF and MFR compared to those with stable CAD. It means that MINOCA patients may have other reasons for reduced myocardial blood flow, such as endothelial dysfunction, thrombophilia, etc., despite the absence of obstructive coronary artery lesion. Further studies are needed to assess added diagnostic and prognostic value of CZT SPECT derived myocardial flow indexes in MINOCA patients.
Assessment of the warranty period of a normal myocardial perfusion scintigraphy in patients with diabetes mellitus: 5 year follow-up of the prospective multicenter BARDOT trial
Authors: Haaf P , Caobelli F , Haenny G , Pfisterer M , Zellweger MJ
Published: February 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Foundation for Research

Background

Asymptomatic diabetic patients with an abnormal myocardial perfusion scintigraphy (MPS) are known to be at an increased risk of major cardiac events (MACE) at 2-years follow-up. It remains unclear whether this finding holds true even for a follow-up of 5 years.

Methods

four hundred patients with type-2 diabetes without coronary artery disease were evaluated clinically and with MPS and followed up for 5 years. Major adverse cardiovascular events (MACE) were defined as cardiac death, myocardial infarction or late coronary revascularization. 

Results

 An abnormal MPS (SSS≥4 or SSS≥2) was found in 87 patients (21.8%). MACE within 5 years occurred in 14 patients with abnormal MPS (16.1%) and in 22 with normal scan (1.7%, p = 0.009); 15 deaths were recorded (3.8%). Patients with normal MPS had lower rates of MACEs than patients with abnormal scans (p = 0.016) (Figure 1A + B). Patients with abnormal MPS who had undergone revascularization had a lower mortality rate and a better event free survival from MI and revascularization than patients with abnormal MPS who had either undergone medical therapy only or could not be revascularized (Figure 1C + D). 

Conclusions

Patients with  normal MPS have a low event rate and may not need retesting within 5 years (warranty period). Patients with an abnormal MPS have higher event rates and may benefit from a combined medical and revascularization approach.

Abstract Figure 1 A-D
Impact of coronary revascularization on regional artery-specific coronary flow capacity: a serial [15O]H2O positron emission tomography perfusion imaging study
Authors: De Winter RW , Jukema RA , Van Diemen PA , Schumacher SP , Driessen RS , Stuijfzand WJ , Bom MJ , Everaars H , Van De Ven PM , Verouden NJ , Nap A , Van Rossum AC , Danad I , Raijmakers PG , Knaapen P
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background. Coronary flow capacity (CFC) combines absolute hyperemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) in a graphical representation of the severity of myocardial perfusion impairment. Studies evaluating the impact of coronary revascularization on CFC as assessed by [15O]H2O positron emission tomography (PET) are lacking.

Purpose. The present study explored the impact of coronary revascularization on regional, artery-specific CFC as assessed by [15O]H2O PET.

Methods. A total of 315 patients (mean age 62 ± 10 years) underwent absolute myocardial perfusion imaging at baseline and directly after either percutaneous or surgical coronary revascularization (at 110 ± 50 days). Revascularized perfusion regions were stratified in 3 CFC groups at baseline: severely reduced CFC (defined as myocardial ischemia), moderately reduced CFC and normal CFC.

Results. Baseline CFC was severely reduced in 262 vessels (70%), moderately reduced in 95 vessels (25%) and normal in 17 vessels (5%). Regional, artery-specific CFC, hMBF and CFR improved after successful revascularization (P < 0.01). In 127/262 regions, CFC increased from severely reduced to moderately reduced and in 29/262 to normal flow after revascularization (p < 0.01 for both). Additionally, 28/95 revascularized regions increased from moderately reduced to normal flow (P = 0.18). Changes in hMBF (severe vs. moderate vs. normal: 0.84 ± 0.73; 0.41 ± 0.60 and 0.35 ± 0.84 mL·min-1·g-1 ) and CFR (0.92 ± 0.83; 0.49 ± 1.00 and -0.39 ± 1.15) were significantly different comparing baseline CFC groups (both p < 0.01). Furthermore, mixed-model analysis including traditional CAD risk factors revealed that baseline CFC and gender were independent predictors of changes in CFC, hMBF and CFR between baseline and follow-up.

Conclusions. Successful revascularization demonstrated a significant and positive impact on regional, artery-specific CFC, hMBF and CFR. Improvements were largest among lower baseline CFC groups. Furthermore, baseline CFC was an independent predictor of change in CFC, hMBF and CFR. These results suggest that the assessment of flow capacity by [15O]H2O PET prior to revascularization may aid in the selection of regions in which absolute myocardial perfusion is most likely to improve.

Abstract Figure 1.
Two-dimensional echocardiography compared to cardiac computed tomography for assessment of left ventricular volume and function in patients with anteroapical aneurysm
Authors: Nemchyna O , Solowjowa N , Dandel M , Hrytsyna Y , Knierim J , Soltani S , Schoenrath F , Falk V , Knosalla C
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background. Two-dimensional (2D) echocardiography is widely accepted method for the assessment of left ventricular (LV) morphology and function after myocardial infarction and for initial preoperative evaluation of patients planned for surgical ventricular repair (SVR). Magnetic resonance imaging and cardiac computer tomography (CT) provide more accurate measurements, but not always available.

Purpose. The aim of this study was to compare 2D-echocardiography and CT for preoperative assessment of patients with LV aneurysm in order to optimize the perioperative management in SVR.

Methods. Patients (n = 179, mean age 62.6 ± 11 years, 23.5% women) with LV anteroapical aneurysm due to myocardial infarction were examined by echocardiography and CT before SVR. LV end-diastolic and end-systolic volumes (LVEDV and LVESV) and ejection fraction (EF) obtained by two methods were compared pairwise. Prognostic role for the prediction of all-cause death was assessed for preoperative parameters in multivariate Cox regression model adjusted for patient age, sex, NYHA class, diabetes mellitus, renal failure, atrial fibrillation and arterial hypertension.

Results. There was a strong correlation for preoperative LVEDV and LVESV measured by echocardiography and CT (r = 0.85, r = 0.87, p < 0.0001), however volumes obtained by echocardiography were smaller compared to those by CT (Table) with higher difference in patients with more dilated LV, as demonstrated by Bland-Altman analysis (Fig.). No significant difference in mean preoperative EF was observed with moderate correlation between two methods (r = 0.67, p < 0.0001). In total 68 patients died during median follow up of 5.3 years (IQR: 1.7-8.7 years) after SVR. Comparable predictive value was demonstrated for LVEDV measured by CT and echocardiography (for 10 ml increase HR = 1.04, p = 0.004 and HR = 1.06, p = 0.0001), as well as for LVESV (for 10 ml increase HR = 1.04, p = 0.001 and HR = 1.07, p = 0.0001) and for EF (for 5% increase HR = 0.83, p = 0.004 and HR = 0.81, p = 0.004).

Conclusion. In patients with LV aneurysm 2D-echocardiography may be used for the assessment of LV volumes and function and have similar prognostic role compared to CT in patients evaluated for SVR. Underestimation of LV volumes by echocardiography must be considered, especially in patients with more dilated LV.

Comparison of CT and echocardiography Parameter CT Echo Mean difference p-value LVEDV, ml LVESV, ml EF, % 289 ± 104 198 ± 97 34 ± 12 222 ± 81 149 ± 67 35 ± 9 67 ± 56 49 ± 51 -0.9 ± 9.2 <0.0001 <0.0001 0.215 Abstract Figure. Bland-Altman plots for LVEDV and LVESV
Natural history and disease progression of early cardiac amyloidosis evaluated by echocardiography
Authors: Itzhaki Ben Zadok O , Eisen A , Shapira Y , Monakier D , Iakobishvili Z , Schwarzenberg S , Abelow A , Ofek H , Kazum S , Hamdan A , Bental T , Sagie A , Kornowski R , Vaturi M
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Since the diagnosis of cardiac amyloidosis (CA) is often delayed, echocardiographic findings are frequently indicative of already advanced cardiomyopathy.

Aims

to describe early echocardiographic features in patients subsequently diagnosed with CA and to delineate disease progression.

Methods

Pre-amyloid diagnosis echocardiographic studies were screened for structural and functional parameters and stratified according to the pathogenetic amyloid subtype (immunoglobulin light-chain (AL) or amyloid transthyretin (ATTR)). Abnormalities were defined based on published guidelines.

Results

Our cohort included 75 CA patients of whom 42 (56%) were diagnosed with AL and 33 (44%) with ATTR. Forty-two patients had an earlier echocardiography exam available for review. Patients presented with increased wall thickness (1.3 (IQR 1.0, 1.5)cm) ≥3 years before the diagnosis of CA and relative wall thickness (RWT) was increased (0.47 (IQR 0.41, 0.50)) ≥7 years pre-diagnosis. Between 1 to 3 years before CA diagnosis restrictive left ventricular (LV) filling pattern was present in 19% of patients and LV ejection fraction (LVEF)≤50% was present in 21% of patients. Right ventricular dysfunction was detected concomitantly with disease diagnosis. The echocardiographic phenotype of ATTR versus AL-CA showed increased RWT (0.74 (IQR 0.62, 0.92) vs. 0.62 (IQR 0.54, 0.76), p = 0.004) and LV mass index (144 (IQR 129, 191) vs. 115 (IQR 105, 146)g/m2,p = 0.020) and reduced LVEF (50 (IQR 44, 58) vs. (60 (IQR 53, 60)%, p = 0.009) throughout the time course of CA progression, albeit survival time was similar.

Conclusions

Increased wall thickness and diastolic dysfunction in CA develop over a time course of several years and can be diagnosed in their earlier stages by standard echocardiography

Abstract Figure. Schematic proposed timeline of CA
Serial right ventricular assessment in patients with hypoplastic left heart syndrome patients (HLHS): a cardiovascular magnetic resonance study
Authors: Sobh M , Gabbert D , Uebing A , Voges I
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Patients with hypoplastic left heart syndrome (HLHS) are at risk for right ventricular (RV) dysfunction over the course of the three-stage surgical palliation with the final step being the completion of the total cavopulmonary connection (TCPC). However, less is known about RV function during follow-up after TCPC completion. We assessed RV function by analysing serial cardiovascular magnetic resonance (CMR) studies in a large cohort of HLHS patients.

Methods

CMR studies from 95 HLHS patients (67 males) were retrospectively analysed. Short axis cine images were used to measure RV end systolic and end diastolic volumes and ejection fraction (RVEF). Oblique cine images showing the atria and right ventricle in a similar manner like a standard "4-chamber view" were used to measure tricuspid annular plane systolic excursion (TAPSE) and long axis strain (LAS).

Results

From the 95 patients, all had at least two and 32 patients had three CMR scans. The first scan was performed at a mean age of 4.9 ± 2.8 years, the second scan at a mean age of 9.3 ± 4 years and the third at a mean age of 14.3 ± 3.7 years. The mean values of RV end diastolic and end systolic volume indexed to body surface area (REDVi, RVESVi) as well as RV ejection fraction (RVEF) at the three time points were: 1) REDVi 92.6 ± 21.9 ml/m2, RVESVi 43 ± 15.1 ml/m2, RVEF 54.2 ± 7.1%; 2) REDVi 93.9 ± 25.6 ml/m2, RVESVi 44.6 ± 18.3 ml/m2, RVEF 53.6 ± 7.8%; 3) REDVi 110.9 ± 41.9 ml/m2, RVESVi 58.1 ± 35 ml/m2, RVEF 50.1 ± 10.1%. There was a statistically significant increase in RVEDVi and RVESVi from the first and the second scan to the third scan (p < 0.01). RVEF was lower at the time of the third scan compared to the first and second scan, but this difference was not statistically significant. TAPSE increased slightly from the first to the third scan (p < 0.05). There was no change in stroke volume and LAS from the first to the third scan. Strong correlations were found between RVEF and LAS as well as between RVEF and TAPSE (r = 0.49 and r=-0.50; p < 0.001, respectively).

Conclusion

Serial assessment of CMR studies in HLHS patients after TCPC completion could demonstrate an increase in indexed RV volumes over time, whereas RV stroke volume, RVEF and LAS largely remain stable.
Evolution of biventricular T1 values in patients with right-sided congenital heart disease
Authors: Burdet O , Pavon AG , Bouchardy J , Blanche C , Monney P , Hugelshofer S , Schwitter J , Rutz T
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Conflicting reports exist on the prevalence and clinical impact of interstitial fibrosis in right ventricular (RV) congenital heart disease (CHD). This study evaluates the longitudinal evolution of native myocardial T1 relaxation time (T1) in RV CHD.

Methods

On a 1.5T scanner, an ECG-triggered modified Look-Locker inversion recovery sequence (scheme 3(3)3(3)5) was acquired on a short-axis basal slice covering the RV and left ventricle (LV) on two consecutive CMR exams. Global and segmental (LV = 6, RV = 4) RV and LV T1 values  were calculated (Figure).

Results

Mean time between CMR exams for 36 included patients (age 34 ± 2y) was 22 ± 2 months. All LV segments and 81/88% of RV segments of first and second CMR could be analyzed, respectively.  T1 increased mildly but not significantly (table). There was no relationship of T1 to pulmonary regurgitation fraction, pulmonary stenosis or RV enddiastolic volume (p > 0.05). Global RV T1 of the second CMR was related to RV ejection fraction (RVEF): r = 0.353, 3.0 ± 1.4, p = 0.038. T1 of the infero-septal LV segment of first and second CMR, global LV T1 of second CMR and increase of T1 of global LV, anterior, antero-lateral and –septal LV segments, were related to age at CMR: r = 0.333 - 0.463, p < 0.05, respectively.

Conclusions

Native T1 values increased mildly in patients with stable RV CHD, which was not statistically significant probably due to the short to median follow-up. Global RV T1 appears to be related to RVEF which could be sign of increasing interstitial fibrosis whereas the relationship of LV T1 to age might be a physiological finding.

First CMR native T1 (ms) Second CMR native T1 (ms) p LV Global 1007 ± 37 1014 ± 39 0.413 LV Anterior 994 ± 53 999 ± 54 0.710 LV Antero-lateral 965 ± 63 981 ± 58 0.186 LV Infero-lateral 1000 ± 52 1004 ± 63 0.695 LV Inferior 1035 42 1037 ± 50 0.744 LV Infero-septal 1028 ± 35 1036 ± 43 0.282 LV Antero-septal 1016 ± 38 1024 ± 48 0.347 RV Global 1091 ± 90 1096 ± 85 0.410 RV Inferior 1112 ± 104 1115 ± 118 0.696 RV Infero-lateral 1061 ± 130 1077 ± 115 0.425 RV Antero-lateral 1046 ± 127 1080 ± 109 0.088 RV Anterior 1088 ± 156 1108 ± 154 0.410 Abstract Figure. Determination of biventricular T1 values
Permanent pacemaker implantation following mitral valve surgery: a retrospective cohort study of risk factors and long-term outcomes
Authors: Helmers Mark R , Shin Max , Iyengar Amit , Arguelles Gabriel R , Mays Jarvis , Han Jason J , Patrick William , Altshuler Peter , Hargrove W Clark , Atluri Pavan
Published: February 2021

OBJECTIVES

Conduction disturbances requiring permanent pacemaker (PPM) implantation remain a complication following valvular surgery. PPMs confer the risk of infection, tricuspid valve regurgitation and pacing-induced cardiomyopathy. Literature examining PPM placement in mitral valve surgery (MVS) is limited.

METHODS

Our institutional mitral valve (MV) database was retrospectively reviewed for adult patients undergoing surgery from 2011 to 2019. Patients with preoperative PPM were excluded. Patients were stratified by the receipt of PPM following their index operations. Multivariable logistic regression was performed to determine patient and operative risk factors for PPM. Subgroup analysis was performed on patients who underwent isolated MVS. Kaplan–Meier analysis and a multivariable Cox proportional hazards model were utilized to assess the association between PPM implantation and long-term survival.

RESULTS

A total of 3391 (2991 non-PPM and 400 PPM) patients met the study criteria. Significant predictors of PPM included increased decade of age (odds ratio: 1.23; 95% confidence interval: 1.12–1.35), concomitant aortic (1.44; 1.10–1.90) and tricuspid valve procedures (2.21; 1.64–2.97) and prior history of myocardial infarction (1.48; 1.07–1.86). In the isolated MV repair population, annuloplasty with ring prosthesis was associated with PPM (3.09; 1.19–8.02). Patients in the replacement population did not have significant identifiable risk factors. There was no survival difference found, and postoperative PPM placement was not found to be an independent predictor of mortality.

CONCLUSIONS

Our primary aim was to elucidate predictors for PPM implantation in MVS and found increasing age and concomitant procedures to be risk factors. Receipt of PPM is associated with worse long-term survival but does not independently predict survival. Among patients undergoing isolated MV repair, use of an annuloplasty ring confers a higher risk of PPM compared to an annuloplasty band.
Pulmonary valve replacement following repair of tetralogy of Fallot: comparison of outcomes between bio- and mechanical prostheses
Authors: Kim Dong-Hee , Choi Eun Seok , Kwon Bo Sang , Yun Tae-Jin , Cha Seul Gi , Baek Jae Suk , Yu Jeong Jin , Kim Young-Hwue , Park Chun Soo
Published: February 2021

OBJECTIVES

The aims of this study were to evaluate and compare the outcomes after pulmonary valve replacement (PVR) with a mechanical prosthesis (MP) and a bioprosthesis (BP).

METHODS

From 2004 through 2017, a total of 131 patients, who had already been repaired for tetralogy or Fallot or its variants, underwent their first PVR with an MP or a BP. Outcomes of interests were prosthesis failure (stenosis >3.5 m/s, regurgitation >mild or infective endocarditis) and reintervention.

RESULTS

The median age at PVR was 19 years. BP and MP were used in 88 (67.2%) and 43 (32.8%) patients, respectively. The median follow-up duration was 7.4 years, and the 10-year survival rate was 96.4%. Risk factors for prosthesis failure were smaller body surface area [hazard ratio (HR) 0.23 per 1 m2, P = 0.047] and smaller prosthesis size (HR 0.73 per 1 mm, P = 0.039). Risk factors for prosthesis reintervention were smaller body surface area (HR 0.11 per 1 m2, P = 0.011) and prosthesis size (HR 0.67 per 1 mm, P = 0.044). Probability of prosthesis failure and reintervention at 10 years were 24.6% (19.5% in BP vs 34.8% in MP, P = 0.34) and 7.8% (5.6% in BP vs 11.9% in MP, P = 0.079), respectively. Anticoagulation-related major thromboembolic events were observed in 4 patients receiving an MP.

CONCLUSIONS

MP might not be superior to BP in terms of prosthesis failure or reintervention. MP should be carefully considered for highly selected patients in the era of transcatheter PVR.
Can we modulate the breastfed infant gut microbiota through maternal diet?
Authors: Sindi Azhar S , Geddes Donna T , Wlodek Mary E , Muhlhausler Beverly S , Payne Matthew S , Stinson Lisa F
Published: February 2021

Initial colonisation of the infant gut is robustly influenced by regular ingestion of human milk, a substance that contains microbes, microbial metabolites, immune proteins and oligosaccharides. Numerous factors have been identified as potential determinants of the human milk and infant gut microbiota, including maternal diet; however, there is limited data on the influence of maternal diet during lactation on either of these. Here, we review the processes thought to contribute to human milk and infant gut bacterial colonisation and provide a basis for considering the role of maternal dietary patterns during lactation in shaping infant gut microbial composition and function. Although only one observational study has directly investigated the influence of maternal diet during lactation on the infant gut microbiome, data from animal studies suggests that modulation of the maternal gut microbiota, via diet or probiotics, may influence the mammary or milk microbiota. Additionally, evidence from human studies suggests that the maternal diet during pregnancy may affect the gut microbiota of the breastfed infant. Together, there is a plausible hypothesis that maternal diet during lactation may influence the infant gut microbiota. If substantiated in further studies, this may present a potential window of opportunity for modulating the infant gut microbiome in early life.
Genetic analysis of four consanguineous multiplex families with inflammatory bowel disease
Authors: Ben-Yosef Noam , Frampton Matthew , Schiff Elena R , Daher Saleh , Abu Baker Fadi , Safadi Rifaat , Israeli Eran , Segal Anthony W , Levine Adam P
Published: February 2021

Background

Family studies support a genetic predisposition to inflammatory bowel diseases (IBD), but known genetic variants only partially explain the disease heritability. Families with multiple affected individuals potentially harbour rare and high-impact causal variants. Long regions of homozygosity due to recent inbreeding may increase the risk of individuals bearing homozygous loss-of-function variants. This study aimed to identify rare and homozygous genetic variants contributing to IBD.

Methods

Four families with known consanguinity and multiple cases of IBD were recruited. In a family-specific analysis, we utilised homozygosity mapping complemented by whole-exome sequencing.

Results

We detected a single region of homozygosity shared by Crohn's disease cases from a family of Druze ancestry, spanning 2.6 Mb containing the NOD2 gene. Whole-exome sequencing did not identify any potentially damaging variants within the region, suggesting that non-coding variation may be involved. In addition, affected individuals in the families harboured several rare and potentially damaging homozygous variants in genes with a role in autophagy and innate immunity including LRRK1, WHAMM, DENND3, and C5.

Conclusion

This study examined the potential contribution of rare, high-impact homozygous variants in consanguineous families with IBD. While the analysis was not designed to achieve statistical significance, our findings highlight genes or loci that warrant further research. Non-coding variants affecting NOD2 may be of importance in Druze patients with Crohn's disease.
Contract Law
Authors: Arvind TT
Published: February 2021

Contract Law provides a uniquely practical approach to the topic. The text is divided into four parts. Part I covers forming contracts. It looks at bargaining and agreeing, and the requirements of mutuality, legal relations, and non-contractual promises. Part II considers issues related to keeping contracts. It examines the assembling of the contract, interpreting the terms of a contract, flexible terms, and changes in contracts. The next part is about regulating contracts. It looks at untrue statements, the limits of hard bargaining, controlling contractual terms, and protecting the public interest. The final part is about enforcing contracts. The text here examines issues relating to breach of contract, compensatory remedies, non-compensatory remedies, and third party matters.
Is There a Hidden Burden of Disease as a Result of Epigenetic Epithelial-to-Mesenchymal Transition Following Chlamydia trachomatis Genital Tract Infection?
Authors: Horner Patrick J , Flanagan Heather , Horne Andrew W
Published: February 2021

Chlamydia trachomatis (CT), the most common bacterial sexually transmitted infection worldwide, has been widely researched for its involvement in many disease pathologies in the reproductive tract, including pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility. Recent findings, through the efforts to understand the pathogenesis of CT, suggest that CT can induce the process of epithelial-to-mesenchymal transition (EMT) through epigenetic changes in the epithelium of the female reproductive tract. This literature review aims to analyze the evidence for CT’s ability to promote EMT and to pinpoint the areas that merit further investigation.
Participation in household decision making and justification of wife beating: evidence from the 2018 Mali Demographic and Health Survey
Authors: Seidu Abdul-Aziz , Dzantor Selorm , Sambah Francis , Ahinkorah Bright Opoku , Ameyaw Edward Kwabena
Published: February 2021

Background

We assessed the association between women's participation in household decision making and justification of wife beating among married women ages 15–49 y in Mali.

Methods

We employed a cross-sectional study design among 7893 women of reproductive age involving a two-stage sampling technique using version 6 of the Mali Demographic and Health Survey (MDHS) data, which was conducted in 2018.

Results

Approximately 37% participated in at least one household decision while 23.4% reported that they would not justify wife beating in any of the stated circumstances. Women who participated in at least one household decision had lower odds (adjusted odds ratio [AOR] 0.834 [confidence interval {CI} 0.744 to 0.935]) of justifying wife beating. With respect to the covariates, we found that women 45–49 y of age had lower odds of justifying wife beating compared with those ages 15–19 y (AOR 0.569 [CI 0.424 to 0.764]). Women with higher education (AOR 0.419 [CI 0.265 to 0.662]) and those whose husbands had secondary education (AOR 0.825 [CI 0.683 to 0.995]) had lower odds of justifying wife beating. Women who lived in urban areas were less likely to justify wife-beating (AOR 0.328 [CI 0.275 to 0.390]) compared with those who lived in rural areas.

Conclusion

This study suggests that participation in household decision making is associated with a significantly lower rate of justifying wife beating in Mali. These results underscore the need for various interventions to empower women to increase women's participation in decision making to reduce justification of domestic violence.
Steal syndrome from a superficial circumflex iliac perforator artery flap in a patient with a hypoplastic posterior tibial artery and severe diabetic peripheral artery disease
Authors: Murphy Grant A , Singh-Moon Rajinder P , Rowe Vincent L , Patel Ketan M , Mazhar Amaan , Cuccia David J , Armstrong David G
Published: February 2021

The use of free flaps in lower extremity reconstructive surgery has seen growing adoption for treating tissue loss in patients with diabetes mellitus and peripheral artery disease as a means for limb preservation. The superficial circumflex iliac perforator artery (SCIP) flap is one of the most commonly utilized flaps in foot reconstruction and has demonstrated benefits over amputation. Patients with impaired vascular and neurologic function are predisposed to complications following lower extremity reconstructive surgery, particularly ischemia in the angiosomes of the arteries used for flap anastomosis. We present the case of a patient who underwent successful SCIP flap reconstruction of the calcaneus but developed gangrene in the forefoot region supplied by a hypoplastic posterior tibial artery in subsequent months. The changes in tissue oxygenation and hemoglobin distribution of the foot are shown using spatial frequency domain imaging throughout the flap healing process and eventual tissue necrosis.
Laboratory Predictors of COVID-19 Pneumonia in Patients with Mild to Moderate Symptoms
Authors: Li Jiaxia , Wan Li , Feng Yuan , Zuo Huilin , Zhao Qian , Ren Jiecheng , Zhang Xiaochu , Xia Mingwu
Published: February 2021

Objective

This research aims to develop a laboratory model that can accurately distinguish pneumonia from nonpneumonia in patients with COVID-19 and to identify potential protective factors against lung infection.

Methods

We recruited 50 patients diagnosed with COVID-19 infection with or without pneumonia. We selected candidate predictors through group comparison and punitive least absolute shrinkage and selection operator (LASSO) analysis. A stepwise logistic regression model was used to distinguish patients with and without pneumonia. Finally, we used a decision-tree method and randomly selected 50% of the patients 1000 times from the same specimen to verify the effectiveness of the model.

Results

We found that the percentage of eosinophils, a high–fluorescence-reticulocyte ratio, and creatinine had better discriminatory power than other factors. Age and underlying diseases were not significant for discrimination. The model correctly discriminated 77.1% of patients. In the final validation step, we observed that the model had an overall predictive rate of 81.3%.

Conclusion

We developed a laboratory model for COVID-19 pneumonia in patients with mild to moderate symptoms. In the clinical setting, the model will be able to predict and differentiate pneumonia vs nonpneumonia before any lung computed tomography findings. In addition, the percentage of eosinophils, a high–fluorescence-reticulocyte ratio, and creatinine were considered protective factors against lung infection in patients without pneumonia.
The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases
Authors: Peng Gui-Xin , Zhang Yong , Wang Qin-Qin , Li Qing-Run , Xu Hong , Wang En-Duo , Zhou Xiao-Long
Published: February 2021

GTPBP3 and MTO1 cooperatively catalyze 5-taurinomethyluridine (τm5U) biosynthesis at the 34th wobble position of mitochondrial tRNAs. Mutations in tRNAs, GTPBP3 or MTO1, causing τm5U hypomodification, lead to various diseases. However, efficient in vitro reconstitution and mechanistic study of τm5U modification have been challenging, in part due to the lack of pure and active enzymes. A previous study reported that purified human GTPBP3 (hGTPBP3) is inactive in GTP hydrolysis. Here, we identified the mature form of hGTPBP3 and showed that hGTPBP3 is an active GTPase in vitro that is critical for tRNA modification in vivo. Unexpectedly, the isolated G domain and a mutant with the N-terminal domain truncated catalyzed GTP hydrolysis to only a limited extent, exhibiting high Km values compared with that of the mature enzyme. We further described several important pathogenic mutations of hGTPBP3, associated with alterations in hGTPBP3 localization, structure and/or function in vitro and in vivo. Moreover, we discovered a novel cytoplasm-localized isoform of hGTPBP3, indicating an unknown potential noncanonical function of hGTPBP3. Together, our findings established, for the first time, the GTP hydrolysis mechanism of hGTPBP3 and laid a solid foundation for clarifying the τm5U modification mechanism and etiology of τm5U deficiency-related diseases.
Role of CxxC-finger protein 1 in establishing mouse oocyte epigenetic landscapes
Authors: Sha Qian-Qian , Zhu Ye-Zhang , Xiang Yunlong , Yu Jia-Li , Fan Xiao-Ying , Li Yan-Chu , Wu Yun-Wen , Shen Li , Fan Heng-Yu
Published: February 2021

During oogenesis, oocytes gain competence and subsequently undergo meiotic maturation and prepare for embryonic development; trimethylated histone H3 on lysine-4 (H3K4me3) mediates a wide range of nuclear events during these processes. Oocyte-specific knockout of CxxC-finger protein 1 (CXXC1, also known as CFP1) impairs H3K4me3 accumulation and causes changes in chromatin configurations. This study investigated the changes in genomic H3K4me3 landscapes in oocytes with Cxxc1 knockout and the effects on other epigenetic factors such as the DNA methylation, H3K27me3, H2AK119ub1 and H3K36me3. H3K4me3 is overall decreased after knocking out Cxxc1, including both the promoter region and the gene body. CXXC1 and MLL2, which is another histone H3 methyltransferase, have nonoverlapping roles in mediating H3K4 trimethylation during oogenesis. Cxxc1 deletion caused a decrease in DNA methylation levels and affected H3K27me3 and H2AK119ub1 distributions, particularly at regions with high DNA methylation levels. The changes in epigenetic networks implicated by Cxxc1 deletion were correlated with the transcriptional changes in genes in the corresponding genomic regions. This study elucidates the epigenetic changes underlying the phenotypes and molecular defects in oocytes with deleted Cxxc1 and highlights the role of CXXC1 in orchestrating multiple factors that are involved in establishing the appropriate epigenetic states of maternal genome.
Human gut microbial communities dictate efficacy of anti-PD-1 therapy in a humanized microbiome mouse model of glioma
Authors: Dees Kory J , Koo Hyunmin , Humphreys J Fraser , Hakim Joseph A , Crossman David K , Crowley Michael R , Nabors L Burton , Benveniste Etty N , Morrow Casey D , McFarland Braden C
Published: February 2021

Background

Although immunotherapy works well in glioblastoma (GBM) preclinical mouse models, the therapy has not demonstrated efficacy in humans. To address this anomaly, we developed a novel humanized microbiome (HuM) model to study the response to immunotherapy in a preclinical mouse model of GBM.

Methods

We used 5 healthy human donors for fecal transplantation of gnotobiotic mice. After the transplanted microbiomes stabilized, the mice were bred to generate 5 independent humanized mouse lines (HuM1-HuM5).

Results

Analysis of shotgun metagenomic sequencing data from fecal samples revealed a unique microbiome with significant differences in diversity and microbial composition among HuM1-HuM5 lines. All HuM mouse lines were susceptible to GBM transplantation, and exhibited similar median survival ranging from 19 to 26 days. Interestingly, we found that HuM lines responded differently to the immune checkpoint inhibitor anti-PD-1. Specifically, we demonstrate that HuM1, HuM4, and HuM5 mice are nonresponders to anti-PD-1, while HuM2 and HuM3 mice are responsive to anti-PD-1 and displayed significantly increased survival compared to isotype controls. Bray-Curtis cluster analysis of the 5 HuM gut microbial communities revealed that responders HuM2 and HuM3 were closely related, and detailed taxonomic comparison analysis revealed that Bacteroides cellulosilyticus was commonly found in HuM2 and HuM3 with high abundances.

Conclusions

The results of our study establish the utility of humanized microbiome mice as avatars to delineate features of the host interaction with gut microbial communities needed for effective immunotherapy against GBM.
The Deep-Time Digital Earth program: data-driven discovery in geosciences
Authors: Wang Chengshan , Hazen Robert M , Cheng Qiuming , Stephenson Michael H , Zhou Chenghu , Fox Peter , Shen Shu-zhong , Oberhänsli Roland , Hou Zengqian , Ma Xiaogang , Feng Zhiqiang , Fan Junxuan , Ma Chao , Hu Xiumian , Luo Bin , Wang Juanle , Schiffries Craig M
Published: February 2021

Current barriers hindering data-driven discoveries in deep-time Earth (DE) include: substantial volumes of DE data are not digitized; many DE databases do not adhere to FAIR (findable, accessible, interoperable and reusable) principles; we lack a systematic knowledge graph for DE; existing DE databases are geographically heterogeneous; a significant fraction of DE data is not in open-access formats; tailored tools are needed. These challenges motivate the Deep-Time Digital Earth (DDE) program initiated by the International Union of Geological Sciences and developed in cooperation with national geological surveys, professional associations, academic institutions and scientists around the world. DDE’s mission is to build on previous research to develop a systematic DE knowledge graph, a FAIR data infrastructure that links existing databases and makes dark data visible, and tailored tools for DE data, which are universally accessible. DDE aims to harmonize DE data, share global geoscience knowledge and facilitate data-driven discovery in the understanding of Earth's evolution.
Use of Temporary Rod and Intraoperative Neuroimaging for Correction of Adolescent Idiopathic Scoliosis: 2-Dimensional Operative Video
Authors: McClendon Jamal , Turcotte Evelyn L , Pai Manish G , Maiti Tanmoy , Singh Rohin , Bendok Bernard R
Published: February 2021

Adolescent idiopathic scoliosis (AIS) is an abnormal lateral curvature of the spine that arises during the pubescent growth spurt. AIS mainly affects females in the age group of 10 to 16 yr, with a prevalence of about 1% to 3% in the at-risk population.
1
Treatment options vary depending on disease presentation and severity. Mild curvature mainly requires periodic observation for disease progression, whereas more moderate curvature can necessitate bracing or corrective surgery.
2

Here, we present the use of a temporary rod and neuroimaging for the correction of Lenke type 1 spinal curvature in an AIS patient. An inferior facetectomy is performed, and a Lenke probe is used for entry into the pedicle and vertebral body. The channel is sounded before and after tapping to check for adequate walls prior to insertion of the pedicle screw. The ARTIS pheno is brought into the field, which uses fluoroscopy to create a 3-dimensional (3D) representation of the instrumentation within the spine. A temporary rod is placed in the concavity, and a combination of corrective techniques, including a rod roll, apical translation, and reduction, is performed to bring up the concavity, derotate the spine, and translate the spine. The permanent rod is then placed in the convexity, and compression is performed to bring down the scapular prominence. The temporary rod is then removed, and a final rod is placed to complete the 3D correction.

The patient consented to the procedure, and an informed written consent was obtained from the patient to use her photographs and video recordings for publication.
Providing psychosocial support for work-from-home educators during the COVID-19 pandemic
Authors: Muldong Venusa M , Garcia Abelardo E , Gozum Ivan Efreaim A
Published: February 2021

A recent article discussed the results of mental support for healthcare professionals and mental care during the COVID-19 pandemic. In the report, the researchers suggest that healthcare professionals must be given psychosocial support during and after the pandemic to prevent any long-term consequence. In this correspondence, this paper proposes that psychosocial support must also be given to educators in a work-from-home setup since they are also affected by the stresses that came with the pandemic.
The Role of Grandparents in Israeli Muslim Families with Intellectually Disabled Fathers: Social Workers’ Perspectives
Authors: Gur Ayelet , Gnaeem-Badran Leena , Stein Michael Ashley
Published: February 2021

Within Israeli Muslim society, men with intellectual disabilities are likely to marry nondisabled women through arranged marriages and create families. This article explores the role of grandparents with these families from the perspective of each family’s social worker. A thematic analysis was conducted of 19 semistructured interviews with Muslim social workers serving Muslim families with intellectually disabled fathers. Consistent with cultural norms, paternal grandparents are extremely involved in the lives of these couples and hold responsibilities in many aspects of these couples’ family lives. Social workers reported that the nondisabled wives, however, viewed the engagement as intrusive and controlling. Maternal grandparents’ contributions were crucially supportive, albeit limited by Muslim cultural norms that placed households under paternal family control. Social workers had conflicted feelings regarding paternal grandparent involvement. Social workers working with Muslim fathers with intellectual disabilities should promote supportive paternal grandparent involvement and ensure that such engagement does not undermine the autonomy or well-being of the nondisabled mothers. Practice guidelines are presented.
“Home Is Where Your Root Is”: Place Making, Belonging, and Community Building among Somalis in Chicago
Authors: Magan Ifrah Mahamud , Padgett Deborah K
Published: February 2021

This qualitative study examines the notion of home as it relates to place making, belonging, and community building. Using a phenomenological method of inquiry, data were gathered through in-depth qualitative interviews with 15 Somali Americans and subjected to transcendental phenomenological analyses. Three major themes were found: (1) the meaning of community: being Somali and Muslim; (2) “We help each other. We are connected”; and (3) “Home is where your root is.” The study findings highlight how Somali participants drew on their faith and culture as foundational to community building and drew on acts of mutual giving and receiving to bind them together even as subjective feelings of “home” could be place based or could transcend geography. Although sometimes disrupted by bias and discrimination, Somalis persevered in defining themselves and pursuing a sense of belonging both within their own community and in the city at large. This study offers an expansive and dynamic view of the meaning of place making, community building, and belonging (home) in the lives of displaced refugees. Both research and practice can benefit from special attention given to the “natural” formation of refugee communities and their role in enhancing adjustment to life in a new land.
Individual variations in “Brain age” relate to early life factors more than to longitudinal brain change
Authors: Vidal-Piñeiro D. , Wang Y. , Krogsrud SK. , Amlien IK. , Baaré WFC. , Bartrés-Faz D. , Bertram L. , Brandmaier A.M. , Drevon CA. , Düzel S. , Ebmeier KP. , Henson RN , Junque C. , Kievit RA , Kühn S. , Leonardsen E. , Lindenberger U. , Madsen KS. , Magnussen F. , Mowinckel AM. , Nyberg L. , Roe JM. , Segura B. , Smith SM. , Sørensen Ø. , Suri S. , Westerhausen R. , Zalesky A. , Zsoldos E. ,   the Australian Imaging Biomarkers and Lifestyle flagship study of ageing, Walhovd KB. , Fjell AM.
Published: February 2021

Brain ageis a widely used index for quantifying individuals’ brain health as deviation from a normative brain aging trajectory. Higher than expectedbrain ageis thought partially to reflect above-average rate of brain aging. We explicitly tested this assumption in two large datasets and found no association between cross-sectionalbrain ageand steeper brain decline measured longitudinally. Rather,brain agein adulthood was associated with early-life influences indexed by birth weight and polygenic scores. The results call for nuanced interpretations of cross-sectional indices of the aging brain and question their validity as markers of ongoing within-person changes of the aging brain. Longitudinal imaging data should be preferred whenever the goal is to understand individual change trajectories of brain and cognition in aging.
Phellem translational landscape throughout secondary development inArabidopsisroots
Authors: Leal Ana Rita , Barros Pedro Miguel , Parizot Boris , Sapeta Helena , Vangheluwe Nick , Andersen Tonni Grube , Beeckman Tom , Oliveira M. Margarida
Published: February 2021

The phellem is a specialized boundary tissue providing the first line of defense against abiotic and biotic stresses in organs undergoing secondary growth. Phellem cells undergo several differentiation steps, which include cell wall suberization, cell expansion and programmed cell death. Yet, the molecular players acting particularly in phellem cell differentiation remain poorly described, particularly in the widely used model plantArabidopsis thaliana.

Using specific marker lines we followed the onset and progression of phellem differentiation inA. thalianaroots, and further targeted the translatome of new developed phellem cells using Translating Ribosome Affinity Purification followed by mRNA sequencing (TRAP-SEQ).

We showed that phellem suberization is initiated early after phellogen (cork cambium) division. The specific translational landscape was organized in three main domains related to energy production, synthesis and transport of cell wall components, and response to stimulus. Novel players in phellem differentiation, related to suberin monomer transport and assembly, as well as novel transcription regulators were identified.

This strategy provided an unprecedented resolution of the transcriptome of developing phellem cells, giving a detailed and specific view on the molecular mechanisms controlling cell differentiation in periderm tissues of the model plantArabidopsis.

Significance statement

To improve the understanding of phellem differentiation into a suberized protective layer, we followed the establishment of periderm inArabidopsisroots and sequenced the phellem-specific translatome. We found that phellem suberization occurs shortly after pericycle cell divisions with the induction of pivotal suberin biosynthesis genes. In parallel, we detected the activation of three central genetic modules acting throughout the phellem differentiation. This study provides a unique and targeted genetic resource for further functional studies of phellem tissues.