A Low-Cost Workflow to Generate Virtual and Physical Three-Dimensional Models of Cardiac Structures.

Purpose: Three-dimensional modeling and printing (3DMP) of anatomical structures from cross-sectional imaging data can enhance the understanding of spatial relationships in complex congenital heart defects. Partially due to the substantial financial, material and personnel resources required, 3DMP is not yet universally used. Here, we describe a workflow that addresses and eliminates these drawbacks.

Surgical Treatment of Atrial Septal Defects.

Atrial septal defects (ASDs) are among the most prevalent congenital cardiac malformations. Closure of the defect and repair of associated cardiac malformations are typically indicated if an ASD is hemodynamically significant or symptomatic. This narrative review aims to summarize key aspects of surgical ASD closures.

Sequence-specific interactions determine viscoelasticity and aging dynamics of protein condensates.

Biomolecular condensates are viscoelastic materials. Here, we investigate the determinants of sequence-encoded and age-dependent viscoelasticity of condensates formed by the prion-like low-complexity domain of the protein hnRNP A1 and its designed variants. We find that the dominantly viscous forms of the condensates are metastable Maxwell fluids.

Dominance analysis to assess solute contributions to multicomponent phase equilibria.

Phase separation in aqueous solutions of macromolecules underlies the generation of biomolecular condensates in cells. Condensates are membraneless bodies, representing dense, macromolecule-rich phases that coexist with the dilute, macromolecule-deficient phases. In cells, condensates comprise hundreds of different macromolecular and small molecule solutes.

Biomolecular condensates can function as inherent catalysts.

We report the discovery that chemical reactions such as ATP hydrolysis can be catalyzed by condensates formed by intrinsically disordered proteins (IDPs), which themselves lack any intrinsic ability to function as enzymes. This inherent catalytic feature of condensates derives from the electrochemical environments and the electric fields at interfaces that are direct consequences of phase separation. The condensates we studied were capable of catalyzing diverse hydrolysis reactions, including hydrolysis and radical-dependent breakdown of ATP whereby ATP fully decomposes to adenine and multiple carbohydrates.

Aortic uncrossing of the left circumflex aorta.

The following video tutorial presents the surgical correction of the left circumflex aortic arch in a 6-month-old boy with severe respiratory distress and stridor. The diagnosis was confirmed using cardiac catheterization and computed tomography. Intraoperative bronchoscopy showed marked compression of the trachea.

Male-female differences following concomitant coronary artery bypass grafting and aortic valve replacement surgery.

Aims: Combined coronary artery bypass grafting (CABG) and aortic valve replacement (AVR), and female sex are associated with increased perioperative mortality in clinical risk scores. This study investigated male-female differences in short-term outcome stratified by age groups.

Methods And Results: All patients undergoing AVR and CABG between January 2001 and June 2021 at our institution were included.

Dominance Analysis: A formalism to uncover dominant energetic contributions to biomolecular condensate formation in multicomponent systems.

Phase separation in aqueous solutions of macromolecules is thought to underlie the generation of biomolecular condensates in cells. Condensates are membraneless bodies, representing dense, macromolecule-rich phases that coexist with the dilute, macromolecule-deficient phase. In cells, condensates comprise hundreds of different macromolecular and small molecule solutes.

Macromolecular condensation organizes nucleolar sub-phases to set up a pH gradient.

Nucleoli are multicomponent condensates defined by coexisting sub-phases. We identified distinct intrinsically disordered regions (IDRs), including acidic (D/E) tracts and K-blocks interspersed by E-rich regions, as defining features of nucleolar proteins. We show that the localization preferences of nucleolar proteins are determined by their IDRs and the types of RNA or DNA binding domains they encompass.

Addition of PEG-interferon to long-term nucleos(t)ide analogue therapy enhances HBsAg decline and clearance in HBeAg-negative chronic hepatitis B: Multicentre Randomized Trial (PAS Study).

We studied whether 48 weeks of PEG-IFN alfa-2a add-on increases HBsAg-decline and clearance in HBeAg-negative patients on long-term nucleo(s)tide analogue (NA) therapy. In this investigator-initiated, randomized, controlled trial conducted in Europe and Canada, HBeAg-negative patients treated with NA > 12 months, with HBVDNA < 200 IU/mL, were enrolled. Patients were randomized 2:1 to 48 weeks of PEG-IFN alfa-2a add-on (180 μg per week) or continued NA-monotherapy with subsequent follow-up to Week 72.

A Deep Learning-Based Approach to Estimate Paneth Cell Granule Area in Celiac Disease.

Context.—: Changes in Paneth cell numbers can be associated with chronic inflammatory diseases of the gastrointestinal tract. So far, no consensus has been achieved on the number of Paneth cells and their relevance to celiac disease (CD).

Establishment of persistent enteric mycobacterial infection following streptomycin pre-treatment.

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of paratuberculosis, a chronic gastrointestinal disease affecting ruminants. This disease remains widespread in part due to the limitations of available diagnostics and vaccines.

Phase separation of protein mixtures is driven by the interplay of homotypic and heterotypic interactions.

Prion-like low-complexity domains (PLCDs) are involved in the formation and regulation of distinct biomolecular condensates that form via phase separation coupled to percolation. Intracellular condensates often encompass numerous distinct proteins with PLCDs. Here, we combine simulations and experiments to study mixtures of PLCDs from two RNA-binding proteins, hnRNPA1 and FUS.

Crohn's Disease Features in Anastomotic Biopsies from Patients With and Without Crohn's Disease: Diagnostic and Prognostic Value.

Endoscopic evidence of disease activity is a critical predictor of clinical relapse in patients with Crohn's disease (CD), and histologic disease activity is evolving as a similarly important end point for patient management. However, classical morphologic features of CD may overlap with postoperative inflammatory changes, confounding the evaluation of anastomotic biopsies. There is a clear unmet need for better characterization of diagnostic and clinically significant histologic features of CD in these surgically altered sites.

Early versus Delayed Surgery in Patients with Left-Sided Infective Endocarditis and Stroke.

Background: Timing of surgery remains controversial in patients with infective endocarditis and stroke. Guidelines on infective endocarditis suggest delaying surgery for up to 4 weeks. However, with early heart failure due to progression of the infection or recurrent septic embolism, urgent surgery becomes imperative.

Phase Separation in Mixtures of Prion-Like Low Complexity Domains is Driven by the Interplay of Homotypic and Heterotypic Interactions.

Prion-like low-complexity domains (PLCDs) are involved in the formation and regulation of distinct biomolecular condensates that form via coupled associative and segregative phase transitions. We previously deciphered how evolutionarily conserved sequence features drive phase separation of PLCDs through homotypic interactions. However, condensates typically encompass a diverse mixture of proteins with PLCDs.

FIREBALL: A tool to fit protein phase diagrams based on mean-field theories for polymer solutions.

Biomolecular condensates form via phase transitions of condensate-specific biomacromolecules. Intrinsically disordered regions featuring the appropriate sequence grammars can contribute via homotypic and heterotypic interactions to the driving forces for phase separation of multivalent proteins. Experiments and computations have matured to the point where the concentrations of coexisting dense and dilute phases can be measured or computed for individual intrinsically disordered regions in complex milieus.

Sequence-specific interactions determine viscoelasticity and aging dynamics of protein condensates.

Biomolecular condensates are viscoelastic materials. Here, we report results from investigations into molecular-scale determinants of sequence-encoded and age-dependent viscoelasticity of condensates formed by prion-like low-complexity domains (PLCDs). The terminally viscous forms of PLCD condensates are Maxwell fluids.

FIREBALL: A tool to fit protein phase diagrams based on mean-field theories for polymer solutions.

Unlabelled: Biomolecular condensates form via phase transitions of condensate-specific biomacromolecules. Intrinsically disordered regions (IDRs) featuring the appropriate sequence grammar can contribute homotypic and heterotypic interactions to the driving forces for phase separation of multivalent proteins. At this juncture, experiments and computations have matured to the point where the concentrations of coexisting dense and dilute phases can be quantified for individual IDRs in complex milieus both and .

Phase Transitions of Associative Biomacromolecules.

Multivalent proteins and nucleic acids, collectively referred to as multivalent associative biomacromolecules, provide the driving forces for the formation and compositional regulation of biomolecular condensates. Here, we review the key concepts of phase transitions of aqueous solutions of associative biomacromolecules, specifically proteins that include folded domains and intrinsically disordered regions. The phase transitions of these systems come under the rubric of coupled associative and segregative transitions.