Discriminating Malignant from Benign Testicular Masses Using Multiparametric Magnetic Resonance Imaging-A Prospective Single-Center Study.

Objective: The objective of this study was to prospectively assess the extent to which magnetic resonance imaging (MRI) can differentiate malignant from benign lesions of the testis. Materials and Methods: All included patients underwent multiparametric testicular MRI, including diffusion-weighted imaging (DWI) and subtraction dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). Subsequently, all patients underwent a histopathological examination via orchiectomy or testicular biopsy/partial resection. The Kolmogorov-Smirnov test, t-test, Mann-Whitney U test, Fisher's exact test, and logistic regression were applied for statistical analysis. Results: We included 48 male patients (median age 37.5 years [range 18-69]) with testicular tumors. The median tumor size on MRI was 2.0 cm for malignant tumors and 1.1 cm for benign tumors (p < 0.05). A statistically significant difference was observed for the type (type 0-III curve, p < 0.05) and pattern of enhancement (homogeneous, heterogeneous, or rim-like, p < 0.01) between malignant and benign tumors. The minimum apparent diffusion coefficient (ADC) value was 0.9 for benign tumors and 0.7 for malignant tumors (each ×103 mm2/s, p < 0.05), while the mean ADC was 0.05. The mean ADC value was significantly lower for malignant tumors; the mean ADC value was 1.1 for benign tumors and 0.9 for malignant tumors (each ×103 mm2/s, p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of multiparametric MRI for differentiating malignant from benign testicular lesions were 94.3%, 76.9%, 91.7%, and 83.3%, respectively. The surgical procedures performed included orchiectomy (n = 33; 71.7%) and partial testicular resection (n = 11; 23.9%). Histopathology (HP) revealed malignancy in 35 patients (72.9%), including 26 with seminomas and 9 with non-seminomatous germ cell tumors (NSGCTs). The HP was benign in 13 (27.1%) patients, including 5 with Leydig cell tumors. Conclusions: Malignant and benign tumors differ in MRI characteristics in terms of the type and pattern of enhancement and the extent of diffusion restriction, indicating that MRI can be an important imaging modality for the accurate diagnosis of testicular lesions.

Thoracic sarcopenia measured by Hounsfield unit average calculation predicts morbidity and mortality in coronary artery bypass grafting.

OBJECTIVES: The aim of the study was to investigate the potential prognostic role of preoperative measurement of erector spinae myosteatosis with Hounsfield Unit Average Calculation (HUAC) as a marker for sarcopenia and frailty in patients undergoing coronary bypass surgery (CABG). METHODS: Preoperative computer tomography (CT) derived measurements of 479 consecutive patients undergoing CABG between January 2017 and December 2019 were retrospectively performed. The erector spinae muscle at the level of the 12th vertebra was manually outlined bilaterally on the axial CT slices and Hounsfield Unit Average Calculation (HUAC) was performed. The lower quartile of muscle density values was defined as myosteatotic and thus sarcopenic. Sarcopenic (n = 121) versus non-sarcopenic patients (n = 358) were compared regarding postoperative morbidity, short-term and long-term mortality. Results were adjusted for age, Body Mass Index (BMI), atrial fibrillation and hypertension using inverse probability weighting (IPW). RESULTS: Sarcopenia was associated with higher 30-day mortality (4.1% vs 0.8% p = 0.012), mid-term mortality after 1 year (9.3% vs 3.1% p = 0.047) and 2 years (10.8% vs 4.2% p = 0.047). Long-term mortality (5 years) was 20.8% for sarcopenic and 13.0% for non-sarcopenic patients but was not found to be significantly different (p = 0.089). Sarcopenia was associated with higher rates of reintubation (7.5% vs 1.1% p < 0.001), sternal wound infections (7.5% vs 2.8% p = 0.039) and acute kidney injury requiring hemodialysis (2.5% vs 0.4% p = 0.021). CONCLUSIONS: In patients undergoing coronary bypass surgery, sarcopenia was associated with increased short-term mortality, mid-term mortality and morbidity. The measurement of erector spinae myosteatosis could be an easy and useful parameter in preoperative risk assessment.

Accessing a Diverse Set of Functional Red-Light Photoswitches by Selective Copper-Catalyzed Indigo N-Arylation.

The ability to correlate the structure of a molecule with its properties is the key to the rational and accelerated design of new functional compounds and materials. Taking photoswitches as an example, the thermal stability of the metastable state is a crucial property that dictates their application in molecular systems. Indigos have recently emerged as an attractive motif for designing photoswitchable molecules due to their red-light addressability, which can be advantageous in biomedical and material applications. The lack of synthetic techniques to derivatize the abundant parent dye and a thorough understanding of the impact of structural factors on the photochemical and thermal properties hinder broad applications of this emerging photoswitch class. Herein, we report an efficient copper-catalyzed indigo N-arylation that enables the installation of a wide variety of aryl moieties carrying useful functional groups. The exclusive selectivity for monoarylation likely originates from a bimetallic cooperative mechanism through a binuclear copper-indigo intermediate. Functional N-aryl-N'-alkylindigos were prepared and shown to photoisomerize efficiently under red light. Moreover, this design allows for the modulation of thermal half-lives through N-aryl substituents, while the N'-alkyl groups enable the independent attachment of functional moieties without affecting the photochromic properties. A strong correlation between the structure of the N-aryl moiety and the thermal stability of the photogenerated Z-isomers was achieved by multivariate linear regression models obtained through a data-science workflow. This work thus builds an avenue leading to versatile red-light photoswitches and a general method for structure-property correlation that is expected to be broadly applicable to the design of photoresponsive molecules.

Right On Time: Ultrafast Charge Separation Before Hybrid Exciton Formation.

Organic/inorganic hybrid systems offer great potential for novel solar cell design combining the tunability of organic chromophore absorption properties with high charge carrier mobilities of inorganic semiconductors. However, often such material combinations do not show the expected performance: while ZnO, for example, basically exhibits all necessary properties for a successful application in light-harvesting, it was clearly outpaced by TiO2 in terms of charge separation efficiency. The origin of this deficiency has long been debated. This study employs femtosecond time-resolved photoelectron spectroscopy and many-body ab initio calculations to identify and quantify all elementary steps leading to the suppression of charge separation at an exemplary organic/ZnO interface. It is demonstrated that charge separation indeed occurs efficiently on ultrafast (350 fs) timescales, but that electrons are recaptured at the interface on a 100 ps timescale and subsequently trapped in a strongly bound (0.7 eV) hybrid exciton state with a lifetime exceeding 5 µs. Thus, initially successful charge separation is followed by delayed electron capture at the interface, leading to apparently low charge separation efficiencies. This finding provides a sufficiently large time frame for counter-measures in device design to successfully implement specifically ZnO and, moreover, invites material scientists to revisit charge separation in various kinds of previously discarded hybrid systems.

Welding PROxAb Shuttles: A Modular Approach for Generating Bispecific Antibodies via Site-Specific Protein-Protein Conjugation.

Targeted protein degradation is an innovative therapeutic strategy to selectively eliminate disease-causing proteins. Exemplified by proteolysis-targeting chimeras (PROTACs), they have shown promise in overcoming drug resistance and targeting previously undruggable proteins. However, PROTACs face challenges, such as low oral bioavailability and limited selectivity. The recently published PROxAb Shuttle technology offers a solution enabling the targeted delivery of PROTACs using antibodies fused with PROTAC-binding domains derived from camelid single-domain antibodies (VHHs). Here, a modular approach to quickly generate PROxAb Shuttles by enzymatically coupling PROTAC-binding VHHs to off-the-shelf antibodies was developed. The resulting conjugates retained their target binding and internalization properties, and incubation with BRD4-targeting PROTACs resulted in formation of defined PROxAb-PROTAC complexes. These complexes selectively induced degradation of the BRD4 protein, resulting in cytotoxicity specifically to cells expressing the antibody's target. The chemoenzymatic approach described herein provides a versatile and efficient solution for generating antibody-VHH conjugates for targeted protein degradation applications, but it could also be used to combine antibodies and VHH binders to generate bispecific antibodies for further applications.

Solar Azo-Switches for Effective E→Z Photoisomerization by Sunlight.

Natural photoactive systems have evolved to harness broad-spectrum light from solar radiation for critical functions such as light perception and photosynthetic energy conversion. Molecular photoswitches, which undergo structural changes upon light absorption, are artificial photoactive tools widely used for developing photoresponsive systems and converting light energy. However, photoswitches generally need to be activated by light of specific narrow wavelength ranges for effective photoconversion, which limits their ability to directly work under sunlight and to efficiently harvest solar energy. Here, focusing on azo-switches-the most extensively studied photoswitches, we demonstrate effective solar E→Z photoisomerization with photoconversions exceeding 80 % under unfiltered sunlight. These sunlight-driven azo-switches are developed by rendering the absorption of E isomers overwhelmingly stronger than that of Z isomers across a broad ultraviolet to visible spectrum. This unusual type of spectral profile is realized by a simple yet highly adjustable molecular design strategy, enabling the fine-tuning of spectral window that extends light absorption beyond 600 nm. Notably, back-photoconversion can be achieved without impairing the forward solar isomerization, resulting in unique light-reversible solar switches. Such exceptional solar chemistry of photoswitches provides unprecedented opportunities for developing sustainable light-driven systems and efficient solar energy technologies.

Li Promoting Long Afterglow Organic Light-Emitting Transistor for Memory Optocoupler Module.

The artificial brain is conceived as advanced intelligence technology, capable to emulate in-memory processes occurring in the human brain by integrating synaptic devices. Within this context, improving the functionality of synaptic transistors to increase information processing density in neuromorphic chips is a major challenge in this field. In this article, Li-ion migration promoting long afterglow organic light-emitting transistors, which display exceptional postsynaptic brightness of 7000 cd m-2 under low operational voltages of 10 V is presented. The postsynaptic current of 0.1 mA operating as a built-in threshold switch is implemented as a firing point in these devices. The setting-condition-triggered long afterglow is employed to drive the photoisomerization process of photochromic molecules that mimic neurotransmitter transfer in the human brain for realizing a key memory rule, that is, the transition from long-term memory to permanent memory. The combination of setting-condition-triggered long afterglow with photodiode amplifiers is also processed to emulate the human responding action after the setting-training process. Overall, the successful integration in neuromorphic computing comprising stimulus judgment, photon emission, transition, and encoding,  to emulate the complicated decision tree of the human brain is demonstrated.

Cardiac MRI after Sudden Cardiac Arrest: A Systematic Review.

Purpose To perform a systematic review to assess the diagnostic and prognostic value of cardiac MRI after sudden cardiac arrest (SCA). Materials and Methods PubMed and Cochrane Library databases were systematically searched for studies investigating cardiac MRI after SCA in adult patients (≥18 years of age). The time frame of the encompassed studies spans from January 2012 to January 2023. The study protocol was preregistered in OSF Registries (www.osf.io/nxaev), and the systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included studies was evaluated using the Newcastle-Ottawa quality assessment scale. Results Fourteen studies involving 1367 individuals, 1257 (91.9%) of whom underwent cardiac MRI, were included. Inconsistent findings were reported on the diagnostic value of cardiac MRI-specific findings. The included studies demonstrated the following main findings: (a) cardiac MRI led to a new or alternative diagnosis in patients with SCA; (b) cardiac MRI identified pathologic or arrhythmogenic substrates; (c) cardiac MRI helped detect myocardial edema (potentially reversible); (d) cardiac MRI provided evidence for the occurrence of adverse events; and (e) functional markers or ventricular dimensions were considered prognostically relevant in a few studies. Relevant challenges in this systematic review were the lack of comparators and reference standards relative to cardiac MRI as the index test and patient selection bias. Conclusion Cardiac MRI following SCA can contribute to the diagnostic process and offer supplementary information essential for treatment planning. Limitations of the review include studies with insufficient comparators and potential bias in patient selection. Systematic review registration link: osf.io/nxaev Keywords: Cardiac MRI, Cardiovascular Disease, Cardiomyopathy, Ischemia, Myocardial Edema, Sudden Cardiac Arrest © RSNA, 2024.

Radiological Parameters for the Detection of Pulmonary Hypertension in Severe Aortic Valve Stenosis and Their Influence on Mortality: Does Sex Matter?

Background: Echocardiography has long been established as the primary noninvasive method for diagnosing pulmonary hypertension (PH) prior to transcatheter aortic valve replacement (TAVR) in patients with severe aortic valve stenosis (AS). In recent years, radiological methods for diagnosing PH have been investigated. Measurements such as the computed tomography angiography (CTA)-derived pulmonary artery (PA) diameter and PA diameter/body surface area (PA/BSA) have shown promising results regarding their diagnostic strength. However, it has yet to be determined if a patient's sex has any impact on the effectiveness of these diagnostic measurements. Methods: In all, 271 patients (51.3% male, mean age 82.6 ± 4.8 years) with severe AS undergoing TAVR were separated into male and female groups. The cut-off values for the diagnosis of PH were calculated for the CTA-derived PA diameter and PA/BSA based on different systolic pulmonal artery pressure values (40-45-50 mmHg). Patients were then subclassified according to measurements above or below these PA diameters and PA/BSA cut-off values. A PA diameter ≥29.5 mm and PA/BSA ≥ 15.7 mm/m2 qualified for PH. The 1-5 year survival rate in these cohorts was further analyzed. Results: Patients with a PA diameter ≥29.5 mm showed a significantly higher 1 year mortality rate (p = 0.014). This observation could only be confirmed for the male sex (p = 0.018) and not for the female sex (p = 0.492). As for the PA/BSA, in patients over the cut-off value, no significant increase in mortality was noted in the overall cohort. However, the male patients showed increased 3 year (p = 0.048) and 5 year mortality rates (p = 0.033). Conclusions: The CTA-obtained PA diameter and PA/BSA are both useful in the diagnosis of PH and mortality risk stratification in patients with severe AS undergoing TAVR, especially in males. Male patients with PA ≥ 29.5 mm or PA/BSA ≥ 15.7 mm/m2 seem to be at a higher risk of death during follow-up after undergoing TAVR. In females, no such correlation was observed.

Photoswitchable Quadruple Hydrogen-Bonding Motif.

Multiple hydrogen-bonding motifs serve as important building blocks for molecular recognition and self-assembly. Herein, a photoswitchable quadruple hydrogen-bonding motif featuring near-complete, reversible, and thermostable conversion between DADA and AADD arrays associated with an alteration of their dimerization constants by over 3 orders of magnitude is reported. The system is based on a diarylethene featuring a ureidopyrimidin-4-ol moiety, which upon photoinduced ring closure and associated loss of aromaticity undergoes enol-keto tautomerization to a ureidopyrimidinone moiety. The latter causes a transformation of the hydrogen-bonding arrays and significantly weakens the free energy of dimerization in the case of the closed isomer. This photoswitchable quadruple hydrogen-bonding motif should allow us to spatially and temporarily direct self-assembly and supramolecular polymerization processes by light.

Revisiting Peri-Aryloxyquinones: From a Forgotten Photochromic System to a Promising Tool for Emerging Applications.

Emerging applications of photochromic compounds demand new molecular designs that can be inspired by some long-known yet currently forgotten classes of photoswitches. In the present review, we remind the community about Peri-AryloxyQuinones (PAQs) and their unique photoswitching behavior originally discovered more than 50 years ago. At the heart of this phenomenon is the light-induced migration of an aromatic moiety (arylotropy) in peri-aryloxy-substituted quinones resulting in ana-quinones. PAQs feature absorbance of both isomers in the visible spectral region, photochromism in the amorphous and crystalline state, and thermal stability of the photogenerated ana-isomer. Particularly noticeable is the high sensitivity of the ana-isomer towards nucleophiles in solution. In addition to the mechanism of molecular photochromism and the underlaying structure-switch relationships, we analyze potential applications and prospects of aryloxyquinones in optically switchable materials and devices. Due to their ability to efficiently photoswitch in the solid state, PAQs are indeed attractive candidates for such materials and devices, including electronics (optically controllable circuits, switches, transistors, memories, and displays), porous crystalline materials, crystalline actuators, photoactivated sensors, and many more. This review is intended to serve as a guide for researchers who wish to use photoswitchable PAQs in the development of new photocontrollable materials, devices, and processes.

Continuous Volumetric 3D Printing: Xolography in Flow.

Additive manufacturing techniques continue to improve in resolution, geometrical freedom, and production rates, expanding their application range in research and industry. Most established techniques, however, are based on layer-by-layer polymerization processes, leading to an inherent trade-off between resolution and printing speed. Volumetric 3D printing enables the polymerization of freely defined volumes allowing the fabrication of complex geometries at drastically increased production rates and high resolutions, marking the next chapter in light-based additive manufacturing. This work advances the volumetric 3D printing technique xolography to a continuous process. Dual-color photopolymerization is performed in a continuously flowing resin, inside a tailored flow cell. Supported by simulations, the flow profile in the printing area is flattened, and resin velocities at the flow cell walls are increased to minimize unwanted polymerization via laser sheet-induced curing. Various objects are printed continuously and true to shape with smooth surfaces. Parallel object printing paves the way for up-scaling the continuous production, currently reaching production rates up to 1.75 mm3 s-1 for the presented flow cell. Xolography in flow provides a new opportunity for scaling up volumetric 3D printing with the potential to resolve the trade-off between high production rates and high resolution in light-based additive manufacturing.

Diaryltriazolium Photoswitch: Reaching a Millisecond Cycloreversion with High Stability and NIR Absorption.

The exceptional thermal stability of diarylethene closed isomers enabled many applications but also prevented utilization in photochromic systems that require rapid thermal reversibility. Herein, we report the diaryltriazolium (DAT+ ) photoswitch undergoing thermal cycloreversion within a few milliseconds and absorption of the closed form in the near-infrared region above 900 nm. Click chemistry followed by alkylation offers modular and fast access to the electron-deficient DAT+ scaffold. In addition to excellent fatigue resistance, the introduced charge increases water solubility, rendering this photoswitch an ideal candidate for exploring biological applications.

Large Bouncing Mass in the Right Atrium: Metastasis of Malignant Melanoma.

This paper presents a rare case of malignant melanoma metastasizing to the heart, highlighting the diagnostic journey, therapeutic considerations, and clinical implications. Enhanced awareness of atypical metastases aids early recognition and treatment strategies for improved patient care. Comprehensive understanding of cardiac involvement in melanoma contributes to better outcomes and clinical decision making. (Level of Difficulty: Beginner.).

Generation and Characterization of Iduronidase-Cleavable ADCs.

A crucial design feature for the therapeutic success of antibody-drug conjugates (ADCs) is the linker that connects the antibody with the drug. Linkers must be stable in circulation and efficiently release the drug inside the target cell, thereby having a fundamental impact on ADC pharmacokinetics and efficacy. The variety of enzymatically cleavable linkers applied in ADCs is limited, and some are believed to be associated with unwanted side effects due to the expression of cleavage-mediating enzymes in nonmalignant cells. Based on a bioinformatic screen of lysosomal enzymes, we identified α-l-iduronidase (IduA) as an interesting candidate for ADC linker cleavage because of its low expression in normal tissues and its overexpression in several tumor types. In the present study, we report a novel IduA-cleavable ADC linker using exatecan and duocarmycin as payloads. We showed the functionality of our linker system in cleavage assays using recombinant IduA or cell lysates and compared it to established ADC linkers. Subsequently, we coupled iduronide-exatecan via interchain cysteines or iduronide-duocarmycin via microbial transglutaminase (mTG) to an anti-CEACAM5 (aCEA5) antibody. The generated iduronide-exatecan ADC showed high serum stability and similar target-dependent tumor cell killing in the subnanomolar range but reduced toxicity on nonmalignant cells compared to an analogous cathepsin B-activatable valine-citrulline-exatecan ADC. Finally, in vivo antitumor activity could be demonstrated for an IduA-cleavable duocarmycin ADC. The presented results emphasize the potential of iduronide linkers for ADC development and represent a tool for further balancing out tumor selectivity and safety.

Room Temperature On-Surface Synthesis of a Vinylene-Linked Single Layer Covalent Organic Framework.

Conjugated single-layered two-dimensional covalent organic frameworks are flat and extended polymer networks with a unique combination of material properties, giving rise to potential applications in sensing, optoelectronics, and photonics. Despite their great potential, thus far only a few reactions to access such extended conjugated 2D polymers have been reported. Here, the on-surface polymerization of the first vinylene-linked single layered two-dimensional covalent organic framework using reversible Knoevenagel polycondensation under solvothermal conditions is described. Self-assembly of the two monomer building blocks at the solid-liquid interface led to the formation of extended covalent networks at room temperature without the need of additional catalysts or reagents. The described approach grants access to extended conjugated 2D polymers under unprecedentedly mild conditions and paves the way to new hybrid material systems.

DiI-CT-A bimodal neural tracer for X-ray and fluorescence imaging.

Here, we present an X-ray-visible neural tracer, referred to as DiI-CT, which is based on the well-established lipophilic indocarbocyanine dye DiI, to which we conjugated two iodine atoms. The tracer is visible with microfocus computed tomography (microCT) imaging and shares the excellent fluorescent tracing properties of DiI. We document the discovery potential of DiI-CT by analyzing the vibrissa follicle-sinus complex, a structure where visual access is poor and 3D tissue structure matters and reveal innervation patterns of the intact follicle in unprecedented detail. In the brain, DiI-CT tracing holds promise for verification evaluation of indirect connectivity measures, such as diffusion tensor imaging. We conclude that the bimodal dye DiI-CT opens new avenues for neuroanatomy.