Changes in pancreatic steatosis by computed tomography 24 months after sleeve gastrectomy in youth with severe obesity.

BACKGROUND: Pancreatic steatosis has been associated with obesity and the metabolic syndrome. Studies in adults have demonstrated improvement in pancreatic steatosis following sleeve gastrectomy (SG) with concomitant improvement in glucose homeostasis. OBJECTIVES: To examine changes in pancreatic steatosis in youth with severe obesity 24 months following SG. SETTING: Academic hospital system. METHODS: Forty-seven youth (13-24 years) with severe obesity (37 females) were followed for 24 months; 23 had SG and 24 were nonsurgical (NS) controls. Attenuations of the pancreas and spleen were measured using computed tomography (CT) at baseline, 12- and 24-month follow-up. Subjects underwent magnetic resonance imaging (MRI) for subcutaneous and visceral adipose tissue (SAT, VAT), dual energy x-ray absorptiometry (DXA) for body composition, blood sampling for glycated hemoglobin (A1C), and fasting and postprandial insulin and glucose. Linear mixed effects (LMEs) models were used to compare within- and between-group changes over 24 months. RESULTS: At baseline, SG had higher body mass index (BMI) versus NS (P = .033). Over 24 months, significant reductions were noted in weight, BMI, VAT, SAT, fat mass (FM), and lean mass (LM) in the SG versus NS groups (P ≤ .0001). There was a significant 24-month decrease in pancreatic steatosis in the SG group (P = .006). In the whole group, 24-month reductions in pancreatic steatosis correlated with BMI and FM decreases. No associations were found between pancreatic steatosis and glucose homeostasis parameters. CONCLUSIONS: Pancreatic steatosis measured by CT improved after SG in youth. Further studies are needed to understand the relationship between pancreatic steatosis and glucose homeostasis.

Strain-resolved de-novo metagenomic assembly of viral genomes and microbial 16S rRNAs.

BACKGROUND: Metagenomics is a powerful approach to study environmental and human-associated microbial communities and, in particular, the role of viruses in shaping them. Viral genomes are challenging to assemble from metagenomic samples due to their genomic diversity caused by high mutation rates. In the standard de Bruijn graph assemblers, this genomic diversity leads to complex k-mer assembly graphs with a plethora of loops and bulges that are challenging to resolve into strains or haplotypes because variants more than the k-mer size apart cannot be phased. In contrast, overlap assemblers can phase variants as long as they are covered by a single read. RESULTS: Here, we present PenguiN, a software for strain resolved assembly of viral DNA and RNA genomes and bacterial 16S rRNA from shotgun metagenomics. Its exhaustive detection of all read overlaps in linear time combined with a Bayesian model to select strain-resolved extensions allow it to assemble longer viral contigs, less fragmented genomes, and more strains than existing assembly tools, on both real and simulated datasets. We show a 3-40-fold increase in complete viral genomes and a 6-fold increase in bacterial 16S rRNA genes. CONCLUSION: PenguiN is the first overlap-based assembler for viral genome and 16S rRNA assembly from large and complex metagenomic datasets, which we hope will facilitate studying the key roles of viruses in microbial communities. Video Abstract.

Chemical inhibition of the integrated stress response impairs the ubiquitin-proteasome system.

Inhibitors of the integrated stress response (ISR) have been used to explore the potential beneficial effects of reducing the activation of this pathway in diseases. As the ISR is in essence a protective response, there is, however, a risk that inhibition may compromise the cell's ability to restore protein homeostasis. Here, we show that the experimental compound ISRIB impairs degradation of proteins by the ubiquitin-proteasome system (UPS) during proteotoxic stress in the cytosolic, but not nuclear, compartment. Accumulation of a UPS reporter substrate that is intercepted by ribosome quality control was comparable to the level observed after blocking the UPS with a proteasome inhibitor. Consistent with impairment of the cytosolic UPS, ISRIB treatment caused an accumulation of polyubiquitylated and detergent insoluble defective ribosome products (DRiPs) in the presence of puromycin. Our data suggest that the persistent protein translation during proteotoxic stress in the absence of a functional ISR increases the pool of DRiPs, thereby hindering the efficient clearance of cytosolic substrates by the UPS.

Effect of Propofol Versus Sevoflurane on Erections during Narcosis in Transurethral Surgery: The PENIS Trial.

Penile erection is unwanted during transurethral interventions as it may be associated with adverse events such as impaired access, prolonged operation time, abortion of the procedure, or a need for ancillary measures to reach penis flaccidity, such as intracorporeal injection of vasoactive drugs. In recent years, anesthesia with propofol has been favored over sevoflurane for environmental reasons. To the best of our knowledge, there have been no prospective randomized clinical trials evaluating the impact of general narcosis medications on the risk of such unwanted penile erections during transurethral surgery. To fill this gap, we have planned a prospective, double-blind (surgeon and patient), single-center, randomized controlled trial. The primary outcome is the occurrence of an intraoperative penile erection. The secondary outcomes are related to the impact of the primary outcome on the surgery, such as changes in operative strategy or operation duration, abortion of the procedure, and adverse events. The plan is to randomize 200 patients undergoing transurethral surgery to receive general anesthesia with either propofol or sevoflurane. The inclusion criteria are men aged <75 yr with an International Index of Erectile Function-5 score of ≥12 points. All men fulfilling the inclusion criteria will be asked to participate. Exclusion criteria are patient characteristics associated with a higher risk of complications with the use of either propofol or sevoflurane. Randomization and treatment allocation will occur after patients give consent. The results will be statistically analyzed using a logistic regression model. This research has received ethical clearance from the local ethics committee (KEK code 2023-01682). The trial is registered on the Swiss National Clinical Trials Portal (SNCTP000005681) and on ClinicalTrial.gov (NCT06378645).

A potent pan-sarbecovirus neutralizing antibody resilient to epitope diversification.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing coronavirus mAbs that are sufficiently potent for clinical development and retain activity despite viral evolution remain elusive. We identified a human mAb, designated VIR-7229, which targets the viral receptor-binding motif (RBM) with unprecedented cross-reactivity to all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently neutralizing SARS-CoV-2 variants since 2019, including the recent EG.5, BA.2.86, and JN.1. VIR-7229 tolerates extraordinary epitope variability, partly attributed to its high binding affinity, receptor molecular mimicry, and interactions with RBM backbone atoms. Consequently, VIR-7229 features a high barrier for selection of escape mutants, which are rare and associated with reduced viral fitness, underscoring its potential to be resilient to future viral evolution. VIR-7229 is a strong candidate to become a next-generation medicine.

Body temperature, systemic inflammation and risk of adverse events in patients with acute coronary syndromes.

BACKGROUND: Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low-cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS. METHODS: From 2012 until 2017, a total of 1044 ACS patients, 517 with STEMI and 527 with NSTE-ACS, were prospectively recruited at the University Hospital Zurich. BT was measured by digital tympanic thermometer along with high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin-T (hs-cTnT) levels prior to coronary angiography. Patients were stratified according to initial BT and uni- and multivariable regression models were fit to assess associations of BT with future MACE risk. RESULTS: Among patients with STEMI, BT was not predictive of 1-year MACE, but a U-shaped relationship between BT and MACE risk was noted in those with NSTE-ACS (p = .029), translating into a 2.4-fold (HR, 2.44, 95% CI, 1.16-5.16) increased 1-year MACE risk in those with BT >36.8°C (reference: 36.6-36.8°C). Results remained robust in multivariable-adjusted analyses accounting for sex, age, diabetes, renal function and hs-cTnT. However, when introducing hs-CRP, the BT-MACE association did not prevail. CONCLUSIONS: In prospectively recruited patients with ACS, initial BT shows a U-shaped relationship with 1-year MACE risk among those with NSTE-ACS, but not in those with STEMI. BT is a broadly available low-cost marker to identify ACS patients with high inflammatory burden, at high risk for recurrent ischaemic events, and thus potentially suitable for an anti-inflammatory intervention. REGISTRATION: ClinicalTrials.gov Identifier: NCT01000701.

Whole-body non-forensic fetal virtopsy using postmortem magnetic resonance imaging at 7 Tesla vs classical autopsy.

OBJECTIVE: To determine the diagnostic accuracy of virtual autopsy using whole-body postmortem ultra-high field magnetic resonance imaging (MRI) at 7 Tesla (T), using a short T2-weighted imaging (T2-WI) protocol, compared with classical autopsy, for detecting structural abnormalities in small second-trimester fetuses. METHODS: Thirty consecutive fetuses at 13-19 weeks' gestation (weight, 17-364 g) were included following spontaneous pregnancy loss or termination of pregnancy. After fixation in 10% formaldehyde solution (48 h to 1 week), all fetuses were scanned using a two-dimensional turbo high-resolution T2-WI protocol with multislice relaxation time, followed by an invasive autopsy. The diagnostic accuracy of virtual autopsy vs classical autopsy was calculated for 990 anatomical structures (30 fetuses × 33 items). Sensitivity, specificity, positive and negative predictive values and Cohen's κ coefficient of agreement, with their 95% CIs, as well as the McNemar test, were used to evaluate the accuracy and agreement of the two diagnostic methods. Analysis was stratified by anatomical segment (nervous, pulmonary, cardiovascular, digestive, renal, facial and skeletal) and across three gestational-age intervals (13-14, 15-16 and 17-19 weeks). RESULTS: Considering classical autopsy as the gold standard, virtual autopsy had a sensitivity of 92.04% (95% CI, 85.42-96.29%) and a specificity of 97.87% (95% CI, 94.64-99.42%), with a positive predictive value of 96.30% (95% CI, 90.78-98.56%) and a negative predictive value of 95.34% (95% CI, 91.61-97.45%), achieving a diagnostic accuracy of 95.68% (95% CI, 92.73-97.68%) for detecting structural abnormalities in second-trimester fetuses. Cohen's κ for virtual vs classical autopsy was 0.907. The diagnostic ability of virtual autopsy at 7 T for malformed fetuses was superior to that of classical autopsy for analyzing the nervous system in small fetuses with pronounced autolysis, equivalent to that of classical autopsy when analyzing pulmonary, cardiovascular and renal systems and inferior when evaluating the fetal intestines. The sensitivity of virtual autopsy at 7 T for describing structural abnormalities increased with gestational age. CONCLUSION: Virtual fetal autopsy using 7-T MRI and a turbo high-resolution T2-WI protocol with multislice relaxation time is a feasible postmortem diagnostic tool for the identification of fetal structural anomalies. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Diverging Elevational Patterns of Tree vs. Epiphyte Species Density, Beta Diversity, and Biomass in a Tropical Dry Forest.

There is evidence to suggest that vascular epiphytes experience low competition for resources (light, water, and nutrients) compared to terrestrial plants. We tested the hypothesis that low resource competition may lead to higher nestedness among vascular epiphyte assemblages compared to trees. We studied the species composition and biomass of epiphytes and trees along an elevation gradient in a tropical dry forest in SW Ecuador. Both life-forms were inventoried on 25 plots of 400 m2 across five elevation levels (550-1250 m). Tree species density and total species richness increased with elevation, whereas basal area and biomass did not show significant trends. Epiphyte species density and richness both increased strongly with elevation, in parallel to biomass. Plot-level compositional changes were similarly strong for both life-forms. We attribute elevational increases in the species richness of trees and epiphytes to increasing humidity, i.e., more mesic growth conditions. We attribute the more pronounced elevational increase in epiphyte biomass, species density, and richness-the latter coupled with a higher degree of nestedness-to the greater moisture dependency of epiphytes and relatively low direct competition for resources. Our study provides a first comparison of elevational trends in epiphyte and tree diversity and biomass for a tropical dry forest.

An hepatitis B and D virus infection model using human pluripotent stem cell-derived hepatocytes.

Current culture systems available for studying hepatitis D virus (HDV) are suboptimal. In this study, we demonstrate that hepatocyte-like cells (HLCs) derived from human pluripotent stem cells (hPSCs) are fully permissive to HDV infection across various tested genotypes. When co-infected with the helper hepatitis B virus (HBV) or transduced to express the HBV envelope protein HBsAg, HLCs effectively release infectious progeny virions. We also show that HBsAg-expressing HLCs support the extracellular spread of HDV, thus providing a valuable platform for testing available anti-HDV regimens. By challenging the cells along the differentiation with HDV infection, we have identified CD63 as a potential HDV co-entry factor that was rate-limiting for HDV infection in immature hepatocytes. Given their renewable source and the potential to derive hPSCs from individual patients, we propose HLCs as a promising model for investigating HDV biology. Our findings offer new insights into HDV infection and expand the repertoire of research tools available for the development of therapeutic interventions.

The small MAF transcription factor MAFG co-opts MITF to promote melanoma progression.

Transcription factor deregulation potently drives melanoma progression by dynamically and reversibly controlling gene expression programs. We previously identified the small MAF family transcription factor MAFG as a putative driver of melanoma progression, prompting an in-depth evaluation of its role in melanoma. MAFG expression increases with human melanoma stages and ectopic MAFG expression enhances the malignant behavior of human melanoma cells in vitro, xenograft models, and genetic mouse models of spontaneous melanoma. Moreover, MAFG induces a melanoma phenotype switch from a melanocytic state to a more dedifferentiated state. Mechanistically, MAFG interacts with the lineage transcription factor MITF which is required for the pro-tumorigenic effects of MAFG. MAFG and MITF co-occupy numerous genomic sites and MAFG overexpression influences the expression of genes harboring binding sites for the MAFG~MITF complex. These results establish MAFG as a potent driver of melanomagenesis through dimerization with MITF and uncover an unappreciated mechanism of MITF regulation.

First Indicator of Relapse in Testicular Cancer and Implications for Follow-up: Analysis of the Swiss Austrian German Testicular Cancer Cohort Study (SAG TCCS).

Background and objective: Follow-up for patients with testicular cancer should ensure early detection of relapses. Optimal schedules and minimum requirements for cross-sectional imaging are not clearly defined, and guideline recommendations differ. Our aim was to analyse the clinical impact of different imaging modalities for detection of relapse in a large prospective cohort (Swiss Austrian German Testicular Cancer Cohort Study, SAG TCCS). Methods: Patients with seminoma or nonseminoma were prospectively enrolled between January 2014 and February 2023 after initial treatment (n = 1175). Follow-up according to the study schedule was individualised for histology and disease stage. Only patients who had received primary treatment were considered. We analysed the total number of imaging modalities and scans identifying relapse and the timing of relapse. Key findings and limitations: We analysed data for 1006 patients (64% seminoma, 36% nonseminoma); 76% had stage I disease. Active surveillance was the most frequent management strategy (65%). Recurrence occurred in 82 patients, corresponding to a 5-yr relapse-free survival rate of 90.1% (95% confidence interval 87.7-92.1%). Median follow-up for patients without relapse was 38.4 mo (interquartile range 21.6-61.0). Cross-sectional imaging of the abdomen was the most important indicator of relapse 57%, abdominal CT accounting for 46% and MRI for 11%. Marker elevation indicated relapse in 24% of cases. Chest X-ray was the least useful modality, indicating relapse in just 2% of cases. Conclusions and clinical implications: On the basis of findings from our prospective register, we have adapted a follow-up schedules with an emphasis on abdominal imaging and a reduction in chest X-rays. This schedule might provide additional guidance for clinicians and will be prospectively evaluated as SAG TCCS continues to enrol patients. Patient summary: We analysed the value of different types of imaging scans for detection of relapse of testicular cancer. We used our findings to propose an optimum follow-up schedule for patients with testicular cancer.

Biomarker-enhanced cardiovascular risk prediction in patients with cancer: a prospective cohort study.

BACKGROUND: Continuously improving cancer-specific survival puts a growing proportion of cancer patients at risk of major adverse cardiovascular events (MACE), but tailored tools for cardiovascular risk prediction remain unavailable. OBJECTIVES: To assess a broad panel of cardiovascular biomarkers and risk factors for the prediction of MACE and cardiovascular death in cancer patients. METHODS: In total, 2192 patients with newly diagnosed or recurrent cancer were followed prospectively for the occurrence of 2-year MACE and 5-year cardiovascular death. Univariable and multivariable risk models were fit to assess independent associations of cardiovascular risk factors and biomarkers with adverse outcomes, and a risk score was developed. RESULTS: Traditional cardiovascular risk factors and selected cancer types were linked to higher MACE risk. While levels of Lp(a), CRP, and GDF-15 did not associate with MACE, levels of ICAM-1, P-/E-/L-selectins, and NT-proBNP were independently linked to 2-year MACE risk. A clinical risk score was derived, assigning +1 point for male sex, smoking, and age of ≥60 years and +2 points for atherosclerotic disease, yielding a bootstrapped C-statistic of 0.76 (95% CI: 0.71-0.81) for the prediction of 2-year MACE. Implementation of biomarker data conferred improved performance (0.83, 95% CI: 0.78-0.88), with a simplified model showing similar performance (0.80, 95% CI: 0.74-0.86). The biomarker-enhanced and simplified prediction models achieved a C-statistic of 0.82 (95% CI: 0.71-0.93) and 0.74 (95% CI: 0.64-0.83) for the prediction of 5-year cardiovascular death. CONCLUSION: Biomarker-enhanced risk prediction strategies allow the identification of cancer patients at high risk of MACE and cardiovascular death. While external validation studies are ongoing, this first-of-its-kind risk score may provide the basis for personalized cardiovascular risk assessment across cancer entities.

Spatial characterization and stratification of colorectal adenomas by deep visual proteomics.

Colorectal adenomas (CRAs) are potential precursor lesions to adenocarcinomas, currently classified by morphological features. We aimed to establish a molecular feature-based risk allocation framework toward improved patient stratification. Deep visual proteomics (DVP) is an approach that combines image-based artificial intelligence with automated microdissection and ultra-high sensitive mass spectrometry. Here, we used DVP on formalin-fixed, paraffin-embedded (FFPE) CRA tissues from nine male patients, immunohistologically stained for caudal-type homeobox 2 (CDX2), a protein implicated in colorectal cancer, enabling the characterization of cellular heterogeneity within distinct tissue regions and across patients. DVP identified DMBT1, MARCKS, and CD99 as protein markers linked to recurrence, suggesting their potential for risk assessment. It also detected a metabolic shift to anaerobic glycolysis in cells with high CDX2 expression. Our findings underscore the potential of spatial proteomics to refine early stage detection and contribute to personalized patient management strategies and provided novel insights into metabolic reprogramming.

A new drying method of thermolabile flexible endoscope channels by laminar and turbulent airflow - a prospective, randomized-controlled, single-center, proof-of-concept trial.

BACKGROUND AND AIMS: International guidelines suggest different possibilities for drying of endoscopes during reprocessing. Clinical results of these available drying methods are not satisfactory. The aim of this study was to compare the drying cycle of a standard endoscope washer-disinfector (EWD) (standard drying method [SD]) with a shortened mandatory drying by the EWD followed by a special drying device using laminar and turbulent air flow (novel drying method [ND]). PATIENTS AND METHODS: Sixty endoscopes (duodenoscopes, colonoscocopes and gastroscopes) from three different manufacturers underwent high-level disinfection and drying depending on the randomization group. Operational time of drying was measured for both groups. Residual fluid in the channels was measured using a laboratory scale. After a 14 day storage period, a sample of the endoscope channels was obtained to determine bacterial contamination. RESULTS: ND had significantly fewer residual water in endoscope channels (SD: 90% vs ND: 0%; p < 0.001) after high-level disinfection and drying, and less bacterial contamination after storage for 14 days (SD: 47% vs ND: 20%; p = 0.028). Time consumed for drying in ND was also significantly shorter (SD: 16min 4sec vs ND: 5min 59sec; p < 0.001). CONCLUSIONS: Drying with a special automatic drying device was superior compared with an EWD's drying program as evidenced by no measurable residual water, reduced microbiological contamination and a more than two-fold decrease in operational time. Thus, drying by laminar and turbulent airflow may represent an attractive alternative to the currently used standard approach in the reprocessing process of flexible endoscopes.

Proenkephalin Improves Cardio-Renal Risk Prediction in Acute Coronary Syndromes: The KID-ACS Score.

BACKGROUND AND AIMS: Circulating proenkephalin (PENK) is a stable endogenous polypeptide with fast response to glomerular dysfunction and tubular damage. This study examined the predictive value of PENK for renal outcomes and mortality in patients with acute coronary syndromes (ACS). METHODS: Proenkephalin was measured in plasma in a prospective multicentre ACS cohort from Switzerland (n=4787) and in validation cohorts from the UK (n=1141), Czechia (n=927), and Germany (n=220). A biomarker-enhanced risk score (KID-ACS score) for simultaneous prediction of in-hospital acute kidney injury (AKI) and 30-day mortality was derived and externally validated. RESULTS: On multivariable adjustment for established risk factors, circulating PENK remained associated with in-hospital AKI (per log2 increase: adjusted odds ratio [OR] 1.53, 95% confidence interval [CI] 1.13-2.09, P=0.007) and 30-day mortality (adjusted hazard ratio [HR] 2.73, 95% CI 1.85-4.02, P<0.001). The KID-ACS score integrates PENK and showed an area under the receiver operating characteristic curve (AUC) of 0.72 (95% CI 0.68-0.76) for in-hospital AKI, and of 0.91 (95% CI 0.87-0.95) for 30-day mortality in the derivation cohort. Upon external validation, KID-ACS achieved similarly high performance for in-hospital AKI (Zurich: AUC 0.73, 95% CI 0.70-0.77; Czechia: AUC 0.75, 95% CI 0.68-0.81; Germany: AUC 0.71, 95% CI 0.55-0.87) and 30-day mortality (UK: AUC 0.87, 95% CI 0.83-0.91; Czechia: AUC 0.91, 95% CI 0.87-0.94; Germany: AUC 0.96, 95% CI 0.92-1.00) outperforming the CA-AKI score and the GRACE 2.0 score, respectively. CONCLUSIONS: Circulating PENK offers incremental value for predicting in-hospital AKI and mortality in ACS. The simple 6-item KID-ACS risk score integrates PENK and provides a novel tool for simultaneous assessment of renal and mortality risk in patients with ACS.

The Effects of Normobaric Hypoxia on the Acute Physiological Responses to Resistance Training: A Narrative Review.

ABSTRACT: Allsopp, GL, Britto, FA, Wright, CR, and Deldicque, L. The effects of normobaric hypoxia on the acute physiological responses to resistance training: a narrative review. J Strength Cond Res XX(X): 000-000, 2024-Athletes have used altitude training for many years as a strategy to improve endurance performance. The use of resistance training in simulated altitude (normobaric hypoxia) is a growing strategy that aims to improve the hypertrophy and strength adaptations to training. An increasing breadth of research has characterized the acute physiological responses to resistance training in hypoxia, often with the goal to elucidate the mechanisms by which hypoxia may improve the training adaptations. There is currently no consensus on the overall effectiveness of hypoxic resistance training for strength and hypertrophy adaptations, nor the underlying biochemical pathways involved. There are, however, numerous interesting physiological responses that are amplified by performing resistance training in hypoxia. These include potential changes to the energy system contribution to exercise and alterations to the level of metabolic stress, hormone and cytokine production, autonomic regulation, and other hypoxia-induced cellular pathways. This review describes the foundational exercise physiology underpinning the acute responses to resistance training in normobaric hypoxia, potential applications to clinical populations, including training considerations for athletic populations. The review also presents a summary of the ideal training parameters to promote metabolic stress and associated training adaptations. There are currently many gaps in our understanding of the physiological responses to hypoxic resistance training, partly caused by the infancy of the research field and diversity of hypoxic and training parameters.

Artificial intelligence in cardiovascular medicine: clinical applications.

Clinical medicine requires the integration of various forms of patient data including demographics, symptom characteristics, electrocardiogram findings, laboratory values, biomarker levels, and imaging studies. Decision-making on the optimal management should be based on a high probability that the envisaged treatment is appropriate, provides benefit, and bears no or little potential harm. To that end, personalized risk-benefit considerations should guide the management of individual patients to achieve optimal results. These basic clinical tasks have become more and more challenging with the massively growing data now available; artificial intelligence and machine learning (AI/ML) can provide assistance for clinicians by obtaining and comprehensively preparing the history of patients, analysing face and voice and other clinical features, by integrating laboratory results, biomarkers, and imaging. Furthermore, AI/ML can provide a comprehensive risk assessment as a basis of optimal acute and chronic care. The clinical usefulness of AI/ML algorithms should be carefully assessed, validated with confirmation datasets before clinical use, and repeatedly re-evaluated as patient phenotypes change. This review provides an overview of the current data revolution that has changed and will continue to change the face of clinical medicine radically, if properly used, to the benefit of physicians and patients alike.

Computationally Efficient IMplicit Training Strategy for UNrolled NEtworks (IMUNNE): A preliminary analysis using accelerated real-time cardiac cine MRI.

OBJECTIVE: Highly-undersampled, dynamic MRI reconstruction, particularly in multi-coil scenarios, is a challenging inverse problem. Unrolled networks achieve state-of-the-art performance in MRI reconstruction but suffer from long training times and extensive GPU memory cost. METHODS: In this work, we propose a novel training strategy for IMplicit UNrolled NEtworks (IMUNNE) for highly-undersampled, multi-coil dynamic MRI reconstruction. It formulates the MRI reconstruction problem as an implicit fixed-point equation and leverages gradient approximation for backpropagation, enabling training of deep architectures with fixed memory cost. This study represents the first application of implicit network theory in the context of real-time cine MRI. The proposed method is evaluated using a prospectively undersampled, real-time cine dataset using radial k-space sampling, comprising balanced steady-state free precession (b-SSFP) readouts. Experiments include a hyperparameter search, head-to-head comparisons with a complex U-Net (CU-Net) and an alternating unrolled network (Alt-UN), and an analysis of robustness under noise perturbations; peak signal-to-noise ratio, structural similarity index, normalized root mean-square error, spatio-temporal entropic difference, and a blur metric were used. RESULTS: IMUNNE produced significantly and slightly better image quality compared to CU-Net and Alt-UN, respectively. Compared with Alt-UN, IMUNNE significantly reduced training and inference times, making it a promising approach for highly-accelerated, multi-coil real-time cine MRI reconstruction. CONCLUSION: IMUNNE strategy successfully applies unrolled networks to image reconstruction of highly-accelerated, real-time radial cine MRI. SIGNIFICANCE: Implicit training enables rapid, high-quality, and cost-effective CMR exams by reducing training and inference times and lowering memory cost associated with advanced reconstruction methods.

Tribulus (Zygophyllaceae) as a case study for the evolution of C2 and C4 photosynthesis.

C2 photosynthesis is a photosynthetic pathway in which photorespiratory CO2 release and refixation are enhanced in leaf bundle sheath (BS) tissues. The evolution of C2 photosynthesis has been hypothesized to be a major step in the origin of C4 photosynthesis, highlighting the importance of studying C2 evolution. In this study, physiological, anatomical, ultrastructural, and immunohistochemical properties of leaf photosynthetic tissues were investigated in six non-C4 Tribulus species and four C4 Tribulus species. At 42°C, T. cristatus exhibited a photosynthetic CO2 compensation point in the absence of respiration (C*) of 21 µmol mol-1, below the C3 mean C* of 73 µmol mol-1. Tribulus astrocarpus had a C* value at 42°C of 55 µmol mol-1, intermediate between the C3 species and the C2 T. cristatus. Glycine decarboxylase (GDC) allocation to BS tissues was associated with lower C*. Tribulus cristatus and T. astrocarpus allocated 86% and 30% of their GDC to the BS tissues, respectively, well above the C3 mean of 11%. Tribulus astrocarpus thus exhibits a weaker C2 (termed sub-C2) phenotype. Increased allocation of mitochondria to the BS and decreased length-to-width ratios of BS cells, were present in non-C4 species, indicating a potential role in C2 and C4 evolution.