Transverse arch stenting and its effect on systemic hypertension.

Background: This study aimed to investigate the safety and efficacy of transverse aortic arch stenting and evaluate the course of hypertension and the act of arch stenting on systemic hypertension. Methods: The transverse aortic arch stenting procedures between January 2007 and May 2023 were retrospectively analyzed. Detailed procedure information, technical aspects, pressure measurements, angiographic data, balloons and stents used, complications, and immediate results were examined. Early and mid-term results were assessed. Results: Eighteen patients (10 males and 8 females; mean age: 14.5±5.3 years; range, 4 to 23 years) were included in the study, all of whom were hypertensive before the procedure. The mean weight was 56.8±19.6 kg. In seven patients, the stent struts had to be dilated due to the stent causing jailing at the entrance of nearby arch vessels. After stenting, there was a significant increase in arch diameter and a decrease in ascending aorta pressure and the pressure gradient across the aorta. There were no early mortality or major complications. Late migration of the stent was observed in one patient. Three patients became normotensive immediately after the intervention, and five became drug-free during the follow-up. The requirement for dual antihypertensive therapy was significantly reduced. Conclusion: Residual transverse arch lesions may contribute to the persistence of systemic hypertension after coarctation treatment. Transverse arch stent implantation can be performed safely with favorable outcomes, facilitating better blood pressure control. However, it should be noted that these patients remain at risk for lifelong hypertension and should be closely monitored in this regard.

The Lifesaving Impact of Transcatheter Interventions in the Early Post-Fontan Palliation Period.

Despite advancements in postoperative outcomes after Fontan surgery, there remains a risk of suboptimal outcomes and significant morbidity in the early postoperative period. Anatomical obstructions in the Fontan pathway can lead to prolonged pleural effusion or ascites, cyanosis, and low cardiac output syndrome (LCOS). Transcatheter interventions offer an alternative to early re-surgery for treating these complications. Over a 13-year period, early catheter angiography, performed within 30 days post-index procedure, was administered to 41 patients, identifying anatomical issues that necessitated re-intervention in 39 cases. This led to transcatheter interventions in 37 (10.4%) of the 344 Fontan surgery patients. The median age was 4.8 years (IQR: 4-9.4), and the median weight was 16.5 kg (IQR: 15-25.2), with females comprising 51.4% (19/37) of this group. The primary indications for the procedures were persistent pleural effusion or ascites in 27 patients (66%), LCOS in 8 patients (20%), and cyanosis in 6 patients (14%). Among the 37 undergoing transcatheter intervention, 30 were treated solely with this method and discharged, three died in ICU follow-up, and four required early re-surgery. No procedural mortality was observed. Our findings demonstrate that transcatheter interventions, including stent implantation, balloon angioplasty, and fenestration dilation, are safe and effective in the early post-Fontan period. Therefore, they should be considered an integral part of the management strategy for this patient group.

A delicate balance: transcriptional control of awn development and yield in barley.

In a recent study, Zhang et al. identified that MADS1-regulated lemma and awn development can positively regulate barley yield. This finding, alongside the demonstration that the function of MADS1 is conserved in wheat, suggests it is an important target for the improvement of Triticeae crops.

Prediction of 30-day, 90-day, and 1-year mortality after colorectal cancer surgery using a data-driven approach.

PURPOSE: To develop prediction models for short-term mortality risk assessment following colorectal cancer surgery. METHODS: Data was harmonized from four Danish observational health databases into the Observational Medical Outcomes Partnership Common Data Model. With a data-driven approach using the Least Absolute Shrinkage and Selection Operator logistic regression on preoperative data, we developed 30-day, 90-day, and 1-year mortality prediction models. We assessed discriminative performance using the area under the receiver operating characteristic and precision-recall curve and calibration using calibration slope, intercept, and calibration-in-the-large. We additionally assessed model performance in subgroups of curative, palliative, elective, and emergency surgery. RESULTS: A total of 57,521 patients were included in the study population, 51.1% male and with a median age of 72 years. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.88, 0.878, and 0.861 for 30-day, 90-day, and 1-year mortality, respectively, and a calibration-in-the-large of 1.01, 0.99, and 0.99. The overall incidence of mortality were 4.48% for 30-day mortality, 6.64% for 90-day mortality, and 12.8% for 1-year mortality, respectively. Subgroup analysis showed no improvement of discrimination or calibration when separating the cohort into cohorts of elective surgery, emergency surgery, curative surgery, and palliative surgery. CONCLUSION: We were able to train prediction models for the risk of short-term mortality on a data set of four combined national health databases with good discrimination and calibration. We found that one cohort including all operated patients resulted in better performing models than cohorts based on several subgroups.

Utility of Balloon Occlusion Testing in Determining Fontan Suitability Among Patients with Elevated Pulmonary Artery Pressure and Additional Antegrade Pulmonary Blood Flow.

In individuals with a single ventricle undergoing evaluation before Fontan surgery, the presence of excessive pulmonary blood flow can contribute to increased pulmonary artery pressure, notably in those who had a Glenn procedure with antegrade pulmonary flow. 28 patients who had previously undergone Glenn anastomosis with antegrade pulmonary blood flow (APBF) and with elevated mean pulmonary artery (mPAP) pressure > 15 mmHg in diagnostic catheter angiography were included in the study. After addressing other anatomical factors that could affect pulmonary artery pressure, APBF was occluded with semi-compliant, Wedge or sizing balloons to measure pulmonary artery pressure accurately. 23 patients (82% of the cohort) advanced to Fontan completion. In this group, median mPAP dropped from 20.5 (IQR 19-22) mmHg to 13 (IQR 12-14) mmHg post-test (p < 0.001). Median PVR post-test was 1.8 (IQR 1.5-2.1) WU m2. SpO2 levels decreased from a median of 88% (IQR 86%-93%) pre-test to 80% (IQR 75%-84%) post-test (p < 0.001). In five patients, elevated mPAP post-test occlusion on diagnostic catheter angiography led to non-completion of Fontan circulation. In this group, median pre- and post-test mPAP were 23 mmHg (IQR 21.5-23.5) and 19 mmHg (IQR 18.5-20), respectively (p = 0.038). Median post-test PVR was 3.8 (IQR 3.6-4.5) WU m2. SpO2 levels decreased from a median of 79% (IQR 76%-81%) pre-test to 77% (IQR 73.5%-80%) post-test (p = 0.039). Our study presents a specialized approach for patients initially deemed unsuitable for Fontan due to elevated pulmonary artery pressures. We were able to successfully complete the Fontan procedure in the majority of these high-risk cases after temporary balloon occlusion test.

Characterization of PetM cytochrome b6f subunit 7 domain-containing protein in tomato.

In recent years, multiple advances have been made in understanding the photosynthetic machinery in model organisms. Knowledge transfer to horticultural important fruit crops is challenging and time-consuming due to restrictions in gene editing tools and prolonged life cycles. Here, we characterize a gene encoding a PetM domain-containing protein in tomato. The CRISPR/Cas9 knockout lines of the PetM showed impairment in the chloroplastic electron transport rate (ETR), reduced CO2 assimilation, and reduction of carotenoids and chlorophylls (Chl) under several light conditions. Further, growth-condition-dependent elevation or repression of Chl a/b ratios and de-epoxidation states were identified, underlining possible impairment compensation mechanisms. However, under low light and glasshouse conditions, there were basal levels in CO2 assimilation and ETR, indicating a potential role of the PetM domain in stabilizing the cytochrome b6f complex (Cb6f) under higher light irradiance and increasing its quantum efficiency. This suggests a potential evolutionary role in which this domain might stabilize the site of the Cb6f regulating ratios of cyclic and linear electron transport and its potential importance during the conquest of terrestrial ecosystems during which plants were exposed to higher irradiance. Finally, the results are discussed with regard to metabolism and their implication to photosynthesis from an agronomic perspective.

Combined endoscopic and laparoscopic surgery (CELS) for early colon cancer in high-risk patients.

BACKGROUND: Local excision of early colon cancers could be an option in selected patients with high risk of complications and no sign of lymph node metastasis (LNM). The primary aim was to assess feasibility in high-risk patients with early colon cancer treated with Combined Endoscopic and Laparoscopic Surgery (CELS). METHODS: A non-randomized prospective feasibility study including 25 patients with Performance Status score ≥ 1 and/or American Society of Anesthesiologists score ≥ 3, and clinical Union of International Cancer Control stage-1 colon cancer suitable for CELS resection. The primary outcome was failure of CELS resection, defined as either: Incomplete resection (R1/R2), local recurrence within 3 months, complication related to CELS within 30 days (Clavien-Dindo grade ≥ 3), death within 30 days or death within 90 days due to complications to surgery. RESULTS: Fifteen patients with clinical T1 (cT1) and ten with clinical T2 (cT2) colon cancer and without suspicion of metastases were included. Failure occurred in two patients due to incomplete resections. Histopathological examination classified seven patients as having pT1, nine as pT2, six as pT3 adenocarcinomas, and three as non-invasive tumors. In three patients, the surgical strategy was changed intraoperatively to conventional colectomy due to tumor location or size. Median length of stay was 1 day. Seven patients had completion colectomy performed due to histological high-risk factors. None had LNM. CONCLUSIONS: In selected patients, CELS resection was feasible, and could spare some patients large bowel resection.

A Challenging Interventional Procedure: Transcatheter Closure of Tubular Patent Ductus Arteriosus in Patients with Pulmonary Hypertension.

Transcatheter closure of the tubular ducts remains the most challenging procedure, with higher complication rates than other types. This study evaluates the characteristics of transcatheter closure of tubular ducts with pulmonary hypertension. 73 patients with tubular ducts who underwent cardiac catheterization for transcatheter PDA closure were analyzed. The mean age and weight were 1.93 ± 2.68 years and 8.83 ± 6.14 kg, respectively. Transcatheter closure was attempted in 72 patients. Four cases (5.5%) were referred to surgery, while the procedure was completed in the remaining (94.5%). Amplatzer duct occluder (ADO) I or Cardiofix duct occluder (CDO) was the most commonly used devices. However, the use of Amplatzer vascular plug (AVP) II raised in recent years. The most common concern was aortic protrusion/stenosis in ADO I/CDO devices, but most regressed during follow-up. Iatrogenic coarctation of the aorta was observed in two with ADO I/CDO. Embolization of the device to the pulmonary artery was observed in three with CDO, AVP II, and AVP I. Significant left pulmonary artery stenosis requiring stenting developed in one after closure with an MVSDO device. Tubular ducts are highly associated with pulmonary arterial hypertension, and transcatheter closure of them is still challenging despite the developing device armamentarium. Although ADO I or similar devices are widely used, off-label devices are usually needed at increasing rates. The AVP II device is unsuitable for short tubular ducts but seems the best option for long ones.

A comprehensive metabolomics and lipidomics atlas for the legumes common bean, chickpea, lentil and lupin.

Legumes represent an important component of human and livestock diets; they are rich in macro- and micronutrients such as proteins, dietary fibers and polyunsaturated fatty acids. Whilst several health-promoting and anti-nutritional properties have been associated with grain content, in-depth metabolomics characterization of major legume species remains elusive. In this article, we used both gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) to assess the metabolic diversity in the five legume species commonly grown in Europe, including common bean (Phaseolus vulgaris), chickpea (Cicer arietinum), lentil (Lens culinaris), white lupin (Lupinus albus) and pearl lupin (Lupinus mutabilis), at the tissue level. We were able to detect and quantify over 3400 metabolites covering major nutritional and anti-nutritional compounds. Specifically, the metabolomics atlas includes 224 derivatized metabolites, 2283 specialized metabolites and 923 lipids. The data generated here will serve the community as a basis for future integration to metabolomics-assisted crop breeding and facilitate metabolite-based genome-wide association studies to dissect the genetic and biochemical bases of metabolism in legume species.

Genome-wide association study unveils ascorbate regulation by PAS/LOV PROTEIN during high light acclimation.

Varying light conditions elicit metabolic responses as part of acclimation with changes in ascorbate levels being an important component. Here, we adopted a genome-wide association-based approach to characterize the response in ascorbate levels on high light (HL) acclimation in a panel of 315 Arabidopsis (Arabidopsis thaliana) accessions. These studies revealed statistically significant SNPs for total and reduced ascorbate under HL conditions at a locus in chromosome 2. Ascorbate levels under HL and the region upstream and within PAS/LOV PROTEIN (PLP) were strongly associated. Intriguingly, subcellular localization analyses revealed that the PLPA and PLPB splice variants co-localized with VITAMIN C DEFECTIVE2 (VTC2) and VTC5 in both the cytosol and nucleus. Yeast 2-hybrid and bimolecular fluorescence complementation analyses revealed that PLPA and PLPB interact with VTC2 and that blue light diminishes this interaction. Furthermore, PLPB knockout mutants were characterized by 1.5- to 1.7-fold elevations in their ascorbate levels, whereas knockout mutants of the cry2 cryptochromes displayed 1.2- to 1.3-fold elevations compared to WT. Our results collectively indicate that PLP plays a critical role in the elevation of ascorbate levels, which is a signature response of HL acclimation. The results strongly suggest that this is achieved via the release of the inhibitory effect of PLP on VTC2 upon blue light illumination, as the VTC2-PLPB interaction is stronger under darkness. The conditional importance of the cryptochrome receptors under different environmental conditions suggests a complex hierarchy underpinning the environmental control of ascorbate levels. However, the data we present here clearly demonstrate that PLP dominates during HL acclimation.

The conditional mitochondrial protein complexome in the Arabidopsis thaliana root and shoot.

Protein complexes are important for almost all biological processes. Hence, to fully understand how cells work, it is also necessary to characterize protein complexes and their dynamics in response to various cellular cues. Moreover, the dynamics of protein interaction play crucial roles in regulating the (dis)association of protein complexes and, in turn, regulating biological processes such as metabolism. Here, mitochondrial protein complexes were investigated by blue native PAGE and size-exclusion chromatography under conditions of oxidative stress in order to monitor their dynamic (dis)associations. Rearrangements of enzyme interactions and changes in protein complex abundance were observed in response to oxidative stress induced by menadione treatment. These included changes in enzymatic protein complexes involving γ-amino butyric acid transaminase (GABA-T), Δ-ornithine aminotransferase (Δ-OAT), or proline dehydrogenase 1 (POX1) that are expected to affect proline metabolism. Menadione treatment also affected interactions between several enzymes of the tricarboxylic acid (TCA) cycle and the abundance of complexes of the oxidative phosphorylation pathway. In addition, we compared the mitochondrial complexes of roots and shoots. Considerable differences between the two tissues were observed in the mitochondrial import/export apparatus, the formation of super-complexes in the oxidative phosphorylation pathway, and specific interactions between enzymes of the TCA cycle that we postulate may be related to the metabolic/energetic requirements of roots and shoots.

Neoadjuvant intratumoral influenza vaccine treatment in patients with proficient mismatch repair colorectal cancer leads to increased tumor infiltration of CD8+ T cells and upregulation of PD-L1: a phase 1/2 clinical trial.

BACKGROUND: In colorectal cancer, the effects of immune checkpoint inhibitors are mostly limited to patients with deficient mismatch repair tumors, characterized by a high grade infiltration of CD8+T cells. Interventions aimed at increasing intratumoral CD8+T-cell infiltration in proficient mismatch repair tumors are lacking. METHODS: We conducted a proof of concept phase 1/2 clinical trial, where patients with non-metastasizing sigmoid or rectal cancer, scheduled for curative intended surgery, were treated with an endoscopic intratumorally administered neoadjuvant influenza vaccine. Blood and tumor samples were collected before the injection and at the time of surgery. The primary outcome was safety of the intervention. Evaluation of pathological tumor regression grade, immunohistochemistry, flow cytometry of blood, tissue bulk transcriptional analyses, and spatial protein profiling of tumor regions were all secondary outcomes. RESULTS: A total of 10 patients were included in the trial. Median patient age was 70 years (range 54-78), with 30% women. All patients had proficient mismatch repair Union of International Cancer Control stage I-III tumors. No endoscopic safety events occurred, with all patients undergoing curative surgery as scheduled (median 9 days after intervention). Increased CD8+T-cell tumor infiltration was evident after vaccination (median 73 vs 315 cells/mm2, p<0.05), along with significant downregulation of messenger RNA gene expression related to neutrophils and upregulation of transcripts encoding cytotoxic functions. Spatial protein analysis showed significant local upregulation of programmed death-ligand 1 (PD-L1) (adjusted p value<0.05) and downregulation of FOXP3 (adjusted p value<0.05). CONCLUSIONS: Neoadjuvant intratumoral influenza vaccine treatment in this cohort was demonstrated to be safe and feasible, and to induce CD8+T-cell infiltration and upregulation of PD-L1 proficient mismatch repair sigmoid and rectal tumors. Definitive conclusions regarding safety and efficacy can only be made in larger cohorts. TRIAL REGISTRATION NUMBER: NCT04591379.

Endoscopic calcium electroporation for colorectal cancer: a phase I study.

Background and study aims Colorectal cancer is one of the most common malignancies, with approximately 20 % of patients having metastatic disease. Local symptoms from the tumor remain a common issue and affect quality of life. Electroporation is a method to permeabilize cell membranes with high-voltage pulses, allowing increased passage of otherwise poorly permeating substances such as calcium. The aim of this study was to determine the safety of calcium electroporation for advanced colorectal cancer. Patients and methods Six patients with inoperable rectal and sigmoid colon cancer were included, all presenting with local symptoms. Patients were offered endoscopic calcium electroporation and were followed up with endoscopy and computed tomography/magnetic resonance scans. Biopsies and blood samples were collected at baseline and at follow-up, 4, 8, and 12 weeks after treatment. Biopsies were examined for histological changes and immunohistochemically with CD3/CD8 and PD-L1. In addition, blood samples were examined for circulating cell-free DNA (cfDNA). Results A total of 10 procedures were performed and no serious adverse events occurred. Prior to inclusion, patients reported local symptoms, such as bleeding (N = 3), pain (N = 2), and stenosis (N = 5). Five of six patients reported symptom relief. In one patient, also receiving systemic chemotherapy, clinical complete response of primary tumor was seen. Immunohistochemistry found no significant changes in CD3 /CD8 levels or cfDNA levels after treatment. Conclusions This first study of calcium electroporation for colorectal tumors shows that calcium electroporation is a safe and feasible treatment modality for colorectal cancer. It can be performed as an outpatient treatment and may potentially be of great value for fragile patients with limited treatment options.

Metabolite-Based Genome-Wide Association Studies of Large-Scale Metabolome Analysis to Illustrate Alterations in the Metabolite Landscape of Plants upon Responses to Stresses.

Given that anthropogenic activities are evoking a profound effect on the climate resulting in more extreme events such as severe drought and heat waves while global demand for food is ever-increasing, understanding plant responses to stresses is critical. As metabolites are fundamental for plant growth regulation and plant lifespan and an important component of yield, illustrating how the metabolite landscape of plant changes following stress will supply important clues as to how to improve the plant resistance to stress. Recently, billions of single-nucleotide polymorphisms (SNPs) have been obtained and used to identify the associations between genetic variants of genomes and relevant crop agronomic traits through different genetic methods such as genome-wide association studies (GWAS). Therefore, in this chapter, we provide comprehensive guidelines concerning the experimental design, metabolite profiling, and metabolite-based genome-wide association studies (mGWAS) of large-scale metabolome analysis to accelerate the future identification of the valuable stress-resistant genes and metabolites.

Artificial intelligence-assisted detection and characterization of colorectal polyps.

Colonoscopy is the golden standard when screening for colorectal cancer, but the colonoscopy quality and the adenoma detection rate (ADR) vary widely among different endoscopists. Artificial intelligence (AI) can reduce performance variability by compensating for perceptual errors. As referred to in this review, several studies have shown that AI-assisted colonoscopy increases ADR significantly. AI will probably contribute to a more accurate diagnosis of patients in the future, but additional large multicenter studies are needed to assess the AI systems' actual clinical value.

ERCP with single-use disposable duodenoscopes in four different set-ups.

Endoscopic retrograde cholangiopancreatography (ERCP) has until now always been performed using a reusable non-sterile duodenoscope. The introduction of the new single-use disposable duodenoscope makes it possible to perform perioperative transgastric and rendezvous ERCP in an almost sterile manner. It also eliminates the risk of patient-to-patient transmission of infection in non-sterile settings. We present four patients who underwent different types of ERCP using a sterile single-use duodenoscope. This case report aims to demonstrate the use and the many potential advantages of the new disposable single-use duodenoscope in both sterile and non-sterile settings.

Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein and hairy roots: a perfect match for gene functional analysis and crop improvement.

Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) gene editing has become a powerful tool in genome manipulation for crop improvement. Advances in omics technologies, including genomics, transcriptomics, and metabolomics, allow the identification of causal genes that can be used to improve crops. However, the functional validation of these genetic components remains a challenge due to the lack of efficient protocols for crop engineering. Hairy roots gene editing using CRISPR/Cas, coupled with omics analyses, provide a platform for rapid, precise, and cost-effective functional analysis of genes. Here, we describe common requirements for efficient crop genome editing, focused on the transformation of recalcitrant legumes, and highlight the great opportunities that gene editing in hairy roots offers for future crop improvement.

A radiographic study of dorsovolar wrist axes and a database of angular measurements on axial computed tomography images.

OBJECTIVES: This study aims to identify the most accurate dorsovolar principal axis of the distal radius and carpus identified on axial computed tomography (CT) sections and to establish normative data for angular measurements among these axes. PATIENTS AND METHODS: Between December 2019 and December 2021, normal axial CT images of wrists of a total of 42 individuals (25 males, 17 females; mean age: 31±8.4 years; range, 18 to 45 years) were retrospectively analyzed. Eight axes were identified on axial CT images: four distal radial axes (the volar cortical, medial cortical, central, and sigmoid notch axes) and four carpal axes (the scapholunate, lunotriquetral, capitohamate, and pisotrapezial axes). Twenty-two angular parameters were measured with reference to four principal axes (the volar cortical, medial cortical, central, and pisotrapezial axes). RESULTS: The mean sigmoid notch rotation (version) angles relative to the four principal axes were 8±5° (range, -2° to 18°), 6±5° (range, -2° to 13°), 1±5° (range, -8° to 14°), and 4±4° (range, -3° to 15°), respectively. The mean scapholunate rotation angles were -13±5° (range, -27° to -6°), -15±6° (range, -29° to -8°), -21±5° (range, -30° to -11°), and -8±5° (range, -28° to -6°), respectively. Among four principal axes, the volar cortical and medial cortical axes were nearly collinear with both of relatively fixed carpal axes. The four principal axes showed angular differences between 2° and 8° with each other. There was no significant difference between men and women for all measurements. CONCLUSION: The axial CT sections can be used to describe the various angulations between the normal wrist axes such as the sigmoid notch and scapholunate joint rotation angles. Despite slight differences among the four principal axes, the volar cortical and medial cortical axes are more consistent with the relatively fixed carpal axes.