Graph learning for particle accelerator operations.

Particle accelerators play a crucial role in scientific research, enabling the study of fundamental physics and materials science, as well as having important medical applications. This study proposes a novel graph learning approach to classify operational beamline configurations as good or bad. By considering the relationships among beamline elements, we transform data from components into a heterogeneous graph. We propose to learn from historical, unlabeled data via our self-supervised training strategy along with fine-tuning on a smaller, labeled dataset. Additionally, we extract a low-dimensional representation from each configuration that can be visualized in two dimensions. Leveraging our ability for classification, we map out regions of the low-dimensional latent space characterized by good and bad configurations, which in turn can provide valuable feedback to operators. This research demonstrates a paradigm shift in how complex, many-dimensional data from beamlines can be analyzed and leveraged for accelerator operations.

Diastereodivergent Catalysis.

Alongside enantioselective catalysis, synthetic chemists are often confronted by the challenge of achieving catalyst control over the relative configuration to stereodivergently access desired diastereomers. Typically, these approaches iteratively or simultaneously control multiple stereogenic units for which dual catalytic methods comprising sequential, relay, and synergistic catalysis emerged as particularly efficient strategies. In this Perspective, the benefits and challenges of catalyst-controlled diastereodivergence in the construction of carbon stereocenters are discussed on the basis of illustrative examples. The concepts are then transferred to diastereodivergent catalysis for atropisomeric systems with twofold and higher-order stereogenicity as well as diastereodivergent catalyst control over E- and Z-configured alkenes.

Atroposelective PIII /PV =O Redox Catalysis for the Isoquinoline-Forming Staudinger-aza-Wittig Reaction.

Herein, we describe the feasibility of atroposelective PIII /PV =O redox organocatalysis by the Staudinger-aza-Wittig reaction. The formation of isoquinoline heterocycles thereby enables the synthesis of a broad range of valuable atropisomers under mild conditions with enantioselectivities of up to 98 : 2 e.r. Readily prepared azido cinnamate substrates convert in high yield with stereocontrol by a chiral phosphine catalyst, which is regenerated using a silane reductant under Brønsted acid co-catalysis. The reaction provides access to diversified aryl isoquinolines, as well as benzoisoquinoline and naphthyridine atropisomers. The products are expeditiously transformed into N-oxides, naphthol and triaryl phosphine variants of prevalent catalysts and ligands. With dinitrogen release and aromatization as ideal driving forces, it is anticipated that atroposelective redox organocatalysis provides access to a multitude of aromatic heterocycles with precise control over their configuration.

A systematic overexpression approach reveals native targets to increase squalene production in Synechocystis sp. PCC 6803.

Cyanobacteria are a promising platform for the production of the triterpene squalene (C30), a precursor for all plant and animal sterols, and a highly attractive intermediate towards triterpenoids, a large group of secondary plant metabolites. Synechocystis sp. PCC 6803 natively produces squalene from CO2 through the MEP pathway. Based on the predictions of a constraint-based metabolic model, we took a systematic overexpression approach to quantify native Synechocystis gene's impact on squalene production in a squalene-hopene cyclase gene knock-out strain (Δshc). Our in silico analysis revealed an increased flux through the Calvin-Benson-Bassham cycle in the Δshc mutant compared to the wildtype, including the pentose phosphate pathway, as well as lower glycolysis, while the tricarboxylic acid cycle predicted to be downregulated. Further, all enzymes of the MEP pathway and terpenoid synthesis, as well as enzymes from the central carbon metabolism, Gap2, Tpi and PyrK, were predicted to positively contribute to squalene production upon their overexpression. Each identified target gene was integrated into the genome of Synechocystis Δshc under the control of the rhamnose-inducible promoter Prha. Squalene production was increased in an inducer concentration dependent manner through the overexpression of most predicted genes, which are genes of the MEP pathway, ispH, ispE, and idi, leading to the greatest improvements. Moreover, we were able to overexpress the native squalene synthase gene (sqs) in Synechocystis Δshc, which reached the highest production titer of 13.72 mg l-1 reported for squalene in Synechocystis sp. PCC 6803 so far, thereby providing a promising and sustainable platform for triterpene production.

Maize Phytocytokines Modulate Pro-Survival Host Responses and Pathogen Resistance.

Phytocytokines are signaling peptides that alert plant cells of danger. However, the downstream responses triggered by phytocytokines and their effect on plant survival are still largely unknown. Here, we have identified three biologically active maize orthologues of phytocytokines previously described in other plants. The maize phytocytokines show common features with microbe-associated molecular patterns (MAMPs), including the induction of immune-related genes and activation of papain-like cysteine proteases. In contrast to MAMPs, phytocytokines do not promote cell death in the presence of wounding. In infection assays with two fungal pathogens, we found that phytocytokines affect the development of disease symptoms, likely due to the activation of phytohormonal pathways. Collectively, our results show that phytocytokines and MAMPs trigger unique and antagonistic features of immunity. We propose a model in which phytocytokines activate immune responses partially similar to MAMPs but, in contrast to microbial signals, they act as danger and survival molecules to the surrounding cells. Future studies will focus on the components determining the divergence of signaling outputs upon phytocytokine activation. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Comparison between intra- and postoperative outcomes of the da Vinci SP and da Vinci Xi robotic platforms in patients undergoing radical prostatectomy.

The new SP robot incorporates a single trocar that houses a flexible camera and three bi-articulated arms, which minimize the number of incisions needed to assess the surgical site, allowing for a less invasive procedure. To compare the postoperative pain scale and outcomes in patients with similar demographic characteristics undergoing robotic-assisted radical prostatectomy (RARP) with SP and Xi robots, One-hundred consecutive patients undergoing RARP with the SP robot were matched, using a propensity score (PS), with 100 patients from a cohort of 1757 who were operated on with the da Vinci Xi from June 2019 to January 2021. We described and compared the perioperative pain scores and outcomes of both groups. The SP group had less blood loss (50 cc vs. 62.5 cc, P < 0.001) and longer operative time (114 min. vs. 94 min, P < 0.001). The only period we could show a difference in postoperative pain scores was 6 h after surgery, with a small advantage for the SP (2 vs. 2.5, P < 0.001). Both groups had satisfactory postoperative continence recovery, 91% vs. 90% for the SP and Xi, respectively. The groups had a mean follow-up of 24.5 and 22 months for SP and Xi, respectively. The tumor stage and percentage of positive surgical margins were similar between groups (15% vs. 15%, P = 1). Patients undergoing RARP with the SP had longer operative times with less blood loss than the Xi. However, despite the lower number of abdominal incisions on the SP, the groups had similar intraoperative performance, and we were unable to demonstrate clinically significant differences in postoperative pain scores between the groups 6, 12, and 18 h after surgery.

The microbiome of kidney stones and urine of patients with nephrolithiasis.

The incidence of nephrolithiasis is rising worldwide. Although it is a multifactorial disease, lifestyle plays a major role in its etiology. Another considerable factor could be an aberrant microbiome. In our observational single-center study, we aimed to investigate the composition of bacteria in kidney stones and urine focusing on patients with features of metabolic syndrome. Catheterized urine and kidney stones were collected prospectively from 100 consecutive patients undergoing endoscopic nephrolithotomy between 2020 and 2021 at our clinic. Microbiome composition was analyzed via 16S rRNA gene amplicon sequencing. Detection of bacteria was successful in 24% of the analyzed kidney stones. These patients had a prolonged length of stay compared to patients without verifiable bacteria in their stones (2.9 vs 1.5 days). Patients with features of metabolic syndrome were characterized by kidney stones colonized with classical gastrointestinal bacteria and displayed a significant enrichment of Enterococcaceae and Enterobacteriaceae. Stones of patients without features of metabolic syndrome characterized by Ureaplasma and Staphylococcaceae. Patients with bacteria in their kidney stones exhibit a longer length of stay, possibly due to more complex care. Patients presenting with features of metabolic syndrome displayed a distinct stone microbiome compared to metabolically fit patients. Understanding the role of bacteria in stone formation could enable targeted therapy, prevention of post-operative complications and new therapeutic strategies.

Benefit and Harm of Active Surveillance for Biopsy-proven Renal Oncocytoma: A Systematic Review and Pooled Analysis.

Context: Active surveillance (AS) of biopsy-proven renal oncocytomas may reduce overtreatment. However, on biopsy, the risk of misdiagnosis owing principally to entities with peculiar hybrids and overlap morphology, and phenotypes argues for early intervention. Objective: To assess the benefit and harm of AS in biopsy-proven renal oncocytoma. Evidence acquisition: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). We systematically searched PubMed, Scopus, and Web of Science databases from September 26 up to October 2021, for studies that analyzed the outcomes of AS in patients with biopsy-proven renal oncocytoma. Evidence synthesis: A total of ten studies with 633 patients met our inclusion criteria and were included for analysis. After a median follow-up of 34.5 mo (95% confidence interval [CI] 30.6-38.4), the overall definitive treatment rate from AS to definitive treatment was 17.3% (n = 75/433, six studies). The pooled pathological agreement between the initial renal mass biopsy and the surgical pathology report was 91.1%. The main indications for surgery during follow-up were rapid tumor growth and patient request. The pooled median growth rate was 1.55 mm/yr (95% CI 0.9-2.2). No metastasis or death related to renal oncocytoma was reported. Conclusions: Annual tumor growth of biopsy-proven renal oncocytoma is low. AS is oncologically safe, with favorable compliance of patients. Crossover to definitive treatment revealed a strong concordance between biopsy and final pathology. Further studies on the long-term outcomes of AS are needed. Patient summary: In this study, we examined the benefit and harm of active surveillance (AS) in biopsy-proven oncocytoma. Based on the available data, AS appears oncologically safe and may represent a promising alternative to immediate treatment. Patients should be included in AS decision discussions.

A validated method for the rapid quantification of melatonin in over-the-counter hypnotics by the atmospheric pressure solid analysis probe (ASAP).

Melatonin is a hormone that regulates the biological day and night cycle. It is mainly produced by the pineal gland during the night. People suffering from insomnia use it as a soporific drug. The aim of this study was to develop a method for the rapid quantification of melatonin in hypnotics. For that purpose, atmospheric pressure solid analysis probe-assisted mass spectrometry was applied, where no chromatographic separation is needed. Thereby, one single analysis takes less than 1 min. Reference measurements were performed with ultra-high-performance liquid chromatography coupled with a quadrupole-time-of-flight mass spectrometer. Both methods were validated and real sample extracts were tested. The coefficients of determination were above 0.97 for both methods. The limits of detection and quantification were below 1 mg kg-1. Both methods gave comparable results. Moreover, the content of melatonin differed from the specified value in many samples. The highest and lowest observed deviations were 78% and 1%, respectively.

Fast and semiquantitative screening for sildenafil in herbal over-the-counter formulations with atmospheric pressure solid analysis probe (ASAP) to prevent medicinal adulteration.

Herbal medicines are commonly used in many countries all around the world. In Western countries they are now gaining more and more popularity, whereas in countries like China and India they have been entrenched for millenniums. Some of these perceived herbal medicines claim to help when suffering from erectile dysfunction. Nevertheless, many of these products are adulterated with PDE5 inhibitors like sildenafil or α-blockers. Patients who suffer from high blood pressure sometimes resort to herbal products, as they are not allowed to take sildenafil because of negative drug-drug interactions with nitrates (often utilized as treatment for coronary diseases). Products which are then adulterated with PDE5 inhibitors, can seriously harm patients. Therefore, this study reports the instant screening of alleged herbal products by employing atmospheric pressure solids analysis probe and high-resolution mass spectrometry to determine adulterants. Three out of 12 investigated products contained sildenafil in ranges from 0.5% to 18%. Multivariate analysis of ambient mass spectrometry measurements revealed encouraging outcomes for distinguishing non-sildenafil and sildenafil adulterated samples. Atmospheric pressure solids analysis probe is therefore a promising method for the rapid determination of sildenafil in herbal products with possible downstream semiquantitative analysis.

Synthesis of Atropisomeric Two-Axis Systems by the Catalyst-Controlled syn- and anti-Selective Arene-Forming Aldol Condensation.

Simultaneous control over the configuration of multiple stereocenters is accomplished by numerous catalytic methods, providing a reliable basis for the synthesis of stereochemically complex targets in isomerically defined form. In contrast, addressing the configurations of multiple stereogenic axes with diastereodivergent catalyst control is thus far only possible by stepwise approaches. Herein we now describe that all four stereoisomers of atropisomeric two-axis systems are directly tractable by assembling a central aromatic unit of teraryls through an arene-forming aldol condensation. By using cinchona alkaloid-based ion-pairing catalysts, the four feasible reaction pathways are differentiated from identical substrates under defined basic conditions without preactivation, thus enabling complete stereodivergence with enantioselectivities of up to 99 : 1 e.r.

Tradução para o português An International Continence Society (ICS) report on the terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD).

INTRODUÇÃO: A terminologia para disfunção neurogênica do trato urinário inferior em adultos (DNTUIA) deve ser definida e organizada com base clínica em um relatório de consenso. MÉTODOS: Este relatório foi criado por um Grupo de Trabalho sob o endosso e diretrizes do Standardization Steering Committee (SSC) da International Continence Society (ICS), auxiliado em intervalos por julgadores externos. Todas as definições relevantes para DNTUIA foram atualizadas com base em pesquisas nos últimos 14 anos. Um extenso processo de 18 rodadas de revisão interna e externa foi realizado para examinar exaustivamente cada definição, com tomada de decisão pela opinião coletiva (consenso). RESULTADOS: O Relatório de Terminologia para a DNTUIA, englobando 97 definições (42 novas e oito modificadas), foi desenvolvido. Este relatório é clinicamente baseado nos diagnósticos definidos mais comuns. Clareza e facilidade de uso têm sido os principais objetivos para torná-lo interpretável por profissionais e pessoas em treinamento em todos os diferentes grupos envolvidos não só na disfunção do trato urinário inferior, mas também em muitas outras especialidades médicas. CONCLUSÃO: Baseado no consenso, o Relatório de Terminologia para a DNTUIA foi produzido para auxiliar na pesquisa e na prática clínica.

Implementing the da Vinci SP Without Increasing Positive Surgical Margins: Experience and Pathologic Outcomes of a Prostate Cancer Referral Center.

Background: Different consoles have been described for the da Vinci single-port (SP) surgery since it was cleared by the FDA in November 2018. However, the literature still lacks studies identifying factors related to the SP learning curve and how to overcome the technological limitations, especially in terms of maintaining acceptable positive surgical margins (PSMs). This study describes our perioperative experience implementing a safe SP approach to radical prostatectomy (RP) while minimizing PSM, especially during the initial learning period. Materials and Methods: We performed a retrospective analysis of 100 consecutive patients with prostate cancer who underwent RP with the SP robot from June 2019 to December 2020 (IRB 237998). We accessed the perioperative data, pathology report, and short-term oncologic outcomes. We also represented our PSM trends in 100 consecutive cases, discussing potential factors for minimizing the learning curve impact on positive margins and outcomes. Medians and interquartile ranges, as well as frequencies and proportions, were reported for continuous and categorical variables, respectively. Results and Limitations: The median follow-up is 14 months (8-17). The cohort has a median age of 62 years (56-68), median prostate-specific antigen of 5.5 (4.3-7.7), median preoperative Sexual Health Inventory for Men (SHIM) of 20, median American Urological Association (AUA) of 7 (3-11), and median body mass index of 25.4 (23.4-27.4). The median total operative time was 114 minutes (104-124), the median console time was 80 minutes (75-90). No intraoperative complications were reported. The overall rate of PSMs was 15% (5% were pT2 and 10% were pT3). Conclusions: The SP approach to RP is feasible, safe, and with acceptable intraoperative performance. In this study, we have described crucial factors for considering selection criteria in candidates for SP-robot-assisted RP. We believe that with an appropriate patient selection, this robot can be safely implemented without increasing positive margins and compromising the outcomes, especially during the learning curve period.

Tradução para o português An International Continence Society (ICS) report on the terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD)

RESUMO Introdução A terminologia para disfunção neurogênica do trato urinário inferior em adultos (DNTUIA) deve ser definida e organizada com base clínica em um relatório de consenso. Métodos Este relatório foi criado por um Grupo de Trabalho sob o endosso e diretrizes do Standardization Steering Committee (SSC) da International Continence Society (ICS), auxiliado em intervalos por julgadores externos. Todas as definições relevantes para DNTUIA foram atualizadas com base em pesquisas nos últimos 14 anos. Um extenso processo de 18 rodadas de revisão interna e externa foi realizado para examinar exaustivamente cada definição, com tomada de decisão pela opinião coletiva (consenso). Resultados O Relatório de Terminologia para a DNTUIA, englobando 97 definições (42 novas e oito modificadas), foi desenvolvido. Este relatório é clinicamente baseado nos diagnósticos definidos mais comuns. Clareza e facilidade de uso têm sido os principais objetivos para torná-lo interpretável por profissionais e pessoas em treinamento em todos os diferentes grupos envolvidos não só na disfunção do trato urinário inferior, mas também em muitas outras especialidades médicas. Conclusão Baseado no consenso, o Relatório de Terminologia para a DNTUIA foi produzido para auxiliar na pesquisa e na prática clínica.

Quantification and cytotoxicity of degradation products (chloropropanols) in sucralose containing e-liquids with propylene glycol and glycerol as base.

Electronic cigarettes (e-cigarettes) have gained increasing popularity in recent years, mostly because they are supposed to be less harmful than regular cigarettes. Therefore, it is highly imperative to investigate possible noxious effects to protect the consumers. E-liquids consist of propylene glycol, glycerol, aroma compounds and sweeteners. One of these sweeteners is a chlorinated version of sucrose, namely sucralose. The aim of this work was to investigate degradation products of sucralose in the presence of propylene glycol and glycerol at different temperatures of commercially available e-cigarettes. Chemical analysis and biological tests were simultaneously performed on e-liquid aerosol condensates. The results of the chemical analysis, which was executed by employing GC-MS/GC-FID, demonstrated high amounts of various chloropropanols. The most abundant one is extremely toxic, namely 3-chloropropane-1,2-diol, which can be detected at concentrations ranging up to 10,000 mg/kg. Furthermore, a cytotoxicity investigation of the condensates was performed on HUVEC/Tert2 cells in which metabolic activity was determined by means of resazurin assay. The cellular metabolic activity significantly decreased by treatment with e-liquid aerosol condensate. Due to the results of this study, we advise against the use of sucralose as sweetener in e-liquids.

Catalytic Cascade Reactions Inspired by Polyketide Biosynthesis.

Aldol reactions belong to the most important methods for carbon-carbon bond formation and are also involved in one of the most astonishing biosynthetic processes: the biosynthesis of polyketides governed by an extraordinarily sophisticated enzymatic machinery. In contrast to the typical linear or convergent strategies followed in chemical synthesis, this late-stage catalysis concept allows Nature to assemble intermediates that are diversified into a broad range of scaffolds, which assume various crucial biological functions. To transfer this concept to small-molecule catalysis to access products beyond the natural systems, a stepwise approach to differentiate increasingly complex substrates was followed by investigating arene-forming polyketide cyclizations. An outline of our efforts to develop and apply these concepts are presented herein.

Preoperative Prediction of Lymph Node Metastasis from Clinical DCE MRI of the Primary Breast Tumor Using a 4D CNN.

In breast cancer, undetected lymph node metastases can spread to distal parts of the body for which the 5-year survival rate is only 27%, making accurate nodal metastases diagnosis fundamental to reducing the burden of breast cancer, when it is still early enough to intervene with surgery and adjuvant therapies. Currently, breast cancer management entails a time consuming and costly sequence of steps to clinically diagnose axillary nodal metastases status. The purpose of this study is to determine whether preoperative, clinical DCE MRI of the primary tumor alone may be used to predict clinical node status with a deep learning model. If possible then many costly steps could be eliminated or reserved for only those with uncertain or probable nodal metastases. This research develops a data-driven approach that predicts lymph node metastasis through the judicious integration of clinical and imaging features from preoperative 4D dynamic contrast enhanced (DCE) MRI of 357 patients from 2 hospitals. Innovative deep learning classifiers are trained from scratch, including 2D, 3D, 4D and 4D deep convolutional neural networks (CNNs) that integrate multiple data types and predict the nodal metastasis differentiating nodal stage N0 (non metastatic) against stages N1, N2 and N3. Appropriate methodologies for data preprocessing and network interpretation are presented, the later of which bolster radiologist confidence that the model has learned relevant features from the primary tumor. Rigorous nested 10-fold cross-validation provides an unbiased estimate of model performance. The best model achieves a high sensitivity of 72% and an AUROC of 71% on held out test data. Results are strongly supportive of the potential of the combination of DCE MRI and machine learning to inform diagnostics that could substantially reduce breast cancer burden.

Parameters of 2-Dimensional Perineal Ultrasonography Before and After Male Sling Procedure for Urinary Incontinence After Radical Prostatectomy.

OBJECTIVE: To compare ultrasonographic patterns of 2-dimensional perineal ultrasonography in men in the preoperative and postoperative periods after transobturator sling deployment for the treatment of urinary incontinence after radical prostatectomy. Radiotherapy and radical prostatectomy are the primary treatments for localized prostate cancer. Studies comparing anatomic changes in men before and after radical prostatectomy based on perineal ultrasonography are scarce in the literature. METHODS: Thirty-one patients from 2 centers were selected for examination and surgery. They were allocated into mild and/or moderate and severe incontinence groups who underwent the transobturator sling procedure between August 2014 and August 2018. Perineal ultrasonography was performed in the preoperative period for 21 of these patients and 3-6 months postoperatively after the transobturator sling procedure for 30 patients. Hypermobility of the proximal urethra and voluntary contraction of the pelvic floor were evaluated during the Valsalva maneuver, perineal contraction and at rest. RESULTS: Clinical improvements of >50% were significantly more frequent in the mild and/or moderate vs severe incontinence group after male sling surgery (P = .035). Patients who demonstrated clinical improvement >50% showed a significantly greater displacement of the posterior portion of the bladder neck during contraction than those with clinical improvement <50% (P = .024). CONCLUSION: The most important finding of this study was the significant difference in the posterior displacement of the bladder neck during contraction in patients who showed an improvement >50% compared with those with an improvement <50%. These data support the use of perineal ultrasonography in evaluating and selecting patients for the male sling procedure.