bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimized infusion rates for N,N‐dimethyltryptamine to achieve a target psychedelic intensity based on a modeling and simulation framework
Authors: Eckernäs Emma , Koomen Jeroen , Timmermann Christopher , Carhart‐Harris Robin , Röshammar Daniel , Ashton Michael
Published: September 2023

N,N‐dimethyltryptamine (DMT) is a psychedelic compound that is being studied as a therapeutic option in various psychiatric disorders. Due to its short half‐life, continuous infusion of DMT has been proposed to extend the psychedelic experience and potential therapeutic effects. The primary aim of this work was to design an infusion protocol for DMT based on a desired level of psychedelic intensity using population pharmacokinetic/pharmacodynamic modeling. As a secondary aim, the impact of choosing a continuous variable or a bounded integer pharmacokinetic/pharmacodynamic model to inform such an infusion protocol was investigated. A previously published continuous variable model and two newly developed bounded integer models were used to assess optimal doses for achieving a target response. Simulations were performed to identify an optimal combination of a bolus dose and an infusion rate. Based on the simulations, optimal doses to achieve intensity ratings between 7 and 9 (possible range = 0–10) were a bolus dose of 16 mg DMT fumarate followed by an infusion rate of 1.4 mg/min based on the continuous variable model and 14 mg with 1.2 mg/min for the two bounded integer models. However, the proportion within target was low (<53%) for all models, indicating that individual dose adjustments would be necessary. Furthermore, some differences between the models were observed. The bounded integer models generally predicted lower proportions within a target of 7–9 with higher proportions exceeding target compared with the continuous variable model. However, results varied depending on target response with the major differences observed at the boundaries of the scale.
Rapid and simple identification of trace amounts of sodium azide in beverages and bodily fluids followed by derivatization and liquid chromatography–electrospray ionization tandem mass spectrometry
Authors: Prihed Hagit , Shifrovitch Avital , Shamai Yamin Tamar , Madmon Moran , Belay Chen , Blanca Merav , Weissberg Avi
Published: September 2023

Rationale

Sodium azide (NaN3) is a toxic chemical agent to humans by ingestion and inhalation with a growing number of intentional exposures and accidental cases over the last few decades. Due to its low molecular weight and lack of any chromophore, its retention and detection by reverse‐phase liquid chromatography–ultraviolet–mass spectrometry methods are a challenging task.

Methods

To be able to confirm azide exposure, we have developed a method to identify azide in both beverages and bodily fluids. The identification of azide (N3−) is based on derivatization with N‐(2‐(bromomethyl)benzyl)‐N,N‐diethylethanaminium bromide (CAX‐B) at 25°C for 15 min followed by LC/ESI‐MS/MS analysis, with no other sample preparation.

Results

The azide after derivatization (CAX‐N3) was stable, retainable by LC and sensitively detected by selected reaction monitoring. The ESI‐MS/MS fragmentation of the M+ precursor ion produced characteristic product ions at m/z 118, 100, 91 and 86. The calibration curves for CAX‐N3 showed linearity over two orders of magnitude with R2 value of 0.99. Low limits of identification of 0.1–0.5 ng/mL were obtained in all investigated matrices (drinking water, tea, orange juice, plasma and urine).

Conclusions

Compared with previously reported chromatography‐based methods, this method that was based on derivatization and LC/ESI‐MS/MS analysis was substantially more sensitive, simpler and faster. The method can be used for forensic investigation to confirm azide exposure from fatal use to much smaller intoxication dose.
Comprehensive metabolite profiling of trimetazidine in camels using high‐resolution accurate mass spectrometry: Implications for doping control
Authors: Nalakath Jahfar , PT Rasik , Kadry Ahmed , Palathinkal Ansar Babu , Praseen Ondern Komathu , Nelliyott Ibrahimwaseem , Hebel Christiana , Selvapalam N. , Nagarajan E. R.
Published: September 2023

Rationale

Trimetazidine and its metabolites are prohibited substances in sports. With a growing number of adverse findings in human athletes, it is crucial to develop doping control strategies that include screening for trimetazidine in animal sports. This study aims to detect and characterize trimetazidine and its metabolites for doping control in camel racing.

Methods

Camel urine and plasma samples were collected from four healthy animals following a single oral dose of trimetazidine. In vitro investigations were conducted using camel liver samples. Liquid–liquid extraction and solid‐phase extraction techniques were employed for the extraction of trimetazidine metabolites from plasma and urine matrices. The metabolites were analyzed using a Thermo Orbitrap Exploris LC‐MS system with optimized settings to achieve maximum sensitivity and accurate mass measurements.

Results

Comprehensive metabolite profiling of trimetazidine in camels revealed the identification of seven phase I and five phase II metabolites. Phase I metabolites were primarily formed through dealkylation, while phase II metabolites were dominated by glucuronide conjugation of demethylated trimetazidine. The findings provided insights into the distinct metabolic pathways and biotransformation patterns of trimetazidine in camels under the experimental conditions.

Conclusion

The developed method enables detection and characterization of trimetazidine and its metabolites in camels. The identified metabolites have the potential to serve as marker metabolites for trimetazidine abuse in camel racing. This study provides valuable insights into the metabolism of trimetazidine in camels.
High‐precision Sr and Nd isotope characterization of BHVO‐2 reference material by thermal ionization mass spectrometry
Authors: Fuenlabrada José M.
Published: September 2023

Rationale

Control over accuracy and precision in isotope geochemical analysis is highly necessary for reliable results. Use of reference materials in Sr and Nd isotope geochemistry provides a means of validating optimal sample preparation and instrument configurations.

Methods

A comprehensive data set of Sr and Nd isotope analyses of BHVO‐2 reference material was obtained by thermal ionization mass spectrometry (TIMS). The intention is to assist other researchers in evaluating isotopic analyses of geological samples with similar chemical matrix.

Results

87Sr/86Sr isotope ratios analyzed in BHVO‐2 reference material over 88 replicas from 2015 to the present provide an average value of 0.703485 ± 0.000024. In turn, 143Nd/144Nd isotope ratios in 62 replicas show an average value of 0.512978 ± 0.000012. The high number of analyses here presented ensures a high reproducibility over time in a non‐certified material for isotopic analysis of these two elements.

Conclusions

This high precision and reproducibility of Sr and Nd analysis by TIMS provide a basis for validation of analytical processes in the absence of certified reference materials and support the correlation of isotopic results between laboratories and the overall improvement in the interpretation of isotope results for geological, environmental and archeological samples.
Molecular Doping Modulation and Applications of Structure‐Sorted Single‐Walled Carbon Nanotubes: A Review
Authors: Liu Ye , Zhao Zhigang , Kang Lixing , Qiu Song , Li Qingwen
Published: September 2023

Single‐walled carbon nanotubes (SWCNTs) that have a reproducible distribution of chiralities or single chirality are among the most competitive materials for realizing post‐silicon electronics. Molecular doping, with its non‐destructive and fine‐tunable characteristics, is emerging as the primary doping approach for the structure‐controlled SWCNTs, enabling their eventual use in various functional devices. This review provides an overview of important advances in the area of molecular doping of structure‐controlled SWCNTs and their applications. The first part introduces the underlying physical process of molecular doping, followed by a comprehensive survey of the commonly used dopants for SWCNTs to date. Then, it highlights how the convergence of molecular doping and structure‐sorting strategies leads to significantly improved functionality of SWCNT‐based field‐effect transistor arrays, transparent electrodes in optoelectronics, thermoelectrics, and many emerging devices. At last, several challenges and opportunities in this field are discussed, with the hope of shedding light on promoting the practical application of SWCNTs in future electronics.
Screening, preparation, and prototyping of metal–organic frameworks for adsorptive carbon capture under humid conditions
Authors: Jiang Long , Yong Jinyuan , Xie Renyu , Xie Pengfei , Zhang Xuejun , Chen Zhijie , Bao Zongbi
Published: September 2023

Adsorption‐based carbon capture has been recognized as an attractive method for mitigating global warming. Metal–organic frameworks (MOFs) are promising candidate adsorbents for this purpose due to their high adsorption uptake and selectivity for carbon dioxide. However, in real‐world applications, such as direct air capture, the presence of moisture in the feed gas may pose a grand challenge for CO2 adsorption in MOFs. This paper aims to address the issue of water–CO2 co‐adsorption in MOFs and present screening criteria for selecting MOFs that preferentially adsorb CO2 under humid conditions. First, we uncover a comprehensive overview of CO2–water co‐adsorption characteristics of various MOFs. Then, the high‐throughput screening methods are summarized. Both computational and experimental efforts have been dedicated to identify the promising MOFs for humid CO2 capture. According to the screening results and adsorption mechanism, the optimal preparation strategies are proposed to modulate the effect of water on CO2 uptake in MOFs. Finally, current MOF‐based CO2 capture prototypes are presented to evaluate their practical feasibility and performance. This work could offer valuable guidance for the development and application of MOFs for CO2 capture in the presence of water and inspire further research in this field.
Propensity score analysis of low‐dose aspirin and bleeding complications in pregnancy
Authors: Souter V. , Painter I. , Sitcov K. , Khalil A.
Published: September 2023

Objective

Low‐dose aspirin (LDA) has been shown to reduce the risk of preterm pre‐eclampsia and it has been suggested that it should be recommended for all pregnancies. However, some studies have reported an association between LDA and an increased risk of bleeding complications in pregnancy. Our aim was to evaluate the risk of placental abruption and postpartum hemorrhage (PPH) in patients for whom their healthcare provider had recommended prophylactic aspirin.

Methods

This multicenter cohort study included 72 598 singleton births at 19 hospitals in the USA, between January 2019 and December 2021. Pregnancies complicated by placenta previa/accreta, birth occurring at less than 24 weeks' gestation, multiple pregnancy or those with data missing for aspirin recommendation were excluded. Propensity scores were calculated using 20 features spanning sociodemographic factors, medical history, year and hospital providing care. The association between LDA recommendation and placental abruption or PPH was estimated by inverse‐probability treatment weighting using the propensity scores.

Results

We included 71 627 pregnancies in the final analysis. Aspirin was recommended to 6677 (9.3%) and was more likely to be recommended for pregnant individuals who were 35 years or older (P < 0.001), had a body mass index of 30 kg/m2 or higher (P < 0.001), had prepregnancy hypertension (P < 0.001) and who had a Cesarean delivery (P < 0.001). Overall, 1.7% of the study cohort (1205 pregnancies) developed preterm pre‐eclampsia: 1.3% in the no‐aspirin and 5.8% in the aspirin group. After inverse‐probability weighting with propensity scores, aspirin was associated with increased risk of placental abruption (adjusted odds ratio (aOR), 1.44 (95% CI, 1.04–2.00)) and PPH (aOR, 1.21 (95% CI, 1.05–1.39)). The aOR translated to a number needed to harm with LDA of 79 (95% CI, 43–330) for PPH and 287 (95% CI, 127–3151) for placental abruption.

Conclusions

LDA recommendation in pregnancy was associated with increased risk for placental abruption and for PPH. Our results support the need for more research into aspirin use and bleeding complications in pregnancy before recommending it beyond the highest‐risk pregnancies. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Prediction using serum glycosylated fibronectin and angiogenic factors of superimposed pre‐eclampsia in women with chronic hypertension
Authors: Sokratous N. , Bednorz M. , Syngelaki A. , Wright A. , Nicolaides K. H. , Kametas N. A.
Published: September 2023

Objective

To compare the predictive performance for delivery with pre‐eclampsia (PE) within 2 weeks of assessment in women with chronic hypertension at 24–41 weeks' gestation between serum glycosylated fibronectin (GlyFn) concentration, serum placental growth factor (PlGF) concentration and soluble fms‐like tyrosine kinase‐1 (sFlt‐1) to PlGF concentration ratio.

Methods

This was a prospective study of 104 women with a singleton pregnancy and chronic hypertension presenting at 24–41 weeks' gestation. Twenty‐six (25.0%) cases developed superimposed PE within 2 weeks of sampling. We compared the predictive performance for superimposed PE between GlyFn, PlGF and the sFlt‐1/PlGF ratio at a fixed screen‐positive rate of approximately 10%.

Results

The median gestational age at sampling was 34.1 (interquartile range, 31.5–35.6) weeks and 84.6% (88/104) of cases were sampled at < 36 weeks. The predictive performance for superimposed PE of the three methods of screening was similar, with detection rates of about 23–27%, at a screen‐positive rate of 11% and a false‐positive rate of about 5%.

Conclusions

Measurement of GlyFn is a simple point‐of‐care test that can be carried out without need for a laboratory and provide results within 10 min of testing. In this respect, it could potentially replace the angiogenic markers that are used currently in the prediction of imminent PE in high‐risk women. However, neither GlyFn nor angiogenic factors are likely to improve the management of women with chronic hypertension because their predictive performance for superimposed PE is poor. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
Strapdown Airborne Gravimetry Based on Aircrafts and UAVs: Postprocessing Algorithms and New Results
Authors: Vyazmin Vadim S. , Golovan Andrey A.
Published: September 2023

The paper describes a new methodology for postprocessing raw data from a strapdown airborne gravimeter based on a navigation-grade inertial measuring unit and global navigation satellite system receivers (one is on board the aircraft and the others are placed on the ground). The key aspects of the methodology’s algorithms are outlined. We also present the numerical results (gravity estimates) from two airborne gravimetry surveys. The surveys were carried out using state-of-the-art strapdown airborne gravimeters on board a fixed-wing aircraft (An-3T) and helicopter-type unmanned aerial vehicle (UAV). In the first survey, the flights were flown in the draped mode with extreme vertical accelerations reaching 2.5 g, which appears to be the first case in airborne gravimetry. In the second survey, the UAV was flying at a constant altitude. The gravity estimation accuracy (RMS) varies from the sub-mGal up to 2-mGal level depending on campaign, with larger values corresponding to the draped flight survey.
A Taste of What You’re Up Against: Two Tales
Authors: Mendes Felipe Cardeneti , Sarna Piotr , Emelyanov Pavel , Dunlop Cynthia
Published: September 2023

What’s more fun than wrestling with database performance? Well, a lot. But that doesn’t mean you can’t have a little fun here. To give you an idea of the complexities you’ll likely face if you’re serious about optimizing database performance, this chapter presents two rather fanciful stories. The technical topics covered here are expanded on throughout the book. But this is the one and only time you’ll hear of poor Joan and Patrick. Let their struggles bring you some valuable lessons, solace in your own performance predicaments… and maybe a few chuckles as well.
Monitoring
Authors: Mendes Felipe Cardeneti , Sarna Piotr , Emelyanov Pavel , Dunlop Cynthia
Published: September 2023

Databases require ongoing care and attention, especially when performance is a priority and the data being stored is growing rapidly and/or changing frequently. Adverse events that could place the business at risk—for example, node failures or a misbehaving client—will inevitably occur. Given the complexity of both databases and data-intensive applications, it’s not a matter of if some combination of factors ends up degrading performance, but when.
Getting Data Closer
Authors: Mendes Felipe Cardeneti , Sarna Piotr , Emelyanov Pavel , Dunlop Cynthia
Published: September 2023

Location, location, location. Sometimes it’s just as important to database performance as it is to real estate. Just as the location of a home influences how quickly it sells, the location of where data “lives” and is processed also matters for response times and latencies.
Medicine, Psychology, and the Welfare State
Authors: Ariaans Mareike , Reibling Nadine , Bleckmann Lisa
Published: September 2023

How does a welfare state develop into a biopsychosocial welfare state? Ariaans, Bleckmann, and Reibling ask this question and provide a much-needed theoretical construct of the medicalization and psychologizations processes that take place within the welfare state. Although medicine and psychology are disciplines that have always been discussed as parts of the healthcare system of welfare states, the link of both disciplines to other areas of the welfare state is unclear, and we still lack an overall theoretical idea as to how the processes of medicalization and psychologization are embedded in the welfare state. By linking dimensions (ideas, institutions, actors) and levels (macro, meso, and micro), Ariaans et al. provide theoretical examples of how the move toward a biopsychosocial welfare state unfolds.
Childhood in Crisis: Are Medicine and Psychology Part of the Problem or Part of the Solution?
Authors: Reibling Nadine , Ariaans Mareike , Hamel Lucas
Published: September 2023

Medicine and psychology are key disciplines when it comes to childhood, particularly if it is problematized. In this chapter, Reibling, Ariaans, and Hamel argue that both the turn of Western welfare states toward social investment and the resulting new interest in children are paradigmatic examples of the shift toward a biopsychosocial welfare state. Medicine and psychology provide ideas, interventions, and professionals that the welfare state relies on in its aim to invest in children. The authors illustrate this idea via three empirical studies that analyze (1) the public communication of professional organizations, (2) the public’s view on children who experience problems, and (3) the institutionalization of learning disorders in Germany.
The Biopsychosocial Welfare State: A New Perspective on Social Policy
Authors: Reibling Nadine
Published: September 2023

How can we understand the biopsychosocial welfare state? What empirical indications are there for the increasing influence of medicine and psychology in advanced welfare states? This chapter answers these questions and additionally discusses how current crises have influenced—and will continue to influence—the medicalization and psychologization of social problems and social policies.
(In)stability of de Sitter vacuum in light of distance conjecture and emergence proposal
Authors: Seo Min-Seok
Published: September 2023

Abstract

The distance conjecture claims that as the modulus traverses along the trans-Planckian geodesic distance, the effective field theory becomes invalid by a descent of a tower of states from UV. Moreover, according to the recent (strong version of) emergence proposal, the kinetic term of the modulus is entirely generated by the wavefunction renormalization in which a tower of states are integrated out. Assuming these two conjectures, we explore the role of a tower of states coupled to the modulus in (in)stability of the de Sitter (dS) vacuum by studying the one-loop effective potential generated by a tower of states. We find that a fermionic tower of states makes the effective potential more or less consistent with the dS swampland conjecture: either the slope or the curvature of the potential is sizeable. In contrast, the effective potential generated by a bosonic tower of states seems to allow the stable dS vacuum. Therefore, in order to argue the instability of the dS vacuum, the additional ingredient like supersymmetry breaking needs to be taken into account.
Renormalizability of nonlocal quantum gravity coupled to matter
Authors: Calcagni Gianluca , Giacchini Breno L. , Modesto Leonardo , de Paula Netto Tibério , Rachwał Lesław
Published: September 2023

Abstract

We extensively study the ultraviolet quantum properties of a nonlocal action for gravity nonminimally coupled to matter. The theory unifies matter and gravity in an action principle such that all the classical solutions of Einstein’s theory coupled to matter are also solutions of the nonlocal theory. At the quantum level, we show that the theory is power-counting super-renormalizable in even dimensions and finite in odd dimensions. A simple extension of the model compatible with the above properties is finite also in even dimensions.
Chirurgische Therapie der Crohn-Krankheit des Dick- und Mastdarms
Authors: Unger Lukas Walter , Riss Stefan
Published: September 2023

Morbus Crohn, eine chronisch-entzündliche Darmerkrankung, kann den gesamten Gastrointestinaltrakt betreffen. Die häufigsten Indikationen für Operationen stellen Dünndarm- sowie ileokolonischer Befall dar. Oftmals resultiert eine chronische Entzündung des terminalen Ileums in enteroenteralen Fisteln zwischen Dünndarm und Dick‑/Mastdarm, welche Resektionen von beiden betroffenen Segmenten notwendig machen. Bis zu 20 % der Patient:innen mit Morbus Crohn leiden an isolierter Crohn-Kolitis ohne extensiven Dünndarmbefall, was in manchen Fällen jedoch ebenfalls eine chirurgische Intervention notwendig macht. Neben den abdominellen Komplikationen von Morbus Crohn sind perianale Fisteln eine der größten Herausforderungen für kolorektale Chirurgen, welche letztlich zu Inkontinenz und Notwendigkeit eines Stomas führen können. Kürzlich veröffentlichte Ergebnisse beschreiben zwar bessere Heilungschancen, ein qualitativ hochwertiger Vergleich der Therapien fehlt jedoch. Dieser Artikel behandelt daher die chirurgische Therapie bei Morbus Crohn des Dick- und Mastdarms sowie perianalem Befall.
Konstanzer Modellprojekt für psychisch belastete Geflüchtete
Authors: Bogatzki Lea , Miredin Julia , Millet Sophie , Lipinski Leonie , Molle Madlen , Rockstroh Brigitte , Mier Daniela , Odenwald Michael
Published: September 2023

Geflüchtete mit psychischen Störungen sind mit Zugangsbarrieren zum psychiatrisch-psychotherapeutische Versorgungssystem konfrontiert. Um diesen Barrieren zu begegnen, wurde im Landkreis Konstanz ein Modellprojekt zur Unterstützung der Gesundheitsversorgung und Integration psychisch belasteter Geflüchteter etabliert (Koordinierte psychotherapeutische Behandlung unter Einbezug von Gesundheitspat:innen; KOBEG) und in einer ersten 3‑jährigen Modellphase evaluiert. Über eine zentrale Koordinierungsstelle werden die Geflüchteten an lokale, niedergelassene Psychotherapeut:innen vermittelt. Sprach- und kultursensitiv geschulte Gesundheitspat:innen (Peers) betreuen und begleiten die Geflüchteten während ihrer Therapie. Die Inanspruchnahme des vermittelten Therapieangebots und Erfahrungen beteiligter Therapeut:innen dienen als Indikatoren für die Effektivität der patengestützten Therapievermittlung. Die Wirksamkeit der therapeutischen Maßnahmen und Begleitung durch Gesundheitspat:innen wurde anhand der psychischen Symptombelastung (Symptomchecklist-27) und Funktionsbeeinträchtigung (Work and Social Adjustment Scale) vor und nach durchschnittlich 10 Monaten Projektteilnahme evaluiert. Im Zentrum der Untersuchung stehen die Geflüchteten (Angebotsinanspruchnahme und psychische Belastung) sowie die Psychotherapeut:innen (berichtete Erfahrungen). Erste Ergebnisse belegen eine überdurchschnittlich hohe Belastung der Geflüchteten zum Zeitpunkt des Erstgesprächs, eine hohe Teilnahmequote und eine geringe Abbruchrate. Die Verlaufserhebung zeigt signifikante Verbesserungen hinsichtlich der psychischen Symptombelastung sowie Funktionsbeeinträchtigung. Die (qualitative) Befragung der Psychotherapeut:innen unterstreicht die Effektivität von KOBEG, 93 % der Therapeut:innen beabsichtigen im Rahmen des Projekts weiterhin mit Geflüchteten zu arbeiten.
Schädel-Hirn-Trauma
Authors: Pinggera D. , Geiger P. , Thomé C.
Published: September 2023

Das Schädel-Hirn-Trauma (SHT) bezeichnet eine durch äußere Gewalteinwirkung bedingte Schädigung des Gehirnparenchyms. Es verursacht massive individuelle und sozioökonomische Folgen aufgrund der hohen Morbidität und Mortalität. Betroffen sind junge Menschen durch Verkehrs- oder Sportunfälle, aber auch zunehmend alte Menschen durch Stürze im häuslichen Umfeld. Der Begriff SHT umfasst mehrere Krankheitsbilder, die sich in Ursache, Prognose und Therapie unterscheiden. Allen gemein sind jedoch komplexe pathophysiologische Kaskaden, die sich sofort nach dem initialen Trauma entwickeln und über mehrere Tage und Wochen anhalten können. In dieser Phase versucht eine medizinische Behandlung, sei sie chirurgisch oder medikamentös, die Folgen des Primärschadens zu reduzieren. Die Erhaltung eines adäquaten zerebralen Perfusionsdrucks und die Reduktion des Hirndrucks stehen im Vordergrund.
Enhancing productivity and efficiency in conventional laser metal deposition process for Inconel 718 - part I: the effects of the process parameters
Authors: Maffia Simone , Chiappini Federico , Maggiani Gianluca , Furlan Valentina , Guerrini Massimo , Previtali Barbara
Published: September 2023

The sustainable energy transition has spurred the development of technologies that minimize material and energy waste, such as additive manufacturing (AM). Laser metal deposition (LMD) is a promising AM technique, but its complexity and limited automation hinder its implementation in production chains. To enhance productivity, the high deposition rate LMD (HDR-LMD) technology has been developed, requiring advanced equipment and powerful laser sources. In contrast, the conventional LMD (C-LMD) process is simpler and less expensive to implement. This study aims to optimize the productivity and efficiency of C-LMD by adjusting laser power, scan speed, powder feed rate, and standoff distance on Inconel 718 single tracks. An innovative approach eliminates the need for cutting specimens to evaluate single tracks, allowing comprehensive geometric and performance characterization with limited operator involvement, making the analysis quicker and more robust. An extensive experimental campaign was conducted to examine the influence of process parameters on track geometry, productivity, and efficiency. A multi-objective optimization procedure identified parameter combinations maximizing productivity while maintaining high efficiency and desirable clad shape. The study attained deposition rates ranging from 700 to 800 g/h, with powder catchment efficiency ranging between 75 and 90%. These results were achieved using parameters including 1775 W of laser power, scan speeds ranging from 960 to 1140 mm/min, powder feed rates between 810 and 1080 g/h, and standoff distance of 9 mm. The study also clearly indicated that further potential for improving C-LMD process performance may be possible. The findings gathered in this paper are the base for the further optimization presented in the second part of the work, which is focused on multi-pass multi-layer and reaches deposition rates of 1500 g/h, promoting the implementation of C-LMD process at industrial level.
From CAD to Plug & Produce
Authors: Nilsson Anders , Danielsson Fredrik , Svensson Bo
Published: September 2023

Industries of low-batches or one-off manufacturing aim for automation that is competitive enough to adapt to new or modified products daily through in-house knowledge that focuses on manufacturing processes and not on machine function programming. To solve this, a complete set of actions that utilize seamless data transfer from product design in CAD to a Plug & Produce automation concept is proposed together with a generic structure for the integration of standard industrial robots into agents. This structure enables agents to handle their local reference coordinate systems and locations relative to a global perspective. Seamless utilization of data from product designs to Plug & Produce will simplify and shorten the time of digital development through concurrently usable text-based and graphical configuration tools of a configurable multi-agent system. Needed data extracts directly from the product design as requirements of operational goals. Extraction of data from the product design, sequence of goals, and process plans, which are recipes of how to solve goals, can by this concept be configured by in-house knowledge that has the process knowledge but not necessarily programming competence.
Extremal index: estimation and resampling
Authors: Ferreira Marta
Published: September 2023

The duration of extremes in time leads to a phenomenon known as clustering of high values, with a strong impact on risk assessment. The extremal index is a measure developed within Extreme Value Theory that quantifies the degree of clustering of high values. In this work we will consider the cycles estimator introduced in Ferreira and Ferreira (Ann Inst Henri Poincare Probab Stat 54(2):587–605, 2018). A reduced bias estimator based on the Jackknife methodology will be presented. The bootstrap technique will also be considered in the inference and will allow to obtain confidence intervals. The performance will be analyzed based on simulation. We found our proposal effective in reducing bias and it compares favorably with some well-known methods. An application of the methods to real data will also be presented.
The role of inflammation and antioxidant defenses in the cardiotoxicity of doxorubicin in elderly CD-1 male mice
Authors: Reis-Mendes Ana , Ferreira Mariana , Duarte José Alberto , Duarte-Araújo Margarida , Remião Fernando , Carvalho Félix , Sousa Emília , Bastos Maria Lourdes , Costa Vera Marisa
Published: September 2023

Doxorubicin (DOX) is a potent chemotherapeutic agent used against several cancer types. However, due to its cardiotoxic adverse effects, the use of this drug may be also life-threatening. Although most cancer patients are elderly, they are poorly represented and evaluated in pre-clinical and clinical studies. Considering this, the present work aims to evaluate inflammation and oxidative stress as the main mechanisms of DOX-induced cardiotoxicity, in an innovative approach using an experimental model constituted of elderly animals treated with a clinically relevant human cumulative dose of DOX. Elderly (18–20 months) CD-1 male mice received biweekly DOX administrations, for 3 weeks, to reach a cumulative dose of 9.0 mg/kg. One week (1W) or two months (2 M) after the last DOX administration, the heart was collected to determine both drug’s short and longer cardiac adverse effects. The obtained results showed that DOX causes cardiac histological damage and fibrosis at both time points. In the 1W-DOX group, the number of nuclear factor kappa B (NF-κB) p65 immunopositive cells increased and a trend toward increased NF-κB p65 expression was seen. An increase of inducible nitric oxide synthase (iNOS) and interleukin (IL)-33 and a trend toward increased IL-6 and B-cell lymphoma-2-associated X (Bax) expression were seen after DOX. In the same group, a decrease in IL-1β, p62, and microtubule-associated protein 1A/1B-light chain 3 (LC3)-I, p38 mitogen-activated protein kinase (MAPK) expression was observed. Contrariwise, the animals sacrificed 2 M after DOX showed a significant increase in glutathione peroxidase 1 and Bax expression with persistent cardiac damage and fibrosis, while carbonylated proteins, erythroid-2-related factor 2 (Nrf2), NF-κB p65, myeloperoxidase, LC3-I, and LC3-II expression decreased. In conclusion, our study demonstrated that in an elderly mouse population, DOX induces cardiac inflammation, autophagy, and apoptosis in the heart in the short term. When kept for a longer period, oxidative-stress-linked pathways remained altered, as well as autophagy markers and tissue damage after DOX treatment, emphasizing the need for continuous post-treatment cardiac monitoring.
New thresholds in semi-quantitative [18F]FDG PET/CT are needed to assess large vessel vasculitis with long-axial field-of-view scanners
Authors: Knappe Luisa , Bregenzer Carola , Gözlügöl Nasir , Mingels Clemens , Alberts Ian , Rominger Axel , Caobelli Federico
Published: September 2023

Aim

[18F]FDG PET/CT proved accurate in the diagnostic work-up of large vessel vasculitis (LVV). While a visual interpretation is currently considered adequate, several attempts have been made to integrate it with a semiquantitative evaluation. In this regard, there is the need to validate current or new thresholds for the semiquantitative parameters on long-axial field of view (LAFOV) scanners.

Methods

We retrospectively evaluated 100 patients (50 with LVV and 50 controls) who underwent [18F]FDG LAFOV PET/CT. Semiquantitative parameters (SUVmax and SUVmean) were calculated for large vessels in 3 districts (supra-aortic [SA], thoracic aorta [TA], and infra-aortic [IA]). Values were also normalized to liver activity (SUVmax/L-SUVmax, and SUVmax/L-SUVmean).

Results

Of the 50 patients diagnosed with LVV, SA vessels were affected in 38 (76%), TA in 42 (84%) and IA vessels in 26 (52%). To-liver normalized values had higher diagnostic accuracy than non-normalized values (AUC always ≥ 0.90 vs. 0.74–0.89). For the SA vessels, best thresholds were 0.66 for SUVmax/L-SUVmax and 0.88 for SUVmax/L-SUVmean; for the TA, 1.0 for SUVmax/L-SUVmax and 1.30 for SUVmax/L-SUVmean; finally, for IA vessels, the best threshold was 0.83 for SUVmax/L-SUVmax and 1.11 for SUVmax/L-SUVmean.

Conclusion

LAFOV [18F]FDG-PET/CT is accurate in the diagnostic workup of LVV, but different threshold in semi-quantitative parameters than reported in literature for standard scanners should be considered.
Angioembolization for Isolated Severe Blunt Splenic Injuries with Hemodynamic Instability: A Propensity Score Matched Analysis
Authors: Aoki Makoto , Matsumoto Shokei , Abe Toshikazu , Zarzaur Ben L. , Matsushima Kazuhide
Published: September 2023

Background

This study aimed to compare patient outcomes after splenic angioembolization (SAE) or splenectomy for isolated severe blunt splenic injury (BSI) with hemodynamic instability, and to identify potential candidates for SAE.

Methods

Adult patients with isolated severe BSI (Abbreviated Injury Scale [AIS] 3–5) and hemodynamic instability between 2013 and 2019 were identified from the American College of Surgeons Trauma Quality Improvement (ACS TQIP) database. Hemodynamic instability was defined as an initial systolic blood pressure (SBP) <90 mmHg, heart rate (HR) >120 bpm, or lowest SBP <90 mmHg within 1 h after admission, with ≥1 unit of blood transfused within 4 h after admission. In‐hospital mortality was compared between splenectomy and SAE groups using 2:1 propensity‐score matching. The characteristics of unmatched and matched splenectomy patients were also compared.

Results

A total of 478 patients met our inclusion criteria (332 splenectomy, 146 SAE). After propensity‐score matching, 166 splenectomy and 83 SAE patients were compared. Approximately 85% of propensity‐score matched patients sustained AIS 3/4 injuries, and 50% presented with normal SBP and HR before becoming hemodynamically unstable. The median time to intervention (splenectomy or SAE) was 137 min (interquartile range 94–183). In‐hospital mortality between splenectomy and SAE groups was not significantly different (5.4% vs. 4.8%, p = 1.000). More than half of unmatched patients in the splenectomy group sustained AIS 5 injuries and presented with initially unstable hemodynamics. The median time to splenectomy in such patients was significantly shorter than in matched splenectomy patients (67 vs. 132 min, p < 0.001).

Conclusion

Splenectomy remains the mainstay of treatment for patients with AIS 5 BSI who present to hospital with hemodynamic instability. However, SAE might be a feasible alternative for patients with AIS 3/4 injuries.
Ab initio calculations of structural, electronic, optical, and magnetic properties of delafossite SMoO2 (S = Na, K, Rb, Cs) for spintronics
Authors: Ismail Khawar , Parveen Ayesha , Zia Ayesha , Razzaq Samia , Murtaz Ghulam , Abbas Syed Muzahir , Foroughi Javad
Published: September 2023

Half metallic ferromagnetic (HMF) are key materials for quantum computing information storage devices and green energy. So, the structural, electronic, optical, and magnetic properties of SMoO2 (S = Na, K, Rb, Cs) are studied by quantum simulations based on density functional theory (DFT) within WIEN2K code. The Perdew − Burke − Ernzerhof (PBE + GGA) was used for the exchange correlation potential to study the said compounds. The volume optimization properties indicated that these compounds have minimum ground state energy in monoclinic crystal structure with space group 12 C2/m. Moreover, electronic band gap properties and density of states (DOS) graphs depicted the metallic nature for spin up a channel and semiconductor nature for spin down channel. This confirms the half-metallic ferromagnetism (HMF), and Heisenberg's classical model confirms the 100% spin polarization. Various frequency dependent optical parameters explain the optical properties. The double exchange process, crystal field energy ∆Ecry, direct Δx(d), and indirect exchange energies Δx(pd), is demonstrated by the quantum ferromagnetic behavior. The negative value of Δx(pd) and magnetic exchange constants confirm the ferromagnetism due to the quantum exchange mechanism of electrons. In addition to the above, it has been noted from the density of states that Mo d-states are responsible for the response of half metallic nature of these compounds. The magnetic parameter values of SMoO2 (S = Na, K, Rb, and Cs) show higher magnetic moment and major contribution coming from the Mo atom. Hence the studied results show that these compounds are valuable materials for spintronic applications.
Slowly cutting, loose seton ligature and staged fistulotomy for healing of idiopathic perianal fistula and influence on anal continence
Authors: Schrader Lisa , Brandstrup Birgitte , Olaison Gunnar
Published: September 2023

Purpose

To investigate the ability of a “slowly cutting, loose seton ligature and staged fistulotomy” to heal perianal fistulas, the time needed with the seton ligature, recurrence rate, influence on anal continence, health-related quality of life (HRQoL), and patient satisfaction.

Methods

Observational single-center study. We reviewed the medical records of all patients with primary surgeries from January 1, 2009, to December 31, 2018. The patients answered a questionnaire pre- and postoperative on anal continence (St. Mark’s incontinence score) and HRQoL (The Short Health Scale). Satisfaction with the operation was answered postoperatively.

Results

Forty-three patients (37 men, 6 women) were included. Initially 41 of 43 healed (95%). Three patients (7%) had a recurrence, two healed after retreatment. The median follow-up was 55 months (IQR, 4). Thirty-four patients (79%) responded to the questionnaire. At follow-up, forty (93%) patients were healed. The median time treated with a seton ligature in the healed patients was 13 months (IQR, 14). St. Mark’s incontinence score preoperative was median 2 (IQR, 9) and after the operation median 1 (IQR, 4). The Short Health Scale improved from median 20 (IQR, 5) preoperatively to 5 (IQR, 5) postoperatively, p < 0.001. Patient satisfaction was median 1 (= very satisfied) (IQR, 1).

Conclusion

A “slowly cutting, loose seton ligature followed by a staged fistulotomy”, heals the vast majority of perianal fistulas with minor or none influence on continence and few recurrences. Patient-reported HRQoL improves greatly, and patient satisfaction is high.
Multisystem inflammatory syndrome in children (MIS-C) and sepsis differentiation by a clinical and analytical score: MISSEP score
Authors: Hernández-García María , Roldan-Berengue Elies , Guitart Carmina , Girona-Alarcón Mònica , Argüello Guillermo , Pino Rosa , F. de Sevilla Mariona , García-García Juan José , Jordan Iolanda
Published: September 2023

Differential diagnosis between Multisystem Inflammatory Syndrome in Children (MIS-C) and other causes of systemic inflammatory response such as sepsis is complex. The aims were to evaluate the differences between pediatric patients with MIS-C and sepsis and to develop a score to distinguish both entities. This was a retrospective study that compared demographic, clinical, diagnostic, and therapeutic data of pediatric patients with MIS-C (cohort 2020–2022) and sepsis (cohorts 2010–2014 and 2017–2018) admitted to a Pediatric Intensive Care Unit (PICU) of a tertiary care hospital. A diagnostic score was developed with variables that differentiated the two conditions. Twenty-nine patients with MIS-C were identified, who were matched 1:3 with patients with sepsis (n = 87). Patients with MIS-C were older (10 vs. 4 years old), and the majority were male (69%). Clinical characteristics that demonstrated differences were prolonged fever and signs and symptoms affecting skin-mucosa and gastrointestinal system. Leukocytes, PCT, and ferritin were higher in sepsis, while thrombocytopenia, lymphopenia, and elevated fibrinogen and adrenomedullin (biomarker with a role for the detection of invasive infections) were more frequent in MIS-C. MIS-C patients presented greater myocardial dysfunction (p < 0.001). Five criteria were selected and included in the MISSEP score after fitting them into a multivariate logistic regression model: fever > 48 hours (20 points), thrombocytopenia < 150 × 103/µL (6 points), abdominal pain (15 points), conjunctival erythema (11 points), and Vasoactive Inotropic Score (VIS) > 10 (7 points). The cutoff > 25 points allowed to discriminate MIS-C from sepsis with a sensitivity of 0.89 and specificity of 0.95.

     Conclusion: MIS-C phenotype overlaps with sepsis. MISSEP score could be useful to distinguish between both entities and direct specific treatment.

What is Known:• Differential diagnosis between Multisystem Inflammatory Syndrome in Children (MIS-C) and other causes of systemic inflammatory response such as sepsis is complex.• It is essential to establish an accurate initial diagnosis and early specific treatment in both cases of MIS-C and sepsis to improve the prognosis of these patients.

What is New:• Patients with MIS-C are older and have characteristic symptoms of prolonged fever, gastrointestinal symptoms, skin-mucosal involvement, and greater myocardial dysfunction, compared to patients with sepsis.• The use of diagnostic scores, such as the MISSEP score, can be very useful to distinguish between the two entities and help direct specific treatment.
The natural history, clinical outcomes, and genotype–phenotype relationship of otoferlin-related hearing loss: a systematic, quantitative literature review
Authors: Ford Charles L. , Riggs William J. , Quigley Tera , Keifer Orion P. , Whitton Jonathon P. , Valayannopoulos Vassili
Published: September 2023

Congenital hearing loss affects one in 500 newborns. Sequence variations in OTOF, which encodes the calcium-binding protein otoferlin, are responsible for 1–8% of congenital, nonsyndromic hearing loss and are the leading cause of auditory neuropathy spectrum disorders. The natural history of otoferlin-related hearing loss, the relationship between OTOF genotype and hearing loss phenotype, and the outcomes of clinical practices in patients with this genetic disorder are incompletely understood because most analyses have reported on small numbers of cases with homogeneous OTOF genotypes. Here, we present the first systematic, quantitative literature review of otoferlin-related hearing loss, which analyzes patient-specific data from 422 individuals across 61 publications. While most patients display a typical phenotype of severe-to-profound hearing loss with prelingual onset, 10–15% of patients display atypical phenotypes, including mild-to-moderate, progressive, and temperature-sensitive hearing loss. Patients’ phenotypic presentations appear to depend on their specific genotypes. For example, non-truncating variants located in and immediately downstream of the C2E calcium-binding domain are more likely to produce atypical phenotypes. Additionally, the prevalence of certain sequence variants and their associated phenotypes varies between populations due to evolutionary founder effects. Our analyses also suggest otoacoustic emissions are less common in older patients and those with two truncating OTOF variants. Critically, our review has implications for the application and limitations of clinical practices, including newborn hearing screenings, hearing aid trials, cochlear implants, and upcoming gene therapy clinical trials. We conclude by discussing the limitations of available research and recommendations for future studies on this genetic cause of hearing loss.
Effect of thoracic cage width on surgery time and postoperative outcome in minimally invasive esophagectomy
Authors: Mann C. , Jezycki T. , Berlth F. , Hadzijusufovic E. , Uzun E. , Mähringer-Kunz A. , Lang H. , Klöckner R. , Grimminger P. P.
Published: September 2023

Introduction

Minimally invasive esophagectomy (MIE) for esophageal cancer is a complex procedure that reduces postoperative morbidity in comparison to open approach. In this study, thoracic cage width as a factor to predict surgical difficulty in MIE was evaluated.

Methods

All patients of our institution receiving either total MIE or robotic-assisted MIE (RAMIE) with intrathoracic anastomosis between February 2016 and April 2021 for esophageal cancer were included in this study. Right unilateral thoracic cage width on the level of vena azygos crossing the esophagus was measured by the horizontal distance between the esophagus and parietal pleura on preoperative computer tomography. Patients’ data as well as operative and postoperative details were collected in a prospective database. Correlation between thoracic cage width with duration of the thoracic procedure and postoperative complication rates was analyzed.

Results

Overall, 313 patients were eligible for this study. Thoracic width on vena azygos level ranged from 85 to 149 mm with a mean of 116.5 mm. In univariate analysis, a small thoracic width significantly correlated with longer duration of the thoracic procedure (p = 0.014). In multivariate analysis, small thoracic width and neoadjuvant therapy were identified as independent factors for long duration of the thoracic procedure (p = 0.006). Regarding postoperative complications, thoracic cage width was a significant risk factor for occurrence of postoperative pneumonia in the multivariate analysis (p = 0.045). Dividing the cohort into two groups of patients with narrow (≤ 107 mm, 19.5%) and wide thoraces (≥ 108 mm, 80.5%), the thoracic procedure was significantly prolonged by 17 min (204 min vs. 221 min, p = 0.014).

Conclusion

A small thoracic cage width is significantly correlated with longer operation time during thoracic phase of a MIE in Europe, which suggests increased surgical difficulty. Patients with small thoracic cage width may preferably be operated by MIE-experienced surgeons.

Graphical abstract