bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐Term Retention Microbubbles with Three‐Layer Structure for Floating Intravesical Instillation Delivery
Authors: Deng Qiurong , Xie Junyi , Kong Shuying , Tang Tianmin , Zhou Jianhua
Published: January 2023

Intravesical instillation is an effective treatment for bladder cancer. However, clinical anticancer agents always suffer rapid excretion by periodic urination, leading to low therapeutic efficacy. Prolonging the retention time of drugs in the bladder is the key challenge for intravesical instillation treatment. Herein, a facile and powerful surface cross‐linking‐freeze drying strategy is proposed to generate ultra‐stable albumin bovine air microbubbles (BSA‐MBs) that can float and adhere to the bladder wall to overcome the excretion of urination and exhibit a remarkable property of long‐term retention in the bladder. More noteworthy, BSA‐MBs are endowed with a specific three‐layer structure, namely, the outer membrane, middle drug loading layer and inner air core, which makes them have a low density to easily float and possess a high drug loading capacity. Based on their unique superiorities, the therapeutic potential of doxorubicin (DOX)‐loaded BSA‐MBs (DOX‐MBs) is exemplified by intravesical instillation for bladder cancer. After injection into the bladder, DOX‐MBs can remain in the bladder for a long time and sustain the release of DOX in urine, exhibiting potent anticancer efficacy. Consequently, the prolonged retention of BSA‐MBs in the bladder renders them as an effective floating drug delivery system for intravesical instillation therapy.
Fabrication of Homogeneous Nanoporous Structure on 4H‐/6H‐SiC Wafer Surface via Efficient and Eco‐Friendly Electrolytic Plasma‐Assisted Chemical Etching
Authors: Zhan Shunda , Liu Bowen , Yu Xuemeng , Chen Xihan , Zeng Guosong , Zhao Yonghua
Published: January 2023

Nanoporous single‐crystal silicon carbide (SiC) is widely used in various applications such as protein dialysis, as a catalyst support, and in photoanodes for photoelectrochemical water splitting. However, the fabrication of nano‐structured SiC is challenging owing to its extreme chemical and mechanical stability. This study demonstrates a highly‐efficient, open‐circuit electrolytic plasma‐assisted chemical etching (EPACE) method without aggressive fluorine‐containing reactants. The EPACE method enables the nano‐structuring of SiC via a plasma‐enveloped microtool traversing over the target material in an electrolyte bath. Through process design, EPACE readily produces a uniform nanoporous layer on a 4H‐SiC wafer in KOH aqueous solution, with adjustable pore diameters in the range 40–130 nm. Plasma diagnosis by optical emission spectrometry (OES) and surface microanalysis reveal that EPACE realizes a nanoporous structure by electrolytic plasma‐assisted oxidation and subsequent thermochemical reduction of an oxide. An increase in voltage or a decrease in etch gap intensifies the plasma and improves the etching efficiency. The maximum etch rate and depth reach 540 nm min−1 and 10 µm, respectively, demonstrating the significant potential of the approach as a time‐saving and sustainable nanofabrication method for industrial applications. Further, the effectiveness of the fabricated SiC nanoporous structure for application in photoelectrochemical water splitting is demonstrated.
Olivine‐Type MgMn0.5Zn0.5SiO4 Cathode for Mg‐Batteries: Experimental Studies and First Principles Calculations
Authors: Pérez‐Vicente Carlos , Rubio Saúl , Ruiz Rafaela , Zuo Wenhua , Liang Ziteng , Yang Yong , Ortiz Gregorio F.
Published: January 2023

Magnesium driven reaction in olivine‐type MgMn0.5Zn0.5SiO4 structure is subject of study by experimental tests and density functional theory (DFT) calculations. The partial replacement of Mn in Oh sites by other divalent metal such as Zn to get MgMn0.5Zn0.5SiO4 cathode is successfully developed by a simple sol–gel method. Its comparison with the well‐known MgMnSiO4 olivine‐type structure with (Mg)M1(Mn)M2SiO4 cations distribution serves as the basis of this study to understand the structure, and the magnesium extraction/insertion properties of novel olivine‐type (Mg)M1(Mn0.5Zn0.5)M2SiO4 composition. This work foresees to extend the study to others divalent elements in olivine‐type (Mg)M1(Mn0.5M0.5)M2SiO4 structure with M = Fe, Ca, Mg, and Ni by DFT calculations. The obtained results indicate that the energy density can be attuned between 520 and 440 W h kg−1 based on two properties of atomic weight and redox chemistry. The presented results commit to open new paths toward development of cathodes materials for Mg batteries.
The Interplay of Organic Spacers and Small Cations for Efficient Dion–Jacobson Perovskite Solar Cells
Authors: Guo Xinlu , Gao Yujia , Long Feng , Lin Lvyang , Wang Yinping , Ho Ngai Kwan , Wei Qi , Xing Guichuan , Shi Tingting , Xie Weiguang , Long Mingzhu , Xu Jianbin
Published: January 2023

2D halide perovskites have displayed wide tunability in structure and physicochemical properties through the diversity and versatility of interlayer spacers. However, the interaction between the large spacer and small cation inside the inorganic framework has not been elucidated yet. Herein, the impact of small‐organic cation on the crystallization kinetics, carrier behavior, and the structure distortion of the low‐dimensional Dion–Jacobson (DJ) perovskite materials and solar cells is systematically studied. The formamidium (FA)‐based DJ film exhibits higher crystal orientation and larger crystal domain induced by slower crystallization as compared to methylammonium‐based one, accompanied with lower trap density, more efficient carrier transfer, and higher photovoltaic performance. As a result, the BDAFA2Pb3I10 perovskite solar cell delivers a champion power conversion efficiency up to 15.34%, which is the highest among FA‐based small‐n DJ series. Theoretical simulation results uncover that the smaller tilting and higher rigidity of the octahedra in the FA‐based DJ systems render more outstanding environmental stability, leading to well‐maintained 85% of its efficiency after prolonged storing time of 1020 h at 65 °C.
A case of rapid canine nephroblastoma presumed metastasis documented with advanced imaging
Authors: Seddon Kathleen , Smith Patrick , Romine Jessica
Published: January 2023

A 1.5‐year‐old, female, entire German shepherd dog was presented for evaluation of an abdominal mass. The dog had a 4‐month history of polydipsia, polyuria, diarrhoea, and weight loss despite polyphagia. Abdominal ultrasound confirmed a large abdominal mass suspected to be uterine in origin. An exploratory celiotomy revealed a 4.3 kg, 26 × 17 × 17 cm multinodular mass entirely encompassing the uterus, left ovary and left kidney. A combined ovariohysterectomy and left nephrectomy were undertaken. Histopathology confirmed stage ΙΙ renal nephroblastoma with favourable histology. Chemotherapy was declined and 86 days following surgery, significant abdominal metastases were identified on a computed tomography scan. The patient was euthanased 113 days after surgery due to progressive disease. This is the first report to display the rapid presumed metastasis of a canine nephroblastoma, without gross metastasis at initial surgical resection, through advanced imaging. This is also the first reported case of polyphagia despite weight loss as a presenting clinical sign.
Introduction: Inhabiting Vulnerability Throughout the Life Course
Authors: Spini Dario , Widmer Eric
Published: January 2023

This chapter presents the vulnerability framework used in the different sections chapters of this book. Vulnerability is defined as a process of resource loss in one or more life domains that threatens individuals in three major steps: (1) an inability to avoid individual, social or environmental stressors, (2) an inability to cope effectively with these stressors, and (3) an inability to recover from stressors or to take advantage of opportunities by a given deadline. The chapter also stresses the importance of resources, reserves and stressors to understand the dynamics of vulnerability throughout the life span. This life course perspective of vulnerability processes is better understood through three main perspectives: multidimensional (across life domains), multilevel (using micro, meso and macro perspectives) and multidirectional (the study of vulnerability life trajectories should envisage all possible directions, namely stability, decline, recovery, growth trajectories and in long-term). We also argue in this chapter that a vulnerability framework enables researcher to understand the craft of our lives and the responses, be they individual (through agency), collective (through support) or institutional (social policies) that can be given to life events, life transitions, and to the stressors that individuals inevitably face sooner or later in their life.
How Family and Other Close Ties Shape Vulnerability Processes
Authors: Rossier Clémentine , Bernardi Laura , Baersywil Marie , Oris Michel , Sapin Marlène , Widmer Eric
Published: January 2023

While close relations include both intimate family members and close friends, the transmission of socioeconomic resource remains largely confined within families. Moreover, family-transmitted values and sociopsychological skills are incorporated during childhood, and emotional and instrumental support is still mainly assumed by family members. These overlapping exchanges mean that family ties constitute durable resource for individuals, but that families are (also) damaging in case of tie dissolution, poor relational quality or gendered family practices. In this chapter, we examine how family and friends affect vulnerability processes differently by using three longitudinal datasets on long-term couples, lone parents, and ageing individuals, as well cross-sectional data on adults’ personal networks, collected with support from LIVES. We found that ambivalent and sometimes negative (i.e., resource depletion) aspects of family relationships emerge, in particular, in situations in which other key resources (including friendship ties) are missing, typically with the occurrence of stressful life events. Conversely, negative family events are more quickly overcome when sufficient resources (including friends) are available. Interestingly, some negative life events, such as job loss, are better dealt with through sparser personal networks. By contrast, normative life events act as densifiers or enlargers of both elective and family networks.
Synthesis: Vulnerability in Context
Authors: Spini Dario , Vacchiano Mattia
Published: January 2023

Vulnerability lies in the articulation of different levels. Constraints or opportunities, resources or stressors to people’ lives unfold at the intersection of micro-individual processes and macro-structural levels during the life course. This section explores five directions through which LIVES addresses these interactions across different meso-level contexts: (1) Vandecasteele and colleagues explain how socio-economic inequalities are structured across neighborhoods and communities, emphasising the importance of geographical contexts; (2) Hoffman and colleagues study inequalities in mental health by considering people’s relational contexts and the interaction between their networks and their social identities; (3) Bonvin and colleagues explain how the implementation of social policies depends on the functioning of organisations and the working conditions of those social agents who are in contact with vulnerable groups; (4) Burton-Jeangros and Vagnoli look at how the vulnerability of HIV-positive women is influenced and negotiated within medical and institutional contexts; (5) Rossier and colleagues focus on the importance of the family context and the structure of opportunities and constraints it provides during the life course. Together, looking at urban, relational and organisational contexts, these studies show important facets of vulnerability at the meso level.
Childhood Socioeconomic Disadvantage and Health in the Second Half of Life: The Role of Gender and Welfare States in the Life Course of Europeans
Authors: Cullati Stéphane , Sieber Stefan , van der Linden Bernadette Wilhelmina Antonia , Orsholits Dan , von Arx Martina , Boisgontier Matthieu P. , Cheval Boris
Published: January 2023

Resources and reserves influence the development of vulnerability in old age. When individuals lack resources throughout their life trajectories, or when they lack reserves to cope with unforeseen events, they become at risk of poor health in old age. The LIFETRAIL project, funded by the NCCR LIVES, examined the life course precursors—especially during childhoohevald—of health in old age. This chapter reviews the findings from the LIFETRAIL project with a reserve’s perspective. First, it describes the role of educational achievements as a potential life course mediator that can reduce the impact of childhood misfortune on health in older age. Second, it considers the role of welfare states as a proxy of structural protection against the risk of socioeconomic adversities during the life course and examine their protecting role on health in old age. Third, it provides empirical analyses describing the potential interactions between education and welfare state on health in old age.
Life Calendars for the Collection of Life Course Data
Authors: Morselli Davide , Berchtold André
Published: January 2023

Life course studies involve the use of longitudinal data. Focusing on vulnerability processes that unfold in the medium or long term only reinforces this use, by requiring long sequences of data. However, traditional prospective data collection methods are not always compatible with restricted research time. The alternative is to collect retrospective data, sometimes in combination with prospective ones, and life calendars are a tool of choice for this kind of task. Although several methodological studies have shown that calendar data outperform conventional retrospective question lists, the quality of retrospective and prospective data is likely not to be the same. Hence, it is crucial to develop life calendars able to enhance the correct recall of past information, and to be able to demonstrate the accuracy of the resulting data. Moreover, with the advent of online data collection, the perspective to replace paper-and-pencil life calendars by electronic ones, and to make them self-administered, could help generalize this kind of data collection, but it also implies additional challenges. This chapter draws on several experiments with life calendars performed within the NCCR LIVES. It shows that life calendars can capture accurate data, and that online calendars have now become more than just a possibility.
Combining Event History and Sequence Analysis to Study Vulnerability over the Life Course
Authors: Studer Matthias , Gauthier Jacques-Antoine , Le Goff Jean-Marie
Published: January 2023

The life-course paradigm insists on the need to study trajectories and how they unfold over time. Two broad families of methodological strategies are generally used for this purpose. The first strategy focuses on the occurrence of events or transitions describing the dynamics of life trajectories. The second strategy emphasizes the holistic nature of trajectories or processes of categorical states by relying on sequence analysis. This chapter reviews recent methodological development combining these two approaches often presented as irreconcilable. “Competing Trajectory Analysis” aims to analyze jointly the occurrence of an event and the “trajectory” that immediately follows it. On the other hand, the “Sequence History Analysis” approach uses sequence analysis to better describe how an unfolding trajectory is linked with the occurrence of an upcoming event. The chapter proposes a theoretical presentation of these approaches discussing their respective strength and weaknesses for life-course research and more specifically the study of vulnerability over the life course. The added value of each approach is illustrated through a study of the relationship between divorce and professional trajectories using the retrospective data from the Swiss Household Panel.
Synthesis: Combining Methods for the Analysis of Vulnerability Processes Across the Life Course
Authors: Berchtold André , Ghisletta Paolo
Published: January 2023

The analysis of vulnerability processes throughout life implies several methodological difficulties. In this review chapter, we look back on more than 10 years of methodological innovations developed within the NCCR LIVES. Concerning data collection issues, although the prospective survey remains the gold standard for obtaining longitudinal data, retrospective data collected through specially adapted tools such as life calendars allow for a rapid completion of data sequences. Moreover, alternative sampling schemes based on network methods can reach individuals not likely to be included in traditional probabilistic samples. This also requires the development and use of more global data collection modes, combining qualitative and quantitative data, and allowing participants to respond in the manner best suited to their specific situations and capacities. What is true regarding data collection is also a requirement for data analysis: it is often essential to combine the strengths of different analytical tools such as traditional longitudinal analyses and survival analysis, the aim being to study the occurrence of specific events without losing sight of an individual’s prior trajectories over their life course. Finally, the chapter also addresses the issues of multichannel analyses and missing data.
When Mobility Meets Gender in the Transnational Life-Course
Authors: Le Feuvre Nicky , Davoine Eric , Cangià Flavia
Published: January 2023

This chapter explores the spillover effects of transnational mobility on professional and private life spheres, paying particular attention to the gender dynamics of vulnerability. From an interdisciplinary perspective, our aim is to explore the vulnerabilities associated with various forms of geographical mobility in societies (see Forbes-Mewett, 2020) characterised by increasing levels ofspatial displacement (Cresswell, 2006; Kaufmann, 2020) and by uneven shifts in gender norms across countries and among social groups (Bornatici et al., 2021; Daly, 2020; Esping-Andersen, 2009). We define transnational mobility as a physical displacement across borders that is imbued with a wide array of meanings, imaginaries and practices (Frello, 2008; Salazar & Smart, 2011). As a complex human experience, mobility is always entangled with other aspects of the life course (Cangià, 2021). Here, we are particularly interested in the interplay between the experience of transnational mobility, including different forms of short- or longterm cross-border relocation, and the gender configurations of professional and family life. Our empirical studies cover a diverse selection of geographically mobile and immobile people, including those who are commonly associated with privileged forms of transnational movement (Amit, 2011) and those who are often perceived as more constrained movers.
Social Policies, Vulnerability and the Life Course: A Complex Nexus
Authors: Bonvin Jean-Michel , Tabin Jean-Pierre , Perriard Anne , Rosenstein Emilie , Lovey Max
Published: January 2023

Social policies are designed to tackle vulnerability processes, providing additional resources to vulnerable target groups and helping them overcome stressing situations. However, empirical observations have shown that social policies may also reinforce vulnerability in certain cases. This can be better explained if one considers vulnerability as a multi-level process. Vulnerability is experienced by individuals at micro-level: it is then characterised by multidimensionality where diverse spheres of life can be affected; vulnerability is then framed as a social issue at macro level, requiring the setting up of adequate policy; this macro notion of vulnerability is then implemented at meso-level by agents that are called to translate the macro level notion of vulnerability into actual public action. There may be a gap or a discrepancy between the different notions of vulnerability as experienced at micro level, framed as social problem at macro level and implemented as public action at meso level. This gap may result in paradoxical situations where social policies do not provide adequate resources or submit their access to stringent conditions acting as stressors, thus reinforcing cumulative disadvantage rather than counteracting it. Examples from studies conducted within the NCCR-LIVES illustrate some of these paradoxical situations.
Exploring the potential of FCC-hh to search for particles from B mesons
Authors: Boyarsky Alexey , Mikulenko Oleksii , Ovchynnikov Maksym , Shchutska Lesya
Published: January 2023

Abstract

The Future Circular hadron Collider (FCC-hh) is a proposed successor of the Large Hadron Collider (LHC). FCC-hh would push both the energy and intensity frontiers of searches for new physics particles. In particular, due to higher energy and luminosity than at the LHC, at FCC-hh there would be produced around ≃ 30 times larger amount of B mesons and ≃ 120 times of W bosons, which then may decay into feebly interacting particles. In this paper we demonstrate the potential of FCC-hh by studying its sensitivity to heavy neutral leptons (HNLs) with masses mN< mB. We consider various locations of a displaced decay volume embedded in the planned infrastructure of FCC-hh. We demonstrate that FCC-hh may substantially improve the reach of the parameter space of HNLs as compared to the searches proposed at the LHC.
Kindliche vordere Kreuzbandruptur mit komplexer Außenmeniskusverletzung und Knorpelfragmentablösung der posterolateralen Tibia
Authors: Szalay Alexander , Runer Armin , Ehmann Yannick , Imhoff Andreas B. , Mehl Julian , Achtnich Andrea
Published: January 2023

Ein 11-jähriger Junge erleidet ein Distorsionstrauma des Kniegelenks mit einer Ruptur des vorderen Kreuzbands (VKB), Läsion des Außenmeniskus und Ablösung eines Knorpelfragments am posterolateralen Tibiaplateau. Aufgrund der konträren Nachbehandlungsschemata dieser schwerwiegenden Kombinationsverletzung erfolgt eine zweizeitige operative Versorgung. In einem ersten arthroskopischen Eingriff werden die Meniskus- und Knorpelverletzung behandelt. Nach stattgefundener Knorpeleinheilung erfolgt eine epiphysenschonende Rekonstruktion des vorderen Kreuzbands.
Pea protein–sugar beet pectin binders can provide cohesiveness in burger type meat analogues
Authors: Moll Pascal , Salminen Hanna , Schmitt Christophe , Weiss Jochen
Published: January 2023

Methylcellulose is commonly used in meat analogues for binding ingredients. In this study, we compared the binding properties of a methylcellulose hydrogel (5% w/w) to a novel, clean-label binder based on a mixture of pea protein and sugar beet pectin (r = 2:1, 22.5% w/w, pH 6.0) with and without laccase addition in a burger type meat analogue. It was shown that the pea protein–pectin binder glued vegetable protein particles and fat mimic particles together prior to cooking and frying, thereby improving forming of the mass into burger patties. Furthermore, sensory analysis revealed that the cohesiveness of the fried burger patties was better when the protein–pectin binder was used. However, the used binder system did not affect the hardness of the burger patties indicating that the binders rather affected the coherence of the structural elements. Burgers with solid fat particles were rated better in terms of appearance as compared to emulsified fat particles, since the former were not visible. This study is useful to better understand meat analogue product design for a higher acceptance among consumers.
Comparing anticipatory and stop-signal response inhibition with a novel, open-source selective stopping toolbox
Authors: Wadsley Corey G. , Cirillo John , Nieuwenhuys Arne , Byblow Winston D.
Published: January 2023

Response inhibition is essential for terminating inappropriate actions and, in some cases, may be required selectively. Selective stopping can be investigated with multicomponent anticipatory or stop-signal response inhibition paradigms. Here we provide a freely available open-source Selective Stopping Toolbox (SeleST) to investigate selective stopping using either anticipatory or stop-signal task variants. This study aimed to evaluate selective stopping between the anticipatory and stop-signal variants using SeleST and provide guidance to researchers for future use. Forty healthy human participants performed bimanual anticipatory response inhibition and stop-signal tasks in SeleST. Responses were more variable and slowed to a greater extent during the stop-signal than in the anticipatory paradigm. However, the stop-signal paradigm better conformed to the assumption of the independent race model of response inhibition. The expected response delay during selective stop trials was present in both variants. These findings indicate that selective stopping can successfully be investigated with either anticipatory or stop-signal paradigms in SeleST. We propose that the anticipatory paradigm should be used when strict control of response times is desired, while the stop-signal paradigm should be used when it is desired to estimate stop-signal reaction time with the independent race model. Importantly, the dual functionality of SeleST allows researchers flexibility in paradigm selection when investigating selective stopping.
Differentiability Properties for Boundary Control of Fluid-Structure Interactions of Linear Elasticity with Navier-Stokes Equations with Mixed-Boundary Conditions in a Channel
Authors: Hintermüller Michael , Kröner Axel
Published: January 2023

In this paper we consider a fluid-structure interaction problem given by the steady Navier Stokes equations coupled with linear elasticity taken from (Lasiecka et al. in Nonlinear Anal 44:54–85, 2018). An elastic body surrounded by a liquid in a rectangular domain is deformed by the flow which can be controlled by the Dirichlet boundary condition at the inlet. On the walls along the channel homogeneous Dirichlet boundary conditions and on the outflow boundary do-nothing conditions are prescribed. We recall existence results for the nonlinear system from that reference and analyze the control to state mapping generalizing the results of (Wollner and Wick in J Math Fluid Mech 21:34, 2019) to the setting of the nonlinear Navier-Stokes equation for the fluid and the situation of mixed boundary conditions in a domain with corners.
Improved benefit of continuing luspatercept therapy: sub-analysis of patients with lower-risk MDS in the MEDALIST study
Authors: Germing Ulrich , Fenaux Pierre , Platzbecker Uwe , Buckstein Rena , Santini Valeria , Díez-Campelo María , Yucel Aylin , Tang Derek , Fabre Shannon , Zhang George , Zoffoli Roberto , Ha Xianwei , Miteva Dimana , Hughes Christina , Komrokji Rami S. , Zeidan Amer M. , Garcia-Manero Guillermo
Published: January 2023

Red blood cell transfusion independence (RBC-TI) is an important goal in treating lower-risk myelodysplastic syndromes with ring sideroblasts. In the phase 3 MEDALIST study, RBC-TI of ≥ 8 weeks was achieved by significantly more luspatercept- versus placebo-treated patients in the first 24 weeks of treatment. In this post hoc analysis, we evaluated RBC transfusion units and visits based on patients’ baseline transfusion burden level and the clinical benefit of luspatercept treatment beyond week 25 in initial luspatercept nonresponders (patients who did not achieve RBC-TI ≥ 8 weeks by week 25) but continued luspatercept up to 144 weeks. RBC transfusion burden, erythroid response, serum ferritin levels, and hemoglobin levels relative to baseline were evaluated. Through week 25, fewer RBC transfusion units and visits were observed in luspatercept-treated patients versus placebo, regardless of baseline transfusion burden. This continued through 144 weeks of luspatercept treatment, particularly in patients with low baseline transfusion burden. Sixty-eight patients were initial nonresponders at week 25 but continued treatment; most (81%) received the maximum dose of luspatercept (1.75 mg/kg). Sixteen percent achieved RBC-TI for ≥ 8 weeks during weeks 25–48, 26% had reduced RBC transfusion burden, 10% achieved an erythroid response, 44% had reduced serum ferritin, and hemoglobin levels increased an average of 1.3 g/dL from baseline. These data have implications for clinical practice, as transfusion units and visits are less in luspatercept-treated patients through week 25 regardless of baseline transfusion burden, and continuing luspatercept beyond week 25 can potentially provide additional clinical benefits for initial nonresponders. Trial registration: NCT02631070.
Real-world treatments and thrombotic events in polycythemia vera patients in the USA
Authors: Verstovsek Srdan , Pemmaraju Naveen , Reaven Nancy L. , Funk Susan E. , Woody Tracy , Valone Frank , Gupta Suneel
Published: January 2023

Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased risk of thrombotic events (TE) and death. Therapeutic interventions, phlebotomy and cytoreductive medications, are targeted to maintain hematocrit levels < 45% to prevent adverse outcomes. This retrospective observational study examined medical and pharmacy claims of 28,306 PV patients initiating treatment for PV in a data period inclusive of 2011 to 2019. Study inclusion required ≥ 2 PV diagnosis codes in the full data period, at least 1 year of PV treatment history, and ≥ 1 prescription claim and medical claim in both 2018 and 2019. Patients having ≥ 2 hematocrit (HCT) test results in linked outpatient laboratory data (2018–2019) were designated as the HCT subgroup (N = 4246). Patients were characterized as high- or low-risk at treatment initiation based on age and prior thrombotic history. The majority of patients in both risk groups (60% of high-risk and 83% of low-risk) initiated treatment with phlebotomy monotherapy, and during a median follow-up period of 808 days, the vast majority (81% low-risk, 74% high-risk) maintained their original therapy during the follow-up period. Hematocrit control was suboptimal in both risk groups; 54% of high-risk patients initiating with phlebotomy monotherapy sometimes/always had HCT levels > 50%; among low-risk patients, 64% sometimes/always had HCT levels above 50%. Overall, 16% of individuals experienced at least 1 TE subsequent to treatment initiation, 20% (n = 3920) among high-risk and 8% (n = 629) among low-risk patients. This real-world study suggests that currently available PV treatments may not be used to full advantage.
Stochastic approximations of higher-molecular by bi-molecular reactions
Authors: Plesa Tomislav
Published: January 2023

Reactions involving three or more reactants, called higher-molecular reactions, play an important role in mathematical modelling in systems and synthetic biology. In particular, such reactions underpin a variety of important bio-dynamical phenomena, such as multi-stability/multi-modality, oscillations, bifurcations, and noise-induced effects. However, as opposed to reactions involving at most two reactants, called bi-molecular reactions, higher-molecular reactions are biochemically improbable. To bridge the gap, in this paper we put forward an algorithm for systematically approximating arbitrary higher-molecular reactions with bi-molecular ones, while preserving the underlying stochastic dynamics. Properties of the algorithm and convergence are established via singular perturbation theory. The algorithm is applied to a variety of higher-molecular biochemical networks, and is shown to play an important role in synthetic biology.
Heteroclinic cycling and extinction in May–Leonard models with demographic stochasticity
Authors: Barendregt Nicholas W. , Thomas Peter J.
Published: January 2023

May and Leonard (SIAM J Appl Math 29:243–253, 1975) introduced a three-species Lotka–Volterra type population model that exhibits heteroclinic cycling. Rather than producing a periodic limit cycle, the trajectory takes longer and longer to complete each “cycle”, passing closer and closer to unstable fixed points in which one population dominates and the others approach zero. Aperiodic heteroclinic dynamics have subsequently been studied in ecological systems (side-blotched lizards; colicinogenic Escherichia coli), in the immune system, in neural information processing models (“winnerless competition”), and in models of neural central pattern generators. Yet as May and Leonard observed “Biologically, the behavior (produced by the model) is nonsense. Once it is conceded that the variables represent animals, and therefore cannot fall below unity, it is clear that the system will, after a few cycles, converge on some single population, extinguishing the other two.” Here, we explore different ways of introducing discrete stochastic dynamics based on May and Leonard’s ODE model, with application to ecological population dynamics, and to a neuromotor central pattern generator system. We study examples of several quantitatively distinct asymptotic behaviors, including total extinction of all species, extinction to a single species, and persistent cyclic dominance with finite mean cycle length.
CTA-determined tricuspid annular dilatation is associated with persistence of tricuspid regurgitation after transcatheter aortic valve replacement
Authors: Löw Kornelia , Steffen Julius , Theiss Hans , Orban Martin , Rizas Konstantinos D. , Haum Magda , Doldi Philipp M. , Stolz Lukas , Gmeiner Jonas , Hagl Christian , Massberg Steffen , Hausleiter Jörg , Braun Daniel , Deseive Simon
Published: January 2023

Aim

The aim of this study was to analyse the predictive value of CTA-determined tricuspid annular dilatation (TAD) on the persistence of tricuspid regurgitation (TR) in patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) and concomitant at least moderate TR.

Methods and results

288 consecutive patients treated with TAVR due to severe AS and concomitant at least moderate TR at baseline were included in the analysis. As cutoff for TAD, the median value of the CTA-determined, to the body surface area-normalized tricuspid annulus diameter (25.2 mm/m2) was used. TAD had no impact on procedural characteristics or outcomes, including procedural death and technical or device failure according to the Valve Academic Research Consortium 3 criteria. However, the primary outcome of the study—TR persistence after TAVR was significantly more frequent in patients with compared to patients without TAD (odds ratio 2.60, 95% confidence interval 1.33–5.16, p < 0.01). Multivariable logistic regression analysis, adjusting for clinical and echocardiographic baseline characteristics, which are known to influence aetiology or severity of TR, confirmed TAD as an independent predictor of TR persistence after TAVR (adjusted odds ratio 2.30, 95% confidence interval 1.20–4.46, p = 0.01). Moreover, 2 year all-cause mortality was significantly higher in patients with persistence or without change of TR compared to patients with TR improvement (log-rank p < 0.01).

Conclusion

In patients undergoing TAVR for severe AS and concomitant at least moderate TR at baseline, TAD is a predictor of TR persistence, which is associated with increased 2-year all-cause mortality.

Graphical abstract
The course of knee extensor strength after total knee arthroplasty: a systematic review with meta-analysis and -regression
Authors: Singla Ravi , Niederer Daniel , Franz Alexander , Happ Kevin , Zilkens Christoph , Wahl Patrick , Behringer Michael
Published: January 2023

Purpose

Muscular strength loss and atrophy are postoperative complications. This systematic review with meta-analysis investigated the course of on knee extensor mass and strength from pre-surgery over total knee arthroplasty to rehabilitation and recovery.

Methods

A systematic literature search was conducted in PubMed (Medline), Cochrane Library (CINAHL, Embase) and Web of Science (until 29th of June 2022). Main inclusion criteria were  ≥ 1 preoperative and  ≥ 1 measurement  ≥ 3-months post-operation and ≥ 1 objective assessment of quadriceps strength, muscle mass or neuromuscular activity, measured at both legs. Studies were excluded if they met the following criteria: further impairment of treated extremity or of the contralateral extremity; further muscle affecting disease, or muscle- or rehabilitation-specific intervention. The Robins-I tool for non-randomized studies, and the Cochrane Rob 2 tool for randomized controlled studies were used for risk of bias rating. Pre-surgery, 3 months, 6 months and 1 year after surgery data were pooled using random effects meta-analyses (standardized mean differences, SMD, Hedge’s g) in contrast to the pre-injury values.

Results

1417 studies were screened, 21 studies on 647 participants were included. Thereof, 13 were non-randomized controlled trails (moderate overall risk of bias in most studies) and 7 were randomized controlled trials (high risk of bias in at least one domain in most studies). Three (k = 12 studies; SMD = − 0.21 [95% confidence interval = − 0.36 to − 0.05], I2 = 4.75%) and six (k = 9; SMD = − 0.10 [− 0.28 to − 0.08]; I2 = 0%) months after total knee arthroplasty, a deterioration in the strength of the operated leg compared with the strength of the non-operated leg was observed. One year after surgery, the operated leg was stronger in all studies compared to the preoperative values. However, this increase in strength was not significant compared to the non-operated leg (k = 6, SMD = 0.18 [− 0.18 to 0.54], I2 = 77.56%).

Conclusion

We found moderate certainty evidence that deficits in muscle strength of the knee extensors persist and progress until 3 months post-total knee arthroplasty in patients with end-stage knee osteoarthritis. Very low certainty evidence exists that preoperatively existing imbalance of muscle strength and mass in favor of the leg not undergoing surgery is not recovered within 1 year after surgery.
No difference in outcomes between large- and small-pore meshes in a prospective, randomized, multicenter trial investigating open retromuscular meshplasty for incisional hernia repair
Authors: Kroh Andreas , Zufacher Markus , Eickhoff Roman , Heise Daniel , Helmedag Marius , Ulmer Florian , Neumann Ulf P. , Conze Joachim , Hilgers Ralf-Dieter , Binnebösel Marcel
Published: January 2023

Study design

A randomized, controlled, prospective multicenter clinical trial with a parallel group design was initiated in eight surgical centers to compare a large-pore polypropylene mesh (Ultrapro®) to a small-pore polypropylene mesh (Premilene®) within a standardized retromuscular meshplasty for incisional hernia repair.

Methods

Between 2004 and 2006, patients with a fascial defect with a minimum diameter of 4 cm after vertical midline laparotomy were recruited for the trial. Patients underwent retromuscular meshplasty with either a large-pore or a small-pore mesh to identify the superiority of the large-pore mesh. Follow-up visits were scheduled at 5 and 21 days and 4, 12, and 24 months after surgery. A clinical examination, a modified short form 36 (SF-36®), a daily activity questionnaire, and an ultrasound investigation of the abdominal wall were completed at every follow-up visit. The primary outcome criterion was foreign body sensation at the 12-month visit, and the secondary endpoint criteria were the occurrence of hematoma, seroma, and chronic pain within 24 months postoperatively.

Results

In 8 centers, 181 patients were included in the study. Neither foreign body sensation within the first year after surgery (27.5% Ultrapro®, 32.2% Premilene®) nor the time until the first occurrence of foreign body sensation within the first year was significantly different between the groups. Regarding the secondary endpoints, no significant differences could be observed. At the 2-year follow-up, recurrences occurred in 5 Ultrapro® patients (5.5%) and 4 Premilene® patients (4.4%).

Conclusion

Despite considerable differences in theoretical and experimental works, we have not been able to identify differences in surgical or patient-reported outcomes between the use of large- and small-pore meshes for retromuscular incisional hernia repair.

Trial registration

Clinical Trials NCT04961346 (16.06.2021) retrospectively registered.
Climatic control of high-resolution stem radius changes in a drought-limited southern boreal forest
Authors: Dulamsuren Choimaa , Coners Heinz , Leuschner Christoph , Hauck Markus
Published: January 2023

Key message

Stem radius changes measured at high temporal resolution in a drought-limited southern boreal forest were primarily related to soil temperature and partly soil moisture variation, but only weakly to VPD.

Forest productivity at the southern fringe of the boreal forest biome in Inner Asia is strongly drought-limited, as is evident from dendrochronological analyses. Using electronic point dendrometers, we studied the climate response of stem radius changes at high temporal resolution (10-min intervals) in a mixed larch–birch forest in northern Mongolia in a drought year and two subsequent moist years. Larch trees showed stronger stem radius fluctuations than birches, and this difference was more pronounced in dry than in moist years. Stem radius changes were most tightly related to soil temperature variation, while soil moisture was the dominant controlling factor only in birch in the dry year. Correlations with the atmospheric vapor pressure deficit (VPD), and even more so with air temperature, were much weaker. While the linkage between radius change and VPD might primarily reflect diurnal transpiration-driven stem shrinkage and expansion, soil temperature is thought to directly affect cambial cell division and elongation during wood formation. We conclude that the phenology of stemwood increment is strongly controlled by soil temperature even in drought-limited southern boreal forests under continental climate due to the combination of cold and dry climate.
A multicentre study on the incidence of respiratory viruses in children with community-acquired pneumonia requiring hospitalization in the setting of the zero-COVID policy in China
Authors: Feng Ziheng , Xu Baoping , Zhong Lili , Chen Jing , Deng Jikui , Luo Zhengxiu , Cao Lingfeng , Tang Yu , Li Changchong , Jin Rong , Deng Li , Shang Yunxiao , Wu Ying , Zhao Hongwei , Feng Qianyu , Chen Xiangpeng , Xu Lili , Xie Zhengde
Published: January 2023

Background

Stringent nonpharmaceutical interventions (NPIs) have been implemented worldwide to combat the COVID-19 pandemic, and the circulation and seasonality of common respiratory viruses have subsequently changed. There have been few multicentre studies or comparisons of the prevalence of respiratory viruses accounting for community-acquired pneumonia (CAP) in hospitalized children between the pre-COVID period and the period after community and school reopening in the setting of the zero-COVID policy.

Methods

We included 1543 children with CAP who required hospitalization from November 1, 2020 to April 30, 2021 (period 1), and 629 children with the same conditions from November 1, 2018, to April 30, 2019 (period 2), in our study. All respiratory samples from these patients were screened for six respiratory viruses (respiratory syncytial virus [RSV], adenovirus [ADV], influenza A virus [Flu A], influenza B virus [Flu B], parainfluenza virus type 1 [PIV1], and parainfluenza virus type 3 [PIV3]) using a multiplex real-time PCR assay.

Results and conclusions

The median ages of the enrolled patients at the time of diagnosis were 1.5 years and 1.0 years for period 1 and period 2, respectively. In period 1, viral pathogens were detected in 50.3% (776/1543) of the enrolled patients. The most frequently identified viral pathogen was RSV (35.9%, 554/1543), followed by PIV3 (9.6%, 148/1543), PIV1 (3.6%, 56/1543), ADV (3.4%, 52/1543), Flu A (1.0%, 16/1543), and Flu B (0.8%, 13/1543). The total detection rates of these six viruses in the peak season of CAP were at the pre-COVID level. The prevalence of Flu A decreased dramatically, and circulation activity was low compared to pre-COVID levels, while the incidence of PIV3 increased significantly. There were no significant differences in the detection rates of RSV, ADV, Flu B, and PIV1 between the two periods. Our results showed that respiratory viruses accounted for CAP in hospitalized children at pre-COVID levels as communities and schools reopened within the zero-COVID policy, although the prevalence aetiology spectrum varied.
Musical Metaverse: vision, opportunities, and challenges
Authors: Turchet Luca
Published: January 2023

The so-called metaverse relates to a vision of a virtual, digital world which is parallel to the real, physical world, where each user owns and interact through his/her own avatar. Music is one of the possible activities that can be conducted in such a space. The “Musical Metaverse” (MM), the metaverse part which is dedicated to musical activities, is currently in its infancy, although is a concept that is constantly evolving and is progressing at a steady pace. However, to the best of the author’s knowledge, as of today an investigation about the opportunities and challenges posed by the MM has not been conducted yet. In this paper, we provide a vision for the MM and discuss what are the opportunities for musical stakeholders offered by current implementations of the MM, as well as we envision those that are likely to occur as the metaverse emerges. We also identify the technical, artistic, ethical, sustainability, and regulatory issues that need to be addressed so for the MM to be created and utilized in efficient, creative, and responsible ways. Given the importance and timeliness of the MM, we believe that a discussion on the related opportunities and concerns is useful to provide developers with guidelines for creating better virtual environments and musical interactions between stakeholders.
The impact of universal, school based, interventions on help seeking in children and young people: a systematic literature review
Authors: Hayes Daniel , Mansfield Rosie , Mason Carla , Santos Joao , Moore Anna , Boehnke Jan , Ashworth Emma , Moltrecht Bettina , Humphrey Neil , Stallard Paul , Patalay Praveetha , Deighton Jessica
Published: January 2023

Reviews into universal interventions to improve help seeking in young people focus on specific concepts, such as behaviour, do not differentiate between interpersonal and intrapersonal help seeking, and often report on statistical significance, rather than effect size. The aim of this review was to address the gaps highlighted above, to investigate the impact of universal, school-based interventions on help-seeking in children and young people, as well as to explore longer term impact. Four databases were searched. Data were extracted on country of origin, design, participant, school, and intervention characteristics, the help-seeking concept measured (e.g. knowledge, attitude/intention, behaviour), the duration between baseline and each follow-up (if applicable) and effect sizes at each follow-up. Quality assessment of the studies was undertaken using the Effective Public Health Practice Project (EPHPP) quality assessment tool. Overall, 14 different interventions met inclusion criteria. The majority of the studies were rated low in the quality assessment. Three constructs were most frequently reported a) intrapersonal attitudes towards help-seeking, b) interpersonal attitudes towards help-seeking and c) intrapersonal intended help-seeking. Findings around intervention effect were mixed. There was tentative evidence that interventions impacting interpersonal attitudes produced small effect sizes when measured between 3 and 6 months post intervention and that when effect sizes were initially observed intrapersonal attitudes, this remained at 3–6 month follow-up. Further work should pay attention to implementation factors, understanding the core ingredients needed to deliver effective interventions and whether embedding mental health education could help sustain or top up effect sizes from help-seeking interventions.