bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of clinical and patient‐reported outcomes in patients with benign euthyroid solitary nodules after ultrasound‐guided percutaneous microwave ablation and endoscopic thyroidectomy
Authors: Yadav Sanjay Kumar , Mehra Akanksha , Agarwal Pawan , Sharma Dhananjaya , Johri Goonj , Mishra Anjali
Published: August 2024

Background

Percutaneous ultrasound‐guided microwave ablation (MWA) for benign solid thyroid nodules is the newest modality for treatment. However, the differences in treatment outcomes between MWA and endoscopic thyroidectomy vestibular approach (TOETVA) for patients with benign euthyroid solitary nodules remain unknown. We are sharing initial results from our prospective study.

Methods

Prospective study between January 2022 and December 2023 was conducted and data were noted at 3 time points in patients planned for treatment (Preoperative, 1 week, and 12 months). Main outcome measures were clinical outcome and comparison of thyroid‐related quality of life using the ThyPRO‐39hin and swallowing‐related quality of life using the SWAL‐QoL.

Results

Of the 36 included patients, 20 patients underwent TOETVA and 16 underwent MWA. Both the groups were comparable in terms of demographic and clinicopathological profiles. The nodule volume reduction rate of patients at 12 months after MWA was 75.10% and 100% for TOETVA. The mean preoperative ThyPRO‐39hin and SWAL‐QoL scores were comparable in all domains between the two groups. Mean ThyPRO‐39hin and SWAL‐QoL scores on postoperative day 7 were significantly better in the MWA group in domains impaired social life (p < 0.0001) and impaired daily life (p = 0.0002). However, at the end of 12 months, mean ThyPRO‐39hin and SWAL‐QoL scores became significantly better in the TOETVA group as compared to the MWA group.

Conclusion

Our findings suggest that transoral endoscopic thyroidectomy results in significant superior clinical outcome, thyroid‐related quality of life, and swallowing‐related quality of life in the long term.
Structure Prediction and Mechanical Properties of Tantalum Carbide (TaC) on ab initio Level
Authors: Zagorac Dejan , Zagorac Jelena , Škundrić Tamara , Pejić Milan , Jovanović Dušica , Schön J. Christian
Published: August 2024

Tantalum carbide (TaC) is an extremely hard, brittle, refractory ceramic material with excellent physical properties, which makes it a desirable material in e. g. aerospace industries. In order to explore the range of feasible modifications of TaC, we have executed a crystal structure prediction study of the TaC chemical system using a multi‐methodological approach, via enthalpy landscape explorations of pristine TaC at different pressures, supplemented by data mining searches in the ICSD database. Local structure relaxations have been accomplished by using Density Functional Theory (DFT). The global minimum is found to correspond to the equilibrium rock salt (NaCl) type modification. Additionally, eight new phases of tantalum carbide are predicted to be feasible: the WC‐type, the NiAs‐type, the 5‐5‐type, the ZnS‐type, the Ring_TaC‐type, the CsCl‐type, the Ortho_TaC‐type, and the Tetra_TaC‐type. Furthermore, the elastic and mechanical properties of the predicted TaC modifications were explored on the DFT level of computation. The promising values of some of the mechanical properties of the proposed tantalum carbide modifications suggest that various scientific, industrial, and technological applications of TaC should be possible.
The Italian Agency for Development Cooperation. Culture as a People-Centered Path to Development: Best Practices from Fragile Areas—An Overview of Actions in Jordan, Palestine, Lebanon, Afghanistan, Pakistan
Authors: Abenante Paola , Strinati Fabio
Published: August 2024

This text outlines the Italian Agency for Development Cooperation’s approach to culture as a tool of Prosperity, which contributes to the creation of favourable conditions for socio-economic development. It argues that such an approach must necessarily be people-centred and attentive to ownership and inclusivity, especially when dealing with culture, understood as a process and product of human expression. To promote culture in development involves prioritizing people’s meanings, goals, tools and, more broadly, societies’ right to self-determination and to establishing their own development priorities. An attention to culture and cultural diversity in development favors a process in which multiple parties come together and leverage their respective tools to achieve shared and more sustainable results. An array of projects carried out by AICS in the Region focused on in this volume, exemplify how, from a methodological and operational standpoint, Italian actions are designed to generate economic activity and participation for and through culture, placing people at the center.
The Italian Agency for Development Cooperation in Lebanon
Authors: Calia Maria Luigia , Piermattei Alessandra
Published: August 2024

The actions presented by AICS Beirut add to the largely positive impact that the Italian Cooperation has had in safeguarding the cultural and natural heritage in the fragile context of Lebanon. These Italian actions are implemented within the Cultural Heritage and Urban Development Program (CHUD), launched in Lebanon as a driver for development and for bolstering national and international tourism. The Cooperation’s activities contribute to the mitigation of heritage degradation risks, while at the same time supporting the upskilling of a large number of local professionals, trained to intervene effectively in securing and preserving Lebanese cultural heritage. In committing to the preservation and valorisation of Lebanese cultural and natural heritage, there is no escaping the structural problems of the monuments, cleaning parts that need curative activities, conserving architectural and decorative elements, consolidating the structures, and making the sites accessible to the local population and visitors. The actions are tailored to the specific goal of enhancing cultural tourism, which is a major source of income in Lebanon, and provides many job opportunities, revitalizing local economies. At the same time, a significant effort has been made to forge a connection between community and territory, in order to increase a sense of belonging, by planning both information days and workshops.
Site Risk Assessment Methods in Archaeological Built Environments: The Case Study of Shobak Castle in Jordan
Authors: Nucciotti Michele , Bala’awi Fadi , Sassu Mauro , Puppio Mario Lucio , Candido Fabio
Published: August 2024

A methodology for risk assessment has been developed, considering the main features of the archaeological site of Shobak Castle within the framework of AICS activities in Jordan. The site, as of the survey date, being an archaeological built environment, exhibits characteristics of a deteriorated urban setting with multiple needs and criticalities. Some areas have been subjected to archaeological excavation, temporary construction works, and subsequent surveys. To plan the rehabilitation works to be carried out by the University of Florence and to establish priorities for long-term management by the Department of Antiquities of Jordan, a comprehensive analysis of the entire Shobak Castle site was conducted. This analysis assessed different levels of risk, both for people and buildings, in accordance with the principles outlined in the Italian Consolidated Act on Safety (Legislative Decree no. 81 of April 9, 2008, and subsequent amendments). The results of this work, which have been documented in various worksheets, are summarized in the risk matrix and a series of safety maps presented herein.
Heritage, Development, Community: Methodological Reflections on Research-Action Experiences
Authors: Loda Mirella
Published: August 2024

This paper discusses the need for interventions by heritage protection experts to interrelate with the social and economic dynamics of the local society. In so doing, the paper stresses the urgency for approaches fit for addressing the complexity of the continuously evolving local systems, and for ensuring community empowerment. Also examined is the effectiveness of technical interventions that are preceded and accompanied by extensive socio-anthropological research into the specific context. Examples are given that show the variety of methods that can be used for this kind of research, and which also proved effective tools for participatory practices.
Cultural Landscape in the Bamiyan Strategic Masterplan 2018
Authors: Loda Mirella , Di Benedetto Gaetano
Published: August 2024

The paper deals with the approach taken for the protection of the cultural landscape in the Bamiyan Strategic Masterplan. It starts by illustrating the evolution of the concept of cultural landscape in the UNESCO documents and the difficulty faced in implementing the Bamiyan Cultural Master Plan (BCMP) of 2004–13. It goes on to describe the measures contained in the Bamiyan Strategic Masterplan (BSMP) of 2018 that are specifically aimed at safeguarding the landscape. Special focus is placed on avoiding population and settlement increases on the valley floor and the bypass road cutting across the valley floor.
Trapped-Ion Quantum Computing
Authors: Frisch Albert , Erhard Alexander , Feldker Thomas , Girtler Florian , Hettrich Max , Huss Wilfried , Jacob Georg , Maier Christine , Mayramhof Gregor , Nigg Daniel , Sommer Christian , Ulmanis Juris , Wodey Etienne , Zangerl Mederika , Monz Thomas
Published: August 2024

The future of quantum information processing requires a stable hardware platform to execute quantum circuits reliably and with low error rates, such that solutions for industrial applications can be built on top of it. Trapped-ion quantum computing, among other platforms, currently proves to be very suitable for the transition from tabletop, lab-based experiments to rack-mounted, on-premise systems which allow operation in data center environments. Several technical challenges need to be solved and controlling many degrees of freedom needs to be optimized and automated, before industrial applications can be successfully implemented on quantum computers situated within data centers. These necessary developments range from the architecture of an ion trap that fundamentally defines the supported instruction sets, over the control electronics and laser systems, which limit the quality of qubit operations, to the optimized compilation of quantum circuits based on qubit properties and gate fidelities. In this chapter, we give an introduction to the ion-trap quantum computing platform, present the current technical state of the art of Alpine Quantum Technologies’ ion-trapping hardware and rack-based quantum computing systems, and highlight parts of the execution stack.
Quantum Software Engineering Issues and Challenges: Insights from Practitioners
Authors: De Stefano Manuel , Pecorelli Fabiano , Palomba Fabio , Taibi Davide , Di Nucci Dario , De Lucia Andrea
Published: August 2024

Quantum computing is an emerging field in which theoretical principles are being transformed into practical applications, largely due to the efforts of the developer community. In order to ensure that quantum software engineering continues to advance, it is vital to understand the experiences, challenges, and aspirations of developers. This chapter is a continuation of our previous work, which provided a comprehensive survey exploring the adoption patterns and common challenges in quantum software engineering. In addition to the survey, we conducted in-depth, semi-structured interviews with practitioners in the field to gain a deeper and more detailed understanding of their perspectives. Through the interviews and survey findings, we have gained nuanced insights into the motivations, hurdles, and outlook of developers toward the rapidly evolving quantum computing landscape. We describe the research methodology in detail, including the tools and techniques used, in order to provide a comprehensive understanding of the research process. Furthermore, we present critical insights from both the survey and interviews, enriching the narrative with fresh perspectives obtained from the post-publication interviews. This chapter is a blend of academic investigation and real-world practitioner insights, aiming to provide a comprehensive understanding of the current state of quantum software engineering. By illuminating the path for future research and development in this dynamic field, we hope to guide the way toward continued progress and innovation.
Verification and Validation of Quantum Software
Authors: Fortunato Daniel , Jiménez-Navajas Luis , Campos José , Abreu Rui
Published: August 2024

Quantum software—like classic software—needs to be designed, specified, developed, and, most importantly, tested by developers. Writing tests is a complex, error-prone, and time-consuming task. Due to the particular properties of quantum physics (e.g., superposition), quantum software is inherently more complex to develop and effectively test than classical software. Nevertheless, some preliminary works have tried to bring commonly used classical testing practices for quantum computing to assess and improve the quality of quantum programs. In this chapter, we first gather 16 quantum software testing techniques that have been proposed for the IBM quantum framework, Qiskit. Then, whenever possible, we illustrate the usage of each technique (through the proposed tool that implements it, if available) on a given running example. We showcase that although several works have been proposed to ease the burn of testing quantum software, we are still in the early stages of testing in the quantum world. Researchers should focus on delivering artifacts that are usable without much hindrance to the rest of the community, and the development of quantum benchmarks should be a priority to facilitate reproducibility, replicability, and comparison between different testing techniques.
Introduction
Authors: Shen Zhihua
Published: August 2024

From July 5 to 7, 2021, the second “Tsinghua Area Studies Forum” with “Areas of the World and the World in Areas” as its theme, was held by the Institute for International and Area Studies (IIAS) at Tsinghua University in Beijing. One hundred and forty-four scholars from 13 countries and 36 universities and research institutions around the world attended the conference.
The Rise of Power and the Evolution of Human Geography in the Slave Trade in Madagascar
Authors: Xiong Xinghan
Published: August 2024

Being one part of the African slave trade, the slave trade in Madagascar is similar to that of the Transatlantic area. Both are destructive commercial activities that cause population loss and exacerbate social unrest and ethnic conflicts. The Kingdom of Imerina, located at Madagascar’s central plateau, thrived in the destructive slave trade by combining its trade dominance with the cultural system and created a new regime. However, different from the slave trade in most African regions, the rise of the Imerina dynasty did not lead to a shift of political and economic center to the coastal area but took on an inland-centered pattern. A comparison between the slave trade in Madagascar and the transatlantic area shows that the human-geographical patterns formed by the slave trade have their own unique historical and geographical attributes, and conclusively justify that the slave trade does not necessarily lead to preferential development of coastal areas.
ACAD10 and ACAD11 allow entry of 4-hydroxy fatty acids into β-oxidation
Authors: Paquay Stéphanie , Duraffourd Julia , Bury Marina , Heremans Isaac P. , Caligiore Francesco , Gerin Isabelle , Stroobant Vincent , Jacobs Jean , Pinon Aymeric , Graff Julie , Vertommen Didier , Van Schaftingen Emile , Dewulf Joseph P. , Bommer Guido T.
Published: August 2024

Hydroxylated fatty acids are important intermediates in lipid metabolism and signaling. Surprisingly, the metabolism of 4-hydroxy fatty acids remains largely unexplored. We found that both ACAD10 and ACAD11 unite two enzymatic activities to introduce these metabolites into mitochondrial and peroxisomal β-oxidation, respectively. First, they phosphorylate 4-hydroxyacyl-CoAs via a kinase domain, followed by an elimination of the phosphate to form enoyl-CoAs catalyzed by an acyl-CoA dehydrogenase (ACAD) domain. Studies in knockout cell lines revealed that ACAD10 preferentially metabolizes shorter chain 4-hydroxy fatty acids than ACAD11 (i.e. 6 carbons versus 10 carbons). Yet, recombinant proteins showed comparable activity on the corresponding 4-hydroxyacyl-CoAs. This suggests that the localization of ACAD10 and ACAD11 to mitochondria and peroxisomes, respectively, might influence their physiological substrate spectrum. Interestingly, we observed that ACAD10 is cleaved internally during its maturation generating a C-terminal part consisting of the ACAD domain, and an N-terminal part comprising the kinase domain and a haloacid dehalogenase (HAD) domain. HAD domains often exhibit phosphatase activity, but negligible activity was observed in the case of ACAD10. Yet, inactivation of a presumptive key residue in this domain significantly increased the kinase activity, suggesting that this domain might have acquired a regulatory function to prevent accumulation of the phospho-hydroxyacyl-CoA intermediate. Taken together, our work reveals that 4-hydroxy fatty acids enter mitochondrial and peroxisomal fatty acid β-oxidation via two enzymes with an overlapping substrate repertoire.
The DERIVO 2 Heal Embolization Device in the Treatment of Ruptured and Unruptured Intracranial Aneurysms: a Retrospective Multicenter Study
Authors: Schwab Roland , Kabbasch Christoph , Goertz Lukas , Kaschner Marius , Weiss Daniel , Loehr Christian , Wensing Hauke , Bester Maxim , Simgen Andreas , Kemmling André , Wendl Christina , Fuchs Erelle , Thormann Maximilian , Behme Daniel , Nordmeyer Hannes
Published: August 2024

Backround

The use of flow diverting stents in the treatment of intracranial aneurysms is associated with a risk of neurological morbidity due to their thrombogenicity. To reduce this risk different surface modifications have been developed. The Derivo 2 Embolization Device (Acandis, Pforzheim, Germany) has proven to be a safe and effective flow diverter. To overcome the risk of thrombo-embolism, the device was modified by adding an anti-thrombogenic fibrin-heparin coating. We aimed to assess the safety and effectiveness of the Derivo 2 heal Embolization Device.

Methods

Retrospective multicenter data from nine German neurovascular centers between February 2022 until December 2023 were used. Patients treated with the Derivo 2 heal Embolization Device for unruptured or ruptured intracranial aneurysms were included. Peri- and postprocedural adverse events, clinical outcomes, and angiographic follow-up results were evaluated.

Results

84 patients (73.8% female; mean age 58.7 years) with 89 aneurysms (mean size 9.8 mm) were included. 87.6% were located in the anterior circulation. Most of them were sidewall aneurysms (88.8%). 96 flow diverters were used. 99.0% were successfully implanted. An in-stent balloon angioplasty was performed in 6.0% of the cases. An additional coiling was performed in 28.6%. Technical difficulties were present in 12.0% of the cases. Thrombotic events occurred in 4.8% with no neurological sequelae. Mortality and morbidity were 0 and 1.2% respectively. Adequate aneurysm occlusion was achieved in 80.7% with a mean follow-up time of 6.6 months.

Conclusion

The Derivo 2 heal Embolization Device showed a satisfying aneurysm occlusion and safety with a low rate of neurological morbidity.
Patienten- und Qualitätsmerkmale bei der Behandlung mit Disulfiram („Antabus“) im deutschsprachigen „Netzwerk alkoholaversive Pharmakotherapie“
Authors: Zimmermann Ulrich S. , Plickert Clemens , Lüdecke Christel , Stuppe Markus , Rosenbeiger Christian , Krisam Yvonne , Link Tobias , Keller Jean , Bühler Gero , Scholz-Hehn Deborah , Havemann-Reinecke Ursula , Wedekind Dirk , Luderer Mathias , Spreer Maik
Published: August 2024

Hintergrund

Seit mehr als 10 Jahren ist Disulfiram in Deutschland nicht mehr zugelassen. Dennoch wird es seitens einer Reihe von Ambulanzen psychiatrischer Fachkliniken sowie niedergelassener Ärzte weiter off-label eingesetzt. Diese haben sich 2018 zum „Netzwerk alkoholaversive Pharmakotherapie“ (NAP) zusammengeschlossen, um die Qualität dieser Behandlungsform aufrechtzuhalten.

Ziel der Arbeit

Beschreibung des gegenwärtigen Behandlungsumfangs, der Patientencharakteristika, der Nebenwirkungen und der begleitenden Therapieangebote der Behandlung mit Disulfiram.

Material und Methoden

Seit 2019 führt das NAP in den beteiligten Zentren jährlich eine retrospektive Erhebung zu oben genannten Parametern durch.

Ergebnisse

Im Zeitraum von 2019 bis 2023 wurden durch 33 Zentren zusammen 1579 Behandlungsfälle erfasst. Bei 152 Patienten wurden insgesamt 241 Trinkereignisse beschrieben, von denen 26 zu stationärer Behandlung ohne Komplikationen oder anhaltende Gesundheitsschäden führten. Häufigste Nebenwirkungen waren in absteigender Reihenfolge Körpergeruch (2,5 %), Müdigkeit, männliche sexuelle Funktionsstörungen, benigner Transaminasenanstieg, allergische Hautreaktionen und Polyneuropathie (0,8 %). Über ein Viertel der Patienten litt komorbid an Depressionen und je ca. 5 % an ADHS, emotional instabilen bzw. anderen Persönlichkeitsstörungen, Traumafolgestörungen sowie Angststörungen. 33 % der Patienten wurden mit Antidepressiva und 12 % mit sedierenden Antipsychotika behandelt. Begleitende Gruppentherapien wurden bei 66 % der Patienten angeboten.

Diskussion

Die Behandlung mit Disulfiram ist legal möglich, allgemein gut verträglich und sicher. Sie wird in den meisten Behandlungszentren als Bestandteil eines Gesamtbehandlungsplanes angeboten, der eine multimodale Behandlung komorbider psychiatrischer Erkrankungen miteinschließt.
Age, period, and cohort trends of substance poisoning, alcohol-related disease, and suicide deaths in Australia, 1980–2019
Authors: Bharat Chrianna , Hopkins Ria E. , Chambers Mark , Degenhardt Louisa , Peacock Amy , Farrell Michael , Yuen Wing See , Man Nicola , Gisev Natasa
Published: August 2024

Purpose

Deaths due to substance poisoning, alcohol-related disease, and suicide pose a critical public health issue, and have been categorized as “deaths of despair” in the US. Whether these deaths represent a distinct phenomenon requires exploration, particularly in other countries.

Methods

This retrospective observational study examines age-period-cohort trends of (combined and cause-specific) substance poisoning, alcohol-related disease, and suicide deaths among Australians aged ≥15-years that occurred between 1980 and 2019 and compares trends between males and females.

Results

Combined mortality rates were initially (1980–1999) relatively stable, reflecting a reduction in alcohol-related disease deaths offset by an increase in substance poisoning deaths. A decline (2000–2006) and subsequent increase (2007–2019) in combined rates were primarily attributable to corresponding changes in both substance poisoning and suicide deaths among males. Distinct age-period-cohort trends were observed between cause of death sub-types, with net drifts: increasing for male (net drift [95% CI]: 3.33 [2.84, 3.83]) and female (2.58 [2.18, 2.98]) substance poisoning deaths; decreasing among male alcohol-related disease (− 1.46 [− 1.75, − 1.16]) and suicide deaths (− 0.52[− 0.69, − 0.36]); and remaining relatively stable for female alcohol-related disease (− 0.28 [− 0.66, 0.09]) and suicide deaths (− 0.25 [− 0.52, 0.01]).

Conclusions

Although combined age-specific trends were relatively stable over the study period, different and distinct patterns were observed within cause-specific deaths, challenging the notion that these causes of death represent a distinct epidemiological phenomenon. These data indicate a critical need to review the appropriateness of guidance for clinical practice, prevention strategies, and policy initiatives aimed at preventing future deaths.
Genotoxicity of selected cannabinoids in human lymphoblastoid TK6 cells
Authors: Kolar Nicol , Bankoglu Ezgi Eyluel , Stopper Helga
Published: August 2024

Natural non-psychoactive cannabinoids such as cannabigerol (CBG), cannabidiol (CBD), cannabichromene (CBC), cannabidivarin (CBDV), and cannabinol (CBN) are increasingly consumed as constituents of dietary products because of the health benefits claims. Cannabinoids may reduce certain types of pain, nausea, and anxiety. Anti-inflammatory and even anti-carcinogenic properties have been discussed. However, there are insufficient data available regarding their potential (geno-)toxic effects. Therefore, we tested CBG, CBD, CBC, CBDV, and CBN for their genotoxic potential and effects on mitosis and cell cycle in human lymphoblastoid TK6 cells. The selected cannabinoids (except CBDV) induced increased micronuclei formation, which was reduced with the addition of a metabolic activation system (S9 mix). CBDV induced micronuclei only after metabolic activation. Mitotic disturbances were observed with all tested cannabinoids, while G1 phase accumulation of cells was observed for CBG, CBD and CBDV. The genotoxic effects occurred at about 1000-fold higher concentrations than are reported as blood levels from human consumption. However, the results clearly indicate a need for further research into the genotoxic effects of cannabinoids. The mechanism of the mitotic disturbance, the shape of the dose–response curves and the possible effects of mixtures of cannabinoids are aspects which need clarification.
Updated analysis of the prescription and evaluation of protein kinase inhibitors for oncology in Germany
Authors: Obst Caecilia S. , Seifert Roland
Published: August 2024

A recent analysis from our group (https://pubmed.ncbi.nlm.nih.gov/37014400/) has shown that the immense costs of the 20 protein kinase inhibitors for oncology approved from 2015 to 2019 are largely caused by drugs whose additional benefit has not been proven. We updated our analysis by adding the newly approved protein kinase inhibitors of the years 2020 and 2021. Based on the 2021 and 2022 Arzneiverordnungsreport (AVR), we expanded our analysis to include a total of nine protein kinase inhibitors newly approved by the European Medicines Agency (EMA) in 2020 and 2021. As a result, 29 protein kinase inhibitors were identified for an update of our analysis. For these 29 drugs, all additional benefit assessments published by the Gemeinsamer Bundesausschuss (GBA) were analyzed. The additional benefit assessments of the GBA were compared with the corresponding assessments of the European Society for Medical Oncology (ESMO), the Deutsche Gesellschaft für Hämatologie und Onkologie (DGHO, German Society for Hematology and Oncology) and the Arzneimittelkommission der deutschen Ärzteschaft (AkdÄ, Drug Commission of the German Medical Association). In addition, a total number of 91 drug advertisements published in the journal Oncology Research and Treatment in 2022 were analyzed. The number of protein kinase inhibitors for which no additional benefit can be found by the GBA is increasing, whereas the number of drugs for which a considerable additional benefit can be found is decreasing. Thus, in the current 2022 (re)assessment of additional benefit by the GBA, no additional benefit was identified for 50% of the drugs (2020, 46%). Nineteen percent were assessed with a minor additional benefit (2020, 18%) and also 19% with a considerable additional benefit (2020, 27%). For 12% of the drugs, the additional benefit could not be quantified by the GBA (2020, 9%). The benefit assessments by other medical societies often differ significantly from those of the GBA, mainly due to different evaluations of various endpoint parameters. In addition, more and more protein kinase inhibitors are being approved as orphan drugs. However, their additional benefit cannot be quantified by the GBA in most cases (78%). In 38% of the advertisements of an oncology journal, protein kinase inhibitors are promoted, which shows the pharmacoeconomic importance of these drugs. In summary, the current additional benefit assessment procedure in Germany is very questionable, and reforms are urgently needed to maintain the stability of the German healthcare system, which is being undermined by the high cost of medicines, particularly for drugs whose additional benefits have not been proven.
Exploring the manganese-dependent interaction between a transcription factor and its corresponding DNA: insights from gas-phase electrophoresis on a nES GEMMA instrument
Authors: Leščić Ašler Ivana , Radman Katarina , Jelić Matošević Zoe , Bertoša Branimir , Weiss Victor U. , Marchetti-Deschmann Martina
Published: August 2024

Manganese ion homeostasis is vital for bacteria and is achieved via manganese-dependent transcription factors. Manganese mediation of transcription factor attachment to the corresponding oligonucleotide sequences can be investigated, e.g. via electrophoretic mobility shift assays (EMSA). Formation of specific biocomplexes leads to differences in the migration pattern upon gel electrophoresis. Focusing on electrophoresis in the gas-phase, applying a nano electrospray gas-phase electrophoretic mobility molecular analyzer (nES GEMMA) also known as nES differential mobility analyzer (nES DMA), and on transcription factors (MntR proteins) from Bacillus subtilis and Mycobacterium tuberculosis, we took interest in the gas-phase electrophoresis of the corresponding biospecific complexes. We compared nES GEMMA, separating analytes in the nanometer regime (a few to several hundred nm in diameter) in the gas-phase in their native state according to particle size, to EMSA data. Indeed we were able to demonstrate manganese-mediated attachment of MntR to target genomic sequences with both analytical techniques. Despite some inherent pitfalls of the nES GEMMA method like analyte/instrument surface interactions, we were able to detect the target complexes. Moreover, we were able to calculate the molecular weight (MW) of the obtained species by application of a correlation function based on nES GEMMA obtained data. As gas-phase electrophoresis also offers the possibility of offline hyphenation to orthogonal analysis techniques, we are confident that nES GEMMA measurements are not just complementary to EMSA, but will offer the possibility of further in-depth characterization of biocomplexes in the future.

Graphical Abstract
Role of allogeneic hematopoietic cell transplantation in VEXAS syndrome
Authors: Dias Ajoy L. , Groarke Emma M. , Hickstein Dennis , Patel Bhavisha
Published: August 2024

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a newly diagnosed syndrome comprising severe systemic inflammatory and hematological manifestations including myelodysplastic syndrome and plasma cell dyscrasia. Since its discovery four years ago, several groups have identified pleomorphic clinical phenotypes, but few effective medical therapies exist which include Janus Kinase (JAK) inhibitors, interleukin inhibitors (IL-1 and IL-6), and hypomethylating agents. Prospective trials are lacking at this time and most patients remain corticosteroid dependent. VEXAS has a high morbidity from frequent life threatening inflammatory symptoms and risk of progression to hematological malignancies and has an overall survival of 50% at 10 years. Allogeneic stem cell transplant (allo-HCT) is a curative option for this disease caused by somatic mutations in the UBA1 gene. Here we outline the role of allo-HCT in treating patients with VEXAS syndrome, highlighting the outcomes from several single-institution studies and case reports. Prospective trials will be required to precisely define the role of allo-HCT in the management of VEXAS syndrome.
Bioimpedance analysis of fat free mass and its subcomponents and relative associations with maximal oxygen consumption in facioscapulohumeral dystrophy
Authors: Crisafulli Oscar , Bottoni Giorgio , Lacetera Jessica , Fassio Federico , Grattarola Luca , Lavaselli Emanuela , Giovanetti Giuseppe , Tupler Rossella , Negro Massimo , D’Antona Giuseppe
Published: August 2024

Purpose

Fat free mass (FFM) is considered the metabolically active component of human body and is positively associated with maximal oxygen uptake (

$${\text{VO}}_{2} {\text{max}}$$

VO
2

max

). However, FFM is composed of metabolically active and inactive subcomponents whose proportion can vary depending on body composition and clinical condition, possibly affecting such association. Although it is known that in facioscapulohumeral dystrophy (FSHD) peculiar changes in body composition occur, it is unclear whether there are alterations in FFM composition and, if so, whether such alterations affect the association towards

$${\text{VO}}_{2} {\text{max}}$$

VO
2

max

compared to healthy subjects (HS).

Methods

To address this issue, 27 FSHD patients (mean age 37.3; 9 female) and 27 sex and age matched HS, underwent an assessment of

$${\text{VO}}_{2} {\text{max}}$$

VO
2

max

by cardiopulmonary exercise tests (CPET) and body composition, with reference to FFM and its subcomponents, by bioimpedance analysis.

Results

In between-groups comparison, patients showed lower amounts of body cell mass (BCM) and intracellular water (ICW) which reflect in lower BCM/FFM ratio and higher extracellular to intracellular water ratio (ECW/ICW). Patients’

$${\text{VO}}_{2} {\text{max}}$$

VO
2

max

was lower than HS and, even if with lower associative values than HS, correlated with FFM and BCM, while BCM/FFM and ECW/ICW ratios associations were observed only in HS.

Conclusion

FSHD patients showed lower amount of BCM and ICW. BCM resulted as the parameter with the highest associative value with VO2max in both groups. Since

$${\text{VO}}_{2} {\text{max}}$$

VO
2

max

is associated with functional ability in dystrophic patients, BCM, rather than FFM, could be an additional body composition-based clinical stratification factor.
Innexin expression and localization in the Drosophila antenna indicate gap junction or hemichannel involvement in antennal chemosensory sensilla
Authors: Prelic Sinisa , Keesey Ian W. , Lavista-Llanos Sofia , Hansson Bill S. , Wicher Dieter
Published: August 2024

Odor detection in insects is largely mediated by structures on antennae called sensilla, which feature a strongly conserved architecture and repertoire of olfactory sensory neurons (OSNs) and various support cell types. In Drosophila, OSNs are tightly apposed to supporting cells, whose connection with neurons and functional roles in odor detection remain unclear. Coupling mechanisms between these neuronal and non-neuronal cell types have been suggested based on morphological observations, concomitant physiological activity during odor stimulation, and known interactions that occur in other chemosensory systems. For instance, it is not known whether cell–cell coupling via gap junctions between OSNs and neighboring cells exists, or whether hemichannels interconnect cellular and extracellular sensillum compartments. Here, we show that innexins, which form hemichannels and gap junctions in invertebrates, are abundantly expressed in adult drosophilid antennae. By surveying antennal transcriptomes and performing various immunohistochemical stainings in antennal tissues, we discover innexin-specific patterns of expression and localization, with a majority of innexins strongly localizing to glial and non-neuronal cells, likely support and epithelial cells. Finally, by injecting gap junction-permeable dye into a pre-identified sensillum, we observe no dye coupling between neuronal and non-neuronal cells. Together with evidence of non-neuronal innexin localization, we conclude that innexins likely do not conjoin neurons to support cells, but that junctions and hemichannels may instead couple support cells among each other or to their shared sensillum lymph to achieve synchronous activity. We discuss how coupling of sensillum microenvironments or compartments may potentially contribute to facilitate chemosensory functions of odor sensing and sensillum homeostasis.
Lymph node ratio prognosticates overall survival in patients with stage IV colorectal cancer
Authors: Naidu K. , Chapuis P. H. , Connell L. , Chan C. , Rickard M. J. F. X. , Ng K-S.
Published: August 2024

Background

Lymph node ratio (LNR) is suggested to address the shortcomings of using only lymph node yield (LNY) or status in colorectal cancer (CRC) prognosis. This study explores how LNR affects survival in patients with metastatic colorectal cancer (mCRC), seeking to provide clearer insights into its application.

Methods

This observational cohort study investigated stage IV patients with CRC (1995–2021) who underwent an upfront resection of their primary tumour at Concord Hospital, Sydney. Clinicopathological data were extracted from a prospective database, and LNR was calculated both continuously and dichotomously (LNR of 0 and LNR > 0). The primary endpoint was overall survival (OS). The associations between LNR and various clinicopathological variables were tested using regression analyses. Kaplan–Meier and Cox regression analyses estimated OS in univariate and multivariate survival models.

Results

A total of 464 patients who underwent a primary CRC resection with clear margins (mean age 68.1 years [SD 13.4]; 58.0% M; colon cancer [n = 339,73.1%]) had AJCC stage IV disease. The median LNR was 0.18 (IQR 0.05–0.42) for colon cancer (CC) resections and 0.21 (IQR 0.09–0.47) for rectal cancer (RC) resections. A total of 84 patients had an LNR = 0 (CC = 66 patients; RC = 18 patients). The 5-year OS for the CC cohort was 10.5% (95% CI 8.7–12.3) and 11.5% (95% CI 8.4–14.6) for RC. Increasing LNR demonstrated a decline in OS in both CC (P < 0.001) and RC (P < 0.001). In patients with non-lymphatic dissemination only (LNR = 0 or N0 status), there was better survival compared with those with lymphatic spread (CC aHR1.50 [1.08–2.07;P = 0.02], RC aHR 2.21 [1.16–4.24;P = 0.02]).

Conclusions

LNR is worthy of consideration in patients with mCRC. An LNR of 0 indicates patients have a better prognosis, underscoring the need for adequate lymphadenectomy to facilitate precise mCRC staging.
Current status and future perspectives of contrast-enhanced ultrasound diagnosis of breast lesions
Authors: Ito Toshikazu , Manabe Hironobu , Kubota Michiyo , Komoike Yoshifumi
Published: August 2024

Advances in various imaging modalities for breast lesions have improved diagnostic capabilities not only for tumors but also for non-tumorous lesions. Contrast-enhanced ultrasound (CEUS) plays a crucial role not only in the differential diagnosis of breast lesions, identification of sentinel lymph nodes, and diagnosis of lymph node metastasis but also in assessing the therapeutic effects of neoadjuvant chemotherapy (NAC). In CEUS, two image interpretation approaches, i.e., qualitative analysis and quantitative analysis, are employed and applied in various clinical settings. In this paper, we review CEUS for breast lesions, including its various applications.
Sick of Leading? Supervisory Responsibility and Its Consequences for Sickness Absenteeism and Sickness Presenteeism
Authors: Funk Stephanie
Published: August 2024

This research examines the impact of leadership positions with supervisory responsibility on two labor-market related health behaviors—sickness absenteeism and sickness presenteeism, i.e., working while being sick. Drawing on the job demands-resources (JD-R) model, this study posits that supervisory responsibility, serving as both a job resource and a demand, reduces sickness absenteeism while concurrently increasing sickness presenteeism behavior. The study identifies permanent availability and time pressure as two key aspects of leadership positions with supervisory responsibility that mediate these relationships. Using German-linked employer-employee data, the empirical results suggested that having supervisory responsibility reduces sickness absenteeism while at the same time elevating the engagement in sickness presenteeism. Furthermore, these relationships are partially mediated by leaders’ need for permanent availability and the time pressure inherent in positions with supervisory responsibility. This research advances our understanding of job characteristics of leadership positions by illustrating that job demands can yield favorable outcomes, offering valuable insights into the complex interplay between leadership positions and leaders’ health behaviors.
Central bank independence, income inequality and poverty: What do the data say?
Authors: Sturm Jan-Egbert , Bodea Cristina , de Haan Jakob , Hicks Raymond
Published: August 2024

This paper examines whether the independence of central banks is related to income inequality and poverty. Following the 2008 financial crisis, independent central banks have been criticized that their actions contribute to an unequal income distribution. Yet, the case can also be made that such independence is orthogonal to income inequality or can even help mitigate it. As proxies for inequality, we employ five-year averages of the Gini coefficient and the poverty gap. Our database consists of a large set of countries, covering a long period. Our fixed effects panel estimates suggest that—despite many claims to the contrary—there is neither a robust relationship between central bank independence and the Gini coefficient nor between independence and the poverty gap. Several robustness checks (using alternative proxies for income inequality and central bank independence, interaction effects, quantile and cross-section regressions) confirm our finding.
Synergistic Anti-Dermatophytic Potential of Nanoparticles and Essential Oils Combinations
Authors: Sayed Mohsen A. , Ghazy Nahla. M. , El-Bassuony Asmaa A. H.
Published: August 2024

Conventional antifungal therapies becoming less effective in treating dermatophytic infections. For this reason, researchers are looking for alternative treatments. The current research has tested the antifungal efficacy of eight novel synthesized metallic nanoparticle compounds: Ag0.49Cr2.51O4, Ag0.99Fe1.01O3, CoLa0.019Fe1.981O4, Co0.99Fe1.99O4, Ag0.99Cr1.01O2, Ca0.99Fe1.99O4, CoBi0.019Fe1.981O4, and Cu0.99Fe1.99O4 were synthesized by a flash auto-combustion reaction to evaluate synergistic potential of the Np’s exhibited antifungal activity in combination with Cinnamon, clove, lemongrass, tea tree and thyme essential oils extracted by soxhlet method against Microsporum canis, Trichophyton tonsurans, T. violaceum, T. verrucosum, and Epidermophyton floccosum. Four nanoparticle compounds exhibited antifungal activity which were: Ag0.49Cr2.51O4, Ag0.99Fe1.01O3, CoLa0.019Fe1.981O4, and Co0.99Fe1.99O4 against all tested dermatophytes. Maximum inhibition was recorded in the cases of Ag0.99Fe1.01O3, Ag0.99Fe1.01O3 + cinnamon against M.canis. Least minimum inhibitory concentrations were attained by Cinnamon against M. canis, Ag0.99Fe1.01O3 against M.canis, T. tonsurans, and T.violaceum, Ag0.99Fe1.01O3+Cinnamon against M. canis, T. violaceum and, T. verrucosum, Ag0.99Fe1.01O3 + Clove, and Ag0.99Fe1.01O3 + Lemongrass against M. canis. The study showed promising results regarding the synergistic antifungal efficacy of nanoparticle compounds combined with essential oils in the cases of Ag0.99Fe1.01O3 with cinnamon, Ag0.99Fe1.01O3 with clove and Ag0.99Fe1.01O3 with lemon grass against all tested dermatophytes.
Wood-derived biochar as a matrix for cost-effective and high-performing composite thermal energy storage materials
Authors: Kouchachvili Lia , Gagnon-Caya Guillaume , Djebbar Reda
Published: August 2024

High energy storage density, affordability, and environmental friendliness are the key requirements for materials used in thermal energy storage systems. A new composite thermal energy storage material (TESM) with all these requirements was fabricated by utilizing a biochar matrix. Biochar was derived from the slow pyrolysis of forestry residues, an abundant source of underutilized biomass in Canada. The results of this experimental study indicate that the carbonization conditions of the biomass affect the structure and surface morphology of the biochar and consequently its thermal properties. Amongst the carbonization conditions that were investigated in this study, a peak temperature of 800 °C with a heating rate of 2.5 °C/min yielded a biochar with an energy storage capacity of 508 J/g. This biochar was then used as a matrix for fabricating the composite TESM with salt hydrate. The composite showed high thermal stability after ten hydration/dehydration cycles with an average thermal energy storage capacity of 3795 J/g. The cost of thermal energy storage in this composite was found to be $0.50 CAD /kWhth.
Mourre theory and spectral analysis of energy-momentum operators in relativistic quantum field theory
Authors: Kruse Janik
Published: August 2024

A central task of theoretical physics is to analyse spectral properties of quantum mechanical observables. In this endeavour, Mourre’s conjugate operator method emerged as an effective tool in the spectral theory of Schrödinger operators. This paper introduces a novel class of examples from relativistic quantum field theory that are amenable to Mourre’s method. By assuming Lorentz covariance and the spectrum condition, we derive a limiting absorption principle for the energy-momentum operators and provide new proofs of the absolute continuity of the energy-momentum spectra. Moreover, under the assumption of dilation covariance, we show that the spectrum of the relativistic mass operator is purely absolutely continuous in$$(0,\infty )$$(0,∞).
Anticausatives in transitive guise
Authors: Schäfer Florian
Published: August 2024

This article discusses verbs of change that allow a formally transitive construal that, nevertheless, has anticausative semantics. Verbs forming such “transitive anticausatives” (e.g., The water raised its temperature) also form canonical anticausatives (cf. The temperature of the water rose). Such verbs differ from verbs that only form canonical anticausatives (cf. The water warmed) in that they do not lexicalize a fixed scale along which they measure change, so that the DP merged in the internal argument position of these verbs (a DP denoting a property concept like the temperature) can determine the actual scale of change. When these verbs form canonical anticausatives, the entity undergoing change along this scale is realized as the possessor of this internal argument DP. When these verbs form transitive anticausatives, the entity undergoing the change is realized in the verb’s canonical external argument position, where it is, however, not assigned any external argument role. Instead, as in the canonical anticausative variant, it is interpreted as the possessor of the internal argument DP. This possessive relation is overtly reflected in English and other languages where the subject of the transitive anticausative construal binds a possessive pronoun in the internal argument DP. After an illustration of the phenomenon in typologically different languages, the article lays out the above semantic properties of the transitive anticausative construal and the verbs occurring in it. It then subsumes transitive anticausatives under the theory of the causative alternation in Alexiadou et al. (2006, 2015) and Schäfer (2008). Particular attention is, thereby, given to the morphological marking that sets apart, in many languages, the lexical causative and the anticausative variant of (a subset of) alternating verbs (cf. English raise/rise). Transitive anticausatives show a theoretically challenging but informative behavior here. Even though the transitive anticausative construal expresses anticausative semantics, its verb necessarily features the morphological marking that is canonically associated with its lexical causative use. This suggests that the morphological difference often found between pairs of lexical causative and anticausative verbs is only indirectly related to causative and anticausative semantics but is ultimately determined by more abstract, syntactic properties.