bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of deep and ovarian endometriosis in women attending a general gynecology clinic: prospective cohort study
Authors: Chaggar P. , Tellum T. , Thanatsis N. , De Braud L. V. , Setty T. , Jurkovic D.
Published: February 2023

Objectives

To assess using transvaginal ultrasound the prevalence of deep and ovarian endometriosis in premenopausal women attending a general gynecology clinic. We also investigated whether the presence of endometriosis was associated with various demographic factors and other pelvic abnormalities.

Methods

This was a prospective observational cohort study carried out between February 2019 and October 2020. Consecutive premenopausal women who attended our general gynecology clinic underwent pelvic ultrasound examination, performed by a single experienced operator. Pregnant women and those with a history of hysterectomy or oophorectomy were excluded. The primary outcome was the prevalence of deep and/or ovarian endometriosis. Secondary outcomes were the anatomical distribution of endometriotic lesions and the association of endometriosis with demographic characteristics and various pelvic abnormalities, which were analyzed using logistic regression and multivariable analysis.

Results

A total of 1026 women were included in the final study sample, of whom 194 (18.9% (95% CI, 16.6–21.4%)) had sonographic evidence of deep and/or ovarian endometriosis. Of the 194 women diagnosed with endometriosis, 106 (54.6% (95% CI, 47.4–61.8%)) were diagnosed with endometriotic nodules only, 26 (13.4% (95% CI, 9.0–19.0%)) with ovarian endometriomas only, and 62 (32.0% (95% CI, 25.5–39.0%)) women had evidence of both. There was a total of 348 endometriotic nodules in 168 women, located most frequently in the retrocervical area (166/348; 47.7% (95% CI, 42.4–53.1%)), uterosacral ligaments (96/348; 27.6% (95% CI, 23.0–32.6%)) and bowel (40/348; 11.5% (95% CI, 8.3–15.3%)). Multivariable analysis found significant positive associations between endometriosis and both adenomyosis (odds ratio (OR), 1.72 (95% CI, 1.10–2.69); P = 0.02) and pelvic adhesions (OR, 25.7 (95% CI, 16.7–39.3); P < 0.001), whilst higher parity (OR, 0.44 (95% CI, 0.24–0.81); P = 0.03) and history of Cesarean section (OR, 0.18 (95% CI, 0.06–0.52); P = 0.002) were associated with a lower occurrence of endometriosis. A total of 75/1026 women (7.3% (95% CI, 5.8–9.1%)) underwent laparoscopy within 6 months of pelvic ultrasound examination. There was very good agreement between ultrasound and surgical findings, with a kappa value of 0.84 (95% CI, 0.69–0.99).

Conclusions

Deep and/or ovarian endometriosis was present in nearly one in five women attending a general gynecology clinic. There were significant positive associations with adenomyosis and pelvic adhesions and negative associations with higher parity and previous Cesarean section. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Clinical utility of expanded non‐invasive prenatal screening compared with chromosomal microarray analysis in over 8000 pregnancies without major structural anomaly
Authors: Maya I. , Salzer Sheelo L. , Brabbing‐Goldstein D. , Matar R. , Kahana S. , Agmon‐Fishman I. , Klein C. , Gurevitch M. , Basel‐Salmon L. , Sagi‐Dain L.
Published: February 2023

Objectives

To evaluate the theoretical added value of two types of non‐invasive prenatal screening (NIPS) expansions in pregnancies without major structural anomalies over the commonly used NIPS for chromosomes 13, 18, 21, X and Y (5‐NIPS) and to compare them with the added value of chromosomal microarray analysis (CMA).

Methods

This was a retrospective cohort study based on CMA results of all pregnancies with normal ultrasound (including pregnancies with soft markers and with abnormal maternal serum screening) that had undergone amniocentesis between January 2013 to February 2022 and were registered in the database of the Rabin Medical Center genetic laboratory. We calculated the theoretical yield of 5‐NIPS and compared the added value of expanded 5‐NIPS for common microdeletions (1p36.3–1p36.2, 4p16.3–4p16.2, 5p15.3–5p15.1, 15q11.2–15q13.1 and 22q11.2) and genome‐wide NIPS (including variants > 5 Mb) with the added value of CMA in the overall cohort and in subgroups according to indication for invasive testing.

Results

Among the 8605 examined pregnancies, 122 (1.4%) clinically significant CMA results were demonstrated. Of these, 44 (36.1%) were theoretically detectable on 5‐NIPS, with the rates of 1.56% in 642 pregnancies with abnormal maternal serum screening, 0.63% in 318 pregnancies with soft markers, 0.62% in 4378 women with advanced maternal age (≥ 35 years) and 0.15% in 3267 women younger than 35 years. In addition to aneuploidies detectable on 5‐NIPS, three (0.03%) cases detectable on 5‐NIPS expanded for common microdeletions and nine (0.10%) cases detectable on genome‐wide NIPS (excluding common microdeletions) were identified in the overall cohort. The added value of expanded NIPS tools over 5‐NIPS was significantly lower compared with that of CMA, for the overall cohort and subgroups.

Conclusions

5‐NIPS and even genome‐wide NIPS would miss 63.9% and 54.1% of clinically significant CMA findings, respectively. The added value of 5‐NIPS expanded to detect common microdeletions over 5‐NIPS is about 0.035%, and the overall added value of genome‐wide NIPS aimed at large CNVs is about 0.14%, both much lower compared with the added value of CMA (0.91%). These findings should assist healthcare practitioners in guiding couples towards informed decision‐making regarding the choice between prenatal invasive testing and NIPS. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
Don't use it? Don't lose it! Why active use is not required for stimuli, resources or “enrichments” to have welfare value
Authors: Decker Samuel , Lavery J. Michelle , Mason Georgia J.
Published: February 2023

Current frameworks for designing and evaluating good enclosures and “enrichments” typically focus on animals' active interactions with these features. This has undoubtedly improved the welfare of zoo‐housed animals over the last 30 years or more. However, literature reviews from this same period identify persistent gaps in how such frameworks are applied: experiences and behaviors that do not rely on active interaction with stimuli or resources are largely ignored, when evaluating the welfare value of enclosures and enrichments within them. Here, we review research evidence demonstrating that active interaction is not always a reliable measure of welfare value, showing that items that elicit little or no interaction can nevertheless still reduce stress and improve well‐being. This evidence largely comes from research on humans, lab animals and farm animals, but also from some zoo studies too. We then investigate why. We review psychology and ethology literatures to show that such welfare benefits can arise from five, non‐mutually exclusive, processes or mechanisms that are well‐understood in humans and domestic animals: (1) some motivations are sated quickly by interaction with resources, yet still have large welfare benefits; (2) active interaction may just be a way to achieve a goal or solve a problem, without being beneficial for welfare in itself; (3) having opportunities for choice and control may be inherently beneficial, even when not acted on; (4) some enclosure features meet social needs for structure, landmarks, and blocked sightlines; and (5) some stimuli may be preferred because they signaled good environments to an animal's ancestors. We use this information to identify  improved ways of enhancing and assessing zoo animal welfare. Incorporating these concepts should expand the scope of behaviors and subjective experiences that are targeted, to now include those that involve little active interaction and yet still are important for good welfare.
Conclusions. Causality Between Plurality and Unity
Authors: Damonte Alessia , Negri Fedra
Published: February 2023

The previous chapters convey the image of causal analysis in public policy and beyond as a fragmented field where research communities seldom learn from each other’s findings. This chapter resumes the ontological, epistemological, and methodological evidence that causal analysis is characterized by a plurality of objects and “incommensurable” interpretations. It also argues that the same evidence pinpoints how this plurality is complementary at every level, and causal structures raise as the elements that link ontology and methodology and can organize heterogeneous findings to improve learning across accounts.
Getting the Most Out of Surveys: Multilevel Regression and Poststratification
Authors: Ornstein Joseph T.
Published: February 2023

Good causal inference requires good measurement; even the most thoughtfully designed research can be derailed by noisy data. Because policy scholars are often interested in public opinion as a key dependent or independent variable, paying careful attention to the sources of measurement error from surveys is an essential step toward detecting causation. This chapter introduces multilevel regression and poststratification (MRP), a method for adjusting public opinion estimates to account for observed imbalances between the survey sample and population of interest. It covers the history of MRP, recent advances, an example analysis with code, and concludes with a discussion of best practices and limitations of the approach.
Pathway Analysis, Causal Mediation, and the Identification of Causal Mechanisms
Authors: Röth Leonce
Published: February 2023

This chapter presents the systematic analysis of causal mechanisms from the perspective of pathway analysis as an essential complement to conventional approaches to causation. It builds on the evidence that credible causal identification defies design-based strategies such as randomization or linear mediation analysis unless their research designs are supported by reliable mechanistic knowledge. The chapter reasons that the reliable causal identification of a mechanism requires the concept of ‘natural indirect effect’ and a double-nested counterfactual strategy. It discusses the empirical quantification of causal mechanisms and its underlying assumptions, offers empirical examples that clarify them, and reviews the conditions and limits of the strategy.
Testing Joint Sufficiency Twice: Explanatory Qualitative Comparative Analysis
Authors: Damonte Alessia
Published: February 2023

Standard Qualitative Comparative Analysis (QCA) applies an eliminative cross-case algorithm to identify which combinations of factors are logically associated with an outcome in a population. As such, it suits the purpose of pinpointing the conditions under which an outcome occurs or fails. However, the explanatory import of its findings only follows if the algorithm identifies theoretically interpretable, logically valid, and empirically plausible causal compounds.

The chapter provides an essential guide to designing an explanatory QCA that meets the three credibility requirements at once. Section 7.2 addresses how to develop starting hypotheses consistent with the assumptions of complex causation to preserve theoretical interpretability. Section 7.3 introduces the Boolean algebra required to model a hypothesis and find which part supports the explanatory claim in the cases at hand. Section 7.4 addresses the issue of gauging conditions to ensure the empirical plausibility of the analysis. Last, Sect. 7.5 summarizes the protocol, illustrated by the replicable example in the online R file.
Exploring Interventions on Social Outcomes with In Silico, Agent-Based Experiments
Authors: Squazzoni Flaminio , Bianchi Federico
Published: February 2023

Agent-Based Modeling (ABM) is a computational method used to examine social outcomes emerging from interaction between heterogeneous agents by computer simulation. It can be used to understand the effect of initial conditions on complex outcomes by exploring fine-grained (multiple-scale, spatial/temporal) observations on the aggregate consequences of agent interaction. By performing in silico experimental tests on policy interventions where ex ante predictions of outcomes are difficult, it can also reduce costs, explore assumptions and boundary conditions, as well as overcome ethical constraints associated with the use of randomized controlled trials in behavioral policy. Here, we introduce the essential elements of ABM and present two simple examples where we assess the hypothetical impact of certain policy interventions while considering different possible reactions of individuals involved in the context. Although highly abstract, these examples suggest that ABM can be either a complement or an alternative to behavioral policy methods, especially when understanding social processes and exploring direct and indirect effects of interventions are important. Prospects and critical problems of these in silico policy experiments are then discussed.
Migration and (De)Securitisation Dynamics at the Local Level: Discourses and Practices in South Tyrol
Authors: Carlà Andrea
Published: February 2023

In the past decades, South Tyrol, an Italian autonomous province with a German- and Ladin-speaking population and a power-sharing system to protect their cultural features, has witnessed the arrival of many migrants from foreign countries. In addition, as result of the increase in the refugee flows in recent years, thousands of asylum-seekers have passed through and settled in the province. Situated within the ‘local turn’ in migration studies and in the interplay between the fields of migration and security studies, this chapter analyses processes of (de)securitisation vis-à-vis migration in South Tyrol. Adopting the Copenhagen School’s understanding of securitisation as a speech act in combination with a sociological variant that highlights the role of practices, the chapter reveals how, to what extent and in what terms (de)securitisation dynamics have unfolded in South Tyrol regarding the settlement of migrant communities and recent refugee flows. I use a qualitative methodology that looks at discourses and practices as they have emerged in party programmes, political speeches, policy and legal documents. In this way, the chapter will offer a genealogy of (de)securitising discourses and practices at the substate level, revealing the anxieties and problems of dealing with migration when the arrival of migrants meets the presence of old minorities.
Migration Strategies at the Time of a Crisis: Asylum Applicants in Finland
Authors: Virkkunen Joni , Koikkalainen Saara , Piipponen Minna
Published: February 2023

During the 2015-2016 ‘migration crisis’ in Europe, more than 38.000 asylum seekers found their way to Finland by travelling through South and Central Europe and from Russia through the Arctic route. In this chapter, we examine the ‘migration crisis’ as a combination of different forms of crises. We focus on the perspective of the asylum applicants: In which ways do ‘crises’ function as drivers of migration for the people on the move? The analysis is based on two sets of qualitative data collected: 18 official asylum application protocols of Syrian migrants who came to Finland through Northern Russia and so-called the Arctic route and 25 interviews with Iraqi asylum seekers. We argue that the possibilities to settle in, and build a home and sentiments of belonging are dependent on the ability to feel secure in one’s everyday life, trust the system and be able to see a future in that place. The failure of this manifests as two types of crises in the lives of our informants: a crisis of trust, and a personal ontological crisis of existence.
Words to describe a black hole
Authors: Chang Chi-Ming , Lin Ying-Hsuan
Published: February 2023

Abstract

We revamp the constructive enumeration of 1/16-BPS states in the maximally supersymmetric Yang-Mills in four dimensions, and search for ones that are not of multi-graviton form. A handful of such states are found for gauge group SU(2) at relatively high energies, resolving a decade-old enigma. Along the way, we clarify various subtleties in the literature, and prove a non-renormalization theorem about the exactness of the cohomological enumeration in perturbation theory. We point out a giant-graviton-like feature in our results, and envision that a deep analysis of our data will elucidate the fundamental properties of black hole microstates.
Screening a small hydrazide-hydrazone combinatorial library for targeting the STAT3 in monocyte-macrophages with insulated reporter transposons
Authors: Mossine Valeri V. , Kelley Steven P. , Waters James K. , Mawhinney Thomas P.
Published: February 2023

The Signal Transducer and Activator of Transcription 3 (STAT3) pharmacological targeting is regarded as a prospective approach to treat cancer, autoimmune disorders, or inflammatory diseases. We have developed a series of reporters of the STAT3, NF-κB, Nrf2, metal-responsive transcription factor-1 (MTF-1), and hypoxia-inducible factor 1α (HIF-1α) transcriptional activation in human monocyte-macrophage line THP-1. The reporter lines were employed to test a set of hydrazide-hydrazones as potential STAT3 inhibitors. A hydrazide-hydrazone library composed of 70 binary combinations of 7 carbonyl and 10 hydrazide components, including a STAT3 inhibitor clinical drug nifuroxazide, has been assembled and screened by the reporters. For the library as a whole, significant correlations between responses of the STAT3 and NF-κB or the STAT3 and HIF-1α reporters in THP-1 monocytes were found. For selected inhibitory combinations, respective hydrazide-hydrazones have been prepared and tested individually. The most potent 2-acetylpyridine 4-chlorobenzoylhydrazone exhibited the STAT3 inhibitory potential significantly exceeding that of nifuroxazide (ED50 2 vs 50 μM respectively) in THP-1 cells. We conclude that insulated reporter transposons could be a useful tool for drug discovery applications.

Graphical Abstract
Radial variation in anatomical wood characteristics and physical properties of Paulownia elongata x Paulownia fortunei hybrid Cotevisa 2 from fast-growing plantations
Authors: Fos Mariano , Oliver-Villanueva Jose-Vicente , Vazquez Miguel
Published: February 2023

The trend of increasing demand for wood raw material is becoming of great global concern. Fast-growing plantations, such as those of Paulownia, are being established in different parts of the world, as a viable alternative to quickly produce quality wood at competitive costs. The presence and proportion of juvenile wood directly influences the capacity and possibilities of industrial transformation for sawn timber, veneer or plywood for furniture, construction or packaging purposes. The objective of the research is to analyze the radial variation of physical and anatomical characteristics of Paulownia elongata x fortune hybrid Cotevisa 2 wood from fast-growing plantations. A sample of 14 trees from a seven-year-old plantation established in Valencia (Spain) with a planting frame of 4 m × 4 m was used. Although there is no data from subsequent rings to the 6th, the obtained results indicate that from the 5th year of growth, the wood of Paulownia elongata x fortunei Cotevisa 2 could stabilize in some key parameters such as the radial growth of the rings, the structure and proportion of the vessels, the structure of the cell wall, the density of the material and the behavior in terms of dimensional stability in the drying process. Thus, for practical purposes, we can indicate that the transition from juvenile wood to mature wood can begin from the 5th year of growth. Enlarging the rotation in few years reduces significantly the presence of juvenile wood and contributes to improve the roundwood quality for added-value solid wood products.
Influence of deoxynivalenol-contaminated feed on the immune response of pigs after PRRSV vaccination and infection
Authors: Pierron Alix , Vatzia Eleni , Stadler Maria , Mair Kerstin H. , Schmidt Selma , Stas Melissa R. , Dürlinger Sophie , Kreutzmann Heinrich , Knecht Christian , Balka Gyula , Lagler Julia , Zaruba Marianne , Rümenapf Till , Saalmüller Armin , Mayer Elisabeth , Ladinig Andrea , Gerner Wilhelm
Published: February 2023

The impact of the Fusarium mycotoxin deoxynivalenol (DON) on the immune response against porcine reproductive and respiratory syndrome virus (PRRSV) vaccination and infection was investigated. Forty-two weaned piglets were separated into seven groups and received three different diets: Low DON (1.09 ppm), High DON (2.81 ppm) or No DON. These three treatments were split further into either vaccinated (Ingelvac PRRSFLEX EU) and challenged with PRRSV 28 days post-vaccination, or only infected at day 28. A seventh group received no DON, no vaccination, and no infection. Two weeks after challenge infection, when pigs were euthanized, the number of IFN-γ producing lymphocytes in the blood of vaccinated animals was lower in pigs on High DON compared to animals on Low DON or No DON. Intracellular cytokine staining showed that vaccinated animals fed with the Low DON diet had higher frequencies of TNF-α/IFN-γ co-producing CD4+ T cells than the other two vaccinated groups, particularly in lung tissue. Vaccinated animals on High DON had similar viral loads in the lung as the non-vaccinated groups, but several animals of the Low DON or No DON group receiving vaccination had reduced titers. In these two groups, there was a negative correlation between lung virus titers and vaccine-specific TNF-α/IFN-γ co-producing CD4+ T cells located either in lung tissue or blood. These results indicate that after PRRSV vaccination and infection, high levels of DON negatively influence immune parameters and clearance of the virus, whereas low DON concentrations have immunomodulatory effects.
Influence of foliar treatments with methyl jasmonate and methyl jasmonate-doped nanoparticles on nitrogen composition of Tempranillo grapes during two vintages
Authors: Garde-Cerdán Teresa , Sáenz de Urturi Itziar , Marín-San Román Sandra , Murillo-Peña Rebeca , Ramírez-Rodríguez Gloria B. , Delgado-López José M. , Pérez-Álvarez Eva P.
Published: February 2023

Nanoparticles are emerging as a cutting-edge technology to improve crop agricultural input efficiency and reduce biotic and abiotic stresses. In viticulture, nanoparticles hold promise for the sustainable application of an elicitor (methyl jasmonate, MeJ), allowing a considerable dosage reduction. Herein, the influence of the foliar application of free MeJ (10 mM) and MeJ nanoformulation (ACP-MeJ, 1 mM MeJ) on Tempranillo grape amino acids content over two vintages (2019 and 2020) was evaluated. While both MeJ treatments provided a significant increase of the amino nitrogen and yeast assimilable nitrogen in the must in 2019, there were no significant differences on these parameters in 2020. In 2019, MeJ treatment enhanced the synthesis of most of the amino acids included in this study, while ACP-MeJ promoted the formation of six amino acids. Hence, the content of total amino acids, with and without proline, was higher after applying MeJ than in the control musts. However, these values were higher for control must than for MeJ samples in 2020. The multivariable analysis confirmed that the vintage factor had a more prominent effect on the overall parameters of the musts. This strong influence of the vintage could be related to the higher rainfall in 2020.
Molecular dynamics of seed priming at the crossroads between basic and applied research
Authors: Pagano Andrea , Macovei Anca , Balestrazzi Alma
Published: February 2023

Key message

The potential of seed priming is still not fully exploited. Our limited knowledge of the molecular dynamics of seed pre-germinative metabolism is the main hindrance to more effective new-generation techniques.

Climate change and other recent global crises are disrupting food security. To cope with the current demand for increased food, feed, and biofuel production, while preserving sustainability, continuous technological innovation should be provided to the agri-food sector. Seed priming, a pre-sowing technique used to increase seed vigor, has become a valuable tool due to its potential to enhance germination and stress resilience under changing environments. Successful priming protocols result from the ability to properly act on the seed pre-germinative metabolism and stimulate events that are crucial for seed quality. However, the technique still requires constant optimization, and researchers are committed to addressing some key open questions to overcome such drawbacks. In this review, an update of the current scientific and technical knowledge related to seed priming is provided. The rehydration–dehydration cycle associated with priming treatments can be described in terms of metabolic pathways that are triggered, modulated, or turned off, depending on the seed physiological stage. Understanding the ways seed priming affects, either positively or negatively, such metabolic pathways and impacts gene expression and protein/metabolite accumulation/depletion represents an essential step toward the identification of novel seed quality hallmarks. The need to expand the basic knowledge on the molecular mechanisms ruling the seed response to priming is underlined along with the strong potential of applied research on primed seeds as a source of seed quality hallmarks. This route will hasten the implementation of seed priming techniques needed to support sustainable agriculture systems.
A Diffuse-Interface Approach for Solid-State Dewetting with Anisotropic Surface Energies
Authors: Garcke Harald , Knopf Patrik , Nürnberg Robert , Zhao Quan
Published: February 2023

We present a diffuse-interface model for the solid-state dewetting problem with anisotropic surface energies in$${\mathbb {R}}^d$$Rdfor$$d\in \{2,3\}$$d∈{2,3}. The introduced model consists of the anisotropic Cahn–Hilliard equation, with either a smooth or a double-obstacle potential, together with a degenerate mobility function and appropriate boundary conditions on the wall. Upon regularizing the introduced diffuse-interface model, and with the help of suitable asymptotic expansions, we recover as the sharp-interface limit the anisotropic surface diffusion flow for the interface together with an anisotropic Young’s law and a zero-flux condition at the contact line of the interface with a fixed external boundary. Furthermore, we show the existence of weak solutions for the regularized model, for both smooth and obstacle potential. Numerical results based on an appropriate finite element approximation are presented to demonstrate the excellent agreement between the proposed diffuse-interface model and its sharp-interface limit.
Analysis of the cervical microbiome in women from the German national cervical cancer screening program
Authors: Condic Mateja , Neidhöfer Claudio , Ralser Damian J. , Wetzig Nina , Thiele Ralf , Sieber Martin , Otten Lucia A. , Warwas Leonie K. , Hoerauf Achim , Mustea Alexander , Parčina Marijo
Published: February 2023

Purpose

Cervical cancer (CC) is caused by a persistent high-risk human papillomavirus (hrHPV) infection. The cervico-vaginal microbiome may influence the development of (pre)cancer lesions. Aim of the study was (i) to evaluate the new CC screening program in Germany for the detection of high-grade CC precursor lesions, and (ii) to elucidate the role of the cervico-vaginal microbiome and its potential impact on cervical dysplasia.

Methods

The microbiome of 310 patients referred to colposcopy was determined by amplicon sequencing and correlated with clinicopathological parameters.

Results

Most patients were referred for colposcopy due to a positive hrHPV result in two consecutive years combined with a normal PAP smear. In 2.1% of these cases, a CIN III lesion was detected. There was a significant positive association between the PAP stage and Lactobacillus vaginalis colonization and between the severity of CC precursor lesions and Ureaplasma parvum.

Conclusion

In our cohort, the new cervical cancer screening program resulted in a low rate of additional CIN III detected. It is questionable whether these cases were only identified earlier with additional HPV testing before the appearance of cytological abnormalities, or the new screening program will truly increase the detection rate of CIN III in the long run. Colonization with U. parvum was associated with histological dysplastic lesions. Whether targeted therapy of this pathogen or optimization of the microbiome prevents dysplasia remains speculative.
Pomalidomide combinations are a safe and effective option after daratumumab failure
Authors: Brioli Annamaria , Gengenbach Laura , Mancuso Katia , Binder Mascha , Ernst Thomas , Heidel Florian H. , Stauch Thomas , Zamagni Elena , Hilgendorf Inken , Hochhaus Andreas , Engelhardt Monika , von Lilienfeld-Toal Marie
Published: February 2023

Purpose

Outcomes of multiple myeloma (MM) patients who are refractory to daratumumab are dismal and no standard of treatment exists for this patients’ population. Here, we investigate the role of pomalidomide combinations in daratumumab-refractory MM patients.

Methods

We performed a retrospective analysis of myeloma patients treated at four referral centers (three in Germany and one in Italy). Review chart identified 30 patients with relapsed and refractory myeloma, who progressed during treatment with daratumumab and were treated with pomalidomide-based combinations in the subsequent lines of therapy.

Results

Responses improved from 37% with daratumumab to 53% with pomalidomide. Of seven patients with extramedullary MM (EMM), four achieved a clinical stabilization with pomalidomide, including one patient with a long-lasting complete response. Median progression-free survival and overall survival were 6 and 12 months, respectively. Pomalidomide combinations were well tolerated, no patient discontinued treatment due to adverse events.

Conclusion

These data show that pomalidomide-based combinations can be an effective and safe salvage regimen for daratumumab-refractory patients, including those with EMM.
In memoriam: Theodor Hiepe (1929–2022)—great German scholar of parasitology
Authors: Matuschewski Kai , Lucius Richard , von Samson-Himmelstjerna Georg
Published: February 2023

Theodor Hiepe (1929-2022) was an outstanding researcher, a world-renowned scientist, a dedicated teacher and a great mentor. During his scientific career, which spanned over 60 years, he made major contributions to many different fields of parasitology. With the passing of Dr. h.c. mult. Theodor Hiepe in September 2022 the scientific community suffered a great loss.
Persistent Features of Laryngeal Injury Following Endotracheal Intubation: A Systematic Review
Authors: Kelly Eileen , Hirschwald Julia , Clemens Julie , Regan Julie
Published: February 2023

This systematic review examined (i) prevalence, severity, and impact of persistent post-extubation laryngeal injury beyond hospital discharge and (ii) differences in persistent laryngeal injury between COVID-19 and non-COVID-19 populations. The review was completed following PRISMA-2020 guidelines. Four databases (PubMed, CINHAL complete, EMBASE, Web of Science) were searched (inception to March 2021). Screening, full text review and data extraction were completed by two reviewers. Primary outcomes were swallow, voice and cough and airway measures obtained after hospital discharge. Quality assessment was measured using Downs & Black Tool and Johanna Briggs Institute Checklist for Cohort Studies. Meta-analysis was not completed due to study heterogeneity. Six cohort studies were included. Total number of participants across the included studies was 436. ICU admission diagnoses included respiratory disease 46% (COVID-19 and non-COVID-19), sepsis 14%, non-sepsis-related organ dysfunction 9%, general medical 11%, general surgical 10%, trauma 2%, ENT 0.6% and other not specified by authors 7%. Outcomes were obtained between 2 and 60 months post hospital discharge. Assessment methods included endoscopic evaluation, clinician ratings and patient-reported outcomes. Persistent features of laryngeal injury identified were airway abnormalities (18.9–27%), dysphonia (13.2–60%) and dysphagia (23–33%). Persistent laryngeal injury was associated with ICU length of stay, respiratory diagnosis and tracheostomy. Study quality ranged from poor-good. This is the first systematic review to examine post-extubation laryngeal injury beyond hospital discharge. Significant gaps in the literature were identified. Given the impact on clinical and patient outcomes, large scale, well-designed research is needed to guide post-ICU service delivery.
A fully implicit and thermodynamically consistent finite element framework for bone remodeling simulations
Authors: Bittens Maximilian , Nackenhorst Udo
Published: February 2023

This work addresses the thermodynamically consistent formulation of bone remodeling as a fully implicit finite element material model. To this end, bone remodeling is described in the framework of thermodynamics for open systems resulting in a thermodynamically consistent constitutive law. In close analogy to elastoplastic material modeling, the constitutive equations are implicitly integrated in time and incorporated into a finite element weak form. A consistent linearization scheme is provided for the subsequent incremental non-linear boundary value problem, resulting in a computationally efficient description of bone remodeling. The presented model is suitable for implementation in any standard finite element framework with quadratic or higher-order element types. Two numerical examples in three dimensions are shown as proof of the efficiency of the proposed method.
TRANSPARENT: a Python tool for designing transcription factor regulatory networks
Authors: Derelitto Carlo , Santoni Daniele
Published: February 2023

Transcription factors are proteins able to selectively bind DNA short traits, namely transcription factors binding sites, in order to regulate gene expression in terms of both repression and activation. Despite plenty of studies focusing on transcription factors and on the role they play in specific biological tasks or diseases, is available in the literature, to our knowledge there is no tool able to automatically provide a list of transcription factors involved in this task and the associated interaction network through a solid computational analysis. TRANScriPtion fActor REgulatory NeTwork (TRANSPARENT) is a user-friendly Python tool designed to help researchers in studying given biological tasks or given diseases in human, by identifying transcription factors controlling and regulating the expression of genes associated with that task or disease. The tool takes in input a list of gene IDs and provides (1) a set of transcription factors that are significantly associated with the input genes, (2) the correspondent P values (i.e., the probability that this observed association was driven by chance) and (3) a transcription factor network that can be directly visualized through STRING database. The effectiveness and reliability of the tool were assessed by applying it to two different test cases: schizophrenia and autism disorders. The obtained results clearly show that identified TFs, for both datasets, are significantly associated with those disorders, in terms of both gene enrichment and coherence with the literature. The proposed tool TRANSPARENT can be a useful instrument to investigate transcription factor networks and unveil the role that TFs play in given biological tasks and diseases.
Total positive curvature and the equality case in the relative isoperimetric inequality outside convex domains
Authors: Fusco N. , Morini M.
Published: February 2023

We settle the case of equality for the relative isoperimetric inequality outside any arbitrary convex set with not empty interior.
Anisotropic Triebel-Lizorkin spaces and wavelet coefficient decay over one-parameter dilation groups, II
Authors: Koppensteiner Sarah , van Velthoven Jordy Timo , Voigtlaender Felix
Published: February 2023

Continuing previous work, this paper provides maximal characterizations of anisotropic Triebel-Lizorkin spaces$$\dot{\textbf{F}}^{\alpha }_{p,q}$$F˙p,qαfor the endpoint case of$$p = \infty $$p=∞and the full scale of parameters$$\alpha \in \mathbb {R}$$α∈Rand$$q \in (0,\infty ]$$q∈(0,∞]. In particular, a Peetre-type characterization of the anisotropic Besov space$$\dot{\textbf{B}}^{\alpha }_{\infty ,\infty } = \dot{\textbf{F}}^{\alpha }_{\infty ,\infty }$$B˙∞,∞α=F˙∞,∞αis obtained. As a consequence, it is shown that there exist dual molecular frames and Riesz sequences in$$\dot{\textbf{F}}^{\alpha }_{\infty ,q}$$F˙∞,qα.
Radiographic ratios for classifying furcation anatomy: proposal of a new evaluation method and an intra-rater and inter-rater operator reliability study
Authors: Limiroli Enrico , Calò Andrea , Limiroli Alessandro , Cortinovis Ivan , Rasperini Giulio
Published: February 2023

Objectives

Even if it seems to be an important anatomical parameter for tissue regeneration, few studies in literature evaluate the “mean measure” of root divergence. Most of them are linear measurements, which hardly describe the dental furcation conformation in its entirety. It is left to the subjectivity of the operator deciding whether a furcation is convergent or divergent. The goal of this study is to create a visual evaluation method using specific measurements applied on endo-oral X-rays to overcome these problems, giving a conformation of the entire interradicular space and its divergence.

Material and methods

A user-friendly software (Paint®, Windows10®) was used to take three different measurements on endo-oral radiographs of upper and lower molars. Three blind operators measured 20 radiographs, to analyze the intra- and inter-operator reproducibility of the measurements. Then, the technique was repeated on 250 radiographic images to identify an average value and define a main conformation of the interradicular space. The ratio of these three measurements allowed to develop a new visual evaluation method of the interradicular space.

Results

Intra and inter-operator reproducibility was statistically confirmed on a sample of 20 anonymous endo-oral radiographs measured by 3 blind operators, indicating that the measurement technique was not operator dependent. Measurement made on 250 X-rays obtained with this technique permitted to subdivide in five groups the conformation of the interradicular space and define a mean value of the interradicular space.

Conclusions

A new anatomical evaluation of the interradicular space in its entirety, which could help the clinicians in diagnostic and decisional phase in the therapy of furcated molars, can be obtained.

Clinical relevance

A pre-operative evaluation of interradicular space conformation could affect therapy treatment choice.
Psychosocial functioning mediates change in motor and cognitive function throughout neurorehabilitation for adults with acquired brain injury (ABI-RESTaRT)
Authors: Mann Georgina , Troeung Lakkhina , Singh Krishneil A , Reddell Curtis , Martini Angelita
Published: February 2023

Objectives

This study aimed to evaluate the mediational role of change in psychosocial abilities, adjustment and participation on change in motor and cognitive function from admission to discharge from a staged community-based brain injury rehabilitation (SCBIR) service in Western Australia, 2011–2020.

Methods

A retrospective cohort study of n = 324 adults with ABI enrolled in SCBIR using routinely collected rehabilitation outcome measures data. Motor and cognitive function were assessed with the UK Functional Independence and Assessment Measure and psychosocial function with the Mayo-Portland Adaptability Inventory-4. Six multilevel mediation regression analyses were conducted to determine whether change in psychosocial function (abilities, adjustment and participation) mediated change in motor and cognitive function from admission to discharge.

Results

Participants demonstrated clinically significant improvements in both motor (+ 11.8, p < 0.001) and cognitive (+ 9.5, p < 0.001) functioning from admission to discharge. Statistically significant improvements in psychosocial abilities (− 4.8, p < 0.001), adjustment (− 2.9, p = 0.001) and participation (− 2.5, p < 0.001) were also seen but were not clinically significant. Mediation analyses showed that participation accounted for 81% of improvements in motor function at discharge and 71% of cognitive function improvements. Adjustment accounted for 26% and 32% of change in motor and cognitive function, respectively. Abilities accounted for 60% of change in cognitive function but did not significantly influence change in motor function. Changes in psychosocial participation fully mediated change in motor function during neurorehabilitation.

Conclusions

Psychosocial function, particularly participation, is an important driver of motor and cognitive recovery throughout neurorehabilitation. Functional rehabilitation programs should target psychosocial improvement as an important mechanism of change.
Prognosis and histology of sporadic synchronous and metachronous meningiomas and comparative analyses with singular lesions
Authors: Kopf Lisa , Warneke Nils , Grauer Oliver , Thomas Christian , Hess Katharina , Schwake Michael , Mannil Manoj , Akkurt Burak Han , Paulus Werner , Stummer Walter , Brokinkel Benjamin , Spille Dorothee Cäcilia
Published: February 2023

Synchronous or metachronous growth of multiple tumors (≥ 2) is found in up to 20% of meningioma patients. However, biological as well as histological features and prognosis are largely unexplored. Clinical and histological characteristics were retrospectively investigated in 95 patients harboring 226 multiple meningiomas (MMs) and compared with 135 cases of singular meningiomas (SM) using uni- and multivariate analyses. In MM, tumors occurred synchronously and metachronously in 62% and 38%, respectively. WHO grade was intra-individually constant in all but two MMs, and histological subtype varied in 13% of grade 1 tumors. MM occurred more commonly in convexity/parasagittal locations, while SM were more frequent at the skull base (p < .001). In univariate analyses, gross total resection (p = .014) and high-grade histology in MM were associated with a prolonged time to progression (p < .001). Most clinical characteristics and rates of high-grade histology were similar in both groups (p ≥ .05, each). Multivariate analyses showed synchronous/metachronous meningioma growth (HR 4.50, 95% CI 2.26–8.96; p < .001) as an independent predictor for progression. Compared to SM, risk of progression was similar in cases with two (HR 1.56, 95% CI .76–3.19; p = .224), but exponentially raised in patients with 3–4 (HR 3.25, 1.22–1.62; p = .018) and ≥ 5 tumors (HR 13.80, 4.06–46.96; p < .001). Clinical and histological characteristics and risk factors for progression do not relevantly differ between SM and MM. Although largely constant, histology and WHO grade occasionally intra-individually vary in MM. A distinctly higher risk of disease progression in MM as compared to SM might reflect different underlying molecular alterations.
Diagnosis and treatment of meralgia paresthetica between 2005 and 2018: a national cohort study
Authors: Schönberg Benn , Pigorsch Mareen , Huscher Doerte , Baruchi Shlomo , Reinsch Jennifer , Zdunczyk Anna , Scholz Christoph , Uerschels Ann-Kathrin , Dengler Nora F.
Published: February 2023

The prevalence of meralgia paresthetica (MP), which is caused by compression of the lateral femoral cutaneous nerve (LFCN), has been increasing over recent decades. Since guidelines and large-scale studies are lacking, there are substantial regional differences in diagnostics and management in MP care. Our study aims to report on current diagnostic and therapeutic strategies as well as time trends in clinical MP management in Germany. Patients hospitalized in Germany between January 1, 2005, and December 31, 2018, with MP as their primary diagnosis were identified using the International Classification of Disease (ICD-10) code G57.1 and standardized operations and procedures codes (OPS). A total of 5828 patients with MP were included. The rate of imaging studies increased from 44% in 2005 to 79% in 2018 (p < 0.001) and that of non-imaging diagnostic studies from 70 to 93% (p < 0.001). Among non-imaging diagnostics, the rates of evoked potentials and neurography increased from 20%/16% in 2005 to 36%/23% in 2018 (p < 0.001, respectively). Rates of surgical procedures for MP decreased from 53 to 37% (p < 0.001), while rates of non-surgical procedures increased from 23 to 30% (p < 0.001). The most frequent surgical interventions were decompressive procedures at a mean annual rate of 29% (± 5) throughout the study period, compared to a mean annual rate of 5% (± 2) for nerve transection procedures. Between 2005 and 2018, in-hospital MP care in Germany underwent significant changes. The rates of imaging, evoked potentials, neurography, and non-surgical management increased. The decompression of the LFCN was substantially more frequent than that of the LFCN transection, yet both types of intervention showed a substantial decrease in in-hospital prevalence over time.
Efficient adsorption of carbon dioxide and methane on activated carbon prepared from glycerol with potassium acetate
Authors: Matos Beatriz , Batista Mary , Pires João
Published: February 2023

In the context of global warming and the energy crisis, emissions to the atmosphere of greenhouse gases such as carbon dioxide (CO2) and methane (CH4) should be reduced, and biomethane from landfill biogas should be recycled. For this, there is a need for affordable technologies to capture carbon dioxide, such as adsorption of biogas on activated carbon produced from industrial wastes. Here we converted glycerol, a largely available by-product from biodiesel production, into activated carbon with the first use of potassium acetate as an activating agent. We studied adsorption of CO2 and CH4 on activated carbon. The results show that activated carbon adsorb CO2 up to 20% activated carbon weight at 250 kPa, and 9% at atmospheric pressure. This is explained by high specific surface areas up to 1115 m2g−1. Moreover, selectivity values up to 10.6 are observed for the separation of CO2/CH4. We also found that the equivalent CO2 emissions from activated carbon synthesis are easily neutralized by their use, even in a small biogas production unit.
On Kosloff Tal-Ezer least-squares quadrature formulas
Authors: Cappellazzo G. , Erb W. , Marchetti F. , Poggiali D.
Published: February 2023

In this work, we study a global quadrature scheme for analytic functions on compact intervals based on function values on quasi-uniform grids of quadrature nodes. In practice it is not always possible to sample functions at optimal nodes that give well-conditioned and quickly converging interpolatory quadrature rules at the same time. Therefore, we go beyond classical interpolatory quadrature by lowering the degree of the polynomial approximant and by applying auxiliary mapping functions that map the original quadrature nodes to more suitable fake nodes. More precisely, we investigate the combination of the Kosloff Tal-Ezer map and least-squares approximation (KTL) for numerical quadrature: a careful selection of the mapping parameter ensures stability of the scheme, a high accuracy of the approximation and, at the same time, an asymptotically optimal ratio between the degree of the polynomial and the spacing of the grid. We will investigate the properties of this KTL quadrature and focus on the symmetry of the quadrature weights, the limit relations for the mapping parameter, as well as the computation of the quadrature weights in the standard monomial and in the Chebyshev bases with help of a cosine transform. Numerical tests on equispaced nodes show that a static choice of the map’s parameter improve the results of the composite trapezoidal rule, while a dynamic approach achieves larger stability and faster convergence, even when the sampling nodes are perturbed. From a computational point of view the proposed method is practical and can be implemented in a simple and efficient way.