bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a machine learning‐based predictive model for prediction of success or failure of medical management for benign prostatic hyperplasia
Authors: Pham Kyle , Ray Al W. , Fernstrum Austin J. , Alfahmy Anood , Ray Soumya , Hijaz Adonis K. , Ju Mingxuan , Sheyn David
Published: February 2023

Objective

To develop a novel predictive model for identifying patients who will and will not respond to the medical management of benign prostatic hyperplasia (BPH).

Methods

Using data from the Medical Therapy of Prostatic Symptoms (MTOPS) study, several models were constructed using an initial data set of 2172 patients with BPH who were treated with doxazosin (Group 1), finasteride (Group 2), and combination therapy (Group 3). K‐fold stratified cross‐validation was performed on each group, Within each group, feature selection and dimensionality reduction using nonnegative matrix factorization (NMF) were performed based on the training data, before several machine learning algorithms were tested; the most accurate models, boosted support vector machines (SVMs), being selected for further refinement. The area under the receiver operating curve (AUC) was calculated and used to determine the optimal operating points. Patients were classified as treatment failures or responders, based on whether they fell below or above the AUC threshold for each group and for the whole data set.

Results

For the entire cohort, the AUC for the boosted SVM model was 0.698. For patients in Group 1, the AUC was 0.729, for Group 2, the AUC was 0.719, and for Group 3, the AUC was 0.698.

Conclusion

Using MTOPS data, we were able to develop a prediction model with an acceptable rate of discrimination of medical management success for BPH.
Effect of compassion fatigue on the caring ability of young psychiatric nurses: A dominance analysis and chain mediation model
Authors: Wang Yu , Li Yingli , Li Wanting , Chen Aixue , Sun Zhuocheng
Published: February 2023

Aims

The aim of this study is to explore the mechanism by which three factors of compassion fatigue affect caring ability in young psychiatric nurses.

Methods

We used the Professional Quality of Life Scale and Caring Ability Inventory to investigate 309 young nurses in three psychiatric hospitals in Heilongjiang. Dominance analysis and chain mediation model were performed to explore the effects of three factors of compassion fatigue on caring ability.

Results

(1) The three factors of compassion fatigue affected the caring ability of young in the order compassion satisfaction > burnout>secondary traumatic stress by dominance analysis; (2) burnout played a partially mediating effect between compassion satisfaction and caring ability; and (3) secondary traumatic stress and burnout had a chain mediating effect between compassion satisfaction and caring ability.

Conclusions

Higher levels of compassion satisfaction had the strongest impact on the caring ability of young psychiatric nurses which could be mediated via burnout and secondary traumatic stress. No patient or public contribution.
Weight loss and modeled cost savings in a digital diabetes prevention program
Authors: Branch OraLee H. , Rikhy Mohit , Auster‐Gussman Lisa A. , Lockwood Kimberly G. , Graham Sarah A.
Published: February 2023

Background

Participation in the National Diabetes Prevention Program (DPP) can improve individual health through reduced risk of type 2 diabetes and save the healthcare system substantial medical costs associated with a diagnosis of type 2 diabetes and its associated complications. There is less evidence of outcomes and cost savings associated with a fully digital delivery of the DPP.

Methods

This study assessed 13,593 members who provided an initial digital weight and subsequently achieved various weight loss and engagement outcomes during their participation in a digital DPP. Analyzed data included both complete observations and missing observations imputed using maximum likelihood estimation. Findings include members' behavioral correlates of weight loss and a literature‐based cost‐savings estimate associated with achieving three mutually exclusive weight loss or engagement benchmarks: ≥5% weight loss, >2% but <5% weight loss, and completion of ≥4 educational lessons.

Results

11,976 members (88%) provided a weight after 2 months of participation, enabling calculation of their weight nadir. Considering complete data, 97% of members maintained or lost weight. Using the imputed data for these calculations, 32.0% of members achieved ≥5%, 32.4% achieved >2% but <5%, 32.0% maintained ±2%, and 3.6% gained weight. Members who lost the most weight achieved their weight nadir furthest into the program (mean day = 189, SE = 1.4) and had the longest active engagement (mean days = 268, SE = 1.4), particularly compared to members who gained weight (mean nadir day = 119, SE = 3.7; active engagement mean days = 199, SE = 4.9) (both p ≤ 0.0001). Modeled 1‐year cost‐savings estimates ranged from $11,229,160 to $12,960,875.

Conclusions

Members of a fully digital DPP achieved clinical and engagement outcomes during their participation in the program that confer important health benefits and cost savings.
Novel prognostication biomarker adipophilin reveals a metabolic shift in uveal melanoma and new therapeutic opportunities
Authors: Matareed Maisoon , Maranou Eleftheria , Koskela Saara A , Mehmood Arfa , Kalirai Helen , Coupland Sarah E , Figueiredo Carlos R
Published: February 2023

Metastatic uveal melanoma remains incurable at present. We previously demonstrated that loss of BAP1 gene expression in tumour cells triggers molecular mechanisms of immunosuppression in the tumour microenvironment (TME) of metastatic uveal melanoma. Adipophilin is a structural protein of lipid droplets involved in fat storage within mammalian cells, and its expression has been identified in uveal melanoma. We comprehensively evaluated adipophilin expression at the RNA (PLIN2) and protein levels of 80 patients of the GDC‐TCGA‐UM study and in a local cohort of 43 primary uveal melanoma samples respectively. PLIN2 expression is a survival prognosticator biomarker in uveal melanoma. Loss of adipophilin expression is significantly associated with monosomy 3 status and nuclear BAP1 losses in uveal melanoma tumours. Integrative transcriptomic and secretome studies show a relationship between transient loss of adipophilin expression and increased levels of tumour‐associated macrophages and hypoxia genes, suggesting PLIN2‐dependent changes in oxygen and lipid metabolism in the TME of low and high‐metastatic risk uveal melanoma. We designed four adipophilin‐based multigene signatures for uveal melanoma prognostication using a transcriptomic and secretome survival‐functional network approach. Adipophilin‐based multigene signatures were validated in BAP1‐positive and BAP1‐negative uveal melanoma cell lines using a next‐generation RNA sequencing approach. We identified existing small molecules, mostly adrenergic, retinoid, and glucocorticoid receptor agonists, MEK, and RAF inhibitors, with the potential to reverse this multigene signature expression in uveal melanoma. Some of these molecules were able to impact tumour cell viability, and carvedilol, an adrenergic receptor antagonist, restored PLIN2 levels, mimicking the expression of normoxia/lipid storage signatures and reversing the expression of hypoxia/lipolysis signatures in co‐cultures of uveal melanoma cells with human macrophages. These findings open up a new research line for understanding the lipid metabolic regulation of immune responses, with implications for therapeutic innovation in uveal melanoma. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Rapid identification of chemical components in vitro and in vivo of Menispermi Rhizoma by integrating UPLC‐Q‐TOF‐MS with data post‐processing strategy
Authors: Wei Jinxia , Wang Yuanyuan , Zhang Yue , Zheng Yanxue , Shao Jia , Cheng Wenbo , Li Yubo
Published: February 2023

Introduction

Menispermi Rhizoma (MR), the dried rhizome of Menispermum dauricum DC. (Menispermaceae), has been used to treat sore throat, enteritis, dysentery, and rheumatic arthralgia. Despite extensive research on its pharmacological effects, the chemical components in vitro and in vivo have not been thoroughly studied.

Objective

To establish an efficient method for rapid classification and identification of alkaloids in MR and its preparations, as well as metabolites in vivo after oral administration of MR.

Methods

Rapid identification of alkaloids and absorbed components of MR was performed using ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF‐MS) coupled with UNIFI software. Moreover, the characteristic fragmentations and neutral losses of different types of alkaloids in MR were summarised to realise the rapid classification of alkaloids.

Results

A total of 55 components were unambiguously or tentatively identified in MR. Among them, 37 and 31 components were found in MR capsules and tablets, respectively. Meanwhile, 109 compounds were tentatively identified in rat plasma, urine and faeces, including 55 prototypes and 54 metabolites. Hydrogenation, hydroxylation, methylation, glucuronic acid and sulphate conjugations were the dominating metabolic fates of alkaloids.

Conclusion

The data post‐processing strategy established could greatly enhance the structural identification efficiency. The results obtained might lay the foundation for further interpretation of clinical effects, mechanism of action and quality control of MR.
Multiplex measurement of protein–peptide dissociation constants using dialysis and mass spectrometry
Authors: Zhao Yu , Grigoryan Gevorg
Published: February 2023

We propose a high‐throughput method for quantitatively measuring hundreds of protein–peptide binding affinities in parallel. In this assay, a solution of protein is dialyzed into a buffer containing a pool of potential binding peptides, such that upon equilibration the relative abundance of a peptide species is mathematically related to that peptide's dissociation constant, Kd. We use isobaric multiplexed quantitative proteomics to simultaneously determine the relative abundance, and hence the Kd and its associated error, for an entire peptide library. We apply this technique, which we call PEDAL (parallel equilibrium dialysis for affinity learning), to determine accurate Kd's between a PDZ domain and hundreds of peptides, spanning an affinity range of multiple orders of magnitude in a single experiment. PEDAL is a convenient, fast, and low‐cost method for measuring large numbers of protein–peptide affinities in parallel, providing a rare combination of true in‐solution binding equilibria with the ability to multiplex.
Factors impacting on sexual function among men on active surveillance for prostate cancer
Authors: Tiruye Tenaw , O'Callaghan Michael , Ettridge Kerry , Jay Alex , Santoro Kerry , Moretti Kim , Beckmann Kerri
Published: February 2023

Background

Active surveillance (AS) aims to reduce overtreatment and minimize the negative side effects of radical therapies (i.e., prostatectomy or radiotherapy) while preserving quality of life. However, a substantial proportion of men can experience a decline in sexual function during AS follow‐up. The aim of this study was to identify predictors of declining sexual function among men on AS.

Methods

Men enrolled from 2008 to 2018 in the South Australian Prostate Cancer Clinical Outcomes Collaborative registry—a prospective clinical registry—were studied. Sexual function outcomes were measured using expanded prostate cancer index composite (EPIC‐26) at baseline and 12‐months postdiagnosis. Multivariable regression models adjusted for baseline score and other sociodemographic and clinical factors were applied to identify predictors of sexual function score at 12‐months.

Results

A total of 554 men were included. Variables that showed significant association with decline in sexual function score at 12‐months were: having two or more biopsies after diagnosis (mean change score (MCS): –16.3, p < 0.001) compared with no biopsy, higher number of positive biopsy cores (MCS: –1.6, p = 0.004), being in older age category (above 70 vs. below 60: MCS: –16.7, p < 0.001; 65−70 vs. below 60: MCS: –9.7, p = 0.024), having had depression (MCS: –9.0, p = 0.020), and impaired physical function (MCS: –10.0, p = 0.031). Greater socioeconomic advantage (highest vs. lowest quintile: MCS: 15.7, p = 0.022) and year of diagnosis (MCS: 2.6 for every year, p < 0.001) were positively associated with 12‐months sexual function score. Neither biopsy type, biopsy timing nor PSA velocity were associated with declines in sexual function.

Conclusions

Our findings suggest that multiple factors affected sexual function during AS. Interventions toward reducing the number of biopsies through less invasive monitory approaches, screening for physical and mental well‐being, and targeted emotional support and counseling services may be helpful for men on AS.
A case of Rasmussen's aneurysm caused by pulmonary nontuberculous mycobacterium
Authors: Plantilla Maya , Nozu Shohei , Nakanishi Norihiko , Ishimaru Yoshihiro
Published: February 2023

Key message

Rasmussen's aneurysm was originally described as a rare cause of hemoptysis in tuberculosis. Dilatation of the pulmonary artery wall is caused by tuberculosis inflammation. Recently, the incidence of non‐tuberculous mycobacterial (NTM) disease has increased; it now exceeds that of tuberculosis. We report a Rasmussen's aneurysm due to NTM.
Ultrastretchable MXene Microsupercapacitors
Authors: Wang Menglu , Feng Shuxuan , Bai Chong , Ji Kang , Zhang Jiaxue , Wang Shaolei , Lu Yanqing , Kong Desheng
Published: February 2023

Stretchable microsupercapacitors represent emerging miniaturized energy‐storage devices for next‐generation deformable electronics. Two‐dimensional (2D) transition metal carbides (MXenes) are considered attractive electrode materials due to their metallic conductivity, hydrophilic surfaces, and excellent processability. Here, an ultrastretchable microsupercapacitor of interdigitated MXene microelectrodes with crumpled surface textures is created. The microsupercapacitor shows a series of attractive properties including a high specific capacitance of ≈185 mF cm−2, ultrahigh stretchability up to 800% area strain, and ≈89.7% retention of the initial capacitance after 1000 stretch–relaxation cycles. In addition to static strains, the microsupercapacitor demonstrates robust mechanical properties to retain stable charging–discharging capability under dynamic stretching at different strain rates. A self‐powering circuit system utilizes four microsupercapacitor packs to power a light‐emitting diode (LED) array, which exhibits stable operations under large tensile strain and skin‐attached wearable settings. The developments offer a generic design strategy to enhance the deformability of microsupercapacitors based on 2D nanomaterials.
Organ‐on‐a‐chip technologies for biomedical research and drug development: A focus on the vasculature
Authors: Soto Veliz Diosangeles , Lin Kai‐Lan , Sahlgren Cecilia
Published: February 2023

Current biomedical models fail to replicate the complexity of human biology. Consequently, almost 90% of drug candidates fail during clinical trials after decades of research and billions of investments in drug development. Despite their physiological similarities, animal models often misrepresent human responses, and instead, trigger ethical and societal debates regarding their use. The overall aim across regulatory entities worldwide is to replace, reduce, and refine the use of animal experimentation, a concept known as the Three Rs principle. In response, researchers develop experimental alternatives to improve the biological relevance of in vitro models through interdisciplinary approaches. This article highlights the emerging organ‐on‐a‐chip technologies, also known as microphysiological systems, with a focus on models of the vasculature. The cardiovascular system transports all necessary substances, including drugs, throughout the body while in charge of thermal regulation and communication between other organ systems. In addition, we discuss the benefits, limitations, and challenges in the widespread use of new biomedical models. Coupled with patient‐derived induced pluripotent stem cells, organ‐on‐a‐chip technologies are the future of drug discovery, development, and personalized medicine.
Mathematical modeling for experimental data to investigate the convective heat transfer in non‐Newtonian nanofluid's flow over a thin needle
Authors: Hassan Mohsan , Rizwan Muhammad
Published: February 2023

The flow of homogeneous non‐Newtonian nanofluid over a horizontal moving thin needle is studied through experimental data‐based mathematical approach. Experimental data is collected for nanofluids which are prepared by spreading the SiO2, MgO, and TiO2 nanoparticles with correspondingly diameters (20–30 nm, 60–70 nm), (20, 40 nm), and (30, 50 nm) at volume fractions (5%–20%) in ethylene glycol (EG). The rheological power‐law model of viscosity is employed on the current experimental data to govern the co‐relation expression and is further used in heat and mass flow equations. The problem is reduced to ordinary differential equations by employing similarity conversion and then numerically solved. The influence of various volume fractions and diameter of nanoparticles on the distribution of velocity and temperature are discussed through the graphical results. Moreover, velocity and thermal boundary layer thicknesses, momentum and displacement thickness, skin friction coefficient, and Nusselt number are also studied in detail and displayed graphically. The results indicate that enhancing nanoparticle volume fraction causes the decline in velocity profile and rise in temperature profiles. On the contrary, the velocity is amplified and temperature is reduced with enhancing the diameter of the nanoparticle. Newtonian model for nanofluid is not valid in all cases. So, a non‐Newtonian model is applied for nanofluid flow that follows the experimental behavior in the current study. This experimental based model has not investigated before.
Optical Manipulation and Recording of Neural Activity with Wavefront Engineering
Authors: Sims Ruth R. , Bendifallah Imane , Blanchard Kris , Tanese Dimitrii , Emiliani Valentina , Papagiakoumou Eirini
Published: February 2023

One of the central goals of neuroscience is to decipher the specific contributions of neural mechanisms to different aspects of sensory perception. Since achieving this goal requires tools capable of precisely perturbing and monitoring neural activity across a multitude of spatiotemporal scales, this aim has inspired the innovation of many optical technologies capable of manipulating and recording neural activity in a minimally invasive manner. The interdisciplinary nature of neurophotonics requires a broad knowledge base in order to successfully develop and apply these technologies, and one of the principal aims of this chapter is to provide some basic but fundamental background information in terms of both physiology and optics in the context of all-optical two-photon neurophysiology experiments. Most of this information is expected to be familiar to readers experienced in either domain, but is presented here with the aim of bridging the divide between disciplines in order to enable physicists and engineers to develop useful optical technologies or for neuroscientists to select appropriate tools and apply them to their maximum potential.

The first section of this chapter is dedicated to a brief overview of some basic principles of neural physiology relevant for controlling and recording neuronal activity using light. Then, the selection of appropriate actuators and sensors for manipulating and monitoring particular neural signals is discussed, with particular attention paid to kinetics and sensitivity. Some considerations for minimizing crosstalk in optical neurophysiology experiments are also introduced. Next, an overview of the state-of-the-art optical technologies is provided, including a description of suitable laser sources for two-photon excitation according to particular experimental requirements. Finally, some detailed, technical, information regarding the specific wavefront engineering approaches known as Generalized Phase Contrast (GPC) and temporal focusing is provided.
Spectrally Focused Stimulated Raman Scattering (sf-SRS) Microscopy for Label-Free Investigations of Molecular Mechanisms in Living Organisms
Authors: Váczi Tamás , Himics László , Bruzzone Matteo , Veres Miklós , dal Maschio Marco
Published: February 2023

Stimulated Raman Scattering (SRS) microscopy is a light-based non-linear imaging method for visualizing a molecule based on its chemical properties, i.e., the vibrational energy states reflecting the molecule’s structure and its environment. This technique, relying on the specificity of the molecule’s spectral fingerprint, enables label-free, high-sensitivity, and high-resolution 3D reconstruction of the distribution and the properties of a molecule within a tissue. Despite its tremendous potentials, the application of SRS is still not frequent in the field of life science, where it could be applied over an extremely broad investigation range, from the study of the molecular interactions at subcellular level to the characterization of tissue alterations in clinical studies. Trying to fill this gap, here, after describing the general principles of SRS, we present the materials and the methods to integrate spectrally focused Stimulated Raman Spectroscopy (sf-SRS) on commercial multiphoton microscopes and highlight the critical aspects to consider.
Light-Based Neuronal Circuit Probing in Living Brains at High Resolution: Constraints and Layouts for Integrating Neuronal Activity Recording and Modulation in Three Dimensions
Authors: Bruzzone Matteo , Chiarello Enrico , Maset Andrea , Megighian Aram , Lodovichi Claudia , dal Maschio Marco
Published: February 2023

Understanding how the brain orchestrates neuronal activity to finely produce and regulate behavior is an intriguing yet challenging task. In the last years, the progressive refinement of optical techniques and light-based molecular tools allowed to start addressing open questions in cellular and systems neuroscience with unprecedented resolution and specificity. Currently, all-optical experimental protocols for simultaneous recording of the activity of large cell populations with the concurrent modulation of the firing rate at cellular resolution represent an invaluable tool. In this scenario, it is becoming everyday more evident the importance of sampling and probing the circuit mechanisms not just in a single plane, but extending the exploration to the entire volume containing the involved circuit components. Here, we focus on the design principles and the hardware architectures of all-optical approaches allowing for studying the neuronal dynamics at cellular resolution across a volume of the brain.
Measure and Dimension of the Free Boundary
Authors: Velichkov Bozhidar
Published: February 2023

This chapter is dedicated to the measure theoretic structure of the free boundary ∂ Ωu. The results presented here are mainly a consequence of the Lipschitz continuity and the non-degeneracy of the minimizer u (Theorem 3.1 and Proposition 4.1).
Introduction
Authors: Hamborg Felix
Published: February 2023

This chapter motivates and summarizes my research to reveal bias in news articles. Section 1.1 highlights the issues caused by slanted news coverage. The importance of these issues cannot be overestimated as systematically biased coverage has already exerted influence on societal decisions, such as in democratic elections. Section 1.2 then briefly summarizes the research gap regarding the identification and communication of media bias. I take the issues caused by bias and the research gap in revealing bias as a motivation to define my research question and derive respective research tasks in Sect. 1.3. Lastly, Sect. 1.4 summarizes the contributions of this thesis and gives an overview of its structure and the integrated publications.
Target Concept Analysis
Authors: Hamborg Felix
Published: February 2023

This chapter details the first component of person-oriented framing analysis: target concept analysis. This component aims to find and resolve mentions of persons, which can be subject to media bias. The chapter introduces and discusses two approaches for this task. First, the chapter introduces an approach for event extraction. The approach extracts answers to the journalistic 5W1H questions, i.e., who did what, when, where, why, and how. The in-text answers to these questions describe a news article’s main event. Afterward, the chapter introduces an approach that is the first to resolve highly context-dependent coreferences across news articles as they commonly occur in the presence of sentence-level bias forms. Our approach can resolve mentions that are coreferential also only in coverage on the same event and that otherwise may even be contradictory, such as “attack” or “self-defense” and “riot” or “protest.” Lastly, the chapter argues for using the latter approach for the target concept analysis component, in particular because of its high classification performance. Another reason for our decision is that using the event extraction approach in the target concept analysis component would require the development of a subsequent approach, i.e., to compare the events extracted from individual articles and resolve them across all articles.
Prototype
Authors: Hamborg Felix
Published: February 2023

This chapter demonstrates the effectiveness of person-oriented framing analysis (PFA) by implementing and evaluating a prototypical system for bias identification and communication. In the single-blind setting of the evaluation, only the PFA prototype consistently, significantly, and most strongly increased respondents’ bias-awareness, i.e., respondents’ motivation and capabilities to contrast news coverage. The study results and a qualitative analysis indicate that a reason for the improved bias-awareness is that the frames identified by PFA are meaningful and indeed present in person-centric news coverage. In contrast, and confirming the findings of Chap. 2, the most effective baselines only facilitate the visibility of potential frames.
Conclusion
Authors: Hamborg Felix
Published: February 2023

This chapter concludes the doctoral thesis by summarizing the previously presented research (Sect. 7.1) and major contributions (Sect. 7.2). Lastly, the chapter discusses the limitations of the presented work and highlights ideas for future research (Sect. 7.3).
Encoding beyond cosmological horizons in de Sitter JT gravity
Authors: Levine Adam , Shaghoulian Edgar
Published: February 2023

Abstract

Black hole event horizons and cosmological event horizons share many properties, making it natural to ask whether our recent advances in understanding black holes generalize to cosmology. To this end, we discuss a paradox that occurs if observers can access what lies beyond their cosmological horizon in the same way that they can access what lies beyond a black hole horizon. In particular, distinct observers with distinct horizons may encode the same portion of spacetime, violating the no-cloning theorem of quantum mechanics. This paradox is due precisely to the observer-dependence of the cosmological horizon — the sharpest difference from a black hole horizon — although we will argue that the gravity path integral avoids the paradox in controlled examples.
How to identify different new neutrino oscillation physics scenarios at DUNE
Authors: Denton Peter B. , Giarnetti Alessio , Meloni Davide
Published: February 2023

Abstract

Next generation neutrino oscillation experiments are expected to measure the remaining oscillation parameters with very good precision. They will have unprecedented capabilities to search for new physics that modify oscillations. DUNE, with its broad band beam, good particle identification, and relatively high energies will provide an excellent environment to search for new physics. If deviations from the standard three-flavor oscillation picture are seen however, it is crucial to know which new physics scenario is found so that it can be verified elsewhere and theoretically understood. We investigate several benchmark new physics scenarios by looking at existing long-baseline accelerator neutrino data from NOvA and T2K and determine at what sensitivity DUNE can differentiate among them. We consider sterile neutrinos and both vector and scalar non-standard neutrino interactions, all with new complex phases, the latter of which could conceivably provide absolute neutrino mass scale information. We find that, in many interesting cases, DUNE will have good model discrimination. We also perform a new fit to NOvA and T2K data with scalar NSI.
JT gravity from partial reduction and defect extremal surface
Authors: Deng Feiyu , An Yu-Sen , Zhou Yang
Published: February 2023

Abstract

We propose the three-dimensional counterpart for Jackiw-Teitelboim gravity coupled with CFT2 bath based on partial reduction. The three-dimensional counterpart is classical AdS gravity with a defect brane which has small fluctuation in transverse direction. We derive full Jackiw-Teitelboim gravity action by considering the transverse fluctuation as a dilaton field. We demonstrate that the fine-grained entropy computed from island formula precisely agrees with that computed from defect extremal surface. Our construction provides a Lorentzian higher dimensional counterpart for Jackiw-Teitelboim gravity glued to a bath and therefore offers a framework to study problems such as black hole information paradox.
Low doses to the heart in daily practice for treating left-sided breast cancer using accelerated partial-breast irradiation by multicatheter brachytherapy and deep-inspiration breath-hold using a SIB
Authors: Knippen Stefan , Schönherr Sven , Schwedas Michael , Teichmann Tobias , Howitz Simon , Mäurer Matthias , Wittig-Sauerwein Andrea , Duma Marciana-Nona
Published: February 2023

Purpose

The aim of this study was to analyze the heart dose for left-sided breast cancer that can be achieved during daily practice in patients treated with multicatheter brachytherapy (MCBT) accelerated partial-breast irradiation (APBI) and deep-inspiration breath-hold (DIBH) whole-breast irradiation (WBI) using a simultaneous integrated tumor bed boost (SIB)—two different concepts which nonetheless share some patient overlap.

Materials and methods

We analyzed the nominal average dose (Dmean) to the heart as well as the biologically effective dose (BED) and the equivalent dose in 2‑Gy fractions (EQD2) for an α/β of 3 in 30 MCBT-APBI patients and 22 patients treated with DIBH plus SIB. For further dosimetric comparison, we contoured the breast planning target volume (PTV) in each of the brachytherapy planning CTs according to the ESTRO guidelines and computed tangential field plans. Mean dose (Dmean), EQD2 Dmean, and BED Dmean for three dosing schemes were calculated: 50 Gy/25 fractions and two hypofractionated regimens, i.e., 40.05 Gy/15 fractions and 26 Gy/5 fractions. Furthermore, we calculated tangential field plans without a boost for the 22 cases treated with SIB with the standard dosing scheme of 40.05 Gy/15 fractions.

Results

MCBT and DIBH radiation therapy both show low-dose exposure of the heart. As expected, hypofractionation leads to sparing of the heart dose. Although MCBT plans were not optimized regarding dose to the heart, Dmean differed significantly between MCBT and DIBH (1.28 Gy vs. 1.91 Gy, p < 0.001) in favor of MCBT, even if the Dmean in each group was very low. In MCBT radiation, the PTV–heart distance is significantly associated with the dose to the heart (p < 0.001), but it is not in DIBH radiotherapy using SIB.

Conclusion

In daily practice, both DIBH radiation therapy as well as MCBT show a very low heart exposure and may thus reduce long term cardiac morbidity as compared to currently available long-term clinical data of patients treated with conventional tangential field plans in free breathing. Our analysis confirms particularly good cardiac sparing with MCBT-APBI, so that this technique should be offered to patients with left-sided breast cancer if the tumor-associated eligibility criteria are fulfilled.
Kindlicher Schwindel – Klinik und Verlauf
Authors: Schnabel Lutz , Dunker Konstanze , Huppert Doreen
Published: February 2023

Hintergrund

Schwindel ist auch im Kindesalter ein häufiges Symptom.

Ziel der Arbeit

Übersicht über Klinik und Verlauf kindlicher Schwindelsyndrome.

Material und Methoden

Auswertung der Hauptdiagnosen von Kindern und Jugendlichen im Deutschen Schwindel- und Gleichgewichtszentrum, LMU München, im Zeitraum Januar 2016 bis Juni 2021; Zusammenstellung relevanter Schwindelsyndrome im Kindesalter.

Ergebnisse

Häufigste Diagnose ist die vestibuläre Migräne, gefolgt von funktionellem Schwindel.

Schlussfolgerungen

In den meisten Fällen ist Schwindel bei Kindern auf gutartige Erkrankungen zurückzuführen und gut zu behandeln. Wichtig ist, seltene und schwerwiegende Ursachen zu erfassen, um eine adäquate Therapie einleiten zu können.
Combined effect of the interlayer temperature with travel speed on features of thin wall WAAM under two cooling approaches
Authors: Teixeira Felipe Ribeiro , Scotti Fernando Matos , Jorge Vinicius Lemes , Scotti Américo
Published: February 2023

This work presents the evaluation of the interlayer temperature (IT) with travel speed (TS) combined effect for a given wire feed speed (WFS) on operational, geometrical, and metallurgical features of thin walls with the same width deposited by wire arc additive manufacturing (WAAM) with a low alloy steel, using or not active cooling. A preliminary experimental design was carried out to define a range of IT that could prevent the molten pool from running down and, then, be used in the main experimental design. The main tests were planned and performed to find different IT and TS combinations for a given WFS capable of depositing walls with the same target effective wall width. After selecting the parameters, six walls were deposited, three under natural cooling (NC) and three under near immersion active cooling (NIAC). A more significant temperature variability along the layer length (ΔT/ΔLL) is observed in increasing IT-TS combination and under NIAC. Regardless of the cooling approach, a worse surface aspect was observed with lower IT and TS. However, NC or NIAC do not affect the wall width (effective or external) or the layer height. On the other hand, they are affected by the IT with TS combination. A shorter production time was obtained on the walls with NIAC and higher IT-TS. No marked microstructural differences were observed comparing the walls, regardless of the cooling approach. However, microstructure tempering (hardness reduction) was observed in the walls deposited with NC using higher IT levels.
Robotically assisted laparoscopic lateral suspension: a step-by-step approach aiming to standardize a novel procedure
Authors: Lange Sören , Chatziioannidou Kyriaki , Dällenbach Patrick
Published: February 2023

Introduction and hypothesis

The aim of this video is to show a step-by-step approach to robotically assisted laparoscopic lateral suspension for pelvic organ prolapse aiming to standardize this procedure.

Methods

This video shows a robotically assisted laparoscopic approach to a POP-Q stage 3 prolapse with a combined anterior and apical defect. First, the trocars are positioned, with one 8-mm trocar, two lateral trocars 5 cm above the anterior–superior iliac spine, and a 10-mm assistant trocar either paraumbilically or suprapubically. Second, the uterovesical pouch is dissected up to 2 cm above the level of the bladder neck. The mesh is then fixed to the vesicovaginal fascia and to the isthmus uteri. Next, a laparoscopic forceps is inserted retroperitoneally through the lateral trocars and the lateral arms of the mesh are pulled retroperitoneally. The peritoneum of the uterovesical fold is sutured, including round ligament plication. Finally, the lateral arms of the peritoneum are fixed to the peritoneum of the abdominal wall.

Conclusions

Robotically assisted laparoscopic lateral suspension is a safe alternative to laparoscopic and robotically assisted laparoscopic sacropexy and very well suited for uterine-preserving POP surgery. This video contributes to the standardization of this procedure, and we believe our video to be useful in helping urogynecologists to perform this innovative procedure.
Efficient PFAS prioritization in non-target HRMS data: systematic evaluation of the novel MD/C-m/C approach
Authors: Zweigle Jonathan , Bugsel Boris , Zwiener Christian
Published: February 2023

Non-target screening (NTS) based on high-resolution mass spectrometry (HRMS) is necessary to comprehensively characterize per- and polyfluoroalkyl substances (PFAS) in environmental, biological, and technical samples due to the very limited availability of authentic PFAS reference standards. Since in trace analysis, MS/MS information is not always achievable and only selected PFAS are present in homologous series, further techniques to prioritize measured HRMS data (features) according to their likelihood of being PFAS are highly desired due to the importance of efficient data reduction during NTS. Kaufmann et al. (J AOAC Int, 2022) presented a very promising approach to separate selected PFAS from sample matrix features by plotting the mass defect (MD) normalized to the number of carbons (MD/C) vs. mass normalized to the number of C (m/C). We systematically evaluated the advantages and limitations of this approach by using ~ 490,000 chemical formulas of organic chemicals (~ 210,000 PFAS, ~ 160,000 organic contaminants, and 125,000 natural organic matter compounds) and calculating how efficiently, and especially which, PFAS can be prioritized. While PFAS with high fluorine content (approximately: F/C > 0.8, H/F < 0.8, mass percent of fluorine > 55%) can be separated well, partially fluorinated PFAS with a high hydrogen content are more difficult to prioritize, which we discuss for selected PFAS. In the MD/C-m/C approach, even compounds with highly positive MDs above 0.5 Da and hence incorrectly assigned to negative MDs can still be separated from true negative mass defect features by the normalized mass (m/C). Furthermore, based on the position in the MD/C-m/C plot, we propose the estimation of the fluorine fraction in molecules for selected PFAS classes. The promising MD/C-m/C approach can be widely used in PFAS research and routine analysis. The concept is also applicable to other compound classes like iodinated compounds.

Graphical Abstract
Weyl remainders: an application of geodesic beams
Authors: Canzani Yaiza , Galkowski Jeffrey
Published: February 2023

We obtain new quantitative estimates on Weyl Law remainders under dynamical assumptions on the geodesic flow. On a smooth compact Riemannian manifold (M, g) of dimension n, let $$\Pi _\lambda $$

Π
λ

denote the kernel of the spectral projector for the Laplacian, $$\mathbb {1}_{[0,\lambda ^2]}(-\Delta _g)$$

1

[
0
,

λ
2

]

(
-

Δ
g

)

. Assuming only that the set of near periodic geodesics over $${W}\subset M$$

W
⊂
M

has small measure, we prove that as $$\lambda \rightarrow \infty $$

λ
→
∞

$$\begin{aligned} \int _{{W}} \Pi _\lambda (x,x)dx=(2\pi )^{-n}{{\,\textrm{vol}\,}}_{_{{\mathbb {R}}^n}}\!(B){{\,\textrm{vol}\,}}_g({W})\,\lambda ^n+O\Big (\frac{\lambda ^{n-1}}{\log \lambda }\Big ), \end{aligned}$$

∫
W

Π
λ

(
x
,
x
)

d
x
=

(
2
π
)

-
n

vol

R

n

(
B
)

vol

g

(
W
)

λ
n

+
O

(

λ

n
-
1

log
λ

)

,

where B is the unit ball. One consequence of this result is that the improved remainder holds on all product manifolds, in particular giving improved estimates for the eigenvalue counting function in the product setup. Our results also include logarithmic gains on asymptotics for the off-diagonal spectral projector $$\Pi _\lambda (x,y)$$

Π
λ

(
x
,
y
)

under the assumption that the set of geodesics that pass near both x and y has small measure, and quantitative improvements for Kuznecov sums under non-looping type assumptions. The key technique used in our study of the spectral projector is that of geodesic beams.
Adoption of Lutetium-177 PSMA radioligand therapy for metastatic castration resistant prostate cancer: a total population analysis in Germany from 2016 to 2020
Authors: Flegar Luka , Thoduka Smita George , Librizzi Damiano , Luster Markus , Zacharis Aristeidis , Heers Hendrik , Eisenmenger Nicole , Ahmadzadehfar Hojjat , Eiber Matthias , Weber Wolfgang , Groeben Christer , Huber Johannes
Published: February 2023

Purpose

This study is to investigate the adoption and current trends of Lutetium-177 PSMA RLT for mCRPC in Germany.

Methods

We analyzed data from the reimbursement.INFO tool based on German hospitals’ quality reports for Lutetium-177 PSMA RLT from 2016 to 2020 and from the nationwide German hospital billing database (Destatis) for general therapy with open radionuclides in combination with prostate cancer from 2006 to 2020. For validation of these billing data, we included the 177Lu-PSMA RLT cycles from two participating institutions from 2016 to 2020. For detection of trends over time we applied linear regression models.

Results

General therapy with open radionuclides increased from 2006 to 2020. We identified a total of 12,553 177Lu-PSMA RLT cycles. The number of 177Lu-PSMA RLTs steadily increased from a total of 1026 therapies in 2016 to 3328 therapies in 2020 (+ 576 RLT/year; p < 0.005). In 2016, 25 departments of nuclear medicine offered this treatment, which increased to 44 nuclear medicine departments in 2020. In 2016, 16% of nuclear medicine departments (4/25) performed more than 100 177Lu-PSMA RLTs, which increased to 36% (16/44) in 2020 (p < 0.005). In 2016, 88% (22/25) of 177Lu-PSMA RLTs were performed at a university hospital, which decreased to 70% (31/44) in 2020. The proportion of patients older than 65 years receiving 177Lu-PSMA RLT increased from 78% in 2016 to 81% in 2020.

Conclusion

Treatment of mCRPC with 177Lu-PSMA RLT has been rapidly increasing in Germany in the recent years providing an additional therapy option. This development is remarkable, because of outstanding formal EMA approval.
Improving Nitrogen Acquisition and Utilization Through Root Architecture Remodelling: Insight from Legumes
Authors: Nadeem Muhammad , Yahya Muhammad , Tong Jingyang , Shah Liaqut , Khan Sana Ullah , Ali Ahmad , Sher Alam , Ullah Najeeb , Waheed Abdul
Published: February 2023

In crop species, nutrient deficiency severely damages plant growth and developmental processes, leading to end-yield penalties. Root architecture remodelling is considered a key factor underpinning nutrient-poor soil environments. Adequate nitrogen (N) supply can play a significant role in sustaining crop productivity on nutrient-deficient soils. However, excessive application of nitrogenous fertilizer may pollute the soil and increase the production cost for the growers. To tackle this problem, crop breeders have made tremendous efforts to improve the N-use efficiency of agricultural crops. This article summarizes the recent progress in identifying QTLs/genes, regulatory pathways, and hormonal crosstalk involved in the growth and development of legumes roots system. Moreover, we have described the progress in microbe–root symbiosis via QTLs/genes regulations, which results in improved N acquisition. Understanding the molecular mechanisms that regulate the root architecture in response to N availability may help to strengthen the root system of legumes and promote environmental friendly and sustainable agriculture.
Sarcopenia of kidney transplant recipients as a predictive marker for reduced graft function and graft survival after kidney transplantation
Authors: Karakizlis H. , Trudel N. , Brose A. , Reinisch A. , Reichert M. , Hecker A. , Bender F. , Askevold I. , Rainer L. , Weimer R. , Krombach G. A. , Padberg W. , Liese J.
Published: February 2023

Purpose

The association between sarcopenia of kidney transplant recipients and outcome after kidney transplantation (KT) has not yet been fully understood and is still considered controversial. The aim of our study was to analyze the impact of pre-transplant sarcopenia on graft function, postoperative complication rates, and survival of the patients after renal transplantation.

Methods

In this retrospective single-center study, all patients who underwent KT (01/2013–12/2017) were included. Demographic data, rejection rates, delayed graft function, and graft and patient survival rates were analyzed. Sarcopenia was measured in computed tomography images by the sex-adjusted Hounsfield unit average calculation (HUAC).

Results

During the study period, 111 single KTs (38 women and 73 men) were performed. Living donor kidney transplants were performed in 48.6%. In total, 32.4% patients had sarcopenia. Sarcopenic patients were significantly older (59.6 years vs. 49.8 years; p < 0.001), had a higher body mass index (BMI = 27.6 kg/m2 vs. 25.0 kg/m2; p = 0.002), and were more likely to receive deceased donor kidneys (72.2% vs. 41.3%; p = 0.002). Interestingly, 3 years after KT, the creatinine serum levels were significantly higher (2.0 mg/dl vs. 1.5 mg/dl; p = 0.001), whereas eGFR (39.9 ml/min vs. 53.4 ml/min; p = 0.001) and graft survival were significantly lower (p = 0.004) in sarcopenic transplant recipients. Sarcopenic patients stayed in hospital significantly longer postoperatively than those who were non-sarcopenic.

Conclusions

At the time of kidney transplantation, sarcopenia was found to predict reduced long-term graft function and diminished graft survival after KT. The early identification of sarcopenic patients can not only enable an optimized selection of recipients, but also the initiation of pre-habilitation programs during the waiting period.
Random transposon mutagenesis identifies genes essential for transformation in Methanococcus maripaludis
Authors: Fonseca Dallas R. , Loppnow Madison B. , Day Leslie A. , Kelsey Elisa L. , Abdul Halim Mohd Farid , Costa Kyle C.
Published: February 2023

Natural transformation, the process whereby a cell acquires DNA directly from the environment, is an important driver of evolution in microbial populations, yet the mechanism of DNA uptake is only characterized in bacteria. To expand our understanding of natural transformation in archaea, we undertook a genetic approach to identify a catalog of genes necessary for transformation in Methanococcus maripaludis. Using an optimized method to generate random transposon mutants, we screened 6144 mutant strains for defects in natural transformation and identified 25 transformation-associated candidate genes. Among these are genes encoding components of the type IV-like pilus, transcription/translation associated genes, genes encoding putative membrane bound transport proteins, and genes of unknown function. Interestingly, similar genes were identified regardless of whether replicating or integrating plasmids were provided as a substrate for transformation. Using allelic replacement mutagenesis, we confirmed that several genes identified in these screens are essential for transformation. Finally, we identified a homolog of a membrane bound substrate transporter in Methanoculleus thermophilus and verified its importance for transformation using allelic replacement mutagenesis, suggesting a conserved mechanism for DNA transfer in multiple archaea. These data represent an initial characterization of the genes important for transformation which will inform efforts to understand gene flow in natural populations. Additionally, knowledge of the genes necessary for natural transformation may assist in identifying signatures of transformation machinery in archaeal genomes and aid the establishment of new model genetic systems for studying archaea.