bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting intracellular cancer proteins with tumor‐microenvironment‐responsive bispecific nanobody‐PROTACs for enhanced therapeutic efficacy
Authors: Deng Changping , Ma Jiacheng , Liu Yuping , Tong Xikui , Wang Lei , Dong Jiayi , Shi Ping , Wang Meiyan , Zheng Wenyun , Ma Xingyuan
Published: January 2025

Proteolysis targeting chimeras (PROTACs) are pivotal in cancer therapy for their ability to degrade specific proteins. However, their non‐specificity can lead to systemic toxicity due to protein degradation in normal cells. To address this, we have integrated a nanobody into the PROTACs framework and leveraged the tumor microenvironment to enhance drug specificity. In this study, we engineered BumPeD, a novel bispecific nanobody‐targeted PROTACs‐like platform, by fusing two nanobodies with a Furin protease cleavage site (RVRR) and a degron sequence (ALAPYIP or KIGLGRQKPPKATK), enabling the tumor microenvironment to direct the degradation of intracellular proteins. We utilized KN035 and Nb4A to target PD‐L1 (programmed death ligand 1) on the cell surface and intracellular Survivin, respectively. In vitro experiments showed that BumPeD triggers Survivin degradation via the ubiquitin‐proteasome pathway, inducing tumor apoptosis and suppressing bladder tumor cell proliferation and migration. In vivo experiments further confirmed BumPeD's robust anti‐tumor efficacy, underscoring its potential as a precise protein degradation strategy for cancer therapy. Our platform provides a systematic approach to developing effective and practical protein degraders, offering a targeted theoretical basis and experimental support for the development of novel degradative drugs, as well as new directions for cancer therapy.
A Geometric Interpretation for the Algebraic Properties of Second‐Order Ordinary Differential Equations
Authors: Paliathanasis A. , Moyo S. , Leach P. G. L.
Published: January 2025

Nowadays, a substantial portion of investigations concerning the symmetry analysis of differential equations predominantly adhere to a framework comprising the following key procedures: (i) the derivation of symmetries, (ii) the determination of an optimal system, (iii) the utilization of these symmetries to construct invariants or conservation laws, facilitating reductions, and where applicable, (iv) the construction of solutions. This reinforces the understanding of symmetry analysis and explores the application of differential geometry and physics to the analysis of selected problems. A demonstration of the utility of symmetries in offering concise solutions for previously extensively studied problems is given with the specific linearization of the Ermakov–Pinney equation and that of another nonmaximal symmetric equation, showcasing how differential geometry can chart novel pathways in the realm of symmetry analysis is given.
A Generalized Single‐Step Multi‐Stage Time Integration Formulation and Novel Designs With Improved Stability and Accuracy
Authors: Wang Yazhou , Adams Nikolaus A. , Tamma Kumar K.
Published: January 2025

This paper focuses upon the single‐step multi‐stage time integration methods for second‐order time‐dependent systems. Firstly, a new and novel generalization of the Runge‐Kutta (RK) and Runge‐Kutta‐Nyström (RKN) methods is proposed, featuring an advanced Butcher table for designing new and optimal algorithms. It encompasses not only the classical multi‐stage methods as subsets, but also introduces novel designs with enhanced accuracy, stability, and numerical dissipation/dispersion properties. Secondly, to sharpen the focus on the present developments, several existing multi‐stage explicit time integration methods (which are of interest and the focus of this paper) are revisited within the proposed unified mathematical framework, such that it highlights the differences, advantages, and disadvantages of various existing methods. Thirdly, the consistency analysis is rigorously demonstrated using both single‐step and multi‐step local truncation errors, addressing the order reduction problem observed in existing methods when applied to nonlinear dynamics problems. Finally, two sets of single‐step, two‐stage, third‐order time‐accurate schemes with controllable numerical dissipation/dispersion at the bifurcation point are presented. In contrast to existing methods, these newly proposed schemes preserve third‐order time accuracy in nonlinear dynamics applications and exhibit improved stability in cases involving physical damping. Numerical examples are demonstrated to verify the theoretical analysis and the superior performance of the proposed schemes compared to existing methods.
Factors Influencing Nursing Interns' Engagement in Fall Prevention Activities in Saudi Arabia
Authors: Asiri Saeed , Kerari Ali
Published: January 2025

Aim

To assess the knowledge, attitudes and engagement of nursing interns regarding fall prevention activities during their internship within hospital settings.

Design

This study used a cross‐sectional design.

Methods

This was a cross‐sectional, descriptive, correlational study. A convenience sample of 187 nursing interns was recruited from three hospitals in Riyadh, Saudi Arabia. A questionnaire was administered to the participants to collect data on their demographics, knowledge, attitudes and engagement in fall prevention. The collected data were analysed using descriptive and inferential statistics.

Results

The participants exhibited insufficient knowledge, relatively negative attitudes and acceptable fall prevention engagement. There was a low‐to‐moderate positive association only between attitude and fall prevention engagement. Moreover, hierarchical multiple regression analysis showed that attitude was the only predictor for fall prevention engagement.

Conclusion

Fall prevention is an important subject that needs more attention from nursing programmes in universities and preceptorship programmes in hospitals to enhance nursing interns' attitudes, knowledge and practices in this regard.

Relevance to Clinical Practice

The findings of this research could be beneficial for clinical coordinators and faculty members to enhance nursing interns' engagement in preventing falls among at‐risk patients.

Patient or Public Contribution

Participants were not involved in the design, conduct, reporting or dissemination of this research.
Development and validation of the Food Noise Questionnaire
Authors: Diktas Hanim E. , Cardel Michelle I. , Foster Gary D. , LeBlanc Monique M. , Dickinson Stephanie L. , Ables Erin M. , Chen Xiwei , Nathan Rebecca , Shapiro Danielle , Martin Corby K.
Published: January 2025

Objective

Food noise has received attention in the media, although no validated questionnaires exist to measure it. This study developed and tested the reliability and validity of the Food Noise Questionnaire (FNQ).

Methods

Participants (N = 400) successfully completed, the FNQ and a demographic questionnaire and self‐reported weight and height. A subsample (n = 150) completed the FNQ 7 days later for test–retest reliability, and this subsample's first FNQ data were subjected to exploratory factor analysis. The remaining subsample (n = 250) completed two preoccupation with food questionnaires to test convergent validity, along with mood, anxiety, and stress questionnaires to test for discriminant validity. Confirmatory factor analysis was conducted using this subsample's FNQ data.

Results

Data from 396 participants were analyzed (4 participants did not complete all FNQ items). The FNQ had excellent internal consistency reliability (Cronbach α = 0.93) and high test–retest reliability (r = 0.79; p < 0.001; mean [SD] = 7.4 [1.0] days between administration). Factor analyses found that the five FNQ items loaded onto a single factor, with good fit indices (χ2[5] = 52.87, p < 0.001; root mean square error of approximation [RMSEA] = 0.20; comparative fit index [CFI] = 0.95; standardized root mean squared residual [SRMR] = 0.03). The FNQ showed good convergent (all r > 0.78; p < 0.001) and discriminant (all r < 0.39; p < 0.001) validity.

Conclusions

The FNQ provides a psychometrically reliable and valid measure of food noise, although further research is needed to evaluate its clinical utility.
Aligning strategic and participatory approaches to agri‐environment scheme design and implementation to enhance nature recovery outcomes
Authors: Baker D. J. , Nye C. , Wheeler R. , Masquelier C. , Binner A. , Gaston K. J. , Heard M. S. , Lobley M. , Smith D. , Maclean I. M. D.
Published: January 2025

Nature recovery requires the provisioning of resources in the right place and in sufficient quantities to support wildlife populations and improve ecological processes. Agri‐environment schemes (AES) have been a major mechanism for delivering environmental management across EU‐farmed landscapes, but measured benefits to nature are often negligible in large part due to a lack of strategic spatial targeting of management actions.

As an example, AES in England are often delivered using a participatory strategy, typically at individual farm scale, with types of management agreements and uptake reflecting the business model and interests of each farm. However, this implementation model can result in poorly distributed conservation resources and, consequently, a failure to recover nature across larger scales, even if individual agreements are delivered well.

Achieving effective, large‐scale nature recovery through AES requires aligning its implementation with spatially targeted approaches that prioritise specific conservation goals. We discuss the rationale for, and major barriers to, aligning AES design and implementation to these approaches. We then highlight how, through the framework of systematic conservation planning, both the strategic and participatory components of AES could be aligned better to enhance nature recovery outcomes.

To ensure AES help achieve nature recovery goals, clear and measurable targets must be set with the type and spatial configuration of actions designed to enable meeting targets. Strategic spatial targeting must also be carried out with the implementation phase in mind, accounting for socio‐economic opportunities and barriers to engagement and acknowledging that uncertainties around farm‐scale implementation mean plans must be adaptable. Participatory approaches for AES design and implementation that support the delivery of spatially targeted management actions are required, most notably by facilitating collaboration or cooperation across farm holdings.

For AES to contribute effectively to nature recovery goals, aligning strategic and participatory approaches in its design and implementation is crucial. This requires uniting knowledge across disciplines and cultures and ensuring that information is shared to support progressive refinement of scheme design and guidance towards achieving overall nature recovery goals.

Read the free Plain Language Summary for this article on the Journal blog.
Comparative Efficacy of Different Cognitive Behavior Therapy Delivery Formats for Depression in Patients With Cancer: A Network Meta‐Analysis of Randomized Controlled Trials
Authors: Duan Liyang , Zhang Shu , Yan Qianwen , Hu Xiaolin
Published: January 2025

Background

Cognitive behavior therapy (CBT) has been shown to be effective in improving depression in patients with cancer. However, diversity exists in the CBT delivery formats, and the optimal delivery format remains unconfirmed.

Objectives

To compare the efficacy of different delivery formats of CBT interventions on depression in patients with cancer.

Design

Network meta‐analysis of randomized controlled trials.

Data Source

Six databases, including PubMed, Web of Science, Embase, CINAHL, the Cochrane Central Register of Controlled Trials and PsycINFO, were searched from inception to May 30, 2024.

Methods

Two reviewers independently conducted study inclusion, data extraction, and risk of bias assessment. A pairwise meta‐analysis and a network meta‐analysis were performed sequentially to determine the efficacy of CBT delivery formats for improving depression in patients with cancer.

Results

A total of 34 randomized controlled trials involving six delivery formats of CBT were included. Face‐to‐face group CBT (SMD = −0.88, 95% CI [−1.33, −0.44]), internet‐based individual CBT (SMD = −0.49, 95% CI [−0.92, −0.06]), app‐based individual CBT (SMD = −0.81, 95% CI [−1.45, −0.18]), and combined delivery formats of CBT for individual (SMD = −0.35, 95% CI [−0.62, −0.09]) were significantly more effective than the inactive control. The ranking probabilities revealed that face‐to‐face group CBT (P‐score = 0.86), app‐based individual CBT (P‐score = 0.74) and internet‐based individual CBT (P‐score = 0.57) were the three most effective delivery formats of CBT.

Conclusions

This study revealed the efficacy ranking of different CBT delivery formats in improving depression in patients with cancer. These findings are expected to provide evidence‐based support for future research and clinical decision making for improving depression in patients with cancer.

Trial Registration

PROSPERO (CRD42024553977)
Cognitive‐Behavioral Intervention for Children With Hematological Cancer Receiving Chemotherapy: A Randomized Controlled Trial
Authors: Melesse Tenaw Gualu , Li William Ho Cheung , Chau Janita Pak Chun , Yimer Mulugeta Ayalew , Gidey Abdulkadir Mohamedsaid , Yitayih Sewbesew
Published: January 2025

Objective

Cognitive‐behavioral intervention (CBI) has shown positive effects in improving psychological and health‐related outcomes in children with cancer. However, no evidence has been found in Ethiopia. This study aimed to evaluate the effects of CBI on anxiety, depression and quality of life (QoL) in Ethiopian children with hematological cancer receiving chemotherapy.

Methods

A parallel, two‐armed, assessor‐blinded, randomized controlled trial was conducted among 76 children randomized (1:1) to receive CBI or usual medical care. The intervention group received five weekly face‐to‐face CBI sessions of 30–40 min each, which included an introduction to CBI; identifying and challenging maladaptive thoughts, beliefs and behavior; behavior activation; deep breathing exercises; and treatment evaluation and relapse prevention. The outcomes were measured at baseline (T0), immediately post‐intervention (T1) and 1 month post‐intervention (T2).

Results

The intervention group showed a significant reduction in anxiety scores from T0 at T1 (β = −6.67, 95% CI [−9.16, −4.19], p < 0.001) and T2 (β = −8.14, 95% CI [−10.70, −5.57], p < 0.001), depression at T1 (β = −4.09, 95% CI [−6.94, −1.23], p = 0.005) and T2 (β = −6.12, 95% CI [−9.10, −3.13], p < 0.001) and improvement in QoL at T2 (β = 3.02, 95% CI [0.49, 5.56], p = 0.019) compared with the control group.

Conclusions

CBI has positive effects in reducing anxiety and depression and in improving QoL in children with hematological cancer receiving chemotherapy. The results suggest the need to incorporate CBI into pediatric hematology‐oncology and studies on its long‐term effects and cost‐effectiveness are warranted.

Trial Registration: ClinicalTrials.gov (NCT05270655). Registered on 08 March 2022.
Detection of Dense Subhypergraphs by Low‐Degree Polynomials
Authors: Dhawan Abhishek , Mao Cheng , Wein Alexander S.
Published: January 2025

Detection of a planted dense subgraph in a random graph is a fundamental statistical and computational problem that has been extensively studied in recent years. We study a hypergraph version of the problem. Let denote the ‐uniform Erdős–Rényi hypergraph model with vertices and edge density . We consider detecting the presence of a planted subhypergraph in a hypergraph, where and . Focusing on tests that are degree‐ polynomials of the entries of the adjacency tensor, we determine the threshold between the easy and hard regimes for the detection problem. More precisely, for , the threshold is given by , and for , the threshold is given by . Our results are already new in the graph case , as we consider the subtle log‐density regime where hardness based on average‐case reductions is not known. Our proof of low‐degree hardness is based on a conditional variant of the standard low‐degree likelihood calculation.
Structural and Morphological Study of MnOx‐C Nanocomposite on Calcination Temperature Dependence
Authors: Hamana Djamel , Zemieche Abdelmalik , Chetibi Loubna , Frégnaux M. , Achour S.
Published: January 2025

Nanosized manganese oxides are considered among the most promising materials for energy storage devices and cancer theranostic applications. Their properties can be significantly influenced by their structural, morphological, and oxidation characteristics at the nanoscale. In this work, Mn oxide‐C nanocomposites (in the range of 10 nm) are synthesized using a green route. Olive leaf extract is used as an organic medium, reducing agent, and carbon source. The prepared nanopowders are then calcined at various temperatures within the typical range for Mn oxides (from 200°C to 1000°C). Phase transitions, as well as structural and morphological properties, are studied using differential scanning calorimetry (DSC), ex situ x‐ray diffraction (XRD), transmission electron microscopy (TEM), and high‐resolution transmission electron microscopy (HRTEM). The oxidation state of Mn ions is analyzed across this temperature range using x‐ray photoelectron spectroscopy (XPS), which is also used to study the carbon film on the Mn oxide surface. This carbon film is further studied using EDS‐TEM mapping. Many phase transformations are observed during heating from room temperature to 1000°C. At 1000°C, particles reduce in size to 9.5 nm and regain a spherical shape, reflecting the formation of Mn₃O₄ alongside Mn₂O₃. XPS reveals significant changes in the oxidation states of manganese and the carbon environments in the nanoparticles.
Anode‐Free Zinc–Bromine Batteries Enabled by a Simple Prenucleation Strategy
Authors: Han Bibo , Zheng Xinhua , Liu Shikai , Wu Song , Yang Jiashuo , Xu Sankui , Liu Zaichun , Wang Rui , Wang Faxing , Wu Yuping
Published: January 2025

The design of anode‐free zinc (Zn) batteries with high reversibility at high areal capacity has received significant attention recently, which is quietly challenging yet. Here, a Zn alloyed interface through electroplating is introduced, providing homogeneous Zn prenucleation sites to stabilize subsequent Zn nucleation and plating. By employing Zn–Cu alloy as a module, the complementary simulations and characterizations confirm that the prenucleation alloyed interfaces achieve a homogeneous electric field distribution and greatly enhance the stability of the Zn anode. Accordingly, the Zn//Zn–Cu@Cu half‐cells show a long cycle life of over 900 h and an average Coulombic efficiency (CE) of 99.8% at an areal capacity of 10 mAh cm−2. The assembled anode‐free zinc–bromine (Zn–Br2) battery exhibits an attractive stable cycling of 11 000 cycles at 1 mAh cm−2, while over 1000 cycles at the higher areal capacity of 10 mAh cm−2. Excitingly, the Zn–Br2 pouch cell with a capacity of 1000 mAh operates stably over 50 cycles, and achieves successful integration with photovoltaic systems. This anode‐free Zn–Br2 batteries constructed through a prenucleation strategy offer new insights into the potential for large‐scale energy storage applications.
Self‐Powered Filterless Narrowband UV Photodetection Triggered by Asymmetric Charge Carrier Generation in a Wide‐Bandgap Halide Perovskite Ferroelectric
Authors: Li Kai , Wu Fafa , Li Xiaoqi , Li Bingxuan , Sun Zhihua , Wang Xinqiang , Liu Xitao , Luo Junhua
Published: January 2025

Narrowband photodetection with selective light detection in ultraviolet (UV) range is particularly pronounced in specialized applications such as targeted wavelength imaging and UV‐phototherapy. In contrast to conventional strategies, ferroelectric materials with pronounced bulk photovoltaic effect (BPVE) provide a novel asymmetric carrier generation concept for achieving filterless spectrally selective photodetection. Herein, for the first time, the realization of self‐powered filterless narrowband UV photodetection is demonstrated in bulk single crystals of a newly developed halide perovskite ferroelectric, 2FEA2EA2Pb2Cl10 (2FEEPC), which exhibits a wide bandgap of 3.36 eV and a remarkable spontaneous polarization (≈3.5 µC cm−2). Benefiting from the strongly distorted inorganic framework with asymmetric delocalized electronic states, 2FEEPC demonstrates a highly wavelength‐dependent BPVE along the polar direction, showing a high narrowband detecting performance with a response peak at UV wavelength of 355 nm and a full‐width‐at‐half‐maximum (FWHM) of ≈15 nm. More interestingly, the ferro‐pyro‐phototronic effect of 2FEEPC endows a colossal gain of up to 600% for photopyroelectric current. This work presents an unprecedented approach to achieve self‐powered filterless narrowband photodetection, thereby shedding light on the development of photosensitive ferroelectrics for spectrally photoelectric applications.
Quality‐in‐Use in Practice: A Study for Context‐Aware Software Systems in Pervasive Environments
Authors: Salomón Sergio , Duque Rafael , Bringas Santos , de Oliveira Káthia Marçal
Published: January 2025

Software quality models have increasingly emphasized human factors and user needs. In 2011, ISO/IEC 25010 introduced the quality‐in‐use (QinU) model, designed to evaluate software quality as an outcome of a user utilizing a system through the evaluation of five characteristics: effectiveness, efficiency, freedom from risk, satisfaction, and context coverage. As a generic reference, this standard has been customized for various software types (e.g., web portals and artificial intelligence systems). This article presents a customization for context‐aware software systems (CASSs), which are software systems that interpret and use context information (regarding the user, the software application features, and the environment) to adapt their functionalities. We are particularly interested in CASS for pervasive, or ubiquitous, environments. To address this goal, each QinU characteristic was analyzed by professionals from the academy and industry, taking into account the CASS features for pervasive/ubiquitous environments. A cyclical process of definition, revision, and improvement based on measurement theory was carried out before empirical validation in case studies. As the main result, a novel set of QinU measures specifically tailored for CASSs in a pervasive environment is provided, considering not only the classic explicit user interactions (e.g., mouse clicks and text input) but also the implicit interactions during everyday activities (e.g., walking or driving), captured through sensors and processed to support the user (e.g., recommending nearby museums and providing driving guidance). This set of measures supports CASS assessment and improvements, offering more accurate and context‐sensitive quality measurement.
Toxoplasmosis in a 9‐month‐old Persian cat treated with prednisolone and ciclosporin for an idiopathic pure red cell aplasia
Authors: Da Silva Adrien , Cuq Benoît
Published: January 2025

A 9‐month‐old Persian cat was presented with an acute onset of lethargy and decreased appetite. Investigations identified presence of a severe non‐regenerative anaemia. Bone marrow cytology and histopathology were consistent with a pure red cell aplasia. Prednisolone and ciclosporin were initiated, but the cat presented with an acute onset of dyspnoea 2 months after diagnosis despite good control of the haematocrit. Respiratory work‐up including a bronchoalveolar lavage identified a pulmonary toxoplasmosis. The cat underwent a cardiopulmonary arrest shortly after diagnosis. We describe the good response of a cat diagnosed with pure red cell aplasia to prednisolone and ciclosporin. Unfortunately, the cat was diagnosed with toxoplasmosis 2 months after diagnosis despite being indoor and being fed a commercial diet. Toxoplasma gondii IgG serology test was negative, suggesting acute infection. This case emphasises the importance of close monitoring of cats undergoing ciclosporin therapy and risk of acquired infection in immunosuppressed feline patients.
Aspects of elastic deformation and nanomaterials past a deviating cone and wedge elongational surfaces driven by a waste discharge concentration
Authors: Vinutha Kalleshachar , Srilatha Pudhari , Zaib Aurang , Madhukesh Javali Kotresh , Khan Umair , Hassan Mehboob Ul
Published: January 2025

This existing work has several beneficial advantages in science and engineering including developing more efficient cooling systems, elastic deformation has a substantial application in the ceramic foam and plastic industries. Environmental applications require waste discharge concentration through a different geometry (Cone and Wedge). The current article examines the influence of a magnetic field (MF) on nanofluid passing through a cone and wedge with mass and heat transmission. Solving nonlinear partial differential equations (PDEs) that employ similarity transformations to transform into a collection of ordinary differential equations. The temperature equation considers physical aspects like elastic deformation, while the concentration equation considers external sources of local contaminants. Using numerical methods (Runge–Kutta–Fehlberg 4th 5th and shooting method), ordinary differential equations and related reduced boundary conditions (BCs) are solved. Plots are used to illustrate the significance of dimensionless constraints and their effects. The novel outcomes show that increases in elastic deformation constraint decrease the temperature distribution, and a rise in the local pollutant external source increases the concentration profile. The rate of mass and heat transfer, as well as fluid surface drag force, is enhanced by including solid volume fraction in combination with other parameters. The cone performs well in the rate of heat transfer and fluid surface drag force, while the wedge is in the rate of mass transmission. The study's outcomes are helpful in several practical applications, including enhanced cooling systems, environmental remediation, processing of materials, and nanotechnology.
Bothersome Pelvic Floor Dysfunction and Quality of Life During Pregnancy and Postpartum in Primiparous Women
Authors: Nestor Sofia , Brynhildsen Jan , Hiyoshi Ayako , Jansson Markus Harry
Published: January 2025

Introduction and Hypothesis

This is a prospective cohort study based on the hypothesis that pregnancy and childbirth are associated with the occurrence of bothersome pelvic floor dysfunction (PFD), which impairs health-related quality of life (HRQoL).

Methods

Primiparous women completed a questionnaire including questions about bothersome PFD and HRQoL in early pregnancy, late pregnancy, 8 weeks postpartum, and 12 months postpartum. HRQoL was measured using the Incontinence Impact Questionnaire, Short Form (IIQ-7). The association between bothersome urinary incontinence (UI) 1 year postpartum and maternal and delivery characteristics was examined using generalized linear models.

Results

The study sample comprised 851 women. The prevalence of bothersome UI increased from 0.7% in early pregnancy to 8.1% at 1 year postpartum. At 1 year postpartum, 22.8% of the women reported PFD with impairment in HRQoL, with a median IIQ-7 score of 14.3. Bothersome UI in late pregnancy (adjusted RR 4.51, 95% CI 1.43–14.26) and 8 weeks postpartum (adjusted RR 10.17, 95% CI 5.45–18.98) were associated with bothersome UI 1 year postpartum.

Conclusions

Most women were not bothered by UI during pregnancy and up to 1 year postpartum and did not report PFD with impairment in HRQoL. Most women who reported PFD with impairment in HRQoL had low IIQ-7 scores, but a few women reported substantial restriction in lifestyle. Bothersome UI in late pregnancy and 8 weeks postpartum was predictive of bothersome UI 1 year postpartum. This indicates the importance of the early identification of these women to provide appropriate counseling and treatment.
DNA mixture deconvolution using fully continuous models EuroForMix and EFMrep
Authors: Schiller Roberta , Fleckhaus Jan , von Máriássy Dagmar , Brune Verena , Bayer Birgit , Anslinger Katja
Published: January 2025

Background and objective

In the molecular genetic context, deconvolution describes the derivation of individual DNA profiles from a DNA mixture. Whereas mixture deconvolution is conventionally carried out manually by an expert, there are various probabilistic software applications to automate the process and two of these applications, EuroForMix (EFM) and EFMrep, are used in numerous forensic laboratories. They are particularly helpful when trace material is degraded or PCR artifacts are present and multiple replicates, if applicable from different DNA extracts, are combined for a better assessment. The aim of this study was to evaluate software-assisted deconvolution (EFM and EFMrep) with respect to correctly derived genotypes or alleles per profile in comparison to manual deconvolution based on a combination of at least two different DNA extracts per case.

Material and methods

To this end, 16 cases from former routine work were selected as examples and re-evaluated with EFM and EFMrep. In all cases, the manually derived profiles were incomplete due to the complexity of the underlying mixtures but still generated a hit in the German DNA Analysis Database (DAD). Likelihood calculations were performed for each match and the corresponding mixtures before the respective profiles were accepted as ground truth and the reference for deconvolution.

Results and conclusion

The results show that both forms of software are a useful addition to manual deconvolution, although they cannot replace it. Thus, when run in parallel they can objectively support the expert when there is uncertainty about an allele or genotype. In several cases it was shown that alleles were not correctly derived despite taking the threshold for the probability of results suggested in the current recommendations into account.
BMP6 participates in the molecular mechanisms involved in APAP hepatotoxicity
Authors: Marañón Patricia , Isaza Stephania C. , Rey Esther , Rada Patricia , García-García Yaiza , Dear James W. , García-Monzón Carmelo , Valverde Ángela M. , Egea Javier , González-Rodríguez Águeda
Published: January 2025

Given the lack of accurate diagnostic methods of acetaminophen (APAP)-induced acute liver failure (ALF), the search for new biomarkers for its diagnosis is an urgent need. The aim of this study was to evaluate the role of bone morphogenetic protein 6 (BMP6) in APAP-induced ALF progression and its potential value as a biomarker of ALF. Hepatic and circulating BMP6 expression was assessed in APAP-treated mice and in serum samples from patients with APAP overdose. In addition, BMP6 expression and release was evaluated in hepatocytes after APAP exposure. BMP6 gene was silenced in Huh7 cells prior to APAP treatment and the culture medium (CM) was added to THP1 cells to evaluate the paracrine effects of hepatocyte BMP6 on APAP toxicity. Hepatic and serum BMP6 levels were increased in mice after APAP-induced ALF. In addition, a positive correlation was observed between circulating BMP6 and ALT activity in patients exposed to APAP overdose. Moreover, hepatocytes expressed and released BMP6 to the CM after APAP treatment. Indeed, the CM from APAP-treated Huh7 cells upregulated M1 and M2 markers in THP1 monocytes. The CM from BMP6-silenced Huh7, which was depleted of BMP6, reduced the expression of M2 markers in THP1 cells. In fact, expression of M2 markers was increased in THP1 cells exposed to BMP6. This study reveals that hepatic BMP6 expression is increased in APAP-induced acute liver injury, positioning it as a potential new biomarker of liver damage severity. Moreover, our data indicate that BMP6 might play a role in the hepatocyte–macrophage crosstalk during APAP-induced hepatotoxicity.
Riemannian acceleration with preconditioning for symmetric eigenvalue problems
Authors: Shao Nian , Chen Wenbin
Published: January 2025

The analysis of the acceleration behavior of gradient-based eigensolvers with preconditioning presents a substantial theoretical challenge. In this work, we present a novel framework for preconditioning on Riemannian manifolds and introduce a metric, the leading angle, to evaluate preconditioners for symmetric eigenvalue problems. We extend the locally optimal Riemannian accelerated gradient method for Riemannian convex optimization to develop the Riemannian acceleration with preconditioning (RAP) for symmetric eigenvalue problems, thereby providing theoretical evidence to support its acceleration. Our analysis of the Schwarz preconditioner for elliptic eigenvalue problems demonstrates that RAP achieves a convergence rate of

$$1-C\kappa ^{-1/2}$$

1
-
C

κ

-
1
/
2

, which is an improvement over the preconditioned steepest descent method’s rate of

$$1-C\kappa ^{-1}$$

1
-
C

κ

-
1

. The exponent in

$$\kappa ^{-1/2}$$

κ

-
1
/
2

is sharp, and numerical experiments confirm our theoretical findings.
How I do it: Modified operation technique for MR Conditional OSIA 3: anterior based flap for covering the implant
Authors: Brill Ioana T. , Dazert Stefan
Published: January 2025

Background

The new OSIA3 is 1.5 T and 3 T MR-Conditional. Skin related issues are the most common complications. Performing MRI, the implant is exposed to magnetic torque forces, thus creating more tension over the incision lines.

Methods

We present a modified surgical technique for implanting OSI300 step-by-step. We prefer an anterior based muscle-periosteal flap to cover the implant as an integral part of the procedure.

Conclusion

The anterior based muscle-periosteal flap and performing a 3-layer-suture appears to be a safe method that does not permit skin-tension directly over the implant and may help preventing implant extrusion especially with the new OSI300.
Null-lagrangians in the micro-inertia contribution of the reduced relaxed micromorphic model. Theoretical and computational insights with applications
Authors: Erel-Demore Félix , Voss Jendrik , Neff Patrizio , Madeo Angela
Published: January 2025

This paper identifies a null-Lagrangian in the reduced relaxed micromorphic model. We show that the introduction of a micro-inertia depending on the skew-symmetric part of

$$\nabla \dot{u}$$

∇

u
˙

with the macroscopic displacement field u does not enrich the dispersion relations of the reduced relaxed micromorphic model. Reciprocally, we show that one can switch from the full micro-inertia (with both sym

$$\nabla \dot{u}$$

∇

u
˙

and skew

$$\nabla \dot{u}$$

∇

u
˙

terms) to the reduced micro-inertia (only sym

$$\nabla \dot{u}$$

∇

u
˙

) without any additional fitting. This is related to the fact that the introduction of such a skew-symmetric term is equivalent to a null-Lagrangian that leaves the bulk response unchanged while modifying the Neumann boundary conditions at the boundaries. Thus, the introduction of the skew-symmetric part of the micro-inertia, while redundant for wave dispersion, may potentially be used to improve the response of finite-size mechanical metamaterials at the homogenized macroscale due to boundary effects.
Retrospective analysis of criteria for oncological completion surgery of neuroendocrine tumors of the appendix
Authors: Wächter Sabine , Panidis Dimitrios , Jesinghaus Moritz , Rinke Anja , Heinzel-Gutenbrunner Monika , Maurer Elisabeth , Bartsch Detlef K.
Published: January 2025

Purpose

Neuroendocrine neoplasms of the appendix (aNET) are rare tumors that are often diagnosed by pathology as an incidental finding after appendectomy for acute appendicitis. Several guidelines proposed risk criteria to indicate oncological completion surgery after appendectomy. The aim of this study was to evaluate the reliability of proposed criteria for completion surgery of aNET.

Methods

Patients with aNET treated at ENETS center of excellence Marburg between 2002 and 2022 were retrieved from a prospective data base. Demographic data, histopathological findings, including formerly proposed criteria to indicate oncological completion surgery, histological results of the completion resection and disease-free survival were evaluated.

Results

82 patients with a median age of 35 (range 8–82) years were analysed. 72 (88%) patients underwent an emergency appendectomy because of acute appendicitis. 11 (13%) patients received an ileocecal resection or right hemicolectomy. Seven (8.5%) patients had lymph node metastases and three (3.6%) patients had distant metastases at the initial operation. 27 (33%) patients underwent completion surgery by right hemicolectomy according to guideline criteria, but postoperative histology detected lymph node and distant metastases in only six (22%) and zero patients resulting in an overtreatment of 21 (75%) patients. A tumor size of > 2 cm was the only significant criterion which was associated with lymph node metastases (p < 0.05). After a median follow-up of 62 months (range 2-264) 76 (96%) of the patients in stages I to III were alive with no evidence of disease.

Conclusion

aNET have an excellent prognosis in stages I-III and distant metastases are rare. Formerly proposed criteria for oncological completion surgery have to be adopted and discussed for every patient, as they might result in an overtreatment in at least 75% of patients.
Action toward sound sources enhances auditory spatial confidence: on the metacognitive consequences of reaching to sounds
Authors: Valzolgher Chiara , Lever Lisa , Rosi Tommaso , Pavani Francesco
Published: January 2025

Each perceptual process is accompanied with an evaluation regarding the reliability of what we are perceiving. The close connection between confidence in perceptual judgments and planning of actions has been documented in studies investigating visual perception. Here, we extend this investigation to auditory perception by focusing on spatial hearing, in which the interpretation of auditory cues can often present uncertainties. We asked if confidence in perceived sound position changes when we interact with the sound source by planning a sound-directed motor action (reaching) vs. a verbal response (naming). We tested 30 participants in a sound localization task in which they were both asked to localize sound sources by reaching them or by naming the labels above them in a within-participants experimental design. Participants performed the task with binaural hearing and with one ear plugged to increase errors and reduce confidence. Results showed that sound localization performance did not differ between reaching and naming, and yet participants felt more confident and required less time to complete the trial when reaching to the sources compared to naming them, regardless of the listening condition. Moreover, we found that during monaural listening the coherence between performance and confidence was reduced in each trial, irrespective of response type, suggesting increased difficulties in metacognitive monitoring. These findings suggest that, even in the case of spatial hearing, motor action planning plays a role in the formulation of confidence judgments, alongside sensory inputs and decision-making processes and stress the importance of including metacognitive measurements into spatial hearing research.
Performance evaluation of the LIOFeron®TB/LTBI IGRA for screening of paediatric LTBI and tuberculosis
Authors: Della Bella Chiara , Motisi Marco Antonio , Venturini Elisabetta , D’Elios Sofia , Asvestopoulou Evangelia , Tamborino Agnese Maria , Galli Luisa , D’Elios Mario Milco , Chiappini Elena
Published: January 2025

Purpose: High-accuracy diagnostic screening tests for Mycobacterium tuberculosis (MTB) infection are required, primarily to detect patients with latent infections (LTBIs) in order to avoid their progression to active tuberculosis disease. The performance of the novel IGRA LIOFeron®TB/LTBI was evaluated in children. The originality of this test is the new MTB antigen contained (l-alanine dehydrogenase), identified as a tool to differentiate active TB from LTBI infection. Methods: From March 2022 to November 2023, a population of 90 children was enrolled and grouped into healthy, active TB or LTBI individuals, based on diagnostic guidelines. The blood of all these participants was tested with LIOFeron®TB/LTBI assay in comparison to diagnosis, as gold standard, and to the current used IGRA QuantiFERON®-TB Gold Plus. Results: The two assays demonstrated an excellent concordance of their results with patients’ diagnosis of MTB infection. The performance of LIOFeron®TB/LTBI assay in terms of accuracy of MTB infection diagnosis was high at ROC analysis (AUC = 0.997), and the test showed 100% sensitivity in LTBI detection. The QuantiFERON®-TB Gold Plus sensitivity for LTBI detection was 85.7%.

Conclusions: Based on the obtained results, the LIOFeron®TB/LTBI assay appears to be a promising test for TB and LTBI screening among paediatric patients.

What is known:• The detection of LTBI in children, exposed to MTB infections, followed by appropriate treatment, has a pivotal role in reducing tuberculosis burden.
• IGRA tests are easy-to-use methods for helping large TB screening in paediatrics.

What is new:• The LIOFeron®TB/LTBI performance evaluation showed 100% of sensitivity in the detection of LTBI patients.
• The LIOFeron®TB/LTBI assay might be useful for the detection of LTBI and active tuberculosis paediatric patients.
Design-based mapping of errors in remote sensing-based land use/land cover maps
Authors: Di Biase R. M. , Marcelli A. , Corona P. , Stehman S. V. , Fattorini L.
Published: January 2025

For the first time, spatially explicit representation of classification errors of land use/land cover (LULC) maps is approached from a design-based perspective. Since LULC maps are typically derived from non-probabilistic training samples, these maps, like the true LULC map, are fixed in a design-based scenario so that the error maps achieved by comparing the satellite-based and true maps are fixed. Based on a probabilistic sample of locations where the true or “reference” class is obtained (i.e., the “reference” class is considered the best representation of the true class), errors can be assessed at these sample locations by comparing the map classes to the reference classes. Then, the presence or absence of errors is interpolated across the entire survey area using the nearest neighbour technique. Under very common sampling schemes used to collect reference sample data, the interpolated error maps are design consistent. A simulation study confirms the design consistency of the interpolated error maps, which converge to the true error map as the reference sample size increases. The U.S. land cover map from the LCMAP program and the Italian forest/non forest map serve as case studies.
Predictive value of enhanced corneal biomechanical parameters for ectasia progression
Authors: Koh Shizuka , Ambrósio Renato , Inoue Ryota , Belin Michael W. , Maeda Naoyuki , Nishida Kohji
Published: January 2025

Purpose

To determine whether corneal biomechanical parameters can predict ectasia progression.

Study design

Retrospective observational study.

Methods

The baseline corneal biomechanical parameters of 64 eyes of 41 young patients (age, < 25 years at the first visit) who were diagnosed with keratoconus (KC) or suspected KC at Osaka University Hospital and followed up for more than two years were reviewed. Suspected KC was defined as borderline cases with no definitive clinical or topographical abnormalities in both eyes. The eyes were divided into progressed (P) and non-progressed (NP) groups using the ABCD grading system of Scheimpflug-based tomography. The Scheimpflug-based corneal biomechanical parameters evaluated included deformation amplitude ratio within 2 mm, integrated radius, Ambrósio relational thickness to the horizontal profile, stiffness parameter at the first applanation, stress–strain index, E-staging, and Corvis Biomechanical Index. The optimized tomographic/biomechanical index (TBIv2), Belin/Ambrósio Enhanced Ectasia Deviation (BAD-D), and inferior-superior axial steepening values from Scheimpflug-based tomography were also evaluated.

Results

Twenty-three and 41 eyes were categorized into the P and NP groups, respectively. Logistic regression analysis showed that age, BAD-D, and TBIv2 could predict ectasia progression. The specificity, sensitivity, and area under the receiver operating characteristic curve (AUROC) values for BAD-D combined with age were 0.82, 0.60, and 0.83, respectively, whereas those for TBIv2 combined with age were 0.65, 0.82, and 0.82, respectively.

Conclusions

Baseline TBIv2 is a potentially useful predictive marker for ectasia progression in young patients, whereas baseline BAD-D could be used for establishing a definitive diagnosis.
Navigating life’s twists and turns: characteristics of life events across adulthood
Authors: Radjenovic Sonja , Rupprecht Fiona S. , Nikitin Jana
Published: January 2025

This study examines whether there are age-related differences in the experience of life events across adulthood. We hypothesized that older adults would report life events that are less anticipated, less normative, less controllable, less positive, and more strenuous than younger adults due to increasing developmental losses and decreasing gains. We investigated how age (linear, quadratic, and cubic) relates to life-event characteristics by comparing different events and analyzing the same events across individuals, to distinguish between the effects observed across life events and those that emerge after accounting for the specific life event in question. Additionally, we hypothesized that older adults would cope better with less favorable events due to their life experience and emotion regulation skills. Analyses of 6,688 participants (18–90 years) showed that while older adults reported less favorable life events, they coped better with the same events than younger adults. The results underscore the importance of distinguishing between age and life event effects. They also show that life-event characteristics are consistently linked to well-being throughout adulthood.
Enzymatic hydrolysis of palm cellulose to yield nanocrystals with potential roles in lipid and cholesterol digestion and absorption
Authors: Chong Wai-Ting , Siow Lee Fong , Chan Eng-Seng , Tey Beng Ti , Lee Yee-Ying
Published: January 2025

Limited research has been conducted to understand the influence of cellulose nanocrystals (CNCs) on lipid and cholesterol digestion and absorption. This study aimed to explore and understand the ability of CNCs to modulate these processes. CNCs were obtained from palm-pressed fiber (PPF) via a green enzymatic hydrolysis method, a more environmentally friendly alternative to the traditional, acid hydrolysis. Enzymatic hydrolysis was performed using the endo-β-D-glucanase derived from Aspergillus sp. The effect of the enzyme concentration (250–1000 U/g) and reaction times (12–72 h) on CNC particle size, morphology, yield and suspension stability were studied. Enzymatic hydrolysis at a concentration 500 U/g and 72 h of incubation successfully produced needle-shaped, shortened, and non-entangled CNCs with an average diameter of 22.76 ± 5.52 nm, length of 342.55 ± 148.69 nm, an aspect ratio of ~ 15, and a crystallinity of 61.45%. Interestingly, the water (22.28 ± 0.85 g/g) and oil (15.08 ± 0.62 g/g) holding capacities of CNCs were four times higher than raw PPF (5.31 ± 0.53 g/g; 3.52 ± 0.32 g/g). The results showed increasing CNCs concentrations decreased lipase activity mobilization, increased cholesterol adsorption capability and retarded bile acid diffusion. 1% of CNCs alone inhibited 54.93% of lipase activity. 1 g of CNCs adsorbed 54.19 ± 10.70 mg of cholesterol and demonstrated a greater bile acid retardation effect than microcrystal cellulose (CNCs: 39.3 ± 10.10%: MCC: 27.05 ± 6.72%). The entrapment of lipase and bile acid by CNCs could affect lipid and cholesterol digestion, potentially benefiting digestion health applications. Furthermore, the presence of CNCs could potentially alleviate hypercholesteremia by adsorbing cholesterol and reducing bile acid diffusion. The results revealed the effectiveness of CNCs extraction from PPF through enzymatic hydrolysis and suggest that CNCs may have health benefits as a functional ingredient for developing of fat- and cholesterol-rich foods with health-promoting properties.