bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi‐omics analyses reveal spatial heterogeneity in primary and metastatic oesophageal squamous cell carcinoma
Authors: Huang Haitao , Li Na , Liang Yingkuan , Li Rutao , Tong Xing , Xiao Jinyuan , Tang Hongzhen , Jiang Dong , Xie Kai , Fang Chen , Chen Shaomu , Li Guangbin , Wang Bin , Wang Jiaqian , Luo Haitao , Guo Lingchuan , Ma Haitao , Jiang Wei , Feng Yu
Published: November 2023

Background

Biopsies obtained from primary oesophageal squamous cell carcinoma (ESCC) guide diagnosis and treatment. However, spatial intra‐tumoral heterogeneity (ITH) influences biopsy‐derived information and patient responsiveness to therapy. Here, we aimed to elucidate the spatial ITH of ESCC and matched lymph node metastasis (LNmet).

Methods

Primary tumour superficial (PTsup), deep (PTdeep) and LNmet subregions of patients with locally advanced resectable ESCC were evaluated using whole‐exome sequencing (WES), whole‐transcriptome sequencing and spatially resolved digital spatial profiling (DSP). To validate the findings, immunohistochemistry was conducted and a single‐cell transcriptomic dataset was analysed.

Results

WES revealed 15.72%, 5.02% and 32.00% unique mutations in PTsup, PTdeep and LNmet, respectively. Copy number alterations and phylogenetic trees showed spatial ITH among subregions both within and among patients. Driver mutations had a mixed intra‐tumoral clonal status among subregions. Transcriptome data showed distinct differentially expressed genes among subregions. LNmet exhibited elevated expression of immunomodulatory genes and enriched immune cells, particularly when compared with PTsup (all P < .05). DSP revealed orthogonal support of bulk transcriptome results, with differences in protein and immune cell abundance between subregions in a spatial context. The integrative analysis of multi‐omics data revealed complex heterogeneity in mRNA/protein levels and immune cell abundance within each subregion.

Conclusions

This study comprehensively characterised spatial ITH in ESCC, and the findings highlight the clinical significance of unbiased molecular classification based on multi‐omics data and their potential to improve the understanding and management of ESCC. The current practices for tissue sampling are insufficient for guiding precision medicine for ESCC, and routine profiling of PTdeep and/or LNmet should be systematically performed to obtain a more comprehensive understanding of ESCC and better inform treatment decisions.
Non‐Newtonian laminar pulsating heat and fluid flow in plane duct
Authors: Altunkaya Ayse Nur , Aydin Orhan , Avci Mete
Published: November 2023

In the present study, laminar pulsating power‐law momentum and heat transfer in a uniformly heated plane duct is studied analytically. Assuming that fully developed conditions exist both hydrodynamically and thermally, a perturbation series method is utilized to derive analytical solutions for the momentum and energy balance equations, and the amplitude is prescribed as the perturbation parameter. For varying values of the power‐law index (), representing pseudoplastic, Newtonian, and dilatant fluids, effects of dimensionless amplitude () and frequency () on periodic and period‐averaged friction factor and Nusselt number are obtained. The results obtained for Newtonian fluid are shown to be in good harmony with the corresponding findings in the open literature.
Testing and treatment‐by‐attitude in psychotherapy for pathological narcissism: A clinical illustration
Authors: Kealy David , Gazzillo Francesco
Published: November 2023

Pathological narcissism is a personality constellation comprising distorted self‐image, maladaptive self‐esteem regulation, and difficulties in intimate relationships. Patients with elevated pathological narcissism may not necessarily meet criteria for narcissistic personality disorder, and may seek treatment for a range of mental health concerns across various clinical settings. An understanding of key principles of control‐mastery theory (CMT) can help clinicians understand the specific goals and challenges of the individual patient with pathological narcissism, and can illuminate ways in which the patient may work in psychotherapy. This paper outlines how patients with pathological narcissism may engage in testing of their pathogenic beliefs, and how therapists can respond in ways that facilitate the patient's sense of safety and foster psychological work. The role of the therapist's attitude is highlighted as a means for countering pathogenic beliefs associated with pathological narcissism. Clinical material from a single case of time‐limited supportive psychotherapy will be used to illustrate these principles and associated therapeutic processes. Insights from CMT regarding pathogenic beliefs and the patient's plan for addressing them can help to explain how therapy works or does not work for patients with pathological narcissism.
Orange peel as a biosource for the synthesis of activated carbon and its application in hydrogen storage
Authors: Juárez Juliana M , Ledesma Brenda C , Beltramone Andrea R , Gómez Costa Marcos B
Published: November 2023

BACKGROUND

The reduction of fossil fuels and the environmental threats caused by their combustion has diverted the attention of the scientific community to search for renewable and environmentally safe energy sources. There are some advances in the development of activated carbons (ACs) from different wastes for use as adsorbents in hydrogen storage. In the present work, different ACs were synthesized using a domestic residue (orange peel) as a carbon source.

RESULTS

To obtain these carbonaceous materials, a chemical activation was performed using phosphoric acid (50 wt%) as activating agent. Different synthesis conditions, acid/precursor ratio and contact time between them were used. The materials obtained through the revaluation of waste were applied to the adsorption of hydrogen as an alternative in the use of green hydrogen. Hydrogen adsorption was related to some textural properties of ACs, such as specific surface area and meso/microporosity. All the materials obtained have a high specific surface area (between 1000 and 1400 m2 g−1) and meso‐ and microporosity. X‐ray powder diffraction, scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, and Raman spectroscopy analyses were performed to characterize these materials.

CONCLUSION

Adsorption increases practically linearly with respect to the specific surface area of ACs. Synergy can be observed between mesopores and micropores since increasing both microporosity and mesoporosity increases hydrogen storage. The highest adsorption capacity was 3.3 wt% at −196.15 °C and 10 bar. © 2023 Society of Chemical Industry (SCI).
Molecular PET/CT mapping of rhACE2 distribution and quantification in organs to aid in SARS‐CoV‐2 targeted therapy
Authors: Wang Zilei , Zhao Chuanke , Li Chuangui , Liu Song , Ding Jin , He Chengxue , Liu Jiayue , Dong Bin , Yang Zhi , Liu Qi , Zhu Hua , Liu Youping
Published: November 2023

Coronavirus disease 2019 (COVID‐19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, poses a significant threat to public health. Angiotensin‐converting enzyme 2 (ACE2) is a key receptor for SARS‐CoV‐2 infection. Recombinant human ACE2 (RhACE2), as a soluble supplement for human ACE2, can competitively block SARS‐CoV‐2 infection. In this study, a mouse organ in situ rhACE2 high aggregation model was constructed for the first time, and in vivo real‐time positron emission tomography (PET) imaging of rhACE2 in the mouse model was performed using an ACE2‐specific agent 68Ga‐HZ20. This radiotracer exhibits reliable radiochemical properties in vitro and maintains a high affinity for rhACE2 in vivo. In terms of probe uptake, 68Ga‐HZ20 showed a good target‐to‐nontarget ratio and was rapidly cleared from the circulatory system and excreted by the kidneys and urinary system. PET imaging with this radiotracer can noninvasively and accurately monitor the content and distribution of rhACE2 in the body, which clarifies that rhACE2 can aggregate in multiple organs, suggesting the preventive and therapeutic potential of rhACE2 for SARS‐CoV‐2 and COVID‐19.
Revisiting the role of endogenous STAT3 in HPV‐positive cervical cancer cells
Authors: Strobel Tobias D. , Weber Maria , Heber Nora , Holzer Angela , Hoppe‐Seyler Karin , Hoppe‐Seyler Felix
Published: November 2023

Novel treatment options for human papillomavirus (HPV)‐induced cancers are urgently required. The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is considered to be constitutively active in HPV‐positive cervical cancer cells and essential for their proliferation. Moreover, STAT3 was reported to undergo mutually stimulatory interactions with the HPV E6/E7 oncogenes. Thus, inhibiting STAT3 in HPV‐positive cancer cells is under discussion to provide a powerful novel therapeutic strategy. We here show that the antifungal drug ciclopirox destabilizes the STAT3 protein by acting as an iron chelator. However, by exploring the functional consequences of STAT3 inhibition in HPV‐positive cancer cells, we obtained several unexpected results. Chemical STAT3 inhibitors heterogeneously affect cervical cancer cell proliferation and those which act antiproliferative also block the growth of STAT3 knockout cells, indicating induction of off‐target effects. In contrast to several chemical inhibitors, genetic inhibition of STAT3 expression by either RNA interference or the CRISPR/Cas9 method does not appreciably affect cervical cancer cell proliferation. Transcriptome analyses indicate that blocking STAT3 expression in HPV‐positive cancer cells has very limited effects on putative STAT3 target genes. Although the targeted inhibition of specific growth‐promoting signaling pathways leads to a feedback activation of STAT3 in cervical cancer cells via Janus kinase 1/2, this does not lead to treatment resistance. Moreover, we did not obtain experimental evidence for a STAT3‐linked activation of HPV E6/E7 oncogene expression or, vice versa, an E6/E7‐dependent activation of STAT3, at endogenous conditions in cervical cancer cells. Collectively, these findings question the essential role of STAT3 in cervical cancer cell proliferation and the strategy to inhibit STAT3 in these cells for therapeutic purposes.
QuantiFERON‐CMV and monitor predict cytomegalovirus, mortality, and graft‐versus‐host disease in transplant recipients
Authors: Souan Lina , Jazar Husam Abu , Nashwan Sura , Sughayer Maher A.
Published: November 2023

Cytomegalovirus (CMV) is the most prevalent infection in recipients of hematopoietic stem cell transplant (HSCT). QuantiFERON‐CMV (QF‐CMV) and QuantiFERON‐Monitor (QFM) assays were used to test whether immune‐competent adult allogeneic HSCT recipients with CMV‐specific T cells can control CMV infection or reactivation. Our data demonstrated a significant correlation between CMV infection measured by CMV‐antigenemia test and QF‐CMV results, graft versus host disease (GvHD), and mortality rates. The QF‐CMV test revealed that CMV‐specific T cells with higher interferon‐γ (IFN‐γ) release were correlated with lower CMV infection rates. There was a significant negative association between QF‐CMV results, GvHD, and mortality rates. Data showed that a one‐unit rise in IFN‐γ was linked with a 12.7% reduction in GvHD and a 20.7% reduction in the mortality odds ratio. In addition, a negative correlation was found between QF‐M results and CMV infection, with the QFM test predicting protection against CMV infection by 1.9%. This is one of the few studies establishing the QF‐CMV test's predictive value for GvHD and mortality, its use to monitor HSCT patients for pre‐emptive therapy, and the use of the QFM test to predict CMV infection and mortality in HSCT patients. Thus, these assays could be utilized to optimize preventive and pre‐emptive therapy procedures to reduce transplant recipient adverse effects and posttransplant therapy costs.
An outbreak of a novel lineage of dengue virus 2 in Vietnam in 2022
Authors: Nabeshima Takeshi , Ngwe Tun Mya Myat , Thuy Nguyen Thi Thu , Hang Nguyen Le Khanh , Mai Le Thi Quynh , Hasebe Futoshi , Takamatsu Yuki ,   Nagasaki University Vietnam Research Group
Published: November 2023

In 2022, a large dengue outbreak was reported in Vietnam, where dengue was endemic. A total of 1889 acute‐phase serum samples were collected from patients with suspected dengue at Vung Tau General Hospital, the core hospital in Vung Tau Province, southern Vietnam. Among the 1889 samples analyzed for laboratory confirmation of dengue virus (DENV) infection, 339 positive cases were identified, of which 130 were primary infections and 209 were secondary infections. DENV‐2 was the dominant serotype in both primary and secondary infection groups. Phylogenetic analysis based on sequences of the envelope protein‐coding region revealed the emergence of a new DENV‐2 lineage during this outbreak.
Mendelian randomization study on the causal effect of serum IgA levels on H7N9 avian influenza A virus susceptibility
Authors: Liao Qijun , Shen Juan , Chen Yongkun , Shu Yuelong
Published: November 2023

Avian influenza A viruses (IAVs) that cross the species barrier to infect humans have the potential to initiate a new pandemic. However, the host factors influencing avian IAV infection remain poorly understood. To address this knowledge gap, we conducted a two‐sample Mendelian randomization (MR) analysis by integrating our in‐house genome‐wide association study (GWAS) of avian IAV H7N9 susceptibility (with 217 cases and 116 controls) with the largest GWAS of serum IgA levels to date (sample size 41 263). Using the inverse‐variance weighted (IVW) method, we discovered that genetically decreased serum IgA levels were associated with an increased risk of H7N9 infection (β = −2.528, 95% confidence interval [CI]: −4.572 to −0.484; p = 0.015). Consistent results were obtained from three other MR methods, including robust IVW estimation (β = −2.506, 95% CI: −4.109 to −0.902; p = 0.002), generalized summary‐data‐based MR (GSMR) (β = −2.238, 95% CI: −4.106 to −0.602; p = 0.019), and MR‐pleiotropy residual sum and outlier (MR‐PRESSO) (β = −2.528, 95% CI: −4.396 to −0.892; p = 0.026). In conclusion, our analysis provided compelling evidence support a causal relationship between genetically predicted serum IgA levels and avian IAV H7N9 susceptibility.
Taste the emotions: pilot for a novel, sensors‐based approach to emotional analysis during coffee tasting
Authors: Tonacci Alessandro , Taglieri Isabella , Sanmartin Chiara , Billeci Lucia , Crifaci Giulia , Ferroni Giuseppe , Braceschi Gian Paolo , Odello Luigi , Venturi Francesca
Published: November 2023

BACKGROUND

Coffee is a natural drink with important properties for the human body and mind, capable of delivering energy and strong emotions, thus being appreciated since ancient times. The qualitative and quantitative assessment of the coffee properties is normally performed by trained panelists, though relying on standardized questionnaires, with possible biases arising. In this study, for the first time in the scientific literature, we applied a technology‐based approach, based on the use of wearable sensors, to study the implicit emotional responses of a small cohort of experienced coffee judges, thus taking this chance to assess the feasibility of this approach in such a scenario. The merging of different technologies for capturing biomedical signals, including electrocardiogram, galvanic skin response, and electroencephalogram, was therefore adopted to retrieve results in terms of the relationships between implicit (i.e. psychophysiological) and explicit (i.e. derived from questionnaires) measurements.

RESULTS

Significant correlations were obtained between biomedical signals and data from the questionnaires within all the sensory domains (olfaction, vision, taste) investigated, particularly concerning autonomic‐related features.

CONCLUSIONS

The results obtained confirmed the viability of this new approach in the psychophysical and emotional assessment in coffee tasting judges, paving the way for a new perspective into the universe of coffee quality assessment panels, eventually transferable to broader scale investigations, somewhat dealing with consumer satisfaction and neuromarketing at large. © 2023 Society of Chemical Industry.
Assessing Swallowing Dysfunction Aggravation in Chronic Obstructive Pulmonary Disease Patients Using Ultrasonic Measurements With Swallowing Movement Parameters
Authors: Huang Yanyan , Zhong Huohu , Xu Zhirong , Su Qichen , Su Shanshan
Published: November 2023

Objective

To investigate the correlation between ultrasonic measurements of swallowing movement parameters and aggravation of swallowing dysfunction in patients with chronic obstructive pulmonary disease (COPD).

Methods

COPD patients with swallowing dysfunction (n = 120) and COPD patients with normal swallowing function (n = 100) treated in our hospital between January 2020 and January 2023 were included in observation and control groups, respectively. The correlation between ultrasonic measurements of swallowing movement parameters and COPD with swallowing dysfunction was analyzed. The observation group was divided into mild and severe groups according to their Gugging Swallowing Screen (GUSS) scores. The correlation between ultrasonic measurements of swallowing movement parameters and COPD exacerbation combined with swallowing dysfunction was analyzed.

Results

In the observation group, Hyoid muscle thickness, hyoid bone displacement, geniohyoid muscle movement distance, HLAS, and CSR were lower compared to the control group, negatively associated with COPD‐related swallowing issues. Conversely, geniohyoid muscle movement time and minimum hyohyoid distance (NHLA) were higher in the observation group, positively correlated with COPD‐related swallowing dysfunction. In COPD patients with swallowing problems, the severe group exhibited lower values for lingual muscle thickness, hyoid bone displacement, geniohyoid muscle movement distance, HLAS, and CSR compared to the mild group, while geniohyoid muscle movement time and NHLA were higher in the severe group. Receiver operating characteristic (ROC) curves were created, indicating the promising diagnostic utility of these parameters for assessing the presence and severity of swallowing dysfunction in COPD patients.

Conclusion

The ultrasonic measurement of swallowing motion parameters can effectively assess swallowing dysfunction in COPD patients.
Bifurcation analysis in a predator–prey model with strong Allee effect on prey and density‐dependent mortality of predator
Authors: Shang Zuchong , Qiao Yuanhua
Published: November 2023

The influences of Allee effect and density‐dependent mortality on population growth are of great significance in ecology. In this paper, we first consider a Gause‐type predator–prey model with simplified Holling type IV functional response, strong Allee effect on prey, and density‐dependent mortality of predator. It is shown that the system exhibits rich and complex dynamics like bistability, local and global bifurcations such as transcritical bifurcation, saddle‐node bifurcation, Hopf bifurcation, cusp bifurcation, Bogdanov–Takens bifurcation, Bautin bifurcation, homoclinic bifurcation, saddle‐node bifurcation of limit cycle, and heteroclinic bifurcation. Next, we separately explore the influences of Allee effect and density‐dependent mortality on the dynamics of the same model. The results show that the strong Allee effect induces the occurrence of heteroclinic bifurcation and the reduction of the number of limit cycles, while the density‐dependent mortality stabilizes the system. Since the analytical expressions of the interior equilibria are difficult to derive, the results are verified numerically.
Effect of chronic deltamethrin exposure on brain transcriptome and metabolome of juvenile crucian carp
Authors: Wu Hao , Gao Jinwei , Xie Zhonggui , Xie Min , Song Rui , Yuan Xiping , Wu Yuanan , Ou Dongsheng
Published: November 2023

Deltamethrin (Del), a widely administered pyrethroid insecticide, has been established as a common contaminant of the freshwater environment and detected in many freshwater ecosystems. In this study, we investigated the changes in brain transcriptome and metabolome of crucian carp after exposure to 0.6 μg/L Del for 28 days. Elevated MDA levels and inhibition of SOD activity indicate damage to the antioxidant system. Moreover, a total of 70 differential metabolites (DMs) were identified using the liquid chromatography‐mass spectrometry, including 32 upregulated and 38 downregulated DMs in the Del‐exposed group. The DMs associated with chronic Del exposure were enriched in steroid hormone biosynthesis, fatty acid metabolism, and glycerophospholipid metabolism for prostaglandin G2, 5‐oxoeicosatetraenoic acid, progesterone, androsterone, etiocholanolone, and hydrocortisone. Transcriptomics analysis revealed that chronic Del exposure caused lipid metabolism disorder, endocrine disruption, and proinflammatory immune response by upregulating the pla2g4, cox2, log5, ptgis, lcn, and cbr expression. Importantly, the integrative analysis of transcriptomics and metabolomics indicated that the arachidonic acid metabolism pathway and steroid hormone biosynthesis were decisive processes in the brain tissue of crucian carp after Del exposure. Furthermore, Del exposure perturbed the tight junction, HIF‐1 signaling pathway, and thyroid hormone signaling pathway. Overall, transcriptome and metabolome data of our study offer a new insight to assess the risk of chronic Del exposure in fish brains.
The secreted peptide BATSP1 promotes thermogenesis in adipocytes
Authors: Cui Xianwei , Zhong Hong , Wu Yangyang , Zhang Zhuo , Zhang Xiaoxiao , Li Lu , He Jin , Chen Chen , Wu Zhenggang , Ji Chenbo
Published: November 2023

Although brown adipose tissue (BAT) has historically been viewed as a major site for energy dissipation through thermogenesis, its endocrine function has been increasingly recognized. However, the circulating factors in BAT that play a key role in controlling systemic energy homeostasis remain largely unexplored. Here, we performed a peptidomic analysis to profile the extracellular peptides released from human brown adipocytes upon exposure to thermogenic stimuli. Specifically, we identified a secreted peptide that modulates adipocyte thermogenesis in a cell-autonomous manner, and we named it BATSP1. BATSP1 promoted BAT thermogenesis and induced browning of white adipose tissue in vivo, leading to increased energy expenditure under cold stress. BATSP1 treatment in mice prevented high-fat diet-induced obesity and improved glucose tolerance and insulin resistance. Mechanistically, BATSP1 facilitated the nucleocytoplasmic shuttling of forkhead transcription factor 1 (FOXO1) and released its transcriptional inhibition of uncoupling protein 1 (UCP1). Overall, we provide a comprehensive analysis of the human brown adipocyte extracellular peptidome following acute forskolin (FSK) stimulation and identify BATSP1 as a novel regulator of thermogenesis that may offer a potential approach for obesity treatment.
Three lines of defense against risks from AI
Authors: Schuett Jonas
Published: November 2023

Organizations that develop and deploy artificial intelligence (AI) systems need to manage the associated risks—for economic, legal, and ethical reasons. However, it is not always clear who is responsible for AI risk management. The three lines of defense (3LoD) model, which is considered best practice in many industries, might offer a solution. It is a risk management framework that helps organizations to assign and coordinate risk management roles and responsibilities. In this article, I suggest ways in which AI companies could implement the model. I also discuss how the model could help reduce risks from AI: it could identify and close gaps in risk coverage, increase the effectiveness of risk management practices, and enable the board of directors to oversee management more effectively. The article is intended to inform decision-makers at leading AI companies, regulators, and standard-setting bodies.
Pure strategy Nash equilibria for bargaining models of collective choice
Authors: Braack Malte , Henning Christian , Ziesmer Johannes
Published: November 2023

This paper considers pure strategy Nash equilibria of non-cooperative legislative bargaining models. In contrast to existing legislative bargaining models, we derive legislators behavior from stochastic utility maximization. This approach allows us to prove the existence of a stationary Pure Local and Global Nash Equilibrium under rather general settings. The mathematical proof is based on a fixed point argument, which can also be used as a numerical method to determine an equilibrium. We characterize the equilibrium outcome as a lottery of legislators’ proposals and prove a Mean Voter Theorem, i.e., proposals result dimension-by-dimension as a weighted mean of legislators’ ideal points and are Pareto-optimal. Based on a simple example, we illustrate different logic of our model compared to mixed strategy equilibrium of the legislative bargaining model suggested by Banks and Duggan (Am Polit Sci Rev 94(1):73–88. https://doi.org/10.2307/2586381, 2000).
Quadrupole magnet design based on genetic multi-objective optimization
Authors: Diehl Eric , Tresckow Moritz von , Scholtissek Lou , Loukrezis Dimitrios , Marsic Nicolas , Müller Wolfgang F. O. , Gersem Herbert De
Published: November 2023

This work suggests to optimize the geometry of a quadrupole magnet by means of a genetic algorithm adapted to solve multi-objective optimization problems. To that end, a non-domination sorting genetic algorithm known as NSGA-III is used. The optimization objectives are chosen such that a high magnetic field quality in the aperture of the magnet is guaranteed, while simultaneously the magnet design remains cost-efficient. The field quality is computed using a magnetostatic finite element model of the quadrupole, the results of which are post-processed and integrated into the optimization algorithm. An extensive analysis of the optimization results is performed, including Pareto front movements and identification of best designs.
Linear hyperelliptic Hodge integrals
Authors: Afandi Adam
Published: November 2023

We provide a closed form expression for linear Hodge integrals on the hyperelliptic locus. Specifically, we find a succinct combinatorial formula for all intersection numbers on the hyperelliptic locus with one $$\lambda $$
λ
-class, and powers of a $$\psi $$
ψ
-class pulled back along the branch map. This is achieved by using Atiyah–Bott localization on a stack of stable maps into the orbifold $$\left[ {\mathbb {P}}^1/{\mathbb {Z}}_2\right] $$

P

1

/

Z
2

.
Optimal Distributed Control for a Viscous Non-local Tumour Growth Model
Authors: Fornoni Matteo
Published: November 2023

In this paper, we address an optimal distributed control problem for a non-local model of phase-field type, describing the evolution of tumour cells in presence of a nutrient. The model couples a non-local and viscous Cahn–Hilliard equation for the phase parameter with a reaction-diffusion equation for the nutrient. The optimal control problem aims at finding a therapy, encoded as a source term in the system, both in the form of radiotherapy and chemotherapy, which could lead to the evolution of the phase variable towards a desired final target. First, we prove strong well-posedness for the system of non-linear partial differential equations. In particular, due to the presence of a viscous regularisation, we can also consider double-well potentials of singular type and cross-diffusion terms related to the effects of chemotaxis. Moreover, the particular structure of the reaction terms allows us to prove new regularity results for this kind of system. Then, turning to the optimal control problem, we prove the existence of an optimal therapy and, by studying Fréchet-differentiability properties of the control-to-state operator and the corresponding adjoint system, we obtain the first-order necessary optimality conditions.
Image quality of DWI at breast MRI depends on the amount of fibroglandular tissue: implications for unenhanced screening
Authors: Wielema Mirjam , Sijens Paul E. , Pijnappel Ruud M. , De Bock Geertruida H. , Zorgdrager Marcel , Kok Marius G. J. , Rainer Eva , Varga Raoul , Clauser Paola , Oudkerk Matthijs , Dorrius Monique D. , Baltzer Pascal A. T.
Published: November 2023

Objectives

To compare image quality of diffusion-weighted imaging (DWI) and contrast-enhanced breast MRI (DCE-T1) stratified by the amount of fibroglandular tissue (FGT) as a measure of breast density.

Methods

Retrospective, multi-reader, bicentric visual grading analysis study on breast density (A–D) and overall image and fat suppression quality of DWI and DCE-T1, scored on a standard 5-point Likert scale. Cross tabulations and visual grading characteristic (VGC) curves were calculated for fatty breasts (A/B) versus dense breasts (C/D).

Results

Image quality of DWI was higher in the case of increased breast density, with good scores (score 3–5) in 85.9% (D) and 88.4% (C), compared to 61.6% (B) and 53.5% (A). Overall image quality of DWI was in favor of dense breasts (C/D), with an area under the VGC curve of 0.659 (p < 0.001). Quality of DWI and DCE-T1 fat suppression increased with higher breast density, with good scores (score 3–5) for 86.9% and 45.7% of density D, and 90.2% and 42.9% of density C cases, compared to 76.0% and 33.6% for density B and 54.7% and 29.6% for density A (DWI and DCE-T1 respectively).

Conclusions

Dense breasts show excellent fat suppression and substantially higher image quality in DWI images compared with non-dense breasts. These results support the setup of studies exploring DWI-based MR imaging without IV contrast for additional screening of women with dense breasts.

Clinical relevance statement

Our findings demonstrate that image quality of DWI is robust in women with an increased amount of fibroglandular tissue, technically supporting the feasibility of exploring applications such as screening of women with mammographically dense breasts.

Key Points

• Image and fat suppression quality of diffusion-weighted imaging are dependent on the amount of fibroglandular tissue (FGT) which is closely connected to breast density.

• Fat suppression quality in diffusion-weighted imaging of the breast is best in women with a high amount of fibroglandular tissue.

• High image quality of diffusion-weighted imaging in women with a high amount of FGT in MRI supports that the technical feasibility of DWI can be explored in the additional screening of women with mammographically dense breasts.

Graphical Abstract
The heat is on: the impact of excessive temperature increments on complications of laser treatment for ureteral and renal stones
Authors: Tonyali Senol , von Bargen Maximilian Ferry , Ozkan Arif , Gratzke Christian , Miernik Arkadiusz
Published: November 2023

Objective

Technological advancements in the field of urology have led to a paradigm shift in the management of urolithiasis towards minimally invasive endourological interventions, namely ureteroscopy and percutaneous nephrolithotomy. However, concerns regarding the potential for thermal injury during laser lithotripsy have arisen, as studies have indicated that the threshold for cellular thermal injury (43 °C) can be exceeded, even with conventional low-power laser settings. This review aims to identify the factors that contribute to temperature increments during laser treatment using current laser systems and evaluate their impact on patient outcomes.

Materials and methods

To select studies for inclusion, a search was performed on online databases including PubMed and Google Scholar. Keywords such as 'temperature' or 'heat' were combined with 'lithotripsy', 'nephrolithotomy', 'ureteroscopy', or 'retrograde intrarenal surgery', both individually and in various combinations.

Results

Various strategies have been proposed to mitigate temperature rise, such as reducing laser energy or frequency, shortening the duration of laser activation, increasing the irrigation fluid flow rate, and using room temperature or chilled water for irrigation. It is important to note that higher irrigation fluid flow rates should be approached cautiously due to potential increases in intrarenal pressure and associated infectious complications. The utilization of a ureteral access sheath (UAS) may offer benefits by facilitating irrigation fluid outflow, thereby reducing intrapelvic pressure and intrarenal fluid temperature.

Conclusion

Achieving a balance between laser power, duration of laser activation, and irrigation fluid rate and temperature appears to be crucial for urologists to minimize excessive temperature rise.
Outcomes of endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) in the treatment of paediatric hydrocephalus: Systematic review and meta-analysis
Authors: Minta Katarzyna Julia , Kannan Siddarth , Kaliaperumal Chandrasekaran
Published: November 2023

Purpose

To evaluate the outcomes of endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) in the treatment of paediatric hydrocephalus.

Methods

We searched PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials databases for articles published from 2000 to May 2023 (last search date May 6, 2023). Keywords searched included “endoscopic third ventriculostomy”, “ventriculoperitoneal shunting”, “paediatric population”, and “outcomes”. Using random-effects models, we compared success rates and complications of ETV and VPS. The primary outcome was ETV vs.VPS success rates, and the secondary outcome was post-treatment complications. Included studies reported on treatment success and complication rates.

Results

Out of 126 articles, 8 RCTs and 1 prospective study were included. Six studies reported primary outcome data (806 patients identified: 464 in ETV group, 342 in VPS group). Combined success rates were 81.8% (n = 283/346) for ETV and 86.7% (n = 182/210) for VPS (median follow-up 41 months). There was no difference in success rates between ETV and VPS groups (risk ratio 0.84, 95% confidence interval 0.80–0.90, I2 = 0%, p = 0.93). Combined complication rates were 4.6% (n = 16/346) in the ETV group and 27.1% (n = 57/210) in the VPS group. ETV had a lower rate of postoperative complications (risk ratio 0.76, 95% confidence interval 0.42–1.38, I2 = 53%, p = 0.04).

Conclusions

Both ETV and VPS are viable surgical options for the management of paediatric hydrocephalus with similar success rates when used as first-line treatment. However, our study concluded that VPS results in a higher complication rate.

Registration

This systematic review and meta-analysis was formally registered in the PROSPERO International database under the registration number CRD42023452907 on the 29th of August 2023.
Review: Toward sustainable management of groundwater in the deserts of Egypt
Authors: El-Agha Doaa E. , Molle Francois , Metwally Mohamed I. , Emara Sobhy R. , Shalby Ahmed , Armanuos Asaad M. , Negm Abdelazim , Gado Tamer A.
Published: November 2023

To achieve its ambitious plans to reclaim its deserts through mega projects, Egypt is heavily relying on fossil or little-recharged groundwater. This article revisits the results and methodologies of the studies conducted over the last two decades on groundwater management and uses in the Western Desert. Most previous studies aimed at simulating different groundwater abstraction scenarios by modeling local areas in aquifer systems, but with poor definitions of boundary conditions and limited historical data. Studies were constrained by the unavailability of data, access difficulties, and high collection costs in desert lands. Thus, to propose reliable sustainable groundwater resources development plans and recommendations for future protection strategies, an open-access monitoring network representing regional aquifers is needed. More investigations based on extensive field visits are essential to monitor environmental, economic, and social conditions, identify constraints, and learn lessons for reclaiming desert lands. Moreover, this review highlighted the need to frame a rational strategy for the long-term sustainable exploitation of non-renewable groundwater in the aquifer systems of Egypt and develop an appropriate exit strategy for desert communities in case of serious water resource depletion.
An analysis of perspectives on groundwater governance arrangements relating to the potential development of unconventional oil and gas in South Africa
Authors: Hemingway Jack R. , Gormally-Sutton Alexandra
Published: November 2023

An analysis of expert perspectives on groundwater governance arrangements in South Africa is presented, particularly those arrangements that are pertinent to the complex and socially and ecologically significant implications of exploiting unconventional oil and gas (UOG). The paper presents a detailed assessment of literature on groundwater governance research, the findings of which are applied as a framework for a series of expert interviews, comprising hydrogeologists, lawyers, engineers, and governance specialists. This methodological approach was adopted as a means to enable an analysis of opinions on the current situation of groundwater governance in South Africa and how fit-for-purpose this is for managing the exploitation of UOG. The analysis was also informed by observation of participants at several relevant decision-making and stakeholder events. Whilst the findings indicated a generally positive evaluation of the initial steps taken to assess UOG impacts and engage relevant communities, recurrent criticisms also are featured across the interviews. Key implications arising from the research include: (1) the need for continued stakeholder engagement, and government follow-through on the outcomes of these processes, (2) the necessity for detailed groundwater-specific regulations to be drafted at the earliest opportunity, to ensure that the energy policy vacuum does not have a negative knock-on effect for effective groundwater management, and (3) the prevalence of significant governance gaps, particularly regarding regulatory and institutional capacity, and the need for continued development of a functional network of institutions to effectively manage UOG exploitation alongside groundwater resources.
Tocilizumab treatment in MOGAD: a case report and literature review
Authors: Schirò Giuseppe , Iacono Salvatore , Andolina Michele , Bianchi Alessia , Ragonese Paolo , Salemi Giuseppe
Published: November 2023

Myelin oligodendrocyte glycoprotein-immunoglobulin G associated disease (MOGAD) is an autoimmune demyelinating disorder of the central nervous system (CNS) which usually occurs with recurrent optic neuritis, transverse myelitis, acute disseminating encephalomyelitis, or brainstem encephalitis. To date, the anti-CD 20 drug rituximab (RTX) is employed in MOGAD although some authors reported the efficacy of Tocilizumab (TCZ) in refractory patients. We present the case of a woman affected by refractory MOGAD who was treated with TCZ after therapy with RTX had failed to prevent relapses. We also conducted a current literature review on TCZ use in MOGAD. A 57-year-old Caucasian woman affected by MOGAD with severe motor impairment and cognitive dysfunction was treated from 2020 to February 2022 with RTX. However, she experienced progressive clinical and cognitive worsening associated with white matter lesions mimicking leukodystrophy. In February 2022, the patient started therapy with TCZ administered with improvement of cognitive performance, walking ability, and brainstem functions. During TCZ, our patient reached the condition of NEDA-3 (no relapse, no increase in disability, no MRI activity on neuroimaging follow-up performed in September 2023). Moreover, the patient experienced paucisymptomatic SARS-CoV-2 infection that did not modify TCZ schedule. To date, there are few evidence on the efficacy and safety of TCZ in MOGAD. However, all the reviewed cases showed that TCZ represents an effective therapy in drug-resistant MOGAD. Our case highlights the efficacy of TCZ in drug resistant MOGAD and strengthens previous reports of TCZ safety and efficacy in MOGAD.
Joint knowledge graph approach for event participant prediction with social media retweeting
Authors: Zhang Yihong , Hara Takahiro
Published: November 2023

Organized event is an important form of human activity. Nowadays, many digital platforms offer organized events on the Internet, allowing users to be organizers or participants. For such platforms, it is beneficial to predict potential event participants. Existing work on this problem tends to borrow recommendation techniques. However, compared to e-commerce items and purchases, events and participation are usually of a much smaller frequency, and the data may be insufficient to learn an accurate prediction model. In this paper, we propose to utilize social media retweeting activity to enhance the learning of event participant prediction models. We create a joint knowledge graph to bridge the social media and the target domain, assuming that event descriptions and tweets are written in the same language. Furthermore, we propose a learning model that utilize retweeting information for the target domain prediction more effectively. We conduct comprehensive experiments in two scenarios with real-world data. In each scenario, we set up training data of different sizes, as well as warm and cold test cases. The evaluation results show that our approach consistently outperforms several baseline models in both warm and cold tests.
De Bello Homomorphico: Investigation of the extensibility of the OpenFHE library with basic mathematical functions by means of common approaches using the example of the CKKS cryptosystem
Authors: Prantl Thomas , Horn Lukas , Engel Simon , Iffländer Lukas , Beierlieb Lukas , Krupitzer Christian , Bauer André , Sakarvadia Mansi , Foster Ian , Kounev Samuel
Published: November 2023

Cloud computing has become increasingly popular due to its scalability, cost-effectiveness, and ability to handle large volumes of data. However, entrusting (sensitive) data to a third party raises concerns about data security and privacy. Homomorphic encryption is one solution that allows users to store and process data in a public cloud without the cloud provider having access to it. Currently, homomorphic encryption libraries only support addition and multiplication; other mathematical functions must be implemented by the user. To this end, we discuss and implement the division, exponential, square root, logarithm, minimum, and maximum function, using the CKKS cryptosystem of the OpenFHE library. To demonstrate that complex applications can be realized with this extended function set, we have used it to homomorphically realize the Box–Cox transform, which is used in many real-world applications, e.g., time-series forecasts. Our results show how the number of iterations required to achieve a given accuracy varies depending on the function. In addition, the execution time for each function is independent of the input and is in the range of ten seconds on a reference machine. With this work, we provide users with insights on how to extend the original restricted function set of the CKKS cryptosystem of the OpenFHE library with basic mathematical functions.
Ethool, a tool to enable legal decision-making in research involving humans using new technologies in Europe: design and usability validation
Authors: Garzo Ainara , Garay-Vitoria Nestor
Published: November 2023

Human participation in technological research projects has become more frequent in recent years. However, most of the technological researchers who organize such experimentation are unaware about the various ethical and legal implications involved. Further, when it is a medical device prototype that is being evaluated, the ethical and legal implications may be even more complex. A review of the laws, standards and recommendations in Europe has been drawn up regarding human participation in new technology co-design, development and evaluation, focusing on technological research for assistive and medical devices. An easy-to-use tool, called Ethool, which acts as a guideline for European technological researchers has been designed and developed. In this manuscript, the iterative usability evaluation of Ethool is explained as well as the improvements made, following participants’ feedback. Ethool was rated as acceptable and usable by participants obtaining a SUS score of 93.0 in its last evaluation. The tool is currently available to be used by any interested parties with the aim of gathering additional feedback.
Edge time series components of functional connectivity and cognitive function in Alzheimer’s disease
Authors: Chumin Evgeny J. , Cutts Sarah A. , Risacher Shannon L. , Apostolova Liana G. , Farlow Martin R. , McDonald Brenna C. , Wu Yu-Chien , Betzel Richard , Saykin Andrew J. , Sporns Olaf
Published: November 2023

Understanding the interrelationships of brain function as measured by resting-state magnetic resonance imaging and neuropsychological/behavioral measures in Alzheimer’s disease is key for advancement of neuroimaging analysis methods in clinical research. The edge time-series framework recently developed in the field of network neuroscience, in combination with other network science methods, allows for investigations of brain-behavior relationships that are not possible with conventional functional connectivity methods. Data from the Indiana Alzheimer’s Disease Research Center sample (53 cognitively normal control, 47 subjective cognitive decline, 32 mild cognitive impairment, and 20 Alzheimer’s disease participants) were used to investigate relationships between functional connectivity components, each derived from a subset of time points based on co-fluctuation of regional signals, and measures of domain-specific neuropsychological functions. Multiple relationships were identified with the component approach that were not found with conventional functional connectivity. These involved attentional, limbic, frontoparietal, and default mode systems and their interactions, which were shown to couple with cognitive, executive, language, and attention neuropsychological domains. Additionally, overlapping results were obtained with two different statistical strategies (network contingency correlation analysis and network-based statistics correlation). Results demonstrate that connectivity components derived from edge time-series based on co-fluctuation reveal disease-relevant relationships not observed with conventional static functional connectivity.