bluuebunny/crossref_metadata_2025 huggingface dataset:
Two body non-leptonic D0 decays from LCSR and implications for$${\Delta a}_{{\text{CP}}}^{{\text{dir}}}$$
Authors: Lenz Alexander , Piscopo Maria Laura , Rusov Aleksey V.
Published: March 2024

Abstract

Motivated by the recent measurements of CP violating effects in singly Cabibbo suppressed D0 decays, we revisit the theoretical predictions of these channels. Using up-to-date values for the decay constants and form factors, we find already within naive QCD factorisation, surprisingly good agreement between the central values of the branching ratios and the corresponding experimental data. We further extend the study of these modes by employing the method of light-cone sum rules (LCSR) with light-meson light-cone distribution amplitudes. Using for the first time this framework to compute the leading contribution to the decay amplitude, we can again describe well the experimental branching ratios for the modes D0 → π+K−, D0 → K+K−, D0 → π+π− and D0 → K+π−. The combination of our results with known predictions for the penguin contributions obtained with LCSR, leads to an upper bound for the value of direct CP violation expected in the Standard Model of $$\left|{\Delta a}_{{\text{CP}}}^{{\text{dir}}}\right|\le 2.4\times {10}^{-4}$$, which is approximately a factor six smaller than the current measurement.
Cone holography with Neumann boundary conditions and brane-localized gauge fields
Authors: Cui Zheng-Quan , Guo Yu , Miao Rong-Xin
Published: March 2024

Abstract

Cone holography is a codimension-n doubly holographic model, which can be interpreted as the holographic dual of edge modes on defects. The initial model of cone holography is based on mixed boundary conditions. This paper formulates cone holography with Neumann boundary conditions, where the brane-localized gauge fields play an essential role. Firstly, we illustrate the main ideas in an AdS4/CFT1 toy model. We show that the U(1) gauge field on the end-of-the-world brane can make the typical solution consistent with Neumann boundary conditions. Then, we generalize the discussions to general codimension-n cone holography by employing brane-localized p-form gauge fields. We also investigate perturbative solutions and prove the mass spectrum of Kaluza-Klein gravitons is non-negative. Furthermore, we prove that cone holography obeys holographic c-theorem. Finally, inspired by the recently proposed chiral model in AdS/BCFT, we construct another type of cone holography with Neumann boundary conditions by applying massive vector (Proca) fields on the end-of-the-world brane.
Superconformal indices for non-Lagrangian theories in five dimensions
Authors: Kim Hee-Cheol , Kim Minsung , Kim Sung-Soo , Zafrir Gabi
Published: March 2024

Abstract

We propose two novel methods for computing the superconformal index of 5d superconformal field theories that cannot be described by conventional Lagrangian descriptions under mass deformations. The first approach involves the use of Higgs branch flows from UV Lagrangian theories, guided by transitions in 5-brane webs in Type IIB string theory. The second method employs the relationship between O7+-plane and O7−-plane with eight D7-branes, which applies to particular non-Lagrangian theories realized by brane configurations involving an O7+-plane. As a concrete application of our method, we compute the superconformal indices for all known rank-1 non-Lagrangian theories, which we also use to identify flavor symmetries and their global forms at the conformal field theory (CFT) fixed points.
Discovery and verification of mmu_Circ_26986/hsa_Circ_0072463 as a potential biomarker and intervention target for sepsis-associated acute kidney injury
Authors: Peng Xujun , Li Huiling , Zhang Wenbo , Zhang Dongshan
Published: March 2024

Approximately 60% of septic patients developed acute kidney injury (AKI). The mortality rate of septic AKI (SA-AKI) is two to three times higher than that of septic without AKI (SA-non-AKI). The actual functions and mechanisms of CircRNAs in the pathophysiology of SA-AKI remain incompletely understood. Herein, we observed that the mmu_Circ_26986 could be induced by lipopolysaccharide (LPS) and cecum ligation and puncture (CLP) in BUMPT cell line and C57BL/6 mouse kidney, respectively. Functionally, mmu_Circ_26986 suppressed BUMPT cell apoptosis induced by LPS. Mechanistically, mmu_Circ_26986 sponged miRNA-29b-1-5p to upregulate the expression of PAK7. Overexpression of mmu_Circ_26986 ameliorated the progression of CLP-stimulated AKI through miRNA-29b-1-5p/PAK7 axis. In addition, we found that hsa_Circ_0072463, homologous to mmu_Circ_26986, suppressed LPS-induced HK-2 cells apoptosis via regulation of miRNA-29b-1-5p/PAK7 axis. Furthermore, sepsis patients with AKI had a higher level of hsa_Circ_0072463 compared to those without AKI. The sensitivity, specificity and AUC of hsa_Circ_0072463 were 78.8%, 87.9% and 0.866, respectively. Spearman's test indicated a noticeable positive correlation between plasma hsa_Circ_0072463 and serum creatinine in sepsis patients (r = 0.725). In summary, this study reveals that the mmu_Circ_26986/hsa_Circ_0072463 miRNA-29b-1-5p/PAK7 axis mediates septic AKI, and hsa_Circ_0072463 is a potential diagnostic marker for septic AKI.
Augmented Lagrangian Acceleration of Global-in-Time Pressure Schur Complement Solvers for Incompressible Oseen Equations
Authors: Lohmann Christoph , Turek Stefan
Published: March 2024

This work is focused on an accelerated global-in-time solution strategy for the Oseen equations, which highly exploits the augmented Lagrangian methodology to improve the convergence behavior of the Schur complement iteration. The main idea of the solution strategy is to block the individual linear systems of equations at each time step into a single all-at-once saddle point problem. By elimination of all velocity unknowns, the resulting implicitly defined equation can then be solved using a global-in-time pressure Schur complement (PSC) iteration. To accelerate the convergence behavior of this iterative scheme, the augmented Lagrangian approach is exploited by modifying the momentum equation for all time steps in a strongly consistent manner. While the introduced discrete grad-div stabilization does not modify the solution of the discretized Oseen equations, the quality of customized PSC preconditioners drastically improves and, hence, guarantees a rapid convergence. This strategy comes at the cost that the involved auxiliary problem for the velocity field becomes ill conditioned so that standard iterative solution strategies are no longer efficient. Therefore, a highly specialized multigrid solver based on modified intergrid transfer operators and an additive block preconditioner is extended to solution of the all-at-once problem. The potential of the proposed overall solution strategy is discussed in several numerical studies as they occur in commonly used linearization techniques for the incompressible Navier–Stokes equations.
Sarcopenia is associated with chemoradiotherapy discontinuation and reduced progression-free survival in glioblastoma patients
Authors: Troschel Fabian M. , Troschel Benjamin O. , Kloss Maren , Jost Johanna , Pepper Niklas B. , Völk-Troschel Amelie S. , Wiewrodt Rainer G. , Stummer Walter , Wiewrodt Dorothee , Eich Hans Theodor
Published: March 2024

Purpose

Sarcopenia may complicate treatment in cancer patients. Herein, we assessed whether sarcopenia measurements derived from radiation planning computed tomography (CT) were associated with complications and tumor progression during radiochemotherapy for glioblastoma.

Methods

Consecutive patients undergoing radiotherapy planning for glioblastoma between 2010 and 2021 were analyzed. Retrocervical muscle cross-sectional area (CSA) was measured via threshold-based semi-automated radiation planning CT analysis. Patients in the lowest sex-specific quartile of muscle measurements were defined as sarcopenic. We abstracted treatment characteristics and tumor progression from the medical records and performed uni- and multivariable time-to-event analyses.

Results

We included 363 patients in our cohort (41.6% female, median age 63 years, median time to progression 7.7 months). Sarcopenic patients were less likely to receive chemotherapy (p < 0.001) and more likely to be treated with hypofractionated radiotherapy (p = 0.005). Despite abbreviated treatment, they more often discontinued radiotherapy (p = 0.023) and were more frequently prescribed corticosteroids (p = 0.014). After treatment, they were more often transferred to inpatient palliative care treatment (p = 0.035). Finally, progression-free survival was substantially shorter in sarcopenic patients in univariable (median 5.1 vs. 8.4 months, p < 0.001) and multivariable modeling (hazard ratio 0.61 [confidence interval 0.46–0.81], p = 0.001).

Conclusion

Sarcopenia is a strong risk factor for treatment discontinuation and reduced progression-free survival in glioblastoma patients. We propose that sarcopenic patients should receive intensified supportive care during radiotherapy and during follow-up as well as expedited access to palliative care.
Design of metamaterial-based heat manipulators using isogeometric level-set topology optimization
Authors: Jansari Chintan , Bordas Stéphane P. A. , Atroshchenko Elena
Published: March 2024

We exploit level-set topology optimization to find the optimal material distribution for metamaterial-based heat manipulators. The level-set function, geometry, and solution field are parameterized using the Non-Uniform Rational B-Spline (NURBS) basis functions to take advantage of easy control of smoothness and continuity. In addition, NURBS approximations can produce conic geometries exactly and provide higher efficiency for higher-order elements. The values of the level-set function at the control points (called expansion coefficients) are utilized as design variables. For optimization, we use an advanced mathematical programming technique, Sequential Quadratic Programming. Taking into account a large number of design variables and the small number of constraints associated with our optimization problem, the adjoint method is utilized to calculate the required sensitivities with respect to the design variables. The efficiency and robustness of the proposed method are demonstrated by solving three numerical examples. We have also shown that the current method can handle different geometries and types of objective functions. In addition, regularization techniques such as Tikhonov regularization and volume regularization have been explored to reduce unnecessary complexity and increase the manufacturability of optimized topologies.
Physicochemical compatibility of caffeine citrate and caffeine base injections with parenteral medications used in neonatal intensive care settings
Authors: De Silva D. Thisuri N. , Petrovski Michael , Strunk Tobias , Mukadam Nabeelah , Page-Sharp Madhu , Moore Brioni R. , Batty Kevin T.
Published: March 2024

Purpose

To investigate the physicochemical compatibility of caffeine citrate and caffeine base injections with 43 secondary intravenous (IV) drugs used in Neonatal Intensive Care Unit (NICU) settings.

Methods

Caffeine citrate (20 mg/mL or 10 mg/mL) or caffeine base injection (10 mg/mL) were mixed in a volume ratio of 1:1 with the secondary drug solution to simulate Y-site co-administration procedures in NICUs. Physical compatibility was evaluated based on visual observation for 2 h, against a black and white background and under polarised light, for changes in colour, precipitation, haze and evolution of gas. Chemical compatibility was determined from caffeine concentration measurements, using a validated high-performance liquid chromatography assay.

Results

Six of the 43 secondary drugs tested (aciclovir, amphotericin (liposomal), furosemide, hydrocortisone, ibuprofen and ibuprofen lysine) were physically incompatible with caffeine citrate undiluted injection (20 mg/mL), at their high-end, clinically relevant concentrations for NICU settings. However, when tested at lower concentrations, hydrocortisone (1 mg/mL) was physicochemically compatible, whereas furosemide (0.2 mg/mL) was physically incompatible with caffeine citrate. The six drugs which showed physical incompatibility with caffeine citrate 20 mg/mL injection were also physically incompatible with caffeine citrate 10 mg/mL solution. All 43 secondary drugs tested were physicochemically compatible with caffeine base injection.

Conclusions

Most secondary test drugs, except aciclovir, amphotericin (liposomal), furosemide, hydrocortisone, ibuprofen and ibuprofen lysine, were physicochemically compatible with caffeine citrate injection. Caffeine base injection was physicochemically compatible with all 43 test drugs tested.
Berge equilibrium, altruism and social welfare
Authors: Haller Hans
Published: March 2024

Welfare and other properties of Berge equilibria are investigated. In particular, we address the questions to what extent Berge equilibrium can select from multiple Nash equilibria; can serve as a substitute for Nash equilibria; can Pareto improve upon Nash equilibrium. Furthermore, some of the recent results on the relation between Berge equilibria and Kantian equilibria are summarized.
On the existence of stationary threshold bilinear processes
Authors: Ghezal Ahmed , Cavicchioli Maddalena , Zemmouri Imane
Published: March 2024

This article investigates some statistical and probabilistic properties of general threshold bilinear processes. Sufficient conditions for the existence of a causal, strictly and weak stationary solution for the equation defining a self-exciting threshold superdiagonal bilinear $$\left( SETBL\right) $$

S
E
T
B
L

process are derived. Then it is shown that under well-specified hypotheses the higher-order moments of the SETBL process are finite. As a result, the skewness and kurtosis indexes are explicitly computed. The exact autocorrelation function is derived with an arbitrarily fixed number of regimes. Also, the covariance functions of the process and its powers are evaluated and the second (respectively, higher)-order structure is shown to be similar to that of a linear process. This implies that the considered process admits an ARMA representation. Finally, necessary and sufficient conditions for the invertibility and geometric ergodicity of a SETBL model are established. Some examples illustrate the obtained theoretical results.
Prosecuting cases of abusive head trauma in Switzerland: a descriptive study of the impact of medical documentation and delay of reporting on judicial outcome
Authors: Held Sarah , Cheseaux Jean-Jacques , Tolsa Jean-François , Depallens Sarah
Published: March 2024

Abusive head trauma (AHT) is a criminal offence that is prosecuted ex officio, following report to the police from physicians or child protection services. The aim of this study was to assess whether the judicial outcome (dismissal vs indictment) was influenced by the quality of the medical documentation and/or the time span between AHT diagnosis and reporting child abuse to the police. The cohort was divided in two groups: 13/23 dismissals (57%) and 10/23 indictments (43%). The diagnostic probability of the AHT cases was certain for both groups. Nonetheless, in fraction of dismissed cases, alternative explanations for the observed lesions seemed plausible to the public prosecutor. Legal files of only 3/12 dismissed cases had a forensic report, while 6/10 cases that were indicted included a forensic report. Further, the legal file of several dismissed cases entirely lacked medical documentation (3/12), which was not the cases for indicted cases. The period between AHT diagnosis and reporting to the police was not different for dismissals (29 ± 19 days) and indictments (7 ± 4 days) (p = 0.32). Physicians filed reports more rapidly (6 ± 1 days) compared to childhood protection service (70 ± 46 days) (p = 0.01) and that may increase the rate of indictments (9/18) compared to reporting via the childhood protection service (1/5). Despite diagnostic certainty, other causes for the lesions were considered as plausible alternative explanations to judicial professionals in several dismissed cases. These seemed to have less medical documentation and forensic evaluations. In addition, more rapid reporting to the police by physicians seems to increase the likelihood of indictments.
Variants in mitochondrial disease genes are common causes of inherited peripheral neuropathies
Authors: Ferreira Tomas , Polavarapu Kiran , Olimpio Catarina , Paramonov Ida , Lochmüller Hanns , Horvath Rita
Published: March 2024

Background

Peripheral neuropathies in mitochondrial disease are caused by mutations in nuclear genes encoding mitochondrial proteins, or in the mitochondrial genome. Whole exome or genome sequencing enable parallel testing of nuclear and mtDNA genes, and it has significantly advanced the genetic diagnosis of inherited diseases. Despite this, approximately 40% of all Charcot-Marie-Tooth (CMT) cases remain undiagnosed.

Methods

The genome-phenome analysis platform (GPAP) in RD-Connect was utilised to create a cohort of 2087 patients with at least one Human Phenotype Ontology (HPO) term suggestive of a peripheral neuropathy, from a total of 10,935 patients. These patients’ genetic data were then analysed and searched for variants in known mitochondrial disease genes.

Results

A total of 1,379 rare variants were identified, 44 of which were included in this study as either reported pathogenic or likely causative in 42 patients from 36 families. The most common genes found to be likely causative for an autosomal dominant neuropathy were GDAP1 and GARS1. We also detected heterozygous likely pathogenic variants in DNA2, MFN2, DNM2, PDHA1, SDHA, and UCHL1. Biallelic variants in SACS, SPG7, GDAP1, C12orf65, UCHL1, NDUFS6, ETFDH and DARS2 and variants in the mitochondrial DNA (mtDNA)-encoded MT-ATP6 and MT-TK were also causative for mitochondrial CMT. Only 50% of these variants were already reported as solved in GPAP.

Conclusion

Variants in mitochondrial disease genes are frequent in patients with inherited peripheral neuropathies. Due to the clinical overlap between mitochondrial disease and CMT, agnostic exome or genome sequencing have better diagnostic yields than targeted gene panels.
Exposure to benzotriazoles and benzothiazoles in Czech male population and its associations with biomarkers of liver function, serum lipids and oxidative stress
Authors: Pálešová Nina , Bláhová Lucie , Janoš Tomáš , Řiháčková Katarína , Pindur Aleš , Šebejová Ludmila , Čupr Pavel
Published: March 2024

Introduction

Benzotriazoles and benzothiazoles (BTs) are high-production volume chemicals as well as widely distributed emerging pollutants with potential health risk. However, information about human exposure to BTs and associated health outcomes is limited.

Objective

We aimed to characterise exposure to BTs among Czech men, including possible occupational exposure among firefighters, its predictors, and its associations with liver function, serum lipids and oxidative stress.

Methods

165 participants (including 110 firefighters) provided urine and blood samples that were used to quantify the urinary levels of 8 BTs (high-performance liquid chromatography-tandem mass spectrometry), and 4 liver enzymes, cholesterol, low-density lipoprotein, and 8-hydroxy-2’-deoxyguanosine. Linear regression was used to assess associations with population characteristics and biomarkers of liver function, serum lipids and oxidative stress. Regression models were adjusted for potential confounding variables and false discovery rate procedure was applied to account for multiplicity.

Results

The BTs ranged from undetected up to 46.8 ng/mL. 2-hydroxy-benzothiazole was the most predominant compound (detection frequency 83%; median 1.95 ng/mL). 1-methyl-benzotriazole (1M-BTR) was measured in human samples for the first time, with a detection frequency 77% and median 1.75 ng/mL. Professional firefighters had lower urinary 1M-BTR compared to non-firefighters. Urinary 1M-BTR was associated with levels of γ-glutamyl transferase (β = − 17.54%; 95% CI: − 26.127, − 7.962).

Conclusion

This is the first study to investigate BT exposure in Central Europe, including potentially exposed firefighters. The findings showed a high prevalence of BTs in the study population, the relevance of 1M-BTR as a new biomarker of exposure, and an urgent need for further research into associated adverse health outcomes.

Graphical abstract
Durability of the moderate-to-heavy-intensity transition is related to the effects of prolonged exercise on severe-intensity performance
Authors: Hamilton Kate , Kilding Andrew E. , Plews Daniel J. , Mildenhall Mathew J. , Waldron Mark , Charoensap Thanchanok , Cox Tobias H. , Brick Matthew J. , Leigh Warren B. , Maunder Ed
Published: March 2024

Purpose

Power output at the moderate-to-heavy-intensity transition decreases during prolonged exercise, and resilience to this has been termed ‘durability’. The purpose of this study was to assess the relationship between durability and the effect of prolonged exercise on severe-intensity performance, and explore intramuscular correlates of durability.

Methods

On separate days, 13 well-trained cyclists and triathletes (V̇O2peak, 57.3 ± 4.8 mL kg−1 min−1; training volume, 12 ± 2.1 h week−1) undertook an incremental test and 5-min time trial (TT) to determine power output at the first ventilatory threshold (VT1) and severe-intensity performance, with and without 150-min of prior moderate-intensity cycling. A single resting vastus lateralis microbiopsy was obtained.

Results

Prolonged exercise reduced power output at VT1 (211 ± 40 vs. 198 ± 39 W, ∆ -13 ± 16 W, ∆ -6 ± 7%, P = 0.013) and 5-min TT performance (333 ± 75 vs. 302 ± 63 W, ∆ -31 ± 41 W, ∆ -9 ± 10%, P = 0.017). The reduction in 5-min TT performance was significantly associated with durability of VT1 (rs = 0.719, P = 0.007). Durability of VT1 was not related to vastus lateralis carnosine content, citrate synthase activity, or complex I activity (P > 0.05).

Conclusion

These data provide the first direct support that durability of the moderate-to-heavy-intensity transition is an important performance parameter, as more durable athletes exhibited smaller reductions in 5-min TT performance following prolonged exercise. We did not find relationships between durability and vastus lateralis carnosine content, citrate synthase activity, or complex I activity.
The ex vivo perfused mouse adrenal gland—a new model to study aldosterone secretion
Authors: Plain Allein , Knödl Laura , Tegtmeier Ines , Bandulik Sascha , Warth Richard
Published: March 2024

Aldosterone is a steroid hormone that is important for maintaining the volume and ionic composition of extracellular fluids and is produced in the zona glomerulosa of the adrenal cortex. The basic mechanisms controlling aldosterone secretion are known. However, more detailed studies on the regulation of aldosterone secretion often fail due to the lack of suitable models: although secretion can be studied in cultured adrenocortical cells under defined conditions, the differentiation status of the cells is difficult to control and the complex anatomy of the adrenal cortex is lost. In living animals, the physiological context is intact, but the influences are manifold and the examination conditions cannot be sufficiently controlled. One method that closes the gap between cell models and studies in living animals is the isolated perfused adrenal gland. In the past, this method has provided important data on the pathophysiology of adrenal glands from larger animals, but the technique was not used in mice. Here, we developed a method for isolation and perfusion of the mouse adrenal gland to study aldosterone secretion. This technique preserves the complex anatomical and functional context of the mouse adrenal cortex, to ensure defined experimental conditions and to minimize extra-adrenal influences. Initial series of experiments with the ex vivo perfused mouse adrenal gland show that this model offers the possibility for unique insights into pathophysiological regulatory principles and is suitable for the use of genetically modified mouse models.
Hydroxy(phenyl)pyruvic acid reductase in Actaea racemosa L.: a putative enzyme in cimicifugic and fukinolic acid biosynthesis
Authors: Jahn Anne , Petersen Maike
Published: March 2024

Main conclusion

Hydroxy(phenyl)pyruvic acid reductase from Actaea racemosa catalyzes dual reactions in reducing 4-hydroxyphenylpyruvic acid as well as β-hydroxypyruvic acid. It thus qualifies to be part of fukinolic and cimicifugic acid biosynthesis and also photorespiration.

The accumulation of fukinolic acid and cimicifugic acids is mainly restricted to Actaea racemosa (Ranunculaceae) and other species of the genus Actaea/Cimicifuga. Cimicifugic and fukinolic acids are composed of a hydroxycinnamic acid part esterified with a benzyltartaric acid moiety. The biosynthesis of the latter is unclear. We isolated cDNA encoding a hydroxy(phenyl)pyruvic acid reductase (GenBank OR393286) from suspension-cultured material of A. racemosa (ArH(P)PR) and expressed it in E. coli for protein production. The heterologously synthesized enzyme had a mass of 36.51 kDa and catalyzed the NAD(P)H-dependent reduction of 4-hydroxyphenylpyruvic acid to 4-hydroxyphenyllactic acid or β-hydroxypyruvic acid to glyceric acid, respectively. The optimal temperature was at 38 °C and the pH optimum at pH 7.5. NADPH is the preferred cosubstrate (Km 23 ± 4 µM). Several substrates are accepted by ArH(P)PR with β-hydroxypyruvic acid (Km 0.26 ± 0.12 mM) followed by 4-hydroxyphenylpyruvic acid (Km 1.13 ± 0.12 mM) as the best ones. Thus, ArH(P)PR has properties of β-hydroxypyruvic acid reductase (involved in photorespiration) as well as hydroxyphenylpyruvic acid reductase (possibly involved in benzyltartaric acid formation).
Resveratrol ameliorates glioblastoma inflammatory response by reducing NLRP3 inflammasome activation through inhibition of the JAK2/STAT3 pathway
Authors: Zhang Chao , Peng Qian , Tang Yuhang , Wang Chengcheng , Wang Shuai , Yu Dong , Hou Shiqiang , Wang Yu , Zhang Lanlan , Lin Ning
Published: March 2024

Objectives

The aim of this study was to investigate the anti-tumor effect of resveratrol (RSV) on glioblastoma (GBM) and its specific mechanism in improving the inflammatory response of the tumor microenvironment. The tumor microenvironment of GBM is highly neuroinflammatory, inducing tumor immunosuppression. Therefore, ameliorating the inflammatory response is an important focus for anti-tumor research.

Methods

The anti-tumor effect of RSV on GBM was demonstrated through in vitro cellular assays, including CCK-8, EdU, PI staining, Transwell, wound healing assay, and flow cytometry. Potential mechanisms of RSV's anti-GBM effects were identified through network pharmacological analysis. In addition, the relationship of RSV with the JAK2/STAT3 signaling pathway and the inflammasome NLRP3 was verified using Western blot.

Results

RSV significantly inhibited cell viability in GBM cell lines LN-229 and U87-MG. Furthermore, it inhibited the proliferation and invasive migration ability of GBM cells, while promoting apoptosis. Network pharmacological analysis revealed a close association between the anti-GBM effects of RSV and the JAK/STAT signaling pathway, as well as inflammatory responses. Western blot analysis confirmed that RSV inhibited the over-activation of the inflammasome NLRP3 through the JAK2/STAT3 signaling pathway. Partial reversal of RSV's inhibition of inflammasome NLRP3 was observed with the addition of the JAK/STAT agonist RO8191.

Conclusions

In vitro, RSV can exert anti-tumor effects on GBM and improve the inflammatory response in the GBM microenvironment by inhibiting the activation of the JAK2/STAT3 signaling pathway. These findings provide new insights into potential therapeutic targets for GBM.
Urocortin-1 promotes colorectal cancer cell migration and proliferation and inhibits apoptosis via inhibition of the p53 signaling pathway
Authors: Guo Xiaolan , Li Ya , Chen Xiangyu , Sun Binghua , Guo Xiaolan
Published: March 2024

Purpose

To investigate the effect of urocortin-1 (UCN-1) on growth, migration, and apoptosis in colorectal cancer (CRC) in vivo and vitro and the mechanism by which UCN-1 modulates CRC cells in vitro.

Methods

The correlation between UCN-1 and CRC was evaluated using The Cancer Genome Atlas (TCGA) database and a tissue microarray. The expression of UCN-1 in CRC cells was assessed using quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting. In vitro, the influence of UCN-1 on the proliferation, apoptosis, and migration of HT-29, HCT-116, and RKO cells was explored using the celigo cell counting assay or cell counting kit-8 (CCK8), flow cytometry, and wound healing or Transwell assays, respectively. In vivo, the effect of UCN-1 on CRC growth and progression was evaluated in nude mice. The downstream pathway underlying UCN-1-mediated regulation of CRC was determined using the phospho-kinase profiler array in RKO cells. Lentiviruses were used to knockdown or upregulate UCN-1 expression in cells.

Results

Both the TCGA and tissue microarray results showed that UCN-1 was strongly expressed in the tissues of patients with CRC. Furthermore, the tissue microarray results showed that the expression of UCN-1 was higher in male than in female patients, and high expression of UCN-1 was associated with higher risk of lymphatic metastasis and later pathological stage. UCN-1 knockdown caused a reduction in CRC cell proliferation, migration, and colony formation, as well as an increase in apoptosis. In xenograft experiments, tumors generated from RKO cells with UCN-1 knockdown exhibited reduced volumes and weights. A reduction in the expression of Ki-67 in xenograft tumors indicated that UCN-1 knockdown curbed tumor growth. The human phospho-kinase array showed that the p53 signaling pathway participated in UCN-1-mediated CRC development. The suppression in migration and proliferation caused by UCN-1 knockdown was reversed by inhibitors of p53 signal pathway, while the increase in cell apoptosis was suppressed. On the other hand, overexpression of UCN-1 promoted proliferation and migration and inhibited apoptosis in CRC cells. Overexpression of p53 reversed the effect of UCN-1 overexpression on CRC development.

Conclusion

UCN-1 promotes migration and proliferation and inhibits apoptosis via inhibition of the p53 signaling pathway.
Rahmenbedingungen einer Forschungsethik der datenintensiven medizinischen Forschung
Authors: Wiesing Urban , Funer Florian
Published: March 2024

Die Forschungs- und Regulierungsebene bei datenintensiver Forschung in der Medizin liegen auseinander. Ein heterogenes Feld aus regulierenden Institutionen mit regional ungleichen Regelungen, sowohl hinsichtlich der Dichte als auch der Restriktivität von Regelungen, steht einer globalen Entwicklung der Technologien entgegen. Trotz oder gerade wegen mangelnder global-gültiger Regulierungen können auch unverbindliche oder nur bedingt verbindliche normative Vorgaben der Orientierung dienen. Doch wie soll eine solche normative Regulierung angesichts datenintensiver Forschung in der Medizin ausgestaltet werden und woran soll sie sich orientieren? Die Frage, wie konkret und detailliert man eine solche Forschung regulieren sollte, lässt sich nur im Einzelfall für bestimmte Situationen und Institutionen beantworten. Ob dabei neue Normen oder Gewichtungen von Normen vorgenommen werden sollen, oder ob die Normen und deren Gewichtung weiterhin bestehen bleiben sollen, lässt sich nur mit Verweis auf starke normative Argumente beantworten. An zwingenden Argumenten für neue Normen angesichts der datenintensiven medizinischen Forschung mangelt es bisher. Dennoch ist eine Umsetzungsarbeit von Normen, egal ob neue oder alte, und deren Anwendung auf eine neue Methode oder Technologie allemal zu erbringen. Es bedarf daher – wie schon bisher – beider: sowohl etablierter und transparent kommunizierter Normen als auch des unabhängigen Urteils zur Anwendung dieser Normen. Angesichts der besonderen Eignung für diese Aufgabe sollten auch weiterhin Ethik-Kommissionen als prozedurale Instanz bei der Bewilligung von datenintensiver Forschung in der Medizin gefordert und befähigt werden, die als unabhängige Institution ein Urteil im Einzelfall anhand vorgegebener Normen fällen. Nichtsdestotrotz können sich die veränderten Praktiken datenintensiver Forschungsprojekte auch in neuen Anforderungen an Ethik-Kommissionen niederschlagen, denen mit Reformen der Arbeitsweise begegnet werden sollte.
Learn & drop: fast learning of cnns based on layer dropping
Authors: Cruciata Giorgio , Cruciata Luca , Lo Presti Liliana , van Gemert Jan , La Cascia Marco
Published: March 2024

This paper proposes a new method to improve the training efficiency of deep convolutional neural networks. During training, the method evaluates scores to measure how much each layer’s parameters change and whether the layer will continue learning or not. Based on these scores, the network is scaled down such that the number of parameters to be learned is reduced, yielding a speed-up in training. Unlike state-of-the-art methods that try to compress the network to be used in the inference phase or to limit the number of operations performed in the back-propagation phase, the proposed method is novel in that it focuses on reducing the number of operations performed by the network in the forward propagation during training. The proposed training strategy has been validated on two widely used architecture families: VGG and ResNet. Experiments on MNIST, CIFAR-10 and Imagenette show that, with the proposed method, the training time of the models is more than halved without significantly impacting accuracy. The FLOPs reduction in the forward propagation during training ranges from 17.83% for VGG-11 to 83.74% for ResNet-152. As for the accuracy, the impact depends on the depth of the model and the decrease is between 0.26% and 2.38% for VGGs and between 0.4 and 3.2% for ResNets. These results demonstrate the effectiveness of the proposed technique in speeding up learning of CNNs. The technique will be especially useful in applications where fine-tuning or online training of convolutional models is required, for instance because data arrive sequentially.
Detection of multitask mental workload using gamma band power features
Authors: Korkmaz Onur Erdem , Korkmaz Sevde Gül , Aydemir Onder
Published: March 2024

Cognitive fatigue occurs in various situations and is an essential condition to detect. In this study, how single and multi-tasking tests affect cognitive workload was examined, and multi-tasking was detected using electroencephalography (EEG) signals. In the cognitive workload paradigm, single-task tests with blocks 1 and 2 and multi-tasking tests with block 3 were created. EEG signals obtained from these blocks were treated as different frequency bands and lengths, and binary classification was performed. Two binary classifications were made: block 1–block 3 and block 2–block 3. According to the results, the highest classification accuracy for block 1–block 3 was obtained as 97.11% using the gamma frequency band and 5-s EEG length. For block 2–block 3, the highest classification accuracy was obtained as 90.88% using the gamma frequency band and 5-s EEG length. As a result, this study distinguished multi-tasking and single task with high classification accuracy. The developed model can be used to detect attention deficit and inability to focus. In addressing the prevalent challenges of distinguishing cognitive fatigue in single—task versus multitasking scenarios, our study offers a new method, which achieve a remarkable accuracy rate, thereby illuminating a new path in the research of cognitive fatigue.
Impact of intraoperative imaging on decision-making during spine surgery: a survey among spine surgeons using simulated intraoperative images
Authors: Bindels Bas J. J. , Hovenier Renée , Groot Olivier Q. , Vincken Koen L. , Rongen Jan J. , Smits Maarten L. J. , Verlaan Jorrit-Jan
Published: March 2024

Purpose

To assess whether the intention to intraoperatively reposition pedicle screws differs when spine surgeons evaluate the same screws with 2D imaging or 3D imaging.

Methods

In this online survey study, 21 spine surgeons evaluated eight pedicle screws from patients who had undergone posterior spinal fixation. In a simulated intraoperative setting, surgeons had to decide if they would reposition a marked pedicle screw based on its position in the provided radiologic imaging. The eight assessed pedicle screws varied in radiologic position, including two screws positioned within the pedicle, two breaching the pedicle cortex < 2 mm, two breaching the pedicle cortex 2–4 mm, and two positioned completely outside the pedicle. Surgeons assessed each pedicle screw twice without knowing and in random order: once with a scrollable three-dimensional (3D) image and once with two oblique fluoroscopic two-dimensional (2D) images.

Results

Almost all surgeons (19/21) intended to reposition more pedicle screws based on 3D imaging than on 2D imaging, with a mean number of pedicle screws to be repositioned of, respectively, 4.1 (± 1.3) and 2.0 (± 1.3; p < 0.001). Surgeons intended to reposition two screws placed completely outside the pedicle, one breaching 2-4mm, and one breaching < 2 mm more often based on 3D imaging.

Conclusion

When provided with 3D imaging, spine surgeons not only intend to intraoperatively reposition pedicle screws at risk of causing postoperative complications more often but also screws with acceptable positions. This study highlights the potential of intraoperative 3D imaging as well as the need for consensus on how to act on intraoperative 3D information.
Correlation between the MNCD classification-based staging of Parkinson’s disease and quality of life: a cross-sectional study
Authors: He Guixiang , Ren Jingru , Shi Haicun , Liu Weiguo , Lu Ming
Published: March 2024

Parkinson’s disease (PD) is a highly heterogeneous neurodegenerative disorder with varying clinical subtypes. Recently, a novel classification called MNCD (Motor/Non-motor/Cognition/Dependency) has been proposed, which can also include staging based on disease severity. We aim to investigate which staging, the MNCD classification and staging or Hoehn and Yahr (H&Y) staging, exhibits a stronger correlation with the 39-item Parkinson’s Disease Questionnaire (PDQ-39). In a cross-sectional study conducted at our single center, 357 PD patients were recruited. Data encompassed scores from various assessments such as the Movement Disorder Society of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts I, II, III and IV, Montreal Cognitive Assessment (MoCA), PDQ-39, and the H&Y scale. The mean age of these patients was 66.4 ± 9.1 years old, and the majority (54.6%) were male. MNCD stages: stage 1 (N = 3, 0.8%), stage 2 (N = 62, 17.4%), stage 3 (N = 187, 52.4%), stage 4 (N = 86, 24.1%), and stage 5 (N = 19, 5.3%). The top 5 most frequent PD-related clinical symptoms were sleep disturbances (89.6%), fatigue (69.7%), mild cognitive impairment (68.9%), constipation (65.8%), and postural instability (65.5%). The PDQ-39 demonstrated a positive correlation with both MNCD staging and H&Y staging. Moreover, the MNCD staging exhibited a stronger correlation with PDQ-39 compared to H&Y staging. The correlation between the MNCD classification and staging with the quality of life in PD patients is more statistically significant compared to the H&Y staging.
Diagnostic utility of ultrasound in pediatric nasal bone fractures: a systematic review and meta-analysis
Authors: Hassankhani Amir , Amoukhteh Melika , Jannatdoust Payam , Valizadeh Parya , Ghadimi Delaram J. , Saeedi Nikoo , Fathi Mobina , Yaghoobpoor Shirin , Adli Paniz , Vasavada Pauravi S. , Gholamrezanezhad Ali
Published: March 2024

Ultrasonography, a radiation-free and cost-effective modality, stands out as a promising tool for evaluating nasal bone fractures. Despite limited literature on its pediatric application, there is an increasing recognition of its potential to enhance diagnostic precision. To evaluate the diagnostic efficacy of ultrasound in detecting pediatric nasal bone fractures. Employing established guidelines, a systematic review and meta-analysis were conducted through a comprehensive literature search in PubMed, Scopus, Web of Science, and Embase databases until December 5, 2023. Inclusion criteria encompassed studies reporting diagnostic accuracy measures of ultrasound in pediatric patients with nasal bone fractures. Data extraction and analysis were undertaken for the selected studies. Involving four studies with 277 patients, ultrasound demonstrated a pooled sensitivity of 66.1% (95% CI: 35.1-87.5%) and specificity of 86.8% (95% CI: 80.1-91.4%) in diagnosing pediatric nasal fractures. The area under the receiver operating characteristic curve (AUC) was 0.88 (95% CI: 0.72–0.93). After excluding an outlier study, sensitivity and specificity increased to 78.0% (95% CI: 65.6-86.9%) and 87.8 (95% CI: 78.1-93.6%), respectively, with an AUC of 0.79 (95% CI: 0.75–0.94). Pooled positive and negative likelihood ratios were 5.11 (95% CI: 2.12–9.15) and 0.40 (95% CI: 0.14–0.77) before exclusion and 6.75 (95% CI: 3.47–12.30) and 0.26 (95% CI: 0.15–0.40) after exclusion of an outlier study, respectively. This study highlighted ultrasonography’s utility in diagnosing pediatric nasal bone fractures with high accuracy and specificity. However, caution is advised in relying solely on ultrasound due to suboptimal overall diagnostic performance, evident in likelihood ratios.
Cysteine- and glycine-rich protein 1 predicts prognosis and therapy response in patients with acute myeloid leukemia
Authors: Hao Qianqian , Liu Yu , Liu Yajun , Shi Luyao , Chen Yufei , Yang Lu , Jiang Zhongxing , Liu Yanfang , Wang Chong , Wang Shujuan , Sun Ling
Published: March 2024

Acute myeloid leukemia (AML) is a heterogeneous disease with a poor prognosis. The current risk stratification system is essential but remains insufficient to select the best schedules. Cysteine-rich protein 1 (CSRP1) is a member of the CSRP family and associated with poor clinicopathological features in many tumors. This study aimed to explore the clinical significance and molecular mechanisms of cysteine- and glycine-rich protein 1 (CSRP1) in AML. RT-qPCR was used to detect the relative expression of CSRP1 in our clinical cohort. Functional enrichment analysis of CSRP1-related differentially expressed genes was carried out by GO/KEGG enrichment analysis, immune cell infiltration analysis, and protein–protein interaction (PPI) network. The OncoPredict algorithm was implemented to explore correlations between CSRP1 and drug resistance. CSRP1 was highly expressed in AML compared with normal samples. High CSRP1 expression was an independent poor prognostic factor. Functional enrichment analysis showed neutrophil activation and apoptosis were associated with CSRP1. In the PPI network, 19 genes were present in the most significant module, and 9 of them were correlated with AML prognosis. The high CSRP1 patients showed higher sensitivity to 5-fluorouracil, gemcitabine, rapamycin, cisplatin and lower sensitivity to fludarabine. CSRP1 may serve as a potential prognostic marker and a therapeutic target for AML in the future.
Expectations and Experiences Among Clinical Staff Regarding Implementation of Digital Pathology: A Qualitative Study at Two Departments of Pathology
Authors: Koefoed-Nielsen Helene , Kidholm Kristian , Frederiksen Marianne H. , Mikkelsen Minne L. N.
Published: March 2024

The aim of this study was to assess and evaluate the individual expectations and experiences regarding the implementation of digital pathology (DIPA) among clinical staff in two of the pathology departments in the Region of Southern Denmark before and during the implementation in their department. Seventeen semi-structured interviews based upon McKinsey 7-S framework were held both prior to and during implementation with both managers and employees at the two pathology departments. The interviewees were pathologists, medical doctors in internship in pathology (interns), biomedical laboratory scientists (BLS), secretaries, and a project lead. Using deductive and inductive coding resulted in five overall themes and appertaining sub-themes. The findings pointed to an overall positive attitude towards DIPA from the beginning. The clinical staff perceived being rewarded already during implementation with benefits such as improved collaboration both inter- and intra-departmentally promoting better acceptance of DIPA. The clinical staff also experienced some challenges, e.g., increase in turnaround times, which affected and concerned staff on a personal level. Especially BLS expressed experiencing a demanding and stressful transition due to unexpected increase in workload as well as some barriers for a potentially better implementation process. The key findings of this study were a need for better preparation of staff through transparent communication of the upcoming challenges of the transition to DIPA, more system-specific training beforehand, more allocation of time and resources in the implementation process, and more focus on BLS’ work tasks in the requirement specifications.
The ‘Good Kiwi’ and the ‘Good Environmental Citizen’?: Dairy, national identity and complex consumption-related values in Aotearoa New Zealand
Authors: Sharp E. L. , Rayne A. , Lewis N.
Published: March 2024

Alongside concerns for animal welfare, concerns for land, water, and climate are undermining established food identities in many parts of the world. In Aotearoa New Zealand, agrifood relations are bound tightly into national identities and the materialities of export dependence on dairying and agriculture more widely. Dairy/ing identities have been central to national development projects and the politics that underpin them for much of New Zealand’s history. They are central to an intransigent agrifood political ontology. For the last decade, however, they have been challenged by the identity politics of ethical food consumption. This paper explores the ensuing contests and asks how they are reshaping agrifood identities. We draw on interviews with 15 participants in Aotearoa New Zealand who have made dietary transitions that reduce or exclude dairy products. Our aim is not to identify a new post-dairying identity or claim a reconfigured national identity, but to examine the collision of production-consumption values in the context of a dominant place-based food identity. We ask how participants navigate contradictory commitments to becoming ‘good environmental citizens’ whilst remaining ‘good national citizens’. The paper offers insights for examining similar struggles elsewhere and the potential to shift agrifood relations and undermine entrenched political ontologies through ethical food consumption values.