bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic engineering of Aspergillus niger for accelerated malic acid biosynthesis by improving NADPH availability
Authors: Wu Na , Wu Xingyu , Zhang Mingyu , Zhang Chi , Xu Qing
Published: May 2024

Microbial production of L‐malic acid from renewable carbon sources has attracted extensive attention. The reduced cofactor NADPH plays a key role in biotransformation because it participates in both biosynthetic reactions and cellular stress responses. In this study, NADPH or its precursors nicotinamide and nicotinic acid were added to the fermentation medium of Aspergillus niger RG0095, which significantly increased the yield of malic acid by 11%. To further improve the titer and productivity of L‐malic acid, we increased the cytoplasmic NADPH levels of A. niger by upregulating the NAD kinases Utr1p and Yef1p. Biochemical analyses demonstrated that overexpression of Utr1p and Yef1p reduced oxidative stress, while also providing more NADPH to catalyze the conversion of glucose into malic acid. Notably, the strain overexpressing Utr1p reached a malate titer of 110.72 ± 1.91 g L−1 after 108 h, corresponding to a productivity of 1.03 ± 0.02 g L−1 h−1. Thus, the titer and productivity of malate were increased by 24.5% and 44.7%, respectively. The strategies developed in this study may also be useful for the metabolic engineering of fungi to produce other industrially relevant bulk chemicals.
Microalgae‐made human vaccines and therapeutics: A decade of advances
Authors: Trujillo Edgar , Monreal‐Escalante Elizabeth , Angulo Carlos
Published: May 2024

Microalgal emergence is a promising platform with two‐decade historical background for producing vaccines and biopharmaceuticals. During that period, microalgal‐based vaccines have reported successful production for various diseases. Thus, species selection is important for genetic transformation and delivery methods that have been developed. Although many vaccine prototypes have been produced for infectious and non‐infectious diseases, fewer studies have reached immunological and immunoprotective evaluations. Microalgae‐made vaccines for Staphylococcus aureus, malaria, influenza, human papilloma, and Zika viruses have been explored in their capacity to induce humoral or cellular immune responses and protective efficacies against experimental challenges. Therefore, specific pathogen antigens and immune system role are important and addressed in controlling these infections. Regarding non‐communicable diseases, these vaccines have been investigated for breast cancer; microalgal‐produced therapeutic molecules and microalgal‐made interferon‐α have been explored for hypertension and potential applications in treating viral infections and cancer, respectively. Thus, conducting immunological trials is emphasized, discussing the promising results observed in terms of immunogenicity, desired immune response for controlling affections, and challenges for achieving the desired protection levels. The potential advantages and hurdles associated with this innovative approach are highlighted, underlining the relevance of assessing immune responses in preclinical and clinical trials to validate the efficacy of these biopharmaceuticals. The promising future of this healthcare technology is also envisaged.
Protein loss during membrane processes in biopharmaceutical manufacturing
Authors: Na Jiwon , Behboudi Ali , Mun Jiwon , Jin Hoeun , Zydney Andrew L. , Baek Youngbin
Published: May 2024

Maximizing product yield in biopharmaceutical manufacturing processes is a critical factor in determining the overall cost of goods, especially given the high value of these biological products. However, there has been relatively limited research on the quantitative analysis of protein losses due to adsorption and fouling during the different membrane filtration processes employed in typical downstream operations. This study aims to provide a comprehensive analysis of protein loss in the range of membrane systems used in downstream processing including clarification, virus removal filtration, ultrafiltration/diafiltration for formulation, and final sterile filtration, all using commercially available membranes with three model proteins (bovine serum albumin, human serum albumin, and immunoglobulin G). The correlation between protein loss and various parameters (i.e., protein type, protein concentration, throughput, membrane morphology, and protein removal mechanism) was also investigated. This study provides important insights into the nature of protein loss during membrane processes as well as a methodology for quantifying protein yield loss in bioprocesses.
Development of an engineered Bacillus subtilis strain for antibiotic‐free sucrose isomerase production
Authors: Li Mingyu , Ren Xiaopeng , Xu Ming , Dong Sitong , Li Xianzhen , Chen Xiaoyi , Wang Conggang , Yang Fan
Published: May 2024

Sucrose isomerase (SIase) catalyzes the hydrolysis and isomerization of sucrose into isomaltulose, a functional sugar extensively used in the food industry. However, the lack of safe and efficient heterologous expression systems for SIase has constrained its production and application. In this study, an engineered Bacillus subtilis strain for antibiotic‐free SIase production was developed via a food‐grade expression system. First, the B. subtilis strain TEA was modified through the CRISPR/Cas9 system, resulting in a mutant strain TEA4, which exhibited enhanced capabilities for recombinant protein expression. For efficient and safe production of SIase, different constitutive and inducible promoters were evaluated. The maltose‐inducible promoter Poglv was found to have an extracellular SIase activity of 21.7 U mL‐1 in engineered strain TEA4. Subsequent optimization of the culture medium further increased SIase activity to 26.4 U mL‐1 during shake flask cultivation. Eventually, using the crude enzyme solution of the engineered strain in biotransformation reactions resulted in a high yield of isomaltulose under high concentrations sucrose, achieving a maximum yield of 83.1%. These findings demonstrated an engineered B. subtilis strain for antibiotic‐free SIase production, paving the way for its scale‐up industrial production and application.
Bridging theory and practice: CFD simulation and interactive VR for conduction heat transfer learning
Authors: Alsurakji Ihab H. , El‐Qanni Amjad , Malhis Tariq , Ahmed Mohannad , Zayed Mohammad , Hmoudah Maryam , Ahmed Wael H. , Najjar Mohammad , Abuabiah Mohammad , Shaqour Bahaa
Published: May 2024

Software simulation programs and virtual reality (VR) have become powerful tools for several educational purposes, and recently, they were used in a wide range of applications. In cases of inaccessibility to labs, workshops, or industries, as happened before in the coronavirus disease 2019 pandemic, these tools could be effectively integrated with practical lab experiments. In this study, a computational fluid dynamics (CFD) simulation and a VR module were utilized to simulate heat transfer by conduction through various experimental cases. The CFD simulation results were obtained using ANSYS/FLUENT software. Meantime, the experimental data were obtained by carrying out three experiments of heat conduction with different heat transfer rates through simple, composite, and different cross‐sectional area bars. At last, the experimental procedure and devices used were virtually constructed using SolidWorks software as three‐dimensional models, which were then extruded into VR and augmented reality models. It was found that the simulation results closely align with the experimental ones, and the temperature profile in both cases has the same behavior with small differences, which indicates the validity of the developed module to be used as a simulation of the actual experiments. In addition to improving knowledge of heat transfer principles, this combination of simulation and VR technology advances many Sustainable Development Goals (SDGs), including advancing quality education (SDG 4) and innovation in higher education (SDG 9). Additionally, this method assists in achieving the course learning objectives by mimicking real‐world lab experiments, guaranteeing that students graduate from the course with the required information and abilities.
Schiff‐Base Aluminum Complexes as Bifunctional Catalysts for the Selective Ring‐Opening Co‐Polymerization of Cyclohexene Oxide and Succinic Anhydride
Authors: Russo Simona , Isnard Florence , Costabile Chiara , Lamberti Marina , Mazzeo Mina
Published: May 2024

The ring‐opening copolymerization (ROCOP) of epoxides and cyclic anhydrides is emerging as a powerful method for the synthesis of polyesters with innovative structures and properties. In this work, a series of dialkyl‐aluminum complexes stabilized by Schiff‐base ligands with different functional side arms (pyridine, amine, or phosphine) and different substituents on the phenoxy moieties have been synthetized and tested as catalysts in the ROCOP of cyclohexene oxide (CHO) and succinic anhydride (SA). The selectivity of the catalysts in the ROCOP was significatively depending on the nature of the pendant arm and/ or of the substituents of the ligand framework. The complexes designed to have a dynamic coordination sphere in which the side arms simulate the role of a neutral cocatalyst favored the desired selectivity, giving poly(CHO‐alt‐SA) with narrow dispersity and negligible ether linkage. NMR investigations and DFT calculations rationalized the observed behavior.
Leakage characteristics of plug flow in the case of pipe leakage
Authors: Ren Tao , Ma Wenjun , Huang Jiangbei , Li Zhiwei , Sun Bin
Published: May 2024

In order to study the changes in two‐phase flow parameters after pipeline damage and the impact of gas injection on water leakage from damaged pipelines, experimental and simulation studies were conducted on the damaged pipelines. The main objective is to compare the void fraction in intact and damaged states and to investigate the factors influencing and variations in gas–liquid leakage flow rates. The results show that increasing the liquid superficial velocity can reduce the difference in void fraction distribution caused by different damage directions. The leakage flow rate is affected by the direction of damage and the superficial velocity of the respective phase. It has been discovered that gas injection in the pipeline can make it easier to find small‐area pipeline damage. The change rate of the volume void fraction shows different changes with the increase in gas proportion in different directions; the shape of the bubble has no bearing on this change.
A review of g‐C3N4‐based photocatalytic materials for photocatalytic CO2 reduction
Authors: Tang Jing , Guo Chuanyu , Wang Tingting , Cheng Xiaoli , Huo Lihua , Zhang Xianfa , Huang Chaobo , Major Zoltán , Xu Yingming
Published: May 2024

Currently, the concentration of carbon dioxide (CO2) has exceeded 400 ppm in the atmosphere. Thus, there is an urgent need to explore CO2 reduction and utilization technologies. Photocatalytic technology can convert CO2 to valuable hydrocarbons (CH4, CH3OH, and C2H5OH, etc.), realizing the conversion of solar energy to chemical energy as well as solving the problems of fossil fuel shortage and global warming. Graphitic carbon nitride (g‐C3N4), as a two‐dimensional nonmetallic semiconductor material, shows great potential in the field of CO2 photoreduction due to its moderate bandgap, easy synthesis method, low cost, and visible light response properties. This review elaborates the research progress of g‐C3N4‐based photocatalysts for photocatalytic CO2 reduction. The modification strategies (e.g., morphology engineering, elemental doping, crystallinity modulation, cocatalyst modification, and constructing heterojunction) of g‐C3N4‐based photocatalysts for CO2 reduction application have been discussed in detail. Finally, the challenges and development prospects of g‐C3N4‐based photocatalytic materials for CO2 reduction are presented.
Performance gap and the timing of corporate social responsibility disclosure‐A trust repair perspective
Authors: Tu Qiuyang , Duan Zhao , Zhou Hong
Published: May 2024

Based on the theory of firm behavior, we explain the voluntary corporate social responsibility (CSR) disclosure behavior of firms from the perspective of trust repair and regard the process of firms' response to the CSR institution as an important way to trust repair for firms' management. We adopt an event history approach with a sample of Chinese firms listed on the A‐share market from 2008 to 2020 and find that faster engagement in CSR disclosure is one of the important trust repair methods for management when firms face performance gaps, and performance gaps positively incentivize firms to voluntarily engage in CSR disclosure. In addition, managers consider the total costs, risks, and benefits of different trust repair methods, there is a substitution effect between different trust repair methods, and the disclosure of internal audit reports and philanthropic donations negatively moderates the relationship between performance gap and CSR disclosure. Our study has important implications for understanding how firm performance affects CSR strategic decisions.
Comparison of three machine learning algorithms for classification of B‐cell neoplasms using clinical flow cytometry data
Authors: Dinalankara Wikum , Ng David P. , Marchionni Luigi , Simonson Paul D.
Published: May 2024

Multiparameter flow cytometry data is visually inspected by expert personnel as part of standard clinical disease diagnosis practice. This is a demanding and costly process, and recent research has demonstrated that it is possible to utilize artificial intelligence (AI) algorithms to assist in the interpretive process. Here we report our examination of three previously published machine learning methods for classification of flow cytometry data and apply these to a B‐cell neoplasm dataset to obtain predicted disease subtypes. Each of the examined methods classifies samples according to specific disease categories using ungated flow cytometry data. We compare and contrast the three algorithms with respect to their architectures, and we report the multiclass classification accuracies and relative required computation times. Despite different architectures, two of the methods, flowCat and EnsembleCNN, had similarly good accuracies with relatively fast computational times. We note a speed advantage for EnsembleCNN, particularly in the case of addition of training data and retraining of the classifier.
Developmental stage‐dependent effects of perceived predation risk on nestling tree swallows (Tachycineta bicolor)
Authors: McNew Sabrina M. , Taff Conor C. , Zimmer Cedric , Uehling Jennifer J. , Ryan Thomas A. , Chang van Oordt David , Houtz Jennifer L. , Injaian Allison S. , Vitousek Maren N.
Published: May 2024

The risk of predation directly affects the physiology, behavior, and fitness of wild birds. Strong social connections with conspecifics could help individuals recover from a stressful experience such as a predation event; however, competitive interactions also have the potential to exacerbate stress. Few studies have investigated the interaction between environmental stressors and the social landscape in wild bird populations. In 2 years of field studies, we experimentally simulated predation attempts on breeding female tree swallows (Tachicyneta bicolor). At the same time, we manipulated female breast plumage color, a key social signal. Simulated predation events on tree swallows early in the nestling period reduced young nestlings' mass by approximately 20% and shortened telomere lengths. Ultimately, only 31% of nestlings in the predation group fledged compared with 70% of control nestlings. However, the effects of experimental manipulations were timing dependent: the following year when we swapped the order of the experimental manipulations and simulated predation during incubation, there were no significant effects of predation on nestling condition or fledging success. Contrary to our expectations, manipulation of the social environment did not affect the response of tree swallows to simulated predation. However, manipulating female plumage during the nestling period did reduce nestling skeletal size and mass, although the effects depended on original plumage brightness. Our data demonstrate that transient stressors on female birds can have carry‐over effects on their nestlings if they occur during critical periods in the breeding season.
Bridging personality dimensions and eating symptoms: A transdiagnostic network approach
Authors: Ruiz‐Gutiérrez Jose , Miras‐Aguilar María del Mar , Rodríguez‐Pérez Noelia , Ventura Ludovica , González Gómez Jana , del Barrio Andrés Gómez , Gónzalez‐Blanch Cesar
Published: May 2024

Objective

Eating disorders (ED) have recently been studied from a network approach, conceptualising them as a complex system of interconnected variables, while highlighting the role of non‐ED symptoms and personality dimensions. This study aims to explore the connections between personality and ED symptoms, identify central nodes, and compare the EDs network to a healthy control network.

Methods

We employed network analysis to examine the personality‐ED symptom connections in 329 individuals with an ED diagnosis and 192 healthy controls. We estimated a regularised partial correlation network and the indices of centrality and bridge centrality to identify the most influential nodes for each group. Network differences between groups were also examined.

Results

Low Self‐Directedness and high Harm avoidance emerged as central bridge nodes, displaying the strongest relationship with ED symptoms. Both networks differed in their global connectivity and structure, although no differences were found in bridge centrality and centrality indices.

Conclusions

These findings shed light on the role of personality dimensions, such as Self‐Directedness and Harm Avoidance in the maintenance of ED psychopathology, supporting the transdiagnostic conceptualisation of ED. This study advances a deeper understanding of the complex interplay between personality dimensions and ED symptoms, offering potential directions for clinical interventions.
Synthesis, characterization, and implementation of BaNiO3 perovskite nanoparticles as thin film supercapacitor electrode
Authors: Janjua Abdul Niqash , Ahmed Aamir , Singh Anoop , Sundramoorthy Ashok K. , Young Sheng‐Joue , Chu Yen‐Lin , Arya Sandeep
Published: May 2024

This work is the first attempt to explore the supercapacitor applications of Barium nickelate (BaNiO3) perovskite nanoparticles. The nanoparticles are synthesized using a simple combustion method and their morphology, elemental composition, and so forth are studied using standard characterization methods such as x‐ray diffraction spectroscopy (XRD), field emission scanning electron microscopy (FESEM), and so forth. The nanoparticles were found to be hexagonal in shape, with an average particle size of 16 nm, and the elemental analysis confirms the successful synthesis of the BaNiO3 perovskite nanoparticles. For electrochemical studies, the electrodes are fabricated over a wearable and flexible conductive fabric (CF) substrate. A slurry paste of the synthesized BaNiO3 nanoparticles is applied over CF and dried overnight, thereby forming a thin film electrode. The fabricated electrode acts as a positive electrode with a high specific capacitance of 508.64 F g−1 at 2.2 A g−1 current density. Upon increasing the current density, the electrode maintains 60% of its specific capacitance and displays 97% cyclic stability over 5000 cycles. The electrochemical impedance spectroscopy (EIS) study indicates excellent conductivity of the electrode, with a bulk resistance of 3.2 Ohms. The electrochemical performance of the fabricated electrode is also compared with various previously reported works and the electrode displays higher specific capacitance and better cyclic stability. These findings suggest that the BaNiO3 perovskite nanoparticles‐based electrode holds promise for utilization as an anode material in supercapacitor applications.
Clinicopathologic and molecular correlates to neoadjuvant chemotherapy‐induced pathologic response in breast angiosarcoma
Authors: Chang Hsin‐Yi , Dermawan Josephine K. , Kuba Maria Gabriela , Crago Aimee M. , Singer Samuel , Tap William , Chi Ping , D'Angelo Sandra , Rosenbaum Evan , Antonescu Cristina R.
Published: May 2024

Both primary and secondary breast angiosarcoma (AS) are characterized by multifocal presentation and aggressive behavior. Despite multimodality therapy, local and distant relapse rates remain high. Therefore, neoadjuvant chemotherapy (NACT) is employed to improve the R0 resection rates and survival, but its benefits remain controversial. Herein, we investigate pathologic and molecular correlates to NACT‐induced histologic response in a group of 29 breast AS, 4 primary and 25 radiation‐associated (RA). The two NACT regimens applied were anthracycline‐ and non‐anthracycline‐based. The pathologic response grade was defined as: I: ≤ 50%, II: 51%–90%, III: 91%–99%, and IV: 100%. An additional 45 primary AS and 102 RA‐AS treated by surgery alone were included for survival comparison. The genomic landscape was analyzed in a subset of cases and compared to a cohort of AS without NACT on a paired tumor‐normal targeted DNA NGS platform. All patients were females, with a median age of 31 years in primary AS and 68 years in RA‐AS. All surgical margins were negative in NACT group. The NACT response was evenly divided between poor (Grades I–II; n = 15) and good responders (Grades III–IV; n = 14). Mitotic count >10/mm2 was the only factor inversely associated with pathologic response. By targeted NGS, all 10 post‐NACT RA‐AS demonstrated MYC amplification, while both primary AS harbored KDR mutations. TMB or other genomic alterations did not correlate with pathologic response. All four patients with Grade IV response remained free of disease. The good responders had a significantly better disease‐specific survival (p = 0.04). There was no survival difference with NACT status or the NACT regimens applied. However, NACT patients with MYC‐amplified tumors showed better disease‐free survival (p = 0.04) compared to MYC‐amplified patients without NACT. The overall survival of NACT group correlated with size >10 cm (p = 0.02), pathologic response (p = 0.04), and multifocality (p = 0.01) by univariate, while only size >10 cm (p = 0.03) remained significant by multivariate analysis.
The well‐worn route revisited: Striatal and hippocampal system contributions to familiar route navigation
Authors: Buckley Matthew , McGregor Anthony , Ihssen Niklas , Austen Joseph , Thurlbeck Simon , Smith Shamus P. , Heinecke Armin , Lew Adina R.
Published: May 2024

Classic research has shown a division in the neuroanatomical structures that support flexible (e.g., short‐cutting) and habitual (e.g., familiar route following) navigational behavior, with hippocampal–caudate systems associated with the former and putamen systems with the latter. There is, however, disagreement about whether the neural structures involved in navigation process particular forms of spatial information, such as associations between constellations of cues forming a cognitive map, versus single landmark‐action associations, or alternatively, perform particular reinforcement learning algorithms that allow the use of different spatial strategies, so‐called model‐based (flexible) or model‐free (habitual) forms of learning. We sought to test these theories by asking participants (N = 24) to navigate within a virtual environment through a previously learned, 9‐junction route with distinctive landmarks at each junction while undergoing functional magnetic resonance imaging (fMRI). In a series of probe trials, we distinguished knowledge of individual landmark‐action associations along the route versus knowledge of the correct sequence of landmark‐action associations, either by having absent landmarks, or “out‐of‐sequence” landmarks. Under a map‐based perspective, sequence knowledge would not require hippocampal systems, because there are no constellations of cues available for cognitive map formation. Within a learning‐based model, however, responding based on knowledge of sequence would require hippocampal systems because prior context has to be utilized. We found that hippocampal–caudate systems were more active in probes requiring sequence knowledge, supporting the learning‐based model. However, we also found greater putamen activation in probes where navigation based purely on sequence memory could be planned, supporting models of putamen function that emphasize its role in action sequencing.
Fluorescent Membrane Probes Obey the Israelachvili Rules
Authors: Bayard Felix , Matile Stefan
Published: May 2024

When developing fluorescent membrane probes, we naturally tend to focus on the fluorophore itself. In this study, we show that sometimes it can be beneficial to shift attention from the center to the periphery, to maximize multiple interfacing with complex changing environments. Palmitylation for hydrophobic interfacing and glutamate dendrons for hydrophilic interfacing are combined to improve the performance of fluorescent flipper probes. We show that to increase performance in membranes, solubility in water is important, and to increase solubility in water, we increase the hydrophobicity of the flipper probe. These seemingly paradoxical measures are taken to satisfy the Israelachvili rules. They state that only inverted cone amphiphiles form soluble micelles in water, while inverted micelles from cone shaped amphiphiles precipitate into hexagonal 1 supramolecular polymers, and the intermediate cylindrical amphiphiles show intermediate behavior dominated by bilayers and lamellar precipitates. The normal micelles obtained from inverted cone flipper amphiphiles prevent precipitation and prepare for efficient transfer into the lipid bilayer membranes. The results are flippers that break all records set by the 2016 original with regard to effective brightness, responsiveness to membrane order, anchoring in disordered membranes, partitioning into membranes of high order, and stable labeling of membranes of interest. The lessons learned confirm the obvious: The Israelachvili rules apply also to fluorescent membrane probes. They promise literally bright perspectives for fluorescent membrane probes.
“What concerns me or what is most interesting to me”: A qualitative study about what influences adolescent engagement with public health issues
Authors: Nguyen Binh , Raeside Rebecca , Kite James , Freeman Becky , Phongsavan Philayrath , Cheng Hoi Lun , Steinbeck Katharine , Baur Louise Alison , Partridge Stephanie Ruth
Published: May 2024

Issues Addressed

Promoting public health messages in adolescence may influence future health outcomes. A better understanding of what influences adolescent engagement with public health issues is needed.

Methods

Adolescents aged 13–19 years from New South Wales, Australia, were recruited via study advertisements to participate in an online focus group. All provided informed consent and completed a short survey including demographics and selection of leading public health issues of concern. Participants attended a 75–90 min focus group conducted through Zoom teleconference that explored top public health issues of concern to participants, and barriers/enablers to engage with these issues. Qualitative data was thematically analysed using NVivo. A working group reached consensus on final themes.

Results

Out of 18 participants (mean 15.4 [SD: 2.2] years; 50% female), most attended high school (83%), spoke predominantly English at home (89%), and resided in metropolitan areas (94%). The top public health issues of concern selected were mental health (56%) and the environment/climate change (56%). From the thematic analysis, underlying drivers of adolescent engagement with public health issues included: personal connection to these issues, broader societal impact, and exposure to public health issues on digital media. Barriers included feeling unempowered, and a lack of support and opportunities.

Conclusions

This study provides insights on the barriers and enablers of adolescents engaging with public health issues of concern to them.

So What?

Understanding this may help health professionals and researchers to design more influential public health campaigns and interventions, including through co‐design processes, which may improve future health outcomes.
Tectorigenin inhibits inflammatory responses in murine inflammatory bowel disease and LPS‐stimulated macrophages via inactivating MAPK signaling pathway
Authors: Huang Hong , Tang Sanhui , Zhou Yanghong , Cai Yi
Published: May 2024

Background

Considering the antihepatitis effects of Tectorigenin (TEC), and the same adenosine mitogen‐activated protein kinase (MAPK) pathway in both hepatitis and inflammatory bowel disease (IBD) models, exploring the role of TEC in IBD is contributive to develop a new treatment strategy against IBD.

Methods

The IBD mouse model was constructed by feeding with dextran sodium sulfate (DSS) and injection of TEC. Afterward, the mouse body weight, colon length, and disease activity index (DAI) were tested to assess the enteritis level. Mouse intestine lesions were detected by hematoxylin and eosin staining. Murine macrophages underwent lipopolysaccharide (LPS) induction to establish an inflammation model. Cell viability was determined by cell counting kit‐8 assay. Enzyme‐linked immunosorbent assay was performed to measure interleukin 6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) levels. Cyclooxygenase‐2 (COX‐2) and inducible nitric oxide synthase (iNOS) expressions were quantified via quantitative reverse transcription polymerase chain reaction. Levels of MAPK pathway‐related proteins (p‐P38, P38, p‐Jun N‐terminal kinase (JNK), JNK, signal‐regulated kinase (ERK), p‐ERK), COX‐2 and iNOS were quantitated by Western blot.

Results

TEC improved the inflammatory response through ameliorating weight loss, shortening colon, and increasing DAI score in IBD mouse. Expressions of intestinal inflammatory factors (IL‐6, TNF‐α, iNOS and COX‐2) and MAPK pathway‐related proteins (p‐P38, p‐JNK, and p‐ERK) were increased both in DSS‐induced mouse intestinal tissue, but TEC inhibited expressions of inflammatory factors. The same increased trend was identified in LPS‐induced macrophages, but TEC improved macrophage inflammation, as evidenced by downregulation of inflammatory factors.

Conclusion

TEC mitigates IBD and LPS‐induced macrophage inflammation in mice via inhibiting MAPK signaling pathway.
Stereotactic radiosurgery and radiotherapy for brainstem metastases: An international multicenter analysis
Authors: Ehret Felix , Rueß Daniel , Blanck Oliver , Fichte Susanne , Chatzikonstantinou Georgios , Wolff Robert , Mose Lucas , Mose Stephan , Fortmann Thomas , Lehrke Ralph , Turna Menekse , Caglar Hale Basak , Mortasawi Farshin , Bleif Martin , Krug David , Ruge Maximilian I. , Fürweger Christoph , Muacevic Alexander
Published: May 2024

Brainstem metastases (BSM) present a significant neuro‐oncological challenge, resulting in profound neurological deficits and poor survival outcomes. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) offer promising therapeutic avenues for BSM despite their precarious location. This international multicenter study investigates the efficacy and safety of SRS and FSRT in 136 patients with 144 BSM treated at nine institutions from 2005 to 2022. The median radiographic and clinical follow‐up periods were 6.8 and 9.4 months, respectively. Predominantly, patients with BSM were managed with SRS (69.4%). The median prescription dose and isodose line for SRS were 18 Gy and 65%, respectively, while for FSRT, the median prescription dose was 21 Gy with a median isodose line of 70%. The 12‐, 24‐, and 36‐month local control (LC) rates were 82.9%, 71.4%, and 61.2%, respectively. Corresponding overall survival rates at these time points were 61.1%, 34.7%, and 19.3%. In the multivariable Cox regression analysis for LC, only the minimum biologically effective dose was significantly associated with LC, favoring higher doses for improved control (in Gy, hazard ratio [HR]: 0.86, p < .01). Regarding overall survival, good performance status (Karnofsky performance status, ≥90%; HR: 0.43, p < .01) and prior whole brain radiotherapy (HR: 2.52, p < .01) emerged as associated factors. In 14 BSM (9.7%), treatment‐related adverse events were noted, with a total of five (3.4%) radiation necrosis. SRS and FSRT for BSM exhibit efficacy and safety, making them suitable treatment options for affected patients.
Decoding pharmacogenomic test interpretation and application to patient care
Authors: Donnelly Roseann S. , Cavallari Larisa H. , McCune Jeannine S. , Trofe‐Clark Jennifer , Formea Christine M. , Hoffecker Glenda , Csere Molly M. , Anderson Keri C. , Bhat Shubha , Mosley Scott A. , Ma Qing , Ferdock Ariel , Hoffman James M. , Hicks J. Kevin , Caudle Kelly E.
Published: May 2024

Pharmacogenomics is a growing area of medicine, and pharmacists across clinical practice settings have the opportunity to individualize medication selection and dosing using genetic data. However, many practicing pharmacists may feel ill‐equipped to interpret pharmacogenomic test results because of insufficient education and training. Evidence‐based, updated, and freely available resources such as the Clinical Pharmacogenetics Implementation Consortium guidelines can help pharmacists interpret and apply pharmacogenomic test results to patient care. Although gaps for the application of pharmacogenomic information exist, this commentary aims to demystify the interpretation of pharmacogenomic test results and empower pharmacists to apply genetic data alongside other clinical variables to optimize medication‐related outcomes for their patients. An “ABCD” framework is proposed to guide pharmacists through the steps: (1) Actionability—Are the gene(s) clinically relevant for the patient? (2) Be Mindful of Limitations—What are the caveats with pharmacogenomic test results and reports? (3) Clinical Practice Guidelines—How do you use pharmacogenomic test results to guide clinical decision‐making? and (4) Document and Discuss—How do you educate the patient about their pharmacogenomic test results and document the results for future use? Key concepts are illustrated using a psychiatric patient case example.
Guiding Dyslipidemia Treatment: A Population Pharmacokinetic–Pharmacodynamic Framework for Obicetrapib
Authors: Dunn Allison , Ditmarsch Marc , Kastelein John J. P. , Kling Douglas , Neild Annie , Davidson Michael H. , Gobburu Joga
Published: May 2024

Obicetrapib is a selective inhibitor of cholesteryl ester transfer protein that is currently in phase 3 of development for the treatment of dyslipidemia as adjunct therapy. The purpose of this study was to comprehensively characterize the pharmacokinetic (PK) and pharmacodynamic (PD) disposition of obicetrapib. Data from 7 clinical trials conducted in healthy adults and those with varying degrees of dyslipidemia were included for model development. The structural model that best described obicetrapib PK was a 3‐compartment model with 4‐compartment transit absorption and first‐order elimination. Body weight was the only covariate found to significantly explain observed variability and was therefore included using allometric scaling on all disposition parameters. For a typical patient weighing 75 kg, the estimated apparent total body clearance and apparent volume of distribution of the central compartment was 0.81 L/h and 36.1 L, respectively. The final PK model parameters were estimated with good precision and were ultimately leveraged to sequentially inform 2 turnover models that describe obicetrapib's effect on low‐density lipoprotein cholesterol (LDL‐C) and high‐density lipoprotein cholesterol (HDL‐C) concentrations. The maximum stimulatory effect of obicetrapib on LDL‐C loss was estimated to be 1.046, while the maximum inhibitory effect of obicetrapib on HDL‐C loss was 0.691. This corresponds to a predicted typical maximum percent change from baseline LDL‐C and HDL‐C of 51.1% and 224%, respectively. The final sequential model described obicetrapib PKPD well and was ultimately able to both demonstrate evidence of internal consistency and support decision‐making throughout the development lifecycle.
Population Pharmacokinetics of Sertraline in Psychiatric and Substance Use Disorders
Authors: Castillo Cinthya Eloisa Chávez , Garibay Susanna Edith Medellín , Segovia Rosa del Carmen Milán , Guzmán Sergio Zarazúa , Cook Helgi Jung , Contreras Marisol Orocio , Moreno Silvia Romano
Published: May 2024

This study aimed to characterize the population pharmacokinetics of sertraline in Mexican patients with psychiatric and substance use disorders. Fifty‐nine patients (13 to 76 years old) treated with doses of sertraline between 12.5 and 100 mg/day were included. Plasma sertraline concentrations were determined in blood samples and five of the main substances of abuse were determined by rapid tests in urine samples. Demographic, clinical, and pharmacogenetic factors were also evaluated. Population pharmacokinetic analysis was performed using NONMEM software with first‐order conditional estimation method. A one‐compartment model with proportional residual error adequately described the sertraline concentrations versus time. CYP2D6*2 polymorphism and CYP2C19 phenotypes significantly influenced sertraline clearance, which had a population mean value of 66 L/h in the final model. The absorption constant and volume of distribution were fixed at 0.855 1/h and 20.2 L/kg, respectively. The model explained 11.3% of the interindividual variability in sertraline clearance. The presence of the CYP2D6*2 polymorphism caused a 23.1% decrease in sertraline clearance, whereas patients with intermediate and poor phenotype of CYP2C19 showed 19.06% and 48.26% decreases in sertraline clearance, respectively. The model was internally validated by bootstrap and visual predictive check. Finally, stochastic simulations were performed to propose dosing regimens to achieve therapeutic levels that contribute to improving treatment response.
Reduced temporal muscle thickness predicts shorter survival in patients undergoing chronic subdural haematoma drainage
Authors: Korhonen Tommi K. , Arponen Otso , Steinruecke Moritz , Pecorella Ilaria , Mee Harry , Yordanov Stefan , Viaroli Edoardo , Guilfoyle Mathew R. , Kolias Angelos , Timofeev Ivan , Hutchinson Peter , Helmy Adel
Published: May 2024

Background

Chronic subdural haematoma (CSDH) drainage is a common neurosurgical procedure. CSDHs cause excess mortality, which is exacerbated by frailty. Sarcopenia contributes to frailty – its key component, low muscle mass, can be assessed using cross‐sectional imaging. We aimed to examine the prognostic role of temporal muscle thickness (TMT) measured from preoperative computed tomography head scans among patients undergoing surgical CSDH drainage.

Methods

We retrospectively identified all patients who underwent CSDH drainage within 1 year of February 2019. We measured their mean TMT from preoperative computed tomography scans, tested the reliability of these measurements, and evaluated their prognostic value for postoperative survival.

Results

One hundred and eighty‐eight (122, 65% males) patients (median age 78 years, IQR 70–85 years) were included. Thirty‐four (18%) patients died within 2 years, and 51 (27%) died at a median follow‐up of 39 months (IQR 34–42 months). Intra‐ and inter‐observer reliability of TMT measurements was good‐to‐excellent (ICC 0.85–0.97, P < 0.05). TMT decreased with age (Pearson's r = −0.38, P < 0.001). Females had lower TMT than males (P < 0.001). The optimal TMT cut‐off values for predicting two‐year survival were 4.475 mm for males and 3.125 mm for females. TMT below these cut‐offs was associated with shorter survival in both univariate (HR 3.24, 95% CI 1.85–5.67) and multivariate (HR 1.86, 95% CI 1.02–3.36) analyses adjusted for age, ASA grade and bleed size. The effect of TMT on mortality was not mediated by age.

Conclusions

In patients with CSDH, TMT measurements from preoperative imaging were reliable and contained prognostic information supplemental to previously known predictors of poor outcomes.
Evaluation of Hepatic Glucose and Palmitic Acid Metabolism in Rodents on High‐Fat Diet Using Deuterium Metabolic Imaging
Authors: Ehret Viktoria , Ustsinau Usevalad , Friske Joachim , Scherer Thomas , Fürnsinn Clemens , Helbich Thomas H. , Philippe Cécile , Krššák Martin
Published: May 2024

Background

One of the main features of several metabolic disorders is dysregulation of hepatic glucose and lipid metabolism. Deuterium metabolic imaging (DMI) allows for assessing the uptake and breakdown of 2H‐labeled substrates, giving specific insight into nutrient processing in healthy and diseased organs. Thus, DMI could be a useful approach for analyzing the differences in liver metabolism of healthy and diseased subjects to gain a deeper understanding of the alterations related to metabolic disorders.

Purpose

Evaluating the feasibility of DMI as a tool for the assessment of metabolic differences in rodents with healthy and fatty livers (FLs).

Study Type

Animal Model.

Population

18 male Sprague Dawley rats on standard (SD, n = 9, healthy) and high‐fat diet (HFD, n = 9, FL disease).

Field Strength/Sequence

Phase‐encoded 1D pulse‐acquire sequence and anatomy co‐registered phase‐encoded 3D pulse‐acquire chemical shift imaging for 2H at 9.4T.

Assessment

Localized and nonlocalized liver spectroscopy was applied at eight time points over 104 minutes post injection. The obtained spectra were preprocessed and quantified using jMRUI (v7.0) and the resulting amplitudes translated to absolute concentration (mM) according to the 2H natural abundance water peak.

Statistical Tests

Two‐way repeated measures ANOVA were employed to assess between‐group differences, with statistical significance at P < 0.05.

Results

DMI measurements demonstrated no significant difference (P = 0.98) in the uptake of [6,6′‐2H2]glucose between healthy and impaired animals (AUCSD = 1966.0 ± 151.5 mM ‐ minutes vs. AUCHFD = 2027.0 ± 167.6 mM·minutes). In the diseased group, the intrahepatic uptake of palmitic acid d‐31 was higher (AUCHFD = 57.4 ± 17.0 mM·minutes, AUCSD = 33.3 ± 10.5 mM·minutes), but without statistical significance owing to substantial in‐group variation (P = 0.73).

Data Conclusion

DMI revealed higher concentrations of palmitic acid in rats with FL disease and no difference in hepatic glucose concentration between healthy and impaired animals. Thus, DMI appears to be a useful tool for evaluating metabolism in rodents with FL disease.

Level of Evidence

2

Technical Efficacy

Stage 3.
Common‐mode current reduction in EMP coupling with the star‐quad cable having a reference conductor
Authors: Lodhi Anmol Abbas , Zhu Yu , Gassab Oussama
Published: May 2024

The coupling of electromagnetic pulse (EMP) with the star‐quad cable having reference conductor is analyzed by using the proposed model, which is based upon multi‐conductor transmission line theory. Expressions for common‐mode (CM) and differential‐mode (DM) currents are developed. Two cases are mainly discussed: the first case is the star‐quad cable with a central reference conductor, and the second case with the outside reference conductor. A rigorous comparison between these two cases shows that when the reference conductor is placed at the center, the magnitude of CM current is reduced dramatically, which is beneficial for electromagnetic compatibility (EMC). The CM current magnitude of the outside reference conductor is relatively very high due to the large CM current loop area, which is the least possible for the central reference conductor. There is no significant change in the DM current magnitude for both cases because the DM current has no direct dependence on the CM current loop area. A commercial software, FEKO, which utilizes the method of momentum (MoM), is used to compare the results of our proposed method, which are in good agreement.
An improved two‐dimensional (2,4) finite‐difference time‐domain method for Lorentz dispersive media
Authors: Zygiridis Theodoros T. , Amanatiadis Stamatios A. , Kantartzis Nikolaos V.
Published: May 2024

The credible solution of discretized Maxwell's equations in spaces occupied by Lorentz dispersive media is the main subject of this work. Specifically, we introduce a finite‐difference time‐domain (FDTD) algorithm with a typical (2,4) structure that features dispersion‐relation‐preserving characteristics and produces reduced numerical errors in two‐dimensional electromagnetic simulations, compared to the standard approach with similar computational requirements. We consider the case of dispersive media with non‐vanishing absorption coefficients and investigate different options for the suitable modification of the spatial approximations, so that the accomplished accuracy is optimized for a given computational overhead. The properties of the proposed FDTD technique are thoroughly examined, both theoretically and in numerical tests, and the performance upgrade compared with the conventional solution is assessed.
Significance of High‐Frequency Sonography for the Subclinical Progression of Rheumatoid Arthritis
Authors: Li Yudan , Zhang Ziteng , Liu Cuicui , Kang Zhilong , Li Zhiyan
Published: May 2024

Objectives

This study aims to investigate the use of high‐frequency sonography as a tool for detecting inflammatory and destructive changes in the hand and foot joints of patients with early and long‐term RA.

Methods

This study employs a prospective cohort design involving 162 patients diagnosed with Rheumatoid arthritis (RA) who meet the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. Patients were divided into two groups based on disease duration: Group 1 (n = 74) included patients with a disease duration of up to 2 years, or early РА (ERA;), Group 2 (n = 88) consisted of patients with a disease duration exceeding 2 years, or long‐term persistent РА (LtRA). All patients underwent a clinical assessment of their joints, as well as radiography and arthrosonography, at the beginning of the study and again at 6 and 12 months later.

Results

In the general group of patients, ultrasound examination revealed signs of synovitis in the joints of the hands more frequently (66%) compared with clinical examination (56% by a number of swollen joints [NSJ] and 55% by a number of painful joints [NPJ], P < .01). After 6 months of treatment, 12% of the patients achieved full US remission and 24% achieved partial US remission.

Conclusions

Within the scope of comprehensive RA diagnostics, arthrosonography of the joints of the hands and feet, utilizing a combination of greyscale and power Doppler, may surpass radiography in detecting early RA. This method allows for a more accurate assessment of disease activity and progression rates.