bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the potency of diazo‐coumarin containing hybrid molecules: Selective inhibition of tumor‐associated carbonic anhydrase isoforms IX and XII
Authors: Yapar Gönül , Lolak Nebih , Bonardi Alessandro , Akocak Suleyman , Supuran Claudiu T.
Published: January 2024

This study introduces a series of ten hybrid molecules DK(1‐10), which combine diazo and coumarin moieties along with diverse aromatic substitutions. The primary objective was to evaluate the inhibitory capabilities of these compounds against four prominent isoforms: the cytosolic hCA I and II, as well as the tumor‐associated membrane‐bound hCA IX and XII. Impressively, the majority of the tested compounds exhibited significant inhibition activity against the tumor‐associated isoforms hCA IX and XII, with KI values ranging from 29.2 to 293.3 nM. Notably, compound DK‐8 displayed particularly robust inhibitory activity against the tumor‐associated membrane‐bound isoforms, hCA IX and XII, yielding KI values of 32.5 and 29.2 nM, respectively. Additionally, another derivative, DK‐9, containing a primary sulfonamide, exhibited notable inhibition against hCA XII with a KI value of 36.4 nM. This investigation aimed to explore the structure‐activity relationships within these compounds, shedding light on how various substitutions and structural components influence their inhibitory potential. As a result, these compounds present promising candidates for further exploration in medicinal and pharmacological research. Their ability to selectively inhibit specific isoforms, particularly those associated with hypoxic tumors, suggests their potential as foundational compounds for the development of novel therapeutic agents.
A call to action to advance patient‐focused and decentralized clinical trials
Authors: Harvey R. Donald , Miller Therica M. , Hurley Patricia A. , Thota Ramya , Black Lora J. , Bruinooge Suanna S. , Boehmer Leigh M. , Fleury Mark E. , Kamboj Jasmine , Rizvi Mujahid A. , Symington Banu E. , Tap William D. , Waterhouse David M. , Levit Laura A. , Merrill Janette K. , Prindiville Sheila A. , Pollastro Teri , Brewer Jamie R. , Byatt Leslie P. , Hamroun Leila , Kim Edward S. , Holland Nicole , Nowakowski Grzegorz S.
Published: January 2024

This commentary is a call to action for a concerted commitment and effort to transform clinical trials and enable people with cancer to participate in clinical trials closer to home. Three key strategies are identified to address major barriers: confront challenges with the interpretation of US Food and Drug Administration Form 1572 requirements (Statement of Investigator); broaden acceptance of local laboratories and imaging centers; and invest in the creation of effective, sustainable partnerships between research centers and local providers.
Predator Odor Stressor, 2,3,5‐Trimethyl‐3‐Thiazoline (TMT): Assessment of Stress Reactive Behaviors During an Animal Model of Traumatic Stress in Rats
Authors: Ornelas Laura C. , Besheer Joyce
Published: January 2024

Animal models utilizing predator odor stress are important in understanding implications for post‐traumatic stress disorder. 2,5‐dihydro‐2,4,5‐trimethylthiazoline (TMT) has been used to measure stress reactive behaviors during TMT exposure, indicative of stress coping behaviors. In addition, long‐term consequences of stress including contextual‐induced stress memory, anxiety‐like and hyperarousal behaviors, and subsequent increases in alcohol self‐administration can also be examined after TMT exposure. In this article, we describe the TMT exposure protocol used in our lab and how we measure different stress‐reactive behaviors that rats engage in during the TMT exposure. Rats are placed in Plexiglass chambers that contain white bedding on the bottom of the chamber and a metal basket in the top right corner containing a filter paper that 10 µl of TMT is pipetted onto. During the 10 min exposure, rats can move around the chamber freely. Exposures are recorded by a video camera for later analysis. During TMT exposure, rats engage in a variety of stress‐reactive behaviors, including digging and immobility behavior. These are two distinctly different types of stress‐induced behavioral coping strategies to measure individual differences in stress responsivity. To examine individual differences, we group rats into TMT‐subgroups based on time spent engaging in digging or immobility behavior. We calculate a digging/immobility ratio score in which we divide the total time spent digging by the total time spent immobile. A cut‐off strategy is used such that rats with a criterion ratio score <1.0 are classified as TMT‐1 (i.e., low digging/high immobility; greater passive coping) and rats with a ratio score >1.0 are classified as TMT‐2 (i.e., high digging/low immobility; greater active coping). Here, we provide a detailed description of the TMT exposure protocol and step‐by‐step process in evaluation of stress‐reactive behaviors. © 2024 Wiley Periodicals LLC.

Basic Protocol 1: Predator odor stressor exposure using TMT

Basic Protocol 2: Description of stress‐reactive behaviors during TMT exposure and formation of TMT‐subgroups
A novel computational tool for tracking cancer energy hijacking from immune cells
Authors: Zhang Hongyi , Li Bo
Published: January 2024

Recent studies revealed a new biological process that malignant cancer cells hijack mitochondria from nearby T cells, providing another potential mechanism for immune evasion. We further confirmed this process at the single‐cell genomic level through MERCI, a novel algorithm for tracking mitochondrial (MT) transfer. Applied to human cancer samples, MERCI identified a new cancer phenotype linked to MT hijacking, correlating with rapid tumour proliferation and poor patient survival. This discovery offers insights into the limitations of current cancer immunotherapies and suggests new therapeutic avenues targeting MT transfer to enhance cancer treatment efficacy.
A miniaturized left‐handed circularly‐polarized printed radiator for direct broadcast satellite application
Authors: Sundar Kola Kalyan , Chatterjee Anirban
Published: January 2024

This article presents a highly compact printed radiator for direct broadcast satellite (DBS) systems that exhibits good gain and left‐handed circular polarization. The inferred pattern is accomplished by etching two isosceles triangles, one from each of the four corners of a square. From the center of the newly acquired structure, a circular geometric design is made up of 16 isosceles‐scaled triangles has been etched. This arrangement induces resonance in the antenna, aligning it with the desired frequency. The proposed antenna is designed using PCB laminated Rogger 5880 material and simulated in a CST EM simulator. The antenna under consideration exhibits a significant size reduction, achieving a miniaturization ratio of 21.03%. The LHCP antenna resonated at 12.61 GHz and offered a decent LHCP gain of 7.95 dBic. It gives 0.56 GHz CP bandwidth, which covers the DBS service band entirely. It also provides 96.43% radiation efficiency and 44.27 dB/m correction factor, respectively. All the measured findings of the prototype agree with its simulated one.
High‐gain horizontally polarised omnidirectional planar antenna using parasitic directors for wireless sensor networks
Authors: Kumar Pratap , Suseela Sreeja Balakrishnapillai , Daiya Vinita , Ebenezer Jemimah , Sankararajan Radha , Jose Melvin Chamakalayil
Published: January 2024

Wireless sensor networks (WSNs) are used to monitor the real‐time parameters of remote/restricted access areas of automation industries which are tightly sealed. In such scenarios, the main challenge is signal transmission in sealed environments. An omnidirectional radiation pattern is preferred as a control link for receiving packets or periodic updates from its neighbouring nodes. However, the gain and directivity of omnidirectional antenna should be sufficient enough to transfer the data to the collecting node. This paper proposes a high‐gain horizontally polarised omnidirectional radiation pattern planar antenna resonating at the 2.45 GHz. The developed microstrip planar antenna offers a very simple and compact structure printed on either side of FR4 epoxy substrate (ε = 4.4) suitable for WSN nodes. A printed dipole director is arranged orthogonally and offers horizontal polarisation. A pair of parasitic elements is placed parallel to dipole radiators to improve the total gain of the antenna. A parallel pair of parasitic elements is placed on an inclination of 45° in antenna design plane for uniform distribution of surface current to achieve the omnidirectional antenna. The symmetrical structure of the radiating element on either side of the substrate avoids the design of the traditional balun structure to reduce the complexity of feeding network. The developed antenna is simulated, fabricated, measured and tested using WSN. The measured radiation (directivity = 3.9 dBi) is maximum at Ⴔ = 0° and Ⴔ = 90°. The frequency response of the antenna indicates a −10 dB fractional bandwidth of 380 MHz (2.24 GHz–2.62 GHz). The measured far‐field response shows a stable average gain of 3.9 dBi over the ISM band. The real‐time received signal strength indicator (RSSI) of the antenna installed in the sensor node observed a success rate of 79.46% with a transmission error of 10%. The observed response of an antenna makes it well‐suitable for WSN in industrial automation.
Trim46 knockout impaired neuronal architecture and caused hypoactive behavior in rats
Authors: Guan Feifei , Gao Shan , Sheng Hanxuan , Ma Yuanwu , Chen Wei , Qi Xiaolong , Zhang Xu , Gao Xiang , Pang Shuo , Zhang Lianfeng , Zhang Li
Published: January 2024

Background

Tripartite motif (TRIM46) is a relatively novel protein that belongs to tripartite motif family. TRIM46 organizes parallel microtubule arrays on the axons, which are important for neuronal polarity and axonal function. TRIM46 is highly expressed in the brain, but its biological function in adults has not yet been determined.

Results

Trim46 knockout (KO) rat line was established using CRISPR/cas9. Trim46 KO rats had smaller hippocampus sizes, fewer neuronal dendritic arbors and dendritic spines, and shorter and more distant axon initial segment. Furthermore, the protein interaction between endogenous TRIM46 and FK506 binding protein 5 (FKBP5) in brain tissues was determined; Trim46 KO increased hippocampal FKBP5 protein levels and decreased hippocampal protein kinase B (Akt) phosphorylation, gamma‐aminobutyric acid type A receptor subunit alpha1 (GABRA1) and glutamate ionotropic receptor NMDA type subunit 1 (NMDAR1) protein levels. Trim46 KO rats exhibited hypoactive behavioral changes such as reduced spontaneous activity, social interaction, sucrose preference, impaired prepulse inhibition (PPI), and short‐term reference memory.

Conclusions

These results demonstrate the significant impact of Trim46 KO on brain structure and behavioral function. This study revealed a novel potential association of TRIM46 with dendritic development and neuropsychiatric behavior, providing new insights into the role of TRIM46 in the brain.
Gingival fibroblast activation by Porphyromonas gingivalis is driven by TLR2 and is independent of the LPS‐TLR4 axis
Authors: Schuster Aureliusz , Nieboga Elwira , Kantorowicz Malgorzata , Lipska Weronika , Kaczmarzyk Tomasz , Potempa Jan , Grabiec Aleksander M
Published: January 2024

Gingival fibroblasts (GFs) are abundant structural cells of the periodontium that contribute to the host's innate immunity by producing cytokines and chemokines in response to oral pathogens, such as Porphyromonas gingivalis. Isolated lipopolysaccharide (Pg‐LPS) is commonly used to study GF responses to P. gingivalis; however, this approach produced conflicting observations regarding its proinflammatory potential and the engagement of specific Toll‐like receptors (TLRs). In this work, we demonstrate that commercially available Pg‐LPS preparations are weak activators of GF innate immune responses compared with live P. gingivalis or other relevant virulence factors, such as P. gingivalis fimbriae or LPS from Escherichia coli. GF's nonresponsiveness to Pg‐LPS can be only partly attributed to the low expression of TLR4 and its accessory molecules, CD14 and LY36, and is likely caused by the unique structure and composition of the Pg‐LPS lipid A. Finally, we combined gene silencing and neutralizing antibody studies to demonstrate that GF response to infection with live P. gingivalis relies predominantly on TLR2. In contrast, the LPS‐TLR4 signaling plays a negligible role in inflammatory cytokine production by GFs exposed to this oral pathogen, confirming that Pg‐LPS stimulation is not an optimal model for studies of GF responses to P. gingivalis.
Quantifying and correcting geolocation error in spaceborne LiDAR forest canopy observations using high spatial accuracy data: A Bayesian model approach
Authors: Shannon Elliot S. , Finley Andrew O. , Hayes Daniel J. , Noralez Sylvia N. , Weiskittel Aaron R. , Cook Bruce D. , Babcock Chad
Published: January 2024

Geolocation error in spaceborne sampling light detection and ranging (LiDAR) measurements of forest structure can compromise forest attribute estimates and degrade integration with georeferenced field measurements or other remotely sensed data. Data integration is especially problematic when geolocation error is not well quantified. We propose a general model that uses airborne laser scanning data to quantify and correct geolocation error in spaceborne sampling LiDAR. To illustrate the model, LiDAR data from NASA Goddard's LiDAR Hyperspectral and Thermal Imager (G‐LiHT) was used with a subset of LiDAR data from NASA's Global Ecosystem Dynamics Investigation (GEDI). The model accommodates multiple canopy height metrics derived from a simulated GEDI footprint kernel using spatially coincident G‐LiHT, and incorporates both additive and multiplicative mapping between the canopy height metrics generated from both datasets. A Bayesian implementation provides probabilistic uncertainty quantification in both parameter and geolocation error estimates. Results show a systematic geolocation error of 9.62 m in the southwest direction. In addition, estimated geolocation errors within GEDI footprints were highly variable, with results showing a 0.45 probability the true footprint center is within 20 m. Estimating and correcting geolocation error via the model outlined here can help inform subsequent efforts to integrate spaceborne LiDAR data, like GEDI, with other georeferenced data.
A computational framework for pharmaco‐mechanical interactions in arterial walls using parallel monolithic domain decomposition methods
Authors: Balzani Daniel , Heinlein Alexander , Klawonn Axel , Knepper Jascha , Nurani Ramesh Sharan , Rheinbach Oliver , Saßmannshausen Lea , Uhlmann Klemens
Published: January 2024

A computational framework is presented to numerically simulate the effects of antihypertensive drugs, in particular calcium channel blockers, on the mechanical response of arterial walls. A stretch‐dependent smooth muscle model by Uhlmann and Balzani is modified to describe the interaction of pharmacological drugs and the inhibition of smooth muscle activation. The coupled deformation‐diffusion problem is then solved using the finite element software FEDDLib and overlapping Schwarz preconditioners from the Trilinos package FROSch. These preconditioners include highly scalable parallel GDSW (generalized Dryja–Smith–Widlund) and RGDSW (reduced GDSW) preconditioners. Simulation results show the expected increase in the lumen diameter of an idealized artery due to the drug‐induced reduction of smooth muscle contraction, as well as a decrease in the rate of arterial contraction in the presence of calcium channel blockers. Strong and weak parallel scalability of the resulting computational implementation are also analyzed.
A randomized study comparing the nutritional effects of radiotherapy with cetuximab versus cisplatin in patients with advanced head and neck cancer
Authors: Berg Malin , Hansson Camilla , Silander Ewa , Bove Mogens , Johansson Leif , Haugen Cange Hedda , Bosaeus Ingvar , Nyman Jan , Hammerlid Eva
Published: January 2024

Background

Head and neck cancer (HNC) patients have a high risk of developing malnutrition. This randomized study aimed to compare the effect of weekly cisplatin or cetuximab combined with radiotherapy on weight loss at 3 months after treatment was started. Secondary outcomes were the prevalence of malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria, feeding tube dependence and health related quality of life from a nutritional perspective.

Methods

Patients from the ARTSCAN III study with advanced HNC were assessed for weight, body composition, enteral tube dependence and selected quality‐of‐life scores (EORTC QLQ‐C30 and QLQ‐H&N35) at diagnosis and 6 weeks 3, 6 and 12 months after treatment initiation.

Results

Of the 80 patients, 38 and 42 were randomized to receive cetuximab and cisplatin treatment, respectively. There was no significant difference in weight loss at 3 months between the two study groups. However, the cetuximab group had significantly less weight loss, fewer enteral feeding tubes and better physical functioning at the end of treatment but more pain‐related problems 3 months after treatment initiation. No differences between the groups were found at 6 and 12 months. The prevalence of malnutrition was not significantly different at any time point.

Conclusion

The hypothesized benefit of concomitant treatment with cetuximab over cisplatin regarding the prevalence of malnutrition was not supported by this study.
Is hardware colonization associated with latent hardware complications and removal in maxillomandibular free flap reconstruction?
Authors: Lee Cameron C. , Dyalram Donita , Lubek Joshua E.
Published: January 2024

Background

The relationship between hardware colonization, latent hardware complications, and hardware removal remains unclear following osteocutaneous free flap reconstruction of the jaws.

Methods

Retrospective cohort study of all patients undergoing free flap reconstruction of the maxilla or mandible from 2016 to 2021.

Results

A total of 240 subjects were included. Hardware colonization was associated with latent hardware complication in bivariate (p ≤ 0.001) and multivariate analysis (p ≤ 0.001). Time to latent hardware complication was 6.87 months earlier in colonized subjects (p ≤ 0.001). Of the 35 subjects undergoing hardware removal, 25 initiated but failed conservative therapy, and resolution of symptoms was achieved in 24 subjects after one operative intervention and 33 subjects after repeat intervention if indicated.

Conclusions

Hardware colonization increases the risk and onset of latent hardware complication. Prompt hardware removal may improve outcomes by leading to faster resolution of symptoms without the burden and cost of conservative therapies.
The paradoxical surplus of health workers in Africa: The need for research and policy engagement
Authors: Hutchinson Eleanor , Kiwanuka Suzanne , Muhindo Richard , Nimwesiga Christine , Balabanova Dina , McKee Martin , Kitutu Freddy Eric
Published: January 2024

In many countries in Africa, there is a ‘paradoxical surplus’ of under and unemployed nurses, midwives, doctors and pharmacists which exists amidst a shortage of staff within the formal health system. By 2030, the World Health Organisation Africa Region may find itself with a shortage of 6.1 million health workers alongside 700,000 un‐ or underemployed health staff. The emphasis in policy debates about human resources for health at most national and global levels is on staff shortage and the need to train more health workers. In contrast, these ‘surplus’ health workers are both understudied and underacknowledged. Little time is given over to understand the economic, political and social factors that have driven their emergence; the ways in which they seek to make a living; the governance challenges that they raise; nor potential interventions that could be implemented to improve employment rates and leverage their expertise. This short communication reflects on current research findings and calls for improved quantitative and qualitative research to support policy engagement at national, regional and global levels.
Forced displacement and the health workforce crisis: Venezuelan healthcare workers in Peru
Authors: Rees Gareth H.
Published: January 2024

The migration of health workforces tends to be economically based benefiting high‐income countries, while draining lower‐income countries of workers and skills However, national instability or civil conflict may also have the effect of forcing out health workers. However, few articles focus on the experiences of these types of migrants. Peru has become the second largest Latin American destination for Venezuelan forced displaced migrants, a number of which are health workers. While the exact numbers of these workers is unknown, it is estimated that 4000 and 3000 doctors and about 2500 nurses and health technicians from Venezuela reside in Peru. These workers find entry into the heath system difficult due to bureaucratic and costly registration and qualification validation procedures. However, during Covid‐19 these conditions were relaxed, and a large number of these heath workers entered the heath workforce. These workers were primarily doctors and worked in urban medical facilities, though there was some distribution across the country's departments. This avenue to the health workforce allowed the mobilisation of dormant health skills and lifted workforce density numbers. Nonetheless, it is too early to see if there have been sustainable improvements, and it remains uncertain how these policies have contributed to the country's UHC goals. Peru's experiences raise the issue of how to mobilise dormant displaced health worker migrants.
Eucapnic pH coupled with arterial cord pH improves hypoxic–ischemic encephalopathy prediction
Authors: Gauci Pierre‐Alexis , Racinet Claude , Ouellet Paul , Daboval Thierry , Trolli Sergio Eleni dit , Delotte Jérôme
Published: January 2024

Objective

To consider the classical use of “pH < 7.0 and/or a base deficiency ≥12 mmol/L” as markers of the risk of neonatal hypoxic–ischemic encephalopathy (HIE), recalling various criticisms of the use of these markers in favor of that of neonatal eucapnic pH, which appears to be a better marker of this risk.

Methods

Fifty‐five cases of acidemia with pH < 7.00 were collected from a cohort from the Nice University Hospital with eight cases of HIE. We compared the receiver operating characteristics curves established from the positive likelihood ratio (+LR) for each case of: umbilical cord artery pH (pHa), neonatal eucapnic pH (pH euc‐n) in isolation (not matched to pHa), and matched pHa to its own pH euc‐n.

Results

The areas under the curve (AUC) are identical for pHa and pH euc‐n, but AUC for the matched pair pHa–pH euc‐n appears superior but non‐significant because of the small number in our cohort. However, using the bootstrap method, the partial AUC for a sensitivity greater than 75% indicates the significant superiority (P < 0.01) of the matched pair pHa–pH euc‐n approach.

Conclusion

The originality of this study lies in the use of two methodologic approaches: (1) standardized partial analysis of the AUCs of the pHa curve and that of pHa matched to its own pH euc‐n, and (2) bootstrap statistical technique, that allowed us to conclude (P < 0.01) that the combined use of pH measured at the cord coupled with its eucapnic correction is better for diagnosing metabolic acidosis and best predicting the risk of HIE.
Wavelet scattering‐ and object detection‐based computer vision for identifying dengue from peripheral blood microscopy
Authors: Dsilva Liora Rosvin , Tantri Shivani Harish , Sampathila Niranjana , Mayrose Hilda , Muralidhar Bairy G. , Belurkar Sushma , Saravu Kavitha , Chadaga Krishnaraj , Hafeez‐Baig Abdul
Published: January 2024

Dengue fever infection is a global health concern. Early disease detection is crucial for averting complications and fatality. Characteristic morphological changes in lymphocytes can be observed on a peripheral blood smear (PBS) in cases of dengue infection. In this research, we have developed automated computer vision models for dengue detection on PBS images using two approaches: wavelet scattering transform (WST)‐based feature engineering and classification and You Only Look Once (YOLO)‐based deep transfer learning for object detection. In the former, Morlet wavelet scattering features extracted from lymphocytes were used as input for five shallow classifiers for image classification. Among these, the support vector machine achieved the best results of 98.7% accuracy using 10‐fold cross‐validation. In the latter, computer vision‐enabled object detection was implemented using five YOLOv8 scaled variants. Among these, YOLOv8s and YOLOv8l attained identical best mean accuracy of 99.3% ± 1.4% across five independent experiments. Our results confirmed the feasibility and excellent diagnostic accuracy for both WST‐ and YOLOv8‐enabled computer vision approaches for diagnosing dengue infection in PBS images. This research incorporates deep machine learning along with AI technology to enhance understanding and capabilities in automated Dengue diagnosis. The significance of this research extends to the broader domain of mosquito‐borne illnesses. However, it is important to note that the findings are limited to the dataset used by the researchers.
Programmable droplet microfluidics for complex multistep bioassays
Authors: Huang Enqi , Wang Yu , Cai Dongyang , Liu Dayu
Published: January 2024

Programmable droplet microfluidics (PDM) refers to a microfluidic device that integrates the functionality of a series of droplets with distinct spatial locations in a designated temporal order. PDM streamlines the intricate workflow of complex bioassays by enabling programmable and macroscopic droplet displacements, in which the droplets serve as reservoirs for reagents, microvalves for liquid insulation, and in some cases micropumps for mass transportation. As these droplets are intangible structures, the need for expensive microfabrication procedures is eliminated. Furthermore, the parallelization of the droplet series provides flexibility in controlling the throughput of the microfluidic analysis system. This paper provides a comprehensive review of PDMs enabled by various microfluidic mechanisms, including magnetism actuation, relative liquid displacement, capillary suction and sequential microdisplacement. Additionally, important applications of PDM systems for nucleic acid detection, immunoassay, drug testing, and sample recovery are also introduced. In conclusion, PDM demonstrates its potential as a highly advantageous tool for executing intricate multistep bioassays on a microfluidic platform. These technologies have exhibited superiority over their traditional counterparts in terms of size reduction, automation, and low sample/reagent consumption.
Sur la variation de la température azéotropique sous l'influence de la pression
Authors: Prigogine I.
Published: January 2024

Après avoir rappelé que l'influence de la pression sur la température azéotropique s'exprime par une formule du type de celle de Clapeyron‐Clausius relative à la tension de vapeur, l'auteur suggère de représenter le logarithme de la pression en fonction de l'inverse de la température azéotropique (en degrés absolus). L'auteur applique, à titre d'exemple, cette représentation aux systèmes eau‐éthanol; éthanol‐acétate d'éthyle; éthanol‐tétrachlorure de carbone. Dans tous les trois cas on obtient très exactement une droite ce qui permet de calculer simplement la chaleur latente de vaporisation azéotropique de ces systèmes.
Contribution au dosage iodométrique du cuivre
Authors: Hambersin J.
Published: January 2024

Une méthode sensible de dosage iodométrique du Cuivre a été mise au point. La présente note résume les essais effectués ainsi que le mode opératoire proposé.

La sensibilité est six fois plus grande que dans la méthode classique.
Bone marrow macrophages are involved in the ineffective hematopoiesis of myelodysplastic syndromes
Authors: Xing Tong , Yao Wei‐Li , Zhao Hong‐Yan , Wang Jing , Zhang Yuan‐Yuan , Lv Meng , Xu Lan‐Ping , Zhang Xiao‐Hui , Huang Xiao‐Jun , Kong Yuan
Published: January 2024

Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective hematopoiesis. Accumulating evidence has shown that macrophages (MΦs) are important components in the regulation of tumor progression and hematopoietic stem cells (HSCs). However, the roles of bone marrow (BM) MΦs in regulating normal and malignant hematopoiesis in different clinical stages of MDS are largely unknown. Age‐paired patients with lower‐risk MDS (N = 15), higher‐risk MDS (N = 15), de novo acute myeloid leukemia (AML) (N = 15), and healthy donors (HDs) (N = 15) were enrolled. Flow cytometry analysis showed increased pro‐inflammatory monocyte subsets and a decreased classically activated (M1) MΦs/alternatively activated (M2) MΦs ratio in the BM of patients with higher‐risk MDS compared to lower‐risk MDS. BM MФs from patients with higher‐risk MDS and AML showed impaired phagocytosis activity but increased migration compared with lower‐risk MDS group. AML BM MΦs showed markedly higher S100A8/A9 levels than lower‐risk MDS BM MΦs. More importantly, coculture experiments suggested that the HSC supporting abilities of BM MΦs from patients with higher‐risk MDS decreased, whereas the malignant cell supporting abilities increased compared with lower‐risk MDS. Gene Ontology enrichment comparing BM MΦs from lower‐risk MDS and higher‐risk MDS for genes was involved in hematopoiesis‐ and immunity‐related pathways. Our results suggest that BM MΦs are involved in ineffective hematopoiesis in patients with MDS, which indicates that repairing aberrant BM MΦs may represent a promising therapeutic approach for patients with MDS.
Novel method for collecting hippocampal interstitial fluid extracellular vesicles (EVISF) reveals sex‐dependent changes in microglial EV proteome in response to Aβ pathology
Authors: Pait Morgan C. , Kaye Sarah D. , Su Yixin , Kumar Ashish , Singh Sangeeta , Gironda Stephen C. , Vincent Samantha , Anwar Maria , Carroll Caitlin M. , Snipes James Andy , Lee Jingyun , Furdui Cristina M. , Deep Gagan , Macauley Shannon L.
Published: January 2024

Brain‐derived extracellular vesicles (EVs) play an active role in Alzheimer's disease (AD), relaying important physiological information about their host tissues. The internal cargo of EVs is protected from degradation, making EVs attractive AD biomarkers. However, it is unclear how circulating EVs relate to EVs isolated from disease‐vulnerable brain regions. We developed a novel method for collecting EVs from the hippocampal interstitial fluid (ISF) of live mice. EVs (EVISF) were isolated via ultracentrifugation and characterized by nanoparticle tracking analysis, immunogold labelling, and flow cytometry. Mass spectrometry and proteomic analyses were performed on EVISF cargo. EVISF were 40–150 nm in size and expressed CD63, CD9, and CD81. Using a model of cerebral amyloidosis (e.g., APPswe, PSEN1dE9 mice), we found protein concentration increased but protein diversity decreased with Aβ deposition. Genotype, age, and Aβ deposition modulated proteostasis‐ and immunometabolic‐related pathways. Changes in the microglial EVISF proteome were sexually dimorphic and associated with a differential response of plaque associated microglia. We found that female APP/PS1 mice have more amyloid plaques, less plaque associated microglia, and a less robust‐ and diverse‐ EVISF microglial proteome. Thus, in vivo microdialysis is a novel technique for collecting EVISF and offers a unique opportunity to explore the role of EVs in AD.
Extracellular vesicle biogenesis of three‐dimensional human pluripotent stem cells in a novel Vertical‐Wheel bioreactor
Authors: Muok Laureana , Sun Li , Esmonde Colin , Worden Hannah , Vied Cynthia , Duke Leanne , Ma Shaoyang , Zeng Olivia , Driscoll Tristan , Jung Sunghoon , Li Yan
Published: January 2024

Extracellular vesicles (EVs) secreted by human‐induced pluripotent stem cells (hiPSCs) have great potential as cell‐free therapies in various diseases, including prevention of blood–brain barrier senescence and stroke. However, there are still challenges in pre‐clinical and clinical use of hiPSC‐EVs due to the need for large‐scale production of a large quantity. Vertical‐Wheel bioreactors (VWBRs) have design features that allow the biomanufacturing of hiPSC‐EVs using a scalable aggregate or microcarrier‐based culture system under low shear stress. EV secretion by undifferentiated hiPSCs expanded as 3‐D aggregates and on Synthemax II microcarriers in VWBRs were investigated. Additionally, two types of EV collection media, mTeSR and HBM, were compared. The hiPSCs were characterized by metabolite and transcriptome analysis as well as EV biogenesis markers. Protein and microRNA cargo were analysed by proteomics and microRNA‐seq, respectively. The in vitro functional assays of microglia stimulation and proliferation were conducted. HiPSCs expanded as 3‐D aggregates and on microcarriers had comparable cell number, while microcarrier culture had higher glucose consumption, higher glycolysis and lower autophagy gene expression based on mRNA‐seq. The microcarrier cultures had at least 17–23 fold higher EV secretion, and EV collection in mTeSR had 2.7–3.7 fold higher yield than HBM medium. Microcarrier culture with mTeSR EV collection had a smaller EV size than other groups, and the cargo was enriched with proteins (proteomics) and miRNAs (microRNA‐seq) reducing apoptosis and promoting cell proliferation (e.g. Wnt‐related pathways). hiPSC‐EVs demonstrated the ability of stimulating proliferation and M2 polarization of microglia in vitro. HiPSC expansion on microcarriers produces much higher yields of EVs than hiPSC aggregates in VWBRs. EV collection in mTeSR increases yield compared to HBM. The biomanufactured EVs from microcarrier culture in mTeSR have exosomal characteristics and are functional in microglia stimulation, which paves the ways for future in vivo anti‐aging study.
Investigation of steric hindrance effect on the interactions between four alkaloids and HSA by isothermal titration calorimetry and molecular docking
Authors: Lv Xinluan , Li Wenjin , Zhang Miao , Wang Ruiyong , Chang Junbiao
Published: January 2024

The binding of four alkaloids with human serum albumin (HSA) was investigated by isothermal titration calorimetry (ITC), spectroscopy and molecular docking techniques. The findings demonstrated that theophylline or caffeine can bind to HAS, respectively. The number of binding sites and binding constants are obtained. The binding mode is a static quenching process. The effects of steric hindrance, temperature, salt concentration and buffer solution on the binding indicated that theophylline and HSA have higher binding affinity than caffeine. The fluorescence and ITC results showed that the interaction between HSA and theophylline or caffeine is an entropy‐driven spontaneous exothermic process. The hydrophobic force was the primary driving factor. The experimental results were consistent with the molecular docking data. Based on the molecular structures of the four alkaloids, steric hindrance might be a major factor in the binding between HSA and these four alkaloids. This study elucidates the mechanism of interactions between four alkaloids and HSA.
Does leader disability status influence the operational performance of teams with individuals with disabilities? An empirical study in the apparel industry
Authors: Cole Dustin , Narayanan Sriram , Vickery Shawnee
Published: January 2024

This research examines the impact of leader disability status on the operational performance of teams that include individuals with disabilities (IWD) using longitudinal micro‐data from an apparel manufacturing company in a competitive integrative employment environment. To aid in developing the research hypotheses and in interpreting the empirical findings, the quantitative analysis is complemented with qualitative data collected through interviews involving managers and workers with and without disabilities at the focal firm and two other large companies that employ IWD. A beneficial moderating effect of leader‐worker disability status similarity on team performance is hypothesized and subsequently tested using Prais‐Winsten regression. The results show that a leader with a disability has a potentially beneficial impact on team performance as the number of workers with disabilities in the team increases, resulting in improved productivity (measured in labor hours per garment) and quality (measured in operator defects per garment). The theoretical, managerial, and policy implications of the study provide actionable insights for the creation of an inclusive labor force.
Microwave‐Assisted Quick Synthesis of Ru(II)‐Based Metallosupramolecular Polymer for Improved Electrochromic Properties
Authors: Rana Utpal , Santra Dines Chandra , Prusti Banchhanidhi , Chakraborty Chanchal , Ikeda Taichi , Saito Yuko , Takeuchi Kazuhiko , Nagahata Ritsuko , Higuchi Masayoshi
Published: January 2024

Metallosupramolecular polymers (MSPs) have reversible electrochromic (EC) characteristics. Transition metal ions and ditopic organic ligands are complexed 1:1 to form MSPs, but the complexation conditions depend on the metal species ions. Herein, a microwave‐assisted (MWA) quick synthesis of a Ru(II)‐based MSP (polyRu–MWA) as a novel preparation method for MSPs is reported. PolyRu–MWA is synthesized under microwave irritation for 60 min using 770 W and 2.45 GHz frequency, whereas a conventionally synthesized Ru(II)‐based MSP (polyRu–CS) is obtained using oil‐bath at 160 °C for 24 h. PolyRu–MWA is found to show much better EC properties than polyRu–CS. A film of polyRu–MWA prepared on an indium tin oxide glass exhibits higher optical contrast (transmittance change, ΔT: 81.39%) than polyRu–CS (67.73%). Coloration efficiency(CE, η) of polyRu–MWA (425.7 cm2 C−1) is also higher than that of polyRu–CS (318.3 cm2 C−1). Interestingly, the charge and discharge current ratio for bleaching and coloring in polyRu–MWA is ≈1.7 times higher than that for polyRu–CS, probably because of the high molecular weight polymer formation in polyRu–MWA. A polyRu–MWA film also displays a longer EC optical memory than polyRu–CS.
On the number of subproblem iterations per coupling step in partitioned fluid‐structure interaction simulations
Authors: Spenke Thomas , Delaissé Nicolas , Degroote Joris , Hosters Norbert
Published: January 2024

In literature, the cost of a partitioned fluid‐structure interaction scheme is typically assessed by the number of coupling iterations required per time step, while ignoring the internal iterations within the nonlinear subproblems. In this work, we demonstrate that these internal iterations have a significant influence on the computational cost of the coupled simulation. Particular attention is paid to how limiting the number of iterations within each solver call can shorten the overall run time, as it avoids polishing the subproblem solution using unconverged coupling data. Based on systematic parameter studies, we investigate the optimal number of subproblem iterations per coupling step. In addition, this work proposes a new convergence criterion for partitioned algorithms that is based solely on the number of subproblem iterations required to reach the subproblem residual tolerances and therefore does not require any additional convergence tolerance for the coupling loop.
Origin differentiation based on volatile constituents of genuine medicinal materials Quisqualis indica L. via HS‐GC‐MS, response surface methodology, and chemometrics
Authors: Dai Lei , Yang Lin , Li Yan , Li Shuya , Yang Dan , Li Yaxuan , He Dan
Published: January 2024

Introduction

Quisqualis indica L. (QIL) has a long history as a traditional Chinese herb in China, but the study of volatile components in QIL from different geographical sources has been relatively rare.

Objectives

To establish an optimal headspace gas chromatography–mass spectrometry (HS‐GC‐MS) method to comprehensively analyse the volatile component profile and screen quality markers of QIL from different origins.

Methods

Response surface methodology (RSM) was used to optimise the conditions for headspace analysis. The volatile components of QIL from four main origins of southwest China were analysed and identified by HS‐GC‐MS. The similarity of all samples of QIL was evaluated by fingerprint. The differences of the volatile components in QIL from different origins were distinguished by chemometrics.

Results

According to the optimal conditions of RSM, a total of 31 volatile components were identified, including fatty acids, aldehydes, alcohols, alkyl pyrazines, and other volatile components. Similarity evaluation presented that there were 26 common volatile components with different contents in all samples. Principal component analysis (PCA) showed that QIL from four different origins could be roughly divided into four categories. Hierarchical cluster analysis (HCA) and orthogonal partial least squares discriminant analysis (OPLS‐DA) indicated that QIL from different origins had obvious regional characteristics.

Conclusion

The optimised HS‐GC‐MS method provided a strategy to rapidly, effectively, and accurately elucidate the volatile component profile of QIL from different origins, and seven important differential components were screened for quality evaluation and origin traceability.
Exploration of the profiles of steroidal saponins from Rhizoma Paridis and their metabolites in rats by UPLC‐Q‐TOF‐MS/MS
Authors: Wu Dong‐Rong , Yang Xiao‐Wen , Zhao Qian , Wang Li‐Xia , Guo Kai , Ye Xiao , Niu Xue‐Mei , Li Sheng‐Hong , Liu Yan
Published: January 2024

Introduction

Steroidal saponins characterised by intricate chemical structures are the main active components of a well‐known traditional Chinese medicine (TCM) Rhizoma Paridis. The metabolic profiles of steroidal saponins in vivo remain largely unexplored, despite their renowned antitumor, immunostimulating, and haemostatic activity.

Objective

To perform a comprehensive analysis of the chemical constituents of Rhizoma Paridis total saponins (RPTS) and their metabolites in rats after oral administration.

Method

The chemical constituents of RPTS and their metabolites were analysed using ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF‐MS/MS).

Results

A reliable UPLC‐Q‐TOF‐MS/MS method was established, and a total of 142 compounds were identified in RPTS. Specifically, diosgenin‐type saponins showed the diagnostic ions at m/z 415.32, 397.31, 283.25, 271.21, and 253.20, whereas pennogenin‐type saponins exhibited the diagnostic ions at m/z 413.31, 395.30, and 251.20. Based on the characteristic fragments and standard substances, 15 specific metabolites were further identified in the faeces, urine, plasma, and bile of rats. The metabolic pathways of RPTS, including phase I reactions (de‐glycosylation and oxidation) and phase II reactions (glucuronidation), were explored and summarised, and the enrichment of metabolites was characterised by multivariate statistical analysis.

Conclusion

The intricate RPTS could be transformed into relatively simple metabolites in rats through de‐glycosylation, which provides a reference for further metabolic studies and screening of active ingredients for TCM.
Quantification and discovery of quality markers from Toddalia asiatica by UHPLC‐MS/MS coupled with chemometrics
Authors: Wang Rui , Yu Chenxi , Shang Ye , Wen Jiake , Wei Wei , Du Kunze , Li Jin , Fang Shiming , Chang Yanxu
Published: January 2024

Introduction

Toddalia asiatica (TA) is a classical traditional Chinese medicine used to treat rheumatoid arthritis and contusions. However, research regarding TA quality control is currently limited.

Objective

We aimed to establish a strategy for identifying quality markers that can be used for the evaluation of the quality of TA.

Method

A rapid and efficient ultra‐high‐performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC‐MS/MS) method was developed for the quantitative determination of 19 compounds in TA from different regions. Then, the extraction process of TA was successively optimized by single‐factor optimization and response surface methodology. Moreover, chemometrics was employed to confirm the correlation between quality and target compounds.

Results

Utilizing the UHPLC‐MS/MS method, separation of the 19 bioactive compounds was achieved within 14 min. The method was validated in terms of linearity (r2 > 0.9982), precision (0.08%–3.70%), repeatability (0.50%–2.54%), stability (2.26%–5.46%), and recovery (95.8%–113%). The optimal extraction process (extraction solvent, 65% ethanol aqueous solution; solid–liquid ratio, 1:20; extraction time, 25 min) was determined with the total content of 19 bioactive compounds as indicator. Significant disparities were observed in the contents of target compounds across different batches of TA. Besides, all samples could be categorized into two distinct groups, and magnoflorine, (−)‐lyoniresinol, nitidine chloride, norbraylin, skimmianine, and decarine were identified as quality markers.

Conclusion

In the present study, we developed a strategy to improve the quality control of TA. In consideration of the pharmacodynamic activity and statistical differences, six compounds are proposed as quality markers for TA.
Real‐world treatment outcomes of immune checkpoint inhibitors used off‐label in oncology: A comprehensive cancer institution experience
Authors: Fontanals Sandra , Esteve Anna , González Andrea , Ibáñez Cristina , Mesía Ricard , Clopés Ana
Published: January 2024

Off‐label use (OLU) is quite common in oncology due to the complexity of cancer and the time‐consuming regulatory process. However, outcomes of OLU in cancer treatment remain unclear. This study aimed to evaluate the overall survival (OS), event‐free survival (EFS), duration of treatment (DOT), and reason for treatment discontinuation in patients receiving immune checkpoint inhibitors (ICI) as OLU for solid tumors from 2011 to 2020. The study collected data on 356 episodes (353 patients), with a median age of 64.4 years, 36.2% women, and 14.6% ECOG ≥ 2. Median OS was 15.7 (11.9–18.7) months, and median EFS was 5.4 (3.8–6.6) months. Men, patients with metastatic disease or ECOG‐PS higher than 1, had worse survival outcomes. The findings derived from this study provide valuable information regarding the real‐world use of ICI‐OLU and contributes to enhancing the decision‐making process for individuals with cancer. Further research on immunotherapy outcomes of OLU in cancer is needed.
Modeling the Training Effect in Exchange‐Biased Bilayers for Large Numbers of Magnetization Reversal Cycles
Authors: Fiedler Johannes , Wortmann Martin , Blachowicz Tomasz , Ehrmann Andrea
Published: January 2024

The exchange bias (EB) is a unidirectional anisotropy that occurs, e.g., upon field‐cooling ferromagnet/antiferromagnet systems. In many material systems, the EB field is reduced from one hysteresis loop to the next measurement. This so‐called training effect (TE) has been investigated in experiments and by means of theoretical efforts by many research groups. The reduction of the EB field as a result of subsequent magnetization reversal processes is often fitted by a power law, usually with the exception of n = 1, or with an equation based on the discretized Landau–Khalatnikov equation, as first suggested by Binek. Few other models, usually with more fitting parameters, have been proposed yet. Herein, it is shown that for large numbers of subsequent magnetization reversal processes in Co/CoO thin film samples, a modified power law or a logarithmic fit can model the TE in most cases as well as the abovementioned, commonly used models.