bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal sizing and placement of capacitors in the isolated microgrid throughout the day considering the demand response program
Authors: Basu Mousumi , Jena Chitralekha , Khan Baseem , Ali Ahmed , Khurshaid Tahir
Published: April 2024

Reactive power compensation (RPC) is a big problem during power system operation. Parenthetically, capacitor allocation and sizing may be the only convenient solution for RPC of power systems. The loss sensitivity factor (LSF) is applied here for finding the optimum capacitor position. This paper presents quasi-oppositional fast convergence evolutionary programming (QOFCEP), fast convergence evolutionary programming (FCEP), and evolutionary programming (EP) for the optimum location and sizing of shunt capacitors in the isolated microgrid (MG) for minimizing total real power loss throughout the day with and without the demand response program (DRP). The 33-node, 69-node, and 118-node isolated MGs have been studied to authenticate the efficacy of the suggested approach. Each MG includes small hydro power plants (SHPPs), solar PV plants (SPVPs), wind turbine generators (WTGs), diesel generators (DGs), and plug-in electric vehicles (PEVs).
A fault diagnosis method for flexible converter valve equipment based on DSC-BIGRU-MA
Authors: Guo Jianbao , Liu Hang , Feng Lei , Zu Lifeng
Published: April 2024

Introduction: Precise fault diagnosis is crucial for enhancing the reliability and lifespan of the flexible converter valve equipment. To address this issue, depthwise separable convolution, bidirectional gate recurrent unit, and multi-head attention module (DSC-BiGRU-MAM) based fault diagnosis approach is proposed.

Methods: By DSC and BiGRU operation, the model can capture the correlation between local features and temporal information when processing sequence data, thereby enhancing the representation ability and predictive performance of the model for complex sequential data. In addition, by incorporating a multi-head attention module, the proposed method dynamically learns important information from different time intervals and channels. The proposed MAM continuously stimulates fault features in both time and channel dimensions during training, while suppressing fault independent expressions. As a result, it has made an important contribution to improving the performance of the fault diagnosis model.

Results and Discussion: Experimental results demonstrate that the proposed method achieves higher accuracy compared to existing methods, with an average accuracy of 95.45%, average precision of 88.67%, and average recall of 89.03%. Additionally, the proposed method has a moderate number of model parameters (17,626) and training time (935 s). Results indicate that the proposed method accurately diagnoses faults in flexible converter valve equipment, especially in real-world situations with noise overlapping signals.
Identification method for inter-turn faults in transformers based on digital twin concept
Authors: Aiqing Ma , Dawei Gao , Tonghui Qin , Wei Wang
Published: April 2024

A transformer inter-turn fault identification method is proposed based on the digital twin concept to tackle the challenges of high operational complexity and low accuracy associated with traditional transformer fault identification methods. Initially, the Bald Eagle Search algorithm is employed to optimize the critical parameters of the Extreme Learning Machine (ELM), determining the optimal input layer weight and hidden layer threshold of the Extreme Learning Machine. Subsequently, leveraging the digital twin concept, a digital replica of the physical transformer is established, enabling multi-physical field coupling simulation encompassing electrical, thermal, and acoustic domains to elucidate the variation patterns of various physical parameters across different operational scenarios and fault scenarios. Furthermore, key physical characteristic parameters such as sound pressure and winding hot spot temperature are carefully selected to drive a fault identification model tailored to inter-turn faults within the framework of the digital twin concept. Through a detailed investigation using 630 kV A/10 kV transformers as a case study, the results exhibit an impressive fault identification accuracy of 95.24% for the proposed method. Comparative analysis reveals notable enhancements in fault identification accuracy of 12.22%, 7.85%, and 3.73% for ELM, Support Vector Machine and Tuna Swarm Optimization—ELM models, respectively. These findings underscore the effectiveness and practicality of the transformer inter-turn fault identification method based on the digital twin concept, offering valuable insights for the real-time monitoring and diagnosis of inter-turn faults in transformers.
Environmental regulations, GHRM and green innovation of manufacturing enterprises: evidence from China
Authors: Tu Yulong , Lu Lei , Wang Shaojie
Published: April 2024

The contradiction between the economy and the environment is becoming more and more prominent. Green innovation is significant for Chinese manufacturing enterprises considering environmental and economic performance. Based on motivation theory and motivation crowding theory, this study aims to explore the impact of environmental regulations on green innovation of Chinese manufacturing enterprises and the mediating role of green human resource management between environmental regulations and green innovation of enterprises. Using structural equation modeling and SPSS macro, the results of the empirical analysis of 127 manufacturing enterprises in Guangdong Province, China, show that command-controlled regulation, market-incentivized regulation, and voluntary regulation positively impact enterprises’ green innovation, and green human resource management positively affects enterprises’ green innovation. Green human resource management only mediates the relationship between voluntary environmental regulation and green innovation. The study systematically reveals the driving mechanism of green innovation in Chinese manufacturing enterprises and enriches the relevant research on green innovation in manufacturing enterprises.
An overview of community livelihoods in Biosphere Reserves: based on the sustainable livelihoods framework for the 21st century
Authors: Yang Lun
Published: April 2024

Biosphere Reserves (BRs) are the protected areas proposed by the Man and the Biosphere Programme for harmonious coexistence between humanity and nature. Human activities represented by community livelihoods have always been one of the critical issues in the protection and development of BRs. However, the lack of comprehensive research on the status quo and problems of community livelihoods in BRs has caused difficulties in policy formulation and management. In the form of a literature review, this study attempts to summarize and sort out the overview of community livelihoods in BRs by screening the academic literature with the keywords of BRs and livelihoods and using the 21st Century Sustainable Livelihood Framework as the road map. As a result, community livelihoods in BRs highly depend on environmental resources, increasing vulnerability. Although establishing BRs has brought financial and business opportunities to the community, it also provides environmental resources, public services, and geographical areas in the climate-environmental context needed for livelihood maintenance. However, community livelihoods and climate-environmental context show a contradictory relationship of ‘mismatch between supply and demand’ in environmental resources and public services in BRs. In geographical areas, the conflicts brought by illegal activities, invasive alien species, and wildlife-human conflicts are also gradually increasing. At the same time, unbalanced physical and financial assets and relational power with mixed praise also challenge the sustainable development of community livelihoods in BRs. Therefore, this study believes that through multi-stakeholder joint efforts, BRs Friendly Community Livelihoods other than the initial livelihood with high environmental resource dependence can be sought for communities through livelihood diversification, community participatory management, and community spatial pattern refinement.
The top 100 most cited articles on mucopolysaccharidoses: a bibliometric analysis
Authors: Liao Ruyu , Geng Rongrong , Yang Yue , Xue Yufan , Chen Lili , Chen Lan
Published: April 2024

Background: Bibliometrics can trace general research trends in a particular field. Mucopolysaccharidoses (MPS), as a group of rare genetic diseases, seriously affect the quality of life of patients and their families. Scholars have devoted themselves to studying MPS’s pathogenesis and treatment modalities and have published many papers. Therefore, we conducted a bibliometric and visual study of the top 100 most highly cited articles to provide researchers with an indication of the current state of research and potential directions in the field.

Methods: The Web of Science Core Collection was searched for articles on MPS from 1 January 1900, to 8 November 2023, and the top 100 most cited articles were screened. The title, year of publication, institution, country, and first author of the articles were extracted and statistically analyzed using Microsoft Excel 2007. Keyword co-occurrence and collaborative networks were analyzed using VOSviewer 1.6.16.

Results: A total of 9,273 articles were retrieved, and the top 100 most cited articles were filtered out. The articles were cited 18,790 times, with an annual average of 188 citations (122–507). Forty-two journals published these articles, with Molecular Genetics and Metabolism and Proceedings of the National Academy of Sciences of the United States being the most published journal (N = 8), followed by Pediatrics (N = 7), Blood (N = 6). The United States (N = 68), the UK (N = 25), and Germany (N = 20) were the top contributing countries. The Royal Manchester Children’s Hospital (N = 20) and the University of North Carolina (N = 18) were the most contributing institutions. Muenzer J was the most prolific author (N = 14).

Conclusion: We conducted a bibliometric and visual analysis of the top 100 cited articles in MPS. This study identifies the most influential articles currently available in the field of MPS, which provides a good basis for a better understanding of the disease and informs future research directions.
Molecular dissection of an immunodominant epitope in Kv1.2-exclusive autoimmunity
Authors: Talucci Ivan , Arlt Friederike A. , Kreissner Kai O. , Nasouti Mahoor , Wiessler Anna-Lena , Miske Ramona , Mindorf Swantje , Dettmann Inga , Moniri Mehrnaz , Bayer Markus , Broegger Christensen Peter , Ayzenberg Ilya , Kraft Andrea , Endres Matthias , Komorowski Lars , Villmann Carmen , Doppler Kathrin , Prüss Harald , Maric Hans M.
Published: April 2024

Introduction

Subgroups of autoantibodies directed against voltage-gated potassium channel (Kv) complex components have been associated with immunotherapy-responsive clinical syndromes. The high prevalence and the role of autoantibodies directly binding Kv remain, however, controversial. Our objective was to determine Kv autoantibody binding requirements and to clarify their contribution to the observed immune response.

Methods

Binding epitopes were studied in sera (n = 36) and cerebrospinal fluid (CSF) (n = 12) from a patient cohort positive for Kv1.2 but negative for 32 common neurological autoantigens and controls (sera n = 18 and CSF n = 5) by phospho and deep mutational scans. Autoantibody specificity and contribution to the observed immune response were resolved on recombinant cells, cerebellum slices, and nerve fibers.

Results

83% of the patients (30/36) within the studied cohort shared one out of the two major binding epitopes with Kv1.2-3 reactivity. Eleven percent (4/36) of the serum samples showed no binding. Fingerprinting resolved close to identical sequence requirements for both shared epitopes. Kv autoantibody response is directed against juxtaparanodal regions in peripheral nerves and the axon initial segment in central nervous system neurons and exclusively mediated by the shared epitopes.

Discussion

Systematic mapping revealed two shared autoimmune responses, with one dominant Kv1.2-3 autoantibody epitope being unexpectedly prevalent. The conservation of the molecular binding requirements among these patients indicates a uniform autoantibody repertoire with monospecific reactivity. The enhanced sensitivity of the epitope-based (10/12) compared with that of the cell-based detection (7/12) highlights its use for detection. The determined immunodominant epitope is also the primary immune response visible in tissue, suggesting a diagnostic significance and a specific value for routine screening.
Counterproductive effects of anti-CD38 and checkpoint inhibitor for the treatment of NK/T cell lymphoma
Authors: Lee Wendy W. L. , Lim Jing Quan , Tang Tiffany P. L. , Tan Daryl , Koh Ser Mei , Puan Kia Joo , Wang Liang Wei , Lim Jackwee , Tan Kim Peng , Chng Wee Joo , Lim Soon Thye , Ong Choon Kiat , Rotzschke Olaf
Published: April 2024

Introduction

Natural killer/T cell lymphoma (NKTL) is an aggressive malignancy associated with poor prognosis. This is largely due to limited treatment options, especially for relapsed patients. Immunotherapies like immune checkpoint inhibitors (ICI) and anti-CD38 therapies have shown promising but variable clinical efficacies. Combining these therapies has been suggested to enhance efficacy.

Methods

We conducted a case study on a relapsed NKTL patient treated sequentially with anti-CD38 followed by ICI (anti-PD1) using cytometry analyses.

Results and Discussion

Our analysis showed an expected depletion of peripheral CD38+ B cells following anti-CD38 treatment. Further analysis indicated that circulating anti-CD38 retained their function for up to 13 weeks post-administration. Anti-PD1 treatment triggered re-activation and upregulation of CD38 on the T cells. Consequently, these anti-PD1-activated T cells were depleted by residual circulating anti-CD38, rendering the ICI treatment ineffective. Finally, a meta-analysis confirmed this counterproductive effect, showing a reduced efficacy in patients undergoing combination therapy. In conclusion, our findings demonstrate that sequential anti-CD38 followed by anti-PD1 therapy leads to a counterproductive outcome in NKTL patients. This suggests that the treatment sequence is antithetic and warrants re-evaluation for optimizing cancer immunotherapy strategies.
The causes and consequences of trained immunity in myeloid cells
Authors: Bhargavi Gunapati , Subbian Selvakumar
Published: April 2024

Conventionally, immunity in humans has been classified as innate and adaptive, with the concept that only the latter type has an immunological memory/recall response against specific antigens or pathogens. Recently, a new concept of trained immunity (a.k.a. innate memory response) has emerged. According to this concept, innate immune cells can exhibit enhanced responsiveness to subsequent challenges, after initial stimulation with antigen/pathogen. Thus, trained immunity enables the innate immune cells to respond robustly and non-specifically through exposure or re-exposure to antigens/infections or vaccines, providing enhanced resistance to unrelated pathogens or reduced infection severity. For example, individuals vaccinated with BCG to protect against tuberculosis were also protected from malaria and SARS-CoV-2 infections. Epigenetic modifications such as histone acetylation and metabolic reprogramming (e.g. shift towards glycolysis) and their inter-linked regulations are the key factors underpinning the immune activation of trained cells. The integrated metabolic and epigenetic rewiring generates sufficient metabolic intermediates, which is crucial to meet the energy demand required to produce proinflammatory and antimicrobial responses by the trained cells. These factors also determine the efficacy and durability of trained immunity. Importantly, the signaling pathways and regulatory molecules of trained immunity can be harnessed as potential targets for developing novel intervention strategies, such as better vaccines and immunotherapies against infectious (e.g., sepsis) and non-infectious (e.g., cancer) diseases. However, aberrant inflammation caused by inappropriate onset of trained immunity can lead to severe autoimmune pathological consequences, (e.g., systemic sclerosis and granulomatosis). In this review, we provide an overview of conventional innate and adaptive immunity and summarize various mechanistic factors associated with the onset and regulation of trained immunity, focusing on immunologic, metabolic, and epigenetic changes in myeloid cells. This review underscores the transformative potential of trained immunity in immunology, paving the way for developing novel therapeutic strategies for various infectious and non-infectious diseases that leverage innate immune memory.
Role of aryl hydrocarbon receptors in infection and inflammation
Authors: Xu Linglan , Lin Luping , Xie Nan , Chen Weiwei , Nong Weihua , Li Ranhui
Published: April 2024

The aryl hydrocarbon receptor (AhR) is a transcription factor that is activated by various ligands, including pollutants, microorganisms, and metabolic substances. It is expressed extensively in pulmonary and intestinal epithelial cells, where it contributes to barrier defense. The expression of AhR is pivotal in regulating the inflammatory response to microorganisms. However, dysregulated AhR expression can result in endocrine disorders, leading to immunotoxicity and potentially promoting the development of carcinoma. This review focuses on the crucial role of the AhR in facilitating and limiting the proliferation of pathogens, specifically in relation to the host cell type and the species of etiological agents involved in microbial pathogen infections. The activation of AhR is enhanced through the IDO1-AhR-IDO1 positive feedback loop, which is manipulated by viruses. AhR primarily promotes the infection of SARS-CoV-2 by inducing the expression of angiotensin-converting enzyme 2 (ACE2) and the secretion of pro-inflammatory cytokines. AhR also plays a significant role in regulating various types of T-cells, including CD4+ T cells and CD8+ T cells, in the context of pulmonary infections. The AhR pathway plays a crucial role in regulating immune responses within the respiratory and intestinal barriers when they are invaded by viruses, bacteria, parasites, and fungi. Additionally, we propose that targeting the agonist and antagonist of AhR signaling pathways could serve as a promising therapeutic approach for combating pathogen infections, especially in light of the growing prevalence of drug resistance to multiple antibiotics.
Myeloid A20 is critical for alternative macrophage polarization and type-2 immune-mediated helminth resistance
Authors: Petta Ioanna , Thorp Marie , Ciers Maarten , Blancke Gillian , Boon Louis , Meese Tim , Van Nieuwerburgh Filip , Wullaert Andy , Grencis Richard , Elewaut Dirk , van Loo Geert , Vereecke Lars
Published: April 2024

Background

Protective immunity against intestinal helminths requires induction of robust type-2 immunity orchestrated by various cellular and soluble effectors which promote goblet cell hyperplasia, mucus production, epithelial proliferation, and smooth muscle contractions to expel worms and re-establish immune homeostasis. Conversely, defects in type-2 immunity result in ineffective helminth clearance, persistent infection, and inflammation. Macrophages are highly plastic cells that acquire an alternatively activated state during helminth infection, but they were previously shown to be dispensable for resistance to Trichuris muris infection.

Methods

We use the in vivo mouse model A20myel-KO, characterized by the deletion of the potent anti-inflammatory factor A20 (TNFAIP3) specifically in the myeloid cells, the excessive type-1 cytokine production, and the development of spontaneous arthritis. We infect A20myel-KO mice with the gastrointestinal helminth Trichuris muris and we analyzed the innate and adaptive responses. We performed RNA sequencing on sorted myeloid cells to investigate the role of A20 on macrophage polarization and type-2 immunity. Moreover, we assess in A20myel-KO mice the pharmacological inhibition of type-1 cytokine pathways on helminth clearance and the infection with Salmonella typhimurium.

Results

We show that proper macrophage polarization is essential for helminth clearance, and we identify A20 as an essential myeloid factor for the induction of type-2 immune responses against Trichuris muris. A20myel-KO mice are characterized by persistent Trichuris muris infection and intestinal inflammation. Myeloid A20 deficiency induces strong classical macrophage polarization which impedes anti-helminth type-2 immune activation; however, it promotes detrimental Th1/Th17 responses. Antibody-mediated neutralization of the type-1 cytokines IFN-γ, IL-18, and IL-12 prevents myeloid-orchestrated Th1 polarization and re-establishes type-2-mediated protective immunity against T. muris in A20myel-KO mice. In contrast, the strong Th1-biased immunity in A20myel-KO mice offers protection against Salmonella typhimurium infection.

Conclusions

We hereby identify A20 as a critical myeloid factor for correct macrophage polarization and appropriate adaptive mucosal immunity in response to helminth and enteric bacterial infection.
The steroid-sparing effect of JAK inhibitors across multiple patient populations
Authors: Conigliaro Paola , Minerba Clara , Vendola Andrea , Fiannacca Luigi , Triggianese Paola , Kroegler Barbara , Greco Elisabetta , Bergamini Alberto , Chimenti Maria Sole
Published: April 2024

Introduction

JAK-inhibitors (JAK-i) represent an effective treatment in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA). Oral glucocorticoids (OGC) are commonly used in combination with JAK-i to reach therapeutic target. We aimed to assess, in a real-life setting, the reduction of OGC dose during JAK-i treatment in active RA and PsA patients.

Methods

We prospectively enrolled 103 patients (88 RA, 15 PsA) treated with JAK-i: 24% bio-naïve (b-naïve), 76% bDMARD-insufficient responders (bDMARD-IR) and 40% difficult to treat (D2T), defined as failure of ≥2 bDMARDs with different mechanism of action. Disease activity (DAS28 and DAPSA, VAS-pain, GH) and OGC dose was collected at baseline and after 3, 6 and 12 months (T3, T6, T12) of treatment.

Results

In all the cohort and in b-naïve patients we reported a reduction of OGC dose at all time-points; bDMARD-IR patients were able to reduce OGC dose at T3 and T12; D2T ones only at T3. We reported an improvement of disease activity and withdrawal of OGC as early as three months of therapy, at all time-points, regardless of line of bDMARD treatment.

Conclusion

Chronic OGC may cause detrimental bone, metabolic, cardiovascular side effects and infections; therefore JAK-i steroid-sparing effect may be beneficial for patients in long-term treatment.
O-GlcNAc transferase regulates collagen deposition and fibrosis resolution in idiopathic pulmonary fibrosis
Authors: Vang Shia , Helton Eric Scott , Guo Yiming , Burpee Bailey , Rose Elex , Easter Molly , Bollenbecker Seth , Hirsch Meghan June , Matthews Emma Lea , Jones Luke Isaac , Howze Patrick Henry , Rajasekaran Vasanthi , Denson Rebecca , Cochran Phillip , Attah Isaac Kwame , Olson Heather , Clair Geremy , Melkani Girish , Krick Stefanie , Barnes Jarrod Wesley
Published: April 2024

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disease that is characterized by an excessive accumulation of extracellular matrix (ECM) proteins (e.g. collagens) in the parenchyma, which ultimately leads to respiratory failure and death. While current therapies exist to slow the progression, no therapies are available to resolve fibrosis.

Methods

We characterized the O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT)/O-GlcNAc axis in IPF using single-cell RNA-sequencing (scRNA-seq) data and human lung sections and isolated fibroblasts from IPF and non-IPF donors. The underlying mechanism(s) of IPF were further investigated using multiple experimental models to modulate collagen expression and accumulation by genetically and pharmacologically targeting OGT. Furthermore, we hone in on the transforming growth factor-beta (TGF-β) effector molecule, Smad3, by co-expressing it with OGT to determine if it is modified and its subsequent effect on Smad3 activation.

Results

We found that OGT and O-GlcNAc levels are upregulated in patients with IPF compared to non-IPF. We report that the OGT regulates collagen deposition and fibrosis resolution, which is an evolutionarily conserved process demonstrated across multiple species. Co-expression of OGT and Smad3 showed that Smad3 is O-GlcNAc modified. Blocking OGT activity resulted in decreased phosphorylation at Ser-423/425 of Smad3 attenuating the effects of TGF-β1 induced collagen expression/deposition.

Conclusion

OGT inhibition or knockdown successfully blocked and reversed collagen expression and accumulation, respectively. Smad3 is discovered to be a substrate of OGT and its O-GlcNAc modification(s) directly affects its phosphorylation state. These data identify OGT as a potential target in pulmonary fibrosis resolution, as well as other diseases that might have aberrant ECM/collagen accumulation.
Navigating accent bias in German: children's social preferences for a second-language accent over a first-language regional accent
Authors: Hanulíková Adriana
Published: April 2024

Spoken language conveys rich sociolinguistic information about a speaker's language background. Previous research indicates that both monolingual and bilingual children use this information when making social decisions. They prefer local speakers whose accent or variety matches their own over speakers of foreign languages or second-language speakers. What remains unclear is how exposure to diverse linguistic communities affects children's preferences for non-local accents. This study examines social preferences for a regional and a second-language accent as a function of prior exposure to diverse accents and languages, measured on a continuous scale. German-speaking primary-school children (aged 7–10) were asked to choose stickers in a forced-choice task using animated cartoon characters. We replicated the observed social preferences for one's local accent. Interestingly, when the local accent was absent, children socially preferred a second-language accent (American) over a first-language regional accent (Bavarian), even though both accents were equally intelligible and relatively unfamiliar to the children, as determined through a sentence repetition task and a geographical classification task. Children's choices were not explained by continuous measures of accent or bilingual exposure. The results suggest a complex interaction of various factors not limited to the speakers' first- or second-language status.
The role of tidal creeks in shaping carbon and nitrogen patterns in a Chinese salt marsh
Authors: Ma Ziwen , Wu Yanan , Zhao Siqi , Pan Yueyan , Liu Jiakai , Zhang Mingxiang , Zhang Zhenming
Published: April 2024

Tidal creeks play a crucial role in lateral transport of carbon and nutrients from tidal salt marshes. However, the specific impact of tidal creek development on carbon and nutrient distribution within the marsh remains poorly understood. The objective of this study is to assess the influence of lateral tidal flooding through the tidal creeks on the spatial distribution of carbon and nitrogen fractions in the soils of a Chinese temperate salt marsh. We conducted a comprehensive analysis of the relative variations in different carbon and nitrogen fractions, along with soil physicochemical and microbial indicators, between the bank soil of the tidal creek and its lateral inland soils across high, middle, and low flats. Our findings highlight that tidal creek development significantly affects the middle flat, leading to substantial variations in organic carbon and total nitrogen. The low flat mainly experiences changes in dissolved inorganic carbon levels. Furthermore, a lateral increase in microbial biomass is observed in the middle flat, indicating that the significantly lower SOC in the middle flat might be ascribed to enhanced microbial decomposition. The lateral enrichment of dissolved inorganic carbon in the low flat is possibly related to the nearshore location and/or abiotic adsorption in inorganic carbon sequestration. Overall, this study demonstrates the critical role of tidal creek development in shaping the distribution patterns of carbon and nitrogen fractions in tidal salt marshes.
Influence of dietary Salicornia europaea L. extract supplementation on feed efficiency of Altay sheep by modifying their gastrointestinal bacteria communities
Authors: Kamal Mahmoud , Lele Wang , Shuzhen Tang , Jiandi Liang , Rongyan Qin , Yanfeng Liu , Wenqi Wang , Xiangyu Chen , Cheng Yanfen
Published: April 2024

This experiment aimed to examine the impact of Salicornia europaea L. extract on sheep growth performance, rumen fermentation variables, nutrient apparent digestibility, and gastrointestinal microbial diversity. Forty-eight male Altay sheep, weighing 32.5 ± 2.8 kg and approximately 3.5 months old, were chosen. Four dietary treatments, each consisting of four replicates and three sheep per replicate, were distributed randomly to the sheep. The pelleted total mixed ration containing Salicornia europaea L. extract at 0.0, 0.2, 0.4, and 0.6% DM was freely available to the sheep in the four treatment groups. The 56-day experiment consisted of 45 days of measurements followed by 11 days of adaptation. The growth performance was not affected by nutrition Salicornia europaea L. extract (p ≤ 0.05), but the feed-to-gain ratio was reduced when the extract was given at 0.4% DM (p ≤ 0.05). Compared to the 0 and 0.2% treatments, the apparent digestibility of DM, OM, NDF, and ADF was substantially greater in the 0.4, and 0.6% treatments. Furthermore, compared to sheep in the 0 and 0.2% groups, sheep in the 0.6% group had a noticeably higher apparent digestibility of CP. As the amount of Salicornia europaea L. extract added to the rumen fluid rose, the molar ratio of acetic acid increased. In contrast, the molar ratio of propionic acid gradually decreased, and the total volatile fatty acid content gradually reduced. Thus, adding a suitable quantity of Salicornia europaea L. extract to the sheep ration is natural and secure, which may improve the environmental sustainability of small ruminant production systems.
Magnetic hybrid nanomaterial based on a natural polymer and an amino acid as pH/temperature dual-responsive nanoplatform for the delivery of tamoxifen
Authors: Torres Jazmín , Cadena Castro Diego , Ancarani Rosario , Bruvera Ignacio , Mendoza Zélis Pedro , Martín Sandra E. , García Mónica C. , Uberman Paula M.
Published: April 2024

Magnetic hybrid nanomaterials offer promising properties for the advancement of nanoplatforms in cancer nanomedicine, particularly in drug delivery applications. These nanoplatforms can effectively respond to various stimuli present at the tumor site, such as pH and temperature fluctuations, allowing for controlled and triggered release of therapeutic payloads. In this study, we present a straightforward methodology for the synthesis of stable hybrid magnetic nanoplatforms (HMNP) based on Fe3O4 nanoparticles, L-cysteine (L-Cys), and hyaluronic acid (HA) as key constituents for the delivery of tamoxifen (TMX). The synthesized superparamagnetic HMNP, Fe3O4-L-Cys-HA, with a size of 11 nm, was successfully loaded with TMX. The incorporation of L-Cys showed superior interaction with the surface of Fe3O4 nanoparticles compared to other L-Cys derivatives explored as ligands. Consequently, L-Cys was selected for further functionalization with HA, providing the HMNP with active targeting properties toward CD44-overexpressed receptors. High loading efficiency of TMX (75%) was achieved via electrostatic interaction between the carboxylate groups exposed by the HMNP and the ammonium group of the TMX side chain. Efficient control in the TMX release towards different receptor media was observed. Notably, the release of TMX from HMNP-TMX was triggered under acidic pH and hyperthermia conditions, showcasing its responsiveness to both stimuli. Furthermore, enhanced anticancer activity of TMX against MDA-MB-231 breast cancer cells was observed when loaded into HMNP (IC50 almost 3-fold lower for HMNP-TMX compared to free TMX), indicating improved cell uptake of TMX-loaded HMNP in comparison to the free drug. Overall, pH/temperature dual-sensitive HMNP demonstrates promising potential as a nanoplatform for cancer nanomedicine, with prospects for magnetic hyperthermia therapy.
CiftiStorm pipeline: facilitating reproducible EEG/MEG source connectomics
Authors: Areces-Gonzalez Ariosky , Paz-Linares Deirel , Riaz Usama , Wang Ying , Li Min , Razzaq Fuleah A. , Bosch-Bayard Jorge F. , Gonzalez-Moreira Eduardo ,   Lifespan Brain Chart Consortium (LBCC),   Global Brain Consortium (GBC),   Cuban Human Brain Mapping Project (CHBMP), Ontivero-Ortega Marlis , Galan-Garcia Lidice , Martínez-Montes Eduardo , Minati Ludovico , Valdes-Sosa Mitchell J. , Bringas-Vega Maria L. , Valdes-Sosa Pedro A.
Published: April 2024

We present CiftiStorm, an electrophysiological source imaging (ESI) pipeline incorporating recently developed methods to improve forward and inverse solutions. The CiftiStorm pipeline produces Human Connectome Project (HCP) and megconnectome-compliant outputs from dataset inputs with varying degrees of spatial resolution. The input data can range from low-sensor-density electroencephalogram (EEG) or magnetoencephalogram (MEG) recordings without structural magnetic resonance imaging (sMRI) to high-density EEG/MEG recordings with an HCP multimodal sMRI compliant protocol. CiftiStorm introduces a numerical quality control of the lead field and geometrical corrections to the head and source models for forward modeling. For the inverse modeling, we present a Bayesian estimation of the cross-spectrum of sources based on multiple priors. We facilitate ESI in the T1w/FSAverage32k high-resolution space obtained from individual sMRI. We validate this feature by comparing CiftiStorm outputs for EEG and MRI data from the Cuban Human Brain Mapping Project (CHBMP) acquired with technologies a decade before the HCP MEG and MRI standardized dataset.
MF-Net: multi-scale feature extraction-integration network for unsupervised deformable registration
Authors: Li Andi , Ying Yuhan , Gao Tian , Zhang Lei , Zhao Xingang , Zhao Yiwen , Song Guoli , Zhang He
Published: April 2024

Deformable registration plays a fundamental and crucial role in scenarios such as surgical navigation and image-assisted analysis. While deformable registration methods based on unsupervised learning have shown remarkable success in predicting displacement fields with high accuracy, many existing registration networks are limited by the lack of multi-scale analysis, restricting comprehensive utilization of global and local features in the images. To address this limitation, we propose a novel registration network called multi-scale feature extraction-integration network (MF-Net). First, we propose a multiscale analysis strategy that enables the model to capture global and local semantic information in the image, thus facilitating accurate texture and detail registration. Additionally, we introduce grouped gated inception block (GI-Block) as the basic unit of the feature extractor, enabling the feature extractor to selectively extract quantitative features from images at various resolutions. Comparative experiments demonstrate the superior accuracy of our approach over existing methods.
Outcomes of percutaneous vertebroplasty in multiple myeloma: a tertiary neurosciences experience with long-term follow-up
Authors: Holmes Hannah E. , Balian Vartan , Kular Saminderjit , Batty Ruth , Connolly Daniel J. A. , Chantry Andrew , Martin Andrew
Published: April 2024

Background

Multiple myeloma is diagnosed in 5,800 people in the United Kingdom (UK) each year with up to 64% having vertebral compression fractures at the time of diagnosis. Painful vertebral compression fractures can be of significant detriment to patients’ quality of life. Percutaneous vertebroplasty aims to provide long-term pain relief and stabilize fractured vertebrae.

Methods and materials

Data was collected from all cases of percutaneous vertebroplasty performed on patients with multiple myeloma from November 2017 to January 2019. Pain scores were measured using the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) pre-procedure, 2 months post procedure and 4 years post-procedure. Procedure related complications and analgesia use were also documented.

Results

22 patients were included with a total of 119 vertebrae treated. Patients reported a significant improvement in overall pain score with a median pre-procedure VAS of 8 and a median post-procedure VAS of 3.5 (p<0.0001). There was a median pre-procedure ODI score of 60% and a median post-procedure ODI score of 36% (p<0000.1). There was improvement across all ODI domains and a 77% reduction in analgesic requirement. There were small cement leaks into paravertebral veins or endplates at 15 levels (12%) which were asymptomatic. There were 8 responders to the long-term follow-up questionnaire at 4 years. This demonstrated an overall stable degree of pain relief in responders with a median VAS of 3.5 and median ODI of 30%.

Conclusion

At this center, vertebroplasty has been shown to reduce both VAS and ODI pain scores and reduce analgesia requirements in patients with VCFs secondary to multiple myeloma with long lasting relief at 4 years post-procedure.
Central venous catheters do not increase the hemorrhagic risk in acute promyelocytic leukemia patients during induction therapy
Authors: Cao Manxiong , Hong Jiaqiong , Zhang Dongqing , Chen Feiheng , Su Yongzhong
Published: April 2024

In acute promyelocytic leukemia (APL), hemorrhage, particularly intracranial hemorrhage, is the most common cause of early death. A central venous catheter (CVC) may provide a greater guarantee of safety and comfort to APL patients. However, CVCs have seldom been attempted in APL patients during induction therapy because of concerns about increasing the risk of hemorrhagic complications after this invasive procedure. To evaluate the hemorrhagic risk after CVC placement in APL patients during induction therapy, we retrospectively analyzed 95 newly diagnosed patients with APL from January 2010 to December 2022. Among these patients, 39 patients in the CVC group and 56 patients in the non-CVC group were included. Laboratory and clinical parameters of the two groups were collected and compared. There were no significant differences in median platelet, fibrinogen (Fbg), D-dimer, prothrombin time (PT), white blood count (WBC) and hemoglobin (Hb) between the CVC and non-CVC groups on the first day of the visit (day 0) and the following days (day 4, day 7, day 11, day 14, day 18 and day 21) (p = 0.382, p = 0.805, p = 0.456, p = 0.902, p = 0.901 and p = 0.097, respectively). The consumption of transfused platelets and Fbg was not significantly different between the CVC group and non-CVC group (5.0 vs. 4.5 units, p = 0.34, and 6.8 vs. 6.0, p = 0.36, respectively). The last day of platelet and Fbg transfusion was also not significantly different (21 vs. 19, p = 0.238 and 7.5 vs. 8.5, p = 0.684, respectively). The incidences of total hemorrhagic events and hemorrhagic death were lower in the CVC group than in the non-CVC group (17.9% vs. 37.5%, p = 0.04 and 0% vs. 16.1%, p = 0.01, respectively). The 30-day survival rate was not significantly different (92.3% vs. 82.1%, respectively, p = 0.145) for the CVC group compared with the non-CVC group. Our study suggested that CVCs did not increase the hemorrhagic risk in APL patients during induction therapy and that a CVC should be considered in this type of clinical situation.
Reconstructive flap surgery in head and neck cancer patients: an interdisciplinary view of the challenges encountered by radiation oncologists in postoperative radiotherapy
Authors: Thariat Juliette , Carsuzaa Florent , Beddok Arnaud , Deneuve Sophie , Marcy Pierre-Yves , Merlotti Anna , Dejean Catherine , Devauchelle Bernard
Published: April 2024

Background

Major advances have been made in reconstructive surgery in the last decades to reduce morbidity in head and neck cancer. Flaps are now present in 80% of patients with oral cavity cancer to cover anatomic, functional, and cosmetic needs. However, gaps in interdisciplinary innovation transfer from surgery to postoperative radiotherapy (poRT) remain challenging. We aimed to provide an interdisciplinary view of the challenges encountered by radiation oncologists in planning head and neck postoperative radiotherapy.

Methods

A systematic and critical review was conducted to address areas of optimization in surgery and radiology that may be relevant to poRT.

Results

Despite extensive surgical literature on flap techniques and salvage surgery, 13 retrospective series were identified, where flap outcomes were indirectly compared between surgery alone or poRT. These low-evidence studies suggest that radiotherapy accelerates flap atrophy, fibrosis, and osteoradionecrosis and deteriorates functional outcomes. Preliminary evidence suggests that tumor spread occurs at the flap–tissue junction rather than in the flaps. One prospective 15-patient study showed 31.3% vs. 39.2% flap volume reduction without or with poRT. In an international consensus, experts recognized the needs for optimized flap-sparing poRT against flap-related functional deterioration and bone damage. CT, MRI, and PET-CT modalities show potential for the delineation of the junction area between native tissues and flap for flap segmentation and to characterize flap-specific changes quantitatively and correlate them with patterns of relapse or complications.

Conclusion

Flap management in poRT is insufficiently documented, but poRT seems to damage flaps. Current gaps in knowledge underscore the need for prospective flap assessment and interdisciplinary trials investigating flap morbidity minimization by flap-sparing poRT planning.
Exploring nature’s antidote: unveiling the inhibitory potential of selected medicinal plants from Kisumu, Kenya against venom from some snakes of medical significance in sub-Saharan Africa
Authors: Okumu Mitchel , Mbaria James , Gikunju Joseph , Mbuthia Paul , Madadi Vincent , Ochola Francis
Published: April 2024

Background: The present study investigated the efficacy of Conyza bonariensis, Commiphora africana, Senna obtusifolia, Warburgia ugandensis, Vernonia glabra, and Zanthoxylum usambarense against Bitis arietans venom (BAV), Naja ashei venom (NAV), and Naja subfulva venom (NSV).

Methods: 40 extracts and fractions were prepared using n-hexane, dichloromethane, ethyl acetate, and methanol. In vitro efficacy against snake venom phospholipase A2 (svPLA2) was determined in 96-well microtiter and agarose-egg yolk coagulation assays. in vivo efficacy against venom-induced cytotoxicity was determined using Artemia salina. Two commercial antivenoms were used for comparison.

Results: The 96-well microtiter assay revealed poor svPLA2 inhibition of BAV by antivenom (range: 20.76% ± 13.29% to 51.29% ± 3.26%) but strong inhibition (>90%) by dichloromethane and hexane fractions of C. africana, hexane and ethyl acetate extracts and fraction of W. ugandensis, dichloromethane fraction of V. glabra, and the methanol extract of S. obtusifolia. The methanol extract and fraction of C. africana, and the hexane extract of Z. usambarense strongly inhibited (>90%) svPLA2 activity in NAV. The hexane and ethyl acetate fractions of V. glabra and the dichloromethane, ethyl acetate, and methanol extracts of C. africana strongly inhibited (>90%) svPLA2 in NSV. The agarose egg yolk coagulation assay showed significant inhibition of BAV by the dichloromethane fraction of C. africana (EC50 = 3.51 ± 2.58 μg/mL), significant inhibition of NAV by the methanol fraction of C. africana (EC50 = 7.35 ± 1.800 μg/mL), and significant inhibition of NSV by the hexane extract of V. glabra (EC50 = 7.94 ± 1.50 μg/mL). All antivenoms were non-cytotoxic in A. salina but the methanol extract of C. africana and the hexane extracts of V. glabra and Z. usambarense were cytotoxic. The dichloromethane fraction of C. africana significantly neutralized BAV-induced cytotoxicity, the methanol fraction and extract of C. africana neutralized NAV-induced cytotoxicity, while the ethyl acetate extract of V. glabra significantly neutralized NSV-induced cytotoxicity. Glycosides, flavonoids, phenolics, and tannins were identified in the non-cytotoxic extracts/fractions.

Conclusion: These findings validate the local use of C. africana and V. glabra in snakebite but not C. bonariensis, S. obtusifolia, W. ugandensis, and Z. usambarense. Further work is needed to isolate pure compounds from the effective plants and identify their mechanisms of action.
Availability, pricing, and affordability of essential medicines for pediatric population in Malawi
Authors: Chiumia Francis Kachidza , Chithope-Mwale Cynthia , Abikoloni Felix , Matchaya Vanessa , Gaviyawo Tadala , Khuluza Felix
Published: April 2024

Objective:

Lack of access to essential medicines negatively impacts on the quality of healthcare delivery and increases morbidity and mortality, especially to the vulnerable pediatric population. We assessed the availability, pricing, and affordability of pediatric formulations in Malawi.

Methodology:

The study was conducted in 76 health facilities (public, faith-based and private pharmacies, and clinics) from the northern and southern regions of Malawi from March to May 2023. We adapted the WHO/HAI method for the assessment of both availability and pricing of medicines. Data on availability were collected from stock card records using a WHO/HAI template and medicine prices were provided by the pharmacy personnel who were managing the facilities. Availability of medicines was calculated as the percentage of facilities which had a stock of the respective medicine at the time of data collection while medicine prices was assessed by calculating the median prices of each medicine. To assess the affordability of the medicines, we calculated the number of days it takes for a person who is receiving the government-set minimum wage to work to pay for a treatment course of common indications. The study was approved by the KUHES ethics committee under the numbers U.12/22/3900 and U.12/22/3903.

Results and conclusion:

The overall availability of pediatric medicines was 38.1% for public health facilities, 53.7% for private retail pharmacies and drug stores, 49.5% for private clinics and 48.3% for Christian Health Association of Malawi (CHAM) facilities. We found the illegal availability of prescription-only medicines of up to 54% in medicine stores. Medicine median prices were higher in the private clinics followed by retail pharmacies and drugs stores. CHAM had the lowest median prices for medicines of all the sectors. More than 50% of medicines were found to be affordable as less than a day’s wage was required to purchase the treatment. We found poor availability of pediatric formulation among public, CHAM, and private sectors in Malawi. This may affect the quality of care among pediatric patients and therefore contribute to morbidity and mortality in Malawi. The supply of medicines and health commodities needs to consider needs of special populations such as children to achieve universal health coverage.