bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of heat-tolerant mungbean genotypes through morpho-physiological evaluation and key gene expression analysis
Authors: Bhardwaj Ragini , Gayacharan  , Gawade Bharat H. , Pathania Pooja , Talukdar Akshay , Kumar Prakash , Khan Suphiya , Singh Gyanendra Pratap
Published: October 2024

Mungbean plays a significant role in global food and nutritional security. However, the recent drastic rise in atmospheric temperature has posed an imminent threat to mungbean cultivation. Therefore, this study investigates the growth and physiological changes of 87 mungbean germplasm lines under heat stress. Genotypes were examined using parameters including leaf area, chlorophyll content, membrane stability index (MSI), stomatal conductance, pollen viability, number of pods per cluster, number of pods per plant, number of seeds/pod, 100-seed weight and grain yield/plant under heat stress and control environments. A wide range of variation was observed for these traits among genotypes under heat stress and control environments. Genotypes were also identified with variable responses under both environments. The phenotypic expression of selected promising accessions was also validated in control environment conditions at the National Phytotron facility. The selected promising genotypes viz., IC76475, IC418452 and IC489062 validated their heat tolerance behavior for key candidate genes revealed by quantitative real-time PCR (qRT-PCR). These mungbean genotypes can act as potential resources in the mungbean improvement programs for heat stress tolerance. This study also provides a comprehensive understanding of the key mechanisms underlying heat tolerance in mungbean.
Human dental pulp stem cells modulate pro-inflammatory macrophages both through cell-to-cell contact and paracrine signaling
Authors: Maccaferri Monia , Pisciotta Alessandra , Carnevale Gianluca , Salvarani Carlo , Pignatti Elisa
Published: October 2024

Introduction

Macrophages play a key role in most of the inflammatory diseases such as Rheumatoid Arthritis (RA), but the mechanism underlying their pathogenesis is still under study. Among stem cells, human dental pulp stem cells (hDPSCs) have attracted attention due to their easy accessibility and immunomodulatory properties, making them a promising adjuvant therapy. In this study, we aimed to evaluate the capacity of hDPSCs to modulate the phenotypes of primary human macrophages. Additionally, we sought to observe the differences induced on macrophages when cultured directly with hDPSCs or through a cell culture insert, mimicking the paracrine communication pathway.

Methods

Monocytes, isolated from buffy coats, were differentiated into pro-inflammatory M1 and anti-inflammatory M2 macrophages. Subsequently, they were cultured with hDPSCs either directly or via a cell-culture insert for 48 hours. Finally, they were analyzed for protein, gene expression, cytokines levels and immunofluorescence.

Results

In our study, we have demonstrated that, hDPSCs, even without priming, can reduce TNFα levels and enhancing IL-10 release in pro-inflammatory macrophages, both through direct contact and paracrine signaling. Furthermore, we found that their effects are more pronounced when in cell-to-cell contact through the decrease of NF-kB and COX-2 expression and of CD80/PD-L1 colocalization. HDPSCs, when in contact with macrophages, showed enhanced expression of NF-kB, COX-2, ICAM-1, PD-L1, FAS-L, TNFα and IFNγ.

Conclusion

We showed that hDPSCs exert immunomodulatory effects on pro-inflammatory macrophages, with cell-to-cell contact yielding a more pronounced outcome compared to paracrine signaling. Our work highlights the immunomodulatory properties of hDPSCs on activated pro-inflammatory macrophages and the potential therapeutic role in inflamed tissue.
Exploring the naturally acquired response to Pvs47 gametocyte antigen
Authors: Soares da Veiga Gisele Tatiane , Donassolo Rafael Amaral , Forcellini Sofia , Ferraboli Julia Weber , Kujbida Junior Mario Antonio , Nisimura Líndice Mitie , Bassai Letícia Werzel , Kessler Rafael Luis , Serpeloni Mariana , Bittencourt Najara Carneiro , Salazar Yanka Evellyn Alves R. , Guimarães Luiz Felipe Ferreira , Louzada Jaime , Barros Dayanne Kamylla Alves da Silva , Lopes Stefanie Costa Pinto , Carvalho Luzia Helena , Nóbrega de Sousa Tais , Kano Flora Satiko , Costa Fabio Trindade Maranhão , Fanini Wowk Pryscilla , Albrecht Letusa
Published: October 2024

Malaria represents a challenging global public health task, with Plasmodium vivax being the predominant parasite in Brazil and the most widely distributed species throughout the world. Developing a vaccine against P. vivax malaria demands innovative strategies, and targeting gametocyte antigens shows promise for blocking transmission prevention. Among these antigens, Pvs47, expressed in gametocytes, has shown remarkable efficacy in transmission blocking. However, remains underexplored in vaccine formulations. This study employed in silico methods to comprehensively characterize the physicochemical properties, structural attributes, epitope presence, and conservation profile of Pvs47. Additionally, we assessed its antigenicity in individuals exposed to malaria in endemic Brazilian regions. Recombinant protein expression occurred in a eukaryotic system, and antigenicity was evaluated using immunoenzymatic assays. The responses of naturally acquired IgM, total IgG, and IgG subclasses were analyzed in three groups of samples from Amazon region. Notably, all samples exhibited anti-Pvs47 IgM and IgG antibodies, with IgG3 predominating. Asymptomatic patients demonstrated stronger IgG responses and more diverse subclass responses. Anti-Pvs47 IgM and IgG responses in symptomatic individuals decrease over time. Furthermore, we observed a negative correlation between anti-Pvs47 IgM response and gametocytemia in samples of symptomatic patients, indicating a gametocyte-specific response. Additionally, negative correlation was observed among anti-Pvs47 antibody response and hematocrit levels. Furthermore, comparative analysis with widely characterized blood antigens, PvAMA1 and PvMSP119, revealed that Pvs47 was equally or more recognized than both proteins. In addition, there is positive correlation between P. vivax blood asexual and sexual stage immune responses. In summary, our study unveils a significant prevalence of anti-Pvs47 antibodies in diverse Amazonian samples and the importance of IgM response for gametocytes depuration. These findings regarding the in silico characterization and antigenicity of Pvs47 provide crucial insights for potential integration into P. vivax vaccine formulations.
Understanding bladder cancer risk: Mendelian randomization analysis of immune cell and inflammatory factor influence
Authors: Un Hiocheng , Wusimanjiang Wumier , Zhan Wenhao , Zhang Xinxin , Li Minghao , Lei Jiahao , Lin Renxuan , Zhang Yuliang , Chen Junxing , Wang Zongren
Published: October 2024

Introduction

The intricate roles of immune cells and inflammatory factors in cancer, particularly their association with the risk of bladder cancer, are not well understood.

Methods

This study aimed to clarify potential causal relationships between these elements and the development of bladder cancer using genome-wide association study (GWAS) summary statistics for 731 immune cell phenotypes and 91 circulating inflammatory factors (cases=2,053; controls=287,137). The primary analytical approach was Inverse Variance Weighting (IVW), supplemented by MR-Egger regression, weighted median, and weighted mode analyses. Sensitivity analyses included Cochran Q test, MR-Egger intercept test, and Leave-one-out test.

Results

The findings indicated that monocytes are positively correlated with an increased risk of bladder cancer. On the contrary, double-negative (DN) T cells, HLA DR+CD8br, and CD28 on CD28+CD45RA+CD8br T cells exhibited an inverse correlation, suggesting a possible protective effect. Furthermore, inflammatory factors IL-20, IL-22RA1, and Eotaxin were significantly associated with an increased risk of bladder cancer.

Discussion

These results suggest that certain immune cell phenotypes and inflammatory factors may play a role in the development of bladder cancer and could serve as potential biomarkers for assessing tumor risk. The findings also offer new insights into the pathogenesis of bladder cancer, indicating a need for further investigation.
Comparison of HBV-specific T cell reactivity across the pregnant, postpartum and non-pregnant women with chronic HBV infection
Authors: Wang Genju , Yue Fangping , Zhang Ziyue , Wu Yandan , Ji Ruixue , Zhou Guanlun , Ji Ying , Shen Chuanlai
Published: October 2024

Objective

To investigate the features of HBV-specific T cell reactivity across the pregnant, postpartum or non-pregnant women with chronic HBV infection.

Methods

A total of 283 patients with chronic HBV infection were enrolled in this study, including 129 patients during pregnancy, 58 patients during postpartum less than 6 months and 96 non-pregnant patients at childbearing age. A universal ELISpot assay was set up using a broad-spectrum T-cell epitope peptide library which containing 103 functionally validated CD8+ T-cell epitopes derived from overall HBsAg, HBc/eAg, HBx and HBpol proteins and fitting to the human leukocyte antigen polymorphisms of Chinese population. Then, The functional HBV-specific T cells in peripheral blood were detected.

Results

The spot-forming units (SFUs) of HBV-specific T cells in the pregnant group showed no statistical difference from the postpartum group, but significantly less than that in the non-pregnant group (p = 0.046). In the untreated patients, the pregnant group displayed HBe/cAg-specific T cells (SFUs) less than the non-pregnant group (P = 0.025) and the postpartum group (P = 0.045). Meanwhile, in the NUCs-treated patients, the three groups presented similar HBV-specific T cell reactivity. Furthermore, the SFUs in the NUCs-treated pregnant group were similar to that in the NUCs-untreated pregnant group. Importantly, ROC analysis demonstrated that the HBV-specific T cells (SFUs) (AUC = 0.742) and combined with HBsAg levels (AUC = 0.775) or with HBeAg level (AUC = 0.78) had a good predictive performance for hepatitis progression during pregnancy group.

Conclusion

Pregnancy can reduce HBV-specific T cell reactivity in the women with chronic HBV infection, and NUCs treatment cannot improve their HBV-specific T cells reactivity. Routine monitoring of HBV-specific T cells during pregnant and postpartum period can provide precise evaluation for immune function and valuable guidance for treatments.
A novel strategy of co-expressing CXCR5 and IL-7 enhances CAR-T cell effectiveness in osteosarcoma
Authors: Hui Xinhui , Farooq Muhammad Asad , Chen Yiran , Ajmal Iqra , Ren Yaojun , Xue Min , Ji Yuzhou , Du Bingtan , Wu Shijia , Jiang Wenzheng
Published: October 2024

Background

Solid tumors are characterized by a low blood supply, complex stromal architecture, and immunosuppressive milieu, which inhibit CAR-T cell entry and survival. CXCR5 has previously been employed to increase CAR-T cell infiltration into CXCL13+ cancers. On the other hand, IL-7 improves the survival and persistence of T cells inside a solid tumor milieu.

Methods

We constructed a novel NKG2D-based CAR (C5/IL7-CAR) that co-expressed CXCR5 and IL-7. The human osteosarcoma cell lines U-2 OS, 143B, and Mg63 highly expressed MICA/B and CXCL13, thus presenting a perfect avenue for the present study.

Results

Novel CAR-T cells are superior in their activation, degranulation, and cytokine release competence, hence lysing more target cells than conventional CAR. Furthermore, CXCR5 and IL-7 co-expression decreased the expression of PD-1, TIM-3, and TIGIT and increased Bcl-2 expression. Novel CAR-T cells show enhanced proliferation and differentiation towards the stem cell memory T cell phenotype. C5/IL7-CAR-T cells outperformed conventional CAR-T in eradicating osteosarcoma in mouse models and displayed better survival. Additionally, CXCR5 and IL-7 co-expression enhanced CAR-T cell numbers, cytokine release, and survival in implanted tumor tissues compared to conventional CAR-T cells. Mechanistically, C5/IL7-CAR-T cells displayed enhanced STAT5 signaling.

Conclusion

These findings highlight the potential of CXCR5 and IL-7 co-expression to improve CAR-T cell therapy efficacy against osteosarcoma.
Transition from acute kidney injury to chronic kidney disease in a long-term murine model of Shiga toxin-induced hemolytic-uremic syndrome
Authors: Wegener Jamila , Dennhardt Sophie , Loeffler Ivonne , Coldewey Sina M.
Published: October 2024

Introduction

Up to 40% of patients with typical hemolytic–uremic syndrome (HUS), characterized by microangiopathic hemolytic anemia and acute kidney injury (AKI), develop long-term consequences, most prominently chronic kidney disease (CKD). The transition from AKI to CKD, particularly in the context of HUS, is not yet fully understood. The objective of this study was to establish and characterize a Shiga toxin (Stx)-induced long-term HUS model to facilitate the study of mechanisms underlying the AKI-to-CKD transition.

Methods

C57BL/6J mice were subjected to 5, 10, 15, or 20 ng/kg Stx on days 0, 3, and 6 of the experiment and were sacrificed on day 14 or day 21 to identify the critical time of turnover from the acute to the chronic state of HUS disease.

Results

Acute disease, indicated by weight loss, plasma neutrophil gelatinase-associated lipocalin (NGAL) and urea, and renal neutrophils, diminished after 14 days and returned to sham level after 21 days. HUS-associated hemolytic anemia transitioned to non-hemolytic microcytic anemia along with unchanged erythropoietin levels after 21 days. Renal cytokine levels indicated a shift towards pro-fibrotic signaling, and interstitial fibrosis developed concentration-dependently after 21 days. While Stx induced the intrarenal invasion of pro-inflammatory M1 and pro-fibrotic M2 macrophages after 14 days, pro-fibrotic M2 macrophages were the dominant phenotype after 21 days.

Conclusion

In conclusion, we established and characterized the first Stx-induced long-term model of HUS. This tool facilitates the study of underlying mechanisms in the early AKI-to-CKD transition following HUS and allows the testing of compounds that may protect patients with AKI from developing subsequent CKD.
A systematic review of immersive educational technologies in medical physics and radiation physics
Authors: Tene Talia , Bonilla García Nataly , Coello-Fiallos Diana , Borja Myrian , Vacacela Gomez Cristian
Published: October 2024

Objective

This systematic review aims to analyze and synthesize the current state of research on the role of immersive technologies, specifically augmented reality (AR), virtual reality (VR), and mixed reality (MR), in medical physics and radiation physics education. The primary focus is to evaluate their impact on learning outcomes, performance, and engagement across various educational contexts.

Methods

We conduct a comprehensive search of four major databases: Scopus, Web of Science, PubMed, and IEEE Xplore, covering the period from 2012 to 2023. A total of 316 articles are initially identified. After removing duplicates and screening for relevance based on titles and abstracts, 107 articles are selected for full-text review. Finally, 37 articles met the inclusion criteria and are included in the analysis. The review follows the PRISMA guidelines and utilizes the PICOS framework to structure the research question.

Analysis

Data extraction focuses on key variables such as the type of immersive technology used, educational context, study design, participant demographics, and measured outcomes. The studies are analyzed for their reported effects on learning outcomes, performance, and engagement.

Results

The review found that immersive technologies significantly enhance learning outcomes and engagement. Specifically, 36.4% of the studies reported increased engagement, while 63.6% of studies focusing on practical skills noted performance improvements. The use of AR, VR, and MR showed broad applicability across different educational levels, from undergraduate courses to professional training programs.

Conclusion

Immersive technologies have considerable potential to transform medical and radiation physics. They enhance student engagement, improve learning outcomes, and boost performance in practical skills. Nevertheless, future research should focus on standardizing methodologies, expanding participant demographics, and exploring long-term impacts on skill retention and clinical practice. This review provides a valuable resource for guiding future research and implementing innovative educational strategies in the dynamic fields of medical physics and radiation physics.
CAR-engineered T cell therapy as an emerging strategy for treating autoimmune diseases
Authors: Vukovic Jovana , Abazovic Dzihan , Vucetic Dusan , Medenica Sanja
Published: October 2024

CAR-T therapy has demonstrated great success in treating hematological malignancies, which has led to further research into its potential in treating other diseases. Autoimmune diseases have great potential to be treated with this therapy due to the possibility of specific targeting of pathological immune cells and cells that produce autoantibodies, which could lead to permanent healing and restoration of immunological tolerance. Several approaches are currently under investigation, including targeting and depleting B cells via CD19 in the early stages of the disease, simultaneously targeting B cells and memory plasma cells in later stages and refractory states, as well as targeting specific autoantigens through the chimeric autoantibody receptor (CAAR). Additionally, CAR-engineered T regulatory cells can be modified to specifically target the autoimmune niche and modulate the pathological immune response. The encouraging results from preclinical studies have led to the first successful use of CAR-T therapy in humans to treat autoimmunity. This paved the way for further clinical studies, aiming to evaluate the long-term safety and efficacy of these therapies, potentially revolutionizing clinical use.
Rifabutin: a repurposed antibiotic with high potential against planktonic and biofilm staphylococcal clinical isolates
Authors: Ferreira Magda , Pinto Margarida , Aires-da-Silva Frederico , Bettencourt Ana , Gaspar Maria Manuela , Aguiar Sandra Isabel
Published: October 2024

Staphylococcus aureus poses a significant threat as an opportunistic pathogen in humans, and animal medicine, particularly in the context of hospital-acquired infections (HAIs). Effective treatment is a significant challenge, contributing substantially to the global health burden. While antibiotic therapy remains the primary approach for staphylococcal infections, its efficacy is often compromised by the emergence of resistant strains and biofilm formation. The anticipated solution is the discovery and development of new antibacterial agents. However, this is a time consuming and expensive process with limited success rates. One potential alternative for addressing this challenge is the repurposing of existing antibiotics. This study investigated the potential of rifabutin (RFB) as a repurposed antibiotic for treating S. aureus infections. The minimum inhibitory concentration (MIC) of rifabutin was assessed by the broth microdilution method, in parallel to vancomycin, against 114 clinical isolates in planktonic form. The minimum biofilm inhibitory concentration (MBIC50) was determined by an adaptation of the broth microdilution method, followed by MTT assay, against a subset of selected 40 clinical isolates organized in biofilms. The study demonstrated that RFB MIC ranged from 0.002 to 6.250 μg/mL with a MIC50 of 0.013 μg/mL. RFB also demonstrated high anti-biofilm activity in the subset of 40 clinical isolates, with confirmed biofilm formation, with no significant MBIC50 differences observed between the MSSA and MRSA strains, in contrast to that observed for the VAN. These results highlight the promising efficacy of RFB against staphylococcal clinical isolates with different resistance patterns, whether in planktonic and biofilm forms.
Recent advances in the use of biogenic nanomaterials and photocatalysts for wastewater treatment: challenges and future prospects
Authors: Sanni Samuel Eshorame , Oni Babalola Aisosa , Okoro Emeka Emmanuel , Pandya Shivani
Published: October 2024

In many parts of the world, the availability of clean water is almost an impossible task owing to the intrusion of contaminants in flowing or stagnant streams which renders them unsafe for use by man. Water pollution is a serious environmental problem that poses serious dangers to humans, the environment and aquatic life. Also, the recent rise in the spate of emerging contaminants as well as bacteria in waters recovered from process streams, manufacturing and other production activities, have resulted in unforeseen consequences including environmental pollution, health related sicknesses (diarrhoea, dysentery, cholera, skin irritations, lung infection, etc.) as well as loss and extinction of aquatic lives, hence, the need to consider viable methods of treating waste waters so as to render them safe for use by these organisms. This will in turn preserve life below water- SDG 14 as well as promote the use of clean water and a healthy environment- SDG 6. Among the several existing nanotechnologies tailored towards the treatment of wastewater, a couple of inorganic toxic nanomaterials/nanosubstances have been adopted which render such treated waters as potential risks to humans and aquatic lives. However, green nanoparticles are considered potent and viable means of treating these waters, especially when literature has it that some nanomaterials are toxic in nature. Furthermore, the paper also reports on some unpopular but very potent emerging green nanomaterials, alongside recent advances, applications, related challenges and ways to address them. Information on future prospects of green nanoparticles as potential long-term sustainable water purification and wastewater treatment technologies are also included; therefore, this study is focused on addressing issues related to SDGs 3 (ensure healthy lives and promote wellbeing), 6 (clean water and sanitation), 12 (responsible consumption and production) and 14 (life below water).
Auditory stimuli suppress contextual fear responses in safety learning independent of a possible safety meaning
Authors: Mombelli Elena , Osypenko Denys , Palchaudhuri Shriya , Sourmpis Christos , Brea Johanni , Kochubey Olexiy , Schneggenburger Ralf
Published: October 2024

Safety learning allows the identification of non-threatening situations, a learning process instrumental for survival and psychic health. In contrast to fear learning, in which a sensory cue (conditioned stimulus, CS) is temporally linked to a mildly aversive stimulus (US), safety learning is studied by presenting the CS and US in an explicitly unpaired fashion. This leads to conditioned inhibition of fear responses, in which sensory cues can acquire a safety meaning (CS-). In one variant of safety learning, an auditory CS- was shown to reduce contextual fear responses during recall, as measured by freezing of mice. Here, we performed control experiments to test whether auditory stimuli might interfere with freezing by mechanisms other than safety learning, a phenomenon also called external inhibition. Surprisingly, when auditory stimulation was omitted during training (US-only controls), such stimuli still significantly suppressed contextual freezing during recall, indistinguishable from the reduction of freezing after regular safety training. The degree of this external inhibition was positively correlated with the levels of contextual freezing preceding the auditory stimulation. Correspondingly, in fear learning protocols which employ a new context during recall and therefore induce lower contextual freezing, auditory stimuli did not induce significant external inhibition. These experiments show that in safety learning protocols that employ contextual freezing, the freezing reduction caused by auditory stimuli during recall is dominated by external inhibition, rather than by learned safety. Thus, in safety learning experiments extensive controls should be performed to rule out possible intrinsic effects of sensory cues on freezing behavior.
Research status and development trends of omics in neuroblastoma a bibliometric and visualization analysis
Authors: Han Mengliang , Niu Huizhong , Duan Fei , Wang Zhaolong , Zhang Zhiguang , Ren Hui
Published: October 2024

Background

Neuroblastoma (NB), a prevalent extracranial solid tumor in children, stems from the neural crest. Omics technologies are extensively employed in NB, and We analyzed published articles on NB omics to understand the research trends and hot topics in NB omics.

Method

We collected all articles related to NB omics published from 2005 to 2023 from the Web of Science Core Collection database. Subsequently, we conducted analyses using VOSviewer, CiteSpace, Bibliometrix, and the Bibliometric online analysis platform (https://bibliometric.com/).

Results

We included a total of 514 articles in our analysis. The increasing number of publications in this field since 2020 indicates growing attention to NB omics, gradually entering a mature development stage. These articles span 50 countries and 1,000 institutions, involving 3,669 authors and 292 journals. The United States has the highest publication output and collaboration with other countries, with Germany being the most frequent collaborator. Capital Medical University and the German Cancer Research Center are the institutions with the highest publication count. The Journal of Proteome Research and the Journal of Biological Chemistry are the most prolific journal and most co-cited journal, respectively. Wang, W, and Maris, JM are the scholars with the highest publication count and co-citations in this field. “Neuroblastoma” and “Expression” are the most frequent keywords, while “classification,” “Metabolism,” “Cancer,” and “Diagnosis” are recent key terms. The article titled “Neuroblastoma” by John M. Maris is the most cited reference in this analysis.

Conclusion

The continuous growth in NB omics research underscores its increasing significance in the scientific community. Omics technologies have facilitated the identification of potential biomarkers, advancements in personalized medicine, and the development of novel therapeutic strategies. Despite these advancements, the field faces significant challenges, including tumor heterogeneity, data standardization issues, and the translation of research findings into clinical practice.
IGF1R inhibition and PD-1 blockade improve anti-tumor immune response in epithelial ovarian cancer
Authors: Somri-Gannam Lina , Meisel-Sharon Shilhav , Hantisteanu Shay , Bar-Noy Tomer , Sigal Emiliya , Groisman Gabriel , Hallak Mordechai , Werner Haim , Bruchim Ilan
Published: October 2024

Introduction

The insulin-like growth factor (IGF) system plays a key role in regulating growth and invasiveness in epithelial ovarian cancer (EOC) and is considered a promising therapeutic target. EOC is an immunosuppressive disease, although there are limited data about the involvement of the IGF1R system in the anti-tumor immune response in the EOC microenvironment.

Methods

In the current study, we hypothesized that IGF 1 receptor (IGF1R) involvement in the maturation of dendritic cells (DC) with the co-inhibition of IGF1R and PD-1 would affect the EOC microenvironment.

Results

We found that DC pretreated with IGF1R inhibitor resulted in fewer EOC cells. Moreover, in vivo experiments conducted with an EOC mouse model, with anti-PD-1/IGF1R combined, resulted in lower tumor weight compared to individual treatments. Additionally, anti-PD-1/IGF1R treatment increased DC by 34% compared with AEW-541 and 40% with anti-PD-1. The combined treatment increased CD8+ T-cell levels compared to AEW-541 alone. RNA-seq data analysis indicated that anti-PD-1/IGF1R led to a more potent immune response, as reflected by altered gene expression levels related to anti-tumor immune response, compared with either treatment alone.

Discussion

These findings provide novel evidence that IGF1R axis inhibition combined with PD-1 blockade may be an effective therapeutic strategy for selected EOC patient populations.
Thrombopoietin mimetic therapy alleviates radiation-induced bone marrow vascular injury in a bone marrow transplant mouse model
Authors: Ghimire Hemendra , Sargur Madabushi Srideshikan , Vercellino Justin , Brooks Jamison , Zuro Darren , Lim Ji Eun , Vishwasrao Paresh , Abdelhamid Amr Mohamed Hamed , Strome Guy , Eichenbaum Gary , Al Malki Monzr , Guha Chandan , Hui Susanta K.
Published: October 2024

Background

There is a need for therapies that can mitigate bone marrow dysfunction and organ toxicity that occur following myeloablative injury and reduced intensity conditioning regimens used in patients undergoing bone marrow transplantation (BMT). The pathogenesis of adverse effects from BMT conditioning has been linked to injury to the vascular endothelium, bone marrow (BM), and other organs.

Objective

To evaluate the impact of the thrombopoietin mimetic drug JNJ-26366821 (TPOm) on BM vascular recovery in mice undergoing myeloablative radiation conditioning followed by BMT.

Study design

TPOm (doses: 0 µg, 300 µg, 1000 µg per Kg body weight) was administered on Days 0 and 7 after BMT, in mice receiving a total body irradiation (TBI) conditioning regimen (5.5 Gy x 2) before congenic BMT. BM donner cell engraftment was analyzed using flow cytometry on Days 7, 14, and 30 post-BMT. The morphological and biophysical properties of the BM vasculature were evaluated by intravital multiphoton microscopy (MPM) and immunofluorescence confocal imaging. Herein, morphological properties involve microvascular density (MVD), vessel diameter, and vascular area, while biophysical properties include transfer rate (Ktrans) of contrast within the BM vascular niche, as well as the fractional volume (vec) of extracellular extravascular tissue (EES).

Results

No significant difference in donor chimerism was observed at days 7, 14, and 30 post-BMT, between TPOm and PBS-treated mice. TPOm intervention improved BM vasculature regeneration in transplanted mice. The MVD, Ktrans, and BM vasculature as well as vascular endothelial growth factor receptor-2 (VEGFR2) in the BM, showed a dose dependent improvement in mice treated with TPOm. On day 14 post-BMT, the group receiving 1000 µg/Kg TPOm showed significant shifts (p-value < 0.05) in MVD, Ktrans, and VEGFR2 expression from their corresponding control types (TPOm dose 0 µg) towards levels comparable to healthy controls.

Conclusion

TPOm intervention augments BM vascular structure and function, which may be important for hematopoietic recovery and bone marrow function in radiation conditioned hematopoietic stem cell transplant patients, in addition to enhancing platelet recovery.
Analysis of different standards for life support technology in manned submersible
Authors: Jiang Lei , Ye Cong , Li Hongxia , Wang Yao , Jiang Nian
Published: October 2024

Life support technology is one of the most critical technologies in manned submersibles, acting for the pilots of the submersible and thus directly affecting its underwater safety. Due to its importance, many countries and international organizations have proposed standards and specifications for life support technology. This paper presents an overview of the life support technology of manned submersibles, comparing the standards proposed for it. Furthermore, it analyzes the specific data of oxygen supply and carbon dioxide absorption, both of which are critical aspects of life support technology in each standard, and identifies the data that is widely acknowledged and recognized as the basis for establishing ISO standard 22252:2020). Finally, ISO standard data such as oxygen and carbon dioxide concentration are further confirmed by the environmental parameters of manned submersibles such as the Fendouzhe.
High-throughput sequencing discovered diverse monopartite and bipartite begomoviruses infecting cucumbers in Saudi Arabia
Authors: Sattar Muhammad Naeem , Almaghasla Mostafa I. , Tahir Muhammad Nouman , El-Ganainy Sherif M. , Chellappan Biju Vadakkemukadiyil , Arshad Muhammad , Drou Nizar
Published: October 2024

Limited research in Saudi Arabia has devolved into the prevalence and genetic diversity of begomoviruses. Utilizing Illumina MiSeq sequencing, we obtained 21 full-length begomovirus sequences (2.7–2.8 kb) from eight cucumber plants grown in fields and greenhouses. We found that two complete begomovirus genomes were variants of the Boushehr strain of tomato yellow leaf curl virus (TYLCV) with nucleotide (nt) sequence identities of 94.7-95.9%. Another full-length genome was a variant of TYLCV-Iran with 94.6% identity. Five full-length sequences closely matched the DNA-A of watermelon chlorotic stunt virus (WmCSV) isolates with 97.9-98.7% nt sequence identities, while five sequences had their highest nt sequence identities (95.8-96.3%) with the DNA-B of WmCSV isolates. Simultaneously, four sequences were 99.1-99.6% identical to the DNA-A of tomato leaf curl Palampur virus (ToLCPalV). Four sequences matched the DNA-B of ToLCPalV reported from Iran and Saudi Arabia with identities ranging from 96.2-100%. Four plants showed a mixed infection of these begomoviruses. Most ORFs showed evidence of negative selection pressure, suggesting that purifying selection plays a crucial role in shaping the diversity of these begomoviruses. Additionally, potential intra- and interspecies recombination events were detected in the TYLCV and WmCSV DNA-B genomic regions. The ToLCPalV isolates identified in this study formed a cluster with the other ToLCPalV isolates reported from Saudi Arabia, Iran and Iraq, representing a unique lineage distinct from ToLCPalV reported from Southeast Asia. High mutation rate and robust selection facilitated the independent evolution of ToLCPalV without recombination. Overall, this study offers valuable insights into the diversity and evolutionary dynamics of begomoviruses infecting cucumber crops in Al-Ahsa, Saudi Arabia.
Comparative genomics and transcriptomics reveal differences in effector complement and expression between races of Fusarium oxysporum f.sp. lactucae
Authors: Bates Helen J. , Pike Jamie , Price R. Jordan , Jenkins Sascha , Connell John , Legg Andrew , Armitage Andrew , Harrison Richard J. , Clarkson John P.
Published: October 2024

This study presents the first genome and transcriptome analyses for Fusarium oxysporum f. sp. lactucae (Fola) which causes Fusarium wilt disease of lettuce. Long-read genome sequencing of three race 1 (Fola1) and three race 4 (Fola4) isolates revealed key differences in putative effector complement between races and with other F. oxysporum ff. spp. following mimp-based bioinformatic analyses. Notably, homologues of Secreted in Xylem (SIX) genes, also present in many other F. oxysporum ff. spp, were identified in Fola, with both SIX9 and SIX14 (multiple copies with sequence variants) present in both Fola1 and Fola4. All Fola4 isolates also contained an additional single copy of SIX8. RNAseq of lettuce following infection with Fola1 and Fola4 isolates identified highly expressed effectors, some of which were homologues of those reported in other F. oxysporum ff. spp. including several in F. oxysporum f. sp. apii. Although SIX8, SIX9 and SIX14 were all highly expressed in Fola4, of the two SIX genes present in Fola1, only SIX9 was expressed as further analysis revealed that SIX14 gene copies were disrupted by insertion of a transposable element. Two variants of Fola4 were also identified based on different genome and effector-based analyses. This included two different SIX8 sequence variants which were divergently transcribed from a shared promoter with either PSE1 or PSL1 respectively. In addition, there was evidence of two independent instances of HCT in the different Fola4 variants. The involvement of helitrons in Fola genome rearrangement and gene expression is discussed.
Perceived feedback and school belonging: the mediating role of subjective well-being
Authors: Li Xinyu , Kuo Yi-Lung , Huggins Thomas J.
Published: October 2024

Introduction

This study examined the interplay between perceived feedback (PF), subjective wellbeing (SWB), and students’ sense of belonging to school (SBS). School belonging is a key factor for decisions regarding academic studies, and is usually impacted by PF. The current study explored whether SWB mediates the established relationship between PF and SBS.

Method

This was achieved by applying a mediation model to PISA 2018 data from 12,058 students in four areas of China.

Results

Perceived feedback positively affected students’ SBS (β = 0.26, p < 0.01); and that SWB partially mediated this relationship between PF and SBS (β = 0.47, p < 0.01).

Discussion

The findings of this study have the potential to contribute to the existing literature on educational psychology and well-being. By shedding light on the mediating role of SWB, the research offers practical implications for educators and policymakers seeking to enhance students’ school belonging and other implications for their academic success. Further research can contribute to this promising area, by focusing on subjective wellbeing and its impact on a range of decisions being made by students during a critical phase of their personal and academic development.
“And I Can Remind Myself That I Am All Of This”: adolescents’ experiences of group-based acceptance and commitment therapy
Authors: Brovold Filippa , Laugen Nina Jakhelln , Grøtte Torun
Published: October 2024

Introduction

A growing body of literature supports the use of Acceptance-and commitment therapy (ACT) for a wide range of mental health problems in children and adolescents, but less is known about ACT when given to adolescents in a group format. Consequently, this study aimed to explore the subjective experiences of adolescents who had completed a group-based ACT for symptoms of anxiety and depression. Adolescents’ perceptions of the core therapeutic processes of ACT and the means used to enhance them, as well as the interplay between ACT processes and the group format, were of primary interest.

Methods

Semi-structured qualitative interviews were conducted with seven adolescents, of which five were girls and two were boys, between 16 and 19 years old. Transcripts were analyzed using reflexive thematic analysis.

Results

The adolescents varied greatly in their experience of ACT’s core processes and the methods used to enhance them. Most found the core processes meaningful and educational, especially appreciating the concept of values and value-based action. However, some perceived the core processes as irrelevant and provocative, particularly interpreting acceptance as “giving up.” The metaphors and practical exercises were experiences as playful and instructive supplements to the more theoretical elements of therapy, but also as childish and embarrassing. The group format facilitated normalization and support and seemed to increase the adolescents’ motivation and adherence to therapeutical work, but it also triggered socially anxious thoughts and self-censoring for some.

Conclusion

The results from the current study support previous literature indicating that group-based ACT is an acceptable and feasible treatment format for adolescents. Yet, the varying experiences underscores the need for further studies exploring how to accommodate the group format to the diverse personal and developmental disparities in this age group. Randomized controlled trials are also needed to compare the effectiveness of individual versus group format of ACT for adolescents.
Realising agency: insights from participatory research with learners in a South African sexual and reproductive health programme
Authors: Coakley Chelsea , Lee Devyn , Pike Carey , Myers Laura , Hartmann Miriam , Oduro Asantewa , Ntlapo Noluthando , Bekker Linda-Gail ,   Youth Investigators of the Goals for Girls study
Published: October 2024

Background

Investing in the capabilities of adolescents is essential to achieving the United Nations Sustainable Development Goals, which focus on realising adolescent girls and young women’s (AGYW) rights to education, health, bodily autonomy and integrity, sexual and reproductive health (SRH) and well-being. Despite significant scientific and programmatic progress in understanding and responding to their unique and intersecting vulnerabilities, AGYW continue to face disproportionate risk of STIs, HIV and early pregnancy. Health promotion and preventative interventions stand to be improved by early and meaningful engagement of AGYW in intervention design and delivery.

Methods

This study employed Youth Participatory Action Research (YPAR) to co-generate lessons for future school-based SRH programming. The 5-step YPAR process included: (1) youth investigator recruitment; (2) youth investigator training and co-design of YPAR methods; (3) youth investigator-led data collection; (4) collaborative analysis and interpretation; and (5) dissemination.

Results

Collaborative analysis revealed improvements in self-concept and bodily autonomy, understanding and formation of healthy relationships and demand for girl-centred health services and information at school. Additionally, the study highlights YPAR’s positive influence on both the collaborative process and outputs of research. Further, it provides further insight into the quantitative biomedical and socio-behavioural findings of a larger experimental impact evaluation, in which it was nested.

Conclusion

Results from YPAR methods point to high programme acceptability and practical lessons to inform future school-based SRH programming. The inclusion of adolescent girls in the design, delivery and evaluation of intervention research that affects their lives is an important strategy for improving acceptability, and also has demonstrated value in building their health and social assets. Future recommendations include parental involvement, and employing quantitative measures for better evaluation of youth engagement, leadership and partnerships in the research process.
Uncovering the determinants of health in deprived urban neighborhoods in Accra, Ghana: a qualitative and participatory reconnaissance study
Authors: Amedzro Nina , Anaseba Dominic , Darkwa Akosua Gyasi , Twumasi Afua , Ayim Andrews , Ansah-Ofei Adelaide Maria , Dovlo Delanyo , Awoonor-Williams John K. , Agongo Erasmus Emmanuel Akurugu , Agyepong Irene Akua , Elsey Helen
Published: October 2024

Background

Delivering primary care services within the context of rapid urbanization and a changing disease burden is a major challenge in sub-Saharan Africa. Rural models of primary care, including the “Community-based Health Planning and Services” (CHPS) programme in Ghana, have shown improved health outcomes. However, adapting these to the urban context has proved problematic. Differences in the determinants of health found in these settings may help to explain the challenges of delivering CHPS in poor urban neighborhoods in Accra. To inform the redesign of CHPS for the urban context, we aimed to understand the determinants driving health and engagement with health services in three informal settlements in Accra.

Methods

This study formed a reconnaissance phase for a subsequent participatory action research study. We used qualitative and participatory methods to explore the influence of wider and proximal determinants on health and the use and perceptions of CHPS. Three transect walks with community leaders across the study settings informed interview guides and the recruitment of suitable participants for key informant and focus group interviews. Using a Framework Approach, we analysed transcripts and reports from these activities and developed themes and sub-themes in participants’ experiences accessing healthcare.

Results

Our findings highlight the importance of wider and proximal determinants of health including physical environment, gender and other social stratifiers including age, ethnicity, religion and disability, on health, health seeking behavior and personal behaviors such as substance misuse, tobacco use and alcohol. Utilization of CHPS was low and seen primarily as a service for maternal and child health. Private providers, ranging from informal drug stores to private clinics, were used most commonly. Community leaders and groups were active, but engagement was limited by opportunity costs for members.

Conclusion

Traditional service delivery packages need to be adapted to include non-communicable diseases driven by risk behaviors such as tobacco, unhealthy diet, alcohol and substance abuse. Assets such as volunteerism and nurses embedded within communities are challenging to attain in complex urban settings, yet other assets exist including occupational associations and a range of informal and private providers that could support delivery of preventive and promotive health care with equitable reach.
Forecasting air passenger traffic and market share using deep neural networks with multiple inputs and outputs
Authors: Jafari Nahid , Lewison Martin
Published: October 2024

Introduction

In this study, we address the challenge of accurate time series forecasting of air passenger demand using historical market demand data from the U.S. commercial aviation industry in the 21st century. Commercial aviation is a major contributor to the U.S. economy, directly or indirectly generating ~US$1.37 trillion annually, or 5% of annual GDP, and supporting more than 10 million jobs (Airlines for America, 2024). Over 1 billion passengers flew through U.S. airports in 2023 (Bureau of Transportation Statistics, 2024a). Using multiple correlated time series inputs predicts future values of multiple interrelated time series and leverages their mutual dependencies to enhance accuracy.

Methods

In this study, we introduce a two-stage algorithm employing a deep neural network for correlated time series forecasting, addressing scenarios where multiple input variables are interrelated. This approach is designed to capture the influence that one time series can exert on another, thereby enhancing prediction accuracy by leveraging these interdependencies. In the first stage, we fit four Recurrent Neural Network (RNN) models to generate accurate univariate forecasts, each functioning as a single input-output model to predict aggregated market demand. The Gated Recurrent Unit (GRU) model was the top performer for our dataset overall. In the second stage, we apply the best fitted model (GRU Model) from Stage 1 to each individual competitor (disaggregated from the market) and then merge all input tensors using the Concatenate function.

Results and discussion

We hope to contribute to the relevant body of knowledge with a deep neural network framework for forecasting market share among competitors in the U.S. commercial aviation industry, as no similar approach has been documented in the literature. Given the importance of the industry, there is potentially great value in applying sophisticated forecasting techniques to achieve accurate predictions of air passenger demand. Moreover, these techniques may have wider applications and can potentially be employed in other contexts.