bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimum Service Package for the integration of female genital schistosomiasis into sexual and reproductive health and rights interventions
Authors: Pillay Leora N. , Umbelino-Walker Isis , Schlosser Delphine , Kalume Christine , Karuga Robinson
Published: June 2024

Introduction

Female genital schistosomiasis (FGS) is a manifestation of infection with schistosomes in the female genital area that affects an estimated 56 million women and girls in Africa. If untreated, FGS can result in severe sexual and reproductive health (SRH) complications. However, FGS is largely unrecognized by SRH providers, and there is no programmatic guidance for the integration of FGS and sexual and reproductive health and rights (SRHR) interventions in the way of a Minimum Service Package (MSP). Therefore, as part of a larger implementation study, an MSP was developed to guide program staff and health planners on how to integrate FGS and SRHR interventions in schistosomiasis-endemic countries.

Materials and methods

In collaboration with 35 experts from six sectors related to FGS, we conducted virtual workshops, engaging the participants within various specialties from around the world to identify a foundational framework for the MSP, as well as the integration points and activities for FGS and SRHR interventions. Several drafts of the MSP were developed, reviewed in virtual workshops, peer-reviewed, and then finalized by the participants.

Results

A participatory and consultative process led to the identification of a foundational framework for the integration of FGS and SRHR interventions, as well as the integration points and activities. This included identifying cadres of staff who would be needed to implement the MSP and the settings in which the service provision would take place.

Discussion

Defining an MSP to guide the integration of a minimum package of FGS services in SRHR interventions is a critical step toward ensuring the prevention, screening, diagnosis, and treatment of women and girls in Africa. The MSP can now be rolled out and tested in a country context to start reducing the burden of this preventable and treatable neglected disease.
The exploration of perioperative hypotension subtypes: a prospective, single cohort, observational pilot study
Authors: Zhao Xu , Zhang Yuanjia , Kou Mengjia , Wang Zhongxing , He Qiulan , Wen Zhishuang , Chen Jingyuan , Song Yiyan , Wu Shihui , Huang Chanyan , Huang Wenqi
Published: June 2024

Background

Hypotension is a risk factor for postoperative complications, but evidence from randomized trials does not support that a higher blood pressure target always leads to optimized outcomes. The heterogeneity of underlying hemodynamics during hypotension may contribute to these contradictory results. Exploring the subtypes of hypotension can enable optimal management of intraoperative hypotension.

Methods

This is a prospective, observational pilot study. Patients who were ≥ 45 years old and scheduled to undergo moderate-to-high-risk noncardiac surgery were enrolled in this study. The primary objective of this pilot study was to investigate the frequency and distribution of perioperative hypotension and its subtypes (hypotension with or without cardiac output reduction). The exposure of hypotension and its subtypes in patients with and without myocardial or acute kidney injury were also explored.

Results

Sixty patients were included in the analysis. 83% (50/60) of the patients experienced perioperative hypotension. The median duration of hypotension for each patient was 8.0 [interquartile range, 3.1–23.3] minutes. Reduced cardiac output was present during 77% of the hypotension duration. Patients suffering from postoperative myocardial or acute kidney injury displayed longer duration and more extensive exposure in all hypotension subtypes. However, the percentage of different hypotension subtypes did not differ in patients with or without postoperative myocardial or acute kidney injury.

Conclusion

Perioperative hypotension was frequently accompanied by cardiac output reduction in moderate-to-high-risk noncardiac surgical patients. However, due to the pilot nature of this study, the relationship between hypotension subtypes and postoperative myocardial or acute kidney injury still needs further exploration.

Clinical trial registration

https://www.chictr.org.cn/showprojEN.html?proj=134260, CTR2200055929.
D for dominant: porcine circovirus 2d (PCV-2d) prevalence over other genotypes in wild boars and higher viral flows from domestic pigs in Italy
Authors: Faustini Giulia , Poletto Francesca , Baston Riccardo , Tucciarone Claudia Maria , Legnardi Matteo , Dal Maso Mariangela , Genna Viviana , Fiorentini Laura , Di Donato Alessandra , Perulli Simona , Cecchinato Mattia , Drigo Michele , Franzo Giovanni
Published: June 2024

Introduction

Porcine circovirus 2 (PCV-2) is a key pathogen for the swine industry at a global level. Nine genotypes, differing in epidemiology and potentially virulence, emerged over time, with PCV-2a, -2b, and -2d being the most widespread and clinically relevant. Conversely, the distribution of minor genotypes appears geographically and temporally restricted, suggesting lower virulence and different epidemiological drivers. In 2022, PCV-2e, the most genetically and phenotypically divergent genotype, was identified in multiple rural farms in North-eastern Italy. Since rural pigs often have access to outdoor environment, the introduction from wild boars was investigated.

Methods

Through a molecular and spatial approach, this study investigated the epidemiology and genetic diversity of PCV-2 in 122 wild boars across different provinces of North-eastern Italy.

Results

Molecular analysis revealed a high PCV-2 frequency (81.1%, 99/122), and classified the majority of strains as PCV-2d (96.3%, 78/81), with sporadic occurrences of PCV-2a (1.2%, 1/81) and PCV-2b (2.5%, 2/81) genotypes. A viral flow directed primarily from domestic pigs to wild boars was estimated by phylogenetic and phylodynamic analyses.

Discussion

These findings attested that the genotype replacement so far described only in the Italian domestic swine sector occurred also in wild boars. and suggested that the current heterogeneity of PCV-2d strains in Italian wild boars likely depends more on different introduction events from the domestic population rather than the presence of independent evolutionary pressures. While this might suggest PCV-2 circulation in wild boars having a marginal impact in the industrial sector, the sharing of PCV-2d strains across distinct wild populations, in absence of a consistent geographical pattern, suggests a complex interplay between domestic and wild pig populations, emphasizing the importance of improved biosecurity measures to mitigate the risk of pathogen transmission.
Deterministic processes dominate microbial assembly mechanisms in the gut microbiota of cold-water fish between summer and winter
Authors: Xu Liangliang , Xiang Peng , Liu Xiaoshuai , Zhao Luying , Chen Hanxi , Li Maohua , Song Zhaobin
Published: June 2024

Exploring the effects of seasonal variation on the gut microbiota of cold-water fish plays an important role in understanding the relationship between seasonal variation and cold-water fish. Gut samples of cold-water fish and environmental samples were collected during summer and winter from the lower reaches of the Yalong River. The results of the 16S rRNA sequencing showed that significant differences were identified in the composition and diversity of gut bacteria of cold-water fish. Co-occurrence network complexity of the gut bacteria of cold-water fish was higher in summer compared to winter (Sum: nodes: 256; edges: 20,450; Win: nodes: 580; edges: 16,725). Furthermore, from summer to winter, the contribution of sediment bacteria (Sum: 5.3%; Win: 23.7%) decreased in the gut bacteria of cold-water fish, while the contribution of water bacteria (Sum: 0%; Win: 27.7%) increased. The normalized stochastic ratio (NST) and infer community assembly mechanisms by phylogenetic bin-based null model analysis (iCAMP) showed that deterministic processes played a more important role than stochastic processes in the microbial assembly mechanism of gut bacteria of cold-water fish. From summer to winter, the contribution of deterministic processes to gut bacteria community assembly mechanisms decreased, while the contribution of stochastic processes increased. Overall, these results demonstrated that seasonal variation influenced the gut bacteria of cold-water fish and served as a potential reference for future research to understand the adaptation of fish to varying environments.
ASFV infection induces macrophage necroptosis and releases proinflammatory cytokine by ZBP1-RIPK3-MLKL necrosome activation
Authors: Zhang Dajun , Hao Yu , Yang Xing , Shi Xijuan , Zhao Dengshuai , Chen Lingling , Liu Huanan , Zhu Zixiang , Zheng Haixue
Published: June 2024

African swine fever (ASF) is an infectious disease characterized by hemorrhagic fever, which is highly pathogenic and causes severe mortality in domestic pigs. It is caused by the African swine fever virus (ASFV). ASFV is a large DNA virus and primarily infects porcine monocyte macrophages. The interaction between ASFV and host macrophages is the major reason for gross pathological lesions caused by ASFV. Necroptosis is an inflammatory programmed cell death and plays an important immune role during virus infection. However, whether and how ASFV induces macrophage necroptosis and the effect of necroptosis signaling on host immunity and ASFV infection remains unknown. This study uncovered that ASFV infection activates the necroptosis signaling in vivo and macrophage necroptosis in vitro. Further evidence showed that ASFV infection upregulates the expression of ZBP1 and RIPK3 to consist of the ZBP1-RIPK3-MLKL necrosome and further activates macrophage necroptosis. Subsequently, multiple Z-DNA sequences were predicted to be present in the ASFV genome. The Z-DNA signals were further confirmed to be present and colocalized with ZBP1 in the cytoplasm and nucleus of ASFV-infected cells. Moreover, ZBP1-mediated macrophage necroptosis provoked the extracellular release of proinflammatory cytokines, including TNF-α and IL-1β induced by ASFV infection. Finally, we demonstrated that ZBP1-mediated necroptosis signaling inhibits ASFV replication in host macrophages. Our findings uncovered a novel mechanism by which ASFV induces macrophage necroptosis by facilitating Z-DNA accumulation and ZBP1 necrosome assembly, providing significant insights into the pathogenesis of ASFV infection.
Generative AI unlocks PET insights: brain amyloid dynamics and quantification
Authors: Bossa Matías Nicolás , Nakshathri Akshaya Ganesh , Berenguer Abel Díaz , Sahli Hichem
Published: June 2024

Introduction

Studying the spatiotemporal patterns of amyloid accumulation in the brain over time is crucial in understanding Alzheimer's disease (AD). Positron Emission Tomography (PET) imaging plays a pivotal role because it allows for the visualization and quantification of abnormal amyloid beta (Aβ) load in the living brain, providing a powerful tool for tracking disease progression and evaluating the efficacy of anti-amyloid therapies. Generative artificial intelligence (AI) can learn complex data distributions and generate realistic synthetic images. In this study, we demonstrate for the first time the potential of Generative Adversarial Networks (GANs) to build a low-dimensional representation space that effectively describes brain amyloid load and its dynamics.

Methods

Using a cohort of 1,259 subjects with AV45 PET images from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we develop a 3D GAN model to project images into a latent representation space and generate back synthetic images. Then, we build a progression model on the representation space based on non-parametric ordinary differential equations to study brain amyloid evolution.

Results

We found that global SUVR can be accurately predicted with a linear regression model only from the latent representation space (RMSE = 0.08 ± 0.01). We generated synthetic PET trajectories and illustrated predicted Aβ change in four years compared with actual progression

Discussion

Generative AI can generate rich representations for statistical prediction and progression modeling and simulate evolution in synthetic patients, providing an invaluable tool for understanding AD, assisting in diagnosis, and designing clinical trials. The aim of this study was to illustrate the huge potential that generative AI has in brain amyloid imaging and to encourage its advancement by providing use cases and ideas for future research tracks.
Establishment and validation of a bad outcomes prediction model based on EEG and clinical parameters in prolonged disorder of consciousness
Authors: Liu Wanqing , Guo Yongkun , Xie Jingwei , Wu Yanzhi , Zhao Dexiao , Xing Zhe , Fu Xudong , Zhou Shaolong , Zhang Hengwei , Wang Xinjun
Published: June 2024

Objective

This study aimed to explore the electroencephalogram (EEG) indicators and clinical factors that may lead to poor prognosis in patients with prolonged disorder of consciousness (pDOC), and establish and verify a clinical predictive model based on these factors.

Methods

This study included 134 patients suffering from prolonged disorder of consciousness enrolled in our department of neurosurgery. We collected the data of sex, age, etiology, coma recovery scales (CRS-R) score, complications, blood routine, liver function, coagulation and other laboratory tests, resting EEG data and follow-up after discharge. These patients were divided into two groups: training set (n = 107) and verification set (n = 27). These patients were divided into a training set of 107 and a validation set of 27 for this study. Univariate and multivariate regression analysis were used to determine the factors affecting the poor prognosis of pDOC and to establish nomogram model. We use the receiver operating characteristic (ROC) and calibration curves to quantitatively test the effectiveness of the training set and the verification set. In order to further verify the clinical practical value of the model, we use decision curve analysis (DCA) to evaluate the model.

Result

The results from univariate and multivariate logistic regression analyses suggested that an increased frequency of occurrence microstate A, reduced CRS-R scores at the time of admission, the presence of episodes associated with paroxysmal sympathetic hyperactivity (PSH), and decreased fibrinogen levels all function as independent prognostic factors. These factors were used to construct the nomogram. The training and verification sets had areas under the curve of 0.854 and 0.920, respectively. Calibration curves and DCA demonstrated good model performance and significant clinical benefits in both sets.

Conclusion

This study is based on the use of clinically available and low-cost clinical indicators combined with EEG to construct a highly applicable and accurate model for predicting the adverse prognosis of patients with prolonged disorder of consciousness. It provides an objective and reliable tool for clinicians to evaluate the prognosis of prolonged disorder of consciousness, and helps clinicians to provide personalized clinical care and decision-making for patients with prolonged disorder of consciousness and their families.
Neural correlates of musical timbre: an ALE meta-analysis of neuroimaging data
Authors: Bellmann Oliver Tab , Asano Rie
Published: June 2024

Timbre is a central aspect of music that allows listeners to identify musical sounds and conveys musical emotion, but also allows for the recognition of actions and is an important structuring property of music. The former functions are known to be implemented in a ventral auditory stream in processing musical timbre. While the latter functions are commonly attributed to areas in a dorsal auditory processing stream in other musical domains, its involvement in musical timbre processing is so far unknown. To investigate if musical timbre processing involves both dorsal and ventral auditory pathways, we carried out an activation likelihood estimation (ALE) meta-analysis of 18 experiments from 17 published neuroimaging studies on musical timbre perception. We identified consistent activations in Brodmann areas (BA) 41, 42, and 22 in the bilateral transverse temporal gyri, the posterior superior temporal gyri and planum temporale, in BA 40 of the bilateral inferior parietal lobe, in BA 13 in the bilateral posterior Insula, and in BA 13 and 22 in the right anterior insula and superior temporal gyrus. The vast majority of the identified regions are associated with the dorsal and ventral auditory processing streams. We therefore propose to frame the processing of musical timbre in a dual-stream model. Moreover, the regions activated in processing timbre show similarities to the brain regions involved in processing several other fundamental aspects of music, indicating possible shared neural bases of musical timbre and other musical domains.
Tackling neurodegeneration in vitro with omics: a path towards new targets and drugs
Authors: Carraro Caterina , Montgomery Jessica V. , Klimmt Julien , Paquet Dominik , Schultze Joachim L. , Beyer Marc D.
Published: June 2024

Drug discovery is a generally inefficient and capital-intensive process. For neurodegenerative diseases (NDDs), the development of novel therapeutics is particularly urgent considering the long list of late-stage drug candidate failures. Although our knowledge on the pathogenic mechanisms driving neurodegeneration is growing, additional efforts are required to achieve a better and ultimately complete understanding of the pathophysiological underpinnings of NDDs. Beyond the etiology of NDDs being heterogeneous and multifactorial, this process is further complicated by the fact that current experimental models only partially recapitulate the major phenotypes observed in humans. In such a scenario, multi-omic approaches have the potential to accelerate the identification of new or repurposed drugs against a multitude of the underlying mechanisms driving NDDs. One major advantage for the implementation of multi-omic approaches in the drug discovery process is that these overarching tools are able to disentangle disease states and model perturbations through the comprehensive characterization of distinct molecular layers (i.e., genome, transcriptome, proteome) up to a single-cell resolution. Because of recent advances increasing their affordability and scalability, the use of omics technologies to drive drug discovery is nascent, but rapidly expanding in the neuroscience field. Combined with increasingly advanced in vitro models, which particularly benefited from the introduction of human iPSCs, multi-omics are shaping a new paradigm in drug discovery for NDDs, from disease characterization to therapeutics prediction and experimental screening. In this review, we discuss examples, main advantages and open challenges in the use of multi-omic approaches for the in vitro discovery of targets and therapies against NDDs.
Optimized precipitation process for the treatment of radioactive effluents from Ni-alloy decontamination using a chemical oxidation reduction process
Authors: Robin Mathurin , Rivonkar Aditya , Suzuki-Muresan Tomo , Abdelouas Abdesselam , Mokili Marcel
Published: June 2024

Nuclear power plays a major role in the generation of electricity with low carbon emissions. However, it generates significant amounts of radioactive waste, mainly from contaminated metallic components such as steam generators. Decontamination is essential for the safe handling and eventual recycling or disposal of these materials. Various decontamination techniques can be utilized but chemical processes are recommended for complex geometries such as the tubular parts of steam generators. COREMIX (Chemical Oxidation REduction using nitric permanganate and oxalic acid MIXture) is a process that is similar to the CORD (Chemical Oxidation Reduction Decontamination) process currently utilized in the industry which involves dissolving the contaminated oxide layers from metallic surfaces. This process generates a large quantity of radioactive effluent that requires appropriate treatment. The objective is to reduce metallic concentration and the radioactivity by precipitating metals in solution as hydroxides M(m-n)(OH)n (with m the oxidation number of the metal M). The optimization of a two-step precipitation protocol is presented here, with a study of the contact time (1–24 h) and the reagents used (NaOH and KOH). The resulting precipitates from this process are characterized using several techniques (FTIR, TGA and XRD). Tests were conducted on surrogate samples to demonstrate the viability of the process on more complex samples. Finally, the optimized protocols were implemented on radioactive Ni-alloy samples. Decontamination factors were calculated portraying the efficiency of both the COREMIX and the subsequent two-stage precipitation process. Characterization of the sludge produced during the process shows that the precipitate obtained at pH 8.5 consists mainly of iron (III) oxide-hydroxides, whereas the precipitate obtained at pH 12 is mainly composed of manganese (II,III) oxide. The optimization steps show that the contact time during the first precipitation and the choice of precipitants does not influence the efficiency of the protocol while the destruction of oxalic acid proves to be critical to quantitatively precipitate chromium. Ultimately, the COREMIX process can effectively decontaminate contaminated Ni-alloy samples, removing between 12% and 14% of the contamination in each cycle. Decontamination of effluent using the precipitation protocol results in a very high decontamination factor of between 3000 and 6000.
The global burden, trends, and inequalities of individuals with developmental and intellectual disabilities attributable to iodine deficiency from 1990 to 2019 and its prediction up to 2030
Authors: Yang Xuesong , Liu Cheng , Liu Yanbo , He Zhigang , Li Juan , Li Yijing , Wu Yanqiong , Manyande Anne , Feng Maohui , Xiang Hongbing
Published: June 2024

Objective

The objective of this study was to assess the global burden of disease for developmental and intellectual disabilities caused by iodine deficiency from 1990 to 2019.

Methods

Using data from the global burden of disease (GBD) 2019, we conducted a cross-country inequity analysis to examine the worldwide burden of developmental and intellectual disabilities caused by the issue of iodine deficiency from 1990 to 2019. Absolute and relative inequality were assessed by the slope index of inequality and the concentration index, respectively. After summarising the latest evidence, we also projected the age-standardized prevalence and years lived with disability (YLD) rates up to 2030 using the BAPC and INLA packages in R statistical software.

Results

In 2019, the global age-standardized prevalence and YLD rates for developmental and intellectual disabilities due to iodine deficiency were 22.54 per 100,000 population (95% UI 14.47 to 29.23) and 4.12 per 100,000 population (95% UI 2.25 to 6.4), respectively. From 1990 to 2019, the age-standardized prevalence and YLD rates of developmental and intellectual disabilities due to iodine deficiency decreased significantly. Geographic distribution showed that areas with lower socio-demographic indices (SDI) were the most affected. The correlation between higher SDI and lower prevalence highlights the role of economic and social factors in the prevalence of the disease. Cross-national inequity analysis shows that disparities persist despite improvements in health inequalities. In addition, projections suggest that the disease burden may decline until 2030.

Conclusion

This research underscores the necessity for targeted interventions, such as enhancing iodine supplementation and nutritional education, especially in areas with lower SDI. We aim to provide a foundation for policymakers further to research effective preventative and potential alternative treatment strategies.
Real-world TRAE association between niraparib and platinum-based chemotherapy
Authors: Wang Linli , Zhou Jieli , Wang Haibin , Han Wenling , Fang Chunyun
Published: June 2024

Background

Pre-clinical studies showed the anti-tumor mechanisms of PARP inhibitors (PARPi) and platinum have some crossover and overlap in the DNA damage repair pathway, patients who respond to platinum-based chemotherapy are also more likely to be sensitive to PARPi. This real-world study mainly aimed to evaluate whether TRAE (treatment-related adverse event) between platinum based chemotherapy (PBC) and niraparib are also associated.

Methods

Patients received niraparib as maintenance treatment or salvage therapy for advanced ovarian cancer at the First Affiliated Hospital of Gannan Medical University from January 2020 to August 2023 were included. Survival data of niraparib treatment and adverse events occurred during the last platinum-based chemotherapy cycle before starting niraparib treatment and during niraparib treatment are documented. Fisher’s exact test were used for correlation analysis.

Results

1. 40 patients treated with niraparib were included in the analysis, including 31 patients treated with niraparib for 1st-line maintenance therapy, 6 patients for PSR (platinum-sensitive recurrence) maintenance therapy, and 3 patients for salvage therapy. The overall median follow-up time was 15.0 months (ranged from 2.2 months to 32.1 months). 2. Overall grade≥3 TRAE (40% vs 70%, p=0.012) including anemia (20% vs 45%, p=0.041) and neutrophil count decreased (17.5% vs 57.5%, p<0.001) was significantly lower during niraparib treatment compared to during chemotherapy. 3. Any grade TRAE (75% vs 100%, p=0.002) including white blood cell count decreased (47.5% vs 87.5%, p<0.001), red blood cell count decreased (57.5% vs 92.5%, p<0.001), anemia (55% vs 87.5%, p<0.001) and neutrophil count decreased (35% vs 85%, p<0.001) were also significantly lower in niraparib treatment group compared with chemotherapy group. No new safety signals were identified.

Conclusion

1. In this real-world practice, we observed that patients with advanced ovarian cancer who experienced any grade and grade ≥3 TRAE during chemotherapy were well tolerated when treated with niraparib, particularly the incidence of any grade and grade ≥3 anemia, and neutrophil count decreased during niraparib treatment were significantly lower compared with that during chemotherapy. 2. For patients with ovarian cancer who have experienced grade ≥3 hematological adverse reactions during prior platinum-based chemotherapy, greater attention should be paid to the monitoring and management of hematological adverse reactions during subsequent treatment with niraparib.
Large-scale, prospective observational study of regorafenib in Japanese patients with advanced gastrointestinal stromal tumors in a real-world clinical setting
Authors: Komatsu Yoshito , Muro Kei , Chosa Masayuki , Hirano Kazufumi , Sunaya Toshiyuki , Ayukawa Koichi , Hattori Kana , Nishida Toshirou
Published: June 2024

Background

Regorafenib improves overall survival (OS) of patients with advanced progressive gastrointestinal stromal tumors (GISTs) after standard chemotherapy in phase III trials in the 3rd-line setting. This large-scale, prospective observational study evaluated the safety and effectiveness of regorafenib in Japanese patients with GIST in a real-world clinical setting.

Methods

Patients with GIST received oral regorafenib at a maximum daily dose of 160 mg for weeks 1–3 of each 4-week cycle (dose could be modified at investigator’s discretion). The primary objective was to assess safety, particularly significant adverse drug reactions (ADRs), as well as the frequency of occurrence of ADRs, hand and foot syndrome (HFS), discontinuation of treatment due to disease progression and adverse events. A Cox proportional hazards model was used to evaluate associations between OS or time to treatment failure (TTF) and baseline characteristics or HFS.

Results

Between August 2013 and March 2021, 143 evaluable patients were enrolled. ADRs occurred in 90.2% of patients and led to treatment discontinuation in 28.3%. The most frequent ADRs were HFS, hypertension, and liver injury. The overall response rate was 11.3% and disease control rate 56.5% (RECIST) based on investigators’ assessments. Median OS was 17.4 months (95% CI 14.24–23.68). Median TTF was 5.3 (95% CI 4.0–6.5) months. Improved OS and TTF responses occurred in patients with an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1.

Conclusion

The outcomes in this real-world study were consistent with those seen in clinical trials. No new safety concerns were identified.

Clinical trial registration

https://clinicaltrials.gov, identifier NCT01933958.
Impact of weekly iron-folic acid supplementation on nutritional status and parasitic reinfection among school-age children and adolescents in Sub-Saharan Africa: a systematic review and meta-analysis
Authors: Kedir Shemsu , Abate Kalkidan Hassen , Mohammed Bekri , Abafita Jemal , Ademe Beyene Wondafrash
Published: June 2024

Background

Two significant etiological factors contributing to iron deficiency anemia, and undernutrition posing substantial public health challenges in Sub-Saharan Africa, are soil-transmitted helminths and malaria. This study carried out the effect of weekly iron-folic acid supplementation (WIFAS) on the nutrition and general health of school-age children and adolescents in Sub-Saharan Africa, a systematic review and meta-analysis have been conducted.

Methods

To find pertinent publications for this study, a thorough search was carried out on May 20, 2023, across five databases: Pubmed (MEDLINE), Web of Science, Scopus, Cochrane Library, and Google Scholar. In addition, a search was conducted on August 23, 2023, to capture any new records. The inclusion criteria for the studies were based on school-age children and adolescent populations, randomized controlled trials, and investigations into the effects of WIFAS. The outcomes of interest were measured through anthropometric changes, malaria, and helminthic reinfection.

Results

A systematic review of 11 articles revealed that WIFAS significantly decreased the risk of schistosomiasis reinfection by 21% among adolescents (risk ratio = 0.79, 95%CI: 0.66, 0.97; heterogeneity I2 = 0.00%, P = 0.02). However, no significant impact was observed on the risk of malaria reinfection (risk ratio = 1.02, 95%CI: 0.92, 1.13; heterogeneity I2 = 0.00%, P = 0.67) or A. Lumbricoides reinfection (risk ratio = 0.95, 95%CI: 0.75, 1.19; heterogeneity I2 = 0.00%, P = 0.65). Moreover, the analysis demonstrated that there is no significant effect of iron-folic acid supplementation in measured height and height for age Z-score (HAZ) of the school-age children (Hedge's g −0.05, 95%CI: −0.3, 0.2; test for heterogeneity I2 = 0.00%, P = 0.7) and (Hedge's g 0.12, 95%CI: −0.13, 0.37; test for heterogeneity I2 = 0.00%, P = 0.36) respectively.

Conclusion

The effectiveness of WIFAS in reducing the risk of schistosomiasis reinfection in adolescents has been demonstrated to be greater than that of a placebo or no intervention. Additionally, the narrative synthesis of iron-folic acid supplementation has emerged as a potential public health intervention for promoting weight change. However, there was no significant association between WIFAS and Ascariasis, trichuriasis, and hookworm. Moreover, the certainty of the evidence for the effects of WIFAS on height and malaria is low and therefore inconclusive. Whereas, the certainty of the evidence for the effectiveness of WIFAS on Schistosomiasis is moderate. Even though the mechanisms need further research WIFAS may be implemented as part of a comprehensive public health strategy to address schistosomiasis in adolescents.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023397898, PROSPERO (CRD42023397898).
Structural analysis and blood-enriching effects comparison based on biological potency of Angelica sinensis polysaccharides
Authors: Tian Yunxia , Shen Xiaorui , Hu Tingting , Liang Ziyu , Ding Yu , Dai Huilian , Liu Xinyuan , Lu Tulin , Yin Fangzhou , Shu Yachun , Guo Zhijun , Su Lianlin , Li Lin
Published: June 2024

Angelica sinensis is a long-standing medicine used by Chinese medical practitioners and well-known for its blood-tonic and blood-activating effects. Ferulic acid, ligustilide, and eugenol in Angelica sinensis activate the blood circulation; however, the material basis of their blood-tonic effects needs to be further investigated. In this study, five homogeneous Angelica sinensis polysaccharides were isolated, and their sugar content, molecular weight, monosaccharide composition, and infrared characteristics determined. Acetylphenylhydrazine (APH) and cyclophosphamide (CTX) were used as inducers to establish a blood deficiency model in mice, and organ indices, haematological and biochemical parameters were measured in mice. Results of in vivo hematopoietic activity showed that Angelica sinensis polysaccharide (APS) could elevate erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), and interleukin-3 (IL-3) serum levels, reduce tumor necrosis factor-α (TNF-α) level in mice, and promote hematopoiesis in the body by regulating cytokine levels. Biological potency test results of the in vitro blood supplementation indicated strongest tonic activity for APS-H2O, and APS-0.4 has the weakest haemopoietic activity. The structures of APS-H2O and APS-0.4 were characterized, and the results showed that APS-H2O is an arabinogalactan glycan with a main chain consisting of α-1,3,5-Ara(f), α-1,5- Ara(f), β-1,4-Gal(p), and β-1,4-Gal(p)A, and two branched chains of β-t-Gal(p) and α-t-Glc(p) connected to each other in a (1→3) linkage to α-1,3,5-Ara(f) on the main chain. APS-0.4 is an acidic polysaccharide with galacturonic acid as the main chain, consisting of α-1,4-GalA, α-1,2-GalA, α-1,4-Gal, and β-1,4-Rha. In conclusion, APS-H2O can be used as a potential drug for blood replenishment in patients with blood deficiency, providing a basis for APS application in clinical treatment and health foods, as well as research and development of new polysaccharide-based drugs.
Anti-angiogenic and antioxidant effects of axitinib in human retinal endothelial cells: implications in diabetic retinopathy
Authors: Lazzara Francesca , Conti Federica , Sasmal Pradip K. , Alikunju Shanavas , Rossi Settimio , Drago Filippo , Platania Chiara Bianca Maria , Bucolo Claudio
Published: June 2024

Diabetic retinopathy is a secondary microvascular complication of diabetes mellitus. This disease progresses from two stages, non-proliferative and proliferative diabetic retinopathy, the latter characterized by retinal abnormal angiogenesis. Pharmacological management of retinal angiogenesis employs expensive and invasive intravitreal injections of biologic drugs (anti-vascular endothelial growth factor agents). To search small molecules able to act as anti-angiogenic agents, we focused our study on axitinib, which is a tyrosine kinase inhibitor and represents the second line treatment for renal cell carcinoma. Axitinib is an inhibitor of vascular endothelial growth factor receptors, and among the others tyrosine kinase inhibitors (sunitinib and sorafenib) is the most selective towards vascular endothelial growth factor receptors 1 and 2. Besides the well-known anti-angiogenic and immune-modulatory functions, we hereby explored the polypharmacological profile of axitinib, through a bioinformatic/molecular modeling approach and in vitro models of diabetic retinopathy. We showed the anti-angiogenic activity of axitinib in two different in vitro models of diabetic retinopathy, by challenging retinal endothelial cells with high glucose concentration (fluctuating and non-fluctuating). We found that axitinib, along with inhibition of vascular endothelial growth factor receptors 1 (1.82 ± 0.10; 0.54 ± 0.13, phosphorylated protein levels in fluctuating high glucose vs. axitinib 1 µM, respectively) and vascular endothelial growth factor receptors 2 (2.38 ± 0.21; 0.98 ± 0.20, phosphorylated protein levels in fluctuating high glucose vs. axitinib 1 µM, respectively), was able to significantly reduce (p < 0.05) the expression of Nrf2 (1.43 ± 0.04; 0.85 ± 0.01, protein levels in fluctuating high glucose vs. axitinib 1 µM, respectively) in retinal endothelial cells exposed to high glucose, through predicted Keap1 interaction and activation of melanocortin receptor 1. Furthermore, axitinib treatment significantly (p < 0.05) decreased reactive oxygen species production (0.90 ± 0.10; 0.44 ± 0.06, fluorescence units in high glucose vs. axitinib 1 µM, respectively) and inhibited ERK pathway (1.64 ± 0.09; 0.73 ± 0.06, phosphorylated protein levels in fluctuating high glucose vs. axitinib 1 µM, respectively) in HRECs exposed to high glucose. The obtained results about the emerging polypharmacological profile support the hypothesis that axitinib could be a valid candidate to handle diabetic retinopathy, with ancillary mechanisms of action.
Overexpression of oHIOMT results in various morphological, anatomical, physiological and molecular changes in switchgrass
Authors: Huang Yanhua , Lai Xianzhi , Liu Changfa , Zhu Wentao , Hao Yongren , Zheng Zehui , Guo Kai
Published: June 2024

Introduction

Melatonin (N-acetyl-5-methoxytryptamine) is a molecule implicated in multiple biological functions, but exerts contrasting effects on plants owing to concentration differences. Hydroxyindole O-methyltransferase (HIOMT), which catalyzes the last step of melatonin synthesis, plays a crucial role in this context.

Methods

Transgenic switchgrass overexpressing oHIOMT with different melatonin levels displayed distinct morphological changes in a concentration-dependent manner. In this study, we divided the transgenic switchgrass into two groups: melatonin-moderate transgenic (MMT) plants and melatonin-rich transgenic (MRT) plants. To determine the concentration-dependent effect of melatonin on switchgrass growth and stress resistance, we conducted comparative morphological, physiological, omics and molecular analyses between MMT, MRT and wild-type (WT) plants.

Results

We found that oHIOMT overexpression, with moderate melatonin levels, was crucial in regulating switchgrass growth through changes in cell size rather than cell number. Moderate levels of melatonin were vital in regulating carbon fixation, stomatal development and chlorophyll metabolism. Regarding salt tolerance, melatonin with moderate levels activated numerous defense (e.g. morphological characteristics, anatomical structure, antioxidant enzymatic properties, non-enzymatic capacity and Na+/K+ homeostasis). Additionally, moderate levels of oHIOMT overexpression were sufficient to increase lignin content and alter monolignol compositions with an increase in the S/G lignin ratio.

Discussion

Taken together, oHIOMT overexpression in switchgrass with different melatonin levels resulted in morphological, anatomical, physiological and molecular changes in a concentration-dependent manner, which characterized by stimulation at low doses and inhibition at high doses. Our study presents new ideas and clues for further research on the mechanisms of the concentration-dependent effect of melatonin.
Combined transcriptome and widely targeted metabolome analysis reveals the potential mechanism of HupA biosynthesis and antioxidant activity in Huperzia serrata
Authors: Wu Hao , Shen Yu , Zou Fen , Yao Shiqing , Chen Yaling , Yang Huilin , Luo Xiangdong
Published: June 2024

Introduction

Huperzia serrata is a traditional Chinese herb that has gained much attention for its production of Huperzine A (HupA). HupA has shown promise on treating Alzheimer's disease (AD). However, the biosynthetic pathway and molecular mechanism of HupA in H. serrata are still not well understood.

Methods

Integrated transcriptome and metabolome analysis was performed to reveal the molecular mechanisms related to HupA biosynthesis and antioxidant activity in Huperzia serrata.

Results

HT (in vitro H. serrata thallus) exhibits higher antioxidant activity and lower cytotoxicity than WH (wild H. serrata). Through hierarchical clustering analysis and qRT-PCR verification, 7 important enzyme genes and 13 transcription factors (TFs) related to HupA biosynthesis were detected. Among them, the average |log2FC| value of CYP (Cytochrome P450) and CAO (Copper amine oxidase) was the largest. Metabolomic analysis identified 12 metabolites involved in the HupA biosynthesis and 29 metabolites related to antioxidant activity. KEGG co-enrichment analysis revealed that tropane, piperidine and pyridine alkaloid biosynthesis were involved in the HupA biosynthesis pathway. Furthermore, the phenylpropanoid, phenylalanine, and flavonoid biosynthesis pathway were found to regulate the antioxidant activity of H. serrata. The study also identified seven important genes related to the regulation of antioxidant activity, including PrAO (primary-amine oxidase). Based on the above joint analysis, the biosynthetic pathway of HupA and potential mechanisms of antioxidant in H. serrata was constructed.

Discussion

Through differential transcriptome and metabolome analysis, DEGs and DAMs involved in HupA biosynthesis and antioxidant-related were identified, and the potential metabolic pathway related to HupA biosynthesis and antioxidant in Huperzia serrata were constructed. This study would provide valuable insights into the HupA biosynthesis mechanism and the H. serrata thallus medicinal value.
Unskilled and unaware: second-order judgments increase with miscalibration for low performers
Authors: Coutinho Mariana Veiga Chetto , Thomas Justin , Fredricks-Lowman Imani , Alkaabi Shama , Couchman Justin J.
Published: June 2024

Overestimation and miscalibration increase with a decrease in performance. This finding has been attributed to a common factor: participants’ knowledge and skills about the task performed. Researchers proposed that the same knowledge and skills needed for performing well in a test are also required for accurately evaluating one’s performance. Thus, when people lack knowledge about a topic they are tested on, they perform poorly and do not know they did so. This is a compelling explanation for why low performers overestimate themselves, but such increases in overconfidence can also be due to statistical artifacts. Therefore, whether overestimation indicates lack of awareness is debatable, and additional studies are needed to clarify this issue. The present study addressed this problem by investigating the extent to which students at different levels of performance know that their self-estimates are biased. We asked 653 college students to estimate their performance in an exam and subsequently rate how confident they were that their self-estimates were accurate. The latter judgment is known as second-order judgments (SOJs) because it is a judgment of a metacognitive judgment. We then looked at whether miscalibration predicts SOJs per quartile. The findings showed that the relationship between miscalibration and SOJs was negative for high performers and positive for low performers. Specifically, for low performers, the less calibrated their self-estimates were the more confident they were in their accuracy. This finding supports the claim that awareness of what one knows and does not know depends in part on how much one knows.
Association between frailty and meaning in life of older adults in nursing home: the mediating effect of psychological resilience
Authors: Zhang Jiquan , Xu Fan , Zhou Yang , Wu Jijun , Li Yuxin , Qing Wei
Published: June 2024

Background

Meaning in life is a crucial aspect of psychological well-being, often overlooked despite its clinical significance. This warrants further investigation, especially regarding its relationship with frailty and psychological resilience.

Objective

This study aims to assess the status and relevance of frailty, psychological resilience, and meaning in life among older adults in Chinese nursing homes. Additionally, it explores the mediating role of psychological resilience between frailty and meaning in life, providing insights to improve the meaning in life for older adults in nursing homes.

Methods

Between August 2022 and November 2022, 302 older adults in Chinese nursing homes were selected using convenience sampling. The study utilized the Socio-demographic Characteristics Questionnaire, Tilburg Frailty Indicator, Connor-Davidson Resilience Scale, and the Source of Meaning Scale for Older Adults. A face-to-face questionnaire survey was conducted, and SPSS 27.0 was employed for analyzing correlations between frailty, psychological resilience, and meaning in life. The mediating effect of psychological resilience was assessed using Model 4 in the Process plug-in.

Results

Older adults in nursing homes exhibited a frailty total score of 4.00 (2.00, 5.00), with a prevalence of 28.5%. Psychological resilience scored 66.00 (51.75, 76.00), and meaning in life scored 149.00 (132.00, 158.25). Frailty showed a negative correlation with both meaning in life and psychological resilience, while meaning in life demonstrated a positive correlation with psychological resilience. Psychological resilience exhibited a partial mediating effect, accounting for 51.04% of the total effect between frailty and meaning in life.

Conclusion

Frailty incidence is high among older adults in nursing homes, with psychological resilience at a general level and meaning in life in the upper middle level. Psychological resilience plays a crucial role as a partial mediator between frailty and meaning in life. Timely assessment of frailty, targeted interventions, and improvements in psychological resilience are essential for enhancing the meaning in life and promoting successful aging.
Non-interpersonal traumatic events in patients with eating disorders: a systematic review
Authors: Johnsen Kirstine Marie , Nielsen Kirstine Franciska , Nilsson Kristine Kahr , Kjaersdam Telléus Gry
Published: June 2024

Objectives

The purpose of the systematic review was to synthesize literature on eating disorders (ED) and non-interpersonal traumatic events (NTE) and consolidate the reported prevalence of NTE in patients with an ED.

Methods

The literature search was performed in Embase, PsycInfo, and PubMed. The keywords in the search were “eating disorder,” “trauma” and “non-interpersonal,” using index-terms and free-search keywords related to NTE and ED. The PRISMA guidelines were followed. Relevant studies were screened using Rayyan.

Results

Of the 16 studies included in the quantitative synthesis, five overall types of NTE were identified: accidents, illness, injury, natural disaster and war. Findings provided tentative evidence for illness and injury being more prevalent in patients suffering from an ED compared to controls. The remaining subtypes of NTE did not show a higher prevalence in patients with an ED when compared to controls. Findings also suggest that those with binge/purge subtype of anorexia nervosa (AN) had a higher prevalence of non-interpersonal traumatic events compared to the restrictive subtype of AN.

Discussion

This systematic review provided a clear synthesis of previous findings related to NTE among patients with an ED. Noteworthy, is that many studies do not take into account if the trauma happened prior or after to ED onset, which may affect the association. Furthermore, the body of research on NTE in patients with ED is exceedingly limited, and more research is needed.