bluuebunny/crossref_metadata_2025 huggingface dataset:
Protocol for a scoping review of traditional medicine research methods, methodologies, frameworks and strategies
Authors: Ijaz Nadine , Hunter Jennifer , Grant Suzanne , Templeman Kate
Published: July 2024

Background

The World Health Organization (WHO) has called for the evidence-informed integration of traditional medicine (TM) into health systems. Research rigor requires a good “fit” between research designs and what is being studied. The expectation that TM research fully adheres to biomedical evidentiary norms potentially creates tensions, as TM paradigms have their own distinct features. A scoping review will be conducted to describe and characterize the research approaches used in TM and their paradigmatic alignment with the TM being studied.

Methods

This scoping review protocol was informed by Joanna Briggs Institute (JBI) methods. This protocol outlines an a priori conceptual framework, provisionally termed “paradigmatic alignment.” The review will include all populations, TM types, research approaches (i.e., methods, methodologies, frameworks, strategies), cultural contexts, and health care settings. Up to 38 English and non-English language databases will be searched sequentially for both published and gray literature until reaching data saturation across relevant concepts and contexts. Analysis will begin deductively, using a pre-piloted data extraction template to describe the TM research approaches. A basic qualitative content analysis of a sample of evidence sources will explore how research approaches are applied or modified to align with the TM therapeutic paradigm, and the manner in which they co-exist, contrast, complement or align with established biomedical research approaches. The findings will be narrated and summarized in charting tables and figures. The review will be reported according to the PRISMA scoping review extension. Consultative engagement with knowledge users across all review stages is planned.

Discussion

Aligned with the principle of Two-Eyed Seeing (Etuaptmumk), wherein Indigenous/traditional and biomedical knowledges may equitably co-exist, this review promises to advance scholarly insights of critical value in an increasingly pluralistic, globalized world.

Clinical trial registration: https://clinicaltrials.gov/, identifier INPLASY2023110071.
Coexistence of a novel NDM-1-encoding MDR plasmid and an IMP-4-encoding IncN-IncU hybrid plasmid in a clinical isolate of Citrobacter freundii BC73
Authors: Liu Na , Tang Biao , Wang Hui , Chen Xiangyang , Wen Peipei , Wang Zhaorui , Chen Xu , Guo Xiaobing , Gou Jianjun , Song Yinsen
Published: July 2024

Objectives

To investigate the genetic characteristics and transmission mechanism of the NDM-1-, IMP-4-, and SHV-12-producing multidrug-resistant (MDR) clinical isolate, Citrobacter freundii BC73.

Methods

C. freundii BC73 was isolated from a urine specimen of a urological patient diagnosed with bladder cancer at a Chinese teaching hospital. Antimicrobial susceptibility testing was carried out using DL-120E susceptibility cards and DL-96A system. Whole genome sequencing (WGS) of the isolate was performed using the Illumina and Oxford Nanopore platforms to analyze the genetic context of drug resistance genes and plasmid characteristics. The phylogenetic tree was constructed and visualized by KSNP3.0 software and iTOL5.0 online database.

Results

C. freundii isolate BC73 co-carrying blaNDM-1, blaIMP-4 and blaSHV-12 were multidrug-resistant. blaNDM-1 and blaIMP-4 were located on a novel IncFIB-like plasmid, pCFBC1, and an IncN-IncU hybrid plasmid, pCFBC2, respectively. The transferability of blaNDM-1 and blaIMP-4 from C. freundii BC73 to E. coli J53 was successfully demonstrated. The genetic context of the blaNDM-1 and blaIMP-4 genes were ISCR27-groEL-∆groES-cutA-dsbD-trpF-bleMBL-blaNDM-1-∆ISAba125-IS3000 and intI1-blaIMP-4-Kl.pn.13-mobC-IS6100, respectively. Additionally, two extensive transposition units (MGE1 in pCFBC1, MGE2 in pCFBC2) were identified and numerous antimicrobial resistance genes were discovered on it.

Conclusion

To our knowledge, our study represents the first characterization of a ST22 C. freundii isolate co-harboring blaNDM-1, blaIMP-4, and blaSHV-12, obtained from a urine sample. The dissemination of this MDR isolate should be of close concern in future clinical surveillance.
Gradient-free training of recurrent neural networks using random perturbations
Authors: Fernández Jesús García , Keemink Sander , van Gerven Marcel
Published: July 2024

Recurrent neural networks (RNNs) hold immense potential for computations due to their Turing completeness and sequential processing capabilities, yet existing methods for their training encounter efficiency challenges. Backpropagation through time (BPTT), the prevailing method, extends the backpropagation (BP) algorithm by unrolling the RNN over time. However, this approach suffers from significant drawbacks, including the need to interleave forward and backward phases and store exact gradient information. Furthermore, BPTT has been shown to struggle to propagate gradient information for long sequences, leading to vanishing gradients. An alternative strategy to using gradient-based methods like BPTT involves stochastically approximating gradients through perturbation-based methods. This learning approach is exceptionally simple, necessitating only forward passes in the network and a global reinforcement signal as feedback. Despite its simplicity, the random nature of its updates typically leads to inefficient optimization, limiting its effectiveness in training neural networks. In this study, we present a new approach to perturbation-based learning in RNNs whose performance is competitive with BPTT, while maintaining the inherent advantages over gradient-based learning. To this end, we extend the recently introduced activity-based node perturbation (ANP) method to operate in the time domain, leading to more efficient learning and generalization. We subsequently conduct a range of experiments to validate our approach. Our results show similar performance, convergence time and scalability when compared to BPTT, strongly outperforming standard node perturbation and weight perturbation methods. These findings suggest that perturbation-based learning methods offer a versatile alternative to gradient-based methods for training RNNs which can be ideally suited for neuromorphic computing applications.
Oral nutritional supplementation with dietary counseling improves linear catch-up growth and health outcomes in children with or at risk of undernutrition: a randomized controlled trial
Authors: Ow Mandy Y. L. , Tran Nga Thuy , Berde Yatin , Nguyen Tu Song , Tran Van Khanh , Jablonka Morgan J. , Baggs Geraldine E. , Huynh Dieu T. T.
Published: July 2024

Introduction

Childhood undernutrition is associated with increased morbidity, mortality and a high socio-economic burden.

Methods

Supporting Pediatric GRowth and Health OUTcomes (SPROUT) is a randomized, controlled trial evaluating the effects of an oral nutritional supplement (ONS) with dietary counseling (DC; n = 164) compared to a DC-only group who continued consuming their habitual milk (n = 166; NCT05239208). Children aged 24–60 months who were at risk or with undernutrition, as defined by weight-for-age [WAZ] < −1 and height-for-age [HAZ] < −1 according to the WHO Growth Standards, and who also met the criterion of weight-for-height [WHZ] < 0, were enrolled in Vietnam.

Results

ONS + DC had a larger WAZ increase at day 120 (primary endpoint) vs. DC (least squares mean, LSM (SE): 0.30 (0.02) vs. 0.13 (0.02); p < 0.001), and larger improvements in all weight, BMI and weight-for-height indices at day 30 and 120 (all p < 0.01). Height gain was larger in ONS + DC in all indices, including height-for-age difference [HAD; cm: 0.56 (0.07) vs. 0.10 (0.07); p < 0.001], at day 120. ONS + DC had larger arm muscle but not arm fat indices, higher parent-rated appetite, physical activity and energy levels, longer night sleep, fewer and shorter awakenings, and better sleep quality than DC.

Conclusion

Adding ONS to DC, compared to DC-alone, improves growth in weight and height, linear catch-up growth, and health outcomes in children with or at risk of undernutrition.
Storage effect on olive oil phenols: cultivar-specific responses
Authors: Vendrell Calatayud Mario , Li Xueqi , Brizzolara Stefano , Tonutti Pietro , Wang Selina C.
Published: July 2024

Introduction

Olive oil is a widely recognized and appreciated food commodity, its quality and health benefits can be compromised when the oil goes through oxidative processes that may occur during production and storage. This study aimed to investigate the effects of the olive genotype on polar phenolic content after seven months of storage.

Methods

Oil produced from eight different olive cultivars (Leccino, Leccio del Corno, Moraiolo, Frantoio, Bianchera, Pendolino, Maurino, and Caninese) grown in southern Tuscany, Italy, were subjected to chemical analysis such as free fatty acids, peroxide value, K232 and K268, phenolics and UPLC-DAD at the beginning of the trial (Control) and seven months later (Stored).

Results and Conclusions

Free fatty acids, peroxide values, K232 and K268, significantly increased, suggesting heightened hydrolysis and oxidation after storage. A cultivar effect was observed, with Leccino, Moraiolo, and Pendolino showing less susceptibility to oxidation (low differences between Control and Stored). In contrast, others (Bianchera and Caninese) are more affected (higher differences between Control and Stored). Phenolics analysis supports this observation, revealing that samples with higher resistance to oxidation exhibit elevated levels of hydroxytyrosol, tyrosol, vanillic acid, caffeic acid, p-coumaric acid, and ferulic acid. Principal Component Analysis highlights that Bianchera and Caninese cultivars correlate with rutin, tyrosol, and pinoresinol. As this research delves into the intricate relationship between genotype diversity, phenolic composition, and oxidative stability, a nuanced understanding emerges, shedding light on how different cultivars may present varying compositions and concentrations of phenols, ultimately influencing the oil’s resistance to the oxidation that occurred during storage.
Comparison of systemic treatments for previously treated patients with unresectable colorectal liver metastases: a systematic review and network meta-analysis
Authors: Jiang Yunlin , Zhao Mingye , Tang Wenxi , Zheng Xueping
Published: July 2024

Background

There is limited evidence of comparative results among different treatments for patients with unresectable colorectal liver metastases (CRLM) who have failed at least one line of previous systemic therapy. We aimed to compare the efficacy of systemic treatments among these patients through this investigation.

Methods

We collected randomized controlled trials (RCTs) reported in English up until July 2023, from databases including PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and prominent conference databases, for this Bayesian network meta-analysis. Phase II or III trials that evaluated at least two therapeutic regimens were included. Primary outcome was overall survival (OS), secondary outcome was progression-free survival (PFS). Hazards ratios (HRs) with 95% confidence intervals (CIs) were used as effect size. Subgroup analysis was performed based on metastatic sites. The current systematic review protocol was registered on PROSPERO (CRD42023420498).

Results

30 RCTs were included, with a total of 13,511 patients. Compared to chemotherapy, multi-targeted therapy (HR 0.57, 95% CI 0.37–0.87) and targeted therapy plus chemotherapy (HR 0.78, 95% CI 0.67–0.91) show significant advantages. Targeted therapy (HR 0.92, 95% CI 0.54–1.57) and local treatment plus chemotherapy (HR 1.03, 95% CI 0.85–1.23) had comparable performance. For patients with liver metastases, TAS-102 plus bevacizumab, aflibercept plus fluorouracil-based combination chemotherapy (CTFU), and bevacizumab plus capecitabine-based combination chemotherapy (CTCA) showed the best outcomes in terms of OS. Bevacizumab plus intensified CTFU, bevacizumab plus CTCA, and HAI followed by single-agent chemotherapy (SingleCT) performed the best regarding PFS. For patients with liver-limited metastases, aflibercept plus CTFU is the optimal choice in OS. For PFS, the best options were HAI followed by SingleCT, aflibercept plus CTFU, and panitumumab plus CTFU. For patients with multiple-site metastases, the best treatments were TAS-102 plus bevacizumab, bevacizumab plus CTCA, bevacizumab plus CTFU, and aflibercept plus CTFU.

Conclusion

Multi-targeted therapy and targeted therapy plus chemotherapy are the best treatment mechanisms. TAS-102 plus bevacizumab is superior in OS, the combination of anti-VEGF drugs like bevacizumab and aflibercept with standard chemotherapy is the preferred option for CRLM patients.
Exploring the mechanisms of Qingdu Fang for the treatment of cervical HR-HPV using UPLC-QTOF-MS, network pharmacology, and cell experimentation
Authors: Wang Shanyun , Li Guangru , Wang Zhuqiang , Luo Qing , Zeng Jianfeng , Xiao Jing
Published: July 2024

Background: Qingdu Fang (QDF) is a traditional Chinese herbal formula with remarkable clinical effect in the treatment of HR-HPV, but its mechanism remains unclear. In this study, UPLC-QTOF-MS was used to detect its components, network pharmacology was used to explore the traditional Chinese medicine monomers and their related targets for the treatment of HR-HPV in QDF. Molecular docking and in vitro experiments were performed to verify the results.

Methods: QDF constituents and active compounds were identified using UPLC-QTOF-MS analysis. TCMSP and GeneCard databases were used to identify active components, targets, and potential therapeutic targets in HR-HPV. PPI network was constructed using the String database to analyze protein-protein interactions. Cytoscape3.7.2 was used to construct PPI networks, while GO enrichment and KEGG pathway analyses with R. The effect of QDF on H8 cell proliferation was measured using the CCK-8 method, and apoptosis and cell cycle was assessed with flow cytometry. The effects of QDF on PI3K/AKT pathway were detected by Western blotting.

Results: A total of 27 compounds were identified on QDF by UPLC-QTOF-MS. Base on Network pharmacology,a total of 254 target genes are involved in the action of QDF on cervical HR-HPV. PPI analysis suggested that TP53, JUN, AKT1, STAT3, TNF and IL6 were potential targets for QDF treatment of HR-HPV. Molecular docking shows that two compounds have strong binding activity with AKT1. CCK-8 and morphological observation have shown that QDF inhibits H8 cell proliferation in a dose-dependent manner. Flow cytometry experiments suggest that QDF induces apoptosis and cell cycle arrest in H8 cells. Western blotting experiments reveal that QDF inhibits the PI3K/AKT signaling pathway.

Conclusion: QDF has a multi-faceted therapeutic approach for HR-HPV, targeting inflammation, oxidation, and apoptosis. It induces apoptosis in H8 cells by inhibiting the PI3K/AKT pathway.
Saponin components in Polygala tenuifolia as potential candidate drugs for treating dementia
Authors: Li Songzhe , Hou Zhitao , Ye Ting , Song Xiaochen , Hu Xinying , Chen Jing
Published: July 2024

Objective

This study aims to elucidate the intervention effects of saponin components from Polygala tenuifolia Willd (Polygalaceae) on dementia, providing experimental evidence and new insights for the research and application of saponins in the field of dementia.

Materials and Methods

This review is based on a search of the PubMed, NCBI, and Google Scholar databases from their inception to 13 May 2024, using terms such as “P. tenuifolia,” “P. tenuifolia and saponins,” “toxicity,” “dementia,” “Alzheimer’s disease,” “Parkinson’s disease dementia,” and “vascular dementia.” The article summarizes the saponin components of P. tenuifolia, including tenuigenin, tenuifolin, polygalasaponins XXXII, and onjisaponin B, as well as the pathophysiological mechanisms of dementia. Importantly, it highlights the potential mechanisms by which the active components of P. tenuifolia prevent and treat diseases and relevant clinical studies.

Results

The saponin components of P. tenuifolia can reduce β-amyloid accumulation, exhibit antioxidant effects, regulate neurotransmitters, improve synaptic function, possess anti-inflammatory properties, inhibit neuronal apoptosis, and modulate autophagy. Therefore, P. tenuifolia may play a role in the prevention and treatment of dementia.

Conclusion

The saponin components of P. tenuifolia have shown certain therapeutic effects on dementia. They can prevent and treat dementia through various mechanisms.
Pharmacokinetic study of Q808 in rhesus monkey using liquid chromatography–tandem mass spectrometry
Authors: Xiao Ning , Li Xiang , Li Wei , Zhao Jialin , Li Yingnan , Wang Limei
Published: July 2024

Background

Q808 is a novel antiepileptic agent currently in development. In this study, we established and validated a LC-MS/MS method for the quantification of Q808 in Rhesus monkey plasma. Furthermore, we applied this method to investigate the pharmacokinetics of Q808 in Rhesus monkeys.

Methods

Samples containing diazepam as an internal standard (IS) were subjected to liquid-liquid extraction (LLE) and separated using a Zorbax Extend C18 column. The detection of Q808 and IS was performed using multiple reaction monitoring mode (MRM), specifically monitoring precursor-to-product ion transitions at m/z 297.9 to 213.9 and m/z 285.2 to 193.1 for Q808 and IS, respectively. For the pharmacokinetic study of Q808, a total of 30 healthy Rhesus monkeys (half male and half female) were administered single oral doses, single IV doses, or multiple oral doses of Q808. Blood samples were collected at predetermined time points for subsequent pharmacokinetic analysis.

Results

The developed LC-MS/MS method exhibited linearity within the concentration range of 1.5–750 ng/mL with intra-day precision ≤8.3% and inter-day precision ≤14.6%. Additionally, accuracy was found to be ≤ 3.4%. In the pharmacokinetic study involving single oral doses of Q808 in Rhesus monkeys, Q808 was absorbed with a median time to peak plasma concentration ranging from 4.50–6.00 h and was eliminated with a terminal elimination half-life (t1/2) between 9.34–11.31 h. No definitive conclusion regarding linear pharmacokinetic characteristics could be drawn. The absolute bioavailability was determined as 20.95%, indicating limited systemic exposure after oral administration. Multiple dosing did not result in significant accumulation based on an accumulation factor Rac value of 1.31.

Conclusion

We have successfully developed and validated a rapid yet sensitive LC-MS/MS method for quantifying levels of Q808 in rhesus monkey plasma for the first time. The determination method and pharmacokinetic characteristics of Q808 in rhesus monkey support the next steps in drug development.
Body mass index is associated with pulmonary gas and blood distribution mismatch in COVID-19 acute respiratory failure. A physiological study
Authors: Bjarnadóttir Kristín J. , Perchiazzi Gaetano , Sidenbladh Caroline Lördal , Larina Aleksandra , Wallin Ewa , Larsson Ing-Marie , Franzén Stephanie , Larsson Anders O. , Sousa Mayson L. A. , Segelsjö Monica , Hansen Tomas , Frithiof Robert , Hultström Michael , Lipcsey Miklos , Pellegrini Mariangela
Published: July 2024

Background

The effects of obesity on pulmonary gas and blood distribution in patients with acute respiratory failure remain unknown. Dual-energy computed tomography (DECT) is a X-ray-based method used to study regional distribution of gas and blood within the lung. We hypothesized that 1) regional gas/blood mismatch can be quantified by DECT; 2) obesity influences the global and regional distribution of pulmonary gas and blood; 3) regardless of ventilation modality (invasive vs. non-invasive ventilation), patients’ body mass index (BMI) has an impact on pulmonary gas/blood mismatch.

Methods

This single-centre prospective observational study enrolled 118 hypoxic COVID-19 patients (92 male) in need of respiratory support and intensive care who underwent DECT. The cohort was divided into three groups according to BMI: 1. BMI<25 kg/m2 (non-obese), 2. BMI = 25–40 kg/m2 (overweight to obese), and 3. BMI>40 kg/m2 (morbidly obese). Gravitational analysis of Hounsfield unit distribution of gas and blood was derived from DECT and used to calculate regional gas/blood mismatch. A sensitivity analysis was performed to investigate the influence of the chosen ventilatory modality and BMI on gas/blood mismatch and adjust for other possible confounders (i.e., age and sex).

Results

1) Regional pulmonary distribution of gas and blood and their mismatch were quantified using DECT imaging. 2) The BMI>40 kg/m2 group had less hyperinflation in the non-dependent regions and more lung collapse in the dependent regions compared to the other BMI groups. In morbidly obese patients, gas and blood were more evenly distributed; therefore, the mismatch was lower than in other patients (30% vs. 36%, p < 0.05). 3) An increase in BMI of 5 kg/m2 was associated with a decrease in mismatch of 3.3% (CI: 3.67% to −2.93%, p < 0.05). Neither the ventilatory modality nor age and sex affected the gas/blood mismatch (p > 0.05).

Conclusion

1) In a hypoxic COVID-19 population needing intensive care, pulmonary gas/blood mismatch can be quantified at a global and regional level using DECT. 2) Obesity influences the global and regional distribution of gas and blood within the lung, and BMI>40 kg/m2 improves pulmonary gas/blood mismatch. 3) This is true regardless of the ventilatory mode and other possible confounders, i.e., age and sex.

Trial Registration

Clinicaltrials.gov, identifier NCT04316884, NCT04474249.
Multi-omics analysis of Populus simonii × P. nigra leaves under Hyphantria cunea stress
Authors: Jiang Jiahui , Fan Gaofeng , Wang Ruiqi , Yao Wenjing , Zhou Boru , Jiang Tingbo
Published: July 2024

Poplar is an important greening and timber tree species in China, which has great economic and ecological values. However, the spread of Hyphantria cunea has become increasingly serious in recent years, resulting in huge economic loss of poplar production. Exploring the molecular mechanism of poplar reponse to H. cunea stress has significant implications for future development of new insect-resistant poplar varieties using genetic engineering technology. In this study, a total of 1039 differentially expressed genes (DEGs), 106 differentially expressed proteins (DEPs) and 212 differentially expressed metabolites (DEMs) were screened from Populus simonii × P. nigra leaves under H. cunea stress by transcriptome, proteomics and metabolomics analysis, respectively. GO and KEGG analysis showed that the DEGs and DEPs are associated with endopeptidase inhibitor activity, stress response, α-linolenic acid metabolism, phenylpropanoid biosynthesis and metabolic pathways, cysteine and methionine metabolism pathways and MAKP signaling pathway. Metabolomics analysis showed the most of DEMs were lipids and lipid molecules, and the pathways associated with transcriptome mainly include plant hormone signal transduction, α-linolenic acid metabolic pathway, amino sugar and nucleotide sugar metabolism, and phenylpropanoid biosynthesis. In particular, multi-omics analysis showed that several pathways such as α-linolenic acid metabolic, phenylpropanoid biosynthesis and metabolic pathway and cysteine and methionine metabolic pathway were significantly enriched in the three omics, which may play an important role in the resistance to pests in poplar.
Expansions and contractions of repetitive DNA elements reveal contrasting evolutionary responses to the polyploid genome shock hypothesis in Brachypodium model grasses
Authors: Decena María Ángeles , Sancho Rubén , Inda Luis A. , Pérez-Collazos Ernesto , Catalán Pilar
Published: July 2024

Brachypodium grass species have been selected as model plants for functional genomics of grass crops, and to elucidate the origins of allopolyploidy and perenniality in monocots, due to their small genome sizes and feasibility of cultivation. However, genome sizes differ greatly between diploid or polyploid Brachypodium lineages. We have used genome skimming sequencing data to uncover the composition, abundance, and phylogenetic value of repetitive elements in 44 representatives of the major Brachypodium lineages and cytotypes. We also aimed to test the possible mechanisms and consequences of the “polyploid genome shock hypothesis” (PGSH) under three different evolutionary scenarios of variation in repeats and genome sizes of Brachypodium allopolyploids. Our data indicated that the proportion of the genome covered by the repeatome in the Brachypodium species showed a 3.3-fold difference between the highest content of B. mexicanum-4x (67.97%) and the lowest of B. stacei-2x (20.77%), and that changes in the sizes of their genomes were a consequence of gains or losses in their repeat elements. LTR-Retand and Tekay retrotransposons were the most frequent repeat elements in the Brachypodium genomes, while Ogre retrotransposons were found exclusively in B. mexicanum. The repeatome phylogenetic network showed a high topological congruence with plastome and nuclear rDNA and transcriptome trees, differentiating the ancestral outcore lineages from the recently evolved core-perennial lineages. The 5S rDNA graph topologies had a strong match with the ploidy levels and nature of the subgenomes of the Brachypodium polyploids. The core-perennial B. sylvaticum presents a large repeatome and characteristics of a potential post-polyploid diploidized origin. Our study evidenced that expansions and contractions in the repeatome were responsible for the three contrasting responses to the PGSH. The exacerbated genome expansion of the ancestral allotetraploid B. mexicanum was a consequence of chromosome–wide proliferation of TEs and not of WGD, the additive repeatome pattern of young allotetraploid B. hybridum of stabilized post-WGD genome evolution, and the genomecontraction of recent core-perennials polyploids (B. pinnatum, B. phoenicoides) of repeat losses through recombination of these highly hybridizing lineages. Our analyses have contributed to unraveling the evolution of the repeatome and the genome size variation in model Brachypodium grasses.
Decreased free D-aspartate levels in the blood serum of patients with schizophrenia
Authors: Garofalo Martina , De Simone Giuseppe , Motta Zoraide , Nuzzo Tommaso , De Grandis Elisa , Bruno Claudio , Boeri Silvia , Riccio Maria Pia , Pastore Lucio , Bravaccio Carmela , Iasevoli Felice , Salvatore Francesco , Pollegioni Loredano , Errico Francesco , de Bartolomeis Andrea , Usiello Alessandro
Published: July 2024

Introduction

Schizophrenia (SCZ) and autism spectrum disorder (ASD) are neurodevelopmental diseases characterized by different psychopathological manifestations and divergent clinical trajectories. Various alterations at glutamatergic synapses have been reported in both disorders, including abnormal NMDA and metabotropic receptor signaling.

Methods

We conducted a bicentric study to assess the blood serum levels of NMDA receptors-related glutamatergic amino acids and their precursors, including L-glutamate, L-glutamine, D-aspartate, L-aspartate, L-asparagine, D-serine, L-serine and glycine, in ASD, SCZ patients and their respective control subjects. Specifically, the SCZ patients were subdivided into treatment-resistant and non-treatment-resistant SCZ patients, based on their responsivity to conventional antipsychotics.

Results

D-serine and D-aspartate serum reductions were found in SCZ patients compared to controls. Conversely, no significant differences between cases and controls were found in amino acid concentrations in the two ASD cohorts analyzed.

Discussion

This result further encourages future research to evaluate the predictive role of selected D-amino acids as peripheral markers for SCZ pathophysiology and diagnosis.
Will urban scale affect health services inequity? The empirical evidence from cities in China
Authors: Wang Hongchuan , Xu Kaibo , Fang Handong , Lin Hui , Zeng Huatang
Published: July 2024

Background

The equity of public resources triggered by city shrinkage is a global challenge. Significantly, the impact of city shrinkage on the allocation of health service resources needs to be better understood. This study explores the impact of population change on government investment and health service delivery in shrinking cities.

Data and method

Using data from China’s Urban Statistical Yearbook (2010–2020), we employ regression discontinuity (RD) and fixed-effect models to examine the causal relationship between city shrinkage and health service provision.

Result

Shrinking cities show significant disparities in health resources, particularly in bed numbers (−1,167.58, p < 0.05) and doctor availability (−538.54, p < 0.05). Economic development (p < 0.01) and financial autonomy (p < 0.01) influence hospital bed distribution. Investments in public services (primary schools and teachers, p < 0.01) affect health resource delivery. Robustness tests support our results.

Conclusion

This study reveals how city shrinkage disrupts health service provision and equity, establishing a causal relationship between city shrinkage/expansion and health resource allocation, emphasizing the imbalance caused by urban population changes. City expansion intensifies competition for health resources, while shrinking cities struggle to provide adequate resources due to government reluctance. Policymakers should adapt health resource allocation strategies to meet patient demands in changing urban landscapes.
Wrack N’ Roll: The Ecological Role of Beach Wrack
Authors: Dee Shannon , Beltran Leah , Billinghurst Jessica , Lavery Paul S. , Serrano Gras Oscar , Whale John W. , Hyndes Glenn
Published: July 2024

Beach wrack is the stinky weed that gets washed up on the beach after a big storm. This weed is made up of old marine plants such as seaweeds and seagrasses, and it gets washed up onto beaches all over the world. Although it can be ugly and smell like rotten eggs, it is very important for the health of our beaches. Lots of tiny animals make their homes in beach wrack, while others feed on it or use it as a hunting ground for their favorite snacks. This feeding frenzy produces nutrients through animal poop and bones, which get delivered back into the water and help to keep our oceans healthy. Coastal development and beach cleaning upset these natural processes and can impact the ecosystems that make our beaches so great.
Aquatic food resources in tropical Africa: a comprehensive analysis
Authors: Okon Ekemini M. , Okocha Reuben C. , Folowosele Deborah O. , Oluwafemi Precious T. , Falana Babatunde M.
Published: July 2024

Aquatic food production holds great promise as a viable solution to tackle the pressing issue of meeting the protein requirements of the African populace. It plays a crucial role in food security and economic growth, especially in tropical Africa. With a fast-expanding population, there is a growing need for aquatic food sources to provide inexpensive protein and essential nutrients. Despite Africa’s vast aquatic food source supplies and the importance of aquatic food in healthy and sustainable diets, several challenges hinder its full exploitation in the tropical African environment. This study, therefore, aims to assess the existing state of aquatic food resources in Africa, examine the nutritional advantages associated with these foods, and identify the problems that hinder their maximal utilization. The findings highlight the differences in aquatic protein consumption across various countries, emphasizing the importance of considering local factors when formulating nutritional interventions and policies. The comparison between the supply of protein from aquatic sources and land animals across African nations revealed a consistent trend of lower availability of aquatic protein. Africa, in particular, had relatively lower per capita consumption values of animal protein. The continent’s average quantity of land animal food significantly surpassed the average aquatic food supply. This suggests a predominant reliance on land animal sources in African countries to meet dietary protein needs. This finding holds significant importance for policymakers, nutritionists, and stakeholders, highlighting the need for targeted strategies to improve protein accessibility in African countries. Moreover, it calls for attention to address any existing imbalances between the utilization of land and aquatic protein sources in the region.
Causes of mortality in military working dog from traumatic injuries
Authors: Storer Amanda P. , Edwards Thomas H. , Rutter Christine R. , Young Grace E. , Mullaney Sara B.
Published: July 2024

Introduction

This study aimed to identify the pathophysiologic causes of death following traumatic injuries in military working dogs (MWDs) and determine the risk factors associated with mortality in MWD following traumatic injuries. The results of this study will allow for better targeting of interventions to ameliorate these pathophysiologic causes of death and inform research priorities directed at the pathophysiology that leads to the death of MWDs.

Methods

The final dataset for this study was compiled by using two previously established datasets. Based on review of available data and supplemental records (when available), MWDs in which a definitive cause of death could be determined were included in the study population. These MWDs were assigned a cause of death based on categories previously identified in studies evaluating service member casualties. A group of MWDs who survived their traumatic injury and had similar mechanisms of injury and types of injury to the deceased MWDs were included to allow for comparison and establishment of risk factors associated with MWD death. Variables collected included breed, age, sex, mechanism of injury, survival/non-survival, type of trauma, mechanism of injury, pathophysiology that led to death and pre-hospital care provided. Statistical analysis included Fishers exact test for categorical variables and univariable and multivariable logistic regression to identify factors associated with the MWD death.

Results

A total of 84 MWDs (33 non-survivors and 51 survivors) were included in this study. Of the 33 MWDs that died, 27 (81.8%) were noted to be dead on arrival. The pathophysiologic causes of death were found to be hemorrhage (45.5% [n = 15]), head trauma (21.2% [n = 7]), catastrophic tissue destruction (15.2% [n = 5]), pneumothorax (9.1% [n = 3]) and one (3% [n = 1]) of each of the following: septic shock, asphyxiation and burns. Military working dogs that did not receive non-DVM care were 3.55 times more likely to die than those that did receive non-DVM care (95% CI 1.03–12.27). The majority of MWDs died of their injuries before reaching veterinary care.

Discussion

To increase the survival of MWDs on the battlefield, further research should focus on developing new interventions and techniques to mitigate the effects of the pathophysiology noted to cause MWD death. Furthermore, given that care by a non-DVM was found to be associated with survival, the implementation of pre-hospital care and early resuscitation techniques should be a continued priority for those treating MWDs at both the point of injury and in the prehospital setting.
COVID-19 Vaccine in Lung and Liver Transplant Recipients Exceeds Expectations: An Italian Real-Life Experience on Immunogenicity and Clinical Efficacy of BNT162b2 Vaccine
Authors: Morlacchi Letizia Corinna , Alicandro Gianfranco , Uceda Renteria Sara , Zignani Nunzio , Giacomel Giovanni , Rossetti Valeria , Sagasta Michele , Citterio Gaia , Lombardi Andrea , Dibenedetto Clara , Antonelli Barbara , Rosso Lorenzo , Lampertico Pietro , Ceriotti Ferruccio , Blasi Francesco , Donato Maria Francesca
Published: July 2024

This study assessed humoral and T cell-mediated immune responses to the BNT162b2 vaccine in orthotopic liver transplant (OLT) and lung transplant (LUT) recipients who received three doses of the vaccine from March 2021 at our institution. Serum samples were collected 60 days post-second and third dose to quantify antibodies against the spike region of SARS-CoV-2 while whole blood samples were collected to analyze the SARS-CoV-2-specific T-cell response using an IFN-γ ELISpot assay. We enrolled 244 OLT and 120 LUT recipients. The third dose increased antibody titres in OLT recipients (from a median value of 131 after the second dose to 5523 IU/mL, p < 0.001) and LUT recipients (from 14.8 to 1729 IU/mL, p < 0.001). T-cell response also increased in OLT recipients (from 8.5 to 23 IFN-γ SFU per 250,000 PBMC, p < 0.001) and LUT recipients (from 8 to 15 IFN-γ SFU per 250,000 PBMC, p < 0.001). A total of 128 breakthrough infections were observed: two (0.8%) OLT recipients were hospitalized due to COVID-19 and one died (0.4%); among LUT recipients, seven were hospitalized (5.8%) and two patients died (1.7%). In conclusion, the three-dose schedule of the BNT162b2 vaccine elicited both humoral and T cell-mediated responses in solid organ transplant recipients. The risk of severe COVID-19 post-vaccination was low in this population.
Adaptive Fuzzy Fault-Tolerant Attitude Control for a Hypersonic Gliding Vehicle: A Policy-Iteration Approach
Authors: Liu Meijie , Hu Changhua , Pei Hong , Li Hongzeng , Hu Xiaoxiang
Published: July 2024

In this paper, adaptive fuzzy fault-tolerant control (AFFTC) for the attitude control system of a hypersonic gliding vehicle (HGV) experiencing an actuator fault is proposed. Actuator faults of the HGV are considered with respect to its actual structure and actuator characteristics. The HGV’s attitude system is firstly represented by a T–S fuzzy model, and then a normal T–S fuzzy controller is designed. A reinforcement learning (RL)-based policy iterative solution algorithm is proposed for the solving of the T-S fuzzy controller. Then, based on the normal T–S controller, a fuzzy FTC controller is proposed in which the control matrices can improve themselves according to the special fault. An integral reinforcement learning (IRL)-based solving algorithm is proposed to reduce the dependence of the design methods on the HGV model. Simulations on three different kinds of actuator faults show that the designed IRL-based FTC can ensure a reliable flight by the HGV.
Leveraging Cooperative Intent and Actuator Constraints for Safe Trajectory Planning of Autonomous Vehicles in Uncertain Traffic Scenarios
Authors: Zhu Yuquan , Lv Juntong , Liu Qingchao
Published: July 2024

This study explores the integration of dynamic vehicle trajectories, vehicle safety factors, static traffic environments, and actuator constraints to improve cooperative intent modeling for autonomous vehicles (AVs) navigating uncertain traffic scenarios. Existing models often focus solely on interactions between dynamic trajectories, limiting their ability to fully interpret the intentions of surrounding vehicles. To address this limitation, we present a more comprehensive approach using the Cooperative Intent Multi-Layer Graph Neural Network (CMGNN) model. The CMGNN analyzes not only the dynamic trajectories but also the lane position relationships, vehicle angle changes, and actuator constraints and performs group interaction analysis. This richer information allows the CMGNN to more accurately capture the cooperative intent and better understand the surrounding vehicle behavior. This study investigated the impact of the CMGNN in the Carla simulator on surrounding vehicle trajectory prediction and AV safe trajectory planning. An innovative mechanism for dynamic trajectory risk assessment is introduced, which takes into account the constraints of the actuators when evaluating trajectory planning metrics. The results show that incorporating cooperative intent and considering the actuator limitations enhanced the CMGNN’s safety and driving efficiency in uncertain scenarios, significantly reducing the probability of AVs colliding. This is achieved as the model dynamically adapts its driving strategy based on the real-time traffic conditions, the perceived intentions of the surrounding vehicles, and the physical constraints of the vehicle actuators.
Space-Based Passive Orbital Maneuver Detection Algorithm for High-Altitude Situational Awareness
Authors: Yang Shihang , Jin Xin , Gong Baichun , Han Fei
Published: July 2024

Orbital maneuver detection for non-cooperative targets in space is a key task in space situational awareness. This study develops a passive maneuver detection algorithm using line-of-sight angles measured by a space-based optical sensor, especially for targets in high-altitude orbit. Emphasis is placed on constructing a new characterization for maneuvers as well as the corresponding detection method. First, the concept of relative angular momentum is introduced to characterize the orbital maneuver of the target quantitatively, and the sensitivity of the proposed characterization is analyzed mathematically. Second, a maneuver detection algorithm based on the new characterization is designed in which sliding windows and correlations are utilized to determine the mutation of the maneuver characterization. Subsequently, a numerical simulation system composed of error models, reference missions and trajectories, and computation models for estimating errors is established. Then, the proposed algorithm is verified through numerical simulations for both long-range and close-range targets. The results indicate that the proposed algorithm is effective. Additionally, the sensitivity of the proposed algorithm to the width of the sliding window, accuracy of the optical sensor, magnitude and number of maneuvers, and different relative orbit types is analyzed, and the sensitivity of the new characterization is verified using simulations.
Development of Scenarios as Problem-Space Descriptions in Aerospace Conceptual Design
Authors: Kindström Andersson Karl , Andersson Kent E.
Published: July 2024

In the defense and security domain, scenarios are often descriptions of stakeholder needs, future events, and the environment. They are used for the elicitation of requirements in development of capabilities, organizations, and technical systems. In the conceptual design of aerospace applications, models of scenarios can also represent and communicate a problem-space, enabling trade-space exploration and system effectiveness robustness analysis, which provide valuable input to decision-makers. This study utilizes design science to develop a scenario framework for solution-agnostic representations of a problem-space for use in aerospace conceptual design- and trade-space exploration. A scenario ontology is developed, describing the constituent concepts of scenarios and their relationships, followed by a method for creating scenarios and evaluating their validity. Within the EU project COLOSSUS, it is demonstrated that the scenario framework has utility both for market-pull and technology-push conceptual design. Establishing an ontology for scenarios and a method for creating them as well as evaluating their validity is another step in improving the aerospace conceptual design phase.
Design of Entire-Flight Pinpoint Return Trajectory for Lunar DRO via Deep Neural Network
Authors: Huang Xuxing , Ding Baihui , Yang Bin , Xie Renyuan , Guo Zhengyong , Sha Jin , Li Shuang
Published: July 2024

Lunar DRO pinpoint return is the final stage of manned deep space exploration via a lunar DRO station. A re-entry capsule suffers from complicated dynamic and thermal effects during an entire flight. The optimization of the lunar DRO return trajectory exhibits strong non-linearity. To obtain a global optimal return trajectory, an entire-flight lunar DRO pinpoint return model including a Moon–Earth transfer stage and an Earth atmosphere re-entry stage is constructed. A re-entry point on the atmosphere boundary is introduced to connect these two stages. Then, an entire-flight global optimization framework for lunar DRO pinpoint return is developed. The design of the entire-flight return trajectory is simplified as the optimization of the re-entry point. Moreover, to further improve the design efficiency, a rapid landing point prediction method for the Earth re-entry is developed based on a deep neural network. This predicting network maps the re-entry point in the atmosphere and the landing point on Earth with respect to optimal control re-entry trajectories. Numerical simulations validate the optimization accuracy and efficiency of the proposed methods. The entire-flight return trajectory achieves a high accuracy of the landing point and low fuel consumption.
Crop Diversification and Fertilization Strategies in a Rainfed System with Drought Periods
Authors: Bosch-Serra Angela D. , Ortiz Carlos , Molina María Gabriela , Shakoor Awais , Parra-Huertas Bárbara
Published: July 2024

Crop diversification and the reduction of nitrogen (N) inputs are key issues in the EU for more sustainable agriculture. An experiment was set up in a semiarid rainfed Mediterranean system. Our hypothesis was that these challenges could be addressed by introducing new crops and using pig slurries (PSs). The experimental factors were N fertilization at sowing (with or without PS) combined (according to a split-block design) with N fertilization as topdressing (the control, two N mineral rates, and two N rates from PS). Barley, rapeseed, and pea performances were evaluated in two different crop sequences: (i) barley–rapeseed or rapeseed–barley after a fallow season, and (ii) barley–pea or pea–barley after a fallow season followed by a non-fertilized barley crop. The results of the four-year study demonstrated that under a spring drought risk, barley performed better than peas in terms of relative crop yield maintenance. After fallow, N can be saved while maintaining the yields and total biomass of barley and rapeseed. In the second crop sequence, maximum pea and barley yields were associated with a minimum topdressing of 60 or 120 kg mineral N ha−1, respectively. However, slurry fertilization at sowing also allowed the highest yields for barley. Rapeseed and peas can be introduced to reduce N fertilization inputs. However, the obtained yield plateau for pea and rapeseed (3 and 4 Mg ha−1, respectively) and the effect of a yield spring drought on pea yields (50% reduction) might be a constraint for the success of EU policies on crop diversification.