bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction by artificial intelligence and immunovalidation of hypoallergenic mite allergen Der f 36 vaccine
Authors: Qin Qiao-Zhi , Tang Jian , Wang Cai-Yun , Xu Zhi-Qiang , Tian Man
Published: March 2024

Background

The house dust mite (HDM) is widely recognized as the most prevalent allergen in allergic diseases. Allergen-specific immunotherapy (AIT) has been successfully implemented in clinical treatment for HDM. Hypoallergenic B-cell epitope-based vaccine designed by artificial intelligence (AI) represents a significant progression of recombinant hypoallergenic allergen derivatives.

Method

The three-dimensional protein structure of Der f 36 was constructed using Alphafold2. AI-based tools were employed to predict B-cell epitopes, which were subsequently verified through IgE-reaction testing. Hypoallergenic Der f 36 was then synthesized, expressed, and purified. The reduced allergenicity was assessed by enzyme-linked immunosorbent assay (ELISA), immunoblotting, and basophil activation test. T-cell response to hypoallergenic Der f 36 and Der f 36 was evaluated based on cytokine expression in the peripheral blood mononuclear cells (PBMCs) of patients. The immunogenicity was evaluated and compared through rabbit immunization with hypoallergenic Der f 36 and Der f 36, respectively. The inhibitory effect of the blocking IgG antibody on the specific IgE-binding activity and basophil activation of Der f 36 allergen was also examined.

Results

The final selected non-allergic B-cell epitopes were 25–48, 57–67, 107–112, 142–151, and 176–184. Hypoallergenic Der f 36 showed significant reduction in IgE-binding activity. The competitive inhibition of IgE-binding to Der f 36 was investigated using the hypoallergenic Der f 36, and only 20% inhibition could be achieved, which is greatly reduced when compared with inhibition by Der f 36 (98%). The hypoallergenic Der f 36 exhibited a low basophil-stimulating ratio similar to that of the negative control, and it could induce an increasing level of IFN‐γ but not Th2 cytokines IL-5 and IL-13 in PBMCs. The vaccine-specific rabbit blocking IgG antibodies could inhibit the patients’ IgE binding and basophil stimulation activity of Derf 36.

Conclusion

This study represents the first application of an AI strategy to facilitate the development of a B-cell epitope-based hypoallergenic Der f 36 vaccine, which may become a promising immunotherapy for HDM-allergic patients due to its reduced allergenicity and its high immunogenicity in inducing blocking of IgG.
Elucidating the changes in the heterogeneity and function of radiation-induced cardiac macrophages using single-cell RNA sequencing
Authors: Cao Chunxiang , Wu Ran , Wang Shubei , Zhuang Lingfang , Chen Peizhan , Li Shuyan , Zhu Qian , Li Huan , Lin Yingying , Li Min , Cao Lu , Chen Jiayi
Published: March 2024

Purpose

A mouse model of irradiation (IR)-induced heart injury was established to investigate the early changes in cardiac function after radiation and the role of cardiac macrophages in this process.

Methods

Cardiac function was evaluated by heart-to-tibia ratio, lung-to-heart ratio and echocardiography. Immunofluorescence staining and flow cytometry analysis were used to evaluate the changes of macrophages in the heart. Immune cells from heart tissues were sorted by magnetic beads for single-cell RNA sequencing, and the subsets of macrophages were identified and analyzed. Trajectory analysis was used to explore the differentiation relationship of each macrophage subset. The differentially expressed genes (DEGs) were compared, and the related enriched pathways were identified. Single-cell regulatory network inference and clustering (SCENIC) analysis was performed to identify the potential transcription factors (TFs) which participated in this process.

Results

Cardiac function temporarily decreased on Day 7 and returned to normal level on Day 35, accompanied by macrophages decreased and increased respectively. Then, we identified 7 clusters of macrophages by single-cell RNA sequencing and found two kinds of stage specific macrophages: senescence-associated macrophage (Cdkn1ahighC5ar1high) on Day 7 and interferon-associated macrophage (Ccr2highIsg15high) on Day 35. Moreover, we observed cardiac macrophages polarized over these two-time points based on M1/M2 and CCR2/major histocompatibility complex II (MHCII) expression. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses suggested that macrophages on Day 7 were characterized by an inflammatory senescent phenotype with enhanced chemotaxis and inflammatory factors, while macrophages on Day 35 showed enhanced phagocytosis with reduced inflammation, which was associated with interferon-related pathways. SCENIC analysis showed AP-1 family members were associated with IR-induced macrophages changes.

Conclusion

We are the first study to characterize the diversity, features, and evolution of macrophages during the early stages in an IR-induced cardiac injury animal model.
Bispecific antibodies tethering innate receptors induce human tolerant-dendritic cells and regulatory T cells
Authors: Lamendour Lucille , Gilotin Mäelle , Deluce-Kakwata Nkor Nora , Lakhrif Zineb , Meley Daniel , Poupon Anne , Laboute Thibaut , di Tommaso Anne , Pin Jean-Jacques , Mulleman Denis , Le Mélédo Guillaume , Aubrey Nicolas , Watier Hervé , Velge-Roussel Florence
Published: March 2024

There is an urgent need for alternative therapies targeting human dendritic cells (DCs) that could reverse inflammatory syndromes in many autoimmune and inflammatory diseases and organ transplantations. Here, we describe a bispecific antibody (bsAb) strategy tethering two pathogen-recognition receptors at the surface of human DCs. This cross-linking switches DCs into a tolerant profile able to induce regulatory T-cell differentiation. The bsAbs, not parental Abs, induced interleukin 10 and transforming growth factor β1 secretion in monocyte-derived DCs and human peripheral blood mononuclear cells. In addition, they induced interleukin 10 secretion by synovial fluid cells in rheumatoid arthritis and gout patients. This concept of bsAb-induced tethering of surface pathogen-recognition receptors switching cell properties opens a new therapeutic avenue for controlling inflammation and restoring immune tolerance.
Cannabidiol exerts multitarget immunomodulatory effects on PBMCs from individuals with psoriasis vulgaris
Authors: Pagano Cristina , Ciaglia Elena , Coppola Laura , Lopardo Valentina , Raimondo Annunziata , Giuseppe Monfrecola , Lembo Serena , Laezza Chiara , Bifulco Maurizio
Published: March 2024

Introduction

The involvement of endocannabinoid system (ECS) in the inflammatory cascade, and the ability of phytocannabinoids, endocannabinoids and their synthetic analogues to modulate it has become an interesting research area for new therapeutic approaches in inflammatory skin diseases. Cannabidiol (CBD) appears to be the most promising among phytocannabinoids, due to the lack of psychotropic effects and low toxicity profile. Its anti-inflammatory action has been highlighted in different preclinical models, ranging from experimental colitis to arthritis and neuroinflammation. Our aim was to evaluate CBD immune-modulatory effects in peripheral blood mononuclear cells (PBMC) of psoriasis individuals with particular attention to both innate and adaptative immune arms.

Methods

We performed in vitro immune functional experiments to analyze CBD action on various immune cells active in psoriatic lesions.

Results

The results showed that CBD produced a shift from Th1 to Th2 response, while boosting cytotoxic activity of Natural Killer (NK) cells. Furthermore, it also exerted a potent action on monocyte differentiation as, after CBD treatment, monocytes from psoriatic individuals were unable to migrate in response to inflammatory stimuli and to fully differentiate into mature dendritic cells. Finally, a M2 skewing of monocyte-derived macrophages by CBD also contributed to the fine tuning of the magnitude of immune responses.

Conclusions

These data uncover new potential immunomodulatory properties of this cannabinoid suggesting a possible therapeutic action in the treatment of multiple inflammatory skin diseases.
Spanish–English bilingual heritage speakers processing of inanimate sentences
Authors: Casper Rachel , Aguirre-Muñoz Zenaida , Spivey Michael , Bortfeld Heather
Published: March 2024

This study investigated how heritage Spanish–English bilinguals integrate their cue hierarchies to process simple sentences in both Spanish and English. Sentence interpretation is achieved by weighing the various cues that are present in the sentence against that language's cue hierarchy. The Unified Competition Model (UCM) suggests that bilinguals show a variety of patterns in sentence interpretation strategies depending on language proficiency. Previous research on heritage Spanish–English bilinguals and late bilinguals has demonstrated differences in cue utilization and sentence interpretation compared to monolinguals. However, good-enough processing suggests that when a sentence does not meet certain heuristics, like the first-noun agent heuristic, a semantic representation of the sentence will be processed instead of a syntactic one. Even with reliable sentential-level cues such as word order, a plausible semantic representation of the sentence is favored. This is especially the case with inanimate–inanimate (IA-IA) sentences, like in the present study, in which there is less reversibility of thematic roles without competing with semantic plausibility. For this study, participants (n = 32) read a total of 80 inanimate sentences in English and Spanish with subject–verb–object and object–verb–subject (OVS) word orders, indicated the subject of the sentences, and completed language proficiency and dominance tasks. When reading Spanish sentences, participants read the OVS word order faster. English proficiency was a significant predictor of sentence reading time and choice selection time but did not predict word choice. The results suggest that IA-IA sentences pose challenges for cue utilization and thematic role assignment due to semantic limitations. This study found that participants may prioritize semantic plausibility over syntactic representations in sentence processing, supporting a good-enough processing model.
Vulnerability to fluctuations in prey and predation landscape in a central place foraging marine predator
Authors: Speakman Cassie N. , McHuron Elizabeth A. , Arnould John P. Y.
Published: March 2024

Introduction

Human-induced environmental change is driving a global redistribution of biodiversity, resulting in shifting prey and predation landscapes. These shifting landscapes can lead to changes in behavior, health, and vital rates, with potential implications for population dynamics.

Methods

In the present study, a state-dependent life-history theory model was developed to investigate the individual- and population-level responses of Australian fur seals (Arctocephalus pusillus doriferus) to changes in prey availability and at-sea mortality risk.

Results

Rates of pregnancy, pup nursing, and abortion were unaffected by prey availability in the simulated population. Likewise, on-land and at-sea durations were largely unaffected by prey availability, with more pronounced affects for nonreproductive and pregnant females than for lactating females. There was a strong influence of prey availability on the proportion of females that were concurrently pregnant and lactating, largely due to an increase in pup abandonments under low prey availability scenarios. This effect on pup abandonments also had flow on effects for pup recruitment. Increasing at-sea mortality risk resulted in greater offspring losses due to maternal death. The combined impact of prey availability and at-sea mortality risk on the number of simulated female offspring reaching sexual maturity was substantial.

Discussion

Consequently, our results suggest high vulnerability of the Australian fur seal population to shifting prey and predation landscapes. These results indicate a need for continued monitoring of Australian fur seal pup production and population dynamics in the face of rapid environmental change.
Analysis of hematological indicators via explainable artificial intelligence in the diagnosis of acute heart failure: a retrospective study
Authors: Yilmaz Rustem , Yagin Fatma Hilal , Colak Cemil , Toprak Kenan , Abdel Samee Nagwan , Mahmoud Noha F. , Alshahrani Amnah Ali
Published: March 2024

Introduction

Acute heart failure (AHF) is a serious medical problem that necessitates hospitalization and often results in death. Patients hospitalized in the emergency department (ED) should therefore receive an immediate diagnosis and treatment. Unfortunately, there is not yet a fast and accurate laboratory test for identifying AHF. The purpose of this research is to apply the principles of explainable artificial intelligence (XAI) to the analysis of hematological indicators for the diagnosis of AHF.

Methods

In this retrospective analysis, 425 patients with AHF and 430 healthy individuals served as assessments. Patients’ demographic and hematological information was analyzed to diagnose AHF. Important risk variables for AHF diagnosis were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) feature selection. To test the efficacy of the suggested prediction model, Extreme Gradient Boosting (XGBoost), a 10-fold cross-validation procedure was implemented. The area under the receiver operating characteristic curve (AUC), F1 score, Brier score, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) were all computed to evaluate the model’s efficacy. Permutation-based analysis and SHAP were used to assess the importance and influence of the model’s incorporated risk factors.

Results

White blood cell (WBC), monocytes, neutrophils, neutrophil-lymphocyte ratio (NLR), red cell distribution width-standard deviation (RDW-SD), RDW-coefficient of variation (RDW-CV), and platelet distribution width (PDW) values were significantly higher than the healthy group (p < 0.05). On the other hand, erythrocyte, hemoglobin, basophil, lymphocyte, mean platelet volume (MPV), platelet, hematocrit, mean erythrocyte hemoglobin (MCH), and procalcitonin (PCT) values were found to be significantly lower in AHF patients compared to healthy controls (p < 0.05). When XGBoost was used in conjunction with LASSO to diagnose AHF, the resulting model had an AUC of 87.9%, an F1 score of 87.4%, a Brier score of 0.036, and an F1 score of 87.4%. PDW, age, RDW-SD, and PLT were identified as the most crucial risk factors in differentiating AHF.

Conclusion

The results of this study showed that XAI combined with ML could successfully diagnose AHF. SHAP descriptions show that advanced age, low platelet count, high RDW-SD, and PDW are the primary hematological parameters for the diagnosis of AHF.
Phosphorus addition increases stability and complexity of co-occurrence network of soil microbes in an artificial Leymus chinensis grassland
Authors: Zhou Xiaoguo , Hu Yutong , Li Huijun , Sheng Jiandong , Cheng Junhui , Zhao Tingting , Zhang Yuanmei
Published: March 2024

Introduction

Understanding the response of cross-domain co-occurrence networks of soil microorganisms to phosphorus stability and the resulting impacts is critical in ecosystems, but the underlying mechanism is unclear in artificial grassland ecosystems.

Methods

In this study, the effects of four phosphorus concentrations, P0 (0 kg P ha−1), P1 (15.3 kg P ha−1), P2 (30.6 kg P ha−1), and P3 (45.9 kg P ha−1), on the cross-domain co-occurrence network of bacteria and fungi were investigated in an artificial Leymus chinensis grassland in an arid region.

Results and discussion

The results of the present study showed that phosphorus addition significantly altered the stem number, biomass and plant height of the Leymus chinensis but had no significant effect on the soil bacterial or fungal alpha (ACE) diversity or beta diversity. The phosphorus treatments all increased the cross-domain co-occurrence network edge, node, proportion of positively correlated edges, edge density, average degree, proximity to centrality, and robustness and increased the complexity and stability of the bacterial-fungal cross-domain co-occurrence network after 3 years of continuous phosphorus addition. Among them, fungi (Ascomycota, Basidiomycota, Mortierellomycota and Glomeromycota) play important roles as keystone species in the co-occurrence network, and they are significantly associated with soil AN, AK and EC. Finally, the growth of Leymus chinensis was mainly due to the influence of the soil phosphorus content and AN. This study revealed the factors affecting the growth of Leymus chinense in artificial grasslands in arid areas and provided a theoretical basis for the construction of artificial grasslands.
Biological control of the native endophytic fungus Pochonia chlamydosporia from the root nodule of Dolichos lablab on Fusarium wilt of banana TR4
Authors: Zhou Yunfan , Yang Limei , Xu Shengtao , Li Shu , Zeng Li , Shang Hui , Li Xundong , Fan Huacai , Zheng Si-Jun
Published: March 2024

Fusarium wilt of banana caused by Fusarium oxysporum f. sp. cubense, Tropical Race 4 (TR4) is a soil-borne disease, and it is devastating. At present, the biological control using antagonistic microorganisms to mitigate TR4 is one of the best strategies as a safe and green way. Yunnan has abundant and diverse microbial resources. Using the dual-culture method, the antagonistic endophytic fungi against TR4 were isolated and screened from the root nodule of Dolichos lablab. The effect of the highest antagonistic activity strain on the morphology of the TR4 mycelium was observed using the scanning electron microscope. According to morphological characteristics and sequence analysis, the strain was identified. The biocontrol effect and plant growth promotion were investigated by greenhouse pot experiment. Using the confocal laser scanning microscope and the real-time fluorescence quantitative PCR, the dynamics of TR4 infestation and the TR4 content in banana plant roots and corms would also be detected. In this study, 18 native endophytic fungi were isolated from a root nodule sample of Dolichos lablab in the mulch for banana fields in Yuxi, Yunnan Province, China. The YNF2217 strain showed a high antagonistic activity against TR4 in plate confrontation experiments, and the inhibition rate of YNF2217 is 77.63%. After TR4 culture with YNF2217 for 7 days in plate confrontation experiments, the morphology of the TR4 mycelium appeared deformed and swollen when observed under a scanning electron microscope. According to morphological characteristics and sequence analysis, the strain YNF2217 was identified as Pochonia chlamydosporia. In the greenhouse pot experiment, the biocontrol effect of YNF2217 fermentation solution on TR4 was 70.97% and 96.87% on banana plant leaves and corms, respectively. Furthermore, YNF2217 significantly promoted the growth of banana plants, such as plant height, leaf length, leaf width, leaf number, pseudostem girth, and both the aboveground and underground fresh weight. Observations of TR4 infestation dynamics in banana roots and corms, along with real-time fluorescence quantitative PCR, verified that YNF2217 inoculation could significantly reduce the TR4 content. Therefore, YNF2217 as P. chlamydosporia, which was found first time in China and reported here, is expected to be an important new fungal resource for the green control of Fusarium wilt of banana in the future.
Methionyl-tRNA synthetase synthetic and proofreading activities are determinants of antibiotic persistence
Authors: Wood Whitney N. , Rubio Miguel Angel , Leiva Lorenzo Eugenio , Phillips Gregory J. , Ibba Michael
Published: March 2024

Bacterial antibiotic persistence is a phenomenon where bacteria are exposed to an antibiotic and the majority of the population dies while a small subset enters a low metabolic, persistent, state and are able to survive. Once the antibiotic is removed the persistent population can resuscitate and continue growing. Several different molecular mechanisms and pathways have been implicated in this phenomenon. A common mechanism that may underly bacterial antibiotic persistence is perturbations in protein synthesis. To investigate this mechanism, we characterized four distinct metG mutants for their ability to increase antibiotic persistence. Two metG mutants encode changes near the catalytic site of MetRS and the other two mutants changes near the anticodon binding domain. Mutations in metG are of particular interest because MetRS is responsible for aminoacylation both initiator tRNAMet and elongator tRNAMet indicating that these mutants could impact translation initiation and/or translation elongation. We observed that all the metG mutants increased the level of antibiotic persistence as did reduced transcription levels of wild type metG. Although, the MetRS variants did not have an impact on MetRS activity itself, they did reduce translation rates. It was also observed that the MetRS variants affected the proofreading mechanism for homocysteine and that these mutants’ growth is hypersensitive to homocysteine. Taken together with previous findings, our data indicate that both reductions in cellular Met-tRNAMet synthetic capacity and reduced proofreading of homocysteine by MetRS variants are positive determinants for bacterial antibiotic persistence.
Evaluation of Adenanthera pavonina-derived compounds against diabetes mellitus: insight into the phytochemical analysis and in silico assays
Authors: Rahman Md. Sojiur , Hosen Md. Eram , Faruqe Md. Omar , Khalekuzzaman Md. , Islam Md. Asadul , Acharjee Uzzal Kumar , Bin Jardan Yousef A. , Nafidi Hiba-Allah , Mekonnen Amare Bitew , Bourhia Mohammed , Zaman Rashed
Published: March 2024

Adenanthera pavonina is a medicinal plant with numerous potential secondary metabolites showing a significant level of antidiabetic activity. The objective of the current study was to identify potential phytochemicals from the methanolic leaf extract of Adenanthera pavonina as therapeutic agents against diabetes mellitus using GC-MS and in silico methods. The GC-MS analysis of the leaf extract revealed a total of 17 phytochemicals. Molecular docking was performed using these phytochemicals, targeting the mutated insulin receptor tyrosine kinase (5hhw), which inhibits glucose uptake by cells. Diazoprogesterone (−9.2 kcal/mol), 2,4,4,7a-Tetramethyl-1-(3-oxobutyl)octahydro-1H-indene-2-carboxylic acid (−6.9 kcal/mol), and 2-Naphthalenemethanol, decahydro-.alpha.,.alpha.,4a-trimethyl-8-methylene-, [2R-(2.alpha.,4a.alpha.,8a.beta.)] (−6.6 kcal/mol) exhibited better binding with the target protein. The ADMET analysis was performed for the top three compounds with the best docking scores, which showed positive results with no observed toxicity in the AMES test. Furthermore, the molecular dynamics study confirmed the favorable binding of Diazoprogesterone, 2,4,4,7a-Tetramethyl-1-(3-oxobutyl)octahydro-1H-indene-2-carboxylic acid and 2-Naphthalenemethanol, decahydro-.alpha.,.alpha.,4a-trimethyl-8-methylene-, [2R-(2.alpha.,4a.alpha.,8a.beta.)] with the receptor throughout the 100 ns simulation period.
Two-sample Mendelian randomization analysis of 91 circulating inflammatory protein levels and amyotrophic lateral sclerosis
Authors: Xiao Chenxu , Gu Xiaochu , Feng Yu , Shen Jing
Published: March 2024

Introduction

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with poorly understood pathophysiology. Recent studies have highlighted systemic inflammation, especially the role of circulating inflammatory proteins, in ALS.

Methods

This study investigates the potential causal link between these proteins and ALS. We employed a two-sample Mendelian Randomization(MR) approach, analyzing data from large-scale genome-wide association studies to explore the relationship between 91 circulating inflammatory proteins and ALS. This included various MR methods like MR Egger, weighted median, and inverse-variance weighted, complemented by sensitivity analyses for robust results.

Results

Significant associations were observed between levels of inflammatory proteins, including Adenosine Deaminase, Interleukin-17C, Oncostatin-M, Leukemia Inhibitory Factor Receptor, and Osteoprotegerin, and ALS risk. Consistencies were noted across different P-value thresholds. Bidirectional MR suggested that ALS risk might influence levels of certain inflammatory proteins.

Discussion

Our findings, via MR analysis, indicate a potential causal relationship between circulating inflammatory proteins and ALS. This sheds new light on ALS pathophysiology and suggests possible therapeutic targets. Further research is required to confirm these results and understand the specific roles of these proteins in ALS.
Cardioid oscillator-based pattern generator for imitating the time-ratio-asymmetrical behavior of the lower limb exoskeleton
Authors: Fu Qiang , Luo Tianhong , Cui TingQiong , Ma Xiangyu , Liang Shuang , Huang Yi , Wang Shengxue
Published: March 2024

Introduction

Periodicity, self-excitation, and time ratio asymmetry are the fundamental characteristics of the human gait. In order to imitate these mentioned characteristics, a pattern generator with four degrees of freedom is proposed based on cardioid oscillators developed by the authors.

Method

The proposed pattern generator is composed of four coupled cardioid oscillators, which are self-excited and have asymmetric time ratios. These oscillators are connected with other oscillators through coupled factors. The dynamic behaviors of the proposed oscillators, such as phase locking, time ratio, and self-excitation, are analyzed via simulations by employing the harmonic balance method. Moreover, for comparison, the simulated trajectories are compared with the natural joint trajectories measured in experiments.

Results and discussion

Simulation and experimental results show that the behaviors of the proposed pattern generator are similar to those of the natural lower limb. It means the simulated trajectories from the generator are self-excited without any additional inputs and have asymmetric time ratios. Their phases are locked with others. Moreover, the proposed pattern generator can be applied as the reference model for the lower limb exoskeleton controlling algorithm to produce self-adjusted reference trajectories.
Polymyxin-induced neuromuscular weakness: a case report
Authors: Chin Amanda X. Y. , Ng Kay W. P. , Chan Yee Cheun , Goh Yihui , Rathakrishnan Rahul
Published: March 2024

Polymyxin-induced neuromuscular blockade is a rare but potentially fatal condition, with majority of cases that were reported between 1962 and 1973. We describe a patient who developed hypercapnic respiratory failure after initiation of polymyxin for multi-drug resistant Escherichia Coli bacteremia, due to polymyxin-induced neuromuscular dysfunction. After cessation of polymyxin, he regained full strength, had complete resolution of ptosis, and was successfully extubated. In light of the renewed use of polymyxin in this era of antimicrobial-resistance, this case aims to raise awareness about this rare but life-threatening condition, which is easily reversible with early recognition and prompt discontinuation of the drug.
Effects of microgravity on neural crest stem cells
Authors: Han Yilin , Barasa Povilas , Zeger Lukas , Salomonsson Sara B. , Zanotti Federica , Egli Marcel , Zavan Barbara , Trentini Martina , Florin Gunnar , Vaerneus Alf , Aldskogius Håkan , Fredriksson Robert , Kozlova Elena N.
Published: March 2024

Exposure to microgravity (μg) results in a range of systemic changes in the organism, but may also have beneficial cellular effects. In a previous study we detected increased proliferation capacity and upregulation of genes related to proliferation and survival in boundary cap neural crest stem cells (BC) after MASER14 sounding rocket flight compared to ground-based controls. However, whether these changes were due to μg or hypergravity was not clarified. In the current MASER15 experiment BCs were exposed simultaneously to μg and 1 g conditions provided by an onboard centrifuge. BCs exposed to μg displayed a markedly increased proliferation capacity compared to 1 g on board controls, and genetic analysis of BCs harvested 5 h after flight revealed an upregulation, specifically in μg-exposed BCs, of Zfp462 transcription factor, a key regulator of cell pluripotency and neuronal fate. This was associated with alterations in exosome microRNA content between μg and 1 g exposed MASER15 specimens. Since the specimens from MASER14 were obtained for analysis with 1 week’s delay, we examined whether gene expression and exosome content were different compared to the current MASER15 experiments, in which specimens were harvested 5 h after flight. The overall pattern of gene expression was different and Zfp462 expression was down-regulated in MASER14 BC μg compared to directly harvested specimens (MASER15). MicroRNA exosome content was markedly altered in medium harvested with delay compared to directly collected samples. In conclusion, our analysis indicates that even short exposure to μg alters gene expression, leading to increased BC capacity for proliferation and survival, lasting for a long time after μg exposure. With delayed harvest of specimens, a situation which may occur due to special post-flight circumstances, the exosome microRNA content is modified compared to fast specimen harvest, and the direct effects from μg exposure may be partially attenuated, whereas other effects can last for a long time after return to ground conditions.
Effect of pine bark extract and its phenolic compounds on selected pathogenic and probiotic bacterial strains
Authors: Sánchez-Moya Teresa , López-Nicolás Rubén , Peso-Echarri Patricia , González-Bermúdez Carlos A. , Frontela-Saseta Carmen
Published: March 2024

Introduction

Inflammatory bowel disease (IBD) comprises a heterogeneous group of chronic diseases as ulcerative colitis (UC) and Crohn’s disease (CD). IBD is the result of a dysregulation of intestinal homeostasis with a host’s loss of tolerance toward normal enteric microflora. Plant-based extracts as phenolic compounds can play a role by modulating the intestinal inflammation response.

Methods

The in vitro antimicrobial activity of French maritime pine bark extract (PBE) and its phenolic constituents has been investigated in this study. Furthermore, the ability of PBE and phenolic compounds (caffeic acid, chlorogenic acid, ferulic acid, gallic acid and taxifolin) to modulate the microbiota has been assessed.

Results

Phenolic compounds and PBE showed a great inhibitory effect on the pathogens growth at the highest concentration assessed (1.25 mg/mL). The growth of E. sakazakii and E. faecalis were affected by the effect of caffeic acid and ferulic acid. Taxifolin showed a very strong activity against Listeria sp. (with a reduction ~98%). Gallic acid revealed antibacterial effect on S. aureus at different concentrations. The inhibitory effect of PBE was highly significant on the growth of E. coli O157:H7. PBE, caffeic acid and chlorogenic acid seem to provide the greatest beneficial effect on the probiotic bacteria. However, the highest concentrations of taxifolin may have impaired the growth of beneficial microbiota.

Conclusion

Present findings could be of interest for considering PBE and/or its phenolic constituents as protectors against gastrointestinal disturbances which lead to ulcerative colitis and Crohn’s disease.
Strengths and weaknesses of food eco-labeling: a review
Authors: Tiboni-Oschilewski Ornella , Abarca Magdalena , Santa Rosa Pierre Fabiana , Rosi Alice , Biasini Beatrice , Menozzi Davide , Scazzina Francesca
Published: March 2024

Food labeling is increasingly expanding and adding more information to the food package. There is strong evidence about nutrition labeling effectiveness in driving food choice, especially if displayed in the front of package (FoP). Despite the growing attention to nutrition and sustainable diets, few countries have implemented sustainable labels or eco-labels that could address economic, social and/or environmental concerns. Implementing new techniques of eco-labeling emerges as a consumer-focused solution. However, evidence of the effectiveness of eco-labeling in driving consumers’ choices is heterogeneous and not univocal. Thus, this review aims to summarize the evidence about the effectiveness of FoP eco-labeling in driving food choice and provide a reference framework of the eco-labeling initiatives relative to food package labeling. This narrative review addresses both the potential benefits as well as the main concerns that arise from the use of eco-labels. Although eco-labeling seems to provide a series of sustainability benefits for producers and consumers, the implementation of such policies should take into consideration potential trade-offs and inter-sectorial coordination to obtain bigger impacts, assuming that a policy itself cannot transform the whole food system. Eco-labeling could be encouraged and implemented within a set of policies shaping sustainable food systems.
Impact of the Coronavirus Disease 2019 pandemic on neoadjuvant chemotherapy use in patients diagnosed with epithelial type ovarian cancer
Authors: Mukherjee Amrita , Shammas Natalie , Xu Lanfang , Cannavale Kimberly L. , Gilfillan Alec D. , Szamreta Elizabeth A. , Monberg Matthew , Hodeib Melissa , Chao Chun R.
Published: March 2024

Introduction

The Coronavirus Disease 2019 (COVID-19) pandemic posed critical challenges in providing care to ovarian cancer (OC) patients, including delays in OC diagnosis and treatment initiation. To accommodate for delays in OC surgery, the Society of Gynecologic Oncology (SGO) recommended preferential use of neoadjuvant chemotherapy during the pandemic. The purpose of this study was to assess the association of the COVID-19 pandemic with neoadjuvant chemotherapy use in patients diagnosed with OC.

Methods

This retrospective cohort study included patients diagnosed with stage II-IV ovarian cancer of epithelial subtype between 01/01/2017-06/30/2021 at Kaiser Permanente Southern California (KPSC), a large integrated healthcare system in the United States. Ovarian cancer patients diagnosed between 2017-2020 were identified from KPSC’s Surveillance, Epidemiology, and End Results (SEER)-affiliated cancer registry. Patients diagnosed in 2021 were identified from the electronic medical records (EMR) using ICD-10 diagnosis codes, followed by medical chart review to validate diagnosis and extract information on histology and stage at diagnosis. March 4, 2020 was used as the cut-off to define pre-pandemic and pandemic periods. Patients diagnosed with COVID-19 between OC diagnosis and treatment completion were excluded. Data on neoadjuvant chemotherapy use were extracted from the cancer registry and EMR, supplemented by chart review. Modified Poisson regression was used to evaluate the association of the pandemic with neoadjuvant chemotherapy use.

Results

Of 566 OC patients, 160 (28.3%) were diagnosed in the pandemic period. Patients diagnosed in the pandemic period were slightly younger (mean age 62.7 vs 64.9 years, p=0.07) and had a higher burden of Charlson comorbidities (p=0.05) than patients diagnosed in pre-pandemic period. No differences in time to treatment initiation were observed by pandemic periods. Neoadjuvant chemotherapy use was documented in 58.7% patients during the pandemic period compared to 47.3% in pre-pandemic period (p=0.01). After adjusting for covariates, patients diagnosed in the pandemic period were 29% more likely to receive neoadjuvant chemotherapy than patients diagnosed in pre-pandemic period [RR(95%CI): 1.29(1.12-1.49)].

Discussions

Ovarian cancer patients diagnosed in the COVID-19 pandemic were more likely to receive neoadjuvant chemotherapy than patients diagnosed before the pandemic. Future research on patient outcomes and trends in the post-pandemic period are warranted.
A case report and a literature review of double mammary pseudoangiomatous stromal hyperplasia associated with galactoma during pregnancy
Authors: Yu Minmin , Shi Guangxi , Gao Zong , Wu Kai , Wei Cuilei , Li Xiaohong , Miao Xiuming
Published: March 2024

Pseudoangiomatous stromal hyperplasia (PASH) is a benign interstitial hyperplasia of the breast that usually occurs in premenopausal or perimenopausal women. It is usually characterized by localized lesions or clear boundary masses, and diffuse double breast enlargement is rare. PASH is considered a hormone-dependent disease that is commonly progesterone related. There are no imaging characteristics, and both benign and suspicious malignant signs can be seen. The definitive diagnosis of PASH depends on a pathological diagnosis, and it is necessary to be vigilant in distinguishing between benign and malignant tumors with similar breast histopathology. Here, we report the case of a 23-year-old multipara patient with bilateral diffuse pseudoangiomatous stromal hyperplasia of the breast during pregnancy who presented with macromastia and reviewed the literature to further understand the clinical features, pathological diagnosis, differential diagnosis, treatment and prognosis of pseudoangiomatous stromal hyperplasia of the breast.
Clinical and pharmacological factors influencing serum clozapine and norclozapine levels
Authors: Mach Anna , Wnorowska Anna , Siwek Marcin , Wojnar Marcin , Radziwoń-Zaleska Maria
Published: March 2024

Background:

Clozapine (CLO) is a very effective antipsychotic, whose use is associated with dose-dependent risk of complications. Due to high interindividual variability in CLO metabolism, there is a need to identify factors affecting the blood concentrations of CLO and its active metabolite, norclozapine (NCLO).

Methods:

A total of 446 blood samples (collected from 233 women and 213 men, aged from 18 to 77 years) were included in this study and analyzed for CLO and NCLO concentrations. The patients were treated at a psychiatric hospital in Warsaw in the years 2016–2021. Serum CLO and NCLO concentrations were determined with high-performance liquid chromatography coupled to UV.

Results:

The following factors were shown to increase serum CLO and NCLO levels: higher CLO dose (p < 0.001), female sex (p < 0.001), nonsmoker status (p < 0.001), the use of more than two additional psychotropic drugs (only in the case of CLO; p = 0.046), concomitant use of beta-blockers (for CLO p = 0.049; for NCLO p < 0.001), and older age (for CLO p < 0.001; for NCLO p = 0.011). Despite the use of CLO at daily doses within the recommended range (200–450 mg), the evaluated serum CLO and NCLO levels were within the therapeutic ranges in only 37% and 75% of cases, respectively, with 5.6% of cases exceeding the CLO toxicity threshold.

Discussion:

The use of CLO at recommended doses does not guarantee achieving therapeutic concentrations of CLO or NCLO. Women and nonsmokers were at the highest risk of having toxic CLO levels.
The possible mechanisms of ferroptosis in sepsis-associated acquired weakness
Authors: Yang Jun , Yan Caihong , Chen Shaolin , Li Min , Miao Yanmei , Ma Xinglong , Zeng Junfa , Xie Peng
Published: March 2024

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, and its morbidity and mortality rates are increasing annually. It is an independent risk factor for intensive care unit-acquired weakness (ICU-AW), which is a common complication of patients in ICU. This situation is also known as sepsis-associated acquired weakness (SAW), and it can be a complication in more than 60% of patients with sepsis. The outcomes of SAW are often prolonged mechanical ventilation, extended hospital stays, and increased morbidity and mortality of patients in ICUs. The pathogenesis of SAW is unclear, and an effective clinical treatment is not available. Ferroptosis is an iron-dependent type of cell death with unique morphological, biochemical, and genetic features. Unlike other forms of cell death such as autophagy, apoptosis, and necrosis, ferroptosis is primarily driven by lipid peroxidation. Cells undergo ferroptosis during sepsis, which further enhances the inflammatory response. This process leads to increased cell death, as well as multi-organ dysfunction and failure. Recently, there have been sporadic reports suggesting that SAW is associated with ferroptosis, but the exact pathophysiological mechanisms remain unclear. Therefore, we reviewed the possible pathogenesis of ferroptosis that leads to SAW and offer new strategies to prevent and treat SAW.
The relationship between personal and professional goals and emotional state in academia: a study on unethical use of artificial intelligence
Authors: Dolunay Ayhan , Temel Ahmet C.
Published: March 2024

Artificial Intelligence (AI) is a concept that has been a subfield of computer science since the 1950s. In recent years, with its growing development power, AI technologies have made significant progress and are now being used in many fields. Like in all areas, the use of AI technologies in academia has provided convenience to academics while also bringing ethical debates. In the literature part of the study, concepts such as AI, academia, academics and academic progress, ethics, ethical theories, academic ethics, and emotional states have been thoroughly examined and defined. In this study, starting from AI and scientific ethics, ethical issues arising from emotional states in academic research have been identified, and concrete solutions to these ethical issues have been proposed. The aim is to discuss the views of academics in order to determine what types of scientific ethical violations and prevention methods are involved. In this context, the semi-structured interview technique, which is one of the qualitative research methods, was preferred as the method. In the study, in-depth semi-structured interviews were conducted with 4 ethics experts and 4 psychology experts selected through snowball sampling technique. The data obtained through semi-structured in-depth interviews will be analyzed using content analysis. Within the context of the literature review and interviews: Ethics is based on the foundation of acting correctly. In this context, scientific ethics can be summarized as acting truthfully and honestly, not distorting data, and not trying to progress unfairly. The use of AI in academia is becoming increasingly widespread. From a positive perspective, this usage significantly contributes to making studies more practical. However, it can lead to problems such as unfair authorship, devaluation of human authorship, and incorrect data. The connection between academics’ professional advancement goals and emotional states becomes prominent in this context. The potential of AI to facilitate progression can lead to unethical use. To prevent such situations, it is recommended to organize training sessions to increase professional awareness, internalize ethics personally, establish ethical committees specific to the field of AI, conduct more effective audits by academic publication and promotion committees, and implement specific regulations for AI. Finally, for future academic studies, it is suggested that the usage of AI in academic research be measured and evaluated by ethics experts. For psychologists, conducting surveys with academics to explore how they use AI in the context of their emotional states and professional advancement goals is recommended.
Suicide and mortality following self-harm in Culturally and Linguistically Diverse communities in Victoria, Australia: insights from a data linkage study
Authors: Pham Thi Thu Le , O'Brien Kerry S. , Liu Sara , Gibson Katharine , Berecki-Gisolf Janneke
Published: March 2024

Background

While cultural backgrounds are well-documented to be relevant to intentional self-harm, little is known about how cultural and linguistically diverse (CALD) backgrounds affect mortality outcomes following self-harm.

Aim

This study aimed to compare the risk of all-cause mortality and suicide after intentional hospital admissions for self-harm among people from CALD (vs. non-CALD) backgrounds.

Method

Linked hospital and mortality data in Victoria, Australia, was used to assess suicide and all-cause death after hospital admissions for self-harm among patients aged 15+ years. All-cause death was identified by following up on 42,122 self-harm patients (hospitalized between 01 July 2007 and 30 June 2019) until death or 15 February 2021. Suicide death was evaluated in 16,928 self-harm inpatients (01 January 2013 and 31 December 2017) until death or 28 March 2018. Cox regression models were fitted to compare mortality outcomes in self-harm patients from CALD vs. non-CALD backgrounds.

Outcomes

During the follow-up periods, 3,716 of 42,122 (8.8%) participants died by any cause (by 15 February 2021), and 304 of 16,928 (1.8%) people died by suicide (by 28 March 2018). Compared to the non-CALD group, CALD intentional self-harm inpatients had a 20% lower risk of all-cause mortality (HR: 0.8, 95% CI: 0.7–0.9) and a 30% lower risk of suicide (HR: 0.7, 95% CI: 049–0.97). Specifically, being from North Africa/Middle East and Asian backgrounds lowered the all-cause mortality risk; however, the suicide risk in Asians was as high as in non-CALD people.

Conclusion

Overall, people from CALD backgrounds exhibited lower risks of all-cause mortality and suicide following hospital admission for self-harm compared to the non-CALD group. However, when comparing risks based on regions of birth, significant variations were observed. These findings underscore the importance of implementing culturally tailored background-specific suicide preventive actions. The study focussed on outcomes following hospital admission for self-harm and did not capture outcomes for cases of self-harm that did not result in hospital admission. This limits generalisability, as some CALD people might avoid accessing healthcare after self-harm due to cultural factors. Future research that not limited to hospital data is suggested to build on the results.
Social determinants of health predict readmission following COVID-19 hospitalization: a health information exchange-based retrospective cohort study
Authors: Sandoval Micaela N. , Mikhail Jennifer L. , Fink Melyssa K. , Tortolero Guillermo A. , Cao Tru , Ramphul Ryan , Husain Junaid , Boerwinkle Eric
Published: March 2024

Introduction

Since February 2020, over 104 million people in the United States have been diagnosed with SARS-CoV-2 infection, or COVID-19, with over 8.5 million reported in the state of Texas. This study analyzed social determinants of health as predictors for readmission among COVID-19 patients in Southeast Texas, United States.

Methods

A retrospective cohort study was conducted investigating demographic and clinical risk factors for 30, 60, and 90-day readmission outcomes among adult patients with a COVID-19-associated inpatient hospitalization encounter within a regional health information exchange between February 1, 2020, to December 1, 2022.

Results and discussion

In this cohort of 91,007 adult patients with a COVID-19-associated hospitalization, over 21% were readmitted to the hospital within 90  days (n = 19,679), and 13% were readmitted within 30  days (n = 11,912). In logistic regression analyses, Hispanic and non-Hispanic Asian patients were less likely to be readmitted within 90  days (adjusted odds ratio [aOR]: 0.8, 95% confidence interval [CI]: 0.7–0.9, and aOR: 0.8, 95% CI: 0.8–0.8), while non-Hispanic Black patients were more likely to be readmitted (aOR: 1.1, 95% CI: 1.0–1.1, p = 0.002), compared to non-Hispanic White patients. Area deprivation index displayed a clear dose–response relationship to readmission: patients living in the most disadvantaged neighborhoods were more likely to be readmitted within 30 (aOR: 1.1, 95% CI: 1.0–1.2), 60 (aOR: 1.1, 95% CI: 1.2–1.2), and 90  days (aOR: 1.2, 95% CI: 1.1–1.2), compared to patients from the least disadvantaged neighborhoods. Our findings demonstrate the lasting impact of COVID-19, especially among members of marginalized communities, and the increasing burden of COVID-19 morbidity on the healthcare system.