bluuebunny/crossref_metadata_2025 huggingface dataset:
The large GTPase Sey1/atlastin mediates lipid droplet- and FadL-dependent intracellular fatty acid metabolism of Legionella pneumophila
Authors: Hüsler Dario , Stauffer Pia , Keller Bernhard , Böck Desirée , Steiner Thomas , Ostrzinski Anne , Vormittag Simone , Striednig Bianca , Swart A Leoni , Letourneur François , Maaß Sandra , Becher Dörte , Eisenreich Wolfgang , Pilhofer Martin , Hilbi Hubert
Published: May 2023

The amoeba-resistant bacterium Legionella pneumophila causes Legionnaires’ disease and employs a type IV secretion system (T4SS) to replicate in the unique, ER-associated Legionella-containing vacuole (LCV). The large fusion GTPase Sey1/atlastin is implicated in ER dynamics, ER-derived lipid droplet (LD) formation, and LCV maturation. Here, we employ cryo-electron tomography, confocal microscopy, proteomics, and isotopologue profiling to analyze LCV-LD interactions in the genetically tractable amoeba Dictyostelium discoideum. Dually fluorescence-labeled D. discoideum producing LCV and LD markers revealed that Sey1 as well as the L. pneumophila T4SS and the Ran GTPase activator LegG1 promote LCV-LD interactions. In vitro reconstitution using purified LCVs and LDs from parental or Δsey1 mutant D. discoideum indicated that Sey1 and GTP promote this process. Sey1 and the L. pneumophila fatty acid transporter FadL were implicated in palmitate catabolism and palmitate-dependent intracellular growth. Taken together, our results reveal that Sey1 and LegG1 mediate LD- and FadL-dependent fatty acid metabolism of intracellular L. pneumophila.
Tryptophan metabolism determines outcome in tuberculous meningitis: a targeted metabolomic analysis
Authors: Ardiansyah Edwin , Avila-Pacheco Julian , Nhat Le Thanh Hoang , Dian Sofiati , Vinh Dao Nguyen , Hai Hoang Thanh , Bullock Kevin , Alisjahbana Bachti , Netea Mihai G , Estiasari Riwanti , Tram Trinh Thi Bich , Donovan Joseph , Heemskerk Dorothee , Chau Tran Thi Hong , Bang Nguyen Duc , Ganiem Ahmad Rizal , Ruslami Rovina , Koeken Valerie ACM , Hamers Raph L , Imran Darma , Maharani Kartika , Kumar Vinod , Clish Clary B , van Crevel Reinout , Thwaites Guy , van Laarhoven Arjan , Thuong Nguyen Thuy Thuong
Published: May 2023

Background:

Cellular metabolism is critical for the host immune function against pathogens, and metabolomic analysis may help understand the characteristic immunopathology of tuberculosis. We performed targeted metabolomic analyses in a large cohort of patients with tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, focusing on tryptophan metabolism.

Methods:

We studied 1069 Indonesian and Vietnamese adults with TBM (26.6% HIV-positive), 54 non-infectious controls, 50 with bacterial meningitis, and 60 with cryptococcal meningitis. Tryptophan and downstream metabolites were measured in cerebrospinal fluid (CSF) and plasma using targeted liquid chromatography–mass spectrometry. Individual metabolite levels were associated with survival, clinical parameters, CSF bacterial load and 92 CSF inflammatory proteins.

Results:

CSF tryptophan was associated with 60-day mortality from TBM (hazard ratio [HR] = 1.16, 95% confidence interval [CI] = 1.10–1.24, for each doubling in CSF tryptophan) both in HIV-negative and -positive patients. CSF tryptophan concentrations did not correlate with CSF bacterial load nor CSF inflammation but were negatively correlated with CSF interferon-gamma concentrations. Unlike tryptophan, CSF concentrations of an intercorrelating cluster of downstream kynurenine metabolites did not predict mortality. These CSF kynurenine metabolites did however correlate with CSF inflammation and markers of blood–CSF leakage, and plasma kynurenine predicted death (HR 1.54, 95% CI = 1.22–1.93). These findings were mostly specific for TBM, although high CSF tryptophan was also associated with mortality from cryptococcal meningitis.

Conclusions:

TBM patients with a high baseline CSF tryptophan or high systemic (plasma) kynurenine are at increased risk of death. These findings may reveal new targets for host-directed therapy.

Funding:

This study was supported by National Institutes of Health (R01AI145781) and the Wellcome Trust (110179/Z/15/Z and 206724/Z/17/Z).
Imaging Microglia Surveillance during Sleep-wake Cycles in Freely Behaving Mice
Authors: Gu Xiaochun , Zhang Lifeng , Zhao Zhong , Fang Huaqiang , Zhao Ting , Ju Shenghong , Chen Xueli , Gao Weizheng , Qian Xiaoyu , Wang Xianhua , Zhang Jue , Cheng Heping
Published: May 2023

Microglia surveillance manifests itself as dynamic changes in cell morphology and functional remodeling in response to fluctuations in the neural environment. Whether and how microglia surveillance is coupled to brain state switches during natural sleep-wake cycles, as well as under sleep deprivation, remain unclear. To address this question, we used miniature two-photon microscopy (mTPM) to acquire time-lapse high-resolution microglia images of the somatosensory cortex, along with EEG/EMG recordings and behavioral video, in freely-behaving mice. We uncovered fast and robust brain state-dependent changes in microglia surveillance, occurring in parallel with sleep dynamics and early-onset phagocytic microglial contraction during sleep deprivation stress. With the aid of the biosensor GRAB
NE2m
, we also detected local norepinephrine fluctuation occurring in a sleep state-dependent manner. We showed that the locus coeruleus-norepinephrine system, which is crucial to sleep homeostasis, is required for both sleep state-dependent and stress-induced microglial responses and involves β
2
-adrenergic receptor signaling. These results provide direct evidence that microglial surveillance is exquisitely tuned to signals and stressors that regulate sleep dynamics and homeostasis so as to adjust its varied roles to complement those of neurons in the brain.
In vivo
imaging with mTPM in freely behaving animals, as demonstrated here, opens a new avenue for future investigation of microglia dynamics and sleep biology in freely behaving animals.
The zebrafish mutant dreammist implicates sodium homeostasis in sleep regulation
Authors: Barlow Ida L , Mackay Eirinn , Wheater Emily , Goel Aimee , Lim Sumi , Zimmerman Steve , Woods Ian , Prober David A , Rihel Jason
Published: May 2023

Sleep is a nearly universal feature of animal behaviour, yet many of the molecular, genetic, and neuronal substrates that orchestrate sleep/wake transitions lie undiscovered. Employing a viral insertion sleep screen in larval zebrafish, we identified a novel gene, dreammist (dmist), whose loss results in behavioural hyperactivity and reduced sleep at night. The neuronally expressed dmist gene is conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na+,K+-ATPase regulator, FXYD1/Phospholemman. Disruption of either fxyd1 or atp1a3a, a Na+,K+-ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. Since atpa1a3a and dmist mutants have elevated intracellular Na+ levels and non-additive effects on sleep amount at night, we propose that Dmist-dependent enhancement of Na+ pump function modulates neuronal excitability to maintain normal sleep behaviour.
Adaptive sentiment analysis using multioutput classification: a performance comparison
Authors: Hariguna Taqwa , Ruangkanjanases Athapol
Published: May 2023

The primary objective of this research is to create a multi-output classification model for sentiment analysis through the combination of 10 algorithms: BernoulliNB, Decision Tree, K-nearest neighbor, Logistic Regression, LinearSVC, Bagging, Stacking, Random Forest, AdaBoost, and ExtraTrees. In doing so, we aim to identify the optimal algorithm performance and role within the model. The data utilized in this study is derived from customer reviews of cryptocurrencies in Indonesia. Our results indicate that LinearSVC and Stacking exhibit a high accuracy (90%) compared to the other eight algorithms. The resulting multi-output model demonstrates an average accuracy of 88%, which can be considered satisfactory. This research endeavors to innovate in adaptive sentiment analysis classification by developing a multi-output model that utilizes a combination of 10 classification algorithms.
Comparison of the chloroplast genomes and phylogenomic analysis of Elaeocarpaceae
Authors: Wang Yihui , Xie Yifei , Jin Jiayi , Li Jinyue , Qiu Xiangdong , Tong Yang , Li Zhongyang , Zhang Zhixiang , Lai Wenling
Published: May 2023

Background

Elaeocarpaceae is a vital family in tropical and subtropical forests. Compared with the important position of Elaeocarpaceae species in forest ecosystem and the concern of medicinal value, the most research on Elaeocarpaceae are classification and taxonomy. Molecular systematics has corrected the morphological misjudgment, and it belongs to Oxalidales. Phylogenetic and divergence time estimates of Elaeocarpaceae is mostly constructed by using chloroplast gene fragments. At present, although there are reports on the chloroplast structure of Elaeocarpaceae, a comprehensive analysis of the chloroplast structure of Elaeocarpaceae is lacking.

Methods

To understand the variation in chloroplast sequence size and structure in Elaeocarpaceae, the chloroplast genomes of nine species were sequenced using the Illumina HiSeq 2500 platform and further assembled and annotated with Elaeocarpus japonicus and Sloanea sinensis (family Elaeocarpaceae) as references. A phylogenomic tree was constructed based on the complete chloroplast genomes of the 11 species representing five genera of Elaeocarpaceae. Chloroplast genome characteristics were examined by using Circoletto and IRscope software.

Results

The results revealed the following: (a) The 11 sequenced chloroplast genomes ranged in size from 157,546 to 159,400 bp. (b) The chloroplast genomes of Elaeocarpus, Sloanea, Crinodendron and Vallea lacked the rpl32 gene in the small single-copy (SSC) region. The large single-copy (LSC) region of the chloroplast genomes lacked the ndhK gene in Elaeocarpus, Vallea stipularis, and Aristotelia fruticosa. The LSC region of the chloroplast genomes lacked the infA gene in genus Elaeocarpus and Crinodendron patagua. (c) Through inverted repeat (IR) expansion and contraction analysis, a significant difference was found between the LSC/IRB and IRA/LSC boundaries among these species. Rps3 was detected in the neighboring regions of the LSC and IRb regions in Elaeocarpus. (d) Phylogenomic analysis revealed that the genus Elaeocarpus is closely related to Crinodendron patagua on an independent branch and Aristotelia fruticosa is closely related to Vallea stipularis, forming a clade with the genus Sloanea. Structural comparisons showed that Elaeocarpaceae diverged at 60 Mya, the genus Elaeocarpus diverged 53 Mya and that the genus Sloanea diverged 0.44 Mya. These results provide new insight into the evolution of the Elaeocarpaceae.
Self-reported interoceptive accuracy and interoceptive attention differentially correspond to measures of visual attention and self-regard
Authors: Benau Erik M.
Published: May 2023

Background

Interoception, the perception of bodily functions and sensations, is a crucial contributor to cognition, emotion, and well-being. However, the relationship between these three processes is not well understood. Further, it is increasingly clear that dimensions of interoception differentially corresponds to these processes, yet this is only recently being explored. The present study addresses two important questions: Are subjective interoceptive accuracy and interoceptive attention related to self-regard and well-being? And are they related to exteroceptive (visual) attention?

Methods

Participants (N = 98; 29% women; aged 23–64 years) completed: a battery of questionnaires to assess subjective accuracy (how well one predicts bodily sensations), interoceptive attention (a tendency to notice bodily signals), self-regard (self-esteem, self-image, life satisfaction), state negative affect (depression, anxiety, and stress), a self-esteem Implicit Association Task (a measure of implicit self-esteem), and a flanker task to assess visual selective attention. Subjective interoceptive accuracy and attention served as dependent variables. Correlations and principal component analysis was used to establish correlations among variables and determine how, or whether, these measures are associated with subjective interoceptive accuracy or attention.

Results

Greater scores on measures of self-regard, implicit self-esteem, cognition and lower negative affect were broadly associated with greater subjective interoceptive accuracy. Conversely, only explicit self-esteem, satisfaction with life, and self-image corresponded to subjective interoceptive attention. An exploratory analysis with a more inclusive scale of interoceptive attention was conducted. Results of this exploratory analysis showed that the broader measure was a stronger correlate to self-regard than subjective interoceptive accuracy, though it, too, did not correlate with visual attention. In short, both subjective interoceptive accuracy and attention corresponded to well-being and mental health, but only accuracy was associated with exteroceptive attention.

Conclusion

These results add to a growing literature suggesting different dimensions of (subjective) interoception differentially correspond to indices of well-being. The links between exteroceptive and interoceptive attention, and their association with merit further study.
Prediction of the spread of African swine fever through pig and carcass movements in Thailand using a network analysis and diffusion model
Authors: Poolkhet Chaithep , Kasemsuwan Suwicha , Thongratsakul Sukanya , Warrasuth Nattachai , Pamaranon Nuttavadee , Nuanualsuwan Suphachai
Published: May 2023

Background

African swine fever (ASF) is a serious contagious viral disease of pigs that affects the pig industry. This study aimed to evaluate the possible African swine fever (ASF) distribution using network analysis and a diffusion model through live pig, carcass, and pig product movement data.

Material and Methods

Empirical movement data from Thailand for the year 2019 were used, and expert opinions were sought to evaluate network properties and the diffusion model. The networks were presented as live pig movement and carcass movement data at the provincial and district levels. For network analysis, a descriptive network analysis was performed using outdegree, indegree, betweenness, fragmentation, and power law distribution, and cutpoints were used to describe movement patterns. For the diffusion model, we simulated each network using spatially different infected locations, patterns, and initial infection sites. Based on expert opinions, the initial infection site, the probability of ASF occurrence, and the probability of the initial infected adopter were selected for the appropriated network. In this study, we also simulated networks under varying network parameters to predict the infection speed.

Results and Conclusions

The total number of movements recorded was 2,594,364. These were divided into 403,408 (403,408/2,594,364; 15.55%) for live pigs and 2,190,956 (2,190,956/2,594,364; 84.45%) for carcasses. We found that carcass movement at the provincial level showed the highest outdegree (mean = 342.554, standard deviation (SD) = 900.528) and indegree values (mean = 342.554, SD = 665.509). In addition, the outdegree and indegree presented similar mean values and the degree distributions of both district networks followed a power-law function. The network of live pigs at provincial level showed the highest value for betweenness (mean = 0.011, SD = 0.017), and the network of live pigs at provincial level showed the highest value for fragmentation (mean = 0.027, SD = 0.005). Our simulation data indicated that the disease occurred randomly due to live pig and carcass movements along the central and western regions of Thailand, causing the rapid spread of ASF. Without control measures, it could spread to all provinces within 5- and 3-time units and in all districts within 21- and 30-time units for the network of live pigs and carcasses, respectively. This study assists the authorities to plan control and preventive measures and limit economic losses caused by ASF.
Dr. Smartphone, can you support my trauma? An informatics analysis study of App Store apps for trauma- and stressor-related disorders
Authors: Ting Amanda , McLachlan Craig
Published: May 2023

Background

Psychological trauma is prevalent in developed countries, with prevalence rates and treatment needs exceeding health system capacity. As telemedicine and out-of-patient care are promoted, there has been an expansion of digital apps to compliment therapeutic stages in psychological trauma. To date there are no reviews that have compared these apps and their clinical utility. This study aims to identify the availability of trauma- and stressor-related mhealth apps, assess their functionality, and review their therapeutic abilities.

Methodology

The authors conducted a systematic search using an iPhone 13 Pro in the Australian IOS App Store to extract trauma- and stressor-related apps that resulted from the search criteria. A cross-adaptation of the Mobile App Rating Scale (MARS) and the Comprehensive App Evaluation Model (CAEM) were used as a framework to produce the mTrauma App Evaluation Conceptual Model and Informatics Framework. App content descriptors were analysed based on their general characteristics, usability, therapeutic focus, clinical utility, data integration. Following an applicability in concordance with psychological trauma-informed delivery.

Results

A total of 234 apps resulting from the search strategy were screened, with 81 apps that met the inclusion criteria. The majority of apps were marketed to 4+ to 17+ years of age, categorised as ‘health and fitness’, with the highest target markets observed for adolescents, children, parents, clinicians, and clients. A total of 43 apps (53.1%) contained a trauma-informed specified section, and 37 (45.7%) incorporated a section useful to support trauma-related symptoms. A significant number of apps there was an absence of therapeutic utility (in 32 apps (39.5%)). Most apps were supporting post-traumatic stress disorder-informed, cognitive behavioural therapy and eye movement desensitisation and reprocessing. Provision of psychoeducation, courses, guided sessions, trainings, self-reflection/journaling, symptom management and progress tracking were highly present.

Conclusions

Trauma-informed mobile apps are available in the App Store, expanding in its target market reach and usability, with an increase of creative psychotherapies being introduced alongside conventional modalities. However, based on the app descriptors, the scarcity of evidenced-based testimonials and therapeutic applicability remains questionable for clinical validity. Although mhealth tools are marketed as trauma-related, current available apps employ a multifunctional approach to general psychological symptomatology, through to associated comorbid conditions and emphasizes on passive activity. For higher uptake on user engagement, clinical application and validity, trauma-apps require curated specification to fulfil its role as complimentary psychological treatment.
1H NMR fecal metabolic phenotyping of periductal fibrosis- and cholangiocarcinoma-specific metabotypes defining perturbation in gut microbial-host co-metabolism
Authors: Treeriya Rujikorn , Ho Phuc N. , Titapun Attapol , Klanrit Poramate , Suksawat Manida , Kulthawatsiri Thanaporn , Sirirattanakul Suphasarang , Loilome Watcharin , Namwat Nisana , Wangwiwatsin Arporn , Chamadol Nittaya , Khuntikeo Narong , Phetcharaburanin Jutarop
Published: May 2023

Background

The liver fluke Opisthorchis viverrini (OV), which subsequently inhabits the biliary system and results in periductal fibrosis (PDF), is one of the primarily causes of cholangiocarcinoma (CCA), a bile duct cancer with an exceptionally high incidence in the northeast of Thailand and other Greater Mekong Subregion (GMS) countries. Insights in fecal metabolic changes associated with PDF and CCA are required for further molecular research related to gut health and potential diagnostic biological marker development.

Methods

In this study, nuclear magnetic resonance (NMR) metabolomics was applied for fecal metabolic phenotyping from 55 fecal water samples across different study groups including normal bile duct, PDF and CCA groups.

Results

By using NMR spectroscopy-based metabolomics, fecal metabolic profiles of patients with CCA or PDF and of individuals with normal bile duct have been established with a total of 40 identified metabolites. Further multivariate statistical analysis and hierarchical clustering heat map have demonstrated the PDF- and CCA-specific metabotypes through various altered metabolite groups including amino acids, alcohols, amines, anaerobic glycolytic metabolites, fatty acids, microbial metabolites, sugar, TCA cycle intermediates, tryptophan catabolism substrates, and pyrimidine metabolites. Compared to the normal bile duct group, PDF individuals showed the significantly elevated relative concentrations of fecal ethanol, glycine, tyrosine, and N-acetylglucosamine whereas CCA patients exhibited the remarkable fecal metabolic changes that can be evident through the increased relative concentrations of fecal uracil, succinate, and 5-aminopentanoate. The prominent fecal metabolic alterations between CCA and PDF were displayed by the reduction of relative concentration of methanol observed in CCA. The metabolic alterations associated with PDF and CCA progression have been proposed with the involvement of various metabolic pathways including TCA cycle, ethanol biogenesis, hexamine pathway, methanol biogenesis, pyrimidine metabolism, and lysine metabolism. Among them, ethanol, methanol, and lysine metabolism strongly reflect the association of gut-microbial host metabolic crosstalk in PDF and/or CCA patients.

Conclusion

The PDF- and CCA-associated metabotypes have been investigated displaying their distinct fecal metabolic patterns compared to that of normal bile duct group. Our study also demonstrated that the perturbation in co-metabolism of host and gut bacteria has been involved from the early step since OV infection to CCA tumorigenesis.
A diversidade de gênero na perspectiva organizacional: um programa de liderança feminina
Authors: Gomes Gisele , Renner Jacinta Sidegum , Meyer Dagmar Elizabeth Estermann
Published: May 2023

Este artigo versa sobre diversidade de gênero nas organizações e tem por objetivo compreender, sob a perspectiva de gestores de uma empresa do ramo financeiro, o processo de constituição do Programa de Liderança para Mulheres e as motivações organizacionais que levaram a essa iniciativa. O Programa de Liderança para Mulheres é uma iniciativa que envolve mulheres associadas e visa a promover a equidade de gênero, considerando a participação na gestão em todos os níveis da organização. Trata-se de uma pesquisa qualitativa, de caráter descritivo, e os dados foram analisados e categorizados. Os instrumentos de pesquisa consistiram em uma entrevista semiestruturada e a observação participante. Participaram da pesquisa oito pessoas com cargos de alta liderança que atuam em diferentes unidades e Centrais regionais no Brasil. Os achados das entrevistas foram classificados e resultaram na criação de duas categorias: a) igualdade, equidade e paridade de gênero, que abarca as motivações para criação do Programa de Liderança para Mulheres bem como, as intersecções com o papel social das organizações na ampliação da consciência sobre o tema na sociedade e; b) relações e tensões entre culturas comunitárias e a cultura organizacional. Evidenciou-se que a busca por igualdade, equidade e paridade de gênero são fatores importante nesse processo organizacional e que os líderes têm um papel social nas organizações. Esse esforço também se traduz na busca pela transformação da questão cultural do espaço ocupado pelas mulheres, em especial pela configuração histórica da organização.
Effect of Carrier Materials, Coinoculation and Sterilization on Survival of Plant Growth Promoting Microbes
Authors: Mwafulirwa Samuel , Kanyada Fortune M.
Published: May 2023

The study was conducted to investigate diverse carrier materials out of agricultural and environmental waste, that plays a role in maintaining the shelf life of plant growth promoting microbes (PGPM) at room temperature for locally produced inoculants in Malawi. Five different formulations divided into sterilized and unsterilized were prepared, using different carrier materials namely; rice bran plus plant extract (RBP), biochar plus plant extract (BP), Filter mud plus plant extract (FMP), rice bran, biochar and plant extracts (RBCP), filter mud, biochar and plant extracts (FMBP). Carrier materials were packed in polyethylene pack (six per each treatment), thereafter each treatment was divided into sterilized and unsterilized. Each treatment was inoculated with either single or multiple inoculants. Survival of PGPM, was based on colony forming units (CFU) on specific selective media namely: modified yeast extract mannitol, pikovskaya’s, Alexandria and basal media for nitrogen fixing microbes, phosphate, potassium and zinc solubilising media respectively. Results revealed that encapsulated formulation of based combination formulation of RBCP in both single and multiple inoculants exerted high stable numbers of PGRM along the storage compared to other formulations. The results also show that unsterilized formulations exert high numbers compared to sterilized which is as a result of hydrogen peroxide accumulation during sterilization. The study reveals that filter mud based formulations currently used in both single and multiple inoculants is not favorable for local environments because microbial numbers decrease after 20 days at room temperature. This makes filter mud formulations usage not favorable for rural smallholder farmers with no refrigeration facilities.
DUS Characterization and Evaluation of Untapped French Bean (Phaseolus vulgaris L.) Genotypes
Authors: Pramanik Kartik , Sahu G. S. , Acharya G. C. , Tripathy P. , Dash M. , Kumari M. , Sahoo M. R. , Koundinya A. V. V. , Mohapatra P. P. , Veera U. R.
Published: May 2023

French bean is being considered as an important legume for human diet having rich source of dietary proteins, minerals and vitamins. Germplasm characterization and evaluation is having great contribution in breeding and crop improvement. Substantial phenotypic and genetic characterization of untapped French bean germplasm are still needed to unlock its breeding potential. Purposefully, 27 diverse French bean genotypes comprising primitive, cultivars, commercial cultivars, farmers grown varieties were collected from different parts of India, characterized as per Distinct, Uniformity and Stability (DUS) and evaluated for associated morpho-phenological traits in randomized complete block design. The screened panel revealed highly significant differences among French bean genotypes for all the traits under study which witnessed the existence of sufficient variability in the French bean genotypes in which first two Principal Component Analysis (PCA) explained 20.03% and 13.32% of the total morphological variability. The genotypes were well scattered in PCA axis forming groups with various traits as per contribution towards the variability. The genotype IC 632961 having desirable traits which could be an elite germplasm for future crop improvement.
In Vitro Preliminary Phytochemical Screening, Acute Toxicity Test and Anti-diarrheal Activity of Methanolic Bixa orellana Seed Extracts by Castor Oil Induced and Magnesium Sulfate Induced Diarrhea Models
Authors: Tonny Tamanna Sharmin , Afroze Ivana , Shifa Sumsunnahar , Sultana Sonia
Published: May 2023

Introduction: One in nine child deaths worldwide are attributable to diarrheal infections, making diarrhea the second largest cause of death among kids younger than the age of 5 years. The Sub-Saharan Africa and South Asia have the highest mortality due to diarrheal diseases. Natural substances of mineral, animal, or plant origins have long been used in medicines, cosmetics, and food goods. Bixa orellana is a Brazil-native plant that also thrives in other parts of South and Central America. It is cultivated in tropical regions, including Peru, Mexico, Ecuador, Indonesia, India, Kenya, and East Africa. Due to the ban on the use of synthetic dyes in food and cosmetics, its use has increased, as it is one of the few authorized dyes by the World Health Organization (WHO) because, in addition to being nontoxic, it does not appear to alter the nutritional content of food. Additionally, 70% of the world's natural coloring additives are sourced from annatto, a common name for Bixa orellana. The leaves and seed extract has been used traditionally in the tropical areas of South Asia to reduce the severity of diarrheal episodes. Therefore, this study was designed to evaluate the anti-diarrheal property of Bixa Orellana seed extracts at different doses comparing with established manufactured drugs corroborating its’ orthodox therapeutic use as an anti-diarrheal agent.

Aim and Objectives: Pharmacological Evaluation of Anti-diarrheal activities in Swiss Albino Mice.

Materials and Methods: The methanolic extract of Bixa Orellana seeds was prepared by traditional method and was used to assess its’ anti-diarrheal property. Anti-diarrheal activity was evaluated in Swiss Albino Mice using Castor oil induced diarrhea and MgSO4 induced diarrhea models respectively.

Observations and Results: Bixa orellana seed extract showed significant 75% Anti-diarrheal activity in the present study when compared to the standard drug Loperamide.

Conclusion: The methanolic seed extract of Bixa Orellana showed prominent Anti-diarrheal activity therefore it ensures safe and efficient traditional uses of Bixa Orellana in times of Diarrhea.
Changes in Minoxidil Prescribing After Media Attention About Oral Use for Hair Loss
Authors: Goodwin Cartwright Brianna M. , Wang Michael , Rodriguez Patricia , Stewart Sarah , Worsham Christopher M. , Stucky Nick , Jena Anupam B.
Published: May 2023

This cross-sectional study investigates rates of prescription of low-dose minoxidil after of publication of a newspaper article on this treatment.
Assessment of Medical Cannabis and Health-Related Quality of Life
Authors: Arkell Thomas R. , Downey Luke A. , Hayley Amie C. , Roth Sebastian
Published: May 2023

Importance

The use of cannabis as a medicine is becoming increasingly prevalent. Given the diverse range of conditions being treated with medical cannabis, as well as the vast array of products and dose forms available, clinical evidence incorporating patient-reported outcomes may help determine safety and efficacy.

Objective

To assess whether patients using medical cannabis report improvements in health-related quality of life over time.

Design, Setting, and Participants

This retrospective case series study was conducted at a network of specialist medical clinics (Emerald Clinics) located across Australia. Participants were patients who received treatment for any indication at any point between December 2018 and May 2022. Patients were followed up every mean (SD) 44.6 (30.1) days. Data for up to 15 follow-ups were reported. Statistical analysis was conducted from August to September 2022.

Exposure

Medical cannabis. Product types and cannabinoid content varied over time in accordance with the treating physician’s clinical judgement.

Main Outcomes and Measures

The main outcome measure was health-related quality of life as assessed using the 36-Item Short Form Health Survey (SF-36) questionnaire.

Results

In this case series of 3148 patients, 1688 (53.6%) were female; 820 (30.2%) were employed; and the mean (SD) age was 55.9 (18.7) years at baseline before treatment. Chronic noncancer pain was the most common indication for treatment (68.6% [2160 of 3148]), followed by cancer pain (6.0% [190 of 3148]), insomnia (4.8% [152 of 3148]), and anxiety (4.2% [132 of 3148]). After commencing treatment with medical cannabis, patients reported significant improvements relative to baseline on all 8 domains of the SF-36, and these improvements were mostly sustained over time. After controlling for potential confounders in a regression model, treatment with medical cannabis was associated with an improvement of 6.60 (95% CI, 4.57-8.63) points to 18.31 (95% CI, 15.86-20.77) points in SF-36 scores, depending on the domain (all P < .001). Effect sizes (Cohen d) ranged from 0.21 to 0.72. A total of 2919 adverse events were reported, including 2 that were considered serious.

Conclusions and Relevance

In this case series study, patients using medical cannabis reported improvements in health-related quality of life, which were mostly sustained over time. Adverse events were rarely serious but common, highlighting the need for caution with prescribing medical cannabis.
Assessment of Use of ICD-9 and ICD-10 Codes for Social Determinants of Health in the US, 2011-2021
Authors: Agarwal Amil R. , Prichett Laura , Jain Amit , Srikumaran Uma
Published: May 2023

This cross-sectional study examines trends in the use of International Classification of Diseases, Ninth Revision (ICD-9) and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes for social determinants of health in the US from 2011 to 2021.
Adaptive observer‐based attack estimation and event‐triggered security control for UAVs
Authors: Pan Kunpeng , Lyu Yang , Yang Feisheng , Pan Quan
Published: May 2023

With the increasingly close connection between unmanned aerial vehicles (UAV) and communication networks, it is facing an increasing number of cybersecurity threats. In this article, an event‐triggered security control problem for UAVs is investigated under the tampered input signal sent by the ground control station. First, a linear model of the lateral movement of UAV is established and the attack description is given. Second, an adaptive observer is developed to reconstruct the attack signal. The reconstructed signal is compensated as system disturbance, and then the safety control strategy with event‐triggered mechanism (ETM) is designed. Furthermore, through the time interval analysis approach, the ETM, state observer, controller and attack signal are unified into a new augment system. Then, the uniformly ultimately bounded analysis and controller/observer synthesis conditions are obtained by using piecewise Lyapunov–Krasovskii functional methods. Furthermore, a sufficient condition for the parameters involving controller gain, observer gain, and the ETM parameters is given via a linear matrix inequality. Finally, simulation results are conducted to verify the effectiveness of the proposed method.
Biodegradable Microrobots for DNA Vaccine Delivery
Authors: Chen Shuxun , Tan Zhiwu , Liao Pan , Li Yanfang , Qu Yun , Zhang Qi , Yang Mingxuan , Chan Kannie Wai Yan , Zhang Li , Man Kwan , Chen Zhiwei , Sun Dong
Published: May 2023

The delivery of nucleic acid vaccine to stimulate host immune responses against Coronavirus disease 2019 shows promise. However, nucleic acid vaccines have drawbacks, including rapid clearance and poor cellular uptake, that limit their therapeutic potential. Microrobots can be engineered to sustain vaccine release and further control the interactions with immune cells that are vital for robust vaccination. Here, the 3D fabrication of biocompatible and biodegradable microrobots via the two‐photon polymerization of gelatin methacryloyl (GelMA) and their proof‐of‐concept application for DNA vaccine delivery is reported. Programmed degradation and drug release by varying the local exposure dose in 3D laser lithography and further functionalized the GelMA microspheres with polyethyleneimine for DNA vaccine delivery to dendritic cell and primary cells is demonstrated. In mice, the DNA vaccine delivered by functionalized microspheres elicited fast, enhanced, and durable antigen expression, which may lead to prolonged protection. Furthermore, we demonstrate the maneuverability of microrobots by fabricating GelMA microspheres on magnetic skeletons. In conclusion, GelMA microrobots may provide an efficient vaccination strategy by controlling the expression duration of DNA vaccines.
Copper‐Single‐Atom Coordinated Nanotherapeutics for Enhanced Sonothermal‐Parallel Catalytic Synergistic Cancer Therapy
Authors: Qi Ye , Ren Shuangsong , Ye Junwei , Bi Shengnan , Shi Lei , Fang Yueguang , Wang Guangyao , Finfrock Y. Zou , Li Jun , Che Ying , Ning Guiling
Published: May 2023

Phototherapy and sonotherapy are recognized by scientific medicine as effective strategies for treating certain cancers. However, these strategies have limitations such as an inability to penetrate deeper tissues and overcome the antioxidant tumor microenvironment. In this study, a novel “BH” interfacial‐confined coordination strategy to synthesize hyaluronic acid‐functionalized single copper atoms dispersed over boron imidazolate framework‐derived nanocubes (HA‐NC_Cu) to achieve sonothermal–catalytic synergistic therapy is reported. Notably, HA‐NC_Cu demonstrates exceptional sonothermal conversion performance under low‐intensity ultrasound irradiation, attained through intermolecular lattice vibrations. In addition, it shows promise as an efficient biocatalyst, able to generate high‐toxicity hydroxyl radicals in response to tumor‐endogenous hydrogen peroxide and glutathione. Density functional theory calculations reveal that the superior parallel catalytic performance of HA‐NC_Cu originates from the CuN4C/B active sites. Both in vitro and in vivo evaluations consistently demonstrate that the sonothermal–catalytic synergistic strategy significantly improves tumor inhibition rate (86.9%) and long‐term survival rate (100%). In combination with low‐intensity ultrasound irradiation, HA‐NC_Cu triggers a dual death pathway of apoptosis and ferroptosis in MDA‐MB‐231 breast cancer cells, comprehensively limiting primary triple‐negative breast cancer. This study highlights the applications of single‐atom‐coordinated nanotherapeutics in sonothermal–catalytic synergistic therapy, which may create new opportunities in biomedical research.
Li‐Ion Transfer Mechanism of Gel Polymer Electrolyte with Sole Fluoroethylene Carbonate Solvent
Authors: Sun Qifang , Wang Su , Ma Yue , Song Dawei , Zhang Hongzhou , Shi Xixi , Zhang Na , Zhang Lianqi
Published: May 2023

Although gel polymer electrolytes (GPEs) represent a promising candidate to address the individual limitations of liquid and solid electrolytes, their extensive development is still hindered due to the veiled Li‐ion conduction mechanism. Herein, the related mechanism in GPEs is extensively studied by developing an in situ polymerized GPE comprising fluoroethylene carbonate (FEC) solvent and carbonate ester segments (F‐GPE). Practically, although with high dielectric constant, FEC fails to effectively transport Li ions when acting as the sole solvent. By sharp contrast, F‐GPE demonstrates superior electrochemical performances, and the related Li‐ion transfer mechanism is investigated using molecular dynamics simulations and 7Li/6Li solid‐state nNMR spectroscopy. The polymer segments are extended with the swelling of FEC, then an electron‐delocalization interface layer is generated between abundant electron‐rich groups of FEC and the polymer ingredients, which works as an electron‐rich “Milky Way” and facilitates the rapid transfer of Li ions by lowering the diffusion barrier dramatically, resulting in a high conductivity of 2.47 × 10−4 S cm−1 and a small polarization of about 20 mV for Li//Li symmetric cell after 8000 h. Remarkably, FEC provides high flame‐retardancy and makes F‐GPE remains stable under ignition and puncture tests.
Half‐Metallic Heusler Alloy/GaN Heterostructure for Semiconductor Spintronics Devices
Authors: Yamada Shinya , Kato Masatoshi , Ichikawa Shuhei , Yamada Michihiro , Naito Takahiro , Fujiwara Yasufumi , Hamaya Kohei
Published: May 2023

Because spin‐orbit coupling in wurtzite semiconductors is relatively weak compared with that in zincblende ones, the III‐nitride semiconductor GaN is a promising material for high‐performance optical semiconductor spintronic devices such as spin lasers. For the purpose of reducing the operating power of spin lasers, it is necessary to demonstrate highly efficient electrical spin injection from a ferromagnetic material into GaN with a low‐resistance contact. Here, an epitaxial half‐metallic Heusler alloy Co2FeAlxSi1−x(CFAS)/GaN heterostructure is developed by inserting an ultrathin Co layer between the CFAS and GaN. The CFAS/n+‐GaN heterojunctions clearly show tunnel conduction with very small rectification and a low resistance‐area product of ≈3.8 kΩµm2, which is several orders of magnitude smaller than those reported in previous work, at room temperature. Nonlocal spin signals and a Hanle effect curve are observed at low temperatures using lateral spin‐valve devices with the CFAS/n+‐GaN contacts, suggesting pure spin current transport in bulk GaN. The spin transport is observed at temperatures as high as room temperature, with a high spin polarization of 0.2 at a low bias voltage less than 2.0 V. This study is expected to open a path to GaN‐based spintronic devices with highly spin‐polarized and low‐resistance contacts.
STOP‐AD portal: Selecting the optimal pharmaceutical for preclinical drug testing in Alzheimer's disease
Authors: Quinney Sara K. , Murugesh Kandasamy , Oblak Adrian , Onos Kristen D. , Sasner Mike , Greenwood Anna K. , Woo Kara H. , Rizzo Stacey J. Sukoff , Territo Paul R.
Published: May 2023

We propose an unbiased methodology to rank compounds for advancement into comprehensive preclinical testing for Alzheimer's disease (AD). Translation of compounds to the clinic in AD has been hampered by poor predictive validity of models, compounds with limited pharmaceutical properties, and studies that lack rigor. To overcome this, MODEL‐AD's Preclinical Testing Core developed a standardized pipeline for assessing efficacy in AD mouse models. We hypothesize that rank‐ordering compounds based upon pharmacokinetic, efficacy, and toxicity properties in preclinical models will enhance successful translation to the clinic. Previously compound selection was based solely on physiochemical properties, with arbitrary cutoff limits, making ranking challenging. Since no gold standard exists for systematic prioritization, validating a selection criteria has remained elusive. The STOP‐AD framework evaluates the drug‐like properties to rank compounds for in vivo studies, and uses an unbiased approach that overcomes the validation limitation by performing Monte‐Carlo simulations.

Highlights

Promising preclinical studies for AD drugs have not translated to clinical success.

Systematic assessment of AD drug candidates may increase clinical translatability.

We describe a well‐defined framework for compound selection with clear selection metrics.
The role of PIMT in Alzheimer's disease pathogenesis: A novel hypothesis
Authors: D'Alessandro Angelo , Lukens John R. , Zimring James C.
Published: May 2023

There are multiple theories of Alzheimer's disease pathogenesis. One major theory is that oxidation of amyloid beta (Aβ) promotes plaque deposition that directly contributes to pathology. A competing theory is that hypomethylation of DNA (due to altered one carbon metabolism) results in pathology through altered gene regulation. Herein, we propose a novel hypothesis involving L‐isoaspartyl methyltransferase (PIMT) that unifies the Aβ and DNA hypomethylation hypotheses into a single model. Importantly, the proposed model allows bidirectional regulation of Aβ oxidation and DNA hypomethylation. The proposed hypothesis does not exclude simultaneous contributions by other mechanisms (e.g., neurofibrillary tangles). The new hypothesis is formulated to encompass oxidative stress, fibrillation, DNA hypomethylation, and metabolic perturbations in one carbon metabolism (i.e., methionine and folate cycles). In addition, deductive predictions of the hypothesis are presented both to guide empirical testing of the hypothesis and to provide candidate strategies for therapeutic intervention and/or nutritional modification.

HIGHLIGHTS

PIMT repairs L‐isoaspartyl groups on amyloid beta and decreases fibrillation.

SAM is a common methyl donor for PIMT and DNA methyltransferases.

Increased PIMT activity competes with DNA methylation and vice versa.

The PIMT hypothesis bridges a gap between plaque and DNA methylation hypotheses.
Nanosized metal or silicon oxides and L‐proline or 4‐hydroxy‐L‐proline in stereoselective synthesis of a dihydropyrimidinethione podand
Authors: Filatova Elena S. , Fedorova Olga V. , Ovchinnikova Irina G. , Chistyakov Konstantin A. , Ganebnykh Ilya N. , Uimin Mikhail A. , Rusinov Gennady L.
Published: May 2023

The stereoselective Biginelli reaction involving a CH‐active podand, thiourea, and benzaldehyde using nanosized metal oxides (NiO, Fe3O4, CuO, Al2O3, SiO2, and TiO2‐SiO2), Brönsted acid, and commercially available chiral inductors (L‐proline or 4‐hydroxy‐L‐proline) was studied. The target dihydropyrimidinethione‐containing podand was obtained with an enantiomeric excess of 70% and a moderate yield under mild conditions in the presence of nanooxide NiO and 4‐hydroxy‐L‐proline. The adsorption of initial reactants and chiral inductor on the surface of nickel nanooxide was studied by IR spectroscopy. The activating and coordinating effect of the nanosized metal oxide on the initial reagents leading to an increasing the chemoselectivity and stereoselectivity of the Biginelli reaction was shown. On the basis of experimental data, one of the probable reaction mechanisms was proposed. This work further expanded the use of nanosized metal oxides in asymmetric catalysis and presented a new method for obtaining a valuable optically active podand with a 3,4‐dihydropyrimidine‐2‐(1H)‐thione moiety. Thus, the obtained results can be of interest for medicinal chemistry in the asymmetric one‐step synthesis of other enantiomerically pure compounds.
The synergetic enhancement of the porous ZrO2@TiO2 heterostructure and the plasmonic silver nanoparticles for efficient surface‐enhanced Raman scattering
Authors: Shi Xiaoyi , Guo Yujie , Li Zhihao , He Meng , Zhu Zhengdong , Sun Xu , Sun Hui , Zhang Maofeng , Li Jianhua , Huang Youju
Published: May 2023

Rapid identification and analysis of pesticide residue on real‐world sample by a portable platform is of growing interest for monitoring food safety and safeguarding human health. Herein, we developed a robust surface‐enhanced Raman spectroscopy (SERS) sensor based on ZrO2@TiO2/Ag substrate for the analysis of pesticide residues. The synergetic effects of the metal organic framework (MOF)‐derived porous ZrO2@TiO2 heterostructure induced charge transfer enhancement and the electromagnetic enhancement from the plasmonic silver nanoparticles (AgNPs) hotspot generate significant SERS enhancement signal. The SERS substrate exhibits superior long‐term stability and signal homogeneity for SERS quantitative analysis. The platform has the capability to detect not only model molecule of 4‐ATP but also pesticides of triazophos and fonofos at the extremely low concentration of 10−8 M. Moreover, we simulate the quantitative detection of pesticide residue on real objects by spraying pesticides on dendrobium and chrysanthemum leaves, followed by transferring to the SERS platform to perform analysis. The nearly linear fitting curve with a wide concentration range suggests the superior qualitative detection capability. Remarkably, two components and three components of the pesticides are readily identified in a rapid way. The approach provides the rapid analysis, low‐cost device, and portable and quantitative pesticide identification and offers a clear path to multicomponent analysis at a trace level.