bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple receptor tyrosine kinases regulate dengue infection of hepatocytes
Authors: Bourgeois Natasha M. , Wei Ling , Ho Nhi N. T. , Neal Maxwell L. , Seferos Denali , Tongogara Tinotenda , Mast Fred D. , Aitchison John D. , Kaushansky Alexis
Published: March 2024

Introduction

Dengue is an arboviral disease causing severe illness in over 500,000 people each year. Currently, there is no way to constrain dengue in the clinic. Host kinase regulators of dengue virus (DENV) infection have the potential to be disrupted by existing therapeutics to prevent infection and/or disease progression.

Methods

To evaluate kinase regulation of DENV infection, we performed kinase regression (KiR), a machine learning approach that predicts kinase regulators of infection using existing drug-target information and a small drug screen. We infected hepatocytes with DENV in vitro in the presence of a panel of 38 kinase inhibitors then quantified the effect of each inhibitor on infection rate. We employed elastic net regularization on these data to obtain predictions of which of 291 kinases are regulating DENV infection.

Results

Thirty-six kinases were predicted to have a functional role. Intriguingly, seven of the predicted kinases – EPH receptor A4 (EPHA4), EPH receptor B3 (EPHB3), EPH receptor B4 (EPHB4), erb-b2 receptor tyrosine kinase 2 (ERBB2), fibroblast growth factor receptor 2 (FGFR2), Insulin like growth factor 1 receptor (IGF1R), and ret proto-oncogene (RET) – belong to the receptor tyrosine kinase (RTK) family, which are already therapeutic targets in the clinic. We demonstrate that predicted RTKs are expressed at higher levels in DENV infected cells. Knockdown of EPHB4, ERBB2, FGFR2, or IGF1R reduces DENV infection in hepatocytes. Finally, we observe differential temporal induction of ERBB2 and IGF1R following DENV infection, highlighting their unique roles in regulating DENV.

Discussion

Collectively, our findings underscore the significance of multiple RTKs in DENV infection and advocate further exploration of RTK-oriented interventions against dengue.
Seismic attenuation and stress on the San Andreas Fault at Parkfield: are we critical yet?
Authors: Malagnini Luca , Nadeau Robert M. , Parsons Tom
Published: March 2024

The Parkfield transitional segment of the San Andreas Fault (SAF) is characterized by the production of frequent quasi-periodical M6 events that break the very same asperity. The last Parkfield mainshock occurred on 28 September 2004, 38 years after the 1966 earthquake, and after the segment showed a ∼22 years average recurrence time. The main reason for the much longer interevent period between the last two earthquakes is thought to be the reduction of the Coulomb stress from the M6.5 Coalinga earthquake of 2 May 1983, and the M6 Nuñez events of June 11th and 22 July 1983. Plausibly, the transitional segment of the SAF at Parkfield is now in the late part of its seismic cycle and current observations may all be relative to a state of stress close to criticality. However, the behavior of the attenuation parameter in the last few years seems substantially different from the one that characterized the years prior to the 2004 mainshock. A few questions arise: (i) Does a detectable preparation phase for the Parkfield mainshocks exist, and is it the same for all events? (ii) How dynamically/kinematically similar are the quasi-periodic occurrences of the Parkfield mainshocks? (iii) Are some dynamic/kinematic characteristics of the next mainshock predictable from the analysis of current data? (e.g., do we expect the epicenter of the next failure to be co-located to that of 2004?) (iv) Should we expect the duration of the current interseismic period to be close to the 22-year “undisturbed” average value? We respond to the questions listed above by analyzing the non-geometric attenuation of direct S-waves along the transitional segment of the SAF at Parkfield, in the close vicinity of the fault plane, between January 2001 and November 2023. Of particular interest is the preparatory behavior of the attenuation parameter as the 2004 mainshock approached, on both sides of the SAF. We also show that the non-volcanic tremor activity modulates the seismic attenuation in the area, and possibly the seismicity along the Parkfield fault segment, including the occurrence of the mainshocks.
Formative assessment in higher education: an exploratory study within programs for professionals in education
Authors: Parmigiani Davide , Nicchia Elisabetta , Murgia Emiliana , Ingersoll Marcea
Published: March 2024

This study explores how prospective professionals in higher education can learn about and apply formative assessment methods relevant to their future educational workplaces. In the academic year 2022–23, 156 pre-service teachers, social workers, and heads of social services took part in a three-stage mixed-method study on university learning experiences involving formative assessment practices. They were exposed to self-, peer-, and group-assessment strategies. Data collected after each stage revealed participants’ perspectives on each method. Findings show that students who engaged in formative assessment comprehended assessment complexity and were motivated to use diverse assessment forms. Formative assessment proves effective for both evaluation and development, supporting higher education students in honing assessment competencies for future professional roles in educational and social sectors.
Distinct effects of rosuvastatin and rosuvastatin/ezetimibe on senescence markers of CD8+ T cells in patients with type 2 diabetes mellitus: a randomized controlled trial
Authors: Ju Sang-Hyeon , Lim Joung Youl , Song Minchul , Kim Ji Min , Kang Yea Eun , Yi Hyon-Seung , Joung Kyong Hye , Lee Ju Hee , Kim Hyun Jin , Ku Bon Jeong
Published: March 2024

Objectives

Chronic low-grade inflammation is widely recognized as a pathophysiological defect contributing to β-cell failure in type 2 diabetes mellitus (T2DM). Statin therapy is known to ameliorate CD8+ T cell senescence, a mediator of chronic inflammation. However, the additional immunomodulatory roles of ezetimibe are not fully understood. Therefore, we investigated the effect of statin or statin/ezetimibe combination treatment on T cell senescence markers.

Methods

In this two-group parallel and randomized controlled trial, we enrolled 149 patients with T2DM whose low-density lipoprotein cholesterol (LDL-C) was 100 mg/dL or higher. Patients were randomly assigned to either the rosuvastatin group (N=74) or the rosuvastatin/ezetimibe group (N=75). The immunophenotype of peripheral blood mononuclear cells and metabolic profiles were analyzed using samples from baseline and post-12 weeks of medication.

Results

The fractions of CD8+CD57+ (senescent CD8+ T cells) and CD4+FoxP3+ (Treg) significantly decreased after intervention in the rosuvastatin/ezetimibe group (−4.5 ± 14.1% and −1.2 ± 2.3%, respectively), while these fractions showed minimal change in the rosuvastatin group (2.8 ± 9.4% and 1.4 ± 1.5%, respectively). The degree of LDL-C reduction was correlated with an improvement in HbA1c (R=0.193, p=0.021). Changes in the CD8+CD57+ fraction positively correlated with patient age (R=0.538, p=0.026). Notably, the fraction change in senescent CD8+ T cells showed no significant relationship with changes in either HbA1c (p=0.314) or LDL-C (p=0.592). Finally, the ratio of naïve to memory CD8+ T cells increased in the rosuvastatin/ezetimibe group (p=0.011), but not in the rosuvastatin group (p=0.339).

Conclusions

We observed a reduction in senescent CD8+ T cells and an increase in the ratio of naive to memory CD8+ T cells with rosuvastatin/ezetimibe treatment. Our results demonstrate the immunomodulatory roles of ezetimibe in combination with statins, independent of improvements in lipid or HbA1c levels.
Comparison of saline infusion test and captopril challenge test in the diagnosis of Chinese with primary aldosteronism in different age groups
Authors: Sun Kaiwen , Gong Minghui , Yu Yang , Yang Minghui , Zhang Ying , Jiang Yinong , Song Wei
Published: March 2024

Background

To explore the diagnostic accuracy and the optimal cutoff value between the saline infusion test (SIT) and captopril challenge test (CCT) [including the value and suppression of plasma aldosterone concentration (PAC)] for primary aldosteronism (PA) diagnosing.

Methods

A total of 318 patients with hypertension were consecutively enrolled, including 126 patients with PA and 192 patients with essential hypertension (EH), in this observational study. The characteristics of patients and laboratory examinations were collected and compared. The comparison between SIT and CCT was carried by drawing the receiver operator characteristic curve (ROC) and calculating the area under the curve (AUC) to explore the diagnostic accuracy and the optimal cutoff value.

Results

The average age was 51.59 ± 10.43 in the PA group and 45.72 ± 12.44 in the EH group (p<0.05). The optimal cutoff value was 10.7 ng/dL for post-CCT PAC, 6.8 ng/dL for post-SIT PAC, and 26.9% for suppression of post-CCT PAC. The diagnostic value of post-CCT PAC was the highest with 0.831 for the AUC and 0.552 for the Youden index. The optimal cutoff value for patients who were <50 years old was 11.5 ng/dL for post-CCT PAC and 8.4 ng/dL for post-SIT PAC. The suppression of post-CCT PAC turned to 18.2% for those of age 50 or older.

Conclusion

Compared with SIT, CCT had a higher diagnostic value when post-CCT PAC was used as the diagnostic criterion in Chinese people, while the selection of diagnostic thresholds depended on patient age.
Deciphering thyroid function and CIMT: a Mendelian randomization study of the U-shaped influence mediated by apolipoproteins
Authors: Zhang Ming-zhu , Zhao Cong , Xing Xiao-ming , Lv Jie
Published: March 2024

Background

Carotid Intima-Media Thickness (CIMT) is a key marker for atherosclerosis, with its modulation being crucial for cardiovascular disease (CVD) risk assessment. While thyroid function’s impact on cardiovascular health is recognized, the causal relationship and underlying mechanisms influencing CIMT remain to be elucidated.

Methods

In this study, Mendelian Randomization (MR) was employed to assess the causal relationship between thyroid function and CIMT. Thyroid hormone data were sourced from the Thyroidomics Consortium, while lipid traits and CIMT measurements were obtained from the UK Biobank. The primary analysis method was a two-sample MR using multiplicative random effects inverse variance weighting (IVW-MRE). Additionally, the study explored the influence of thyroid hormones on lipid profiles and assessed their potential mediating role in the thyroid function-CIMT relationship through multivariate MR analysis.

Results

The study revealed that lower levels of Free Thyroxine (FT4) within the normal range are significantly associated with increased CIMT. This association was not observed with free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), or TPOAb. Additionally, mediation analysis suggested that apolipoprotein A-I and B are involved in the relationship between thyroid function and CIMT. The findings indicate a potential U-shaped curve relationship between FT4 levels and CIMT, with thyroid hormone supplementation in hypothyroid patients showing benefits in reducing CIMT.

Conclusion

This research establishes a causal link between thyroid function and CIMT using MR methods, underscoring the importance of monitoring thyroid function for early cardiovascular risk assessment. The results advocate for the consideration of thyroid hormone supplementation in hypothyroid patients as a strategy to mitigate the risk of carotid atherosclerosis. These insights pave the way for more targeted approaches in managing patients with thyroid dysfunction to prevent cardiovascular complications.
Proinflammatory cytokines suppress nonsense-mediated RNA decay to impair regulated transcript isoform processing in pancreatic β cells
Authors: Ghiasi Seyed M. , Marchetti Piero , Piemonti Lorenzo , Nielsen Jens H. , Porse Bo T. , Mandrup-Poulsen Thomas , Rutter Guy A.
Published: March 2024

Introduction

Proinflammatory cytokines are implicated in pancreatic ß cell failure in type 1 and type 2 diabetes and are known to stimulate alternative RNA splicing and the expression of nonsense-mediated RNA decay (NMD) components. Here, we investigate whether cytokines regulate NMD activity and identify transcript isoforms targeted in ß cells.

Methods

A luciferase-based NMD reporter transiently expressed in rat INS1(832/13), human-derived EndoC-ßH3, or dispersed human islet cells is used to examine the effect of proinflammatory cytokines (Cyt) on NMD activity. The gain- or loss-of-function of two key NMD components, UPF3B and UPF2, is used to reveal the effect of cytokines on cell viability and function. RNA-sequencing and siRNA-mediated silencing are deployed using standard techniques.

Results

Cyt attenuate NMD activity in insulin-producing cell lines and primary human ß cells. These effects are found to involve ER stress and are associated with the downregulation of UPF3B. Increases or decreases in NMD activity achieved by UPF3B overexpression (OE) or UPF2 silencing raise or lower Cyt-induced cell death, respectively, in EndoC-ßH3 cells and are associated with decreased or increased insulin content, respectively. No effects of these manipulations are observed on glucose-stimulated insulin secretion. Transcriptomic analysis reveals that Cyt increases alternative splicing (AS)-induced exon skipping in the transcript isoforms, and this is potentiated by UPF2 silencing. Gene enrichment analysis identifies transcripts regulated by UPF2 silencing whose proteins are localized and/or functional in the extracellular matrix (ECM), including the serine protease inhibitor SERPINA1/α-1-antitrypsin, whose silencing sensitizes ß-cells to Cyt cytotoxicity. Cytokines suppress NMD activity via UPR signaling, potentially serving as a protective response against Cyt-induced NMD component expression.

Conclusion

Our findings highlight the central importance of RNA turnover in ß cell responses to inflammatory stress.
Thyroid function and polycystic ovary syndrome: a Mendelian randomization study
Authors: Zhao Zhendan , Gao Yuehua , Pei Xiaoqing , Wang Wenhao , Wang Ruixian , Zhang Huawei
Published: March 2024

Background

Multiple evidence suggests that thyroid function is associated with polycystic ovary syndrome (PCOS), but whether thyroid function is causally related to PCOS is unclear. To investigate whether the association reflect causality, a Mendelian randomization (MR) analysis was conducted.

Methods

Single nucleotide polymorphisms (SNPs) involved in this study were acquired from The ThyroidOmics Consortium and the IEU Open Genome-wide association study (GWAS) database, respectively. In forward MR analysis, we included normal free thyroxine (FT4, n=49,269), normal thyroid-stimulating hormone (TSH, n=54,288), hypothyroidism (n=53,423) and hyperthyroidism (n=51,823) as exposure. The outcome was defined as PCOS in a sample size of 16,380,318 individuals. The exposure in the reverse MR analyses was chosen as PCOS, while the outcome consisted of the four phenotypes of thyroid function. The inverse-variance weighted (IVW) method was performed as the major analysis, supplemented by sensitivity analyses.

Results

The occurrence of PCOS was associated with increased risk of hyperthyroidism (IVW, OR=1.08, 95%CI=1.02-1.13, P=0.004). No evidence suggested that other phenotypes of thyroid function were related to PCOS.

Conclusions

Our findings demonstrate a cause-and-effect connection between PCOS and hyperthyroidism. The study established foundation for further investigation for interaction between thyroid function and PCOS.
Energy-efficient mobile node localization using CVA technology and SAI algorithm
Authors: Zhang Boliang , Shen Lu , Yao Jiahua , Luo Wuman , Tang Su-Kit
Published: March 2024

In the evolving landscape of the Internet of Things (IoT), Mobile Wireless Sensor Networks (MWSN) play a pivotal role, particularly in dynamic environments requiring mobile sensing capabilities. A primary challenge in MWSNs is achieving accurate node positioning with minimal energy consumption, as these networks often consist of battery-powered, mobile sensors where energy replenishment is difficult. This paper addresses the critical problem of energy-efficient node localization in MWSNs. We propose a novel positioning approach leveraging Cooperative Virtual Array (CVA) technology, which strategically utilizes the mobility of nodes to enhance positioning accuracy while conservatively using energy resources. The methodology revolves around optimizing the number of transceiver nodes, considering factors such as node moving speed, total energy consumption, and positioning errors. Central to our approach is the Signal Arrival and Interaction (SAI) algorithm, an innovative technique devised for efficient and precise mobile node localization, replacing traditional Time of Arrival (ToA) methods. Our simulations, conducted under various scenarios, demonstrate the significant advantages of the CVA-based positioning algorithm. Results show a marked reduction in energy consumption and robust performance in mobile node scenarios. Key findings include substantial improvements in localization accuracy and energy efficiency, highlighting the potential of our approach in enhancing the operational sustainability of MWSNs. The implications of this research are far-reaching for IoT applications, particularly those involving mobile sensors, such as in smart cities, industrial monitoring, and disaster management. By introducing a novel, energy-efficient positioning method, our work contributes to the advancement of MWSN technology, offering a sustainable solution to the challenge of mobile node localization.
Forest types outpaced tree species in centroid-based range shifts under global change
Authors: Abbasi Akane O. , Woodall Christopher W. , Gamarra Javier G. P. , Hui Cang , Picard Nicolas , Ochuodho Thomas , de-Miguel Sergio , Sahay Rajeev , Fei Songlin , Paquette Alain , Chen Han Y. H. , Catlin Ann Christine , Liang Jingjing
Published: March 2024

Introduction

Mounting evidence suggests that geographic ranges of tree species worldwide are shifting under global environmental changes. Little is known, however, about if and how these species’ range shifts may trigger the range shifts of various types of forests. Markowitz’s portfolio theory of investment and its broad application in ecology suggest that the range shift of a forest type could differ substantially from the range shifts of its constituent tree species.

Methods

Here, we tested this hypothesis by comparing the range shifts of forest types and the mean of their constituent species between 1970–1999 and 2000–2019 across Alaska, Canada, and the contiguous United States using continent-wide forest inventory data. We first identified forest types in each period using autoencoder neural networks and K-means cluster analysis. For each of the 43 forest types that were identified in both periods, we systematically compared historical range shifts of the forest type and the mean of its constituent tree species based on the geographic centroids of interpolated distribution maps.

Results

We found that forest types shifted at 86.5 km·decade-1 on average, more than three times as fast as the average of constituent tree species (28.8 km·decade-1). We showed that a predominantly positive covariance of the species range and the change of species relative abundance triggers this marked difference.

Discussion

Our findings provide an important scientific basis for adaptive forest management and conservation, which primarily depend on individual species assessment, in mitigating the impacts of rapid forest transformation under climate change.
Association of autoimmune and allergic diseases with senile cataract: a bidirectional two-sample Mendelian randomization study
Authors: Yuan Weichen , Li Xiangrui , Wang Guan , Qu Bo , Zhao Fangkun
Published: March 2024

Background

Many observational studies have been reported that patients with autoimmune or allergic diseases seem to have a higher risk of developing senile cataract, but the views are not consistent. In order to minimize the influence of reverse causality and potential confounding factors, we performed Mendelian Randomization (MR) analysis to investigate the genetic causal associations between autoimmune, allergic diseases and senile cataract.

Methods

Single nucleotide polymorphisms associated with ten common autoimmune and allergic diseases were obtained from the IEU Open genome-wide association studies (GWAS) database. Summary-level GWAS statistics for clinically diagnosed senile cataract were obtained from the FinnGen research project GWAS, which consisted of 59,522 individuals with senile cataracts and 312,864 control individuals. MR analysis was conducted using mainly inverse variance weighted (IVW) method and further sensitivity analysis was performed to test robustness.

Results

As for ten diseases, IVW results confirmed that type 1 diabetes (OR = 1.06; 95% CI = 1.05-1.08; p = 2.24×10-12), rheumatoid arthritis (OR = 1.05; 95% CI = 1.02-1.08; p = 1.83×10-4), hypothyroidism (OR = 2.4; 95% CI = 1.42-4.06; p = 1.12×10-3), systemic lupus erythematosus (OR = 1.02; 95% CI = 1.01-1.03; p = 2.27×10-3), asthma (OR = 1.02; 95% CI = 1.01-1.03; p = 1.2×10-3) and allergic rhinitis (OR = 1.07; 95% CI = 1.02-1.11; p = 2.15×10-3) were correlated with the risk of senile cataract. Celiac disease (OR = 1.04; 95% CI = 1.01-1.08; P = 0.0437) and atopic dermatitis (OR = 1.05; 95% CI = 1.01-1.10; P = 0.0426) exhibited a suggestive connection with senile cataract after Bonferroni correction. These associations are consistent across weighted median and MR Egger methods, with similar causal estimates in direction and magnitude. Sensitivity analysis further proved that these associations were reliable.

Conclusions

The results of the MR analysis showed that there were causal relationships between type 1 diabetes, rheumatoid arthritis, hypothyroidism, systemic lupus erythematosus, asthma, allergic rhinitis and senile cataract. To clarify the possible role of autoimmune and allergy in the pathophysiology of senile cataract, further studies are needed.
Origins and functions of eosinophils in two non-mucosal tissues
Authors: Day Katie S. , Rempel Lucas , Rossi Fabio M. V. , Theret Marine
Published: March 2024

Eosinophils are a type of granulocyte named after the presence of their eosin-stained granules. Traditionally, eosinophils have been best known to play prominent roles in anti-parasitic responses and mediating allergic reactions. Knowledge of their behaviour has expanded with time, and they are now recognized to play integral parts in the homeostasis of gastrointestinal, respiratory, skeletal muscle, adipose, and connective tissue systems. As such, they are implicated in a myriad of pathologies, and have been the target of several medical therapies. This review focuses on the lifespan of eosinophils, from their origins in the bone marrow, to their tissue-resident role. In particular, we wish to highlight the functions of eosinophils in non-mucosal tissues with skeletal muscle and the adipose tissues as examples, and to discuss the current understanding of their participation in diseased states in these tissues.
Effects and potential mechanisms of exercise and physical activity on eye health and ocular diseases
Authors: Zhang Qiuxiang , Jiang Yuxian , Deng Chaohua , Wang Junming
Published: March 2024

In the field of eye health, the profound impact of exercise and physical activity on various ocular diseases has become a focal point of attention. This review summarizes and elucidates the positive effects of exercise and physical activities on common ocular diseases, including dry eye disease (DED), cataracts, myopia, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD). It also catalogues and offers exercise recommendations based on the varying impacts that different types and intensities of physical activities may have on specific eye conditions. Beyond correlations, this review also compiles potential mechanisms through which exercise and physical activity beneficially affect eye health. From mitigating ocular oxidative stress and inflammatory responses, reducing intraocular pressure, enhancing mitochondrial function, to promoting ocular blood circulation and the release of protective factors, the complex biological effects triggered by exercise and physical activities reveal their substantial potential in preventing and even assisting in the treatment of ocular diseases. This review aims not only to foster awareness and appreciation for how exercise and physical activity can improve eye health but also to serve as a catalyst for further exploration into the specific mechanisms and key targets through which exercise impacts ocular health. Such inquiries are crucial for advancing innovative strategies for the treatment of eye diseases, thereby holding significant implications for the development of new therapeutic approaches.
The molecular detection of carbapenem markers with a two-levels amplification screening protocol: epidemiological and resistome insights
Authors: Calvo Maddalena , Migliorisi Giuseppe , Maugeri Gaetano , Bongiorno Dafne , Bonomo Carmelo , Nicitra Emanuele , Scalia Guido , Stefani Stefania
Published: March 2024

Objectives

Carbapenem-resistance is a challenging healthcare concern and require specific stewardship programs. Monitoring workflows include the identification from surveillance samples, such as rectal swabs. Although culture assays represent the gold standard, data report a significant effectiveness in detecting carbapenemases genes directly from rectal swabs. The aim of this study was to evaluate the REALQUALITY Carba-Screen kit (AB ANALITICA, Padova, Italy) in detecting carbapenemases genes directly from rectal swabs, also comparing its effectiveness to culture assays results. A next-generation sequencing (NGS) was performed to investigate the positive samples about resistance markers and sequence type (ST).

Methods

A number of 136 rectal swabs were collected from the University Hospital Policlinico of Catania critical wards. The samples simultaneously underwent culture and molecular assays (REALQUALITY Carba-Screen kit). The molecular method included two-steps. The first step (1 h and 6 min) rapidly excluded negative samples, while the second one (1 h and 6 min) included only positive samples for a resistance confirmation. All the positive culture samples underwent NGS analysis.

Results

Statistical evaluations demonstrated high sensitivity (100%) and detection rates (92.6%) for the REALQUALITY Carba-Screen kit, which mostly correlated to the standard workflow. All the culture positive results matched the positive molecular results, which were mainly confirmed by the NGS resistome analysis. The identified ST appeared to be diversified and different from the clinically significative strains of the same setting, furnishing interesting epidemiological evidence.

Conclusion

The molecular detection allowed a coordinate approach in a high-prevalence multi-drug-resistance area. The rapid identification with a multi-step procedure accelerated the infection control procedures, while the preliminary negative results reduced the overtreatment episodes. The molecular method efficacy was confirmed through the NGS. In conclusion, the molecular screening could initially lead to a more conservative approach, which may be reevaluated after a culture result about the microorganisms’ identification and susceptibility profile.
Co-inoculation of the endophytes Bacillus thuringiensis CAPE95 and Paenibacillus polymyxa CAPE238 promotes Tropaeolum majus L. growth and enhances its root bacterial diversity
Authors: Dal’Rio Isabella , Lopes Eliene dos Santos , Santaren Karen Caroline Ferreira , Rosado Alexandre Soares , Seldin Lucy
Published: March 2024

Tropaeolum majus L. is a versatile edible plant that is widely explored due to its medicinal properties and as a key element in intercropping systems. Its growth could be improved by the use of biofertilizers that can enhance nutrient uptake by the plant or provide tolerance to different abiotic and biotic stresses. In a previous study, 101 endophytes isolated from T. majus roots showed more than three plant growth-promoting (PGP) features in vitro, such as phosphate mineralization/solubilization, production of siderophores, antimicrobial substances and indole-related compounds, and presence of the nifH gene. To provide sustainable alternatives for biofertilization, the genomes of two promising endophytes—CAPE95 and CAPE238—were sequenced to uncover metabolic pathways related to biofertilization. Greenhouse experiments were conducted with 216 seeds and 60 seedlings, half co-inoculated with the endophytes (treatment) and half inoculated with 1X PBS (control), and the impact of the co-inoculation on the plant’s bacteriome was accessed through 16S rRNA gene metabarcoding. The strains CAPE95 and CAPE238 were taxonomically assigned as Bacillus thuringiensis and Paenibacillus polymyxa, respectively. Metabolic pathways related to the enhancement of nutrient availability (nitrogen fixation, sulfate-sulfur assimilation), biosynthesis of phytohormones (indole-3-acetic acid precursors) and antimicrobial substances (bacilysin, paenibacillin) were found in their genomes. The in vivo experiments showed that treated seeds exhibited faster germination, with a 20.3% higher germination index than the control on the eleventh day of the experiment. Additionally, treated seedlings showed significantly higher plant height and leaf diameters (p < 0.05). The bacterial community of the treated plants was significantly different from that of the control plants (p < 0.001) and showed a higher richness and diversity of species (Chao and Shannon indexes, p < 0.001). A higher relative abundance of potential synergistic PGP bacteria was also shown in the bacteriome of the treated plants, such as Lysinibacillus and Geobacter. For the first time, co-inoculation of B. thuringiensis and P. polymyxa was shown to have great potential for application as a biofertilizer to T. majus plants. The bacterial consortium used here could also be explored in other plant species in the future.
Pathogenicity of Streptococcus iniae causing mass mortalities of yellow catfish (Tachysurus fulvidraco) and its induced host immune response
Authors: Xu Hongsen , Zhu Nengbin , Chen Yiling , Yue Huamei , Zhuo Meiqin , Wangkahart Eakapol , Liang Qianrong , Wang Rui
Published: March 2024

The outbreak of mass mortality occurred in Tachysurus fulvidraco farm in Hubei province of China. The pathogenic strain of Streptococcus iniae (termed 2022SI08) was isolated and identified from diseased T. fulvidraco, based on morphological, physiological, and biochemical characteristics, as well as 16S rRNA gene sequence and phylogenetic analysis. Further, the whole genome of isolate S. iniae was sequenced and predicted to contain one single circular chromosome of 1,776,777 bp with a GC content of 37.14%. The genomic sequence analysis showed that 2022SI08 was positive for 204 virulent and 127 antibiotic resistant genes. The experimental challenge demonstrated the high pathogenicity of the retrieved isolate of S. iniae, with a median lethal dosage (LD50) 9.53 × 105 CFU/g. Histopathological examination indicated that the 2022SI08 strain could induce extensive tissue cell degeneration, necrosis, hemorrhage, and inflammation in the skin, gill, fin, spleen, liver, kidney, intestine, eye, and brain. Moreover, the innate immune enzyme activities in serum such as acid phosphatase and alkaline phosphatase were increased significantly at 24 and 48 h post infection (hpi) and then decreased at 168 hpi. The transcriptional profile of immune associated gene in T. fulvidraco following bacterial infection was detected at each point of time, and the results revealed clear transcriptional activation of those genes, which proving their reacting and regulatory role during the response of the host against S. iniae infection. The results revealed that S. iniae was an etiological agent in the mass mortalities of T. fulvidraco and this research will be conducive for increasing our understanding on pathogenesis and host defensive system in S. iniae invasion.
Representational maps in the brain: concepts, approaches, and applications
Authors: Noda Takahiro , Aschauer Dominik F. , Chambers Anna R. , Seiler Johannes P.-H. , Rumpel Simon
Published: March 2024

Neural systems have evolved to process sensory stimuli in a way that allows for efficient and adaptive behavior in a complex environment. Recent technological advances enable us to investigate sensory processing in animal models by simultaneously recording the activity of large populations of neurons with single-cell resolution, yielding high-dimensional datasets. In this review, we discuss concepts and approaches for assessing the population-level representation of sensory stimuli in the form of a representational map. In such a map, not only are the identities of stimuli distinctly represented, but their relational similarity is also mapped onto the space of neuronal activity. We highlight example studies in which the structure of representational maps in the brain are estimated from recordings in humans as well as animals and compare their methodological approaches. Finally, we integrate these aspects and provide an outlook for how the concept of representational maps could be applied to various fields in basic and clinical neuroscience.
Comparative efficacy of acupuncture point stimulation treatments for dialysis patients with uremic pruritus: a systematic review and network meta-analysis
Authors: Lu Po-Hsuan , Chuo Hui-En , Chiu Ling-Ya , Lai Chien-Cheng , Wang Jen-Yu , Lu Ping-Hsun
Published: March 2024

Background

Uremic pruritus (UP) is a common complication of chronic kidney disease that causes sleep disturbances and increases all-cause mortality. Currently, the first-line medications for UP exhibit inadequate pruritus control with adverse effects. Various acupuncture point stimulation treatments (APSTs) have been shown to be effective as adjuvant therapies in UP, and a network meta-analysis can offer relative efficacy estimates for treatments for which head-to-head studies have not been performed.

Methods

We conducted a random-effects network meta-analysis on a consistency model to compare the different APSTs for UP. The primary outcomes were the mean visual analog scale (VAS) score and effectiveness rate (ER).

Results

The network meta-analysis retrieved 27 randomized controlled trials involving 1969 patients. Compared with conventional treatment alone, combination treatment with acupuncture (mean difference, −2.63; 95% confidence interval, −3.71 to −1.55) was the most effective intervention in decreasing VAS scores, followed by acupoint injection and massage (mean difference, −2.04; 95% confidence interval, −3.96 to −0.12). In terms of the ER, conventional treatment with acupuncture and hemoperfusion (risk ratio, 14.87; 95% confidence interval, 2.18 to 101.53) was superior to other therapeutic combinations. Considering the VAS score and ER, combination treatment with acupoint injection and massage showed benefits in treating UP.

Conclusion

Our network meta-analysis provided relative efficacy data for choosing the optimal adjuvant treatment for UP. Combined treatment with acupuncture was more effective than conventional treatment only and was the most promising intervention for treating UP.

Systematic review registration: PROSPERO (CRD42023425739: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023425739).
Predictors of overload in parents of children with neuromuscular diseases
Authors: Rodríguez A. A. , García M. , Martínez Oscar , López-Paz J. F. , García I. , Pérez-Nuñez P. , Amayra I.
Published: March 2024

Introduction

Parents of children with neuromuscular diseases experience multiple difficulties in their daily lives that affect their physical and psychological health. The risk factors for these health issues have not been sufficiently investigated. Therefore, the aim of this study was to analyze the potential predictors of overload in these parents, including QoL, somatic symptomatology, life satisfaction, psychological adjustment and certain sociodemographic variables.

Methods

A cross-sectional research study was conducted among parents who are caregivers for children with NMD in Spain. A convenience sample of 110 parents who were contacted by associations and hospitals was used. Variables were evaluated using the sociodemographic questionnaire, CarerQol-7D, PHQ-15, Barthel Index, Psychological Adaptation Scale, Zarit Overload Scale and Satisfaction with Life Scale.

Results

One of the most relevant findings of the present study is the identification of 3 overload groups (mild to moderate, moderate to severe, and severe overload) based on life satisfaction and somatic symptom scores within the predictive model of the discriminate analysis. Wilk’s lambda of the discriminant function was 0.568, χ2 (2, n = 55) = 8.815, p < 0.001.

Discussion

This study presents a model that reveals the influence of unemployment, having a child with a severe level of dependency, the presence of somatic symptomatology and life satisfaction on caregiver overload. Likewise, the caregiver’s self-esteem could be a protective factor against overload.
Multiple sclerosis in a 4-year-old boy: a case report and literature review
Authors: Arkar Ula , Vipotnik Vesnaver Tina , Osredkar Damjan , Perković Benedik Mirjana , Bizjak Neli
Published: March 2024

Pediatric onset multiple sclerosis (POMS) in the very young is a very rare entity and presents a difficult diagnostic challenge due to overlapping signs and symptoms with other diseases. We present a 4-year-old boy who initially presented with right-sided hemiparesis and demyelinating lesions on MRI. Follow-up MRI examinations 3 and 6 months later revealed new demyelinating lesions. Ten months after initial presentation, he presented with right-sided hemiparesis, central facial nerve palsy on the right side and new demyelinating lesions on MRI. Two clinical events and new MRI lesions on follow-up MRIs confirmed the diagnosis of POMS. He was treated with rituximab and experienced no further relapses or radiological progression during the follow-up period.
Combined cortical thickness and blink reflex recovery cycle to differentiate essential tremor with and without resting tremor
Authors: Calomino Camilla , Quattrone Andrea , Bianco Maria Giovanna , Nisticò Rita , Buonocore Jolanda , Crasà Marianna , Vaccaro Maria Grazia , Sarica Alessia , Quattrone Aldo
Published: March 2024

Objective

To investigate the performance of structural MRI cortical and subcortical morphometric data combined with blink-reflex recovery cycle (BRrc) values using machine learning (ML) models in distinguishing between essential tremor (ET) with resting tremor (rET) and classic ET.

Methods

We enrolled 47 ET, 43 rET patients and 45 healthy controls (HC). All participants underwent brain 3 T-MRI and BRrc examination at different interstimulus intervals (ISIs, 100–300 msec). MRI data (cortical thickness, volumes, surface area, roughness, mean curvature and subcortical volumes) were extracted using Freesurfer on T1-weighted images. We employed two decision tree-based ML classification algorithms (eXtreme Gradient Boosting [XGBoost] and Random Forest) combining MRI data and BRrc values to differentiate between rET and ET patients.

Results

ML models based exclusively on MRI features reached acceptable performance (AUC: 0.85–0.86) in differentiating rET from ET patients and from HC. Similar performances were obtained by ML models based on BRrc data (AUC: 0.81–0.82 in rET vs. ET and AUC: 0.88–0.89 in rET vs. HC). ML models combining imaging data (cortical thickness, surface, roughness, and mean curvature) together with BRrc values showed the highest classification performance in distinguishing between rET and ET patients, reaching AUC of 0.94 ± 0.05. The improvement in classification performances when BRrc data were added to imaging features was confirmed by both ML algorithms.

Conclusion

This study highlights the usefulness of adding a simple electrophysiological assessment such as BRrc to MRI cortical morphometric features for accurately distinguishing rET from ET patients, paving the way for a better classification of these ET syndromes.
Urinary incontinence rehabilitation of after radical prostatectomy: a systematic review and network meta-analysis
Authors: Yu Kai , Bu Fan , Jian Tengteng , Liu Zejun , Hu Rui , Chen Sunmeng , Lu Ji
Published: March 2024

Purpose

The aim of this study is to provide treatment for patients with urinary incontinence at different periods after radical prostatectomy.

Methods

The PubMed, Embase, Cochrane, and Web of Science were searched for all literature on the effectiveness on urinary control after radical prostate cancer between the date of database creation and 15 November 2023 and performed a quality assessment. A network meta-analysis was performed using RevMan 5.3 and Stata 17.0 software and evaluated using the surface under the cumulative ranking curve.

Results

The results of the network meta-analysis showed that pelvic floor muscle therapy including biofeedback with professional therapist–guided treatment demonstrated better results at 1 month to 6 months; electrical stimulation, biofeedback, and professional therapist guidance may be more effective at 3 months of treatment; professional therapist–guided recovery may be less effective at 6 months of treatment; and combined therapy demonstrated better results at 1 year of treatment. During the course of treatment, biofeedback with professional therapist–guided treatment may have significant therapeutic effects in the short term after surgery, but, in the long term, the combination of multiple treatments (pelvic floor muscle training+ routine care + biofeedback + professional therapist–guided treatment + electrical nerve stimulation therapy) may address cases of urinary incontinence that remain unrecovered long after surgery.

Conclusion

In general, all treatment methods improve the different stages of functional recovery of the pelvic floor muscles. However, in the long term, there are no significant differences between the treatments. Given the cost-effectiveness, pelvic floor muscle training + routine care + biofeedback + professional therapist–guided treatment + electrical nerve stimulation therapy within 3 months and pelvic floor muscle + routine care after 3 months may be a more economical option to treat urinary incontinence.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=331797, identifier CRD42022331797.
Effect of NAT2, GSTM1 and CYP2E1 genetic polymorphisms on plasma concentration of isoniazid and its metabolites in patients with tuberculosis, and the assessment of exposure-response relationships
Authors: Ulanova Viktorija , Kivrane Agnija , Viksna Anda , Pahirko Leonora , Freimane Lauma , Sadovska Darja , Ozere Iveta , Cirule Andra , Sevostjanovs Eduards , Grinberga Solveiga , Bandere Dace , Ranka Renate
Published: March 2024

Objectives: Isoniazid is a key drug in the chemotherapy of tuberculosis (TB), however, interindividual variability in pharmacokinetic parameters and drug plasma levels may affect drug responses including drug induced hepatotoxicity. The current study investigated the relationships between isoniazid exposure and isoniazid metabolism-related genetic factors in the context of occurrence of drug induced hepatotoxicity and TB treatment outcomes.

Methods: Demographic characteristics and clinical information were collected in a prospective TB cohort study in Latvia (N = 34). Time to sputum culture conversion (tSCC) was used as a treatment response marker. Blood plasma concentrations of isoniazid (INH) and its metabolites acetylisoniazid (AcINH) and isonicotinic acid (INA) were determined at three time points (pre-dose (0 h), 2 h and 6 h after drug intake) using liquid chromatography-tandem mass spectrometry. Genetic variations of three key INH-metabolizing enzymes (NAT2, CYP2E1, and GSTM1) were investigated by application PCR- and Next-generation sequencing-based methods. Depending on variables, group comparisons were performed by Student’s t-test, one-way ANOVA, Mann-Whitney-Wilcoxon, and Kruskal-Wallis tests. Pearson correlation coefficient was calculated for the pairs of normally distributed variables; model with rank transformations were used for non-normally distributed variables. Time-to-event analysis was performed to analyze the tSCC data. The cumulative probability of tSCC was obtained using Kaplan-Meier estimators. Cox proportional hazards models were fitted to estimate hazard rate ratios of successful tSCC.

Results: High TB treatment success rate (94.1%) was achieved despite the variability in INH exposure. Clinical and demographic factors were not associated with either tSCC, hepatotoxicity, or INH pharmacokinetics parameters. Correlations between plasma concentrations of INH and its metabolites were NAT2 phenotype-dependent, while GSTM1 genetic variants did not showed any effects. CYP2E1*6 (T > A) allelic variant was associated with INH pharmacokinetic parameters. Decreased level of AcINH was associated with hepatotoxicity, while decreased values of INA/INH and AcINH/INH were associated with month two sputum culture positivity.

Conclusion: Our findings suggest that CYP2E1, but not GSTM1, significantly affects the INH pharmacokinetics along with NAT2. AcINH plasma level could serve as a biomarker for INH-related hepatotoxicity, and the inclusion of INH metabolite screening in TB therapeutic drug monitoring could be beneficial in clinical studies for determination of optimal dosing strategies.
AI-assisted literature exploration of innovative Chinese medicine formulas
Authors: Chung Meng-Chi , Su Li-Jen , Chen Chien-Lin , Wu Li-Ching
Published: March 2024

Objective: Our study provides an innovative approach to exploring herbal formulas that contribute to the promotion of sustainability and biodiversity conservation. We employ data mining, integrating keyword extraction, association rules, and LSTM-based generative models to analyze classical Traditional Chinese Medicine (TCM) texts. We systematically decode classical Chinese medical literature, conduct statistical analyses, and link these historical texts with modern pharmacogenomic references to explore potential alternatives.

Methods: We present a novel iterative keyword extraction approach for discerning diverse herbs in historical TCM texts from the Pu-Ji Fang copies. Utilizing association rules, we uncover previously unexplored herb pairs. To bridge classical TCM herbal pairs with modern genetic relationships, we conduct gene-herb searches in PubMed and statistically validate this genetic literature as supporting evidence. We have expanded on the present work by developing a generative language model for suggesting innovative TCM formulations based on textual herb combinations.

Results: We collected associations with 7,664 PubMed cross-search entries for gene-herb and 934 for Shenqifuzheng Injection as a positive control. We analyzed 16,384 keyword combinations from Pu-Ji Fang’s 426 volumes, employing statistical methods to probe gene-herb associations, focusing on examining differences among the target genes and Pu-Ji Fang herbs.

Conclusion: Analyzing Pu-Ji Fang reveals a historical focus on flavor over medicinal aspects in TCM. We extend our work on developing a generative model from classical textual keywords to rapidly produces novel herbal compositions or TCM formulations. This integrated approach enhances our comprehension of TCM by merging ancient text analysis, modern genetic research, and generative modeling.