bluuebunny/crossref_metadata_2025 huggingface dataset:
Myositis-associated antibodies predict the severity of lung involvement in adult patients with inflammatory myositis − a cohort study of 70 adult patients with myositis in a single center
Authors: Marklund Josefin , Hanna Balsam , Jin Tao , Pullerits Rille
Published: March 2024

Introduction

Idiopathic inflammatory myopathies (IIMs) encompass a diverse group of diseases characterized by considerable variability in clinical manifestations, antibody profiles, and responsiveness to immunosuppressive therapies. This study aimed to investigate the association between organ involvement and distinct myositis autoantibodies in individuals with IIM in a single-center cohort.

Methods

Patients with ICD diagnoses M33.1, M33.2, M33.9, or M609 who (1) had been tested with Euroline blot assay for myositis autoantibodies and (2) met the classification criteria of definite/probable polymyositis (PM) or dermatomyositis (DM), anti-synthetase syndrome (ASS), or inclusion body myositis (IBM) were included. Medical journals were retrospectively examined with respect to clinical disease features.

Results

Seventy patients (median age 58 years; 66% females) were included and represented the following diagnosis: PM (n = 23), DM (n = 21), ASS (n = 23), and IBM (n = 3). Most of the patients (87%) presented a muscle biopsy indicative of myositis. The presence of autoantibodies was as follows: myositis-specific antibodies, MSA (n = 53), myositis-associated antibodies, MAA (n = 33), both MSA + MAA (n = 24), MSA only (n = 29), MAA only (n = 9), no MSA, or MAA (n = 8). Anti-Jo-1 was the most common MSA (19%), whereas the most common MAA was anti-Ro/SSA52 (31%). We observed a significant association between antibody patterns and lung disease. In our cohort, 47% of the patients in the whole study group, 86% of patients with anti-SSA52, and 100% with anti-Jo-1 had pulmonary involvement. Patients with both MSA and MAA had a higher incidence of lung disease and decreased CO-diffusion capacity. This was especially prominent in anti-Ro/SSA52-positive patients. Interestingly, none of the patients suffered from lung disease if only antibodies against Mi-2α, Mi-2β, NXP2, HMGCR, and TIF1γ were present or no MSA/MAA were detected.

Discussion:

The simultaneous presence of both MAA and MSA indicates an increased risk of lung involvement in patients with inflammatory myopathies. The presence of any MAA, and especially anti-Ro/SSA52, is associated with more severe pulmonary disease. Our data suggest that MAA antibodies might be relevant markers for early detection and treatment of lung involvement in IIM.
Innovative research methodologies in the EU regulatory framework: an analysis of EMA qualification procedures from a pediatric perspective
Authors: Giannuzzi Viviana , Bertolani Arianna , Torretta Silvia , Reggiardo Giorgio , Toich Eleonora , Bonifazi Donato , Ceci Adriana
Published: March 2024

Introduction

The European Medicines Agency (EMA) offers scientific advice to support the qualification procedure of novel methodologies, such as preclinical and in vitro models, biomarkers, and pharmacometric methods, thereby endorsing their acceptability in medicine research and development (R&D). This aspect is particularly relevant to overcome the scarcity of data and the lack of validated endpoints and biomarkers in research fields characterized by small samples, such as pediatrics.

Aim

This study aimed to analyze the potential pediatric interest in methodologies qualified as “novel methodologies for medicine development” by the EMA.

Methods

The positive qualification opinions of novel methodologies for medicine development published on the EMA website between 2008 and 2023 were identified. Multi-level analyses were conducted to investigate data with a hierarchical structure and the effects of cluster-level variables and cluster-level variances and to evaluate their potential pediatric interest, defined as the possibility of using the novel methodology in pediatric R&D and the availability of pediatric data. The duration of the procedure, the type of methodology, the specific disease or disease area addressed, the type of applicant, and the availability of pediatric data at the time of the opinion release were also investigated.

Results

Most of the 27 qualifications for novel methodologies issued by the EMA (70%) were potentially of interest to pediatric patients, but only six of them reported pediatric data. The overall duration of qualification procedures with pediatric interest was longer than that of procedures without any pediatric interest (median time: 7 months vs. 3.5 months, respectively; p = 0.082). In parallel, qualification procedures that included pediatric data lasted for a longer period (median time: 8 months vs. 6 months, respectively; p = 0.150). Nephrology and neurology represented the main disease areas (21% and 16%, respectively), while endpoints, biomarkers, and registries represented the main types of innovative methodologies (32%, 26%, and 16%, respectively).

Discussion

Our results underscore the importance of implementing innovative methodologies in regulatory-compliant pediatric research activities. Pediatric-dedicated research infrastructures providing regulatory support and strategic advice during research activities could be crucial to the design of ad hoc pediatric methodologies or to extend and validate them for pediatrics.
Ribosomal mutations enable a switch between high fitness and high stress resistance in Listeria monocytogenes
Authors: Koomen Jeroen , Ma Xuchuan , Bombelli Alberto , Tempelaars Marcel H. , Boeren Sjef , Zwietering Marcel H. , den Besten Heidy M. W. , Abee Tjakko
Published: March 2024

Multiple stress resistant variants of Listeria monocytogenes with mutations in rpsU encoding ribosomal protein RpsU have previously been isolated after a single exposure to acid stress. These variants, including L. monocytogenes LO28 variant V14 with a complete deletion of the rpsU gene, showed upregulation of the general stress sigma factor Sigma B-mediated stress resistance genes and had a lower maximum specific growth rate than the LO28 WT, signifying a trade-off between stress resistance and fitness. In the current work V14 has been subjected to an experimental evolution regime, selecting for higher fitness in two parallel evolving cultures. This resulted in two evolved variants with WT-like fitness: 14EV1 and 14EV2. Comparative analysis of growth performance, acid and heat stress resistance, in combination with proteomics and RNA-sequencing, indicated that in both lines reversion to WT-like fitness also resulted in WT-like stress sensitivity, due to lack of Sigma B-activated stress defense. Notably, genotyping of 14EV1 and 14EV2 provided evidence for unique point-mutations in the ribosomal rpsB gene causing amino acid substitutions at the same position in RpsB, resulting in RpsB22Arg-His and RpsB22Arg-Ser, respectively. Combined with data obtained with constructed RpsB22Arg-His and RpsB22Arg-Ser mutants in the V14 background, we provide evidence that loss of function of RpsU resulting in the multiple stress resistant and reduced fitness phenotype, can be reversed by single point mutations in rpsB leading to arginine substitutions in RpsB at position 22 into histidine or serine, resulting in a WT-like high fitness and low stress resistance phenotype. This demonstrates the impact of genetic changes in L. monocytogenes’ ribosomes on fitness and stress resistance.
Characteristics of SARS-CoV-2 Omicron BA.5 variants in Shanghai after ending the zero-COVID policy in December 2022: a clinical and genomic analysis
Authors: Liu Pengcheng , Cai Jiehao , Tian He , Li Jingjing , Lu Lijuan , Xu Menghua , Zhu Xunhua , Fu Xiaomin , Wang Xiangshi , Zhong Huaqing , Jia Ran , Ge Yanling , Zhu Yanfeng , Zeng Mei , Xu Jin
Published: March 2024

Introduction

An unprecedented surge of Omicron infections appeared nationwide in China in December 2022 after the adjustment of the COVID-19 response policy. Here, we report the clinical and genomic characteristics of SARS-CoV-2 infections among children in Shanghai during this outbreak.

Methods

A total of 64 children with symptomatic COVID-19 were enrolled. SARS-CoV-2 whole genome sequences were obtained using next-generation sequencing (NGS) technology. Patient demographics and clinical characteristics were compared between variants. Phylogenetic tree, mutation spectrum, and the impact of unique mutations on SARS-CoV-2 proteins were analysed in silico.

Results

The genomic monitoring revealed that the emerging BA.5.2.48 and BF.7.14 were the dominant variants. The BA.5.2.48 infections were more frequently observed to experience vomiting/diarrhea and less frequently present cough compared to the BF.7.14 infections among patients without comorbidities in the study. The high-frequency unique non-synonymous mutations were present in BA.5.2.48 (N:Q241K) and BF.7.14 (nsp2:V94L, nsp12:L247F, S:C1243F, ORF7a:H47Y) with respect to their parental lineages. Of these mutations, S:C1243F, nsp12:L247F, and ORF7a:H47Y protein were predicted to have a deleterious effect on the protein function. Besides, nsp2:V94L and nsp12:L247F were predicted to destabilize the proteins.

Discussion

Further in vitro to in vivo studies are needed to verify the role of these specific mutations in viral fitness. In addition, continuous genomic monitoring and clinical manifestation assessments of the emerging variants will still be crucial for the effective responses to the ongoing COVID-19 pandemic.
Frequency-dependent alterations in functional connectivity in patients with Alzheimer’s Disease spectrum disorders
Authors: Hu Hanjun , Wang Luoyu , Abdul Sammad , Tang Xue , Feng Qi , Mu Yuzhu , Ge Xiuhong , Liao Zhengluan , Ding Zhongxiang
Published: March 2024

Background

In the spectrum of Alzheimer’s Disease (AD) and related disorders, the resting-state functional magnetic resonance imaging (rs-fMRI) signals within the cerebral cortex may exhibit distinct characteristics across various frequency ranges. Nevertheless, this hypothesis has not yet been substantiated within the broader context of whole-brain functional connectivity. This study aims to explore potential modifications in degree centrality (DC) and voxel-mirrored homotopic connectivity (VMHC) among individuals with amnestic mild cognitive impairment (aMCI) and AD, while assessing whether these alterations differ across distinct frequency bands.

Methods

This investigation encompassed a total of 53 AD patients, 40 aMCI patients, and 40 healthy controls (HCs). DC and VMHC values were computed within three distinct frequency bands: classical (0.01–0.08 Hz), slow-4 (0.027–0.073 Hz), and slow-5 (0.01–0.027 Hz) for the three respective groups. To discern differences among these groups, ANOVA and subsequent post hoc two-sample t-tests were employed. Cognitive function assessment utilized the mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA). Pearson correlation analysis was applied to investigate the associations between MMSE and MoCA scores with DC and VMHC.

Results

Significant variations in degree centrality (DC) were observed among different groups across diverse frequency bands. The most notable differences were identified in the bilateral caudate nucleus (CN), bilateral medial superior frontal gyrus (mSFG), bilateral Lobule VIII of the cerebellar hemisphere (Lobule VIII), left precuneus (PCu), right Lobule VI of the cerebellar hemisphere (Lobule VI), and right Lobule IV and V of the cerebellar hemisphere (Lobule IV, V). Likewise, disparities in voxel-mirrored homotopic connectivity (VMHC) among groups were predominantly localized to the posterior cingulate gyrus (PCG) and Crus II of the cerebellar hemisphere (Crus II). Across the three frequency bands, the brain regions exhibiting significant differences in various parameters were most abundant in the slow-5 frequency band.

Conclusion

This study enhances our understanding of the pathological and physiological mechanisms associated with AD continuum. Moreover, it underscores the importance of researchers considering various frequency bands in their investigations of brain function.
Case report: A cystic capillary hemangioma located at the conus medullaris mimicking hemangioblastoma
Authors: Sun Jiachen , Li Jiuhong , Ayi Ziba , Yang Feilong , Hu Junlin , Hui Xuhui , Chen Haifeng , He Jiaojiang
Published: March 2024

Capillary hemangiomas, usually found in skin and mucosal tissues, are rarely encountered within the spinal cord, presenting a significant diagnostic challenge. We report a rare case of intradural extramedullary capillary hemangioma at the conus medullaris in a 66-year-old female patient. Our initial diagnosis leaned towards a cystic hemangioblastoma based on MRI findings due to the presence of cystic formation with an enhanced mural nodule. However, surgical exploration and subsequent pathological examination revealed the lesion as a capillary hemangioma. To the authors’ knowledge, this case may represent the first documented instance of a spinal capillary hemangioma that mimics a cystic hemangioblastoma.
Analysis of risk factors related to the progression rate of hemifacial spasm
Authors: Xu Fei , Gu Pengju , Yuan Huan , Jiang Li , Xie Yanfeng , Shi Quanhong , Zhan Yan
Published: March 2024

Introduction

Although there have been many researches on the etiology and risk factors with the onset of hemifacial spasm, researches on the risk factors related to progression rate are limited. This study aims to analyze the risk factors related to the progression rate of hemifacial spasm.

Methods

The study enrolled 142 patients who underwent microvascular decompression for hemifacial spasm. Based on the duration and severity of symptoms, patients were classified into rapid progression group and slow progression group. To analyze risk factors, univariate and multivariate logistic regression analyses were conducted. Of 142 patients with hemifacial spasm, 90(63.3%) were classified as rapid progression group, 52(36.7%) were classified as slow progression group.

Results

In the univariate analysis, there were significant statistical differences between the two groups in terms of age of onset (P = 0.021), facial nerve angle (P < 0.01), hypertension (P = 0.01), presence of APOE ε4 expression (P < 0.01) and different degrees of brainstem compression in the Root Entry Zone (P < 0.01). In the multivariable analyses, there were significant statistical differences between the two groups in terms of age of symptom onset (P < 0.01 OR = 6.591), APOE ε4 (P < 0.01 OR = 5.691), brainstem compression (P = 0.006 OR = 5.620), and facial nerve angle (P < 0.01 OR = 5.758). Furthermore, we found no significant correlation between the severity of facial spasms and the progression rate of the disease (t = 2.47, P = 0.12>0.05).

Conclusion

According to our study, patients with facial nerve angle ≤ 96.5°, severer compression of the brainstem by offending vessels, an onset age > 45 years and positive expression of APOE ε4, may experience faster progression of hemifacial spasm.
Assessing resting-state brain functional connectivity in adolescents and young adults with narcolepsy using functional near-infrared spectroscopy
Authors: Wenhong Chen , Xiaoying Mo , Lingli Shi , Binyun Tang , Yining Wen , Mingming Zhao , Yian Lu , Lixia Qin , Wenyu Hu , Fengjin Pan
Published: March 2024

This study aimed to elucidate the alterations in the prefrontal cortex’s functional connectivity and network topology in narcolepsy patients using functional near-infrared spectroscopy (fNIRS). Twelve narcolepsy-diagnosed patients from Guangxi Zhuang Autonomous Region’s People’s Hospital Sleep Medicine Department and 11 matched healthy controls underwent resting fNIRS scans. Functional connectivity and graph theory analyses were employed to assess the prefrontal cortex network’s properties and their correlation with clinical features. Results indicated increased functional connectivity in these adolescent and young adult patients with narcolepsy, with significant variations in metrics like average degree centrality and node efficiency, particularly in the left middle frontal gyrus. These alterations showed correlations with clinical symptoms, including depression and sleep efficiency. However, the significance of these findings was reduced post False Discovery Rate adjustment, suggesting a larger sample size is needed for validation. In conclusion, the study offers initial observations that alterations in the prefrontal cortex’s functional connectivity may potentially act as a neurobiological indicator of narcolepsy, warranting further investigation with a larger cohort to substantiate these findings and understand the underlying mechanisms.
Graph neural network based on brain inspired forward-forward mechanism for motor imagery classification in brain-computer interfaces
Authors: Xue Qiwei , Song Yuntao , Wu Huapeng , Cheng Yong , Pan Hongtao
Published: March 2024

Introduction

Within the development of brain-computer interface (BCI) systems, it is crucial to consider the impact of brain network dynamics and neural signal transmission mechanisms on electroencephalogram-based motor imagery (MI-EEG) tasks. However, conventional deep learning (DL) methods cannot reflect the topological relationship among electrodes, thereby hindering the effective decoding of brain activity.

Methods

Inspired by the concept of brain neuronal forward-forward (F-F) mechanism, a novel DL framework based on Graph Neural Network combined forward-forward mechanism (F-FGCN) is presented. F-FGCN framework aims to enhance EEG signal decoding performance by applying functional topological relationships and signal propagation mechanism. The fusion process involves converting the multi-channel EEG into a sequence of signals and constructing a network grounded on the Pearson correlation coeffcient, effectively representing the associations between channels. Our model initially pre-trains the Graph Convolutional Network (GCN), and fine-tunes the output layer to obtain the feature vector. Moreover, the F-F model is used for advanced feature extraction and classification.

Results and discussion

Achievement of F-FGCN is assessed on the PhysioNet dataset for a four-class categorization, compared with various classical and state-of-the-art models. The learned features of the F-FGCN substantially amplify the performance of downstream classifiers, achieving the highest accuracy of 96.11% and 82.37% at the subject and group levels, respectively. Experimental results affirm the potency of FFGCN in enhancing EEG decoding performance, thus paving the way for BCI applications.
Cuproptosis in stroke: focusing on pathogenesis and treatment
Authors: Xing Liwei , Wang Zhifeng , Hao Zhihui , Pan Pan , Yang Aiming , Wang Jian
Published: March 2024

Annually, more than 15 million people worldwide suffer from stroke, a condition linked to high mortality and disability rates. This disease significantly affects daily life, impairing everyday functioning, executive function, and cognition. Moreover, stroke severely restricts patients’ ability to perform daily activities, diminishing their overall quality of life. Recent scientific studies have identified cuproptosis, a newly discovered form of cell death, as a key factor in stroke development. However, the role of cuproptosis in stroke remains unclear to researchers. Therefore, it is crucial to investigate the mechanisms of cuproptosis in stroke’s pathogenesis. This review examines the physiological role of copper, the characteristics and mechanisms of cuproptosis, the differences and similarities between cuproptosis and other cell death types, and the pathophysiology of cuproptosis in stroke, focusing on mitochondrial dysfunction and immune infiltration. Further research is necessary to understand the relationship between previous strokes and cuproptosis and to clarify the mechanisms behind these associations.
Computer modeling of digestive processes in the alimentary tract and their physiological regulation mechanisms: closing the gap between digestion models and in vivo behavior
Authors: van Aken George A.
Published: March 2024

Introduction

A model has been developed for in silico simulation of digestion and its physiological feedback mechanisms.

Methods

The model is based on known physiology described in the literature and is able to describe the complexity of many simultaneous processes related to food digestion.

Results

Despite the early stage of development of the model, it already encompasses a large number of processes that occur simultaneously, enabling the prediction of a large number of post-prandial physiological markers, which can be highly functional in combination with in vitro, organ-on-a-chip and digital twin models purposed to measure the physiological properties of organs and to predict the effect of adjusted food composition in normal and diseased states.

Discussion

Input from and collaboration between science fileds is needed to further develop and refine the model and to connect with in vitro, in vivo, and ex vivo (organ-on-a-chip) models.
A refined prediction model for survival in hepatocellular carcinoma patients treated with transarterial chemoembolization
Authors: Lee Hae Lim , Kim Seok Hwan , Kim Hee Yeon , Lee Sung Won , Song Myeong Jun
Published: March 2024

Background/Aims

Transarterial chemoembolization (TACE) is widely performed as a major treatment for hepatocellular carcinoma (HCC) patients, and there is a need to stratify patients for whom the most benefit from the treatment. This study aimed to develop a refined prediction model for overall survival (OS) in patients undergoing TACE as a first-line treatment in a large cohort and validate its performance.

Methods

A total of 2,632 patients with HCC of Barcelona Clinic Liver Cancer stage A or B who underwent TACE between 2008 and 2017 were enrolled. The patients were randomly assigned to a training cohort (n = 1,304) or a validation cohort (n = 1,328). Independent predictors of OS were used to develop a prediction model.

Results

The median age of patients in the entire cohort was 63 years, with the majority having hepatitis B virus (56.6%) and being classified as Child-Pugh class A (82.4%). We developed a new prognostic model, called the TACE-prognostic (TP) score, based on tumor burden (sum of the largest tumor diameter and tumor number), alpha-fetoprotein, and Albumin-Bilirubin grade. Patients were classified into five risk groups according to TP scores, with median survival significantly differentiated in both training and validation cohorts (P < 0.001). The new model consistently outperformed other currently available models in both the training and validation cohorts.

Conclusion

This newly developed TP scoring system has the potential to be a useful tool in identifying ideal candidates of TACE and predicting OS with favorable performance and discrimination. However, further external validation is needed to confirm its effectiveness.
Cuproptosis in glioblastoma: unveiling a novel prognostic model and therapeutic potential
Authors: Qin Zhigang , Yang Bin , Jin Xingyi , Zhao Hang , Liu Naijie
Published: March 2024

Glioblastoma, a notably aggressive brain tumor, is characterized by a brief survival period and resistance to conventional therapeutic approaches. With the recent identification of “Cuproptosis,” a copper-dependent apoptosis mechanism, this study aimed to explore its role in glioblastoma prognosis and potential therapeutic implications. A comprehensive methodology was employed, starting with the identification and analysis of 65 cuproptosis-related genes. These genes were subjected to differential expression analyses between glioblastoma tissues and normal counterparts. A novel metric, the “CP-score,” was devised to quantify the cuproptosis response in glioblastoma patients. Building on this, a prognostic model, the CP-model, was developed using Cox regression techniques, designed to operate on both bulk and single-cell data. The differential expression analysis revealed 31 genes with distinct expression patterns in glioblastoma. The CP-score was markedly elevated in glioblastoma patients, suggesting an intensified cuproptosis response. The CP-model adeptly stratified patients into distinct risk categories, unveiling intricate associations between glioblastoma prognosis, immune response pathways, and the tumor’s immunological environment. Further analyses indicated that high-risk patients, as per the CP-model, exhibited heightened expression of certain immune checkpoints, suggesting potential therapeutic targets. Additionally, the model hinted at the possibility of personalized therapeutic strategies, with certain drugs showing increased efficacy in high-risk patients. The CP-model offers a promising tool for glioblastoma prognosis and therapeutic strategy development, emphasizing the potential of Cuproptosis in cancer treatment.
Current status and challenges in timely detection of cervical cancer in Mexico: expert consensus
Authors: Barquet-Muñoz Salim Abraham , Arteaga-Gómez Cristina , Díaz-López Elsa , Rodríguez-Trejo Amelia , Marquez-Acosta Janeth , Aranda-Flores Carlos
Published: March 2024

Cervical cancer is a significant public health problem in low- and middle-income countries, accounting for 85% of new cases worldwide. Due to poorly organized screening programs, cervical cancer is more likely to develop in vulnerable groups who do not initiate or rarely undergo screening. Cervical cytology and detecting high-risk human papillomavirus types are the recommended screening tools. Further, these strategies allow for accurately identifying women at a higher risk of cervical cancer and establishing screening times. New detection tools, such as novel biomarkers or automatic HPV detection in the vagina or urine, can improve screening coverage. This review aims to identify the challenges faced by detection programs and screening tools in Mexico to provide evidence-based recommendations to improve early detection programs for cervical cancer.
Osimertinib in the treatment of resected EGFR-mutated non-small cell lung cancer: a cost-effectiveness analysis in the United States
Authors: Huo Gengwei , Song Ying , Liu Wenjie , Cao Xuchen , Chen Peng
Published: March 2024

Background: In the double-blind phase III ADAURA randomized clinical trial, adjuvant osimertinib showed a substantial overall survival benefit in patients with stage IB to IIIA, EGFR-mutated, completely resected non-small cell lung cancer (NSCLC). We conduct a cost-effectiveness analysis comparing the use of adjuvant osimertinib to placebo in patients with stage IB to IIIA, EGFR-mutated, resected NSCLC.

Methods: Based on the results obtained from the ADAURA trial, a Markov model with three-state was employed to simulate patients who were administered either osimertinib or placebo until disease recurrence or completion of the study period (3 years). Quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER) were calculated with a willingness-to-pay (WTP) threshold of $150,000 per QALY. Both univariate and probabilistic sensitivity analyses were carried out to explore the robustness of the model.

Results: Osimertinib produced additional 1.59 QALYs with additional costs of $492,710 compared to placebo, giving rise to ICERs of $309,962.66/QALY. The results of the univariate sensitivity analysis indicated that the utility of disease-free survival (DFS), cost of osimertinib, and discount rate had the greatest impact on the outcomes. Probabilistic sensitivity analysis showed that osimertinib exhibited a 0% chance of being considered cost-effective for patients using a WTP threshold $150,000/QALY.

Conclusion: In our model, osimertinib was unlikely to be cost-effective compared to placebo for stage IB to IIIA, EGFR-mutated, completely resected NSCLC patients from the perspective of a U.S. payer at a WTP threshold of $150,000 per QALY.
Transgenic line for characterizing GABA-receptor expression to study the neural basis of olfaction in the yellow-fever mosquito
Authors: Rouyar Angela , Patil Anandrao A. , Leon-Noreña Melissa , Li Ming , Coutinho-Abreu Iliano V. , Akbari Omar S. , Riffell Jeff A.
Published: March 2024

The mosquito Aedes aegypti is an important vector of diseases including dengue, Zika, chikungunya, and yellow fever. Olfaction is a critical modality for mosquitoes enabling them to locate hosts, sources of nectar, and sites for oviposition. GABA is an essential neurotransmitter in olfactory processing in the insect brain, including the primary olfactory center, the antennal lobe. Previous work with Ae. aegypti has suggested that antennal lobe inhibition via GABA may be involved in the processing of odors. However, little is known about GABA receptor expression in the mosquito brain, or how they may be involved in odor attraction. In this context, generating mutants that target the mosquito’s olfactory responses, and particularly the GABAergic system, is essential to achieve a better understanding of these diverse processes and olfactory coding in these disease vectors. Here we demonstrate the potential of a transgenic line using the QF2 transcription factor, GABA-B1QF2−ECFP, as a new neurogenetic tool to investigate the neural basis of olfaction in Ae. aegypti. Our results show that the gene insertion has a moderate impact on mosquito fitness. Moreover, the line presented here was crossed with a QUAS reporter line expressing the green fluorescent protein and used to determine the location of the metabotropic GABA-B1 receptor expression. We find high receptor expression in the antennal lobes, especially the cell bodies surrounding the antennal lobes. In the mushroom bodies, receptor expression was high in the Kenyon cells, but had low expression in the mushroom body lobes. Behavioral experiments testing the fruit odor attractants showed that the mutants lost their behavioral attraction. Together, these results show that the GABA-B1QF2−ECFP line provides a new tool to characterize GABAergic systems in the mosquito nervous system.
Pollen transcriptomic analysis provided insights into understanding the molecular mechanisms underlying grafting-induced improvement in potato fertility
Authors: Zhang Xing , Bai Lei , Li Maoxing , Li Youhan , Hu Ronghai , Guo Huachun
Published: March 2024

Introduction

Heterologous grafting has been proven to be a valid approach to improving potato fertility, especially when grafting potatoes with other Solanaceae family plants. However, the mechanisms underlying grafting-induced improvement in potato fertility are still unknown.

Methods

In this study, a poor-fertility potato cultivar “Qingshu No. 9” (Q9) was grafted with a tomato cultivar “Zhongyan988” (ZY988) to study the effects of heterologous grafting in the former. The tuber yield was controlled by different grafting and cultivation approaches, and the correlation between tuber yield and pollen vigor was studied. Comparative transcriptomic analysis of the potential mechanisms of pollen in potato scion fertility changes.

Result

Grafting with the tomato rootstock effectively promoted the flower and fruit formation in the scion potato and improved its pollen viability by 15%–20%. In addition, a significant negative correlation was observed between the potato tuber yield and pollen viability, suggesting a potential impact on the metabolic regulatory network related to tuber formation. From the comparative transcriptomic analysis between the pollens from Q9 self-grafted plants and Q9-tomato grafting scion, 513 differentially expressed genes (DEGs) were identified. These DEGs were found to be related to gametophyte and pollen development, carbohydrate metabolism, and protein processing. Thus, these DEGs might be involved in improved fertility after reduced tuberization in plants subjected to heterologous grafting.

Discussion

Potato/tomato heterologous grafting significantly improved the pollen viability of scion potatoes and was associated with the absence of potato tubers. Heterologous grafting promotes the transcription of genes related to protein processing, carbohydrate metabolism, and pollen development in pollen cells, resulting in the production of fertile pollen. Our results provided initial clues to understanding the improvement of potato fertility using the heterologous grafting method, which might be a useful tool in assisted potato breeding.
There is no happiness in positive affect: the pervasive misunderstanding of the rotated circumplex model
Authors: LaRowe Lisa R. , Connell Bohlen Lauren , Williams David M.
Published: March 2024

Research on positive affect (PA) and negative affect (NA) is often guided by the rotational variant of the circumplex model of affect (RCMA). According to the RCMA, PA and NA are posited to be orthogonal, with PA ranging from the union of positive valence and high activation (e.g., excited) to the union of negative valence and low activation (e.g., sluggish), and NA ranging from the union of negative valence and high activation (e.g., distressed) to the union of positive valence and low activation (e.g., relaxed). However, many authors incorrectly interpret the RCMA as positing that positively valenced affect (i.e., pleasure) and negatively valenced affect (i.e., displeasure)—rather than PA and NA, as defined in the RCMA—are orthogonal. This “received view” of the RCMA has led to significant confusion in the literature. The present paper articulates the “received view” of the RCMA and characterizes its prevalence in psychological research. A random sample of 140 empirical research articles on affect published in 14 high-impact journals covering a range of psychological subdisciplines were reviewed. Over half of the articles subscribing to the RCMA showed evidence of the “received view,” demonstrating that misuse of the terms PA and NA in the context of the RCMA is rampant in the psychological literature. To reduce continued confusion in the literature, we recommend abandoning use of the terms positive affect and negative affect. We further recommend referring to the two dimensions of the RCMA as positive activation and negative activation, and the two poles of the valence dimension as positive valence and negative valence (or pleasure and displeasure).
Blood pharming: exploring the progress and hurdles in producing in-vitro red blood cells for therapeutic applications
Authors: Hassan Hammad , Rajput Sheerien
Published: March 2024

Transfusion Medicine is facing mounting challenges, including but not limited to donor availability, blood supply shortages, and transfusion-associated complications, such as immunogenicity and transmission of viral infections. ‘Blood Pharming’, for in vitro Red Blood Cells (RBC) synthesis, offers a potentially effective approach to addressing the challenges and risks associated with the transfusion of blood and related products. This innovative approach employs cells from variable sources such as Hematopoietic stem cells (HSCs), induced pluripotent stem cells (iPSCs), or immortalized progenitor cell lines, directing their differentiation towards erythropoiesis in an in-vitro environment that mimics the normal bone marrow niche required for erythropoiesis. This review article provides a comprehensive analysis of the progress and hurdles in blood pharming, emphasizing in vitro RBC synthesis for clinical application. In-vitro large-scale production of RBCs offers cutting-edge advantages, such as consistent scalability, the capacity to acquire desired blood phenotypes, and a significant reduction in transfusion-related infections, however, substantial molecular and methodological challenges still need to be addressed before the transfer of this approach from bench to bedside. The review discusses the challenges in ensuring scalability that matches demand and supply, the structural and functional integrity of in-vitro synthesized RBCs compared to their in-vivo counterparts, and the cost-effective methods of RBC synthesis in vitro. It also highlights the importance of implementing thorough characterization and testing protocols to comply with regulatory standards. Additionally, it delves into the ethical concerns associated with commercializing such products. In summary, this review examines the progress and obstacles in the field of in-vitro blood pharming. Through a comprehensive analysis of the present state of the discipline, ongoing scholarly investigations, and prospective avenues of inquiry, our objective is to contribute to a more profound comprehension of the potential impact of synthetic RBCs on the transformation of transfusion medicine.
Exploring the similarities between risk factors triggering depression in humans and elevated in-cage “inactive but awake” behavior in laboratory mice
Authors: Schmitt Oceane , Finnegan Emily , Trevarthen Anna , Wongsaengchan Chanakarn , Paul Elizabeth S. , Mendl Michael , Fureix Carole
Published: March 2024

Introduction

Depression is a human mental disorder that can also be inferred in non-human animals. This study explored whether time spent inactive but awake (“IBA”) in the home-cage in mice was further triggered by risk factors similar to those increasing vulnerability to depression in humans (early life stress, genetic predispositions, adulthood stress).

Methods

Eighteen DBA/2 J and 18 C57BL/6 J females were tested, of which half underwent as pups a daily maternal separation on post-natal days 2–14 (early-life stress “ELS”) (other half left undisturbed). To assess the effect of the procedure, the time the dams from which the 18 subjects were born spent active in the nest (proxy for maternal behavior) was recorded on post-natal days 2, 6, 10 and 14 for 1 h before separation and following reunion (matched times for controls), using live instantaneous scan sampling (total: 96 scans/dam). For each ELS condition, about half of the pups were housed post-weaning (i.e., from 27 days old on average) in either barren (triggering IBA and depression-like symptoms) or larger, highly enriched cages (n = 4–5 per group). Time mice spent IBA post-weaning was observed blind to ELS treatment using live instantaneous scan sampling in two daily 90-min blocks, two days/week, for 6 weeks (total: 192 scans/mouse). Data were analyzed in R using generalized linear mixed models.

Results

The dams were significantly more active in the nest over time (p = 0.016), however with no significant difference between strains (p = 0.18), ELS conditions (p = 0.20) and before/after separation (p = 0.83). As predicted, post-weaning barren cages triggered significantly more time spent IBA in mice than enriched cages (p < 0.0001). However, neither ELS (p = 0.4) nor strain (p = 0.84) significantly influenced time mice spent IBA, with no significant interaction with environmental condition (ELS × environment: p = 0.2861; strain × environment: p = 0.5713).

Discussion

Our results therefore only partly support the hypothesis that greater time spent IBA in mice is triggered by risk factors for human depression. We discuss possible explanations for this and further research directions.
Survey of hereditary angioedema episodes and quality of life impairment through a patient-participatory registry
Authors: Morioke Satoshi , Aikyo Tatsuki , Tanaka Akio , Matsubara Daiki , Saito Ryo , Iwamoto Kazumasa , Yamasaki Chisato , Kogetsu Atsushi , Hamakawa Nao , Isono Moeko , Yamamoto Beverley Anne , Matsumura Yasushi , Takeda Toshihiro , Manabe Shiro , Javaid Muhammad Kassim , Barrett Joe , Gray Nathanael , Kaye Jane , Kato Kazuto , Hide Michihiro
Published: March 2024

Hereditary angioedema (HAE) adversely affects patients’ social and daily life significantly, and the disease burden is high. We recruited study participants from a patient-participatory registry, Rare and Undiagnosed Diseases Study (RUDY) Japan, to better understand the broader effect of HAE on patients’ lives. Thirteen patients with HAE who registered between January 2019 and March 2021 completed an online questionnaire to record details of episodes and the angioedema quality of life (AE-QoL) questionnaire, in which they described the degree to which QoL was impaired. In all, 58 episodes were recorded, and self-reported data were accumulated from 24 returned AE-QoL questionnaires. The episodes peaked between approximately 06:00 and 07:00 h and between approximately 16:00 and 20:00 h. Of the 58 episodes, 38 (65.5%) were treated; 24 (63.2%) were treated at patients’ homes. The drugs used in treatment were hospital-administered human C1-inhibitor preparations for 14 episodes and home-administered icatibant for 26 episodes. Time between episode onset and treatment initiation and between episode onset and full recovery tended to be shorter with icatibant treatment at home. The total AE-QoL score was 37.1 ± 22.9, indicating great impairment of QoL, with particularly high scores in the fatigue/mood and fears/shame domains. Most previous studies of real-world HAE episodes have been retrospective, based on patients’ memories. Collaboration between patients and researchers revealed the location of episodes, the time of day they appeared, treatments for episodes, and the degree to which patients’ QoL was impaired by HAE in this prospective study.
Classification and Molecular Functions of Heparan Sulfate Proteoglycans and Their Molecular Mechanisms with the Receptor
Authors: Matsuzaka Yasunari , Yashiro Ryu
Published: March 2024

Heparan sulfate proteoglycans are highly glycosylated proteins in which heparan sulfate, a glycosaminoglycan sugar chain, is an acidic sugar chain consisting of a repeating disaccharide structure of glucuronic acid and N-acetylglucosamine is locally sulfated. Syndecan, one of the transmembrane HSPGs, functions as a receptor that transmits signals from the extracellular microenvironment to the inside of the cell. In the vascular system, heparan sulfate proteoglycans, a major component of the glycocalyx, enable the binding of various plasma-derived molecules due to their diversity, epimerization of glycosaminoglycans chains, long chains, and sulfation. Heparan sulfate proteoglycans present in the extracellular matrix serve as a reservoir for bioactive molecules such as chemokines, cytokines, and growth factors. Aberrant expression of heparan sulfate proteoglycans, heparanase, and sulfatase is observed in many pathological conditions. Therefore, it can be applied to therapeutic strategies for a wide range of fields including Alzheimer’s disease, heart failure, cancer, organ transplants, diabetes, chronic inflammation, aging, and autoimmune diseases.
The Influence of Lyophilization Pretreatment and Whey Content on Whey and Gelatin-Based Hydrogels
Authors: Lopes Pompilia Mioara , Fechete Radu , Minteuan Felicia , Mare Liviu , Moldovan Dumitrița , Moldovan Marioara , Cuc Stanca , Saroși Codruța Liana , Popescu Violeta
Published: March 2024

Whey and gelatin, natural polymers within the protein category, find widespread use in hydrogel formulations applied across the food, medical, and pharmaceutical industries. This study presents new characteristics of hydrogels based on whey, gelatin, and copper sulfate as a consequence of the additional steps in the preparation method, specifically refrigeration and freezing storage followed by lyophilization. The water state in hydrogels prior to lyophilization impacts the morphological appearance, with refrigerated hydrogels exhibiting a more regular and dense pore distribution, as shown by the Scanning Electron Microscopy (SEM) images. This observation aligns with the higher mobility of polymer chains indicated by T2 distributions in 1H nuclear magnetic resonance (RMN) relaxometry measurements. Changes in the intensity and amide-specific wavenumbers of the FTIR spectra of whey and gelatin proteins are evident in the Fourier Transformed Infrared (FTIR) spectra of crosslinked and frozen hydrogels before lyophilization. Moreover, the reinforcing effect in the hydrogel matrix, noted in mechanical tests, is attributed to increased polymer chain content and copper sulfate crosslinking.
Functionalized Gelatin/Polysaccharide Hydrogels for Encapsulation of Hepatocytes
Authors: Willems Christian , Qi Fangdi , Trutschel Marie-Luise , Groth Thomas
Published: March 2024

Liver diseases represent a considerable burden to patients and healthcare systems. Hydrogels play an important role in the engineering of soft tissues and may be useful for embedding hepatocytes for different therapeutic interventions or the development of in vitro models to study the pathogenesis of liver diseases or testing of drugs. Here, we developed two types of hydrogels by crosslinking hydrazide-functionalized gelatin with either oxidized dialdehyde hyaluronan or alginate through the formation of hydrazone bonds. Gel formulations were studied through texture analysis and rheometry, showing mechanical properties comparable to those of liver tissue while also demonstrating long-term stability. The biocompatibility of hydrogels and their ability to host hepatocytes was studied in vitro in comparison to pure gelatin hydrogels crosslinked by transglutaminase using the hepatocellular line HepG2. It was found that HepG2 cells could be successfully embedded in the hydrogels, showing no signs of gel toxicity and proliferating in a 3D environment comparable to pure transglutaminase cross-linked gelatin hydrogels used as control. Altogether, hydrazide gelatin in combination with oxidized polysaccharides makes stable in situ gelling systems for the incorporation of hepatocytes, which may pave the way for use in liver tissue engineering and drug testing.
Evaluation of the Impact of Climate Change on the Water Balance of the Mixteco River Basin with the SWAT Model
Authors: Colín-García Gerardo , Palacios-Vélez Enrique , López-Pérez Adolfo , Bolaños-González Martín Alejandro , Flores-Magdaleno Héctor , Ascencio-Hernández Roberto , Canales-Islas Enrique Inoscencio
Published: March 2024

Assessing the impact of climate change is essential for developing water resource management plans, especially in areas facing severe issues regarding ecosystem service degradation. This study assessed the effects of climate change on the hydrological balance using the SWAT (Soil and Water Assessment Tool) hydrological model in the Mixteco River Basin (MRB), Oaxaca, Mexico. Temperature and precipitation were predicted with the projections of global climate models (GCMs) from the Coupled Model Intercomparison Project Phase 6 (CMIP6); the bias was corrected using CMhyd software, and then the best performing GCM was selected for use in the SWAT model. According to the GCM MPI-ESM1-2-LR, precipitation might decrease by between 83.71 mm and 225.83 mm, while temperature might increase by between 2.57 °C and 4.77 °C, causing a greater atmospheric evaporation demand that might modify the hydrological balance of the MRB. Water yield might decrease by 47.40% and 61.01% under the climate scenarios SP245 and SSP585, respectively. Therefore, adaptation and mitigation measures are needed to offset the adverse impact of climate change in the MRB.
Trichoscopy of Androgenetic Alopecia: A Systematic Review
Authors: Kuczara Agata , Waśkiel-Burnat Anna , Rakowska Adriana , Olszewska Małgorzata , Rudnicka Lidia
Published: March 2024

Background: Androgenetic alopecia, the most common cause of non-scarring hair loss, is a consequence of the gradual miniaturization of the hair follicles. In the majority of male androgenetic alopecia cases, a patient’s history and clinical evaluation may be sufficient to establish the diagnosis, while for women, they should be supplemented with trichoscopy. Methods: The PubMed and Scopus databases were used to collate published studies and to analyze the most typical trichoscopic findings in patients diagnosed with androgenetic alopecia. A total of 34 articles were retrieved after exclusion. Results: The most common features identified using trichoscopy included hair diameter variability (94.07% of patients), vellus hairs (66.45%) and the peripilar sign (43.27%). Others, such as the honeycomb pattern, yellow and white dots, were less relevant. Conclusions: We concluded that hair diameter variability, vellus hairs and the peripilar sign represented valuable indicators for the diagnosis of androgenetic alopecia.