bluuebunny/crossref_metadata_2025 huggingface dataset:
Adolescent binge ethanol impacts H3K36me3 regulation of synaptic genes
Authors: Brocato Emily R. , Wolstenholme Jennifer T.
Published: March 2023

Adolescence is marked in part by the ongoing development of the prefrontal cortex (PFC). Binge ethanol use during this critical stage in neurodevelopment induces significant structural changes to the PFC, as well as cognitive and behavioral deficits that can last into adulthood. Previous studies showed that adolescent binge ethanol causes lasting deficits in working memory, decreases in the expression of chromatin remodeling genes responsible for the methylation of histone 3 lysine 36 (H3K36), and global decreases in H3K36 in the PFC. H3K36me3 is present within the coding region of actively-transcribed genes, and safeguards against aberrant, cryptic transcription by RNA Polymerase II. We hypothesize that altered methylation of H3K36 could play a role in adolescent binge ethanol-induced memory deficits. To investigate this at the molecular level, ethanol (4 g/kg, i.g.) or water was administered intermittently to adolescent mice. RNA-and ChIP-sequencing were then performed within the same tissue to determine gene expression changes and identify genes and loci where H3K36me3 was disrupted by ethanol. We further assessed ethanol-induced changes at the transcription level with differential exon-use and cryptic transcription analysis – a hallmark of decreased H3K36me3. Here, we found ethanol-induced changes to the gene expression and H3K36me3-regulation of synaptic-related genes in all our analyses. Notably, H3K36me3 was differentially trimethylated between ethanol and control conditions at synaptic-related genes, and Snap25 and Cplx1 showed evidence of cryptic transcription in males and females treated with ethanol during adolescence. Our results provide preliminary evidence that ethanol-induced changes to H3K36me3 during adolescent neurodevelopment may be linked to synaptic dysregulation at the transcriptional level, which may explain the reported ethanol-induced changes to PFC synaptic function.
Serum miRNA modulations indicate changes in retinal morphology
Authors: Aggio-Bruce Riemke , Schumann Ulrike , Cioanca Adrian V. , Chen Fred K. , McLenachan Samuel , Heath Jeffery Rachael C. , Das Shannon , Natoli Riccardo
Published: March 2023

Background

Age-related macular degeneration (AMD) is the leading cause of vision loss in the developed world and the detection of its onset and progression are based on retinal morphological assessments. MicroRNA (miRNA) have been explored extensively as biomarkers for a range of neurological diseases including AMD, however differences in experimental design and the complexity of human biology have resulted in little overlap between studies. Using preclinical animal models and clinical samples, this study employs a novel approach to determine a serum signature of AMD progression.

Methods

Serum miRNAs were extracted from mice exposed to photo-oxidative damage (PD; 0, 1, 3 and 5 days), and clinical samples from patients diagnosed with reticular pseudodrusen or atrophic AMD. The expression of ~800 miRNAs was measured using OpenArray™, and differential abundance from controls was determined using the HTqPCR R package followed by pathway analysis with DAVID. MiRNA expression changes were compared against quantifiable retinal histological indicators. Finally, the overlap of miRNA changes observed in the mouse model and human patient samples was investigated.

Results

Differential miRNA abundance was identified at all PD time-points and in clinical samples. Importantly, these were associated with inflammatory pathways and histological changes in the retina. Further, we were able to align findings in the mouse serum to those of clinical patients.

Conclusion

In conclusion, serum miRNAs are a valid tool as diagnostics for the early detection of retinal degeneration, as they reflect key changes in retinal health. The combination of pre-clinical animal models and human patient samples led to the identification of a preliminary serum miRNA signature for AMD. This study is an important platform for the future development of a diagnostic serum miRNA panel for the early detection of retinal degeneration.
Role of glutamate in the development of visual pathways
Authors: Majumdar Sriparna
Published: March 2023

Glutamate is an important amino acid, metabolite and excitatory neurotransmitter, which is found in its free form in the extracellular spaces of the central nervous system (CNS). More than half of all synapses in CNS release glutamate. It is the main neurotransmitter driving the light responses in the retina. All types of photoreceptors, bipolar, ganglion and one type of glycinergic amacrine cells express specific subtypes of vesicular glutamate transporters and are the main source of endogenous glutamate in retina, besides Müller glia that are responsible for glutamate homeostasis, release and reuptake. Reduced or excessive extracellular glutamate was detected in the synaptic clefts of several naturally occurring or transgenic eye disease models, in which network rewiring and altered functions were observed. These led to the hypothesis that glutamate is one of the extrinsic signals for visual pathway development. This minireview examines experimental evidences supporting, or refuting, the influence of glutamate on prenatal and postnatal retinal development.
Intra-arterial vasodilators infusion for management of reversible cerebral vasoconstriction syndrome in a 12-year-old girl: A case report
Authors: Rizzati Frida , Marie Guillaume , Chanez Vivianne , Ferry Thomas , Natterer Julia , Longchamp David , Saliou Guillaume , Perez Maria-Helena
Published: March 2023

Reversible cerebral vasoconstriction syndrome (RCVS) is a vascular disease characterized by diffuse transient vasoconstriction and vasodilatation of the cerebral arteries. It is commonly associated with recurrent severe acute headaches with or without focal neurological deficits due to hemorrhages, infarcts, and even posterior reversible encephalopathy syndrome. The optimal management of acute neurologic deficits caused by RCVS is still uncertain. Calcium channel blockers (CCBs) such as nimodipine or verapamil have been reported to be effective in adult series. Intra-arterial injection of nimodipine, verapamil, and milrinone has recently been demonstrated to be safe and effective for treating severe segmental vasoconstriction in adults. CCBs are the most used treatment in the available pediatric literature. Intra-arterial vasodilators have been reported in some rare pediatric reports with more severe diseases, but their utility is still under investigation. We report a case of a 12-year-old girl who underwent a severe course of RCVS complicated by multiple cerebral infarcts, treated by several sessions of intra-arterial vasodilators infusion.
Exploring barriers of childhood full vaccination among children living in Siraro District, West Arsi Zone, Oromia region, Ethiopia: A qualitative study
Authors: Guye Ararso Hordofa , Nigussie Tadesse , Tesema Mengistu , Shambi Dame Banti , Diriba Berhanu Senbeta , Tefera Esayas Mekonen , Girma Yeabsira
Published: March 2023

Background

Childhood immunization is one of the most effective global public health interventions to reduce childhood morbidity and mortality. However, some children remain not fully vaccinated in developing countries due to defaulting from full vaccination, which can put them at risk of acquiring vaccine-preventable disease outbreaks. The barriers to full vaccination were well explored in Ethiopia using a qualitative approach. The study aimed to explore barriers to full childhood vaccination in Siraro District, West Arsi Zone, Oromia, Ethiopia.

Methods

A qualitative study was conducted in Siraro District through 15 key informant health workers interviews and 6 in-depth interviews with children’s mothers from April 20 to May 15, 2022. Data were collected by semi-structured questionnaires and captured using audio tape recorders and field note-taking. A heterogeneous purposive sampling technique was used to select representative study participants. Data transcription and translation were done according to the respondents’ verbatim from the local language to English. Data coding and key categories were identified and analyzed using thematic analysis. Finally, data were presented in narrative forms using respondents' own words as an illustration.

Result

Twenty-one study participants were interviewed and included in this study. Of the explored barriers to full childhood vaccination, the evidence from the respondents was integrated from subcategories and presented as a whole within each thematic area. Five thematic areas emerged from interviews of the participants through thematic analysis of the data. The identified barriers were forgetting the next vaccination schedule, migration of parents, work overload, lack of knowledge and awareness, rumors, and misinformation. Additionally, vaccination service delivery-related barriers such as vaccine vials not being opened for a few children, fear of vaccine side effects, closed health posts during visits by mothers for vaccination, and absence of health extension workers at health posts were the key barriers to full childhood vaccination.

Conclusion

Forgetting vaccination schedule, migration of parents, work overload, rumors, and misinformation, fear of vaccine side effects, vaccine vial not opened for few children, closed health posts during visiting by mothers, absence of health extension workers from health posts were the key barriers to the full vaccination status of children. Thus, the district health office should work on barriers to full vaccination by strengthening vaccination service delivery and improving vaccination awareness through a health extension program.
Case report: Pediatric anti-gamma aminobutyric acid-B receptor encephalitis with benign prognosis
Authors: Wang Yeping , Ren Xiaoyan , Shen Yu , Hua Yi , Xu Lu , Zhang Weiran , Sheng Guoxia , Jiang Peifang , Yuan Zhefeng , Liu Liu , Gao Feng
Published: March 2023

Objective

To explore the clinical characteristics of pediatric anti-gamma-aminobutyric acid-B receptor (GABABR) encephalitis to enhance the understanding and improve the diagnostic and therapeutic strategies for this disease.

Methods

We report a rare case of a female pediatric patient with anti-GABABR encephalitis who was treated at the Children's Hospital of Zhejiang University School of Medicine. Literature search was performed to explore the clinical characteristics of pediatric anti-GABABR encephalitis.

Results

The patient exhibited recurrent epileptic seizure, status epilepticus, and psychiatric symptoms at the age of 11 years and 10 months. Anti-GABABR antibodies were positive in cerebrospinal fluid and serum. Brain magnetic resonance imaging (MRI) exhibited abnormal signals in the left hippocampus. Symptoms and abnormality of brain MRI were improved after administration of immunosuppressants, anti-seizure and antipsychotic drugs. Two of pediatric anti-GABABR encephalitis with clinical data were identified through literature search. Analysis of these three cases suggested that the pediatric patients primarily experienced limbic encephalitis, with no tumor incidence. A favorable immunotherapy response was demonstrated with a superior prognosis in all the cases.

Conclusions

We reported a pediatric anti-GABABR encephalitis case with early age of onset. Promt autoimmune antibody testing and tumor screening, as well as immunomodulatory treatment immediately after a definitive diagnosis are warranted to improve prognosis.
The relation between radiographic manifestation and clinical characteristics of congenital radioulnar synostosis in children: A retrospective study from multiple centers
Authors: Hong Pan , Tan Wei , Zhou Wei-Zheng , Zheng Yu , Li Jin , Zheng PengFei , Tang Xin
Published: March 2023

Objective

To review the radiographic manifestation and clinical appearance of children with congenital radioulnar synostosis (CRUS) retrospectively.

Study design

Retrospective cohort study of children with CRUS from multiple medical centers.

Results

A total of 329 patients (male 259, female 70) with an average age of 5.4 years (0.5–16 years old), were included in this study. In particular, 145 patients (145/329, 44.1%) demonstrated bilateral involvement, and 184 patients (left 123, right 61) demonstrated unilateral involvement. As for Clear and Omery (C&O) classification, most patients belonged to Type III, and then followed by Type IV. As for Chinese Multi-center Pediatric Orthopedic Study Group (CMPOS) classification, most patients belonged to Type III, and then followed by Type II and Type I. In C&O Type III, 92.03% patients demonstrated severe pronation. According to CMPOS classification, 92.98% Type I patients demonstrated neutral to mild pronation, 72.17% Type II patients demonstrated moderate pronation, and 92.03% Type III patients demonstrated severe pronation. The age distribution showed no significant difference between C&O Type II and IV (P = 0.96); the pronation ankylosis severity showed no significant difference between C&O Type II and IV (P = 0.387).

Conclusion

Although CRUS is a rare forearm deformity, there are certain relation between radiographic manifestation and clinical forearm functional restriction. CRUS patients of C&O or CMPOS Type III classification might suffer severe pronation deformity and warrant early intervention.
Emodin ameliorates renal injury and fibrosis via regulating the miR-490-3p/HMGA2 axis
Authors: Wang Liulin , Wang Xuerui , Li Gang , Zhou Shanshan , Wang Rui , Long Qi , Wang Min , Li Liang , Huang Hai , Ba Yuanming
Published: March 2023

Renal fibrosis is a major pathological feature of chronic kidney disease (CKD). While emodin is reported to elicit anti-fibrotic effects on renal injury, little is known about its effects on microRNA (miRNA)-modulated mechanisms in renal fibrosis. In this study, we established a unilateral ureteral obstruction (UUO) model and a transforming growth factor (TGF)-β1-induced normal rat renal tubular epithelial cell line (NRK-52E) model to investigate the protective effects of emodin on renal fibrosis and its miRNA/target gene mechanisms. Dual-luciferase assay was performed to confirm the direct binding of miRNA and target genes in HEK293 cells. Results showed that oral administration of emodin significantly ameliorated the loss of body weight and the increase in physicochemical parameters, including serum uric acid, creatinine, and urea nitrogen in UUO mice. Inflammatory cytokines, including tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin (IL)-1β, but not IL-6, were down-regulated by emodin administration. Emodin decreased the expression levels of TGF-β1 and fibrotic-related proteins, including alpha-smooth muscle actin, Collagen IV, and Fibronectin, and increased the expression of E-cadherin. Furthermore, miR-490-3p was decreased in UUO mice and negatively correlated with increased expression of high migration protein A2 (HMGA2). We further confirmed HMGA2 was the target of miR-490-3p. Transfection of miR-490-3p mimics decreased, while transfection of miR-490-3p inhibitors increased fibrotic-related proteins and HMGA2 expression levels in TGF-β1-induced NRK-52E cells. Furthermore, transfection of miR-490-3p mimics enhanced the anti-fibrotic effects of emodin, while transfection of miR-490-3p inhibitors abolished the protective effects of emodin. Thus, as a novel target of emodin that prevents renal fibrosis in the HMGA2-dependent signaling pathway, miR-490-3p has potential implications in CKD pathology.
Potential of natural flavonols and flavanones in the treatment of ulcerative colitis
Authors: Li Cailan , Tang Ying , Ye Yonghao , Zuo Manhua , Lu Qiang
Published: March 2023

Ulcerative colitis (UC) is an inflammatory bowel disease generally characterized by chronic, persistent, recurrent, and non-specific ulcers of the intestine. Its main clinical manifestations include abdominal pain, diarrhea, and bloody stools. This disease is difficult to cure and even carries the risk of canceration. It has been listed as a modern refractory disease by the World Health Organization. Though a large amount of drugs are available for the inhibition of UC, the conventional treatment such as aminosalicylic acids, glucocorticoids, immunosuppressors, and biological agents possess certain limitations and serious side effects. Therefore, it is urgently needed for safe and effective drugs of UC, and natural-derived flavonols and flavanones showed tremendous potential. The present study concentrated on the progress of natural-derived flavonols and flavanones from edible and pharmaceutical plants for the remedy of UC over the last two decades. The potential pharmaceutical of natural-derived flavonols and flavanones against UC were closely connected with the modulation of gut microflora, gut barrier function, inflammatory reactions, oxidative stress, and apoptosis. The excellent efficacy and safety of natural flavonols and flavanones make them prospective drug candidates for UC suppression.
Emerging trends and research foci of berberine on tumor from 2002 to 2021: A bibliometric article of the literature from WoSCC
Authors: Yuan Runzhu , Tan Yao , Sun Ping-Hui , Qin Bo , Liang Zhen
Published: March 2023

Background: Cancer, also known as a malignant tumor, is caused by the activation of oncogenes, which leads to the uncontrolled proliferation of cells that results in swelling. According to the World Health Organization (WHO), cancer is one of the main causes of death worldwide. The main variables limiting the efficacy of anti-tumor treatments are side effects and drug resistance. The search for natural, safe, low toxicity, and efficient chemical compounds in tumor research is essential. Berberine is a pentacyclic isoquinoline quaternary ammonium alkaloid isolated from Berberis and Coptis that has long been used in clinical settings. Studies in recent years have reported the use of berberine in cancer treatment. In this study, we performed a bibliometric analysis of berberine- and tumor-related research.

Materials and methods: Relevant articles from January 1, 2002, to December 31, 2021, were identified from the Web of Science Core Collection (WOSCC) of Clarivate Analytics. Microsoft Excel, CiteSpace, VOSviewer, and an online platform were used for the literary metrology analysis.

Results: A total of 1368 publications had unique characteristics. Publications from China were the most common (783 articles), and Y. B. Feng (from China) was the most productive author, with the highest total citations. China Medical University (Taiwan) and Sun Yat-sen University (China) were the two organizations with the largest numbers of publications (36 each). Frontiers in Pharmacology was the most commonly occurring journal (29 articles). The present body of research is focused on the mechanism, molecular docking, and oxidative stress of berberine in tumors.

Conclusion: Research on berberine and tumors was thoroughly reviewed using knowledge map and bibliometric methods. The results of this study reveal the dynamic evolution of berberine and tumor research and provide a basis for strategic planning in cancer research.
Evolutionary and phylogenetic analyses of 11 Cerasus species based on the complete chloroplast genome
Authors: Wan Tian , Qiao Bai-xue , Zhou Jing , Shao Ke-sen , Pan Liu-yi , An Feng , He Xu-sheng , Liu Tao , Li Ping-ke , Cai Yu-liang
Published: March 2023

The subgenus Cerasus, one of the most important groups in the genus Prunus sensu lato, comprises over 100 species; however, the taxonomic classification and phylogenetic relationships of Cerasus remain controversial. Therefore, it is necessary to reconstruct the phylogenetic tree for known Cerasus species. Here, we report the chloroplast (cp) genome sequences of 11 Cerasus species to provide insight into evolution of the plastome. The cp genomes of the 11 Cerasus species (157,571–158,830 bp) displayed a typical quadripartite circular structure. The plastomes contain 115 unique genes, including 80 protein-coding genes, four ribosomal RNAs, and 31 transfer RNAs. Twenty genes were found to be duplicated in inverted repeats as well as at the boundary. The conserved non-coding sequences showed significant divergence compared with the coding regions. We found 12 genes and 14 intergenic regions with higher nucleotide diversity and more polymorphic sites, including matK, rps16, rbcL, rps16-trnQ, petN-psbM, and trnL-trnF. During cp plastome evolution, the codon profile has been strongly biased toward the use of A/T at the third base, and leucine and isoleucine codons appear the most frequently. We identified strong purifying selection on the rpoA, cemA, atpA, and petB genes; whereas ccsA, rps19, matK, rpoC2, ycf2 and ndhI showed a signature of possible positive selection during the course of Cerasus evolution. In addition, we further analyzed the phylogenetic relationships of these species with 57 other congenic related species.Through reconstructing the Cerasus phylogeny tree, we found that true cherry is similar to the flora of China forming a distinct group, from which P. mahaleb was separated as an independent subclade. Microcerasus was genetically closer to Amygdalus, Armeniaca, and Prunus (sensu stricto) than to members of true cherry, whereas P. japonica and P. tomentosa were most closely related to P. triloba and P. pedunculata. However, P. tianshanica formed a clade with P. cerasus, P. fruticosa, P. cerasus × P. canescens ‘Gisela 6’, and P. avium as a true cherry group. These results provide new insights into the plastome evolution of Cerasus, along with potential molecular markers and candidate DNA barcodes for further phylogenetic and phylogeographic analyses of Cerasus species.
Deciphering the antimicrobial activity of multifaceted rhizospheric biocontrol agents of solanaceous crops viz., Trichoderma harzianum MC2, and Trichoderma harzianum NBG
Authors: Rahman Mehjebin , Borah Sapna Mayuri , Borah Pradip Kr. , Bora Popy , Sarmah Bidyut Kumar , Lal Milan Kumar , Tiwari Rahul Kumar , Kumar Ravinder
Published: March 2023

The Solanaceae family is generally known to be the third most economically important plant taxon, but also harbors a host of plant pathogens. Diseases like wilt and fruit rot of solanaceous crops cause huge yield losses in the field as well as in storage. In the present study, eight isolates of Trichoderma spp. were obtained from rhizospheric micro-flora of three solanaceous crops: tomato, brinjal, and chili plants, and were subsequently screened for pre-eminent biocontrol activity against three fungal (Fusarium oxysporum f. sp. lycopersicum, Colletotrichum gloeosporioides, and Rhizoctonia solani) and one bacterial (Ralstonia solanacearum) pathogen. Morphological, ITS, and tef1α marker-based molecular identification revealed eight isolates were different strains of Trichoderma. Seven isolates were distinguished as T. harzianum while one was identified as T. asperellum. In vitro antagonistic and biochemical assays indicated significant biocontrol activity governed by all eight isolates. Two fungal isolates, T. harzianum MC2 and T. harzianum NBG were further evaluated to decipher their best biological control activity. Preliminary insights into the secondary metabolic profile of both isolates were retrieved by liquid chromatography-mass spectrometry (LC-MS). Further, a field experiment was conducted with the isolates T. harzianum MC2 and T. harzianum NBG which successfully resulted in suppression of bacterial wilt disease in tomato. Which possibly confer biocontrol properties to the identified isolates. The efficacy of these two strains in suppressing bacterial wilt and promoting plant growth in the tomato crop was also tested in the field. The disease incidence was significantly reduced by 47.50% and yield incremented by 54.49% in plants treated in combination with both the bioagents. The results of scanning electron microscopy were also in consensus with the in planta results. The results altogether prove that T. harzianum MC2 and T. harzianum NBG are promising microbes for their prospective use in agricultural biopesticide formulations.
Vitamin C biofortification of broccoli microgreens and resulting effects on nutrient composition
Authors: Kathi Shivani , Laza Haydee , Singh Sukhbir , Thompson Leslie , Li Wei , Simpson Catherine
Published: March 2023

The consumption of plants plays an important role in human health. In addition to providing macro and micronutrients, plants are the sole sources of several phytonutrients that play a major role in disease prevention. However, in modern diets, increased consumption of cheaper, processed foods with poor nutritional value over fruits and vegetables leads to insufficient consumption of essential nutrients such as vitamin C. Taking supplements can address some of the insufficient nutrients in a diet. However, supplements are not as diverse or bioavailable as the nutrients in plants. Improving the abundance of nutrients in plants will reduce the amounts that need to be consumed, thereby reducing the price barrier and use of supplements. In this study, broccoli (Brassica oleracea var. italica) microgreens grown in a controlled environment were biofortified for increased vitamin C content. The microgreens grown on growing pads were treated with supplemental nutrient solutions. Treatments were applied four to five days after germination and included four different concentrations of ascorbic acid specifically, 0% (control), 0.05%, 0.1%, 0.25% and 0.5%, added to the nutrient solution. Microgreens with turgid cotyledons and appearance of tip of first true leaves were harvested about 14 days after germination and were analyzed for biomass, chlorophylls, carotenoids, vitamin C and other minerals content. The ascorbic acid improved the microgreens’ fresh biomass, percent dry matter, chlorophylls, carotenoids, vitamin C, and potassium content. Moreover, this study also mapped out the correlation between ascorbic acid, phytochemicals, and broccoli microgreens’ mineral composition. The total vitamin C was positively correlated to K and negatively correlated to chlorophylls, N, P, Mg, Ca, S, and B (p < 0.01). These relationships can be applied in future vitamin C biofortification research across different microgreens. In conclusion, vitamin C was increased up to 222% by supplemental ascorbic acid without being detrimental to plant health and mineral composition.
Genetic gains in tropical maize hybrids across moisture regimes with multi-trait-based index selection
Authors: Singamsetti Ashok , Zaidi Pervez H. , Seetharam Kaliyamoorthy , Vinayan Madhumal Thayil , Olivoto Tiago , Mahato Anima , Madankar Kartik , Kumar Munnesh , Shikha Kumari
Published: March 2023

Unpredictable weather vagaries in the Asian tropics often increase the risk of a series of abiotic stresses in maize-growing areas, hindering the efforts to reach the projected demands. Breeding climate-resilient maize hybrids with a cross-tolerance to drought and waterlogging is necessary yet challenging because of the presence of genotype-by-environment interaction (GEI) and the lack of an efficient multi-trait-based selection technique. The present study aimed at estimating the variance components, genetic parameters, inter-trait relations, and expected selection gains (SGs) across the soil moisture regimes through genotype selection obtained based on the novel multi-trait genotype–ideotype distance index (MGIDI) for a set of 75 tropical pre-released maize hybrids. Twelve traits including grain yield and other secondary characteristics for experimental maize hybrids were studied at two locations. Positive and negative SGs were estimated across moisture regimes, including drought, waterlogging, and optimal moisture conditions. Hybrid, moisture condition, and hybrid-by-moisture condition interaction effects were significant (p≤ 0.001) for most of the traits studied. Eleven genotypes were selected in each moisture condition through MGIDI by assuming 15% selection intensity where two hybrids, viz., ZH161289 and ZH161303, were found to be common across all the moisture regimes, indicating their moisture stress resilience, a unique potential for broader adaptation in rainfed stress-vulnerable ecologies. The selected hybrids showed desired genetic gains such as positive gains for grain yield (almost 11% in optimal and drought; 22% in waterlogging) and negative gains in flowering traits. The view on strengths and weaknesses as depicted by the MGIDI assists the breeders to develop maize hybrids with desired traits, such as grain yield and other yield contributors under specific stress conditions. The MGIDI would be a robust and easy-to-handle multi-trait selection process under various test environments with minimal multicollinearity issues. It was found to be a powerful tool in developing better selection strategies and optimizing the breeding scheme, thus contributing to the development of climate-resilient maize hybrids.
Siblings, shopping, and sustainability: Birth-order differences in green consumption
Authors: Otterbring Tobias , Sundgot-Borgen Christine , Bratland-Sanda Solfrid , Trangsrud Lise Katrine Jepsen
Published: March 2023

Several studies have examined the role of birth order in shaping human personality, but fewer have tested this variable in relation to other pressing issues. We conducted a birth-order study on green consumption, which enabled us to detect a small-to-moderate effect size equivalent tor= 0.15 ord= 0.30 with sufficient statistical power (N= 335). To capture green consumption, participants indicated their tendency to express the value of environmental protection through purchases and consumption behaviors. Firstborns (vs. laterborns) consistently expressed lower concerns linked to environmental protection in their purchase patterns. While the effect size of this finding was small-to-moderate by conventional standards and in direct contrast to the findings from a recent article on the same topic, these results could still be informative to address challenges associated with climate change considering the number of individuals with siblings in the world and the ease with which birth-order data can be collected.
Development of a computerized 2D rating scale for continuous and simultaneous evaluation of two dimensions of a sensory stimulus
Authors: Hoeppli Marie-Eve , Thurston Taylor S. , Roy Mathieu , Light Alan R. , Amann Markus , Gracely Richard H. , Schweinhardt Petra
Published: March 2023

Introduction

One-dimensional rating scales are widely used in research and in the clinic to assess individuals’ perceptions of sensory stimuli. Although these scales provide essential knowledge of stimulus perception, their limitation to one dimension hinders our understanding of complex stimuli.

Methods

To allow improved investigation of complex stimuli, a two-dimensional scale based on the one-dimensional Gracely Box Scale was developed and tested in healthy participants on a visual and an auditory task (rating changes in brightness and size of circles and rating changes in frequency and sound pressure of sounds, which was compared to ratings on one-dimensional scales). Before performing these tasks, participants were familiarized with the intensity descriptors of the two-dimensional scale by completing two tasks. First, participants sorted the descriptors based on their judgment of the intensity of the descriptors. Second, participants evaluated the intensity of the descriptors by pressing a button for the duration they considered matching the intensity of the descriptors or squeezing a hand grip dynamometer as strong as they considered matching the intensity of the descriptors.

Results

Results from these tasks confirmed the order of the descriptors as displayed on the original rating scale. Results from the visual and auditory tasks showed that participants were able to rate changes in the physical attributes of visual or auditory stimuli on the two-dimensional scale as accurately as on one-dimensional scales.

Discussion

These results support the use of a two-dimensional scale to simultaneously report multiple dimensions of complex stimuli.
Treatment patterns, adherence to international guidelines, and financial mechanisms of the market access of advanced breast cancer therapy in Bulgaria
Authors: Karanyotova Stephanie , Topova Branimira , Petrova Elina , Doychev Peter , Kapitanska Eliana , Petrova Guenka , Mitkova Zornitsa , Dimitrova Maria
Published: March 2023

Introduction

Breast cancer is the most common type of cancer affecting women in Europe. Advanced breast cancer (ABC) poses a significant therapeutic challenge, and therefore, timely access to treatment is crucial. The aim of the present study was to evaluate the treatment patterns and patients' access to new therapies for ABC in Bulgaria.

Methods

We conducted a retrospective study in the period 2008–2021. Based on the European Medicines Agency (EMA) database, we analyzed a number of medicinal products with marketing authorization for ABC in the last 13 years. Time to market access was evaluated as the degree of availability, which is measured by the number of medicines that are available to patients (availability index, AI), and the average time elapsed between obtaining a marketing authorization and time to inclusion in the Positive Drug List. Data were analyzed through descriptive statistics via Microsoft Excel version 10.

Results

The average time to access was 564 days for targeted therapy. The availability and compliance index for chemotherapy and hormonal therapy in advanced breast cancer was 1, while the average AI for targeted therapy was 0.67. Patient access to targeted oncology therapy of ABC is above average for Europe and takes 1–2 years.

Conclusion

Faster access is more evident for biosimilars. National regulatory requirements for pricing and reimbursement have a major impact on market access.
Serosurvey of Trypanosoma cruzi in persons experiencing homelessness and shelter workers of Brazil
Authors: Kmetiuk Louise Bach , Gonçalves Gustavo , Chechia Do Couto Anahi , Biondo Alexander Welker , Figueiredo Fabiano Borges
Published: March 2023

Although Chagas disease, caused by Trypanosoma cruzi, has been associated with social vulnerability worldwide, producing disability and mortality, no study to date has assessed this protozoal infection in persons experiencing homelessness. Accordingly, the present study aimed to assess anti-T. cruzi antibodies by Wiener Chagatest ELISA recombinant v.3.0 in serum samples of persons experiencing homelessness and related shelter workers in São Paulo, a city with reported vectors but no recent autochthonous case report. Overall, seropositivity to T. cruzi resulted in three of 203 (1.5%) persons experiencing homelessness and two of 87 (2.3%) shelter workers, with similar seroprevalence likely associated with their past social vulnerability. Although the seropositivity in persons experiencing homelessness and shelter workers was within 0 to 25.1% seroprevalence for chronic Chagas disease in the general Brazilian population, the disease has almost decreased 2-fold from the 1980s to 2000s, and such a wide range may not reflect the local disease status. In addition, the authors hypothesized that the similar seroprevalence and exposure between homeless persons and shelter workers herein may be more associated with shared past and present low-income social vulnerability than migratory movements, which may also include infection by sharing injecting drugs, vertical transmission, or blood transfusion. Thus, future studies are needed to confirm the active transmission of Chagas disease in São Paulo city. Moreover, Chagas disease should be considered as differential diagnosis in homeless persons and shelter workers, even in major disease-free Brazilian or other worldwide cities, mostly due to early exposure and vulnerable living conditions.
Case report: The gait deviation index may predict neurotherapeutic effects of FES-assisted gait training in children with cerebral palsy
Authors: Behboodi Ahad , Sansare Aswhini , Zahradka Nicole , Lee Samuel C. K.
Published: March 2023

Background

Children with cerebral palsy (CP) show progressive loss of ambulatory function characterized by kinematic deviations at the hip, knee, and ankle. Functional electrical stimulation (FES) can lead to more typical lower limb kinematics during walking by eliciting appropriately timed muscle contractions. FES-assisted walking interventions have shown mixed to positive results in improving lower limb kinematics through immediate correction of gait during the application of FES, or long-term, persisting effects of non-FES-assisted gait improvements following multi-week FES-assisted gait training, at the absence of stimulation, i.e., neurotherapeutic effects. It is unknown, however, if children with CP will demonstrate a neurotherapeutic response following FES-assisted gait training because of the CP population's heterogeneity in gait deviations and responses to FES. Identifying the neurotherapeutic responders is, therefore, important to optimize the training interventions to those that have higher probability of benefiting from the intervention.

Objective

The purpose of this case study was to investigate the relationship between immediate and neurotherapeutic effects of FES-assisted walking to identify responders to a FES-assisted gait training protocol.

Methods

The primary outcome was Gait Deviation Index (GDI) and secondary outcome was root mean squared error (RMSE) of the lower extremity joint angles in the sagittal plane between participants with CP and a typically developing (TD) dataset. Potential indicators were defined as immediate improvements from baseline during FES-assisted walking followed by neurotherapeutic improvements at the end of training.

Case description

Gait analysis of two adolescent female participants with spastic diplegia (Gross Motor Function Classification System level II and III) was conducted at the start and end of a 12-week FES-assisted treadmill training protocol. Participant 1 had scissoring crouch gait, while participant 2 had jump gait.

Outcomes

The GDI showed both immediate (presence of FES) and neurotherapeutic (absence of FES after training period) improvements from baseline in our two participants. Joint angle RMSE showed mixed trends between immediate and neurotherapeutic changes from baseline. The GDI warrants investigation in a larger sample to determine if it can be used to identify responders to FES-assisted gait training.
Development of a combination of noradrenergic and antimuscarinic drugs for the treatment of obstructive sleep apnea: Challenges and progress
Authors: Taranto-Montemurro Luigi , Pho Huy , White David P.
Published: March 2023

Obstructive sleep apnea (OSA) is a disorder characterized by repetitive collapse of the upper airway during sleep, leading to intermittent hypoxia and sleep fragmentation. The combination of noradrenergic and antimuscarinic drugs has emerged as a potential pharmacological treatment option for OSA, with the most promising combination being atomoxetine plus aroxybutynin. This combination is currently undergoing extensive experimentation and will be soon tested in phase 3 studies. Other noradrenergic drugs including reboxetine, and other antimuscarinics including fesoterodine, hyoscine butylbromide, solifenacin, and biperiden have been tested. The increasing interest in OSA pharmacotherapy is driven by advances in our understanding of the pathophysiology of the disease and accumulating evidence of the surprising effectiveness of this drug combination. However, challenges remain in accurately measuring the severity of OSA, which can impact our ability to fully understand the efficacy of these medications. Further research is ongoing to address these challenges and to optimize the use of noradrenergic and antimuscarinic drugs for the treatment of OSA.
Effects of an 8-week multimodal program on thoracic posture, glenohumeral range of motion and serve performance in competitive young tennis players
Authors: Le Solliec Tom , Blache Yoann , Rogowski Isabelle
Published: March 2023

Introduction

Intensive tennis practice is known to generate sport-specific adaptations at the shoulder region and influence the sagittal spinal curvature. However, increased thoracic kyphosis decreases the shoulder functional capacity, which could limit tennis performance. Therefore, the aim of this study was to investigate the effects of an 8-week multimodal program on thoracic posture, glenohumeral range of motion, and serve performance in competitive young tennis players.

Methods

Eighteen male and four female players (age: 16.0 ± 2.4 years, height: 170.7 ± 11.0 cm; mass: 62.1 ± 11.5 kg; International Tennis Number: 3–4) performed their regular training during 8 weeks, which was used as a reference period, and implemented a multimodal program including stretching, strengthening, and myofascial release exercises, four times per week during 8 additional weeks, which corresponded to the intervention period. The thoracic curvature angle and mobility, the biacromial and interscapular distances, the glenohumeral range of motion and the tennis serve performance were assessed three times, i.e., before and after the regular training and after the 8-week multimodal program.

Results

The results showed that the 8-week regular training had no significant effects on thoracic curvature angle [effect size (ES) = 0.02–0.36, p = 0.06–0.46] and mobility (ES = 0.05–0.26, p = 0.13–0.42), biacromial (ES = 0.05, p = 0.18) and interscapular distances (ES = 0.03, p = 0.45), ranges of motion in glenohumeral internal (ES = 0.04, p = 0.43) and external rotation (ES = 0.43, p = 0.06), and tennis serve accuracy (ES = 0.33, p = 0.07) and velocity (ES = 0.09, p = 0.35). The 8-week multimodal program increased moderately the thoracic mobility (ES = 0.55, p = 0.01), moderately to strongly the serve accuracy and velocity (ES = 0.65, p = 0.003, for both), strongly decreased the interscapular distance (ES = 1.02, p < 0.001), and strongly increased the range of motion in glenohumeral internal (ES = 0.90, p < 0.001) and external rotation (ES = 1.49, p < 0.001).

Discussion

These findings indicated that an 8-week multimodal program, including spine and glenohumeral mobility and shoulder girdle strength exercises, performed four times per week during 8 weeks, is moderately relevant to rectify the sagittal thoracic curvature in competitive tennis players, while such a program may help regain the range of motion in glenohumeral rotation without tennis serve performance impairment.
Neurointerventional infusion of hemoglobin oxygen carrier prevents brain damage from acute cerebral ischemia in rats
Authors: Gao Hong , Peng Han , Yang Hua , Li Qiuping , Xiang Xin
Published: March 2023

Aim

To save brain cells in acute cerebral infarction by injecting hemoglobin oxygen carrier (HBOC) into the blood vessel blockage of the cerebral infarction site through a microcatheter.

Methods

120 male rats were divided into four groups: control (CTRL), ischemia (I), ischemia + low perfusion (I + LP), and ischemia + high perfusion (I + HP). Perfusion groups (ischemia, I + LP, and I + HP) underwent MCAO surgery with intraluminal monofilament. These groups were subdivided into 6 h, 12 h, and 24 h (n = 10/group). RT-PCR, Western-Blot, immunohistochemistry, and apoptosis assays were used to detect apoptosis, hypoxia range and extent, and ischemia.

Results

Compared with the I group, the neurological deficit sign scores of the I + HP group were statistically significant at 12 h. Compared with the I group, the neurological deficit sign scores of the I + LP group and the I + HP group were statistically significant at 24 h. At all time points, compared with the I group and the I + LP group, Caspase-3, HIF-1α, and Cytochrome C protein levels were significantly decreased in the I + HP group. Bcl-2 and BAX mRNA levels were also significantly decreased in the same group. TNF-α, IL-6, and IL-1β cytokines were significantly decreased in the I + HP group as well. The infarct size of rats in the I + HP group was smaller than that of the I + LP group, which was smaller than ischemia alone. Time of perfusion had an obvious effect as infarct size was smaller with longer perfusion. The number of Nissl stained cells in the I + HP group was increased compared with the ischemia and the I + LP group, and was proportional to the time of perfusion.

Conclusion

Time- and rate-controlled perfusion of HBOC to acutely occluded cerebral vascular regions through microcatheters can effectively protect ischemic brain tissue in rats.
Case report Iatrogenic parasitic leiomyoma: the surgeon's invisible hand
Authors: Emery Shahzia Lambat , Pluchino Nicola , Martino Antonella , Mauri Fabio , Petignat Patrick , Dubuisson Jean
Published: March 2023

Uterine leiomyoma is the most common benign tumour of the uterus in women of reproductive age. When removed surgically, a mini-invasive procedure is preferentially used (laparoscopic or robotic) and the extraction of the specimen can be managed by power morcellation. In this consecutive case-series, we present three cases of parasitic leiomyoma that appeared following previous surgical management of leiomyoma using the technique of laparoscopic myomectomy with uncontained power morcellation. The time frame in between the initial surgery and the diagnosis of the parasitic leiomyoma was 5.7 years. All three patients were diagnosed with endometriosis: 2 cases prior to the initial surgery and 1 case after the initial surgery. One hypothesis could be that, due to pelvic inflammation, endometriosis is a risk factor for iatrogenic parasitic leiomyoma development in case of uncontained morcellation of leiomyoma during myomectomy.
Network motifs and hypermotifs in TGFβ-induced epithelial to mesenchymal transition and metastasis
Authors: Sai Bhavani Gottumukkala , Palanisamy Anbumathi
Published: March 2023

Epithelial to mesenchymal transition (EMT) is a complex, non-linear, dynamic multistep process that plays an integral role in the development of metastatic cancers. A diverse range of signaling molecules, along with their associated pathways, were observed to be involved in promoting EMT and cancer metastasis. Transforming growth factor–β (TGFβ), through its SMAD-dependent and SMAD-independent signaling, orchestrates numerous regulators that converge on key EMT transcription factors (TFs). These TFs further govern the phenotypic transition of cancer cells from epithelial to mesenchymal states. This study explores the TGFβ signaling pathway and its unique network architecture to understand their information processing roles in EMT. Two coherent type 1 feed forward network motifs regulating the expression of SNAIL and N-cadherin were observed. SNAIL, which is one of the crucial regulators of EMT, links both the coherent type 1 feed forward loops (C1FFLs) leading to hypermotif-like structure (Adler and Medzhitov, 2022). Systems modeling and analysis of these motifs and hypermotifs illustrated several interesting emergent information processing roles of the regulators involved. The known roles of these regulators, as described in the literature, were highly correlated with the emergent properties observed. The motifs illustrated persistence detection and noise filtration in regulating the expression of SNAIL and N-cadherin. Along with these system-level properties, the hypermotif architecture also exhibited temporal expression of GLI, SNAIL, ZEB, and N-cadherin. Furthermore, a hypothetical three-layered C1FFL hypermotif was postulated and analyzed. The analysis revealed various interesting system-level properties. However, possible existence of such real biological networks needs further exploration both theoretically and experimentally. Deciphering these network motifs and hypermotifs has provided an additional understanding of the complex biological phenomenon, such as EMT in cancer metastasis.