bluuebunny/crossref_metadata_2025 huggingface dataset:
New insights of metabolite abnormalities in the thalamus of rats with iminodiproprionitrile-induced tic disorders
Authors: Yu Jingru , Yao Xuan , Zhang Xin , Hao Juanjuan
Published: September 2023

Introduction

This study aimed to investigate pathological changes in the “Glutamate (Glu)-γ-aminobutyric acid (GABA)” loop and apply widely targeted metabolomic analysis technology to comprehensively explore metabolite abnormalities/ in the thalamus of rats with tic disorders (TD).

Methods

Wistar rats were randomized into control, TD, and tiapride (Tia) groups. Iminodipropionitrile (IDPN) was used to induce TD in rats. The Tia group was administered tiapride. Neurotransmitter levels in the thalamus of rats in the three groups were measured using UPLC-3Q MS. And, the protein expression levels of Glu decarboxylase (GAD65/67) and GABA transporter protein (GAD-T) were measured using western blotting. The mRNA expression levels of these genes were evaluated using real-time polymerase chain reaction. Lastly, other metabolites in the thalamus were detected by widely targeted metabolomic analysis between TD and Control group rats.

Results

The Glu level, Glu/GABA ratio, and Asp level in the TD group were significantly higher (all p < 0.001) than those of the Control group, whereas the GABA and Gly levels were lower (p < 0.001 and p = 0.009, respectively). The Tia group exhibited a significant reduction in the Glu level (p = 0.001) compared with the TD group. The protein expression level of GAD67 in TD group was higher (p = 0.009) and the mRNA expression levels of GAD65, GAD67, and GAT-1 were lower (p < 0.05) than those of the Control group. The Tia group did not display any differences in GAD65, GAD67, or GAT-1 expression. Widely targeted metabolomic analysis revealed that 34 substances were abnornal between the TD and Control groups (9 upregulated and 25 downregulated). Neurosteroids (progesterone, corticosterone) exhibited distinct differences. Metabolite analysis using the Kyoto encyclopedia for genes and genomes indicated that the steroid hormone biosynthesis pathway may be involved in TD pathogenesis.

Conclusion

This study revealed metabolic abnormalities in the thalamus of rats with TD. The interaction between neurotransmitters and neurosteroid biosynthesis represents a new direction for future studies.
Donor/recipient origin of lung cancer after lung transplantation by DNA short tandem repeat analysis
Authors: De Wolf Julien , Robin Edouard , Vallee Alexandre , Cohen Justine , Hamid Abdul , Roux Antoine , Leguen Morgan , Beaurepere Romane , Bieche Ivan , Masliah-Planchon Julien , Glorion Matthieu , Allory Yves , Sage Edouard ,   the Foch lung transplant group
Published: September 2023

Background

Lung cancer is more common in posttransplant recipients than in the general population. The objective of this study was to examine the chimerism donor/recipient cell origin of graft cancer in recipients of lung transplant.

Methods

A retrospective chart review was conducted at Foch Hospital for all lung transplantations from 1989 to 2020. Short tandem repeat PCR (STR-PCR) analysis, the gold standard technique for chimerism quantification, was used to determine the donor/recipient cell origin of lung cancers in transplant patients.

Results

Fourteen (1.4%) of the 1,026 patients were found to have graft lung cancer after lung transplantation, and one developed two different lung tumors in the same lobe. Among the 15 lung tumors, 10 (67%) presented with adenocarcinoma, four (27%) with squamous cell carcinoma and one with small cell lung cancer. STR analysis showed that the origin of the cancer was the donor in 10 patients (71%), the recipient in three patients (21%), and was undetermined in one patient. Median time to diagnosis was 62 months.

Conclusion

The prevalence of lung cancer in lung transplant recipients is very low. However, the results of our study showed heterogeneity of genetic alterations, with 21% being of recipient origin. Our results highlight the importance of donor selection and medical supervision after lung transplantation.
Phenotypic heterogeneity drives differential disease outcome in a mouse model of triple negative breast cancer
Authors: Thankamony Archana P. , Ramkomuth Sonny , Ramesh Shikha T. , Murali Reshma , Chakraborty Priyanka , Karthikeyan Nitheesh , Varghese Binitha Anu , Jaikumar Vishnu Sunil , Jolly Mohit Kumar , Swarbrick Alexander , Nair Radhika
Published: September 2023

The triple negative breast cancer (TNBC) subtype is one of the most aggressive forms of breast cancer that has poor clinical outcome and is an unmet clinical challenge. Accumulating evidence suggests that intratumoral heterogeneity or the presence of phenotypically distinct cell populations within a tumor play a crucial role in chemoresistance, tumor progression and metastasis. An increased understanding of the molecular regulators of intratumoral heterogeneity is crucial to the development of effective therapeutic strategies in TNBC. To this end, we used an unbiased approach to identify a molecular mediator of intratumoral heterogeneity in breast cancer by isolating two tumor cell populations (T1 and T2) from the 4T1 TNBC model. Phenotypic characterization revealed that the cells are different in terms of their morphology, proliferation and self-renewal ability in vitro as well as primary tumor formation and metastatic potential in vivo. Bioinformatic analysis followed by Kaplan Meier survival analysis in TNBC patients identified Metastasis associated colon cancer 1 (Macc1) as one of the top candidate genes mediating the aggressive phenotype in the T1 tumor cells. The role of Macc1 in regulating the proliferative phenotype was validated and taken forward in a therapeutic context with Lovastatin, a small molecule transcriptional inhibitor of Macc1 to target the T1 cell population. This study increases our understanding of the molecular underpinnings of intratumoral heterogeneity in breast cancer that is critical to improve the treatment of women currently living with the highly aggressive TNBC subtype.
Arthralgia adverse events due to immune-checkpoint inhibitors for lung cancer patients: a systematic review and meta-analysis
Authors: Zou Defang , Wang Xiaoping , Sun Yamin , Wang Xi , Lu Chang , Wang Aiyun , Wang Xia , Yang Yan
Published: September 2023

Background

Immune agents targeting Programmed cell death-1 (PD-1) are a new type of cancer treatment drugs. By inhibiting the interaction between PD-1 and PD-L1, the ability of the immune system to attack tumor cells is enhanced. These immune preparations have shown significant efficacy in the treatment of various malignant tumors. However, like other drugs, immune preparations targeting PD-1 may also cause side effects, including arthralgia. Therefore, we conduct a meta-analysis to assess whether immune-checkpoint inhibitors targeting programmed cell death-1 in lung cancer patients will lead to arthralgia adverse events.

Methods

We conducted a comprehensive search across multiple databases, including PubMed, Medline (Ovid), Web of Science, Cochrane, Embase, Scopus, CKNI, Wang fang, VIP database, Sino Med, and Clinical Trails, to identify relevant studies. The search encompassed articles published up until June 20th, 2023. The primary outcome is adverse events about arthralgia and secondary outcomes are any other related with arthralgia. Data extraction was carried out by two independent individuals, and the Cochrane Risk of Bias tool version 2.0 was employed to assess the included studies. The systematic review and meta-analysis were conducted using RevMan 5.3 software.

Results

12 studies are included in the meta-analysis. All included studies were determined to have a low risk of random sequence generation bias. The meta-analysis result showed that arthralgia RR = 1.11, 95% CI [0.88, 1.40], I2 = 56%, back pain RR = 1.86, 95% CI [1.07, 3.26], I2 = 84%, myalgia RR = 0.49, 95% CI [0.27, 0.88], I2 = 86% and muscular pain RR = 1.97, 95% CI [1.40, 2.77], I2 = 23%.

Conclusion

The use of targeted inhibitors may lead to an increased incidence of back pain, while potentially reducing the occurrence of myalgia. On the other hand, immune-checkpoint inhibitors targeting programmed cell death-1 in lung cancer patients may not cause arthralgia and muscular pain.
Advance in integrating platinum-based chemotherapy with radiotherapy for locally advanced nasopharyngeal carcinoma
Authors: Zhu Fubin , Wu Yidan , Wang Hua
Published: September 2023

Nasopharyngeal carcinoma (NPC) is a malignant tumor characterized by the malignant transformation of nasopharyngeal epithelial cells. It is highly sensitive to radiation therapy, making radiotherapy the primary treatment modality. However, 60-80% of patients are initially diagnosed with locally advanced NPC (LA-NPC), where radiotherapy alone often fails to achieve desirable outcomes. Therefore, combining radiotherapy with chemotherapy has emerged as an effective strategy to optimize treatment for LA-NPC patients. Among the various chemotherapy regimens, concurrent chemoradiotherapy (CCRT) using platinum-based drugs has been established as the most commonly utilized approach for LA-NPC patients. The extensive utilization of platinum drugs in clinical settings underscores their therapeutic potential and emphasizes ongoing efforts in the development of novel platinum-based complexes for anticancer therapy. The aim of this review is to elucidate the remarkable advances made in the field of platinum-based therapies for nasopharyngeal carcinoma, emphasizing their transformative impact on patient prognosis.
Long acting growth hormone (LAGH), an update
Authors: Grillo Margaret Steiner , Frank Jacklyn , Saenger Paul
Published: September 2023

In 1957, Maurice Raben at Yale was able to isolate and purify growth hormone from cadaveric pituitary glands. Pituitary growth hormone was the only way to treat children with growth hormone (GH) deficiency, until 1985 when recombinant GH became available for daily subcutaneous injection. For many years, the pediatric endocrine community longed for a long-acting recombinant GH formulation that would decrease the inconvenience of daily injections. Several mechanisms were employed to develop a GH that is rapidly absorbed into the blood stream after subcutaneous injection, but provides slow removal from the circulatory system to potentially optimize patient adherence to GH therapy. Four long-acting growth hormones are currently available in the world, or are close to regulatory approval. They are: (1) Pegylated formulations, (2) Prodrug formulations which are converted into active drug, (3) Nonvalent transient albumin binding GH compounds and (4) GH fusion proteins where a protein si fused with GH. All four formulations have undergone detailed phase 3 studies and were found to show non-inferiority in these clinical studies. All four demonstrate a safety and tolerability profile that is comparable to that of daily somatropin with an excellent adherence profile.
Not one, but many: developing a multi-indication pricing model for medicines in Belgium
Authors: Maes Ingrid , Kok Eline , De Torck Pieter-Jan , Mestre-Ferrandiz Jorge , Simoens Steven
Published: September 2023

Back ground: Current pricing and reimbursement models that focus on one indication at a time are not suited to address the market access of multi-indication medicines. Therefore, the aim of this study is to co-create with Belgian stakeholders a multi-indication pricing model and procedural pathway, to identify conditions for implementation, and to illustrate the multi-indication pricing model with a case study.

Methods: Different multi-indication pricing models were identified from the literature, case studies and pilots in other countries. Semi-structured interviews were conducted with 21 representatives from the National Institute for Health and Disability Insurance, insurance funds, clinicians, patients, the policy cell of the Minister of Health, pharmaceutical industry and academia. These provided insight in the opinions of stakeholders about possible multi-indication pricing models and their feasibility in the Belgian context. Agreement on the preferred multi-indication pricing model and procedural pathway was reached in a multi-stakeholder round table.

Results: The international review generated four main multi-indication pricing models that vary in terms of whether a uniform price or differential prices are applied, whether prices are adjusted for the volume and/or value of the medicine in each indication, and whether a proactive or retroactive dynamic pricing approach is used. However, Belgian stakeholders preferred a fifth model, which sets a single price as the volume- and value-weighted average price across all indications at launch. Over time, the price is adapted based on volume and value of the medicine in real-life practice for each indication. To implement this model, a legal framework, horizon scanning and early dialogue, data infrastructure, an evidence plan for the medicine, technical expertise and governance model need to be developed.

Conclusion: Although the multi-indication pricing model preferred by Belgian stakeholders raises the administrative burden, it allows for the price of a medicine to vary during the lifecycle based on its initial and real-life performance in multiple indications.
Recent advances in medicinal compounds related to corneal crosslinking
Authors: Qin Danyi , Han Yi , Wang Lixiang , Yin Hongbo
Published: September 2023

Corneal crosslinking (CXL) is the recognized technique to strengthen corneal collagen fibers through photodynamic reaction, aiming to halt progressive and irregular changes in corneal shape. CXL has greatly changed the treatment for keratoconus (KCN) since it was introduced in the late 1990’s. Numerous improvements of CXL have been made during its developing course of more than 20 years. CXL involves quite a lot of materials, including crosslinking agents, enhancers, and supplements. A general summary of existing common crosslinking agents, enhancers, and supplements helps give a more comprehensive picture of CXL. Either innovative use of existing materials or research and development of new materials will further improve the safety, effectiveness, stability, and general applicability of CXL, and finally benefit the patients.
A review of the pathophysiology and the role of ion channels on bronchial asthma
Authors: Figueiredo Indyra Alencar Duarte , Ferreira Sarah Rebeca Dantas , Fernandes Jayne Muniz , Silva Bagnólia Araújo da , Vasconcelos Luiz Henrique César , Cavalcante Fabiana de Andrade
Published: September 2023

Asthma is one of the main non-communicable chronic diseases and affects a huge portion of the population. It is a multifactorial disease, classified into several phenotypes, being the allergic the most frequent. The pathophysiological mechanism of asthma involves a Th2-type immune response, with high concentrations of allergen-specific immunoglobulin E, eosinophilia, hyperreactivity and airway remodeling. These mechanisms are orchestrated by intracellular signaling from effector cells, such as lymphocytes and eosinophils. Ion channels play a fundamental role in maintaining the inflammatory response on asthma. In particular, transient receptor potential (TRP), stock-operated Ca2+ channels (SOCs), Ca2+-activated K+ channels (IKCa and BKCa), calcium-activated chloride channel (TMEM16A), cystic fibrosis transmembrane conductance regulator (CFTR), piezo-type mechanosensitive ion channel component 1 (PIEZO1) and purinergic P2X receptor (P2X). The recognition of the participation of these channels in the pathological process of asthma is important, as they become pharmacological targets for the discovery of new drugs and/or pharmacological tools that effectively help the pharmacotherapeutic follow-up of this disease, as well as the more specific mechanisms involved in worsening asthma.
Distinct pleiotropic effects of direct oral anticoagulants on cultured endothelial cells: a comprehensive review
Authors: Atzemian Natalia , Kareli Dimitra , Ragia Georgia , Manolopoulos Vangelis G.
Published: September 2023

Direct Oral Anticoagulants (DOACs) have simplified the treatment of thromboembolic disease. In addition to their established anticoagulant effects, there are indications from clinical and preclinical studies that DOACs exhibit also non-anticoagulant actions, such as anti-inflammatory and anti-oxidant actions, advocating overall cardiovascular protection. In the present study, we provide a comprehensive overview of the existing knowledge on the pleiotropic effects of DOACs on endothelial cells (ECs) in vitro and their underlying mechanisms, while also identifying potential differences among DOACs. DOACs exhibit pleiotropic actions on ECs, such as anti-inflammatory, anti-atherosclerotic, and anti-fibrotic effects, as well as preservation of endothelial integrity. These effects appear to be mediated through inhibition of the proteinase-activated receptor signaling pathway. Furthermore, we discuss the potential differences among the four drugs in this class. Further research is needed to fully understand the pleiotropic effects of DOACs on ECs, their underlying mechanisms, as well as the heterogeneity between various DOACs. Such studies can pave the way for identifying biomarkers that can help personalize pharmacotherapy with this valuable class of drugs.
Therapeutic potential of Ganoderma lucidum polysaccharide peptide in Doxorubicin-induced nephropathy: modulation of renin-angiotensin system and proteinuria
Authors: Fang Hui , Lin Dongmei , Li Xinxuan , Wang Lianfu , Yang Teng
Published: September 2023

Introduction: In the Doxorubicin (DOX)-induced nephropathy model, proteinuria is a manifestation of progressive kidney injury. The pathophysiology of renal illness is heavily influenced by the renin-angiotensin system (RAS). To reduce renal RAS activation and proteinuria caused by DOX, this study evaluated the effectiveness of Ganoderma lucidum polysaccharide peptide (GL-PP), a new glycopeptide produced from Ganoderma lucidum grown on grass.

Methods: Three groups of BALB/c male mice were created: control, DOX, and DOX + GL-PP. GL-PP (100 mg/kg) was administered to mice by intraperitoneal injection for 4 weeks following a single intravenous injection of DOX (10 mg/kg via the tail vein).

Results: After 4 weeks, full-length and soluble pro(renin) receptor (fPRR/sPRR) overexpression in DOX mouse kidneys, which is crucial for the RAS pathway, was dramatically inhibited by GL-PP therapy. Additionally, GL-PP successfully reduced elevation of urinary renin activity and angiotensin II levels, supporting the idea that GL-PP inhibits RAS activation. Moreover, GL-PP showed a considerable downregulation of nicotinamide adenine nucleotide phosphate oxidase 4 (NOX4) expression and a decrease in hydrogen peroxide (H2O2) levels. GL-PP treatment effectively reduced glomerular and tubular injury induced by DOX, as evidenced by decreased proteinuria, podocyte damage, inflammation, oxidative stress, apoptosis, and fibrosis.

Discussion: GL-PP inhibits intrarenal PRR/sPRR-RAS activation and upregulation of NOX4 and H2O2, suggesting potential therapeutic approaches against DOX-induced nephropathy.
Autophagy impairment in human bile duct carcinoma cells
Authors: Petrungaro Simonetta , de Franchis Valerio , Filippini Antonio , Facchiano Antonio , Gaudio Eugenio , Giampietri Claudia
Published: September 2023

Bile duct epithelial cells, named cholangiocytes, may undergo a neoplastic transformation leading to cholangiocarcinoma. The role autophagy plays in cancer is still debated and few information are available in cholangiocarcinoma. We report in vitro data, at least in part validated in vivo,i ndicating that autophagy is impaired in intrahepatic cholangiocarcinoma cells, as compared to healthy cholangiocytes, evaluated through LC3II and p62 Western blot analyses. Autophagy impairment was found to be associated with low expression of TFEB protein and high expression of three proteins i.e., c-FLIP, caspase-10 and cleaved BCLAF-1, as compared to healthy cholangiocytes. We highlight biological effects of autophagy impairment in cholangiocarcinoma showing that autophagy induction, via rapamycin, as well as caspase inhibition, via Q-VD-OPh, are able to reduce proliferation marker PCNA level, colony size and protein content of cultured cholangiocarcinoma cells. The increased protein expression of p62, c-FLIP, caspase-10 observed in vitro in cholangiocarcinoma cells was paralleled by significant increase at gene expression levels in vivo; in fact, significant increase of transcript levels of p62, c-FLIP and caspase-10 was observed in 34 biopsies from human cholangiocarcinoma patients compared to 9 biopsies from 9 healthy controls, as reported in the GEPIA2 public database. The significant increase of p62 level in cholangiocarcinoma was found as a relatively uncommon finding in solid cancers, since it was also found in only 7 cancer types out of 31 cancer types investigated, including melanoma and hepatocarcinoma. In conclusion, we present data suggesting a molecular machinery controlling autophagy in cholangiocytes and autophagy impairment in cholangiocarcinoma.
Gene silencing of cathepsins B and L using CTV-based, plant-mediated RNAi interferes with ovarial development in Asian citrus psyllid (ACP), Diaphorina citri
Authors: Ibanez Freddy , Vieira Rocha Sâmara , Dawson William O. , El-Mohtar Choaa , Robertson Cecile , Stelinski Lukasz L. , Soares-Costa Andrea
Published: September 2023

Diaphorina citri Kuwayama (Hemiptera: Liviidae) is a vector of the bacteria Candidatus Liberibacter americanus (CLam) and Candidatus Liberibacter asiaticus (CLas), which are phloem-restricted and associated with the most important and destructive worldwide citrus disease, Huanglongbing (HLB). Currently, no cure for HLB has been described. Therefore, measures have focused on reducing D. citri populations. In these insects, cathepsin B (DCcathB) and L (DCcathL) enzymes play an important role in digestion, and are involved in embryogenesis, immune defense, and ecdysis. In this study, we used a CTV-based vector to deliver dsRNA (CTV-dsRNA) into Citrus macrophylla plants targeting DCcathB and DCcathL genes in D. citri that fed on the phloem of these CTV-RNAi infected plants. Subsequently, we evaluated expression of DCcathB and DCcathL genes as well as the Vitellogenin (Vg) gene by RT-qPCR in D. citri fed on CTV-dsRNA occurring in plant phloem. It was found that a defective phenotype in D. citri females as a result of knockdown of DCcathB and DCcathL genes mediated by CTV dsRNA. These results showed that Psyllids fed on plants treated with the CTV-dsRNA exhibited downregulation of the Vg gene, one of the most important genes associated with embryogenic and female development, which was associated with dsRNA-mediated silencing of the two cathepsin genes. Based on our findings, a CTV-based strategy for delivering RNAi via plants that targets DCcathB and DCcathL genes may represent a suitable avenue for development of dsRNA-based tools to manage D. citri that limits the spread of HLB.
Assessment of molybdenum application on soybean physiological characteristics in maize-soybean intercropping
Authors: Jamali Zameer Hussain , Ali Shahzaib , Qasim Muhammad , Song Chun , Anwar Muhammad , Du Junbo , Wang Yu
Published: September 2023

Soybean is a leguminous crop known for its efficient nitrogen utilization and ease of cultivation. However, its intercropping with maize may lead to severe reduction in its growth and yield due to shading effect of maize. This issue can be resolved by the appropriate application of essential plant nutrient such as molybdenum (Mo). Aim of this study was to assess the effect of Mo application on the morphological and physiological characteristics of soybean intercropped with maize. A two-year field experiment was conducted for this purpose, and Mo was applied in the form of sodium molybdate (Na2MoO4), and four different levels were maintained i.e., 0, 60, 120 and 180 g ha-1. Soybean exhibited varying responses to different levels of molybdenum (Mo) application. Notably, in both sole and intercropped cropping systems, the application of Mo at a rate of 120 g ha-1demonstrated the highest level of promise compared to other application levels. However, most significant outcomes were pragmatic in soybean-maize intercropping, as application of Mo @ 120 g ha-1significantly improved soybean growth and yield attributes, including leaf area index (LAI; 434 and 441%), total plant biomass (430 and 461%), transpiration rate (15 and 18%), stomatal conductance (9 and 11%), and yield (15 and 20%) during year 2020 and 2021 respectively, as compared to control treatment. Similarly, Mo @ 120 g ha-1application resulted in highest total grain yield (626.0 and 725.3 kg ha-1) during 2020 and 2021 respectively, which exceeded the grain yields of other Mo levels under intercropping. Moreover, under Mo application level (120 g ha-1), grain NPK and Mo contents during years 2020 and 2021 were found to be 1.15, 0.22, 0.83 and 68.94 mg kg-1, and 1.27, 0.25, 0.90 and 72.18 mg kg−1under intercropping system increased the value as compared to control treatment. Findings of current study highlighted the significance of Mo in enhancing soybean growth, yield, and nutrient uptake efficiency in maize-soybean intercropping systems.
Multilayered regulation of iron homeostasis in Arabidopsis
Authors: Spielmann Julien , Fanara Steven , Cotelle Valérie , Vert Grégory
Published: September 2023

Iron (Fe) is an essential micronutrient for plant growth and development due to its role in crucial processes such as photosynthesis and modulation of the redox state as an electron donor. While Fe is one of the five most abundant metals in the Earth’s crust, it is poorly accessible to plants in alkaline soils due to the formation of insoluble complexes. To limit Fe deficiency symptoms, plant have developed a highly sophisticated regulation network including Fe sensing, transcriptional regulation of Fe-deficiency responsive genes, and post-translational modifications of Fe transporters. In this mini-review, we detail how plants perceive intracellular Fe status and how they regulate transporters involved in Fe uptake through a complex cascade of transcription factors. We also describe the current knowledge about intracellular trafficking, including secretion to the plasma membrane, endocytosis, recycling, and degradation of the two main Fe transporters, IRON-REGULATED TRANSPORTER 1 (IRT1) and NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 1 (NRAMP1). Regulation of these transporters by their non-Fe substrates is discussed in relation to their functional role to avoid accumulation of these toxic metals during Fe limitation.
Establishment of targeted mutagenesis in soybean protoplasts using CRISPR/Cas9 RNP delivery via electro−transfection
Authors: Subburaj Saminathan , Agapito-Tenfen Sarah Zanon
Published: September 2023

The soybean (Glycine max L.) is an important crop with high agronomic value. The improvement of agronomic traits through gene editing techniques has broad application prospects in soybean. The polyethylene glycol (PEG)-mediated cell transfection has been successfully used to deliver the CRISPR/Cas9-based ribonucleoprotein (RNP) into soybean protoplasts. However, several downstream analyses or further cell regeneration protocols might be hampered by PEG contamination within the samples. Here in this study, we attempted to transfect CRISPR/Cas9 RNPs into trifoliate leaf-derived soybean protoplasts using Neon electroporation to overcome the need for PEG transfection for the first time. We investigated different electroporation parameters including pulsing voltage (V), strength and duration of pulses regarding protoplast morphology, viability, and delivery of CRISPR/Cas9. Electroporation at various pulsing voltages with 3 pulses and 10 ms per pulse was found optimal for protoplast electro-transfection. Following electro-transfection at various pulsing voltages (500 V, 700 V, 1,000 V, and 1,300 V), intact protoplasts were observed at all treatments. However, the relative frequency of cell viability and initial cell divisions decreased with increasing voltages. Confocal laser scanning microscopy (CLSM) confirmed that the green fluorescent protein (GFP)-tagged Cas9 was successfully internalized into the protoplasts. Targeted deep sequencing results revealed that on-target insertion/deletion (InDel) frequencies were increased with increasing voltages in protoplasts electro-transfected with CRISPR/Cas9 RNPs targeting constitutive pathogen response 5 (CPR5). InDel patterns ranged from +1 bp to −6 bp at three different target sites in CPR5 locus with frequencies ranging from 3.8% to 8.1% following electro-transfection at 1,300 V and 2.1% to 3.8% for 700 V and 1,000 V, respectively. Taken together, our results demonstrate that the CRISPR/Cas9 RNP system can be delivered into soybean protoplasts by the Neon electroporation system for efficient and effective gene editing. The electro-transfection system developed in this study would also further facilitate and serve as an alternative delivery method for DNA-free genome editing of soybean and other related species for genetic screens and potential trait improvement.
Fine mapping of the major gene BhHLS1 controlling seed size in wax gourd (Benincasa hispida)
Authors: Yang Wenrui , Wang Peng , Liu Ting , Nong Lifeng , Cheng Zhikui , Su Liwen , Bai Wenhui , Deng Yan , Chen Zhihao , Liu Zhengguo
Published: September 2023

Introduction/Background

The seed size of wax gourds is an important agronomic trait; however, the associated genes have not yet been reported.

Methods

In this study, we used a high-density genetic map constructed based on F8 recombinant inbred line populations derived from a cross between MY-1 (large seed) and GX-71 (small seed) strains to detect quantitative trait locis (QTLs) for seed-size-related traits in wax gourd over a two-year period.

Results

Two stable QTLs (qSL10 and qSW10) for seed length (SL) and seed width (SW) on chromosome 10 were repeatedly detected over two years (2021–2022). qSL10 had a phenotypic variation rate of 75.30% and 80.80% in 2021 and 2022, respectively. Whereas, qSW10 had a phenotypic variation rate of 66.60% and 73.80% in 2021 and 2022, respectively. Further, a single nucleotide polymorphism mutation was found to cause early termination of Bch10G006400 (BhHLS1) translation in GX-71 through sequencing analysis of candidate genes. Based on gene functional annotation and quantitative real-time PCR analyses, BhHLS1 encoded a probable N-acetyltransferase HLS1-like protein and its expression level was significantly different between parents. Therefore, BhHLS1 is a major candidate gene associated with a one-factor polymorphism regulating the SL and SW of wax gourds. Finally, based on variation in the BhHLS1 sequence, a cleaved amplified polymorphic sequence marker was developed for the molecular marker-assisted breeding of wax gourds.

Discussion

Overall, this study is of great significance for the genetic improvement of seed size, verification of gene functions, and cultivation of specific germplasm resources for wax gourds.
Intra- and inter-brain coupling and activity dynamics during improvisational music therapy with a person with dementia: an explorative EEG-hyperscanning single case study
Authors: Maidhof Clemens , Müller Viktor , Lartillot Olivier , Agres Kat , Bloska Jodie , Asano Rie , Odell-Miller Helen , Fachner Jörg
Published: September 2023

Objective

Real-life research into the underlying neural dynamics of improvisational music therapy, used with various clinical populations, is largely lacking. This single case study explored within-session differences in musical features and in within- and between-brain coupling between a Person with Dementia (PwD) and a music therapist during a music therapy session.

Methods

Dual-EEG from a music therapist and a PwD (male, 31 years) was recorded. Note density, pulse clarity and synchronicity were extracted from audio-visual data. Three music therapists identified moments of interest and no interest (MOI/MONI) in two drum improvisations. The Integrative Coupling Index, reflecting time-lagged neural synchronization, and musical features were compared between the MOI and MONI.

Results

Between-brain coupling of 2 Hz activity was increased during the MOI, showing anteriority of the therapist’s neural activity. Within-brain coupling for the PwD was stronger from frontal and central areas during the MOI, but within-brain coupling for the therapist was stronger during MONI. Differences in musical features indicated that both acted musically more similar to one another during the MOI.

Conclusion

Within-session differences in neural synchronization and musical features highlight the dynamic nature of music therapy.

Significance

The findings contribute to a better understanding of social and affective processes in the brain and (interactive) musical behaviors during specific moments in a real-life music therapy session. This may provide insights into the role of such moments for relational-therapeutic processes.
Perspective-taking with affected others to promote climate change mitigation
Authors: Koessler Ann-Kathrin , Heinz Nicolai , Engel Stefanie
Published: September 2023

Prior evidence suggests that perspective-taking may promote pro-environmental behavior, at least for low-cost behaviors or local environmental problems. Climate change, however, requires costly mitigation efforts and is a global problem. Thus, in this study, we examine whether perspective-taking in the context of climate change is effective in promoting mitigation behaviors, including actual and/or costly behaviors, the mechanisms through which perspective-taking works, and if the distance to the person adversely affected by climate change matters for the effect. We conducted an online experiment with a non-student sample from Germany (n = 557), utilizing a 2 × 2 factorial design, to investigate the impact of perspective-taking and distance on three outcome measures: a climate donation, signing a petition, and approval of mitigation policies. We find that perspective-taking does not promote these mitigation behaviors, yet it raises the degree perspective-takers value and – for close others – feel connected with the affected person. Exploratory analysis shows that dispositional perspective-taking and empathic concern are correlated with mitigation behaviors.
Organizational culture and leadership behaviors: is manager’s psychological health the missing piece?
Authors: Dextras-Gauthier Julie , Gilbert Marie-Hélène , Dima Justine , Adou Laetitia Bomoya
Published: September 2023

Background

In a context where organizations struggle to attract and retain highly qualified workers, organizations need to prioritize the psychological health of employees as a retention factor. To do so, they need to provide a healthy work environment. As an integral part of the employee experience, managers are an important factor in employee retention. In past studies, researchers have focused on the importance of leadership in boosting employees’ health without, however, considering factors encouraging such behavior in managers. Recently, some scholars have become interested in managers’ health as a resource allowing them to adopt good leadership behavior. Indeed, these studies reveal interesting links between managers’ emotional state and their behavior as leaders. Other studies, underscore the importance of considering the organizational context to better understand managers’ psychological health that may influence their leadership behaviors. This study proposes to examine the complex process by which organizational culture influences managers’ psychological health, which acts as a resource favoring the adoption of good leadership behaviors that are known to be constructive and have positive effects on employee.

Methods

Path analyses with the CALIS procedure SAS software, version 9.4 were conducted on a sample of 522 managers in three healthcare facilities in the province of Quebec, Canada.

Results

The results revealed that group culture is associated with the two indicators of managers’ psychological health at work. The results also demonstrated that managers’ psychological distress at work is positively related to transactional and laissez-faire leadership styles whereas psychological well-being at work is positively related to transformational and transactional leadership. Concerning indirect associations, there is a significant and positive indirect association between group culture and transformational leadership and there is also a significant and negative association between group culture and laissez-faire leadership. Finally, there is also an indirect association between hierarchical culture and transactional leadership.

Conclusion

Our study provides a more in-depth understanding of the relationship between organizational culture and leadership styles. More specifically, our findings highlight the benefits of implementing a group organizational culture to enhance psychological well-being, reduce psychological distress symptoms and promote good leadership behaviors.
Development of a motivational regulatory strategy scale for Indonesian learners of Japanese
Authors: Yamashita Junko
Published: September 2023

Opportunities for LOTE (Languages Other Than English) speakers to engage with their target language are limited, making it challenging to sustain motivation. The aim of this study is to develop and validate a scale for measuring motivational regulatory strategies among Japanese-language learners and investigate their relationship with motivational factors. This research specifically focuses on Indonesian learners of Japanese who have a non-Kanji (Chinese characters) background and are studying Japanese as a foreign language. The motivational regulatory strategies scale comprises six factors and has demonstrated adequate internal consistency and factor structure. The findings indicate a positive correlation between integrative motivation and these six strategies, suggesting that learners’ integrative motivation may promote the adoption of these strategies. Furthermore, this study emphasizes the significance of the opportunity control strategy, where learners actively seek chances to expose themselves to their target language. Future research is recommended to implement the developed scale in educational settings. Conducting surveys that encompass learners from diverse cultural backgrounds and embarking on longitudinal studies should also be considered.
Mediterranean diet is associated with better gastrointestinal health and quality of life, and less nutrient deficiency in children/adolescents with disabilities
Authors: Bakırhan Hande , Özkaya Volkan , Pehlivan Merve
Published: September 2023

Background

Children and adolescents with disabilities face various nutritional problems. This study aimed to examine dietary characteristics, nutritional status and problems, gastrointestinal health, and quality of life in children and adolescents with disabilities.

Methods

This study included 5–18 years old children and adolescents (n = 1,991) with disabilities. We used the Mediterranean Diet Quality Index (KIDMED), the Gastrointestinal Symptom Rating Scale (GSRS), and the Pediatric Quality of Life Inventory (PedsQL) to assess diet characteristics, gastrointestinal problems, and life quality. We collected retrospective 24-h food record to assess energy and nutrient intakes.

Results

The rate of stunting in children with disabilities varies between 16.5% and 19.8%. When comparing disability types, more children with physical disabilities were underweight (8.8% vs. 6.7%) and stunted (19.8% vs. 16.5%), while more children with intellectual disabilities were tall (7.9% vs. 5.5%) and overweight/obese (21.1 vs. 17.2%; p < 0.05). Wasting (9.3%) and overweight/obesity (23.8%) were more common in children with disabilities aged 5–7 years (p < 0.001). Eating problems such as loss of appetite, food refusal, food neophobia, and food selectivity were more common in children aged 5–7 years, and problems with fast eating and overeating were more common in adolescents aged 13–18 years (p < 0.05). Among children and adolescents with disabilities, the nutrients with inadequate intakes were vitamin E, vitamin B1, folate, potassium, calcium, and iron, while the nutrients with intakes above the requirements were proteins, carbohydrates, vitamins A, B2, B6, B12, and C, phosphorus, zinc, and sodium. Participants with good Mediterranean diet quality had higher energy and nutrient intakes and higher percentages of meeting nutrient requirements (p < 0.05). KIDMED scores were negatively correlated with GSRS total (r = −0.14, p < 0.001) and subcomponent scores (abdominal pain, diarrhea, reflux, indigestion, and constipation; p < 0.05), and significantly and positively correlated with PedsQL total (r = 0.12, p < 0.001). A one-unit increase in the GSRS score resulted in a 14.4 times decrease in the PedsQL score, and a one-unit increase in the KIDMED score resulted in a 10.8 times increase in the PedsQL score (p = 0.001).

Conclusion

Overweight/obesity, stunting/wasting, nutritional problems, and deficiencies are common among disabled children and adolescents. Mediterranean diet is associated with a better quality of life, and gastrointestinal health in children with disabilities.
Enhanced expiratory rebreathing space for high loop gain sleep apnea treatment
Authors: Quinn Thomas , Thomas Robert Joseph , Heckman Eric James
Published: September 2023

The pathophysiology of sleep apnea goes beyond anatomic predisposition to airway collapse and includes additional factors such as arousal threshold and loop gain. High loop gain is a prominent feature in central and complex sleep apnea (with a mixture of obstructive and central features) where relative hypocapnia can lead to respiratory instability and periodic breathing. Existing therapies, including continuous positive airway pressure (CPAP) and adaptive servo-ventilators, often inadequately treat sleep apnea with high loop gain features. Enhanced expiratory rebreathing space (EERS) targets prevention of the hypocapnia that triggers central events in sleep by increasing dead space in amounts less than typical tidal volumes. This is accomplished by covering traditional exhalation ports on positive airway pressure masks and adding small additional tubing with distal exhalation and safety valves. This technique reduces carbon dioxide (CO2) blow-off during arousals and the associated large recovery breaths, typically producing a maximal increase in resting CO2 by 1–2 mmHg, thus increasing the CO2 reserve and making it less likely to encounter the hypocapnic apneic threshold. Typically, the amount of EERS is titrated in response to central events and periodic breathing rather than aiming for a goal CO2 level. Ideally CO2 monitoring is used during titration of EERS and the technique is avoided in the setting of baseline hypercapnia. This method has been used in clinical practice at our sleep center for over 15 years, and retrospective data suggests an excellent safety profile and high rates of successful therapy including in patients who have previously failed CPAP therapy. Limitations include decreased effectiveness in the setting of leak and decreased tolerance of the bulkier circuit. EERS represents a simple, affordable modification of existing positive airway pressure modalities for treatment of central and complex sleep apnea. Areas of future study include randomized controlled trials of the technique and study of use of EERS in combination with adaptive ventilation, and pharmacologic adjuncts targeting high loop gain physiology.
‘‘I felt marvellous e-cycling. If I had long hair I would have flicked it”: a qualitative investigation of the factors associated with e-cycling engagement among adults with type 2 diabetes
Authors: Bourne Jessica E. , Leary Sam , England Clare , Searle Aidan
Published: September 2023

Background

Physical activity (PA) is a key component in the management of type 2 diabetes. However, this population have low rates of PA engagement. Electrically assisted cycling has been identified as a means through which to increase PA by incorporating activity into daily life, while overcoming some of the barriers to conventional cycling. The determinants of e-cycling among people living with chronic disease are largely unknown. The aim of this research was to explore the determinants of e-cycling among individuals with type 2 diabetes using the Theoretical Domains Framework (TDF) and the Capability, Opportunity and Motivation for Behaviour change model (COM-B). This information is important for determining the suitability of future e-cycling initiatives and, if appropriate, inform future e-cycling interventions.

Method

One-to-one semi structured interviews were conducted with 16 participants from the e-cycling arm of a pilot randomised controlled trial between September 2019 and April 2020. The TDF was used to develop the interview guide. The framework method of analysis was used, incorporating both deductive and inductive reasoning. A conceptual model of the factors that influence e-cycling in this population was created.

Results

The most commonly reported TDF domains were skills, knowledge, belief about capabilities, belief about consequences and environmental context and resources. Specifically, e-bike training facilitated e-cycling engagement by providing participants with the skills, knowledge, and confidence needed to ride the e-bike and ride on the road. In addition, the enjoyment of e-cycling was a key facilitator to engagement. Participants engaged in e-cycling to improve their health rather than for environmental reasons. Most barriers to e-cycling related to the natural or physical environment.

Conclusion

This study provides insight into the personal, social, and environmental factors associated with e-cycling in this population. The findings of this study can be used to develop a more refined e-cycling intervention targeting the factors identified as influencing e-cycling engagement. In addition, this information will help in the selection of mechanistic outcome measures for evaluation.
Pharmacokinetic–pharmacodynamic analysis of cefmetazole against extended-spectrum β-lactamase-producing Enterobacteriaceae in dogs using Monte Carlo Simulation
Authors: Kusumoto Mizuki , Motegi Tomoki , Uno Haruna , Yokono Mizuki , Harada Kazuki
Published: September 2023

Introduction

The spread of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) is a serious concern in companion animal medicine owing to their ability to develop multidrug resistance. Cefmetazole (CMZ) is a candidate drug for treating ESBL-E infections; however, its regimen in dogs has not been established. In this study, we investigated the pharmacokinetic (PK) indices of CMZ in dogs and performed PK–pharmacodynamic (PD) analyses using Monte Carlo Simulation (MCS).

Methods

In total, six healthy dogs received an intravenous bolus dose of CMZ (40 mg/kg body weight). Serum CMZ concentrations were evaluated using liquid chromatography–mass spectrometry, and PK indices were determined based on non-compartmental analysis. The PK–PD cut-off (COPD) values were calculated as the highest minimum inhibitory concentration (MIC) that achieved ≥90% probability of target attainment for a target value of unbounded drug concentration exceeding 40% of the dosing interval. The cumulative fraction of response (CFR) was calculated based on the MIC distribution of wild-type ESBL-E from companion animals.

Results

The area under the concentration–time curve and elimination half-time were 103.36 ± 7.49 mg·h/L and 0.84 ± 0.07 h, respectively. MCS analysis revealed that COPD values for regimens of 40 mg/kg q12, q8h, and q6h were ≤ 0.5, ≤2, and ≤ 4 μg/mL, respectively. A regimen of 40 mg/kg q6h was estimated to achieve a CFR of 80–90% for Escherichia coli and Klebsiella pneumoniae. By contrast, all regimens exhibited a CFR of ≤70% for Proteus mirabilis and Enterobacter cloacae.

Discussion

We conclude that CMZ at 40 mg/kg q6h could be a viable treatment regimen for dogs infected with ESBL-producing Escherichia coli and Klebsiella pneumoniae.