bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging trends on the mechanism of pelvic organ prolapse from 1997 to 2022: visualization and bibliometric analysis
Authors: Yu Xia , Lin Wenyi , Zheng Xuemei , He Li , Yang Zhenglin , Lin Yonghong
Published: June 2023

Objective

At present, there is no feature description of the mechanism of pelvic organ prolapse (POP) in the literature. This study aimed to map the emerging trends regarding the mechanism of POP from inception to 2022 by bibliometric analysis and to analyze its research hotspots and frontiers.

Methods

We downloaded pertinent publications from inception to 2022 from the Web of Science Core Collection (WoSCC) on 30 June 2022. The data were then examined using the Bibliometrix program in R (Version 4.1.0), CiteSpace software, the Online Analysis Platform of Literature Metrology (https://bibliometric.com), and a bibliometrix online interface.

Results

A total of 290 qualified records on the mechanism of POP were identified and included in the analysis. The most productive journal was International Urogynecology Journal. Bump RC and Olsen AL were the most cited authors. Extracellular matrix, collagen, apoptosis, elastin, oxidative stress, gene expression, matrix metalloproteinase, and tissue engineering were among the 25 most relevant terms. According to the analysis of trending topics, tissue engineering has become a new research hotspot.

Conclusion

Extracellular matrix remodeling, oxidative stress and apoptosis are the three main directions for studying the mechanism of POP. In addition, tissue engineering has become a new research hotspot. In the future, in-depth research on the interaction between different mechanisms will be carried out, and attempts will be made to combine biomimetic materials and seed cells to achieve the regeneration and reconstruction of POP-related organs.
A study of the correlation between stroke and gut microbiota over the last 20years: a bibliometric analysis
Authors: Han Shengnan , Cai Longhui , Chen Peipei , Kuang Weihong
Published: June 2023

Purpose

This study intends to uncover a more thorough knowledge structure, research hotspots, and future trends in the field by presenting an overview of the relationship between stroke and gut microbiota in the past two decades.

Method

Studies on stroke and gut microbiota correlations published between 1st January 2002 and 31st December 2021 were retrieved from the Web of Science Core Collection and then visualized and scientometrically analyzed using CiteSpace V.

Results

A total of 660 papers were included in the study, among which the United States, the United Kingdom, and Germany were the leading research centers. Cleveland Clinic, Southern Medical University, and Chinese Academy of Science were the top three institutions. The NATURE was the most frequently co-cited journal. STANLEY L HAZEN was the most published author, and Tang WHW was the most cited one. The co-occurrence analysis revealed eight clusters (i.e., brain-gut microbiota axis, fecal microbiome transplantation, gut microbiota, hypertension, TMAO, ischemic stroke, neuroinflammation, atopobiosis). “gut microbiota,” “Escherichia coli,” “cardiovascular disease,” “risk,” “disease,” “ischemic stroke,” “stroke,” “metabolism,” “inflammation,” and “phosphatidylcholine” were the most recent keyword explosions.

Conclusion

Findings suggest that in the next 10 years, the number of publications produced annually may increase significantly. Future research trends tend to concentrate on the mechanisms of stroke and gut microbiota, with the inflammation and immunological mechanisms, TMAO, and fecal transplantation as hotspots. And the relationship between these mechanisms and a particular cardiovascular illness may also be a future research trend.
The oral bacteriomes of patients with allergic rhinitis and asthma differ from that of healthy controls
Authors: Pérez-Losada Marcos , Castro-Nallar Eduardo , Laerte Boechat José , Delgado Luís , Azenha Rama Tiago , Berrios-Farías Valentín , Oliveira Manuela
Published: June 2023

Allergic rhinitis and asthma are two of the most common chronic respiratory diseases in developed countries and have become a major public health concern. Substantial evidence has suggested a strong link between respiratory allergy and upper airway dysbacteriosis, but the role of the oral bacteriota is still poorly understood. Here we used 16S rRNA massive parallel sequencing to characterize the oral bacteriome of 344 individuals with allergic rhinitis (AR), allergic rhinitis with asthma (ARAS), asthma (AS) and healthy controls (CT). Four of the most abundant (>2%) phyla (Actinobacteriota, Firmicutes, Fusobacteriota, and Proteobacteria) and 10 of the dominant genera (Actinomyces, Fusobacterium, Gemella, Haemophilus, Leptotrichia, Neisseria, Porphyromonas, Prevotella, Streptococcus,andVeillonella) in the oral cavity differed significantly (p≤ 0.03) between AR, ARAS or AS and CT groups. The oral bacteriome of ARAS patients showed the highest intra-group diversity, while CT showed the lowest. All alpha-diversity indices of microbial richness and evenness varied significantly (p≤ 0.022) in ARAS vs. CT and ARAS vs. AR, but they were not significantly different in AR vs. CT. All beta-diversity indices of microbial structure (Unifrac, Bray-Curtis, and Jaccard distances) differed significantly (p≤ 0.049) between each respiratory disease group and controls. Bacteriomes of AR and ARAS patients showed 15 and 28 upregulated metabolic pathways (PICRUSt2) mainly related to degradation and biosynthesis (p< 0.05). A network analysis (SPIEC-EASI) of AR and ARAS bacteriomes depicted simpler webs of interactions among their members than those observed in the bacteriome of CT, suggesting chronic respiratory allergic diseases may disrupt bacterial connectivity in the oral cavity. This study, therefore, expands our understanding of the relationships between the oral bacteriome and allergy-related conditions. It demonstrates for the first time that the mouth harbors distinct bacteriotas during health and allergic rhinitis (with and without comorbid asthma) and identifies potential taxonomic and functional microbial biomarkers of chronic airway disease.
HINT, a code for understanding the interaction between biomolecules: a tribute to Donald J. Abraham
Authors: Kellogg Glen E. , Marabotti Anna , Spyrakis Francesca , Mozzarelli Andrea
Published: June 2023

A long-lasting goal of computational biochemists, medicinal chemists, and structural biologists has been the development of tools capable of deciphering the molecule–molecule interaction code that produces a rich variety of complex biomolecular assemblies comprised of the many different simple and biological molecules of life: water, small metabolites, cofactors, substrates, proteins, DNAs, and RNAs. Software applications that can mimic the interactions amongst all of these species, taking account of the laws of thermodynamics, would help gain information for understanding qualitatively and quantitatively key determinants contributing to the energetics of the bimolecular recognition process. This, in turn, would allow the design of novel compounds that might bind at the intermolecular interface by either preventing or reinforcing the recognition. HINT, hydropathic interaction, was a model and software code developed from a deceptively simple idea of Donald Abraham with the close collaboration with Glen Kellogg at Virginia Commonwealth University. HINT is based on a function that scores atom–atom interaction using LogP, the partition coefficient of any molecule between two phases; here, the solvents are water that mimics the cytoplasm milieu and octanol that mimics the protein internal hydropathic environment. This review summarizes the results of the extensive and successful collaboration between Abraham and Kellogg at VCU and the group at the University of Parma for testing HINT in a variety of different biomolecular interactions, from proteins with ligands to proteins with DNA.
Mapping of Notch signaling in the developing organ of Corti in common marmosets
Authors: Hosoya Makoto , Fujioka Masato , Okano Hideyuki , Ozawa Hiroyuki
Published: June 2023

Introduction

The well-regulated development of the sensory epithelium is essential for hearing. This process involves the specification of a pro-sensory epithelium containing common progenitors that differentiate into hair and supporting cells. Notch signaling is one of the most critical pathways during these processes, and its modification is thought to be a feasible approach for treating hearing loss. Despite interspecies differences between rodents and primates or humans, most of our current knowledge regarding cochlear development has been obtained from rodent models.

Methods

We therefore examined and mapped the expression patterns of Notch signal components in the developing cochlea of the common marmoset (Callithrix jacchus), a small monkey species native to the New World, a primate model animal.

Results

In contrast to the preserved expression patterns of the Notch signaling components in the hair cell differentiation between primates and rodents, we unveiled relatively large interspecies differences during the maturation of supporting cells.

Discussion

This improved knowledge of Notch signaling during primate cochlear development will facilitate the development of future regenerative therapies.
A case for hybrid BCIs: combining optical and electrical modalities improves accuracy
Authors: Almajidy Rand Kasim , Mottaghi Soheil , Ajwad Asmaa A. , Boudria Yacine , Mankodiya Kunal , Besio Walter , Hofmann Ulrich G.
Published: June 2023

Near-infrared spectroscopy (NIRS) is a promising research tool that found its way into the field of brain-computer interfacing (BCI). BCI is crucially dependent on maximized usability thus demanding lightweight, compact, and low-cost hardware. We designed, built, and validated a hybrid BCI system incorporating one optical and two electrical modalities ameliorating usability issues. The novel hardware consisted of a NIRS device integrated with an electroencephalography (EEG) system that used two different types of electrodes: Regular gelled gold disk electrodes and tri-polar concentric ring electrodes (TCRE). BCI experiments with 16 volunteers implemented a two-dimensional motor imagery paradigm in off- and online sessions. Various non-canonical signal processing methods were used to extract and classify useful features from EEG, tEEG (EEG through TCRE electrodes), and NIRS. Our analysis demonstrated evidence of improvement in classification accuracy when using the TCRE electrodes compared to disk electrodes and the NIRS system. Based on our synchronous hybrid recording system, we could show that the combination of NIRS-EEG-tEEG performed significantly better than either single modality only.
Dual functional states of working memory realized by memristor-based neural network
Authors: Wang Hongzhe , Pan Xinqiang , Wang Junjie , Sun Mingyuan , Wu Chuangui , Yu Qi , Liu Zhen , Chen Tupei , Liu Yang
Published: June 2023

Working memory refers to the brain's ability to store and manipulate information for a short period. It is disputably considered to rely on two mechanisms: sustained neuronal firing, and “activity-silent” working memory. To develop a highly biologically plausible neuromorphic computing system, it is anticipated to physically realize working memory that corresponds to both of these mechanisms. In this study, we propose a memristor-based neural network to realize the sustained neural firing and activity-silent working memory, which are reflected as dual functional states within memory. Memristor-based synapses and two types of artificial neurons are designed for the Winner-Takes-All learning rule. During the cognitive task, state transformation between the “focused” state and the “unfocused” state of working memory is demonstrated. This work paves the way for further emulating the complex working memory functions with distinct neural activities in our brains.
A case report of primary para-testicular spindle cell rhabdomyosarcoma
Authors: Su Peng , Yang Ying , Wang Xiaomin , Chen Shulian , Zhang Neng , Yang Hua
Published: June 2023

Para-testicular rhabdomyosarcoma (PTRMS) is a rare tumor, and it accounts for 7% of all rhabdomyosarcoma tumors. Among all the rhabdomyosarcoma (RMS) types, the spindle cell RMS is extremely rare. The present study describes a case of a para-testicular spindle cell RMS that was treated with a radical inguinal orchiectomy (RIO) and right scrotal resection. A 17-year-old male patient presented with a half-year history of a rapidly growing, painless, right scrotal mass. His CT of the pelvic cavity showed a mixed-density mass in the right scrotum, and the maximum cross-sectional area was approximately 76.5 mm × 64.5 mm. An X-ray of the chest demonstrated no evidence of metastasis, and a local surgical excision was performed subsequently. The histopathological and immunohistochemical examination confirmed the final diagnosis of spindle cell RMS. As a newly diagnosed case, strict and regular follow-up is needed. This article focuses on the importance of prompt recognition, diagnosis, pathological features, and appropriate management of para-testicular spindle cell RMS.
G protein-coupled receptor GPR68 inhibits lymphocyte infiltration and contributes to gender-dependent melanoma growth
Authors: Ye Shangmei , Zhu Yunfeng , Zhong Dongmei , Song Xiaodong , Li Jialin , Xiao Fang , Huang Zhilei , Zhang Wenjie , Wu Mingyue , Zhang Kangdi , Xiang Fu-li , Xu Jie
Published: June 2023

Introduction

Melanoma is a common and aggressive type of skin cancer with rising incidence rate globally. Gender is one of the determining factors, and overall males have a higher risk of developing melanoma as well as worse prognosis. Emerging evidence show that GPR68, a G protein-coupled receptor that is sensitive to acid and mechanical stimulations for cellular microenvironment, plays an important role in tumor biology. However, whether GPR68 is involved in gender-dependent regulation of tumor growth is unclear.

Methods

We established a syngeneic melanoma model in Gpr68-deficient mice and investigated tumor growth in males and females. The GPR68 activation-induced cellular responses of melanocytes, including intracellular calcium dynamics, proliferation and migration were measured. The landscape of tumor-infiltrating immune cells were analyzed by flow cytometry and the expression various cytokines were checked by qRT-PCR.

Results

GPR68 is required for melanoma growth in males but dispensable in females. GPR68 is expressed and functional in B16-F10 melanocytes, but the activity of the receptor does not directly contribute to proliferation and migration of the cells. GPR68 inhibits infiltration of CD45+ lymphocytes, CD8+ T cells and NK cells in melanoma in male mice, but has no apparent effect in females. Furthermore, GPR68 functionally inhibits the expression of IFNγ in the tumor infiltrating CD8+ T cells and NK cells as well as the inflammatory cytokine expression in the spleen in male mice but not in females. Our results show the gender-dependent modulatory effect of GPR68 on tumor-infiltrating immune cells and their tumor-killing capacity.

Discussion

GPR68 is sensor for acid and mechanical stimulations, which are two important factors in the microenvironment associated with tumor growth and metastasis. Our results suggest a prominent role of the receptor molecules in tumor biology in a gender-dependent manner. Since GPCRs are more feasible to develop small molecule drugs compared to transcription factors, our study demonstrates the potential of GPR68 as a novel druggable therapeutic target for melanoma in male patients.
Sudden cardiac arrest in a child with Gitelman syndrome: a case report and literature review
Authors: Zieg Jakub , Tavačová Terezia , Balaščáková Miroslava , Peldová Petra , Fencl Filip , Kubuš Peter
Published: June 2023

Salt-losing tubulopathies are well-recognised diseases predisposing to metabolic disturbances in affected patients. One of the most severe complications can be life-threatening arrhythmias causing sudden cardiac arrest. We present here the first case of a pediatric patient with Gitelman syndrome associated sudden cardiac arrest without precipitating event. A 10-year-old boy collapsed due to ventricular fibrillation in the Prague tram. Lay cardiopulmonary resuscitation was initiated and external defibrillation restored sinus rhythm within minutes. Initial laboratory examination revealed severe hypokalemia requiring large amounts of electrolyte supplementation. Genetic testing focused to tubulopathies was performed and the diagnosis of Gitelman syndrome was made following the identification of two pathogenic variants in SLC12A3 gene (c.2633 + 1G>A and c.2221G>A). Implantable cardioverter-defibrillator was implanted to prevent sudden cardiac death. The patient was in a good clinical condition with satisfactory electrolyte serum levels at the last follow-up. Causes of electrolyte abnormalities in children should be identified early to prevent the development of rare but potentially fatal complications.
Mushroom polysaccharides from Grifola frondosa (Dicks.) Gray and Inonotus obliquus (Fr.) Pilat ameliorated dextran sulfate sodium-induced colitis in mice by global modulation of systemic metabolism and the gut microbiota
Authors: Sun Runbin , Jin Dandan , Fei Fei , Xu Zhi , Cao Bei , Li Juan
Published: June 2023

Introduction: Polysaccharides from Grifola frondosa (Dicks.) Gray (HSH) and Inonotus obliquus (Fr.) Pilat (BHR) showed noticeable effects on dextran sulfate sodium (DSS)-induced colitis, but their systemic modulation effects have not been fully revealed. This study aimed to investigate the regulation of the gut microbiota and systemic metabolism by HSH and BHR in DSS-induced colitis.

Methods: C57BL/6J mice were given DSS (2.5%) in water and were treated with HSH and BHR (200 mg/kg/day) by gavage. Body weight and colon length were recorded, and H&E and AB-PAS staining of the colon were conducted to evaluate the model and the protective effect of the polysaccharides. Additionally, an LC-QTOF/MS-based untargeted metabolomic platform was used to identify the metabolites in the serum, colon tissue, gut contents, and faeces and investigate differential metabolites and metabolic pathways. 16S rDNA gene sequencing was used to measure the composition of bacterial communities.

Results: The results showed that the mouse colitis model was established successfully, as evidenced by an increased disease activity index score [2.83 ± 0.62 vs. 0.06 ± 0.14 (p < 0.001)] and shortened colon length [5.43 ± 0.64 cm vs. 7.04 ± 0.29 cm (p < 0.001)], and HSH and BHR ameliorated DSS-induced colitis by improving the disease activity index (2.17 ± 0.28 and 1.83 ± 0.29, respectively) and restoring the colon length (6.12 ± 0.30 cm and 6.62 ± 0.35 cm, respectively). HSH and BHR significantly modulated metabolites involved in aromatic amino acid metabolism, the citrate cycle, purine metabolism, pyrimidine metabolism, etc. HSH and BHR increased the Chao1 index by 64.25% and 60.25%, respectively, and they increased the Shannon index by 13.02% and 10.23%, respectively. They both reversed the increase in the abundances of g_Odoribacter, g_Clostridium, g_AF12, g_Parabacteroides and g_Turicibacter and reversed the decrease in the abundance of g_unclassified_Bacteria induced by DSS. Specifically, HSH reversed the reductions in g_unclassified_Lactobacillales and g_Ruminococcus, and BHR reversed the decreases in g_unidentified_Coriobacteriaceae and g_unclassified_Firmicutes.

Discussion: These results suggested that HSH and BHR may ameliorate DSS-induced colitis by global modulation of systemic metabolism and the gut microbiota. Targeting the gut microbiota may be a potentially effective strategy to modulate systemic metabolism and treat colitis.
Zhilong Huoxue Tongyu capsule attenuates intracerebral hemorrhage induced redox imbalance by modulation of Nrf2 signaling pathway
Authors: Mazhar Maryam , Yang Guoqiang , Xu Houping , Liu Yulin , Liang Pan , Yang Luyin , Spáčil Roman , Shen Hongping , Zhang Dechou , Ren Wei , Yang Sijin
Published: June 2023

Background: One of the severely debilitating and fatal subtypes of hemorrhagic stroke is intracerebral hemorrhage (ICH), which lacks an adequate cure at present. The Zhilong Huoxue Tongyu (ZLHXTY) capsule has been utilized effectively since last decade to treat ICH, in some provinces of China but the scientific basis for its mechanism is lacking. Purpose: To investigate the neuroprotective role of ZLHXTY capsules for ICH-induced oxidative injury through the regulation of redox imbalance with the Nrf2 signaling pathway.

Methods: Autologous blood injection model of ICH in C57BL/6J mice was employed. Three treatment groups received ZLHXTY once daily through oral gavage at doses 0.35 g/kg, 0.7 g/kg, and 1.4 g/kg, started after 2 h and continued for 72 h of ICH induction. The neurological outcome was measured using a balance beam test. Serum was tested for inflammatory markers IL-1β, IL-6, and TNF-α through ELISA, oxidative stress through hydrogen peroxide content assay, and antioxidant status by total antioxidant capacity (T-AOC) assay. Nuclear extract from brain tissue was assayed for Nrf2 transcriptional factor activity. RT-qPCR was performed for Nfe2l2, Sod1, Hmox1, Nqo1, and Mgst1; and Western blotting for determination of protein expression of Nrf2, p62, Pp62, Keap, HO1, and NQO1. Fluoro-jade C staining was also used to examine neuronal damage.

Results: ZLHXTY capsule treatment following ICH demonstrated a protective effect against oxidative brain injury. Neurological scoring showed improvement in behavioral outcomes. ELISA-based identification demonstrated a significant decline in the expression of serum inflammatory markers. Hydrogen peroxide content in serum was found to be reduced. The total antioxidant capacity was also reduced in serum, but the ZLHXTY extract showed a concentration-dependent increase in T-AOC speculating at its intrinsic antioxidant potential. Nrf2 transcriptional factor activity, mRNA and protein expression analyses revealed normalization of Nrf2 and its downstream targets, which were previously elevated as a result of oxidative stress induced by ICH. Neuronal damage was also reduced markedly after ZLHXTY treatment as revealed by Fluoro-jade C staining. Conclusion: ZLHXTY capsules possess an intrinsic antioxidant potential that can modulate the ICH-induced redox imbalance in the brain as revealed by the normalization of Nrf2 and its downstream antioxidant targets.
Comparative evaluation of clinical glycemic control markers treated with imeglimin and its effect on erythrocytes in patients with type 2 diabetes mellitus: study protocol of a single-arm, open-label, prospective, exploratory trial
Authors: Osonoi Takeshi , Shirabe Shinichiro , Saito Miyoko , Hosoya Mitsuru , Douguchi Satako , Ofuchi Kensuke , Katoh Makoto
Published: June 2023

Background: Imeglimin is a novel type 2 diabetes (T2D) drug that is expected to improve mitochondrial function. In its phase 3 clinical trials in Japanese patients with T2D, the hemoglobin A1c (HbA1c) decrease following imeglimin administration was slow, reaching a plateau after 20–24 weeks of treatment. In general, the erythrocyte lifespan may be a factor when HbA1c shows an abnormal value. Therefore, this study will comparatively evaluate HbA1c and other markers of glycemic control in patients with T2D after imeglimin administration and also examine the effects of imeglimin on erythrocytes.

Methods: This single-arm, open-label, prospective, exploratory study is designed to evaluate the divergence between HbA1c and glycoalbumin (GA) or 1,5-anhydroglucitol (1,5-AG) and the glycemic reduction rate in 30 patients with T2D with inadequate glycemic control when imeglimin 2,000 mg is administered for 6 months. In addition, we will examine the effect on erythrocytes, the presumed cause of this divergence. We will measure sustained glycemic variability using flash glucose monitoring and examine the relationship between changes in these indices and HbA1c. Moreover, because prolonged erythrocyte lifespan is a possible cause of falsely high HbA1c levels, erythrocyte lifespan, erythrocyte deformability, and hemoglobin concentration will be evaluated as effects of imeglimin on erythrocytes. Furthermore, if imeglimin has an ameliorative effect on erythrocyte deformability, it may improve peripheral arterial disease; thus, we will also evaluate the toe-brachial pressure index, a measure of this effect.

Discussion: In this study, if imeglimin administration results in diverging rates of hypoglycemic effect between HbA1c and GA or 1,5-AG and prolongs erythrocyte lifespan, GA and 1,5-AG, rather than HbA1c, will be considered appropriate measures of the hypoglycemic effect in the early stages of imeglimin administration. If imeglimin improves erythrocyte deformability, it may also be a new treatment strategy for peripheral arterial disease, a chronic complication of T2D.

Ethics and dissemination: The study protocol was scientifically and ethically reviewed and approved by the Certified Clinical Research Review Board of Toho University (approval number: THU22002). The study protocol was registered in the Japan Registry of Clinical Trials (jRCT) in December 2022 (jRCTs031220489).
Mechanism of sorafenib resistance associated with ferroptosis in HCC
Authors: Guo Lingling , Hu Cuntao , Yao Mengwen , Han Guang
Published: June 2023

Hepatocellular carcinoma (HCC) is the most familiar primary hepatic malignancy with a poor prognosis. The incidence of HCC and the associated deaths have risen in recent decades. Sorafenib is the first drug to be approved by the Food and Drug Administration (FDA) for routine use in the first-line therapy of patients with advanced HCC. However, only about 30% of patients with HCC will be benefited from sorafenib therapy, and drug resistance typically develops within 6 months. In recent years, the mechanisms of resistance to sorafenib have gained the attention of a growing number of researchers. A promising field of current studies is ferroptosis, which is a novel form of cell death differing from apoptosis, necroptosis, and autophagy. This process is dependent on the accumulation of intracellular iron and reactive oxygen species (ROS). Furthermore, the increase in intracellular iron levels and ROS can be significantly observed in cells resistant to sorafenib. This article reviews the mechanisms of resistance to sorafenib that are related to ferroptosis, evaluates the relationship between ferroptosis and sorafenib resistance, and explores new therapeutic approaches capable of reversing sorafenib resistance in HCC through the modulation of ferroptosis.
Elucidation of the binding mode of organic polysulfides on the human TRPA1 receptor
Authors: Nemes Balázs , László Szabolcs , Zsidó Balázs Zoltán , Hetényi Csaba , Feher Adam , Papp Ferenc , Varga Zoltan , Szőke Éva , Sándor Zoltán , Pintér Erika
Published: June 2023

Introduction: Previous studies have established that endogenous inorganic polysulfides have significant biological actions activating the Transient Receptor Potential Ankyrin 1 (TRPA1) receptor. Organic polysulfides exert similar effects, but they are much more stable molecules, therefore these compounds are more suitable as drugs. In this study, we aimed to better understand the mechanism of action of organic polysulfides by identification of their binding site on the TRPA1 receptor.

Methods: Polysulfides can readily interact with the thiol side chain of the cysteine residues of the protein. To investigate their role in the TRPA1 activation, we replaced several cysteine residues by alanine via site-directed mutagenesis. We searched for TRPA1 mutant variants with decreased or lost activating effect of the polysulfides, but with other functions remaining intact (such as the effects of non-electrophilic agonists and antagonists). The binding properties of the mutant receptors were analyzed by in silico molecular docking. Functional changes were tested by in vitro methods: calcium sensitive fluorescent flow cytometry, whole-cell patch-clamp and radioactive calcium-45 liquid scintillation counting.

Results: The cysteines forming the conventional binding site of electrophilic agonists, namely C621, C641 and C665 also bind the organic polysulfides, with the key role of C621. However, only their combined mutation abolished completely the organic polysulfide-induced activation of the receptor.

Discussion: Since previous papers provided evidence that organic polysulfides exert analgesic and anti-inflammatory actions in different in vivo animal models, we anticipate that the development of TRPA1-targeted, organic polysulfide-based drugs will be promoted by this identification of the binding site.
The effect of burst suppression on cerebral blood flow and autoregulation: a scoping review of the human and animal literature
Authors: Siddiqi A. Zohaib , Froese Logan , Gomez Alwyn , Sainbhi Amanjyot Singh , Stein Kevin , Park Kangyun , Vakitbilir Nuray , Zeiler Frederick A.
Published: June 2023

Background:Burst suppression (BS) is an electroencephalography (EEG) pattern in which there are isoelectric periods interspersed with bursts of cortical activity. Targeting BS through anaesthetic administration is used as a tool in the neuro-intensive care unit but its relationship with cerebral blood flow (CBF) and cerebral autoregulation (CA) is unclear. We performed a systematic scoping review investigating the effect of BS on CBF and CA in animals and humans.

Methods:We searched MEDLINE, BIOSIS, EMBASE, SCOPUS and Cochrane library from inception to August 2022. The data that were collected included study population, methods to induce and measure BS, and the effect on CBF and CA.

Results:Overall, there were 66 studies that were included in the final results, 41 of which examined animals, 24 of which examined humans, and 1 of which examined both. In almost all the studies, BS was induced using an anaesthetic. In most of the animal and human studies, BS was associated with a decrease in CBF and cerebral metabolism, even if the mean arterial pressure remained constant. The effect on CA during periods of stress (hypercapnia, hypothermia, etc.) was variable.

Discussion:BS is associated with a reduction in cerebral metabolic demand and CBF, which may explain its usefulness in patients with brain injury. More evidence is needed to elucidate the connection between BS and CA.
Bunch microclimate influence amino acids and phenolic profiles of Pinot noir grape berries
Authors: Moukarzel Romy , Parker Amber K. , Schelezki Olaf J. , Gregan Scott M. , Jordan Brian
Published: June 2023

Introduction

The increase of temperature due to climate change at different phenological stages of grapevine has already been demonstrated to affect accumulation of primary and secondary metabolites in grape berries. This has a significant implication for Pinot noir especially in New Zealand context as these compounds can have direct and indirect effects on wine quality.

Methods

This study investigates how varying bunch microclimate through changes in temperature applied at veraison stage can affect: fresh weight, total soluble solids, the accumulation of anthocyanins, total phenolics and amino acids of the grape berries. This was studied over two growing seasons (2018/19 and 2019/20) with Pinot noir vines being grown at two different temperatures in controlled environment (CE) chambers. The vines were exposed to 800 µmol/m2/s irradiance with diurnal changes in day (22°C or 30°C) and night (15°C) temperatures. This experimental set up enabled us to determine the accumulation of these metabolite at harvest (both seasons) and throughout berry development (second season).

Results and discussion

The results showed that berry weight was not influenced by temperature increase. The total soluble solids (TSS) were significantly increased at 30°C, however, this was not at the expense of berry weight (i.e., water loss). Anthocyanin content was reduced at higher temperature in the first season but there was no change in phenolic content in response to temperature treatments in either season. The concentrations of total amino acids at harvest increased in response to the higher temperature in the second season only. In addition, in the time course analysis of the second season, the accumulation of amino acids was increased at mid-ripening and ripening stage with the increased temperature. Significant qualitative changes in amino acid composition specifically the α-ketoglutarate family (i.e., glutamine, arginine, and proline) were found between the two temperatures.

Significance

This study is the first to provide detailed analysis and quantification of individual amino acids and phenolics in Pinot noir in response to changes in temperature applied at veraison which could aid to develop adaptation strategies for viticulture in the future.
Genome-wide association identifies key loci controlling blackberry postharvest quality
Authors: Chizk T. Mason , Clark John R. , Johns Carmen , Nelson Lacy , Ashrafi Hamid , Aryal Rishi , Worthington Margaret L.
Published: June 2023

Introduction

Blackberry (Rubus subgenus Rubus) is a soft-fruited specialty crop that often suffers economic losses due to degradation in the shipping process. During transportation, fresh-market blackberries commonly leak, decay, deform, or become discolored through a disorder known as red drupelet reversion (RDR). Over the past 50 years, breeding programs have achieved better fruit firmness and postharvest quality through traditional selection methods, but the underlying genetic variation is poorly understood.

Methods

We conducted a genome-wide association of fruit firmness and RDR measured in 300 tetraploid fresh-market blackberry genotypes from 2019-2021 with 65,995 SNPs concentrated in genic regions of the R. argutus reference genome.

Results

Fruit firmness and RDR had entry-mean broad sense heritabilities of 68% and 34%, respectively. Three variants on homologs of polygalacturonase (PG), pectin methylesterase (PME), and glucan endo-1,3-β-glucosidase explained 27% of variance in fruit firmness and were located on chromosomes Ra06, Ra01, and Ra02, respectively. Another PG homolog variant on chromosome Ra02 explained 8% of variance in RDR, but it was in strong linkage disequilibrium with 212 other RDR-associated SNPs across a 23 Mb region. A large cluster of six PME and PME inhibitor homologs was located near the fruit firmness quantitative trait locus (QTL) identified on Ra01. RDR and fruit firmness shared a significant negative correlation (r = -0.28) and overlapping QTL regions on Ra02 in this study.

Discussion

Our work demonstrates the complex nature of postharvest quality traits in blackberry, which are likely controlled by many small-effect QTLs. This study is the first large-scale effort to map the genetic control of quantitative traits in blackberry and provides a strong framework for future GWAS. Phenotypic and genotypic datasets may be used to train genomic selection models that target the improvement of postharvest quality.
Alterations in the odor profile of plants in cultivar mixtures affect aphid host-location behavior
Authors: Tous-Fandos Alba , Gallinger Jannicke , Enting Arnoud , Chamorro-Lorenzo Lourdes , Sans Serra F. Xavier , Ninkovic Velemir
Published: June 2023

The effect of cultivar mixtures on aphid control is attributed to the masking or alteration of host-preferred cultivar odor cues. However, the underlying physiological mechanism remains unclear. This study assessed alterations in the volatile emissions of wheat cultivars grown together (Florence-Aurora and Forment; Florence-Aurora and Montcada) and the consequences for the olfactory preference of aphids. Volatile organic compounds were collected from wheat plants grown in a laboratory under mixed or monoculture conditions and subsequently analyzed. The odor profiles of Florence-Aurora and Montcada were indistinguishable from each other. However, the odors of Florence-Aurora and Forment grown in monocultures differed significantly from those emitted by their mixture. The Florence-Aurora and Forment mixture induced plant physiological responses that affected the emission of single volatile compounds and, consequently, altered volatile organic compound ratios. English grain aphids (Sitobion avenae) were less attracted to the odors of Florence-Aurora and Forment when grown as a mixture than the combination of the odors from Florence-Aurora and Forment monocultures. Moreover, aphids preferred clean air over the odor from the Florence-Aurora and Forment mixture but preferred the odor from the Florence-Aurora and Montcada mixture over clean air. This study highlights the beneficial effects of intraspecific plant diversity on aphid control by altering plant odors in response to plant-plant interactions. The emission of less attractive odor cues consequently affects plant-aphid interactions; hence, less attractive odors are likely to impair aphid host-locating behavior. This effect was exclusive to certain cultivar mixtures, which supports the “right neighbor” concept.
Heat stress affects tassel development and reduces the kernel number of summer maize
Authors: Liu Pan , Yin Baozhong , Gu Limin , Zhang Shaoyun , Ren Jianhong , Wang Yandong , Duan Weiwei , Zhen Wenchao
Published: June 2023

Maize grain yield is drastically reduced by heat stress (HTS) during anthesis and early grain filling. However, the mechanism of HTS in reproductive organs and kernel numbers remains poorly understood. From 2018 to 2020, two maize varieties (ND372, heat tolerant; and XY335, heat sensitive) and two temperature regimens (HTS, heat stress; and CK, natural control) were evaluated, resulting in four treatments (372CK, 372HTS, 335CK, and 335HTS). HTS was applied from the nine-leaf stage (V9) to the anthesis stage. Various morphological traits and physiological activities of the tassels, anthers, and pollen from the two varieties were evaluated to determine their correlation with kernel count. The results showed that HTS reduced the number of florets, tassel volume, and tassel length, but increased the number of tassel branches. HTS accelerates tassel degradation and reduces pollen weight, quantity, and viability. Deformation and reduction in length and volume due to HTS were observed in both the Nongda 372 (ND372) and Xianyu 335 (XY335) varieties, with the average reductions being 22.9% and 35.2%, respectively. The morphology of the anthers changed more conspicuously in XY335 maize. The number of kernels per spike was reduced in the HTS group compared with the CK group, with the ND372 and XY335 varieties showing reductions of 47.3% and 59.3%, respectively. The main factors underlying the decrease in yield caused by HTS were reductions in pollen quantity and weight, tassel rachis, and branch length. HTS had a greater effect on the anther shape, pollen viability, and phenotype of XY335 than on those of ND372. HTS had a greater impact on anther morphology, pollen viability, and the phenotype of XY335 but had no influence on the appearance or dissemination of pollen from tassel.
The effect of reading literary fiction on the theory of mind skills among persons with schizophrenia and normal controls
Authors: Fekete Judit , Pótó Zsuzsanna , Varga Eszter , Hebling Dóra , Herold Márton , Albert Noémi , Pethő Borbála , Tényi Tamás , Herold Róbert
Published: June 2023

Introduction

Recent research data suggest that theory of mind (ToM) skills may improve after reading literary fiction. However, beside this short term favorable effect, regular long-term reading of literary fiction may also support ToM development or may improve ToM performance. The presence of impaired ToM abilities is well-documented in schizophrenia; however, the role of reading in these deficits is unknown. In the present study our aim was to assess the effect of prior reading experiences on theory of mind performance in patients with schizophrenia, and in healthy controls.

Materials and methods

ToM assessment was done with the Short Story Task, which is based on the interpretation of a Hemingway short story. After reading the short story, questions were asked in an interview format regarding comprehension, explicit and implicit ToM skills, then comparative analysis of schizophrenia patients was performed (n = 47) and matched to a normal control (n = 48) group concerning deficits of ToM abilities. Participants were also stratified according to their prior reading experiences.

Results

Previous reading experience was associated with better comprehension and explicit ToM performance both in patients with schizophrenia, and in healthy controls. However, the explicit ToM performance of patients with prior reading was still weaker compared to healthy controls with reading experiences. Path model analysis revealed that reading had a direct positive effect on ToM, and an indirect effect through improving comprehension.

Conclusions

Prior reading experience is associated with better ToM performance not just in healthy controls but also in patients living with schizophrenia. Previous reading experience also improves comprehension, which in turn has a favorable impact on ToM. Our results support the idea that literary fiction reading may have a therapeutic potential in the rehabilitation of schizophrenia.
Effectiveness of four vaccines in preventing SARS-CoV-2 infection in Almaty, Kazakhstan in 2021: retrospective population-based cohort study
Authors: Nabirova Dilyara , Horth Roberta , Smagul Manar , Nukenova Gaukhar , Yesmagambetova Aizhan , Singer Daniel , Henderson Alden , Tsoy Alexey
Published: June 2023

Background

In February 2021 Kazakhstan began offering COVID-19 vaccines to adults. Breakthrough SARS-CoV-2 infections raised concerns about real-world vaccine effectiveness. We aimed to evaluate effectiveness of four vaccines against SARS-CoV-2 infection.

Methods

We conducted a retrospective cohort analysis among adults in Almaty using aggregated vaccination data and individual-level breakthrough COVID-19 cases (≥14 days from 2nd dose) using national surveillance data. We ran time-adjusted Cox-proportional-hazards model with sensitivity analysis accounting for varying entry into vaccinated cohort to assess vaccine effectiveness for each vaccine (measured as 1-adjusted hazard ratios) using the unvaccinated population as reference (N = 565,390). We separately calculated daily cumulative hazards for COVID-19 breakthrough among vaccinated persons by age and vaccination month.

Results

From February 22 to September 1, 2021, in Almaty, 747,558 (57%) adults were fully vaccinated (received 2 doses), and 108,324 COVID-19 cases (11,472 breakthrough) were registered. Vaccine effectiveness against infection was 79% [sensitivity estimates (SE): 74%–82%] for QazVac, 77% (SE: 71%–81%) for Sputnik V, 71% (SE: 69%–72%) for Hayat-Vax, and 70% (SE: 65%–72%) for CoronaVac. Among vaccinated persons, the 90-day follow-up cumulative hazard for breakthrough infection was 2.2%. Cumulative hazard was 2.9% among people aged ≥60 years versus 1.9% among persons aged 18–39 years (p < 0.001), and 1.2% for people vaccinated in February–May versus 3.3% in June–August (p < 0.001).

Conclusion

Our analysis demonstrates high effectiveness of COVID-19 vaccines against infection in Almaty similar to other observational studies. Higher cumulative hazard of breakthrough among people ≥60 years of age and during variant surges warrants targeted booster vaccination campaigns.
What is a consistent glycan composition dataset?
Authors: Saba Federico , Mariethoz Julien , Lisacek Frederique
Published: June 2023

Introduction: One of the main challenges in bioinformatics has been and still is, the comparison of entities through the development of algorithms for similarity scoring and data clustering according to biologically relevant aspects. Glycoinformatics also faces this challenge, in particular regarding the automated comparison of protein and/or tissue glycomes, that remains a relatively uncharted territory.

Methods: Low and high throughput experimental glycomic and glycoproteomic results were collected, revealing a bias toward N-linked glycomes. Then, N-glycomes were considered and represented as networks of related glycan compositions as opposed to lists of glycans. They were processed and compared through a java application generating graphs and another producing a similarity matrix based on graph content. Several scoring schemes (e.g., Jaccard index or cosine) were tested and evaluated using the Matthews Correlation Coefficient, in order to capture a meaningful protein and tissue N-glycome similarity.

Results: Assuming that a glycome corresponds to a well-connected graph of glycan compositions, graph comparison has revealed gaps that can be interpreted as inconsistencies. The outcome of systematic graph comparison is both formal and practical. In principle, it is shown that the idiosyncrasy of current glycome data limits the definition of appropriate estimates for systematically comparing N-glycomes. Yet, several potentially interesting criteria could be identified in a series of use cases detailed in the study.

Discussion: Differentially expressed glycomes are usually compared manually, but the resulting work tends to remain in publications due to the lack of dedicated tools. Even manually, cross-comparison is challenging mostly because different sets of features are used from one study to the other. The work presented here enables laying down guidelines for developing a software tool comparing glycomes based on appropriate definitions of similarity and suitable methods for its evaluation and implementation.
The interface of gambling and cultural practices: a Tongan male perspective in Aotearoa | New Zealand
Authors: Fehoko Edmond S. , Bellringer Maria E. , Fairbairn-Dunlop Peggy
Published: June 2023

Introduction

For over 30 years, Pacific people have been identified as more at risk of developing problem gambling behaviors than the general population. That observation has not changed despite the increase in treatment service providers, Pacific gambling literature and problem-gambling literature, which are primarily quantitative-based. This article explores the interface of gambling and cultural practices from a Tongan male perspective to consider whether status advancement and rank contribute to the problem-gambling statistics and the qualitative reasons why Tongan peoples engage in gambling activities.

Methods

A phenomenological approach using the talanoa research method was employed to carry out this study. A total of 46 Tongan males participated in this study. Interpretative Phenomenological Analysis was employed to interpret the data. The ethical approval reference number 16/452 for this research was granted by the Auckland University of Technology Ethics Committee (AUTEC).

Results

Participants noted the concept of fatongia as a motivating factor for Tongans to engage in gambling activities, which, in turn, elevates family and village status and rank.

Discussion

Strategies and recommendations around raising cultural awareness with treatment providers are critical to understanding Tongan gambling in New Zealand.