bluuebunny/crossref_metadata_2025 huggingface dataset:
Variability of the innate immune response is globally constrained by transcriptional bursting
Authors: Alachkar Nissrin , Norton Dale , Wolkensdorfer Zsofia , Muldoon Mark , Paszek Pawel
Published: June 2023

Transcription of almost all mammalian genes occurs in stochastic bursts, however the fundamental control mechanisms that allow appropriate single-cell responses remain unresolved. Here we utilise single cell genomics data and stochastic models of transcription to perform global analysis of the toll-like receptor (TLR)-induced gene expression variability. Based on analysis of more than 2000 TLR-response genes across multiple experimental conditions we demonstrate that the single-cell, gene-by-gene expression variability can be empirically described by a linear function of the population mean. We show that response heterogeneity of individual genes can be characterised by the slope of the mean-variance line, which captures how cells respond to stimulus and provides insight into evolutionary differences between species. We further demonstrate that linear relationships theoretically determine the underlying transcriptional bursting kinetics, revealing different regulatory modes of TLR response heterogeneity. Stochastic modelling of temporal scRNA-seq count distributions demonstrates that increased response variability is associated with larger and more frequent transcriptional bursts, which emerge via increased complexity of transcriptional regulatory networks between genes and different species. Overall, we provide a methodology relying on inference of empirical mean-variance relationships from single cell data and new insights into control of innate immune response variability.
Iron accumulation in the ventral tegmental area in Parkinson's disease
Authors: Zhang Dongling , Yao Junye , Sun Junyan , Wang Junling , Chen Lili , He Hongjian , Wu Tao
Published: June 2023

Introduction

The ventral tegmental area (VTA) is less affected compared to substantia nigra pars compacta (SNc) in Parkinson's disease (PD). This study aimed to quantitatively evaluate iron content in the VTA across different stages of PD in order to help explain the selective loss of dopamine neurons in PD.

Methods

Quantitative susceptibility mapping (QSM) data were obtained from 101 PD patients, 35 idiopathic rapid eye movement sleep behavior disorder (RBD) patients, and 62 healthy controls (HCs). The mean QSM values in the VTA and SNc were calculated and compared among the groups.

Results

Both RBD and PD patients had increased iron values in the bilateral SNc compared with HCs. RBD and PD patients in the Hoehn–Yahr (H & Y) stage 1 did not show elevated iron values in the VTA, while PD patients with more than 1.5 H & Y staging had increased iron values in bilateral VTA compared to HCs.

Discussion

This study shows that there is no increased iron accumulation in the VTA during the prodromal and early clinical stages of PD, but iron deposition increases significantly as the disease becomes more severe.
Machine learning-based segmentation of the rodent hippocampal CA2 area from Nissl-stained sections
Authors: Takeuchi Yuki , Yamashiro Kotaro , Noguchi Asako , Liu Jiayan , Mitsui Shinichi , Ikegaya Yuji , Matsumoto Nobuyoshi
Published: June 2023

The hippocampus is a center of learning, memory, and spatial navigation. This region is divided into the CA1, CA2, and CA3 areas, which are anatomically different from each other. Among these divisions, the CA2 area is unique in terms of functional relevance to sociality. The CA2 area is often manually detected based on the size, shape, and density of neurons in the hippocampal pyramidal cell layer, but this manual segmentation relying on cytoarchitecture is impractical to apply to a large number of samples and dependent on experimenters’ proficiency. Moreover, the CA2 area has been defined based on expression pattern of molecular marker proteins, but it generally takes days to complete immunostaining for such proteins. Thus, we asked whether the CA2 area can be systematically segmented based on cytoarchitecture alone. Since the expression pattern of regulator of G-protein signaling 14 (RGS14) signifies the CA2 area, we visualized the CA2 area in the mouse hippocampus by RGS14-immunostaining and Nissl-counterstaining and manually delineated the CA2 area. We then established “CAseg,” a machine learning-based automated algorithm to segment the CA2 area with the F1-score of approximately 0.8 solely from Nissl-counterstained images that visualized cytoarchitecture. CAseg was extended to the segmentation of the prairie vole CA2 area, which raises the possibility that the use of this algorithm can be expanded to other species. Thus, CAseg will be beneficial for investigating unique properties of the hippocampal CA2 area.
Lymphoplasmapheresis versus plasma exchange in severe myasthenia gravis: a retrospective cohort study
Authors: Duan Weiwei , Jiang Fei , Cai Haobing , Li Bijuan , Ouyang Song , Yin Weifan , Zeng Qiuming , Yang Huan
Published: June 2023

Background

Lymphoplasmapheresis (LPE) is a new therapy developed on the basis of traditional plasma exchange (PE) in combination with leukapheresis. Currently, it remains unclear whether PE and LPE show differences in efficacy for severe MG.

Methods

A retrospective analysis was conducted on 198 MG patients, 75 in the PE group and 123 in the LPE group, and the patients’ Myasthenia Gravis Foundation of America (MGFA) Clinical Classification was Class IV. The treatment outcome was the change in Quantitative Myasthenia Gravis Score (QMGS) from baseline to the end of treatment. Propensity score matching (PSM) was applied for the balance of confounders between the two groups.

Results

In this study cohort, the safety profile of LPE and PE was good and no serious adverse events were observed. Based on PSM, 62 patients treated with LPE and 62 patients treated with PE were entered into a comparative efficacy analysis. In the PE group, patients underwent a total of 232 replacements, with a mean of 3.74. PE significantly improved the patients’ QMGS performance, with the mean QMGS decreasing from 22.98 ± 4.03 points at baseline to 18.34 ± 5.03 points after treatment, a decrease of 4.68 ± 4.04 points (p < 0.001). A decrease of ≥3 points in QMGS was considered a significant improvement, with a treatment response rate of 67.7% in the PE group. In the LPE group, patients received a total of 117 replacements, with a mean of 1.89. The patients’ mean QMGS was 23.19 ± 4.11 points at baseline and was 16.94 ± 5.78 points after treatment, a decrease of 6.26 ± 4.39 points (p < 0.001). The improvement in QMGS was more significant in patients treated with LPE compared to the PE group (p = 0.039). The treatment response rate in the LPE group was 79%, which was not significantly different compared to the PE group (p = 0.16). The LEP group had a shorter mean length of stay compared to the PE group (10.86 ± 3.96 vs. 12.14 ± 4.14 days), but the difference was not statistically significant (p = 0.13). During the 2-month follow-up period, LPE may be associated with better functional outcomes for patients, with lower QMG score and relapse rate. LPE and PE were both effective in reducing the levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and AChR-Ab. Compared to PE, LPE was superior in the reduction of AChR-Ab titer.

Conclusion

In severe MG, LPE may be a more preferred treatment option than PE. It achieves treatment outcomes that are not inferior to or even better than PE with fewer replacements. This study provides further evidence to support the application of LPE as a new treatment option for MG.
Emotionally clocked out: cell-type specific regulation of mood and anxiety by the circadian clock system in the brain
Authors: Francis T. Chase , Porcu Alessandra
Published: June 2023

Circadian rhythms are self-sustained oscillations of biological systems that allow an organism to anticipate periodic changes in the environment and optimally align feeding, sleep, wakefulness, and the physiological and biochemical processes that support them within the 24 h cycle. These rhythms are generated at a cellular level by a set of genes, known as clock genes, which code for proteins that inhibit their own transcription in a negative feedback loop and can be perturbed by stress, a risk factor for the development of mood and anxiety disorders. A role for circadian clocks in mood and anxiety has been suggested for decades on the basis of clinical observations, and the dysregulation of circadian rhythms is a prominent clinical feature of stress-related disorders. Despite our understanding of central clock structure and function, the effect of circadian dysregulation in different neuronal subtypes in the suprachiasmatic nucleus (SCN), the master pacemaker region, as well as other brain systems regulating mood, including mesolimbic and limbic circuits, is just beginning to be elucidated. In the brain, circadian clocks regulate neuronal physiological functions, including neuronal activity, synaptic plasticity, protein expression, and neurotransmitter release which in turn affect mood-related behaviors via cell-type specific mechanisms. Both animal and human studies have revealed an association between circadian misalignment and mood disorders and suggest that internal temporal desynchrony might be part of the etiology of psychiatric disorders. To date, little work has been conducted associating mood-related phenotypes to cell-specific effects of the circadian clock disruptions. In this review, we discuss existing literature on how clock-driven changes in specific neuronal cell types might disrupt phase relationships among cellular communication, leading to neuronal circuit dysfunction and changes in mood-related behavior. In addition, we examine cell-type specific circuitry underlying mood dysfunction and discuss how this circuitry could affect circadian clock. We provide a focus for future research in this area and a perspective on chronotherapies for mood and anxiety disorders.
The impact of bone marrow sparing on organs at risk dose for cervical cancer: a Pareto front analysis
Authors: Kuipers Sander , Godart Jérémy , Corbeau Anouk , Sharfo Abdul Wahab , Breedveld Sebastiaan , Mens Jan Willem , de Boer Stephanie , Nout Remi , Hoogeman Mischa
Published: June 2023

Background and purpose

To quantify the increase in bladder and rectum dose of a bone marrow sparing (BMS) VMAT strategy for primary treatment of locally advanced cervical cancer (LACC).

Materials and methods

Twenty patients with stage IB-IVA cervical cancer were selected for this study. The whole Pelvic Bones (PB) was taken as substitute for bone marrow. For every patient, Pareto-optimal plans were generated to explore the trade-off between rectum, bladder, and PB mean dose. The PB mean dose was decreased in steps of 1 Gy. For each step, the increase in rectum and bladder mean dose was quantified. The increase in mean dose of other OAR compared to no BMS was constrained to 1 Gy.

Results

In total, 931 plans of 19 evaluable patients were analyzed. The average [range] mean dose of PB without BMS was 22.8 [20.7-26.2] Gy. When maximum BMS was applied, the average reduction in mean PB dose was 5.4 [3.0-6.8] Gy resulting in an average mean PB dose of 17.5 [15.8-19.8] Gy. For <1 Gy increase in both the bladder and the rectum mean dose, the PB mean dose could be decreased by >2 Gy, >3 Gy, >4 Gy, and >5 Gy for 19/19, 13/19, 5/19, and 1/19 patients, respectively.

Conclusion

Based on the comprehensive three-dimensional Pareto front analysis, we conclude that 2-5 Gy BMS can be implemented without a clinically relevant increase in mean dose to other OAR. If BMS is too dominant, it results in a large increase in mean dose to other OAR. Therefore, we recommend implementing moderate BMS for the treatment of LACC patients with VMAT.
Outcome and toxicity of ifosfamide, carboplatin, and etoposide versus gemcitabine and vinorelbine regimen for pediatric patients with relapsed or refractory Hodgkin’s lymphoma
Authors: Mahdy Ahmed , Hamoda Asmaa , Zaher Ahmed , Khorshed Eman , Elwakeel Madeha , Hassanein Omneya , Sidhom Iman
Published: June 2023

Background

Pediatric classical Hodgkin lymphoma (CHL) is a curable disease; however, the optimal salvage regimen is unclear for relapsed/refractory (R/R) disease. This study aimed to compare response rates, toxicity, event-free survival (EFS), and overall survival (OS) of ifosfamide, carboplatin, and etoposide (ICE) with gemcitabine and vinorelbine (GV) regimen after first-line doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) in pediatric patients with R/R CHL.

Methods

This is a retrospective cohort study of 132 pediatric patients with R/R CHL treated from July 2012 to December 2020 with ICE (n = 82) or GV (n = 50).

Results

The median age at relapse was 13.9 years, and 68.2% were men. Rates of complete response, partial response, and progressive disease before consolidation were 50.6%, 3.7%, and 45.7% for ICE and 28.5%, 0%, and 71.5% for GV (P = 0.011). By multivariate analysis, regimen (P = 0.002), time to relapse (P = 0.0001), and B-symptoms (P = 0.002) were independent factors to lower response rates. Hematological toxicity, electrolyte disturbance, hemorrhagic cystitis, infectious complications, and hospital admission for fever neutropenia were statistically significant higher for the ICE regimen. Treatment-related mortalities were 2.4% for ICE and 2% for GV (P = 0.86). The 3-year EFS was 39.3% ± 11.4% for ICE and 24.9% ± 12.5% for GV (P = 0.0001), while 3-year OS was 69.3% ± 10.6% and 74% ± 12.9% (P = 0.3), respectively. By multivariate analysis, regimen (P = 0.0001), time to relapse (P = 0.011), B-symptoms (P = 0.001), and leukocytosis (P = 0.007) were significant for EFS, while anemia (P = 0.008), and progressive disease on early response evaluation (P = 0.022) were significant for OS.

Conclusions

The ICE regimen had a better overall response rate and EFS, but higher toxicity, than GV; however, OS and mortality were similar.
Candidate genes for obstructive sleep apnea in non-syndromic children with craniofacial dysmorphisms – a narrative review
Authors: Marincak Vrankova Zuzana , Krivanek Jan , Danek Zdenek , Zelinka Jiri , Brysova Alena , Izakovicova Holla Lydie , Hartsfield James K. , Borilova Linhartova Petra
Published: June 2023

Pediatric obstructive sleep apnea (POSA) is a complex disease with multifactorial etiopathogenesis. The presence of craniofacial dysmorphisms influencing the patency of the upper airway is considered a risk factor for POSA development. The craniofacial features associated with sleep-related breathing disorders (SRBD) – craniosynostosis, retrognathia and micrognathia, midface and maxillary hypoplasia – have high heritability and, in a less severe form, could be also found in non-syndromic children suffering from POSA. As genetic factors play a role in both POSA and craniofacial dysmorphisms, we hypothesize that some genes associated with specific craniofacial features that are involved in the development of the orofacial area may be also considered candidate genes for POSA. The genetic background of POSA in children is less explored than in adults; so far, only one genome-wide association study for POSA has been conducted; however, children with craniofacial disorders were excluded from that study. In this narrative review, we discuss syndromes that are commonly associated with severe craniofacial dysmorphisms and a high prevalence of sleep-related breathing disorders (SRBD), including POSA. We also summarized information about their genetic background and based on this, proposed 30 candidate genes for POSA affecting craniofacial development that may play a role in children with syndromes, and identified seven of these genes that were previously associated with craniofacial features risky for POSA development in non-syndromic children. The evidence-based approach supports the proposition that variants of these candidate genes could lead to POSA phenotype even in these children, and, thus, should be considered in future research in the general pediatric population.
The impact of non-pharmaceutical interventions on premature births during the COVID-19 pandemic: a nationwide observational study in Korea
Authors: Lee Ji Young , Park Joonsik , Lee Myeongjee , Han Minkyung , Jung Inkyung , Lim Sung Min , Baek Jee Yeon , Kang Ji-Man , Park Min Soo , Ahn Jong Gyun
Published: June 2023

Background

Non-pharmaceutical interventions (NPIs), such as social distancing and hand washing, have been associated with a decline in the preterm birth rate worldwide. We aimed to evaluate whether the preterm birth rate in Korea during the coronavirus disease 2019 lockdown has changed compared to that in previous years.

Method

A birth registry from the Korea Statistical Information Service, which is a nationwide official database, was used to include all births claimed to have occurred between 2011 and 2020. Newborns with gestational age (GA) less than 22 weeks and birth weight less than 220 g were excluded. The pre-NPI period was designated as January 2011 to January 2020, and the NPI period was defined as February 2020 to December 2020. We assessed the effect of NPI on the incidence of prematurity per 100 births using an interrupted time-series quasi-experimental design and implementing an autoregressive integrated moving average (ARIMA) model.

Results

From 2011 to 2020, a total of 3,931,974 live births were registered, among which 11,416 were excluded. Consequently, the final study population included 3,920,558 live births (both singleton and multiple births) among which 275,009 (7.0%) were preterm. The preterm birth rate was significantly higher during the NPI period (8.68%) compared to that in the pre-NPI period (6.92%) (P < 0.001). The ARIMA model showed that in all singleton and multiple births, except those in July (observed 9.24, expected 8.54, [95% prediction interval {PI} 8.13–8.96], percent difference 7.81%), September (observed 7.89, expected 8.35, [95% PI 7.93–8.76], percent difference −5.66%), and December (observed 9.90, expected 9.40, [95% PI 8.98–9.82], percent difference 5.2%), most observed values were within the 95% PI of the expected values and showed an increasing trend.

Conclusion

In this nationwide observational study, the trend in premature birth rate did not significantly change due to NPI implementation in Korea, as it had been increasing since 2011. The trend of Korea's birth rate appears to be unaffected by the implementation of NPIs; however, further studies with a longer follow-up period are needed.
Effects of the Chinese herbal formula San-Huang Gu-Ben Zhi-Ke treatment on stable chronic obstructive pulmonary disease: a randomized, double-blind, placebo-controlled trial
Authors: Lyu Tianyi , Li Demin , Lei Xiang , Zhang Yuteng , Cheng Shilei , Shu Xinyang , Zhang Hongchun
Published: June 2023

Objective: The aim of this study was to evaluate the efficacy and safety of the Chinese herbal formula San-Huang Gu-Ben Zhi-Ke (SHGBZK) as a treatment for patients with stable chronic obstructive pulmonary disease (COPD) diagnosed with lung-spleen Qi deficiency.

Method: A randomized, double-blind, placebo-controlled trial was designed. 98 adults aged between 40 and 80 years with stable COPD diagnosed with lung-spleen Qi deficiency were included. All participants received basic treatment for COPD. Patients in the experimental group took SHGBZK, while the control group took placebo. The primary outcome was the frequency of acute exacerbation. The secondary outcomes were lung function, symptom score, exercise capacity and quality of life.

Results: Of 98 patients who underwent randomization, 50 patients in the SHGBZK group and 48 in the placebo group were included in the full analysis set. After 24-week therapy and 28-week follow-up, patients in treatment group had significant improvements in symptom, exercise capacity and quality of life. After Subgroup analysis, the frequency of acute exacerbation in patients with a COPD Assessment Test (CAT) score of at least 10 or a modified Medical Research Council (mMRC) score of at least 2 was significantly lower in the SHGBZK group than in the placebo group. Lung function in patients with frequent exacerbation was significantly higher in the SHGBZK group than in the placebo group. The incidence of adverse events was generally similar in the two groups.

Conclusion: SHGBZK had beneficial effects on symptom, exercise capacity and quality of life in stable COPD patients. SHGBZK also had the potential to reduce the frequency of exacerbation and improve lung function in specific groups of COPD patients.

Clinical Trial Registration:https://www.chictr.org.cn/showproj.html?proj=26933, identifier ChiCTR1800016349
Antiaging effects of dietary supplements and natural products
Authors: Gao Lulu , Liu Xudong , Luo Xiaoyan , Lou Xiaofan , Li Pusen , Li Xian , Liu Xiaomeng
Published: June 2023

Aging is an inevitable process influenced by genetics, lifestyles, and environments. With the rapid social and economic development in recent decades, the proportion of the elderly has increased rapidly worldwide, and many aging-related diseases have shown an upward trend, including nervous system diseases, cardiovascular diseases, metabolic diseases, and cancer. The rising burden of aging-related diseases has become an urgent global health challenge and requires immediate attention and solutions. Natural products have been used for a long time to treat various human diseases. The primary cellular pathways that mediate the longevity-extending effects of natural products involve nutrient-sensing pathways. Among them, the sirtuin, AMP-activated protein kinase, mammalian target of rapamycin, p53, and insulin/insulin-like growth factor-1 signaling pathways are most widely studied. Several studies have reviewed the effects of individual natural compounds on aging and aging-related diseases along with the underlying mechanisms. Natural products from food sources, such as polyphenols, saponins, alkaloids, and polysaccharides, are classified as antiaging compounds that promote health and prolong lifeviavarious mechanisms. In this article, we have reviewed several recently identified natural products with potential antiaging properties and have highlighted their cellular and molecular mechanisms. The discovery and use of dietary supplements and natural products that can prevent and treat multiple aging-related diseases in humans will be beneficial. Thus, this review provides theoretical background for existing dietary supplements and natural products as potential antiaging agents.
Traditional herbal medicine for anorexia in patients with cancer: a systematic review and meta-analysis of randomized controlled trials
Authors: Park Su Bin , Yoon Jee-Hyun , Kim Eun Hye , Jin Hayun , Yoon Seong Woo
Published: June 2023

Background: The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of traditional herbal medicine (THM) for improving anorexia in patients with cancer.

Methods: We searched for randomized controlled trials (RCTs) that evaluated orally administered THM for cancer-related anorexia using 10 databases from the inception to 1 August 2021. The primary outcome was an improvement in anorexia, measured with the total effective rate (TER) or visual analog scale (VAS). The secondary outcomes were the changes in body weight, the Karnofsky performance scale, acylated ghrelin, and adverse events. We used the Cochrane risk of bias assessment tool and the Grading of Recommendations Assessment, Development, and Evaluation method to assess the quality of the studies and the quality of the evidence.

Results: A total of 26 RCTs were included, of which 23 were subjected to quantitative analysis. THM showed a significant improvement in anorexia measured with the TER [risk ratio (RR) 1.12, 95% confidence intervals (CI) 1.04–1.20] than appetite stimulants with moderate quality evidence and in the Karnofsky performance scale (RR 1.38, 95% CI 1.12–1.70) with low quality evidence but not in body weight gain (RR 0.98, 95% CI 0.80–1.20). THM showed a significant improvement in anorexia measured with the TER (RR 1.74, 95% CI 1.23–2.48) compared with usual care with low-quality evidence but did not significantly improve the VAS score (mean difference 0.72, 95% CI 0.00–1.43) or the level of acylated ghrelin (mean difference 0.94, 95% CI 1.08–2.97). There were no serious adverse events.

Conclusion: This review suggests that THM may be considered a safe alternative therapeutic option for improving anorexia in patients with cancer. Nonetheless, more rigorous RCTs are needed due to methodological limitations.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero, identifier CRD42021276508.
Aedes aegypti salivary gland extract alleviates acute itching by blocking TRPA1 channels
Authors: Cerqueira Anderson R. A. , Rodrigues Leandro , Coavoy-Sánchez Silvia Abigail , Teixeira Simone A. , Feitosa Karla B. , Taniguchi Erika Y. , Lopes Lucia R. , Cassola Antônio C. , Muscará Marcelo N. , Sá-Nunes Anderson , Costa Soraia K. P.
Published: June 2023

Aedes aegypti (Ae. aegypti) saliva induces a variety of anti-inflammatory and immunomodulatory activities. Interestingly, although it is known that mosquito bites cause allergic reactions in sensitised hosts, the primary exposure of humans to Ae. aegypti does not evoke significant itching. Whether active components in the saliva of Ae. aegypti can counteract the normal itch reaction to injury produced by a histaminergic or non-histaminergic pathway in vertebrate hosts is unknown. This study investigated the effects of Ae. aegypti mosquito salivary gland extract (SGE) on sensitive reactions such as itching and associated skin inflammation. Acute pruritus and plasma extravasation were induced in mice by the intradermal injection of either compound 48/80 (C48/80), the Mas-related G protein-coupled receptor (Mrgpr) agonist chloroquine (CQ), or the transient receptor potential ankyrin 1 (TRPA1) agonist allyl isothiocyanate (AITC). The i.d. co-injection of Ae. aegypti SGE inhibited itching, plasma extravasation, and neutrophil influx evoked by C48/80, but it did not significantly affect mast cell degranulation in situ or in vitro. Additionally, SGE partially reduced CQ- and AITC-induced pruritus in vivo, suggesting that SGE affects pruriceptive nerve firing independently of the histaminergic pathway. Activation of TRPA1 significantly increased intracellular Ca2+ in TRPA-1-transfected HEK293t lineage, which was attenuated by SGE addition. We showed for the first time that Ae. aegypti SGE exerts anti-pruriceptive effects, which are partially regulated by the histamine-independent itch TRPA1 pathway. Thus, SGE may possess bioactive molecules with therapeutic potential for treating nonhistaminergic itch.
Postsynaptic density radiation signature following space irradiation
Authors: Impey Soren , Pelz Carl , Riparip Lara-Kirstie , Tafessu Amanuel , Fareh Fatema , Zuloaga Damian G. , Marzulla Tessa , Stewart Blair , Rosi Susanna , Turker Mitchell S. , Raber Jacob
Published: June 2023

Introduction: The response of the brain to space radiation is an important concern for astronauts during space missions. Therefore, we assessed the response of the brain to 28Si ion irradiation (600 MeV/n), a heavy ion present in the space environment, on cognitive performance and whether the response is associated with altered DNA methylation in the hippocampus, a brain area important for cognitive performance.

Methods: We determined the effects of 28Si ion irradiation on object recognition, 6-month-old mice irradiated with 28Si ions (600 MeV/n, 0.3, 0.6, and 0.9 Gy) and cognitively tested two weeks later. In addition, we determined if those effects were associated with alterations in hippocampal networks and/or hippocampal DNA methylation.

Results: At 0.3 Gy, but not at 0.6 Gy or 0.9 Gy, 28Si ion irradiation impaired cognition that correlated with altered gene expression and 5 hmC profiles that mapped to specific gene ontology pathways. Comparing hippocampal DNA hydroxymethylation following proton, 56Fe ion, and 28Si ion irradiation revealed a general space radiation synaptic signature with 45 genes that are associated with profound phenotypes. The most significant categories were glutamatergic synapse and postsynaptic density.

Discussion: The brain’s response to space irradiation involves novel excitatory synapse and postsynaptic remodeling.
Transient drought during flowering modifies the grain proteome of bread winter wheat
Authors: Lakhneko Olha , Stasik Oleg , Škultéty Ľudovit , Kiriziy Dmytro , Sokolovska-Sergiienko Oksana , Kovalenko Mariia , Danchenko Maksym
Published: June 2023

Drought is among the most limiting factors for sustainable agricultural production. Water shortage at the onset of flowering severely affects the quality and quantity of grain yield of bread wheat (Triticum aestivum). Herein, we measured oxidative stress and photosynthesis-related parameters upon applying transient drought on contrasting wheat cultivars at the flowering stage of ontogenesis. The sensitive cultivar (Darunok Podillia) showed ineffective water management and a more severe decline in photosynthesis. Apparently, the tolerant genotype (Odeska 267) used photorespiration to dissipate excessive light energy. The tolerant cultivar sooner induced superoxide dismutase and showed less inhibited photosynthesis. Such a protective effect resulted in less affected yield and spectrum of seed proteome. The tolerant cultivar had a more stable gluten profile, which defines bread-making quality, upon drought. Water deficit caused the accumulation of medically relevant proteins: (i) components of gluten in the sensitive cultivar and (ii) metabolic proteins in the tolerant cultivar. We propose specific proteins for further exploration as potential markers of drought tolerance for guiding efficient breeding: thaumatin-like protein, 14-3-3 protein, peroxiredoxins, peroxidase, FBD domain protein, and Ap2/ERF plus B3 domain protein.
Amaranth Genomic Resource Database: an integrated database resource of Amaranth genes and genomics
Authors: Singh Akshay , Mahato Ajay Kumar , Maurya Avantika , Rajkumar S. , Singh A. K. , Bhardwaj Rakesh , Kaushik S. K. , Kumar Sandeep , Gupta Veena , Singh Kuldeep , Singh Rakesh
Published: June 2023

Amaranth (Amaranthus L.) is native to Mexico and North America, where it was cultivated thousands of years ago, but now amaranth is grown worldwide. Amaranth is one of the most promising food crops with high nutritional value and belongs to the family Amaranthaceae. The high-quality genome assembly of cultivated amaranth species (A. hypochondriacus, A. cruentus) and wild/weedy species (A. tuberculatus, A. hybridus, and A. palmeri) has already been reported; therefore, we developed an Amaranth Genomic Resource Database (AGRDB) to provide access to all the genomic information such as genes, SSRs, SNPs, TFs, miRNAs, and transporters in one place. The AGRDB database contains functionally annotated gene information with their sequence details, genic as well as genomic SSRs with their three sets of primers, transcription factors classified into different families with their sequence information and annotation details, putative miRNAs with their family, sequences, and targeted gene details, transporter genes with their superfamily, trans-membrane domain details, and details of genic as well as nongenic SNPs with 3′ and 5′ flanking sequence information of five amaranth species. A database search can be performed using the gene ID, sequence ID, sequence motif, motif repeat, family name, annotation keyword, scaffold or chromosome numbers, etc. This resource also includes some useful tools, including JBrowse for the visualization of genes, SSRs, SNPs, and TFs on the respective amaranth genomes and BLAST search to perform a BLAST search of the user’s query sequence against the amaranth genome as well as protein sequences. The AGRDB database will serve as a potential platform for genetic improvement and characterization of this futuristic crop. The AGRDB database will be accessible via the link: http://www.nbpgr.ernet.in:8080/AmaranthGRD/.
Preparation of physiologically active inside-out vesicles from plant inner mitochondrial membranes
Authors: Ehmke Leander , Hause Gerd , Klösgen Ralf Bernd , Bennewitz Bationa
Published: June 2023

For many metabolites, the major barrier between cytosol and mitochondrial matrix is the inner membrane of mitochondria, the site of the respiratory electron transport chain. In consequence, it houses numerous transporters which facilitate the controlled exchange of metabolites, ions, and even proteins between these cellular compartments. While their import into the organelle can be studied with isolated mitochondria or mitoplasts, the analysis of their export from the matrix into the intermembrane space or even the cytosol demands for more sophisticated approaches. Among those, inside-out inner membrane vesicles are particularly useful, since they allow the direct presentation of the potential export substrates to the membrane without prior import into the organelle. Here we present a protocol for the isolation of such inside-out vesicles of the inner membrane of plant mitochondria based on repeated freeze/thaw-cycles of freshly prepared mitoplasts. Electron microscopy and Western analysis could show that the majority of the vesicles have single envelope membranes in an inside-out topology. The vesicles are furthermore physiologically active, as demonstrated by assays measuring the enzymatic activities of Complex I (NADH dehydrogenase), Complex V (ATP synthase) and the mitochondrial processing peptidase (MPP) associated with Complex III. Hence, the method presented here provides a good basis for further studies of the inner mitochondrial membrane and mitochondrial export processes.
Linking heart rate variability to psychological health and brain structure in adolescents with and without conduct disorder
Authors: Cubillo Ana , Tkalcec Antonia , Oldenhof Helena , Unternaehrer Eva , Raschle Nora , Kohls Gregor , Nauta-Jansen Lucres , Hervas Amaia , Fernandez-Rivas Aranzazu , Konrad Kerstin , Popma Arne , Freitag Christine , de Brito Stephane , Fairchild Graeme , Stadler Christina
Published: June 2023

Aims

Heart rate variability (HRV) measures have been suggested in healthy individuals as a potential index of self-regulation skills, which include both cognitive and emotion regulation aspects. Studies in patients with a range of psychiatric disorders have however mostly focused on the potential association between abnormally low HRV at rest and specifically emotion regulation difficulties. Emotion regulation deficits have been reported in patients with Conduct Disorder (CD) however, the association between these emotion regulation deficits and HRV measures has yet to be fully understood. This study investigates (i) the specificity of the association between HRV and emotion regulation skills in adolescents with and without CD and (ii) the association between HRV and grey matter brain volumes in key areas of the central autonomic network which are involved in self-regulation processes, such as insula, lateral/medial prefrontal cortices or amygdala.

Methods

Respiratory sinus arrhythmia (RSA) measures of HRV were collected from adolescents aged between 9–18 years (693 CD (427F)/753 typically developing youth (TD) (500F)), as part of a European multi-site project (FemNAT-CD). The Inverse Efficiency Score, a speed-accuracy trade-off measure, was calculated to assess emotion and cognitive regulation abilities during an Emotional Go/NoGo task. The association between RSA and task performance was tested using multilevel regression models. T1-weighted structural MRI data were included for a subset of 577 participants (257 CD (125F); 320 TD (186F)). The CerebroMatic toolbox was used to create customised Tissue Probability Maps and DARTEL templates, and CAT12 to segment brain images, followed by a 2 × 2 (sex × group) full factorial ANOVA with RSA as regressor of interest.

Results

There were no significant associations between RSA and task performance, neither during emotion regulation nor during cognitive regulation trials. RSA was however positively correlated with regional grey matter volume in the left insula (pFWE = 0.011) across all subjects.

Conclusion

RSA was related to increased grey matter volume in the left insula across all subjects. Our results thus suggest that low RSA at rest might be a contributing or predisposing factor for potential self-regulation difficulties. Given the insula’s role in both emotional and cognitive regulation processes, these brain structural differences might impact either of those.
Psychopathology in female offenders of terrorism and violent extremism: a systematic review
Authors: Rakhshandehroo Sadaf , Duits Nils , Bergman Dick , Verkes Robbert-Jan , Kempes Maaike
Published: June 2023

Introduction

Terrorism and violent extremism are major social threats worldwide and are committed not only by men but also by women. Previous research has shown indications of psychopathology, among other personal and contextual factors, as a potential risk factor for perpetrating terrorist and violent extremist crimes. Despite the fact that women have engaged in acts of terrorism and violent extremism throughout history, the vast majority of literature on psychopathology so far has been mainly focused on men with terrorist and violent extremist behavior. As women's engagement in terrorism and violent extremism is increasing, and gender differences in psychopathology in offenders of terrorism or violent extremism may exist based on empirical evidence for such differences in offenders of violence, gender-informed research into psychopathology as a potential risk factor for offending is of pivotal importance for improving the effectiveness of counter-terrorism interventions. The present systematic review was designed to examine what empirical knowledge exists on the presence and potential contributing role of psychopathology in female perpetrators of terrorism or violent extremism.

Methods

A literature search was conducted to identify primary source studies in PsycINFO, PubMed, Embase, Web of Science, and Sociological Abstracts. ASReview as an artificial intelligence software was used to screen references.

Results

In total, eight studies were included, of which only two studies distinguished prevalence rates and types of psychopathology separately for women, indicating personality disorder as most common. All four out of the eight studies that reported on the relationship between psychopathology and terrorism and violent extremism assumed psychopathology to be a contributing factor in engaging in terrorist or violent extremist acts. However, none of these four studies reported on potentially present female-specific mechanisms of the role of psychopathology in offenses.

Discussion

The present systematic review draws the striking conclusion that there is a lack of clearly described empirical studies on psychopathology in female perpetrators of terrorism and violent extremism and emphasizes the importance of more future empirically based inquiries on this topic by the forensic psychiatric field.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=275354, identifier: CRD42021275354.
Abnormal dynamic functional network connectivity in patients with early-onset bipolar disorder
Authors: Hu Ziyi , Zhou Chun , He Laichang
Published: June 2023

Objective

To explore the changes in dynamic functional brain network connectivity (dFNC) in patients with early-onset bipolar disorder (BD).

Methods

Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 39 patients with early-onset BD and 22 healthy controls (HCs). Four repeated and stable dFNC states were characterised by independent component analysis (ICA), sliding time windows and k-means clustering, and three dFNC temporal metrics (fraction of time, mean dwell time and number of transitions) were obtained. The dFNC temporal metrics and the differences in dFNC between the two groups in different states were evaluated, and the correlations between the differential dFNC metrics and neuropsychological scores were analysed.

Results

The dFNC analysis showed four connected patterns in all subjects. Compared with the HCs, the dFNC patterns of early-onset BD were significantly altered in all four states, mainly involving impaired cognitive and perceptual networks. In addition, early-onset BD patients had a decreased fraction of time and mean dwell time in state 2 and an increased mean dwell time in state 3 (p < 0.05). The mean dwell time in state 3 of BD showed a positive correlation trend with the HAMA score (r = 0.4049, p = 0.0237 × 3 > 0.05 after Bonferroni correction).

Conclusion

Patients with early-onset BD had abnormal dynamic properties of brain functional network connectivity, suggesting that their dFNC was unstable, mainly manifesting as impaired coordination between cognitive and perceptual networks. This study provided a new imaging basis for the neuropathological study of emotional and cognitive deficits in early-onset BD.
A retrospective database study on 2-year weight trajectories in first-episode psychosis
Authors: Chua Yi Chian , Abdin Edimansyah , Tang Charmaine
Published: June 2023

Introduction

It is critical to focus on individual weight profiles in line with efforts to tailor treatment, given the heterogeneous nature of the clinical population. This study aims to identify and describe possible two-year weight trajectories among patients accepted to the Early Psychosis Intervention Programme (EPIP) in Singapore.

Methods

De-identified data was extracted from EPIP’s standing database for patients accepted from 2014 to 2018 with a schizophrenia spectrum disorder. Data collected at fixed time-points (baseline, 1-year, and 2-year) included anthropometric measures (height and weight), and sociodemographic (age, sex, highest education level, and vocational status) and clinical (duration of untreated psychosis, number of inpatient admissions, and scores on the Positive and Negative Syndrome Scale and Global Assessment of Functioning) information.

Results

A total of 391 complete data sets were included for main analyses. Those with missing weight data were more likely to be males, older at baseline, have a highest education level of tertiary and above at baseline, and have a longer duration of untreated psychosis. The weight change across two years resulted in the following membership breakdown: 151 (38.6%) in super high risk; 133 (34.0%) in high risk mitigated; 17 (4.3%) in at risk; 34 (8.8%) in delayed risk; and 56 (14.4%) in low risk.

Discussion

The lack of pharmacological, dietary, and physical activity data is a significant limitation in this study; however, the results reinforce the justification for future studies to prospectively capture and examine the influence of these data, with the aim of early detection and weight intervention for high risk groups.
Adverse effects of antipsychotics on sleep in patients with schizophrenia. Systematic review and meta-analysis
Authors: Valencia Carlo Yarmila Elena , Saracco-Alvarez Ricardo Arturo , Valencia Carlo Verónica Angela , Vázquez Vega Daniela , Natera Rey Guillermina , Escamilla Orozco Raul Ivan
Published: June 2023

Introduction

Our objective was to conduct a systematic review and meta-analysis of adverse effects on sleep in patients with schizophrenia receiving antipsychotic treatment.

Methods

A systematic search was performed in PubMed, Cochrane Central, Embase, Toxline, Ebsco, Virtual Health Library, Web of Science, SpringerLink, and in Database of abstracts of Reviews of Effects of Randomized Clinical Trials to identify eligible studies published from January 1990 to October 2021. The methodological quality of the studies was evaluated using the CONSORT list, and the Cochrane bias tool. Network meta-analysis was performed using the Bayesian random-effects model, with multivariate meta-regression to assess the association of interest.

Results

87 randomized clinical trials were identified that met the inclusion criteria, and 70 articles were included in the network meta-analysis. Regarding the methodological quality of the studies, 47 had a low or moderate bias risk. The most common adverse effects on sleep reported in the studies were insomnia, somnolence, and sedation. The results of the network meta-analysis showed that ziprasidone was associated with an increased risk of insomnia (OR, 1.56; 95% credible interval CrI, 1.18–2.06). Several of the included antipsychotics were associated with a significantly increased risk of somnolence; haloperidol (OR, 1.90; 95% CrI, 1.12–3.22), lurasidone (OR, 2.25; 95% CrI, 1.28–3.97) and ziprasidone (OR, 1.79; 95% CrI, 1.06–3.02) had the narrowest confidence intervals. In addition, perphenazine (OR, 5.33; 95% CrI, 1.92–14.83), haloperidol (OR, 2.61; 95% CrI, 1.14–5.99), and risperidone (OR, 2.41; 95% CrI, 1.21–4.80) were associated with an increased risk of sedation compared with placebo, and other antipsychotics did not differ. According to the SUCRAs for insomnia, chlorpromazine was ranked as the lowest risk of insomnia (57%), followed by clozapine (20%), while flupentixol (26 %) and perospirone (22.5%) were associated with a lower risk of somnolence. On the other hand, amisulpride (89.9%) was the safest option to reduce the risk of sedation.

Discussion

Insomnia, sedation, and somnolence were the most frequent adverse effects on sleep among the different antipsychotics administered. The evidence shows that chlorpromazine, clozapine, flupentixol, perospirone, and amisulpride had favorable safety profiles. In contrast, ziprasidone, perphenazine, haloperidol, and risperidone were the least safe for sleep.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017078052, identifier: PROSPERO 2017 CRD42017078052.
Walk the line: a systemic perspective on stress experienced by emergency medical personnel by comparing military and civilian prehospital settings
Authors: Van Puyvelde Martine , Van Herck Jolien , Van den Bossche Jeroen , Goethals Frederic , Gijbels Daisy , Detaille Frederic , Pattyn Nathalie
Published: June 2023

Introduction

Emergency Medicine (EM) personnel in both military and civilian prehospital settings are often exposed to stressful and extreme events. Therefore, a cross-pollination between both contexts in terms of coping strategies may generate new information for purposes of training, prevention, and support programs. In the current study, we aimed at comparing both contexts to understand the type of stress events personnel experience; whether experience differs between civilian and military personnel; and how they cope with it.

Methods

We used a mixed method approach, combining the results of a quantitative questionnaire and a thematic analysis of 23 in-depth semi-structured interviews to gain additional qualitative information.

Results

Whereas the questionnaire pointed to a significant preference for task-oriented coping over avoidant and emotion-oriented coping, the interviews offered a more nuanced insight, showing a constant aim to position themselves on a continuum between emotional disconnection from the patient to preserve operationality on the one hand; and remaining enough empathic to preserve humanity on the other hand. We further identified an ambivalent awareness regarding emotions and stress, a vulnerable disbalance between an excessive passion for the job with the sacrifice of own's personal life (for a growing volatile and dangerous working environment) and a lack of recognition from both the patient and organizational environment. The combination of these factors may carry the risk for moral injury and compassion fatigue. Therefore, mutual trust between the organizational level and EM personnel as well as among team members is crucial.

Discussion

The results are discussed from a systemic SHELL perspective, indicating how the specific profile of EM personnel relates to the software, hardware, environmental and liveware components of their professional and private life. Trainings on stress- and risk awareness should be approached both on an individual and systemic level, knowing that there is clearly no “one-size-fits-all” manner.