bluuebunny/crossref_metadata_2025 huggingface dataset:
Regular, low-dose methadone for reducing breathlessness in people experiencing or at risk of neurotoxic effects from morphine: A single-center case series
Authors: Sobanski Piotr Z. , Currow David C.
Published: December 2022

Breathlessness is a common symptom suffered by people living with advanced malignant and non-malignant diseases, one which significantly limits their quality of life. If it emerges at minimal exertion, despite the maximal, guidelines-directed, disease-specific therapies, it should be considered persistent and obliges clinicians to prescribe symptomatic, non-pharmacological, and pharmacological treatment to alleviate it. Opioids are recommended for the symptomatic treatment of persistent breathlessness, with morphine most extensively studied for this indication. It is extensively metabolized in the liver into water-soluble 3- and 6-glucuronides, excreted by the kidneys. In the case of advanced renal failure, the glucuronides accumulate, mainly responsible for toxicity 3-glucuronides. Some people, predominantly those with advanced renal failure, develop neurotoxic effects after chronic morphine, even when prescribed at a very low dose. A single-center case series of consecutive patients experiencing neurotoxic effects after long-term, low-dose morphine or at risk of such effects were transferred to methadone to avoid the accumulation of neurotoxic metabolites. Over the course of 4.5 years, 26 patients have been treated with methadone in the median dose of 3.0 mg/24 h p.o., for persisting breathlessness. Sixteen of them had been treated previously with an opioid (usually morphine) at the median dose of 7.0 mg/24 h (morphine oral daily dose equivalent). They were transferred to methadone, with the median dose of 3.0 mg/24 h orally (methadone oral daily dose equivalent), and the median morphine-to-methadone dose ratio was 2.5:1. All patients experienced a meaningful improvement in breathlessness intensity after methadone, by a median of 5 points (range 1–8) on the 0–10 numerical rating scale (NRS) in the whole group, and by 2 points (range 0–8) in those pretreated with other opioids, mainly morphine. Low-dose methadone can be considered an efficient alternative to morphine for reducing breathlessness in people experiencing neurotoxic effects or at risk of developing them following treatment with morphine.
The impact of multifactorial factors on the Quality of Life of Behçet's patients over 10 years
Authors: Senusi Amal A. , Mather John , Ola Dennis , Bergmeier Lesley A. , Gokani Bindi , Fortune Farida
Published: December 2022

Objective

This study analyses the 2020 survey and reviews the 2009, 2014 surveys to ascertain which Behçet's symptoms, personal and family status, patients' lifestyle, and work-related outcomes impacted on Health-Related Quality of Life (HRQoL).

Methods

Four hundred and fifty-nine Behçet's patients submitted an online survey/questionnaire. Patients provided information on socio-demographic characteristics, disease duration, historical and current symptoms, systemic and topical medication, health related lifestyle, work-related outcomes regarding employment status and claiming benefits and Quality of Life (QoL) measured by EQ-5D index.

Results

Four hundred and nineteen patients met the inclusion criteria, and 371 who had full data (Males: Females: Others = 84:285:2, mean–age = 41.1 ± 23.3:38 ± 13.2:40 ± 5). The main symptoms associated with patients seeking medical care were mouth ulcers 30% and genital ulcers 23%, joint 14%, and eye problems 9%. The EQ-5D index for 2009, 2014, 2020 was (mean ± SD); 0.47 ± 0.38, 0.42 ± 0.37, 0.34 ± 0.40, respectively, p < 0.05. 2020 patients had the worst values of the five domains compared to 2014 and 2009. Interestingly, mobility value was the same over the 10 years of monitoring patients. Behçet's syndrome (BS) symptoms that had significant negative impact on QoL were; 2009 (arthropathy, neurological problems, pathergy reaction, and stomach/bowel symptoms), 2014 (arthropathy, headache, neurological problems, pathergy reaction, and skin lesions), 2020 (arthropathy, neurological problems, and stomach/bowel symptoms). The 2014 and 2020 surveys reported the QoL is significantly better in patients on immunosuppressant, who did sport, continued in employment and not receiving benefits.

Conclusion

Joints and neurological symptoms are the main symptoms which had negative impact on BS patients over the 10 years, sociodemographic (gender, age, marital, and education status), lifestyle (medication, cannabis, drinking wine, and regular exercise), employment status (employee and no career change), and accessing benefits (never claim benefit) had significant influence on patients' HRQoL.
Magnetic activation of TREK1 triggers stress signalling and regulates neuronal branching in SH-SY5Y cells
Authors: Rotherham Michael , Moradi Yasamin , Nahar Tasmin , Mosses Dominic , Telling Neil , El Haj Alicia J.
Published: December 2022

TWIK-related K+ 1 (TREK1) is a potassium channel expressed in the nervous system with multiple functions including neurotransmission and is a prime pharmacological target for neurological disorders. TREK1 gating is controlled by a wide range of external stimuli including mechanical forces. Previous work has demonstrated that TREK1 can be mechano-activated using magnetic nanoparticles (MNP) functionalised with antibodies targeted to TREK1 channels. Once the MNP are bound, external dynamic magnetic fields are used to generate forces on the TREK channel. This approach has been shown to drive cell differentiation in cells from multiple tissues. In this work we investigated the effect of MNP-mediated TREK1 mechano-activation on early stress response pathways along with the differentiation and connectivity of neuronal cells using the model neuronal cell line SH-SY5Y. Results showed that TREK1 is well expressed in SH-SY5Y and that TREK1-MNP initiate c-Myc/NF-κB stress response pathways as well as Nitrite production after magnetic stimulation, indicative of the cellular response to mechanical cues. Results also showed that TREK1 mechano-activation had no overall effect on neuronal morphology or expression of the neuronal marker βIII-Tubulin in Retinoic Acid (RA)/Brain-derived Neurotrophic factor (BDNF) differentiated SH-SY5Y but did increase neurite number. These results suggest that TREK1 is involved in cellular stress response signalling in neuronal cells, which leads to increased neurite production, but is not involved in regulating RA/BDNF mediated neuronal differentiation.
A review on the role of miR-671 in human disorders
Authors: Ghafouri-Fard Soudeh , Askari Arian , Hussen Bashdar Mahmud , Rasul Mohammed Fatih , Hatamian Sevak , Taheri Mohammad , Kiani Arda
Published: December 2022

miR-671 is encoded by a gene on 7q36.1 and contributes to the pathogenesis of a variety of disorders, including diverse types of cancers, atherosclerosis, ischemic stroke, liver fibrosis, osteoarthritis, Parkinson’s disease, rheumatoid arthritis, acute myocardial infarction and Crohn’s disease. In the context of cancer, different studies have revealed opposite roles for this miRNA. In brief, it has been shown to be down-regulated in pancreatic ductal carcinoma, ovarian cancer, gastric cancer, osteosarcoma, esophageal squamous cell carcinoma and myelodysplastic syndromes. Yet, miR-671 has been up-regulated in glioma, colorectal cancer, prostate cancer and hepatocellular carcinoma. Studies in breast, lung and renal cell carcinoma have reported inconsistent results. The current review aims at summarization of the role of miR-671 in these disorders focusing on its target mRNA in each context and dysregulated signaling pathways. We also provide a summary of the role of this miRNA as a prognostic factor in malignancies.
The longitudinal association between possible new sarcopenia and the depression trajectory of individuals and their intimate partners
Authors: Tian Yufeng , Hu Zhigang , Song Xinyu , Yang Ailan
Published: December 2022

Background

It is currently unknown whether the dynamic nature of depression affects the development of sarcopenia. Herein, this study aims to assess the association between possible new sarcopenia and the depression trajectory of individuals and their intimate partners through a 4-year longitudinal cohort study.

Methods

Our study included 784 pairs of individuals without possible sarcopenia and their spouses from the China Health and Retirement Longitudinal Study (CHARLS) 2011. All individuals and their spouses received three assessments of the Center for Epidemiologic Studies Depression 10-item (CESD-10) scale in 2011, 2013, and 2015. According to the diagnostic algorithm recommended by the Asian Working Group for Sarcopenia (AWGS) 2019, we evaluated the incidence of possible sarcopenia in individuals in 2015. Latent class analysis (LCA) was used to identify a longitudinal depression trajectory of individuals and their spouses during a 4-year follow-up. Subsequently, we assessed the relationship between possible sarcopenia and depression trajectory using three generalized additive models.

Results

In 2015, 24.87% (195/784) of individuals were diagnosed with possible sarcopenia. LCA identified five depression trajectories: a persistently high risk of depression in individuals and their spouses (reference; class 1 = 34 [4.3%]); a persistently low risk of depression in individuals and their spouses (class 2 = 526 [67.1%]); a high risk of depression in individuals and a low risk of depression in spouses (class 3 = 46 [5.9%]); a low risk of depression in individuals and a high risk of depression in spouses (class 4 = 116 [14.8%]); and a reduced risk of depression in individuals and their spouses (class 5 = 62 [7.9%]). The highest incidence of possible sarcopenia was shown in class 1, followed by classes 3 and 5. Classes 2 (adjusted relative risk (RR) = 0.44, 95% confidence interval (CI): 0.20–0.97) and 4 (adjusted RR = 0.40, 95%CI: 0.17–0.96) had a significantly lower incidence of possible sarcopenia than class 1. Subgroup analysis demonstrated that the incidence of possible sarcopenia in class 4 was obviously higher in women (38.89%) than in men (18.4%).

Conclusions

Our study indicates a persistently high risk of depression in individuals to develop possible sarcopenia. In addition, a persistently high risk of depression in intimate partners potentially increases the risk of possible new sarcopenia, especially in female individuals who are at low risk of depression.
Strain-dependent regulation of hippocampal long-term potentiation by dopamine D1/D5 receptors in mice
Authors: Hagena Hardy , Stacho Martin , Laja Arthur , Manahan-Vaughan Denise
Published: December 2022

The magnitude and persistency of long-term potentiation (LTP) in the rodent hippocampus is species-dependent: rats express more robust and more prolonged LTP in response to a broader afferent frequency range than mice. The C57Bl/6 mouse is an extremely popular murine strain used in studies of hippocampal synaptic plasticity and spatial learning. Recently it was reported that it expresses impoverished LTP compared to other murine strains. Given the important role of the dopamine D1/D5 receptor (D1/D5R) in the maintenance of LTP and in memory consolidation, we explored to what extent strain-dependent differences in LTP in mice are determined by differences in D1/D5R-control. In CaOlaHsd mice, robust LTP was induced that lasted for over 24 h and which was significantly greater in magnitude than LTP induced in C57Bl/6 mice. Intracerebral treatment with a D1/D5R-antagonist (SCH23390) prevented both the early and late phase of LTP in CaOlaHsd mice, whereas only late-LTP was impaired in C57Bl/6 mice. Treatment with a D1/D5R-agonist (Chloro-PB) facilitated short-term potentiation (STP) into LTP (> 24 h) in both strains, whereby effects became evident earlier in CaOlaHsd compared to C57Bl/6 mice. Immunohistochemical analysis revealed a significantly higher expression of D1-receptors in the stratum lacunosum moleculare of CaOlaHsd compared to C57Bl/6 mice. These findings highlight differences in D1/D5R- dependent regulation of strain-dependent variations in hippocampal LTP in C57Bl/6 and CaOlaHsd mice, that may be mediated, in part, by differences in the expression of D1R in the hippocampus.
Real-time route planning of unmanned aerial vehicles based on improved soft actor-critic algorithm
Authors: Zhou Yuxiang , Shu Jiansheng , Zheng Xiaolong , Hao Hui , Song Huan
Published: December 2022

With the application and development of UAV technology and navigation and positioning technology, higher requirements are put forward for UAV maneuvering obstacle avoidance ability and real-time route planning. In this paper, for the problem of real-time UAV route planning in the unknown environment, we combine the ideas of artificial potential field method to modify the state observation and reward function, which solves the problem of sparse rewards of reinforcement learning algorithm, improves the convergence speed of the algorithm, and improves the generalization of the algorithm by step-by-step training based on the ideas of curriculum learning and transfer learning according to the difficulty of the task. The simulation results show that the improved SAC algorithm has fast convergence speed, good timeliness and strong generalization, and can better complete the UAV route planning task.
Neuromodulatory effects of transcranial magnetic stimulation on language performance in healthy participants: Systematic review and meta-analysis
Authors: Qu Xingfang , Wang Zichao , Cheng Yao , Xue Qingwei , Li Zimu , Li Lu , Feng Liping , Hartwigsen Gesa , Chen Luyao
Published: December 2022

Background

The causal relationships between neural substrates and human language have been investigated by transcranial magnetic stimulation (TMS). However, the robustness of TMS neuromodulatory effects is still largely unspecified. This study aims to systematically examine the efficacy of TMS on healthy participants’ language performance.

Methods

For this meta-analysis, we searched PubMed, Web of Science, PsycINFO, Scopus, and Google Scholar from database inception until October 15, 2022 for eligible TMS studies on language comprehension and production in healthy adults published in English. The quality of the included studies was assessed with the Cochrane risk of bias tool. Potential publication biases were assessed by funnel plots and the Egger Test. We conducted overall as well as moderator meta-analyses. Effect sizes were estimated using Hedges’g (g) and entered into a three-level random effects model.

Results

Thirty-seven studies (797 participants) with 77 effect sizes were included. The three-level random effects model revealed significant overall TMS effects on language performance in healthy participants (RT: g = 0.16, 95% CI: 0.04–0.29; ACC: g = 0.14, 95% CI: 0.04–0.24). Further moderator analyses indicated that (a) for language tasks, TMS induced significant neuromodulatory effects on semantic and phonological tasks, but didn’t show significance for syntactic tasks; (b) for cortical targets, TMS effects were not significant in left frontal, temporal or parietal regions, but were marginally significant in the inferior frontal gyrus in a finer-scale analysis; (c) for stimulation parameters, stimulation sites extracted from previous studies, rTMS, and intensities calibrated to the individual resting motor threshold are more prone to induce robust TMS effects. As for stimulation frequencies and timing, both high and low frequencies, online and offline stimulation elicited significant effects; (d) for experimental designs, studies adopting sham TMS or no TMS as the control condition and within-subject design obtained more significant effects.

Discussion

Overall, the results show that TMS may robustly modulate healthy adults’ language performance and scrutinize the brain-and-language relation in a profound fashion. However, due to limited sample size and constraints in the current meta-analysis approach, analyses at a more comprehensive level were not conducted and results need to be confirmed by future studies.

Systematic review registration

[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=366481], identifier [CRD42022366481].
autohrf-an R package for generating data-informed event models for general linear modeling of task-based fMRI data
Authors: Purg Nina , Demšar Jure , Anticevic Alan , Repovš Grega
Published: December 2022

The analysis of task-related fMRI data at the level of individual participants is commonly based on general linear modeling (GLM), which allows us to estimate the extent to which the BOLD signal can be explained by the task response predictors specified in the event model. The predictors are constructed by convolving the hypothesized time course of neural activity with an assumed hemodynamic response function (HRF). However, our assumptions about the components of brain activity, including their onset and duration, may be incorrect. Their timing may also differ across brain regions or from person to person, leading to inappropriate or suboptimal models, poor fit of the model to actual data, and invalid estimates of brain activity. Here, we present an approach that uses theoretically driven models of task response to define constraints on which the final model is computationally derived using actual fMRI data. Specifically, we developed autohrf–an R package that enables the evaluation and data-driven estimation of event models for GLM analysis. The highlight of the package is the automated parameter search that uses genetic algorithms to find the onset and duration of task predictors that result in the highest fitness of GLM based on the fMRI signal under predefined constraints. We evaluated the usefulness of the autohrf package on two original datasets of task-related fMRI activity, a slow event-related spatial working memory study and a mixed state-item study using the flanker task, and on a simulated slow event-related working memory data. Our results suggest that autohrf can be used to efficiently construct and evaluate better task-related brain activity models to gain a deeper understanding of BOLD task response and improve the validity of model estimates. Our study also highlights the sensitivity of fMRI analysis with GLM to precise event model specification and the need for model evaluation, especially in complex and overlapping event designs.
Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review
Authors: Zhao Bo , Yang Miao , Wang Zhiwei , Yang Qiqiong , Zhang Yimo , Qi Xiaokun , Pan Shuyi , Yu Yingxin
Published: December 2022

Background

Neuronal intranuclear inclusion disease (NIID) is a rare chronic progressive neurodegenerative disease, with complex and diverse clinical manifestations and pathological eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous systems and visceral organs. Improvements in diagnostic methods such as skin biopsy and gene testing are helpful in revealing the clinical and genetic characters of NIID.

Materials and methods

We presented two cases of NIID diagnosed by using NOTCH2NLC gene testing and skin biopsy. Diffusion weighted imaging (DWI) showed high linear intensity in corticomedullary junction. We also reviewed all the published NIID cases with positive NOTCH2NLC GGC repeat expansion and skin biopsy results in PubMed.

Results

Patient 1 was a 63-year-old male who carried 148 GGC repeats and presented with progressive tremor and limb weakness. Patient 2 was a 62-year-old woman who carried 131 GGC repeats and presented with tremors, memory loss and headaches. The most common clinical manifestation of 63 NIID patients in this study was cognitive impairment, followed by tremors. In our study, almost all the patients were from East Asia, the male to female ratio was 1:1.26, with an age of onset of 54.12 ± 14.12 years, and an age of diagnosis of 60.03 ± 12.21 years. Symmetrical high signal intensity at the corticomedullary junction on DWI were revealed in 80.96% of the patients. For the GGC repeat numbers, the majority of GGC repeats were in the 80–119 intervals, with few GGC repeats above 160. The number of GGC repetitions was significantly higher in patients presented with muscle weakness than in other clinical manifestations.

Conclusion

NIID is a neurodegenerative disease caused by aberrant polyglycine (polyG) protein aggregation. NIID mostly occurs in the elderly population in East Asia, with cognitive dysfunction as the most common symptom. Staging NIID based on clinical presentation is inappropriate because most patients with NIID have overlapping symptoms. In our study, there was no significant correlation between the number of GGC repeats and different phenotypes except for muscle weakness. Abnormal trinucleotides repeat and PolyG protein aggregation maybe common pathogenic mechanism in neurodegenerative diseases and cerebrovascular diseases, which needs to be confirmed by more studies.
Proteomic analysis of spinal cord tissue in a rat model of cancer-induced bone pain
Authors: Yang Heyu , Wu Ji , Zhen Shuqing , Hu Yindi , Li Dai , Xie Min , Zhu Haili
Published: December 2022

Background

Cancer-induced bone pain (CIBP) is a moderate to severe pain and seriously affects patients’ quality of life. Spinal cord plays critical roles in pain generation and maintenance. Identifying differentially expressed proteins (DEPs) in spinal cord is essential to elucidate the mechanisms of cancer pain.

Methods

CIBP rat model was established by the intratibial inoculation of MRMT-1 cells. Positron emission tomography (PET) scan and transmission electron microscopy (TEM) were used to measure the stats of spinal cord in rats. Label free Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) were used to analyze the whole proteins from the lumbar spinal cord. Differentially expressed proteins (DEPs) were performed using Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and verified using Western blot and immunofluorescence assay.

Results

In the current study, CIBP rats exhibited bone damage, spontaneous pain, mechanical hyperalgesia, and impaired motor ability. In spinal cord, an hypermetabolism and functional abnormality were revealed on CIBP rats. An increase of synaptic vesicles density in active zone and a disruption of mitochondrial structure in spinal cord of CIBP rats were observed. Meanwhile, 422 DEPs, consisting of 167 up-regulated and 255 down-regulated proteins, were identified among total 1539 proteins. GO enrichment analysis indicated that the DEPs were mainly involved in catabolic process, synaptic function, and enzymic activity. KEGG pathway enrichment analysis indicated a series of pathways, including nervous system disease, hormonal signaling pathways and amino acid metabolism, were involved. Expression change of synaptic and mitochondrial related protein, such as complexin 1 (CPLX1), synaptosomal-associated protein 25 (SNAP25), synaptotagmin 1 (SYT1), aldehyde dehydrogenase isoform 1B1 (ALDH1B1), Glycine amidinotransferase (GATM) and NADH:ubiquinone oxidoreductase subunit A11 (NDUFA11), were further validated using immunofluorescence and Western blot analysis.

Conclusion

This study provides valuable information for understanding the mechanisms of CIBP, and supplies potential therapeutic targets for cancer pain.
Assessing the interfacial corrosion mechanism of Inconel 617 in chloride molten salt corrosion using multi-modal advanced characterization techniques
Authors: Copeland-Johnson Trishelle M. , Murray Daniel J. , Cao Guoping , He Lingfeng
Published: December 2022

The United States Department of Energy (DOE) has committed to expanding the domestic clean energy portfolio in response to the rising challenges of energy security in the wake of climate change. Accordingly, the construction of a series of Generation IV reactor technologies are being demonstrated, including sodium-cooled, small modular, and molten chloride fast reactors (MCFRs). To date, there are no fully qualified structural materials for constructing MCFRs. A number of commercial structural alloys have been considered for the construction of MCFRs, including alloys from the Inconel and Hastelloy series. Informed qualification of structural materials for the construction of MCFRs in the future can only be ensured by expanding the current fundamental knowledgebase of information pertaining to material performance under environmental stressors relevant to operation of the reactor, including corrosion susceptibility. The purpose of this investigation is to illustrate how a correlative multi-modal electron microscopy characterization approach, including the novel application of focused-ion beam 3D reconstruction capabilities, can elucidate the corrosion mechanism of a candidate structural material Inconel 617 for MCFR in NaCl-MgCl2 eutectic salt at 700°C for 1,000 h. Evidence of intergranular corrosion, Ni and Fe dealloying, and Cr-O enrichment along the grain boundary, which most likely corresponds to Cr2O3, is a phenomenon that has been documented in other Ni-based superalloys exposed to chloride molten salt systems. Additional corrosion products, including the formation of insoluble MgAl2O4, within the porous network produced by the salt attack is a novel observation. In addition, Mo3Si5 and τ2 precipitates are detected in the alloy bulk and are dissolved by the salt. Furthermore, the lack of detection of design γ′ precipitates in Inconel 617 after 1,000 h could indicate that the molten salt corrosion mechanism has indirectly induced a phase transformation of Al2TiNi (τ2) and Ni3(Al,Ti) (γ’) phase. This investigation provides a comprehensive understanding of molten salt corrosion mechanisms in a complex material system such as a commercial structural alloy for applications in MCFRs.
Association of serum lycopene concentrations with all-cause and cardiovascular mortality among individuals with chronic kidney disease: A cohort study
Authors: Zhong Qiang , Piao YongYi , Yin Shan , Zhang KangYi
Published: December 2022

Background

Lycopene is one of the hydrocarbon carotenoids which is largely studied for its strong antioxidant and anti-inflammatory properties, as well as improvement of endothelial function and anti-arteriosclerosis effects. The use of lycopene has been shown to reduce mortality in the general population. However, few studies have examined the association between serum lycopene level and all-cause and cardiovascular mortality among participants with chronic kidney disease (CKD).

Method

This study included 7,683 adults with CKD from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994) and NHANES 2001–2006. Mortality status and cause of death were ascertained by linkage to National Death Index records through 31 December 2018. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% CIs for mortality from all-cause and cardiovascular disease (CVD).

Result

During a median follow-up time of 309 months, there were 5,226 total deaths. The median (interquartile range) serum lycopene concentration was 20.0 (12.0, 32.0) μg/dl. After fully adjusted, restricted cubic spline analyses reported that higher serum lycopene concentrations were significantly associated with decreased risk of all-cause and CVD mortality in participants with CKD (P < 0.001, P = 0.001). When extreme quartiles of serum lycopene concentrations were compared, the multivariable-adjusted HR (95% CI) was 0.778 (0.714–0.848) for all-cause mortality (P < 0.001), and 0.791 (0.692–0.905) for CVD mortality (P < 0.001). Specifically, higher serum lycopene decreased the risk of all-cause and CVD mortality at both CKD stage 1–2 and stage 3–5. Further subgroup analyses and sensitivity analyses supported the current results.

Conclusion

Higher serum lycopene was independently associated with a decreased risk of all-cause and CVD mortality in patients with CKD. These findings suggested that maintain serum lycopene concentrations could lower mortality risk in CKD patients.
Effects of osteoblast-derived extracellular vesicles on aggressiveness, redox status and mitochondrial bioenergetics of MNNG/HOS osteosarcoma cells
Authors: Ponzetti Marco , Ucci Argia , Puri Chiara , Giacchi Luca , Flati Irene , Capece Daria , Zazzeroni Francesca , Cappariello Alfredo , Rucci Nadia , Falone Stefano
Published: December 2022

Osteosarcoma is the most common primary bone malignancy. The crosstalk between osteosarcoma and the surrounding tumour microenvironment (TME) drives key events that lead to metastasization, one of the main obstacles for definitive cure of most malignancies. Extracellular vesicles (EVs), lipid bilayer nanoparticles used by cells for intercellular communication, are emerging as critical biological mediators that permit the interplay between neoplasms and the tumour microenvironment, modulating re-wiring of energy metabolism and redox homeostatic processes. We previously showed that EVs derived from the human osteosarcoma cells influence bone cells, including osteoblasts. We here investigated whether the opposite could also be true, studying how osteoblast-derived EVs (OB-EVs) could alter tumour phenotype, mitochondrial energy metabolism, redox status and oxidative damage in MNNG/HOS osteosarcoma cells.These were treated with EVs obtained from mouse primary osteoblasts, and the following endpoints were investigated: i) cell viability and proliferation; ii) apoptosis; iii) migration and invasive capacity; iv) stemness features; v) mitochondrial function and energy metabolism; vi) redox status, antioxidant capacity and oxidative molecular damage. OB-EVs decreased MNNG/HOS metabolic activity and viability, which however was not accompanied by impaired proliferation nor by increased apoptosis, with respect to control. In addition, OB-EV-treated cells exhibited a significant reduction of motility and in vitro invasion as compared to untreated cells. Although the antioxidant N-acetyl-L-cysteine reverted the cytotoxic effect of OB-EVs, no evidence of oxidative stress was observed in treated cells. However, the redox balance of glutathione was significantly shifted towards a pro-oxidant state, even though the major antioxidant enzymatic protection did not respond to the pro-oxidant challenge. We did not find strong evidence of mitochondrial involvement or major energy metabolic switches induced by OB-EVs, but a trend of reduction in seahorse assay basal respiration was observed, suggesting that OB-EVs could represent a mild metabolic challenge for osteosarcoma cells. In summary, our findings suggest that OB-EVs could serve as important means through which TME and osteosarcoma core cross-communicate. For the first time, we proved that OB-EVs reduced osteosarcoma cells’ aggressiveness and viability through redox-dependent signalling pathways, even though mitochondrial dynamics and energy metabolism did not appear as processes critically needed to respond to OB-EVs.
Bridging the gap in neonatal resuscitation in Zambia
Authors: Mutesu-Kapembwa Kunda , Lakhwani Jyoti , Benkele Rodgers Gift , Machona Sylvia , Shamalavu Mwila Sekeseke , Chintende Jean Musonda , Chisela Susan Mwila , Kapoma Sharon , Mwanza Jackson , Chelu Wisdom , Mwendafilumba Martha , Kapembwa Kenneth , Gaertner Vincent D.
Published: December 2022

Neonatal resuscitation has been poorly instituted in many parts of Africa and most neonatal resuscitation algorithms are adapted from environments with abundant resources. Helping Babies Breathe (HBB) is an algorithm designed for resource-limited situations and most other algorithms are designed for resource-rich countries. However, there are neonatal referral centers in resource-limited countries who may provide more advanced resuscitation. Thus, we developed a neonatal resuscitation algorithm for a resource-limited country (Zambia) which considers more advanced interventions in situations where they can be provided. The algorithm described in this paper is based on the Newborn Life Support algorithm from the UK as well as the HBB algorithm and accounts for all situations in a resource-limited country. Most importantly, it focuses on non-invasive ventilation but includes advice on more advanced resuscitation including intravenous access, fluid management, chest compressions and adrenaline for resuscitation. Although intubation skills are included in neonatal training workshops, it is not the main focus of the algorithm as respiratory support equipment is scarce or lacking in most health facilities in Zambia. A home-grown neonatal resuscitation algorithm for a resource-limited country such as Zambia is likely to bridge the gap between limited situations requiring only bag and mask ventilation and better equipped institutions where more advanced resuscitation is possible. This algorithm will be rolled out in all training institutions and delivery facilities across Zambia over the next months.
Epidemiology of autism spectrum disorders: Global burden of disease 2019 and bibliometric analysis of risk factors
Authors: Li Yang-An , Chen Ze-Jian , Li Xiao-Dan , Gu Ming-Hui , Xia Nan , Gong Chen , Zhou Zhao-Wen , Yasin Gvzalnur , Xie Hao-Yu , Wei Xiu-Pan , Liu Ya-Li , Han Xiao-Hua , Lu Min , Xu Jiang , Huang Xiao-Lin
Published: December 2022

Background

To explore the geographical pattern and temporal trend of autism spectrum disorders (ASD) epidemiology from 1990 to 2019, and perform a bibliometric analysis of risk factors for ASD.

Methods

In this study, ASD epidemiology was estimated with prevalence, incidence, and disability-adjusted life-years (DALYs) of 204 countries and territories by sex, location, and sociodemographic index (SDI). Age-standardized rate (ASR) and estimated annual percentage change (EAPC) were used to quantify ASD temporal trends. Besides, the study performed a bibliometric analysis of ASD risk factors since 1990. Publications published were downloaded from the Web of Science Core Collection database, and were analyzed using CiteSpace.

Results

Globally, there were estimated 28.3 million ASD prevalent cases (ASR, 369.4 per 100,000 populations), 603,790 incident cases (ASR, 9.3 per 100,000 populations) and 4.3 million DALYs (ASR, 56.3 per 100,000 populations) in 2019. Increases of autism spectrum disorders were noted in prevalent cases (39.3%), incidence (0.1%), and DALYs (38.7%) from 1990 to 2019. Age-standardized rates and EAPC showed stable trend worldwide over time. A total of 3,991 articles were retrieved from Web of Science, of which 3,590 were obtained for analysis after removing duplicate literatures. “Rehabilitation”, “Genetics & Heredity”, “Nanoscience & Nanotechnology”, “Biochemistry & Molecular biology”, “Psychology”, “Neurosciences”, and “Environmental Sciences” were the hotspots and frontier disciplines of ASD risk factors.

Conclusions

Disease burden and risk factors of autism spectrum disorders remain global public health challenge since 1990 according to the GBD epidemiological estimates and bibliometric analysis. The findings help policy makers formulate public health policies concerning prevention targeted for risk factors, early diagnosis and life-long healthcare service of ASD. Increasing knowledge concerning the public awareness of risk factors is also warranted to address global ASD problem.
Using Drosophila melanogaster as a suitable platform for drug discovery from natural products in inflammatory bowel disease
Authors: Xiu Minghui , Wang Yixuan , Yang Dan , Zhang Xueyan , Dai Yuting , Liu Yongqi , Lin Xingyao , Li Botong , He Jianzheng
Published: December 2022

Inflammatory bowel disease (IBD) is a chronic and life-treating inflammatory disease that can occur in multiple parts of the human intestine and has become a worldwide problem with a continually increasing incidence. Because of its mild early symptoms, most of them will not attract people’s attention and may cause more serious consequences. There is an urgent need for new therapeutics to prevent disease progression. Natural products have a variety of active ingredients, diverse biological activities, and low toxicity or side effects, which are the new options for preventing and treating the intestinal inflammatory diseases. Because of multiple genetic models, less ethical concerns, conserved signaling pathways with mammals, and low maintenance costs, the fruit fly Drosophila melanogaster has become a suitable model for studying mechanism and treatment strategy of IBD. Here, we review the advantages of fly model as screening platform in drug discovery, describe the conserved molecular pathways as therapetic targets for IBD between mammals and flies, dissect the feasibility of Drosophila model in IBD research, and summarize the natural products for IBD treatment using flies. This review comprehensively elaborates that the benefit of flies as a perfact model to evaluate the therapeutic potential of phytochemicals against IBD.
Using statistical parametric mapping to assess the association of duty factor and step frequency on running kinetic
Authors: Patoz Aurélien , Lussiana Thibault , Breine Bastiaan , Piguet Eliott , Gyuriga Jonathan , Gindre Cyrille , Malatesta Davide
Published: December 2022

Duty factor (DF) and step frequency (SF) were previously defined as the key running pattern determinants. Hence, this study aimed to investigate the association of DF and SF on 1) the vertical and fore-aft ground reaction force signals using statistical parametric mapping; 2) the force related variables (peaks, loading rates, impulses); and 3) the spring-mass characteristics of the lower limb, assessed by computing the force-length relationship and leg stiffness, for treadmill runs at several endurance running speeds. One hundred and fifteen runners ran at 9, 11, and 13 km/h. Force data (1000 Hz) and whole-body three-dimensional kinematics (200 Hz) were acquired by an instrumented treadmill and optoelectronic system, respectively. Both lower DF and SF led to larger vertical and fore-aft ground reaction force fluctuations, but to a lower extent for SF than for DF. Besides, the linearity of the force-length relationship during the leg compression decreased with increasing DF or with decreasing SF but did not change during the leg decompression. These findings showed that the lower the DF and the higher the SF, the more the runner relies on the optimization of the spring-mass model, whereas the higher the DF and the lower the SF, the more the runner promotes forward propulsion.
Moderate exercise protects against joint disease in a murine model of osteoarthritis
Authors: Huesa C. , Dunning L. , MacDougall K. , Fegen M. , Ortiz A. , McCulloch K. , McGrath S. , Litherland G. J. , Crilly A. , Van ‘T Hof R. J. , Ferrell W. R. , Goodyear C. S. , Lockhart J. C.
Published: December 2022

Exercise is recommended as a non-pharmacological therapy for osteoarthritis (OA). Various exercise regimes, with differing intensities and duration, have been used in a range of OA rodent models. These studies show gentle or moderate exercise reduces the severity of OA parameters while high intensity load bearing exercise is detrimental. However, these studies were largely conducted in rats or in mouse models induced by severe injury, age or obesity, whilst destabilization of the medial meniscus (DMM) in mice has become a widely accepted model due to its lower variability, moderate progression and timescale. The present study was undertaken to provide insight into the effect of moderate exercise on early joint pathology in the DMM mouse model. Exercise was induced a week after induction by forced wheel walking for three or 7 weeks. Joints were analyzed by microcomputed tomography and histology. Assessment of skeletal parameters revealed that exercise offered protection against cartilage damage after 7 weeks of exercise, and a temporary protection against osteosclerosis was displayed after 3 weeks of exercise. Furthermore, exercise modified the metaphyseal trabecular microarchitecture of the osteoarthritic leg in both time points examined. Collectively, our findings corroborate previous studies showing that exercise has an important effect on bone in OA, which subsequently, at 8 weeks post-induction, translates into less cartilage damage. Thus, providing an exercise protocol in a surgical mouse model of OA, which can be used in the future to further dissect the mechanisms by which moderate exercise ameliorates OA.
Alan Fincham and the era of enamel protein Biochemistry
Authors: Diekwisch Thomas G. H.
Published: December 2022

Enamel research experienced an unprecedented period of growth during the latter part of the 20th century until today. This growth is in part due to the contributions of a number of iconic scientists such as Alan G. Fincham, the focus of the present review. Alan was involved in many of the seminal discoveries of this time, including the identification of the critical amelogenin peptides TRAP and LRAP, the determination of the amelogenin amino acid sequence, the identification of the sole serin-16 phosphorylation site, and the amelogenin nanosphere theory. Alan was also a superb mentor to graduate students and others. His experience and leadership related to problem-based learning greatly affected predoctoral dental education at the University of Southern California and in the United States.
Genetic basis of the early heading of high-latitude weedy rice
Authors: Li Zhuan , Gui Rui , Yu Xiaoyu , Liang Chengwei , Cui Juan , Zhao Xue , Zhang Xuemin , Yu Pengcheng , Chen Wenfu , Sun Jian
Published: December 2022

Japonica rice (Oryza sativa L.) is an important staple food in high-latitude regions and is widely distributed in northern China, Japan, Korea, and Europe. However, the genetic diversity of japonica rice is relatively narrow and poorly adapted. Weedy rice (Oryza sativa f. spontanea) is a semi-domesticated rice. Its headings are earlier than the accompanied japonica rice, making it a potential new genetic resource, which can make up for the defects of wild rice that are difficult to be directly applied to japonica rice improvement caused by reproductive isolation. In this study, we applied a natural population consisting of weedy rice, japonica landrace, and japonica cultivar to conduct a genome-wide association study (GWAS) of the heading date and found four loci that could explain the natural variation of the heading date in this population. At the same time, we developed recombinant inbred lines (RILs) crossed by the early-heading weedy rice WR04-6 and its accompanied japonica cultivar ShenNong 265 (SN265) to carry out a QTL mapping analysis of the heading date and mapped four quantitative trait locus (QTLs) and three epistatic effect gene pairs. The major locus on chromosome 6 overlapped with the GWAS result. Further analysis found that two genes, Hd1 and OsCCT22, on chromosome 6 (Locus 2 and Locus 3) may be the key points of the early-heading character of weedy rice. As minor effect genes, Dth7 and Hd16 also have genetic contributions to the early heading of weedy rice. In the process of developing the RIL population, we introduced fragments of Locus 2 and Locus 3 from the weedy rice into super-high-yielding japonica rice, which successfully promoted its heading date by at least 10 days and expanded the rice suitable cultivation area northward by about 400 km. This study successfully revealed the genetic basis of the early heading of weedy rice and provided a new idea for the genetic improvement of cultivated rice by weedy rice.
Putting China on the couch: Reflections on the development of psychohistory in China
Authors: Meng Fei , Wang Bo , Chen Jian
Published: December 2022

In the process of reconstructing the history of Chinese psychology, psychohistory once drew little attention. Although applying psychological tools to historical studies has not been a new research method for Chinese historians, when it comes to psychohistory in its modern sense, it inevitably sounds exotic and novel to Chinese academia. However, the significance of psychohistory, especially the one with practical relevance, should not be underestimated. Thus, the history and the deficiency of psychohistory need to be clarified. Based on the macro-historical logic, the development of psychohistory in China can be recounted and divided into four stages, namely (1) before 1902, the pre-scientific stage of psychohistory, (2) 1902–1949, the introduction of modern psychohistory, (3) 1949–1978, the tortuous and lopsided development of psychohistory, and (4) 1978–present, the revival of diverse approaches in psychohistory. The possibilities of psychohistory as we find in such a process, in all its reality, reside in the fact that it could combine the history of ideas with reality and the history of society with ideas, which would undoubtedly improve our understanding of the intertwinement of the human psyche and the social mechanisms, in brief, the historical dynamics. In addition, psychohistory could also help solve psychological problems that the populations in modern times are currently facing. Despite all of these virtues, in terms of indigenization (particularization), generalization (universalization), trans-regional communication, and disciplinary institutionalization, there is still some way for psychohistory in China to go.
Neuroticism and fear of COVID-19 during the COVID-19 pandemic: Testing the mediating role of intolerance of uncertainty and sense of control among Chinese high school students
Authors: Zhang Donghuan , Fan Min , Meng Lingyi , Zheng Xifu
Published: December 2022

Since the COVID-19 pandemic broke out in 2019, neuroticism has been proven a predictor of fear of COVID-19 infection. However, only few studies have been conducted on the factors affecting the relationship between neuroticism and this kind of fear. The present study is aimed at analyzing the role intolerance of uncertainty (IU) and sense of control (SOC) play in relation to neuroticism and the fear of COVID-19. We conducted a cross-sectional study in Guangdong and Guangxi provinces, China, and we collected complete datasets from 792 high school students. The main results can be described as follows: (a) individuals with high neuroticism tended to have higher intolerance of uncertainty (IU) and a lower sense of control (SOC); (b) IU and SOC played a mediating role between neuroticism and fear of COVID-19, and a serial mediation effect was found between these factors; (c) after controlling for both IU and SOC, the effect of neuroticism on fear was no longer significant. The results suggested a critical role of IU and sense of control in the causal relationship between neuroticism and fear.
Executives’ ESG cognition and enterprise green innovation: Evidence based on executives’ personal microblogs
Authors: Wang Deli , Luo Yonggen , Hu Shiyang , Yang Qi
Published: December 2022

Based on cognitive theory, we investigated the influence of executives’ ESG cognition on corporate green innovation using data from Chinese manufacturing listed companies from 2010 to 2019. The paper first constructs a metric of ESG cognition of company executives by presenting a quantitative analysis of data from their personal microblogs using textual analysis. The findings show that executive ESG perceptions significantly improve corporate green innovation. After addressing the endogeneity issue through a series of robustness tests, the findings of this paper still held true. Further research found that the enhancement effect of executive ESG perceptions on firms’ green innovation level was mainly found in the sample without heavy pollution and with lower financing constraints and a higher marketization process. This study makes an important contribution to the research on corporate green innovation based on the perspective of executive ESG cognition while also providing a theoretical basis and practical reference for corporate green innovation practices.