bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary Study on the Combination Effect of Clindamycin and Low Dose Trimethoprim-Sulfamethoxazole on Severe Pneumocystis Pneumonia After Renal Transplantation
Authors: Gu Zhun-Yong , Liu Wen-Jun , Huang Dan-Lei , Liu Yu-Jing , He Hong-Yu , Yang Cheng , Liu Yi-Mei , Xu Ming , Rong Rui-Ming , Zhu Du-Ming , Luo Zhe , Ju Min-Jie
Published: May 2022

Objective

Evaluate the effect of the combination of clindamycin with low-dose trimethoprim-sulfamethoxazole (TMP/SMX) regimen on sever Pneumocystis pneumonia (PCP) after renal transplantation.

Method

20 severe PCP patients after renal transplantation were included in this historical-control, retrospective study. A 10 patients were treated with the standard dose of TMP/SMX (T group), the other 10 patients were treated with the combination of clindamycin and low dose TMP/SMX (CT group).

Results

Although there was no significant difference in the hospital survival between the two groups, the CT protocol improved the PaO2/FiO2 ratio more significantly and rapidly after the 6th ICU day (1.51 vs. 0.38, P = 0.014). CT protocol also ameliorated the pulmonary infiltration and the lactate dehydrogenase level more effectively. Moreover, the CT protocol reduced the incidence of pneumomediastinum (0 vs. 50%, P = 0.008), the length of hospital staying (26.5 vs. 39.0 days, P = 0.011) and ICU staying (12.5 vs. 22.5 days, P = 0.008). Furthermore, more thrombocytopenia (9/10 vs. 3/10, P = 0.020) was emerged in the T group than in the CT group. The total adverse reaction rate was much lower in the CT group than in the T group (8/80 vs. 27/80, P < 0.001). Consequently, the dosage of TMP/SMX was reduced in 8 patients, while only 2 patients in the CT group received TMP/SMX decrement (P = 0.023).

Conclusion

The current study proposed that clindamycin combined with low-dose TMP/SMX was more effective and safer the than single use of TMP/SMX for severe PCP patients after renal transplantation (NCT 04328688).
Negative Impact of Comorbidity on Health-Related Quality of Life Among Patients With Stroke as Modified by Good Diet Quality
Authors: Pham Thu T. M. , Vu Manh-Tan , Luong Thuc C. , Pham Khue M. , Nguyen Lien T. K. , Nguyen Minh H. , Do Binh N. , Nguyen Hoang C. , Tran Tuan V. , Nguyen Thao T. P. , Le Hoang P. , Tran Cuong Q. , Nguyen Kien T. , Yang Shwu-Huey , Hu Chaur-Jong , Bai Chyi-Huey , Duong Tuyen Van
Published: May 2022

Background

Comorbidity, along with aging, affects stroke-induced health-related quality of life (HRQoL). We examined the potential role of diet quality in modifying the association between comorbidity and HRQoL in patients with stroke.

Methods

A cross-sectional study was conducted on 951 patients with stroke from December 2019 to December 2020 across Vietnam. Comorbidity was assessed using the Charlson Comorbidity Index (CCI) items and classified into two groups (none vs. one or more). Diet quality was evaluated using the Dietary Approaches to Stop Hypertension Quality (DASH-Q) questionnaire, and HRQoL was measured using the RAND-36, with a higher score indicating better diet quality or HRQoL, respectively. Besides, socio-demographics, health-related behaviors (e.g., physical activity, smoking, and drinking), disability (using WHODAS 2.0), and health literacy were also assessed. Linear regression analysis was utilized to explore the associations and interactions.

Results

The proportion of patients with stroke aged ≥65 years and having comorbidity were 53.7 and 49.9%, respectively. The HRQoL scores were 44.4 ± 17.4. The diet quality was associated with higher HRQoL score (regression coefficient, B, 0.14; (95% confidence interval, 95% CI, 0.04, 0.23; p = 0.004), whereas comorbidity was associated with lower HRQoL score (B, −7.36; 95% CI, −9.50, −5.23; p < 0.001). In interaction analysis, compared to patients without comorbidity and having the lowest DASH-Q score, those with comorbidity and higher DASH-Q score had a higher HRQoL score (B, 0.21; 95% CI, 0.03, 0.39; p = 0.021).

Conclusion

The findings showed that good diet quality could modify the adverse impact of comorbidity on HRQoL in patients with stroke. Diet quality should be considered as a strategic intervention to improve the HRQoL of patients with stroke, especially those with comorbidity, and to promote healthier aging.
Chronic Obstructive Pulmonary Disease With Asthma-Like Features in the General Population in China
Authors: Huang Kewu , Chung Kian Fan , Yang Ting , Xu Jianying , Yang Lan , Zhao Jianping , Zhang Xiangyan , Bai Chunxue , Kang Jian , Ran Pixin , Shen Huahao , Wen Fuqiang , Chen Yahong , Sun Tieying , Shan Guangliang , Lin Yingxiang , Xu Guodong , Wu Sinan , Wang Ying , Gu Xiaoying , Wang Ruiying , Shi Zhihong , Xu Yongjian , Ye Xianwei , Song Yuanlin , Wang Qiuyue , Zhou Yumin , Li Wen , Ding Liren , Wan Chun , Yao Wanzhen , Guo Yanfei , Xiao Fei , Lu Yong , Peng Xiaoxia , Xiao Dan , Bu Xiaoning , Zhang Hong , Zhang Xiaolei , An Li , Zhang Shu , Cao Zhixin , Zhan Qingyuan , Yang Yuanhua , Liang Lirong , Wang Wenjun , Dai Huaping , Cao Bin , He Jiang , Wang Chen
Published: May 2022

Background

Patients with features of both asthma and chronic obstructive pulmonary disease (COPD) are seen commonly in the clinic but less is known in the general population. We investigated the prevalence and the heterogeneity of COPD with concomitant features of asthma in Chinese adult population.

Methods

COPD was defined as post-bronchodilator ratio of forced expiratory volume in 1s (FEV1) to forced vital capacity of less than the lower limits of normal. COPD with concomitant features of asthma was defined as either COPD with asthma diagnosed by self-reported physician-diagnosis or by presence of current wheeze, or as COPD with high bronchodilator response (HBR) defined as an increase in FEV1 >15% and >400 ml after bronchodilator.

Results

COPD with concomitant features of asthma was found in 1.62% (95% CI 1.31–2.00) of adults (≥20 years) or in 15.2% (95% CI 13.0–17.7) of COPD patients. Compared with COPD with HBR, COPD with asthma diagnosis or wheeze were older (61.8 ± 1.1 years vs. 47.4 ± 2.8 years, P < 0.001), and with a lower post-bronchodilator FEV1%pred (68.2 ± 2.3 vs. 96.6 ± 3.4, P < 0.001). Age, smoking status, biomass use and allergic rhinitis were associated with increasing prevalence of COPD with asthma diagnosis or wheeze, and had greater impaired health status, more comorbidities and more acute exacerbations in the preceding 12 months.

Conclusions

COPD with concomitant features of asthma is common in people with COPD and those with COPD with asthma diagnosis or wheeze experience worse clinical severity than COPD with HBR. These findings will help toward the definition of the asthma-COPD overlap condition.
Dual-Role Ubiquitination Regulation Shuttling the Entire Life Cycle of the Flaviviridae
Authors: Cai Dongjie , Liu Lingli , Tian Bin , Fu Xingxin , Yang Qiyuan , Chen Jie , Zhang Yilin , Fang Jing , Shen Liuhong , Wang Ya , Gou Liping , Zuo Zhicai
Published: May 2022

Ubiquitination is a reversible protein post-translational modification that regulates various pivotal physiological and pathological processes in all eukaryotes. Recently, the antiviral immune response is enhanced by the regulation of ubiquitination. Intriguingly, Flaviviridae viruses can ingeniously hijack the ubiquitination system to help them survive, which has become a hot topic among worldwide researchers. The Flaviviridae family members, such as HCV and CSFV, can cause serious diseases of humans and animals around the world. The multiple roles of ubiquitination involved in the life cycle of Flaviviridae family would open new sight for future development of antiviral tactic. Here, we discuss recent advances with regard to functional roles of ubiquitination and some ubiquitin-like modifications in the life cycle of Flaviviridae infection, shedding new light on the antiviral mechanism research and therapeutic drug development.
Gene sdaB Is Involved in the Nematocidal Activity of Enterobacter ludwigii AA4 Against the Pine Wood Nematode Bursaphelenchus xylophilus
Authors: Zhao Yu , Yuan Zhibo , Wang Shuang , Wang Haoyu , Chao Yanjie , Sederoff Ronald R. , Sederoff Heike , Yan He , Pan Jialiang , Peng Mu , Wu Di , Borriss Rainer , Niu Ben
Published: May 2022

Bursaphelenchus xylophilus, a plant parasitic nematode, is the causal agent of pine wilt, a devastating forest tree disease. Essentially, no efficient methods for controlling B. xylophilus and pine wilt disease have yet been developed. Enterobacter ludwigii AA4, isolated from the root of maize, has powerful nematocidal activity against B. xylophilus in a new in vitro dye exclusion test. The corrected mortality of the B. xylophilus treated by E. ludwigii AA4 or its cell extract reached 98.3 and 98.6%, respectively. Morphological changes in B. xylophilus treated with a cell extract from strain AA4 suggested that the death of B. xylophilus might be caused by an increased number of vacuoles in non-apoptotic cell death and the damage to tissues of the nematodes. In a greenhouse test, the disease index of the seedlings of Scots pine (Pinus sylvestris) treated with the cells of strain AA4 plus B. xylophilus or those treated by AA4 cell extract plus B. xylophilus was 38.2 and 30.3, respectively, was significantly lower than 92.5 in the control plants treated with distilled water and B. xylophilus. We created a sdaB gene knockout in strain AA4 by deleting the gene that was putatively encoding the beta-subunit of L-serine dehydratase through Red homologous recombination. The nematocidal and disease-suppressing activities of the knockout strain were remarkably impaired. Finally, we revealed a robust colonization of P. sylvestris seedling needles by E. ludwigii AA4, which is supposed to contribute to the disease-controlling efficacy of strain AA4. Therefore, E. ludwigii AA4 has significant potential to serve as an agent for the biological control of pine wilt disease caused by B. xylophilus.
Regular Low-Intensity Exercise Prevents Cognitive Decline and a Depressive-Like State Induced by Physical Inactivity in Mice: A New Physical Inactivity Experiment Model
Authors: Kim Jimmy , Park Jonghyuk , Mikami Toshio
Published: May 2022

Regular exercise has already been established as a vital strategy for maintaining physical healthviaexperimental results in humans and animals. In addition, numerous human studies have reported that physical inactivity is a primary factor that causes obesity, muscle atrophy, metabolic diseases, and deterioration in cognitive function and mental health. Regardless, an established animal experimental method to examine the effect of physical inactivity on physiological, biochemical, and neuroscientific parameters is yet to be reported. In this study, we made a new housing cage, named as the physical inactivity (PI) cage, to investigate the effect of physical inactivity on cognitive function and depressive-like states in mice and obtained the following experimental results by its use. We first compared the daily physical activity of mice housed in the PI and standard cages using the nano-tag method. The mice’s physical activity levels in the PI cage decreased to approximately half of that in the mice housed in the standard cage. Second, we examined whether housing in the PI cage affected plasma corticosterone concentration. The plasma corticosterone concentration did not alter before, 1 week, or 10 weeks after housing. Third, we investigated whether housing in the PI cage for 10 weeks affected cognitive function and depressive behavior. Housing in an inactive state caused a cognitive decline and depressive state in the mice without increasing body weight and plasma corticosterone. Finally, we examined the effect of regular low-intensity exercise on cognitive function and depressive state in the mice housed in the PI cage. Physical inactivity decreased neuronal cell proliferation, blood vessel density, and gene expressions of vascular endothelial growth factors and brain-derived neurotrophic factors in the hippocampus. In addition, regular low-intensity exercise, 30 min of treadmill running at a 5–15 m/min treadmill speed 3 days per week, prevented cognitive decline and the onset of a depressive-like state caused by physical inactivity. These results showed that our novel physical inactivity model, housing the mice in the PI cage, would be an adequate and valuable experimental method for examining the effect of physical inactivity on cognitive function and a depressive-like state.
Identification of Novel Cerebrospinal Fluid Biomarkers for Cognitive Decline in Aneurysmal Subarachnoid Hemorrhage: A Proteomic Approach
Authors: Liu Fan , Bao Yun , Qiu Binghui , Mao Jian , Liao Xixian , Huang Haorun , Zhang An , Zhang Guozhong , Qi Songtao , Mei Fen
Published: May 2022

Background

Cognitive impairment commonly occurs in aneurysmal subarachnoid hemorrhage (aSAH) survivors. Cerebrospinal fluid (CSF) biomarkers have been proven useful in several central neurological disorders. No such diagnostic biomarkers are available for predicting cognitive impairment after aSAH to date. Here, we aimed to identify novel CSF biomarkers for cognitive deficits after aSAH using an in-depth proteomic approach.

Methods

We applied mass spectrometry with data independent acquisition (DIA) quantification to identify biomarker candidates in CSF samples from a well-characterized cohort comprising patients with impaired cognition (n = 9) and patients with intact cognition (n = 9). The potential biological processes and signaling pathways associated with differential proteins were analyzed using R software. The candidates were further validated in a larger independent cohort (n = 40) using ELISA. The diagnostic utility of these proteins was investigated by using receiver operating characteristic curve analysis.

Results

In total, we identified 628 proteins. The discovery cohort revealed that 115 proteins were differentially expressed in cognitive impairment patients compared to patients with intact cognition (P < 0.05). Independent cohort replication confirmed NCAM2, NPTXR, NRXN2, RELN, and CNTN2 as sensitive and specific candidate biomarkers for disorders of cognition. Lower CSF levels of all biomarker candidates, except RELN, were associated with more pronounced cognitive decline.

Conclusion

We identified and validated five CSF biomarkers for cognitive impairment in aSAH patients. These particular proteins have important predictive and discriminative potential for cognitive impairment in aSAH and could be potential targets for early disease intervention.
The Glial Cells Respond to Spinal Cord Injury
Authors: Wang Ruideng , Zhou Rubing , Chen Zhengyang , Gao Shan , Zhou Fang
Published: May 2022

It is been over 100 years since glial cells were discovered by Virchow. Since then, a great deal of research was carried out to specify these further roles and properties of glial cells in central nervous system (CNS). As it is well-known that glial cells, such as astrocytes, microglia, oligodendrocytes (OLs), and oligodendrocyte progenitor cells (OPCs) play an important role in supporting and enabling the effective nervous system function in CNS. After spinal cord injury (SCI), these glial cells play different roles in SCI and repair. In this review, we will discuss in detail about the role of glial cells in the healthy CNS and how they respond to SCI.
Safety and Efficacy of Cell Transplantation on Improving Motor Symptoms in Patients With Parkinson’s Disease: A Meta-Analysis
Authors: Wang Jiaming , Tian Yu , Shi Xin , Feng Zhaohai , Jiang Lei , Hao Yujun
Published: May 2022

Background

The past four decades have seen the growing use of tissue or cell transplants in Parkinson’s disease (PD) treatment. Parkinson’s cell therapy is a promising new treatment; however, efficacy of cell transplantation for Parkinson’s disease are entirely unclear.

Objective

To conduct a meta-analysis and a systematic review of the efficacy of cell therapy in patients with PD.

Methods

A systematic literature review and meta-analysis of 10 studies were performed to assess the efficacy of cell therapy in Parkinson’s patients. To achieve this, we compared the change in Unified Parkinson’s Disease Rating Scale (UPDRS) II and III scale scores to baseline and assessed the incidence of transplant-related adverse events. The MINORS score and the I2 index were applied to evaluate the quality of studies between-study heterogeneity, respectively.

Results

The literature search yielded 10 articles (n = 120). The improvement in motor function based on the UPDRSIII assessment was −14.044 (95% CI: −20.761, −7.327) (p < 0.001), whereas improvement in daily living ability based on the UPDRSII assessment was −5.661 (95% CI: −7.632, −3.689) (p < 0.001).

Conclusion

The present findings demonstrate important clues on the therapeutic effect of cell therapy in alleviating motor impairment and daily living ability in PD patients.
Infra-Low Frequency Neurofeedback in the Treatment of Patients With Chronic Eating Disorder and Comorbid Post-Traumatic Stress Disorder
Authors: Winkeler Anna , Winkeler Markus , Imgart Hartmut
Published: May 2022

The treatment of patients suffering from an eating disorder and a comorbid post-traumatic stress disorder is challenging and often leads to poor outcomes. In a randomized control trial, we evaluated to what extent adding Infra-Low Frequency (ILF) neurofeedback could improve symptom reduction within an established inpatient treatment program. In a randomized two-group design, patients suffering from an eating disorder (anorexia nervosa, bulimia nervosa, or binge eating disorder) and comorbid post-traumatic stress disorder (N = 36) were examined while attending an inpatient treatment program in a clinic for psychosomatic disorders. The intervention group received ILF neurofeedback in addition to regular therapy, while the control group received “media-supported relaxation” as a placebo intervention. At the beginning and at the end of their treatment, all participants completed the Eating Disorder Examination-Questionnaire (EDE-Q) as a measure of eating disorder psychopathology and the Impact of Event Scale-Revised (IES-R) in order to assess symptoms of post-traumatic stress. Changes in EDE-Q and IES-R scores over time served as primary outcomes as well as an increase in body mass index in underweight patients. Secondary outcomes were the perceived benefit of the received intervention, global assessment of psychological treatment success, and complications in the course of treatment. Statistical evaluation was carried out with repeated measurement analysis of variance for the primary outcomes and with t-tests and Fisher’s exact test for the secondary outcomes. Our results indicate better treatment outcomes in the ILF neurofeedback group with regard to trauma-associated avoidance as well as with regard to restraint eating and increase in body weight. Furthermore, patients who had received ILF neurofeedback rated the intervention they received and, in tendency, their overall treatment more positively and they experienced fewer complications in the course of treatment. ILF neurofeedback is very well accepted by patients and seems to provide a relevant additional benefit in some aspects of symptom reduction. Findings confirm the feasibility of embedding this treatment approach in an inpatient setting and support the case for a larger study for greater statistical power.

Clinical Trial Registration: “Infra-Low Frequency Neurofeedback training in the treatment of patients with eating disorder and comorbid post-traumatic stress disorder”; German Clinical Trials Registry (https://www.drks.de; Identifier: DRKS00027826).
Complement Dependent Synaptic Reorganisation During Critical Periods of Brain Development and Risk for Psychiatric Disorder
Authors: Westacott Laura J. , Wilkinson Lawrence S.
Published: May 2022

We now know that the immune system plays a major role in the complex processes underlying brain development throughout the lifespan, carrying out a number of important homeostatic functions under physiological conditions in the absence of pathological inflammation or infection. In particular, complement-mediated synaptic pruning during critical periods of early life may play a key role in shaping brain development and subsequent risk for psychopathology, including neurodevelopmental disorders such as schizophrenia and autism spectrum disorders. However, these disorders vary greatly in their onset, disease course, and prevalence amongst sexes suggesting complex interactions between the immune system, sex and the unique developmental trajectories of circuitries underlying different brain functions which are yet to be fully understood. Perturbations of homeostatic neuroimmune interactions during different critical periods in which regional circuits mature may have a plethora of long-term consequences for psychiatric phenotypes, but at present there is a gap in our understanding of how these mechanisms may impact on the structural and functional changes occurring in the brain at different developmental stages. In this article we will consider the latest developments in the field of complement mediated synaptic pruning where our understanding is beginning to move beyond the visual system where this process was first described, to brain areas and developmental periods of potential relevance to psychiatric disorders.
Contribution of Amygdala Histone Acetylation in Early Life Stress-Induced Visceral Hypersensitivity and Emotional Comorbidity
Authors: Guan Le , Shi Xi , Tang Ying , Yan Yan , Chen Liang , Chen Yu , Gao Guangcheng , Lin Chun , Chen Aiqin
Published: May 2022

Patients with irritable bowel syndrome (IBS) experience not only enhanced visceral pain but also emotional comorbidities, such as anxiety and depression. Early life stress (ELS) is a high-risk for the development of IBS. Literatures have reported an important epigenetic modulation in sustaining extrinsic phenotypes. The amygdala is closely related to the regulation of visceral functions and emotional experiences. In this study, we hypothesized that ELS-induced reprogramming inappropriate adaptation of histone acetylation modification in the amygdala may result in visceral hypersensitivity and anxiety-like behaviors in ELS rats. To test this hypothesis, the model of ELS rats was established by neonatal colorectal dilatation (CRD). Visceral hypersensitivity was assessed based on the electromyography response of the abdominal external oblique muscle to CRD. Emotional comorbidities were examined using the elevated plus maze test, open field test, and sucrose preference test. Trichostatin A (TSA) and C646 were microinjected into the central amygdala (CeA) individually to investigate the effects of different levels of histone acetylation modification on visceral hypersensitivity and emotion. We found neonatal CRD resulted in visceral hypersensitivity and anxiety-like behaviors after adulthood. Inhibiting histone deacetylases (HDACs) in the CeA by TSA enhanced visceral sensitivity but did not affect anxiety-like behaviors, whereas inhibiting HAT by C646 attenuated visceral hypersensitivity in ELS rats. Interestingly, CeA treatment with TSA induced visceral sensitivity and anxiety-like behaviors in the control rats. Western blot showed that the expressions of acetylated 9 residue of Histone 3 (H3K9) and protein kinase C zeta type (PKMζ) were higher in the ELS rats compared to those of the controls. The administration of the PKMζ inhibitor ZIP into the CeA attenuated visceral hypersensitivity of ELS rats. Furthermore, the expression of amygdala PKMζ was enhanced by TSA treatment in control rats. Finally, western blot and immunofluorescence results indicated the decrease of HDAC1 and HDAC2 expressions, but not HDAC3 expression, contributed to the enhancement of histone acetylation in ELS rats. Our results support our hypothesis that amygdala-enhanced histone acetylation induced by stress in early life results in visceral hypersensitivity and anxiety-like behaviors in ELS rats, and reversing the abnormal epigenetic mechanisms may be crucial to relieve chronic symptoms in ELS rats.
No Effects of Photobiomodulation on Prefrontal Cortex and Hippocampal Cytochrome C Oxidase Activity and Expression of c-Fos Protein of Young Male and Female Rats
Authors: Gutiérrez-Menéndez Alba , Martínez Juan A. , Méndez Marta , Arias Jorge L.
Published: May 2022

The role of light in our biological processes and systems is extensively known. In addition, the use of light devices has been introduced in the field of healthcare as an opportunity to administer power light at specific wavelengths to improve our body functions and counteract light deficiency. One of these techniques is photobiomodulation (PBM), which uses red to infrared light in a non-invasive way to stimulate, heal, regenerate, and protect tissue. The main proposed mechanism of action is the stimulation of the cytochrome c oxidase (CCO), the terminal enzyme in the mitochondrial electron transport chain. PBM has achieved positive effects on brain activity and behavioral function of several adult animal models of health and disease, the potential use of this technique in developing stages is not surprising. This research aims to examine the effects of PBM on the prefrontal cortex and hippocampus of 23 day-old healthy male (n= 31) and female (n= 30) Wistar rats. Three groups of each sex were used: a PBM group which received 5 days of PBM, a device group submitted to the same conditions but without light radiation, and a control basal group. CCO histochemistry and c-Fos immunostaining were used to analyze brain metabolic activity and immediate early genes activation, respectively. Results displayed no metabolic differences between the three groups in both sexes. The same results were found in the analysis of c-Fos positive cells, reporting no differences between groups. This research, in contrast to the PBM consequences reported in healthy adult subjects, showed a lack of PBM effects in the brain markers we examined in young healthy rat brains. At this stage, brain function, specifically brain mitochondrial function, is not disturbed so it could be that the action of PBM in the mitochondria may not be detectable using the analysis of CCO activity and c-Fos protein expression. Further studies are needed to examine in depth the effects of PBM in brain development, cognitive functions and postnatal disorders, along with the exploration of the optimal light parameters.
The Relationship Between Auditory-Motor Integration, Interoceptive Awareness, and Self-Reported Stuttering Severity
Authors: Assaneo M. Florencia , Ripollés Pablo , Tichenor Seth E. , Yaruss J. Scott , Jackson Eric S.
Published: May 2022

Stuttering is a neurodevelopmental speech disorder associated with motor timing that differs from non-stutterers. While neurodevelopmental disorders impacted by timing are associated with compromised auditory-motor integration and interoception, the interplay between those abilities and stuttering remains unexplored. Here, we studied the relationships between speech auditory-motor synchronization (a proxy for auditory-motor integration), interoceptive awareness, and self-reported stuttering severity using remotely delivered assessments. Results indicate that in general, stutterers and non-stutterers exhibit similar auditory-motor integration and interoceptive abilities. However, while speech auditory-motor synchrony (i.e., integration) and interoceptive awareness were not related, speech synchrony was inversely related to the speaker’s perception of stuttering severity as perceived by others, and interoceptive awareness was inversely related to self-reported stuttering impact. These findings support claims that stuttering is a heterogeneous, multi-faceted disorder such that uncorrelated auditory-motor integration and interoception measurements predicted different aspects of stuttering, suggesting two unrelated sources of timing differences associated with the disorder.
Small Extracellular Vesicles in Milk Cross the Blood-Brain Barrier in Murine Cerebral Cortex Endothelial Cells and Promote Dendritic Complexity in the Hippocampus and Brain Function in C57BL/6J Mice
Authors: Zhou Fang , Ebea Pearl , Mutai Ezra , Wang Haichuan , Sukreet Sonal , Navazesh Shya , Dogan Haluk , Li Wenhao , Cui Juan , Ji Peng , Ramirez Denise M. O. , Zempleni Janos
Published: May 2022

Human milk contains large amounts of small extracellular vesicles (sEVs) and their microRNA cargos, whereas infant formulas contain only trace amounts of sEVs and microRNAs. We assessed the transport of sEVs across the blood-brain barrier (BBB) and sEV accumulation in distinct regions of the brain in brain endothelial cells and suckling mice. We further assessed sEV-dependent gene expression profiles and effects on the dendritic complexity of hippocampal granule cells and phenotypes of EV depletion in neonate, juvenile and adult mice. The transfer of sEVs across the BBB was assessed by using fluorophore-labeled bovine sEVs in brain endothelial bEnd.3 monolayers and dual chamber systems, and in wild-type newborn pups fostered to sEV and cargo tracking (ECT) dams that express sEVs labeled with a CD63-eGFP fusion protein for subsequent analysis by serial two-photon tomography and staining with anti-eGFP antibodies. Effects of EVs on gene expression and dendritic architecture of granule cells was analyzed in hippocampi from juvenile mice fed sEV and RNA-depleted (ERD) and sEV and RNA-sufficient (ERS) diets by using RNA-sequencing analysis and Golgi-Cox staining followed by integrated neuronal tracing and morphological analysis of neuronal dendrites, respectively. Spatial learning and severity of kainic acid-induced seizures were assessed in mice fed ERD and ERS diets. bEnd.3 cells internalized sEVs by using a saturable transport mechanism and secreted miR-34a across the basal membrane. sEVs penetrated the entire brain in fostering experiments; major regions of accumulation included the hippocampus, cortex and cerebellum. Two hundred ninety-five genes were differentially expressed in hippocampi from mice fed ERD and ERS diets; high-confidence gene networks included pathways implicated in axon guidance and calcium signaling. Juvenile pups fed the ERD diet had reduced dendritic complexity of dentate granule cells in the hippocampus, scored nine-fold lower in the Barnes maze test of spatial learning and memory, and the severity of seizures was 5-fold higher following kainic acid administration in adult mice fed the ERD diet compared to mice fed the ERS diet. We conclude that sEVs cross the BBB and contribute toward optimal neuronal development, spatial learning and memory, and resistance to kainic acid-induced seizures in mice.
Analysis of Furan in Red Pepper Powder Treated by Three Methods-Boiling, Roasting, and Frying
Authors: Kim Sookyoung , Lee Haeun , Lee Kwang-Geun
Published: May 2022

In this study, furan analysis was conducted on dried red pepper powder treated by three cooking methods (boiling, roasting, and frying). A total of 144 samples were prepared and their furan levels were analysed using automated solid-phase micro-extraction gas chromatography-mass spectrometry. The furan concentration in boiled soup ranged from 1.26 to 4.65 ng/g, and from 7.37 to 27.68 ng/g for boiled red pepper samples. For the roasting method, a furan concentration between 6.66 and 761.37 ng/g was detected. For the frying method, the furan level of edible oils ranged from 3.93 to 125.88 ng/g, and a concentration ranging from 4.88 to 234.52 ng/g was detected for the fried red pepper samples. The cooking method using edible oil obtained a higher furan concentration than the water-based method. Samples using corn germ oil (linoleic acid-rich oil) obtained the highest furan concentration among the four edible oils. In all cooking methods, the higher the heating temperature and time, the higher the furan concentration detected. A kinetic study was conducted using the roasting model system and the apparent activation energy was 60.5 kJ/mol. The results of this study could be useful as a database for furan concentration in dried red pepper powder according to various cooking methods.
Maternal Organic Selenium Supplementation Relieves Intestinal Endoplasmic Reticulum Stress in Piglets by Enhancing the Expression of Glutathione Peroxidase 4 and Selenoprotein S
Authors: Ding Dajiang , Mou Daolin , Zhu Heng , Jiang Xuemei , Che Lianqiang , Fang Zhengfeng , Xu Shengyu , Lin Yan , Zhuo Yong , Li Jian , Huang Chao , Zou Yuanfeng , Li Lixia , Wu De , Feng Bin
Published: May 2022

Endoplasmic reticulum (ER) stress, which can be induced by reactive oxygen species (ROS) and multiple factors, is associated with numerous intestinal diseases. The organic selenium source 2-hydroxy-4-methylselenobutanoic acid (HMSeBA), has been proved to decrease intestinal inflammation and autophagy by improving the expression of selenoproteins. However, it remains unclear whether HMSeBA could alleviate intestinal ER stress by decreasing excessive production of ROS products. This study was conducted to investigate the effect of maternal HMSeBA supplementation on the regulation of intestinal ER stress of their offspring and the regulatory mechanism. Sows were supplemented with HMSeBA during gestation and jejunal epithelial (IPEC-J2) cells were treatment with HMSeBA. Results showed that maternal HMSeBA supplementation significantly upregulated mRNA level of selenoprotein S (SELS) in the jejunum of newborn and weaned piglets compared with the control group, while decreased the gene expression and protein abundance of ER stress markers in the jejunum of LPS challenged weaned piglets. In addition, HMSeBA treatment significantly increased the expression of glutathione peroxidase 4 (GPX4) and SELS, while decreased ROS level and the expression of ER stress markers induced by hydrogen peroxide (H2O2) in IPEC-J2 cells. Furthermore, knockdown of GPX4 did not enhance the ERS signal induced by H2O2, but the lack of GPX4 would cause further deterioration of ER stress signal in the absence of SELS. In conclusion, maternal HMSeBA supplementation might alleviate ROS induced intestinal ER stress by improving the expression of SELS and GPX4 in their offspring. Thus, maternal HMSeBA supplementation might be benefit for the intestinal health of their offspring.
Long-Term Clinical Outcomes in Treatment-Naïve Patients With Orbital Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma: A Single-Center Study
Authors: Min Gi-June , Kim Sung Eun , Kim Tong Yoon , Jeon Young-Woo , O Joo Hyun , Choi Byung-Ock , Park Gyeongsin , Yang Suk-Woo , Cho Seok-Goo
Published: May 2022

Ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (OAML) is the most common type of ocular lymphoma with a higher prevalence in Asia than in Western countries. OAML represents 1%–2% of all non-Hodgkin’s lymphoma, 5%–15% of extranodal lymphomas, and approximately 55% of orbital malignancies. “Watch and wait” after biopsy or surgical resection, radiation therapy, and systemic treatment, including antibiotics administration and chemotherapy with various combinations of regimens can be considered for OAML treatment. Radiotherapy is adapted for limited-stage disease with excellent clinical outcomes of 85–100% complete remission and relatively superior local control efficacy and treatment duration. In contrast, chemotherapy has rarely been tested as frontline therapy. Nonetheless, several studies have reported a favorable response and long duration of progression-free survival using chemotherapy adaptations. When the disease involves both eyes or spreads beyond the conjunctiva, the risk of recurrence increases and limited-stage OAML has a recurrence rate of approximately 25% following radiotherapy only. Therefore, although recent consensus in the literature is that patients with limited-stage OAML recommended treating with radiation, physicians may choose the treatment modality not only by its efficiency but also by its adverse events profile and patients’ well-being. Herein, we present a large single-center study on OAML that included 292 patients who were followed up for up to 237 months. We collected and analyzed real-world data focusing on treatment outcomes and the role of radiotherapy as frontline therapy, and aimed to compare outcomes and complication profiles of chemotherapy, especially in limited-stage OAML, to identify an optimal treatment strategy.
Obesity Does Not Increase Perioperative Outcomes in Older Patients Undergoing Thoracoscopic Anatomic Lung Cancer Surgery
Authors: Tong Chaoyang , Li Tingting , Shen Yaofeng , Zhu Hongwei , Zheng Jijian , Wu Jingxiang
Published: May 2022

Objectives

To investigate the relationship between obesity status and perioperative outcomes in elderly patients undergoing thoracoscopic anatomic lung cancer surgery.

Methods

From January 2016 to December 2018, we performed a monocentric retrospective cohort study among 4164 consecutive patients aged 65 years or older who underwent thoracoscopic anatomic lung cancer surgery at Shanghai Chest Hospital. Two groups were stratified by body mass index (BMI): nonobese (BMI<28kg/m2) and obese status (BMI≥28kg/m2). Using a 1:1 propensity score matching (PSM) analysis to compare perioperative outcomes between two groups.

Results

4035 older patients were eventually enrolled, with a mean age of 69.8 years (range: 65-87), and 305 patients were eligible for obese status, with a mean BMI of 29.8 ± 1.7kg/m2. Compared with nonobese patients, obese patients were more likely to have higher rates of intraoperative hypoxemia (1.2% vs 3.9%, P=0.001) and new-onset arrhythmia (2.3% vs 4.3%, P=0.034). The difference in intraoperative transfusion and conversion rates and postoperative outcomes regarding pulmonary complications, new-onset arrhythmia, transfusion, length of hospital stay, 30-day readmission and hospitalization costs between two groups were not significant (P>0.05). After a 1:1 PSM analysis, the difference in both intraoperative and postoperative complications among two groups were not significant (P>0.05). In subgroup analysis, patients with BMI≥30kg/m2 had a similar incidence of perioperative complications compared to patients with BMI between 28 and 30 kg/m2 (P>0.05).

Conclusions

Our research data support evidence for “obesity paradox” and also contribute the growing body of evidence that obesity in older patients should not exclude candidates for thoracoscopic anatomic lung cancer surgery.
Serum Levels of MicroRNA-371a-3p (M371) Can Predict Absence or Presence of Vital Disease in Residual Masses After Chemotherapy of Metastatic Seminoma
Authors: Dieckmann Klaus-Peter , Klemke Markus , Grobelny Francesca , Radtke Arlo , Dralle-Filiz Inken , Wülfing Christian , Belge Gazanfer
Published: May 2022

Background

Radiological evaluation of postchemotherapy residual masses of metastatic seminoma is characterized by poor diagnostic accuracy. Serum levels of microRNA-371a-3p (M371) involve high specificity and sensitivity for the primary diagnosis of seminoma. We evaluated if M371 levels can indicate the presence of vital disease in postchemotherapy residual masses in patients with metastatic seminoma.

Methods

Twenty-three seminoma patients (median age 52 years) with residual masses had posttreatment measurements of serum M371 levels (group A), fourteen of whom had measurements also beforehand. The posttreatment results were compared with the clinical outcome during follow-up. Eleven patients with complete remission after treatment of metastatic seminoma (group B) and 33 men with non-malignant testicular diseases (group C) served as controls. M371 serum levels were measured by quantitative real-time PCR using miR-30b-5p as endogenous control. An evaluation was performed with descriptive statistical methods.

Results

Twenty-two patients of Group A had uneventful follow-up so far, twenty-one of whom had M371 level <5, and one other had a mildly elevated level below relative quantity (RQ) = 10. One patient with a level of RQ = 26.2 rapidly progressed. The median posttreatment M371 level of the non-progressing patients of group A is not significantly different from the median level of the control group with complete remission (B). Before treatment, the median M371 levels in groups A and B were 507.6 and 143.9, respectively. In both groups, significant drops in M371 levels resulted from treatment.

Conclusion

Normal M371 serum levels at the time of completion of treatment of metastatic seminoma indicate the absence of vital seminoma in residual masses, while elevated levels >RQ = 10 predict the presence of disease. The optimal timing of M371 measurement after chemotherapy and the appropriate cutoff level still need to be determined. Based on the present results, measuring serum M371 levels involves the potential of a novel tool for assessing postchemotherapy residual masses of metastatic seminoma.
Portrayals of Pain in Children's Popular Media: Mothers' and Fathers' Beliefs and Attitudes
Authors: Pavlova Maria , Mueri Kendra , Kennedy Madison , Wallwork Sarah , Moseley G. Lorimer , Jordan Abbie , Noel Melanie
Published: May 2022

Evidence suggests that children's popular media may model maladaptive and distorted experiences of pain to young children. In a recent study, pain depicted in popular media targeting 4–6-year-olds was frequently and unrealistically portrayed, evoked little response or empathy from observing characters, and perpetuated unhelpful gender stereotypes. Parents play a critical role in both children's pain experiences and children's media consumption. Yet, no study to date has examined parents' beliefs and attitudes regarding how pain is portrayed in media for young children. The present study aimed to fill this gap by examining how parents perceive and appraise painful instances depicted in children's popular media. Sixty parents (48% fathers) of children aged 4 to 6 years completed a semi-structured interview to assess their general beliefs and attitudes toward how pain is portrayed in children's media. Inductive reflexive thematic analysis was conducted to identify and analyze key patterns in the data. Qualitative analyses generated two major themes representing parental beliefs regarding pain that is portrayed in children's media: “entertaining pain” and “valuable lessons”. Findings reveal that parents believe that pain portrayed in popular media serves either a function of entertaining and amusing children or can provide valuable lessons about appropriate emotional responses and empathic reactions. Further, pain portrayals could also instill valuable lessons and provide children with a point of reference and language for their own painful experiences. Parents serve as a primary socialization agent for young children; thus, it is important that parents remain aware of underlying messages about how pain is portrayed in children's popular media so that they can optimally discuss these portrayals, promote their children's pain education and understanding and positively impact future pain experiences.
The Construction and Exploration of a Comprehensive MicroRNA Centered Regulatory Network in Foxtail Millet (Setaria italica L.)
Authors: Deng Yang , Zhang Haolin , Wang Hailong , Xing Guofang , Lei Biao , Kuang Zheng , Zhao Yongxin , Li Congcong , Dai Shaojun , Yang Xiaozeng , Wei Jianhua , Zhang Jiewei
Published: May 2022

MicroRNA (miRNA) is an essential endogenous post-transcriptional regulatory factor, and foxtail millet (Setaria italica L.) is an ideal C4 model cereal that is a highly valuable crop in semiarid and arid areas. The Research on comprehensive and high confidence identification and annotation of foxtail millet miRNAs needs to be strengthened, and to our knowledge, there is no information on the regulatory network of foxtail millet miRNA. In this study, 136 high confidence miRNAs were identified through high-throughput sequencing of the small RNAs in seven tissues at the shooting and grain filling stages of foxtail millet. A total of 2,417 target genes were obtained by combining computational biology software and degradome sequencing methods. Furthermore, an analysis using transcriptome sequencing revealed the relationships between miRNAs and their target genes and simultaneously explored key regulatory modules in panicles during the grain filling stage. An miRNA regulatory network was constructed to explore the functions of miRNA in more detail. This network, centered on miRNAs and combining upstream transcriptional factors and downstream target genes, is primarily composed of feed forward loop motifs, which greatly enhances our knowledge of the potential functions of miRNAs and uncovers numerous previously unknown regulatory links. This study provides a solid foundation for research on the function and regulatory network of miRNAs in foxtail millet.
B3 Transcription Factors Determine Iron Distribution and FERRITIN Gene Expression in Embryo but Do Not Control Total Seed Iron Content
Authors: Grant-Grant Susana , Schaffhauser Macarena , Baeza-Gonzalez Pablo , Gao Fei , Conéjéro Geneviève , Vidal Elena A. , Gaymard Frederic , Dubos Christian , Curie Catherine , Roschzttardtz Hannetz
Published: May 2022

Iron is an essential micronutrient for humans and other organisms. Its deficiency is one of the leading causes of anemia worldwide. The world health organization has proposed that an alternative to increasing iron content in food is through crop biofortification. One of the most consumed part of crops is the seed, however, little is known about how iron accumulation in seed occurs and how it is regulated. B3 transcription factors play a critical role in the accumulation of storage compounds such as proteins and lipids. Their role in seed maturation has been well characterized. However, their relevance in accumulation and distribution of micronutrients like iron remains unknown. In Arabidopsis thaliana and other plant models, three master regulators belonging to the B3 transcription factors family have been identified: FUSCA3 (FUS3), LEAFY COTYLEDON2 (LEC2), and ABSCISIC ACID INSENSITIVE 3 (ABI3). In this work, we studied how seed iron homeostasis is affected in B3 transcription factors mutants using histological and molecular approaches. We determined that iron distribution is modified in abi3, lec2, and fus3 embryo mutants. For abi3-6 and fus3-3 mutant embryos, iron was less accumulated in vacuoles of cells surrounding provasculature compared with wild type embryos. lec2-1 embryos showed no difference in the pattern of iron distribution in hypocotyl, but a dramatic decrease of iron was observed in cotyledons. Interestingly, for the three mutant genotypes, total iron content in dry mutant seeds showed no difference compared to wild type. At the molecular level, we showed that genes encoding the iron storage ferritins proteins are misregulated in mutant seeds. Altogether our results support a role of the B3 transcription factors ABI3, LEC2, and FUS3 in maintaining iron homeostasis in Arabidopsis embryos.
Integration of Transcriptome and Metabolome Reveals the Formation Mechanism of Red Stem in Prunus mume
Authors: Qiu Like , Zheng Tangchun , Liu Weichao , Zhuo Xiaokang , Li Ping , Wang Jia , Cheng Tangren , Zhang Qixiang
Published: May 2022

Prunus mume var. purpurea, commonly known as “Red Bone”, is a special variety with pink or purple-red xylem. It is famous due to gorgeous petals and delightful aromas, playing important roles in urban landscaping. The regulation mechanism of color formation in P. mume var. purpurea stem development is unclear. Here, we conducted a comprehensive analysis of transcriptome and metabolome in WYY (‘Wuyuyu' accession, red stem) and FLE (‘Fei Lve' accession, green stem), and found a total of 256 differential metabolites. At least 14 anthocyanins were detected in WYY, wherein cyanidin 3,5-O-diglucoside and peonidin3-O-glucoside were significantly accumulated through LC-MS/MS analysis. Transcriptome data showed that the genes related to flavonoid-anthocyanin biosynthesis pathways were significantly enriched in WYY. The ratio of dihydroflavonol 4-reductase (DFR) and flavonol synthase (FLS) expression levels may affect metabolic balance in WYY, suggesting a vital role in xylem color formation. In addition, several transcription factors were up-regulated, which may be the key factors contributing to transcriptional changes in anthocyanin synthesis. Overall, the results provide a reference for further research on the molecular mechanism of xylem color regulation in P. mume and lay a theoretical foundation for cultivating new varieties.