bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Total Variation Regularized Expectation Maximization Reconstruction on 68Ga-DOTA-TATE PET/CT Images in Patients With Neuroendocrine Tumor
Authors: Liu Lin , Liu Hanxiang , Xu Shijie , Zhang Shumao , Tao Yi , Mok Greta S. P. , Chen Yue
Published: March 2022

Objective

The aim of this study was to investigate the effects of the total variation regularized expectation maximization (TVREM) reconstruction on improving 68Ga-DOTA-TATE PET/CT images compared to the ordered subset expectation maximization (OSEM) reconstruction.

Method

A total of 17 patients with neuroendocrine tumors who underwent clinical 68Ga-DOTA-TATE PET/CT were involved in this study retrospectively. The PET images were acquired with either 3 min-per-bed (min/bed) acquisition time and reconstructed with OSEM (2 iterations, 20 subsets, and a 3.2-mm Gaussian filter) and TVREM (seven penalization factors = 0.01, 0.07, 0.14, 0.21, 0.28, 0.35, and 0.42) for 2 and 3 min-per-bed (min/bed) acquisition time using list-mode. The SUVmean of the liver, background variability (BV), signal-to-noise ratios (SNR), SUVmax of the lesions and tumor-to-background ratios (TBR) were measured. The mean percentage difference in the SNR and TBR between TVREM with difference penalization factors and OSEM was calculated. Qualitative image quality was evaluated by two experienced radiologists using a 5-point score scale (5-excellent, 1-poor).

Results

In total, 63 lesions were analyzed in this study. The SUVmean of the liver did not differ significantly between TVREM and OSEM. The BV of all TVREM groups was lower than OSEM groups (all p < 0.05), and the BV of TVREM 2 min/bed group with penalization factor of 0.21 was considered comparable to OSEM 3 min/bed group (p = 0.010 and 0.006). The SNR, SUVmax and TBR were higher for all TVREM groups compared to OSEM groups (all p < 0.05). The mean percentage difference in the SNR and TBR was larger for small lesions (<10 mm) than that for medium (≥10 mm but < 20 mm) and large lesions (≥20 mm). The highest image quality score was given to TVREM 2 min/bed group with penalization factor of 0.21 (3.77 ± 0.26) and TVREM 3 min/bed group with penalization factor of 0.35 (3.77 ± 0.26).

Conclusion

TVREM could reduce image noise, improve the SNR, SUVmax and TBR of the lesions, and has the potential to preserves the image quality with shorter acquisition time.
A Longitudinal Nine-Year Study of the Molecular Epidemiology of Carbapenemase-Producing Enterobacterales Isolated From a Regional Hospital in Taiwan: Predominance of Carbapenemase KPC-2 and OXA-48
Authors: Duong Tran Thi Thuy , Tsai Ya-Min , Wen Li-Li , Chiu Hui-Chuan , Chen Pek Kee , Thuy Tran Thi Dieu , Kuo Pei-Yun , Hidrosollo Jazon Harl , Wang Shining , Zhang Yen-Zhen , Lin Wei-Hung , Wang Ming-Cheng , Kao Cheng-Yen
Published: March 2022

Enterobacterales clinical isolates are now being resistant to clinically achievable concentrations of most commonly used antibiotics that makes treatment of hospitalized patients very challenging. We hereby determine the molecular characteristics of carbapenemase genes in carbapenem-resistant Enterobacterales (CRE) isolates in Taiwan. A total of 455 CRE isolates were identified between August 2011 to July 2020. Minimum inhibitory concentrations for selected carbapenems were tested using Vitek 2, and carbapenemase genes were determined using polymerase chain reaction in combination with sequencing. Phenotypic detection of carbapenemase was determined by modified carbapenem inactivation method (mCIM) and EDTA-modified carbapenem inactivation method (eCIM) to validate our PCR screening results. Pulsed-field gel electrophoresis (PFGE) was used to determine the clonality of carbapenemase-producing Enterobacterales (CPE) isolates, and the transferability of carbapenemase-carrying plasmids was determined by conjugation assays. A slight increase in carbapenem-resistant E. coli (CREC) was observed, however, the prevalence of carbapenem-resistant K. pneumoniae (CRKP) was steady, during 2011–2020. The dominant species among our CRE was K. pneumoniae (270/455, 59.3%), followed by E. coli (81/455, 17.8%), Morganella morganii (32/455, 7.0%), and Enterobacter cloacae (25/455, 5.5%). From 2011 to 2020, the total percentage of CPE increased steadily, accounting for 61.0% of CRE in 2020. Moreover, 122 of 455 CRE isolates (26.8%) were CPE. Among the CPE isolates, the dominant carbapenemase gene was blaOXA–48–like (54/122, 44.3%), and the second most common carbapenemase gene was blaKPC–2 (47/122, 38.5%). The sensitivity and specificity for mCIM to detect carbapenemase in the 455 isolates were both 100% in this study. The PFGE results showed that 39 carbapenemase-producing E. coli and 69 carbapenemase-producing K. pneumoniae isolates carrying blaKPC–2 and/or blaNDM–5 could be classified into 5 and 12 clusters, respectively. In conclusion, our results showed an increase in CPE isolates in Taiwan. Moreover, the distribution of carbapenemase and antimicrobial susceptibility in CPE were associated with PFGE typing.
Polysaccharide Regulation of Intestinal Flora: A Viable Approach to Maintaining Normal Cognitive Performance and Treating Depression
Authors: Wang Xinzhou , Cheng Lu , Liu Yanan , Zhang Ruilin , Wu Zufang , Weng Peifang , Zhang Peng , Zhang Xin
Published: March 2022

The intestinal tract of a healthy body is home to a large variety and number of microorganisms that will affect every aspect of the host’s life. In recent years, polysaccharides have been found to be an important factor affecting intestinal flora. Polysaccharides are widely found in nature and play a key role in the life activities of living organisms. In the intestinal tract of living organisms, polysaccharides have many important functions, such as preventing the imbalance of intestinal flora and maintaining the integrity of the intestinal barrier. Moreover, recent studies suggest that gut microbes can influence brain health through the brain-gut axis. Therefore, maintaining brain health through polysaccharide modulation of gut flora deserves further study. In this review, we outline the mechanisms by which polysaccharides maintain normal intestinal flora structure, as well as improving cognitive function in the brain via the brain-gut axis by virtue of the intestinal flora. We also highlight the important role that gut microbes play in the pathogenesis of depression and the potential for treating depression through the use of polysaccharides to modulate the intestinal flora.
Differential Relationships Between Brain Structure and Dual Task Walking in Young and Older Adults
Authors: Hupfeld Kathleen E. , Geraghty Justin M. , McGregor Heather R. , Hass C. J. , Pasternak Ofer , Seidler Rachael D.
Published: March 2022

Almost 25% of all older adults experience difficulty walking. Mobility difficulties for older adults are more pronounced when they perform a simultaneous cognitive task while walking (i.e., dual task walking). Although it is known that aging results in widespread brain atrophy, few studies have integrated across more than one neuroimaging modality to comprehensively examine the structural neural correlates that may underlie dual task walking in older age. We collected spatiotemporal gait data during single and dual task walking for 37 young (18–34 years) and 23 older adults (66–86 years). We also collected T1-weighted and diffusion-weighted MRI scans to determine how brain structure differs in older age and relates to dual task walking. We addressed two aims: (1) to characterize age differences in brain structure across a range of metrics including volumetric, surface, and white matter microstructure; and (2) to test for age group differences in the relationship between brain structure and the dual task cost (DTcost) of gait speed and variability. Key findings included widespread brain atrophy for the older adults, with the most pronounced age differences in brain regions related to sensorimotor processing. We also found multiple associations between regional brain atrophy and greater DTcost of gait speed and variability for the older adults. The older adults showed a relationship of both thinner temporal cortex and shallower sulcal depth in the frontal, sensorimotor, and parietal cortices with greater DTcost of gait. Additionally, the older adults showed a relationship of ventricular volume and superior longitudinal fasciculus free-water corrected axial and radial diffusivity with greater DTcost of gait. These relationships were not present for the young adults. Stepwise multiple regression found sulcal depth in the left precentral gyrus, axial diffusivity in the superior longitudinal fasciculus, and sex to best predict DTcost of gait speed, and cortical thickness in the superior temporal gyrus to best predict DTcost of gait variability for older adults. These results contribute to scientific understanding of how individual variations in brain structure are associated with mobility function in aging. This has implications for uncovering mechanisms of brain aging and for identifying target regions for mobility interventions for aging populations.
Transcranial Direct Current Stimulation May Reduce Prefrontal Recruitment During Dual Task Walking in Functionally Limited Older Adults – A Pilot Study
Authors: Jor’dan Azizah J. , Bernad-Elazari Hagar , Mirelman Anat , Gouskova Natalia A. , Lo On-Yee , Hausdorff Jeffrey M. , Manor Brad
Published: March 2022

Introduction

Transcranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (dlPFC) improves dual task walking in older adults, when tested just after stimulation. The acute effects of tDCS on the cortical physiology of walking, however, remains unknown.

Methods

In a previous study, older adults with slow gait and executive dysfunction completed a dual task walking assessment before and after 20 min of tDCS targeting the left dlPFC or sham stimulation. In a subset of seven participants per group, functional near-infrared spectroscopy (fNIRS) was used to quantify left and right prefrontal recruitment defined as the oxygenated hemoglobin response to usual and dual task walking (ΔHbO2), as well as the absolute change in this metric from usual to dual task conditions (i.e., ΔHbO2cost). Paired t-tests examined pre- to post-stimulation differences in each fNIRS metric within each group.

Results

The tDCS group exhibited pre- to post-stimulation reduction in left prefrontal ΔHbO2cost (p = 0.03). This mitigation of dual task “cost” to prefrontal recruitment was induced primarily by a reduction in left prefrontal ΔHbO2 specifically within the dual task condition (p = 0.001), an effect that was observed in all seven participants within this group. Sham stimulation did not influence ΔHbO2cost or ΔHbO2 in either walking condition (p > 0.35), and neither tDCS nor sham substantially influenced right prefrontal recruitment (p > 0.16).

Discussion

This preliminary fNIRS data suggests that tDCS over the left dlPFC may modulate prefrontal recruitment, as reflected by a relative reduction in the oxygen consumption of this brain region in response to dual task walking.
Well-Being Is Associated With Local to Remote Cortical Connectivity
Authors: Li Yubin , Li Chunlin , Jiang Lili
Published: March 2022

Wellbeing refers to cognitive and emotional appraisal of an individual’s life and social functioning, which is of great significance to the quality of life of an individual and society. Previous studies have revealed the neural basis of wellbeing, which mostly focused on human brain morphology or network-level connectivity. However, local-to-remote cortical connectivity, which plays a crucial role in defining the human brain architecture, has not been investigated in wellbeing. To examine whether wellbeing was associated with local-to-remote cortical connectivity, we acquired resting-state images from 60 healthy participants and employed the Mental Health Continuum Short Form to measure wellbeing, including three dimensions, namely, emotional wellbeing, psychological wellbeing, and social wellbeing. Functional homogeneity (ReHo) and seed-based functional connectivity were used to evaluate local-to-remote cortical connectivity in these participants. For local connectivity, our results showed that ReHo in the right orbitofrontal sulcus was significantly positively correlated with psychological wellbeing but negatively correlated with social wellbeing. For remote connectivity, connectivity within the right orbitofrontal cortex and interhemispheric connectivity of the orbitofrontal sulcus were both positively associated with psychological wellbeing; functional connectivity between the right orbitofrontal sulcus and the left postcentral sulcus was positively associated with social wellbeing. Our results showed that wellbeing was indeed associated with local-to-remote cortical connectivity, and our findings supplied a new perspective of distance-related neural mechanisms of wellbeing.
Age-Dependent Neuropsychiatric Symptoms in the NF-κB/c-Rel Knockout Mouse Model of Parkinson’s Disease
Authors: Parrella Edoardo , Del Gallo Federico , Porrini Vanessa , Gussago Cristina , Benarese Marina , Fabene Paolo Francesco , Pizzi Marina
Published: March 2022

Non-motor symptoms are frequently observed in Parkinson’s disease (PD) and precede the onset of motor deficits by years. Among them, neuropsychiatric symptoms, including anxiety, depression, and apathy, are increasingly considered as a major challenge for patients with PD and their caregivers. We recently reported that mice lacking the nuclear factor-κB (NF-κB)/c-Rel protein (c-rel–/– mice) develop an age-dependent PD-like pathology and phenotype characterized by the onset of non-motor symptoms, including constipation and hyposmia, starting at 2 months of age, and motor deficits at 18 months. To assess whether c-rel–/– mice also suffer from neuropsychiatric symptoms, in this study we tested different cohorts of wild-type (wt) and c-rel–/– mice at 3, 6, 12, and 18–20 months with different behavioral tests. Mice lacking c-Rel displayed anxiety and depressive-like behavior starting in the premotor phase at 12 months, as indicated by the analysis with the open field (OF) test and the forced swim test with water wheel (FST), respectively. A deficit in the goal-oriented nesting building test was detected at 18–20 months, suggesting apathetic behavior. Taken together, these results indicate that c-rel–/– mice recapitulate the onset and the progression of PD-related neuropsychiatric symptoms. Therefore, this animal model may represent a valuable tool to study the prodromal stage of PD and for testing new therapeutic strategies to alleviate neuropsychiatric symptoms.
Pre-stroke Physical Inactivity and Stroke Severity in Male and Female Patients
Authors: Salmantabar Pegah , Abzhandadze Tamar , Viktorisson Adam , Reinholdsson Malin , Sunnerhagen Katharina S.
Published: March 2022

Introduction

Females experience more severe ischemic strokes than do males. A higher pre-stroke physical activity level is associated with less severe stroke. The primary aim of this study was to explore the association between pre-stroke physical inactivity and stroke severity in male and female patients.

Methods

This was a retrospective, registry-based study. The data were retrieved from two stroke registries from 2014 to 2019. The primary explanatory variable was physical activity level before the stroke, assessed using the Saltin-Grimby Physical Activity Level Scale. The outcome was moderate to severe stroke at hospital admission, assessed using the National Institutes of Health Stroke Scale (NIHSS). A moderate to severe stroke was defined as a NIHSS score of ≥6. Binary logistic regression analysis was performed to explore if physical inactivity before the stroke could explain stroke severity in male and female patients.

Results

In total, we included 4,535 patients with ischemic stroke. Female patients (n = 2,145) had a mean age of 76 years, 35% had a moderate to severe stroke, and 64% were physically inactive pre-stroke. Male patients (n = 2,390) had a mean age of 72 years, 25% had a moderate to severe stroke, and 49% were physically inactive pre-stroke. Physical inactivity was associated with higher odds for moderate to severe stroke in both sexes (females' odds ratio [OR], 2.7, 95% confidence interval [CI]: 2.2–3.3, p < 0.001 and males' OR, 2.06, 95% CI: 1.7–2.5, p < 0.001). The association remained significant in the adjusted models.

Conclusions

Physically inactive females and males had higher odds of experiencing a moderate to severe stroke. However, the OR of female patients was somewhat higher than that of male patients.
No Evidence for a Boost in Psychosocial Functioning in Older Age After a 6-Months Physical Exercise Intervention
Authors: Düzel Sandra , Drewelies Johanna , Polk Sarah E. , Misgeld Carola , Porst Johanna , Wolfarth Bernd , Kühn Simone , Brandmaier Andreas M. , Wenger Elisabeth
Published: March 2022

The beneficial effects of physical exercise on physical health and cognitive functioning have been repeatedly shown. However, evidence of its effect on psychosocial functioning in healthy adults is still scarce or inconclusive. One limitation of many studies examining this link is their reliance on correlational approaches or specific subpopulations, such as clinical populations. The present study investigated the effects of a physical exercise intervention on key factors of psychosocial functioning, specifically well-being, stress, loneliness, and future time perspective. We used data from healthy, previously sedentary older adults (N = 132) who participated in a 6-month at-home intervention, either engaging in aerobic exercise or as part of a control group who participated in foreign language-learning or reading of selected native-language literature. Before and after the intervention, comprehensive cardiovascular pulmonary testing and a psychosocial questionnaire were administered. The exercise group showed significantly increased fitness compared to the control group. Contrary to expectations, however, we did not find evidence for a beneficial effect of this fitness improvement on any of the four domains of psychosocial functioning we assessed. This may be due to pronounced stability of such psychological traits in older age, especially in older adults who show high levels of well-being initially. Alternatively, it may be that the well-documented beneficial effects of physical exercise on brain structure and function, as well as cognition differ markedly from beneficial effects on psychosocial functioning. While aerobic exercise may be the driving factor for the former, positive effects on the latter may only be invoked by other aspects of exercise, for example, experiences of mastery or a feeling of community.
Anomalous Levels of CD47/Signal Regulatory Protein Alpha in the Hippocampus Lead to Excess Microglial Engulfment in Mouse Model of Perioperative Neurocognitive Disorders
Authors: Shui Min , Sun Yi , Lin Dandan , Xue Ziyi , Liu Jianhui , Wu Anshi , Wei Changwei
Published: March 2022

Background

Perioperative neurocognitive disorders (PNDs) are common complications of surgical patients, which can lead to prolonged hospitalization, increased complications, and decreased independence and quality of life. However, the underlying molecular mechanisms of PND remain largely obscure. Microglia activation and synapse loss were observed in PND. Cluster of differentiation 47 (CD47), which can bind to its receptor signal regulatory protein alpha (SIRPα) and generate “do not eat me” signal, protects synapses from excessive pruning. Therefore, we aimed to evaluate the potential role of CD47–SIRPα signaling in PND.

Methods

The tibial fracture surgery was performed in aged C57BL/6 mice for PND model establishment. The expression of CD47 and SIRPα in the hippocampus was assessed. Synaptic plasticity, dendritic spine density, microglial engulfment, and hippocampal-dependent memory function were evaluated after model establishment and intervention with SIRPα overexpression.

Results

CD47 and SIRPα expression in the hippocampus were both decreased after the surgery. SIRPα overexpression showed reduced engulfment within host microglia, but a total effect of excessive synapse engulfment decreased dendritic spine density and post-synaptic density protein 95 (PSD95) expression. SIRPα overexpression could not improve the synaptic dysfunction and cognitive impairment in PND. In addition, SIRPα overexpression led to increased CD47 and Iba1 expression.

Conclusion

Anesthesia and surgery affect CD47–SIRPα signaling. SIRPα overexpression could not ameliorate the cognitive impairment in PND mice. One reason may be that the increased Iba1 expression leads to a total effect of excessive synapse engulfment, which results in decreased dendritic spine density and PSD95 expression.
Increased Excursions to Functional Networks in Schizophrenia in the Absence of Task
Authors: Farinha Miguel , Amado Conceição , Morgado Pedro , Cabral Joana
Published: March 2022

Schizophrenia is a chronic psychotic disorder characterized by the disruption of thought processes, perception, cognition, and behaviors, for which there is still a lack of objective and quantitative biomarkers in brain activity. Using functional magnetic resonance imaging (fMRI) data from an open-source database, this study investigated differences between the dynamic exploration of resting-state networks in 71 schizophrenia patients and 74 healthy controls. Focusing on recurrent states of phase coherence in fMRI signals, brain activity was examined for intergroup differences through the lens of dynamical systems theory. Results showed reduced fractional occupancy and dwell time of a globally synchronized state in schizophrenia. Conversely, patients exhibited increased fractional occupancy, dwell time and limiting probability of being in states during which canonical functional networks—i.e., Limbic, Dorsal Attention and Somatomotor—synchronized in anti-phase with respect to the rest of the brain. In terms of state-to-state transitions, patients exhibited increased probability of switching to Limbic, Somatomotor and Visual networks, and reduced probability of remaining in states related to the Default Mode network, the Orbitofrontal network and the globally synchronized state. All results revealed medium to large effect sizes. Combined, these findings expose pronounced differences in the temporal expression of resting-state networks in schizophrenia patients, which may relate to the pathophysiology of this disorder. Overall, these results reinforce the utility of dynamical systems theory to extend current knowledge regarding disrupted brain dynamics in psychiatric disorders.
Decision Making as a Learned Skill in Mice and Humans
Authors: Posner Michael I. , Weible Aldis P. , Voelker Pascale , Rothbart Mary K. , Niell Cristopher M.
Published: March 2022

Attention is a necessary component in many forms of human and animal learning. Numerous studies have described how attention and memory interact when confronted with a choice point during skill learning. In both animal and human studies, pathways have been found that connect the executive and orienting networks of attention to the hippocampus. The anterior cingulate cortex, part of the executive attention network, is linked to the hippocampus via the nucleus reuniens of the thalamus. The parietal cortex, part of the orienting attention network, accesses the hippocampus via the entorhinal cortex. These studies have led to specific predictions concerning the functional role of each pathway in connecting the cortex to the hippocampus. Here, we review some of the predictions arising from these studies. We then discuss potential methods for manipulating the two pathways and assessing the directionality of their functional connection using viral expression techniques in mice. New studies may allow testing of a behavioral model specifying how the two pathways work together during skill learning.
Mechanism of Longevity Extension of Caenorhabditis elegans Induced by Schizophyllum commune Fermented Supernatant With Added Radix Puerariae
Authors: Deng Yongfei , Liu Han , Huang Qian , Tu Lingyun , Hu Lu , Zheng Bisheng , Sun Huaiqing , Lu Dengjun , Guo Chaowan , Zhou Lin
Published: March 2022

Schizophyllum commune (S. commune) fermented supernatant with added Radix Puerariae (SC-RP) showed significant antioxidant activity in our previous work. However, the possible lifespan and healthspan extending the capacity of Caenorhabditis elegans (C. elegans) and the underlying mechanism were not illuminated. In this study, the effect of SC-RP on extending the lifespan and improving stress resistance of C. elegans were examined. Additionally, the underlying lifespan extending molecular mechanisms of SC-RP were explored. Treated with SC-RP at 10 μg/mL, the lifespan of C. elegans increased by 24.89% (P < 0.01). Also, SC-RP prolonged the healthspan of the nematode, including reducing lipofuscin levels, improving mobility and enhancing resistance to oxidative stress and heat shock. Moreover, superoxide dismutase and catalase activities were increased for SC-RP treated C. elegans. Meantime the intracellular levels of thiobarbituric acid reactive substances (TBARS) and reactive oxygen species (ROS) were attenuated. Express levels of eight genes including daf-2, daf-16, sod-3, skn-1, gst-4, clk-1, age-1 and mev-1 were analyzed by RT-PCR method for possible C. elegan anti-aging mechanisms of SC-RP. Expression levels of key genes daf-2, gst-4 and sod-3 were up-regulated, while that of daf-16, skn-1, and clk-1 were down-regulated. The results suggest that SC-RP could extend the lifespan and healthspan of C. elegans significantly, and the IIS pathway, SKN-1/Nrf2 pathway and mitochondrial metabolism pathway were primarily considered associated. Thus, SC-RP is a potential component to improve aging and aging-related symptoms as new functional materials.
Identification of Long Noncoding RNAs Associated With the Clinicopathological Features of Papillary Thyroid Carcinoma Complicated With Hashimoto’s Thyroiditis
Authors: Zhang Yu , Lu Kai-Ning , Ding Jin-Wang , Peng You , Pan Gang , Teng Li-Song , Luo Ding-Cun
Published: March 2022

Long noncoding RNAs (lncRNAs) play a significant role in cancer biology. This study aimed to determine the roles of lncRNAs in establishing the differences in clinical features between patients with papillary thyroid carcinoma (PTC) without Hashimoto’s thyroiditis (HT) and patients with PTC and HT. In the present study, we detected the differentially expressed lncRNAs between tumor tissues of patients with PTC with or without HT through lncRNA microarrays. The data were verified and analyzed through qRT-PCR, cell viability, cell cycle and bioinformatics analyses. We found that 1031 lncRNAs and 1338 mRNAs were abnormally expressed in 5 tissue samples of PTC complicated with HT [PTC/HT (+)] compared with 5 samples of PTC without HT [PTC/HT (-)]. Gene Ontology and pathway analyses of the mRNAs suggested that several biological processes and pathways, particularly immune system processes, were induced in the PTC/HT (+) tissues. Twenty lncRNAs were verified in 31 PTC/HT (+) and 64 PTC/HT (-) specimens by qRT-PCR, and the results were consistent with the microarray data. Specifically, ENST00000452578, a downregulated lncRNA in PTC/HT(+), was negatively correlated with the tumor size. Cell viability assays revealed that ENST00000452578 could inhibit cell proliferation. Our results indicate that lncRNAs and mRNAs play an important role in establishing the different clinical characteristics between patients with PTC/HT(+) and patients with PTC/HT(-), and might provide new insights from the perspective of RNA for obtaining a further understanding of the clinical features related to PTC with HT.
Identification of a Mitochondria-Related Gene Signature to Predict the Prognosis in AML
Authors: Jiang Nan , Zhang Xinzhuo , Chen Qi , Kantawong Fahsai , Wan Shengli , Liu Jian , Li Hua , Zhou Jie , Lu Bin , Wu Jianming
Published: March 2022

Mitochondria-related metabolic reprogramming plays a major role in the occurrence, development, drug resistance, and recurrence of acute myeloid leukemia (AML). However, the roles of mitochondria-related genes (MRGs) in the prognosis and immune microenvironment for AML patients remain largely unknown. In this study, by least absolute shrinkage and selection operator (LASSO) Cox regression analysis, 4 MRGs’ (HPDL, CPT1A, IDH3A, and ETFB) signature was established that demonstrated good robustness in TARGET AML datasets. The univariate and multivariate Cox regression analyses both demonstrated that the MRG signature was a robust independent prognostic factor in overall survival prediction with high accuracy for AML patients. Based on the risk score calculated by the signature, samples were divided into high- and low-risk groups. Gene set enrichment analysis (GSEA) suggested that the MRG signature is involved in the immune-related pathways. Via immune infiltration analysis and immunosuppressive genes analysis, we found that MRG risk of AML patients was strikingly positively correlated with an immune cell infiltration and expression of critical immune checkpoints, indicating that the poor prognosis might be caused by immunosuppressive tumor microenvironment (TME). In summary, the signature based on MRGs could act as an independent risk factor for predicting the clinical prognosis of AML and could also reflect an association with the immunosuppressive microenvironment, providing a novel method for AML metabolic and immune therapy based on the regulation of mitochondrial function.
Tumor Treating Fields Suppression of Ciliogenesis Enhances Temozolomide Toxicity
Authors: Shi Ping , Tian Jia , Ulm Brittany S. , Mallinger Julianne C. , Khoshbouei Habibeh , Deleyrolle Loic P. , Sarkisian Matthew R.
Published: March 2022

Tumor Treating Fields (TTFields) are low-intensity, alternating intermediate-frequency (200 kHz) electrical fields that extend survival of glioblastoma patients receiving maintenance temozolomide (TMZ) chemotherapy. How TTFields exert efficacy on cancer over normal cells or interact with TMZ is unclear. Primary cilia are microtubule-based organelles triggered by extracellular ligands, mechanical and electrical field stimulation and are capable of promoting cancer growth and TMZ chemoresistance. We found in both low- and high-grade patient glioma cell lines that TTFields ablated cilia within 24 h. Halting TTFields treatment led to recovered frequencies of elongated cilia. Cilia on normal primary astrocytes, neurons, and multiciliated/ependymal cells were less affected by TTFields. The TTFields-mediated loss of glioma cilia was partially rescued by chloroquine pretreatment, suggesting the effect is in part due to autophagy activation. We also observed death of ciliated cells during TTFields by live imaging. Notably, TMZ and TTFields have opposing effects on glioma ciliogenesis. TMZ-induced stimulation of ciliogenesis in both adherent cells and gliomaspheres was blocked by TTFields. Surprisingly, the inhibitory effects of TTFields and TMZ on tumor cell recurrence are linked to the relative timing of TMZ exposure to TTFields and ARL13B+ cilia. Finally, TTFields disrupted cilia in patient tumors treated ex vivo. Our findings suggest that the efficacy of TTFields may depend on the degree of tumor ciliogenesis and relative timing of TMZ treatment.
Case Report: Niraparib-Related Pulmonary Embolism During the Treatment of BRCA Mutant Advanced Ovarian Cancer
Authors: Wei Qiang , Chen Dong-Sheng , Liu Yuan-Hua
Published: March 2022

Niraparib, an oral, potent, highly selective poly (ADP-ribose) polymerase (PARP) inhibitor, has promising clinical benefit for maintenance treatment of patients with ovarian cancer in partial response to platinum-based chemotherapy, especially in patients with BRCA mutation. In publicly available niraparib treatment-related adverse events, gastrointestinal disorders and hematological toxicities were most commonly reported with manageable safety profile. Herein, we first describe a severe and never-reported pulmonary embolism (PE) associated with the use of niraparib in a patient with BRCA mutation advanced high-grade serous ovarian cancer and received anticoagulant therapy after PE. There have been no reports of PE caused by the use of niraparib in patients with advanced high-grade serous ovarian cancer; knowledge of the occurrence of PE after the use of niraparib may assist other clinicians in managing this rare but potentially serious toxic effect.
OSgc: A Web Portal to Assess the Performance of Prognostic Biomarkers in Gastric Cancer
Authors: Xie Longxiang , Wang Qiang , Yan Zhongyi , Han Yali , Ma Xiaoyu , Li Huimin , Zhang Lu , Li Xianzhe , Guo Xiangqian
Published: March 2022

Evaluating the prognostic value of genes of interest in different populations of gastric cancer (GC) is difficult and time-consuming for basic and translational researchers even though many datasets are available in public dataset depositories. In the current study, we developed a robust web-based portal called OSgc (Online consensus Survival analysis of gastric cancer) that enables easy and swift verification of known and novel biomarker candidates in GC. OSgc is composed of gene expression profiling data and clinical follow-up information of 1,824 clinical GC cases, which are collected from 7 public independent datasets derived from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). By OSgc, users input the official gene symbol and will promptly retrieve the Kaplan–Meier survival plot with hazard ratio (HR) and log rank p value on the output webpage, by which users could assess the prognostic value of interesting genes for GC patients. Five survival end points containing overall survival, progression-free survival, progression-free interval, relapse-free survival, and disease-free survival could be measured in OSgc. OSgc can greatly help cancer biologists and clinicians to explore the effect of gene expression on patient survival. OSgc is freely available without restrictions at http://bioinfo.henu.edu.cn/GC/GCList.jsp.
Ozone Layer Depletion and Emerging Public Health Concerns - An Update on Epidemiological Perspective of the Ambivalent Effects of Ultraviolet Radiation Exposure
Authors: Umar Sheikh Ahmad , Tasduq Sheikh Abdullah
Published: March 2022

Solar ultraviolet (UV) radiation exposure is the primary etiological agent responsible for developing cutaneous malignancies. Avoiding excessive radiation exposure, especially by high-risk groups, is recommended to prevent UV-induced photo-pathologies. However, optimal sun exposure is essential for the healthy synthesis of about 90% of vitamin D levels in the body. Insufficient exposure to UV-B is linked to vitamin D deficiency in humans. Therefore, optimal sun exposure is necessary for maintaining a normal state of homeostasis in the skin. Humans worldwide face a major existential threat because of climate change which has already shown its effects in several ways. Over the last 4 to 5 decades, increased incidences in skin cancer cases have led international health organizations to develop strong sun protection measures. However, at the same time, a growing concern about vitamin D deficiency is creating a kind of exposure dilemma. Current knowledge of UV exposure to skin outweighs the adverse effects than the beneficial roles it offers to the body, necessitating a correct public health recommendation on optimal sun exposure. Following an appropriate recommendation on optimal sun exposure will lead to positive outcomes in protecting humans against the adverse effects of strict recommendations on sun protection measures. In this short review, we spotlight the ambivalent health effects of UV exposure and how ozone layer depletion has influenced these effects of UVR. Further, our aim remains to explore how to lead towards a balanced recommendation on sun protection measures to prevent the spurt of diseases due to inadequate exposure to UV-B.
The Temporal Relationship Between Local School Closure and Increased Incidence of Pediatric Diabetic Ketoacidosis
Authors: McCluskey Casey K. , Zee-Cheng Janine E. , Klein Margaret J. , Scanlon Matthew C. , Rotta Alexandre T. , Remy Kenneth E. , Carroll Christopher L. , Shein Steven L.
Published: March 2022

Importance

The incidence of pediatric diabetic ketoacidosis (DKA) increased early in the COVID-19 pandemic, but the relative contribution of behavioral changes and viral-related pathophysiology are unknown.

Objective

To evaluate the relationship between school closure date and onset of increased DKA to help clarify the etiology of the increased incidence.

Design

A multi-center, quality-controlled Pediatric Intensive Care Unit (PICU) database was used to identify the number of admissions to a participating PICU with DKA on each calendar day from 60 days before local school closure to 90 days after, and compared to baseline data from the same periods in 2018–2019. Interrupted time series and multiple linear regression analyses were used to identify admission rates that differed significantly between 2020 and baseline.

Setting

Eighty-one PICUs in the United States

Participants: Children ages 29 days to 17 years admitted to a PICU with DKA

Exposures: Statewide school closure

Main outcome/measure: Rate of admission to the PICU for DKA.

Results

There were 1936 admissions for children with DKA in 2020 and 1795 admissions/year to those same PICUs in 2018-2019. Demographics and clinical outcomes did not differ before school closure, but pandemic-era patients were less often white and had longer hospital length of stay in the post-school closure period. The difference between 2020 admissions and 2018-2019 admissions was not different than zero before school closure, and significantly higher than zero after school closure, but was significantly increased in 2020 at >30 days after school closure (p = 0.039).

Conclusions/Relevance

An increase in pediatric DKA admissions began one month after school closures. Given that behavioral changes started near school closure dates and viral activity peaked weeks after, this suggests that behavioral factors may not be the primary etiology and it is possible that SARS-CoV-2 infection may have direct effects on pediatric DKA.
Efficacy and Safety of Daprodustat Vs rhEPO for Anemia in Patients With Chronic Kidney Disease: A Meta-Analysis and Trial Sequential Analysis
Authors: Fu Zhangning , Geng Xiaodong , Chi Kun , Song Chengcheng , Wu Di , Liu Chao , Hong Quan
Published: March 2022

Introduction: Daprodustat, a novel hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI), its efficacy and safety remain unclear. Thus, we conducted this meta-analysis aiming at investigating its efficacy and safety on the treatment of patients with chronic kidney disease (CKD)-related anemia.

Methods: We systematically searched for relevant studies in PubMed, Embase, Cochrane Library and Clinical Trial Registries databases from inception until December 2021. We selected randomized controlled trials comparing daprodustat with recombinant human erythropoietin (rhEPO) in anemia patients with CKD with or without dialysis.

Results: Seven studies including 7933 patients met the inclusion criteria. For both nondialysis-dependent (NDD-) CKD and dialysis-dependent (DD-) CKD patients, the pooled results showed that there was no significant difference in the changes in hemoglobin levels between the daprodustat and rhEPO groups (mean difference (MD) = −0.01, 95% confidence interval (CI) = −0.38, 0.35, p = 0.95; MD = 0.15, 95% CI = −0.29, 0.60, p = 0.50; respectively). In addition, a significant increase in transferrin saturation (TSAT), total iron binding capacity (TIBC) and total iron was observed in daprodustat groups compared with rhEPO groups in DD-CKD patients (p < 0.05). As for safety, the overall frequency of adverse events was similar between the daprodustat and rhEPO groups in DD-CKD patients (relative risk (RR) = 0.99, 95%CI = 0.92, 1.06, p = 0.76), and the trial sequential analysis (TSA) confirmed this result. But for NDD-CKD patients, the incidence of adverse events in the daprodustat groups was significantly higher than that of rhEPO groups (RR = 1.04, 95%CI = 1.01,1.07, p = 0.02), while the TSA corrected this result. No trend of increasing incidence of serious adverse events was found in all daprodustat treated patients, but the TSA could not confirm this result.

Conclusion: Although daprodustat was noninferior to rhEPO in correcting anemia in both NDD-CKD and DD-CKD patients, it seemed to have a better effect on optimizing iron metabolism in DD-CKD patients. Daprodustat may be a promising alternative for the treatment of anemia in patients with CKD. However, due to the lack of included studies, future researches are needed to further evaluate the therapeutic effect of daprodustat.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42021229636.
A Comprehensive Review of the Main Lignan Components of Schisandra chinensis (North Wu Wei Zi) and Schisandra sphenanthera (South Wu Wei Zi) and the Lignan-Induced Drug-Drug Interactions Based on the Inhibition of Cytochrome P450 and P-Glycoprotein Activities
Authors: Zhang Feng , Zhai Jianxiu , Weng Nan , Gao Jie , Yin Jun , Chen Wansheng
Published: March 2022

Wu Wei Zi is the dried fruit of Schisandra chinensis (Turcz.) Baill. or Schisandra sphenanthera Rehd. et Wils. (family Magnoliaceae). As a homology of medicine and food, it has been widely used in China for thousands of years, to tonify the kidney, and ameliorate neurological, cardiovascular, liver, and gastrointestinal disorders. As its increasing health benefits and pharmacological value, many literatures have reported that the combination of Wu Wei Zi in patients has led to fluctuations in the blood level of the combined drug. Therefore, it is extremely important to evaluate its safety concern such as drug-drug interactions (DDIs) when patients are under the poly-therapeutic conditions. This review summarized the effects of Wu Wei Zi extract and its major lignan components on cytochrome P450 and P-glycoprotein activities, the change of which could induce metabolic DDIs. Our review also elaborated on the differences of the major lignan components of the two Schisandra species, as well as the absorption, distribution, metabolism, and elimination of the major lignans. In conclusion, these results would enhance our understanding of the DDI mechanisms involving Wu Wei Zi, and may potentially untangle some differing and conflicting results in the future.
Hypericum lanceolatum Lam. Medicinal Plant: Potential Toxicity and Therapeutic Effects Based on a Zebrafish Model
Authors: Gence Laura , Fernezelian Danielle , Bringart Matthieu , Veeren Bryan , Christophe Armelle , Brion François , Meilhac Olivier , Bascands Jean-Loup , Diotel Nicolas
Published: March 2022

Hypericum lanceolatum Lam. (H. lanceolatum) is a traditional medicinal plant from Reunion Island used for its pleiotropic effects mainly related to its antioxidant activity. The present work aimed to 1) determine the potential toxicity of the plant aqueous extract in vivo and 2) investigate its putative biological properties using several zebrafish models of oxidative stress, regeneration, estrogenicity, neurogenesis and metabolic disorders. First, we characterized the polyphenolic composition by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and identified chlorogenic acid isomers, quercetin and kaempferol derivatives as the major compounds. We then evaluated for the first time the toxicity of an aqueous extract of H. lanceolatum and determined a maximum non-toxic concentration (MNTC) in zebrafish eleutheroembryos from 0 to 96 hpf following OECD (Organization for Economic Cooperation and Development) guidelines. This MNTC test was also determined on hatched eleutheroembryos after 2 days of treatment (from 3 to 5 dpf). In our study, the anti-estrogenic effects of H. lanceolatum are supported by the data from the EASZY assay. In a tail amputation model, we showed that H. lanceolatum at its MNTC displays antioxidant properties, favors immune cell recruitment and tissue regeneration. Our results also highlighted its beneficial effects in metabolic disorders. Indeed, H. lanceolatum efficiently reduces lipid accumulation and body mass index in overfed larva- and adult-models, respectively. In addition, we show that H. lanceolatum did not improve fasting blood glucose levels in a hyperglycemic zebrafish model but surprisingly inhibited neurogenesis impairment observed in diabetic conditions. In conclusion, our study highlights the antioxidant, pro-regenerative, anti-lipid accumulation and pro-neurogenic effects of H. lanceolatum in vivo and supports the use of this traditional medicinal plant as a potential alternative in the prevention and/or treatment of metabolic disorders.
“Existential Catastrophe Anxiety”: Phenomenology of Fearful Emotions in a Subset of Service Users With Severe Mental Health Conditions
Authors: Heggdal Didrik , Borgejordet Synne , Fosse Roar
Published: March 2022

A subset of people with severe mental health conditions feels they are on the verge of losing control, even in the absence of external threats or triggers. Some go to extreme ends to avoid affective arousal and associated expectations of a possible, impending catastrophe. We have learned about such phenomenological, emotional challenges in a group of individuals with severe, composite mental health problems and psychosocial disabilities. These individuals have had long treatment histories in the mental health care system. They have been encountered at a specialized inpatient ward offering exposure-based therapy that aims at restoring self-regulation and recovery. We describe the phenomenology of anxiety and fear presented by these service users, a fear we have coined existential catastrophe anxiety (ECa). We also suggest a set of underlying, interacting, psychological mechanisms that may give rise to ECa, before comparing ECa with three other constructs previously described in the literature—annihilation anxiety, ontological insecurity, and affect phobia. These comparisons show several similarities, but also unique qualities with ECa and its suggested underlying mechanisms. The conceptualization of ECa may aid clinicians in addressing extreme experiential turmoil and engage service users in empowering therapeutic projects.
The Effect of Abusive Supervision on Employee Creativity: The Mediating Role of Negative Affect and Moderating Role of Interpersonal Harmony
Authors: Chen Lili , Ye Zhixiao , Shafait Zahid , Zhu Hongying
Published: March 2022

This study investigates the relationship between abusive supervision and employee creativity by shedding light on the mediating role of negative affect and the moderating role of interpersonal harmony. Based on affective events theory, it was hypothesized that abusive supervision impacts employees’ negative affect and their creativity. Data from a questionnaire survey of 398 Chinese employee–supervisor dyads were collected and analyzed. The results support our hypotheses, address unexplored theoretical predictions, and suggest that organizations should deal with the factors undermining employees’ emotions to improve their creativity.