bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between the LACE+ index and unplanned 30-day hospital readmissions in hospitalized patients with stroke
Authors: Jun-O'Connell Adalia H. , Grigoriciuc Eliza , Silver Brian , Kobayashi Kimiyoshi J. , Osgood Marcey , Moonis Majaz , Henninger Nils
Published: October 2022

Background

The LACE+ index is used to predict unplanned 30-day hospital readmissions, but its utility to predict 30-day readmission in hospitalized patients with stroke is unknown.

Methods

We retrospectively analyzed 1,657 consecutive patients presenting with ischemic or hemorrhagic strokes, included in an institutional stroke registry between January 2018 and August 2020. The primary outcome of interest was unplanned 30-day readmission for any reason after index hospitalization for stroke. The 30-day readmission risk was categorized by LACE+ index to high risk (≥78), medium-to-high risk (59–77), medium risk (29–58), and low risk (≤ 28). Kaplan-Meier analysis, Log rank test, and multivariable Cox regression analysis (with backward elimination) were used to determine whether the LACE+ score was an independent predictor for 30-day unplanned readmission.

Results

The overall 30-day unplanned readmission rate was 11.7% (194/1,657). The median LACE+ score was higher in the 30-day readmission group compared to subjects that had no unplanned 30-day readmission [74 (IQR 67–79) vs. 70 (IQR 62–75); p < 0.001]. On Kaplan-Meier analysis, the high-risk group had the shortest 30-day readmission free survival time as compared to medium and medium-to-high risk groups (p < 0.01, each; statistically significant). On fully adjusted multivariable Cox-regression, the highest LACE+ risk category was independently associated with the unplanned 30-day readmission risk (per point: HR 1.67 95%CI 1.23–2.26, p = 0.001).

Conclusion

Subjects in the high LACE+ index category had a significantly greater unplanned 30-day readmission risk after stroke as compared to lower LACE+ risk groups. This supports the validity of the LACE+ scoring system for predicting unplanned readmission in subjects with stroke. Future studies are warranted to determine whether LACE+ score-based risk stratification can be used to devise early interventions to mitigate the risk for unplanned readmission.
Are we really unconscious in “unconscious” states? Common assumptions revisited
Authors: Sevenius Nilsen Andre , Juel Bjørn E. , Thürer Benjamin , Aamodt Arnfinn , Storm Johan F.
Published: October 2022

In the field of consciousness science, there is a tradition to categorize certain states such as slow-wave non-REM sleep and deep general anesthesia as “unconscious”. While this categorization seems reasonable at first glance, careful investigations have revealed that it is not so simple. Given that (1) behavioral signs of (un-)consciousness can be unreliable, (2) subjective reports of (un-)consciousness can be unreliable, and, (3) states presumed to be unconscious are not always devoid of reported experience, there are reasons to reexamine our traditional assumptions about “states of unconsciousness”. While these issues are not novel, and may be partly semantic, they have implications both for scientific progress and clinical practice. We suggest that focusing on approaches that provide a more pragmatic and nuanced characterization of different experimental conditions may promote clarity in the field going forward, and help us build stronger foundations for future studies.
Impact of early brain lesions on the optic radiations in children with cerebral palsy
Authors: Araneda Rodrigo , Ebner-Karestinos Daniela , Dricot Laurance , Herman Enimie , Hatem Samar M. , Friel Kathleen M. , Gordon Andrew M. , Bleyenheuft Yannick
Published: October 2022

Due to their early brain lesion, children with unilateral spastic cerebral palsy (USCP) present important changes in brain gray and white matter, often manifested by perturbed sensorimotor functions. We predicted that type and side of the lesion could influence the microstructure of white matter tracts. Using diffusion tensor imaging in 40 children with USCP, we investigated optic radiation (OR) characteristics: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). First, we compared the OR of the lesional and non-lesional hemisphere. Then we evaluated the impact of the brain lesion type (periventricular or cortico-subcortical) and side in the differences observed in the lesional and non-lesional OR. Additionally, we examined the relationship between OR characteristics and performance of a visuospatial attention task. We observed alterations in the OR of children with USCP on the lesional hemisphere compared with the non-lesional hemisphere in the FA, MD and RD. These differences were influenced by the type of lesion and by the side of the lesion. A correlation was also observed between FA, MD and RD and the visuospatial assessment mainly in children with periventricular and right lesions. Our results indicate an important role of the timing and side of the lesion in the resulting features of these children’s OR and probably in the compensation resulting from neuroplastic changes.
Activation of dopamine D2 receptors attenuates neuroinflammation and ameliorates the memory impairment induced by rapid eye movement sleep deprivation in a murine model
Authors: Ugalde-Muñiz Perla , Hernández-Luna María Guadalupe , García-Velasco Stephany , Lugo-Huitrón Rafael , Murcia-Ramírez Jimena , Martínez-Tapia Ricardo Jesus , Noriega-Navarro Roxana , Navarro Luz
Published: October 2022

The proinflammatory state, which may be induced by sleep deprivation, seems to be a determining factor in the development of neurodegenerative processes. Investigations of mechanisms that help to mitigate the inflammatory effects of sleep disorders are important. A new proposal involves the neurotransmitter dopamine, which may modulate the progression of the immune response by activating receptors expressed on immune cells. This study aimed to determine whether dopamine D2 receptor (D2DR) activation attenuates the proinflammatory response derived from rapid eye movement (REM) sleep deprivation in mice. REM sleep deprivation (RSD) was induced in 2-month-old male CD1 mice using the multiple platform model for three consecutive days; during this period, the D2DR receptor agonist quinpirole (QUIN) was administered (2 mg/kg/day i.p.). Proinflammatory cytokine levels were assessed in serum and homogenates of the brain cortex, hippocampus, and striatum using ELISAs. Long-term memory deficits were identified using the Morris water maze (MWM) and novel object recognition (NOR) tests. Animals were trained until learning criteria were achieved; then, they were subjected to RSD and treated with QUIN for 3 days. Memory evocation was determined afterward. Moreover, we found RSD induced anhedonia, as measured by the sucrose consumption test, which is commonly related to the dopaminergic system. Our data revealed increased levels of proinflammatory cytokines (TNFα and IL-1β) in both the hippocampus and serum from RSD mice. However, QUIN attenuated the increased levels of these cytokines. Furthermore, RSD caused a long-term memory evocation deficit in both the MWM and NOR tests. In contrast, QUIN coadministration during the RSD period significantly improved the performance of the animals. On the other hand, QUIN prevented the anhedonic condition induced by RSD. Based on our results, D2DR receptor activation protects against memory impairment induced by disturbed REM sleep by inhibiting neuroinflammation.
Efficacy of miRNA-modified mesenchymal stem cell extracellular vesicles in spinal cord injury: A systematic review of the literature and network meta-analysis
Authors: Yang Zhelun , Rao Jian , Liang Zeyan , Xu Xiongjie , Lin Fabin , Lin Yike , Wang Chunhua , Chen Chunmei
Published: October 2022

Background

Although some previous studies have indicated that extracellular vesicles (EVs) secreted from miRNA-modified mesenchymal stem cells (MSCs) may be more effective as compared with control EVs in the treatment of rats with spinal cord injuries (SCI), the efficacy of this treatment modality remains controversial.

Objectives

The current study comprehensively evaluated the efficacy of different administered doses of EVs, including miRNA-overexpressing MSCs-derived EVs, among SCI rats. The efficacy of EVs' treatment was evaluated in different SCI models to provide evidence for preclinical trials.

Methods

We extensively searched the following databases to identify relevant studies: PubMed, Embase, Scopus, The Cochrane Library, and Web of Science (from inception to July 20, 2022). Two trained investigators independently screened literature, extracted the data, and evaluated literature quality.

Results

Thirteen studies were included in this network meta-analysis. The results demonstrated that miRNA-overexpressing MSCs-derived EVs (100 and 200 μg of total protein of EVs) significantly improved hind limb motor function in rats at early stages of SCI (i.e., at 3 days after injury) as compared with EVs (100 and 200 μg of total protein of EVs, respectively). However, in the middle and late stages (14 and 28 days), there were no statistically significant differences between EVs with 200 μg dosages and miRNA-loaded EVs with 100 μg dosages. In the late stages (28 days), there were no statistically significant differences between EVs with 100 μg dosages and miRNA-loaded EVs with 200 μg dosages. We found that miRNA-overexpressing MSCs-derived EVs significantly improved motor function among early-stage SCI rats in a compression and contusion model (3 days) as compared with MSCs-derived EVs and miRNA-overexpressing MSCs-derived EVs likewise significantly improved motor function among SCI rats in a contusion model at middle and late stages (14 and 28 days).

Conclusion

Our results suggest that miRNA-overexpressing MSCs-derived EVs (200 μg of total protein of EVs) may be the best choice for the effective treatment of SCI, and miRNA-overexpressing MSCs-derived EVs may likewise be the best choice for treating contusions. However, there are some risks of bias in our included studies, and the mechanisms underlying the efficacy of EVs remain unclear.

Systematic review registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=282051, identifier: CRD42021282051.
The distinctive role of menthol in pain and analgesia: Mechanisms, practices, and advances
Authors: Li Ziping , Zhang Haoyue , Wang Yigang , Li Yize , Li Qing , Zhang Linlin
Published: October 2022

Menthol is an important flavoring additive that triggers a cooling sensation. Under physiological condition, low to moderate concentrations of menthol activate transient receptor potential cation channel subfamily M member 8 (TRPM8) in the primary nociceptors, such as dorsal root ganglion (DRG) and trigeminal ganglion, generating a cooling sensation, whereas menthol at higher concentration could induce cold allodynia, and cold hyperalgesia mediated by TRPM8 sensitization. In addition, the paradoxical irritating properties of high concentrations of menthol is associated with its activation of transient receptor potential cation channel subfamily A member 1 (TRPA1). Under pathological situation, menthol activates TRPM8 to attenuate mechanical allodynia and thermal hyperalgesia following nerve injury or chemical stimuli. Recent reports have recapitulated the requirement of central group II/III metabotropic glutamate receptors (mGluR) with endogenous κ-opioid signaling pathways for menthol analgesia. Additionally, blockage of sodium channels and calcium influx is a determinant step after menthol exposure, suggesting the possibility of menthol for pain management. In this review, we will also discuss and summarize the advances in menthol-related drugs for pathological pain treatment in clinical trials, especially in neuropathic pain, musculoskeletal pain, cancer pain and postoperative pain, with the aim to find the promising therapeutic candidates for the resolution of pain to better manage patients with pain in clinics.
Plasticity of the hypocretinergic/orexinergic system after a chronic treatment with suvorexant in rats. Role of the hypocretinergic/orexinergic receptor 1 as an autoreceptor
Authors: Carrera-Cañas Carlos , de Andrés Isabel , Callejo Marta , Garzón Miguel
Published: October 2022

The hypothalamic hypocretinergic/orexinergic (Hcrt/Ox) system is involved in many physiological and pathophysiological processes. Malfunction of Hcrt/Ox transmission results in narcolepsy, a sleep disease caused in humans by progressive neurodegeneration of hypothalamic neurons containing Hcrt/Ox. To explore the Hcrt/Ox system plasticity we systemically administered suvorexant (a dual Hcrt/Ox receptor antagonist) in rats to chronically block Hcrt/Ox transmission without damaging Hcrt/Ox cells. Three groups of eight rats (four males and four females) received daily i.p. injections of suvorexant (10 or 30 mg/kg) or vehicle (DMSO) over a period of 7 days in which the body weight was monitored. After the treatments cerebrospinal fluid (CSF) Hcrt1/OxA concentration was measured by ELISA, and hypothalamic Hcrt/OxR1 and Hcrt/OxR2 levels by western blot. The systemic blockade of the Hcrt/Ox transmission with the suvorexant high dose produced a significant increase in body weight at the end of the treatment, and a significant decrease in CSF Hcrt1/OxA levels, both features typical in human narcolepsy type 1. Besides, a significant overexpression of hypothalamic Hcrt/OxR1 occurred. For the Hcrt/OxR2 two very close bands were detected, but they did not show significant changes with the treatment. Thus, the plastic changes observed in the Hcrt/Ox system after the chronic blockade of its transmission were a decrease in CSF Hcrt1/OXA levels and an overexpression of hypothalamic Hcrt/OxR1. These findings support an autoregulatory role of Hcrt/OxR1 within the hypothalamus, which would induce the synthesis/release of Hcrt/Ox, but also decrease its own availability at the plasma membrane after binding Hcrt1/OxA to preserve Hcrt/Ox system homeostasis.
Dynorphin/kappa opioid receptor system regulation on amygdaloid circuitry: Implications for neuropsychiatric disorders
Authors: Limoges Aaron , Yarur Hector E. , Tejeda Hugo A.
Published: October 2022

Amygdaloid circuits are involved in a variety of emotional and motivation-related behaviors and are impacted by stress. The amygdala expresses several neuromodulatory systems, including opioid peptides and their receptors. The Dynorphin (Dyn)/kappa opioid receptor (KOR) system has been implicated in the processing of emotional and stress-related information and is expressed in brain areas involved in stress and motivation. Dysregulation of the Dyn/KOR system has also been implicated in various neuropsychiatric disorders. However, there is limited information about the role of the Dyn/KOR system in regulating amygdala circuitry. Here, we review the literature on the (1) basic anatomy of the amygdala, (2) functional regulation of synaptic transmission by the Dyn/KOR system, (3) anatomical architecture and function of the Dyn/KOR system in the amygdala, (4) regulation of amygdala-dependent behaviors by the Dyn/KOR system, and (5) future directions for the field. Future work investigating how the Dyn/KOR system shapes a wide range of amygdala-related behaviors will be required to increase our understanding of underlying circuitry modulation by the Dyn/KOR system. We anticipate that continued focus on the amygdala Dyn/KOR system will also elucidate novel ways to target the Dyn/KOR system to treat neuropsychiatric disorders.
The Aurantii Fructus Immaturus flavonoid extract alleviates inflammation and modulate gut microbiota in DSS-induced colitis mice
Authors: Chen Si-Yuan , Zhou Qing Yi-Jun , Chen Lin , Liao Xin , Li Ran , Xie Tao
Published: October 2022

Inflammatory bowel disease (IBD) is a chronic, relapsing immune-mediated disease that always leads to a progressive loss of intestinal function. Therefore, it is important to find potential therapeutic drugs. This study was conducted to elucidate the effect of Aurantii Fructus immaturus flavonoid extract (AFI, 8% neohesperidin, 10% naringin) on DSS-induced intestinal inflammation and the gut microbiome. To explore the mechanism of action by which AFI protects against intestinal inflammation, a total of 50 mice were randomly divided into 5 groups [CG (control group), MG (model group), AFI low dose, AFI middle dose, and AFI high dose] and received 2.5% DSS for 7 days. Then, mice in the AFI groups were orally administered different doses of AFI for 16 days. The results showed that, compared with the MG group, the food intake and body weight were increased in the AFI groups, but the water intake was lower. Additionally, AFI significantly alleviated DSS-induced colitis symptoms, including disease activity index (DAI), and colon pathological damage. The levels of IL-6, IL-1β and TNF-α in serum and colon tissue were significantly decreased. The diversity and abundance of the intestinal microbiota in the AFI group were decreased. The relative abundance of Bacteroidota was increased, and the relative abundance of Firmicutes was decreased. AFI plays an important role in alleviating DSS-induced intestinal inflammation and regulating Oscillospira, Prevotellaceae and Lachnospiraceae in the intestine at low, medium and high doses, respectively. This report is a pioneer in the assessment of AFI. This study not only demonstrated the anti-inflammatory activity of AFI but also identified the microbiota regulated by different concentrations of AFI.
Integration of ATAC-seq and RNA-seq analysis identifies key genes affecting intramuscular fat content in pigs
Authors: Xu Zhong , Wu Junjing , Zhou Jiawei , Zhang Yu , Qiao Mu , Sun Hua , Li Zipeng , Li Lianghua , Chen Nanqi , Oyelami Favour Oluwapelumi , Peng Xianwen , Mei Shuqi
Published: October 2022

Meat quality is one of the most important economic traits in pig breeding and production, and intramuscular fat (IMF) content is the major factor in improving meat quality. The IMF deposition in pigs is influenced by transcriptional regulation, which is dependent on chromatin accessibility. However, how chromatin accessibility plays a regulatory role in IMF deposition in pigs has not been reported. Xidu black is a composite pig breed with excellent meat quality, which is an ideal research object of this study. In this study, we used the assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing (RNA-seq) analysis to identify the accessible chromatin regions and key genes affecting IMF content in Xidu black pig breed with extremely high and low IMF content. First, we identified 21,960 differential accessible chromatin peaks and 297 differentially expressed genes. The motif analysis of differential peaks revealed several potential cis-regulatory elements containing binding sites for transcription factors with potential roles in fat deposition, including Mef2c, CEBP, Fra1, and AP-1. Then, by integrating the ATAC-seq and RNA-seq analysis results, we found 47 genes in the extremely high IMF (IMF_H) group compared with the extremely low IMF (IMF_L) group. For these genes, we observed a significant positive correlation between the differential gene expression and differential ATAC-seq signal (r2 = 0.42). This suggests a causative relationship between chromatin remodeling and the resulting gene expression. We identified several candidate genes (PVALB, THRSP, HOXA9, EEPD1, HOXA10, and PDE4B) that might be associated with fat deposition. Through the PPI analysis, we found that PVALB gene was the top hub gene. In addition, some pathways that might regulate fat cell differentiation and lipid metabolism, such as the PI3K-Akt signaling pathway, MAPK signaling pathway, and calcium signaling pathway, were significantly enriched in the ATAC-seq and RNA-seq analysis. To the best of our knowledge, our study is the first to use ATAC-seq and RNA-seq to examine the mechanism of IMF deposition from a new perspective. Our results provide valuable information for understanding the regulation mechanism of IMF deposition and an important foundation for improving the quality of pork.
Effectiveness of a teaching unit on the willingness to consume insect-based food – An intervention study with adolescents from Germany
Authors: Szczepanski Lena , Dupont Jacqueline , Schade Fenja , Hellberg Henrike , Büscher Milan , Fiebelkorn Florian
Published: October 2022

This study investigated the effect of a four-lesson teaching unit titled “Entomophagy and Sustainability” on the willingness of adolescents in Germany to consume insect-based food (N = 114; MAge = 15.77 years; SDAge = 1.12 years; female = 58.8%). The main aim of the study was to test whether the teaching unit can induce long-term changes in selected nutritional-psychological factors (food disgust, food neophobia, food technology neophobia), attitudes, knowledge, and the willingness to consume insect-based food. For this purpose, a paper-pencil questionnaire was conducted immediately before (pre-test), immediately after (post-test), and approximately six weeks after (follow-up test) the teaching unit. Although significant changes in food disgust, food neophobia, food technology neophobia, attitudes, and knowledge were recorded, adolescents’ willingness to consume insect-based food was not significantly increased. Attitudes were identified as the strongest predictor of adolescents’ willingness to consume, while knowledge was not a significant predictor. Conclusions and recommendations that can be applied to other educational interventions are provided to increase the effectiveness of the teaching unit.
Swallowing function after acute ischemic stroke: Development and validation of a novel clinical prognostic model
Authors: Zhang Peiliang , Zhang Wenbo , Shi Wujie , Weng Jianbin , Zhang Zhongyuan , Lin Chao , Wang Ning , Shen Zhipeng , Chen Zhi-Lin
Published: October 2022

Background

Predicting the duration of dysphagia after acute ischemic stroke (AIS) is important for clinical treatment decisions.

Objective

The purpose of this study is to assess the swallowing function of AIS patients and to develop and validate a prognostic model for the need for nasogastric tube (NGT) in these patients.

Materials and methods

We included 554 AIS patients during 2018–2019 as the development group and had 186 AIS patients as the external validation group. The primary end point of the study was the retention of NGT in patients 1 week after admission (Functional Oral Intake Scale ≤ 4). Swallowing function and stroke-associated pneumonia (SAP) at 1 month post-onset were also the objectives of this study. The volume-viscosity swallow test (V-VST) was used to assess the patient’s impaired swallowing function. The Predictive model was built by logistic regression.

Results

Overall, a total of 104 patients required indwelling NGT at 1 week of AIS onset in development group. The final prognostic model includes 5 variables: age (OR: 1.085, 95%CI: 1.049–1.123), neutrophil-to-lymphocyte ratio (NLR) (OR: 1.332, 95%CI: 1.090–1.626), NIHSS (OR: 1.092, 95%CI: 1.025–1.164), history of drinking (OR: 2.532, 95%CI: 1.452–4.417) and stroke location (Subtentorial vs. Supratentorial, OR: 1.954, 95%CI: 1.088–3.509). The prediction model had an AUC of 0.810, while the external validation group was 0.794.

Conclusion

In stroke patients, it is very important to decide early whether to indwell a NGT. The nomogram will support decision making for NGT insertion and help these patients recover from their condition.
A cross-sectional study on dietary assessment, oral hygiene behavior, and oral health status of adolescent girls
Authors: Mahriani Yuni , Indriyanti Ratna , Musnamirwan Iwan Ahmad , Setiawan Arlette Suzy
Published: October 2022

Adolescents are a population group that is vulnerable to nutritional problems other than toddlers, especially young women. Special attention to the dietary issues of adolescent girls needs to be obtained along with the increase in the adolescent population in Indonesia because this affects the growth and development of the body and will impact adult nutrition problems. The purpose of the study was to analyze the relationship between diet assessment and oral health status of adolescent girls, the relationship between oral hygiene behavior and oral health status of adolescent girls, and the simultaneous relationship between dietary assessment and oral hygiene behavior with the oral health status of adolescent girls. Analytical research using the survey method was conducted on 96 young women in two junior high schools in Bandung. Assessment of diet seen from eating behavior and anthropometric examination. Eating behavior using the Adolescent Food Habit Checklist Index questionnaire and anthropometric investigations were carried out by looking at body height, body weight, and Mid Upper Arm Circumference using the standards from the Indonesian Minister of Health Regulation 2020. Oral hygiene behavior using the Oral Hygiene Behavior Index questionnaire. Oral health status using the Dental Health Status Assessment. The results were statistically analyzed with Spearman’s Rank Correlation, and Multiple Linear Regression tests showed no significant relationship between dietary assessment and oral health status (eating behavior with a p-value = 0.429 and anthropometric examination with a p-value = 0.262). A significant association between oral hygiene behavior and oral health status, with a p-value of 0.003, while there is no simultaneous relationship between diet assessment and oral hygiene behavior with oral health status, with multiple r2 = 13.2%.
The prognostic nutritional index, an independent predictor of overall survival for newly diagnosed follicular lymphoma in China
Authors: Ge Jingjing , Lei Yaxin , Wen Qing , Zhang Yue , Kong Xiaoshuang , Wang Wenhua , Qian Siyu , Hou Huting , Wang ZeYuan , Wu Shaoxuan , Dong Meng , Ding Mengjie , Wu Xiaolong , Feng Xiaoyan , Zhu Linan , Zhang Mingzhi , Chen Qingjiang , Zhang Xudong
Published: October 2022

Objective

The prognostic nutritional index (PNI) is an important prognostic factor for survival outcomes in various hematological malignancies. The current study focused on exploring the predictive value of the PNI in newly diagnosed follicular lymphoma (FL) in China.

Materials and methods

The clinical indicators and follow-up data of 176 patients who received chemotherapy or immunotherapy combined with chemotherapy with FL in our hospital from January 2016 to March 2022 were retrospectively analyzed. Cox proportional hazard model was used for univariate and multivariate analyses. Kaplan–Meier curves were used to calculate survival rates and draw survival curves. The log-rank test was applied to compare differences between groups.

Results

The optimal cut-off value of PNI was 44.3. All patients were divided into a high PNI group (>44.3) and a low PNI group (≤44.3). The low PNI group had a low CR rate and a high risk of death, with a tendency toward POD24, and Both OS and PFS were worse than those in the high PNI group. PNI was able to predict OS and PFS in FL patients and was the only independent predictor of OS (P = 0.014 HR 5.024; 95%CI 1.388∼18.178) in multivariate analysis. PNI could re-stratify patients into groups of high FLIPI score, high FLIPI2 score, no POD24, and rituximab combined with chemotherapy. Moreover, integrating PNI into the FLIPI and FLIPI2 models improved the area under the curve (AUC) for more accurate survival prediction and prognosis.

Conclusion

PNI is a significant prognostic indicator for newly diagnosed FL in China that can early identify patients with poor prognosis and guide clinical treatment decisions.
Amino acid metabolism in primary bone sarcomas
Authors: Jiménez Jennifer A. , Lawlor Elizabeth R. , Lyssiotis Costas A.
Published: October 2022

Primary bone sarcomas, including osteosarcoma (OS) and Ewing sarcoma (ES), are aggressive tumors with peak incidence in childhood and adolescence. The intense standard treatment for these patients consists of combined surgery and/or radiation and maximal doses of chemotherapy; a regimen that has not seen improvement in decades. Like other tumor types, ES and OS are characterized by dysregulated cellular metabolism and a rewiring of metabolic pathways to support the biosynthetic demands of malignant growth. Not only are cancer cells characterized by Warburg metabolism, or aerobic glycolysis, but emerging work has revealed a dependence on amino acid metabolism. Aside from incorporation into proteins, amino acids serve critical functions in redox balance, energy homeostasis, and epigenetic maintenance. In this review, we summarize current studies describing the amino acid metabolic requirements of primary bone sarcomas, focusing on OS and ES, and compare these dependencies in the normal bone and malignant tumor contexts. We also examine insights that can be gleaned from other cancers to better understand differential metabolic susceptibilities between primary and metastatic tumor microenvironments. Lastly, we discuss potential metabolic vulnerabilities that may be exploited therapeutically and provide better-targeted treatments to improve the current standard of care.
Treatment options for acute myeloid leukemia patients aged <60 years
Authors: Visani Giuseppe , Chiarucci Martina , Paolasini Sara , Loscocco Federica , Isidori Alessandro
Published: October 2022

Treatment of acute myeloid leukemia (AML) has changed over the last few years, after the discovery of new drugs selectively targeting AML blasts. Although 3/7 remains the standard of care for most AML patients, several new targeted agents (such as FLT3 inhibitors, CPX-351, gemtuzumab ozogamicin, BCL-2 inhibitor, and oral azacitidine), either as single agents or combined with standard chemotherapy, are approaching clinical practice, starting a new era in AML management. Moreover, emerging evidence has demonstrated that high-risk AML patients might benefit from both allogeneic stem cell transplant and maintenance therapy, providing new opportunities, as well as new challenges, for treating clinicians. In this review, we summarize available data on first-line therapy in young AML patients focusing on targeted therapies, integrating established practice with new evidence, in the effort to outline the contours of a new therapeutic paradigm, that of a “total therapy”, which goes beyond obtaining complete remission.
Malnutrition management in oncology: An expert view on controversial issues and future perspectives
Authors: Bossi Paolo , De Luca Raffaele , Ciani Oriana , D’Angelo Elisa , Caccialanza Riccardo
Published: October 2022

Cancer and anticancer treatments can lead to several negative side effects, including malnutrition. Despite the recognized need for adequate nutritional support in cancer patients, in daily clinical practice, nutrition is still not considered one of the first aspects to be considered. Malnutrition negatively affects the clinical outcomes, treatment response, and overall survival of cancer patients. In this study, three of the most controversial issues related to malnutrition, which emerged during an Italian Consensus Conference, were addressed specifically for patients with head and neck as well as gastrointestinal cancer. The timing of nutritional evaluation and intervention, extension of the Enhanced Recovery after Surgery (ERAS®) protocols, and cost-effectiveness of nutritional interventions have been considered. This study aimed to illustrate the state-of-the art of each issue and hypothesize future perspectives and actions to be taken, trying to suggest a new nutritional management model for cancer patients in Italy that overcomes the critical issues encountered. Of note, the timely diagnosis of nutritional issue appears to be essential to ensure the correct management of malnourished cancer patients as well as those who are at high risk of malnutrition. Standardized protocols, screening tests, and the inclusion of nutritional parameters in patient medical records would help to achieve good clinical outcomes. Finally, appropriate nutritional support is also associated with cost savings, and it seems necessary to promote its clinical and economic value to obtain improvements in both outcomes and management costs.
Loss of exosomal micro-RNA-200b-3p from hypoxia cancer-associated fibroblasts reduces sensitivity to 5-flourouracil in colorectal cancer through targeting high-mobility group box 3
Authors: Yuan Hang , Chen Bingchen , Chai Rui , Gong Wenjing , Wan Ziang , Zheng Boan , Hu Xinye , Guo Yang , Gao Shan , Dai Qiaoqiong , Yu Peng , Tu Shiliang
Published: October 2022

Hypoxia-mediated tumor progression is a major problem in colorectal cancer (CRC). MicroRNA (miR)-200b-3p can attenuate tumorigenesis in CRC, while exosomal miRNAs derived from cancer-associated fibroblasts (CAFs) can promote cancer progression. Nevertheless, the function of exosomal miR-200b-3p derived from CAFs in CRC remains unclear. In this study, CAFs and normal fibroblasts (NFs) were isolated from CRC and adjacent normal tissues. Next, exosomes were isolated from the supernatants of CAFs cultured under normoxia and hypoxia. Cell viability was tested using the cell counting kit-8 assay, and flow cytometry was used to assess cell apoptosis. Cell invasion and migration were evaluated using the transwell assay. Dual-luciferase was used to investigate the relationship between miR-200b-3p and high-mobility group box 3 (HMBG3). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the miR-200b-3p and HMBG3 level. Our results found that the miR-200b-3p level was sharply reduced in CRC tissues compared to adjacent normal tissues. Additionally, the miR-200b-3p level was reduced in exosomes derived from hypoxic CAFs compared to exosomes derived from CAFs under normoxia. Exosomes derived from hypoxic CAFs weakened the sensitivity of CRC cells to 5-fluorouracil (5-FU) compared to hypoxic CAFs-derived exosomes. However, hypoxic CAFs-derived exosomes with upregulated miR-200b-3p increased the sensitivity of CRC cells to 5-fluorouracil (5-FU) compared to hypoxic CAFs-derived exosomes. In addition, HMBG3 was identified as the downstream target of miR-200b-3p in CRC cells, and its overexpression partially reversed the anti-tumor effect of the miR-200b-3p agomir on CRC via the mediation of the β-catenin/c-Myc axis. Furthermore, compared to exosomes derived from normoxia CAFs, exosomes derived from hypoxic CAFs weakened the therapeutic effects of 5-FU on CRC in vivo via the upregulation of HMGB3 levels. Collectively, the loss of exosomal miR-200b-3p in hypoxia CAFs reduced the sensitivity to 5-FU in CRC by targeting HMGB3. Thus, our research outlines a novel method for the treatment of CRC.
Antitumor effect and mechanism of FZD7 polypeptide vaccine
Authors: Hua Zhongke , Han Yu , Liu Kan , Yang Hua , Zhou Cai , Chen Fengyi , Nie Shenglan , Li Mengqing , Yu Qinyao , Wei Yunpeng , Wu Christina C. N. , Wang Xiaomei
Published: October 2022

The resistant cells that proliferate after radiotherapy and chemotherapy are primarily tumor stem cells with high stem marker expression, and their presence is the primary cause of tumor dispersion. The Wnt signaling receptor Frizzled family receptor 7 (FZD7) is linked to the maintenance of stem cell features as well as cancer progression. Frizzled-7 (FZD7), a key receptor for Wnt/-catenin signaling, is overexpressed in TNBC, suggesting that it could be a viable target for cancer therapy. We employed bioinformatics to find the best-scoring peptide, chemically synthesized FZD7 epitope antigen, and binding toll-like receptor 7 agonists (T7). Under GMP conditions, peptides for vaccines were produced and purified (>95%). In vivo and vitro tests were used to assess tumor cell inhibition. In vitro, the FZD7-T7 vaccination can boost the maturity of BMDC cells considerably. In mice, the FZD7 - T7 vaccine elicited the greatest immunological response. Significant tumor development inhibition was seen in BALB/c mice treated with FZD7 - T7 in prevention experiments (P < 0.01). Multiple cytokines that promote cellular immune responses, such as interferon (IFN)-γ (P < 0.05), interleukin (IL)-12 (P < 0.05), and IL-2 (P < 0.01), were shown to be considerably elevated in mice inoculated with FZD7- T7. Furthermore, we evaluated safety concerns in terms of vaccine composition to aid in the creation of successful next-generation vaccines. In conclusion, the FZD7-T7 vaccine can activate the immune response in vivo and in vitro, and play a role in tumor suppression. Our findings reveal a unique tumor-suppressive role for the FZD7 peptide in TNBC.
Cost and effectiveness of microwave ablation versus video-assisted thoracoscopic surgical resection for ground-glass nodule lung adenocarcinoma
Authors: Han Xiaoying , Wei Zhigang , Zhao Zhenxing , Yang Xia , Ye Xin
Published: October 2022

Purpose

To retrospectively evaluate the cost and effectiveness in consecutive patients with ground-glass nodules (GGNs) treated with video-assisted thoracoscopic surgery (VATS; i.e., wedge resection or segmentectomy) or microwave ablation (MWA).

Materials and methods

From May 2017 to April 2019, 204 patients who met our study inclusion criteria were treated with VATS (n = 103) and MWA (n = 101). We calculated the rate of 3-year overall survival (OS), local progression-free survival (LPFS), and cancer−specific survival (CSS), as well as the cost during hospitalization and the length of hospital stay.

Results

The rates of 3-year OS, LPFS, and CSS were 100%, 98.9%, and 100%, respectively, in the VATS group and 100%, 100% (p = 0.423), and 100%, respectively, in the MWA group. The median cost of VATS vs. MWA was RMB 54,314.36 vs. RMB 21,464.98 (p < 0.001). The length of hospital stay in the VATS vs. MWA group was 10.0 vs. 6.0 d (p < 0.001).

Conclusions

MWA had similar rates of 3-year OS, LPFS, and CSS for patients with GGNs and a dramatically lower cost and shorter hospital stay compared with VATS. Based on efficacy and cost, MWA provides an alternative treatment option for patients with GGNs.
Laparoscopic treatment for an intrapancreatic accessory spleen: A case report
Authors: Zhang Yihan , Shi Guodong , Meng Lingdong , Wu Jing , Hu Qingqiao , Xv Dong , Zhang Kai , Lu Zipeng , Wu Junlii , Jiang Kuirong
Published: October 2022

Malignant pancreatic tumors have early metastasis, aggressive behavior and poor prognosis. Surgeons often need to judge whether a patient needs prompt surgery when a pancreatic lesion is found. The accessory spleen is a congenital developmental malformation rather than a tumor and does not require surgical resection. Here, we report a 47-year-old man who underwent routine gastroscopic examination, and a submucosal eminence of the duodenal bulb was detected. The patient was asymptomatic and laboratory tests were unremarkable. Duodenal neuroendocrine neoplasm (G2) was considered following endoscopic submucosal dissection (ESD). Further examination showed a lesion in the tail of the pancreas and multiple accessory spleens. The lesion in the tail of the pancreas was Ga-68 positive and was highly considered a pancreatic neuroendocrine tumor (pNET). Based on this clinical evidence, laparoscopic spleen-preserving distal pancreatectomy (Kimura) was performed. However, the results of the postoperative pathological diagnosis indicated an intrapancreatic accessory spleen (IPAS). Given the findings of this case, we should explore more accurate diagnostic methods for IPAS to avoid unnecessary surgery.
Inhibition of induced-hepatic cancer in vivo through IQGAP1-shRNA gene therapy and modulation of TRAIL-induced apoptosis pathway
Authors: Zoheir Khairy M. A. , Abd-Rabou Ahmed A. , Darwish Ahmed M. , Abdelhafez Mohamed A. , Mahrous Karima F.
Published: October 2022

Background

Liver cancer is the deadliest malignancy among common tumors. It is the top cause of cancer-related deaths in Egypt, and it is characterized by increasing occurrence among the population. The objective of this study was to determine the outcome of pre-treatment of IQGAP1-shRNA on induced mouse hepatocellular carcinoma model and evaluate the potency of this IQGAP1-shRNA plasmid to recover hepatic cancer as a new tool of cancer therapy. Therefore, we will use RNA interference (RNAi) technology to silence IQGAP1 oncogene to completely recover the chemically induced models for hepatic cancer by designing short RNAi specific for IQGAP1 gene in HCC cells in vivo and construct new vectors suitable for this purpose. We assigned mice into three groups: the first negative control group (NC) was injected with saline, the second control group was injected with shRNA (shNC), the third positive control group was injected with diethylnitrosamine (DENAA), and the fourth group was treated with the IQGAP1-shRNA prior to its exposure to DENA.

Results

Our results revealed that the treated group with IQGAP1-shRNA with DENA developed very few cases of hepatic cancer when compared with the positive control group. The positive control group exhibited significant increases in the liver function level as well as a decrease in serum albumin levels when compared to both the treated and the negative control groups. The altered levels of the serum α-fetoprotein as well as of the tumor necrosis factor-alpha, and interleukin-4 in DENA-treated mice were significantly ameliorated by IQGAP1-shRNA administration. Flow cytometer analyses have indicated that the silencing of IQGAP1 cannot significantly modulate DENA-induced apoptosis in the circulating blood cells. Moreover, the elevated mRNA expression levels of IQGAP1, IQGAP3, KRas, HRas, interleukin-8, nuclear factor kappa B, caspase-3, caspase-9 and Bcl-2, were significantly decreased by the IQGAP1-shRNA treatment. However, the IQGAP2, DR4, DR5, p53 and BAX genes were found to be significantly up-regulated post-therapy. In agreement with these findings, IQGAP1-shRNA was able to modulate the DENA-induced histological changes in the mice liver which were represented by severe necrosis and hydropic degenerative changes.

Conclusion

Our study revealed that IQGAP1-shRNA was able to preserve hepatocyte integrity and the liver histological architecture through the regulation of the expression of IQGAPs, Ras, TRAILs and IL-8 receptors, as well as of pro-apoptotic and anti-apoptotic genes. Therefore, the silencing of IQGAP1 could be part of a promising therapeutic strategy against hepatic cancer.
Social relationships and relational pain in brain tumor patients and their partners
Authors: Boccia Maria L.
Published: October 2022

Partners play an important role in both the general well-being and the care needs of patients. The dynamic between brain tumor treatment and patients’ families is a complex bidirectional relationship. Cancer diagnosis and treatments which leave patients compromised impact the nature and quality of their relationships, and these in turn impact the ability of their partners to care for them. This paper will review the nature of the impact of diagnosis and treatment on relationships and how couples and families respond to the disruption of cancer treatments. The impact of how emotional and social pain effect their relationships and their ability to engage in care will be addressed.
Therapeutic hypothermia for encephalopathic newborns with congenital heart defect: A cross-sectional survey on current practices and opinions in Germany
Authors: Boos Vinzenz , Berger Felix
Published: October 2022

Background

Therapeutic hypothermia (TH) reduces neonatal mortality and long-term neurodevelopmental impairment in infants with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) caused by perinatal asphyxia. There is an increasing trend to apply TH in other indications and populations, such as infants with mild HIE or neonates with congenital heart defects (CHD), even though there is little evidence to support or refute this.

Objective

The aim of this survey was to analyze practice variations with respect to TH use in neonates with CHD and to assess expert opinions on this topic across tertiary neonatal departments in Germany.

Methods/Design

A web-based survey was sent to all tertiary neonatal departments in Germany. The questionnaire contained 32 multiple-choice questions. The survey inquired current practices on TH in newborns with CHD and expert opinions on various clinical scenarios.

Main results

A total 80 (51.3%) neonatal departments partially completed the survey, and 69 (44.2%) respondents filled out the whole questionnaire. All 80 (100.0%) departments perform TH. TH is offered by 76 (95.0%) respondents to encephalopathic newborns with simple CHD. In infants with critical/complex CHD, TH is offered after perinatal asphyxial HIE and in newborns with encephalopathy after severe acidosis associated with cardiac complications by 25 (31.3%), or 17 (22.1%) respondents, respectively, whereas a clear majority of centers reject TH in these infants. Unclear effects of TH on any ongoing prostaglandin therapy (57.6 and 52.3%, respectively), an increased risk for adverse reactions during TH (51.6 and 52.3%, respectively) and lack of evidence (33.3 and 53.8%, respectively) are the most frequently cited reasons for not performing TH in these infants. The majority of experts from neonatal departments providing comprehensive care for neonates with severe CHD support the initiation of TH in encephalopathic neonates.

Discussion

The considerable heterogeneity in the use of TH in neonates with CHD emphasizes the need for further research to optimize treatment strategies for these patients.
Skeletal muscle deficits are associated with worse exercise performance in pediatric pulmonary hypertension
Authors: Avitabile Catherine M. , McBride Michael G. , Harris Matthew A. , Whitehead Kevin K. , Fogel Mark A. , Paridon Stephen M. , Zemel Babette S.
Published: October 2022

Background

Skeletal muscle deficits are associated with worse exercise performance in adults with pulmonary hypertension (PH) but the impact is poorly understood in pediatric PH.

Objective

To study muscle deficits, physical inactivity, and performance on cardiopulmonary exercise test (CPET) and exercise cardiac magnetic resonance (eCMR) in pediatric PH.

Methods

Youth 8–18 years participated in a prospective, cross-sectional study including densitometry (DXA) for measurement of leg lean mass Z-score (LLMZ), handheld dynamometer with generation of dominant and non-dominant handgrip Z-scores, Physical Activity Questionnaire (PAQ), CPET, and optional eCMR. CPET parameters were expressed relative to published reference values. CMR protocol included ventricular volumes and indexed systemic flow at rest and just after supine ergometer exercise. Relationships between LLMZ, PAQ score, and exercise performance were assessed by Pearson correlation and multiple linear regression.

Results

There were 25 participants (13.7 ± 2.8 years, 56% female, 64% PH Group 1, 60% functional class I); 12 (48%) performed both CPET and eCMR. Mean LLMZ (–0.96 ± 1.14) was associated with PAQ score (r = 50, p = 0.01) and with peak oxygen consumption (VO2) (r = 0.74, p = < 0.001), VO2 at anaerobic threshold (r = 0.65, p < 0.001), and peak work rate (r = 0.64, p < 0.01). Higher handgrip Z-scores were associated with better CPET and eCMR performance. On regression analysis, LLMZ and PAQ score were positively associated with peak VO2, while handgrip Z-score and PAQ score were positively associated with peak work rate.

Conclusion

Muscle mass and strength are positively associated with exercise performance in pediatric PH. Future studies should determine the effect of rehabilitation programs on muscle properties and exercise performance.