bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum 4-hydroxynonenal associates with the recurrence of patients with primary cerebral infarction
Authors: Liu Xingliang , Bai Meiling , Fan Lei , Lou Zhan
Published: November 2022

Background

4-Hydroxynonenal (4-HNE), an α, β-unsaturated hydroxyalkenal, has been found to be associated with aspirin resistance, which is a risk factor for recurrent cerebral infarction. However, its effect on recurrent cerebral infarction is less defined. We designed this study to investigate the association between 4-HNE and increased risk of recurrent cerebral infarction.

Methods

We recruited 189 patients with primary cerebral infarction from 2017 to 2019. According to the recurrence of cerebral infarction during the 3-year follow-up period, they were divided into two groups, namely, the non-recurrence group (n = 93) and the recurrence group (n = 96). All patients were analyzed to explore the risk factors for the recurrence of primary cerebral infarction and the predictive value of serum 4-HNE for the recurrence of cerebral infarction.

Results

The levels of serum 4-HNE in patients of the recurrence group were significantly higher than that in patients of the non-recurrence group. There was a positive correlation between serum 4-HNE levels and the serum levels of triglyceride (r = 0.448, p = 0.008) and low-density lipoprotein cholesterol (LDL-C; r = 0.442, p = 0.002) in primary cerebral infarction patients. Cox proportional hazards modeling showed that demographic and certain clinical parameters, such as age, serum triglyceride levels, the National Institutes of Health Stroke Scale (NIHSS) scores, and serum 4-HNE levels, were independent factors for the recurrence in patients. The results of the receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) value of serum 4-HNE in patients with cerebral infarction recurrence was 0.703, and when the cutoff value of serum 4-HNE was set at 42.34 ng/ml, the sensitivity and specificity values of serum 4-HNE in predicting recurrent cerebral infarction were 79.20 and 52.70%, respectively.

Conclusion

Serum 4-HNE is an independent risk factor for the recurrence of patients with primary cerebral infarction, and it may become a new intervention way to prevent the recurrence of patients with cerebral infarction.
Clinical features, radiological findings, and prognostic factors for primary intracranial chordoid meningioma
Authors: Jie Danyang , Liu Zhiyong , He Wenbo , Wang Shumin , Teng Haibo , Xu Jianguo
Published: November 2022

Objectives

Chordoid meningioma (CM) is an infrequent histologic subtype of meningiomas. Owing to its low occurrence, this subtype has been rarely described. Our subject was to explore the clinical features, radiological characteristics, and prognostic factors of primary intracranial chordoid meningioma.

Methods

We reviewed the medical records and collected follow-up information of 34 cases who had been surgically treated and histologically diagnosed with CM at the Department of Neurosurgery, West-China Hospital of Sichuan University, from January 2009 to December 2021.

Results

Among all 7,950 meningioma cases, the proportion of primary intracranial CM was 0.43% (34/7,950). The median diagnosis age was 47 (ranging from 12 to 74) and the gender ratio (male to female) was 2.1:1. For radiological features, heterogeneous enhancement, skull base, and ventricular localization, cystic degeneration and dural tail sign were common in CM cases. In treatment, gross total resection (GTR) was achieved in 22/34 cases (64.7%) and subtotal resection (STR) was achieved in 12/34 cases (35.3%). Further, 11/34 patients (32.4%) had received postoperative adjuvant radiotherapy (RT). The follow-up duration ranged from 4 to 157 months after operation. The progression rate was 20.7% (6/29) and the median of PFS was 38 months. By survival analysis, accepting adjuvant radiotherapy and achieving GTR were correlated with longer progression-free survival for prognosis.

Conclusion

CM is a rare subtype of meningiomas. In our series, it mainly involved adults and did not show a predilection for women compared with meningiomas in general. For a better prognosis, gross total resection and postoperative adjuvant radiotherapy are recommended. Nevertheless, due to the restriction of the series sample, patients lost for follow-up and inherent biases of a retrospective study, more cases and a shorter follow-up duration are needed for better management of chordoid meningioma.
Neuroform atlas stent-assisted coiling of tiny wide-necked intracranial aneurysms
Authors: Dong Linggen , Chen Xiheng , Wang Jiejun , Zhang Longhui , Zhao Zhiqiang , Peng Qichen , Liu Peng , Lv Ming
Published: November 2022

Objective

To investigate the safety and efficacy of Neuroform Atlas stent-assisted coiling for the treatment of tiny wide-necked intracranial aneurysms and evaluate risk factors associated with procedure-related complications.

Methods

We retrospectively examined 46 patients with 46 tiny wide-necked aneurysms who were treated using Atlas stent-assisted coiling at our institution from August 2020 to May 2022. Patient and aneurysm characteristics, procedural details, procedure-related complications, and angiographic and clinical outcomes were analyzed.

Results

A total of 10 patients presented with aneurysmal rupture. Atlas stent placement was successful in all patients. Angiography immediately after the procedure showed complete occlusion in 38 patients (82.6%), neck remnant in 7 (15.2%), and partial occlusion in 1 (2.2%). The mean angiographic follow-up was 8.4 months (range, 6–16). At the last follow-up, angiography showed complete occlusion in 41 patients (89.1%) and neck remnant in 5 (10.9%). No aneurysm recurrence or in-stent stenosis occurred. Incidence of procedure-related complications was 10.8% (intraprocedural aneurysm rupture, two cases; acute thrombosis, two cases; and coil migration, one case); only one patient (2.2%) experienced procedural neurological morbidity. The mean clinical follow-up was 9.7 months. A favorable outcome was achieved in 45 patients (97.8%). In univariate logistic regression analysis, aneurysm size (odds ratio, 4.538; P = 0.045) was significantly associated with procedure-related complications. However, multivariate analysis found no independent risk factors.

Conclusion

Atlas stent-assisted coiling of tiny wide-necked intracranial aneurysms is feasible and effective. Outcomes and occlusion rates are favorable and morbidity is low. The complication rate may be higher in larger tiny aneurysms.
The pharmacokinetics of continuous subcutaneous levodopa/carbidopa infusion: Findings from the ND0612 clinical development program
Authors: LeWitt Peter A. , Stocchi Fabrizio , Arkadir David , Caraco Yoseph , Adar Liat , Perlstein Itay , Case Ryan , Giladi Nir
Published: November 2022

Background

While treatment with levodopa remains the cornerstone of Parkinson's disease (PD) management, chronic oral therapy is often associated with the development of motor complications, that correlate to fluctuating levodopa plasma concentrations, limiting its clinical utility. Continuous infusion is considered to be the optimal delivery route for treating PD patients with motor fluctuations, but current infusion systems require invasive surgery. Subcutaneous infusion of (SC) levodopa has the potential to provide a better tolerated and more convenient route of continuous levodopa delivery. ND0612 is in development as a combination product providing continuous levodopa/carbidopa via a minimally invasive, subcutaneous delivery system for PD patients experiencing motor response fluctuations. We present pharmacokinetic results from a series of studies that analyzed plasma concentrations after SC levodopa delivery with ND0612 to inform the clinical development program.

Methods

We performed a series of six Phase I and II studies to characterize the pharmacokinetics of levodopa and carbidopa derived from ND0612 infusion with/without adjunct oral therapy of the same ingredients. These studies were conducted in healthy volunteers and in PD patients experiencing motor response fluctuations while on their current levodopa therapy regimen.

Results

Taken together, the results demonstrate dose-proportionality dependent on rate of subcutaneous levodopa infusion leading to stable and sustained plasma concentrations of levodopa. Subcutaneous infusion of ND0612 administered with oral levodopa/carbidopa maintained near-constant, therapeutic levodopa plasma concentrations, thereby avoiding the troughs in levodopa plasma concentrations that are associated with OFF time in PD. The data generated in this series of studies also confirmed that a levodopa/carbidopa dose ratio of 8:1 would be the most reasonable choice for ND0612 development.

Conclusions

This series of clinical pharmacokinetic studies have demonstrated that ND0612, administered continuously with a levodopa concentration of 60 mg/ml combined with carbidopa 7.5 mg/ml, and complemented with oral levodopa/carbidopa, is suitable for 24 h continuous administration in patients with PD. The stable plasma concentrations of levodopa achieved predict utility of ND0612 as a parenteral formulation for achieving clinically useful delivery of levodopa for PD patients.
Does acupuncture therapy affect peripheral inflammatory cytokines of major depressive disorder? A protocol for the systematic review and meta-analysis
Authors: Zhao Ya-Nan , Zhang Shuai , Chen Yu , Wang Yu , Chen Hao , Duan Yu-Ting , Li Shao-Yuan , Zhang Zi-Xuan , Wang Yi-Fei , Xin Chen , Li Liang , Rong Pei-Jing
Published: November 2022

Background

Acupuncture is widely used as adjuvant therapy for major depressive disorder (MDD). There is robust evidence that inflammation is closely associated with MDD. To date, only a few numbers of studies have investigated the potential relationship between acupuncture and the change of inflammatory biomarkers in patients with MDD. Additionally, the results are inconsistent among studies. The current study aims to provide a comprehensive, systematic review of the association between acupuncture and changes in peripheral inflammation of patients with MDD, and clarify the alterations of inflammatory cytokines before and after acupuncture treatment by meta-analysis.

Methods and analysis

This study will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible randomized controlled trials (RCTs) reporting acupuncture, with inflammatory cytokines as the outcome measured before and after intervention in patients with MDD, were searched in electronic databases, such as PubMed, Embase, Cochrane, SINOMED, Wanfang, China national knowledge infrastructure (CNKI), and Chongqing VIP (CQVIP). Primary outcomes of interest will be validated to measure the levels of inflammatory cytokines before and after acupuncture treatment in patients with MDD.

Discussion

Acupuncture can drive anti-inflammatory effects, as well as symptom changes in MDD, which may represent a viable, multi-faceted treatment approach in MDD.

Systematic review registration

[PROSPERO], identifier [CRD42021289207 on 04 December 2021].
The convergent effects of primary school physical activity, sleep, and recreational screen time on cognition and academic performance in grade 9
Authors: Ramer Jared Donald , Santiago-Rodríguez María Enid , Vukits Amanda Joan , Bustamante Eduardo Esteban
Published: November 2022

Lab-based experiments and randomized controlled trials consistently demonstrate improvements in youth cognition following physical activity (PA), while cross-sectional studies suggest that sedentary behavior (especially recreational screen time [RST]) and poor sleep are inversely related to cognition. However, little is known about how these 24-h movement behaviors—sleep, PA, and sedentary behavior—converge to affect youth cognition. Therefore, the purpose of this study is to test the associations between childhood 24-h movement behaviors and adolescent cognition using a longitudinal design and examine moderating effects of each behavior. This study utilized structural equation modeling with data from the NICHD Study of Early Child Care and Youth Development (N = 1,364, 52% female, 80% White). Independent variables—sleep, RST, and PA—were collected in grade 5. Dependent variables of cognitive and academic performance were collected at grade 9, including the Stroop task, Woodcock-Johnson, and Tower of London. Grade 5 PA was inversely associated with grade 9 cognition, but this relationship was no longer significant once grade 5 cognition was controlled for in analyses. Grade 5 sleep was positively related to grade 9 cognition, whether baseline cognition was controlled for or not. Finally, grade 5 RST was inversely related to cognition and academic performance, regardless of whether baseline values were controlled. Moderation analyses showed the relationship between grade 5 RST and grade 9 cognition was moderated by grade 5 PA, while the relationship between grade 5 PA and grade 9 cognition was moderated by grade 5 sleep. In each case, more PA and sleep blunted the negative relationships. These findings extend evidence that greater sleep promotes cognition and greater RST impairs cognition, by affirming these relationships over a longer period. They extend the evidence by demonstrating that the longitudinal relationship between individual 24-h movement behavior and cognition is moderated by other behaviors.
East Wind, West Wind: Toward the modernization of traditional Chinese medicine
Authors: Yagüe Ernesto , Sun He , Hu Yunhui
Published: November 2022

Traditional Chinese medicine (TCM) has used herbal remedies for more than 2,000 years. The use of complimentary therapies has increased dramatically during the last years, especially in the West, and the incorporation and modernization of TCM in current medical practice is gaining momentum. We reflect on the main bottlenecks in the modernization of arcane Chinese herbal medicine: lack of standardization, safety concerns and poor quality of clinical trials, as well as the ways these are being overcome. Progress in these areas will facilitate the implementation of an efficacy approach, in which only successful clinical trials lead to the molecular characterization of active compounds and their mechanism of action. Traditional pharmacological methodologies will produce novel leads and drugs, and we describe TCM successes such as the discovery of artemisinin as well as many others still in the pipeline. Neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease, cancer and cardiovascular disease are the main cause of mortality in the Western world and, with an increasing old population in South East Asia, this trend will also increase in the Far East. TCM has been used for long time for treating these diseases in China and other East Asian countries. However, the holistic nature of TCM requires a paradigm shift. By changing our way of thinking, from “one-target, one-drug” to “network-target, multiple-component-therapeutics,” network pharmacology, together with other system biology methodologies, will pave the way toward TCM modernization.
Analyzing pericytes under mild traumatic brain injury using 3D cultures and dielectric elastomer actuators
Authors: Wu Yi-Han , Park Thomas I-H , Kwon Eryn , Feng Sheryl , Schweder Patrick , Dragunow Mike , Shim Vickie , Rosset Samuel
Published: November 2022

Traumatic brain injury (TBI) is defined as brain damage due to an external force that negatively impacts brain function. Up to 90% of all TBI are considered in the mild severity range (mTBI) but there is still no therapeutic solution available. Therefore, further understanding of the mTBI pathology is required. To assist with this understanding, we developed a cell injury device (CID) based on a dielectric elastomer actuator (DEA), which is capable of modeling mTBI via injuring cultured cells with mechanical stretching. Our injury model is the first to use patient-derived brain pericyte cells, which are ubiquitous cells in the brain involved in injury response. Pericytes were cultured in our CIDs and mechanically strained up to 40%, and by at least 20%, prior to gene expression analysis. Our injury model is a platform capable of culturing and stretching primary human brain pericytes. The heterogeneous response in gene expression changes in our result may suggest that the genes implicated in pathological changes after mTBI could be a patient-dependent response, but requires further validation. The results of this study demonstrate that our CID is a suitable tool for simulating mTBI as an in vitro stretch injury model, that is sensitive enough to induce responses from primary human brain pericytes due to mechanical impacts.
Focusing on cyclin-dependent kinases 5: A potential target for neurological disorders
Authors: Tian Zhen , Feng Bin , Wang Xing-Qin , Tian Jiao
Published: November 2022

Cyclin-dependent kinases 5 (Cdk5) is a special member of proline-directed serine threonine kinase family. Unlike other Cdks, Cdk5 is not directly involved in cell cycle regulation but plays important roles in nervous system functions. Under physiological conditions, the activity of Cdk5 is tightly controlled by p35 or p39, which are specific activators of Cdk5 and highly expressed in post-mitotic neurons. However, they will be cleaved into the corresponding truncated forms namely p25 and p29 under pathological conditions, such as neurodegenerative diseases and neurotoxic insults. The binding to truncated co-activators results in aberrant Cdk5 activity and contributes to the initiation and progression of multiple neurological disorders through affecting the down-stream targets. Although Cdk5 kinase activity is mainly regulated through combining with co-activators, it is not the only way. Post-translational modifications of Cdk5 including phosphorylation, S-nitrosylation, sumoylation, and acetylation can also affect its kinase activity and then participate in physiological and pathological processes of nervous system. In this review, we focus on the regulatory mechanisms of Cdk5 and its roles in a series of common neurological disorders such as neurodegenerative diseases, stroke, anxiety/depression, pathological pain and epilepsy.
Ferroptosis-related differentially expressed genes serve as new biomarkers in ischemic stroke and identification of therapeutic drugs
Authors: Zhang Yinjiang , Zhang Yashuo , Yao Rongfei , He Xu , Zhao Linyi , Zuo Xiangyu , Lu Binan , Pang Zongran
Published: November 2022

Background

Iron is an essential nutrient element, and iron metabolism is related to many diseases. Ferroptosis is an iron-dependent form of regulated cell death associated with ischemic stroke (IS). Hence, this study intended to discover and validate the possible ferroptosis-related genes involved in IS.

Materials and methods

GSE16561, GSE37587, and GSE58294 were retrieved from the GEO database. Using R software, we identified ferroptosis-related differentially expressed genes (DEGs) in IS. Protein-protein interactions (PPIs) and enrichment analyses were conducted. The ROC curve was plotted to explore the diagnostic significance of those identified genes. The consistent clustering method was used to classify the IS samples. The level of immune cell infiltration of different subtypes was evaluated by ssGSEA and CIBERSORT algorithm. Validation was conducted in the test sets GSE37587 and GSE58294.

Results

Twenty-one ferroptosis-related DEGs were detected in IS vs. the normal controls. Enrichment analysis shows that the 21 DEGs are involved in monocarboxylic acid metabolism, iron ion response, and ferroptosis. Moreover, their expression levels were pertinent to the age and gender of IS patients. The ROC analysis demonstrated remarkable diagnostic values of LAMP2, TSC22D3, SLC38A1, and RPL8 for IS. Transcription factors and targeting miRNAs of the 21 DEGs were determined. Vandetanib, FERRIC CITRATE, etc., were confirmed as potential therapeutic drugs for IS. Using 11 hub genes, IS patients were categorized into C1 and C2 subtypes. The two subtypes significantly differed between immune cell infiltration, checkpoints, and HLA genes. The 272 DEGs were identified from two subtypes and their biological functions were explored. Verification was performed in the GSE37587 and GSE58294 datasets.

Conclusion

Our findings indicate that ferroptosis plays a critical role in the diversity and complexity of the IS immune microenvironment.
Comparing meat abstainers with avid meat eaters and committed meat reducers
Authors: Verain Muriel C. D. , Dagevos Hans
Published: November 2022

Shifting our eating patterns toward less animal-based and more plant-based diets is urgently needed to counter climate change, address public health issues, and protect animal welfare. Although most consumers agree that these are important topics, many consumers are not particularly willing to decrease the meat intensity of their diets. In supporting consumers to shift their diets, it is important to understand consumers’ attitudes, motivations, and preferences related to meat consumption and to take differences across consumers on these aspects into account. This study aims to in-depth research meat abstainers (vegetarians and vegans), and to explore how and to what extent they differ from avid meat eaters and committed meat reducers in terms of their (1) socio-demographic characteristics, (2) attitudes and norms, (3) food choice motives, and (4) food preferences and behavior. A survey has been conducted among a representative sample of Dutch adults. Comparisons show that meat abstainers (N = 198) differ from committed meat reducers (N = 171) and avid meat eaters (N = 344) on the four included categories of variables. In terms of demographics, we largely confirm the stereotype of vegans and vegetarians being highly educated females. In attitudes and norms, large differences exist with meat abstainers being least pro-meat and avid meat eaters being most pro-meat. Food choice motives confirm this, with meat abstainers valuing animal welfare and a good feeling higher than committed meat reducers and avid meat eaters. Finally, differences across the groups are most pronounced in terms of their food preferences and consumption, with a much higher appreciation of plant-based protein sources among meat abstainers, a high appreciation of non-meat animal-based proteins across committed meat reducers and a high appreciation of meat products among avid meat eaters. This shows that although differences across the groups are gradual and expected, in terms of reduction motivations and preferences of protein sources the three groups (frequent meat consumption-meat reduction-meat avoidance) are very distinct, which makes it unlikely to expect big shifts from one group to another in the short term.
Non-coding RNAs: The link between maternal malnutrition and offspring metabolism
Authors: Zeng Yuan , Wu Yifan , Zhang Qian , Xiao Xinhua
Published: November 2022

Early life nutrition is associated with the development and metabolism in later life, which is known as the Developmental Origin of Health and Diseases (DOHaD). Epigenetics have been proposed as an important explanation for this link between early life malnutrition and long-term diseases. Non-coding RNAs (ncRNAs) may play a role in this epigenetic programming. The expression of ncRNAs (such as long non-coding RNA H19, microRNA-122, and circular RNA-SETD2) was significantly altered in specific tissues of offspring exposed to maternal malnutrition. Changes in these downstream targets of ncRNAs lead to abnormal development and metabolism. This review aims to summarize the existing knowledge on ncRNAs linking the maternal nutrition condition and offspring metabolic diseases, such as obesity, type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD).
Dietary protein improves flesh quality by enhancing antioxidant ability via the NF-E2-related factor 2/Kelch-like ECH-associated protein 1 signaling pathway in softshell turtle (Pelodiscus sinensis)
Authors: Kou Hongyan , Hu Junru , Liu Xueting , Zhao Lijuan , Zhang Kai , Pan Xunbin , Wang Anli , Miao Yutao , Lin Li
Published: November 2022

An 8-week feeding trial was performed to assess the influence of a gradient of protein levels (14.38–45.23%) on flesh quality, skin color, amino acid profile, collagen, antioxidant capability, and antioxidant-related signaling molecule expression of the softshell turtle (Pelodiscus sinensis). Hardness, gumminess, chewiness, and yellowness values in the plastron and carapace, along with collagen, superoxide dismutase, catalase, total antioxidant capacity, and glutathione peroxidase, all improved with elevating dietary protein up to 26.19%, after which they leveled off. Additionally, total amino acids, flavor amino acids, essential amino acids, and non-essential amino acids in the muscle, as well as the expression of copper/zinc superoxide dismutase, glutathione peroxidase, catalase, manganese superoxide dismutase, NF-E2-related factor 2 were all enhanced by increasing the dietary protein level but not changed by higher protein levels. When dietary protein levels were less than 26.19%, the mRNA expression of Kelch-like ECH-associated protein 1, malondialdehyde, and redness values in the carapace and plastron were reduced, as was the lightness values of the carapace, all of which plateaued at higher protein levels. Using catalase activity and malondialdehyde as the indicators and applying a broken-line analysis, the optimal dietary protein level for P. sinensis was inferred to be 26.07 and 26.06% protein, respectively. In summary, an optimal protein input improved turtle flesh quality by strengthening antioxidant capacity in muscle tissue and by regulating the expression of antioxidant-related enzymes via the Nrf2/keap1 signaling pathway.
Prognostic prediction by a novel integrative inflammatory and nutritional score based on least absolute shrinkage and selection operator in esophageal squamous cell carcinoma
Authors: Feng Jifeng , Wang Liang , Yang Xun , Chen Qixun , Cheng Xiangdong
Published: November 2022

Background

This study aimed to establish and validate a novel predictive model named integrative inflammatory and nutritional score (IINS) for prognostic prediction in esophageal squamous cell carcinoma (ESCC).

Materials and methods

We retrospectively recruited 494 pathologically confirmed ESCC patients with surgery and randomized them into training (n = 346) or validation group (n = 148). The least absolute shrinkage and selection operator (LASSO) Cox proportional hazards (PH) regression analysis was initially used to construct a novel predictive model of IINS. The clinical features and prognostic factors with hazard ratio (HRs) and 95% confidence intervals (CIs) grouped by IINS were analyzed. Nomogram was also established to verify the prognostic value of IINS.

Results

According to the LASSO Cox PH regression analysis, a novel score of IINS was initially constructed based on 10 inflammatory and nutritional indicators with the optimal cut-off level of 2.35. The areas under the curve (AUCs) of IINS regarding prognostic ability in 1-year, 3-years, and 5-years prediction were 0.814 (95% CI: 0.769–0.854), 0.748 (95% CI: 0.698–0.793), and 0.792 (95% CI: 0.745–0.833) in the training cohort and 0.802 (95% CI: 0.733–0.866), 0.702 (95% CI: 0.621–0.774), and 0.748 (95% CI: 0.670–0.816) in the validation cohort, respectively. IINS had the largest AUCs in the two cohorts compared with other prognostic indicators, indicating a higher predictive ability. A better 5-years cancer-specific survival (CSS) was found in patients with IINS ≤ 2.35 compared with those with IINS > 2.35 in both training cohort (54.3% vs. 11.1%, P < 0.001) and validation cohort (53.7% vs. 18.2%, P < 0.001). The IINS was then confirmed as a useful independent factor (training cohort: HR: 3.000, 95% CI: 2.254–3.992, P < 0.001; validation cohort: HR: 2.609, 95% CI: 1.693–4.020, P < 0.001). Finally, an IINS-based predictive nomogram model was established and validated the CSS prediction (training set: C-index = 0.71 and validation set: C-index = 0.69, respectively).

Conclusion

Preoperative IINS is an independent predictor of CSS in ESCC. The nomogram based on IINS may be used as a potential risk stratification to predict individual CSS and guide treatment in ESCC with radical resection.
Certain dietary patterns including potatoes are associated with higher and lower diet quality and physiological measures in children and adults, NHANES 2001-2018
Authors: Fulgoni Kristin , Fulgoni Victor L.
Published: November 2022

A large percentage of daily vegetable intake is attributed to white potatoes, but limited information is available on how potatoes are incorporated into dietary patterns in the US. Therefore, the objective of this study was to determine food patterns that include potatoes and to compare the associated diet quality and association with biomarkers to a food pattern without potatoes. Data from American subjects 2-18 and 19 years and older who participated in the What We Eat in America portion of the National Health and Nutrition Examination Survey cycles 2001-2018 were utilized in the current study. Diet quality was assessed using the Healthy Eating Index-2015. Anthropometric variables included body mass index (BMI), waist circumference, and weight. Biomarkers analyzed included glucose, insulin, triglycerides, HDL-, LDL-, and total cholesterol. Multiple food clusters containing potatoes were identified with several having higher and lower diet quality as compared to a food pattern without potatoes. Children and adolescents in one potato cluster had lower BMI, waist circumference, and body weight compared to those in a no potato dietary pattern, whereas adults in 3 potato clusters had higher anthropometric variables than those in a no potato pattern. In adults, some dietary patterns including potatoes were also associated with lower and higher HDL and total cholesterol and higher insulin levels. The percentage of calories from potatoes across patterns was small, ∼9-12%, suggesting the differences observed in diet quality and biomarkers were due to other food categories consumed in the pattern. This study suggests there are ways to incorporate potatoes as part of a healthy eating pattern but depends more on the other foods included in the diet.
Novel surgical procedure for preventing anastomotic leakage following colorectal cancer surgery: A propensity score matching study
Authors: Tang Gang , Pi Feng , Zhang Da-Hong , Qiu Yu-Hao , Wei Zheng-Qiang
Published: November 2022

Hypoperfusion is the main cause of anastomotic leakage (AL) following colorectal surgery. The conventional method for evaluating anastomotic perfusion is to observe color change and active bleeding of the resection margin of the intestine and the pulsation of mesenteric vessels. However, the accuracy of this method is low, which may be due to insufficient observation time. A novel surgical procedure that separates the mesentery in advance at the intended transection site can delay the observation of anastomotic perfusion, and can potentially detect more anastomotic sites with insufficient vascular supply and reduce the rate of AL. This study aimed to investigate the effects of a novel surgical procedure on AL following sigmoid colon and rectal cancer surgeries. A total of 343 patients who underwent rectal and sigmoid colon cancer surgeries were included in the study. From August 2021 to June 2022, patients with sigmoid colon or rectal cancer underwent a new surgical procedure of pre-division of the mesentery (PDM) at the intended transection site (PDM group). Patients with colorectal cancer who underwent conventional surgical procedures from August 2018 to July 2021 were categorized as the non-PDM group. Symptomatic AL (SAL) within 30 days and other outcomes were retrospectively analyzed using propensity score matching and compared between the two groups. The incidences of SAL were 1.3% and 11.3% in the PDM and non-PDM groups, respectively. PDM significantly reduced the SAL rate in sigmoid colon and rectal cancer surgeries (P = 0.009). The incidence of total postoperative complications (P < 0.05) was significantly lower in the PDM group than that in the non-PDM group. There were no significant differences between the two groups for operative time (P = 0.662), intraoperative blood loss (P = 0.651), intraoperative blood transfusion (P = 0.316), and intensive care rate (P = 1). The length of postoperative hospital stay (P = 0.010) and first exhaust (P = 0.001) and defecation time (P < 0.05) were shorter in the PDM group than in the non-PDM group. PDM can effectively prevent AL, and this procedure can be safely performed in sigmoid colon and rectal cancer surgeries.
A novel approach for eliminating metal artifacts based on MVCBCT and CycleGAN
Authors: Cao Zheng , Gao Xiang , Chang Yankui , Liu Gongfa , Pei Yuanji
Published: November 2022

Purpose

To develop a metal artifact reduction (MAR) algorithm and eliminate the adverse effects of metal artifacts on imaging diagnosis and radiotherapy dose calculations.

Methods

Cycle-consistent adversarial network (CycleGAN) was used to generate synthetic CT (sCT) images from megavoltage cone beam CT (MVCBCT) images. In this study, there were 140 head cases with paired CT and MVCBCT images, from which 97 metal-free cases were used for training. Based on the trained model, metal-free sCT (sCT_MF) images and metal-containing sCT (sCT_M) images were generated from the MVCBCT images of 29 metal-free cases and 14 metal cases, respectively. Then, the sCT_MF and sCT_M images were quantitatively evaluated for imaging and dosimetry accuracy.

Results

The structural similarity (SSIM) index of the sCT_MF and metal-free CT (CT_MF) images were 0.9484, and the peak signal-to-noise ratio (PSNR) was 31.4 dB. Compared with the CT images, the sCT_MF images had similar relative electron density (RED) and dose distribution, and their gamma pass rate (1 mm/1%) reached 97.99% ± 1.14%. The sCT_M images had high tissue resolution with no metal artifacts, and the RED distribution accuracy in the range of 1.003 to 1.056 was improved significantly. The RED and dose corrections were most significant for the planning target volume (PTV), mandible and oral cavity. The maximum correction of Dmean and D50 for the oral cavity reached 90 cGy.

Conclusions

Accurate sCT_M images were generated from MVCBCT images based on CycleGAN, which eliminated the metal artifacts in clinical images completely and corrected the RED and dose distributions accurately for clinical application.
Investigation of the impact of machine operating parameters on beam delivery time and its correlation with treatment plan characteristics for synchrotron-based proton pencil beam spot scanning system
Authors: Liang Xiaoying , Beltran Chris , Liu Chunbo , Shen Jiajian , Bues Martin , Furutani Keith M.
Published: November 2022

Purpose

To investigate the beam delivery time (BDT) reduction due to the improvement of machine parameters for Hitachi synchrotron-based proton PBS system.

Methods

BDTs for representative treatment plans were calculated to quantitatively estimate the BDT improvement from our 2015 system at Mayo Clinic in Arizona to our system to be implemented in 2025 at Mayo Clinic in Florida, and to a hypothetical future system. To specifically assess how each incremental improvement in the operating parameters reduced the total BDT, for each plan, we simulated the BDT 10,368 times with various settings of the nine different operating parameters. The effect of each operating parameter on BDT reduction and its correlation with treatment plan characteristics were analyzed. The optimal number of multiple energy extraction (MEE) layers per spill for different systems was also investigated.

Results

The median (range) decrease in BDT was 60% (56%-70%) from the 2015 to the 2025 system. The following incremental improvement in parameters of the 2015 system for the 2025 system played an important role in this decreased BDT: beam intensity (8 to 20 MU/s), recapture efficiency (50% to 80%), number of MEE layers per spill (4 to 8), scanning magnet preparation and verification time (1.9 to 0.95 msec), and MEE layer switch time (200 to 100 msec). Reducing the total spill change time and scanning magnet preparation and verification time from those of the 2025 system further reduced BDT in the hypothetical future system. 8 MEE layers per spill is optimal for a system with 50% recapture efficiency; 16 MEE layers per spill is optimal for a system with 80% recapture efficiency; and more than 16 MEE layers per spill is beneficial only for a system close to 100% recapture efficiency.

Conclusions

We systematically studied the effect of each machine operating parameter on the reduction in total BDT and its correlation with treatment plan characteristics. Our findings will aid new and existing synchrotron-based proton beam therapy centers to make balanced decisions on BDT benefits vs. costs when considering machine upgrade or new system selection.
Integrin α6β4 signals through DNA damage response pathway to sensitize breast cancer cells to cisplatin
Authors: Chen Min , Marrs Brock , Qi Lei , Knifley Teresa , Weiss Heidi L. , D’Orazio John A. , O’Connor Kathleen L.
Published: November 2022

Integrin α6β4 is highly expressed in triple negative breast cancer (TNBC) and drives its most aggressive traits; however, its impact on chemotherapeutic efficacy remains untested. We found that integrin α6β4 signaling promoted sensitivity to cisplatin and carboplatin but not to other chemotherapies tested. Mechanistic investigations revealed that integrin α6β4 stimulated the activation of ATM, p53, and 53BP1, which required the integrin β4 signaling domain. Genetic manipulation of gene expression demonstrated that mutant p53 cooperated with integrin α6β4 for cisplatin sensitivity and was necessary for downstream phosphorylation of 53BP1 and enhanced ATM activation. Additionally, we found that in response to cisplatin-induced DNA double strand break (DSB), integrin α6β4 suppressed the homologous recombination (HR) activity and enhanced non-homologous end joining (NHEJ) repair activity. Finally, we discovered that integrin α6β4 preferentially activated DNA-PK, facilitated DNA-PK-p53 and p53-53BP1 complex formation in response to cisplatin and required DNA-PK to enhance ATM, 53BP1 and p53 activation as well as cisplatin sensitivity. In summary, we discovered a novel function of integrin α6β4 in promoting cisplatin sensitivity in TNBC through DNA damage response pathway.
Active surveillance in long period of total neoadjuvant therapy in rectal cancer: Early prediction of poor regression response
Authors: Zhang Haoyu , Cao Ke , Li Ganbin , Zhai Zhiwei , Wei Guanghui , Qu Hao , Wang Zhenjun , Han Jiagang
Published: November 2022

Aim

To analyze locally advanced rectal cancer (LARC) patients and tumor characteristics during the period of total neoadjuvant therapy (TNT) and explore the risk factors that may predict poor tumor regression in response to TNT.

Materials and methods

The data of 120 LARC patients who received TNT from December 2016 and September 2019 in our hospital were retrospectively analyzed. The clinicopathological characteristics of patients with different tumor regression responses were compared. Then we divided patients into two groups according to the carcinoembryonic antigen (CEA) clearance pattern after chemoradiation to explore risk factors that might predict the tumor regression response.

Results

Of 120 LARC patients, 34 (28.3%) exhibited poor regression. Stratified analysis by tumor response showed that patients with poor response to TNT were more likely to obtain elevated CEA during the course of TNT (all P < 0.05). For those with elevated pretreatment CEA, fewer patients with poor response obtained normal CEA after chemoradiation (13.6% vs. 72.7%, P < 0.001). Besides, less patients’ CEA levels in the poor response group decreased by greater than 50% after chemoradiation when compared with that in the good response group (18.2% vs. 60.6%, P = 0.002). Stratified analysis by CEA clearance pattern after chemoradiation showed patients who obtained an elevated pretreatment CEA and decreased by less than 50% after chemoradiation were more likely to have poor response to TNT compared to others (76.2% vs. 18.2%, P < 0.001). Logistic multivariate analysis revealed that cN2 (95% CI 1.553-16.448), larger tumors (95% CI 2.250-21.428) and CEA clearance pattern after chemoradiation (95% CI 1.062-66.992) were independent risk factors for poor tumor regression response.

Conclusion

Approximately one-fourth of LARC patients with TNT achieved a poor regression response. Here, cN2, larger tumor size before treatment and elevated CEA levels were considered predictive features of a poor response. Active surveillance of CEA levels during the TNT course are potentially important, and CEA levels after chemoradiation might have important implications for the tumor response to TNT.
Accelerated partial breast irradiation in early stage breast cancer
Authors: Galavis Paulina E. , Abeloos Camille Hardy , Cheng Pine C. , Hitchen Christine , McCarthy Allison , Purswani Juhi M. , Shah Bhartesh , Taneja Sameer , Gerber Naamit K.
Published: November 2022

Accelerated partial breast irradiation (APBI) is increasingly used to treat select patients with early stage breast cancer. However, radiation technique, dose and fractionation as well as eligibility criteria differ between studies. This has led to controversy surrounding appropriate patients for APBI and an assessment of the toxicity and cosmetic outcomes of APBI as compared to whole breast irradiation (WBI). This paper reviews existing data for APBI, APBI delivery at our institution, and ongoing research to better define patient selection, treatment delivery, dosimetric considerations and toxicity outcomes.
Applying post-neoadjuvant pathologic stage as prognostic tool in esophageal squamous cell carcinoma
Authors: Han Weiming , Deng Wei , Wang Qifeng , Ni Wenjie , Li Chen , Zhou Zongmei , Liang Jun , Chen Dongfu , Feng Qinfu , Bi Nan , Zhang Tao , Wang Xin , Deng Lei , Wang Wenqing , Liu Wenyang , Wang Jianyang , Xue Qi , Mao Yousheng , Liu Xiangyang , Fang Dekang , Li Jian , Wang Dali , Zhao Jun , Xiao Zefen
Published: November 2022

Background

It is still uncertain whether the newly released eighth American Joint Committee on Cancer (AJCC) post-neoadjuvant pathologic (yp) tumor-node-metastasis (TNM) stage for esophageal carcinoma can perform well regarding patient stratification. The current study aimed to assess the prognostication ability of the eighth AJCC ypTNM staging system and attempted to explore how to facilitate the staging system for more effective evaluation of prognosis.

Materials and methods

A total of 486 patients treated with neoadjuvant radiotherapy/chemoradiotherapy (nRT/CRT) were enrolled. ypN stage was reclassified by recursive partitioning. Prognostic performance, monotonicity, homogeneity, and discriminatory of yp and modified yp (myp) staging systems were assessed by time-dependent receiver operating characteristic (ROC), linear trend log-rank test, likelihood ratio χ2 test, Harrell’s c statistic, and Akaike information criterion (AIC).

Results

The ypT stage, ypN stage, and pathologic response were significant prognostic factors of overall survival. Survival was not discriminated well using the eighth AJCC ypN stage and ypTNM stage. Recursive partitioning reclassified mypN0-N2 as metastasis in 0, 1–2, and ≥3 regional lymph nodes. Applying the ypT stage, mypN stage, and pathologic response to construct the myp staging system, the myp stage performed better in time-dependent ROC, linear trend log-rank test, likelihood ratio χ2 test, Harrell’s c statistic, and AIC.

Conclusions

The eighth AJCC ypTNM staging system performed well in differentiating prognosis to some extent. By reclassifying the ypN stage and enrolling pathologic response as a staging element, the myp staging system holds significant potential for prognostic discrimination.
Specific signature biomarkers highlight the potential mechanisms of circulating neutrophils in aneurysmal subarachnoid hemorrhage
Authors: Weng Weipin , Cheng Fan , Zhang Jie
Published: November 2022

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating hemorrhagic stroke with high disability and mortality. Neuroinflammation and the immunological response after aSAH are complex pathophysiological processes that have not yet been fully elucidated. Therefore, attention should be paid to exploring the inflammation-related genes involved in the systemic response to the rupture of intracranial aneurysms.

Methods: The datasets of gene transcriptomes were downloaded from the Gene Expression Omnibus database. We constructed a gene co-expression network to identify cluster genes associated with aSAH and screened out differentially expressed genes (DEGs). The common gene was subsequently applied to identify hub genes by protein-protein interaction analysis and screen signature genes by machine learning algorithms. CMap analysis was implemented to identify potential small-molecule compounds. Meanwhile, Cibersort and ssGSEA were used to evaluate the immune cell composition, and GSEA reveals signal biological pathways.

Results: We identified 602 DEGs from the GSE36791. The neutrophil-related module associated with aSAH was screened by weighted gene co-expression network analysis (WGCNA) and functional enrichment analysis. Several small molecular compounds were predicted based on neutrophil-related genes. MAPK14, ITGAM, TLR4, and FCGR1A have been identified as crucial genes involved in the peripheral immune activation related to neutrophils. Six significant genes (CST7, HSP90AB1, PADI4, PLBD1, RAB32, and SLAMF6) were identified as signature biomarkers by performing the LASSO analysis and SVM algorithms. The constructed machine learning model appears to be robust by receiver-operating characteristic curve analysis. The immune feature analysis demonstrated that neutrophils were upregulated post-aSAH and PADI4 was positively correlated with neutrophils. The NETs pathway was significantly upregulated in aSAH.

Conclusion: We identified core regulatory genes influencing the transcription profiles of circulating neutrophils after the rupture of intracranial aneurysms using bioinformatics analysis and machine learning algorithms. This study provides new insight into the mechanism of peripheral immune response and inflammation after aSAH.