The scalable precision medicine open knowledge engine (SPOKE): a massive knowledge graph of biomedical information.

MOTIVATION: Knowledge graphs (KGs) are being adopted in industry, commerce and academia. Biomedical KG presents a challenge due to the complexity, size and heterogeneity of the underlying information. RESULTS: In this work, we present the Scalable Precision Medicine Open Knowledge Engine (SPOKE), a biomedical KG connecting millions of concepts via semantically meaningful relationships. SPOKE contains 27 million nodes of 21 different types and 53 million edges of 55 types downloaded from 41 databases. The graph is built on the framework of 11 ontologies that maintain its structure, enable mappings and facilitate navigation. SPOKE is built weekly by python scripts which download each resource, check for integrity and completeness, and then create a 'parent table' of nodes and edges. Graph queries are translated by a REST API and users can submit searches directly via an API or a graphical user interface. Conclusions/Significance: SPOKE enables the integration of seemingly disparate information to support precision medicine efforts. AVAILABILITY AND IMPLEMENTATION: The SPOKE neighborhood explorer is available at https://spoke.rbvi.ucsf.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Poor nutritional status is associated with the severity of omicron infection in the older adults.

BACKGROUND: The Omicron wave of Coronavirus disease 2019 (COVID-19) remains the dominant strain worldwide. The studies of nutritional status in geriatric people with COVID-19 Omicron variant are limited. Thus, the aim of this study was to investigate the incidence of poor nutritional status among Omicron infected older patients, and to explore the correlation between the nutritional status and the severity of Omicron infection in older patients. METHODS: This is a retrospective cross-sectional study. According to the clinical symptoms, patients were divided into two groups: mild and moderate to severe. Mini Nutritional Assessment short-form (MNA-SF) was conducted when patients were admitted and poor nutritional status was defined as MNA-SF score of 0-11. The inflammatory markers including neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and systemic inflammatory index (SII) were calculated and compared between two groups. RESULTS: Total of 324 patients were enrolled, with median [interquartile range (IQR)] age of 73 (17) years. Overall, 241 cases were mild, 83 cases were moderate to severe at the time of diagnosis and that 54.3% of patients had poor nutritional status. Patients with poor nutritional status were found to be older (P < 0.001) and less vaccinated (P < 0.001), with a longer virus shedding duration (P = 0.022), more comorbidities (≥ 2) (P = 0.004) and higher value of NLR (P < 0.001), PLR (P < 0.001) and SII (P = 0.012). Vaccination, cycle threshold value in ORF1ab gene (OR CT value) and female, higher MNA-SF score was negatively connected with probability of moderate to severe infection. For every 1 score increase in MNA-SF, the odds ratio of moderate to severe infection decreased by 14.8% [adjusted odds ratio (aOR), 0.852; 95% confidence interval (CI): 0.734-0.988; P = 0.034]. CONCLUSIONS: Older patients with poor nutritional status are more likely to develop moderate to severe Omicron infection.

The association of dietary inflammatory potential with sarcopenia in Chinese community-dwelling older adults.

BACKGROUND: Dietary-induced inflammation is potentially associated with sarcopenia. Nevertheless, few studies have investigated the structure of the inflammatory diet and its correlation with muscle function and performance in both the upper and lower limbs. This study was performed to explore the association of the dietary inflammatory index (DII) with sarcopenia and its diagnostic parameters. METHODS: We conducted a cross-sectional survey on a sample of 515 Chinese community-dwelling older adults selected through multistage cluster sampling from three districts in Shanghai. DII scores were calculated using a validated food frequency questionnaire. Sarcopenia and its diagnostic parameters were determined based on the definition set by the Asian Working Group on Sarcopenia (AWGS). RESULTS: The mean age of study participants was 71.31 ± 4.71 years. The prevalence of sarcopenia in the cohort was 12.4%. Older adults in the highest DII quartile had a 3.339 times increased risk of sarcopenia compared to those in the lowest quartile (OR Quartile4vs1:3.339, 95%CI: 1.232, 9.052, p-trend: 0.004) after adjusting for confounding factors. Additionally, a more pro-inflammatory diet was associated with lower appendicular skeletal muscle index (ASMI) (OR Quartile4vs1: 3.005, 95%CI: 1.275, 7.318, p-trend: 0.005), a higher 5-times sit-stand test time score (OR Quartile4vs1: 4.942, 95%CI: 1.745, 13.993, p-trend: 0.005), and lower gait speed (OR Quartile4vs1: 2.392, 95%CI: 1.104, 5.185, p-trend: 0.041) after adjusting for confounding factors. However, there was no significant association between DII, handgrip strength, and Short Physical Performance Battery (SPPB) score in either the unadjusted or adjusted model. CONCLUSION: This study found that the association between consuming a more pro-inflammatory diet and sarcopenia in Chinese community-dwelling older adults was mainly due to underlying low intakes of dietary energy, protein, and anti-inflammatory foods, and not due to the high intake of pro-inflammatory foods. Meanwhile, DII was more highly correlated with lower limb muscle strength and performance compared to upper limb muscle strength.

Effects of pre-operative enteral immunonutrition for esophageal cancer patients treated with neoadjuvant chemoradiotherapy: protocol for a multicenter randomized controlled trial (point trial, pre-operative immunonutrition therapy).

BACKGROUND: Neoadjuvant chemoradiation followed by esophagectomy has been established as the first-line treatment for locally advanced esophageal cancer. Postoperative enteral nutrition has been widely used to improve perioperative outcomes. However, whether to implement preoperative nutritional intervention during neoadjuvant therapy is yet to be verified by prospective studies. METHODS: POINT trial is a multicenter, open-labeled, randomized controlled trial. A total of 244 patients with surgically resectable esophageal cancer are randomly assigned to nutritional therapy group (arm A) or control group (arm B) with a 2:1 ratio. Both groups receive neoadjuvant chemotherapy with concurrent radiotherapy based on the CROSS regimen followed by minimally invasive esophagectomy. The primary endpoint is the rate of nutrition and immune-related complications after surgery. Secondary endpoints include completion rate of neoadjuvant chemoradiation and related adverse events, rate of pathological complete response, perioperative outcomes, nutritional status, overall survival, progression-free survival and quality of life. DISCUSSION: This trial aims to verify whether immunonutrition during neoadjuvant chemoradiation can reduce the rate of complications and improve perioperative outcomes. Frequent communication and monitoring are essential for a multicenter investigator-initiated trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04513418. The trial was prospectively registered on 14 August 2020, https://www. CLINICALTRIALS: gov/ct2/show/NCT04513418 .

Cognitive impairment is associated with sarcopenia mainly related to attention and calculation in hospitalized Chinese elderly men.

BACKGROUND AND OBJECTIVES: Sarcopenia and cognitive impairment are the most prevalent causes of disability in older individuals. The aim of this study was to assess the prevalence of sarcopenia and the association between cognitive impairment and sarcopenia in older patients. METHODS AND STUDY DESIGN: A cross-sectional study was undertaken, comprised 250 male patients aged 65 and over. Sarcopenia was defined using the diagnostic recommended consensus by the Asian Working Group for sarcopenia, and the participants were classified into the sarcopenia and non-sarcopenia groups according to this definition. The cognitive functions of older patients were assessed using the Mini-Mental State Examination (MMSE). After bivariate analyses, a multivariate logistic regression model was constructed to determine the association of study variables with sarcopenia. RESULTS: The prevalence of sarcopenia and cognitive impairment was 20.8% and 19.6% respectively. Additionally, we found 10.8% patients had nutritional risk, 19.6% patients had cognitive impairment in this study. Multivariate analysis identified age (OR: 1.11, 95% Cl 1.03, 1.19, p=0.008), cognitive impairment (OR: 4.06, 95% Cl 1.42, 11.6, p=0.009) and nutritional risk (OR: 13.7, 95% Cl 3.06, 61.2, p=0.001) were significantly associated with sarcopenia. The prevalence of sarcopenia significantly increased stepwise with lower MMSE score. Additionally, the score on the attention and calculation (OR=0.68, 95% Cl: 0.51, 0.91, p=0.009) subsection of the MMSE was associated with the presence of sarcopenia. MMSE score was correlated with the fat free mass, handgrip strength (p<0.05). CONCLUSIONS: Cognitive impairment, especially in the calculation and attention, and nutritional risk, are associated with sarcopenia in hospitalized Chinese male elderly. Adequate nutritional support may be the key to solving these diseases.

Opposite Neural Trajectories of Apolipoprotein E ϵ4 and ϵ2 Alleles with Aging Associated with Different Risks of Alzheimer's Disease.

The apolipoprotein E (APOE) ϵ4 allele is a confirmed genetic risk factor and the APOE ϵ2 allele is a protective factor related to late-onset Alzheimer's disease (AD). Intriguingly, recent studies demonstrated similar brain function alterations between APOE ϵ2 and ϵ4 alleles, despite their opposite susceptibilities to AD. To address this apparent discrepancy, we recruited 129 cognitively normal elderly subjects, including 36 ϵ2 carriers, 44 ϵ3 homozygotes, and 49 ϵ4 carriers. All subjects underwent resting-state functional MRI scans. We hypothesized that aging could influence the APOE ϵ2 and ϵ4 allele effects that contribute to their appropriate AD risks differently. Using the stepwise regression analysis, we demonstrated that although both ϵ2 and ϵ4 carriers showed decreased functional connectivity (FC) compared with ϵ3 homozygotes, they have opposite aging trajectories in the default mode network-primarily in the bilateral anterior cingulate cortex. As age increased, ϵ2 carriers showed elevated FC, whereas ϵ4 carriers exhibited decreased FC. Behaviorally, the altered DMN FC positively correlated with information processing speed in both ϵ2 and ϵ4 carriers. It is suggested that the opposite aging trajectories between APOE ϵ2 and ϵ4 alleles in the DMN may reflect the antagonistic pleiotropic properties and associate with their different AD risks.

Immunity factor contributes to altered brain functional networks in individuals at risk for Alzheimer's disease: Neuroimaging-genetic evidence.

Clusterin (CLU) is recognized as a secreted protein that is related to the processes of inflammation and immunity in the pathogenesis of Alzheimer's disease (AD). The effects of the risk variant of the C allele at the rs11136000 locus of the CLU gene are associated with variations in the brain structure and function. However, the relationship of the CLU-C allele to architectural disruptions in resting-state networks in amnestic mild cognitive impairment (aMCI) subjects (i.e., individuals with elevated risk of AD) remains relatively unknown. Using resting-state functional magnetic resonance imaging and an imaging genetic approach, this study investigated whether individual brain functional networks, i.e., the default mode network (DMN) and the task-positive network, were modulated by the CLU-C allele (rs11136000) in 50 elderly participants, including 26 aMCI subjects and 24 healthy controls. CLU-by-aMCI interactions were associated with the information-bridging regions between resting-state networks rather than with the DMN itself, especially in cortical midline regions. Interestingly, the complex communications between resting-state networks were enhanced in aMCI subjects with the CLU rs11136000 CC genotype and were modulated by the degree of memory impairment, suggesting a reconstructed balance of the resting-state networks in these individuals with an elevated risk of AD. The neuroimaging-genetic evidence indicates that immunity factors may contribute to alterations in brain functional networks in aMCI. These findings add to the evidence that the CLU gene may represent a potential therapeutic target for slowing disease progression in AD.

Nutrition Status, Nutrition Support Therapy, and Food Intake are Related to Prolonged Hospital Stays in China: Results from the NutritionDay 2015 Survey.

BACKGROUND AND AIMS: Malnutrition is a common and critical problem that greatly influences the clinical outcomes of hospitalized patients. Nutrition support therapy and food intake, in addition to disease-related factors, are also important to maintain the nutrition status of patients. In light of this, we aimed to examine the risk factors associated with malnutrition in 3 hospitals in China. METHODS: This project was part of the NutritionDay audit, an international daylong cross-sectional audit investigating the nutritional intervention profiles of hospitalized patients. Seven standardized questionnaires were used, and malnutrition was defined as a body mass index <18.5 kg/m2 or unintentional weight loss >5% in last 3 months. RESULTS: A total of 842 hospitalized patients from 9 units in 3 Chinese hospitals participated in the project on November 19, 2015. Among them, 825 were included in the analyses. Malnutrition was identified in 29.3% of the patients and oral nutrition was the primary nutrition support therapy administered (n = 623, 75.6%). Age, nutrition support, and food intake during the past week were independent risk factors for malnutrition. Furthermore, nutrition status, nutrition support therapy, and food intake during the past week were associated with prolonged length of stay. CONCLUSIONS: The prevalence of malnutrition in Chinese hospitals was similar to that in European hospitals. Nutrition status was associated with age, nutrition support, and food intake, which was closely related to patients' clinical outcome, such as prolonged hospital stays as confirmed in this study. More studies are needed to determine why nutrition intake is often inadequate and to determine efficient methods for correcting the nutrition status of patients.

Preoperative body composition measured by bioelectrical impedance analysis can predict pancreatic fistula after pancreatic surgery.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains one of the most severe complications after pancreatic surgery. The methods for predicting pancreatic fistula are limited. We aimed to investigate the predictive value of body composition parameters measured by preoperative bioelectrical impedance analysis (BIA) on the development of POPF. METHODS: A total of 168 consecutive patients undergoing pancreatic surgery from March 2022 to December 2022 at our institution were included in the study and randomly assigned at a 3:2 ratio to the training group and the validation group. All data, including previously reported risk factors for POPF and parameters measured by BIA, were collected. Risk factors were analyzed by univariable and multivariable logistic regression analysis. A prediction model was established to predict the development of POPF based on these parameters. RESULTS: POPF occurred in 41 of 168 (24.4%) patients. In the training group of 101 enrolled patients, visceral fat area (VFA) (odds ratio [OR] = 1.077, P = 0.001) and fat mass index (FMI) (OR = 0.628, P = 0.027) were found to be independently associated with POPF according to multivariable analysis. A prediction model including VFA and FMI was established to predict the development of POPF with an area under the receiver operating characteristic curve (AUC) of 0.753. The efficacy of the prediction model was also confirmed in the internal validation group (AUC 0.785, 95% CI 0.659-0.911). CONCLUSIONS: Preoperative assessment of body fat distribution by BIA can predict the risk of POPF after pancreatic surgery.

Topologically convergent and divergent structural connectivity patterns between patients with remitted geriatric depression and amnestic mild cognitive impairment.

Alzheimer's disease (AD) can be conceptualized as a disconnection syndrome. Both remitted geriatric depression (RGD) and amnestic mild cognitive impairment (aMCI) are associated with a high risk for developing AD. However, little is known about the similarities and differences in the topological patterns of white matter (WM) structural networks between RGD and aMCI. In this study, diffusion tensor imaging and deterministic tractography were used to map the human WM networks of 35 RGD patients, 38 aMCI patients, and 30 healthy subjects. Furthermore, graph theoretical methods were applied to investigate the alterations in the global and regional properties of the WM network in these patients. First, both the RGD and aMCI patients showed abnormal global topology in their WM networks (i.e., reduced network strength, reduced global efficiency, and increased absolute path length) compared with the controls, and there were no significant differences in these global network properties between the patient groups. Second, similar deficits of the regional and connectivity characteristics in the WM networks were primarily found in the frontal brain regions of RGD and aMCI patients compared with the controls, while a different nodal efficiency of the posterior cingulate cortex and several prefrontal brain regions were also observed between the patient groups. Together, our study provides direct evidence for the association of a great majority of convergent and a minority of divergent connectivity of WM structural networks between RGD and aMCI patients, which may lead to increasing attention in defining a population at risk of AD.

Microbial dysbiosis in oral squamous cell carcinoma: A systematic review and meta-analysis.

Objective: The aim of this study was to summarize previously published data and assess the alterations in the composition of the oral microbiome in OSCC using a systematic review and meta-analysis. Design: Electronic databases were systematically searched for studies on the oral microbiome in OSCC published before December 2021. Qualitative assessments of compositional variations at the phylum level were performed. The meta-analysis on abundance changes of bacteria genera was performed via a random-effects model. Results: A total of 18 studies involving 1056 participants were included. They consisted of two categories of studies: 1) case-control studies (n = 9); 2) nine studies that compared the oral microbiome between cancerous tissues and paired paracancerous tissues. At the phylum level, enrichment of Fusobacteria but depletion in Actinobacteria and Firmicutes in the oral microbiome was demonstrated in both categories of studies. At the genus level, Fusobacterium showed an increased abundance in OSCC patients (SMD = 0.65, 95% CI: 0.43-0.87, Z = 5.809, P = 0.000) and in cancerous tissues (SMD = 0.54, 95% CI: 0.36-0.72, Z = 5.785, P = 0.000). The abundance of Streptococcus was decreased in OSCC (SMD = -0.46, 95% CI: -0.88-0.04, Z = -2.146, P = 0.032) and in cancerous tissues (SMD = -0.45, 95% CI: -0.78-0.13, Z = -2.726, P = 0.006). Conclusions: Disturbances in the interactions between enriched Fusobacterium and depleted Streptococcus may participate in or prompt the occurrence and development of OSCC and could be potential biomarkers for detection of OSCC.

Creation of an ustekinumab external control arm for Crohn's disease using electronic health records data: A pilot study.

BACKGROUND: Randomized trials are the gold-standard for clinical evidence generation, but they can sometimes be limited by infeasibility and unclear generalizability to real-world practice. External control arm (ECA) studies may help address this evidence gaps by constructing retrospective cohorts that closely emulate prospective ones. Experience in constructing these outside the context of rare diseases or cancer is limited. We piloted an approach for developing an ECA in Crohn's disease using electronic health records (EHR) data. METHODS: We queried EHR databases and manually screened records at the University of California, San Francisco to identify patients meeting the eligibility criteria of TRIDENT, a recently completed interventional trial involving an ustekinumab reference arm. We defined timepoints to balance missing data and bias. We compared imputation models by their impacts on cohort membership and outcomes. We assessed the accuracy of algorithmic data curation against manual review. Lastly, we assessed disease activity following treatment with ustekinumab. RESULTS: Screening identified 183 patients. 30% of the cohort had missing baseline data. Nonetheless, cohort membership and outcomes were robust to the method of imputation. Algorithms for ascertaining non-symptom-based elements of disease activity using structured data were accurate against manual review. The cohort consisted of 56 patients, exceeding planned enrollment in TRIDENT. 34% of the cohort was in steroid-free remission at week 24. CONCLUSION: We piloted an approach for creating an ECA in Crohn's disease from EHR data by using a combination of informatics and manual methods. However, our study reveals significant missing data when standard-of-care clinical data are repurposed. More work will be needed to improve the alignment of trial design with typical patterns of clinical practice, and thereby enable a future of more robust ECAs in chronic diseases like Crohn's disease.

Abnormal insula functional network is associated with episodic memory decline in amnestic mild cognitive impairment.

Abnormalities of functional connectivity in the default mode network (DMN) recently have been reported in patients with amnestic mild cognitive impairment (aMCI), Alzheimer's disease (AD) or other psychiatric diseases. As such, these abnormalities may be epiphenomena instead of playing a causal role in AD progression. To date, few studies have investigated specific brain networks, which extend beyond the DMN involved in the early AD stages, especially in aMCI. The insula is one site affected by early pathological changes in AD and is a crucial hub of the human brain networks. Currently, we explored the contribution of the insula networks to cognitive performance in aMCI patients. Thirty aMCI and 26 cognitively normal (CN) subjects participated in this study. Intrinsic connectivity of the insula networks was measured, using the resting-state functional connectivity fMRI approach. We examined the differential connectivity of insula networks between groups, and the neural correlation between the altered insula networks connectivity and the cognitive performance in aMCI patients and CN subjects, respectively. Insula subregional volumes were also investigated. AMCI subjects, when compared to CN subjects, showed significantly reduced right posterior insula volumes, cognitive deficits and disrupted intrinsic connectivity of the insula networks. Specifically, decreased intrinsic connectivity was primarily located in the frontal-parietal network and the cingulo-opercular network, including the anterior prefrontal cortex (aPFC), anterior cingulate cortex, operculum, inferior parietal cortex and precuneus. Increased intrinsic connectivity was primarily situated in the visual-auditory pathway, which included the posterior superior temporal gyrus and middle occipital gyrus. Conjunction analysis was performed; and significantly decreased intrinsic connectivity in the overlapping regions of the anterior and posterior insula networks, including the bilateral aPFC, left dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, and anterior temporal pole was found. Furthermore, the disrupted intrinsic connectivity was associated with episodic memory (EM) deficits in the aMCI patients and not in the CN subjects. These findings demonstrated that the functional integration of the insula networks plays an important role in the EM process. They provided new insight into the neural mechanism underlying the memory deficits in aMCI patients.

Association of the interleukin 1 beta gene and brain spontaneous activity in amnestic mild cognitive impairment.

PURPOSE: The inflammatory response has been associated with the pathogenesis of Alzheimer's disease (AD). The purpose of this study is to determine whether the rs1143627 polymorphism of the interleukin-1 beta (IL-1ß) gene moderates functional magnetic resonance imaging (fMRI)-measured brain regional activity in amnestic mild cognitive impairment (aMCI). METHODS: Eighty older participants (47 with aMCI and 33 healthy controls) were recruited for this study. All of the participants were genotyped for variant rs1143627 in the IL1B gene and were scanned using resting-state fMRI. Brain activity was assessed by amplitude of low-frequency fluctuation (ALFF). RESULTS: aMCI patients had abnormal ALFF in many brain regions, including decreases in the inferior frontal gyrus, the superior temporal lobe and the middle temporal lobe, and increases in the occipital cortex (calcarine), parietal cortex (Pcu) and cerebellar cortex. The regions associated with an interaction of group X genotypes of rs1143627 C/T were the parietal cortex (left Pcu), frontal cortex (left superior, middle, and medial gyrus, right anterior cingulum), occipital cortex (left middle lobe, left cuneus) and the bilateral posterior lobes of the cerebellum. Regarding the behavioral significance, there were significant correlations between ALFF in different regions of the brain and with the cognitive scores of each genotype group. CONCLUSIONS: The present study provided evidence that aMCI patients had abnormal ALFF in many brain regions. Specifically, the rs1143627 C/T polymorphism of the IL1B gene may modulate regional spontaneous brain activity in aMCI patients.

Association between Dietary Inflammatory Index and Sarcopenia in Crohn's Disease Patients.

BACKGROUND: Chronic inflammation is a pathophysiological cause of sarcopenia in Crohn's disease (CD) patients. However, the potential impact of diet-related inflammation on sarcopenia has not yet been adequately investigated. We examined the associations between Dietary Inflammatory Index (DII) and sarcopenia in CD patients. METHODS: A total of 140 CD patients from Ruijin Hospital in Shanghai were included in this cross-sectional study. DII scores were calculated from the dietary data collected using a validated food frequency questionnaire (FFQ). Sarcopenia was determined according to the Asian Working Group for Sarcopenia. Multivariable logistic regression analyses were performed to determine the association between DII and sarcopenia. RESULTS: The mean DII score was 0.81 ± 2.13, ranging from -3.24 to 4.89. The overall prevalence of sarcopenia was 26.4%. The higher DII score significantly increased the risk of sarcopenia in CD patients (ORQuartile4vs1: 9.59, 95% CI: 1.69, 54.42, ptrend = 0.031) in the multivariable model after adjusting for more potential confounders. Moreover, CD patients with a lower DII had a significantly higher appendicular skeletal muscle mass index (ASMI, ORQuartile4vs1: 5.48, 95% CI: 1.51, 19.87, ptrend = 0.018) after adjusting for age, gender, BMI, smoking status and drinking status model. Yet, there were no significant differences between DII and ASMI after adjusting for more potential confounders. Additionally, no significant association was observed between DII and handgrip strength in the multivariable-adjusted models. CONCLUSIONS: Pro-inflammatory diet was associated with increased risk of sarcopenia in CD patients. CD patients should have a proper intake of energy and protein. These patients could also benefit from supplementation with enteral nutrition due to its anti-inflammatory potential.

Role of perioperative nutritional status and enteral nutrition in predicting and preventing post-operative complications in patients with Crohn's disease.

Background: Perioperative immune-nutritional status is correlated with post-operative outcomes. This study aimed to evaluate whether pre-operative nutritional status could predict post-operative complications in patients with Crohn's disease (CD) and whether pre-operative enteral nutrition (EN) can prevent post-operative complications. Methods: This retrospective cohort study analyzed the electronic health records of 173 patients diagnosed with CD in Ruijin Hospital, Shanghai, China, between August 2015 and May 2021: 122 patients had pre-operative nutritional support while 51 patients underwent surgery without pre-operative nutritional support. The pre-operative nutritional status, disease activity index, disease-related data, frequency of multiple surgery, operative data, and post-operative characters in each group were compared to determine whether the nutritional support and status could significantly affect post-operative outcome. One-to-one propensity score matching (PSM) was performed to limit demographic inequalities between the two groups. Results: After PSM, no statistically significant differences were found in pre-operative patient basic characteristics between the two groups of 47 patients (98 patients in all) included in this study. Overall, 21 patients developed 26 post-operative complications. In terms of pre-operative nutritional status, the level of serum albumin (ALB), pre-albumin (pre-ALB), and hemoglobin (Hb) in the nutrition group were statistically higher than that in the control group. We also observed a statistically significant decrease in post-operative complications, need for emergency surgery, and staged operations, while the rate of laparoscopic surgery was higher in the nutrition group compared to the non-nutritional group. Post-operative complications were related to pre-operative nutritional condition, which indicated that EN may improve the nutritional status and reduced the rate of post-operative complications. Conclusion: Pre-operative nutritional status is correlated with post-operative outcomes while EN plays a positive role in preventing the post-operative complications. EN is useful for improving the pre-operative nutritional status and reducing the post-operative adverse events for CD patients undergoing surgery.

A Panel of E2F Target Gene Signature Predicting the Prognosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma is one of the most malignant tumors, and the therapeutic effects of traditional treatments are poor. It is urgent to explore and identify new biomarkers and therapeutic targets to develop novel treatments which are individualized and effective. Three hallmarks, including E2F targets, G2M checkpoint and DNA repair, were collected by GSEA analysis. The panel of E2F-related gene signature consisted of five genes: HN1, KIF4A, CDCA3, CDCA8 and SSRP1. They had various mutation rates ranging from 0.8 to 5% in hepatocellular carcinoma, and patients with gene mutation had poorer prognosis. Among these genes, HN1 has the greatest mutation rate, and SSRP1 has the greatest impact on the model with a B (COX) value of 0.8842. Patients with higher expression of these genes had poorer prognosis. Kaplan-Meier curves in stratified survival analysis confirmed that patients with high risk scores had poor prognosis (p < 0.05). The results of univariate and multivariate COX survival analysis showed that risk score was closely related to the overall survival of patients with hepatocellular carcinoma. For clinical validation, we found that all the genes in the model were upregulated in hepatocellular carcinoma tissues compared to normal liver tissues, which was consistent with the previous results we obtained. Our study demonstrated that a panel of E2F target genes signature including five genes could predict the prognosis of hepatocellular carcinoma. This panel gene signature can facilitate the development of individualized and effective treatment for hepatocellular carcinoma.

The methylation modification of m6A regulators contributes to the prognosis of ovarian cancer.

Background: Ovarian cancer (OV) is the leading cause of death in gynecological cancer. The dysregulation of N6-methyladenosine (m6A) modification is commonly found in cancers. However, there is a lack of research into m6A RNA methylation regulators in OV. Methods: The RNA-Seq of 379 OV tissues and 88 healthy ovarian tissues was downloaded from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, respectively. A Gene Ontology (GO) functional analysis was performed to verify the function of m6A RNA methylation regulators. Kaplan-Meier (K-M) curves and the log-rank (Mantel-Cox) test were used for the survival analysis. A Cox regression analysis was used to identify the genes related to overall survival (OS) and build the prediction model. Results: m6A RNA methylation regulators were dysregulated in OV tissues compared with normal tissues (P<0.05), and patients with a high expression of KIAA1429 and YTHDC2 had a poor prognosis (P<0.05). A prognostic model was constructed based on the m6A RNA methylation regulators. Based on the risk signature, the patients were classified into high- and low-risk groups. The low-risk group's OS rate was significantly better than that of the high-risk group. The validity and accuracy of the prognostic model were verified by using TCGA and Gene Expression Omnibus (GEO) datasets, and the risk score from the prognostic model acted as an independent prognostic indicator in predicting the survival of OV patients. Conclusions: m6A RNA methylation regulators were dysregulated in OV tissues. More importantly, the prognostic model comprising the five selected m6A RNA methylation regulators could be a valuable tool for predicting the prognosis of OV patients.

Body Mass Index and Disease Activity Are Associated With Moderate to Severe Disability in Crohn's Disease: A Cross-Sectional Study in Shanghai.

Background: The inflammatory bowel disease disability index (IBD-DI) was used to access body functional consequences and disease burden. However, Chinese population data are considerably limited. Objective: We aimed to screen for disability in patients with Crohn's disease (CD) and to assess potential associations with clinical parameters as well as indices related to sarcopenia. Methods: This cross-sectional study includes 146 CD patients from Ruijin Hospital in Shanghai, China. All patients were screened for disability and sarcopenia on the basis of the IBD-DI scale, and the criteria for Asian Working Group for Sarcopenia, respectively. Clinical and demographic variables were collected. Results: Approximately 52.05% of the subjects suffered from moderate or severe disabilities. The prevalence of sarcopenia (48.68 vs. 31.43%, P = 0.043), Patient-Generated Subjective Global Assessment score or PG-SGA≥4 (39.47 vs. 17.14%, P = 0.003), and high-level C- reactive protein (27.63 vs. 11.43%, P = 0.021) were higher in patients with moderate to severe disability than in those without to minimal disability. By multivariate regression modeling, the following were identified as independent factors related to moderate to severe disability: disease activity (OR:10.47, 95% CI: 2.09-52.42) and body mass index (BMI) (OR:4.11, 95% CI: 1.80-9.38). Conclusions: Disability is common in CD patients. Our study showed that moderate to severe disability is not directly associated with muscle mass or muscle quantity but is mostly correlated with disease activity as well as BMI. Thus, close monitoring and follow-up should be conducted on patients who are at high risk of disability, and effective measures should be taken, which may be the best way to prevent disability.

The Influencing Factors of Nutrition and Diet Health Knowledge Dissemination Using the WeChat Official Account in Health Promotion.

Background: The promotion of a healthy diet via health education is a component of the "Healthy China 2030" plan. However, few studies have reported whether health knowledge about nutrition and diet has gained public attention, and whether it is needed by the public. Methods: The numbers of views, shares, and reads of articles published by the official WeChat account of a hospital in China were accessed. The influence index was obtained via the entropy analysis of these three indices. A questionnaire survey was developed based on the purpose of the study and the conclusion of the content analysis, which conducted to analyze users' requirements for health knowledge and their influencing factors. Moreover, risk factors were explored by logistic regression models. Results: Of the 103 articles considered in this study, four articles in the Top 10 were related to nutrition and diet. The influence index of nutrition and diet knowledge was found to be the highest in the content analysis (p < 0.05). The higher degrees of humor (ß = 0.224, p = 0.027), nutrition and diet articles (ß = 0.776, p = 0.034), and cover articles (ß = 0.312, p = 0.021) have significant influences on the influence index. In total, 581 questionnaires were obtained, and 78.1% of the respondents reported believing that the health knowledge of greatest concern was that related to nutrition and diet. Multivariate logistic regression analyses were conducted to explore the associations between the features of the articles and users reading nutrition and diet knowledge; it was found that gender (female, OR: 4.651, 95%Cl: 2.598, 8.325, and p < 0.001), age (young adult, OR: 0.358, 95%Cl: 0.266, 0.481, and p < 0.001), cancer precaution knowledge (OR: 4.333, 95%Cl: 2.262, 8.299, and p < 0.001), traditional Chinese medicine (OR: 2.121, 95%Cl: 1.064, 4.230, and p = 0.033), the knowledge acquisition approach [circle of friends (OR: 2.586, 95%Cl: 1.373, 4.868, and p = 0.003), social media (OR: 2.183, 95%Cl: 1.204, 3.960, and p = 0.010)), hospitals (OR: 3.194, 95%Cl: 1.793, 5.692, and p < 0.001), television media (OR: 4.348, 95%Cl: 2.341, 8.077, and p < 0.001)], and social media strategies [professionalism and authority (OR: 2.354, 95%Cl: 1.231, 4.505, and p = 0.006)] have statistically significant relationships with users reading nutrition and diet knowledge. Conclusion: Nutrition and diet knowledge could contribute to WeChat user engagement of health information dissemination. Nutrition professionals should improve the scientific popularization ability and effectively use social media for health promotion.