bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Validation of the Immune Regulator CXCR4 as a Novel Promising Target for Gastric Cancer
Authors: Xue Shuai , Ma Ming , Bei Songhua , Li Fan , Wu Chenqu , Li Huanqing , Hu Yanling , Zhang Xiaohong , Qian YanQing , Qin Zhe , Jiang Jun , Feng Li
Published: July 2021

Immune checkpoint blockade has attracted a lot of attention in the treatment of human malignant tumors. We are trying to establish a prognostic model of gastric cancer (GC) based on the expression profile of immunoregulatory factor-related genes. Based on the TCGA database, we identified 234 differentially expressed immunoregulatory factors. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) conducted enrichment analysis to clarify the biological functions of differential expression of immunoregulatory factors. STRING database predicted the interaction network between 234 differently expressed immune regulatory factors. The expression of 11 immunoregulatory factors was significantly related to the overall survival of gastric cancer patients. Univariate Cox regression analysis, Kaplan–Meier analysis and multivariate Cox regression analysis found that immunomodulatory factors were involved in the progression of gastric cancer and promising biomarkers for predicting prognosis. Among them, CXCR4 was related to the low survival of GC patients and a key immunomodulatory factor in GC. Based on TCGA data, the high expression of CXCR4 in GC was positively correlated with the advanced stage and grade of gastric cancer and related to poor prognosis. Univariate analysis and multivariate analysis indicated that CXCR4 was an independent prognostic indicator for TCGA gastric cancer patients. In vitro functional studies had shown that CXCR4 promoted the proliferation, migration, and invasion of gastric cancer cells. In summary, this study has determined the prognostic value of 11 immunomodulatory factors in gastric cancer. CXCR4 is an independent prognostic indicator for gastric cancer patients, which may help to improve the individualized prognostic prediction of GC and provide candidates for the diagnosis and treatment of GC.
Can Broadly Neutralizing HIV-1 Antibodies Help Achieve an ART-Free Remission?
Authors: Hsu Denise C. , Mellors John W. , Vasan Sandhya
Published: July 2021

Many broadly neutralizing antibodies (bnAbs) targeting the HIV-1 envelope glycoprotein are being assessed in clinical trials as strategies for HIV-1 prevention, treatment, and antiretroviral-free remission. BnAbs can neutralize HIV-1 and target infected cells for elimination. Concerns about HIV-1 resistance to single bnAbs have led to studies of bnAb combinations with non-overlapping resistance profiles. This review focuses on the potential for bnAbs to induce HIV-1 remission, either alone or in combination with latency reversing agents, therapeutic vaccines or other novel therapeutics. Key topics include preliminary activity of bnAbs in preclinical models and in human studies of HIV-1 remission, clinical trial designs, and antibody design strategies to optimize pharmacokinetics, coverage of rebound-competent virus, and enhancement of cellular immune functions.
Explaining Recruitment Stochasticity at a Species’ Range Margin
Authors: Westerbom Mats , Kraufvelin Patrik , Mustonen Olli , Díaz Eliecer
Published: July 2021

Advancing our understanding of how environmental variability affects the distribution of organisms is crucial for ecology and conservation. The exploration of changes in demographic patterns close to species distribution margins is important as populations here may provide a window into future population changes also elsewhere. However, the knowledge of factors causing recruitment variation is still inadequate in many systems and this deficiency is particularly evident close to species’ distribution borders. We studied the spatiotemporal variability in recruit-adult dynamics in a blue mussel,Mytilus trossulus, population to get insights into how environmental variables drive variation in recruitment and how this variability affects adult population growth. Thirty sites along a wave exposure gradient were monitored during four consecutive years. From each site, mussels were collected both from artificial recruitment units and from natural mussel beds. Our results showed high year-to-year variation in recruitment strength with high spatial variation. Mussel recruitment to artificial units and later recruitment to the benthos correlated highly. Juvenile abundances 1 year later paralleled prior recruitment strengths and caused synchronous but time-lagged changes in adult cohorts. Seawater salinity was the strongest predictor for recruitment variation, whereas sea temperature and wave exposure had low predictive power for this early life stage. For juveniles and for adults in the benthos, wave exposure explained the variation best, whereas temperature and especially salinity explained less. The results indicate that (a) the studied blue mussel population is strongly driven by variation in recruitment strength that (b) drives the size of the later cohorts, and the population is possibly even (c) recruitment limited in some years. Our study predicts a challenging future for this range population, resulting from a higher frequency of recruitment failure caused by a deteriorating sea climate. Knowledge about factors underlying variation in recruitment is thus essential for forecasting the future of this range population and for conserving its future state.
Acute Kidney Injury and Early Predictive Factors in COVID-19 Patients
Authors: Liu Jiaye , Wang Tingyan , Cai Qingxian , Huang Deliang , Sun Liqin , He Qing , Wang Fu-Sheng , Chen Jun
Published: July 2021

Objectives: Our objective was to explore the incidence and early predictive factors of acute kidney injury in coronavirus disease 2019 (COVID-19) patients.

Method: We established a retrospective cohort of 408 patients who were admitted to Shenzhen Third People's Hospital in Shenzhen, China, between January 1 and March 31, 2020. Clinical outcomes and renal function were monitored until April 12, 2020, with a median follow-up duration of 21 days [interquartile range (IQR) = 14–33].

Results: When first admitted to hospital (baseline), 19.36% (79/408) presented renal dysfunction [estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2]. During follow-up, 3.9% (16/408) developed acute kidney injury (AKI). Age ≥60 years [hazard ratio (HR) = 4.78, 95% CI = 1.10–20.69], PaO2/FiO2 ratio <300 (HR = 3.48, 95% CI = 1.04–11.62), and higher creatinine (HR = 1.04, 95% CI = 1.01–1.07) at baseline independently predicted the risk of AKI. Respectively, 25.0% (102/408), 3.9% (16/408), 0.5% (2/408), 1.0% (4/408), and 0.2% (1/408) experienced G2, G3a, G3b, G4, and G5 as their most severe category during hospitalization, while 69.4% (283/408) had normal eGFRs throughout the follow-up period. When finally discharged from hospital, there were 12.5% (51/408) of patients with abnormal eGFRs.

Conclusions: COVID-19 patients can be at risk of AKI and continuous eGFR decline during hospitalization, which can be early predicted by baseline factors. Some individuals still had renal dysfunction when finally discharged from hospital.
Acute and Chronic Management of Ocular Disease in Stevens Johnson Syndrome/Toxic Epidermal Necrolysis in the USA
Authors: Metcalfe Derek , Iqbal Omer , Chodosh James , Bouchard Charles S. , Saeed Hajirah N.
Published: July 2021

Stevens Johnson syndrome and toxic epidermal necrolysis are on a spectrum of a severe, immune-mediated, mucocutaneous disease. Ocular involvement occurs in the vast majority of cases and severe involvement can lead to corneal blindness. Treatment in the acute phase is imperative in mitigating the severity of chronic disease. Advances in acute treatment such as amniotic membrane transplantation have shown to significantly reduce the severity of chronic disease. However, AMT is not a panacea and severe chronic ocular disease can and does still occur even with aggressive acute treatment. Management of chronic disease is equally critical as timely intervention can prevent worsening of disease and preserve vision. This mini-review describes the acute and chronic findings in SJS/TEN and discusses medical and surgical management strategies.
Probable Causes and Risk Factors for Positive SARS-CoV-2 Testing in Recovered Patients: Evidence From Guangzhou, China
Authors: Luo Lei , Liu Dan , Zhang Zhoubin , Li Zhihao , Xie Chaojun , Wang Zhenghe , Chen Zongqiu , Zhang Peidong , Zhang Xiru , Zhang Yujie , Zhong Wenfang , Zhang Wenting , Yang Pei , Huang Qingmei , Song Weiqi , Wang Hui , Mao Chen
Published: July 2021

Some patients retested positive for SARS-CoV-2 following negative testing results and discharge. However, the potential risk factors associated with redetectable positive testing results in a large sample of patients who recovered from COVID-19 have not been well-estimated. A total of 745 discharged patients were enrolled between January 30, 2020, and September 9, 2020, in Guangzhou, China. Data on the clinical characteristics, comorbidities, drug therapy, RT-PCR testing, and contact modes to close contacts were collected. Patients who tested positive for SARS-CoV-2 after discharge were confirmed by guidelines issued by China. The repositive rate in different settings was calculated. Among 745 discharged patients, 157 (21.1%; 95% CI, 18.2–24.0%) tested repositive and the repositive rate was 16.8% (95% CI, 14.1–24.0%) for nasopharyngeal swabs and 9.7% (95% CI, 7.0–12.5%) for anal swabs. Among them, 55 (35.0%) were asymptomatic, 15 (9.6%) had mild symptoms, 83 (52.9%) had moderate symptoms, and 4 (2.6%) had severe symptoms at the first admission. The days from discharge to repositivity was 8.0 (IQR, 8.0–14.0). Most repositive patients were without clinical symptoms, and lymphocyte cell counts were higher than before being discharged. The likelihood of repositive testing for SARS-CoV-2 RNA was significantly higher among patients who were of younger age (OR, 3.88; 95% CI, 1.74–8.66, 0–17 years old), had asymptomatic severity (OR, 4.36; 95% CI, 1.47–12.95), and did not have clinical symptoms (OR, 1.89; 95% CI, 1.32–2.70, without fever). No other positive patients emerged within the families or close contacts of repositive patients. Our findings support prolonged but intermittent viral shedding as the probable cause for this phenomenon; we need to familiarize with the possibility that the virus will remain endemic.
The Axenic and Gnotobiotic Mosquito: Emerging Models for Microbiome Host Interactions
Authors: Steven Blaire , Hyde Josephine , LaReau Jacquelyn C. , Brackney Doug E.
Published: July 2021

The increasing availability of modern research tools has enabled a revolution in studies of non-model organisms. Yet, one aspect that remains difficult or impossible to control in many model and most non-model organisms is the presence and composition of the host-associated microbiota or the microbiome. In this review, we explore the development of axenic (microbe-free) mosquito models and what these systems reveal about the role of the microbiome in mosquito biology. Additionally, the axenic host is a blank template on which a microbiome of known composition can be introduced, also known as a gnotobiotic organism. Finally, we identify a “most wanted” list of common mosquito microbiome members that show the greatest potential to influence host phenotypes. We propose that these are high-value targets to be employed in future gnotobiotic studies. The use of axenic and gnotobiotic organisms will transition the microbiome into another experimental variable that can be manipulated and controlled. Through these efforts, the mosquito will be a true model for examining host microbiome interactions.
Predicting Age From Behavioral Test Performance for Screening Early Onset of Cognitive Decline
Authors: Statsenko Yauhen , Habuza Tetiana , Charykova Inna , Gorkom Klaus Neidl-Van , Zaki Nazar , Almansoori Taleb M. , Baylis Gordon , Ljubisavljevic Milos , Belghali Maroua
Published: July 2021

Background: Neuronal reactions and cognitive processes slow down during aging. The onset, rate, and extent of changes vary considerably from individual to individual. Assessing the changes throughout the lifespan is a challenging task. No existing test covers all domains, and batteries of tests are administered. The best strategy is to study each functional domain separately by applying different behavioral tasks whereby the tests reflect the conceptual structure of cognition. Such an approach has limitations that are described in the article.

Objective: Our aim was to improve the diagnosis of early cognitive decline. We estimated the onset of cognitive decline in a healthy population, using behavioral tests, and predicted the age group of an individual. The comparison between the predicted (“cognitive”) and chronological age will contribute to the early diagnosis of accelerated aging.

Materials and Methods: We used publicly available datasets (POBA, SSCT) and Pearson correlation coefficients to assess the relationship between age and tests results, Kruskal-Wallis test to compare distribution, clustering methods to find an onset of cognitive decline, feature selection to enhance performance of the clustering algorithms, and classification methods to predict an age group from cognitive tests results.

Results: The major results of the psychophysiological tests followed a U-shape function across the lifespan, which reflected the known inverted function of white matter volume changes. Optimal values were observed in those aged over 35 years, with a period of stability and accelerated decline after 55–60 years of age. The shape of the age-related variance of the performance of major cognitive tests was linear, which followed the trend of lifespan gray matter volume changes starting from adolescence. There was no significant sex difference in lifelong dynamics of major tests estimates. The performance of the classification model for identifying subject age groups was high.

Conclusions: ML models can be designed and utilized as computer-aided detectors of neurocognitive decline. Our study demonstrated great promise for the utility of classification models to predict age-related changes. These findings encourage further explorations combining several tests from the cognitive and psychophysiological test battery to derive the most reliable set of tests toward the development of a highly-accurate ML model.
A Computational Study of Astrocytic GABA Release at the Glutamatergic Synapse: EAAT-2 and GAT-3 Coupled Dynamics
Authors: Flanagan Bronac , McDaid Liam , Wade John Joseph , Toman Marinus , Wong-Lin KongFatt , Harkin Jim
Published: July 2021

Neurotransmitter dynamics within neuronal synapses can be controlled by astrocytes and reflect key contributors to neuronal activity. In particular, Glutamate (Glu) released by activated neurons is predominantly removed from the synaptic space by perisynaptic astrocytic transporters EAAT-2 (GLT-1). In previous work, we showed that the time course of Glu transport is affected by ionic concentration gradients either side of the astrocytic membrane and has the propensity for influencing postsynaptic neuronal excitability. Experimental findings co-localize GABA transporters GAT-3 with EAAT-2 on the perisynaptic astrocytic membrane. While these transporters are unlikely to facilitate the uptake of synaptic GABA, this paper presents simulation results which demonstrate the coupling of EAAT-2 and GAT-3, giving rise to the ionic-dependent reversed transport of GAT-3. The resulting efflux of GABA from the astrocyte to the synaptic space reflects an important astrocytic mechanism for modulation of hyperexcitability. Key results also illustrate an astrocytic-mediated modulation of synaptic neuronal excitation by released GABA at the glutamatergic synapse.
The Impacts of Surgery and Intracerebral Electrodes in C57BL/6J Mouse Kainate Model of Epileptogenesis: Seizure Threshold, Proteomics, and Cytokine Profiles
Authors: Tse Karen , Beamer Edward , Simpson Deborah , Beynon Robert J. , Sills Graeme J. , Thippeswamy Thimmasettappa
Published: July 2021

Intracranial electroencephalography (EEG) is commonly used to study epileptogenesis and epilepsy in experimental models. Chronic gliosis and neurodegeneration at the injury site are known to be associated with surgically implanted electrodes in both humans and experimental models. Currently, however, there are no reports on the impact of intracerebral electrodes on proteins in the hippocampus and proinflammatory cytokines in the cerebral cortex and plasma in experimental models. We used an unbiased, label-free proteomics approach to identify the altered proteins in the hippocampus, and multiplex assay for cytokines in the cerebral cortex and plasma of C57BL/6J mice following bilateral surgical implantation of electrodes into the cerebral hemispheres. Seven days following surgery, a repeated low dose kainate (KA) regimen was followed to induce status epilepticus (SE). Surgical implantation of electrodes reduced the amount of KA necessary to induce SE by 50%, compared with mice without surgery. Tissues were harvested 7 days post-SE (i.e., 14 days post-surgery) and compared with vehicle-treated mice. Proteomic profiling showed more proteins (103, 6.8% of all proteins identified) with significantly changed expression (p < 0.01) driven by surgery than by KA treatment itself without surgery (27, 1.8% of all proteins identified). Further, electrode implantation approximately doubled the number of KA-induced changes in protein expression (55, 3.6% of all identified proteins). Further analysis revealed that intracerebral electrodes and KA altered the expression of proteins associated with epileptogenesis such as inflammation (C1q system), neurodegeneration (cystatin-C, galectin-1, cathepsin B, heat-shock protein 25), blood–brain barrier dysfunction (fibrinogen-α, serum albumin, α2 macroglobulin), and gliosis (vimentin, GFAP, filamin-A). The multiplex assay revealed a significant increase in key cytokines such as TNFα, IL-1β, IL-4, IL-5, IL-6, IL-10, IL12p70, IFN-γ, and KC/GRO in the cerebral cortex and some in the plasma in the surgery group. Overall, these findings demonstrate that surgical implantation of depth electrodes alters some of the molecules that may have a role in epileptogenesis in experimental models.
Eosinophil-to-Neutrophil Ratio Predicts Poor Prognosis of Acute Ischemic Stroke Patients Treated With Intravenous Thrombolysis
Authors: Cai Haoye , Huang Honghao , Yang Chenguang , Ren Junli , Wang Jianing , Gao Beibei , Pan Wenjing , Sun Fangyue , Zhou Xinbo , Zeng Tian , Hu Jingyu , Chen Yilin , Zhang Shunkai , Chen Guangyong
Published: July 2021

Background and Purpose: The eosinophil-to-neutrophil ratio (ENR) was recently reported as a novel inflammatory marker in acute ischemic stroke (AIS). However, few studies reported the predictive value of ENR in AIS patients, especially for those with intravenous thrombolysis.

Methods: Two hundred sixty-six AIS patients receiving intravenous thrombolysis were retrospectively recruited in this study and followed up for 3 months and 1 year. The Modified Rankin Scale (mRS) and the time of death were recorded. Poor outcome was defined as mRS 3–6. After excluding patients who were lost to follow-up, the remaining 250 patients were included in the 3-month prognosis analysis and the remaining 223 patients were included in the 1-year prognosis analysis.

Results: ENR levels in the patients were lower than those in the healthy controls. The optimal cutoff values for the ability of ENR × 102 to predict 3-month poor outcome were 0.74 with 67.8% sensitivity and 77.3% specificity. Patients with ENR × 102 ≥ 0.74 have a lower baseline National Institutes of Health Stroke Scale (NIHSS) score (median: 7 vs. 11, p < 0.001). After multivariate adjustment, patients with ENR × 102 ≥ 0.74 were more likely to come to a better 3-month outcome (OR = 0.163; 95% CI, 0.076–0.348, p < 0.001). At the 1-year follow-up, the patients with ENR × 102 ≥ 0.74 showed a lower risk of mortality (HR = 0.314; 95% CI, 0.135–0.731; p = 0.007).

Conclusions: A lower ENR is independently associated with a 3-month poor outcome and a 3-month and 1-year mortality in AIS patients treated with intravenous thrombolysis.
A Case Report: Effect of Robotic Exoskeleton Based Therapy on Neurological and Functional Recovery of a Patient With Chronic Stroke
Authors: Singh Neha , Saini Megha , Kumar Nand , Srivastava M. V. Padma , Kumaran S. Senthil , Mehndiratta Amit
Published: July 2021

Background: In this study, a novel electromechanical robotic exoskeleton was developed for the rehabilitation of distal joints. The objective was to explore the functional MRI and the neurophysiological changes in cortical-excitability in response to exoskeleton training for a 9-year chronic stroke patient.

Case-Report: The study involved a 52-year old female patient with a 9-year chronic stroke of the right hemisphere, who underwent 20 therapy sessions of 45 min each. Cortical-excitability and clinical-scales: Fugl-Mayer (FM), Modified Ashworth Scale (MAS), Brunnstrom-Stage (BS), Barthel-Index (BI), Range of Motion (ROM), were assessed pre-and post-therapy to quantitatively assess the motor recovery.

Clinical Rehabilitation Impact: Increase in FM wrist/hand by 6, BI by 10, and decrease in MAS by 1 were reported. Ipsilesional Motor Evoked Potential (MEP) (obtained using Transcranial Magnetic Stimulation) was increased by 98 μV with a decrease in RMT by 6% and contralesional MEP was increased by 43 μV with a decrease in RMT by 4%. Laterality Index of Sensorimotor Cortex (SMC) reduced in precentral- gyrus (from 0.152 to −0.707) and in postcentral-gyrus (from 0.203 to −0.632).

Conclusion: The novel exoskeleton-based training showed improved motor outcomes, cortical excitability, and neuronal activation. The research encourages the further investigation of the potential of exoskeleton training.
Risk Factors of Anterior Circulation Intracranial Aneurysm Rupture: Extracranial Carotid Artery Tortuosity and Aneurysm Morphologic Parameters
Authors: Pei Yusong , Xu Zhihua , Liang Guobiao , Jin Hai , Duan Yang , Yang Benqiang , Qiao Xinxin , You Hongrui , Xing Dengxiang
Published: July 2021

Background: This study was conducted to explore the risk factors of anterior circulation intracranial aneurysm rupture based on extracranial carotid artery (ECA) tortuosity.

Methods: This retrospective study, conducted from January 1, 2017, to March 1, 2021, collected and reviewed the clinical and imaging data of 308 patients with anterior circulation intracranial aneurysm [133 (43.2%) patients in the ruptured aneurysm group; 175 (56.8%) patients in the unruptured aneurysm group]. Computed tomography angiography (CTA) of the head and neck was used to determine the ECA tortuosity (normal, simple tortuosity, kink, coil) and the morphologic parameters of the aneurysms. The relationship of aneurysm rupture to ECA tortuosity and the morphologic parameters were analyzed.

Results: After univariate analysis, kink, angle of flow inflow (FA), aspect ratio (AR), aneurysm length (L), the distance from the tortuosity to the aneurysm (distance), and size ratio (SR) were significantly correlated with anterior circulation intracranial aneurysm rupture (p < 0.05). Spearman correlation analysis showed that ECA tortuosity was correlated with FA and SR (p < 0.05). Multiple logistic analyses showed that FA [odds ratio (OR), 1.013; 95% CI, 1.002–1.025], SR (OR, 1.521; 95% CI, 1.054–2.195), and kink (OR, 1.823; 95% CI, 1.074–3.096) were independently associated with aneurysm rupture.

Conclusion: Study results suggest that FA, SR, and ECA kink were independent risk factors associated with anterior circulation intracranial aneurysm rupture.
Evaluation of Attachment Style and Social Support in Patients With Severe Migraine. Applications in Doctor-Patient Relationships and Treatment Adherence
Authors: Belot Rose-Angélique , Bouteloup Margaux , Bonnet Magalie , Parmentier Anne-Laure , Magnin Eloi , Mauny Frédéric , Vuillier Fabrice
Published: July 2021

Objectives: The aim of this observational study was to describe social support and patterns of attachment among patients with migraine. We hypothesized that in comparison to the general population, insecure attachment is overrepresented in migraine patients, and that these patients have less social support. We also aimed to study the specific relationship between attachment and social support. We hypothesized that patients with an insecure attachment style have less social support than patients with a secure attachment style.

Methods: A total of 101 consecutive patients (88.1% women) aged between 25 and 60 (average age = 41.4) were recruited at the Specialized Center for the Consultation of Primary Headaches at the Regional University Hospital Center of Besançon (France). Migraine impact and disability were evaluated using the Headache Impact Test (HIT-6) questionnaire and Migraine Disability Assessment (MIDAS) questionnaire. Patients also completed several self-administered psychological questionnaires in their validated French versions: the Medical Outcome Survey 36-Item Short-Form Health Survey, the Cungi Scale, the State-Trait Anxiety Inventory, the Beck Depression Inventory, the Relationship Scales Questionnaire and the Sarason's Social Support Questionnaire.

Results: The distribution of attachment profiles was different from that of the general population, with an overrepresentation of insecure attachment styles (p = 0.018). Our study showed that migraine patients had less social support than the general population, both in terms of the number of people providing support (p = 0.002) and the level of satisfaction concerning this social support (p = 0.000). We also found that neither the number of available persons score nor the satisfaction score were statistically different between the four attachment categories (p = 0.49). Patient's attachment style and social support influence the patient-doctor relationship, the therapeutic alliance and health behaviors such as treatment adherence.

Conclusions: Based on the data we obtained, we developed applications in patient care for people with particular attachment styles and low social support. A treatment plan adapted to the patient's attachment profile should be created to develop “precision medicine” using a personalized approach to the doctor-patient relationship. We would also recommend encouraging patients to participate in support groups, in order to strengthen their attachment systems and gain social support.

Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03577548, identifier NCT03577548.
MRI Radiomic Signature of White Matter Hyperintensities Is Associated With Clinical Phenotypes
Authors: Bretzner Martin , Bonkhoff Anna K. , Schirmer Markus D. , Hong Sungmin , Dalca Adrian V. , Donahue Kathleen L. , Giese Anne-Katrin , Etherton Mark R. , Rist Pamela M. , Nardin Marco , Marinescu Razvan , Wang Clinton , Regenhardt Robert W. , Leclerc Xavier , Lopes Renaud , Benavente Oscar R. , Cole John W. , Donatti Amanda , Griessenauer Christoph J. , Heitsch Laura , Holmegaard Lukas , Jood Katarina , Jimenez-Conde Jordi , Kittner Steven J. , Lemmens Robin , Levi Christopher R. , McArdle Patrick F. , McDonough Caitrin W. , Meschia James F. , Phuah Chia-Ling , Rolfs Arndt , Ropele Stefan , Rosand Jonathan , Roquer Jaume , Rundek Tatjana , Sacco Ralph L. , Schmidt Reinhold , Sharma Pankaj , Slowik Agnieszka , Sousa Alessandro , Stanne Tara M. , Strbian Daniel , Tatlisumak Turgut , Thijs Vincent , Vagal Achala , Wasselius Johan , Woo Daniel , Wu Ona , Zand Ramin , Worrall Bradford B. , Maguire Jane M. , Lindgren Arne , Jern Christina , Golland Polina , Kuchcinski Grégory , Rost Natalia S.
Published: July 2021

Objective

Neuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes.

Methods

We analyzed a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images with total brain and WMH segmentations. Radiomic features were extracted from normal-appearing brain tissue (brain mask–WMH mask). Radiomics-based prediction of personalized WMH burden was done using ElasticNet linear regression. We built a radiomic signature of WMH with stable selected features predictive of WMH burden and then related this signature to clinical variables using canonical correlation analysis (CCA).

Results

Radiomic features were predictive of WMH burden (R2 = 0.855 ± 0.011). Seven pairs of canonical variates (CV) significantly correlated the radiomics signature of WMH and clinical traits with respective canonical correlations of 0.81, 0.65, 0.42, 0.24, 0.20, 0.15, and 0.15 (FDR-corrected p-valuesCV1–6 < 0.001, p-valueCV7 = 0.012). The clinical CV1 was mainly influenced by age, CV2 by sex, CV3 by history of smoking and diabetes, CV4 by hypertension, CV5 by atrial fibrillation (AF) and diabetes, CV6 by coronary artery disease (CAD), and CV7 by CAD and diabetes.

Conclusion

Radiomics extracted from T2-FLAIR images of AIS patients capture microstructural damage of the cerebral parenchyma and correlate with clinical phenotypes, suggesting different radiographical textural abnormalities per cardiovascular risk profile. Further research could evaluate radiomics to predict the progression of WMH and for the follow-up of stroke patients’ brain health.
A Pilot Study of Nutritional Status Prior to Bariatric Surgery in South China
Authors: Sun Linli , Wang Chunxia , Sun Wei , Wang Chunjiang
Published: July 2021

Objective: The was a pilot study to assess the biochemical and historical information about bariatric patients before undergoing the surgery in the aim of identifying nutritional deficiencies and their prevalence from 2015 to 2020.

Methods: Clinical data of 247 patients (105 males and 142 females) were included. Vitamins, trace elements, electrolytes, albumin, globulin, hemoglobin, folate, ferritin, microalbuminuria (MAU), and parathyroid hormone (PTH) levels were determined to explore the nutritional status according to gender, age, high body mass index (BMI), and waist circumstance (WC).

Results: The mean age, mean BMI, and mean WC of the candidates were 32.95 ± 10.46 years, 38.01 ± 7.11 kg/m2, and 117.04 ± 16.18 cm, respectively. The prevalence of preoperative nutritional deficiencies was 76.88% for 25 (OH) vitamin D, 19.84% for globulin, 11.74% for albumin, 11.02% for sodium, 8.33% for folic acid, 10.48% (male) and 6.34% (female) for chloride, 4.05% for calcium, 3.07% (male) and 0.70%(female) for ferritin, 11.90% for elevated PTH, and 44.96% for MAU. Males exhibited increased prevalence of globulin and MAU relative to females (P < 0.05). Older groups are more likely to exhibit albumin deficiency (P = 0.007), globulin deficiency (P = 0.003), and zinc deficiency (P = 0.015). In addition, 25 (OH) D deficiency and albumin deficiency were more common in patients with BMI ≥ 47.5 kg/m2 (P = 0.049 and 0.015, respectively). Wider WC (≥150 cm) exhibited higher rates of albumin deficiencies (P = 0.011).

Conclusion: Electrolyte and nutritional deficiencies were common in patients prior to bariatric surgery in South China. Routine evaluation of electrolyte and nutritional levels should be carried out in this population.
Circular RNA TAF4B Promotes Bladder Cancer Progression by Sponging miR-1298-5p and Regulating TGFA Expression
Authors: Zhang Xiaoting , Li Xiaofeng , Fu Xian , Yu Mengli , Qin Guicheng , Chen Guihong , Huang Chenchen
Published: July 2021

Background

Bladder cancer (Bca) is the most common malignant tumor of the urinary system. Circular RNAs (circRNAs) have been recognized as key regulators in tumorigenesis. However, the molecular mechanisms underlying circRNAs involved in the progression of BCa remain largely unknown.

Methods

We detected the expression level of circular RNA TAF4B (circTAF4B) by qRT-PCR assay. Cell proliferation was evaluated by CCK-8 and colony formation assays. Wound healing and Transwell assays were performed to measure cell migration and invasion capability. Moreover, we performed qRT-PCR and western blotting assays to determine the expression levels of epithelial-mesenchymal transition (EMT) markers. A nuclear/cytoplasmic fractionation assay was used to measure the subcellular location of circTAF4B. RNA pull-down and dual-luciferase reporter assays were used to detect the target microRNA of circTAF4B. A mouse xenograft model was produced to analyze the effect of circTAF4B on the tumorigenesis of BCa.

Results

In this study, we identified a novel circular RNA, circTAF4B, that is significantly upregulated in BCa and correlated with poor prognosis. Downregulated circTAF4B abolished the growth, metastasis and EMT process in BCa cells. Mechanistically, we found that circTAF4B facilitated the expression of transforming growth factor A (TGFA) by sponging miR-1298-5p. Finally, circTAF4B enhanced the proliferation and EMT process of BCa cells in vivo.

Conclusion

In summary, our study demonstrated that circTAF4B played a carcinogenic role in the growth, metastasis, and EMT process of BCa by regulating the miR-1298-5p/TGFA axis. Thus, circTAF4B may become a diagnostic and therapeutic target for BCa.
The Survival Effect of Chest Wall With or Without Regional Lymphatic Radiotherapy for Breast Cancer Patients With T3~4N0M0
Authors: Li Guanqiao , Yao Jia , Chen Junni , Cai Baizhen , Lin Xiangying , Chen Zetan , Chen Jiawei , Wang Han , Yang Shiping
Published: July 2021

Background

Peripheral lymphatic radiotherapy in patients with pT3N0M0 and pT4N0M0 breast cancer has been a matter of considerable debate among radiation oncologists. This is the first report in a non-Caucasian population.

Patients and Methods

The study included 165 pT3N0M0 and pT4N0M0 patients. Univariate, multivariate, propensity score matching (PSM), and Kaplan-Meier analyses were conducted to evaluate the survival of patients. We also review all the literature about regional lymph nodes radiation in T3-4N0M0 patients and summarize them with tables to compare with the present study.

Results

The median follow-up duration was 58.7 months. Multivariate analyses showed that advance T stage and grade were dependent poor prognostic factors for OS, DMFS, LRFS, and DFS between group A (chest wall radiation) and group B (chest wall and regional lymph nodes radiation). The overall survival (OS), disease-free survival (DFS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were not significantly different between group A and group B. The 5-year OS rate was 92.3% vs 89.7% for group A and group B, respectively (P=0.819). The 5-year LRFS rate was 94.9% vs 94.3% for group A and group B, respectively (P=0.852). Fifty-four pairs of patients were selected after propensity score matching (PSM) analysis was conducted. There was also no significant difference between group A and group B in regard to the OS, DFS, LRFS, and DMFS rates after PSM. The patients included in previous studies were all Caucasians, and our study was focused on non-Caucasians. The cases of previous studies were 10 to 20 years ago, but our study has more recent cases. The radiotherapy techniques of previous studies were conventional, and the techniques used in our study were three-dimensional conformal radiotherapy (3DCRT) or intensity modulated radiotherapy (IMRT).

Conclusion

Both our study and previous studies suggested that regional lymph nodes radiation cannot improve the survival rate for breast cancer patients with T3-4N0M0 in non-Caucasian population. Advance T stage and grade were the dependent poor prognostic factors for T3-4N0M0 patients.
Large-Section Histopathology Can Better Indicate the Immune Microenvironment and Predict the Prognosis of Pancreatic Ductal Adenocarcinoma Than Small-Section Histopathology
Authors: Ding Guiling , Guo Meng , Yang Yelin , Sun Chen , Wu Shengyong , Liu Xingchen , Wang Jin , Jiang Hui , Liu Yanfang , Zheng Jianming
Published: July 2021

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor and is insensitive to radiotherapy and chemotherapy, as it is highly correlated with its complex tumor microenvironment (TME). A comprehensive description of PDAC’s immune microenvironment at the pathological level has not been reported, thus limiting its treatment. Previous studies have shown that large-section histopathology (LSH) can reveal the complete structure and margin of the tumor on a single slice and effectively reflect intratumoral heterogeneity. LSH, as opposed to classic small-section histopathology (SSH), can also be used to explore the infiltration state of immune cells in different regions. In the current study, EnVision immunohistochemical staining was used to explore the panoramic distribution of CD4-, CD8-, CD15-, CD20-, and CD56 (surface markers of helper T cells, cytotoxic T cells, neutrophils, B cells, and NK cells, respectively)-positive cells in 102 pairs of paraffin wax-embedded PDAC samples (LSH vs SSH) for the first time. These indicators were then analyzed, and correlations of clinicopathological characteristics with clinical prognoses were analyzed. The findings of this study show that LSH can effectively indicate more immune cells than SSH. Upregulated CD4, CD8, CD20, and CD56 or downregulated CD15 was correlated with a good prognosis in PDAC patients. However, analysis of SSH showed that only upregulated CD4 and CD8 can be used as indicators of a good prognosis. Multivariate Cox regression analysis showed that 7 variables, namely, pTNM stage (P=0.002), PDL1 expression (P=0.001), CDX2 expression (P=0.008), DPC4 expression (P=0.004), CD4 expression in LSH (P<0.001), CD8 expression in LSH (P=0.010) and CD15 expression in LSH (P=0.031), were significantly correlated with the prognosis of PDAC patients. The findings of this study indicate that LSH is an effective tool for a panoramic assessment of the immune microenvironment in pancreatic cancer patients.
A Novel Nomogram Based on Hepatic and Coagulation Function for Evaluating Outcomes of Intrahepatic Cholangiocarcinoma After Curative Hepatectomy: A Multi-Center Study of 653 Patients
Authors: Cai Yunshi , Zhang Bohan , Li Jiaxin , Li Hui , Liu Hailing , Xie Kunlin , Du Chengyou , Wu Hong
Published: July 2021

Background and Aims

Hepatic and coagulation function are routine laboratory tests prior to curative hepatectomy. The prognostic value of gamma-glutamyl transpeptidase (GGT) to platelet ratio (GPR) and international normalized ratio (INR) in surgically treated patients with intrahepatic cholangiocarcinoma (ICC) remains unclear.

Methods

ICC patients received curative hepatectomy in two west China centers were included. Time-dependent ROC curves were conducted to compare established indexes with prognostic value for ICC. GPR-INR score was introduced and evaluated using the Time-dependent AUC curve and Kaplan-Meier survival analysis. A novel nomogram based on the GPR-INR score was proposed; Harrell’s C-index, calibration curve and decision curve analysis were used to assess this nomogram.

Results

A total of 653 patients were included. The areas under ROC curves of GPR and INR in OS and RFS were superior to other indexes. Patients with a high GPR-INR score (1,2) presented significantly decreased overall survival (OS) and recurrence-free survival (RFS); GPR-INR sore, along with several clinicopathological indexes were selected into the nomogram, the calibration curve for OS probability showed good coincidence between the nomogram and the actual surveillance. The C-index of the nomogram was 0.708 (derivation set) and 0.746 (validation set), which was more representative than the C-indexes of the GPR-INR score (0.597, 0.678). In decision curve analysis, the net benefits of the nomogram in derivation and validation set were higher than Barcelona Clinic Liver Cancer staging (BCLC) classification and American Joint Committee on Cancer (AJCC) TNM 8th staging system.

Conclusions

The proposed nomogram generated superior discriminative ability to established staging systems; it is profitable to applicate this nomogram in clinical practice.
The Use of Conditioning Open-Label Placebo in Opioid Dose Reduction: A Case Report and Literature Review
Authors: Estudillo-Guerra Maria A. , Mesia-Toledo Ines , Schneider Jeffrey C. , Morales-Quezada Leon
Published: July 2021

Introduction: Adequate pain management for inpatients in rehabilitation units is essential for achieving therapeutic goals. Opioid treatments are commonly prescribed, but these are associated with numerous adverse effects, including the risk of addiction and decreased quality of life. Conditioning an open-label placebo is a promising approach to extend the analgesic effect of the opioid while reducing its overall dosage.

Objectives: To describe a patient's experience in using conditioning open-label placebo (COLP) as a pharmaco-behavioral intervention to decrease opioid intake and its side effects after inpatient rehabilitation discharge, and to perform a literature review about the use of open-label placebo in pain.

Methods: This case study has been extracted from a clinical trial initiated in 2018. A 61-year-old male was recruited at a tertiary rehabilitation hospital after suffering a traumatic sport-related injury and orthopedic surgery. Pain management included prescription of non-steroidal anti-inflammatory drugs (NSAIDs) and short-acting oxycodone. After trial participation, the patient requested off-label COLP treatment to help him decrease outpatient opioid utilization.

Results: After COLP treatment, the patient could discontinue oxycodone intake (a reduction from 15 morphine equivalents/day) after rehabilitation discharge. Moreover, opioid side effects decreased from 46 to 9 points on the numerical opioid side-effects scale. A literature review identified five clinical trials using “honest” open-label placebo (OLP) or COLP as an experimental intervention for pain control. From these studies, two were in the area of chronic lower back pain, one in post spine surgery, one in irritable bowel syndrome, and another in spinal cord injury and polytrauma. Four studies reported positive outcomes related to pain control, while one study showed no significant differences in pain management between treatment-as-usual and the COLP group.

Conclusion: The case report illustrates how a pharmaco-behavioral intervention can facilitate downward opioid titration safely after inpatient rehabilitation. It initiates a discussion about new approaches for opioid management using conditioning and the patient's expectation of pain relief.
C646 Protects Against DSS-Induced Colitis Model by Targeting NLRP3 Inflammasome
Authors: Xu Xueming , Li Jing , Long Xiuyan , Tao Sifan , Yu Xiaoyu , Ruan Xixian , Zhao Kai , Tian Li
Published: July 2021

Numerous pieces of evidence have identified that the NLRP3 inflammasome plays a pivotal role in the development and pathogenesis of colitis. Targeting the NLRP3 inflammasome represents a potential therapeutic treatment. Our previous studies have suggested that acetylation of NLRP3 is indispensable to NLRP3 inflammasome activation, and some acetyltransferase inhibitors could suppress the NLRP3 inflammasome activation. Here, we identified that C646, an inhibitor of histone acetyltransferase p300, exerts anti-inflammatory effects in DSS-induced colitis mice by targeting the NLRP3 inflammasome. Mechanistically, C646 not only inhibits NF-κB activation, leading to the decreased expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and NLRP3, but also suppresses the NLRP3 inflammasome assembly by disrupting the interaction between NLRP3 and ASC. In addition, C646 attenuated the LPS-induced acute systemic inflammation model. Thus, our results demonstrate the ability of C646 to suppress the NLRP3 inflammasome activity and its potential application in the treatment of inflammatory bowel disease.
The Composite of 3, 4-Dihydroxyl-Phenyl Lactic Acid and Notoginsenoside R1 Attenuates Myocardial Ischemia and Reperfusion Injury Through Regulating Mitochondrial Respiratory Chain
Authors: Yan Li , Pan Chun-Shui , Liu Yu-Ying , Cui Yuan-Chen , Hu Bai-He , Chang Xin , Wei Xiao-Hong , Huang Ping , Liu Jian , Fan Jing-Yu , Li Quan , Sun Kai , Yan Lu-Lu , He Ke , Han Jing-Yan
Published: July 2021

Aim

3,4-Dihydroxyl-phenyl lactic acid (DLA) and notoginsenoside R1 (R1) are known to protect ischemia and reperfusion (I/R) injury by targeting Sirtuin1/NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 10/the Mitochondrial Complex I (Sirt-1/NDUFA10/Complex I) and Rho-associated kinase/adenosine triphosphate (ROCK/ATP) ATP synthase δ subunit (ATP 5D), respectively. We hypothesized that a composite of the two may exhibit a more potent effect on I/R injury. The study was designed to test this hypothesis.

Materials and Methods

Male Sprague–Dawley rats underwent left anterior descending artery occlusion and reperfusion, with or without DLA, R1, or a combination of 3,4-dihydroxyl-phenyl lactic acid and notoginsenoside R1 (DR) pretreatment. Heart function, myocardial morphology, myocardial infarct, myocardial blood flow (MBF), apoptosis, vascular diameter, and red blood cell (RBC) velocity in venules were evaluated. Myeloperoxidase (MPO), malondialdehyde (MDA), and 8-oxo-deoxyguanosine (8-OHdG) were assessed. The content of ATP, adenosine diphosphate (ADP), and adenosine monophosphate (AMP), the activity of mitochondrial respiratory chain Complex I and its subunit NDUFA10, the Mitochondrial Complex V (Complex V) and its subunit ATP 5D, Sirt-1, Ras homolog gene family, member A (RhoA), ROCK-1, and phosphorylated myosin light chain (P-MLC) were evaluated. R1 binding to Sirt-1 was determined by surface plasmon resonance.

Results

DLA inhibited the expression of Sirt-1, the reduction in Complex I activity and its subunit NDUFA10 expression, the increase in MPO, MDA, and 8-OhdG, and apoptosis. R1 inhibited the increase in the expression of RhoA/ROCK-1/P-MLC, the reduction of Complex V activity and its subunit ATP 5D expression, alleviated F-actin, and myocardial fiber rupture. Both DLA and R1 reduced the myocardial infarction size, increased the velocities of RBC in venules, and improved MBF and heart function impaired by I/R. DR exhibited effects similar to what was exerted, respectively, by DLA and R1 in terms of respiratory chain complexes and related signaling and outcomes, and an even more potent effect on myocardial infarct size, RBC velocity, heart function, and MBF than DLA and R1 alone.

Conclusion

A combination of 3,4-dihydroxyl-phenyl lactic acid and notoginsenoside R1 revealed a more potent effect on I/R injury via the additive effect of DLA and R1, which inhibited not only apoptosis caused by low expression of Sirt-1/NDUFA10/Complex I but also myocardial fiber fracture caused by RhoA/ROCK-1 activation and decreased expression of ATP/ATP 5D/Complex V.