bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and Functional Brain Connectivity Uniquely Contribute to Episodic Memory Performance in Older Adults
Authors: Alm Kylie H. , Soldan Anja , Pettigrew Corinne , Faria Andreia V. , Hou Xirui , Lu Hanzhang , Moghekar Abhay , Mori Susumu , Albert Marilyn , Bakker Arnold
Published: July 2022

In this study, we examined the independent contributions of structural and functional connectivity markers to individual differences in episodic memory performance in 107 cognitively normal older adults from the BIOCARD study. Structural connectivity, defined by the diffusion tensor imaging (DTI) measure of radial diffusivity (RD), was obtained from two medial temporal lobe white matter tracts: the fornix and hippocampal cingulum, while functional connectivity markers were derived from network-based resting state functional magnetic resonance imaging (rsfMRI) of five large-scale brain networks: the control, default, limbic, dorsal attention, and salience/ventral attention networks. Hierarchical and stepwise linear regression methods were utilized to directly compare the relative contributions of the connectivity modalities to individual variability in a composite delayed episodic memory score, while also accounting for age, sex, cerebrospinal fluid (CSF) biomarkers of amyloid and tau pathology (i.e., Aβ42/Aβ40 and p-tau181), and gray matter volumes of the entorhinal cortex and hippocampus. Results revealed that fornix RD, hippocampal cingulum RD, and salience network functional connectivity were each significant independent predictors of memory performance, while CSF markers and gray matter volumes were not. Moreover, in the stepwise model, the addition of sex, fornix RD, hippocampal cingulum RD, and salience network functional connectivity each significantly improved the overall predictive value of the model. These findings demonstrate that both DTI and rsfMRI connectivity measures uniquely contributed to the model and that the combination of structural and functional connectivity markers best accounted for individual variability in episodic memory function in cognitively normal older adults.
The Cardiovascular Literature-Based Risk Algorithm (CALIBRA): Predicting Cardiovascular Events in Patients With Non-Dialysis Dependent Chronic Kidney Disease
Authors: Neri Luca , Lonati Caterina , Titapiccolo Jasmine Ion , Nadal Jennifer , Meiselbach Heike , Schmid Matthias , Baerthlein Barbara , Tschulena Ulrich , Schneider Markus P. , Schultheiss Ulla T. , Barbieri Carlo , Moore Christoph , Steppan Sonia , Eckardt Kai-Uwe , Stuard Stefano , Bellocchio Francesco
Published: July 2022

Background and Objectives

Cardiovascular (CV) disease is the main cause of morbidity and mortality in patients suffering from chronic kidney disease (CKD). Although it is widely recognized that CV risk assessment represents an essential prerequisite for clinical management, existing prognostic models appear not to be entirely adequate for CKD patients. We derived a literature-based, naïve-bayes model predicting the yearly risk of CV hospitalizations among patients suffering from CKD, referred as the CArdiovascular, LIterature-Based, Risk Algorithm (CALIBRA).

Methods

CALIBRA incorporates 31 variables including traditional and CKD-specific risk factors. It was validated in two independent CKD populations: the FMC NephroCare cohort (European Clinical Database, EuCliD®) and the German Chronic Kidney Disease (GCKD) study prospective cohort. CALIBRA performance was evaluated by c-statistics and calibration charts. In addition, CALIBRA discrimination was compared with that of three validated tools currently used for CV prediction in CKD, namely the Framingham Heart Study (FHS) risk score, the atherosclerotic cardiovascular disease risk score (ASCVD), and the Individual Data Analysis of Antihypertensive Intervention Trials (INDANA) calculator. Superiority was defined as a ΔAUC>0.05.

Results

CALIBRA showed good discrimination in both the EuCliD® medical registry (AUC 0.79, 95%CI 0.76-0.81) and the GCKD cohort (AUC 0.73, 95%CI 0.70-0.76). CALIBRA demonstrated improved accuracy compared to the benchmark models in EuCliD® (FHS: ΔAUC=-0.22, p<0.001; ASCVD: ΔAUC=-0.17, p<0.001; INDANA: ΔAUC=-0.14, p<0.001) and GCKD (FHS: ΔAUC=-0.16, p<0.001; ASCVD: ΔAUC=-0.12, p<0.001; INDANA: ΔAUC=-0.04, p<0.001) populations. Accuracy of the CALIBRA score was stable also for patients showing missing variables.

Conclusion

CALIBRA provides accurate and robust stratification of CKD patients according to CV risk and allows score calculations with improved accuracy compared to established CV risk scores also in real-world clinical cohorts with considerable missingness rates. Our results support the generalizability of CALIBRA across different CKD populations and clinical settings.
Clinical Outcomes After Ventriculo-Peritoneal Shunting in Patients With Classic vs. Complex NPH
Authors: Goh Eng Tah , Lock Christine , Tan Audrey Jia Luan , Tan Bee Ling , Liang Sai , Pillay Robin , Kumar Sumeet , Ahmad-Annuar Azlina , Narayanan Vairavan , Kwok Janell , Tan Yi Jayne , Ng Adeline SL , Tan Eng King , Czosnyka Zofia , Czosnyka Marek , Pickard John D. , Keong Nicole C.
Published: July 2022

Objective

Normal pressure hydrocephalus (NPH) is a neurological condition characterized by a clinical triad of gait disturbance, cognitive impairment, and urinary incontinence in conjunction with ventriculomegaly. Other neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and vascular dementia share some overlapping clinical features. However, there is evidence that patients with comorbid NPH and Alzheimer's or Parkinson's disease may still exhibit good clinical response after CSF diversion. This study aims to evaluate clinical responses after ventriculo-peritoneal shunt (VPS) in a cohort of patients with coexisting NPH and neurodegenerative disease.

Methods

The study has two components; (i) a pilot study was performed that specifically focused upon patients with Complex NPH and following the inclusion of the Complex NPH subtype into consideration for the clinical NPH programme, (ii) a retrospective snapshot study was performed to confirm and characterize differences between Classic and Complex NPH patients being seen consecutively over the course of 1 year within a working subspecialist NPH clinic. We studied the characteristics of patients with Complex NPH, utilizing clinical risk stratification and multimodal biomarkers.

Results

There was no significant difference between responders and non-responders to CSF diversion on comorbidity scales. After VPS insertion, significantly more Classic NPH patients had improved cognition compared to Complex NPH patients (p = 0.005). Improvement in gait and urinary symptoms did not differ between the groups. 26% of the Classic NPH group showed global improvement of the triad, and 42% improved in two domains. Although only 8% showed global improvement of the triad, all Complex NPH patients improved in gait.

Conclusions

Our study has demonstrated that the presence of neurodegenerative disorders co-existing with NPH should not be the sole barrier to the consideration of high-volume tap test or lumbar drainage via a specialist NPH programme. Further characterization of distinct cohorts of NPH with differing degrees of CSF responsiveness due to overlay from neurodegenerative or comorbidity risk burden may aid toward more precise prognostication and treatment strategies. We propose a simplistic conceptual framework to describe NPH by its Classic vs. Complex subtypes to promote the clinical paradigm shift toward subspecialist geriatric neurosurgery by addressing needs for rapid screening tools at the clinical-research interface.
Clinical Application of Different Vertical Position Tests for Posterior Canal-Benign Paroxysmal Positional Vertigo-Cupulolithiasis
Authors: Wang Wenting , Yan Shuangmei , Zhang Sai , Han Rui , Li Dong , Liu Yihan , Zhang Ting , Liu Shaona , Wu Yuexia , Li Ya , Yang Xu , Gu Ping
Published: July 2022

Background

Posterior canal-benign paroxysmal positional vertigo-cupulolithiasis (PC-BPPV-cu) is a new and controversial type of benign paroxysmal positional vertigo (BPPV). At present, there are few relevant clinical studies as to whether the Half Dix-Hallpike test (Half D-HT) induces more obvious nystagmus than the Dix Hallpike test (D-HT) and straight head hanging test (SHH) in patients with PC-BPPV-cu.

Objectives

To investigate the clinical characteristics of PC-BPPV-cu, and analyze the diagnostic significance of the Dix-Hallpike test (D-HT), Half D-HT, and straight head hanging (SHH) test in these patients.

Methods

A total of 46 patients with PC-BPPV-cu were enrolled, and divided into two groups (N = 23): a group A (induction order: D-HT, Half D-HT, SHH) and a group B (induction order: Half D-HT, D-HT, SHH).

Results

Among 46 patients with PC-BPPV-cu, the bilateral and unilateral abnormality rates of the disease side were 5 cases and 41 cases, respectively. There were significant differences in the proportion of torsional-upbeating nystagmus and upbeating nystagmus among the three headhanging positions in 46 patients with PC-BPPV-cu (P < 0.001). The slow phase velocity (SPV) of induced nystagmus at half D-HT supine position was slower than D-HT supine position (P < 0.05) and SHH supine position (P < 0.05). The nystagmus latency of D-HT supine position was significantly shorter than half D-HT (P < 0.05) and SHH (P < 0.05). PC-BPPV-cu patients were accompanied by 53.5% semicircular canal paresis, 69.6% audiological abnormalities, 76% cervical vestibular evoked myogenic potential (cVEMP), and 75% video head impulse test (vHIT) abnormalities, the concordance rates of the four detection methods were similar (χ2 = 0.243, P = 0.970).

Conclusions

The Half D-HT is simple and feasible, but might have a risk of false-negative diagnoses of the torsional-upbeating nystagmus and upbeating nystagmus. The D-HT is still a classic induction method for PC-BPPV-cu. The two complement each other and may aid in the diagnosis of PC-BPPV-cu patients. Future clinical applications of Half D-HT require extensive research to determine its diagnostic efficacy.
The Effect of Non-immersive Virtual Reality Exergames Versus Band Stretching on Cardiovascular and Cerebral Hemodynamic Response: A Functional Near-Infrared Spectroscopy Study
Authors: Zheng Yuxin , You Tingting , Du Rongwei , Zhang Jiahui , Peng Tingting , Liang Junjie , Zhao Biyi , Ou Haining , Jiang Yongchun , Feng Huiping , Yilifate Anniwaer , Lin Qiang
Published: July 2022

Background

Exercise is one of the effective ways to improve cognition. Different forms of exercises, such as aerobic exercise, resistance exercise, and coordination exercise, have different effects on the improvement of cognitive impairment. In recent years, exergames based on Non-Immersive Virtual Reality (NIVR-Exergames) have been widely used in entertainment and have gradually been applied to clinical rehabilitation. However, the mechanism of NIVR-Exergames on improving motor cognition has not been clarified. Therefore, the aim of this study is to find whether NIVR-Exergames result in a better neural response mechanism to improve the area of the cerebral cortex related to motor cognition under functional near-infrared spectroscopy (fNIRS) dynamic monitoring in comparison with resistance exercise (resistance band stretching).

Methods

A cross-over study design was adopted in this study, and 15 healthy young subjects (18–24 years old) were randomly divided into group A (n = 8) and group B (n = 7) according to a computerized digital table method. Task 1 was an NIVR-Exergame task, and Task 2 was resistance band stretching. Group A first performed Task 1, rested for 30 min (i.e., a washout period), and then performed Task 2. Group B had the reverse order. The fNIRS test was synchronized in real time during exercise tasks, and heart rate measurements, blood pressure measurements, and 2-back task synchronization fNIRS tests were performed at baseline, Post-task 1, and Post-task 2. The primary outcomes were beta values from the general linear model (GLM) in different regions of interest (ROIs), and the secondary outcomes were heart rate, blood pressure, reaction time of 2-back, and accuracy rate of 2-back.

Results

The activation differences of Task 1 and Task 2 in the right premotor cortex (PMC) (P = 0.025) and the left PMC (P = 0.011) were statistically significant. There were statistically significant differences in the activation of the right supplementary motor area (SMA) (P = 0.007), left dorsolateral prefrontal cortex (DLPFC) (P = 0.031), left and right PMC (P = 0.005; P = 0.002) between baseline and Post-task 1. The differences in systolic pressure (SBP) between the two groups at three time points among women were statistically significant (P1 = 0.009, P2 < 0.001, P3 = 0.044).

Conclusion

In this study, we found that NIVR-Exergames combined with motor and challenging cognitive tasks can promote the activation of SMA, PMC and DLPFC in healthy young people compared with resistance exercise alone, providing compelling preliminary evidence of the power for the rehabilitation of motor and cognitive function in patients with central nervous system diseases.
Ependymal Cilia: Physiology and Role in Hydrocephalus
Authors: Ji Weiye , Tang Zhi , Chen Yibing , Wang Chuansen , Tan Changwu , Liao Junbo , Tong Lei , Xiao Gelei
Published: July 2022

Cerebrospinal fluid (CSF), a colorless liquid that generally circulates from the lateral ventricles to the third and fourth ventricles, provides essential nutrients for brain homeostasis and growth factors during development. As evidenced by an increasing corpus of research, CSF serves a range of important functions. While it is considered that decreased CSF flow is associated to the development of hydrocephalus, it has recently been postulated that motile cilia, which line the apical surfaces of ependymal cells (ECs), play a role in stimulating CSF circulation by cilia beating. Ependymal cilia protrude from ECs, and their synchronous pulsing transports CSF from the lateral ventricle to the third and fourth ventricles, and then to the subarachnoid cavity for absorption. As a result, we postulated that malfunctioning ependymal cilia could disrupt normal CSF flow, raising the risk of hydrocephalus. This review aims to demonstrate the physiological functions of ependymal cilia, as well as how cilia immobility or disorientation causes problems. We also conclude conceivable ways of treatment of hydrocephalus currently for clinical application and provide theoretical support for regimen improvements by investigating the relationship between ependymal cilia and hydrocephalus development.
Preventive Effects of Long-Term Intake of Plant Oils With Different Linoleic Acid/Alpha-Linolenic Acid Ratios on Acute Colitis Mouse Model
Authors: Wang Xianshu , Yue Hao , Zhang Haonan , Wan Lei , Ji Shuxia , Geng Chong
Published: July 2022

Objective

To investigate the preventive effects of plant oils with different linoleic acid/alpha-linolenic acid (LA/ALA) ratios against colitis symptoms, and dysbiosis of gut microbiota in acute colitis mouse model.

Methods

Sixty male C57BL/6 mice were assigned into six groups (n = 10): three groups were fed low-fat diets with low, medium, and high LA/ALA ratios; and three groups were fed with high-fat diets with low, medium, and high LA/ALA ratios. After 3 months of diet, the mice were exposed to dextran sodium sulfate solution to induce acute colitis. The severity of colitis was estimated by disease activity index (DAI) and histopathological examination. 16S rRNA gene sequencing was used for the analysis of gut microbiota.

Results

Plant oils with a lower LA/ALA ratio showed higher alleviating effects on the symptoms of colitis, which were accompanied by the better prebiotic characteristics manifested as effectively inhibiting the abnormal expansion of phylum Proteobacteria and genus Escherichia-Shigella in the gut microbiota of colitis mouse models.

Conclusion

A potential IBD prevention strategy of reducing the LA/ALA ratio in the daily consumed plant oils was proposed in this study. Furthermore, based on the optimized LA/ALA ratio, this preventive effect might not be weakened by the high intake of plant oils.
Novel Mechanisms for Post-Transplant Maintenance Therapy in Acute Myeloid Leukemia
Authors: Manobianco Steven A. , Rakiewicz Tara , Wilde Lindsay , Palmisiano Neil D.
Published: July 2022

Allogeneic stem cell transplantation has improved survival for patients with acute myeloid leukemia (AML), especially for patients with disease at high risk of relapse. However, relapse remains the most common cause of treatment failure and death in the post-transplant period. Maintenance therapy, an extended course of treatment after achieving remission to reduce the rate of relapse, is an important component of the treatment of various hematologic malignancies; however, its role in the treatment of AML is far less well-defined. Recently, there has been significant interest in the use of novel therapeutic agents as maintenance therapy after allogeneic stem cell transplant, utilizing new mechanisms of treatment and more favorable toxicity profiles. In this review, we will discuss the mechanistic and clinical data for post-transplant maintenance therapies in AML. Then, we will review several emergent and current clinical trials which aim to incorporate novel agents into maintenance therapy regimens.
Durvalumab After Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer: Inferior Outcomes and Lack of Health Equity in Hispanic Patients Treated With PACIFIC Protocol (LA1-CLICaP)
Authors: Raez Luis E. , Arrieta Oscar , Chamorro Diego F. , Soberanis-Piña Pamela Denisse , Corrales Luis , Martín Claudio , Cuello Mauricio , Samtani Suraj , Recondo Gonzalo , Mas Luis , Zatarain-Barrón Zyanya Lucia , Ruíz-Patiño Alejandro , García-Robledo Juan Esteban , Ordoñez-Reyes Camila , Jaller Elvira , Dickson Franco , Rojas Leonardo , Rolfo Christian , Rosell Rafael , Cardona Andrés F.
Published: July 2022

Objectives

To compare the rate disparity between outcomes (overall survival (OS), progression-free survival (PFS), and safety) of concurrent chemoradiation (cCRT) followed by durvalumab in two patient cohorts with locally advanced (LA) stage III non-small cell lung cancer (NSCLC), one non-Hispanic White (NHW), and the other Latin-American.

Methods

A multicenter retrospective study was performed, including 80 Hispanic and 45 NHW LA stage III NSCLC patients treated with cCRT followed by durvalumab. Both cohorts were analyzed in terms of main outcomes (OS, PFS, and safety) and compared between them and with the PACIFIC trial population outcomes. The efficacy-effectiveness gap was assessed using an efficacy-effectiveness (EE) factor that was calculated by dividing each cohort median overall survival by the corresponding reference OS from the PACIFIC trial. In both cohorts, results of PD-L1 testing were recorded, and the main outcomes were compared according to PD-1 expression levels (≥50%, 1–49%, and <1%).

Results

For the entire population (N=125), the overall response rate (ORR) was 57.6% (N=72), and 18.4% (N=25) achieved stable disease. OS was 26.3 months (95%CI 23.9-28.6), and PFS was 20.5 months (95%CI 18.0-23.0). PFS assessed by ethnicity showed a median for the Hispanic population of 19.4 months (95%CI 16.4-22.5) and 21.2 months (95%CI 17.2-23.3; p=0.76) for the NHW group. OS by race showed a significant difference in favor of the NHW group, with a median OS of 27.7 months (95%CI 24.6-30.9) vs. 20.0 months (95%CI 16.4-23.5) for Hispanics. (P=0.032). Unadjusted 12-month and 24-month OS was 86.6% (95%CI 79.9–88.0) and 46.6% (95%CI 40.2–48.3) for NHW compared to 82.5% (95%CI 77.1–84.2) and 17.5% (95%CI 15.6-24.5) in Hispanics. NHW had an EE factor of 0.78 and Hispanics had 0.58, showing a reduction in survival versus NHW and PACIFIC of 20% and 42%, respectively. HR for the OS among NHWs and Hispanics was 1.53 (95%CI 1.12-1.71; P=0.052) and 2.31 (95%CI 1.76-2.49; P=0.004). Fifty-six patients (44.8%) had some degree of pneumonitis due to cCRT plus durvalumab. There was no difference in the proportion of pneumonitis according to race (P=0.95), and the severity of pneumonitis was not significantly different between Hispanics and NHWs (P=0.41).

Conclusions

Among patients with LA stage III NSCLC, NHW had better survival outcomes when compared to Hispanics, with an OS that seems to favor the NHW population and with an EE factor that shows a shorter survival in Hispanics compared with NHW and with the PACIFIC trial group.
Goblet Cell Adenocarcinoma of the Appendix: A Systematic Review and Incidence and Survival of 1,225 Cases From an English Cancer Registry
Authors: Palmer Kieran , Weerasuriya Scott , Chandrakumaran Kandiah , Rous Brian , White Benjamin E. , Paisey Sangeeta , Srirajaskanthan Rajaventhan , Ramage John K.
Published: July 2022

Background

Goblet cell adenocarcinoma (GCA) of the appendix is a rare and aggressive tumour with varying nomenclature and classification systems. This has led to heterogeneity in published data, and there is a lack of consensus on incidence, survival, and management.

Methods

We provide an overview of GCA with a comprehensive systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology and a retrospective analysis of all cases recorded in the English National Cancer Registration and Analysis Service database between 1995 and 2018. The Kaplan–Meier estimator was used to calculate overall survival, and Cox proportional hazards regression was used to identify prognostic factors.

Results

The systematic review demonstrated an incidence of 0.05–0.3 per 100,000 per year among North American registry studies. The 1-, 3-, and 5-year survival rate was 95.5%, 85.9%–87.6%, and 76.0%–80.6%, respectively. Age, stage, and grade were identified as prognostic factors for survival. Our analysis included 1,225 cases. Age-standardised incidence was 0.0335 per year in 1995 and gradually rose to 0.158 per year in 2018. The 1-, 3-, and 5-year survival rate was 90.0% [95% confidence interval (95% CI): 85.4–94.0], 76.0% (95% CI: 73.8–80.9), and 68.6% (95% CI: 65.9–72.2), respectively. On univariate Cox regression analyses, female sex, stage, and grade were associated with worse overall survival. On multivariate analysis, only stage remained a statistically significant prognostic factor.

Conclusions

GCA of the appendix is rare, but incidence is increasing. We report a lower incidence and survival than North American registry studies. Higher stage was associated with decreased survival. Further prospective studies are required to establish optimal management.
Chemopreventive Potential of Dietary Nanonutraceuticals for Prostate Cancer: An Extensive Review
Authors: Chopra Hitesh , Bibi Shabana , Goyal Rajat , Gautam Rupesh K. , Trivedi Rashmi , Upadhyay Tarun Kumar , Mujahid Mohd Hasan , Shah Mohammad Ajmal , Haris Muhammad , Khot Kartik Bhairu , Gopan Gopika , Singh Inderbir , Kim Jin Kyu , Jose Jobin , Abdel-Daim Mohamed M. , Alhumaydhi Fahad A. , Emran Talha Bin , Kim Bonglee
Published: July 2022

There are more than two hundred fifty different types of cancers, that are diagnosed around the world. Prostate cancer is one of the suspicious type of cancer spreading very fast around the world, it is reported that in 2018, 29430 patients died of prostate cancer in the United State of America (USA), and hence it is expected that one out of nine men diagnosed with this severe disease during their lives. Medical science has identified cancer at several stages and indicated genes mutations involved in the cancer cell progressions. Genetic implications have been studied extensively in cancer cell growth. So most efficacious drug for prostate cancer is highly required just like other severe diseases for men. So nutraceutical companies are playing major role to manage cancer disease by the recommendation of best natural products around the world, most of these natural products are isolated from plant and mushrooms because they contain several chemoprotective agents, which could reduce the chances of development of cancer and protect the cells for further progression. Some nutraceutical supplements might activate the cytotoxic chemotherapeutic effects by the mechanism of cell cycle arrest, cell differentiation procedures and changes in the redox states, but in other, it also elevate the levels of effectiveness of chemotherapeutic mechanism and in results, cancer cell becomes less reactive to chemotherapy. In this review, we have highlighted the prostate cancer and importance of nutraceuticals for the control and management of prostate cancer, and the significance of nutraceuticals to cancer patients during chemotherapy.
Evaluation of Pharmacokinetics of Boronophenylalanine and Its Uptakes in Gastric Cancer
Authors: Tang Futian , Wei Yujie , Zhang Shining , Wang Jianrong , Gu Wenjiao , Tang Fenxia , Peng Xiaohuan , Wei Yucai , Liu Jiangyan , Chen Weiqiang , Zhang Shixu , Gu Long , Li Yumin
Published: July 2022

Boron neutron capture therapy (BNCT), a cellular-level particle radiation therapy, combines boron compounds selectively delivered to tumor tissue with neutron irradiation. Boronophenylalanine (BPA) is a boron compound widely used in malignant melanoma, malignant brain tumors, and recurrent head and neck cancer. However, neither basic nor clinical research was reported for the treatment of gastric cancer using BPA. Selective distribution of boron in tumors rather than that in blood or normal tissue prior to neutron irradiation is required for the successful treatment of BNCT. This study evaluated the pharmacokinetics and safety of 10B-labeled BPA (10B-BPA, abbreviated as BPA) and its uptakes in gastric cancer. Pharmacokinetics and safety were evaluated in Sprague–Dawley (SD) rats intravenously injected with BPA. The uptakes of boron in gastric cancer cell line MKN45 and in cell-derived xenografts (CDX) and patient-derived xenografts (PDX) animal models were measured. The results showed that the boron concentration in the blood of rats decreased fast in the first 30 min followed by a steady decrease following the observation time, having a half-life of 44.11 ± 8.90 min and an AUC-last of 815.05 ± 62.09 min×μg/ml. The distribution of boron in different tissues (heart, liver, lung, stomach, and small intestine) of rats revealed a similar pattern in blood except for that in the brain, kidney, and bladder. In MKN45 cells, boron concentration increased in a time- and concentration-dependent manner. In both CDX and PDX animal models, the boron is preferentially distributed in tumor tissue rather than in blood or normal tissues. In addition, BPA had no significant adverse effects in rats. Taken together, the results suggested that BPA revealed a fast decrease in boron concentration in rats and is more likely to distribute in tumor cells and tissue.
A Prospective Observational Study to Assess Attachment Representations With Regard to Neurocognitive and Behavioral Outcomes in Children Born Very Prematurely in the Loire Infant Follow-Up Team (LIFT Cohort)
Authors: Riquin Elise , Sandnes Ramona , Bacro Fabien , Vinay Aubeline , Miljkovitch Raphaële , Rouger Valérie , Rakotonjanahary Josué , Gascoin Géraldine , Müller Jean-Baptiste
Published: July 2022

Context and purpose

Prematurity is a situation that can disrupt parent-child interactions. We hypothesize that establishing relationships with parents in a context of extreme prematurity can alter the development of secure attachment representations in the child. Furthermore, we hypothesize that secure maternal representations and their possible interactions with prematurity factors prevent the development of insecure or disorganized attachment in the child. In addition, maternal representations and their possible interactions with factors related to prematurity may prevent or accentuate the development of an insecure or disorganized attachment in the child.

Methods and analysis

This is a longitudinal, prospective, exploratory, and bi-centric study. Children born in the neonatal intensive care units of Angers or Nantes University Hospitals with a gestational age of up to 28 weeks will be included in the study. The main objective is to describe the attachment representations at 3 and 5 years through the Attachment Story Completion Task scales and to analyze them in regard to the children’s neurocognitive and behavioral outcomes as well as maternal attachment and mental health.

Ethics

The study file received a favorable opinion for the implementation of this research on February 18, 2020 - ID-RCB no. 2019-A03352-55 (File 2-20-007 id6699) 2°HPS. This study has received authorization from the French Data Protection Authority (CNIL) under no. 920229.

Discussion

A better understanding of attachment representations in extreme prematurity and their possible associations with children’s neurocognitive and behavioral outcomes as well as maternal attachment and mental health could pave the way for individualized care at an early stage, or even interventions during the neonatal period to improve the outcome of these vulnerable newborns.

Trial registration

[ClinicalTrials.gov], identifier [NCT04304846].
Two Children With Steroid-Resistant Significant Proteinuria Due to Nonsense Mutations of the TRIM8 Gene: A Case Report and Literature Review
Authors: Li Xiaojie , Wei Yaqin , Wang Meiqiu , Jia Lili , Shi Zhuo , Yang Xiao , Ju Tao , Kuang Qianhuining , Xia Zhengkun , Gao Chunlin
Published: July 2022

Background

TRIM8 gene mutations have been reported as the genetic basis of autosomal dominant (AD) neuro-renal syndrome in children, which presents with epileptic encephalopathy, focal segmental glomerulosclerosis (FSGS), developmental delay, and mental retardation. In this study, we report the cases of two children with significant proteinuria due to de novo nonsense mutations of the TRIM8 gene.

Case Presentation

Case 1 was a 7-year-old girl who presented with proteinuria and developmental delay, and her renal biopsy showed FSGS. She developed end-stage renal disease (ESRD) 3 years after onset. Case 2 was another 7-year-old girl who developed proteinuria only at age 3, and renal biopsy showed glomerular segmental mesangial proliferative lesions. The two girls underwent genetic testing but we did not find a positive result in the whole exon. However, cluster analysis revealed two new nonsense mutations of the TRIM8 gene (c.1461C>A, p.Tyr 487* and c.1453C>T, p.Gln485*).

Conclusions

We reported the clinical manifestation of this neuro-renal syndrome for the first time in China. It is necessary to perform genetic testing in children with steroid-resistant significant proteinuria to identify its etiology and avoid the side effects of immunosuppressants.
Cerebral Oxygenation and Metabolism After Hypoxia-Ischemia
Authors: Dhillon Simerdeep K. , Gunn Eleanor R. , Lear Benjamin A. , King Victoria J. , Lear Christopher A. , Wassink Guido , Davidson Joanne O. , Bennet Laura , Gunn Alistair J.
Published: July 2022

Perinatal hypoxia-ischemia (HI) is still a significant contributor to mortality and adverse neurodevelopmental outcomes in term and preterm infants. HI brain injury evolves over hours to days, and involves complex interactions between the endogenous protective and pathological processes. Understanding the timing of evolution of injury is vital to guide treatment. Post-HI recovery is associated with a typical neurophysiological profile, with stereotypic changes in cerebral perfusion and oxygenation. After the initial recovery, there is a delayed, prolonged reduction in cerebral perfusion related to metabolic suppression, followed by secondary deterioration with hyperperfusion and increased cerebral oxygenation, associated with altered neurovascular coupling and impaired cerebral autoregulation. These changes in cerebral perfusion are associated with the stages of evolution of injury and injury severity. Further, iatrogenic factors can also affect cerebral oxygenation during the early period of deranged metabolism, and improving clinical management may improve neuroprotection. We will review recent evidence that changes in cerebral oxygenation and metabolism after HI may be useful biomarkers of prognosis.
Assessment of the Potential of Sarcandra glabra (Thunb.) Nakai. in Treating Ethanol-Induced Gastric Ulcer in Rats Based on Metabolomics and Network Analysis
Authors: Li Chao , Wen Rou , Liu DeWen , Yan LiPing , Gong Qianfeng , Yu Huan
Published: July 2022

Gastric ulcer (GU) is one of the most commonly diagnosed diseases worldwide, threatening human health and seriously affecting quality of life. Reports have shown that the Chinese herbal medicine Sarcandra glabra (Thunb.) Nakai (SGN) can treat GU. However, its pharmacological effects deserve further validation; in addition, its mechanism of action is unclear. An acute gastric ulcer (AGU) rat model induced by alcohol was used to evaluate the gastroprotective effect of SGN by analysis of the histopathological changes in stomach tissue and related cytokine levels; the potential mechanisms of action of SGN were investigated via serum metabolomics and network pharmacology. Differential metabolites of rat serum were identified by metabolomics and the metabolic pathways of the identified metabolites were enriched via MetaboAnalyst. Furthermore, the critical ingredients and candidate targets of SGN anti-AGU were elucidated. A compound-reaction-enzyme-gene network was established using Cytoscape version 3.8.2 based on integrated analysis of metabolomics and network pharmacology. Finally, molecular docking was applied to verify the acquired key targets. The results showed that SGN exerted a certain gastroprotective effect via multiple pathways and targets. The effects of SGN were mainly caused by the key active ingredients isofraxidin, rosmarinic, and caffeic acid, which regulate hub targets, such as PTGS2, MAPK1, and KDR, which maintain the homeostasis of related metabolites. Signal pathways involved energy metabolism as well as immune and amino acid metabolism. Overall, the multi-omics techniques were proven to be promising tools in illuminating the mechanism of action of SGN in protecting against diseases. This integrated strategy provides a basis for further research and clinical application of SGN.
Biosimilar Use and Switching in Belgium: Avenues for Integrated Policymaking
Authors: Barbier Liese , Simoens Steven , Declerck Paul , Vulto Arnold G. , Huys Isabelle
Published: July 2022

Background: By improving the affordability and accessibility of biologicals, biosimilar competition provides important benefits to healthcare systems and patients. In Belgium, biosimilar uptake and competition is limited compared to other European markets. Whereas other countries have initiated structured biosimilar introduction or switching plans, no such framework or guiding principles are yet available in Belgium.

Objective: This study aims to develop recommendations that can inform policy action in Belgium on biosimilar use, especially in the context of switch decision-making, and this by drawing from the perspectives of healthcare professionals involved in procuring, prescribing, switching and dispensing biologicals including biosimilars.

Methods: This study made use of the consensus-building Nominal Group Technique, consisting of a three-step process 1) individual grading, 2) three structured Focus Group Discussions, 3) final individual grading involving an expert group of Belgian healthcare professionals (physician specialists and hospital pharmacists).

Results: Participants (n = 13) voiced challenges with the use of biosimilars and switching in practice, and a lack of incentives to use them. Six concrete areas for policy development to support stakeholders with biosimilar use and switch decision-making were identified: 1) address stakeholder hesitations regarding (multiple) switching, 2) provide meaningful incentives, 3) guide healthcare professionals with product decision-making, 4), align practical product modalities when possible, 5) involve healthcare professionals in policy making, and 6) provide practical switch support and patient information material, particularly in the ambulatory care setting. For each area, specific consensus-based recommendations were developed. Furthermore, a set of switch management and patient communication principles was derived, including amongst others, generating buy-in from involved stakeholders prior to switching and communicating with a one-voice message.

Conclusion: Without cohesive actions to reduce hurdles and without tangible benefits or steering mechanisms, changes in biosimilar use are unlikely in Belgium. To overcome this and stimulate market competitiveness, this study advances a set of concrete policy recommendations. At large, policy makers should develop an integrated policy framework, with a pro-active, best-value biological implementation roadmap that provides guidance and compelling measures to incentivize healthcare professionals to use biosimilars. Particular consideration should go to the ambulatory care setting, since drivers for biosimilar use are quasi absent in this context.
Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitors vs. Dipeptidyl Peptidase-4 Inhibitors in Frail People With Diabetes Who Were Recently Hospitalized
Authors: Wood Stephen J , Bell J Simon , Magliano Dianna J , Shaw Jonathan E , Cesari Matteo , Ilomaki Jenni
Published: July 2022

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT-2Is) reduce heart failure (HF) hospitalizations and major adverse cardiovascular events (MACE) in general type 2 diabetes populations. The objective of this study was to determine whether SGLT-2Is vs. dipeptidyl peptidase-4 inhibitors (DPP-4Is) are associated with reductions in MACE, HF hospitalizations and mortality in frail people with type 2 diabetes.

Methods: We conducted a cohort study of all patients aged ≥30 years with type 2 diabetes discharged from a hospital in Victoria, Australia between January 2014 and March 2018 who received SGLT-2Is or DPP-4Is within 60 days of discharge. Follow-up commenced 60 days after initial discharge, and MACE, HF hospitalization and mortality were recorded. Cox proportional hazards regression with competing risks and stabilized inverse probability of treatment weights (IPTWs), was used to generate subdistribution hazard ratios (sHRs) with 95% confidence intervals (CIs). Analyses were stratified into frailty quartiles according to Hospital Frailty Risk Scores (HFRS).

Results: Of the 32,043 patients, (41.9% female and 5.9% ≥80 years) in the cohort, 5,152 (16.1%) received SGLT-2Is. Overall, SGLT-2I versus DPP-4I recipients had lower rates of MACE (sHR 0.51; 95% CI 0.46–0.56), HF hospitalization (sHR 0.42; 95% CI 0.36–0.49) and mortality (HR 0.38; 95% CI 0.33–0.43). People with HFRSs in the fourth quartile who received SGLT-2Is versus DPP-4Is also had reduced rates of MACE (sHR 0.37; 95% CI 0.29–0.46), HF hospitalization (sHR 0.43; 95% CI 0.33–0.56) and mortality (HR 0.32; 95% CI 0.25–0.41).

Conclusion: SGLT-2Is may be preferred to DPP-4Is for preventing MACE, HF hospitalizations and mortality in frail people with type 2 diabetes.
Adherence to Statin Therapy and Attainment of LDL Cholesterol Targets in an Outpatient Population of Type 2 Diabetes Patients: Analysis in the DIAbetes and LifEstyle Cohort Twente (DIALECT)
Authors: Beernink Jelle M. , Oosterwijk Milou M. , van Boven Job F. M. , Heerspink Hiddo J. L. , Bakker Stephan J. L. , Navis Gerjan , Nijboer Roos M. , Gant Christina M. , Haverkate Heleen , Kruik-Kollöffel Willemien J. , Laverman Gozewijn D.
Published: July 2022

Objective: To assess adherence to statin therapy and its association with sociodemographic data, medical characteristics, LDLc levels, and LDLc target attainment in real-world T2D patients treated in secondary care.

Research Design and Methods: Cross-sectional analyses were performed on baseline data of 393 patients in the DIAbetes and LifEstyle Cohort Twente (DIALECT). The medication possession ratio (MPR), calculated with pharmacy dispensing data, was used to determine adherence to statins for an intended period of 24 months. Statins were included in the analyses if they were used for at least six consecutive months with at least three dispenses. Adherence was defined as an MPR ≥80%. Associations with adherence were assessed using descriptive statistics and binary logistic regression.

Results: Overall, 80% of the patients had a statin prescription and of those, 89% were adherent. The proportion of patients who reached LDLc targets of ≤2.5 mmol/L and <1.8 mmol/L differed significantly between the adherent, nonadherent and non-statin group (90% vs. 74% vs. 46%; p < 0.01 and 56% vs. 26% vs. 6%; p < 0.01, respectively). Serum LDLc levels were lower in the adherent versus the nonadherent and non-statin group (1.76 ± 0.60 vs. 2.23 ± 0.90 vs. 2.71 ± 0.67 mmol/L; p < 0.01). Higher HbA1c levels were independently associated with nonadherence (OR: 1.05, 95% CI 1.01–1.08; p < 0.01). Mediation adherence (OR: 2.88, 95% CI 1.04–7.97; p = 0.041) and lower BMI (OR: 0.88, 95% CI 0.81–0.96; p < 0.01) were independently associated with attaining the LDLc target of ≤2.5 mmol/L.

Conclusion: In patients with T2D treated in secondary care, statin adherence was relatively high and was associated with significantly lower LDLc levels. It is important to identify nonadherence as it appeared an important determinant of failure to reach LDLc targets. The finding that many patients who failed to attain LDLc targets did not receive statin treatment offers an opportunity to improve diabetes care.
Dendrobium huoshanense C.Z.Tang et S.J.Cheng: A Review of Its Traditional Uses, Phytochemistry, and Pharmacology
Authors: Gao Leilei , Wang Fang , Hou Tingting , Geng Chunye , Xu Tao , Han Bangxing , Liu Dong
Published: July 2022

Dendrobium huoshanense, a traditional medicinal and food homologous plant, belongs to the family Orchidaceae and has a long history of medicinal use. It is reported that the stem of D. huoshanense has a variety of bioactive ingredients such as polysaccharides, flavonoids, sesquiterpenes, phenols, etc. These bioactive ingredients make D. huoshanense remarkable for its pharmacological effects on anti-tumor, immunomodulation, hepatoprotective, antioxidant, and anticataract activities. In recent years, its rich pharmacological activities have attracted extensive attention. However, there is no systematic review focusing on the chemical compositions and pharmacological effects of D. huoshanense. Therefore, the present review aims to summarize current research on the chemical compositions and pharmacological activities of D. huoshanense. This study provides valuable references and promising ideas for further investigations of D. huoshanense.
Bromopropylate Imidazoliumyl Substituted Silicon Phthalocyanine for Mitochondria-Targeting, Two-Photon Imaging Guided in Vitro Photodynamic Therapy
Authors: Chen Kuizhi , Hou Jialin , Huang Bingcheng , Xiao Shuanghuang , Li Xia , Sun Hong , Peng Yiru
Published: July 2022

Maximization of phototoxic damage on tumor is essential for effective anticancer photodynamic therapy (PDT). Highly cancer-cell-organelle-specific delivery of efficient photosensitizers (PSs) in vitro and in vivo is in great demand. In this paper, a novel water-soluble mitochondria targeted cationic bromopropylate imidazoliumyl axially substituted silicon (IV) phthalocyanine (Br-ID-SiPc) is developed to improve PDT efficiency by enhancing the subcellular localization of photosensitizers. Benefiting from the targeting capability of bromopropylate imidazoliumyl, Br-ID-SiPc can selectively accumulate in mitochondria after cellular uptake, this process could be tracked by two-photon imaging. Br-ID-SiPc effectively damaged the circular plasmid DNA of mitochondria and induced HO-8910 cells apoptosis. Our results indicate that Br-ID-SiPc is a potential photosensitizer which can be used as a mitochondria-targeting and two-photon fluorescent imaging molecule for PDT of cancers.
Potential Roles of PTEN on Longevity in Two Closely Related Argopecten Scallops With Distinct Lifespans
Authors: Xu Hanzhi , Lu Xia , Wang Chunde , Ning Junhao , Chen Min , Wang Yuan , Yuan Ke
Published: July 2022

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) has been found to regulate longevity through the PI3K/Akt/FoxO pathway and maintenance of genome integrity in worms, flies, and mammals. However, limited information is available on the roles of PTEN in longevity of aquatic animals. Here we extended this paradigm using two closely related Argopecten scallops, Argopecten purpuratus, and Argopecten irradians, with significantly distinct life spans, which are commercially important bivalve species for fishery and aquaculture in China, United States, Peru, and Chile. The ORFs of the ApPTEN and AiPTEN were 1,476 and 1,473 bp, which encoded 491 and 490 amino acids, respectively. There were 48 synonymous and 16 non-synonymous SNPs and one InDel of three nucleotides between ApPTEN and AiPTEN, resulting in variations in 15 amino acids and lack of S453 in AiPTEN. Differences in conformation and posttranslational modification were predicted between ApPTEN and AiPTEN, which may indicate different activities of ApPTEN and AiPTEN. When the animals were subjected to nutrition restriction, the expression of both ApPTEN and AiPTEN was upregulated, with AiPTEN responded faster and more robust than ApPTEN. Ionizing radiation induced significantly elevated expression of ApPTNE but not AiPTEN in the adductor muscle, and the mortality rate of A. purpuratus was significantly lower than that of A. irradians, indicating that ApPTNE may play a protective role by maintaining the genome integrity. RNAi of ApPTNE significantly downregulated the expression of its downstream regulated genes known to favor longevity, such as FoxO, Mn-SOD, and CAT. These results indicated that PTEN may contribute to the longevity of A. purpuratus through regulation of nutrient availability and genomic stability, probably via PI3K/Akt/FoxO pathway. Our study may provide new evidence for understanding of the conservative functions of PTEN in regulation of lifespan in animals and human, and it may also benefit the selection of scallops strains with long lifespan and thus larger size.
Combined Analysis of the Transcriptome and Metabolome Revealed the Mechanism of Petal Coloration in Bauhinia variegata
Authors: Zhang Geng , Yang Xiaohui , Xu Fang , Wei Dan
Published: July 2022

Bauhinia variegata petals are colorful, rich in anthocyanins, and have ornamental, nutritional, and medicinal value. However, the regulatory mechanism of anthocyanin accumulation in B. variegata remains unclear. In this study, a combined analysis of the metabolome and transcriptome was performed in red and white B. variegata cultivars in the early, middle, and blooming stages. A total of 46 different anthocyanins were identified, of which 27 showed marked differences in accumulation between the two cultivars, and contribute to their different petal colors. Malvidin 3-O-galactoside, peonidin 3-O-galactoside, cyanidin 3-O-glucoside, cyanidin 3-O-galactoside, and malvidin 3-O-glucoside were much more abundant in the second stage of flowering. In the blooming stage, except for the anthocyanins mentioned, delphinidin 3-O-galactoside and petunidin 3-O-galactoside were the most abundant anthocyanins in the red flowers, indicating that malvidin, peonidin, cyanidin, delphinidin, and petunidin were all responsible for the red color of petals in B. variegata. RNA sequencing identified 2,431 differentially expressed genes (DEGs), of which 26 were involved in the anthocyanin synthesis pathway. Correlations between the anthocyanin biosynthesis-related DEGs and anthocyanin contents were explored, and the DEGs involved in anthocyanin accumulation in B. variegata petals were identified. Eighteen of these DEGs encoded key catalytic enzymes, such as anthocyanidin reductase (ANR) and flavonoid-3′5′-hydroxylase (F3′5′H), and 17 of them encoded transcription factors (TFs) belonging to 14 families (including MYB, NAC, SPL, ERF, and CHR28). These results improve our understanding of the roles of anthocyanins, catalytic enzymes, and TFs in B. variegata petal-color expression.