bluuebunny/crossref_metadata_2025 huggingface dataset:
FN-OCT: Disease Detection Algorithm for Retinal Optical Coherence Tomography Based on a Fusion Network
Authors: Ai Zhuang , Huang Xuan , Feng Jing , Wang Hui , Tao Yong , Zeng Fanxin , Lu Yaping
Published: June 2022

Optical coherence tomography (OCT) is a new type of tomography that has experienced rapid development and potential in recent years. It is playing an increasingly important role in retinopathy diagnoses. At present, due to the uneven distributions of medical resources in various regions, the uneven proficiency levels of doctors in grassroots and remote areas, and the development needs of rare disease diagnosis and precision medicine, artificial intelligence technology based on deep learning can provide fast, accurate, and effective solutions for the recognition and diagnosis of retinal OCT images. To prevent vision damage and blindness caused by the delayed discovery of retinopathy, a fusion network (FN)-based retinal OCT classification algorithm (FN-OCT) is proposed in this paper to improve upon the adaptability and accuracy of traditional classification algorithms. The InceptionV3, Inception-ResNet, and Xception deep learning algorithms are used as base classifiers, a convolutional block attention mechanism (CBAM) is added after each base classifier, and three different fusion strategies are used to merge the prediction results of the base classifiers to output the final prediction results (choroidal neovascularization (CNV), diabetic macular oedema (DME), drusen, normal). The results show that in a classification problem involving the UCSD common retinal OCT dataset (108,312 OCT images from 4,686 patients), compared with that of the InceptionV3 network model, the prediction accuracy of FN-OCT is improved by 5.3% (accuracy = 98.7%, area under the curve (AUC) = 99.1%). The predictive accuracy and AUC achieved on an external dataset for the classification of retinal OCT diseases are 92 and 94.5%, respectively, and gradient-weighted class activation mapping (Grad-CAM) is used as a visualization tool to verify the effectiveness of the proposed FNs. This finding indicates that the developed fusion algorithm can significantly improve the performance of classifiers while providing a powerful tool and theoretical support for assisting with the diagnosis of retinal OCT.
The Recognition of Facial Expressions Under Surgical Masks: The Primacy of Anger
Authors: Proverbio Alice M. , Cerri Alice
Published: June 2022

Background

The need to wear surgical masks in everyday life has drawn the attention of psychologists to the negative effects of face covering on social processing. A recent but not homogeneous literature has highlighted large costs in the ability to recognize emotions.

Methods

Here it was investigated how mask covering impaired the recognition of facial mimicry in a large group of 220 undergraduate students. Sex differences in emotion recognition were also analyzed in two subgroups of 94 age-matched participants. Subjects were presented with 112 pictures displaying the faces of eight actors (4 women and 4 men) wearing or not wearing real facemasks, and expressing seven emotional states (neutrality, surprise, happiness, sadness, disgust, anger and fear). The task consisted in categorizing facial expressions while indicating the emotion recognizability with a 3-point Likert scale. Scores underwent repeated measures ANOVAs.

Results

Overall, face masking reduced emotion recognition by 31%. All emotions were affected by mask covering except for anger. Face covering was most detrimental to sadness and disgust, both relying on mouth and nose expressiveness. Women showed a better performance for subtle expressions such as surprise and sadness, both in masked and natural conditions, and men for fear recognition (in natural but especially masked conditions).

Conclusion

Anger display was unaffected by masking, also because corrugated forehead and frowning eyebrows were clearly exposed. Overall, facial masking seems to polarize non-verbal communication toward the happiness/anger dimension, while minimizing emotions that stimulate an empathic response in the observer.
Dose-Dependent Regulation on Prefrontal Neuronal Working Memory by Dopamine D1 Agonists: Evidence of Receptor Functional Selectivity-Related Mechanisms
Authors: Yang Yang , Kocher Susan D. , Lewis Mechelle M. , Mailman Richard B.
Published: June 2022

Low doses of dopamine D1 agonists improve working memory-related behavior, but high doses eliminate the improvement, thus yielding an ‘inverted-U’ dose-response curve. This dose-dependency also occurs at the single neuron level in the prefrontal cortex where the cellular basis of working memory is represented. Because signaling mechanisms are unclear, we examined this process at the neuron population level. Two D1 agonists (2-methyldihydrexidine and CY208,243) having different signaling bias were tested in rats performing a spatial working memory-related T-maze task. 2-Methyldihydrexidine is slightly bias toward D1-mediated β-arrestin-related signaling as it is a full agonist at adenylate cyclase and a super-agonist at β-arrestin recruitment, whereas CY208,243 is slightly bias toward D1-mediated cAMP signaling as it has relatively high intrinsic activity at adenylate cyclase, but is a partial agonist at β-arrestin recruitment. Both compounds had the expected inverted U dose-dependency in modulating prefrontal neuronal activities, albeit with important differences. Although CY208,243 was superior in improving the strength of neuronal outcome sensitivity to the working memory-related choice behavior in the T-maze, 2-methyldihydrexidine better reduced neuron-to-neuron variation. Interestingly, at the neuron population level, both drugs affected the percentage, uniformity, and ensemble strength of neuronal sensitivity in a complicated dose-dependent fashion, but the overall effect suggested higher efficiency and potency of 2-methyldihydrexidine compared to CY208,243. The differences between 2-methyldihydrexidine and CY208,243 may be related to their specific D1 signaling. These results suggest that D1-related dose-dependent regulation of working memory can be modified differentially by functionally selective ligands, theoretically increasing the balance between desired and undesired effects.
Eating Hubs in Multiple Sclerosis: Exploring the Relationship Between Mediterranean Diet and Disability Status in Italy
Authors: Felicetti Federica , Tommasin Silvia , Petracca Maria , De Giglio Laura , Gurreri Flavia , Ianniello Antonio , Nistri Riccardo , Pozzilli Carlo , Ruggieri Serena
Published: June 2022

Background

Multiple Sclerosis (MS) is a complex disease in which multiple factors contribute to disability accrual. Mediterranean Diet (MeDi) has shown beneficial effects across neurodegenerative diseases. We hypothesize that specific food habits, rather than global adherence to MeDi, might impact on MS. We aimed to (i) evaluate differences in adherence to MeDi between people living with MS (PwMS) and healthy controls (HC); (ii) characterize eating patterns in PwMS and HC, identifying the most influential MeDi items for each group by the use of network analysis; (iii) explore the relationship between patients' eating habits and disability.

Materials and Methods

In this cross-sectional study, we consecutively recruited 424 PwMS and 165 matched HC. Data were obtained through the administration of self-reported questionnaires. Expanded Disability Status Scale (EDSS) and Fatigue Severity Scale (FSS) were evaluated in the MS population. We performed between-groups comparisons via unpaired two-sample t-test and X2 test as appropriate. We calculated food networks in both MS cases and HC using and tested the association between hub nodes and disability. Finally, we conducted a post-hoc analysis, investigating the relationship between food items, lifestyle factors (smoking, exercise) and clinical outcomes.

Results

Most participants adhered sufficiently to MeDi. Exploring each group separately, fruit, vegetables, cereal, and fish were identified as hubs in PwMS, while meat and alcohol were identified as hubs in HC. Hubs were all inter-correlated, indicating that eating habits of PwMS include a large intake of all the foods identified as hubs. EDSS was predicted by the intake of vegetables (beta = −0.36, p < 0.03) and fish (beta = −0.34, p < 0.02). The model including smoking pack/year, International Physical Activity Questionnaire (IPAQ) score and intake of “negative foods” predicted 6% of the variance in EDSS (p < 0.001), while the model including smoking pack/year and IPAQ score predicted 4% of the variance in FSS (p < 0.001).

Conclusions

We identified a sufficient adherence to MeDi in our population. PwMS showed overall a healthier dietary pattern than HC. Vegetables and fish intake were associated with disability outcomes. Future longitudinal studies applying integrated approaches are needed to understand lifestyle added value to the use of standard pharmacological therapies.
Consumers' Response to Sugar Label Formats in Packaged Foods: A Multi-Methods Study in Brazil
Authors: Scapin Tailane , Fernandes Ana Carolina , Shahid Maria , Pettigrew Simone , Khandpur Neha , Bernardo Greyce Luci , Uggioni Paula Lazzarin , Proença Rossana Pacheco da Costa
Published: June 2022

Providing information about the sugar content of packaged foods on product labels is an important strategy to lower consumers' sugar intake. This study assessed the effect of exposure to different sugar labels on consumers' understanding of the sugar content of foods and their food choices. In the first phase, five focus groups were conducted with a convenience sample of Brazilian adults to explore their perceptions about food labelling in general and sugar labelling in particular. Based on the qualitative results, four sugar label formats were developed and subsequently tested in a five-arm study on 1,277 adults via a randomised controlled online survey. The formats were: (i) no sugar information—control, (ii) total and added sugar content displayed in the Nutrition Information Panel (NIP), (iii) a front-of-package (FoP) octagonal warning for “high-in-sugar” products, (iv) a FoP magnifying glass warning for “high-in-sugar” products, and (v) a “high-in-sugar” warning text embedded on the NIP. Participants from the focus groups reported being confused about the meaning of “sugar” and “added sugar” on food labels and indicated that more interpretive labels, such as the FoP warnings, would help them choose products with low sugar content. In the experiment, all intervention sugar label formats improved participants' understanding of the sugar content of the tested food products, with the FoP warnings (iii and iv) showing the best results. While non-significant differences among label conditions were observed for food choices, the FoP octagonal warning prompted participants to choose high-in-sugar products less often. Given current public policy agendas aiming to reduce added sugar intake, there is a need to strengthen food labelling policies and nutrition disclosure policies that target the display of added sugar and build consumer awareness in using these tools to avoid high-in-sugar products.
Local Ablative Treatment Improves Survival in ESCC Patients With Specific Metastases, 2010–2016: A Population-Based SEER Analysis
Authors: Yang Hui , Wang Kunlun , Li Yan , Li Shenglei , Yuan Ling , Ge Hong
Published: June 2022

Background

We aimed to explore the role of local ablative treatment (LAT) in metastatic esophageal squamous cell cancer (ESCC) patients who received chemotherapy and identify patients who will most likely benefit.

Methods

We analyzed data of metastatic ESCC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. The chi-square test was used to evaluate the unadjusted clinicopathological categorical variables between the two groups. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors of overall survival. Propensity score matching (PSM) was used to adjust the differences between the two groups.

Results

Overall, 720 metastatic ESCC patients treated with chemotherapy were analyzed in this study; 63.2% of patients (n = 455) received LAT, including radiotherapy (n = 444), primary site surgery (n = 12), or lymph node dissection (n = 27). Gender (HR = 1.220, 95% CI: 1.024–1.453, p = 0.026), bone metastases (HR = 1.559, 95% CI: 1.292–1.882, p < 0.001), and liver metastases (HR = 1.457, 95% CI: 1.237–1.716, p < 0.001) were independent prognostic factors in the entire population. However, LAT was not an independent prognostic factor. Further subgroup analyses showed that LAT improved OS from 8.0 months to 10.0 months in patients with metastases other than bone/liver (HR = 0.759, 95% CI: 0.600–0.961, p = 0.022). LAT was not a prognostic factor in patients with bone/liver metastases (HR = 0.995, 95% CI: 0.799–1.239, p = 0.961). After PSM, the median OS was 8.0 months (95% CI: 7.2–8.8 months) and patients who received LAT had a better OS than patients without LAT (HR = 0.796, 95% CI: 0.653–0.968, p = 0.023). Patients with metastases other than bone/liver could benefit from LAT compared with those with bone/liver metastases.

Conclusions

Our study indicated that metastatic ESCC patients with metastases other than bone/liver could derive additional benefit from LAT with systemic chemotherapy.
The Value of Lymph Node Dissection in Patients With Node-Positive Upper Urinary Tract Urothelial Cancer: A Retrospective Cohort Study
Authors: Xia Hao-ran , Li Shu-guang , Zhai Xing-quan , Liu Min , Guo Xiao-xiao , Wang Jian-ye
Published: June 2022

Purpose

The value of lymphadenectomy during radical nephroureterectomy (RNU) remains unclear. This study aimed to determine the effects of the removed lymph node (RLN) counts, positive lymph node (pLN) counts, and pLN density (pLND) on survival outcomes in patients with node-positive upper urinary tract urothelial cancer (UTUC).

Methods

A total of 306 patients with node-positive UTUC in the Surveillance, Epidemiology, and End Results database between 2004 and 2016 were identified. Multivariable Cox regression analyses were used to evaluate the effect of RLN counts, pLN counts, and pLND on survival outcomes. The maximally selected rank statistics were used to determine the most informative cutoff value for pLND on survival outcomes.

Results

The RLN counts or pLN counts were not associated with survival outcomes, whereas higher pLND was associated with lower cancer-specific survival (CSS) and overall survival (OS) [hazard ratio (HR) 1.75, P = 0.014 and HR 1.62, P = 0.036, respectively]. The most informative cutoff value for pLND in relation to survival was 27%. Patients with pLND ≥27% had worse 5-year survival rates than those with pLND <27% (52.9% vs. 75.9% for CSS and 18.7% vs. 34.2% for OS, each P < 0.05). Furthermore, the multivariable Cox regression model with pLND could predict 5-year CSS (AUC 0.732 vs. 0.647) or OS (AUC 0.704 vs. 0.621) more accurately than the model without pLND.

Conclusions

For patients with node-positive UTUC, more lymph nodes removed do not offer a better therapeutic effect. However, pLND provides additional prognostic value.
Development and Validation of Prognostic Model for Lung Adenocarcinoma Patients Based on m6A Methylation Related Transcriptomics
Authors: Li Huijun , Liu Song-Bai , Shen Junjie , Bai Lu , Zhang Xinyan , Cao Jianping , Yi Nengjun , Lu Ke , Tang Zaixiang
Published: June 2022

Existing studies suggest that m6A methylation is closely related to the prognosis of cancer. We developed three prognostic models based on m6A-related transcriptomics in lung adenocarcinoma patients and performed external validations. The TCGA-LUAD cohort served as the derivation cohort and six GEO data sets as external validation cohorts. The first model (mRNA model) was developed based on m6A-related mRNA. LASSO and stepwise regression were used to screen genes and the prognostic model was developed from multivariate Cox regression model. The second model (lncRNA model) was constructed based on m6A related lncRNAs. The four steps of random survival forest, LASSO, best subset selection and stepwise regression were used to screen genes and develop a Cox regression prognostic model. The third model combined the risk scores of the first two models with clinical variable. Variables were screened by stepwise regression. The mRNA model included 11 predictors. The internal validation C index was 0.736. The lncRNA model has 15 predictors. The internal validation C index was 0.707. The third model combined the risk scores of the first two models with tumor stage. The internal validation C index was 0.794. In validation sets, all C-indexes of models were about 0.6, and three models had good calibration accuracy. Freely online calculator on the web at https://lhj0520.shinyapps.io/LUAD_prediction_model/.
Clinicopathological Characteristics and Prognosis of HER2-Low Early-Stage Breast Cancer: A Single-Institution Experience
Authors: Xu Hangcheng , Han Yiqun , Wu Yun , Wang Yan , Li Qing , Zhang Pin , Yuan Peng , Luo Yang , Fan Ying , Chen Shanshan , Cai Ruigang , Li Qiao , Ma Fei , Xu Binghe , Wang Jiayu
Published: June 2022

Background

Human epidermal growth factor 2 (HER2)-low breast cancer, which is defined as HER2 1+ or 2+ in immunohistochemistry without gene amplification, accounts for a considerable part of all breast cancers. However, it remains controversial whether HER2-low breast cancer is a distinct entity. Our aim was to compare the clinicopathological features and survival outcomes between HER2-zero and HER2-low early breast cancer.

Methods

The study was a retrospective analysis that enrolled 1,039 patients with available HER2 expression data in a single institute from 2013 to 2014, of whom 262 HER2-positive patients were excluded from the subsequent analysis. The remaining patients were divided into HER2-zero and HER2-low groups. Each group was further categorized into a hormone receptor (HR)-positive and an HR-negative subgroup. Clinicopathological characteristics were collected and compared between HER2-zero and HER2-low groups. The primary endpoint was disease-free survival (DFS) and overall survival (OS), which were analyzed using the Kaplan–Meier method with log-rank test, landmark analysis, and Cox proportional hazards model.

Results

A total of 777 non-HER2-positive patients were included in this analysis, of whom 126, 552, 53, and 46 patients were HR-positive/HER2-zero, HR-positive/HER2-low, HR-negative/HER2-zero, and HR-negative/HER2-low, respectively. No significant difference in DFS and OS was detected between the HER2-zero group and the HER2-low group when paired by HR status. Landmark analysis with a time point set at 5 years indicated that HR-positive/HER2-low patients had a better DFS compared with HR-positive/HER2-zero patients after 5 years (p = 0.0047). HER2-low status was an independent prognostic factor for DFS after 5 years [hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.13–0.75, p = 0.01].

Conclusion

The clinicopathological characteristics and prognosis of HER2-zero and HER2-low breast cancer were similar regardless of HR status. Patients with HR-positive/HER2-low tumors tended to have a better DFS than their HR-positive/HER2-zero counterparts after 5 years.
Identification of Metabolism-Related Gene-Based Subgroup in Prostate Cancer
Authors: Yu Guopeng , Liang Bo , Yin Keneng , Zhan Ming , Gu Xin , Wang Jiangyi , Song Shangqing , Liu Yushan , Yang Qing , Ji Tianhai , Xu Bin
Published: June 2022

Prostate cancer is still the main male health problem in the world. The role of metabolism in the occurrence and development of prostate cancer is becoming more and more obvious, but it is not clear. Here we firstly identified a metabolism-related gene-based subgroup in prostate cancer. We used metabolism-related genes to divide prostate cancer patients from The Cancer Genome Atlas into different clinical benefit populations, which was verified in the International Cancer Genome Consortium. After that, we analyzed the metabolic and immunological mechanisms of clinical beneficiaries from the aspects of functional analysis of differentially expressed genes, gene set variation analysis, tumor purity, tumor microenvironment, copy number variations, single-nucleotide polymorphism, and tumor-specific neoantigens. We identified 56 significant genes for non-negative matrix factorization after survival-related univariate regression analysis and identified three subgroups. Patients in subgroup 2 had better overall survival, disease-free interval, progression-free interval, and disease-specific survival. Functional analysis indicated that differentially expressed genes in subgroup 2 were enriched in the xenobiotic metabolic process and regulation of cell development. Moreover, the metabolism and tumor purity of subgroup 2 were higher than those of subgroup 1 and subgroup 3, whereas the composition of immune cells of subgroup 2 was lower than that of subgroup 1 and subgroup 3. The expression of major immune genes, such as CCL2, CD274, CD276, CD4, CTLA4, CXCR4, IL1A, IL6, LAG3, TGFB1, TNFRSF4, TNFRSF9, and PDCD1LG2, in subgroup 2 was almost significantly lower than that in subgroup 1 and subgroup 3, which is consistent with the results of tumor purity analysis. Finally, we identified that subgroup 2 had lower copy number variations, single-nucleotide polymorphism, and neoantigen mutation. Our systematic study established a metabolism-related gene-based subgroup to predict outcomes of prostate cancer patients, which may contribute to individual prevention and treatment.
Temozolomide – Just a Radiosensitizer?
Authors: Kaina Bernd , Beltzig Lea , Strik Herwig
Published: June 2022

Radiation concomitant with the DNA methylating drug temozolomide (TMZ) is the gold standard in the treatment of glioblastoma. In this adjuvant setting, TMZ is regarded to be a radiation sensitizer. However, similar to ionising radiation, TMZ induces DNA double-strand breaks and is itself a potent trigger of apoptosis, cellular senescence and autophagy, suggesting that radiation and TMZ act independently. Although cell culture experiments yielded heterogeneous results, some data indicate that the cytotoxic effect of radiation was only enhanced when TMZ was given before radiation treatment. Based on the molecular mechanism of action of TMZ, the importance of specific TMZ and radiation-induced DNA lesions, their repair as well as their interactions, possible scenarios for an additive or synergistic effect of TMZ and radiation are discussed, and suggestions for an optimal timing of radio-chemical treatments are proposed.
Technical and Diagnostic Issues in Whole Slide Imaging Published Validation Studies
Authors: Rizzo Paola Chiara , Girolami Ilaria , Marletta Stefano , Pantanowitz Liron , Antonini Pietro , Brunelli Matteo , Santonicco Nicola , Vacca Paola , Tumino Nicola , Moretta Lorenzo , Parwani Anil , Satturwar Swati , Eccher Albino , Munari Enrico
Published: June 2022

Objective

Digital pathology with whole-slide imaging (WSI) has many potential clinical and non-clinical applications. In the past two decades, despite significant advances in WSI technology adoption remains slow for primary diagnosis. The aim of this study was to identify common pitfalls of WSI reported in validation studies and offer measures to overcome these challenges.

Methods

A systematic search was conducted in the electronic databases Pubmed-MEDLINE and Embase. Inclusion criteria were all validation studies designed to evaluate the feasibility of WSI for diagnostic clinical use in pathology. Technical and diagnostic problems encountered with WSI in these studies were recorded.

Results

A total of 45 studies were identified in which technical issues were reported in 15 (33%), diagnostic issues in 8 (18%), and 22 (49%) reported both. Key technical problems encompassed slide scan failure, prolonged time for pathologists to review cases, and a need for higher image resolution. Diagnostic challenges encountered were concerned with grading dysplasia, reliable assessment of mitoses, identification of microorganisms, and clearly defining the invasive front of tumors.

Conclusion

Despite technical advances with WSI technology, some critical concerns remain that need to be addressed to ensure trustworthy clinical diagnostic use. More focus on the quality of the pre-scanning phase and training of pathologists could help reduce the negative impact of WSI technical difficulties. WSI also seems to exacerbate specific diagnostic tasks that are already challenging among pathologists even when examining glass slides with conventional light microscopy.
Longitudinal Changes in Circulating Metabolites and Lipoproteins After Breast Cancer Treatment
Authors: Giskeødegård Guro F. , Madssen Torfinn S. , Sangermani Matteo , Lundgren Steinar , Wethal Torgeir , Andreassen Trygve , Reidunsdatter Randi J. , Bathen Tone F.
Published: June 2022

The multimodal treatment of breast cancer may induce long term effects on the metabolic profile and increase the risk of future cardiovascular disease. In this study, we characterized longitudinal changes in serum lipoprotein subfractions and metabolites after breast cancer treatment, aiming to determine the long-term effect of different treatment modalities. Further, we investigated the prognostic value of treatment-induced changes in breast cancer-specific and overall 10-year survival. In this study, serum samples from breast cancer patients (n = 250) were collected repeatedly before and after radiotherapy, and serum metabolites and lipoprotein subfractions were quantified by NMR spectroscopy. Longitudinal changes were assessed by univariate and multivariate data analysis methods applicable for repeated measures. Distinct changes were detectable in levels of lipoprotein subfractions and circulating metabolites during the first year, with similar changes despite large differences in treatment regimens. We detect increased free cholesterol and decreased esterified cholesterol levels of HDL subfractions, a switch towards larger LDL particles and higher total LDL-cholesterol, in addition to a switch in the glutamine-glutamate ratio. Non-survivors had different lipid profiles from survivors already at baseline. To conclude, our results show development towards an atherogenic lipid profile in breast cancer patients with different treatment regimens.
Ruptured Hepatocellular Carcinoma: What Do Interventional Radiologists Need to Know?
Authors: Yan Jingxin , Li Ting , Deng Manjun , Fan Haining
Published: June 2022

Rupture of HCC (rHCC) is a life-threatening complication of hepatocellular carcinoma (HCC), and rHCC may lead to a high rate of peritoneal dissemination and affect survival negatively. Treatment for rHCC mainly includes emergency surgery, interventional therapies, and palliative treatment. However, the management of rHCC should be carefully evaluated. For patients with severe bleeding, who are not tolerant to open surgery, quick hemostatic methods such as rupture tissue ablation and TAE/TACE can be performed. We described clinical presentation, prognosis, complication, interventional management, and current evidence of rHCC from the perspective of interventional radiologists. Overall, our review summarized that interventional therapies are necessary for most patients with rHCC to achieve hemostasis, even in some patients with Child–Pugh C. Moreover, TAE/TACE followed by staged hepatectomy is a beneficial treatment for rHCC according to current clinical evidence. TAE/TACE is the first choice for most patients with rHCC, and appropriate interventional treatment may provide staged surgery opportunities for those who are not tolerant to emergency surgery to reach an ideal prognosis.
Using Telemedicine Strategy to Implementing Nutrition Management for Neonates After Congenital Heart Disease Surgery: A New Nutrition Management Strategy
Authors: Zhang Qi-Liang , Lin Wen-Hao , Lin Shi-Hao , Cao Hua , Chen Qiang
Published: June 2022

Objective

The purpose of this study was to investigate the effect of remote nutrition management on promoting the growth and development of neonates after congenital heart disease (CHD) surgery.

Materials and Methods

This study retrospectively analyzed the clinical data of 32 neonates after CHD surgery who received remote nutrition management from January 2021 to July 2021 in our hospital. The clinical data of 30 neonates after CHD surgery, who did not receive remote nutrition management from June 2020 to December 2020, was used as control. The growth and development of the two groups were compared.

Results

Three months after discharge, the weight, height, and weight-for-age z score (WAZ) of the intervention group was significantly higher than those of the control group. The amount of milk in the intervention group was also significantly more than that of the control group, and more neonates in the intervention group added high-energy milk or breast milk fortifier than the intervention group. The parental care ability of the intervention group was significantly higher than that of the control group. The incidence of respiratory tract infection and readmission in the intervention group was significantly lower than that in the control group.

Conclusion

As a new nutrition management strategy for neonates after CHD surgery, remote nutrition management can effectively improve the nutritional status of neonates and promote their growth and development.
Simultaneous Onset of Pediatric Systemic Lupus Erythematosus in Twin Brothers: Case Report
Authors: Raupov Rinat K. , Suspitsin Evgeny N. , Imelbaev Artur I. , Kostik Mikhail M.
Published: June 2022

There are hundreds of twin adult patients with systemic lupus erythematosus (SLE), but male children with SLE are rarely affected. Two monozygotic twin brothers developed SLE at the age of 11 years during 1 month. The index brother manifested with Henoch-Shonlein purpura, accompanied by ANA positivity, and later developed critical left femoral arterial stenosis with high levels of anti-dsDNA, antiphospholipid antibodies, hypocomplementemia, and Coombs-positive hemolytic anemia. At that time his twin brother had only identical autoimmune findings and developed clinical manifestation (myositis and fasciitis) a month later. Both twins had increased IFN-score and shared a heterozygous variant in the RNASEL gene. Index patients developed scalp rash and nephritis 6 months after their parents refused the treatment which has been lasted for 1 year after disease diagnostics.

Conclusion

The simultaneous onset of the pediatric SLE in the male twin is a very rare situation suspected monogenic origin of the disease. Further functional studies are required to confirm the causative role of the mutation.
An Efficient UPLC-MS/MS Method Established to Detect Relugolix Concentration in Rat Plasma
Authors: Xing Liying , Liu Ya-nan , Yao Hongye , Wang Tingting , Xie Fuchen , Luo Shunbin , Luo Pingping , Tang Shengling
Published: June 2022

Relugolix, a gonadotropin-releasing hormone (GnRH) receptor antagonist, has been well studied in the treatment of endometriosis symptomatic. It is mainly metabolized by the CYP3A subfamily of P450 enzymes, while minorly metabolized by CYP2C8. Daidzein in different dose groups exhibited a certain induction on the mRNA expression level of CYP3A4 and resulted in the potent induction of CYP3A4. However, it is still unknown whether daidzein and relugolix interact. We developed an effective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method to study the effect of daidzein on the pharmacokinetics of relugolix in rats after oral administration of 12 mg/kg relugolix in a single or mixed of 50 mg/kg daidzein. The results showed that the method had respectable linearity (r2 > 0.999) on the scale of 0.7–1000 ng/mL. The intra-day precision was between 3.0% and 8.4% in this assay, and the inter-day was between 4.0% and 11.7%. The intra-day accuracy was from -4.3% to 6.1%, and the inter-day was 2.9% to 12.1%. Another three key indicators, including the stability, the recovery rate of extraction and the new technique’s matrix effect, were perfectly in accord with the test verification rule in the biological medium by the United States Food and Drug Administration. Meanwhile, treatment with daidzein led to a decrease in Cmax and AUC0–t of relugolix by about 15.56% and 21.36%, respectively. Although there was no statistical difference in pharmacokinetic parameters, it reflected the induction trend of daidzein on relugolix metabolism for food-drug interaction. It would provide reference and improvement value for subsequent experiments.
Antirheumatoid Arthritic Effects of Sabia parviflora Wall. Leaf Extracts via the NF-κB Pathway and Transient Receptor Potential Protein Family
Authors: Zhou Yongqiang , Zhao Yamin , Xu Hui , Zhao Xiaoyan , Zhao Chunli , Zhou Tao , Zhang Yongping
Published: June 2022

As an important traditional medicine of Buyi and Miao ethnic groups in Guizhou, Sabia parviflora Wall. provides antiviral properties against hepatitis, eliminates wind and dampness, and exhibits anti-inflammatory and pain relief properties. It has also been shown to treat rheumatoid arthritis (RA) and other diseases. However, the pharmacodynamic mechanism of S. parviflora Wall. for RA has not been reported. In this study, we identified the effective compounds of S. parviflora Wall. leaves against RA and discussed the mechanism against complete Freund’s adjuvant-induced arthritis (AIA) based on inflammatory proteins and transient receptor potential (TRP) proteins. S. parviflora Wall. leaf extracts (0.64 g/kg, 0.32 g/kg, and 0.16 g/kg, once daily) were given orally for 21 days. On the 15th day of complete Freund’s adjuvant-induced RA, the effects of this medicine on RA rats were investigated. S. parviflora Wall. extracts increased body weight, decreased foot swelling, and reduced thymus and spleen indices in model rats. Most of pannus in the synovial tissue of RA rats disappeared upon treatment, and the local inflammatory cells were greatly reduced when given the fraction of n-butanol (0.64 g/kg/d, 0.32 g/kg/d, and 0.16 g/kg/d) of 70% alcohol-soluble fraction of S. parviflora Wall. leaves. In addition, the release of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-15 (IL-15), and vascular endothelial growth factor (VEGF) in the RA rat serum was inhibited. The active compounds inhibited the expression of TNF-α, IL-1β, IL-6, IL-10, IL-15 and nuclear factor kappa-Bp65 (NF-κBp65) inflammatory protein and TRP protein transient receptor potential melastatin-5 (TRPM-5) and transient receptor potential channel-6 (TRPC-6), to reduce the expression of VEGF in synovial tissue of RA rats and relieve redness and edema. High-performance liquid chromatography identified six flavonoids and three triterpenoid saponins as active compounds. These findings suggest S. parviflora Wall. leaves may play a role in RA treatment by inhibiting the release of inflammatory factors as well as participating in the inflammatory protein expression in the NF-κB pathway and TRP protein family.
Identification of Key Pathways Involved in White Strain of Hypsizygus marmoreus Extracts-Induced Cell Death of Human Hepatoma Hep3B Cells by Next Generation Sequencing
Authors: Li Wei-Sung , Lee Kun-Tsung Denzel , Chen Li-Yun , You Bang-Jau , Lee Hong-Zin
Published: June 2022

White strain of Hypsizygus marmoreus is named as white genius mushroom (WGM) and is a popular food in Taiwan. We have confirmed the cytotoxicity of WGM extracts on human Hep3B liver cancer cells. A total of 8711 significantly differential genes were identified through large-scale transcriptome sequencing. According to the KEGG pathway enrichment analysis, autophagy, mitophagy and apoptosis pathways were identified as significant in WGM extracts-treated cells. WGM extracts induced a dose-dependent generation of reactive oxygen species (ROS) and membrane-enclosed vacuoles in Hep3B cells. The inhibition of ROS by the ROS scavengers blocked the induction of cell death and vacuoles formation. We suggested that the cell death and membrane-enclosed vacuoles induced by WGM extracts are dependent on ROS production in Hep3B cells. (2E,6E)-3,7,11,15,19,23,27,31,35-Nonamethylhexatriaconta-2,6,34-triene-1,11,15,19,23,27,31-heptol and (18:2) lysophosphatidylcholine were identified in WGM extracts. In addition to being a very popular edible mushrooms, WGM may be developed into a dietary supplement or dietary chemopreventive agent for the cancer treatment.
Efficacy and Safety of Non-Steroidal Mineralocorticoid Receptor Antagonists in Patients With Chronic Kidney Disease and Type 2 Diabetes: A Systematic Review Incorporating an Indirect Comparisons Meta-Analysis
Authors: Jiang Xinrui , Zhang Zhengji , Li Chunlu , Zhang Shijin , Su Qiang , Yang Siyun , Liu Xin , Hu Ying , Pu Xiaofeng
Published: June 2022

Background: The non-steroidal mineralocorticoid receptor antagonists (MRAs) are promising treatments in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). We conducted a meta-analysis to explore the efficacy and safety of the non-steroidal MRAs (finerenone, apararenone, esaxerenone) and detect the differences among them.

Methods: We searched several databases for eligible randomized controlled trials (RCTs) investigating non-steroidal MRAs versus placebo in patients with CKD and T2D. We performed a conventional meta-analysis separately, and then indirect comparisons for efficacy and safety outcomes were conducted among these included drugs.

Results: Eight RCTs with 14,450 subjects were enrolled. In patients with CKD and T2D, a greater reduction in urinary albumin-to-creatinine ratio (UACR) (WMD −0.40, 95% CI −0.48 to −0.32, p < 0.001), estimated glomerular filtration rate (eGFR) (WMD −2.69, 95% CI −4.47 to −0.91, p = 0.003), systolic blood pressure (SBP) (WMD −4.84, 95% CI −5.96 to −3.72, p < 0.001) and a higher risk of hyperkalemia (RR 2.07, 95% CI 1.86 to 2.30, p < 0.001) were observed in the non-steroidal MRAs versus placebo; there is no significant difference in the incidence of serious adverse events between two groups (RR 1.32, 95% CI 0.98 to 1.79, p = 0.067). Compared with finerenone, esaxerenone showed no significant difference in UACR reduction (WMD 0.24, 95% CI −0.016 to 0.496, p = 0.869); apararenone and esaxerenone showed greater decreases in SBP (WMD 1.37, 95% CI 0.456 to 2.284, p = 0.010; WMD 3.11, 95% CI 0.544 to 5,676, p = 0.021).

Conclusions: Despite the moderate increased risk of hyperkalemia, use of non-steroidal MRAs could reduce proteinuria and SBP in patients with CKD and T2D. In terms of renoprotection, esaxerenone and finerenone may have similar effects. Esaxerenone and apararenone may have better antihypertensive effects than finerenone. The head-to-head RCTs are still needed to compare the differences of the efficacy and safety in these non-steroidal MRAs.
Optimal Indicator of Death for Using Real-World Cancer Patients' Data From the Healthcare System
Authors: Jang Suk-Chan , Kwon Sun-Hong , Min Serim , Jo Ae-Ryeo , Lee Eui-Kyung , Nam Jin Hyun
Published: June 2022

Background: Information on patient’s death is a major outcome of health-related research, but it is not always available in claim-based databases. Herein, we suggested the operational definition of death as an optimal indicator of real death and aim to examine its validity and application in patients with cancer.

Materials and methods: Data of newly diagnosed patients with cancer between 2006 and 2015 from the Korean National Health Insurance Service—National Sample Cohort data were used. Death indicators were operationally defined as follows: 1) in-hospital death (the result of treatment or disease diagnosis code from claims data), or 2) case wherein there are no claims within 365 days of the last claim. We estimated true-positive rates (TPR) and false-positive rates (FPR) for real death and operational definition of death in patients with high-, middle-, and low-mortality cancers. Kaplan−Meier survival curves and log-rank tests were conducted to determine whether real death and operational definition of death rates were consistent.

Results: A total of 40,970 patients with cancer were recruited for this study. Among them, 12,604 patients were officially reported as dead. These patients were stratified into high- (lung, liver, and pancreatic), middle- (stomach, skin, and kidney), and low- (thyroid) mortality groups consisting of 6,626 (death: 4,287), 7,282 (1,858), and 6,316 (93) patients, respectively. The TPR was 97.08% and the FPR was 0.98% in the high mortality group. In the case of the middle and low mortality groups, the TPR (FPR) was 95.86% (1.77%) and 97.85% (0.58%), respectively. The overall TPR and FPR were 96.68 and 1.27%. There was no significant difference between the real and operational definition of death in the log-rank test for all types of cancers except for thyroid cancer.

Conclusion: Defining deaths operationally using in-hospital death data and periods after the last claim is a robust alternative to identifying mortality in patients with cancer. This optimal indicator of death will promote research using claim-based data lacking death information.
Unpredictable Sound Stress Model Causes Migraine-Like Behaviors in Mice With Sexual Dimorphism
Authors: Viero Fernanda Tibolla , Rodrigues Patrícia , Frare Julia Maria , Da Silva Náthaly Andrighetto Ruviaro , Ferreira Marcella de Amorim , Da Silva Ana Merian , Pereira Gabriele Cheiran , Ferreira Juliano , Pillat Micheli Mainardi , Bocchi Guilherme Vargas , Nassini Romina , Geppetti Pierangelo , Trevisan Gabriela
Published: June 2022

Migraine represents one of the major causes of disability worldwide and is more prevalent in women; it is also related to anxiety symptoms. Stress, such as sound stress, is a frequently reported trigger in migraine patients, but the underlying mechanisms are not fully understood. However, it is known that patients with migraine have higher levels of plasma inflammatory cytokines and calcitonin gene-related peptide (CGRP). Stress mediated by unpredictable sound is already used as a model of painful sensitization, but migraine-like behaviors and sexual dimorphism have not yet been evaluated. This study characterized nociception and anxiety-related symptoms after the induction of sound stress in mice. C57BL/6 mice (20–30 g) were exposed to unpredictable sound stress for 3 days, nonconsecutive days. We observed enhanced plasma corticosterone levels on day 1 after stress induction. First, 7 days after the last stress session, mice developed hind paw and periorbital mechanical allodynia, grimacing pain behavior, anxiety-like symptoms, and reduced exploratory behavior. The nociceptive and behavioral alterations detected in this model were mostly shown in female stressed mice at day 7 post-stress. In addition, on day 7 post-stress nociception, these behaviors were consistently abolished by the CGRP receptor antagonist olcegepant (BIBN4096BS, 100 mg/kg by intraperitoneal route) in female and male stressed mice. We also demonstrated an increase in interleukine-6 (IL-6), tumor necrosis factor (TNF-α), and CGRP levels in stressed mice plasma, with female mice showing higher levels compared to male mice. This stress paradigm allows further preclinical investigation of mechanisms contributing to migraine-inducing pain.
Sigma-1 Receptors in Depression: Mechanism and Therapeutic Development
Authors: Ren Peng , Wang Jingya , Li Nanxi , Li Guangxiang , Ma Hui , Zhao Yongqi , Li Yunfeng
Published: June 2022

Depression is the most common type of neuropsychiatric illness and has increasingly become a major cause of disability. Unfortunately, the recent global pandemic of COVID-19 has dramatically increased the incidence of depression and has significantly increased the burden of mental health care worldwide. Since full remission of the clinical symptoms of depression has not been achieved with current treatments, there is a constant need to discover new compounds that meet the major clinical needs. Recently, the roles of sigma receptors, especially the sigma-1 receptor subtype, have attracted increasing attention as potential new targets and target-specific drugs due to their translocation property that produces a broad spectrum of biological functions. Even clinical first-line antidepressants with or without affinity for sigma-1 receptors have different pharmacological profiles. Thus, the regulatory role of sigma-1 receptors might be useful in treating these central nervous system (CNS) diseases. In addition, long-term mental stress disrupts the homeostasis in the CNS. In this review, we discuss the topical literature concerning sigma-1 receptor antidepressant mechanism of action in the regulation of intracellular proteostasis, calcium homeostasis and especially the dynamic Excitatory/Inhibitory (E/I) balance in the brain. Furthermore, based on these discoveries, we discuss sigma-1 receptor ligands with respect to their promise as targets for fast-onset action drugs in treating depression.
Bibliometric Analysis of Global Research on Cancer Photodynamic Therapy: Focus on Nano-Related Research
Authors: Cheng Kunming , Guo Qiang , Shen Zefeng , Yang Weiguang , Wang Yulin , Sun Zaijie , Wu Haiyang
Published: June 2022

A growing body of research has illuminated that photodynamic therapy (PDT) serves as an important therapeutic strategy in oncology and has become a hot topic in recent years. Although numerous papers related to cancer PDT (CPDT) have been published, no bibliometric studies have been conducted to summarize the research landscape, and highlight the research trends and hotspots in this field. This study collected 5,804 records on CPDT published between 2000 and 2021 from Web of Science Core Collection. Bibliometric analysis and visualization were conducted using VOSviewer, CiteSpace, and one online platform. The annual publication and citation results revealed significant increasing trends over the past 22 years. China and the United States, contributing 56.24% of the total publications, were the main driving force in this field. Chinese Academy of Sciences was the most prolific institution. Photodiagnosis and Photodynamic Therapy and Photochemistry and Photobiology were the most productive and most co-cited journals, respectively. All keywords were categorized into four clusters including studies on nanomaterial technology, clinical applications, mechanism, and photosensitizers. “nanotech-based PDT” and “enhanced PDT” were current research hotspots. In addition to several nano-related topics such as “nanosphere,” “nanoparticle,” “nanomaterial,” “nanoplatform,” “nanomedicine” and “gold nanoparticle,” the following topics including “photothermal therapy,” “metal organic framework,” “checkpoint blockade,” “tumor microenvironment,” “prodrug” also deserve further attention in the near future.