bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic and therapeutic potential of RNASET2 in Crohn’s disease: Disease-risk polymorphism modulates allelic-imbalance in expression and circulating protein levels and recombinant-RNASET2 attenuates pro-inflammatory cytokine secretion
Authors: Biener-Ramanujan Eva , Rosier Florian , Coetzee Simon G. , McGovern Dermot D. P. , Hazelett Dennis , Targan Stephan R. , Gonsky Rivkah
Published: November 2022

Ribonuclease T2 gene (RNASET2) variants are associated in genome wide association studies (GWAS) with risk for several autoimmune diseases, including Crohn’s disease (CD). In T cells, a functional and biological relationship exists between TNFSF15-mediated enhancement of IFN−γ production, mucosal inflammation and RNASET2. Disease risk variants are associated with decreased mRNA expression and clinical characteristics of severe CD; however, functional classifications of variants and underlying molecular mechanisms contributing to pathogenesis remain largely unknown. In this study we demonstrate that allelic imbalance of RNASET2 disease risk variant rs2149092 is associated with transcriptional and post-transcriptional mechanisms regulating transcription factor binding, promoter-transactivation and allele-specific expression. RNASET2 mRNA expression decreases in response to multiple modes of T cell activation and recovers following elimination of activator. In CD patients with severe disease necessitating surgical intervention, preoperative circulating RNASET2 protein levels were decreased compared to non-IBD subjects and rebounded post-operatively following removal of the inflamed region, with levels associated with allelic carriage. Furthermore, overexpression or treatment with recombinant RNASET2 significantly reduced IFN-γ secretion. These findings reveal that RNASET2 cis- and trans-acting variation contributed regulatory complexity and determined expression and provide a basis for linking genetic variation with CD pathobiology. These data may ultimately identify RNASET2 as an effective therapeutic target in a subset of CD patients with severe disease.
Derivation of predicted no-effect concentrations for thirty-five pharmaceuticals and personal care products in freshwater ecosystem
Authors: Fan Hailin , Wang Yuwen , Liu Xiaojuan , Wang Yolina Yu Lin , Kazmi Syed Shabi Ul Hassan , Ohore Okugbe Ebiotubo , Liu Wenhua , Wang Zhen
Published: November 2022

Pharmaceuticals and personal care products (PPCPs) are contaminants of emerging concern. PPCPs have been detected in various environmental matrices, posing potential threat to human health and environment quality. Thus far, there are no water quality guidelines (WQGs) established for PPCPs for the protection of freshwater organisms and ecosystems. In this study, we used the species sensitivity distribution (SSD) and assessment factor (AF) approaches to derive the 5% hazardous concentrations (HC5) of 35 selected PPCPs using acute and chronic toxicity data. The predicted no-effect concentrations (PNECs) and the acute-to-chronic ratios (ACRs) of chemicals were inherently computed to support the derivation of WQGs and for ecological risk assessment. Among these, endocrine-disrupting chemicals and antipsychotics were shown to pose a greater threat to the freshwater environment and organisms. The highest PNEC was recorded for chloramphenicol (3,620 μg/L) and the lowest for fluoxetine (0.0000291 μg/L), which could have significant ecological risks. In addition, the commonly used default ACRs do not seem to provide adequate support for the prediction of chronic toxicity thresholds and WQGs, as the highest ACRs of these drugs reached 39,100 (e.g., chloramphenicol). The findings of this study provide critical scientific information regarding the development of WQGs for environmental management and the risk control of PPCPs.
Effect of water temperature on embryonic development of Protunus trituberculatus in an off-season breeding mode
Authors: He Jie , Wan Litao , Yu Huaihua , Peng Yingying , Zhang Dongxu , Xu Wenjun
Published: November 2022

Portunus trituberculatus (swimming crab) is an important breeding crab in China. The current breeding mode of swimming crab is still the traditional “spring seedling and winter harvest” breeding mode. In recent years, researchers have begun to explore a new off-season breeding mode through autumn seedling. In this study, the rate of embryonic development, embryo antioxidant ability and hatching rate of swimming crab in different water temperatures in an off-season breeding mode (breeding in early autumn) and digestive enzyme activity of newly hatched larvae were compared. The results showed that the duration of each development stage of swimming crab embryos was gradually reduced with increasing water temperature. The total development time was 9.43 d at 27°C and only 6.88 d at 33°C. These effects were accompanied by an increase in the development rate from 0.11 d-1 to 0.15 d-1. The total effective accumulated temperature under the 4 temperature conditions was basically maintained at about 150°C·d (147.08 ∼ 153.62°C·d), and there was no significant difference between different groups. The development of embryos at 27°C and 29°C was very synchronous, and no abnormal embryos were observed. Conversely, at 31°C, the later stage of development exhibited asynchrony, and diapause and death were noted in some embryos. At 33°C, more embryos died. The embryo hatching rate was approximately 70% at 27°C and 29°C, and the rate was significantly reduced at 31°C and 33°C. Specifically, the rate was only 13.89% at 33°C. As the water temperature increased, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) as well as the total antioxidant capacity (T-AOC) and malondialdehyde (MDA) levels of embryos increased first and then decreased, reaching the highest value at 31°C. Catalase (CAT) activity exhibited the opposite trend which was the lowest at 29 °C with a value of only 0.17 U/mg prot and the highest at 33°C with a value of up to 0.51 U/mg prot. At temperatures of 27°C, 29°C and 31°C, the differences in various digestive enzymes of newly hatched larvae primarily manifested as the high activities of pepsin (PEP) and α-amylase (AMS) at 31°C, and other differences were not obvious. At 33°C during embryonic development, the activities of various digestive enzymes were relatively low, especially the activities of trypsin (TPS) and cellulase (CL), which were significantly lower than those of the other three temperature groups. Therefore, judging from the antioxidant index of embryos and the digestive enzyme activity of newly hatched larvae, the embryonic development was still good when the water temperature was 31°C, accompanied by water temperatures above 31°C that seriously affected enzyme activity. Overall, a temperature below 31°C represents the appropriate temperature for embryonic development in autumn in swimming crabs.
Are plankton nets a thing of the past? An assessment of in situ imaging of zooplankton for large-scale ecosystem assessment and policy decision-making
Authors: Giering Sarah L. C. , Culverhouse Phil F. , Johns David G. , McQuatters-Gollop Abigail , Pitois Sophie G.
Published: November 2022

Zooplankton are fundamental to aquatic ecosystem services such as carbon and nutrient cycling. Therefore, a robust evidence base of how zooplankton respond to changes in anthropogenic pressures, such as climate change and nutrient loading, is key to implementing effective policy-making and management measures. Currently, the data on which to base this evidence, such as long time-series and large-scale datasets of zooplankton distribution and community composition, are too sparse owing to practical limitations in traditional collection and analysis methods. The advance of in situ imaging technologies that can be deployed at large scales on autonomous platforms, coupled with artificial intelligence and machine learning (AI/ML) for image analysis, promises a solution. However, whether imaging could reasonably replace physical samples, and whether AI/ML can achieve a taxonomic resolution that scientists trust, is currently unclear. We here develop a roadmap for imaging and AI/ML for future zooplankton monitoring and research based on community consensus. To do so, we determined current perceptions of the zooplankton community with a focus on their experience and trust in the new technologies. Our survey revealed a clear consensus that traditional net sampling and taxonomy must be retained, yet imaging will play an important part in the future of zooplankton monitoring and research. A period of overlapping use of imaging and physical sampling systems is needed before imaging can reasonably replace physical sampling for widespread time-series zooplankton monitoring. In addition, comprehensive improvements in AI/ML and close collaboration between zooplankton researchers and AI developers are needed for AI-based taxonomy to be trusted and fully adopted. Encouragingly, the adoption of cutting-edge technologies for zooplankton research may provide a solution to maintaining the critical taxonomic and ecological knowledge needed for future zooplankton monitoring and robust evidence-based policy decision-making.
Effect of electroacupuncture on the repair of stress ulcer injury in neurocritical patients: A randomized clinical trial
Authors: Li He , Li Li-li , Wang Jian , Wang Yong-qiang , Wang Lan , Yuan Lan , Chen Wen-ting , Song Jian-gang
Published: November 2022

Background

Stress ulcer (SU) is one of the main causes of prolonged hospital stay, poor prognosis, and increased mortality in critically ill patients. This study aimed to investigate the effect of electroacupuncture (EA) on SU in patients with severe neurological diseases and explore its possible mechanisms.

Methods

Taking patients with SU in adult neurocritical care as the research object, they were randomly divided into the EA group and the control group. Through the perioperative EA intervention, the following indicators were documented: main observation indicator (the effective rate of SU treatment), secondary observation indicators (gastric juice pH, gastric juice occult blood test, and stool occult blood test), related mechanisms [repair factors trefoil factor family 2 (TFF2), vascular endothelial growth factor (VEGF), and heat shock protein 70 (HSP70)], complications during hospitalization, and intensive care unit (ICU) stay time.

Results

Compared with the control treatment, EA increased the effective rate of SU treatment (85.4% for the EA group, 57.5% for the control group, risk difference: 27.9% (95% CI: 8.3%–45.1%); P < 0.01). EA increased the success rate of gastric juice pH treatment on days 1, 2, and 3 (P < 0.01 for day 1, P < 0.05 for days 2 and 3). EA lowered the positive rate of gastric occult blood test on days 1 and 3 (all P-values < 0.05) and the positive rate of fecal occult blood test on day 3 (P < 0.05). EA also reduced the ICU stay time (P < 0.01) and total hospitalization time (P < 0.05). Compared with day 0, all serum repair factors (VEGF, HSP70, and TFF2) of both groups significantly increased on days 1, 3, and 5 (all P-values < 0.01). Compared with the control group, VEGF in the EA group was increased on days 3 and 5 (all P-values < 0.01); HSP70 was increased on days 1, 3, and 5 (P < 0.05 for day 1, P < 0.01 for days 3 and 5); and TFF2 was increased on days 1, 3, and 5 (all P-values < 0.01).

Conclusion

Electroacupuncture promoted the repair of SU damage in severe neurological disease, and its effect was related to enhancing the expression of gastric mucosal repair factors.

Clinical trial registration

[https://www.chictr.org.cn/showprojen.aspx?proj=127012], identifier [ChiCTR2100046701].
Transferability of real-world data across borders for regulatory and health technology assessment decision-making
Authors: Jaksa Ashley , Arena Patrick J. , Chan Kelvin K. W. , Ben-Joseph Rami H. , Jónsson Páll , Campbell Ulka B.
Published: November 2022

Recently, there has been increased consideration of real-world data (RWD) and real-world evidence (RWE) in regulatory and health technology assessment (HTA) decision-making. Due to challenges in identifying high-quality and relevant RWD sources, researchers and regulatory/HTA bodies may turn to RWD generated in locales outside of the locale of interest (referred to as “transferring RWD”). We therefore performed a review of stakeholder guidance as well as selected case studies to identify themes for researchers to consider when transferring RWD from one jurisdiction to another. Our review highlighted that there is limited consensus on defining decision-grade, transferred RWD; certain stakeholders have issued relevant guidance, but the recommendations are high-level and additional effort is needed to generate comprehensive guidance. Additionally, the case studies revealed that RWD transferability has not been a consistent concern for regulatory/HTA bodies and that more focus has been put on the evaluation of internal validity. To help develop transferability best practices (alongside internal validity best practices), we suggest that researchers address the following considerations in their justification for transferring RWD: treatment pathways, nature of the healthcare system, incidence/prevalence of indication, and patient demographics. We also recommend that RWD transferability should garner more attention as the use of imported RWD could open doors to high-quality data sources and potentially reduce methodological issues that often arise in the use of local RWD; we thus hope this review provides a foundation for further dialogue around the suitability and utility of transferred RWD in the regulatory/HTA decision-making space.
The potential role of RNA N6-methyladenosine in primary Sjögren’s syndrome
Authors: Xiao Qiufeng , Wu Xunyao , Deng Chuiwen , Zhao Lidan , Peng Linyi , Zhou Jiaxin , Zhang Wen , Zhao Yan , Fei Yunyun
Published: November 2022

Objective

The pathogenesis of primary Sjögren’s syndrome (pSS) remains incompletely understood. The N6-methyladenosine (m6A) RNA modification, the most abundant internal transcript modification, has close associations with multiple diseases. This study aimed to investigate the role of m6A in patients with pSS.

Materials and methods

This study enrolled 44 patients with pSS, 50 age- and gender-matched healthy controls (HCs), and 11 age- and gender-matched patients with non-SS sicca. We detected the messenger RNA (mRNA) levels of m6A elements (including METTL3, WTAP, RBM15, ALKBH5, FTO, YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2), ISG15, and USP18 in peripheral blood mononuclear cells (PBMCs) from patients with pSS, patients with non-SS sicca, and HCs. The clinical characteristics and laboratory findings of patients with pSS and patients with non-SS sicca were also collected. We used binary logistic regression to determine if m6A elements were risk factors for pSS.

Results

The mRNA levels of m6A writers (METTL3 and RBM15), erasers (ALKBH5 and FTO), and readers (YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2) were all significantly higher in PBMCs from patients with pSS than in HCs. The mRNA levels of m6A writers (METTL3 and WTAP) and readers (YTHDF2, YTHDF3, and YTHDC2) were lower in PBMCs from patients with pSS compared to patients with non-SS sicca. The expression of METTL3, RBM15, FTO, YTHDF1, YTHDF2, YTHDC1, and YTHDC2 was positively correlated with the level of C-reactive protein (CRP) of patients with pSS. The mRNA level of YTHDF1 in PBMCs from patients with pSS was negatively correlated with the EULAR Sjögren’s syndrome disease activity index (ESSDAI) score. In patients with pSS, FTO, YTHDC1, and YTHDC2 were also related to white blood cells (WBCs), neutrophils, lymphocytes, and monocytes. Increased mRNA level of ALKBH5 in PBMCs was a risk factor for pSS, as determined by binary logistic regression analysis. The mRNA level of ISG15 was positively correlated with that of FTO, YTHDF2, YTHDF3, and YTHDC2 in patients with pSS.

Conclusion

Compared with HCs, the expression of METTL3, RBM15, ALKBH5, FTO, YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2 was considerably higher in PBMCs from patients with pSS. In comparison with patients with non-SS sicca, the expression of METTL3, WTAP, YTHDF2, YTHDF3, and YTHDC2 was reduced in PBMCs from patients with pSS. The m6A elements correlating with clinical variables may indicate the disease activity and inflammation status of pSS. Elevated expression of ALKBH5 was a risk factor for pSS. The dynamic process of m6A modification is active in pSS. m6A elements (FTO, YTHDF2, YTHDF3, or YTHDC2) might target ISG15, stimulate the expression of ISG15, and activate the type I IFN signaling pathway, playing an active role in initiating the autoimmunity in pSS.
Innovative approaches to service integration addressing the unmet needs of irritable bowel syndrome patients and new approaches for the needs of IBS patients
Authors: Gentile Maurizio , De Luca Vincenzo , Patalano Roberta , Laudisio Daniela , Tramontano Giovanni , Lindner-Rabl Sonja , Mercurio Lorenzo , Salvatore Elena , Farrell John , Roller-Wirnsberger Regina , Kubitschke Lutz , Triassi Maria , Colao Annamaria , Illario Maddalena ,   Vigour Consortium
Published: November 2022

Background

Irritable bowel syndrome (IBS) is a common multifactorial condition that affects the large intestine and is characterized by chronic and relapsing abdominal pain and altered bowel habit. IBS is due to a combination of genetic, environmental and dietary factors. It's usually a lifelong problem very frustrating to live with and can have a big impact on quality of life, as single-agent therapy ra.

Objective

To analyze the approaches and solutions that address the social and health unmet needs of patients with IBS.

Design

A quantitative-qualitative approach was adopted in the current study to identify and specify key digital solution and high impact user scenarios applied to IBS patients, through an adaptation of the “Blueprint on Digital Transformation in Health and Care in an Ageing Society” persona methodology.

Settings

Digital health solutions bring the potential of supporting health interventions through mobile apps, wearable devices, telemedicine.

Patients

A Survey was administered to a group of patients in an anonymous form, and no need for Medical Ethical Committee approval was identified.

Interventions

The theoretical elaboration IBS personas was developed through an interdisciplinary Focus Group, which also mapped the pathway for the patient's management.

Main outcome

Three main needs were identified to be met to improve IBS patient's lifestyle: access to psychological support, mHealth solutions supporting diet and adapted physical activity, and home-based digital health support. mHealth intervention has been identified for diet adherence, physical exercise and psychological well-being. The process has been mapped and adapted to integrate the new solutions into the care pathway.

Limitation

Further research is needed to evaluate how mHealth services enable IBS patients to manage their conditions and improve their quality of life.

Conclusion

The person-centered approach was implemented through a multidisciplinary Focus group that enabled the identification of the need for a mHealth intervention.
Integrated physiological, metabolomic, and proteome analysis of Alpinia officinarum Hance essential oil inhibits the growth of Fusarium oxysporum of Panax notoginseng
Authors: Liu Xiao-Yun , Huo Ying-Ying , Yang Jing , Li Tian-Tian , Xu Fu-Rong , Wan He-Ping , Li Jia-Nan , Wu Chun-Hong , Zhang Yong-Hong , Dong Xian
Published: November 2022

Fusarium oxysporum is the main pathogen of Panax notoginseng root rot, and chemical fungicides remain the primary measures to control the disease. Plant essential oil (EO) is a volatile plant secondary metabolic product that does not produce any residue to replace chemical pesticide. To comprehensively understand the antifungal mechanism of Alpinia officinarum Hance EO, the physiological indicators, proteome and metabolome were analyzed using F. oxysporum spores and hyphae treated with different EO concentrations. The cell membrane was damaged after both low and high concentrations of EO treatment, along with leakage of the cell contents. To resist the destruction of membrane structure, fungi can increase the function of steroid biosynthesis and expression of these catalytic enzymes, including squalene monooxygenase (SQLE), sterol 14alpha-demethylase (CYP51, CYP61A), delta14-sterol reductase (TM7SF2, ERG4), methylsterol monooxygenase (MESO1), and sterol 24-C-methyltransferase (SMT1). Furthermore, the tricarboxylic acid cycle (TCA) was influenced by inhibiting the expression of glutamate synthase (GLT1), 4-aminobutyrate aminotransferase (ABAT), and succinate-semialdehyde dehydrogenase (gabD); increasing malate and gamma-aminobutyric acid (GABA); and decreasing citrate content. The spore germination rate and mycelia growth were decreased because the expression of cohesin complex subunit SA-1/2 (IRR1) and cohesion complex subunit (YCS4, BRN1, YCG1) were inhibited. Particularly, under high EO concentrations, cyclin-dependent kinase (CDC28) and DNA replication licensing factor (MCM) were further inhibited to disrupt the cell cycle and meiosis, thus affecting cell division. The results of this study will enrich the understanding of the antifungal mechanism of EOs and provide an important basis to develop new plant-derived fungicides.
Biological nitrogen removal from low carbon wastewater
Authors: Kosgey Kiprotich , Zungu Phumza Vuyokazi , Bux Faizal , Kumari Sheena
Published: November 2022

Nitrogen has traditionally been removed from wastewater by nitrification and denitrification processes, in which organic carbon has been used as an electron donor during denitrification. However, some wastewaters contain low concentrations of organic carbon, which may require external organic carbon supply, increasing treatment costs. As a result, processes such as partial nitrification/anammox (anaerobic ammonium oxidation) (PN/A), autotrophic denitrification, nitritation-denitritation and bioelectrochemical processes have been studied as possible alternatives, and are thus evaluated in this study based on process kinetics, applicability at large-scale and process configuration. Oxygen demand for nitritation-denitritation and PN/A is 25% and 60% lower than for nitrification/denitrification, respectively. In addition, PN/A process does not require organic carbon supply, while its supply for nitritation-denitritation is 40% less than for nitrification/denitrification. Both PN/A and nitritation-denitritation produce less sludge compared to nitrification/denitrification, which saves on sludge handling costs. Similarly, autotrophic denitrification generates less sludge compared to heterotrophic denitrification and could save on sludge handling costs. However, autotrophic denitrification driven by metallic ions, elemental sulfur (S) and its compounds could generate harmful chemicals. On the other hand, hydrogenotrophic denitrification can remove nitrogen completely without generation of harmful chemicals, but requires specialized equipment for generation and handling of hydrogen gas (H2), which complicates process configuration. Bioelectrochemical processes are limited by low kinetics and complicated process configuration. In sum, anammox-mediated processes represent the best alternative to nitrification/denitrification for nitrogen removal in low- and high-strength wastewaters.
Acetyl-CoA: An interplay between metabolism and epigenetics in cancer
Authors: Hao Yang , Yi Qin , XiaoWu Xu , WeiBo Chen , GuangChen Zu , XueMin Chen
Published: November 2022

Due to its high mortality and severe economic burden, cancer has become one of the most difficult medical problems to solve today. As a key node in metabolism and the main producer of energy, acetyl-coenzyme A (acetyl-CoA) plays an important role in the invasion and migration of cancer. In this review, we discuss metabolic pathways involving acetyl-CoA, the targeted therapy of cancer through acetyl-CoA metabolic pathways and the roles of epigenetic modifications in cancer. In particular, we emphasize that the metabolic pathway of acetyl-CoA exerts a great impact in cancer; this process is very different from normal cells due to the “Warburg effect”. The concentration of acetyl-CoA is increased in the mitochondria of cancer cells to provide ATP for survival, hindering the growth of normal cells. Therefore, it may be possible to explore new feasible and more effective treatments through the acetyl-CoA metabolic pathway. In addition, a growing number of studies have shown that abnormal epigenetic modifications have been shown to play contributing roles in cancer formation and development. In most cancers, acetyl-CoA mediated acetylation promotes the growth of cancer cells. Thus, acetylation biomarkers can also be detected and serve as potential cancer prediction and prognostic markers.
The moderating effect of cognitive reserve on cognitive function in patients with Acute Ischemic Stroke
Authors: Li Fanfan , Kong Xiangjing , Zhu Huanzhi , Xu Hanzhang , Wu Bei , Cao Yanpei , Li Juan
Published: November 2022

Background

Recovery of cognitive function after stroke has inter-individual variability. The theory of cognitive reserve offers a potential explanation of the variability in cognitive function after stroke.

Objective

This study aimed to investigate the moderating effect of cognitive reserve on the relationship between the stroke severity and cognitive function after stroke.

Materials and methods

A total of 220 patients with Acute Ischemic Stroke (AIS) were recruited in 2021 from two stroke centers in Nanjing, China. The National Institutes of Health Stroke Scale (NIHSS) was used to assess stroke severity upon admission. Cognitive Reserve Index questionnaire (CRIq) and validated Montreal Cognitive Assessment, Changsha Version (MoCA-CS) were used to assess cognitive reserve and cognitive function within 7 days after stroke onset, respectively. A series of multivariate linear regression models were applied to test the moderating effect of cognitive reserve.

Results

Patients with a higher level of cognitive reserve had better cognitive function after stroke compared with those with a lower level of cognitive reserve (β = 0.074, p = 0.003). The interaction of NIHSS and cognitive reserve was statistically significant (β = −0.010, p = 0.045) after adjusting for some key covariates [e.g., age, marital status, Oxfordshire Community Stroke Project (OCSP) classification, Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification, cerebral vascular stenosis, diabetes and atrial fibrillation].

Conclusion

Cognitive reserve may help to buffer the effect of stroke-related pathology on cognitive decline in Chinese acute stroke patients. Enhancing cognitive reserve in stroke patients may be one of the potential strategies for preventing vascular dementia.
Combination of PI-RADS score and PSAD can improve the diagnostic accuracy of prostate cancer and reduce unnecessary prostate biopsies
Authors: Wang Changming , Yuan Lei , Shen Deyun , Zhang Bin , Wu Baorui , Zhang Panrui , Xiao Jun , Tao Tao
Published: November 2022

Objectives

The purpose of this study is to evaluate the diagnostic accuracy of the clinical variables of patients with prostate cancer (PCa) and to provide a strategy to reduce unnecessary biopsies.

Patients and methods

A Chinese cohort that consists of 833 consecutive patients who underwent prostate biopsies from January 2018 to April 2022 was collected in this retrospective study. Diagnostic ability for total PCa and clinically significant PCa (csPCa) was evaluated by prostate imaging–reporting and data system (PI-RADS) score and other clinical variables. Univariate and multivariable logistic regression analyses were performed to figure out the independent predictors. Diagnostic accuracy was estimated by plotting receiver operating characteristic curves.

Results

The results of univariate and multivariable analyses demonstrated that the PI-RADS score (P < 0.001, OR: 5.724, 95% CI: 4.517–7.253)/(P < 0.001, OR: 5.199, 95% CI: 4.039–6.488) and prostate-specific antigen density (PSAD) (P < 0.001, OR: 2.756, 95% CI: 1.560–4.870)/(P < 0.001, OR: 4.726, 95% CI: 2.661–8.396) were the independent clinical factors for predicting total PCa/csPCa. The combination of the PI-RADS score and PSAD presented the best diagnostic performance for the detection of PCa and csPCa. For the diagnostic criterion of “PI-RADS score ≥ 3 or PSAD ≥ 0.3”, the sensitivity and negative predictive values were 94.0% and 93.1% for the diagnosis of total PCa and 99.2% and 99.3% for the diagnosis of csPCa, respectively. For the diagnostic criterion “PI-RADS score >3 and PSAD ≥ 0.3”, the specificity and positive predictive values were 96.8% and 92.6% for the diagnosis of total PCa and 93.5% and 82.4% for the diagnosis of csPCa, respectively.

Conclusions

The combination of the PI-RADS score and PSAD can implement the extraordinary diagnostic performance of PCa. Many patients may safely execute active surveillance or take systematic treatment without prostate biopsies by stratification according to the PI-RADS score and the value of PSAD.
Improve follicular thyroid carcinoma diagnosis using computer aided diagnosis system on ultrasound images
Authors: Zheng Huan , Xiao Zebin , Luo Siwei , Wu Suqing , Huang Chuxin , Hong Tingting , He Yan , Guo Yanhui , Du Guoqing
Published: November 2022

Objective

We aim to leverage deep learning to develop a computer aided diagnosis (CAD) system toward helping radiologists in the diagnosis of follicular thyroid carcinoma (FTC) on thyroid ultrasonography.

Methods

A dataset of 1159 images, consisting of 351 images from 138 FTC patients and 808 images from 274 benign follicular-pattern nodule patients, was divided into a balanced and unbalanced dataset, and used to train and test the CAD system based on a transfer learning of a residual network. Six radiologists participated in the experiments to verify whether and how much the proposed CAD system helps to improve their performance.

Results

On the balanced dataset, the CAD system achieved 0.892 of area under the ROC (AUC). The accuracy, recall, precision, and F1-score of the CAD method were 84.66%, 84.66%, 84.77%, 84.65%, while those of the junior and senior radiologists were 56.82%, 56.82%, 56.95%, 56.62% and 64.20%, 64.20%, 64.35%, 64.11% respectively. With the help of CAD, the metrics of the junior and senior radiologists improved to 62.81%, 62.81%, 62.85%, 62.79% and 73.86%, 73.86%, 74.00%, 73.83%. The results almost repeated on the unbalanced dataset. The results show the proposed CAD approach can not only achieve better performance than radiologists, but also significantly improve the radiologists’ diagnosis of FTC.

Conclusions

The performances of the CAD system indicate it is a reliable reference for preoperative diagnosis of FTC, and might assist the development of a fast, accessible screening method for FTC.
Assessment of biochemical outcomes in patients with primary aldosteronism after adrenalectomy based on CT scan diagnosis of unilateral adenoma without adrenal vein sampling
Authors: Zhang Ming , Bian Ge , Tian Jingyan , Yang Weijie , Wang Xiaoqing , Chi Changliang
Published: November 2022

Purpose

The purpose of this study was to assess the surgical outcomes of patients with primary aldosteronism when surgery was based only on CT finding of unilateral adenoma without adrenal vein sampling (AVS).

Methods

This is a retrospective review of the records of patients who had undergone retroperitoneal laparoscopic adrenalectomy for primary aldosteronism based on CT scan finding of unilateral adenoma and had a follow-up of at least 6–12 months from January 2012 to December 2020 in a single center; decision for adrenalectomy was based on CT scan, and AVS was not used. The clinical and biochemical outcomes were accessed using the standardized primary aldosteronism surgical outcome (PASO) criteria. Patient’s demographics and preoperative factors were analyzed to assess for independent predictor of surgical success.

Results

According to the PASO criteria, 172 patients finally enrolled in the training dataset, and 20 patients enrolled in the validation dataset. In the training dataset, complete clinical success was achieved in 71 patients (41.3%), partial success in 87 (50.6%), and absent success in 14 (8.1%). Biochemical outcomes showed that 151 patients (87.8%) were completely cured, 14 patients (8.1%) got a partial biochemical success, and an absent biochemical success was found in seven patients (4.1%). Multivariate logistic regression analysis showed that age, body mass index (BMI), tumor size, mean arterial pressure (MAP), and serum potassium were the most independent factors for incomplete biochemical success. Based on the results of statistical analysis, our study constructed a nomogram prognostic evaluation model for patients after unilateral primary aldosterone surgery.

Conclusions

Laparoscopic adrenalectomy for patients with primary aldosteronism base on CT scan finding of a unilateral adenoma without AVS had a high rate of complete biochemical cure at 12 months. Risk factors for incomplete biochemical success include age, BMI, tumor size, MAP, and serum potassium. Our study constructed a nomogram prognostic evaluation model for patients after unilateral primary aldosterone surgery. The nomogram accurately and reliably predicted the incomplete biochemical success.
Functional properties of circular RNAs and research progress in gastric cancer
Authors: Ding Ping’an , Liu Pengpeng , Wu Haotian , Yang Peigang , Tian Yuan , Zhao Qun
Published: November 2022

Circular RNAs (circRNAs) are a class of closed circular non-coding RNAs widely exist in eukaryotes, with high stability and species conservation. A large number of studies have shown that circRNAs are abnormally expressed in various tumor tissues, and are abundant in plasma with long half-life and high specificity, which may be served as potential tumor biomarkers for early diagnosis, treatment and prognosis of malignant tumors. However, the role of circRNAs is still poorly understood in gastric cancer. This article reviews the research progress of circRNAs in gastric cancer in recent years so as to explore the relationship between circRNAs and the occurrence and the development of gastric cancer, and provide new ideas for the diagnosis and treatment of gastric cancer.
Case report: A relevant misdiagnosis: Photosensitive epilepsy mimicking a blinking tic
Authors: Burlo Francesca , Barbi Egidio , Carrozzi Marco , Zanus Caterina
Published: November 2022

Blinking in children is most frequently a functional and transient symptom. Nonetheless, sometimes it is the first clinical manifestation of a neurological disorder. The differential diagnosis between voluntary actions, tics and other neurological disorders among which seizures may be challenging and misdiagnosis is common. A 6-year-old girl in good health was admitted for a recent history of bilateral eye blinking. Blinking did not interfere with the girl's activities. The patients reported that blinking seemed to be triggered by sunlight exposure and that girl sometimes seemed to be attracted by the sunlight. Ophthalmological diseases had been already excluded. The girl was addressed to our hospital for neurological consultation, as tic disease was considered the most probable hypothesis. Neurological examination was negative. In the field of differential diagnosis of photosensitive abnormal eyelid movements, the hypothesis of seizures was explored and further investigated with a video-EEG recording with light stimulation. This exam demonstrated a photoparoxysmal response (PPR) to intermittent photic stimulation with appearance on EEG of bilateral spike and polyspike waves associated with eyelid jerks. This girl suffers from generalized epilepsy with photosensitivity. Photosensitivity is a common feature of many epilepsy syndromes, mainly occurring in children and adolescents. To control the seizures, it is essential to avoid the triggering stimulus, by wearing specific glasses. Additional antiseizures treatment is often necessary, at first with valproate and levetiracetam, and ethosuximide, lamotrigine, and benzodiazepines as the second choice. Overlapping phenomenology of seizures and movement disorders is well known in paediatric clinical practice. Moreover, epilepsy and movement disorder may coexist, mainly in children. Seizures with semeiology limited to eye motor manifestations may mimic functional blinking, tics, and other motor events frequently observed in childhood. Differentiating seizures from other non-epileptic paroxysmal movements may be challenging and specialist evaluation is needed for proper treatment and prognostic counselling.
Systems biology reveals anatabine to be an NRF2 activator
Authors: Messinis Dimitris E. , Poussin Carine , Latino Diogo A. R. S. , Eb-Levadoux Yvan , Dulize Remi , Peric Dariusz , Guedj Emmanuel , Titz Bjoern , Ivanov Nikolai V. , Peitsch Manuel C. , Hoeng Julia
Published: November 2022

Anatabine, an alkaloid present in plants of the Solanaceae family (including tobacco and eggplant), has been shown to ameliorate chronic inflammatory conditions in mouse models, such as Alzheimer’s disease, Hashimoto’s thyroiditis, multiple sclerosis, and intestinal inflammation. However, the mechanisms of action of anatabine remain unclear. To understand the impact of anatabine on cellular systems and identify the molecular pathways that are perturbed, we designed a study to examine the concentration-dependent effects of anatabine on various cell types by using a systems pharmacology approach. The resulting dataset, consisting of measurements of various omics data types at different time points, was analyzed by using multiple computational techniques. To identify concentration-dependent activated pathways, we performed linear modeling followed by gene set enrichment. To predict the functional partners of anatabine and the involved pathways, we harnessed the LINCS L1000 dataset’s wealth of information and implemented integer linear programming on directed graphs, respectively. Finally, we experimentally verified our key computational predictions. Using an appropriate luciferase reporter cell system, we were able to demonstrate that anatabine treatment results in NRF2 (nuclear factor-erythroid factor 2-related factor 2) translocation, and our systematic phosphoproteomic assays showed that anatabine treatment results in activation of MAPK signaling. While there are certain areas to be explored in deciphering the exact anti-inflammatory mechanisms of action of anatabine and other NRF2 activators, we believe that anatabine constitutes an interesting molecule for its therapeutic potential in NRF2-related diseases.
The protective effect of natural medicines against excessive inflammation and oxidative stress in acute lung injury by regulating the Nrf2 signaling pathway
Authors: Luan Rumei , Ding Dongyan , Yang Junling
Published: November 2022

Acute lung injury (ALI) is a common critical disease of the respiratory system that progresses into acute respiratory distress syndrome (ARDS), with high mortality, mainly related to pulmonary oxidative stress imbalance and severe inflammation. However, there are no clear and effective treatment strategies at present. Nuclear factor erythroid 2-related factor 2(Nrf2) is a transcription factor that interacts with multiple signaling pathways and regulates the activity of multiple oxidases (NOX, NOS, XO, CYP) related to inflammation and apoptosis, and exhibits antioxidant and anti-inflammatory roles in ALI. Recently, several studies have reported that the active ingredients of natural medicines show protective effects on ALI via the Nrf2 signaling pathway. In addition, they are cheap, naturally available, and possess minimal toxicity, thereby having good clinical research and application value. Herein, we summarized various studies on the protective effects of natural pharmaceutical components such as polyphenols, flavonoids, terpenoids, alkaloids, and polysaccharides on ALI through the Nrf2 signaling pathway and demonstrated existing gaps as well as future perspectives.
Inosine: A bioactive metabolite with multimodal actions in human diseases
Authors: Kim In Soo , Jo Eun-Kyoung
Published: November 2022

The nucleoside inosine is an essential metabolite for purine biosynthesis and degradation; it also acts as a bioactive molecule that regulates RNA editing, metabolic enzyme activity, and signaling pathways. As a result, inosine is emerging as a highly versatile bioactive compound and second messenger of signal transduction in cells with diverse functional abilities in different pathological states. Gut microbiota remodeling is closely associated with human disease pathogenesis and responses to dietary and medical supplementation. Recent studies have revealed a critical link between inosine and gut microbiota impacting anti-tumor, anti-inflammatory, and antimicrobial responses in a context-dependent manner. In this review, we summarize the latest progress in our understanding of the mechanistic function of inosine, to unravel its immunomodulatory actions in pathological settings such as cancer, infection, inflammation, and cardiovascular and neurological diseases. We also highlight the role of gut microbiota in connection with inosine metabolism in different pathophysiological conditions. A more thorough understanding of the mechanistic roles of inosine and how it regulates disease pathologies will pave the way for future development of therapeutic and preventive modalities for various human diseases.
Pharmacological effects of natural medicine ginsenosides against Alzheimer’s disease
Authors: Shi Zhikun , Chen Hongyu , Zhou Xu , Yang Wei , Lin Yang
Published: November 2022

Ginsenosides are the most important pharmacological active ingredient of ginseng, with multiple biological therapeutic targets, mild action and no side effects. It is having shown beneficial effects in vitro and in vivo models of AD. In this review, we analyze large literature, summarize the inhibition of ginsenosides fibrous extracellular deposition of β-amyloid (Aβ) and neurofibrillary tangles (NFTs) of possible mechanisms, and explain the effects of ginsenosides on AD neuroprotection from the aspects of antioxidant, anti-inflammatory, and anti-apoptosis, prove the potential of ginsenosides as a new class of drugs for the treatment of AD. In addition, according to the current clinical application status of natural drugs, this paper analysis the delivery route and delivery mode of ginsenosides from the perspective of pharmacokinetics, providing a deeper insight into the clinical application of ginsenosides in the treatment of AD.
A digital hologram-based encryption and compression method for 3D models
Authors: Sun Yukai , Zhao Meirong , Niu Pingjuan , Zheng Yelong , Liu Chuntian , Zhang Shiyu , Bai Songqi , Guo Jinwei
Published: November 2022

This study proposes a novel method to compress and decompress the 3D models for safe transmission and storage. The 3D models are first extracted to become 3D point clouds, which would be classified by the K-means algorithm. Then, these nearby 3D point clouds are converted into a computer-generated hologram (CGH) by calculating the point distribution on the hologram plane using the optical wavefront propagation method. The computer-generated hologram (CGH) contains the spatial coordinate information on point clouds, which can be decompressed using the convolutional neural network (CNN) method. The decompression accuracy of 3D point clouds is quantitatively assessed by normalized correlation coefficients (NCCs), reflecting the correlation between two points and influenced by the hologram resolution, the convolution kernel, and the diffraction distance. Numerical simulations have shown that the novel method can reconstruct a high-quality 3D point cloud with an accuracy of 0.1 mm.
The significance of cephalopod beaks as a research tool: An update
Authors: Xavier José C. , Golikov Alexey V. , Queirós José P. , Perales-Raya Catalina , Rosas-Luis Rigoberto , Abreu José , Bello Giambattista , Bustamante Paco , Capaz Juan C. , Dimkovikj Valerie H. , González Angel F. , Guímaro Hugo , Guerra-Marrero Airam , Gomes-Pereira José N. , Hernández-Urcera Jorge , Kubodera Tsunemi , Laptikhovsky Vladimir , Lefkaditou Evgenia , Lishchenko Fedor , Luna Amanda , Liu Bilin , Pierce Graham J. , Pissarra Vasco , Reveillac Elodie , Romanov Evgeny V. , Rosa Rui , Roscian Marjorie , Rose-Mann Lisa , Rouget Isabelle , Sánchez Pilar , Sánchez-Márquez Antoni , Seixas Sónia , Souquet Louise , Varela Jaquelino , Vidal Erica A. G. , Cherel Yves
Published: November 2022

The use of cephalopod beaks in ecological and population dynamics studies has allowed major advances of our knowledge on the role of cephalopods in marine ecosystems in the last 60 years. Since the 1960’s, with the pioneering research by Malcolm Clarke and colleagues, cephalopod beaks (also named jaws or mandibles) have been described to species level and their measurements have been shown to be related to cephalopod body size and mass, which permitted important information to be obtained on numerous biological and ecological aspects of cephalopods in marine ecosystems. In the last decade, a range of new techniques has been applied to cephalopod beaks, permitting new kinds of insight into cephalopod biology and ecology. The workshop on cephalopod beaks of the Cephalopod International Advisory Council Conference (Sesimbra, Portugal) in 2022 aimed to review the most recent scientific developments in this field and to identify future challenges, particularly in relation to taxonomy, age, growth, chemical composition (i.e., DNA, proteomics, stable isotopes, trace elements) and physical (i.e., structural) analyses. In terms of taxonomy, new techniques (e.g., 3D geometric morphometrics) for identifying cephalopods from their beaks are being developed with promising results, although the need for experts and reference collections of cephalopod beaks will continue. The use of beak microstructure for age and growth studies has been validated. Stable isotope analyses on beaks have proven to be an excellent technique to get valuable information on the ecology of cephalopods (namely habitat and trophic position). Trace element analyses is also possible using beaks, where concentrations are significantly lower than in other tissues (e.g., muscle, digestive gland, gills). Extracting DNA from beaks was only possible in one study so far. Protein analyses can also be made using cephalopod beaks. Future challenges in research using cephalopod beaks are also discussed.