bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Impact of the Khatanga and Lena (Laptev Sea) Runoff on the Distribution and Grazing of Zooplankton
Authors: Pasternak Anna , Drits Alexander , Arashkevich Elena , Flint Mikhail
Published: April 2022

The ecosystems of the Arctic Ocean and their expected changes in a context of Global climate processes are crucially dependent on the freshwater input. The freshwater signal is assumed to be the main structuring factor for the marine fauna on the shallow shelf of the Siberian Arctic seas. The Laptev Sea, as a part of the world’s widest continental shelves surrounding the Arctic Ocean, is a key area for understanding the land–ocean interaction in high latitude regions. The largest freshwater input is provided by the deltaic Lena river followed by the estuarine Khatanga river. The plumes of these rivers differ considerably in their hydrophysical characteristics, suggesting differential impacts on ecosystems of the adjacent shelf. The key component of pelagic ecosystems is zooplankton, which transfers energy from primary producers to higher trophic levels and modifies sedimentations processes. This study is focused on the influence of river discharge on zooplankton in the Laptev Sea at the end of productive season. We studied zooplankton biomass, species composition, distribution patterns of the dominant species and assessed herbivorous feeding rates and grazing pressure of these species along a transect from the inner Khatanga Gulf northward to the continental slope, and a transect in the Lena plume influenced area in August-September 2017. Despite large spatial extension of the Khatanga plume, the impact of river discharge on zooplankton species composition was restricted mainly to the inner Gulf where the brackish species shaped the community. Contrary to the Khatanga input, the Lena freshwater inflow was highly variable and under certain conditions (discharge rate, wind forcing) governed the structure of zooplankton community over a vast shelf area. Distribution patterns of zooplankton biomass, ingestion rates and grazing impact of the dominant species on phytoplankton over the shelf influenced by the Khatanga and Lena plumes were similar. Analysis of our results on demographic structure of Calanus glacialis suggests that seasonal development of the population was largely controlled by the time of ice retreat. Observed climatic changes in the Arctic were not reflected in the total zooplankton biomass and composition of the dominant species.
Modeling the Effects of Seasonal Fishing Moratorium on the Ecosystem of the Minjiang Estuary in Southeastern China
Authors: Kong Yefu , Kang Bin , Shi Xiaotao
Published: April 2022

China’s marine fisheries have made a huge contribution to the world’s food supply at the expense of wild resources collapse by overfishing. Accordingly, the government has introduced a series of measures represented by seasonal fishing moratorium to achieve sustainable fisheries. To evaluate the impact of the seasonal fishing moratorium on the ecosystem of the Minjiang Estuary in southeastern China, three ecosystem models, one in 2006, one in 2016 after 10 years seasonal fishing moratorium, and one in 2016 simulated under the scenario without a fishing moratorium, were constructed by Ecopath with Ecosim. Based on the 2016 model, the status of the Minjiang Estuary ecosystem after 50 years was simulated under four scenarios of different combinations of fishing pressure and durations of the fishing moratorium. The results showed that in the 2016 model, parameters as total ecosystem flow, mean fishing trophic level, and Finn’s index were 9,235.407 t km−2 year−1, 2.94, and 0.920, respectively, all significantly higher than those extracted from the 2016 simulated model, suggesting the effectiveness of the seasonal fishing moratorium. Under scenario analysis, extending the fishing moratorium by 3 months and reducing fishing pressure by 50% showed synergistic effects to achieve a better result than the current fishing moratorium strategy.
Evaluation of Natural Extracts as Promising Components of Bioactive Coatings for Orthopedic Implants
Authors: Kravanja Katja Andrina , Finšgar Matjaž , Knez Željko , Knez Marevci Maša
Published: April 2022

The development of drug-eluting bioactive coatings for orthopedic implants has gained increased interest in recent years with an intent to reduce postoperative complications and improve tissue regeneration at the implant interface. Due to the remarkable benefits of natural polyphenolic components, such as antioxidant, antimicrobial, anti-inflammatory, anti-cancer and bioactive activity, and their ubiquitous availability in nature, they are promising candidates for incorporation into bioactive coatings of advanced medical devices in future clinical applications. However, further research is needed to address all challenges. This review aims to highlight the prosperity of natural compounds widely available in nature loaded in implantable devices, summarize the “state of the art” in this field, identify the challenges, and accordingly suggest the optimal preparation methods and characterization.
Effect of Calcium Sulphate Pre-crosslinking on Rheological Parameters of Alginate Based Bio-Inks and on Human Corneal Stromal Fibroblast Survival in 3D Bio-Printed Constructs
Authors: Kostenko Anastassia , Swioklo Stephen , Connon Che J.
Published: April 2022

The principle of three-dimensional (3D) bio-printing involves integration of biomaterials, live cells and controlled motor systems for creating complex biomimetic constructs. Bio-ink is one of the most important components in the process of 3D bio-printing and needs to be sufficiently viscous to be dispensed as a free-standing filament but be biocompatible to maintain cell viability and function. Alginate has been used widely for 3D bio-printing due to its biocompatibility, tunable properties, rapid gelation, low cost, and ability to be functionalized to direct cell behavior. By tuning the physiochemical parameters of alginate-based bio-inks, such as viscosity, improvements in print resolution, fidelity and growth characteristics of encapsulated cells can be achieved. This study aimed to improve the printability of low concentration alginate bio-inks by utilizing calcium sulphate (CaSO4) pre-crosslinking. A variety of alginates, differing in their viscosity, molecular weight and b-D-mannuronate and α-L-guluronate residues were investigated by wet spinning and bio-printing. Rheological and structural properties of pre-crosslinked alginates were characterized with the aim of mitigating the resolution problems associated with the use of low percentage alginate bio-inks, more favorable for maintaining cell viability. Pre-crosslinking produced a significant effect on viscosity of biomaterials improving their suitability for the bio-printing process and influencing the final resolution of the printed structure. Medium viscosity high b-D-mannuronate containing alginate (MVM) showed the highest degree of viscosity change compared to the control (p < 0.0001; n = 6), assessed by single value viscometry analysis and shear rheology, after pre-crosslinking and was subsequently used in experiments with cells. The survival of human corneal stromal fibroblasts (CSFs) was assessed using CellTiterGlo metabolic assay and confirmed with Calcein acetoxymethyl and Ethidium homodimer -1 live/dead staining in pre-crosslinked alginate fibers and bio-printed lattices. Encapsulation of CSFs in pre-crosslinked alginate-based bio-inks did not have a detrimental effect on CSF viability compared to the non-pre-crosslinked control over 7 days under standard cell culture conditions (p > 0.05, n = 3). Overall, printability of low percentage alginate bio-inks was improved by pre-crosslinking without affecting the biocompatibility of the bio-inks.
Development and Validation of a Prognostic Nomogram for Prognosis in Patients With Renal Artery Stenosis
Authors: Li Yan , Ma Na , Zhang Yuewei , Wang Siyu , Sun Youjing , Li Mengpu , Ai Hu , Zhu Hui , Wang Yang , Li Peng , Guo Fajin , Li Yongjun , Ren Junhong
Published: April 2022

Background and Objective

Renal artery stenosis (RAS) is associated with an increased risk of renal function deterioration (RFD). Our previous study showed that renal cortical blood perfusion assessed by contrast-enhanced ultrasound (CEUS) was an important related factor for RFD in RAS patients. Based on several conventional related factors confirmed by previous studies, we aimed to establish and verify a CEUS+ scoring system to evaluate the risk of RFD at 1 year of follow-up in RAS patients.

Methods

This study was a single-center retrospective study. A total of 497 elderly RAS patients (247 in the training group and 250 in the verification group) admitted to the Beijing Hospital from January 2016 to December 2019 were included. The baseline characteristics of the patients on admission (including general conditions, previous medical history, blood pressure, blood creatinine, RAS, and cortical blood perfusion in the affected kidney) and renal function [glomerular filtration rate (GFR)] at 1-year of follow-up were collected. We used the univariate and multivariate logistic regressions to establish a CEUS+ scoring system model, the receiver operating characteristic (ROC) curve and area under the curve (AUC) to evaluate prediction accuracy, and the decision curve analysis and nomogram to evaluate the clinical application value of CEUS+ scoring system model.

Results

Among the 497 patients enrolled, 266 (53.5%) were men, with an average age of (51.7 ± 19.3) years. The baseline clinical-radiomic data of the training group and the verification group were similar (all p > 0.05). Multivariate logistic regression analysis results showed that age [Odds ratio (OR) = 1.937, 95% confidence interval (CI): 1.104–3.397), diabetes (OR = 1.402, 95% CI: 1.015–1.938), blood pressure (OR = 1.575, 95% CI: 1.138–2.182), RAS (OR = 1.771, 95% CI: 1.114–2.816), and area under ascending curve (AUCi) (OR = 2.131, 95% CI: 1.263–3.596) were related factors for the renal function deterioration after 1 year of follow-up (all p < 0.05). The AUC of the ROC curve of the CEUS+ scoring system model of the training group was 0.801, and the Youden index was 0.725 (specificity 0.768, sensitivity 0.813); the AUC of the ROC curve of the validation group was 0.853, Youden index was 0.718 (specificity 0.693, sensitivity 0.835). There was no significant difference in ROC curves between the two groups (D = 1.338, p = 0.325). In addition, the calibration charts of the training and verification groups showed that the calibration curve of the CEUS+ scoring system was close to the standard curve (p = 0.701, p = 0.823, both p > 0.10).

Conclusion

The CEUS+ scoring system model is helpful in predicting the risk of worsening renal function in elderly RAS patients.
The Research Landscape of Multiple Endocrine Neoplasia Type 1 (2000–2021): A Bibliometric Analysis
Authors: Feng Chenzhe , Chen Haolin , Huang Leyi , Feng Yeqian , Chang Shi
Published: April 2022

Introduction

This study aimed to investigate the landscape of Multiple Endocrine Neoplasia Type 1 research during the last 22 years using machine learning and text analysis.

Method

In December 2021, all publications indexed under the MeSH term “Multiple Endocrine Neoplasia Type 1” were obtained from PubMed. The whole set of search results was downloaded in XML format, and metadata such as title, abstract, keywords, mesh words, and year of publication were extracted from the original XML files for bibliometric evaluation. The Latent Dirichlet allocation (LDA) topic modeling method was used to analyze specific themes.

Results

This study eventually contained 1,407 publications. Among them, there are 768 (54.58%) case reports and reviews. Text analysis based on MeSH words revealed that the most often studied clinical areas include therapy efficacy, prognosis, and genetic diagnosis. The majority of basic study is focused on genetic alterations. The LDA topic model further identifies three topic clusters include basic research, treatment cluster, and diagnosis cluster. In the basic research cluster, many studies are focused on the expression of Menin. The primary focus of the therapy cluster is pancreatic resections and parathyroidectomy. In the diagnose cluster, the main focus is on Genetic Diagnosis and screening strategies for Hereditary Cancer Syndrome.

Conclusion

The current state of research on MEN1 is far from adequate. Research on rare diseases MEN1 necessitates implementing a broad research program involving multiple centers to advance MEN1 research together.
Exploring Variability of Trichodesmium Photophysiology Using Multi-Excitation Wavelength Fast Repetition Rate Fluorometry
Authors: Zhu Yuanli , Feng Yuanyuan , Browning Thomas J. , Wen Zuozhu , Hughes David J. , Hao Qiang , Zhang Ruifeng , Meng Qicheng , Wells Mark L. , Jiang Zhibing , Dissanayake P. A. K. N. , Priyadarshani W. N. C. , Shou Lu , Zeng Jiangning , Chai Fei
Published: April 2022

Fast repetition rate fluorometry (FRRf) allows for rapid non-destructive assessment of phytoplankton photophysiology in situ yet has rarely been applied to Trichodesmium. This gap reflects long-standing concerns that Trichodesmium (and other cyanobacteria) contain pigments that are less effective at absorbing blue light which is often used as the sole excitation source in FRR fluorometers—potentially leading to underestimation of key fluorescence parameters. In this study, we use a multi-excitation FRR fluorometer (equipped with blue, green, and orange LEDs) to investigate photophysiological variability in Trichodesmium assemblages from two sites. Using a multi-LED measurement protocol (447+519+634 nm combined), we assessed maximum photochemical efficiency (Fv/Fm), functional absorption cross section of PSII (σPSII), and electron transport rates (ETRs) for Trichodesmium assemblages in both the Northwest Pacific (NWP) and North Indian Ocean in the vicinity of Sri Lanka (NIO-SL). Evaluating fluorometer performance, we showed that use of a multi-LED measuring protocol yields a significant increase of Fv/Fm for Trichodesmium compared to blue-only excitation. We found distinct photophysiological differences for Trichodesmium at both locations with higher average Fv/Fm as well as lower σPSII and non-photochemical quenching (NPQNSV) observed in the NWP compared to the NIO-SL (Kruskal–Wallis t-test df = 1, p < 0.05). Fluorescence light response curves (FLCs) further revealed differences in ETR response with a lower initial slope (αETR) and higher maximum electron turnover rate (ETRPSIImax) observed for Trichodesmium in the NWP compared to the NIO-SL, translating to a higher averaged light saturation EK (= ETRPSIImax/αETR) for cells at this location. Spatial variations in physiological parameters were both observed between and within regions, likely linked to nutrient supply and physiological stress. Finally, we applied an algorithm to estimate primary productivity of Trichodesmium using FRRf-derived fluorescence parameters, yielding an estimated carbon-fixation rate ranging from 7.8 to 21.1 mgC mg Chl-a–1 h–1 across this dataset. Overall, our findings demonstrate that capacity of multi-excitation FRRf to advance the application of Chl-a fluorescence techniques in phytoplankton assemblages dominated by cyanobacteria and reveals novel insight into environmental regulation of photoacclimation in natural Trichodesmium populations.
QuantiFERON-TB Gold Plus Assay in Patients With Latent vs. Active Tuberculosis in a Low Incidence Setting: Level of IFN-γ, CD4/CD8 Responses, and Release of IL-2, IP-10, and MIG
Authors: Carrère-Kremer Séverine , Kolia-Diafouka Pratt , Pisoni Amandine , Bolloré Karine , Peries Marianne , Godreuil Sylvain , Bourdin Arnaud , Van de Perre Philippe , Tuaillon Edouard
Published: April 2022

Objectives

We analyzed the results of the QuantiFERON Glod Plus assay (QFT) and cytokine patterns associated with active tuberculosis (ATB) among patients with positive QFT.

Methods

A total of 195 patients are QFT-positive, among which 24 had an ATB and 171 had a latent tuberculosis infection (LTBI). Interferon-gamma (IFN-γ) secretion was analyzed relative to interleukin-2 (IL-2), IFN-γ inducible protein or CXCL-10 (IP-10), and monokine induced by IFN-γ or CXCL-9 (MIG) secretion, and then compared between two sets of peptide antigens [tube 1 - cluster of differentiation 4 (CD4+) T cell stimulation; tube 2 - CD4+/CD8+ T cell response].

Results

Higher IFN-γ responses were measured in the ATB group (p = 0.0089). The results showed that there was a lower ratio of tube 1/tube 2 IFN-γ concentrations in the ATB group (p = 0.0009), and a median [interquartile ranges (IQR)] difference between the two sets at −0.82 IU/ml (−1.67 to 0.18) vs. −0.07 IU/ml (−0.035 to 0.11, p < 0.0001) in the ATB group compared to the LTBI group, respectively. In addition, patients with low ratios of IL-2/IFN-γ, IP-10/IFN-γ, and MIG/IFN-γ were much more likely to have ATB.

Conclusion

High levels of IFN-γ secretion, preferential IFN-γ response in tube 2, and lower secretion of IL-2, IP-10, and MIG release relative to IFN-γ secretion were more likely observed in subjects with ATB. These features of T cell response may be helpful in low prevalence settings to suspect ATB in patients tested positive for IFN-γ release assays (IGRA).
Contribution of Infrared Spectroscopy to the Understanding of Amyloid Protein Aggregation in Complex Systems
Authors: Ami Diletta , Mereghetti Paolo , Natalello Antonino
Published: April 2022

Infrared (IR) spectroscopy is a label-free and non-invasive technique that probes the vibrational modes of molecules, thus providing a structure-specific spectrum. The development of infrared spectroscopic approaches that enable the collection of the IR spectrum from a selected sample area, from micro- to nano-scale lateral resolutions, allowed to extend their application to more complex biological systems, such as intact cells and tissues, thus exerting an enormous attraction in biology and medicine. Here, we will present recent works that illustrate in particular the applications of IR spectroscopy to the in situ characterization of the conformational properties of protein aggregates and to the investigation of the other biomolecules surrounding the amyloids. Moreover, we will discuss the potential of IR spectroscopy to the monitoring of cell perturbations induced by protein aggregates. The essential support of multivariate analyses to objectively pull out the significant and non-redundant information from the spectra of highly complex systems will be also outlined.
Autopromotion of K-Ras4B Feedback Activation Through an SOS-Mediated Long-Range Allosteric Effect
Authors: He Xuan , Du Kui , Wang Yuanhao , Fan Jigang , Li Mingyu , Ni Duan , Lu Shaoyong , Bian Xiaolan , Liu Yaqin
Published: April 2022

The Ras-specific guanine nucleotide exchange factors Son of Sevenless (SOS) regulates Ras activation by converting inactive GDP-bound to active GTP-bound states. The catalytic activity of Ras is further allosterically regulated by GTP−Ras bound to a distal site through a positive feedback loop. To address the mechanism underlying the long-range allosteric activation of the catalytic K-Ras4B by an additional allosteric GTP–Ras through SOS, we employed molecular dynamics simulation of the K-Ras4BG13D•SOScat complex with and without an allosteric GTP-bound K-Ras4BG13D. We found that the binding of an allosteric GTP−K-Ras4BG13D enhanced the affinity between the catalytic K-Ras4BG13D and SOScat, forming a more stable conformational state. The peeling away of the switch I from the nucleotide binding site facilitated the dissociation of GDP, thereby contributing to the increased nucleotide exchange rate. The community networks further showed stronger edge connection upon allosteric GTP−K-Ras4BG13D binding, which represented an increased interaction between catalytic K-Ras4BG13D and SOScat. Moreover, GTP−K-Ras4BG13D binding transmitted allosteric signaling pathways though the Cdc25 domain of SOS that enhanced the allosteric regulatory from the K-Ras4BG13D allosteric site to the catalytic site. This study may provide an in-depth mechanism for abnormal activation and allosteric regulation of K-Ras4BG13D.
The Attenuation Value Within the Non-hypodense Region on Non-contrast Computed Tomography of Spontaneous Cerebral Hemorrhage: A Long-Neglected Predictor of Hematoma Expansion
Authors: Chen Yong , Cao Dan , Guo Zheng-Qian , Ma Xiao-Ling , Ou Yi-Bo , He Yue , Chen Xu , Chen Jian
Published: April 2022

Background and Purpose

The ability of attenuation value of the non-hypodense region of hematoma in non-contrast computed tomography (NCCT) for predicting hematoma expansion (HE) remains unclear. Our purpose is to explore this relationship.

Methods

Two cohorts of patients were collected for analysis. The region where we measured hematoma attenuation values was limited to the non-hypodense region that was not adjacent to the normal brain tissue on NCCT. The critical attenuation value was derived via receiver operating characteristic (ROC) curve analysis in the derivation cohort and its predictive ability was validated in the validation cohort. Independent relationships between predictors, such as critical attenuation value of the non-hypodense region and HE were analyzed using the least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic analysis.

Results

The results showed that the attenuation value <64 Hounsfield units (HU) was independently associated with HE [odds ratio (OR), 4.118; 95% confidential interval (CI), 1.897–9.129, p < 0.001] and the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the curve (AUC) for predicting HE were 36.11%, 81.71%, 1.97, 0.78, 44.8%, 75.7%, and 0.589, respectively.

Conclusions

Our research explored and validated the relationship between the attenuation value of the non-hypodense region of hematoma and HE. The attenuation value < 64 HU was an appropriate indicator of early HE.
Control of Vascular Risk Factors and Response to Stroke Symptoms in Argentina During the COVID-19 Quarantine. The SIFHON-COVID Population Survey
Authors: Rodríguez Pérez María S. , Rosales Julieta S. , Dossi Daiana E. , Ameriso Sebastián F.
Published: April 2022

Background and Objectives

In preparation for the suspected influx of COVID-19 patients, many healthcare systems reduced or discontinued provision of “non-urgent” care. This decision had potential impact on stroke prevention and management. We conducted a large population survey to assess the effect of mandatory social isolation on routine health controls, emergency consultations and other stroke care-related behaviors of the population during the pandemic.

Methods

We distributed multiple-choice anonymous questionnaires through the institutional email database and through the email database of clients of a beverage delivery company. Most respondents resided in the metropolitan area of Buenos Aires. This is the area where the infection rates were highest and restriction measures were hardest. The survey assessed demographic characteristics and actual and potential behaviors of people regarding medical checkups, risk factors control, medication provision and response to onset of symptoms consistent with stroke or TIA. Surveys were sent during May 2020, the strictest period of the quarantine in Argentina.

Results

A total of 10,303 questionnaires were completed. Thirty-seven percent of the respondents were older than 60 years, 74% were women and 16% lived alone. Vascular risk factors were present in 39% of the individuals. Seventy-six percent did not continue with their regular medical checkups during the mandatory social and preventive isolation, 21% had difficulty obtaining medical prescriptions and only 38% considered that health institutions had implemented reliable safety measures to avoid exposure to COVID-19. When asked about response in case of onset of stroke symptoms, 9% would not consult given the context of the pandemic. Six percent reported having had symptoms consistent with stroke or TIA but only 35% went to a hospital. The vast majority of the respondents said they were awaiting for the end of the quarantine to resume their usual medical care.

Conclusions

The implementation of a quarantine may have some serious adverse effects on the prevention, diagnosis and treatment of stroke. These undesirable aspects should be taken into consideration in the planning, communication and implementation of health policies.
The Evolution of Modern Ablative Surgery for the Treatment of Obsessive-Compulsive and Major Depression Disorders
Authors: Mustroph Martina Laetitia , Cosgrove G. Rees , Williams Ziv M.
Published: April 2022

In this review, we describe the evolution of modern ablative surgery for intractable psychiatric disease, from the original image-guided cingulotomy procedure described by Ballantine, to the current bilateral anterior cingulotomy using MRI-guided stereotactic techniques. Extension of the single lesion bilateral cingulotomy to the extended bilateral cingulotomy and subsequent staged limbic leucotomy (LL) is also discussed. Other ablative surgeries for psychiatric disease including subcaudate tractotomy (SCT) and anterior capsulotomy (AC) using modern MRI-guided ablative techniques, as well as radiosurgical capsulotomy, are described. Finally, the potential emerging role of MR-guided focused ultrasound (MRgFUS) for treating conditions such as major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) is discussed.
Physicochemical Properties and in vitro Digestibility of Myofibrillar Proteins From the Scallop Mantle (Patinopecten yessoensis) Based on Ultrahigh Pressure Treatment
Authors: Liu Xiaohan , Mao Kemin , Sang Yaxin , Tian Guifang , Ding Qiuyue , Deng Wenyi
Published: April 2022

The utilization of myofibrillar proteins (MPs) from the scallop mantle was limited due to its poor digestibility in vitro. In this study, structural properties and in vitro digestibility of MP were evaluated after modified by ultra-high pressure (UHP) at different pressures (0.1, 100, 200, 300, 400, and 500 MPa). The results showed that high pressure could significantly increase the ordered structure content like α-helix, inhibit the formation of disulfide bonds, and decrease surface hydrophobicity. Moreover, MP possessed the optimal solubility and in vitro digestibility properties at 200 MPa due to the minimum particle size and turbidity, relatively dense and uniform microstructure. The results indicated that the UHP treatment was an effective method to improve the digestibility of MP from scallop mantle and lay a theoretical basis for the functional foods development of poor digestion people and comprehensive utilization of scallop mantles.
Thymic Carcinoma: A Review
Authors: Alqaidy Doaa , Moran Cesar A.
Published: April 2022

The diagnosis of thymic carcinoma may pose significant problems not necessarily in the histopathological diagnosis but rather in assigning the thymus as specific origin. Often the tissue available for interpretation is obtained via a mediastinocopic biopsy, which raises two different issues -minimal tissue and lack of specific features to make a carcinoma of thymic origin. In addition, if to that conundrum we add that there is no magic immunohistochemical stain that will unequivocally lead to the interpretation of thymic carcinoma, then we are left with a true clinical-radiological-pathological correlation. In this review, we will highlight some of those challenges that diagnostic surgical pathologists may encounter in the histopathological assessment of thymic carcinoma as well as in the staging of these tumors.
Clinical Outcome of CT-Guided Iodine-125 Radioactive Seed Implantation for Intrahepatic Recurrent Hepatocellular Carcinoma: A Retrospective, Multicenter Study
Authors: Yuan Qianqian , Ma Yanli , Wu Linlin , Song Yuqing , He Chuang , Huang Xuequan , Yang Chongshuang , Liu Bin , Han Hongmei , Zhang Kaixian , Wang Junjie
Published: April 2022

The efficacy and safety of CT-Guided Iodine-125 Radioactive Seed Implantation (RSI) for the treatment of intrahepatic recurrent hepatocellular carcinoma (rHCC) were analyzed in this multicenter retrospective study. We reviewed the medical records of patients with rHCC treated with I-125 seed implantation at four different hospitals in China from December 2011 and January 2021. The local progression-free survival (LPFS),liver PFS, and overall survival (OS) were calculated, and the short-term efficacy and treatment-related toxicities were evaluated. A total of 82 patients were enrolled; the median follow-up time was 46 months (range, 3–80 months). The 1-, 3- and 5-year LPFS rates were 63.8%, 27.1%, and 7.9%, respectively, and the corresponding OS rates were 74.8%, 32.9%, and 12.6%, respectively. Univariate analysis showed that factors influencing LPFS included the maximum lesion diameter, Barcelona Clinic Liver Cancer (BCLC) stage, interval between treatment and recurrence, and D90. Multivariate analyses revealed that the BCLC stage, interval between treatment and recurrence, and D90 were independent factors influencing LPFS, whereas BCLC stage, D90, and short-term efficacy were independent factors influencing OS. In summary, I-125 seed implantation is a safe and effective treatment for rHCC. The BCLC stage, interval, and D90 were found to influence the local control. A larger, prospective study is required to confirm the dose-response curve for Iodine-125 RSI of rHCC.
CpG Site-Specific Methylation-Modulated Divergent Expression of PRSS3 Transcript Variants Facilitates Nongenetic Intratumor Heterogeneity in Human Hepatocellular Carcinoma
Authors: Lin Shuye , Xu Hanli , Pang Mengdi , Zhou Xiaomeng , Pan Yuanming , Zhang Lishu , Guan Xin , Wang Xiaoyue , Lin Bonan , Tian Rongmeng , Chen Keqiang , Zhang Xiaochen , Yang Zijiang , Ji Fengmin , Huang Yingying , Wei Wu , Gong Wanghua , Ren Jianke , Wang Ji Ming , Guo Mingzhou , Huang Jiaqiang
Published: April 2022

Background

Hepatocellular carcinoma (HCC) is one of the most lethal human tumors with extensive intratumor heterogeneity (ITH). Serine protease 3 (PRSS3) is an indispensable member of the trypsin family and has been implicated in the pathogenesis of several malignancies, including HCC. However, the paradoxical effects of PRSS3 on carcinogenesis due to an unclear molecular basis impede the utilization of its biomarker potential. We hereby explored the contribution of PRSS3 transcripts to tumor functional heterogeneity by systematically dissecting the expression of four known splice variants of PRSS3 (PRSS3-SVs, V1~V4) and their functional relevance to HCC.

Methods

The expression and DNA methylation of PRSS3 transcripts and their associated clinical relevance in HCC were analyzed using several publicly available datasets and validated using qPCR-based assays. Functional experiments were performed in gain- and loss-of-function cell models, in which PRSS3 transcript constructs were separately transfected after deleting PRSS3 expression by CRISPR/Cas9 editing.

Results

PRSS3 was aberrantly differentially expressed toward bipolarity from very low (PRSS3Low) to very high (PRSS3High) expression across HCC cell lines and tissues. This was attributable to the disruption of PRSS3-SVs, in which PRSS3-V2 and/or PRSS3-V1 were dominant transcripts leading to PRSS3 expression, whereas PRSS3-V3 and -V4 were rarely or minimally expressed. The expression of PRSS3-V2 or -V1 was inversely associated with site-specific CpG methylation at the PRSS3 promoter region that distinguished HCC cells and tissues phenotypically between hypermethylated low-expression (mPRSS3-SVLow) and hypomethylated high-expression (umPRSS3-SVHigh) groups. PRSS3-SVs displayed distinct functions from oncogenic PRSS3-V2 to tumor-suppressive PRSS3-V1, -V3 or PRSS3-V4 in HCC cells. Clinically, aberrant expression of PRSS3-SVs was translated into divergent relevance in patients with HCC, in which significant epigenetic downregulation of PRSS3-V2 was seen in early HCC and was associated with favorable patient outcome.

Conclusions

These results provide the first evidence for the transcriptional and functional characterization of PRSS3 transcripts in HCC. Aberrant expression of divergent PRSS3-SVs disrupted by site-specific CpG methylation may integrate the effects of oncogenic PRSS3-V2 and tumor-suppressive PRSS3-V1, resulting in the molecular diversity and functional plasticity of PRSS3 in HCC. Dysregulated expression of PRSS3-V2 by site-specific CpG methylation may have potential diagnostic value for patients with early HCC.
(-)-Epigallocatechin-3-Gallate (EGCG) Modulates the Composition of the Gut Microbiota to Protect Against Radiation-Induced Intestinal Injury in Mice
Authors: Cai Shang , Xie Li-Wei , Xu Jia-Yu , Zhou Hao , Yang Chao , Tang Lin-Feng , Tian Ye , Li Ming
Published: April 2022

The high radiosensitivity of the intestinal epithelium limits the outcomes of radiotherapy against abdominal malignancies, which results in poor prognosis. Currently, no effective prophylactic or therapeutic strategy is available to mitigate radiation toxicity in the intestine. Our previous study revealed that the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) attenuates radiation-induced intestinal injury (RIII). The aim of the present study was to determine the effect of EGCG on the intestinal flora of irradiated mice. EGCG administration reduced radiation-induced intestinal mucosal injury, and significantly increased the number of Lgr5+ intestinal stem cells (ISCs) and Ki67+ crypt cells. In addition, EGCG reversed radiation-induced gut dysbiosis, restored the Firmicutes/Bacteroidetes ratio, and increased the abundance of beneficial bacteria. Our findings provide novel insight into EGCG-mediated remission of RIII, revealing that EGCG could be a potential modulator of gut microbiota to prevent and treat RIII.
The Role of a Longitudinal, Multidisciplinary Clinic in Building a Unique Research Collaborative
Authors: Gonzales Alexandria A. , Mastrolonardo Alexander , Winget Kenna , Ragulojan Malavan , Fleming Adam J. , Singh Sheila K.
Published: April 2022

Multidisciplinary neuro-oncology clinics allow collaboration between various specialties and training levels. Building a tenable clinical research program based in the longitudinal dialogue and practice of collaborative clinicians and trainees can bridge clinical observations to research execution. However, forming a research team around a multidisciplinary clinic’s activities is constrained by a lack of literature or guidelines. As well, challenges in sustaining team logistics, communication, and productivity can persist without a standardized team framework. This perspective discusses the state of research teams in clinical oncology, and uses experiences from the McMaster Pediatric Brain Tumour Study Group to guide those seeking to form a research team based on the collective activities and observations of a multidisciplinary clinic.
Prognostic Role of Pretreatment C-Reactive Protein to Albumin Ratio in Urological Cancers: A Systematic Review and Meta-Analysis
Authors: Wu Minhong , Zhou Yan , Chen Qingsheng , Yu Zhiling , Gu Hongyong , Lin Pengxiu , Li Yanling , Liu Cailing
Published: April 2022

Background

To investigate the potential prognostic role of C-reactive protein to albumin ratio (CAR) in patients with urinary cancers, including renal cell carcinoma (RCC), bladder cancer (BC), and prostate cancer (PC).

Methods

We searched and screened literatures with PubMed, Embase, Cochrane Library, and Web of Science in January 2022. We applied combined hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the associations.

Results

Thirteen studies including 2,941 cases were analyzed in our study. Merged results indicated that highly pretreated CAR was associated with inferior overall survival (HR 2.21, 95% CI 1.86-2.62, p < 0.001) and progression-free survival (HR 1.85, 95% CI 1.36-2.52, p < 0.001) for urinary cancers. In a subgroup analysis of OS by tumor type, CAR can be a predictor in RCC (HR 2.10, 95% CI 1.72-2.56), BC (HR 3.35, 95% CI 1.94-5.80), and PC (HR 2.20, 95% CI 1.43-3.37). In a subgroup analysis of PFS by tumor type, CAR can be a predictor in BC (HR 1.76, 95% CI 1.03-3.02), and RCC (HR 1.90, 95% CI 1.25-2.89). The reliability and robustness of results were confirmed.

Conclusions

High pretreated CAR was effective predictor of poor survival in patients with urinary cancers and can act as prognostic factor for these cases.

Systematic Review Registration

PROSPERO (CRD42022306414).
A Study to Evaluate Accuracy and Validity of the EFAI Computer-Aided Bone Age Diagnosis System Compared With Qualified Physicians
Authors: Cheng Chi-Fung , Liao Ken Ying-Kai , Lee Kuan-Jung , Tsai Fuu-Jen
Published: April 2022

Study Objectives

In previous research, we built a deep neural network model based on Inception-Resnet-v2 to predict bone age (EFAI-BAA). The primary objective of the study was to determine if the EFAI-BAA was substantially concordant with the qualified physicians in assessing bone ages. The secondary objective of the study was to determine if the EFAI-BAA was no different in the clinical rating (advanced, normal, or delayed) with the qualified physicians.

Method

This was a retrospective study. The left-hand X-ray images of male subjects aged 3–16 years old and female subjects aged 2–15 years old were collected from China Medical University Hospital (CMUH) and Asia University Hospital (AUH) retrospectively since the trial began until the included image amount reached 368. This was a blinded study. The qualified physicians who ran, read, and interpreted the tests were blinded to the values assessed by the other qualified physicians and the EFAI-BAA.

Results

The concordance correlation coefficient (CCC) between the EFAI-BAA (EFAI-BAA), the evaluation of bone age by physician in Kaohsiung Veterans General Hospital (KVGH), Taichung Veterans General Hospital (TVGH2), and in Taipei Tzu Chi Hospital (TZUCHI-TP) was 0.9828 (95% CI: 0.9790–0.9859, p-value = 0.6782), 0.9739 (95% CI: 0.9681–0.9786, p-value = 0.0202), and 0.9592 (95% CI: 0.9501–0.9666, p-value = 0.4855), respectively.

Conclusion

There was a consistency of bone age assessment between the EFAI-BAA and each one of the three qualified physicians (CCC = 0.9). As the significant difference in the clinical rating was only found between the EFAI-BAA and the qualified physician in TVGH2, the performance of the EFAI-BAA was considered similar to the qualified physicians.
Time Interval From Early-Term Antenatal Corticosteroids Administration to Delivery and the Impact on Neonatal Outcomes
Authors: Li Jing , Zhang Jing , Hao Qingfei , Du Yanna , Lu Jie , Chen Haoming , Cheng Xiuyong
Published: April 2022

Objectives

To determine the association between the time interval from antenatal corticosteroids administration to delivery and neonatal complications in diabetic mothers undergoing early term (37+0 to 38+6 weeks) scheduled cesarean section (ETSCS).

Study Design

A retrospective cohort study of women with any form of diabetes in pregnancy undergoing ETSCS was included. Cases were stratified into the following groups based on the time interval from the first dose of corticosteroids administration to delivery: <2, 2–7, and >7 days. Women undergoing ETSCS, who did not receive corticosteroids were included as controls. We assessed the association between the time interval and neonatal outcomes in a multivariate regression model that controlled for potential confounders. Primary outcomes were the incidence of respiratory distress syndrome (RDS)/transient tachypnea of the newborn (TTN) and neonatal hypoglycemia.

Results

The study cohort comprised 1,165 neonates. Of those, 159 (13.6%) were delivered within 2 days of maternal corticosteroids administration, 131 (11.2%) were delivered within 2–7 days after maternal corticosteroids administration, and 137 (11.8%) delivered more than 7 days after maternal corticosteroids administration. The remaining 738 (63.3%) were not exposed to corticosteroids. Multivariate analysis demonstrated that delivery within any time of antenatal corticosteroids administration was not associated with decreased risks of RDS/TTN. The risk of neonatal hypoglycemia was highest in the delivery of <2 days group (adjusted odds ratio [aOR]: 2.684, 95% confidence interval [CI]: 1.647–4.374 for control group; aOR: 2.827, 95% CI: 1.250–6.392 for delivery 2–7 days group; aOR:2.975, 95% CI: 1.265–6.996 for delivery >7 days group).

Conclusions

Corticosteroids treatment for diabetic mothers undergoing ETSCS was not associated with beneficial neonatal respiratory outcomes. In addition, delivery, <2 days after antenatal corticosteroids administration was associated with an increased risk of neonatal hypoglycemia.
LPM3770277, a Potent Novel CDK4/6 Degrader, Exerts Antitumor Effect Against Triple-Negative Breast Cancer
Authors: Qiu Jiahao , Bai Xinfa , Zhang Wenjing , Ma Mingxu , Wang Wenyan , Liang Ye , Wang Hongbo , Tian Jingwei , Yu Pengfei
Published: April 2022

Triple negative breast cancer (TNBC) is a subtype of breast cancer with significant malignancy and poor prognosis but effective treatments are limited. Given the critical role of CDK4/6 in cell cycle and the apparent success of CDK4/6 inhibitors against certain cancer, this study attempted to utilize hydrophobic tagging technology to develop a CDK4/6 degrader against TNBC. We based on the chemical structure of the major metabolite of a clinically approved CDK4/6 inhibitor, abemaciclib, to synthesize three compounds and evaluated their in vitro cytotoxicity. LPM3770277 stood out as the most promising compound which was further confirmed by a series of binding and CDK4/6 degradation studies. LPM3770277 was able to bind to CDK4/6, and time-dependently and dose-dependently increased CDK4/6 protein degradation. Mechanistic study revealed that LPM3770277 exerted its CDK4/6 degradation effect via two machineries: proteasome and lysosome-promoted autophagy. Using in vivo TNBC xenograft cancer model, we found that LPM3770277 demonstrated superior anti-tumor efficacy and safety as compared to abemaciclib, although both compounds exerted similar effects on cell cycle arrest. In conclusion, this study for the first time developed and characterized a CDK4/6 degrader against TNBC using hydrophobic tags, which strongly suggests the viability of hydrophobic tags as a strategy to develop potential treatments against TNBC.
Agathisflavone as a Single Therapy or in Association With Mesenchymal Stem Cells Improves Tissue Repair in a Spinal Cord Injury Model in Rats
Authors: do Nascimento Ravena P. , de Jesus Lívia B. , Oliveira-Junior Markley S. , Almeida Aurea M. , Moreira Eduardo L. T. , Paredes Bruno D. , David Jorge M. , Souza Bruno S. F. , de Fátima D. Costa Maria , Butt Arthur M. , Silva Victor Diogenes A. , Costa Silvia L.
Published: April 2022

Agathisflavone is a flavonoid with anti-neuroinflammatory and myelinogenic properties, being also capable to induce neurogenesis. This study evaluated the therapeutic effects of agathisflavone—both as a pharmacological therapy administeredin vivoand as anin vitropre-treatment aiming to enhance rat mesenchymal stem cells (r)MSCs properties–in a rat model of acute spinal cord injury (SCI). Adult male Wistar rats (n= 6/group) underwent acute SCI with an F-2 Fogarty catheter and after 4 h were treated daily with agathisflavone (10 mg/kg ip, for 7 days), or administered with a single i.v. dose of 1 × 106rMSCs either unstimulated cells (control) or pretreated with agathisflavone (1 µM, every 2 days, for 21 daysin vitro). Control rats (n= 6/group) were treated with a single dose methylprednisolone (MP, 60 mg/kg ip). BBB scale was used to evaluate the motor functions of the animals; after 7 days of treatment, the SCI area was analyzed after H&E staining, and RT-qPCR was performed to analyze the expression of neurotrophins and arginase. Treatment with agathisflavone alone or with of 21-day agathisflavone–treated rMSCs was able to protect the injured spinal cord tissue, being associated with increased expression of NGF, GDNF and arginase, and reduced macrophage infiltrate. In addition, treatment of animals with agathisflavone alone was able to protect injured spinal cord tissue and to increase expression of neurotrophins, modulating the inflammatory response. These results support a pro-regenerative effect of agathisflavone that holds developmental potential for clinical applications in the future.
Overshoot Structure Near the Earth’s Subsolar Magnetopause Generated by Magnetopause Motions
Authors: Song Xiaojian , Zuo Pingbing , Shen Zhenning , Feng Xueshang , Xu Xiaojun , Wang Yi , Jiang Chaowei , Luo Xi
Published: April 2022

For magnetopause crossing events, the observed magnetospheric magnetic fields in the vicinity of the subsolar magnetopause frequently present an overshoot structure; that is, in small vicinity of the magnetopause, the closer to the magnetopause, the stronger the magnetospheric magnetic field is. In this investigation, an automatic identification algorithm is developed to rapidly and effectively search the magnetopause crossing events using THEMIS data from 2007 to 2021. Nearly 59% of magnetopause crossing events identified near the subsolar region appear an overshoot structure. The statistical result shows that, for overshoot cases, the normalized change rate of magnetospheric magnetic field near the magnetopause is linearly related to the normalized magnetopause velocity, which means that the overshoot structure may be caused by the redistribution of the magnetospheric magnetic field due to the rapid magnetopause motion.
Adrenergic Modulation of Erythropoiesis After Trauma
Authors: Munley Jennifer A. , Kelly Lauren S. , Mohr Alicia M.
Published: April 2022

Severe traumatic injury results in a cascade of systemic changes which negatively affect normal erythropoiesis. Immediately after injury, acute blood loss leads to anemia, however, patients can remain anemic for as long as 6 months after injury. Research on the underlying mechanisms of such alterations of erythropoiesis after trauma has focused on the prolonged hypercatecholaminemia seen after trauma. Supraphysiologic elevation of catecholamines leads to an inhibitive effect on erythropoiesis. There is evidence to show that alleviation of the neuroendocrine stress response following trauma reduces these inhibitory effects. Both beta blockade and alpha-2 adrenergic receptor stimulation have demonstrated increased growth of hematopoietic progenitor cells as well as increased pro-erythropoietic cytokines after trauma. This review will describe prior research on the neuroendocrine stress response after trauma and its consequences on erythropoiesis, which offer insight into underlying mechanisms of prolonged anemia postinjury. We will then discuss the beneficial effects of adrenergic modulation to improve erythropoiesis following injury and propose future directions for the field.
An Aminobutyric Acid Transaminase in Zea mays Interacts With Rhizoctonia solani Cellulase to Participate in Disease Resistance
Authors: Guo Xiuna , Chen Jinyin , Gao Mengyi , Li Duochuan
Published: April 2022

Corn sheath blight, caused by AG1-IA, a fusion group of Rhizoctonia solani, which acts as a kind of necrotrophic fungal pathogen, poses a global threat to the production of Zea mays. Although cellulase plays a crucial role in R. solani infections, how plants respond to it is still poorly understood. In this study, we identified a gamma-aminobutyric acid transaminase (GABA-T), ZmGABA-T, in Z. mays that interacts with a cell wall–degrading enzyme (CWDE), EG1, in the cell membrane, using yeast two-hybrid assay, co-immunoprecipitation (Co-IP), and bimolecular fluorescence complementation assays. We found that the combination of EG1 and ZmGABA-T suppressed the allergic necrosis induced by EG1. We also found that the substrate of GABA-T–GABA, can inhibit the transcription of EG1. Transient expression of ZmGABA-T inhibited R. solani infection in Nicotiana benthamiana. The homolog in Oryza sativa, OsGABA-T, could also interact with EG1 to suppress the allergic necrosis induced by EG1. The OsGABA-T knocked out plants displayed enhanced susceptibility to R. solani and showed larger lesions. In conclusion, our results suggest that ZmGABA-T inhibits allergic necrosis induced by EG1 based on the combination with EG1, producing resistance to R. solani infection.