bluuebunny/crossref_metadata_2025 huggingface dataset:
Coastal landscape pattern optimization based on the spatial distribution heterogeneity of ecological risk
Authors: Yi Lin , Ma Sunjie , Tao Shiwei , Zhang Jiyi , Wang Jiujuan
Published: October 2022

The increasingly intensified development of coastal cities causes excessive consumption of natural resources, leading to environmental damage and increasing conflict between development and ecological protection. In addition to emphasizing ecological development, planners should pay more attention to the practical optimization and regulation of the developed landscape pattern. Taking Dafeng as an example, this study constructs a landscape-pattern optimization method suitable for the spatial distribution heterogeneity of ecological risk-level units in the coastal zone. The study is based on (a) an analysis of the composition and evolution characteristics of Dafeng’s coastal landscape elements, (b) the landscape pattern index of the ecosystem’s overall risk assessment, and (c) the minimal cumulative resistance (MCR) model. The study uses an ecosystem service value to build a resistance model by analyzing the medium and high-risk composition and distribution characteristics of space unit elements. Finally, 23 ecological sources, 14 ecological nodes, and 17 ecological corridors (total length 169.63 km) were built. The optimized coastal zone landscape pattern jointly protects the landscape area of high ecological value by 462.02 km2. The total ecological value is 105,01.71 million yuan. Landscape connectivity has been optimized, as well as the ecosystem’s stability and total service value. The optimization method proposed in this paper can reduce the protection area and cost. The spatial optimization unit is highly targeted, providing new ideas for the coastal cities to implement their ecological development and protection strategies.
Regional wave model climate projections for coastal impact assessments under a high greenhouse gas emission scenario
Authors: Su Jian , Murawski Jens , Nielsen Jacob W. , Madsen Kristine S.
Published: October 2022

In the future, shifts in wind storms across the North and Baltic Seas are highly unpredictable, challenging the projection of wave conditions for managing coastal hazards. Moreover, regional sea level rise (SLR), with very large uncertainty, complicates the situation for stakeholders seeking recommendations for climate adaptation plans. The purpose of this study is to examine the change of the storm surge and wind wave components of the water level due to climate change in a low tidal range Køge Bay near the entrance of the Baltic Sea. Under a high greenhouse gas emission scenario RCP8.5, we employed a regional climate model (HIRHAM) forced wave model (WAM) and focused on the wave model results during the “storm surge conditions” (exceeding 20 years storm surge events) and “stormy conditions” (exceeding 90th percentile of wave heights). We find that the change in both wave height and period in the future is negligible under “stormy conditions”. Nevertheless, under “storm surge conditions” when considering SLR, the simulated wave height is projected to double in the near future (mid-century) under RCP 8.5, and the wave period may also increase by about 1.5 seconds. This is because some high significant wave height events in the future are associated with the storm surge events when considering SLR. The findings suggest that the combined effects of mean sea level rise, storm surge and waves are likely to increase the risk to a bay with geography and exposure comparable to Køge Bay. As a result, the future plan for climate engineering protection should place a premium on the additional wave energy protection associated with storm surges.
Clinical features and prognostic factors of pulmonary carcinosarcoma: A nomogram development and validation based on surveillance epidemiology and end results database
Authors: Zhang Ming-Yi , Tang Lian-Sha , Qin Zhao-Juan , Hao Ya-Ting , Cheng Ke , Zheng Ai
Published: October 2022

Background

Pulmonary carcinosarcoma (PCS) is a rare but aggressive malignant disease in the lung. It is characterized by coexisting histologic elements of carcinomatous and sarcomatous components. This study aimed to comprehensively understand the clinical features of PCS and develop a nomogram for prognostic prediction of PCS patients.

Methods

Data were collected from the Surveillance Epidemiology and End Results (SEER) database between 1975 and 2018. Propensity-score matching (PSM) was used to match the demographic characteristic of the PCS vs. pulmonary sarcoma (PS). Cancer-specific survival (CSS) and overall survival (OS) were the main endpoints of the survival of patients and were evaluated using the Kaplan Meier curves and Cox proportional hazards regression. We further randomly split enrolled PCS patients from SEER into the training and validation sets. All independent predictors for OS of the training set were integrated to create a predictive nomogram. The performance of the nomogram was determined by discrimination, calibration ability, clinical usefulness, and risk stratification ability both in the training and validation cohorts. In addition, the clinical data of PCS patients from the West China Hospital were also retrospectively analyzed by this model.

Results

A total of 428 PCS patients and 249 PS patients were enrolled from SEER. Compared to pure PS, PCS was associated with significantly better survival in the unmatched cohorts, whereas non-significantly better survival after PSM. In subgroup analysis, PCS showed significantly worse survival than pure PS in subgroups among the race, marital status, and radiation treatment. A nomogram was constructed for PCS patients’ survival prediction by combining the independent risk factors, including gender, stage, surgery, radiation, and chemotherapy. The nomogram showed good discrimination, calibration, and predictive power in the training and validation sets. Risk stratification analysis indicated that the nomogram scores efficiently divided PCS patients into low and high-risk groups.

Conclusion

PCS is a rare malignant disease of the lung with distinct clinical features. It had a comparable survival compared with pure PS in the matched cohorts. In addition, a nomogram was developed and validated for predicting the OS in PCS patients.
The change of plasma metabolic profile and gut microbiome dysbiosis in patients with rheumatoid arthritis
Authors: Zhu Jing , Wang Tingting , Lin Yifei , Xiong Minghao , Chen Jianghua , Jian Congcong , Zhang Jie , Xie Huanhuan , Zeng Fanwei , Huang Qian , Su Jiang , Zhao Yi , Li Shilin , Zeng Fanxin
Published: October 2022

Objective

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, which is associated with progressive disability, systemic complications, and early death. But its etiology and pathogenesis are not fully understood. We aimed to investigate the alterations in plasma metabolite profiles, gut bacteria, and fungi and their role of them in the pathogenesis of RA.

Methods

Metabolomics profiling of plasma from 363 participants including RA (n = 244), systemic lupus erythematosus (SLE, n = 50), and healthy control (HC, n = 69) were performed using the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The differentially expressed metabolites were selected among groups and used to explore important metabolic pathways. Gut microbial diversity analysis was performed by 16S rRNA sequencing and ITS sequencing (RA = 195, HC = 269), and the specific microbial floras were identified afterward. The diagnosis models were established based on significant differential metabolites and microbial floras, respectively.

Results

There were 63 differential metabolites discovered between RA and HC groups, mainly significantly enriched in the arginine and proline metabolism, glycine, serine, and threonine metabolism, and glycerophospholipid metabolism between RA and HC groups. The core differential metabolites included L-arginine, creatine, D-proline, ornithine, choline, betaine, L-threonine, LysoPC (18:0), phosphorylcholine, and glycerophosphocholine. The L-arginine and phosphorylcholine were increased in the RA group. The AUC of the predictive model was 0.992, based on the combination of the 10 differential metabolites. Compared with the SLE group, 23 metabolites increased and 61 metabolites decreased in the RA group. However, no significant metabolic pathways were enriched between RA and SLE groups. On the genus level, a total of 117 differential bacteria genera and 531 differential fungal genera were identified between RA and HC groups. The results indicated that three bacteria genera (Eubacterium_hallii_group, Escherichia-Shigella, Streptococcus) and two fungal genera (Candida and Debaryomyces) significantly increased in RA patients. The AUC was 0.80 based on a combination of six differential bacterial genera and the AUC was 0.812 based on a combination of seven differential fungal genera. Functional predictive analysis displayed that differential bacterial and differential fungus both were associated with KEGG pathways involving superpathway of L-serine and glycine biosynthesis I, arginine, ornithine, and proline interconversion.

Conclusion

The plasma metabolism profile and gut microbe profile changed markedly in RA. The glycine, serine, and threonine metabolism and arginine and proline metabolism played an important role in RA.
Identification of mRNA expression biomarkers associated with epilepsy and response to valproate with co-expression analysis
Authors: Min Jun , Chen Qinglan , Wu Wenyue , Zhao Jing , Luo Xinming
Published: October 2022

Purpose

Valproate (VPA) resistance was reported to be an important predictor of intractable epilepsy. We conducted this study to identify candidate biomarkers in peripheral blood correlated with VPA resistance.

Methods

The microarray dataset (GSE143272) was downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed to construct co-expression modules and obtain the most prominent module associated with VPA resistance. Differentially expressed genes (DEGs) between VPA-responsive and VPA-resistant patients were obtained using the “Limma” package in R. The intersections between the most prominent module and DEGs were identified as target genes. Metascape was performed to discover the possible involved pathways of the target genes. GeneCards database was used to know the function of each target gene.

Results

All genes in the GSE143272 were divided into 24 different modules. Among these modules, the darkred module showed a pivotal correlation with VPA resistance. A total of 70 DEGs between VPA-responsive and VPA-resistant patients were identified. After taking the intersection, 25 target genes were obtained. The 25 target genes were significantly enriched in T cell receptor recognition, T cell receptor signaling pathway, regulation of T cell activation, cytokine–cytokine receptor interaction, and in utero embryonic development. Half of the target genes (CD3D, CD3G, CXCR3, CXCR6, GATA3, GZMK, IL7R, LIME1, SIRPG, THEMIS, TRAT1, and ZNF683) were directly involved in the T cell development, migration, and activation signaling pathway.

Conclusion

We identified 25 target genes prominently associated with VPA resistance, which could be potential candidate biomarkers for epilepsy resistance in peripheral blood. The peripheral blood T cells may play a crucial role in VPA resistance. Those genes and pathways might become therapeutic targets with clinical usefulness in the future.
The relationship of α-hydroxybutyrate dehydrogenase with 1-year outcomes in patients with intracerebral hemorrhage: A retrospective study
Authors: Limin Zhang , Alsamani Rasha , Jianwei Wu , Yijun Shi , Dan Wang , Yuehong Sun , Ziwei Liu , Huiwen Xu , Dongzhi Wang , Xingquan Zhao , Guojun Zhang
Published: October 2022

Background and aims

Cardiac enzymes are recognized as a valuable tool for predicting the prognosis of various cardiovascular diseases. The prognostic value of alpha-hydroxybutyrate dehydrogenase (α-HBDH) in patients with intracerebral hemorrhage (ICH) was ambiguous and not evaluated.

Methods

Two hundred and thirteen Chinese patients with ICH participated in the study from December 2018 to December 2019. Laboratory routine tests and cardiac enzymes, including α-HBDH level, were examined and analyzed. All the patients were classified into two groups by the median value of α-HBDH: B1 <175.90 and B2 ≥175.90 U/L. The clinical outcomes included functional outcome (according to modified Rankin Scale (mRS) score ≥3), all-cause death, and recurrent cerebro-cardiovascular events 1 year after discharge. Associations between the α-HBDH and the outcomes were evaluated using logistic regression analysis. Univariate survival analysis was performed by the Kaplan–Meier method and log-rank test.

Results

Of the 213 patients, 117 had α-HBDH ≥175.90 U/L. Eighty-two patients had poor functional outcomes (mRS≥3). During the 1-year follow-up, a total of 20 patients died, and 15 of them had α-HBDH ≥175.90 U/L during the follow-up time. Moreover, 24 recurrent events were recorded. After adjusting confounding factors, α-HBDH (≥175.90) remained an indicator of poor outcome (mRS 3-6), all-cause death, and recurrent cerebro-cardiovascular events. The ORs for B2 vs. B1 were 4.78 (95% CI: 2.60 to 8.78, P = 0.001), 2.63 (95% CI: 0.80 to 8.59, P = 0.11), and 2.40 (95% CI: 0.82 to 7.02, P = 0.11) for poor functional outcomes with mRS ≥ 3, all-cause death, and recurrent cerebro-cardiovascular events, respectively.

Conclusion

Increased α-HBDH at admission was independently related to poor functional outcome and all-cause mortality in patients with ICH at 1-year follow-up.
Impairment of muscular endothelial cell regeneration in dermatomyositis
Authors: Lemmer D. , Schmidt J. , Kummer K. , Lemmer B. , Wrede A. , Seitz C. , Balcarek P. , Schwarze K. , Müller G. A. , Patschan D. , Patschan S.
Published: October 2022

Background and aim

Inflammatory myopathies are heterogeneous in terms of etiology, (immuno)pathology, and clinical findings. Endothelial cell injury, as it occurs in DM, is a common feature of numerous inflammatory and non-inflammatory vascular diseases. Vascular regeneration is mediated by both local and blood-derived mechanisms, such as the mobilization and activation of so-called proangiogenic cells (PACs) or early endothelial progenitor cells (eEPCs). The current study aimed to evaluate parameters of eEPC integrity in dermatomyositis (DM), compared to necrotizing myopathy (NM) and to non-myopathic controls.

Methods

Blood samples from DM and NM patients were compared to non-myositis controls and analyzed for the following parameters: circulating CD133+/VEGFR-2+ cells, number of colony-forming unit endothelial cells (CFU-ECs), concentrations of angiopoietin 1, vascular endothelial growth factor (VEGF), and CXCL-16. Muscle biopsies from DM and NM subjects underwent immunofluorescence analysis for CXCR6, nestin, and CD31 (PECAM-1). Finally, myotubes, derived from healthy donors, were stimulated with serum samples from DM and NM patients, subsequently followed by RT-PCR for the following candidates: IL-1β, IL-6, nestin, and CD31.

Results

Seventeen (17) DM patients, 7 NM patients, and 40 non-myositis controls were included. CD133+/VEGFR-2+ cells did not differ between the groups. Both DM and NM patients showed lower CFU-ECs than controls. In DM, intramuscular CD31 abundances were significantly reduced, which indicated vascular rarefaction. Muscular CXCR6 was elevated in both diseases. Circulating CXCL-16 was higher in DM and NM in contrast, compared to controls. Serum from patients with DM but not NM induced a profound upregulation of mRNS expression of CD31 and IL-6 in cultured myotubes.

Conclusion

Our study demonstrates the loss of intramuscular microvessels in DM, accompanied by endothelial activation in DM and NM. Vascular regeneration was impaired in DM and NM. The findings suggest a role for inflammation-associated vascular damage in the pathogenesis of DM.
A multivariate comparison of electroencephalogram and functional magnetic resonance imaging to electrocorticogram using visual object representations in humans
Authors: Ebrahiminia Fatemeh , Cichy Radoslaw Martin , Khaligh-Razavi Seyed-Mahdi
Published: October 2022

Today, most neurocognitive studies in humans employ the non-invasive neuroimaging techniques functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG). However, how the data provided by fMRI and EEG relate exactly to the underlying neural activity remains incompletely understood. Here, we aimed to understand the relation between EEG and fMRI data at the level of neural population codes using multivariate pattern analysis. In particular, we assessed whether this relation is affected when we change stimuli or introduce identity-preserving variations to them. For this, we recorded EEG and fMRI data separately from 21 healthy participants while participants viewed everyday objects in different viewing conditions, and then related the data to electrocorticogram (ECoG) data recorded for the same stimulus set from epileptic patients. The comparison of EEG and ECoG data showed that object category signals emerge swiftly in the visual system and can be detected by both EEG and ECoG at similar temporal delays after stimulus onset. The correlation between EEG and ECoG was reduced when object representations tolerant to changes in scale and orientation were considered. The comparison of fMRI and ECoG overall revealed a tighter relationship in occipital than in temporal regions, related to differences in fMRI signal-to-noise ratio. Together, our results reveal a complex relationship between fMRI, EEG, and ECoG signals at the level of population codes that critically depends on the time point after stimulus onset, the region investigated, and the visual contents used.
Bioaffinity ultrafiltration coupled with HPLC-ESI-MS/MS for screening potential α-glucosidase inhibitors from pomegranate peel
Authors: Shi Rujie , Zhou Nong , Zhang Han , Gong Min , Han Lin
Published: October 2022

Pomegranate peel (PoP) contains plenty of bioactive compounds and exhibits strong activity to prevent postprandial hyperglycaemia and improve diabetes mellitus. Presently, bioaffinity ultrafiltration coupled with high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) is employed to screen and identify the efficient α-glucosidase inhibitors in PoP and the detailed inhibitory mechanisms are further investigated. The results show that many substances, including ellagic acid, kaempferol, gallic acid, and resveratrol in PoP reveal strong activity to inhibit α-glucosidase and ellagic acid (EA) is screened as the most effective compound. Further research indicates that EA plays a competitive and reversible inhibition role against α-glucosidase with the value of Ki was 6.24 × 105 mol/L. EA also directly interacts with the amino acids of α-glucosidase mainly via van der Waals forces and hydrogen bonds, thereby, influencing the secondary structure and stability of α-glucosidase. Finally, the α-glucosidase inhibitory activity of EA is further confirmed to significantly reduce postprandial blood glucose in vivo.
Establishment of a quality evaluation system of sweet potato starch using multivariate statistics
Authors: Ma Chen , Zhang Yi , Yue Ruixue , Zhang Wenting , Sun Jian , Ma Zhimin , Niu Fuxiang , Zhu Hong , Liu Yunfeng
Published: October 2022

Background

The quality of starch greatly affects the quality of processed products. There are many indexes for quality evaluation of starch. Currently, amylose content is considered the chief index in the quality evaluation of sweet potato starch, which is entirely based on tradition (experience) method. The existing evaluation standards lack quality evaluation standards for sweet potato starch.

Purpose

To screen reasonable evaluation indexes of sweet potato starch, and establish a scientific and systematic evaluation system of sweet potato starch.

Methods

Twenty-two components and quality indexes of sweet potato starch were measured. The evaluation indexes of sweet potato starch were screened based on a statistical description, correlation analysis, and principal component analysis (PCA), and a quality evaluation model of sweet potato starch for brewing was established based on analytic hierarchy process. The calculated values of the model were verified by linear fitting with standardized sensory evaluation values.

Results

The coefficient of variation of total starch content (%), amylose content (%), amylopectin content (%), L* value, ΔE, water absorption capacity (g/g), and pasting temperature was less than 6%, while the coefficient of variation of other indexes was larger. In addition, there were different degrees of correlation among the indexes. PCA was used to identify interrelated variables, and the first six principal components together account for 82.26% of the total variability. Then, seven core indexes — setback (cp), rate of regression (%), ratio of amylose to amylopectin (%), gel strength (kgf/cm2), a* value, ash content (%), and solubility (%) — were selected from the six principal components according to the load value of the rotation matrix. These seven core indexes replaced the original 22 indexes to simplify the evaluation of sweet potato starch. The quality evaluation model of sweet potato starch was Y = 0.034X2 + 0.321X6 + 0.141X8 + 0.08X17 + 0.023X19 + 0.08X21 + 0.321X22.

Conclusion

The comprehensive evaluation system of sweet potato starch can accurately predict the quality of sweet potato starch. The development of such a system is of great significance to the post-harvest processing of high-starch sweet potato and the breeding of high-quality and high-starch sweet potato varieties.
Research on construction method and validity mechanism of robust analysis model in snow peach quality detection based on visible-near infrared spectroscopy
Authors: Hao Yong , Li Xiyan , Zhang Chengxiang , Lei Zuxiang
Published: October 2022

Visible-near infrared (Vis-NIR) spectra analysis method is widely used in the quality grading of bulk fruits with its rapid, non-destructive, diverse detection modes and flexible modular integration scheme. However, during the online grading of fruits, the random mechanized way of dropping fruit onto the conveyor belt method and the open detection environment led to more spectral abnormal samples, which affect the accuracy of the detection. In this paper, the soluble solids content (SSC) of snow peach is quantitatively analyzed by static and online detection methods. Several spectral preprocessing methods including Norris-Williams Smoothing (NWS), Savitzky-Golay Smoothing (SGS), Continuous Wavelet Derivative (CWD), Multivariate Scattering Correction (MSC), and Variable Sorting for Normalization (VSN) are adopted to eliminate spectral rotation and translation errors and improve the signal-to-noise ratio. Monte Carlo Uninformative Variable Elimination (MCUVE) method is used for the selection of optimal characteristic modeling variables. Partial Least Squares Regression (PLSR) is used to model and analyze the preprocessed spectra and the spectral variables optimized by MCUVE, and the effectiveness of the method is evaluated. Sparse Partial Least Squares Regression (SPLSR) and Sparse Partial Robust M Regression (SPRMR) are used for the construction of robust models. The results showed that the SGS preprocessing method can effectively improve the analysis accuracy of static and online models. The MCUVE method can realize the extraction of stable characteristic variables. The SPRMR model based on SGS preprocessing method and the effective variables has the optimal analysis results. The analysis accuracy of snow peach static model is slightly better than that of online analytical model. Through the test results of the PLSR, SPLSR and SPRMR models by the artificially adding noise test method, it can be seen that the SPRMR method eliminates the influence of abnormal samples on the model during the modeling process, which can effectively improve the anti-noise ability and detection reliability.
Physical characterization of frozen fruits from eight cultivars of the North American pawpaw (Asimina triloba)
Authors: Adainoo Bezalel , Crowell Brendan , Thomas Andrew L. , Lin Chung-Ho , Cai Zhen , Byers Patrick , Gold Michael , Krishnaswamy Kiruba
Published: October 2022

Pawpaw (Asimina triloba [L.] Dunal) is an underutilized fruit native to North America. The fruit has a short shelf life, and browns and softens rapidly after harvesting. These characteristics present a challenge to the advancement of pawpaw as an economically viable specialty crop. This study evaluated the physical characteristics of frozen fruits from eight cultivars of the pawpaw fruit to establish the processing potential of pawpaw fruits. The results show that freeze-thaw cycle may have influenced the peel thickness, peel color, and pulp color of the fruits. Fruits of the Susquehanna cultivar had the highest fruit weight and pulp weight, making them potentially the most suitable for pulp processing. The pawpaw fruits had almost neutral pH ranging between 6.07 ± 0.21 and 6.47 ± 0.11, which could contribute to the rapid browning on exposure to air since an acidic pH is important for slowing enzymatic browning. To aid pawpaw juice extraction, enzymatic treatments may be necessary to increase the juice yield from the pulp. Overleese fruits may be the best for pawpaw juice production. These findings can aid in the selection of processing equipment and guide processors in their efforts to utilize pawpaw fruits to avoid postharvest and post-processing losses.
Proanthocyanidins-loaded complex coacervates-based drug delivery attenuates oral squamous cell carcinoma cells metastatic potential through down-regulating the Akt signaling pathway
Authors: Liu Ju-Fang , Wee Yinshen , Luo Shen-Dean , Chang Shwu-Fen , Jia Shihai , Feng Sheng-Wei , Huang Huei-Mei , Lin Jiann-Her , Wang Ching-Shuen
Published: October 2022

Oral cancer, constituted up to 90% by squamous cell carcinomas, is a significant health burden globally. Grape seed proanthocyanidins (PA) have been suggested as a potential chemopreventive agent for oral cancer. However, their efficacy can be restricted due to the low bioavailability and bioaccessibility. Inspired by sandcastle worm adhesive, we adapted the concept of complex coacervation to generate a new type of drug delivery platform. Complex coacervates are a dense liquid phase formed by the associative separation of a mixture of oppositely charged polyelectrolytes, can serve as a drug delivery platform to protect labile cargo. In this study, we developed a complex coacervates-based delivery of PA. The release kinetics was measured, and anticancer effects were determined in two human tongue squamous cell carcinoma cell lines. The results showed that complex coacervate successfully formed and able to encapsulate PA. Additionally, PA were steadily released from the system in a pH-dependent manner. The drug delivery system could significantly inhibit the cell proliferation, migration, and invasion of cancer cells. Moreover, it could markedly reduce the expression of certain matrix metalloproteinases (MMP-2, 9, and 13) crucial to metastatic processes. We also found that suppression of protein kinase B (Akt) pathway might be the underlying mechanism for these anticancer activities. Taken together, complex coacervates-based delivery of PA can act as an effective anticancer approach for oral cancer therapy.
Deregulated calcium signaling in blood cancer: Underlying mechanisms and therapeutic potential
Authors: Immanuel Tracey , Li Jixia , Green Taryn N. , Bogdanova Anna , Kalev-Zylinska Maggie L.
Published: October 2022

Intracellular calcium signaling regulates diverse physiological and pathological processes. In solid tumors, changes to calcium channels and effectors via mutations or changes in expression affect all cancer hallmarks. Such changes often disrupt transport of calcium ions (Ca2+) in the endoplasmic reticulum (ER) or mitochondria, impacting apoptosis. Evidence rapidly accumulates that this is similar in blood cancer. Principles of intracellular Ca2+ signaling are outlined in the introduction. We describe different Ca2+-toolkit components and summarize the unique relationship between extracellular Ca2+ in the endosteal niche and hematopoietic stem cells. The foundational data on Ca2+ homeostasis in red blood cells is discussed, with the demonstration of changes in red blood cell disorders. This leads to the role of Ca2+ in neoplastic erythropoiesis. Then we expand onto the neoplastic impact of deregulated plasma membrane Ca2+ channels, ER Ca2+ channels, Ca2+ pumps and exchangers, as well as Ca2+ sensor and effector proteins across all types of hematologic neoplasms. This includes an overview of genetic variants in the Ca2+-toolkit encoding genes in lymphoid and myeloid cancers as recorded in publically available cancer databases. The data we compiled demonstrate that multiple Ca2+ homeostatic mechanisms and Ca2+ responsive pathways are altered in hematologic cancers. Some of these alterations may have genetic basis but this requires further investigation. Most changes in the Ca2+-toolkit do not appear to define/associate with specific disease entities but may influence disease grade, prognosis, treatment response, and certain complications. Further elucidation of the underlying mechanisms may lead to novel treatments, with the aim to tailor drugs to different patterns of deregulation. To our knowledge this is the first review of its type in the published literature. We hope that the evidence we compiled increases awareness of the calcium signaling deregulation in hematologic neoplasms and triggers more clinical studies to help advance this field.
Blood–brain barrier and brain structural changes in lung cancer patients with non-brain metastases
Authors: Zhang Da-Fu , Ma Huan , Yang Guang-Jun , Zhang Zhi-Ping , He Yin-Fu , Feng Mao-Yang , Shan Bao-Ci , Xu Xiu-Feng , Ding Ying-Ying , Cheng Yu-Qi
Published: October 2022

Purpose

To explore the relationship between blood-brain barrier (BBB) leakage and brain structure in non-brain metastasis lung cancer (LC) by magnetic resonance imaging (MRI) as well as to indicate the possibility of brain metastasis (BM) occurrence.

Patients and methods

MRI were performed in 75 LC patients and 29 counterpart healthy peoples (HCs). We used the Patlak pharmacokinetic model to calculate the average leakage in each brain region according to the automated anatomical labeling (AAL) atlas. The thickness of the cortex and the volumes of subcortical structures were calculated using the FreeSurfer base on Destrieux atlas. We compared the thickness of the cerebral cortex, the volumes of subcortical structures, and the leakage rates of BBB, and evaluated the relationships between these parameters.

Results

Compared with HCs, the leakage rates of seven brain regions were higher in patients with advanced LC (aLC). In contrast to patients with early LC (eLC), the cortical thickness of two regions was decreased in aLCs. The volumes of twelve regions were also reduced in aLCs. Brain regions with increased BBB penetration showed negative correlations with thinner cortices and reduced subcortical structure volumes (P<0.05, R=-0.2 to -0.50). BBB penetration was positively correlated with tumor size and with levels of the tumor marker CYFRA21-1 (P<0.05, R=0.2–0.70).

Conclusion

We found an increase in BBB permeability in non-BM aLCs that corresponded to a thinner cortical thickness and smaller subcortical structure volumes. With progression in LC staging, BBB shows higher permeability and may be more likely to develop into BM.
Insulin-like growth factor 2 receptor is a key immune-related gene that is correlated with a poor prognosis in patients with triple-negative breast cancer: A bioinformatics analysis
Authors: Zhong Ying , Ren Xinyu , Cao Xi , Xu Yali , Song Yu , Zhou Yidong , Mao Feng , Shen Songjie , Wang Zhe , Sun Qiang
Published: October 2022

Background

Immunotherapy plays an important role in the treatment of triple-negative breast cancer (TNBC). This study aimed to identify immune-related genes that are associated with the prognosis of patients with TNBC as possible targets of immunotherapy, alongside their related tumor-infiltrating lymphocytes (TILs).

Methods

The clinical data and gene expression profiles of patients with breast cancer were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and divided into training (n = 1,053) and verification (n = 508) groups. CIBERSORT was used to predict the differences in immune cell infiltration in patient subsets that were stratified according to risk. Gene Ontology (GO) enrichment analysis was used to identify pathways associated with immune-related genes in patient subsets that were stratified according to risk. The clinical data and insulin-like growth factor 2 receptor (IGF2R) expression profiles of patients with breast cancer were extracted from METABRIC. The expression of IGF2R and TILs were evaluated in a cohort containing 282 untreated patients with TNBC. The correlations of IGF2R expression, TILs, and clinicopathological parameters with patient prognosis were analyzed in the whole cohort.

Results

The prognostic model, which was composed of 26 immune-related gene pairs, significantly distinguished between high- and low-risk patients. Univariate and multivariate analyses indicated that the model was an independent prognostic factor for breast cancer. Among the identified genes, the expression of IGF2R significantly distinguished between high- and low-risk patients in TCGA (P = 0.008) and in METABRIC patients (P < 0.001). The expression of IGF2R was significantly associated with clinical risk factors such as TNBC, estrogen receptor (ER)–negative expression, human epidermal growth factor receptor 2 (HER2)–positive expression, and age ≤60 years old in METABRIC patients. In addition, the patients with IGF2R-positive expression had lower disease-free survival (DFS) rates than those with IGF2R-negative expression in the TNBC cohort (67.8% vs. 78.5%, P = 0.023). IGF2R expression also was significantly negatively correlated with TILs, particularly with CD8+ TILs and CD19+ TILs in the cohort of patients with TNBC.

Conclusion

IGF2R can be used as an indicator of a poor prognosis in patients with TNBC and as a potential target and research direction for TNBC immunotherapy in the future.
A phase II study of buparlisib in relapsed or refractory thymomas
Authors: Abu Zaid Mohammad I. , Radovich Milan , Althouse Sandra , Liu Hao , Spittler Aaron J. , Solzak Jeffrey , Badve Sunil , Loehrer Patrick J.
Published: October 2022

Purpose

To investigate the efficacy and safety of buparlisib, an oral pan-PI3K inhibitor, in relapsed or refractory thymomas.

Methods

This was a single center, single arm, open label phase II trial of buparlisib in patients with recurrent thymoma who have progressed after at least one prior line of treatment. The primary endpoint was objective response rate (complete response [CR] + partial response [PR]). Secondary endpoints included toxicity; progression free survival (PFS); overall survival (OS); disease control rate (DCR), i.e., the percentage of patients who achieve either PR or CR or stable disease [SD] for at least 4 months.

Results

Between 10/13/2014 and 1/18/2017, 14 patients with stage IV disease were enrolled. Median age was 58y (23–74). 71% were females and 71% white. All patients had WHO B2 (29%) or B3 (71%) thymoma. Patients received buparlisib for a median of 4.5m (2–33). At a median follow up of 16.6m (2.4–31.3), onr patients (7%) achieved a PR. DCR was 50%. Median PFS was 11.1m (95% CI 2.9 – 18.8). Median OS, updated as of March, 2021 was 22.5m (10.7–31.3). Most common grade 3-4 adverse events related to buparlisib were dyspnea (21%), rash (14%), elevated transaminases (14%), cough (7%), pneumonitis (7%), anxiety (7%), fatigue (7%) and hyperglycemia (7%). Reasons for treatment discontinuation included progression of disease (n= 5), rash (n=4), pulmonary toxicity (n=3), sinusitis (n=1), and disseminated toxoplasmosis plus autoimmune cholangitis (n=1). As of 3/2021, 8 patients have died, 7 due to disease progression and 1 due to central nervous system toxoplasmosis and autoimmune cholangitis.

Conclusion

Buparlisib showed modest activity in patients with relapsed or refractory thymomas. Further investigation of PI3K pathway targeted therapy in thymoma is warranted. (clinicaltrials.gov ID: NCT02220855).

Clinical trial registration

clinicaltrials.gov, identifier (NCT02220855)
Case report: Going through pregnancy safely after twice partial nephrectomy for bilateral kidneys with HLRCC-associated RCC
Authors: Dai Kunhan , Jiang Wencheng , Chen Siyu , Luo Shengjun , Ding Siwei , Wang Delin
Published: October 2022

Background

HLRCC-associated RCC (hereditary leiomyomatosis and renal cell cancer-associated renal cell carcinoma) caused by germline mutations of the fumarate hydratase (FH) gene is a rare autosomal dominant genetic renal cancer. At present, there are no reports of bilateral kidneys with HLRCC-associated RCC, let alone safe pregnancy after twice partial nephrectomy for bilateral kidney HLRCC-associated RCC.

Case presentation

We report a 25-year-old woman with bilateral renal tumors detected by ultrasound screening during a routine checkup. CT revealed a soft tissue mass in the parenchyma of the left kidney and a nodular soft tissue mass in the lower pole of the right kidney. She underwent robot-assisted laparoscopic left partial nephrectomy and underwent laparoscopic right partial nephrectomy 3 months after the first surgery. Heterozygous mutation in the FH gene on the patient’s tumor tissue was detected by genetic testing. Combined with the patient’s medical history, microstructure and immunohistochemical staining of tumor tissue, and genetic test results, the pathological reports after two operations concluded HLRCC-associated RCC. Then, she was injected with interferon and nivolumab as a preventative treatment against tumor recurrence. Up to 38 months after surgery, having given birth to a baby, till now there was no tumor progression.

Conclusions

This is a clinically significant case, as it provides a reference for pregnancy in patients undergoing partial nephrectomy for bilateral kidneys with HLRCC-associated RCC and may indicate an effective approach to preventing tumor recurrence by nivolumab in patients with HLRCC-associated RCC.
A bone-based 3D scaffold as an in-vitro model of microenvironment–DLBCL lymphoma cell interaction
Authors: Ceccato Jessica , Piazza Maria , Pizzi Marco , Manni Sabrina , Piazza Francesco , Caputo Ilaria , Cinetto Francesco , Pisoni Lorena , Trojan Diletta , Scarpa Riccardo , Zambello Renato , Tos Angelo Paolo Dei , Trentin Livio , Semenzato Gianpietro , Vianello Fabrizio
Published: October 2022

About 30% of patients with diffuse large B-cell lymphoma (DLBCL) relapse or exhibit refractory disease (r/r DLBCL) after first-line immunochemotherapy. Bone marrow (BM) involvement confers a dismal prognosis at diagnosis, likely due to the interaction between neoplastic cells and a complex tumor microenvironment (TME). Therefore, we developed a 3D in-vitro model from human decellularized femoral bone fragments aiming to study the role of mesenchymal stromal cells (MSC) and the extracellular matrix (ECM) in the adaptation, growth, and drug resistance of DLBCL lymphoma cells. The 3D spatial configuration of the model was studied by histological analysis and confocal and multiphoton microscopy which allowed the 3D digital reproduction of the structure. We proved that MSC adapt and expand in the 3D scaffold generating niches in which also other cell types may grow. DLBCL cell lines adhered and grew in the 3D scaffold, both in the presence and absence of MSC, suggesting an active ECM–lymphocyte interaction. We found that the germinal center B-cell (GCB)-derived OCI-LY18 cells were more resistant to doxorubicin-induced apoptosis when growing in the decellularized 3D bone scaffold compared to 2D cultures (49.9% +/- 7.7% Annexin V+ cells in 2D condition compared to 30.7% + 9.2% Annexin V+ 3D adherent cells in the ECM model), thus suggesting a protective role of ECM. The coexistence of MSC in the 3D scaffold did not significantly affect doxorubicin-induced apoptosis of adherent OCI-LY18 cells (27.6% +/- 7.3% Annexin V+ 3D adherent cells in the ECM/MSC model after doxorubicin treatment). On the contrary, ECM did not protect the activated B-cell (ABC)-derived NU-DUL-1 lymphoma cell line from doxorubicin-induced apoptosis but protection was observed when MSC were growing in the bone scaffold (40.6% +/- 5.7% vs. 62.1% +/- 5.3% Annexin V+ 3D adherent cells vs. 2D condition). These data suggest that the interaction of lymphoma cells with the microenvironment may differ according to the DLBCL subtype and that 2D systems may fail to uncover this behavior. The 3D model we proposed may be improved with other cell types or translated to the study of other pathologies with the final goal to provide a tool for patient-specific treatment development.
The learning curve for robot-assisted radical cystectomy with total intracorporeal urinary diversion based on radical cystectomy pentafecta
Authors: Noh Tae Il , Shim Ji Sung , Kang Sung Gu , Cheon Jun , Pyun Jong Hyun , Kang Seok Ho
Published: October 2022

Objective

To analyze the learning curve for robot- assisted radical cystectomy (RARC) with total intracorporeal urinary diversion (ICUD) in terms of both time efficiency and quality of surgery based on radical cystectomy (RC)-pentafecta.

Patients and methods

We identified 203 consecutive patients who underwent RARC with ICUD of the ileal conduit (IC, 85) and orthotopic neobladder (ONB, 118) performed by a single surgeon between 2011 and 2021. We grouped ten consecutive patients into time-associated blocks according to the operation order. Process efficiency and operation quality were measured based on the surgeon’s console time and attainment/score sum of RC-pentafecta. The overcoming point of the learning curve was defined graphically and statistically.

Results

The mean follow-up period was 44.5 ± 30.7 months. Of the 203 patients, 109 (53.7%) attained the five criteria of RC-pentafecta (ONB vs IC, 50.6% vs. 55.9%, p = 0.35). The attainment rate and sum of the RC-pentafecta score of the third group were not significantly different from those of all patients (40.0% vs. 53.7%, p = 0.369, 4.00 ± 1.05 vs. 4.41 ± 0.75, p = 0.137, respectively), and the proficiency in operation quality was satisfactory in the third group. The console times continually improved and stabilized after the 140th case (IC, 60; ONB, 80), and the attainment rate and sum of the RC-pentafecta were significantly different between before and after the 140th case (p<0.001).

Conclusion

A single surgeon’s learning curve for RARC with ICUD and pelvic lymph node dissection (PLND) showed an acceptable level of proficiency after 30 consecutive cases in terms of the operation quality. However, for an expert surgeon, 140 cases were required to reach a plateau in time efficiency and second leap with the RC-pentafecta. RARC with ICUD and PLND can be performed safely without compromising functional outcomes and complications through sharing and transmission of standardized techniques.
Health-related quality of life measured by EQ-5D-3L for the spouses of breast cancer patients
Authors: Sun Li-Fei , Huang Sheng , Li Yun-Fen , Yang Zhuang-Qing , Yang Xiao-Juan , Zou Jie-Ya , Wang Xiao-Wen , Nie Jian-Yun
Published: October 2022

To explore factors influencing the health-related quality of life of spouses of breast cancer patients and the suitable questionnaires for this purpose. A cross-sectional study was conducted in the Third Affiliated Hospital of Kunming Medical University. The spouses of breast cancer patients were included and evaluated via face-to-face interviews. Self-designed demographic characteristics and disease-related questionnaires, the 12-item health survey questionnaire (SF-12), the three-level European five-dimensional health status scale (EQ-5D-3L), and the Social Support Rate Scale (SSRS) were used. The internal consistency reliability measure Cronbach’s coefficient, criterion-related validity, construct validity, and sensitivity were used to evaluate the applicability of the EQ-5D-3L. Univariate and multivariate analyses were performed to analyze the factors associated with the health-related quality of life of spouses of breast cancer patients. We investigated a total of 100 spouses of breast cancer patients. Cronbach’s α, the internal consistency reliability coefficient, was 0.502. The EQ-5D-3L health utility score was moderately correlated with PCS-12 (r=0.46, p=0.0001) and weakly correlated with MCS-12 (r=0.35, p=0.0001). The EQ-5D-3L health utility score for the spouses of breast cancer patients was 0.870, and the EQ-VAS was 78.3. In multivariate analysis, social support and cognition of the treatment effect were factors that influenced the EQ-5D-3L health utility score. The EQ-5D-3L has good reliability, validity, and sensitivity for measuring the physiological aspects of the health-related quality of life of spouses of BC patients. EQ-5D-3L was considered suitable for this study.
A spotlight on alkaloid nanoformulations for the treatment of lung cancer
Authors: S. M. Sindhoor , Naveen N. Raghavendra , Rao GSN Koteswara , Gopan Gopika , Chopra Hitesh , Park Moon Nyeo , Alshahrani Mohammed Merae , Jose Jobin , Emran Talha Bin , Kim Bonglee
Published: October 2022

Numerous naturally available phytochemicals have potential anti-cancer activities due to their vast structural diversity. Alkaloids have been extensively used in cancer treatment, especially lung cancers, among the plant-based compounds. However, their utilization is limited by their poor solubility, low bioavailability, and inadequacies such as lack of specificity to cancer cells and indiscriminate distribution in the tissues. Incorporating the alkaloids into nanoformulations can overcome the said limitations paving the way for effective delivery of the alkaloids to the site of action in sufficient concentrations, which is crucial in tumor targeting. Our review attempts to assess whether alkaloid nanoformulation can be an effective tool in lung cancer therapy. The mechanism of action of each alkaloid having potential is explored in great detail in the review. In general, Alkaloids suppress oncogenesis by modulating several signaling pathways involved in multiplication, cell cycle, and metastasis, making them significant component of many clinical anti-cancerous agents. The review also explores the future prospects of alkaloid nanoformulation in lung cancer. So, in conclusion, alkaloid based nanoformulation will emerge as a potential gamechanger in treating lung cancer in the near future.