bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of a tumor microenvironment-related prognostic signature in lung adenocarcinoma and immune infiltration analysis*
Authors: Li Zhou , Feng Yanqi , Li Piao , Wang Shennan , Li Ruichao , Xia Shu
Published: June 2023

Objective

Tumor-infiltrating immune cells and stromal cells in the tumor microenvironment (TME) significantly affect the prognosis of and immune response to lung adenocarcinoma (LUAD). In this study, we aimed to develop a novel TME-related prognostic model based on immune and stromal genes in LUAD.

Methods

LUAD data from the TCGA database were used as the training cohort, and three Gene Expression Omnibus (GEO) datasets were used as the testing cohort. The Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data algorithm was used to analyze the immune and stromal genes involved in the TME. Kaplan-Meier and Cox regression analyses were used to identify prognostic genes and construct a TME-related prognostic model. Gene set enrichment analysis and TIMER were used to analyze the immune features and signaling pathways of the model.

Results

A TME-related prognostic model based on six hub genes was generated that significantly stratified patients into the high- and low-risk groups in terms of overall survival. The model had strong predictive ability in both the training (TCGA) and testing (GEO) datasets and could serve as an independent prognostic factor for LUAD. Moreover, the low-risk group was characterized by greater immune cell infiltration and antitumor immune activity than the high-risk group. Importantly, the signature was closely associated with immune checkpoint molecules, which may serve as a predictor of patient response to immunotherapy. Finally, the hub genes BTK, CD28, INHA, PIK3CG, TLR4, and VEGFD were considered novel prognostic biomarkers for LUAD and were significantly correlated with immune cells.

Conclusion

The TME-related prognostic model could effectively predict the prognosis and reflect the TME status of LUAD. These six hub genes provided novel insights into the development of new therapeutic strategies.
Expression and prediction of genes related to IGF2BP3 in gastric cancer*
Authors: Li Yulong , Yang Yang , Sun Ruifang
Published: June 2023

Objective

Gastric cancer (GC) is one of the most prevalent cancers worldwide and is associated with high morbidity and mortality rates. The IGF2 mRNA-binding protein (IGF2BP) participates in a variety of cancers. The aim of this study was to analyze the expression of IGF2BP3 and explore the genes related to IGF2BP3 in GC.

Methods

Bioinformatics software was used to analyze the expression of IGF2BP1, IGF2BP2, and IGF2BP3 in tumors, and the expression of IGF2BPs in the GSE118897 dataset. Immunohistochemistry was performed to detect the protein level of IGF2BP3 in GC samples. cBioPortal was used to query gene alteration of IGF2BP3. LinkedOmics was used to identify genes related to IGF2BP3.

Results

Sangerbox analysis showed that the expression of all IGF2BP family members was higher in GC. cBioporta analysis showed that gene alteration of IGF2BP3 in stomach adenocarcinoma included mutation and amplificatio. LinkedOmics analysis showed that many genes were correlated with IGF2BP3, such as PLAGL2, GET4, IGF2BP1, HMGA2, CLDN6, HOXC13, SMARCA2, TMEM66, CIRBP, NFIX, SLC25A12, and CYB5D2.

Conclusion

In this study, we founded that IGF2BP3 was overexpressed in GC. Furthermore, this study identified potential genes related to IGF2BP3 in GC, which should be studied further.
Role of chemokines in the hepatocellular carcinoma microenvironment and their translational value in immunotherapy*
Authors: Wang Yijun , Sun Mengyu , Zhang Tongyue , Feng Yangyang , Luo Xiangyuan , Xie Meng , Ji Xiaoyu , Liu Danfei , Huang Wenjie , Xia Limin
Published: June 2023

The difficulty of early diagnosis, high tumor heterogeneity, and high recurrence and metastasis rates lead to an unsatisfactory treatment status for hepatocellular carcinoma (HCC). HCC is a typical inflammation-driven tumor. Chronic inflammation allows nascent tumors to escape immunosurveillance. Chemokines are small, soluble, secreted proteins that can regulate the activation and trafficking of immune cells during inflammation. Several studies have shown that various chemokines with overarching functions disrupt the immune microenvironment during the initiation and progression of HCC. The dysregulated chemokine network in HCC contributes to multiple malignant processes, including angiogenesis, tumor proliferation, migration, invasion, tumor low response, and resistance to immune therapy. Here, we summarize the current studies focusing on the role of chemokines and their receptors in the HCC immune microenvironment, highlighting potential translational therapeutic uses for modulating the chemokine system in HCC.
Recent advances in targeted therapy for ovarian cancer
Authors: Qin Tianyu , Chen Gang
Published: June 2023

The global burden of ovarian cancer is gradually increasing while patients still suffer from relatively limited treatment options. With recent advances in the decoding of the molecular landscape of ovarian cancer, more options in targeted strategy were offered and can therefore be tailored in different clinical settings for individual patient. Targeting of the abnormal angiogenesis process is the first significant clinical breakthrough which revolutionized the treatment of advanced ovarian cancer, followed by the advent of poly-(ADP)-ribose polymerase (PARP) inhibitors. These two strategies represented by bevacizumab and olaparib respectively underwent tests of numerous clinical trials. In recent years, immune checkpoint inhibitors (ICIs) have been incorporated into the blueprint of ovarian cancer treatment though the effectiveness still left much to be desired. Herein, we systematically outlined recent advances in targeted therapy for ovarian cancer and summarized the landmark clinical trials for each targeted therapy including angiogenesis inhibitors, PARP inhibitors and ICIs.
Metabolic reprogramming drives homeostasis and specialization of regulatory T cells in cancer
Authors: Li Le , Xiong Zezhong , Hu Zhiquan , Zeng Xing , Wang Zhihua
Published: June 2023

Transcription factor forkhead box P3 (Foxp3)+ regulatory T (Treg) cells are receiving increasing attention because this unique subset of T cells is characterized by exerting negative regulatory function of cellular immune responses. The resultant suppression of anti-tumor immunity in the tumor microenvironment (TME) is regarded as a major obstacle to immunotherapies in a plethora of cancers. Thus, an integrated understanding of the intrinsic correlation between tumors and Treg cell biology is urgently required. This review focuses on the peculiar biochemical effects of tumor metabolic environments on Tregs and how Tregs orchestrate internal metabolic switches and altered metabolic pathways and molecules to survive and function after the remodeling of homeostasis and specialization, providing new directions for immunotherapies.
Mechanism of lncRNA SNHG19 miR-299-5p MAPK6 signaling axis promoting metastasis of non-small cell lung cancer cells
Authors: Zhong Qian , Qiu Rong
Published: June 2023

Objective

The aim of this study was to explore the mechanism behind lncRNA small nucleolar RNA host gene 19 (lncRNA SNHG19)/microrNA-299-5P (miR-299-5p)/mitogen-activated protein kinase 6 (MAPK6) signaling axis promoting metastasis of non-small cell lung cancer (NSCLC).

Methods

To analyze the abnormal expression of lncRNAs in NSCLC, 50 surgically resected NSCLC and adjacent tissue samples were collected from August 2021 to August 2022. The mRNA expression levels of lncRNA SNHG19, Mir-299-5p, and MAPK6 were detected by qRT-PCR. The functions of lncRNA SNHG19, Mir-299-5p and MAPK6 were investigated by CCK-8, clone formation, EdU, scratch, Transwell western blotting (WB)and in vivo xenograft assay. RNA fluorescence in-situ hybridization (FISH), RNA pull-down, dual luciferase reporter, and RNA co-immunoprecipitation assays were used to explore the mechanism of action between lncRNA SNHG19, miR-299-5p, and MAPK6.

Results

High expression of lncRNA SNHG19 was correlated with poor prognosis, tumor size, lymph node metastasis, and TNM stage in NSCLC patients (P < 0.05). Cell function experiments showed that lncRNA SNHG19 could improve the proliferation, clone formation, migration, and invasion ability of A549 cells both in vitro and in vivo (all P < 0.05) and increased the relative expression levels of vimentin and MAPK6 (P < 0.05). The relative expression level of E-cadherin was decreased (P < 0.05). lncRNA SNHG19 can interact with Mir-299-5p and regulate the expression level of MAPK6.

Conclusion

lncRNA SNHG19 is upregulated in NSCLC tissues and cells, and its high expression is associated with tumor progression and poor survival. Moreover, it can act as a molecular sponge for Mir-299-5p to regulate MAPK6 expression and promote the proliferation and metastasis of A549 cells.
A novel derivative of Genistein inhibits proliferation of ovarian cancer HO-8910 cells by regulating reactive oxygen species*
Authors: Gao Yanping , Dong Zhiyong , Bai Jun
Published: June 2023

Objective

To investigate the anticancer effect of a novel derivative of genistein (5-hydroxy-4′-nitro-7-propionyloxy-genistein, HNPG) on human ovarian cancer HO-8910 cells and its possible molecular mechanism.

Methods

HO-8910 cells were cultured in vitro, and the inhibitory effect of HNPG on proliferation was determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The effect of HNPG on inducing apoptosis was examined using FCM with Annexin V-FITC and propidium iodide staining. The effect of HNPG on regulating reactive oxygen species (ROS) was measured using FCM with 2′,7′-di chlorodihydro-fluorescein diacetate staining. The effect of HNPG on modulating mitochondrial membrane potential (MMP) was determined using FCM with lipophilic cationic dye 2 (6 Amino 3 imino 3H xanthen 9 yl) benzoic acid methyl ester (Rh123) staining. The bioactivity of superoxide dismutase (SOD) and catalase (CAT) and the content of glutathione (GSH) and malondialdehyde (MDA) were detected using enzyme-linked immunosorbent assay. The related apoptotic proteins, including bcl-2, bax, cyt-c, and cleaved-caspase-3, were assessed using western blotting.

Results

HNPG exhibited dramatic antitumor activity against HO-8910 cells in vitro, inhibited proliferation, and induced apoptosis in a time- and dose-dependent manner. These effects were accompanied by reduced bioactivity of SOD and CAT, reduced GSH content, and enhanced MDA content. Simultaneously, the amount of ROS was increased and the level of MMP was reduced, along with upregulation of mitochondrial apoptosis pathway-related proteins, bax, cyt-c, and cleaved-caspase-3; bcl-2 protein was downregulated.

Conclusion

HNPG inhibited proliferation of human ovarian cancer HO-8910 cells in vitro, which might be related to decreased bioactivity of SOD and CAT. HNPG also reduced GSH content, which resulted in ROS accumulation in cells, damaged the integrity of mitochondrial membrane, and induced cell apoptosis.
Hypoxia-inducible factor-2α and its missense mutations: potential role in HCC diagnosis, progression, and prognosis and underlying mechanism
Authors: Li Jun , Yan Yibo , Wang Ganxin , Huang Zaozao
Published: June 2023

Objective

This study aims to gain further the potential mechanisms of HIF-2α in tumor progression and tumorigenesis.

Methods

Mined The Cancer Genome Atlas (TCGA) dataset. In total, 421 participants were enrolled in the TCGAHepatocellular Carcinoma (HCC) study, comprising 371 patients with cancer and 50 healthy controls. From the 371 tumor samples, three samples containing the missense mutation of the HIF-2α gene were compared with 368 wild-type samples to identify differentially expressed genes (DEGs).

Results

After filtering, univariate Cox regression and multivariate Cox regression analyses showed that the differentially expressed genes (DEGs) progestagen-associated endometrial protein (PAEP) PNLIPRP2, MIR147B, and pregnancy zone protein (PZP) were significantly correlated with the survival times of patients with HCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) v6.8 database to detect the functional annotation of these four DEGs as well as hub genes obtained from protein-protein interaction (PPI) network analysis using the STRING v10 database. Our analysis focused on the PAEP and PZP genes, whose protein expressions were downregulated in samples with HIF-2α missense mutation. The hub genes of PAEP and PZP were identified using PPI network analysis. Subsequent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that PAEP and its hub genes were highly enriched in the TGF-β pathway, which is consistent with the analysis of PZP.

Conclusion

Our study proved that the missense mutation of HIF-2α induces the upregulation of PAEP, which is positively related to the poor prognosis of patients with HCC, as it may upregulate the TGF-β pathway. In contrast, PZP downregulation showed the opposite phenomenon, as it may downregulate the TGF-β pathway.
The correlation between the hemoglobin-to-red cell distribution width ratio and all-cause mortality in patients with malignant tumors and sepsis: A retrospective cohort study using the MIMIC-IV database
Authors: Zhang Shu , Xu Shan , Liao Rui , Qin Kaixiu
Published: June 2023

Objective

The aim of the study was to investigate the correlation between the hemoglobin-to-red cell distribution width ratio (HRR) and all-cause mortality in patients with malignant tumors and sepsis.

Methods

All patients who met the inclusion criteria of the Medical Information Mart for Intensive Care (MIMIC)-IV were selected and divided into four groups according to the quartile range of HRR distribution. Kaplan-Meier (K-M) analysis was used to plot the 28-day survival curve, and the log-rank test was used to compare the prognosis in each HRR group. A Cox proportional hazards regression model was used to evaluate the prognosis of HRR as both a continuous and categorical variable, and a restricted cubic spline was used to study the effect of HRR, as a continuous variable, on the mortality in patients with malignant tumors and sepsis. Interaction and subgroup analyses were performed to evaluate the consistency of correlations.

Results

A total of 3926 patients were included in the study, including 934 patients in the HRR ≤ 4.97 group, 988 patients in the 4.97 < HRR ≤ 6.26 group, 1005 patients in the 6.26 < HRR ≤ 7.84 group, and 999 patients in the HRR ≥ 7.84 group. According to the K-M analysis, the 28-day survival rate was the lowest in the HRR ≤ 4.97 group (59.53%), and there were significant differences in survival rates among different HRR levels (P < 0.001). The Cox proportional hazards regression model found that after adjusting for various potential confounding factors, HRR was negatively correlated with 28-day and 365-day mortality, and the risk of death in the HRR ≥ 7.84 group was significantly lower than that in the HRR ≤ 4.97 group (P = 0.030 and P = 0.008, respectively). The restricted cubic spline plot revealed a linear and negative relationship between the HRR and the 28-day and 365-day mortality rates. Subgroup analysis revealed an interaction between HRR, blood urea nitrogen, and SAPS II scores (P = 0.010 and P = 0.048, respectively).

Conclusion

Low HRR is an independent risk factor for all-cause mortality in patients with malignant tumors and sepsis and could be used as a prognostic indicator for these patients.
Radiofrequency localization of nonpalpable breast cancer in a multicentre prospective cohort study: feasibility, clinical acceptability, and safety
Authors: Christenhusz Anke , den Dekker Bianca M. , van Dalen Thijs , Jongen Lisa , van der Schaaf Margreet C. , Alic Lejla , ten Haken Bennie , Pijnappel Ruud M. , Dassen Anneriet E.
Published: June 2023

Purpose

In breast conserving surgery, accurate lesion localization is essential for obtaining adequate surgical margins. Preoperative wire localization (WL) and radioactive seed localization (RSL) are widely accepted methods to guide surgical excision of nonpalpable breast lesions but are limited by logistical challenges, migration issues, and legislative complexities. Radiofrequency identification (RFID) technology may offer a viable alternative. The purpose of this study was to evaluate the feasibility, clinical acceptability, and safety of RFID surgical guidance for localization of nonpalpable breast cancer.

Methods

In a prospective multicentre cohort study, the first 100 RFID localization procedures were included. The primary outcome was the percentage of clear resection margins and re-excision rate. Secondary outcomes included procedure details, user experience, learningcurve, and adverse events.

Results

Between April 2019 and May 2021, 100 women underwent RFID guided breast conserving surgery. Clear resection margins were obtained in 89 out of 96 included patients (92.7%), re-excision was indicated in three patients (3.1%). Radiologists reported difficulties with the placement of the RFID tag, partially related to the relatively large needle-applicator (12-gauge). This led to the premature termination of the study in the hospital using RSL as regular care. The radiologist experience was improved after a manufacturer modification of the needle-applicator. Surgical localization involved a low learning curve. Adverse events (n = 33) included dislocation of the marker during insertion (8%) and hematomas (9%). The majority of adverse events (85%) occurred using the first-generation needle-applicator.

Conclusion

RFID technology is a potential alternative for non-radioactive and non-wire localization of nonpalpable breast lesions.
Agency and Intra-textual co-creation in Punchdrunk Enrichment’s Immersive Story Worlds for Children
Authors: Osborne Gareth
Published: June 2023

Recent immersive theatre practices being developed by UK theatre companies invite children to believe that a book story has come to life and is really happening to them within their school environment. The thrill of being able act within a story motivates children’s embodied agency to physically explore an immersive set installation and acts of creative writing performed during the story experience, which allow children to co-create the narrative alongside the adult practitioners. These acts are fictionalised into the narrative frame of the children as heroic story writers, offering new perspectives on how child co-creation of adult narratives can be enabled intra-textually, within the bounds of the adult-initiated story, rather than extra-textually after it has finished, as is the case with fan fiction. However, it raises questions about the nature and limits of this co-creative agency the experiences purport to elicit from their child participants, especially in terms of their critical agency to manipulate fictional devices presented to them through such a hyper-real aesthetic. Drawing on theories of children’s literature and participatory performance, this article argues that it is the way these immersive productions uncannily overlay real and fictional temporalities that enables the child participants’ critical agency within them. Approaches for further participatory, practice-based research in this understudied corner of children’s reading universes are suggested for harnessing the potential of immersive story worlds to generate research data from within children’s first aesthetic engagement with stories.
Social Skills and Cognitive Training to Support Work-Related Skills and Job Placement in a Group of Autistic Adults
Authors: Brighenti S. , Mustacchia L. , Cicinelli G. , Chieregato S. , Comella C. , Torrero L. , Granata F. , Keller R.
Published: June 2023

Autistic people may have difficulties in finding and keeping a job. Studies highlight that only 34% of autistic people are employed compared to 54% of people with disability. 58% of people with ASD have never had a job. Social cognition and cognitive strains may also have a significant impact on working life. The primary goal of our project is supporting autistic people through a training program focused on neuropsychological and social skills training to improve participant’ job skills. Through an Individual Placement and Support model the project involved various Partners to guide, identify skills and interests, provide cognitive and psychological support for autistic people. Results highlighted neuropsychological training efficacy, especially in inhibitory control and good rate of employment status at the end of the project. Findings are encouraging and underline the importance of a multidisciplinary approach to support autistic people in their work life considering their expectations, needs and inclinations.
Identifying Central Negative Thoughts Using Experience Sampling and Network Analysis
Authors: Marian Ştefan , Sava Florin Alin
Published: June 2023

Purpose

Network analysis has promised to inform clinical practice about what should be prioritised in treating different psychological disorders. However, the pure phenomenological approach adopted by network analysis did not help advance this goal considerably. We propose a theoretical approach based on the cognitive model of psychopathology.

Method

We used a multivariate vector-autoregression model to analyse the networks of anxious symptoms, depressive symptoms, and negative automatic thoughts. In a preliminary study, we identified the most common negative thoughts and then monitored them alongside symptoms of anxiety and depression in a sample of undergraduate students three times per day for three weeks.

Results

Results revealed that negative thoughts have a high bridge outdegree in the temporal network (predict the occurrence of symptoms), while symptoms have a high bridge outdegree (are predicted by thoughts). Thoughts related to self-criticism, like “There is something wrong with me”, were the most central for both anxiety and depression and could be considered priority targets for cognitive interventions.

Conclusions

Adopting a theoretical approach has proven helpful in providing concrete targets for therapy instead of just identifying central symptoms, as it is typically done in network studies. Future network studies could also consider adopting an approach based on a psychotherapeutic theory about the aetiology of psychopathology.
Candrakīrti on the Use and Misuse of the Chariot Argument
Authors: Jones Dhivan Thomas
Published: June 2023

The publication in 2015 (ed. Li) of Chap. 6 of the rediscovered Sanskrit text of Candrakīrti’sMadhyamakāvatāra(MA) allows us to witness more directly Candrakīrti’s careful and deliberate critique of the ‘chariot argument’ for the merely conventional existence of the self in Indian Abhidharmic thought. I argue that in MA 6.140–141, Candrakīrti alludes to the use of the chariot argument in theMilindapañhaas negating only the view of a permanent self (compared to an elephant), rather than negating ego-identification (compared to a snake in its hole). In contrast to this misuse of the chariot argument, in MA 6.150–165 Candrakīrti uses the chariot argument as an allegory to enable the meditator to refute the basis of ego-identification in seven ways. Candrakīrti’s use of the chariot argument does not establish any theory about the self or not-self, but acts as a guide to meditation as part of philosophy as a spiritual practice with the goal of liberation.
Achieving SDG 14 in an equitable and just way
Authors: Haas Bianca
Published: June 2023

Sustainable Development Goal (SDG) 14—life below water—significantly elevated global awareness of the importance of the oceans. It is also a key SDG for achieving the other 16 goals and targets. However, the global community is a long way off achieving this goal and serious equity concerns have been raised in the context of SDG 14. This perspective paper provides a summary of the overall progress, or the lack thereof, in achieving SDG 14 and examines some of the obstacles which might undermine the achievement of this goal, such as weak indicators and a lack of recognition of Indigenous and traditional knowledge. This paper also provides recommendations on how countries and stakeholders could take a step closer to achieving SDG 14. Overall, reiterating the calls of global experts, it is imperative that SDG 14 is implemented in an equitable and just way, without further discriminating against developing countries and vulnerable communities.
An atypical expression of core α-Dystroglycan and Laminin-α2 in skin fibroblasts of patients with congenital muscular dystrophies
Authors: Sabry Sahar , Issa Mahmoud Y , Abdel-Hamid Mohamed S , Eissa Noura R , Abdel-Ghafar Sherif F , Ibrahim Mona M , Zaki Maha S
Published: June 2023

Background

Congenital muscular dystrophies (CMDs) result from genetically inherited defects in the biosynthesis and/or the posttranslational modification (glycosylation) of laminin-α2 and α-dystroglycan (α-DG), respectively. The interaction between both proteins is responsible for the stability and integrity of the muscle cell. We aimed to study the expression profiles of both proteins in two classes of CMDs.

Subjects and methods

Whole-exome sequencing (WES) was done for four patients with neuromuscular manifestations. The expression of core α-DG and laminin-α2 subunit in skin fibroblasts and MCF-7 cells was assessed by western blot.

Results

WES revealed two cases with nonsense mutations; c.2938G > T and c.4348 C > T, in LAMA2 encodes laminin-α2. It revealed also two cases with mutations in POMGNT1 encode protein O-mannose beta-1,2-N-acetylglucosaminyltransferase mutations. One patient had a missense mutation c.1325G > A, and the other had a synonymous variant c.636 C > T. Immunodetection of core α-DG in skin fibroblasts revealed the expression of truncated forms of core α-DG accompanied by reduced expression of laminin-α2 in POMGNT1-CMD patients and one patient with LAMA2-CMD. One patient with LAMA2-CMD had overexpression of laminin-α2 and expression of a low level of an abnormal form of increased molecular weight core α-DG. MCF-7 cells showed truncated forms of core α-CDG with an absent laminin-α2.

Conclusion

A correlation between the expression pattern/level of core α-DG and laminin-α2 could be found in patients with different types of CMD.
Propagation of keystone-woody species as a first step in restoration of an overgrazed seasonal dry forest
Authors: Martínez-Gálvez Fernanda , Baskin Carol C. , Croce Johanna , Dalmasso Antonio , Tálamo Andrés
Published: June 2023

In degraded forest ecosystems, reintroduction of keystone-woody species is an important step for restoration because it provides regeneration niches. However, lack of information on how to propagate species restricts the use of native species; specially in tropical dry forests where seed germination is seasonal and is synchronized with the onset of the wet season. We evaluated the dormancy-breaking and germination requirements of nine keystone-woody species from Dry Chaco Forest. Most fresh viable seeds of the keystone species are nondormant, but viability decreases during dry-cold storage restricting the use of some species. Seeds of three keystone species germinated to higher percentages in light than darkness and those of five species germinated equally well in light and darkness; seeds of Castela coccinea germinated to higher percentages in darkness than in light. Alternating vs. constant temperatures had no effect on germination in seven species. Seeds of Anisocapparis speciosa and Cynophalla retusa were nondormant and remained viable for only 1 month during cold-dry storage; and 62–95% of the seeds of the other seven species were nondormant. Dormancy-break was studied in five of the seven species; seeds of four species had physiological dormancy and one had physical dormancy. Dormancy-breaking was promoted by environmental conditions in the habitat, i.e. warm stratification, after seed dispersal. Castela coccinea, Achatocarpus praecox, Mimosa detinens, and Capparicordis tweedieana are the most suitable keystone species for the restoration of overgrazed areas in the Dry Chaco Forest because their seeds germinate to a high percentage and retain viability during dry storage at low temperatures. Seeds of Mimosa detinens and Capparicordis tweedieana required mechanical scarification and 6-weeks of warm stratification, respectively, for dormancy-break.
Bladder perforation as a complication of transurethral resection of bladder tumors: the predictors, management, and its impact in a series of 1570 at a tertiary urology institute
Authors: Osman Yasser , Elawdy Mohamed , Taha Diaa-Eldin , Zahran Mohamed H. , Abouelkheir Rasha T. , Sharaf Doaa Elsayed , Mosbah Ahmed , Ali-El Dein Bedeir
Published: June 2023

Objectives

To report the incidence, predictors, the impact of bladder perforation (BP), and our protocol of management in patients who underwent trans-urethral resection of bladder tumor (TURBT).

Methods

This is a retrospective study, between 2006 and 2020, on patients who underwent TURBT for non-muscle-invasive bladder cancer (NMIBC). Bladder perforation was defined as any full thickness resection of the bladder wall. Bladder perforations were managed based on their severity and type. Small BP with no or mild symptoms were managed with prolongation of urethral catheters. Those with significant extraperitoneal extravasations were managed by insertion of a tube drain (TD). Abdominal exploration was done for extensive BP and all intraperitoneal extravasations.

Results

Our study included 1,570 patients, the mean age was 58 ± 11 years and 86% were males. Bladder perforation was recorded in 10% (n = 158) of the patients. The perforation was extraperitoneal in 95%, and in 86%, the perforation was associated with no symptoms, mild symptoms, or mild fluid extravasation that required only prolongation of the urethral catheter. On the other hand, active intervention was required for the 21 remaining patients (14%) with TD being the most frequent management. History of previous TURBT (p = 0.001) and obturator jerk (p = 0.0001) were the only predictors for BP.

Conclusions

The overall incidence of bladder perforation is 10%; however, 86% required only prolongation of urethral catheter. Bladder perforation did not affect the probability for tumor recurrence, tumor progression nor radical cystectomy.
Equity in mathematics education
Authors: Vithal Renuka , Brodie Karin , Subbaye Reshma
Published: June 2023

This paper reviews research on equity in mathematics education (excluding gender equity) for the period 2017–2022. From the publications identified, five themes were distilled: conceptualizations and framing of equity in mathematics education; research methodologies and researcher positionalities; equity-focused practices, pedagogies and teacher education; equitable mathematics curriculum content, access and pathways; and equity in mathematics education at system levels, nationally and internationally. The review concludes by engaging some of the critique and suggests future directions for research. The research demonstrates that there is growing voice and visibility of equity-focused studies in mathematics education and that conceptualizations of equity have broadened and deepened through an increasing diversity of studies in this area. At the same time, the review also shows the dominance of the Global North in shaping equity discourses and the paucity of research on equity in mathematics education from the Global South.
Thresholds and tipping points are tempting but not necessarily suitable concepts to address anthropogenic biodiversity change—an intervention
Authors: Hillebrand Helmut , Kuczynski Lucie , Kunze Charlotte , Rillo Marina C. , Dajka Jan-Claas
Published: June 2023

Thresholds and tipping points are frequently used concepts to address the risks of global change pressures and their mitigation. It is tempting to also consider them to understand biodiversity change and design measures to ensure biotic integrity. Here, we argue that thresholds and tipping points do not work well in the context of biodiversity change for conceptual, ethical, and empirical reasons. Defining a threshold for biodiversity change (a maximum tolerable degree of turnover or loss) neglects that ecosystem multifunctionality often relies on the complete entangled web of species interactions and invokes the ethical issue of declaring some biodiversity dispensable. Alternatively defining a threshold for pressures on biodiversity might seem more straightforward as it addresses the causes of biodiversity change. However, most biodiversity change appears to be gradual and accumulating over time rather than reflecting a disproportionate change when transgressing a pressure threshold. Moreover, biodiversity change is not in synchrony with environmental change, but massively delayed through inertia inflicted by population dynamics and demography. In consequence, formulating environmental management targets as preventing the transgression of thresholds is less useful in the context of biodiversity change, as such thresholds neither capture how biodiversity responds to anthropogenic pressures nor how it links to ecosystem functioning. Instead, addressing biodiversity change requires reflecting the spatiotemporal complexity of altered local community dynamics and temporal turnover in composition leading to shifts in distributional ranges and species interactions.
Relevance of Zearalenone and its modified forms in bakery products
Authors: Pfleger Franz , Schwake-Anduschus Christine
Published: June 2023

Zearalenone is a frequently occurring and well-known mycotoxin developed in cereals before and during the harvest period by Fusarium spp. mainly in maize and wheat. In addition to the main form, various modified forms (phase I and II metabolites) were detected, in some cases in high amounts. These modified forms can be harmful for human health due to their different toxicity, which can be much higher compared to the parent toxin. In addition, the parent toxin can be cleaved from the phase I and II metabolites during digestion. A risk of correlated and additive adverse effects of the metabolites of ZEN phase I and II in humans and animals is evident. ZEN is considered in many studies on its occurrence in grain-based foods and some studies are dedicated to the behavior of ZEN during food processing. This is not the case for the ZEN phase I and II metabolites, which are only included in a few occurrence reports. Their effects during food processing is also only sporadically addressed in studies to date. In addition to the massive lack of data on the occurrence and behavior of ZEN modified forms, there is also a lack of comprehensive clarification of the toxicity of the numerous different ZEN metabolites detected to date. Finally, studies on the fate during digestion of the relevant ZEN metabolites will be important in the future to further clarify their relevance in processed foods such as bakery products.
AURKB activates EMT through PI3K/AKT signaling axis to promote ICC progression
Authors: Ma Peng , Hao Ying , Wang Wei , Zhang Yue-Feng , Yu Kai-Huan , Wang Wei-Xing
Published: June 2023

Intrahepatic cholangiocarcinoma (ICC) is a fatal disease and the molecular mechanism of its progression remains unknown. Aurora Kinase B (AURKB) is a central regulator of chromosome separation and cytokinesis and is abnormally expressed in a variety of cancer cells. This research aimed to explore the effect of AURKB in occurrence and metastasis of ICC. We found that AURKB showed a progressive up-regulation pattern from normal bile duct tissue to ICC with high invasion. Our data showed that AURKB significantly promoted ICC cell proliferation, induced epithelial-mesenchymal transition (EMT), migration and invasion through gain- and loss- of function experiments. Invivoresults consistently showed that AURKB up-regulation not only promoted tumor growth, but also promoted tumor metastasis. Importantly, we discovered that AURKB regulates the expressions of EMT-related genes via PI3K/AKT signaling axis. Herein, our results suggest that AURKB induced EMT through the activation of PI3K/AKT signaling pathway is critical to the progression of ICC, which may be a prospective therapeutic treatment for overcoming ICC metastasis and progression.
Energy optimal 3D flight path planning for unmanned aerial vehicle in urban environments
Authors: Rienecker Hannes , Hildebrand Veit , Pfifer Harald
Published: June 2023

This paper presents a general approach to compute energy optimal flight paths for unmanned aerial vehicle (UAV) in urban environments. To minimize the energy required, the flight path is optimized by exploiting local wind phenomena, i.e., upwind and tailwind areas from the airflow around buildings. A realistic wind field of a model urban environment typical for continental Europe is generated using PALM, a Large Eddy Simulation tool. The calculated wind field feeds into the flight path planning algorithm to minimize the energy required. A specifically tailored A-Star-Algorithm is used to optimize flight trajectories. The approach is demonstrated on a delivery UAV benchmark scenario. Energy optimal flight paths are compared to shortest way trajectories for 12 different scenarios. It is shown that energy can be saved significantly while flying in a city using knowledge of the current wind field.
Evaluation of carbon dioxide supercritical fluid extraction (CO2-SFE) on carotenoids recovery from red yeast cells
Authors: Larocca Vincenzo , Martino Maria , Trupo Mario , Magarelli Rosaria Alessandra , Spagnoletta Anna , Ambrico Alfredo
Published: June 2023

In this work, the performance of carotenoids extraction from Rhodotorula spp red yeast (strain ELP2022) using supercritical CO2 (CO2-SFE) was compared to the traditional technique with organic solvent. For this purpose, the yeast was cultured in liquid medium, pre-treated with glass beads in 0.1 M NaHCO3, and lyophilized. The extraction by CO2-SFE was carried out using a bench scale equipment at 300, 400, and 500 bar whilst maintaining a constant CO2 flow rate (6 mL/min) and temperature (40 °C) resulting in an average extraction yields of 60.8 ± 1.1, 68.0 ± 1.4, and 67.6 ± 1.4 µg of total carotenoids per g of yeast (dry weight), respectively. Based on these results, three other experiments at 400 bar and a CO2 flow rate of 6 L/min were also performed. In specific, the temperature was increased up to 60 °C, and ethanol as a co-solvent was added at 40 and 60 °C. The results showed that the temperature does not have a significant effect on the extraction of carotenoids. On the contrary, the yields improved significantly in the presence of the co-solvent, and the percentage of recovery reached the mean values of 71.70% ± 1.4 and 73.86% ± 1.9 at 40 and 60 °C, respectively. Furthermore, from chromatographic analysis, four major peaks were observed and identified as torularhodin, torulene, γ-carotene, and β-carotene which represented about 53.4%, 6.4%, 8.3%, and 26.9% of total carotenoids, respectively. Therefore, these promising results show the potential of this green technique for obtaining high-value products, such as carotenoids, from yeasts and therefore avoiding the use of dangerous solvents.
Adsorptive removal of siloxanes from biogas: recent advances in catalyst reusability and water content effect
Authors: Vali Seyed Alireza , Moral-Vico Javier , Font Xavier , Sánchez Antoni
Published: June 2023

The valorization of biogas as a renewable energy source faces a major obstacle regarding its purification. Siloxane is one of the impurities that cause problems such as damages to equipment of combustion engines, turbines, and boilers used for biogas conversion to heat and electricity. In this review, adsorption for siloxane removal is widely discussed, with two specific approaches: adsorbents sensitivity to water and regeneration, two essential points for industrial application. Thus, determining factors in adsorbents capacity, reusability, and water tolerance including textural properties, surface functional groups, and hydrophobicity are deeply analyzed. Studies oriented to the optimization of traditional adsorbents such as activated carbon, silica gel, and aluminosilicates as well as newly emerging adsorbents such as metal organic frameworks, graphene oxides, and waste-derived materials are studied in detail in terms of reusability and water tolerance. Although activated carbon is commercially used, its low selectivity, pore blockage due to siloxane polymerization, and unsuccessful regeneration make it disadvantageous. Silica gel, however, shows better reusability as a result of less adsorbent-adsorbate dissociation energy. In addition, aluminosilicates, despite its low adsorption capacity, proved to be more practical for real biogas due to their high hydrophobicity. Graphene oxide cost and energy efficiency in their synthesis make them more industrially appealing candidates despite their low adsorption capacity. Finally, metal organic frameworks demonstrated high selectivity, high adsorption capacity, and more efficient regeneration and therefore have more advantages and less drawbacks, although the number of published studies is still limited.
The use of therapeutic drug monitoring to highlight an over-looked drug-drug interaction leading to imatinib treatment failure
Authors: Gagno Sara , Buonadonna Angela , Dalle Fratte Chiara , Guardascione Michela , Zanchetta Martina , Posocco Bianca , Orleni Marco , Canil Giovanni , Roncato Rossana , Cecchin Erika , Toffoli Giuseppe
Published: June 2023

Background

Chronic oral anticancer therapies, are increasingly prescribed and present new challenges including the enhanced risk of overlooked drug-drug interactions (DDIs). Lengthy treatments and patients’ management by different professionals can lead to serious prescribing errors that therapeutic drug monitoring (TDM) can help identifying thus allowing a more effective and safer treatment of patients with polypharmacy.

Objectives

This report aims to exemplify how an intensified pharmacological approach could help in the clinical monitoring of patients on chronic treatments.

Methods

A patient with gastrointestinal stromal tumor was referred to our clinical pharmacology service due to tumor progression while on imatinib therapy. The investigation was based on TDM, pharmacogenetics, DDI evaluation and Circulating tumor DNA (ctDNA) analysis. The patient underwent repeated blood samplings to measure imatinib and norimatinib plasma concentrations through a validated LC-MS/MS method. Polymorphisms affecting genes involved in imatinib metabolism and transport were investigated using SNPline PCR Genotyping System. Drug-drug interactions were evaluated though Lexicomp. ctDNA analysis was performed on MiSeq platform.

Results

TDM analysis revealed that the patient was underexposed to imatinib (Cmin = 406 ng/mL; target Cmin = 1100 ng/mL). Subsequent DDI analysis highlighted a dangerous interaction with carbamazepine, via CYP3A4 and P-gp strong induction, omitted at the time of imatinib treatment start. No relevant pharmacogenetic variants were identified and appropriate compliance to treatment was ascertained. ctDNA monitoring was performed to assess potential tumor-related resistance to imatinib. Carbamazepine was cautiously switched to a non-interacting antiepileptic drug, restoting IMA plasma concentration (i.e. Cmin = 4298 ng/mL). The progression of the disease, which in turn led to the patient’s death, was also witnessed by an increasing fraction of ctDNA in plasma.

Conclusion

The active pharmacological monitoring allowed the identification of a dangerous previously over-looked DDI leading to IMA under-exposure. The switch to a different antiepileptic treatment, reversed the effect of DDI, restoring therapeutic IMA plasmatic concentrations.

Graphical abstract
Is Bitcoin gathering dust? An analysis of low-amount Bitcoin transactions
Authors: Loporchio Matteo , Bernasconi Anna , Di Francesco Maesa Damiano , Ricci Laura
Published: June 2023

In the Bitcoin protocol, dust refers to small amounts of currency that are lower than the fee required to spend them in a transaction. Although “economically irrational”, dust is commonly used for achieving unconventional side effects, rather than exchanging value. For instance, dust might be linked to on-chain services or to malicious activity, such as dust attacks attempting to break users’ pseudonymity. To study this phenomenon, this paper presents an in depth analysis of Bitcoin transactions involving dust, showing how dust is created and consumed. We identify the top dust creators and consumers and discuss how consumption has evolved over time. Finally, we use the data to identify transactions suspected of being part of dust attacks and quantify their impact on address deanonymization. Our results show that dust is mainly related to on-chain betting services. Transactions likely to be part of dust attacks are a minority of dust creating transactions but, despite their relatively low number, they have a disproportionately high effect on helping attackers to break address pseudonymity.
The Association of Hypertension with Increased Mortality Rate During the COVID-19 Pandemic: An Update with Meta-analysis
Authors: Al-Qudimat Ahmad R. , Ameen Ayisha , Sabir Doaa M. , Alkharraz Heba , Elaarag Mai , Althani Aisha , Singh Kalpana , Alhimoney Wassim M. , Al-Zoubi Raed M. , Aboumarzouk Omar M.
Published: June 2023

Background and Aim

The impact of multiple risk factors on COVID-19 mortality has been previously reported in multiple systematic reviews and meta-analyses. The aim of this review is to provide a comprehensive update on the association between hypertension (HTN) and mortality in patients with COVID-19.

Methods

A systematic review and meta-analysis were performed and followed the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. A search was achieved using PubMed, Scopus, and Cochrane Databases for research publications on hypertension, COVID-19, and mortality published between December 2019 and August 2022.

Results

A total of 23 observational studies involving 611,522 patients from 5 countries (China, Korea, the UK, Australia, and the USA) were included in our study. The confirmed number of COVID-19 with HTN cases in each study ranged from 5 to 9964. The mortality ranged from 0.17% to 31% in different studies. Pooled results show that the mortality rate of COVID-19 among the included studies ranges from a minimum of 0.39 (95% CI 0.13–1.12) to a maximum of 5.74 (95% CI 3.77–8.74). Out of the 611,522 patients, 3119 died which resulted in an overall mortality prevalence of 0.5%. Subgroup analyses indicated that patients with COVID-19 who have hypertension and male patients had slightly less risk of mortality than female patients [the percentage of men > 50%; OR 1.33: 95% CI (1.01, 1.76); the percentage of men ≤ 50%: OR 2.26; and 95% CI (1.15, 4.48)]. Meta-regression analysis results also showed a statistically significant association between hypertension and COVID-19 mortality.

Conclusion

This systematic review and meta-analysis suggest that hypertension may not be the only risk factor associated with the increased mortality rate during the COVID-19 pandemic. In addition, a combination of other comorbidities and old age appears to increase the risk of mortality from COVID-19.

Graphical Abstract