bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-carcinogenic Health Risk Assessment and Predicting of Organic and Heavy Metal Pollution of Groundwater around Osisioma, Nigeria, using Artificial Neural Networks and Multi-Linear Modeling Principles
Authors: Chigoziem Akakuru Obinna , Uzoma Njoku Benedict , Uchechukwu Obinna-Akakuru Annabel , Akudinobi Bernard E. , Philip Obasi , Godwin Aigbadon , Bright Onyeanwuna Uzochi
Published: September 2022

Non-carcinogenic health risk assessment and predicting of organic and heavy metal pollution of groundwater around Osisioma, Nigeria, using Artificial Neural Networks and Multi-Linear Modeling Principles has been done. 30 groundwater samples were collected systematically and analyzed for organic and heavy metal pollutants. The results of the analysis showed that the heavy metals and organic pollutants within the study area contributed to the pollution of groundwater resources in the locality. However, copper, ethylbenzene, xylene and toluene were within the recommended standard, whereas arsenic, iron, chromium, lead, and benzene were above the recommended standard for drinking water. Correlation matrix and principal component analysis assessment indicated weak correlation and that organic pollutants were major contributors to the loadings. The Contamination factor, Pollution load index, Metal pollution index, Geoaccumulation index, Potential ecological risk index, Elemental Contamination Index, and overall Metal Contamination Index showed no significant pollution, whereas the Heavy Metal Evaluation Index, Pollution Index of Groundwater results showed worrisome impact of the anthropogenic activities on the groundwater quality. Health risk assessment showed that children are more at risk than adults as it related to taking polluted water. MLR models performed better than the ANN. Seven (7) mathematical models were generated for the prediction of pollution indices. Based on the results, this study recommends regular monitoring of groundwater resources and the integration of ANN and MLR modeling approaches for the prediction of pollution indices.
Synthesis, structural characterization and effect of surface modification on magnetization of hybrid manganese ferrite nanoparticle
Authors: Dan Shabnam , Chattree Amit , Naskar Jishnu , Kamsonlian Suantak
Published: September 2022

Paramagnetic Poly-methyl methacrylate (PMMA) and Poly ethylene glycol (PEG) functionalized manganese ferrite (PMMA-PEG-MF) nanoparticles were synthesized through a facile and efficient method. The resulting nanoparticles (NPs) were characterized using PSA, EDX, FT-IR, TEM, XRD, SEM, TGA and VSM techniques. The PMMA-PEG-MF NPs were nanocrystalline and depicted plate like particles with a mean size of around 70 nm as compared to the size of the MnFe2O4 nanoparticles which was observed to be 66 nm. The EDX validated the existence of metal ions and the modifiers (polymethylmethacrylate and polyethylene glycol) in the NPs. The FTIR confirmed the functionalization of MnFe2O4 NPs with PMMA and PEG. The XRD studies revealed that the synthesized MF and PMMA-PEG-MF NPs were crystalline and had a cubic spinel structure with a crystallite size of 14.64 nm and 14.42 nm and lattice parameter was calculated to be 6.20 Å and 3.90 Å respectively. The SEM micrograph revealed highly agglomerated nanostructures in the MnFe2O4 NPs; however, the extent of agglomeration reduced significantly post modification with PMMA and PEG. The TGA study exhibited an overall weight loss of 2.86% and 25.11% for MnFe2O4 and PMMA-PEG-MF NPs respectively. Magnetization measurements showed a substantial reduction in the saturation magnetization (Ms) and magnetic moment (µB) after modifying MnFe2O4 with PMMA and PEG. A saturation magnetization of 0.0056 emu/g was derived for PMMA and PEG modified MnFe2O4 NPs, as compared to 23 emu/g for MnFe2O4 magnetic NPs, suggesting paramagnetic behaviour of the synthesized NPs.
Morphological identification, molecular characterization and optimization of cultivation for Acrobeloides maximus species extracted from bitter gourd (Momordica charantia) field at Gujarat, India.
Authors: Thakar Shweta Prakashkumar , Chauhan Sunita , Highland Hyacinth , George Linz-Buoy
Published: September 2022

Background
Free-living nematodes are very important part of agricultural soil ecosystems, especially members of the Cephalobidae family. Morphological and morphometric analysis is efficient for genus-level classification of Cephalobidae members, but to achieve species-level identification, molecular characterization is imperative.
Methods and Results
The nematodes extracted from the collected soil of the bitter gourd field were cultivated on NGM (nutrient growth medium) agar plates under standardized laboratory conditions. The morphological characteristics of 42 females and 6 males were captured under a digital microscope and processed using the ImageJ analysis tool for De-Man measurements and compared with previously submitted databases. DNA barcoding was carried out with the 18S small RNA subunit gene, and the resulting sequence was then processed to BLASTN after alignment and annotation. The phylogenetic tree was constructed from the processed data files and further evaluated by branch lengths and bootstrap values. Blast analysis showed 98% similarity with the A. maximus strain, which was also supported by high bootstrap values (96%). Acrobeloides maximus was identified based on morphological features described by Throne, 1925 and confirmed by molecular characterization.
Conclusion
The nematodes collected from the soil sample were cultivated and identified as A. maximus by a combined approach of morphological, pictorial, morphometric, and molecular analysis, which may further be used in the future identification of Acrobeloides spp. To our knowledge, this is the first recorded A. maximus from the bitter gourd field of Gujarat, India. Pictogram and measurement of eggs inside the female body is also shown for A. maximus for the first time.
Stress granules affect the dual PI3K/mTOR inhibitor response by regulating the mitochondrial unfolded protein response
Authors: Lin Nan , Sun Liankun , Chai Jiannan , Qi Hang , Zhao Yuanxin , Ma Jiaoyan , Xia Meihui , Xiaoqing Hu
Published: September 2022

Drug resistance remains a challenge in ovarian cancer. In addition to aberrant activation of relevant signaling pathways, the adaptive stress response is emerging as a new spotlight of drug resistance in cancer cells. Stress granules (SGs) are one of the most important features of the adaptive stress response, and there is increasing evidence that SGs promote drug resistance in cancer cells. In the present study, we compared two types of ovarian cancer cells, A2780 and SKOV3, using the dual PI3K/mTOR inhibitor, PKI-402. We found that SGs were formed and SGs could intercept the signaling factor ATF5 and regulate the response of mitochondrial unfolded protein(mtUPR)in A2780 cells. Therefore, exploring the network formed between SGs and membrane-bound organelles, such as mitochondria, may provide new insight into the mechanisms of action of antitumor drugs.
Fruit and vegetable intake and the risk of cataract: insights from the UK Biobank Study
Authors: Fan Huiya , Han Xiaotong , Shang Xianwen , Zhu Zhuoting , Mingguang He , Xu Guihua , Chen Zilin , Deng Ruidong
Published: September 2022

Purpose: To investigate the association between fruit and vegetable (F&V) intakeand the risk of cataract.
Design: Prospective cohort study.
Methods: We included 72,160 participants who were free of cataract at baseline from the UK Biobank. Frequency and type of F&V intake were assessed using a web-based 24-h dietary questionnaire from 2009 to 2012. Development of cataract during the follow-up was defined by self-report or hospital inpatient records up to 2021. Cox proportional regression models were used to estimate the association between F&V intake and incident cataract.
Results: During a mean follow-up of 9.1 years, 5753 participants developed cataract with a corresponding incidence of 8.0%. After adjusting for multiple demographic, medical and lifestyle covariates, higher intake of F&V were associated with a lower risk of cataract (≥6.5 vs. <2 servings/week: hazards ratio [HR]: 0.82, 95% CI: 0.76 to 0.89; P < 0.0001). Regarding specific types, significant reduced risk of cataract was found for higher intake of legumes (P = 0.0016), tomatoes (≥5.2 vs. <1.8 servings/week: HR: 0.94, 95% CI: 0.88 to 1.00), and apple and pear (>7 vs. <3.5 servings/week: 0.89, 95% CI: 0.83 to 0.94; P < 0.0001), but not for cruciferous vegetables, green leafy vegetables, berry, citrus fruit or melon. Smokers were found to benefit more from F&V intake than former and never smokers. Men also could benefit more from higher vegetable intake than women.
Conclusions: More F&V intake, especially legumes, tomatoes, apple and pear was associated with lower risk of cataract in this UK Biobank cohort.
CircRNA MBOAT2 promotes intrahepatic cholangiocarcinoma progression and lipid metabolism reprogramming by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export
Authors: Yu Xiaopeng , Tong Huanjun , Chen Jialu , Tang Chenwei , Wang Shuqing , Si Yu , Wang Shouhua , Tang Zhaohui
Published: September 2022

The carcinogenic role of FASN by regulating lipid metabolism reprogramming has been well established in multiple tumors. However, whether mechanisms during intrahepatic cholangiocarcinoma (ICC) progression such as circRNAs regulate FASN expression remains unknown. Here we demonstrate a lipid metabolism related circRNA, circMBOAT2 (has_circ_0007334 in circBase), frequently upregulated in ICC tissues, and positively correlated with ICC malignant features. Knockdown circMBOAT2 inhibits growth and metastasis of ICC cells. Mechanistically, circMBOAT2 combines with PTBP1 and protect PTBP1 from ubiquitin/proteasome-dependent degradation, impairing the function of PTBP1 to transfer FASN mRNA from the nucleus to the cytoplasm. Moreover, circMBOAT2 and FASN have the same effect on fatty acid profile, unsaturated fatty acids instead of saturated fatty acids are primarily regulated and associated with malignant behaviors of ICC cells. The levels of lipid peroxidation and ROS were significantly higher when FASN was knocked down and recovered when circMBOAT2 was overexpressed. Our results identified that circMBOAT2 was upregulated in ICC and promoted progression by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export, which altered lipid metabolic profile and regulated redox homeostasis in ICC, suggesting that circMBOAT2 may serve as an available therapeutic target for ICC with active lipid metabolism.
Strong extended SWIR cavity resonances in a single GeSn nanowire
Authors: Kim Youngmin , Assali Simone , Joo Hyo-Jun , Koelling Sebastian , Chen Melvina , Luo Lu , Shi Xuncheng , Burt Daniel , Ikonic Zoran , Nam Donguk , Moutanabbir Oussama
Published: September 2022

Nanowires are promising platforms for realizing ultra-compact light sources for photonic integrated circuits. In contrast to impressive progress on light confinement and stimulated emission in III-V and II-VI semiconductor nanowires, there has been no experimental demonstration showing the potential to achieve strong cavity effects in a bottom-up grown single group-IV nanowire, which is a prerequisite for realizing silicon-compatible infrared nanolasers. Herein, we address this limitation and present the first experimental observation of cavity-enhanced strong photoluminescence from a single Ge/GeSn core/shell nanowire. A sufficiently large Sn content (~ 10 at%) in the GeSn shell leads to a direct bandgap gain medium, allowing a strong reduction in a material loss upon optical pumping. Efficient optical confinement in a single nanowire enables many round trips of emitted photons between two facets of a nanowire, achieving a narrow width of 3.3 nm. Our demonstration opens new possibilities for ultrasmall on-chip light sources towards realizing photonic-integrated circuits in the underexplored range of extended SWIR.
A combined bioinformatics and experimental approach identifies RMI2 as a Wnt/β-catenin signaling target gene related to hepatocellular carcinoma
Authors: Tsai Hung-Wen , Cheng Shu-Wen , Chen Chou-Cheng , Chen I-Wen , Ho Chung-Liang
Published: September 2022

Background: The Wnt/β-catenin signaling pathway plays an important role in embryogenesis and tumorigenesis. In human cancer, abnormal activity of Wnt/β-catenin signaling pathway induces overexpressed of downstream genes, and initiate oncogene. There are several target genes known to be key players in tumorigenesis, such as c-myc, cyclin D1, MMPs or survivin. Therefore, identifying the target genes of Wnt/β-catenin signaling pathway is important to understanding Wnt/β-catenin-mediated carcinogenesis. In this study, we developed a combined bioinformatics and experimental approach to find potential target genes.
Methods: Luciferase reporter assay was used to analyze the promoter activity of RMI2. WST1 cell proliferation assays and transwell assays were performed to determine the proliferation and migration capacities of RMI2 overexpressing or knockdown stable hepatic cells. Finally, xenograft experiments were performed to measure the tumor formation capacity in vivo.
Results: The results showed that RMI2 mRNA was upregulated after LiCl treatment and Wnt3a-conditioned mediumin a culture of SK-hep-1 cell lines. A chromatin immunoprecipitation (ChIP) assay showed that the β-catenin/T cell-specific factor (TCF) complex binds to the putative TCF binding site of the RMI2 promoter. We then found a TCF binding site at –333/–326 of the RMI2 promoter, which is crucial for β-catenin responsiveness in liver cell lines. RMI2was overexpressed in hepatoma tissue and cell lines, and it promoted the migration and invasion of HCC cells. Moreover, RMI2 upregulated the expression of epithelial-mesenchymal transition (EMT) markers and the Wnt3a/β-catenin-related genes, but silencing RMI2 had the opposite effects. Notably, the expression of RMI2 was positively correlated with the clinical data of HCC patients who had significantly shorter overall survival (OS) and disease-free survival (DFS) (Both : P < 0.05). In addition, a total of 373 HCC patients’ data from the Caner Genome Atlas project (TCGA) were used to validate our findings.
Conclusions: Taking all these findings together, we determined that RMI2 was a new target gene of the Wnt/β-catenin signaling pathway.We also found that RMI2 promotes EMT markers, HCC cell invasion, and metastasis, which indicated that RMI2 is a potential target for preventing or at least mitigating the progression of HCC.
Lead or Cadmium Co-Contamination Alters Benzene and Toluene Degrading Bacterial Communities
Authors: Konya Aniko , Fiddler Brice , Bunch Olivia , Hess Kendra , Ferguson Cade , Krzmarzick Mark
Published: September 2022

Co-contamination of hydrocarbons with heavy metals in soils often complicates and hinders bioremediation. A comprehensive characterization of site-specific degraders at contaminated sites can help determine if in situ bioremediation processes are sufficient. This study aimed to identify differences in benzene and toluene degradation rates and the microbial communities enriched under aerobic conditions when different concentrations of Cd and Pb are introduced. Microcosms were used to study the degradation of 0.23 mM benzene or 0.19 mM toluene under various concentrations of Pb (up to 240 µM) and Cd (up to 440 µM). Soil collected from a stormwater retention basin receiving runoff from a large parking lot was utilized to seed the microcosms. The hydrocarbon degradation time and rates were measured. After further rounds of amendment and degradation of benzene and toluene, 16S rRNA gene amplicon sequencing and quantitative PCR were used to ascertain the microbial communities enriched under the various concentrations of the heavy metals. The initial degradation time for toluene and benzene was 7 to 9 days and 10 to 13 days, respectively. Degradation rates were similar for each hydrocarbon despite the concentration and presence of metal co-contaminant, however, the enriched microbial communities under each condition differed. Microcosms without metal co-contaminant contained a diversity of putative benzene and toluene degrading bacteria. Cd strongly reduced the richness of the microbial communities. With higher levels of heavy metals, genera such as Ralstonia, Cupriavidus, Azoarcus, and Rhodococcus became more dominant under various conditions. The study finds that highly efficient benzene- and toluene-degrading consortia can develop under variations of heavy metal co-contamination, but the consortia are dependent on the heavy metal type and concentrations.
High Glucose modulates the cancer cell fate by regulation of mTOR-HDAC-microRNA axis
Authors: RAMAIAH Mekala JANAKI , Kumar Kurappalli Rohil , Sriniva Ramalingam Prasanna , Moparthi NageswaraRao , Reddy Rajasekhar , Dirisala Vijay Ramu , Rao Kummarsetti Veerabhadra , Naushad Shaik Mohammad
Published: September 2022

Glioblastoma multiforme (GBM) is the most dangerous cancers of the brain. Despite availability of various treatment modalities, GBM chemotherapy remains obscure. Cancer metabolism is considered as one of the important factors for the tumor aggressiveness. Glucose is an important energy source for the cellular metabolism and was found to affect the GBM cancer aggressiveness, and chemo-resistance. Studies have found that GBM cancer is driven by epigenetic proteins. HDACs are important epigenetic proteins that regulate the gene expression by chromatin epigenetics changes, and there by involved in gene transcription in cancer cells. In this study, we have evaluated the role of glucose on GBM cancer cells and identified the cell viability effects. Further, the cell-cycle studies have indicated the apoptotic effects of high dose of glucose. Further the histone deacetylase (HDAC) gene expression was examined during increased glucose availability. We have observed a drastic enhancement in HDAC gene expression. Further, the cancer cell metabolism was analysed by studying the gene expression pertaining to mammalian target of rapamycin (mTOR) pathway. Glucose has induced changes in gene expression of class I HDACs and mTOR pathway genes. Furthermore, the study has also identified the microRNA modulatory effect of glucose. The molecular modelling studies have indicated the interaction of glucose with mTOR, Rictor and caspase-3 proteins suggesting the functional regulatory role of glucose on the expression of genes. The caspase-3 (i. e. the effector caspase) studies confirmed the effect of glucose on caspase-3 activity and the effect was enhanced by the treatment with mTOR complex inhibitors. Proteomic study has identifed the involvement of MAPK, Rho kinase, S6 kinase pathways, Bromodomain, histone acetyl transferases during combined treatment of mTOR complex inhibitor and high glucose combination treatment. Thus, the present study has elucidated the role of glucose on GBM cancer proliferation, and molecular modulatory effect mediated by glucose by varying the chromatin epigenetics, and microRNA modulation.
Perceptions of friendship, peers and influence on smoking according to socioeconomic status and tobacco control context: A systematic review and meta-ethnography of qualitative research
Authors: Littlecott Hannah J. , Moore Graham. F. , Evans Rhiannon. E. , Melendez-Torres G.J. , McCann Mark , Reed Hayley , Mann Mala , Dobbie Fiona , Jennings Stephen , Donaldson Caitlyn , Hawkins Jemma
Published: September 2022

Background

The relationship between smoking and interpersonal influences has been well established within the literature. There has been a cultural shift in denormalisation and a reduction in tobacco smoking. Despite this, socioeconomic inequality in smoking has prevailed. This highlights the pressing need to understand health inequalities in relation to adolescents’ smoking attitudes across smoking normalisation and socioeconomic contexts.

Methods

The search was conducted in July 2019 and updated in March 2022
within 11 databases and secondary sources. Search terms included
schools, adolescents, smoking, peers, social norms and qualitative
research. Screening was conducted by two researchers independently
and in duplicate. Study quality was assessed using the eight-item
Evidence for Policy and Practice Information and Co-ordinating
Centre (EPPI-centre) tool for the appraisal of qualitative studies.
Results were synthesised using a meta-narrative lens for
meta-ethnography and compared across smoking normalisation
contexts.

Results
Forty one studies were included and five themes were developed, mapping onto the socio ecological model. The social processes by which adolescents take up smoking differed according to a mixture of school type, peer group structure, socioeconomic composition and the smoking culture within the school, as well as the wider cultural context. Data available from smoking denormalised contexts, described changes in social interactions around smoking to cope with its stigmatisation. This was manifested through direct peer influence, whereby more subtle techniques were employed, group belonging whereby smoking was less likely to be seen as a key determinant of group membership and smoking was less commonly reported to be used as a social tool, and popularity and identity construction, whereby smoking was perceived more negatively in a post-legislative context.
Conclusions
This meta-ethnography is the first study to demonstrate, drawing on international data, that peer processes relating to socioeconomic inequalities in adolescent smoking may undergo changes as norms for smoking within society change. Future research should focus on understanding how differences across school-level socioeconomic contexts manifest once post-legislative norms have been established, to inform the adaptation of interventions.
Detection by network inversion filter of long-term and short-term slow slip events, using a very dense GNSS Network in Shikoku, Japan, during 2018–2022
Authors: Ozawa Shinzaburo , Munekane Hiroshi
Published: September 2022

A study of slow slip events is important in understanding the mechanism and friction properties of plate interfaces. We imaged the state of plate interface between the subducting Philippine Sea plate and overriding Amur plate beneath Shikoku Island, Japan, by applying a network inversion filter to the position time series of the Global Navigation Satellite System from January 2018 to April 2022. The results of network inversion filtering show 14 short-term slow slip events associated with low-frequency earthquakes along with long-term slow slip events in the Bungo Channel, central Shikoku, and Kii-channel Japan. The long-term slow slip events in the Bungo, central Shikoku, and Kii-channels are spatially separated from each other, suggesting independent events. The recurrence interval of the central Shikoku slow slip event remains unclear. A Kii-channel slow-slip event occurs with an irregular recurrence interval. The estimated moments of the Bungo, central Shikoku, and Kii-channel slow slip events were Mw7.0, Mw6.5, and Mw6.3, respectively, with a rigidity of 30 GPa. The estimated moment magnitude of the short-term slow slip events ranges from Mw5.4 to Mw6.2. The major detected short-term slow slip events are consistent with the detected events from tilt meter analysis by the National Institute of Earth Science and Disaster Resilience of Japan. Most of the detected slow slip events are associated with low-frequency earthquakes, and some exhibited spatial propagation. Spatio-temporal relationship between low-frequency earthquakes and aseismic slip may provide us with the insight into the physical processes between them.
Low-Complexity Information and Sensing Beamforming Optimization for Multi-User Multi-Target MIMO ISAC Systems
Authors: Zhu Minghe , Li Lei , Xia Shuqiang , Chang Tsung-hui
Published: September 2022

Integrated sensing and communication (ISAC) has been envisioned as a key enabler in the next generation wireless networks. In this paper, we consider the joint information and sensing beamforming design in a multi-user and multi-target multi-input multi-output (MUMT-MIMO) ISAC system, where a transmit BS and a sensing BS collaborate to sense targets, and the transmit BS sends information streams to communication users at the same time. To optimize the sensing performance and guarantee the communication throughput, we formulate a joint beamforming design problem to minimize the trace of the weighted Cramer-Rao bound (CRB) of target parameters subject to the sum rate constraint. The problem is challenging to solve due to the intricate non-convex objective function and constraints. We firstly exploit the weighted mean square error minimization (WMMSE) and semidefinite relaxation (SDR) techniques to devise a WMMSE-SDR algorithm that can achieve a KKT point of the problem.

The SDR can be shown to be tight for a sub-problem in the WMMSE-SDR algorithm, which implies zero duality for the sub-problem. Based on this property and fractional programming (FP) techniques, we further reformulate the beamforming problem as a min-max form with simple constraints which then can be efficiently solved by first-order min-max optimization algorithms. Finally, the proposed algorithms are evaluated extensively in simulation. Numerical results show that both proposed algorithms can achieve promising performance in sensing and communication, and the low-complexity algorithm has a significantly reduced computation time.
The Agreement Between Syringing, Dacryocystography, and Dacryoendoscopy Findings in Lacrimal Duct Obstruction
Authors: Nakamura Jutaro , Kamao Tomoyuki , Mitani Arisa , Mizuki Nobuhisa , Shiraishi Atsushi
Published: September 2022

Purpose
We retrospectively investigated the agreement of the diagnostic findings of syringing, dacryocystography (DCG), and dacryoendoscopy in the obstruction of the lacrimal drainage system (LDS).
Methods
We examined 113 patients (211 LDS) who underwent syringing, DCG, and dacryoendoscopy for preoperative evaluation of LDS obstruction. Obstruction was compared by classifying the grade and the site of obstruction into three levels, respectively. The diagnostic agreement between the tests was assessed by determining the weighted Kappa value.
Results
25 male (49 LDS) and 88 female patients (162 LDS) were included in this study. LDS obstruction was observed in 77.4% of the cases by syringing, 60.0% by DCG, and 81.3% by dacryoendoscopy. Regarding the agreement in the obstruction grade, Cohen's Kappa value for DCG and dacryoendoscopy was 0.65 (95%CI: 0.56–0.74). Meanwhile, the DCG and dacryoendoscopy showed consistency in the site of obstruction in 77.9% of the cases. DCG found no obstruction in 38.4% of all cases, whereas 47.9% of them showed stenosis or obstruction by dacryoendoscopy. When discrepancies were observed between syringing and dacryoendoscopy to detect the site of obstruction, the combination of syringing and DCG reached the dacryoendoscopy findings at the 99% level.
Conclusions
"Substantial" agreements were found between the diagnostic findings of the three examinations. Among them, the highest agreement was between syringing and dacryoendoscopy in determining the site of obstruction. The lowest agreements were between syringing and DCG in diagnosing the grade and the site of obstruction.
Xanthatin and 8-epi-xanthatin as new potential colchicine binding site inhibitors: a computational study
Authors: Alpízar-Pedraza Daniel , Veulens Ania de la Nuez , Ginarte Yoanna María Álvarez , Piloto-Ferrer Janet , Sánchez-Lamar Ángel
Published: September 2022

Phytocompounds xanthatin and 8-epi-xanthatin, obtained from Xanthium chinese Mill, showed antitumoral activity in vitro, related to the microtubules destabilizing properties of these phytocompounds. However, the exact binding pocket on tubulin of these isomers remains unknown. The aim of this work is, to develop a comprehensive computational strategy to understand and eventually predict the structure-activity relationship of xanthatin and 8-epi-xanthatin, with the destabilizing-antimitotic binding domain in tubulin heterodimer and to propose a putative binding site for these phytocompounds into the microtubule destabilizing agents binding sites in the tubulin heterodimer. A molecular docking was performed using the xanthanolides conformers as ligands and several tubulin structures obtained from the Protein Data Bank as receptor. The xanthanolides-tubulin complexes were energy minimized by molecular dynamics simulations at vacuum and their stability was evaluated by solvated molecular dynamics simulations during 100 ns. Xanthanolides showed higher stability into the colchicine and pironetin binding sites, whit a greater affinity for the former. In addition, the xanthanolides and non-classical colchicine binding site inhibitors share a high structural similarity.
Relative hypercoagulopathy of the SARS-CoV-2 Beta and Delta variants when compared to the less severe Omicron variants is related to TEG parameters, the extent of fibrin amyloid microclots, and the severity of clinical illness.
Authors: Grobbelaar Lize M , Kruger Arneaux , Venter Chantelle , Burger Este M , Laubscher Gert Jacobus , Maponga Tongai G , Kotze Maritha J , Kwaan Hau C. , Miller Joseph B , Fulkerson Daniel , Huff Wei , Chang Eric , Wiarda Grant , Bunch Connor M , Walsh Mark M , Raza Syed , Zamlut Mahmud , Moore Hunter B , Moore Ernest E. , Neal Matthew D , Kell Douglas B , Pretorius Etheresia
Published: September 2022

Earlier variants of SARS-CoV-2 have been associated with plasma hypercoagulability (as judged by thromboelastography) and an extensive formation of fibrin amyloid microclots, which are considered to contribute to the pathology of the coronavirus 2019 disease (COVID-19). The newer Omicron variants appear to be far more transmissible, but less virulent, even when taking immunity acquired from previous infections or vaccination into account. We here show that while the clotting parameters associated with Omicron variants are significantly raised over those of healthy, matched controls, they are only raised to levels significantly lower than those seen with more severe variants such as Beta and Delta. We also observed that individuals infected with Omicron variants manifested less extensive microclot formation in platelet poor plasma compared to those harbouring the more virulent variants. The measurement of clotting effects between the different variants acts as a kind of ‘internal control’ that demonstrates the relationship between the extent of coagulopathies and the virulence of the variant of interest. This adds to the evidence that microclots play an important role in determining the severity of symptoms observed in COVID-19.
Measurement of cerebrospinal fluid lactate levels in pediatric patients with suspected ventriculoperitoneal shunt infection. Retrospective cohort study
Authors: Fernández Jose Pablo , Acosta Natalia , Flores Tamara , Fernández Gabriela
Published: September 2022

Introduction: Ventriculoperitoneal shunt (VPS) infection is a severe complication. Its early diagnosis could help to decrease morbidity and treatment costs. Lactate has been used for the diagnosis of other central nervous system infections. The aim of this study is to determine the usefulness of lactate for the diagnosis of VPS infection. Methodology: Retrospective cohort study. Patients who consulted between May 2019 and May 2022 with VPS dysfunction had lactate measured. Means were compared according to culture results. A ROC curve was performed to determine the appropriate cut-off point.Result: Lactate has a high negative predictive value, but low positive predictive value, for the diagnosis of ventriculitis.
The Efficacy and Safety of Nab-Paclitaxel Plus Gemcitabine versus mFOLFIRINOX in the First-Line Treatment of Metastatic Pancreatic Cancer: A Retrospective Study.
Authors: Yang Lei , Su Jing , Wang Wenbo , Zhou Fuxiang
Published: September 2022

Background
Nab-paclitaxel plus Gemcitabine (AG) and modified FOLFIRINOX (FFX) are two systemic therapies that have been widely used as standard first-line chemotherapy regimens in metastatic pancreatic cancer. However, since there is no clinical trial to directly compare the efficacy and safety of the two regimens, it is not clear which regimen is more effective. In this study, we aim to examine and compare the efficacy and safety of AG and FFX as first-line chemotherapy regimens in Chinese patients with metastatic pancreatic cancer in a real-world setting.
Methods
We retrospectively evaluated the outcomes of 41 patients who diagnosed with metastatic pancreatic cancer and were treated with either AG (n = 21) or FFX (n = 20) as first-line chemotherapy between March 2017 and February 2022 at Zhongnan hospital of Wuhan University.
Results
Of 41 patients in this study, 21 were treated with AG and 20 were treated with FFX as first-line chemotherapy. No significant differences in baseline characteristics were found between the two groups. The objective response rate (ORR)was 14.3% in the AG group and 20.0% in the FFX group. The disease control rate (DCR) was 71.4% in the AG group and 60.0% in the FFX group. There was no significant difference in PFS or OS between the AG group and the FFX group.The median progression-free survival (PFS) was 5.27 months (95% confidence interval [CI], 4.08–6.46) in the AG group and 3.67 months (95% CI, 2.28–5.05, p = 0.192)in the FFX group.The median overall survival (OS) was 10.03 months (95% CI, 7.33–12.63) in the AG group and 9.02 months (95% CI,6.02–11.98, p = 0.464) in the FFX group.The second-line treatment rate was 47.1% in the AG group and 55.0% in the FFX group. Immune checkpoint inhibitors (ICIs) based regimens are common second-line treatment options whether in AG or FFX group. Significantly more grade 3–4 peripheral neuropathy occurred in the AG than the FFX groups (4 (19.0%) vs 0 (0.0%), p = 0.040*).The patients in the PNI(Prognostic nutrition index) ≥ 45 group had a significant longer median OS (PNI ≥ 45 vs PNI < 45: 10.34 vs 6.90 mo, P = 0.005).
Conclusion
AG and FFX showed comparable efficacy outcomes in patients with metastatic pancreatic cancer. Pancreatic cancer patients receiving first-line chemotherapy with good nutritional status are likely to have a better prognosis.
Discovering Ordered Motif Combinations in EZH2 Interacting Long Non-coding RNAs
Authors: Whorley Raymond , Waters Ella , Kalu Azuma , Crea Francesco , Laney Robin
Published: September 2022

Background
EZH2 is linked to cancer, interacting in various ways with some long non-coding RNAs but not others. It is reasonable to assume that the interacting sequences have physical interaction sites which are not present in the non-interacting ones. We hypothesise that these interaction sites correspond to motifs (short subsequences) which appear in a particular order. We have developed software to find such ordered motif combinations. The software can also suggest where larger scale similarities between and within lncRNAs may be found by calculating mean information content.
Results
We investigated motifs of length 5 to 11, with up to 3 motifs per combination, in murine lncRNAs. Appearing in 13 out of 59 interacting lncRNAs, 4 combinations comprising 2 motifs of length 6 have been identified as EZH2 interaction site candidates which can be further investigated.
Conclusions
Our predictions can be tested experimentally to ascertain whether or not these combinations really do constitute interaction sites. For example, genome editing can be employed to measure the cellular and molecular effects of ablating these sequences in the EZH2-interacting lncRNAs. In addition, computational and advanced microscopy methodologies can be employed to locate these motifs within the tri-dimensional structure of these lncRNAs.
Development of multifunctional celastrol nanoparticles to enhance antitumor effects by interfering with the function of mitochondria in breast cancer
Authors: Qin Yanru , Wang Zhongjie , Wang Xueyuan , Zhang Tianyu , Hu Yixue , Wang Dongna , Sun Hui , Zhang Liefeng , Zhu Yongqiang
Published: September 2022

Mitochondria play an important role in genesis and development of tumor, and are also drug targets. Herein, we developed a multifunctional celastrol (cela) nanoparticles with a positive core and a negative outer layer. Firstly, the mitochondrial targeted material: triphenyl phosphonium-tocopherol polyethylene glycol succinate (TPP-TPGS, TT) was synthesized, and prepared TT/PLGA@cela nanoparticles (NPs). Then, the positive charge on the surface was neutralized using tumor targeted and pH sensitive chondroitin sulfate-folic acid (CS-FA) material to obtain CS-FA/TT/PLGA@cela NPs. Characterization revealed CS-FA/TT/PLGA@cela NPs to be globular particles with smooth surfaces and an average diameter of 100 nm. This construct could improve the uptake in 4T1 cells. After CS-FA/TT/PLGA@cela NPs entered cancer cells, CS-FA was degraded, then the positively charged TT/PLGA@cela NPs were exposed and completed lysosomal escape, finally localizing to mitochondria. Subsequently, in the alkaline environment of mitochondria, cela is released to kill cancer cells. Meanwhile, the results of the mitochondrial respiration test and mitochondrial membrane potential assay demonstrated that CS-FA/TT/PLGA@cela NPs exerted mitochondrial injury and damage. Moreover, the NPs remarkably enhanced proapoptotic protein expression in 4T1 cells. Importantly, this nanoplatform was able to achieve excellent anti-cancer effectsin vivo. Together, the results indicated that the mitochondria-targeting CS-FA/TT/PLGA@cela NPs potentially represent a signifcant advancement in breast cancer treatment.
Cannabidiol Inhibited Reproductive Ability of Zebrafish (Danio Rerio) with Gender-Dependent Manner
Authors: LI LIN , Fan Bei , Kong Zhiqiang , Zhang Yifan , Zhao Mengying , Jesus Simal-Gandara , Wang Fengzhong , LI Minmin
Published: September 2022

Cannabidiol (CBD), a medically active component of hemp, is a popular ingredient in healthcare and personal-care products. The increasing demand for CBD and the legalization of hemp growth may promote chronic exposure of non-target organisms and animals to CBD. In the present study, the reproductive toxicity of CBD was investigated using zebrafish as a model organism. With CBD treatment, parent female zebrafish spawned less with higher natural mortality and malformation rates, showed a decreased gonadosomatic index with an increased percentage of pre-mature oocytes and sperm and had an increased hepatosomatic index. The value of estrogen/testosterone (E2/T) decreased in female zebrafish and increased in male zebrafish. Vitellogenin content was decreased in both female and male zebrafish. Reproductive-related genes were downregulated in the zebrafish brain and liver, whereas esr-α, esr-β, and ar were downregulated in ovaries and upregulated in testicles. Sex hormone synthesis genes were downregulated in ovaries and upregulated in testicles, except for cyp11a, in contrast to the other genes. Apoptosis-related genes were upregulated in the zebrafish brain, gonad, and liver. These results show that CBD might damage the hypothalamus-pituitary-gonad-liver axis function by inducing an apoptotic response, further inhibiting zebrafish reproductive ability in a sex-dependent manner.
Novel 2-hydroxynapthyl functionalized aluminum-based metal-organic framework for fluorescence detection of Zn 2+ in the aqueous medium
Authors: Kaur Manpreet , garg Deepika , Yusuf Mohamad , Malik Ashok Kumar
Published: September 2022

A new aluminum-based metal-organic framework (MOF), namelyMIL-53-HNA, was synthesized using low-cost Schiff base linker, 2-(2-hydroxynapthyl-1-imine)terephthalic acid (coded as H2HNA). Because of an excellent fluorescent features of this synthesized MOF, we decided to test its suitability for detecting heavy metal ions in aqueous solution. It is interesting to note that the MIL-53-HNA chemosensor could detect Zn2+ ions in water via turn-on response with good sensitivity and selectivity without being interferedfrom diverse metal ions including Na+, Cd2+, Cu2+, Ni2+, Al3+, Pb2+, Co2+, and Fe3+. The selectivity of this sensortowards Zn2+ ions in aqueous solution could be explained through preferential complexation of these ions via free hydroxyl and imine groups present inside its pore cages. This selective complexation suppressed the photo-induced electron-transfer (PET) process from imine (-CH=N-) double bond to the naphthalene group. This suppression of PET process restored the fluorescence of the naphthalene group in the Zn2+treated MIL-53-HNA chemosensor which ultimatelyled to enhancement of itsfluorescence intensity. Theoreticalcalculations have also been done to provide a thorough explanation of thisturn-on mechanistic response of MIL-53-HNA towards Zn2+ions. Additionally, this sensor showed extremely low limit of detection (LOD), 6.8 µM, demonstrated its exceptional Zn2+ detection capabilities. Low cost, excellent stability, sensitivity, and selectivity are the most promising characteristics of this synthesized chemosensor which make it suitable for wastewater treatment.
How to Rejuvenate Traditional Markets
Authors: Andriana Denny , Smith Julia A , Reid Gavin C
Published: September 2022

We propose a research agenda for exploring the efficacy of indigenous markets, with pasar in Indonesia as an example. The piecemeal application of policies across multiple provinces has been variable in its success. Indonesia offers a rich and varied palette of research projects, aimed at exploring the unique marketplace phenomenon of pasar. Our initial finding is that there is a considerable advantage of Jakarta over Bandung pasar, in terms of both tangible and intangible measures of quality.Article Type: Research Corner
Medication adherence and cognitive performance in schizophrenia-spectrum and bipolar disorder: results from the PsyCourse Study
Authors: Senner Fanny , Hiendl Lena , Bengesser Susanne , Adorjan Kristina , Anghelescu Ion-George , Baune Bernhard , Budde Monika , Dannlowski Udo , Dietrich Detlef , Falkai Peter , Fallgatter Andreas , Hasan Alkomiet , Heilbronner Maria , Jäger Markus , Juckel Georg , Kalman Janos , Konrad Carsten , Kohshour Mojtaba Oraki , Papiol Sergi , Reich-Erkelenz Daniela , Reimer Jens , Schaupp Sabrina , Schmauß Max , Senner Simon , Spitzer Carsten , Vogl Thomas , Zimmermann Jörg , Heilbronner Urs , Schulte Eva , Schulze Thomas G. , Reininghaus Eva , Kirchner Sophie-Kathrin , Dalkner Nina
Published: September 2022

Existing guidelines recommend psychopharmacological treatment for the management of schizophrenia and bipolar disorder as part of holistic treatment concepts. About half of patients do not take their medication regularly, although treatment adherence can prevent exacerbations and re-hospitalizations. To date, the relationship of medication adherence and cognitive performance is understudied. Therefore, this study investigated the relationship between medication adherence and cognitive performance by analyzing the data of 862 participants with schizophrenia-spectrum and bipolar disorders (mean [SD] age, 41.9 [12.48] years; 44.8% female) from a multicenter study (PsyCourse Study). Z-scores for three cognitive domains were calculated, global functioning was measured with the Global Assessment of Functioning Scale, and adherence was assessed by a self-rating questionnaire. We evaluated four multiple linear regression models and built three clusters with hierarchical cluster analyses. Higher adherence behavior (p < 0.001) was associated with better global functioning but showed no impact on the cognitive domains learning and memory, executive function, and psychomotor speed. The hierarchical cluster analysis resulted in three clusters with different cognitive performance, but patients in all clusters showed similar adherence behavior. The study identified cognitive subgroups independent of diagnoses, but no differences were found in the adherence behavior of the patients in these new clusters. In summary, medication adherence was associated with global but not cognitive functioning in patients with schizophrenia-spectrum and bipolar disorders. In both diagnostic groups, cognitive function might be influenced by various factors but not by medication adherence.
Improvements in histological technique for the ecotoxicological assessment using small biological samples
Authors: SANTANA LIGIA , Damasceno Évila P. , Loureiro Susana , Soares Amadeu M.V.M. , Pousão-Ferreira Pedro , Abessa Denis M. S. , Martins Roberto , Pavlaki Maria D.
Published: September 2022

Histological techniques consist of traditional and very important tools for a better understanding of cellular morphology and physiology in ecotoxicological studies. Despite bioassays generally recommending the use of small test organisms, based on some advantages as their low maintenance costs and large replicates’ number, the histological processing of small organisms is not commonly used due to demanding laboratorial handling. The present study proposes an accessible protocol for a histological method in fish larvae with a maximum length of 8 mm, as well as the use of histopathological biomarkers on Senegal sole larvae for ecotoxicological testing. Eight-day old larvae of Solea senegalensis obtained from breeders' natural spawns in cultivation conditions were submitted to histological processing by an adjusted protocol comprising fixation, agarose array pre-embedding, paraffin embedding, slides preparation, and image analysis by light optical microscope coupled to a digital camera. Low-cost and easy-to-use alternatives were applied in the technique execution. The histological steps were detailed and the multiple tissues and cellular structures of the S. senegalensis larvae were described and discussed. This can be considered a valuable background information for ecotoxicological studies where changes in cell morphology and physiology are expected.
Adaptation of a psycho-educative group programme to improve coping in dementia caregiving: a feasibility study with mixed-methods
Authors: Pihet Sandrine , Clément Marie , Terrapon Eugenie , Kipfer Stephanie
Published: September 2022

Background
As the number of people living with dementia rapidly increases worldwide, the support provided by their informal caregivers remains key to the sustainability of most healthcare systems, this voluntary contribution representing 40% of the costs of dementia worldwide. Informal caregiving in dementia, however, is linked to long periods of chronic stress with frequent and serious negative consequences on the health and quality of life of the caregiver. A psycho-educative group intervention focusing on coping with the daily stress of dementia caregiving (“Learning to feel better… to help better”), developed in French-speaking Canada and showing broad effects on quality of life, was selected with the aim of 1) adapting it to a new cultural context (French-speaking Switzerland) based on identified facilitators and barriers, using a participative approach; and 2) conducting a feasibility study to evaluate whether the adapted programme showed similar or improved feasibility and effects compared to the original Canadian programme.
Methods
A mixed-methods concurrent nested design was used to evaluate the feasibility and the effects on five quantitative core outcomes. Additional qualitative data helped document in depth the acceptability and impact of the intervention.
Results
We shortened the programme from 30 to 21 hours in total, which resulted in increased accessibility, in terms of facilitated recruitment of participants and inclusion of a broader range of informal caregivers. There were significant reductions in subjective burden (effect size: d=-0.32) and psychological distress (d=-0.48), as well as decreases in the stress reactions of informal caregivers related to the behaviour problems of the persons with dementia (d=-0.57). The qualitative results emphasized the usefulness of providing informal caregivers with structured procedures for efficiently tackling everyday challenges, and of enabling learning through a variety of channels and activities.
Conclusions
Substantial improvements are associated with this 21-hour group intervention, organised in 7 sessions of 3 hours each, focused on learning more efficient strategies to cope with the daily stress of dementia caregiving. This intervention empowered informal caregivers to master their daily challenges with more confidence, satisfaction and calm.
Trial registration:
ISRCTN13512408 (registration date 17.05.2021, retrospectively registered).