bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advances of MXene-Based Electrochemical Immunosensors
Authors: Yang Meiqing , Lu Haozi , Liu Song
Published: June 2022

Electrochemical immunosensors are the largest class of affinity biosensing devices with strong practicability. In recent years, MXenes have become hotspot materials of electrochemical biosensors for their excellent properties, including large specific surface area, good electrical conductivity, high hydrophilicity and rich functional groups. In this review, we firstly introduce the composition and structure of MXenes, as well as their properties relevant to the construction of biosensors. Then, we summarize the recent advances of MXenes-based electrochemical immunosensors, focusing on the roles of MXenes in various electrochemical immunosensors. Finally, we analyze current problems of MXenes-based electrochemical immunosensors and propose an outlook for this research field.
Performance of the Compliant Foil Gas Seal with Surface Micro-Textured Top Foil
Authors: Xu Jie , Yu Shurong , Ding Xuexing , Jiang Haitao , Li Lu
Published: June 2022

In various fields, micro-textures have been successfully applied to the surface of friction pairs to effectively improve flow field and friction performance. This paper aims to investigate how different textures affect the sealing performance of compliant foil gas film seals. In theoretical simulations, a facile method for characterizing the shape of micro-textures is proposed, and the equilibrium relationship between the gas film pressure, gas film thickness, and foil deformation is established. The transient Reynolds equation considering the eccentric convergence problem and abrupt Rayleigh step changes is solved to analyze the static and dynamic characteristics. The results show that (i) compared with the directionality of the texture, the gas volume accommodated by the texture has a greater impact on the sealing performance, and a convergent texture can effectively control the leakage rate; (ii) when the texture depth exceeds 9 μm, the sealing system may be unstable; (iii) the compliant foil seal is well suited to higher-speed service conditions, and the inverted triangular texture shows the best comprehensive sealing performance.
Behavioral Response of Multiple Rainbow Trout to Vertically Suspended Environmental Enrichment
Authors: Huysman Nathan , Robidoux Michael , Morris Benj , Voorhees Jill M. , Krebs Eric , Barnes Michael E.
Published: June 2022

Vertically suspended environmental enrichment improves the rearing performance of fish during aquaculture production, but the reason for this improvement is unclear. This study documented the behavior of groups of rainbow trout (Oncorhynchus mykiss), as indicated by their in-tank location preferences, in response to vertically suspended structure. The location of both experienced and naïve fish (with or without prior exposure to vertically suspended enrichment) in both barren and enriched tanks was recorded. In-tank locations were significantly different for experienced fish in both barren and enriched tanks but were similar for naïve fish. When observations were combined for both the presence and absence of enrichment, naïve fish locations were significantly different from experienced fish. Locations were also significantly different for all fish in enriched compared to barren tanks. These results indicate that trout location is influenced by the presence of vertically suspended environmental enrichment and that learning from prior experience with enrichment occurs.
Comparison of the Impact of Ship Emissions in Northern Europe and Eastern China
Authors: Schwarzkopf Daniel A. , Petrik Ronny , Matthias Volker , Quante Markus , Yu Guangyuan , Zhang Yan
Published: June 2022

It is well known that ship emissions contribute significantly to atmospheric pollution. However, the impact on air quality can regionally vary, as influenced by parameters such as the composition of the regional shipping fleet, state of background atmospheric pollution, and meteorological aspects. This study compared two regions with high shipping densities in 2015. These include the North and Baltic Seas in Europe and the Yellow and East China Seas in China. Here, a key focal point is an evaluation of differences and similarities of the impacts of ship emissions under different environmental conditions, particularly between regions with medium (Europe) and high air pollution (China). To assess this, two similarly performed chemical transport model runs were carried out with highly resolved bottom-up ship emission inventories for northern Europe and China, calculated with the recently developed MoSES model, publicly available emissions data for nonshipping sources (EDGAR, MEIC). The performance of the model was evaluated against measurement data recorded at coastal stations. Annual averages at affected coastal regions for NO2, SO2, O3 and PM2.5 were modeled in Europe to be 3, below 0.3, 2.5, 1 and in China 3, 2, 2–8, 1.5, respectively, all given in μg/m3. In highly affected regions, such as large harbors, the contributions of ship-related emissions modeled in Europe were 15%, 0.3%, −12.5%, 1.25% and in China were 15%, 6%, −7.5%, 2%, respectively. Absolute pollutant concentrations from ships were modeled slightly higher in China than in Europe, albeit the relative impact was smaller in China due to higher emissions from other sectors. The different climate zones of China and the higher level of atmospheric pollution were found to seasonally alter the chemical transformation processes of ship emissions. Especially in northern China, high PM concentrations during winter were found to regionally inhibit the transformation of ship exhausts to secondary PM, and reduce the impact of ship-related aerosols, compared to Europe.
A Recommendation Model for Selling Rules in the Telecom Retail Industry
Authors: Ou Tsung-Ying , Tsai Wen-Lung , Lee Yi-Chen , Chang Tien-Hsiang , Lee Shih-Hsiung , Huang Fen-Fen
Published: June 2022

The recommendation of the optimal selling rules for any product or service is challenging, owing to the complexity of the customer’s behavior and the competitiveness existing in the telecom retail industry. This study proposes a recommendation model for selling rules that utilizes a hybrid decision-making approach based on K-means and the C5.0 decision tree to analyze the historical sales information of telecom retailers. To evaluate the efficacy of the proposed recommendation model, it was used to analyze original data from a case company. The results indicated that the proposed hybrid decision-making approach resulted in sales content with a high gross profit and high agreement rates. The experimental results show each cluster that can be used to identify rules for the combination of good tariff items in different tariff ranges. Rules for the recommendation of special tariffs are also established to assist salespeople.
Effect of Mechanical Activation and Carbon Coating on Electrochemistry of TiNb2O7 Anodes for Lithium-Ion Batteries
Authors: Kosova Nina V. , Tsydypylov Dmitry Z.
Published: June 2022

TiNb2O7 anode material with a Wadsley–Roth crystallographic shear structure was prepared by solid-state synthesis at a relatively low temperature (1000 °C) and a short calcination time (4 h) using preliminary mechanical activation of the reagent mixture. The as-prepared final product was then ball milled in a planetary mill with and without carbon black. The crystal structure and morphology of the samples were studied by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Electrochemical performance was studied in a galvanostatic mode in varied voltage intervals and at different cycling rates in combination with in situ electrochemical impedance spectroscopy (EIS) measurements. The resistance measured using in situ EIS had the highest values at the end of the discharge and the lowest when charging. The lithium diffusion coefficient, determined by galvanostatic intermittent titration technique (GITT), in samples milled with and without carbon black was an order of magnitude higher than that for the pristine sample. It was shown that improved electrochemical performance of the carbon composite TiNb2O7/C (reversible capacity of 250 mAh g−1 at C/10 with Coulomb efficiency of ~99%) was associated with improved conductivity due to the formation of a conductive carbon matrix and uniform distribution of submicron particles by size.
Model-Guided Metabolic Rewiring for Gamma-Aminobutyric Acid and Butyrolactam Biosynthesis in Corynebacterium glutamicum ATCC13032
Authors: Zhang Yun , Zhao Jing , Wang Xueliang , Tang Yuan , Liu Shuwen , Wen Tingyi
Published: June 2022

Gamma-aminobutyric acid (GABA) can be used as a bioactive component in the pharmaceutical industry and a precursor for the synthesis of butyrolactam, which functions as a monomer for the synthesis of polyamide 4 (nylon 4) with improved thermal stability and high biodegradability. The bio-based fermentation production of chemicals using microbes as a cell factory provides an alternative to replace petrochemical-based processes. Here, we performed model-guided metabolic engineering of Corynebacterium glutamicum for GABA and butyrolactam fermentation. A GABA biosynthetic pathway was constructed using a bi-cistronic expression cassette containing mutant glutamate decarboxylase. An in silico simulation showed that the increase in the flux from acetyl-CoA to α-ketoglutarate and the decrease in the flux from α-ketoglutarate to succinate drove more flux toward GABA biosynthesis. The TCA cycle was reconstructed by increasing the expression of acn and icd genes and deleting the sucCD gene. Blocking GABA catabolism and rewiring the transport system of GABA further improved GABA production. An acetyl-CoA-dependent pathway for in vivo butyrolactam biosynthesis was constructed by overexpressing act-encoding ß-alanine CoA transferase. In fed-batch fermentation, the engineered strains produced 23.07 g/L of GABA with a yield of 0.52 mol/mol from glucose and 4.58 g/L of butyrolactam. The metabolic engineering strategies can be used for genetic modification of industrial strains to produce target chemicals from α-ketoglutarate as a precursor, and the engineered strains will be useful to synthesize the bio-based monomer of polyamide 4 from renewable resources.
Prediction of Major Histocompatibility Complex Binding with Bilateral and Variable Long Short Term Memory Networks
Authors: Jiang Limin , Tang Jijun , Guo Fei , Guo Yan
Published: June 2022

As an important part of immune surveillance, major histocompatibility complex (MHC) is a set of proteins that recognize foreign molecules. Computational prediction methods for MHC binding peptides have been developed. However, existing methods share the limitation of fixed peptide sequence length, which necessitates the training of models by peptide length or prediction with a length reduction technique. Using a bidirectional long short-term memory neural network, we constructed BVMHC, an MHC class I and II binding prediction tool that is independent of peptide length. The performance of BVMHC was compared to seven MHC class I prediction tools and three MHC class II prediction tools using eight performance criteria independently. BVMHC attained the best performance in three of the eight criteria for MHC class I, and the best performance in four of the eight criteria for MHC class II, including accuracy and AUC. Furthermore, models for non-human species were also trained using the same strategy and made available for applications in mice, chimpanzees, macaques, and rats. BVMHC is composed of a series of peptide length independent MHC class I and II binding predictors. Models from this study have been implemented in an online web portal for easy access and use.
Sensitive and Stable Electrochemical Sensor for Folic Acid Determination Using a ZIF-67/AgNWs Nanocomposite
Authors: Sun Yujiao , Wang Xue , Zhang Hao
Published: June 2022

An electrochemical sensor using silver nanowires (AgNWs)-doped with a zeolite-like metal–organic framework (ZIF-67) was developed for highly sensitive and stable determination of folic acid (FA). The ZIF-67/AgNWs nanocomposite was prepared by a one-step reaction via a template method and drop-coated onto the surface of a screen-printed carbon electrode (SPCE) to form a ZIF-67/AgNWs@SPCE electrochemical sensing platform. The electrochemical square wave voltammetry (SWV) curve for this sensing platform was measured in an electrolyte solution containing FA under the optimum experimental conditions. The redox peak current of FA (IFA) increased with increases in the FA concentration (CFA). There was a linear relationship between IFA and CFA in the range of 0.1 μM to 10 μM, and the determination limit was 30 nM. The ZIF-67/AgNWs@SPCE was used as an electrochemical sensor for FA which maintained a good stability over 7 days and showed good determination performance in real samples with a high recovery rate (100.9–102.1%, n = 6).
Lower Posterior Cingulate N-Acetylaspartate to Creatine Level in Early Detection of Biologically Defined Alzheimer’s Disease
Authors: Chen Qianyun , Abrigo Jill , Liu Wanting , Han Elyia Yixun , Yeung David Ka Wai , Shi Lin , Au Lisa Wing Chi , Deng Min , Chen Sirong , Leung Eric Yim Lung , Ho Chi Lai , Mok Vincent Chung Tong , Chu Winnie Chiu Wing
Published: June 2022

Alzheimer’s disease (AD) was recently defined as a biological construct to reflect neuropathologic status, and both abnormal amyloid and tau are required for a diagnosis of AD. We aimed to determine the proton MR spectroscopic (1H-MRS) patterns of the posterior cingulate in biologically defined AD. A total of 68 participants were included in this study, comprising 37 controls, 16 early AD, and 15 late AD, who were classified according to their amyloid and tau status and presence of hippocampal atrophy. Compared with controls, early AD showed lower N-acetylaspartate (NAA)/creatine (Cr) (p = 0.003), whereas late AD showed lower NAA/Cr and higher myoInositol (mI)/Cr (all with p < 0.05). Lower NAA/Cr correlated with a greater global amyloid load (r = −0.47, p < 0.001) and tau load (r = −0.51, p < 0.001) and allowed a discrimination of early AD from controls (p < 0.001). Subgroup analysis showed that NAA/Cr also allowed a differentiation of early AD from controls in the cognitively unimpaired subjects, with an area under the receiver operating characteristics curve, sensitivity, and specificity of 0.96, 100%, and 83.8%, respectively. Lower posterior cingulate NAA levels may help to inform underlying neuropathologic changes in the early stage of AD.
Resting-State Neuronal Activity and Functional Connectivity Changes in the Visual Cortex after High Altitude Exposure: A Longitudinal Study
Authors: Zhang Xinjuan , Kang Taishan , Liu Yanqiu , Yuan Fengjuan , Li Minglu , Lin Jianzhong , Zhang Jiaxing
Published: June 2022

Damage to the visual cortex structures after high altitude exposure has been well clarified. However, changes in the neuronal activity and functional connectivity (FC) of the visual cortex after hypoxia/reoxygenation remain unclear. Twenty-three sea-level college students, who took part in 30 days of teaching at high altitude (4300 m), underwent routine blood tests, visual behavior tests, and magnetic resonance imaging scans before they went to high altitude (Test 1), 7 days after they returned to sea level (Test 2), as well as 3 months (Test 3) after they returned to sea level. In this study, we investigated the hematological parameters, behavioral data, and spontaneous brain activity. There were significant differences among the tests in hematological parameters and spontaneous brain activity. The hematocrit, hemoglobin concentration, and red blood cell count were significantly increased in Test 2 as compared with Tests 1 and 3. As compared with Test 1, Test 3 increased amplitudes of low-frequency fluctuations (ALFF) in the right calcarine gyrus; Tests 2 and 3 increased ALFF in the right supplementary motor cortex, increased regional homogeneity (ReHo) in the left lingual gyrus, increased the voxel-mirrored homotopic connectivity (VMHC) value in the motor cortex, and decreased FC between the left lingual gyrus and left postcentral gyrus. The color accuracy in the visual task was positively correlated with ALFF and ReHo in Test 2. Hypoxia/reoxygenation increased functional connection between the neurons within the visual cortex and the motor cortex but decreased connection between the visual cortex and motor cortex.
Spike-Dependent Dynamic Partitioning of the Locus Coeruleus Network through Noradrenergic Volume Release in a Simulation of the Nucleus Core
Authors: Baral Shristi , Hosseini Hassan , More Kaushik , Fabrin Thomaz M. C. , Braun Jochen , Prigge Matthias
Published: June 2022

The Locus coeruleus (LC) modulates various neuronal circuits throughout the brain. Its unique architectural organization encompasses a net of axonal innervation that spans the entire brain, while its somatic core is highly compact. Recent research revealed an unexpected cellular input specificity within the nucleus that can give rise to various network states that either broadcast norepinephrine signals throughout the brain or pointedly modulate specific brain areas. Such adaptive input–output functions likely surpass our existing network models that build upon a given synaptic wiring configuration between neurons. As the distances between noradrenergic neurons in the core of the LC are unusually small, neighboring neurons could theoretically impact each other via volume transmission of NE. We therefore set out to investigate if such interaction could be mediated through noradrenergic alpha2-receptors in a spiking neuron model of the LC. We validated our model of LC neurons through comparison with experimental patch-clamp data and identified key variables that impact alpha2-mediated inhibition of neighboring LC neurons. Our simulation confirmed a reliable autoinhibition of LC neurons after episodes of high neuronal activity that continue even after neuronal activity subsided. Additionally, dendro-somatic synapses inhibited spontaneous spiking in the somatic compartment of connected neurons in our model. We determined the exact position of hundreds of LC neurons in the mouse brain stem via a tissue clearing approach and, based on this, further determined that 25 percent of noradrenergic neurons have a neighboring LC neuron within less than a 25-micrometer radius. By modeling NE diffusion, we estimated that more than 15 percent of the alpha2-adrenergic receptors fraction can bind NE within such a diffusion radius. Our spiking neuron model of LC neurons predicts that repeated or long-lasting episodes of high neuronal activity induce partitioning of the gross LC network and reduce the spike rate in neighboring neurons at distances smaller than 25 μm. As these volume-mediating neighboring effects are challenging to test with the current methodology, our findings can guide future experimental approaches to test this phenomenon and its physiological consequences.
Association between Incidental Pelvic Inflammation and Aggressive Prostate Cancer
Authors: Chakravarty Dimple , Ratnani Parita , Huang Li , Dovey Zachary , Sobotka Stanislaw , Berryhill Roy , Merisaari Harri , Al Shaarani Majd , Rai Richa , Jambor Ivan , Yadav Kamlesh K. , Mittan Sandeep , Parekh Sneha , Kodysh Julia , Wagaskar Vinayak , Brody Rachel , Cordon-Cardo Carlos , Rykunov Dmitry , Reva Boris , Davicioni Elai , Wiklund Peter , Bhardwaj Nina , Nair Sujit S. , Tewari Ashutosh K.
Published: June 2022

The impact of pelvic inflammation on prostate cancer (PCa) biology and aggressive phenotype has never been studied. Our study objective was to evaluate the role of pelvic inflammation on PCa aggressiveness and its association with clinical outcomes in patients following radical prostatectomy (RP). This study has been conducted on a retrospective single-institutional consecutive cohort of 2278 patients who underwent robot-assisted laparoscopic prostatectomy (RALP) between 01/2013 and 10/2019. Data from 2085 patients were analyzed to study the association between pelvic inflammation and adverse pathology (AP), defined as Gleason Grade Group (GGG) > 2 and ≥ pT3 stage, at resection. In a subset of 1997 patients, the association between pelvic inflammation and biochemical recurrence (BCR) was studied. Alteration in tumor transcriptome and inflammatory markers in patients with and without pelvic inflammation were studied using microarray analysis, immunohistochemistry, and culture supernatants derived from inflamed sites used in functional assays. Changes in blood inflammatory markers in the study cohort were analyzed by O-link. In univariate analyses, pelvic inflammation emerged as a significant predictor of AP. Multivariate cox proportional-hazards regression analyses showed that high pelvic inflammation with pT3 stage and positive surgical margins significantly affected the time to BCR (p ≤ 0.05). PCa patients with high inflammation had elevated levels of pro-inflammatory cytokines in their tissues and in blood. Genes involved in epithelial-to-mesenchymal transition (EMT) and DNA damage response were upregulated in patients with pelvic inflammation. Attenuation of STAT and IL-6 signaling decreased tumor driving properties of conditioned medium from inflamed sites. Pelvic inflammation exacerbates the progression of prostate cancer and drives an aggressive phenotype.
Impact of Age on Multimodality Treatment and Survival in Locally Advanced Rectal Cancer Patients
Authors: De Nes Lindsey C. F. , Heil Thea C. , Verhoeven Rob H. A. , Lemmens Valery E. P. P. , Rutten Harm J. , De Wilt Johannes H. W. , Vissers Pauline A. J.
Published: June 2022

Background: Optimal treatment for locally advanced rectal cancer is neoadjuvant (chemo)radiation followed by radical surgery. This is challenging in the aging population because of frequently concomitant comorbidity. We analyzed whether age below and above 70 years is associated with differences in treatment strategy and outcome in this population-based study. Methods: Data between 2008 and 2016 were extracted from the Netherlands Cancer Registry with follow-up until 2021. Differences in therapy, referral and outcome were analyzed using χ2 tests, multivariable logistic regression and relative survival analysis. Results: In total, 6524 locally advanced rectal cancer patients were included. A greater proportion of patients <70 years underwent resection compared to older patients (89% vs. 71%). Patients ≥70 years were more likely treated with neoadjuvant radiotherapy (OR 3.4, 95% CI 2.61–4.52), than with chemoradiation (OR 0.3, 95% CI 0.23–0.37) and less often referred to higher volume hospitals for resection (OR 0.7, 95% CI 0.51–0.87). Five-year relative survival after resection following neoadjuvant therapy was comparable and higher for both patients <70 years and ≥70 years (82% and 77%) than after resection only. Resection only was associated with worse survival in the elderly compared to younger patients (56% vs. 75%). Conclusion: Elderly patients with locally advanced rectal cancer received less intensive treatment and were less often referred to higher volume hospitals for surgery. Relative survival was good and comparable after optimal treatment in both age groups. Effort is necessary to improve guideline adherence, and multimodal strategies should be tailored to age, comorbidity and performance status.
At the Crossroads of Life and Death: The Proteins That Influence Cell Fate Decisions
Authors: Dhokia Vinesh , Moss John A. Y. , Macip Salvador , Fox Joanna L.
Published: June 2022

When a cell is damaged, it must decide how to respond. As a consequence of a variety of stresses, cells can induce well-regulated programmes such as senescence, a persistent proliferative arrest that limits their replication. Alternatively, regulated programmed cell death can be induced to remove the irreversibly damaged cells in a controlled manner. These programmes are mainly triggered and controlled by the tumour suppressor protein p53 and its complex network of effectors, but how it decides between these wildly different responses is not fully understood. This review focuses on the key proteins involved both in the regulation and induction of apoptosis and senescence to examine the key events that determine cell fate following damage. Furthermore, we examine how the regulation and activity of these proteins are altered during the progression of many chronic diseases, including cancer.
Synergistic Tumor Inhibition via Energy Elimination by Repurposing Penfluridol and 2-Deoxy-D-Glucose in Lung Cancer
Authors: Lai Tsung-Ching , Lee Yueh-Lun , Lee Wei-Jiunn , Hung Wen-Yueh , Cheng Guo-Zhou , Chen Ji-Qing , Hsiao Michael , Chien Ming-Hsien , Chang Jer-Hwa
Published: June 2022

Energy metabolism is the basis for cell growth, and cancer cells in particular, are more energy-dependent cells because of rapid cell proliferation. Previously, we found that penfluridol, an antipsychotic drug, has the ability to trigger cell growth inhibition of lung cancer cells via inducing ATP energy deprivation. The toxic effect of penfluridol is related to energy metabolism, but the underlying mechanisms remain unclear. Herein, we discovered that treatment of A549 and HCC827 lung cancer cells with penfluridol caused a decrease in the total amount of ATP, especially in A549 cells. An Agilent Seahorse ATP real-time rate assay revealed that ATP production rates from mitochondrial respiration and glycolysis were, respectively, decreased and increased after penfluridol treatment. Moreover, the amount and membrane integrity of mitochondria decreased, but glycolysis-related proteins increased after penfluridol treatment. Furthermore, we observed that suppression of glycolysis by reducing glucose supplementation or using 2-deoxy-D-glucose (2DG) synergistically enhanced the inhibitory effect of penfluridol on cancer cell growth and the total amount of mitochondria. A mechanistic study showed that the penfluridol-mediated energy reduction was due to inhibition of critical regulators of mitochondrial biogenesis, the sirtuin 1 (SIRT1)/peroxisome-proliferator-activated receptor co-activator-1α (PGC-1α) axis. Upregulation of the SIRT1/PGC-1α axis reversed the inhibitory effect of penfluridol on mitochondrial biogenesis and cell viability. Clinical lung cancer samples revealed a positive correlation between PGC-1α (PPARGC1A) and SIRT1 expression. In an orthotopic lung cancer mouse model, the anticancer activities of penfluridol, including growth and metastasis inhibition, were also enhanced by combined treatment with 2DG. Our study results strongly support that a combination of repurposing penfluridol and a glycolysis inhibitor would be a good strategy for enhancing the anticancer activities of penfluridol in lung cancer.
Potential Prognostic Markers for Relapsed/Refractory vs. Responsive Acute Myeloid Leukemia
Authors: Vitkevičienė Aida , Skliutė Giedrė , Žučenka Andrius , Borutinskaitė Veronika , Navakauskienė Rūta
Published: June 2022

Acute myeloid leukemia (AML) is a heterogeneous disease. A significant proportion of AML patients is refractory to clinical treatment or relapses. Our aim is to determine new potential AML clinical treatment prognosis markers. We investigated various cell fate and epigenetic regulation important gene level differences between refractory and responsive AML patient groups at diagnosis stage and after clinical treatment using RT-qPCR. We demonstrated that oncogenic MYC and WT1 and metabolic IDH1 gene expression was significantly higher and cell cycle inhibitor CDKN1A (p21) gene expression was significantly lower in refractory patients’ bone marrow cells compared to treatment responsive patients both at diagnosis and after clinical treatment. Moreover, we determined that, compared to clinical treatment responsive patients, refractory patients possess a significantly higher gene expression of histone deacetylase 2 (HDAC2) and epigenetic DNA modulator TET1 and a significantly lower gene expression of lysine acetyltransferase 6A (KAT6A) and nucleosome remodeling and deacetylase (NuRD) complex component GATAD2A. We suggest that MYC, WT1, IDH1, CDKN1A, HDAC2, TET1, KAT6A and GATAD2A gene expression changes might characterize refractory AML. Thus, they might be useful for AML prognosis. Additionally, we suggest that epigenetic modulation might be beneficial in combination with standard treatment.
Amelanotic Uveal Melanomas Evaluated by Indirect Ophthalmoscopy Reveal Better Long-Term Prognosis Than Pigmented Primary Tumours—A Single Centre Experience
Authors: Markiewicz Anna , Donizy Piotr , Nowak Monika , Krzyziński Mateusz , Elas Martyna , Płonka Przemysław M. , Orłowska-Heitzmann Jolanta , Biecek Przemysław , Hoang Mai P. , Romanowska-Dixon Bożena
Published: June 2022

(1) Background: There is a constant search for new prognostic factors that would allow us to accurately determine the prognosis, select the type of treatment, and monitor the patient diagnosed with uveal melanoma in a minimally invasive and easily accessible way. Therefore, we decided to evaluate the prognostic role of its pigmentation in a clinical assessment. (2) Methods: The pigmentation of 154 uveal melanomas was assessed by indirect ophthalmoscopy. Two groups of tumours were identified: amelanotic and pigmented. The statistical relationships between these two groups and clinical, pathological parameters and the long-term survival rate were analyzed. (3) Results: There were 16.9% amelanotic tumours among all and they occurred in younger patients (p = 0.022). In pigmented melanomas, unfavourable prognostic features such as: epithelioid cells (p = 0.0013), extrascleral extension (p = 0.027), macronucleoli (p = 0.0065), and the absence of BAP1 expression (p = 0.029) were statistically more frequently observed. Kaplan–Meier analysis demonstrated significantly better overall (p = 0.017) and disease-free (p < 0.001) survival rates for patients with amelanotic tumours. However, this relationship was statistically significant for lower stage tumours (AJCC stage II), and was not present in larger and more advanced stages (AJCC stage III). (4) Conclusions: The results obtained suggested that the presence of pigmentation in uveal melanoma by indirect ophthalmoscopy was associated with a worse prognosis, compared to amelanotic lesions. These findings could be useful in the choice of therapeutic and follow-up options in the future.
Long-Term Tubular Dysfunction in Childhood Cancer Survivors; DCCSS-LATER 2 Renal Study
Authors: Kooijmans Esmee C. M. , van der Pal Helena J. H. , Pluijm Saskia M. F. , van der Heiden-van der Loo Margriet , Kremer Leontien C. M. , Bresters Dorine , van Dulmen-den Broeder Eline , van den Heuvel-Eibrink Marry M. , Loonen Jacqueline J. , Louwerens Marloes , Neggers Sebastian J. C. , Ronckers Cécile , Tissing Wim J. E. , de Vries Andrica C. H. , Kaspers Gertjan J. L. , Bökenkamp Arend , Veening Margreet A. ,   on behalf of the Dutch LATER Study Group
Published: June 2022

The aim of this nationwide cross-sectional cohort study was to determine the prevalence of and risk factors for tubular dysfunction in childhood cancer survivors (CCS). In the DCCSS-LATER 2 Renal study, 1024 CCS (≥5 years after diagnosis), aged ≥ 18 years at study, treated between 1963 and 2001 with potentially nephrotoxic therapy (i.e., nephrectomy, abdominal radiotherapy, total body irradiation, cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide, or hematopoietic stem cell transplantation) participated, and 500 age- and sex-matched participants from Lifelines acted as controls. Tubular electrolyte loss was defined as low serum levels (magnesium < 0.7 mmol/L, phosphate < 0.7 mmol/L and potassium < 3.6 mmol/L) with increased renal excretion or supplementation. A α1-microglobulin:creatinine ratio > 1.7 mg/mmol was considered as low-molecular weight proteinuria (LMWP). Multivariable risk analyses were performed. After median 25.5 years follow-up, overall prevalence of electrolyte losses in CCS (magnesium 5.6%, potassium 4.5%, phosphate 5.5%) was not higher compared to controls. LMWP was more prevalent (CCS 20.1% versus controls 0.4%). LMWP and magnesium loss were associated with glomerular dysfunction. Ifosfamide was associated with potassium loss, phosphate loss (with cumulative dose > 42 g/m2) and LMWP. Cisplatin was associated with magnesium loss and a cumulative dose > 500 mg/m2 with potassium and phosphate loss. Carboplatin cumulative dose > 2800 mg/m2 was associated with potassium loss. In conclusion, long-term tubular dysfunction is infrequent. Yet, ifosfamide, cisplatin and carboplatin are risk factors.
BET and CDK Inhibition Reveal Differences in the Proliferation Control of Sympathetic Ganglion Neuroblasts and Adrenal Chromaffin Cells
Authors: Sriha Jessica , Louis-Brennetot Caroline , Pierre-Eugène Cécile , Baulande Sylvain , Raynal Virginie , Kramdi Amira , Adameyko Igor , Ernsberger Uwe , Deller Thomas , Delattre Olivier , Janoueix-Lerosey Isabelle , Rohrer Hermann
Published: June 2022

Neuroblastoma arising from the adrenal differ from ganglionic neuroblastoma both genetically and clinically, with adrenal tumors being associated with a more severe prognosis. The different tumor properties may be linked to specific tumor founder cells in adrenal and sympathetic ganglia. To address this question, we first set up cultures of mouse sympathetic neuroblasts and adrenal chromaffin cells. These cultures were then treated with various proliferation inhibitors to identify lineage-specific responses. We show that neuroblast and chromaffin cell proliferation was affected by WNT, ALK, IGF1, and PRC2/EZH2 signaling inhibitors to a similar extent. However, differential effects were observed in response to bromodomain and extraterminal (BET) protein inhibitors (JQ1, GSK1324726A) and to the CDK-7 inhibitor THZ1, with BET inhibitors preferentially affecting chromaffin cells, and THZ1 preferentially affecting neuroblasts. The differential dependence of chromaffin cells and neuroblasts on BET and CDK signaling may indicate different mechanisms during tumor initiation in sympathetic ganglia and adrenal.
Endolysosome Iron Chelation Inhibits HIV-1 Protein-Induced Endolysosome De-Acidification-Induced Increases in Mitochondrial Fragmentation, Mitophagy, and Cell Death
Authors: Halcrow Peter W. , Kumar Nirmal , Quansah Darius N. K. , Baral Aparajita , Liang Braelyn , Geiger Jonathan D.
Published: June 2022

People with human immunodeficiency virus-1 (PLWH) experience high rates of HIV-1-associated neurocognitive disorders (HANDs); clinical symptoms range from being asymptomatic to experiencing HIV-associated dementia. Antiretroviral therapies have effectively prolonged the life expectancy related to PLWH; however, the prevalence of HANDs has increased. Implicated in the pathogenesis of HANDs are two HIV-1 proteins, transactivator of transcription (Tat) and gp120; both are neurotoxic and damage mitochondria. The thread-like morphological features of functional mitochondria become fragmented when levels of reactive oxygen species (ROS) increase, and ROS can be generated via Fenton-like chemistry in the presence of ferrous iron (Fe2+). Endolysosomes are central to iron trafficking in cells and contain readily releasable Fe2+ stores. However, it is unclear whether the endolysosome store is sufficient to account for insult-induced increases in levels of ROS, mitochondrial fragmentation, autophagy, and cell death. Using U87MG astrocytoma and SH-SY5Y neuroblastoma cells, we determined that chloroquine (CQ), Tat, and gp120 all (1) de-acidified endolysosomes, (2) decreased endolysosome numbers and increased endolysosome sizes, (3) increased mitochondrial numbers (fragmentation), (4) increased autophagosome numbers, (5) increased autolysosome numbers, (6) increased mitochondrial fragments within endolysosomes, and (7) increased cell death. These effects were all blocked by the endolysosome-specific iron chelator deferoxamine (DFO). Thus, the endolysosome de-acidification-induced release of endolysosome Fe2+ is sufficient to account for inter-organellar signaling events and cell biology consequences of HIV-1 proteins, including mitochondrial fragmentation, autophagy, and cell death.
Genetically Engineered Organisms: Possibilities and Challenges of Heavy Metal Removal and Nanoparticle Synthesis
Authors: Iravani Siavash , Varma Rajender S.
Published: June 2022

Heavy metal removal using genetically engineered organisms (GEOs) offer more cost and energy-efficient, safer, greener, and environmentally-friendly opportunities as opposed to conventional strategies requiring hazardous or toxic chemicals, complex processes, and high pressure/temperature. Additionally, GEOs exhibited superior potentials for biosynthesis of nanoparticles with significant capabilities in bioreduction of heavy metal ions that get accumulated as nanocrystals of various shapes/dimensions. In this context, GEO-aided nanoparticle assembly and the related reaction conditions should be optimized. Such strategies encompassing biosynthesized nanoparticle conforming to the green chemistry precepts help minimize the deployment of toxic precursors and capitalize on the safety and sustainability of the ensuing nanoparticle. Different GEOs with improved uptake and appropriation of heavy metal ions potentials have been examined for bioreduction and biorecovery appliances, but effective implementation to industrial-scale practices is nearly absent. In this perspective, the recent developments in heavy metal removal and nanoparticle biosynthesis using GEOs are deliberated, focusing on important challenges and future directions.
Mechanical Properties and Residual Stress Measurement of TiN/Ti Duplex Coating Using HiPIMS TiN on Cold Spray Ti
Authors: Dang Nhat Minh , Lin Wen-Yen , Wang Zhao-Ying , Alidokht Sima Ahmad , Chromik Richard R. , Chen Terry Yuan-Fang , Lin Ming-Tzer
Published: June 2022

This study investigated the mechanical properties and the residual stress of high-power impulse magnetron sputtering (HiPIMS) titanium nitride (TiN) thin film capping on cold spray titanium (Ti) coating. This TiN/Ti duplex coating was deposited on the Ti substrate, and the cold spray titanium (Ti) coating was prepared in three cases with different numbers of layers. The study determined Young’s modulus, hardness, and roughness of TiN thin film and cold spray Ti coatings by nano-indentation and AFM. The residual stress measurement of TiN/Ti duplex coating was conducted using the ring-core drilling method. A focused ion beam (FIB) drilled the TiN/Ti duplex coating with various milling depth steps. The corresponding images were obtained with a scanning electron microscope (SEM). The relationship between surface deformations and relaxation stress after each milling depth step was obtained using the digital image correlation (DIC) method. The results showed TiN/Ti duplex coating exhibited excellent mechanical properties, and the residual stresses were not significantly changing with different Ti cold spray substrates, showing the feasibility of coating technology for the future applications in the aerospace industry.
Research on the Wear Characteristics of the Hook Teeth of Cotton Pickers
Authors: Li Haiyang , Fu Xiuqing , Wang Hongbiao , Zhang Hongwen , Gu Yanqing , Du Xintian , Tao Yichen , Li Jia
Published: June 2022

As a key core component of cotton pickers, the spindle is prone to wear of the hook teeth. This research explores the wear characteristics of the spindle hook teeth of cotton pickers under different working areas. The sampled spindles were cut, the element composition and hardness of the spindle hook tooth coating and substrate were determined, the surface morphology of the spindle hook tooth was characterized, and its wear area and coating thickness were extracted. Results show that the main constituent elements of the coating and substrate are Cr and Fe, respectively, the hardness of the coating is about 1020 HV0.1, and the hardness of the substrate is 470~840 HV0.1. During the field operation, scratches appeared on the surface of the coating, the coating thickness layer gradually decreased, and the coating peeled off as the operating area increased. Afterward, scratches and oxidized particles appeared on the surface of the substrate, the wear rate accelerated, and the wear area gradually increased. The wear of the spindle hook teeth started to appear from the front and rear tooth tips up to the tooth edge, the back of the tooth, and the doffering edge, hence forming a long boot-shaped wear area.
Just Breathe: Improving LEP Outcomes through Long Interval Breathing
Authors: Wold Andrew , Boehme Rebecca , Thordstein Magnus
Published: June 2022

Background: Laser-evoked potentials (LEPs) constitute an objective clinical diagnostic method used to investigate the functioning of the nociceptor system, including signaling in thin peripheral nerve fibers: Aδ and C fibers. There is preliminary evidence that phase locking LEPs with the breathing cycle can improve the parameters used to evaluate LEPs. Methods: We tested a simple breathing protocol as a low-cost improvement to LEP testing of the hands. Twenty healthy participants all underwent three variants of LEP protocols: following a video-guided twelve-second breathing instruction, watching a nature video, or using the classic LEP method of focusing on the hand being stimulated. Results: The breath protocol produced significantly shorter latencies as compared with the nature or classic protocol. It was also the least prone to artifacts and was deemed most acceptable by the subjects. There was no difference between the protocols regarding LEP amplitudes. Conclusions: Using a breathing video can be a simple, low-cost improvement for LEP testing in research and clinical diagnostics.
Analysis Phase of Lean Six Sigma Methodology with Scaled-Down Laboratory Experiments for an Industrial-Scale Biogas Plant
Authors: Cinar Samet , Cinar Senem Önen , Ng She Ming , Kuchta Kerstin
Published: June 2022

Although the benefits of the Lean Six Sigma (LSS) methodology have been proven for more than 20 years, it is still underutilized in environmental science, (e.g., in anaerobic digestion and biogas production). In order to obtain a structural and data-oriented perspective for process optimization in the renewable energy sector, LSS application must be considered one of the most valuable tools. To inform this paper, the LSS analysis phase was conducted in a scaled-down environment through detailed laboratory experiments. Results showed not only the feasibility of LSS application in biogas technology, but also some useful findings such as possible root causes for low production, such as impurities, waiting time, and existing pre-treatment methods for the defined problem. The results of the experiments show that the use of old substrates can reduce the biogas production up to half of the production with fresh substrates, and that even a 10% sand content can reduce the production up to 14.2%, which shows the need for a solution to these two issues.
CAMBRA Protocol Efficacy: A Systematic Review and Critical Appraisal
Authors: Coelho Ana , Amaro Inês , Iunes Tainá , Paula Anabela , Marto Carlos Miguel , Saraiva José , Ferreira Manuel Marques , Carrilho Eunice
Published: June 2022

The Caries Management by Risk Assessment (CAMBRA) protocol consists of analyzing the patient’s profile by assessing the risk and protective factors and assigning a risk level to the patient to allow an individualized treatment plan, which combines restorative treatments with a preventive chemical therapy. This systematic review and critical appraisal aim to evaluate the effectiveness of the CAMBRA protocol in reducing the incidence of caries lesions and oral bacterial load. An electronic search was carried out in the Cochrane Library, PubMed, Web of Science, Scopus, and Embase databases. Clinical studies evaluating the incidence of dental caries lesions and/or the reduction of cariogenic bacterial load (Streptococcus mutans and/or Lactobacilli spp.), with at least an intervention group that follows the CAMBRA protocol and a control group published up until January 2022, were included. The methodological quality assessment of the included clinical studies was assessed through the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The quality of the case-control study was evaluated according to the Methodological Index for Non-Randomized Studies (ROBINS-I). There is currently no scientific evidence to recommend the integration of the CAMBRA protocol into clinical practice. The results reported by the studies included in the systematic review do not suggest a decrease in the incidence of dental caries lesions and/or bacterial load. There is a clear need for the development of new clinical studies with an adequate methodology and follow-up, both for the CAMBRA protocol and for its components individually.
Recent Advancements in Selenium-Based Cathode Materials for Lithium Batteries: A Mini-Review
Authors: Khan Mustafa , Ding Xuli , Zhao Hongda , Wang Yuxin , Zhang Ning , Chen Xiaojing , Xu Jiahao
Published: June 2022

Selenium (Se)-based cathode materials have garnered considerable interest for lithium-ion batteries due to their numerous advantages, including low cost, high volumetric capacity (3268 mAh cm−3), high density (4.82 g cm−3), ability to be cycled to high voltage (4.2 V) without failure, and environmental friendliness. However, they have low electrical conductivity, low coulombic efficiency, and polyselenide solubility in electrolytes (shuttle effect). These factors have an adverse effect on the electrochemical performance of Li-Se batteries, rendering them unsuitable for real-world use. In this study, we briefly examined numerous approaches to overcoming these obstacles, including selecting an adequate electrolyte, the composition of Se with carbonaceous materials, and the usage of metal selenide base electrodes. Furthermore, we examined the effect of introducing interlayers between the cathode and the separator. Finally, the remaining hurdles and potential study prospects in this expanding field are proposed to inspire further insightful work.