bluuebunny/crossref_metadata_2025 huggingface dataset:
Apps for Smart Groundwater Monitoring and Assessments: A Case Study of Regideso Catchment in Kimbanseke
Authors: Kabuya Ange Kalala , Alowo Rebecca , Nkhonjera German K.
Published: March 2022

There are various groundwater data bases and scanty/sketchy groundwater monitoring and information systems. Groundwater monitoring has been difficult in the Southern African region, particularly, the Democratic Republic of Congo (DRC), for the water administrative authorities. Water clients do not submit the required compulsory critical data for effective monitoring of water use. This, combined with the absence of limits to boreholes dug by permit holders to the water authorities, has led to challenges in decision-making and groundwater conservation. In this mixed method research, using an Android telephone, well data (water levels) and climatic related information such as precipitation were assembled and sent to a composed store through a sort code/USSD/Instrument free line in texts (SMS). This is proficient through a 3G/GSM/GPRS module that is part of the sensor equipment to be used for this procedure. Once in the store, requests were used to recuperate data in the required design. Additionally, a cloud framework at the point where a long-lasting file was followed up. Although the experimentation is still on-going for the case of the Kimbanseke catchment in DRC, the preliminary findings are that the Kimbanseke catchment has a fluctuating abstraction rate resulting from no clear monitoring mechanism, and that research on the development of an application and/or MS Excel© monitoring spreadsheet, using the scores, and ranking of the factors, is necessary. Therefore, a study was carried out with the aim of creating an analysis application for groundwater sustainability in the Kimbanseke catchment. An application for monitoring and evaluation of the groundwater level should be considered so that the sustainable yield is routinely adjusted for the Kimbanseke catchment.
The Hands of Fortune: Margaret Bourke-White’s Magazine Photographs of Manual Work in the Early Years of the Depression
Authors: Haran Barnaby
Published: March 2022

In 1931, Fortune published an article entitled ‘American Workingman’, a survey of labor in the midst of the worsening Depression, with an emblematic composite image of hands at work to indicate the manual character and the diverse jobs of industrial work. The picture conveys the polysemy of hands as a synecdoche of labor, and witnesses the prevalence of close-up depictions of hands at work in other Fortune features on specific industries, from which these fragments derived. This article explores the implications of Fortune’s representation of the ‘hands of labor’ at a time of escalating industrial conflict, defined by redundancies, strikes, and protests. If Fortune was a self-styled ‘super-class’ publication for a corporate elite, conceived for the ‘heads’ of industry, then to what extent do these othered hands operate ideologically to represent labor’s compliance at a time of crisis? If abstracted hands were ubiquitous in modernist photography, then Bourke-White’s images also equated a putative subgenre of Communist iconography, in which the hand, or fist, connoted proletarian solidarity and strength. Yet leftist militant agitation provoked antipathy in Fortune, and so I examine the representation of labor in the article and the magazine more broadly as industrial relations intensified in the 1930s. I consider further the extent these automatic hands allude to the narrative of ‘technological displacement’, or workerless factories, as a response to strikes.
Passive Sampling as a Tool to Assess Atmospheric Pesticide Contamination Related to Vineyard Land Use
Authors: Martin Stéphan , Dévier Marie-Hélène , Cruz Justine , Duporté Geoffroy , Barron Emmanuelle , Gaillard Juliette , Le Menach Karyn , Pardon Patrick , Augagneur Sylvie , Flaud Pierre-Marie , Villenave Éric , Budzinski Hélène
Published: March 2022

The massive use of pesticides in agriculture has led to widespread contamination of the environment, particularly the atmospheric compartment. Thirty-six pesticides, most used in viticulture, were monitored in ambient air using polyurethane foams as passive air samplers (PUF-PAS). Spatiotemporal data were collected from the samplers for 10 months (February–December 2013), using two different sampling times (1 and 2 months) at two different sites in a chateau vineyard in Gironde (France). A high-volume active air sampler was also deployed in June. Samples were extracted with dichloromethane using accelerated solvent extraction (ASE) (PUFs from both passive and active) or microwave-assisted extraction (MAE) (filters from active sampling). Extracts were analyzed by both gas and liquid chromatography coupled with tandem mass spectrometry. A total of 23 airborne pesticides were detected at least once. Concentrations in PUF exposed one month ranged from below the limits of quantification (LOQs) to 23,481 ng PUF−1. The highest concentrations were for folpet, boscalid, chlorpyrifos-methyl, and metalaxyl-m—23,481, 17,615, 3931, and 3324 ng PUF−1. Clear seasonal trends were observed for most of the pesticides detected, the highest levels (in the ng m−3 range or the µg PUF−1 range) being measured during their application period. Impregnation levels at both sites were heterogeneous, but the same pesticides were involved. Sampling rates (Rs) were also estimated using a high-volume active air sampler and varied significantly from one pesticide to another. These results provide preliminary information on the seasonality of pesticide concentrations in vineyard areas and evidence for the effectiveness of PUF-PAS to monitor pesticides in ambient air.
Influence of Trade Winds on the Detection of Trans-Hemispheric Swells near the Canary Islands
Authors: Megías Emilio , García-Román Manuel
Published: March 2022

Trade winds are common in the Canary Islands archipelago and affect not only the weather of the islands but also the local wave climate. On the other hand, the arrival in the Canaries of swells from the Southern Hemisphere is little known, but usual. The records of these swells arriving in the Canary Islands have two clear peaks throughout the year, one in spring and the other in autumn. In this work, how the trade winds influence the detection of this type of swells is studied. It is estimated that only approximately half of this type of wave that reaches the Canary Islands could be adequately recorded in the buoy output data tables by the action of these winds. Therefore, their effects may be underestimated in local wave climate studies.
Existence of Mild Solutions for Hilfer Fractional Evolution Equations with Almost Sectorial Operators
Authors: Zhou Mian , Li Chengfu , Zhou Yong
Published: March 2022

In this paper, we obtain new sufficient conditions of the existence of mild solutions for Hilfer fractional evolution equations in the cases that the semigroup associated with an almost sectorial operator is compact as well as noncompact. Our results improve and extend some recent results in references.
N-1 Perfusion Platform Development Using a Capacitance Probe for Biomanufacturing
Authors: Rittershaus Emily S. C. , Rehmann Matthew S. , Xu Jianlin , He Qin , Hill Charles , Swanberg Jeffrey , Borys Michael C. , Li Zheng-Jian , Khetan Anurag
Published: March 2022

Fed-batch process intensification with a significantly shorter culture duration or higher titer for monoclonal antibody (mAb) production by Chinese hamster ovary (CHO) cells can be achieved by implementing perfusion operation at the N-1 stage for biomanufacturing. N-1 perfusion seed with much higher final viable cell density (VCD) than a conventional N-1 batch seed can be used to significantly increase the inoculation VCD for the subsequent fed-batch production (referred as N stage), which results in a shorter cell growth phase, higher peak VCD, or higher titer. In this report, we incorporated a process analytical technology (PAT) tool into our N-1 perfusion platform, using an in-line capacitance probe to automatically adjust the perfusion rate based on real-time VCD measurements. The capacitance measurements correlated linearly with the offline VCD at all cell densities tested (i.e., up to 130 × 106 cells/mL). Online control of the perfusion rate via the cell-specific perfusion rate (CSPR) decreased media usage by approximately 25% when compared with a platform volume-specific perfusion rate approach and did not lead to any detrimental effects on cell growth. This PAT tool was applied to six mAbs, and a platform CSPR of 0.04 nL/cell/day was selected, which enabled rapid growth and maintenance of high viabilities for four of six cell lines. In addition, small-scale capacitance data were used in the scaling-up of N-1 perfusion processes in the pilot plant and in the GMP manufacturing suite. Implementing a platform approach based on capacitance measurements to control perfusion rates led to efficient process development of perfusion N-1 for supporting high-density CHO cell cultures for the fed-batch process intensification.
Integrated In Silico Analyses Identify PUF60 and SF3A3 as New Spliceosome-Related Breast Cancer RNA-Binding Proteins
Authors: García-Cárdenas Jennyfer M. , Armendáriz-Castillo Isaac , Pérez-Villa Andy , Indacochea Alberto , Jácome-Alvarado Andrea , López-Cortés Andrés , Guerrero Santiago
Published: March 2022

More women are diagnosed with breast cancer (BC) than any other type of cancer. Although large-scale efforts have completely redefined cancer, a cure remains unattainable. In that respect, new molecular functions of the cell should be investigated, such as post-transcriptional regulation. RNA-binding proteins (RBPs) are emerging as critical post-transcriptional modulators of tumorigenesis, but only a few have clear roles in BC. To recognize new putative breast cancer RNA-binding proteins, we performed integrated in silico analyses of all human RBPs (n = 1392) in three major cancer databases and identified five putative BC RBPs (PUF60, TFRC, KPNB1, NSF, and SF3A3), which showed robust oncogenic features related to their genomic alterations, immunohistochemical changes, high interconnectivity with cancer driver genes (CDGs), and tumor vulnerabilities. Interestingly, some of these RBPs have never been studied in BC, but their oncogenic functions have been described in other cancer types. Subsequent analyses revealed PUF60 and SF3A3 as central elements of a spliceosome-related cluster involving RBPs and CDGs. Further research should focus on the mechanisms by which these proteins could promote breast tumorigenesis, with the potential to reveal new therapeutic pathways along with novel drug-development strategies.
Selected Phenolic Acids Inhibit the Initial Growth of Ambrosia artemisiifolia L.
Authors: Šćepanović Maja , Košćak Laura , Šoštarčić Valentina , Pismarović Laura , Milanović-Litre Ana , Kljak Kristina
Published: March 2022

This study aimed to investigate whether different doses of specific phenolic acids (chlorogenic acid, caffeic acid, ferulic acid, gallic acid, protocatechuic acid, p-hydroxybenzoic acid, syringic acid, vanillic acid, and p-coumaric acid), alone or in combination, can inhibit the early growth of the common ragweed (Ambrosia artemisiifolia L., Asterales: Asteraceae). A seed bioassay was performed in Petri dishes and placed in a climate chamber to assess the effects of five dose levels of phenolic acids to radicle and shoot length, as well seedling biomass of A. artemisiifolia. The lowest dose of phenolic acid corresponded to the natural phenolic acid concentration previously reported in dry plant tissue samples from Brassicaceae cover crop plants. Results show that the inhibition of the early growth of A. artemisiifolia depends strongly on phenolic acid. Across different treatments, high doses of phenolic acids significantly shortened shoots and radicles, as well as reduced seedling biomass. Treating seeds with ferulic acid alone, vanillic acid alone, p-hydroxybenzoic acid alone, or a mixture of all phenolic acids significantly reduced all early growth parameters. The estimated effective dose for the 50% inhibition (ED50) of radicle growth in A. artemisiifolia seedlings was 368.39 ± 59.85 × 10−8 mol with ferulic acid, 135.41 ± 17.65 × 10−8 mol with p-coumaric acid, 810.36 ± 134.15 × 10−8 mol with p-hydroxybenzoic acid, and 160.11 ± 12.30 × 10−8 mol with the combination of all phenolic acids.
Differences in Corticosterone Release Rates of Larval Spring Salamanders (Gyrinophilus porphyriticus) in Response to Native Fish Presence
Authors: Bryant Amanda R. , Gabor Caitlin R. , Swartz Leah K. , Wagner Ryan , Cochrane Madaline M. , Lowe Winsor H.
Published: March 2022

Invasive fish predators are an important factor causing amphibian declines and may have direct and indirect effects on amphibian survival. For example, early non-lethal exposure to these stressors may reduce survival in later life stages, especially in biphasic species. In amphibians, the glucocorticoid hormone corticosterone is released by the hypothalamo–pituitary–interrenal axis (HPI), as an adaptive physiological response to environmental stressors. The corticosterone response (baseline and response to acute stressors) is highly flexible and context dependent, and this variation can allow individuals to alter their phenotype and behavior with environmental changes, ultimately increasing survival. We sampled larvae of the spring salamander (Gyrinophilus porphyriticus) from two streams that each contained predatory brook trout (Slavelinus fontinalis) in the lower reaches and no predatory brook trout in the upper reaches. We measured baseline and stress-induced corticosterone release rates of larvae from the lower and upper reaches using a non-invasive water-borne hormone assay. We hypothesized that corticosterone release rates would differ between larvae from fish-present reaches and larvae from fish-free reaches. We found that baseline and stressor-induced corticosterone release rates were downregulated in larvae from reaches with fish predators. These results indicate that individuals from reaches with predatory trout are responding to fish predators by downregulating corticosterone while maintaining an active HPI axis. This may allow larvae more time to grow before metamorphosing, while also allowing them to physiologically respond to novel stressors. However, prolonged downregulation of corticosterone release rates can impact growth in post-metamorphic individuals.
Antitumor Efficacy of EGFR-Targeted Recombinant Immunotoxin in Human Head and Neck Squamous Cell Carcinoma
Authors: Xie Guiqin , Shan Liang , Liu Yuanyi , Wu Tzyy-Choou , Gu Xinbin
Published: March 2022

Over 90% of head and neck squamous cell carcinoma (HNSCC) overexpresses the epidermal growth factor receptor (EGFR). However, the EGFR-targeted monotherapy response rate only achieves 10–30% in HNSCC. Recombinant immunotoxin (RIT) often consists of an antibody targeting a tumor antigen and a toxin (e.g., diphtheria toxin [DT]) that kills cancer cells. We produced a humanized RIT, designated as hDT806, targeting overexpressed EGFR and investigated its effects in HNSCC. Distinct from the EGFR-targeted tyrosine kinase inhibitor erlotinib or antibody cetuximab, hDT806 effectively suppressed cell proliferation in the four HNSCC lines tested (JHU-011, -013, -022, and -029). In JHU-029 mouse xenograft models, hDT806 substantially reduced tumor growth. hDT806 decreased EGFR protein levels and disrupted the EGFR signaling downstream effectors, including MAPK/ERK1/2 and AKT, while increased proapoptotic proteins, such as p53, caspase-9, caspase-3, and the cleaved PAPR. The hDT806-induced apoptosis of HNSCC cells was corroborated by flow cytometric analysis. Furthermore, hDT806 resulted in a drastic inhibition in RNA polymerase II carboxy-terminal domain phosphorylation critical for transcription and a significant increase in the γH2A.X level, a DNA damage marker. Thus, the direct disruption of EGFR signaling, transcription inhibition, DNA damage, as well as apoptosis induced by hDT806 may contribute to its antitumor efficacy in HNSCC.
Intracellular Localization and Gene Expression Analysis Provides New Insights on LEA Proteins’ Diversity in Anhydrobiotic Cell Line
Authors: Kondratyeva Sabina A. , Voronina Taisiya A. , Nesmelov Alexander A. , Miyata Yugo , Tokumoto Shoko , Cornette Richard , Vorontsova Maria V. , Kikawada Takahiro , Gusev Oleg A. , Shagimardanova Elena I.
Published: March 2022

Anhydrobiosis, an adaptive ability to withstand complete desiccation, in the nonbiting midge Polypedilum vanderplanki, is associated with the emergence of new multimember gene families, including a group of 27 genes of late embryogenesis abundant (LEA) proteins (PvLea). To obtain new insights into the possible functional specialization of these genes, we investigated the expression and localization of PvLea genes in a P. vanderplanki-derived cell line (Pv11), capable of anhydrobiosis. We confirmed that all but two PvLea genes identified in the genome of P. vanderplanki are expressed in Pv11 cells. Moreover, PvLea genes are induced in Pv11 cells in response to anhydrobiosis-inducing trehalose treatment in a manner highly similar to the larvae of P. vanderplanki during the real induction of anhydrobiosis. Then, we expanded our previous data on PvLEA proteins localization in mammalian cells that were obtained using C-terminal fusions of PvLEA proteins and green fluorescent protein (GFP). We investigated PvLEA localization using N- and C-terminal fusions with GFP in Pv11 cells and the Sf9 insect cell line. We observed an inconsistency of PvLEA localization between different fusion types and different cell cultures, that needs to be taken into account when using PvLEA in the engineering of anhydrobiotic cell lines.
Microtube Array Membrane Hollow Fiber Assay (MTAM-HFA)—An Accurate and Rapid Potential Companion Diagnostic and Pharmacological Interrogation Solution for Cancer Immunotherapy (PD-1/PD-L1)
Authors: Huang Wan-Ting , Yun Tsao , Chew Chee-Ho , Chen Amanda , Wei Po-Li , Lee Kang-Yun , Lee Hsin-Lun , Feng Po-Hao , Chiou Jeng-Fong , Chen Ching-Mei , Chen Chien-Chung
Published: March 2022

Immunotherapy is one of the most promising forms of cancer treatment. In particular, immune checkpoint blockers (ICBs) represent some of the leading candidates which many drug developers have heavily invested in. During pre-clinical development and prior to human clinical trials, animal tests are a critical component for determining the safety and efficacy of newly developed ICBs for cancer treatment. In this study, we strive to demonstrate the feasibility of using hollow fiber assay microtube array membrane (MTAM-HFA) in the screening of anti-cancer ICBs. The MTAM-HFA process was carried out by encapsulating peripheral blood mononuclear cells (PBMCs) and the target cancer cells (cell lines or primary cells) and subcutaneously implanting them into Balb/C mice. At predetermined time points combination regimens of PD-1/PD-L1+ were administered accordingly and at a predetermined time point, the MTAMs were retrieved, and cell viability assays were carried out. The outcomes of the MTAM-HFA were compared against the clinical outcome of patients. Clinical comparison demonstrated excellent correlation between the screening outcome of MTAM-HFA of PD-1/PD-L1+ combination therapy and the clinical outcome of the lung cancer patients. Basic cell studies revealed that the utilization of MTAM-HFA in PD-1/PD-L1+ combination therapy revealed enhanced T-cell activity upon the administration of the PD-1/PD-L1 drug; thereby resulting in the reduction of tumor cell viability by up to 70%, and the cytotoxic effects by 82%. The outcome was echoed in the in vivo cell studies. This suggested that the MTAM-HFA system is suitable for use in PD-1/PD-L1+ screening and the accuracy, rapidity and cost effectiveness made it extremely suitable for application as a companion diagnostic system in both personalized medicine for cancer treatment and could potentially be applied to screen for candidate compounds in the development of next generation PD-1/PD-L1+ combination therapies.
Fungal Extracellular Lipases from Coffee Plantation Environments for the Sustainable Management of Agro-Industrial Coffee Biomass
Authors: Syedd-León Randall , Solano-Campos Frank , Campos-Rodríguez Jorge , Pereira-Arce Daniela , Villegas-Peñaranda Luis Roberto , Sandoval-Barrantes Manuel
Published: March 2022

Coffee wastes have large amounts of by-products rich in phenolic compounds such as chlorogenic and caffeic acid, with potential applications for developing fine chemicals such as caffeic acid phenethyl ester (CAPE). A screening for microorganisms was undertaken in a coffee plantation environment to isolate native tropical species able to modify secondary metabolites present in this kind of biomass enzymatically. From the screening, 130 fungal strains could grow in lipase inducer media. Fungal strains were identified via ITS-based sequencing. Classification based on BLAST assigned 51 isolates to 12 different genera, including Absidia, Aspergillus, Cunninghamella, Fusarium, Metarhizium, Meyerozyma, Mucor, Neocosmospora, Papiliotrema, Penicillium, Rhizopus, and Trichoderma. DNA sequencing identified 14 putative extracellular lipases. According to the extracellular lipase activity, the most promising strain was identified as Fusarium sp. by DNA barcoding. Extracellular lipases from this strain exhibited maximal hydrolytic activity at a temperature of 45 °C, a pH of 7.00, and 200 ppm of NaCl, with an affinity towards substrates having carbon chain lengths of 8 or longer. Under these conditions, lipase instead of esterase activity is the main feature. The Km and Vmax values calculated using p-nitrophenyl palmitate (pNPP) as hydrolysis substrate were 0.003 mM and 299.8 μmol min−1 mg−1, respectively. Fusarium sp. lipases presented high stability during freeze–thawing, allowing the storage of enzyme solutions at −20 °C, but not as a lyophilized powder. According to our kinetic study, these lipases catalyzed CAPE hydrolysis, showing a progressive decrease in the concentration of the CAPE and a correspondent increase in the caffeic acid concentration as a product of this hydrolysis. Being able to carry out this type of reaction under mild conditions shows that Fusarium sp. lipases recognize CAPE as substrate and suggest CAPE synthesis (reverse reaction) and transformation can be engineered, using caffeic acid from coffee biomass, as a potential industrial application for these lipases.
Mechanistic Insights into Inorganic Nitrite-Mediated Vasodilation of Isolated Aortic Rings under Oxidative/Hypertensive Conditions and S-Nitros(yl)ation of Proteins in Germ-Free Mice
Authors: Stamm Paul , Kalinovic Sanela , Oelze Matthias , Steven Sebastian , Czarnowski Alexander , Kvandova Miroslava , Bayer Franziska , Reinhardt Christoph , Münzel Thomas , Daiber Andreas
Published: March 2022

The prevalence and clinical importance of arterial hypertension are still growing. Inorganic nitrite (NO2−) represents an attractive dietary antihypertensive agent, but its metabolism and mode of action, which we aimed to investigate with the present study, are not completely understood. Isolated aortic rings from rats were treated ex vivo with oxidants, and rats were infused in vivo with angiotensin-II. Vascular responses to acetylcholine (ACh) and nitrite were assessed by isometric tension recording. The loss of vasodilatory potency in response to oxidants was much more pronounced for ACh as compared to nitrite ex vivo (but not in vivo with angiotensin-II). This effect may be caused by the redox regulation of conversion to xanthine oxidase (XO). Conventionally raised and germ-free mice were treated with nitrite by gavage, which did not improve ACh-mediated vasodilation, but did increase the plasma levels of S-nitros(yl)ated proteins in the conventionally-raised, but not in the germ-free mice. In conclusion, inorganic nitrite represents a dietary drug option to treat arterial hypertension in addition to already established pharmacological treatment. Short-term oxidative stress did not impair the vasodilatory properties of nitrite, which may be beneficial in cardiovascular disease patients. The gastrointestinal microbiome appears to play a key role in nitrite metabolism and bioactivation.
Correction: Alfaro-Arnedo et al. IGF1R as a Potential Pharmacological Target in Allergic Asthma. Biomedicines 2021, 9, 912
Authors: Alfaro-Arnedo Elvira , López Icíar P. , Piñeiro-Hermida Sergio , Ucero Álvaro C. , González-Barcala Francisco J. , Salgado Francisco J. , Pichel José G.
Published: March 2022

In the original article [...]
Targeted Accumulation of Macrophages Induced by Microbeam Irradiation in a Tissue-Dependent Manner
Authors: Trappetti Verdiana , Fazzari Jennifer , Fernandez-Palomo Cristian , Smyth Lloyd , Potez Marine , Shintani Nahoko , de Breuyn Dietler Bettina , Martin Olga A. , Djonov Valentin
Published: March 2022

Radiation therapy (RT) is a vital component of multimodal cancer treatment, and its immunomodulatory effects are a major focus of current therapeutic strategies. Macrophages are some of the first cells recruited to sites of radiation-induced injury where they can aid in tissue repair, propagate radiation-induced fibrogenesis and influence tumour dynamics. Microbeam radiation therapy (MRT) is a unique, spatially fractionated radiation modality that has demonstrated exceptional tumour control and reduction in normal tissue toxicity, including fibrosis. We conducted a morphological analysis of MRT-irradiated normal liver, lung and skin tissues as well as lung and melanoma tumours. MRT induced distinct patterns of DNA damage, reflecting the geometry of the microbeam array. Macrophages infiltrated these regions of peak dose deposition at variable timepoints post-irradiation depending on the tissue type. In normal liver and lung tissue, macrophages clearly demarcated the beam path by 48 h and 7 days post-irradiation, respectively. This was not reflected, however, in normal skin tissue, despite clear DNA damage marking the beam path. Persistent DNA damage was observed in MRT-irradiated lung carcinoma, with an accompanying geometry-specific influx of mixed M1/M2-like macrophage populations. These data indicate the unique potential of MRT as a tool to induce a remarkable accumulation of macrophages in an organ/tissue-specific manner. Further characterization of these macrophage populations is warranted to identify their organ-specific roles in normal tissue sparing and anti-tumour responses.
Dental-Pulp Stem Cells as a Therapeutic Strategy for Ischemic Stroke
Authors: Nito Chikako , Suda Satoshi , Nitahara-Kasahara Yuko , Okada Takashi , Kimura Kazumi
Published: March 2022

Regenerative medicine aims to restore human functions by regenerating organs and tissues using stem cells or living tissues for the treatment of organ and tissue defects or dysfunction. Clinical trials investigating the treatment of cerebral infarction using mesenchymal stem cells, a type of somatic stem cell therapy, are underway. The development and production of regenerative medicines using somatic stem cells is expected to contribute to the treatment of cerebral infarction, a central nervous system disease for which there is no effective treatment. Numerous experimental studies have shown that cellular therapy, including the use of human dental pulp stem cells, is an attractive strategy for patients with ischemic brain injury. This review describes the basic research, therapeutic mechanism, clinical trials, and future prospects for dental pulp stem cell therapy, which is being investigated in Japan in first-in-human clinical trials for the treatment of patients with acute cerebral ischemia.
Longitudinal [18F]GE-180 PET Imaging Facilitates In Vivo Monitoring of TSPO Expression in the GL261 Glioblastoma Mouse Model
Authors: Holzgreve Adrien , Pötter Dennis , Brendel Matthias , Orth Michael , Weidner Lorraine , Gold Lukas , Kirchner Maximilian A. , Bartos Laura M. , Unterrainer Lena M. , Unterrainer Marcus , Steiger Katja , von Baumgarten Louisa , Niyazi Maximilian , Belka Claus , Bartenstein Peter , Riemenschneider Markus J. , Lauber Kirsten , Albert Nathalie L.
Published: March 2022

The 18 kDa translocator protein (TSPO) is increasingly recognized as an interesting target for the imaging of glioblastoma (GBM). Here, we investigated TSPO PET imaging and autoradiography in the frequently used GL261 glioblastoma mouse model and aimed to generate insights into the temporal evolution of TSPO radioligand uptake in glioblastoma in a preclinical setting. We performed a longitudinal [18F]GE-180 PET imaging study from day 4 to 14 post inoculation in the orthotopic syngeneic GL261 GBM mouse model (n = 21 GBM mice, n = 3 sham mice). Contrast-enhanced computed tomography (CT) was performed at the day of the final PET scan (±1 day). [18F]GE-180 autoradiography was performed on day 7, 11 and 14 (ex vivo: n = 13 GBM mice, n = 1 sham mouse; in vitro: n = 21 GBM mice; n = 2 sham mice). Brain sections were also used for hematoxylin and eosin (H&E) staining and TSPO immunohistochemistry. [18F]GE-180 uptake in PET was elevated at the site of inoculation in GBM mice as compared to sham mice at day 11 and later (at day 14, TBRmax +27% compared to sham mice, p = 0.001). In GBM mice, [18F]GE-180 uptake continuously increased over time, e.g., at day 11, mean TBRmax +16% compared to day 4, p = 0.011. [18F]GE-180 uptake as depicted by PET was in all mice co-localized with contrast-enhancement in CT and tissue-based findings. [18F]GE-180 ex vivo and in vitro autoradiography showed highly congruent tracer distribution (r = 0.99, n = 13, p < 0.001). In conclusion, [18F]GE-180 PET imaging facilitates non-invasive in vivo monitoring of TSPO expression in the GL261 GBM mouse model. [18F]GE-180 in vitro autoradiography is a convenient surrogate for ex vivo autoradiography, allowing for straightforward identification of suitable models and scan time-points on previously generated tissue sections.
Taste-Driven Responsiveness to Fat and Sweet Stimuli in Mouse Models of Bariatric Surgery
Authors: Dastugue Aurélie , Le May Cédric , Ledoux Séverine , Le Bourgot Cindy , Delaby Pascaline , Bernard Arnaud , Besnard Philippe
Published: March 2022

A preferential consumption of healthier foods, low in fat and sugar, is often reported after bariatric surgery, suggesting a switch of taste-guided food choices. To further explore this hypothesis in well-standardized conditions, analysis of licking behavior in response to oily and sweet solutions has been realized in rats that have undergone a Roux-en-Y bypass (RYGB). Unfortunately, these studies have produced conflicting data mainly due to methodological differences. Paradoxically, whereas the vertical sleeve gastrectomy (VSG) becomes the most commonly performed bariatric surgery worldwide and is easier to perform and standardize in small animals, its putative impacts on the orosensory perception of energy-dense nutrients remains unknown. Using brief-access licking tests in VSG or RYGB mice, we found that (i) VSG induces a significant reduction in the fat mass in diet-induced obese (DIO) mice, (ii) VSG partially corrects the licking responses to lipid and sucrose stimuli which are degraded in sham-operated DIO mice, (iii) VSG improves the willingness to lick oily and sucrose solutions in DIO mice and (iv) RYGB leads to close outcomes. Altogether, these data strongly suggest that VSG, as RYGB, can counteract the deleterious effect of obesity on the orosensory perception of energy-dense nutrients in mice.
Addressing Blood–Brain Barrier Impairment in Alzheimer’s Disease
Authors: Sharma Chanchal , Woo Hanwoong , Kim Sang Ryong
Published: March 2022

The blood–brain barrier (BBB) plays a vital role in maintaining the specialized microenvironment of the brain tissue. It facilitates communication while separating the peripheral circulation system from the brain parenchyma. However, normal aging and neurodegenerative diseases can alter and damage the physiological properties of the BBB. In this review, we first briefly present the essential pathways maintaining and regulating BBB integrity, and further review the mechanisms of BBB breakdown associated with normal aging and peripheral inflammation-causing neurodegeneration and cognitive impairments. We also discuss how BBB disruption can cause or contribute to Alzheimer’s disease (AD), the most common form of dementia and a devastating neurological disorder. Next, we document overlaps between AD and vascular dementia (VaD) and briefly sum up the techniques for identifying biomarkers linked to BBB deterioration. Finally, we conclude that BBB breakdown could be used as a biomarker to help diagnose cognitive impairment associated with normal aging and neurodegenerative diseases such as AD.
Peripheral Blood Levels of Brain-Derived Neurotrophic Factor in Patients with First Episode Psychosis: A Systematic Review and Meta-Analysis
Authors: Singh Sukhbir , Roy Dipta , Marzouk Taylor , Zhang Jian-Ping
Published: March 2022

Background: Peripheral blood level of brain-derived neurotrophic factor (BDNF) may be used as a diagnostic and/or prognostic marker for schizophrenia. Previous studies were inconsistent. A systematic review was conducted to examine whether BDNF level is different in patients with first episode psychosis (FEP) compared to health controls (HC) and whether it changes after treatment. Methods: Literature search was done in PubMed, Web of Science, and Google Scholar following standard procedures. Hedges’ g was used as the measure of effect size (ES), which was pooled with random effects model. Publication bias and moderator effects were examined. Results: Search yielded 29 studies with a total sample size of 2912. First meta-analysis included 27 studies with FEP vs. HC comparison. Pooled ES was −0.63, p < 0.001, indicating that BDNF level was lower in FEP than in HC. Studies were heterogeneous, and moderator analysis showed that studies of younger patient, higher symptom severity, and more drug naïve had larger ES. Second meta-analysis examined change in BDNF levels before and after antipsychotic treatment in eight studies. A pooled ES of −0.003 (p = 0.96) showed no change in peripheral BDNF level after treatment. Conclusion: Peripheral BDNF level was decreased in FEP compared to HC, but it did not change after treatment.
Relapsing High—Grade Glioma from Peritumoral Zone: Critical Review of Radiotherapy Treatment Options
Authors: Lo Greco Maria Chiara , Milazzotto Roberto , Liardo Rocco Luca Emanuele , Acquaviva Grazia , La Rocca Madalina , Altieri Roberto , Certo Francesco , Barbagallo Giuseppe Maria , Basile Antonio , Foti Pietro Valerio , Palmucci Stefano , Pergolizzi Stefano , Pontoriero Antonio , Spatola Corrado
Published: March 2022

Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, with a median survival of about 15 months. After the prior treatment, GBM tends to relapse within the high dose radiation field, defined as the peritumoral brain zone (PTZ), needing a second treatment. In the present review, the primary role of ionizing radiation in recurrent GBM is discussed, and the current literature knowledge about the different radiation modalities, doses and fractionation options at our disposal is summarized. Therefore, the focus is on the necessity of tailoring the treatment approach to every single patient and using radiomics and PET/MRI imaging to have a relatively good outcome and avoid severe toxicity. The use of charged particle therapy and radiosensitizers to overcome GBM radioresistance is considered, even if further studies are necessary to evaluate the effectiveness in the setting of reirradiation.
Communicative Participation in Dysarthria: Perspectives for Management
Authors: Page Allyson D. , Yorkston Kathryn M.
Published: March 2022

Communicative participation is restricted in many conditions associated with dysarthria. This position paper defines and describes the construct of communicative participation. In it, the emergence of this construct is reviewed, along with the predictors of and variables associated with communicative participation in the dysarthrias. In doing so, the features that make communicative participation unique and distinct from other measures of dysarthria are highlighted, through emphasizing how communicative participation cannot be predicted solely from other components of the World Health Organization’s International Classification of Functioning, Disability and Health (ICF), including levels of impairment or activity limitations. Next, the empirical literature related to the measurement of communicative participation and how this research relates to dysarthria management is presented. Finally, the development of robust clinical measures of communicative participation and approaches to management is described from the point of view of the clinician. We argue that communicative participation should be a primary focus of treatment planning and intervention to provide patient-centered, holistic, and value-based clinical interventions which are responsive to the needs of individuals living with dysarthria.
Mathematics and Numerosity but Not Visuo-Spatial Working Memory Correlate with Mathematical Anxiety in Adults
Authors: Maldonado Moscoso Paula A. , Castaldi Elisa , Arrighi Roberto , Primi Caterina , Caponi Camilla , Buonincontro Salvatore , Bolognini Francesca , Anobile Giovanni
Published: March 2022

Many individuals, when faced with mathematical tasks or situations requiring arithmetic skills, experience exaggerated levels of anxiety. Mathematical anxiety (MA), in addition to causing discomfort, can lead to avoidance behaviors and then to underachievement. However, the factors inducing MA and how MA deploys its detrimental effects are still largely debated. There is evidence suggesting that MA affects working memory capacity by further diminishing its limited processing resources. An alternative account postulates that MA originates from a coarse early numerical cognition capacity, the perception of numerosity. In the current study, we measured MA, math abilities, numerosity perception and visuo-spatial working memory (VSWM) in a sample of neurotypical adults. Correlational analyses confirmed previous studies showing that high MA was associated with lower math scores and worse numerosity estimation precision. Conversely, MA turned out to be unrelated to VSWM capacities. Finally, partial correlations revealed that MA fully accounted for the relationship between numerosity estimation precision and math abilities, suggesting a key role for MA as a mediating factor between these two domains.
Failure Analysis of Transmission Tower in Full-Scale Tests
Authors: Gao Xiuyun , Yi Rong , Zhang Lingquan , Jiang Xiao , Li Jiaxiang
Published: March 2022

With the rapid development of Ultra-High Voltage (UHV) transmission lines, it is necessary to study the performance of UHV transmission towers. First, we performed full-scale tests on a transmission tower under seven loading patterns. Then, the test results were compared with the calculation results of the Chinese tower design software Transmission Tower Analysis Program (TTA), and the failure location of the tower and the stress characteristics of the key parts were studied. Finally, we discuss the influence of bolt slippage and a new joint on the tower performance, and propose some design proposals for the current Chinese code, based on the test results. The results show that a bolt slip will significantly increase the displacement of the transmission tower, but the residual displacement can correct it. The new joint design has good mechanical performance. The bracing member at the bottom of the tower leg is located at the connection of the tower leg and the foundation, and there is a significant sudden change in stiffness, which we recommend designing according to 4% of the axial force of the main members.
Quantitative Multiparametric Ultrasound (mpUS) in the Assessment of Inconclusive Cervical Lymph Nodes
Authors: Lerchbaumer Markus H. , Wakonig Katharina Margherita , Arens Philipp , Dommerich Steffen , Fischer Thomas
Published: March 2022

Background: Enlarged cervical lymph nodes (CLN) are preferably examined by ultrasound (US) by using criteria such as size and echogenicity to assess benign and suspicious CLN, which should be histologically evaluated. This study aims to assess the differentiation of malign and benign CLN by using multiparametric US applications (mpUS). Methods: 101 patients received a standardized US protocol prior to surgical intervention using B-mode–US, shear-wave elastography (SWE) and contrast-enhanced ultrasound (CEUS). SWE was assessed by 2D real-time SWE conducting a minimum of five measurements, CEUS parameters were assessed with post-processing perfusion software. Histopathological confirmation served as the gold standard. Results: B-mode–US and SWE analysis of 104 CLN (36 benign, 68 malignant) showed a significant difference between benign and malignant lesions, presenting a larger long axis and higher tissue stiffness (both p < 0.001). Moreover, tissue stiffness assessed by SWE was significantly higher in CLN with regular B-mode–US criteria (Solbiati Index > 2 and short-axis < 1 cm, p < 0.001). No perfusion parameter on CEUS showed a significant differentiation between benign and malignant CLN. Discussion: As the only multiparametric parameter, SWE showed higher tissue stiffness in malignant CLN, also in subgroups with regular B-mode criteria. This fast and easy application may be a promising noninvasive tool to US examination to ameliorate the sonographic differentiation of inconclusive CLN.
MaasPenn Radiomics Reproducibility Score: A Novel Quantitative Measure for Evaluating the Reproducibility of CT-Based Handcrafted Radiomic Features
Authors: Ibrahim Abdalla , Barufaldi Bruno , Refaee Turkey , Silva Filho Telmo M. , Acciavatti Raymond J. , Salahuddin Zohaib , Hustinx Roland , Mottaghy Felix M. , Maidment Andrew D. A. , Lambin Philippe
Published: March 2022

The reproducibility of handcrafted radiomic features (HRFs) has been reported to be affected by variations in imaging parameters, which significantly affect the generalizability of developed signatures and translation to clinical practice. However, the collective effect of the variations in imaging parameters on the reproducibility of HRFs remains unclear, with no objective measure to assess it in the absence of reproducibility analysis. We assessed these effects of variations in a large number of scenarios and developed the first quantitative score to assess the reproducibility of CT-based HRFs without the need for phantom or reproducibility studies. We further assessed the potential of image resampling and ComBat harmonization for removing these effects. Our findings suggest a need for radiomics-specific harmonization methods. Our developed score should be considered as a first attempt to introduce comprehensive metrics to quantify the reproducibility of CT-based handcrafted radiomic features. More research is warranted to demonstrate its validity in clinical contexts and to further improve it, possibly by the incorporation of more realistic situations, which better reflect real patients’ situations.
Elucidation of Focal Adhesion Kinase as a Modulator of Migration and Invasion and as a Potential Therapeutic Target in Chronic Lymphocytic Leukemia
Authors: Burley Thomas A. , Hesketh Andrew , Bucca Giselda , Kennedy Emma , Ladikou Eleni E. , Towler Benjamin P. , Mitchell Simon , Smith Colin P. , Fegan Christopher , Johnston Rosalynd , Pepper Andrea , Pepper Chris
Published: March 2022

The retention and re-migration of Chronic Lymphocytic Leukemia cells into cytoprotective and proliferative lymphoid niches is thought to contribute to the development of resistance, leading to subsequent disease relapse. The aim of this study was to elucidate the molecular processes that govern CLL cell migration to elicit a more complete inhibition of tumor cell migration. We compared the phenotypic and transcriptional changes induced in CLL cells using two distinct models designed to recapitulate the peripheral circulation, CLL cell migration across an endothelial barrier, and the lymph node interaction between CLL cells and activated T cells. Initially, CLL cells were co-cultured with CD40L-expressing fibroblasts and exhibited an activated B-cell phenotype, and their transcriptional signatures demonstrated the upregulation of pro-survival and anti-apoptotic genes and overrepresentation of the NF-κB signaling pathway. Using our dynamic circulating model, we were able to study the transcriptomics and miRNomics associated with CLL migration. More than 3000 genes were altered when CLL cells underwent transendothelial migration, with an overrepresentation of adhesion and cell migration gene sets. From this analysis, an upregulation of the FAK signaling pathway was observed. Importantly, PTK2 (FAK) gene expression was significantly upregulated in migrating CLL cells (PTK2 Fold-change = 4.9). Here we demonstrate that TLR9 agonism increased levels of p-FAK (p ≤ 0.05), which could be prevented by pharmacological inhibition of FAK with defactinib (p ≤ 0.01). Furthermore, a reduction in CLL cell migration and invasion was observed when FAK was inhibited (p ≤ 0.0001), supporting a role for FAK in both CLL migration and tissue invasion. When taken together, our data highlights the potential for combining FAK inhibition with current targeted therapies as a more effective treatment regime for CLL.
Second-Generation JK-206 Targets the Oncogenic Signal Mediator RHOA in Gastric Cancer
Authors: Beak Myeonghun , Park Sungjin , Kim Jin-Hee , Eom Hyo Jin , Lee Ho-Yeon , Kim Yon Hui , Lee Jinhyuk , Nam Seungyoon
Published: March 2022

Ras homologous A (RHOA), a signal mediator and a GTPase, is known to be associated with the progression of gastric cancer (GC), which is the fourth most common cause of death in the world. Previously, we designed pharmacologically optimized inhibitors against RHOA, including JK-136 and JK-139. Based on this previous work, we performed lead optimization and designed novel RHOA inhibitors for greater anti-GC potency. Two of these compounds, JK-206 and JK-312, could successfully inhibit the viability and migration of GC cell lines. Furthermore, using transcriptomic analysis of GC cells treated with JK-206, we revealed that the inhibition of RHOA might be associated with the inhibition of the mitogenic pathway. Therefore, JK-206 treatment for RHOA inhibition may be a new therapeutic strategy for regulating GC proliferation and migration.
E-Cadherin-Deficient Cells Are Sensitive to the Multikinase Inhibitor Dasatinib
Authors: Bougen-Zhukov Nicola , Decourtye-Espiard Lyvianne , Mitchell Wilson , Redpath Kieran , Perkinson Jacqui , Godwin Tanis , Black Michael A. , Guilford Parry
Published: March 2022

The CDH1 gene, encoding the cell adhesion protein E-cadherin, is one of the most frequently mutated genes in gastric cancer and inactivating germline CDH1 mutations are responsible for the cancer syndrome hereditary diffuse gastric cancer (HDGC). CDH1-deficient gastric cancers exhibit high AKT serine/threonine kinase 3 (AKT3) expression, but specific drugs against this AKT isoform are not available. We therefore used two publicly available datasets to identify AKT3-associated genes which could be used to indirectly target AKT3. Reactome analysis identified an enrichment of extracellular matrix remodelling genes in AKT3-high gastric cancers. Of the 51 genes that were significantly correlated with AKT3 (but not AKT1), discoidin domain receptor tyrosine kinase 2 (DDR2) showed the strongest positive association. Treatment of isogenic human cells and mouse gastric and mammary organoids with dasatinib, a small molecule inhibitor of multiple kinases including SRC, BCR-ABL and DDR2, preferentially slowed the growth and induced apoptosis of E-cadherin-deficient cells. Dasatinib treatment also preferentially slowed the growth of gastric and mammary organoids harbouring both Cdh1 and Tp53 mutations. In organoid models, dasatinib treatment was associated with decreased phosphorylation of total AKT, with a stronger effect seen in Cdh1-deficient organoids. Treatment with combinations of dasatinib and an inhibitor of AKT, MK2206, enhanced the effect of dasatinib in breast MCF10A cells. In conclusion, targeting the DDR2-SRC-AKT3 axis with dasatinib represents a promising approach for the chemoprevention and chemotherapy of gastric and breast cancers lacking E-cadherin.