bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of Suture Pullout Forces of the Pancreatic Duct and Capsule
Authors: Gong Alex T. , Bidinger Sophia L. , DeSchmidt Aleah M. , Batista Joaquin E. , Song Agnes Y. , Schul Alyssa L. , Wang Everet Y. , Norfleet Jack E. , Palavecino Martin E. , Sweet Robert M.
Published: June 2022

A thorough biomechanical understanding of human organs is of increasing importance for designing and improving a wide range of medical technologies from simulators to medical devices. Despite the crucial need for data, little procedure-specific biomechanical testing on human tissue has been published. Specifically, pancreatic duct anastomosis, which has high rates of complications related to pancreatic duct leakage and patency, could benefit from improved assistive technologies. This study aims to help characterize the biomechanics of this critical step of the procedure by measuring the suture pullout force (SPOF) of the pancreatic duct and capsule. 216 tests were performed on 33 fresh, unfixed donated human pancreases. A previously reported uniaxial testing frame, was used to measure the SPOF of the pancreases. The mean pancreatic duct SPOF was 2.62 ± 1.11 N and the mean pancreatic capsule SPOF was 1.99 ± 1.33 N. To our knowledge, this is the first reported human pancreatic duct and capsule suture pullout measurement. These data can be used to inform a wide variety of biomedical technologies with primary interest in high-fidelity training simulators.
Rapamycin Improves Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Renoprotective Effect against Cisplatin-Induced Acute Nephrotoxicity in Rats by Inhibiting the mTOR/AKT Signaling Pathway
Authors: Awadalla Amira , Hussein Abdelaziz M. , El-Far Yousra M. , El-Senduny Fardous F. , Barakat Nashwa , Hamam Eman T. , Abdeen Hanaa M. , El-Sherbiny Mohamed , Serria Mohamed S. , Sarhan Amira A. , Sena Asmaa M. , Shokeir Ahmed A.
Published: June 2022

Objective: Because the poor survival of transplanted cells in a hostile microenvironment limits stem cell therapy, in the current study, we investigated the effect of rapamycin (Rapa)-preactivated autophagy on the survival and homing of transplanted adipose mesenchymal stem cells (ADMSCs) in a rat model of cisplatin (Cis)-induced nephrotoxicity, as well as the possible role of the mTOR/AKT signaling pathway. Materials and methods: In vitro, ADMSCs isolated from rats were treated with 50 nmol/L rapamycin for 2 h, after which the cytoprotective and autophagy-inducing effects of Rapa were investigated. The cis-induced acute nephrotoxicity rat model was constructed in vivo. ADMSCs and Rapa-ADMSCs were administered into the tail vein before Cis therapy. At 3, 7, and 10 days after Cis injection, all animals were euthanized. The renal functions and morphology as well as autophagy response were assessed. Results: The pretreatment of cultured ADMSCs with Rapa caused a significant increase in autophagic activities and lysosome production of the cells, with a significant increase in the secretion of SDF-1, IL-10 and autophagy promoter LC3 and Beclin from these cells, while mTOR/AKT pathways were inhibited. In addition, the transplantation of Rapa-pretreated ADMSCs restored the kidney functions and morphology dramatically. Renal expression of SDF-1 and HIF1 was upregulated, while expression of IL-6, NF-kB and TGF-β1 was downregulated. Conclusions: We concluded that the preactivation of autophagy with Rapa improves the survival and differentiation of the transplanted ADMSCs by inhibiting the mTOR/AKT signaling pathway, which in turn could significantly attenuate the Cis-induced acute renal injury.
Investigation of Conditions for Capture of Live Legionella pneumophila with Polyclonal and Recombinant Antibodies
Authors: Paladines Lucas , Hassen Walid M. , Chawich Juliana , Dübel Stefan , Lévesque Simon , Dubowski Jan J. , Frost Eric H.
Published: June 2022

Since Legionella pneumophila has caused punctual epidemics through various water systems, the need for a biosensor for fast and accurate detection of pathogenic bacteria in industrial and environmental water has increased. In this report, we evaluated conditions for the capture of live L. pneumophila on a surface by polyclonal antibodies (pAb) and recombinant antibodies (recAb) targeting the bacterial lipopolysaccharide. Using immunoassay and PCR quantification, we demonstrated that, when exposed to live L. pneumophila in PBS or in a mixture containing other non-target bacteria, recAb captured one third fewer L. pneumophila than pAb, but with a 40% lower standard deviation, even when using the same batch of pAb. The presence of other bacteria did not interfere with capture nor increase background by either Ab. Increased reproducibility, as manifested by low standard deviation, is a characteristic that is coveted for biosensing. Hence, the recAb provided a better choice for immune adhesion in biosensors even though it was slightly less sensitive than pAb. Polyclonal or recombinant antibodies can specifically capture large targets such as whole bacteria, and this opens the door to multiple biosensor approaches where any of the components of the bacteria can then be measured for detection or characterisation.
An Efficient Enzyme-Less Uric Acid Sensor Development Based on PbO-Doped NiO Nanocomposites
Authors: Alam Md Mahmud , Asiri Abdullah M. , Rahman Mohammed M.
Published: June 2022

Here, the voltammetric electrochemical approach was applied to detect uric acid (UA) in a conductive sensing medium (phosphate buffer solution-PBS) by using PbO-doped NiO nanocomposites (NCs)-decorated glassy carbon electrode (GCE) performing as working electrode. The wet-chemically prepared PbO-doped NiO NCs were subjected to characterization by the implementation of XRD, FESEM, XPS, and EDS analysis. The modified GCE was used to detect uric acid (UA) in an enzyme-free conductive buffer (PBS) of pH = 7.0. As the outcomes of this study reveal, it exhibited good sensitivity of 0.2315 µAµM−1cm−2 and 0.2233 µAµM−1cm−2, corresponding to cyclic (CV) and differential pulse (DPV) voltammetric analysis of UA, respectively. Furthermore, the proposed UA sensor showed a wider detection (0.15~1.35 mM) range in both electrochemical analysis methods (CV & DPV). In addition, the investigated UA sensor displayed appreciable limit of detection (LOD) of 41.0 ± 2.05 µM by CV and 43.0 ± 2.14 µM by DPV. Good reproducibility performance, faster response time and long-time stability in detection of UA were perceived in both electrochemical analysis methods. Finally, successful analysis of the bio-samples was performed using the recovery method, and the results were found to be quite acceptable in terms of accuracy. Thus, the findings indicate a reliable approach for the development of 5th generation biosensors using metal-oxides as sensing substrate to fulfill the requirements of portable use for in situ detection.
Will Brazilian City Dwellers Actively Engage in Urban Conservation? A Case Study with the Charismatic Neotropical Blue-and-Yellow Macaw (Ara ararauna)
Authors: Angeoletto Fabio , Tryjanowski Piotr , Santos Jeater , Martinez-Miranzo Beatriz , Leandro Deleon , Bohrer João , Johann Juciane Maria , Fellowes Mark D. E.
Published: June 2022

The Blue-and-yellow macaw (Ara ararauna) is a charismatic and easily recognized species. While they are classified as being of “least concern” in the International Union for Conservation of Nature (IUCN) Red List, their populations are declining. In Brazil, the accelerated destruction of one of its key habitats, the Cerrado biome, is a principal cause of their decreasing abundance. As with other species affected by loss of the Cerrado, active conservation measures are required. While usually rare in urban ecosystems, Ara ararauna occurs and breeds in small numbers in the city of Rondonópolis, a medium-sized city located in Mato Grosso, Central-West Region of Brazil. Blue-and-yellow macaw pairs nest in the tops of dead palm trees, but as the macaws are nest-site limited and suitable dead trees are scarce in urban areas, the installation of artificial nest sites in domestic backyards could help that urban population to thrive. To investigate whether local people would be willing to engage with conservation efforts and in particular to support macaw conservation, we surveyed the attitudes of Rondonópolis residents to measure: (1) citizens’ preferences among the bird species that occur in the city; (2) the average area of their yards, and (3) the willingness of residents to: (a) plant fruit trees to attract macaws to their yards and (b) to install artificial nests in their yards. Larger and more colorful birds (Ara ararauna, the Red-and-green macaw Ara chloropterus and Toco Toucan Ramphastos toco) were the bird species most valued across all socio-economic groups, suggesting that the charismatic species would be more likely to be supported by urbanites. Overall, people had good biodiversity knowledge, with respondents being able to identify half of our sample of local bird species, on average, and almost half had seen a nest site. The great majority were willing to plant fruit trees (78%) and provide nest sites (70%) for macaws. This willingness to engage was not affected by socioeconomic differences. These data indicate that a municipal macaw conservation program could be successful in Rondonópolis, and we argue that macaws could be a flagship species which would benefit wider efforts to engage Brazilian urbanites in active engagement with nature.
Glioma-Associated Microglia Characterization in the Glioblastoma Microenvironment through a ‘Seed-and Soil’ Approach: A Systematic Review
Authors: Menna Grazia , Mattogno Pier Paolo , Donzelli Carlo Maria , Lisi Lucia , Olivi Alessandro , Della Pepa Giuseppe Maria
Published: June 2022

Background and aim: Ever since the discovery of tumor-associated immune cells, there has been growing interest in the understanding of the mechanisms underlying the crosstalk between these cells and tumor cells. A “seed and soil” approach has been recently introduced to describe the glioblastoma (GBM) landscape: tumor microenvironments act as fertile “soil” and interact with the “seed” (glial and stem cells compartment). In the following article, we provide a systematic review of the current evidence pertaining to the characterization of glioma-associated macrophages and microglia (GAMs) and microglia and macrophage cells in the glioma tumor microenvironment (TME). Methods: An online literature search was launched on PubMed Medline and Scopus using the following research string: “((Glioma associated macrophages OR GAM OR Microglia) AND (glioblastoma tumor microenvironment OR TME))”. The last search for articles pertinent to the topic was conducted in February 2022. Results: The search of the literature yielded a total of 349 results. A total of 235 studies were found to be relevant to our research question and were assessed for eligibility. Upon a full-text review, 58 articles were included in the review. The reviewed papers were further divided into three categories based on their focus: (1) Microglia maintenance of immunological homeostasis and protection against autoimmunity; (2) Microglia crosstalk with dedifferentiated and stem-like glioblastoma cells; (3) Microglia migratory behavior and its activation pattern. Conclusions: Aggressive growth, inevitable recurrence, and scarce response to immunotherapies are driving the necessity to focus on the GBM TME from a different perspective to possibly disentangle its role as a fertile ‘soil’ for tumor progression and identify within it feasible therapeutic targets. Against this background, our systematic review confirmed microglia to play a paramount role in promoting GBM progression and relapse after treatments. The correct and extensive understanding of microglia–glioma crosstalk could help in understanding the physiopathology of this complex disease, possibly opening scenarios for improvement of treatments.
Integrating Distribution-Based and Anchor-Based Techniques to Identify Minimal Important Change for the Tinnitus Functional Index (TFI) Questionnaire
Authors: Fackrell Kathryn , Hall Deborah Ann , Barry Johanna , Hoare Derek James
Published: June 2022

The Tinnitus Functional Index (TFI) was developed to be responsive to small treatment-related changes in the impact of tinnitus. Yet, no studies have integrated anchor-based and distribution-based techniques to produce a single Minimal Important Change (MIC) score. Here, we evaluated the responsiveness and interpretability of the TFI, determining for the first time a robust MIC score in a UK clinical population. Two-hundred and fifty-five patients with tinnitus participated in this prospective longitudinal validation study. Distribution-based estimates (Standard Error of Measurement, Smallest Detectable Change and Effect size) and anchor-based estimates of important change (minimal clinically important difference and Receiver Operator Curve optimal value) were calculated and then integrated using a visual anchor-based MIC distribution plot. A reduction in score of −14 was determined as the MIC estimate that exceeds the measurement error, most of the variability and reliably identifies patients demonstrating true improvement. It is therefore recommended that a reduction of 14 points should be used as a minimum change required when calculating statistical power and sample size in tinnitus intervention studies and assessing patients in clinical practice.
Multi-Task Learning for Concurrent Prediction of Thermal Comfort, Sensation and Preference in Winters
Authors: Lala Betty , Rizk Hamada , Kala Srikant Manas , Hagishima Aya
Published: June 2022

Indoor thermal comfort immensely impacts the health and performance of occupants. Therefore, researchers and engineers have proposed numerous computational models to estimate thermal comfort (TC). Given the impetus toward energy efficiency, the current focus is on data-driven TC prediction solutions that leverage state-of-the-art machine learning (ML) algorithms. However, an occupant’s perception of indoor thermal comfort (TC) is subjective and multi-dimensional. Different aspects of TC are represented by various standard metrics/scales viz., thermal sensation (TSV), thermal comfort (TCV), and thermal preference (TPV). The current ML-based TC prediction solutions adopt the Single-task Learning approach, i.e., one prediction model per metric. Consequently, solutions often focus on only one TC metric. Moreover, when several metrics are considered, multiple ML models for a single indoor space lead to conflicting predictions, rendering real-world deployment infeasible. This work addresses these problems by leveraging Multi-task Learning for TC prediction in naturally ventilated buildings. First, a survey-and-measurement study is conducted in the composite climatic region of north India, in 14 naturally ventilated classrooms of 5 schools, involving 512 primary school students. Next, the dataset is analyzed for important environmental, physiological, and psycho-social factors that influence thermal comfort of children. Further, “DeepComfort”, a deep neural network based Multi-task Learning model is proposed. DeepComfort predicts multiple TC output metrics viz., TSV, TPV, and TCV, simultaneously through a single model. It is validated on ASHRAE-II database and the primary student dataset created in this study. It demonstrates high F1-scores, Accuracy (≈90%), and generalization capability, despite the challenges of illogical responses and data imbalance. DeepComfort is also shown to outperform 6 popular metric-specific single-task machine learning algorithms.
Using Aerosol OT in Hexane Solution to Synthesize Calcium Nitrate Self-Healing Refined Microcapsules for Construction Applications
Authors: Taqa Ala Abu , Suleiman Ghassan , Senouci Ahmed , Mohsen Mohamed O.
Published: June 2022

The micro-encapsulation procedure of calcium nitrate in urea-formaldehyde shell is well known. The most recent developed method for the synthesis of the calcium nitrate self-healing micro-capsules was based on the in-situ polymerization using water-in-oil emulsion. Although the microcapsules’ yield was significantly improved using this approach, incorporating the micro-capsules into concrete mixes has been found to reduce strength. One potential strength reduction cause might be the presence of sulfonic acid as a component in the continuous (oil) phase. As the anionic surfactant, Aerosol OT (AOT) has been widely used to prepare water-in-oil emulsions and to form aggregates in non-polar solvents; submicron calcium nitrate refined microcapsules were synthesized using AOT in hexane solution. While the aqueous phase in the original encapsulation procedure has not been altered, the continuous organic phase was prepared by dissolving AOT in hexane. The prepared microcapsules were characterized using Scanning Electron Microscopy (SEM). The preliminary assessment of the effect of incorporating of the refined microcapsules into cementitious materials has been carried out by preparing mortar mixes using 75% capsules’ concentration (by weight of cement). The reported yield values, average shell thickness, and average diameter of the prepared microcapsules were found satisfactory. Moreover, the mortar samples containing calcium nitrate refined microcapsules that were prepared using the proposed method did not experience significant reduction in their mechanical properties. Hence, such encapsulation procedure may be adopted for further investigation of the self-healing efficiency in cementitious materials of the microcapsules prepared using the proposed procedure. Future work shall be directed towards this end.
Seismic Fragility Analysis of Mega-Frame with Vibration Control Substructure Based on Dual Surrogate Model and Active Learning
Authors: Xiao Yanjie , Zhang Xun’an , Yue Feng , Shahzad Muhammad Moman , Wang Xinwei , Fan Buqiao
Published: June 2022

Seismic fragility analysis of a mega-frame with vibration control substructure (MFVCS) considering structural uncertainties is computationally expensive. Dual surrogate model (DSM) can be used to improve computational efficiency, whereas the proper selection of design of experiments (DoE) is a difficult work in the DSM-based seismic fragility analysis (DSM-SFA) method. To efficiently assess the seismic fragility with sufficient accuracy, this paper proposes an improved DSM-SFA method based on active learning (AL). In this method, the Kriging model is employed for surrogate modeling to obtain the predicted error of approximation. An AL sampling strategy is presented to update the DoE adaptively, and the refinement of the surrogate models can reduce the error of the probability result computed by the Monte Carlo (MC) simulation. A numerical example was studied to verify the effectiveness and feasibility of the improved procedure. This method was applied to the fragility analysis of an MFVCS and a mega-frame structure (MFS). The finite element models were established using OpenSeesPy and SAP2000 software, respectively, and the correctness of the MFVCS model was verified. The results show that MFVCS is less vulnerable than MFS and has better seismic performance.
Time-Dependent Behavior of Composite Steel–Recycled Aggregate Concrete Beams via Thermomechanical Finite Element Modeling
Authors: Yang Jinsheng , Liu Changyong , Wang Qinghe , Geng Yue
Published: June 2022

This paper aims to investigate the impact of recycled coarse aggregate (RCA) on the time-dependent behavior of composite steel–recycled aggregate concrete (RAC) beams. The FE models of the composite beams were established, and a parametric study was conducted to obtain the primary factors. Furthermore, the design method for predicting the long-term deflection was proposed by including the shrinkage deflection component. The results showed that the RCA replacement ratio significantly influenced the long-term deflection of composite beams; the long-term deflection of composite beams with 100% RCA increased by 3.5–17.2% compared with those without RCA. Moreover, using uniform shrinkage and creep models led to a 4.5–10.3% overestimation of the long-term deflection of the composite beams with the composite slabs due to nonuniform shrinkage and creep distributions. Finally, the proposed design procedures could accurately predict the long-term deflection of the composite steel–RAC beams, and the difference between the calculated and FE results ranged from 0.961 to 0.986.
Magmas Inhibition in Prostate Cancer: A Novel Target for Treatment-Resistant Disease
Authors: Yang Jianhui , Das Bhaskar C. , Aljitawi Omar , Kumar Avinash , Das Sasmita , Van Veldhuizen Peter
Published: June 2022

The purpose of our study was to evaluate Magmas as a potential target in prostate cancer. In addition, we evaluated our synthetic Magmas inhibitor (BT#9) effects on prostate cancer and examined the molecular mechanism of BT#9. A cell viability assay showed that treatment with BT#9 caused a significant decrease in the viability of DU145 and PC3 prostate cancer cells with little effect on the viability of WPMY-1 normal prostate cells. Western blot proved that BT#9 downregulated the Magmas protein and caspase-3 activation. Flow cytometry studies demonstrated increased apoptosis and disturbed mitochondrial membrane potential. However, the main mode of cell death was caspase-independent necrosis, which was correlated with the accumulation of mitochondrial and intra-cellular Reactive Oxygen Species (ROS). Taken together, our data suggest Magmas is a potential molecular target for the treatment of prostate cancer and that Magmas inhibition results in ROS-dependent and caspase-independent necrotic cell death.
Cancer-Induced Metabolic Rewiring of Tumor Endothelial Cells
Authors: Lidonnici Jacopo , Santoro Massimo M. , Oberkersch Roxana E.
Published: June 2022

Cancer is a leading cause of death worldwide. If left untreated, tumors tend to grow and spread uncontrolled until the patient dies. To support this growth, cancer cells need large amounts of nutrients and growth factors that are supplied and distributed to the tumor tissue by the vascular system. The aberrant tumor vasculature shows deep morphological, molecular, and metabolic differences compared to the blood vessels belonging to the non-malignant tissues (also referred as normal). A better understanding of the metabolic mechanisms driving the differences between normal and tumor vasculature will allow the designing of new drugs with a higher specificity of action and fewer side effects to target tumors and improve a patient’s life expectancy. In this review, we aim to summarize the main features of tumor endothelial cells (TECs) and shed light on the critical metabolic pathways that characterize these cells. A better understanding of such mechanisms will help to design innovative therapeutic strategies in healthy and diseased angiogenesis.
Feasibility of Implementing Cancer-Specific Community-Based Exercise Programming: A Multi-Centre Randomized Trial
Authors: McNeely Margaret L. , Suderman Kirsten , Yurick Janice L. , Nishimura Kathryn , Sellar Christopher , Ospina Paula A. , Pituskin Edith , Lau Harold , Easaw Jacob C. , Parliament Matthew B. , Joy Anil A. , Culos-Reed S. Nicole
Published: June 2022

Background: There is growing recognition of the importance of reporting preliminary work on the feasibility of a trial. The present study aimed to assess the feasibility of (1) a proposed fitness testing battery, and (2) processes related to the implementation of cancer-specific exercise programming in a community setting. Methods/Design: A randomized controlled implementation feasibility trial was performed in advance of a large-scale implementation study. Eligible participants within 18 months of a cancer diagnosis were randomized to immediate or delayed community-based exercise at YMCA locations in Calgary and Edmonton, Canada for an 8-week period. The primary outcome for the trial was the feasibility of the physical fitness testing battery, defined as a 70% or greater completion rate across the 24-week study period. The Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework was used to evaluate processes related to implementation of the exercise program across the two sites. Results: Eighty participants were recruited, 73 (91%) completed the 8-week trial, and 68 (85%) completed the 16- and 24-week follow-ups. Sixty participants (75%) completed the full physical fitness test battery at each time point, and 59 (74%) completed the patient-reported outcome measures. Statistically significant between-group differences were found in favor of the exercise group for functional aerobic capacity, upper and lower extremity strength, and symptoms. Differences were found between the sites, however, in completion rates and processes related to program implementation. Discussion: Findings suggest the need for minor adaptations to the physical fitness battery and outcome measures to better fit the community context. While findings support feasibility, context-specific challenges related to implementation processes were identified.
Inhibitors of the Actin-Bundling Protein Fascin-1 Developed for Tumor Therapy Attenuate the T-Cell Stimulatory Properties of Dendritic Cells
Authors: Zeyn Yanira , Harms Gregory , Tubbe Ingrid , Montermann Evelyn , Röhrig Nadine , Hartmann Maike , Grabbe Stephan , Bros Matthias
Published: June 2022

Background: Stimulated dendritic cells (DCs), which constitute the most potent population of antigen-presenting cells (APCs), express the actin-bundling protein Fascin-1 (Fscn1). In tumor cells, de novo expression of Fscn1 correlates with their invasive and metastatic properties. Therefore, Fscn1 inhibitors have been developed to serve as antitumor agents. In this study, we were interested in better understanding the impact of Fscn1 inhibitors on DCs. Methods: In parallel settings, murine spleen cells and bone-marrow-derived DCs (BMDCs) were stimulated with lipopolysaccharide in the presence of Fscn1 inhibitors (NP-G2-044 and BDP-13176). An analysis of surface expression of costimulatory and coinhibitory receptors, as well as cytokine production, was performed by flow cytometry. Cytoskeletal alterations were assessed by confocal microscopy. The effects on the interactions of BMDCs with antigen-specific T cells were monitored by time lapse microscopy. The T-cell stimulatory and polarizing capacity of BMDCs were measured in proliferation assays and cytokine studies. Results: Administration of Fscn1 inhibitors diminished Fscn1 expression and the formation of dendritic processes by stimulated BMDCs and elevated CD273 (PD-L2) expression. Fscn1 inhibition attenuated the interaction of DCs with antigen-specific T cells and concomitant T-cell proliferation. Conclusions: Systemic administration of Fscn1 inhibitors for tumor therapy may also modulate DC-induced antitumor immune responses.
Extracellular Vesicle-Based Bronchoalveolar Lavage Fluid Liquid Biopsy for EGFR Mutation Testing in Advanced Non-Squamous NSCLC
Authors: Kim In Ae , Hur Jae Young , Kim Hee Joung , Kim Wan Seop , Lee Kye Young
Published: June 2022

To overcome the limitations of the tissue biopsy and plasma cfDNA liquid biopsy, we performed the EV-based BALF liquid biopsy of 224 newly diagnosed stage III-IV NSCLC patients and compared it with tissue genotyping and 110 plasma liquid biopsies. Isolation of EVs from BALF was performed by ultracentrifugation. EGFR genotyping was performed through peptide nucleic acid clamping-assisted fluorescence melting curve analysis. Compared with tissue-based genotyping, BALF liquid biopsy demonstrated a sensitivity, specificity, and concordance rates of 97.8%, 96.9%, and 97.7%, respectively. The performance of BALF liquid biopsy was almost identical to that of standard tissue-based genotyping. In contrast, plasma cfDNA-based liquid biopsy (n = 110) demonstrated sensitivity, specificity, and concordance rates of 48.5%, 86.3%, and 63.6%, respectively. The mean turn-around time of BALF liquid biopsy was significantly shorter (2.6 days) than that of tissue-based genotyping (13.9 days; p < 0.001). Therefore, the use of EV-based BALF shortens the time for confirmation of EGFR mutation status for starting EGFR-TKI treatment and can hence potentially improve clinical outcomes. As a result, we suggest that EV-based BALF EGFR testing in advanced lung NSCLC is a highly accurate rapid method and can be used as an alternative method for lung tissue biopsy.
Toxicity and Clinical Results after Proton Therapy for Pediatric Medulloblastoma: A Multi-Centric Retrospective Study
Authors: Ruggi Alessandro , Melchionda Fraia , Sardi Iacopo , Pavone Rossana , Meneghello Linda , Kitanovski Lidija , Zaletel Lorna Zadravec , Farace Paolo , Zucchelli Mino , Scagnet Mirko , Toni Francesco , Righetto Roberto , Cianchetti Marco , Prete Arcangelo , Greto Daniela , Cammelli Silvia , Morganti Alessio Giuseppe , Rombi Barbara
Published: June 2022

Medulloblastoma is the most common malignant brain tumor in children. Even if current treatment dramatically improves the prognosis, survivors often develop long-term treatment-related sequelae. The current radiotherapy standard for medulloblastoma is craniospinal irradiation with a boost to the primary tumor site and to any metastatic sites. Proton therapy (PT) has similar efficacy compared to traditional photon-based radiotherapy but might achieve lower toxicity rates. We report on our multi-centric experience with 43 children with medulloblastoma (median age at diagnosis 8.7 years, IQR 6.6, M/F 23/20; 26 high-risk, 14 standard-risk, 3 ex-infant), who received active scanning PT between 2015 and 2021, with a focus on PT-related acute-subacute toxicity, as well as some preliminary data on late toxicity. Most acute toxicities were mild and manageable with supportive therapy. Hematological toxicity was limited, even among HR patients who underwent hematopoietic stem-cell transplantation before PT. Preliminary data on late sequelae were also encouraging, although a longer follow-up is needed.
Reducing Immunosuppression in Patients with De Novo Lung Carcinoma after Liver Transplantation Could Significantly Prolong Survival
Authors: Pesthy Sina , Wegener Elisa , Ossami Saidy Ramin Raul , Timmermann Lea , Uluk Deniz , Aydin Mustafa , Dziodzio Tomasz , Schoening Wenzel , Lurje Georg , Öllinger Robert , Frost Nikolaj , Fehrenbach Uli , Rückert Jens-Carsten , Neudecker Jens , Pratschke Johann , Eurich Dennis
Published: June 2022

(1) Background: Liver transplantation (LT) is an established treatment for selected patients with end-stage liver disease resulting in a subsequent need for long-term immunosuppressive therapy. With cumulative exposure to immunosuppression (IS), the risk for the development of de novo lung carcinoma increases. Due to limited therapy options and prognosis after diagnosis of lung cancer, the question of the mode and extent of IS in this particular situation is raised. (2) Methods: All patients diagnosed with de novo lung cancer in the follow-up after LT were identified from the institution’s register of liver allograft recipients (Charité—Universitätsmedizin Berlin, Germany) transplanted between 1988 and 2021. Survival analysis was performed based on the IS therapy following diagnosis of lung cancer and the oncological treatment approach. (3) Results: Among 3207 adult LTs performed in 2644 patients at our institution, 62 patients (2.3%) developed de novo lung carcinoma following LT. Lung cancer was diagnosed at a median interval of 9.7 years after LT (range 0.7–27.0 years). Median survival after diagnosis of lung carcinoma was 13.2 months (range 0–196 months). Surgical approach with curative intent significantly prolonged survival rates compared to palliative treatment (median 67.4 months vs. 6.4 months). Reduction of IS facilitated a significant improvement in survival (median 38.6 months vs. 6.7 months). In six patients (9.7%) complete IS weaning was achieved with unimpaired liver allograft function. (4) Conclusion: Reduction of IS therapy after the diagnosis of de novo lung cancer in LT patients is associated with prolonged survival. The risk of acute rejection does not appear to be increased with restrictive IS management. Therefore, strict reduction of IS should be an early intervention following diagnosis. In addition, surgical resection should be attempted, if technically feasible and oncologically meaningful.
The Role of Indoleamine 2, 3-Dioxygenase 1 in Regulating Tumor Microenvironment
Authors: Huang Xinting , Zhang Feng , Wang Xiaobo , Liu Ke
Published: June 2022

Indoleamine 2, 3-dioxygenase 1 (IDO1) is a rate-limiting enzyme that metabolizes an essential amino acid tryptophan (Trp) into kynurenine (Kyn), and it promotes the occurrence of immunosuppressive effects by regulating the consumption of Trp and the accumulation of Kyn in the tumor microenvironment (TME). Recent studies have shown that the main cellular components of TME interact with each other through this pathway to promote the formation of tumor immunosuppressive microenvironment. Here, we review the role of the immunosuppression mechanisms mediated by the IDO1 pathway in tumor growth. We discuss obstacles encountered in using IDO1 as a new tumor immunotherapy target, as well as the current clinical research progress.
Metabolic Profiling of Mice with Deletion of the Orphan G Protein-Coupled Receptor, GPR37L1
Authors: Mouat Margaret A. , Wilkins Brendan P. , Ding Eileen , Govindaraju Hemna , Coleman James L. J. , Graham Robert M. , Turner Nigel , Smith Nicola J.
Published: June 2022

Understanding the neurogenic causes of obesity may reveal novel drug targets to counter the obesity crisis and associated sequelae. Here, we investigate whether the deletion of GPR37L1, an astrocyte-specific orphan G protein-coupled receptor, affects whole-body energy homeostasis in mice. We subjected male Gpr37l1−/− mice and littermate wildtype (Gpr37l1+/+, C57BL/6J background) controls to either 12 weeks of high-fat diet (HFD) or chow feeding, or to 1 year of chow diet, with body composition quantified by EchoMRI, glucose handling by glucose tolerance test and metabolic rate by indirect calorimetry. Following an HFD, Gpr37l1−/− mice had similar glucose handling, body weight and fat mass compared with wildtype controls. Interestingly, we observed a significantly elevated respiratory exchange ratio in HFD- and chow-fed Gpr37l1−/− mice during daylight hours. After 1 year of chow feeding, we again saw no differences in glucose and insulin tolerance or body weight between genotypes, nor in energy expenditure or respiratory exchange ratio. However, there was significantly lower fat mass accumulation, and higher ambulatory activity in the Gpr37l1−/− mice during night hours. Overall, these results indicate that while GPR37L1 may play a minor role in whole-body metabolism, it is not a viable clinical target for the treatment of obesity.
Planetary Health and Traditional Medicine: A Potential Synergistic Approach to Tackle Antimicrobial Resistance
Authors: Oladunjoye Iyiola , Tajudeen Yusuf , Oladipo Habeebullah , El-Sherbini Mona
Published: June 2022

Antimicrobials are compounds that impede the activities of bacteria, viruses, parasites, or fungi. Continuous antimicrobial overuse, misuse, and improper use for human, animal, and agricultural purposes are raising concerns about antibiotic residue pollution in the environment, and antibiotic resistance genes (ARGs). Because antimicrobial-resistant diseases are linked to human–-microbial ecosystems, environmental pollution from antibiotic residue and ARGs alters the makeup and diversity of human gut microbiota, putting resistance under selection pressure. This perspective proposes that antibiotic-induced microbiome depletion is linked to environmental quality and has repercussions for human health via the gut microbiome’s sensitive ecosystem. This has stimulated new global efforts and multidisciplinary, integrative approaches to addressing Antimicrobial Resistance (AMR) awareness in communities. Several academic papers published in recent years have shown that medicinal plant extracts are effective against diseases on WHO’s pathogen priority lists (PPL), such as the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). Traditional medicine, with its knowledge of medicinal plants, promises to be a valuable source of next-generation powerful antimicrobials. Examples include the recent discovery of Artemisinin, a highly active antimalarial drug derived from Artemisia annua, and the discovery of Taxol, an active chemotherapeutic drug derived from the bark of the Pacific yew, Taxus brevifolia. The connections between small and large ecosystems’ vitality, biodiversity protection, and human health have been acknowledged by Planetary Health principles. To address these intertwined concerns, a Planetary Health and Traditional Medicine approach can be adopted, and antimicrobial resistance can be addressed by expanding the screening of medicinal plants for bioactive compounds.
Correlates of Sub-Optimal Feeding Practices among under-5 Children amid Escalating Crises in Lebanon: A National Representative Cross-Sectional Study
Authors: Hoteit Maha , Ibrahim Carla , Saadeh Danielle , Al-Jaafari Marwa , Atwi Marwa , Alasmar Sabine , Najm Jessica , Sacre Yonna , Hanna-Wakim Lara , Al-Jawaldeh Ayoub
Published: June 2022

Sub-optimal feeding practices among under-5 children are the major drivers of malnutrition. This study aims to assess the prevalence of malnutrition and the factors affecting exclusive breastfeeding, bottle feeding, and complementary feeding practices among under 5 children amid the COVID-19 pandemic as well as the economic and the political crises in Lebanon. A nationally representative stratified random sample of mother–child dyads (n = 511) was collected from households using a stratified cluster sampling design. The survey inquired about infant’s feeding and complementary feeding practices using a valid questionnaire. Anthropometric measurements of the mother and child were collected. Multivariate logistic regression was conducted to explore the determinants associated with under-5 children’s practices. The prevalence of underweight, stunting, wasting, overweight and obese children was 0.5%, 8.4%, 6.7%, 16.8% and 8.9%, respectively. In total, among under-5 children, the prevalence of ever breastfeeding, exclusive breastfeeding, and bottle feeding at birth was 95.1%, 59.1% and 25.8%, respectively. Half the children in this study started solid foods between 4 and 6 months. Regression analysis showed that supporting breastfeeding at hospital (aOR = 8.20, 95% CI (3.03–22.17)) and husband’s support (aOR = 3.07, 95% CI (1.9–4.92)) were associated with increased breastfeeding odds. However, mother’s occupation (aOR = 0.18, 95% CI (0.55–0.58)) was inversely associated with breastfeeding practices. Male children (aOR = 2.119, 95% CI (1.37–3.27), mothers diagnosed with COVID-19 (aOR = 0.58, 95% CI (0.35–0.95)), and bottle feeding at hospital (aOR = 0.5, 95% CI (0.32–0.77)) were more likely to induce early initiation of solid foods at 4 months of age. This study demonstrated non-negligible rates of malnutrition, low prevalence of exclusive breastfeeding, and high rates of early introduction of formula feeding and solid foods among Lebanese under-5-children amid escalating crises.
Cholecystokinin Outcome on Markers of Intestinal IgA Antibody Response
Authors: Morales-Magaña Juan , Arciniega-Martínez Ivonne Maciel , Drago-Serrano Maria Elisa , Reséndiz-Albor Aldo Arturo , Jarillo-Luna Rosa Adriana , Cruz-Baquero Andrea , Gómez-López Modesto , Guzmán-Mejía Fabiola , Pacheco-Yépez Judith
Published: June 2022

Cholecystokinin 8 (CCK8) is an entero-octapeptide that participates in crosstalk with components of intestinal immunity via the CCK receptor (CCKR), but its role in modulation of the IgA response is not fully known under physiological conditions. Male eight-week-old BALB/c mice each were intraperitoneally injected once during 7 days with CCK8, devazapide (CCKR1 antagonist), L365,260 (CCKR2 antagonist) or vehicle (sham group). In intestinal lavages, total and secretory IgA (SIgA) were determined by ELISA; in lamina propria, IgA+ B lymphocytes and IgA+ plasma cells were analyzed by flow cytometry; mRNA levels of polymeric immunoglobulin receptor (pIgR) in epithelial cells and α chain, interleukins (ILs) in lamina propria cells were assessed by qRTPCR. Regarding the sham conditions, IgA+ plasma-cell percentage and IL-2, IL-5, IL-10 and transforming growth factor-β (TGF-β) mRNA levels were either increased by CCK8 or decreased by both CCKR antagonists. For IgA/SIgA responses, IL-4/IL-6 mRNA levels were decreased by all drugs and pIgR mRNA was increased by CCK8 and reduced by L365,260. IgA+ B cell percentage and α chain mRNA levels were elicited by CCK8 and L365,260. Data suggested a presumable differential role of CCK/CCKR on the IgA-response; outcome of L365,260 on the elicitation of IgA+ B cells and α chain mRNA needs further examination.
Improved Performance of Ceramic Solar Absorber Particles Coated with Black Oxide Pigment Deposited by Resonant Acoustic Mixing and Reaction Sintering
Authors: Alkan Gözde , Mechnich Peter , Pernpeintner Johannes
Published: June 2022

Spherical particles based on bauxite-type raw materials, commonly referred to as proppants, are state-of-the-art for particle receivers of concentrated solar power plants. Particles are heated in a fluidized reactor by focused sunlight and are transported to a heat-exchanger or a storage tank. Therefore, key properties for absorber particles are high solar absorptance and mechanical endurance. Due to their relatively poor content of color-giving transition-metal cations, bauxite-derived proppants show limited solar absorptance, which is even deteriorating by long-term heat exposure. A deep-black Cu, Mn, Fe- pigment with a spinel structure was employed to coat standard proppants in order to improve solar absorptance. The coating process was performed by high-energy, high-speed mixing of proppants and small quantities of spinel powders in a resonant acoustic mixer. A continuous powder coating is achieved by electrostatic attraction between the proppant surface and the coating particles. Consolidation and strong attachment of the coating is achieved by the subsequent sintering beyond the spinel melting temperature. Chemical reaction and bonding between spinel coating and proppant lead to the incorporation of Al, Mg and Ti into the spinel structure. Coated bauxite proppants exhibit a significantly improved, long-term stable solar absorption accompanied by a promising abrasion resistance. The presented coating methodology is considered to be scalable to industrial production.
Loss of Migratory Traditions Makes the Endangered Patagonian Huemul Deer a Year-Round Refugee in Its Summer Habitat
Authors: Flueck Werner , Smith-Flueck Jo , Escobar Miguel , Zuliani Melina , Fuchs Beat , Geist Valerius , Heffelfinger James , Black-Decima Patricia , Gizejewski Zygmunt , Vidal Fernando , Barrio Javier , Molinuevo Silvina , Monjeau Adrian , Hoby Stefan , Jiménez Jaime
Published: June 2022

The huemul (Hippocamelus bisulcus) is endangered, with 1500 deer split into >100 subpopulations along 2000 km of the Andes. Currently occupied areas are claimed-erroneously-to be critical prime habitats. We analyzed historical spatiotemporal behavior since current patterns represent only a fraction of pre-Columbian ones. Given the limited knowledge, the first group (n = 6) in Argentina was radio-marked to examine spatial behavior. Historically, huemul resided year-round in winter ranges, while some migrated seasonally, some using grasslands >200 km east of their current presence, reaching the Atlantic. Moreover, huemul anatomy is adapted to open unforested habitats, also corroborated by spotless fawns. Extreme naivety towards humans resulted in early extirpation on many winter ranges—preferentially occupied by humans, resulting in refugee huemul on surrounding mountain summer ranges. Radio-marked huemul remained in small ranges with minimal altitudinal movements, as known from other subpopulations. However, these resident areas documented here are typical summer ranges as evidenced by past migrations, and current usage for livestock. The huemul is the only cervid known to use mountain summer ranges year-round in reaction to anthropogenic activities. Losing migratory traditions is a major threat, and may explain their presently prevalent skeletal diseases, reduced longevity, and lacking recolonizations for most remaining huemul subpopulations.
Retrospective Analysis of the Development of Human Thyroglobulin during Pregnancy in Patients with Treated Non-Recurrent Differentiated Thyroid Cancer
Authors: Baumgarten Justus , Happel Christian , Groener Daniel , Staudt Jennifer , Bockisch Benjamin , Sabet Amir , Grünwald Frank , Rink Thomas
Published: June 2022

Aim: Therapy success in patients with differentiated thyroid cancer (DTC) after thyroidectomy and radioiodine therapy (RIT) is proven by permanent decrease in human thyroglobulin (hTg) to <1 ng/mL. In this retrospective analysis hTg development before, during and after pregnancy were analyzed. Material and methods: A descriptive analysis of hTg courses in 47 women with 57 pregnancies under levothyroxine substitution was performed after treatment of DTC without evidence of residual or recurrent disease. We compared hTg levels before, during and after pregnancies. A median of four measurements were performed during pregnancy. Results: In five out of the 47 patients at least one hTg increase to ≥1.0 ng/mL occurred during pregnancy (P1: 1.1; P2: 1.75; P3: 1.0; P4: 1.1; P5: 1.07 ng/mL). In another three cases an increase to ≥0.5 ng/mL occurred. After delivery, all patients returned to undetectable hTg levels. Human Tg maxima during pregnancy were significantly elevated according to Friedman´s Chi2 and p Holm–Bonferroni. Conclusion: In women with ablative thyroid therapy after DTC, a temporary elevation in hTg levels during pregnancy may occur. The reason therefore remains unclear and requires further investigation.
Promising Therapeutic Impact of a Selective Estrogen Receptor Downregulator, Fulvestrant, as Demonstrated In Vitro upon Low-Grade Serous Ovarian Carcinoma Cell Lines
Authors: Shanta Kamrunnahar , Nakayama Kentaro , Hossain Mohammad Mahmud , Razia Sultana , Ishibashi Tomoka , Ishikawa Masako , Yamashita Hitomi , Kanno Kosuke , Sato Seiya , Nakayama Satoru , Otsuki Yoshiro , Kyo Satoru
Published: June 2022

Few studies have reported hormonal agent use in the treatment of low-grade serous ovarian carcinomas (LGSOCs), which are chemoresistant. Considering the need for novel effective therapies, we investigated the hormone receptor expression and hormonal inhibition efficacy in LGSOCs. Using immunohistochemistry, we assessed the estrogen receptor (ER) expression status in 33 cases of histologically confirmed serous ovarian tumors, including 10, 11, and 12 cases of LGSOCs, serous borderline tumors (SBTs), and serous cystadenomas (SCAs), respectively. The genetic background reported in our previous study was used in the current study. MPSC1 cells, which were established from LGSOCs, were used in cell proliferation assays. We observed a higher ER expression in LGSOCs and SBTs than in SCAs (70%, 81%, and 50%, respectively). Thus, LGSOCs and SBTs exhibit higher ER expression than SCAs. Moreover, the PIK3CA mutation positively correlated with ER expression in LGSOCs (p = 0.0113). MPSC1 cells showed low ER expression on Western blotting. MPSC1 cell proliferation was significantly inhibited by fulvestrant (a selective ER downregulator). The activation of ER and PI3K/AKT signaling pathways may play an important role in LGSOC carcinogenesis. ER downregulation with fulvestrant or combination therapy with PI3K inhibitors is a possible novel treatment for patients with LGSOCs.