bluuebunny/crossref_metadata_2025 huggingface dataset:
Pendampingan Pembuatan Keripik Pisang pada Msyarakat (Suatu Pendekatan Dakwah)
Authors: Abdullah Nuraeni , Subaedah Subaedah
Published: July 2020

PkMD ini bertujuan untuk memberi keterampilan kepada masyarakat untuk mengolah hasil pertanian mereka untuk menjadi usaha kecil yang dapat menambah penghasilan keluarga. Metode pelaksanaannya melalui empat tahap: Sosialisasi Program, Tahap Persiapan, Tahap Pelaksanaan,danEvaluasi.  Pertama,  Sosialisasi Program, untuk menyampaikan maksud dan tujuan program melalui ketua MajeLis Taklim Jabal Rahmah,  dan membuat kesempakatan tentang waktu dan tempat pelaksanaan program. Kedua, tahap Persiapan, yakni Tim PkMD mempersiapkan alat dan bahan-bahan yang dibutuhkan melalui eksperimen, dan selanjutnya mempersiapkan alat dan bahan yang baik dan bermutu. Alat pemotong yang digunakan adalah  “Stainless Steel Series Multi-purpose Combination Grater”. Aneka keripik pisang yang dipraktikkan adalah  rasa original, manis, keju, coklat dan rasa balado manis pedas.  Ketiga,  Tahap Pelaksanaan, kegiatan pendampingan dilakukan  full day yang berlangsung pada hari Ahad, tanggal 1 Desember 2019 mulai jam 09.00 – 17.00. Diawali dengan pencerahan tentang “Etika Memulai dan Menjalankan Usaha”, penjelasan tentang teknik penggunaan alat dan pembuatan keripik,  kemudian dilanjutkan dengan praktik pembuatan keripik sampai pengemasan. Hasil yang dicapai adalah 15 orang peserta yang terdiri dari ibu rumah tangga, remaja putri dan putra telah mampu membuat keripik pisang yang gurih, halal, dan higenis, punya semangat yang tinggi untuk menjalankan dan mengembangkannya. Keempat, Evaluasi, dilakuakan dengan menganalisis hasil observasi Tim selama peroses pendampingan berlangsung bahwa para peserta mengikuti kegiatan ini dengan antusias dan kerjasama yang baik.  dan  hasil wawancara dengan perwakilan kelompok menyatakan bahwa, hal-hal yang baru mereka peroleh dari pendampingan ini terutama adalah alat, kemasan dan label. Dapat disimpulkan bahwa kegiatan ini telah berhasil dengan baik sesuai target yang direncanakan, namun masih perlu pendampingan selanjutnya untuk pengembangannya.
THE PARADOX OF THE FLIPPED CLASSROOM: ONE METHOD, MANY INTENTIONS
Authors: Bäcklund Johan , Hugo Martin
Published: July 2020

The Flipped Classroom is a teaching model where content attainment is shifted forward to outside of class, to be followed up by the teacher in class. In Sweden this way of teaching has become very popular during recent years. But what is gained by this way of teaching? Research on the Flipped Classroom in the context of the Swedish High School system is close to non-existent; why studies within this field are of great importance.
In order to find appropriate informants, an electronic survey was constructed. Informants matching the selection criteria were then selected for qualitative interviews. In total nine informants agreed to participate in interviews (semi-structured) to describe their experiences from flipping their own classrooms.
The informants reported that the transition from more conventional ways of teaching to using the Flipped Classroom entailed major changes. The informants pointed out that the process of moving away from the more conventional way of teaching improved their teaching. All of the informants expressed they all used the Flipped Classroom methodology but they all did it with different goals in mind and their approach varied a lot. By using the same terminology, it might seem that they worked with the Flipped Classroom in similar ways, but the results show they did not. Herein lies the problem: Teachers say they flip their classrooms, which they do, but they do not share the same goals or approaches, just the term: The Flipped Classroom.
Keywords: flipped classroom, flipped education, qualitative interviews, teaching methodology.
Noninvasive markers for esophageal varices in children with cirrhosis
Authors: Rahmani Parisa , Farahmand Fatemeh , Heidari Ghobad , Sayarifard Azadeh
Published: July 2020

Background: The diagnosis of esophageal varices (EV) is based on the findings of esophagogastroduodenoscopy (EGD), biopsy, and serum markers. Thus, noninvasive cost-effective tests through which high-risk EV children can be diagnosed are needed.Purpose: This cross-sectional study aimed to identify the noninvasive markers for EV in children with liver cirrhosis.Methods: A total of 98 children with liver cirrhosis were evaluated in this study. The spleen size, platelet count, serum albumin, liver function test results, and risk scores were evaluated prior to endoscopy. The endoscopic investigations aimed to identify the presence of EV and red signs, and determine varices sizes.Results: Endoscopy revealed varices in 43 subjects (43.9%). The spleen size, platelet count, international normalized ratio, aspartate aminotransferase to platelet ratio index (APRI), platelet count to spleen size ratio, and risk score differed significantly between patients with and without EV on univariate analysis; however, the logistic regression analysis showed no differences, indicating that none of these parameters were independently associated with the presence of EV.Conclusion: Platelet count, risk score, platelet count to spleen size, and APRI can be useful tools for the identification of highrisk patients with EV and might reduce the need for invasive methods like EGD.
Strategy of Insan Kamil in Building Green Education
Authors: Budiyanti Nurti , Aziz Asep Abdul , Erihadiana Mohamad
Published: July 2020

The reality of life illustrates the low level of human concern on environment. In fact, it undeniably promotes environmental damage nationally and globally. Therefore, the ecosystem damage in various places and regions has become a serious threat to the survival of the life of the universe. Humans are closely related to nature and they have a great responsibility to protect the universe. In regard to this issue. This article provides an overview of the ideal human strategy, namely Insan Kamil, as a means of increasing awareness of our status as ‘Abdun and our role as caliph in instilling awareness of environmental love through Green Education. This study employed a qualitative approach in the form of literature study in collecting data. The result found that Insan Kamil is considered as a human who is trying to realize his status as a servant of Allah and his role as khalifatullah who has a Divine vision to worship Allah and they also have mission in maintaining natural order and prosperity of the environment. Through the approach of spiritual education, its strategy must be applied within family, school, and community. Thus, it is clear that the strategy of this Insan Kamil is not only in the scope of formal education, but non-formal and in-formal education must also have the same objective integration in order to foster awareness of environmental love through Green Education.

Keywords: Strategy of Insan Kamil, Green Educaiton
No Home-Like Place: Delusions of Home in Born in Exile
Authors: Dennis Richard
Published: July 2020

George Gissing was obsessed with the question of ‘home’, in his own restless mobility as well as that of his characters, whose domestic circumstances he invariably enumerated in detail. Gissing's Born in Exile moves between real and fictional locations in London, Exeter, and the industrial north of England, but also between a variety of lodgings, chambers, and houses which accommodate, constrain, and only occasionally liberate their occupants. Their contradictory and volatile attitudes to these ‘homes’ parallel Gissing's unstable reactions to his own lodgings and highlight the relative nature of locations between town and country as well as differences in perception of the same physical surroundings. Descriptions of and debates about ‘home’ in Born in Exile provide a prelude to Gissing's later, more dogmatic pronouncements in The Private Papers of Henry Ryecroft, also penned – in fiction – from the perspective of the country around Exeter.
Spatial Variability of Grouting Layer of Shield Tunnel and Its Effect on Ground Settlement
Authors: Wang Zhongzheng , Jin Dalong , Shi Chenghua
Published: July 2020

This study aims to investigate the effect of the spatial variability of grouting-layer thickness on ground-surface settlement caused by shield tunneling and to provide a rational prediction method. The spatial characteristics of grouting layers were obtained based on statistical analysis. The random finite element method was used to study the effect of spatial variability of different parameters on ground-surface settlement. Simulation results indicate that the spatial variability of the grouting layer has a negative impact on ground settlement. The surface settlement will be underestimated without considering the spatial characteristics of the grouting layer. Thus, a reliable prediction approach of the maximum ground settlement was proposed to control the construction quality.
Analysis of Protein Disorder Predictions in the Light of a Protein Structural Alphabet
Authors: de Brevern Alexandre G.
Published: July 2020

Intrinsically-disordered protein (IDP) characterization was an amazing change of paradigm in our classical sequence-structure-function theory. Moreover, IDPs are over-represented in major disease pathways and are now often targeted using small molecules for therapeutic purposes. This has had created a complex continuum from order-that encompasses rigid and flexible regions-to disorder regions; the latter being not accessible through classical crystallographic methodologies. In X-ray structures, the notion of order is dictated by access to resolved atom positions, providing rigidity and flexibility information with low and high experimental B-factors, while disorder is associated with the missing (non-resolved) residues. Nonetheless, some rigid regions can be found in disorder regions. Using ensembles of IDPs, their local conformations were analyzed in the light of a structural alphabet. An entropy index derived from this structural alphabet allowed us to propose a continuum of states from rigidity to flexibility and finally disorder. In this study, the analysis was extended to comparing these results to disorder predictions, underlying a limited correlation, and so opening new ideas to characterize and predict disorder.
Skin-Integrated Wearable Systems and Implantable Biosensors: A Comprehensive Review
Authors: Rodrigues Daniela , Barbosa Ana I. , Rebelo Rita , Kwon Il Keun , Reis Rui L. , Correlo Vitor M.
Published: July 2020

Biosensors devices have attracted the attention of many researchers across the world. They have the capability to solve a large number of analytical problems and challenges. They are future ubiquitous devices for disease diagnosis, monitoring, treatment and health management. This review presents an overview of the biosensors field, highlighting the current research and development of bio-integrated and implanted biosensors. These devices are micro- and nano-fabricated, according to numerous techniques that are adapted in order to offer a suitable mechanical match of the biosensor to the surrounding tissue, and therefore decrease the body’s biological response. For this, most of the skin-integrated and implanted biosensors use a polymer layer as a versatile and flexible structural support, combined with a functional/active material, to generate, transmit and process the obtained signal. A few challenging issues of implantable biosensor devices, as well as strategies to overcome them, are also discussed in this review, including biological response, power supply, and data communication.
PVR and ICAM-1 on Blast Crisis CML Stem and Progenitor Cells with TKI Resistance Confer Susceptibility to NK Cells
Authors: Kim Nayoung , Kim Mi-Yeon , Cho Young-Uk , Chen WenYong , Lee Kyoo-Hyung , Kim Hun Sik
Published: July 2020

The BCR-ABL1 fusion gene generating an oncogenic tyrosine kinase is a hallmark of chronic myeloid leukemia (CML), which can be successfully targeted by BCR-ABL1 tyrosine kinase inhibitors (TKIs). However, treatment-free remission has been achieved in a minority of patients due to evolving TKI resistance and intolerance. Primary or acquired resistance to the approved TKIs and progression to blast crisis (BC), thus, remain a major clinical challenge that requires alternative therapeutic strategies. Here, we first demonstrate that donor natural killer (NK) cells prepared using a protocol adopted in clinical trials can efficiently eliminate CML-BC blasts, with TKI resistance regardless of BCR-ABL1 mutations, and preferentially target CD34+CD38− leukemic stem cells (LSC), a potential source of disease relapse. Mechanistically, the predominant expression of PVR, a ligand for the NK cell-activating DNAM-1 receptor, in concert with ICAM-1, a ligand for NK cell adhesion, confer this susceptibility to NK cells, despite the lack of ligands for NKG2D, a principal NK cell activating receptor, as an immune evasion mechanism. With these mechanistic insights, our findings provide a proof-of-concept that donor NK cell-based therapy is a viable strategy for overcoming TKI resistance in CML, particularly the advanced, multi-TKI-resistant CML with dismal outcome.
Genetic and Molecular Basis of Heterogeneous NK Cell Responses against Acute Leukemia
Authors: Makanga Dhon Roméo , Da Rin de Lorenzo Francesca , David Gaëlle , Willem Catherine , Dubreuil Léa , Legrand Nolwenn , Guillaume Thierry , Peterlin Pierre , Lebourgeois Amandine , Béné Marie Christine , Garnier Alice , Chevallier Patrice , Gendzekhadze Ketevan , Cesbron Anne , Gagne Katia , Clemenceau Béatrice , Retière Christelle
Published: July 2020

Natural killer (NK) cells are key cytotoxic effectors against malignant cells. Polygenic and polymorphic Killer cell Immunoglobulin-like Receptor (KIR) and HLA genes participate in the structural and functional formation of the NK cell repertoire. In this study, we extensively investigated the anti-leukemic potential of NK cell subsets, taking into account these genetic parameters and cytomegalovirus (CMV) status. Hierarchical clustering analysis of NK cell subsets based on NKG2A, KIR, CD57 and NKG2C markers from 68 blood donors identified donor clusters characterized by a specific phenotypic NK cell repertoire linked to a particular immunogenetic KIR and HLA profile and CMV status. On the functional side, acute lymphoblastic leukemia (ALL) was better recognized by NK cells than acute myeloid leukemia (AML). However, a broad inter-individual disparity of NK cell responses exists against the same leukemic target, highlighting bad and good NK responders. The most effective NK cell subsets against different ALLs expressed NKG2A and represented the most frequent subset in the NK cell repertoire. In contrast, minority CD57+ or/and KIR+ NK cell subsets were more efficient against AML. Overall, our data may help to optimize the selection of hematopoietic stem cell donors on the basis of immunogenetic KIR/HLA for ALL patients and identify the best NK cell candidates in immunotherapy for AML.
Circulating Tumor Cell Detection Technologies and Clinical Utility: Challenges and Opportunities
Authors: Habli Zeina , AlChamaa Walid , Saab Raya , Kadara Humam , Khraiche Massoud L.
Published: July 2020

The potential clinical utility of circulating tumor cells (CTCs) in the diagnosis and management of cancer has drawn a lot of attention in the past 10 years. CTCs disseminate from tumors into the bloodstream and are believed to carry vital information about tumor onset, progression, and metastasis. In addition, CTCs reflect different biological aspects of the primary tumor they originate from, mainly in their genetic and protein expression. Moreover, emerging evidence indicates that CTC liquid biopsies can be extended beyond prognostication to pharmacodynamic and predictive biomarkers in cancer patient management. A key challenge in harnessing the clinical potential and utility of CTCs is enumerating and isolating these rare heterogeneous cells from a blood sample while allowing downstream CTC analysis. That being said, there have been serious doubts regarding the potential value of CTCs as clinical biomarkers for cancer due to the low number of promising outcomes in the published results. This review aims to present an overview of the current preclinical CTC detection technologies and the advantages and limitations of each sensing platform, while surveying and analyzing the published evidence of the clinical utility of CTCs.
We Don’t Talk about It: Cancer Pain and American Indian Survivors
Authors: Hodge Felicia Schanche , Itty Tracy Line , Samuel-Nakamura Christine , Cadogan Mary
Published: July 2020

Pain is a common symptom among cancer survivors, yet is rarely talked about by American Indians. Understanding the reasons for reduced communication by American Indian cancer survivors is important for healthcare providers, family members, and others providing treatment and support for cancer symptoms. Thirteen focus groups with Southwest American Indian adult cancer survivors were audiotaped and transcribed as part of a randomized intervention to remove barriers to cancer symptom management. Constant comparative methods were employed in the data analysis, topic categories were grouped for comparison, and final assessment followed Grounded Theory methods. Findings were categorized into two major groupings: communication with family members and communication with health care providers. Within these two groupings, three themes emerged to describe cancer pain experiences and communication barriers: (1) We don’t talk about it, (2) Respect for healthcare providers; and (3) Culturally prohibitive topics on death and pain experiences. Not talking about their cancer diagnosis and cancer-related pain leaves many American Indian cancer survivors without much-needed social support, contributing to reduced treatment compliance and access to healthcare. Findings have implications for educational interventions and quality of life improvement for American Indian and other underrepresented communities.
DEK Expression in Breast Cancer Cells Leads to the Alternative Activation of Tumor Associated Macrophages
Authors: Pease Nicholas A. , Shephard Miranda S. , Sertorio Mathieu , Waltz Susan E. , Vinnedge Lisa M. Privette
Published: July 2020

Breast cancer (BC) is the second leading cause of cancer deaths among women. DEK is a known oncoprotein that is highly expressed in over 60% of breast cancers and is an independent marker of poor prognosis. However, the molecular mechanisms by which DEK promotes tumor progression are poorly understood. To identify novel oncogenic functions of DEK, we performed RNA-Seq analysis on isogenic Dek-knockout and complemented murine BC cells. Gene ontology analyses identified gene sets associated with immune system regulation and cytokine-mediated signaling and differential cytokine and chemokine expression was confirmed across Dek-proficient versus Dek-deficient cells. By exposing murine bone marrow-derived macrophages (BMDM) to tumor cell conditioned media (TCM) to mimic a tumor microenvironment, we showed that Dek-expressing breast cancer cells produce a cytokine milieu, including up-regulated Tslp and Ccl5 and down-regulated Cxcl1, Il-6, and GM-CSF, that drives the M2 polarization of macrophages. We validated this finding in primary murine mammary tumors and show that Dek expression in vivo is also associated with increased expression of M2 macrophage markers in murine tumors. Using TCGA data, we verified that DEK expression in primary human breast cancers correlates with the expression of several genes identified by RNA-Seq in our murine model and with M2 macrophage phenotypes. Together, our data demonstrate that by regulating the production of multiple secreted factors, DEK expression in BC cells creates a potentially immune suppressed tumor microenvironment, particularly by inducing M2 tumor associated macrophage (TAM) polarization.
Characterisation of Ovarian Cancer Cell Line NIH-OVCAR3 and Implications of Genomic, Transcriptomic, Proteomic and Functional DNA Damage Response Biomarkers for Therapeutic Targeting
Authors: Bradbury Alice , O’Donnell Rachel , Drew Yvette , Curtin Nicola J. , Sharma Saha Sweta
Published: July 2020

In order to be effective models to identify biomarkers of chemotherapy response, cancer cell lines require thorough characterization. In this study, we characterised the widely used high grade serous ovarian cancer (HGSOC) cell line NIH-OVCAR3 using bioinformatics, cytotoxicity assays and molecular/functional analyses of DNA damage response (DDR) pathways in comparison to an ovarian cancer cell line panel. Bioinformatic analysis confirmed the HGSOC-like features of NIH-OVCAR3, including low mutation frequency, TP53 loss and high copy number alteration frequency similar to 201 HGSOCs analysed (TCGA). Cytotoxicity assays were performed for the standard of care chemotherapy, carboplatin, and DDR targeting drugs: rucaparib (a PARP inhibitor) and VE-821 (an ATR inhibitor). Interestingly, NIH-OVCAR3 cells showed sensitivity to carboplatin and rucaparib which was explained by functional loss of homologous recombination repair (HRR) identified by plasmid re-joining assay, despite the ability to form RAD51 foci and absence of mutations in HRR genes. NIH-OVCAR3 cells also showed high non-homologous end joining activity, which may contribute to HRR loss and along with genomic amplification in ATR and TOPBP1, could explain the resistance to VE-821. In summary, NIH-OVCAR3 cells highlight the complexity of HGSOCs and that genomic or functional characterization alone might not be enough to predict/explain chemotherapy response.
Machine Learning Approach to Forecast Chemotherapy-Induced Haematological Toxicities in Patients with Rhabdomyosarcoma
Authors: Cuplov Vesna , André Nicolas
Published: July 2020

Developing precision medicine is a major trend in clinical oncology. The main adverse effects of ifosfamide, actinomycin D and vincristine (IVA) treatment for rhabdomyosarcoma are haematological toxicities such as neutropenia or thrombocytopenia. The severity of these effects vary among patients but their dynamic profiles are similar. A non-empirical adjustment of the chemotherapy dose to avoid severe toxicities could help secure the treatment administration. Twenty-four patients with rhabdomyosarcoma treated with IVA chemotherapy courses were selected. Before and during each cycle, routine multiple blood cell counts were performed allowing for a dynamic study of the haematological toxicities. We developed a machine learning analysis using a gradient boosting regression technique to forecast the ifosfamide induced haematological toxicities as a function of neutrophils and platelets initial levels and the initial ifosfamide dose. To validate models’ accuracy, predicted and observed neutrophils and platelets levels were compared. The model was able to reproduce the dynamic profiles of the haematological toxicities. Among all cycles, the mean absolute errors between predicted and observed neutrophils and platelets levels were 1.0 and 72.8 G/L, respectively. Adjusting a patient’s ifosfamide dose based upon the predicted haematological toxicity levels at the end of a treatment cycle could enable tailored treatment.
The Value of PD-L1 Expression as Predictive Biomarker in Metastatic Renal Cell Carcinoma Patients: A Meta-Analysis of Randomized Clinical Trials
Authors: Carretero-González Alberto , Lora David , Martín Sobrino Isabel , Sáez Sanz Irene , Bourlon María T. , Anido Herranz Urbano , Martínez Chanzá Nieves , Castellano Daniel , de Velasco Guillermo
Published: July 2020

Immune checkpoint inhibitors (ICIs) are soluble antibodies that have dramatically changed the outcomes including overall survival in a subset of kidney tumors, specifically in renal cell carcinoma (RCC). To date, there is no a single predictive biomarker approved to be used to select the patients that achieve benefit from ICIs targeting. It seems reasonable to analyze whether the programmed death-ligand 1 (PD-L1) expression could be useful. To assess the role of PD-L1 expression as a potential predictive biomarker for benefit of ICIs in RCC patients, we performed a search of randomized clinical trials (RCTs) comparing ICIs (monotherapy or in combination with other therapies) to standard of care in metastatic RCC patients according to PRISMA guidelines. Trials must have included subgroup analyses evaluating the selected outcomes (progression-free survival (PFS) and overall survival (OS)) in different subsets of patients according to PD-L1 expression on tumor samples. Hazard ratios with confidence intervals were used as the measure of efficacy between groups. A total of 4635 patients (six studies) were included (ICIs arm: 2367 patients; standard of care arm: 2268 patients). Globally, PFS and OS results favored ICIs. Differential expression of PD-L1 on tumor samples could select a subset of patients who could benefit more in terms of PFS (those with higher levels; p-value for difference between subgroups: <0.0001) but it did not seem to impact in OS results (p-value for difference: 0.63). As different methods to assess PD-L1 positivity were used among trials, this heterogeneity could have an influence on the results. PD-L1 could represent a biomarker to test PFS in clinical trials but its value for OS is less clear. In this meta-analysis, the usefulness of PD-L1 expression as a predictive biomarker to select treatment in metastatic RCC patients was not clearly shown.
Characterization of mTOR Activity and Metabolic Profile in Pediatric Rhabdomyosarcoma
Authors: Felkai Luca , Krencz Ildikó , Kiss Dorottya Judit , Nagy Noémi , Petővári Gábor , Dankó Titanilla , Micsík Tamás , Khoor András , Tornóczky Tamás , Sápi Zoltán , Sebestyén Anna , Csóka Monika
Published: July 2020

mTOR activation has been observed in rhabdomyosarcoma (RMS); however, mTOR complex (mTORC) 1 inhibition has had limited success thus far. mTOR activation alters the metabolic pathways, which is linked to survival and metastasis. These pathways have not been thoroughly analyzed in RMSs. We performed immunohistochemistry on 65 samples to analyze the expression of mTOR complexes (pmTOR, pS6, Rictor), and several metabolic enzymes (phosphofructokinase, lactate dehydrogenase-A, β-F1-ATPase, glucose-6-phosphate dehydrogenase, glutaminase). RICTOR amplification, as a potential mechanism of Rictor overexpression, was analyzed by FISH and digital droplet PCR. In total, 64% of the studied primary samples showed mTOR activity with an mTORC2 dominance (82%). Chemotherapy did not cause any relevant change in mTOR activity. Elevated mTOR activity was associated with a worse prognosis in relapsed cases. RICTOR amplification was not confirmed in any of the cases. Our findings suggest the importance of the Warburg effect and the pentose-phosphate pathway beside a glutamine demand in RMS cells. The expression pattern of the studied mTOR markers can explain the inefficacy of mTORC1 inhibitor therapy. Therefore, we suggest performing a detailed investigation of the mTOR profile before administering mTORC1 inhibitor therapy. Furthermore, our findings highlight that targeting the metabolic plasticity could be an alternative therapeutic approach.
Photobiomodulation Therapy in Oral Mucositis and Potentially Malignant Oral Lesions: A Therapy Towards the Future
Authors: Hanna Reem , Dalvi Snehal , Benedicenti Stefano , Amaroli Andrea , Sălăgean Tudor , Pop Ioana Delia , Todea Doina , Bordea Ioana Roxana
Published: July 2020

Photobiomodulation therapy (PBMT) is an effective treatment modality, which has the significant advantage of enhancing a patient’s quality of life (QoL) by minimising the side effects of oral cancer treatments, as well as assisting in the management of potentially cancerous lesions. It is important to note that the major evidence-based documentation neither considers, nor tackles, the issues related to the impact of PBMT on tumour progression and on the downregulation of cellular proliferation improvement, by identifying the dose- and time-dependency. Moreover, little is known about the risk of this therapy and its safety when it is applied to the tumour, or the impact on the factor of QoL. The review aimed to address the benefits and limitations of PBMT in premalignant oral lesions, as well as the conflicting evidence concerning the relationship between tumour cell proliferation and the applied dose of photonic energy (fluence) in treating oral mucositis induced by head and neck cancer (H&N) treatments. The objective was to appraise the current concept of PBMT safety in the long-term, along with its latent impact on tumour reaction. This review highlighted the gap in the literature and broaden the knowledge of the current clinical evidence-based practice, and effectiveness, of PBMT in H&N oncology patients. As a result, the authors concluded that PBMT is a promising treatment modality. However, due to the heterogeneity of our data, it needs to undergo further testing in well-designed, long-term and randomised controlled trial studies, to evaluate it with diligent and impartial outcomes, and ensure laser irradiation’s safety at the tumour site.
The Impact on Survival and Morbidity of Portal–Mesenteric Resection During Pancreaticoduodenectomy for Pancreatic Head Adenocarcinoma: A Systematic Review and Meta-Analysis of Comparative Studies
Authors: Fancellu Alessandro , Petrucciani Niccolò , Porcu Alberto , Deiana Giulia , Sanna Valeria , Ninniri Chiara , Perra Teresa , Celoria Valentina , Nigri Giuseppe
Published: July 2020

Background: The literature is conflicting regarding oncological outcome and morbidity associated to portal–mesenteric resection during pancreaticoduodenectomy (PD) in patients with pancreatic head adenocarcinoma (PHAC). Methods: A meta-analysis of studies comparing PD plus venous resection (PD+VR) and standard PD exclusively in patients with adenocarcinoma of the pancreatic head was conducted. Results: Twenty-three cohort studies were identified, which included 6037 patients, of which 28.6% underwent PD+VR and 71.4% underwent standard PD. Patients who received PD+VR had lower 1-year overall survival (OS) (odds radio OR 0.79, 95% CI 0.67–0.92, p = 0.003), 3-year OS (OR 0.72, 95% CI 0.59–0.87, p = 0.0006), and 5-year OS (OR 0.57, 95% CI 0.39–0.83, p = 0.003). Patients in the PD+VR group were more likely to have a larger tumor size (MD 3.87, 95% CI 1.75 to 5.99, p = 0.0003), positive lymph nodes (OR 1.24, 95% CI 1.06–1.45, p = 0.007), and R1 resection (OR 1.74, 95% CI 1.37–2.20, p < 0.0001). Thirty-day mortality was higher in the PD+VR group (OR 1.93, 95% CI 1.28–2.91, p = 0.002), while no differences between groups were observed in rates of total complications (OR 1.07, 95% CI, 0.81–1.41, p = 0.65). Conclusions: Although PD+VR has significantly increased the resection rate in patients with PHAC, it has inferior survival outcomes and higher 30-day mortality when compared with standard PD, whereas postoperative morbidity rates are similar. Further research is needed to evaluate the role of PD+VR in the context of multimodality treatment of PHAC.
Depletion of Macrophages Improves Therapeutic Response to Gemcitabine in Murine Pancreas Cancer
Authors: Buchholz Soeren M. , Goetze Robert G. , Singh Shiv K. , Ammer-Herrmenau Christoph , Richards Frances M. , Jodrell Duncan I. , Buchholz Malte , Michl Patrick , Ellenrieder Volker , Hessmann Elisabeth , Neesse Albrecht
Published: July 2020

Background: The tumor microenvironment (TME) is composed of fibro-inflammatory cells and extracellular matrix (ECM) components. However, the exact contribution of the various TME compartments towards therapeutic response is unknown. Here, we aim to dissect the specific contribution of tumor-associated macrophages (TAMs) towards drug delivery and response in pancreatic ductal adenocarcinoma (PDAC). Methods: The effect of gemcitabine was assessed in human and murine macrophages, human pancreatic stellate cells (hPSCs), and tumor cells (L3.6pl, BxPC3 and KPC) in vitro. The drug metabolism of gemcitabine was analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Preclinical studies were conducted using KrasG12D;p48-Cre and KrasG12D;p53172H;Pdx-Cre mice to investigate gemcitabine delivery at different stages of tumor progression and upon pharmacological TAM depletion. Results: Gemcitabine accumulation was significantly increased in murine PDAC tissue compared to pancreatic intraepithelial neoplasia (PanIN) lesions and healthy control pancreas tissue. In vitro, macrophages accumulated and rapidly metabolized gemcitabine resulting in a significant drug scavenging effect for gemcitabine. Finally, pharmacological TAM depletion enhanced therapeutic response to gemcitabine in tumor-bearing KPC mice. Conclusion: Macrophages rapidly metabolize gemcitabine in vitro, and pharmacological depletion improves the therapeutic response to gemcitabine in vivo. Our study supports the notion that TAMs might be a promising therapeutic target in PDAC.
Combining Xylose Reductase from Spathaspora arborariae with Xylitol Dehydrogenase from Spathaspora passalidarum to Promote Xylose Consumption and Fermentation into Xylitol by Saccharomyces cerevisiae
Authors: Mouro Adriane , dos Santos Angela A. , Agnolo Denis D. , Gubert Gabriela F. , Bon Elba P. S. , Rosa Carlos A. , Fonseca César , Stambuk Boris U.
Published: July 2020

In recent years, many novel xylose-fermenting yeasts belonging to the new genus Spathaspora have been isolated from the gut of wood-feeding insects and/or wood-decaying substrates. We have cloned and expressed, in Saccharomyces cerevisiae, a Spathaspora arborariae xylose reductase gene (SaXYL1) that accepts both NADH and NADPH as co-substrates, as well as a Spathaspora passalidarum NADPH-dependent xylose reductase (SpXYL1.1 gene) and the SpXYL2.2 gene encoding for a NAD+-dependent xylitol dehydrogenase. These enzymes were co-expressed in a S. cerevisiae strain over-expressing the native XKS1 gene encoding xylulokinase, as well as being deleted in the alkaline phosphatase encoded by the PHO13 gene. The S. cerevisiae strains expressing the Spathaspora enzymes consumed xylose, and xylitol was the major fermentation product. Higher specific growth rates, xylose consumption and xylitol volumetric productivities were obtained by the co-expression of the SaXYL1 and SpXYL2.2 genes, when compared with the co-expression of the NADPH-dependent SpXYL1.1 xylose reductase. During glucose-xylose co-fermentation by the strain with co-expression of the SaXYL1 and SpXYL2.2 genes, both ethanol and xylitol were produced efficiently. Our results open up the possibility of using the advantageous Saccharomyces yeasts for xylitol production, a commodity with wide commercial applications in pharmaceuticals, nutraceuticals, food and beverage industries.
Glia and Neural Stem and Progenitor Cells of the Healthy and Ischemic Brain: The Workplace for the Wnt Signaling Pathway
Authors: Knotek Tomas , Janeckova Lucie , Kriska Jan , Korinek Vladimir , Anderova Miroslava
Published: July 2020

Wnt signaling plays an important role in the self-renewal, fate-commitment and survival of the neural stem/progenitor cells (NS/PCs) of the adult central nervous system (CNS). Ischemic stroke impairs the proper functioning of the CNS and, therefore, active Wnt signaling may prevent, ameliorate, or even reverse the negative effects of ischemic brain injury. In this review, we provide the current knowledge of Wnt signaling in the adult CNS, its status in diverse cell types, and the Wnt pathway’s impact on the properties of NS/PCs and glial cells in the context of ischemic injury. Finally, we summarize promising strategies that might be considered for stroke therapy, and we outline possible future directions of the field.
DNA Methylation Dysfunction in Chronic Kidney Disease
Authors: Ingrosso Diego , Perna Alessandra F.
Published: July 2020

Renal disease is the common denominator of a number of underlying disease conditions, whose prevalence has been dramatically increasing over the last two decades. Two aspects are particularly relevant to the subject of this review: (I) most cases are gathered under the umbrella of chronic kidney disease since they require—predictably for several lustrums—continuous clinical monitoring and treatment to slow down disease progression and prevent complications; (II) cardiovascular disease is a terrible burden in this population of patients, in that it claims many lives yearly, while only a scant minority reach the renal disease end stage. Why indeed a review on DNA methylation and renal disease? As we hope to convince you, the present evidence supports the role of the existence of various derangements of the epigenetic control of gene expression in renal disease, which hold the potential to improve our ability, in the future, to more effectively act toward disease progression, predict outcomes and offer novel therapeutic approaches.
Sensing, Signaling, and Secretion: A Review and Analysis of Systems for Regulating Host Interaction in Wolbachia
Authors: Lindsey Amelia R. I.
Published: July 2020

Wolbachia (Anaplasmataceae) is an endosymbiont of arthropods and nematodes that resides within host cells and is well known for manipulating host biology to facilitate transmission via the female germline. The effects Wolbachia has on host physiology, combined with reproductive manipulations, make this bacterium a promising candidate for use in biological- and vector-control. While it is becoming increasingly clear that Wolbachia’s effects on host biology are numerous and vary according to the host and the environment, we know very little about the molecular mechanisms behind Wolbachia’s interactions with its host. Here, I analyze 29 Wolbachia genomes for the presence of systems that are likely central to the ability of Wolbachia to respond to and interface with its host, including proteins for sensing, signaling, gene regulation, and secretion. Second, I review conditions under which Wolbachia alters gene expression in response to changes in its environment and discuss other instances where we might hypothesize Wolbachia to regulate gene expression. Findings will direct mechanistic investigations into gene regulation and host-interaction that will deepen our understanding of intracellular infections and enhance applied management efforts that leverage Wolbachia.
TLR4 Receptor D299G/T399I Haplotype Polymorphism Is Associated with Insulin Resistance in Obese Female Subjects
Authors: Sharif Elham , Al-Wakeel Mariam , Mohamed Afnan , kerkadi Abdelhamid , Rizk Nasser
Published: July 2020

Background: Activation of Toll-like-receptor 4 (TLR4) causes chronic inflammation that can result in obesity and metabolic syndrome (MeS). Aim: This study aimed to investigate the role of TLR4 polymorphisms of TLR4D299G/T399I, and its impact on protein expression of TLR4 in obese female subjects. Methodology: A prospective cross-sectional association study was performed on Arab female subjects from Qatar University. The subjects were categorized according to BMI classifications into two groups: “obese; n = 69” and “non-obese; n = 136”. Anthropometric measurements, weight (kg), height (m) and waist circumference (WC) were evaluated, and the body mass index (BMI) was calculated. Fasting blood samples were collected, and assessment of glucose, lipid profile, C-reactive protein (CRP), leptin, IL-6 and insulin was performed. Insulin resistance was computed using HOMA-IR. Genotyping of the TLR4 polymorphisms of TLR4D299G (rs4986790) and TLR4T399I (rs4986791) was performed by the 5′ nuclease assay by TaqMan MGB probe. Flow cytometry was used to evaluate the monocyte cell surface expression of TLR4. Results: The frequency distribution of the genotype revealed that homozygous AA is the most frequent among obese subjects (86.4%) for (TLR4D299G, A > G) and the homozygous CC genotype is the most frequent (92.4%) for (TLR4T399I, C > T). Haplotype analysis of TLR4 D299G/T399I showed that GT carriers had a significant association with increased probability of insulin resistance (odds ratio = 4.73; 95% CI 1.19–18.90; p-value = 0.016). The monocyte cell surface of TLR4 was significantly higher by 1.3 folds in obese compared to non-obese subjects. Conclusions: TLR4 D299G/T399I haplotype polymorphism is associated with an increased risk of insulin resistance with the upregulation of TLR4 protein expression in obese subjects.
Evidence of Interspecific Chromosomal Diversification in Rainbowfishes (Melanotaeniidae, Teleostei)
Authors: Majtánová Zuzana , Unmack Peter J. , Prasongmaneerut Tulyawat , Shams Foyez , Srikulnath Kornsorn , Ráb Petr , Ezaz Tariq
Published: July 2020

Rainbowfishes (Melanotaeniidae) are the largest monophyletic group of freshwater fishes occurring in Australia and New Guinea, with 112 species currently recognised. Despite their high taxonomic diversity, rainbowfishes remain poorly studied from a cytogenetic perspective. Using conventional (Giemsa staining, C banding, chromomycin A3 staining) and molecular (fluorescence in situ hybridisation with ribosomal DNA (rDNA) and telomeric probes) cytogenetic protocols, karyotypes and associated chromosomal characteristics of five species were examined. We covered all major lineages of this group, namely, Running River rainbowfish Melanotaenia sp., red rainbowfish Glossolepis incisus, threadfin rainbowfish Iriatherina werneri, ornate rainbowfish Rhadinocentrus ornatus, and Cairns rainbowfish Cairnsichthys rhombosomoides. All species had conserved diploid chromosome numbers 2n = 48, but karyotypes differed among species; while Melanotaenia sp., G. incisus, and I. werneri possessed karyotypes composed of exclusively subtelo/acrocentric chromosomes, the karyotype of R. ornatus displayed six pairs of submetacentric and 18 pairs of subtelo/acrocentric chromosomes, while C. rhombosomoides possessed a karyotype composed of four pairs of submetacentric and 20 pairs of subtelo/acrocentric chromosomes. No heteromorphic sex chromosomes were detected using conventional cytogenetic techniques. Our data indicate a conserved 2n in Melanotaeniidae, but morphologically variable karyotypes, rDNA sites, and heterochromatin distributions. Differences were observed especially in taxonomically divergent species, suggesting interspecies chromosome rearrangements.
Identifying Candidate Genes for Hypoxia Adaptation of Tibet Chicken Embryos by Selection Signature Analyses and RNA Sequencing
Authors: Liu Xiayi , Wang Xiaochen , Liu Jing , Wang Xiangyu , Bao Haigang
Published: July 2020

The Tibet chicken (Gallus gallus) lives on the Qinghai–Tibet Plateau and adapts to the hypoxic environment very well. The objectives of this study was to obtain candidate genes associated with hypoxia adaptation in the Tibet chicken embryos. In the present study, we used the fixation index (Fst) and cross population extended haplotype homozygosity (XPEHH) statistical methods to detect signatures of positive selection of the Tibet chicken, and analyzed the RNA sequencing data from the embryonic liver and heart with HISAT, StringTie and Ballgown for differentially expressed genes between the Tibet chicken and White leghorn (Gallus gallus, a kind of lowland chicken) embryos hatched under hypoxia condition. Genes which were screened out by both selection signature analysis and RNA sequencing analysis could be regarded as candidate genes for hypoxia adaptation of chicken embryos. We screened out 1772 genes by XPEHH and 601 genes by Fst, and obtained 384 and 353 differentially expressed genes in embryonic liver and heart, respectively. Among these genes, 89 genes were considered as candidate genes for hypoxia adaptation in chicken embryos. ARNT, AHR, GSTK1 and FGFR1 could be considered the most important candidate genes. Our findings provide references to elucidate the molecular mechanism of hypoxia adaptation in Tibet chicken embryos.
Stem Cell Conditioned Medium Treatment for Canine Spinal Cord Injury: Pilot Feasibility Study
Authors: Vikartovska Zuzana , Kuricova Maria , Farbakova Jana , Liptak Tomas , Mudronova Dagmar , Humenik Filip , Madari Aladar , Maloveska Marcela , Sykova Eva , Cizkova Dasa
Published: July 2020

Spinal cord injury (SCI) involves nerve damage and often leads to motor, sensory and autonomic dysfunctions. In the present study, we have designed a clinical protocol to assess the feasibility of systemic delivery of allogenic canine bone marrow tissue-derived mesenchymal stem cell conditioned medium (BMMSC CM) to dogs with SCI. Four client-owned dogs with chronic SCI lasting more than six months underwent neurological and clinical evaluation, MRI imaging and blood tests before being enrolled in this study. All dogs received four intravenous infusions with canine allogenic BMMSC CM within one month. Between the infusions the dogs received comprehensive physiotherapy, which continued for three additional months. No adverse effects or complications were observed during the one, three and six months follow-up periods. Neither blood chemistry panel nor hematology profile showed any significant changes. All dogs were clinically improved as assessed using Olby locomotor scales after one, three and six months of BMMSC CM treatment. Furthermore, goniometric measurements revealed partial improvement in the range of joint motion. Bladder function improved in two disabled dogs. We conclude that multiple delivery of allogenic cell-derived conditioned medium to dogs with chronic SCI is feasible, and it might be clinically beneficial in combination with physiotherapy.
How Europe Is Preparing Its Core Solution for Exascale Machines and a Global, Sovereign, Advanced Computing Platform
Authors: Kovač Mario , Notton Philippe , Hofman Daniel , Knezović Josip
Published: July 2020

In this paper, we present an overview of the European Processor Initiative (EPI), one of the cornerstones of the EuroHPC Joint Undertaking, a new European Union strategic entity focused on pooling the Union’s and national resources on HPC to acquire, build and deploy the most powerful supercomputers in the world within Europe. EPI started its activities in December 2018. The first three years drew processor and platform designers, embedded software, middleware, applications and usage experts from 10 EU countries together to co-design Europe’s first HPC Systems on Chip and accelerators with its unique Common Platform (CP) technology. One of EPI’s core activities also takes place in the automotive sector, providing architectural solutions for a novel embedded high-performance computing (eHPC) platform and ensuring the overall economic viability of the initiative.
A Sustainable Approach for Cadmium Recovery from Oxide Using Molten Salt Slag
Authors: Blumbergs Ervins , Serga Vera , Platacis Ernests , Maiorov Michail , Brekis Arturs , Shishkin Andrei
Published: July 2020

Alkaline nickel-cadmium batteries are among the most used industrial high-power sources. Despite stricter environmental requirements, nickel-cadmium batteries still remain as the main choice for highly reliable power sources for heavy-loaded equipment. Therefore, recovery of cadmium (Cd) from spent batteries is a challenge for the modern recycling industry, particularly as it displays high bio-toxicity. The present study describes a new green approach for Cd recovery from cadmium oxide (CdO). The paper discusses using a ternary chloride composition consisting of calcium, potassium and sodium chloride, thereby avoiding the release of Cd vapour from the reaction volume during the reduction reaction from CdO. For the protective slag layer during the reduction process (which occurs at 650 °C), a 0.515:0.0796:0.405 molar ratio of CaCl2:KCl:NaCl was chosen, with the aim of achieving a melting point at 483 °C. To describe phase and elemental composition of obtained products X-ray diffraction analysis and energy dispersive X-ray spectroscopy, respectively, were applied. Electron and optical microscopy were used for morphological observations. The presence of the metallic Cd was noted. During the reduction reaction, it was noted that slag separated into two parts: a protective upper layer and bottom layer. It was also noted that metallic Cd accumulated with increasing reaction time in the bottom part of the slag.