Miracle-dz/UniFAR-FTUs huggingface dataset:
Potential Role of Hsp70 and Activated NK Cells for Prediction of Prognosis in Glioblastoma Patients

Despite rapid progress in the treatment of many cancers, glioblastoma remains a devastating disease with dismal prognosis. The aim of this study was to identify chaperone- and immune-related biomarkers to improve prediction of outcome in glioblastoma. Depending on its intra- or extracellular localization the major stress-inducible heat shock protein 70 (Hsp70) fulfills different tasks. In the cytosol Hsp70 interferes with pro-apoptotic signaling pathways and thereby protects tumor cells from programmed cell death. Extracellular Hsp70 together with pro-inflammatory cytokines are reported to stimulate the expression of activatory NK cell receptors, recognizing highly aggressive human tumor cells that present Hsp70 on their cell surface. Therefore, intra-, extracellular and membrane-bound Hsp70 levels were assessed in gliomas together with activatory NK cell receptors. All gliomas were found to be membrane Hsp70-positive and high grade gliomas more frequently show an overexpression of Hsp70 in the nucleus and cytosol. Significantly elevated extracellular Hsp70 levels are detected in glioblastomas with large necrotic areas. Overall survival (OS) is more favorable in patients with low Hsp70 serum levels indicating that a high Hsp70 expression is associated with an unfavorable prognosis. The data provide a first hint that elevated frequencies of activated NK cells at diagnosis might be associated with a better clinical outcome.
Genomic and Transcriptomic Characterization of Canine Osteosarcoma Cell Lines: A Valuable Resource in Translational Medicine

Osteosarcoma (OSA) represents the most common primary bone tumor in dogs and is characterized by a highly aggressive behavior. Cell lines represent one of the most suitable and reproducible pre-clinical models, and therefore the knowledge of their molecular landscape is mandatory to investigate oncogenic mechanisms and drug response. The present study aims at determining variants, putative driver genes, and gene expression aberrations by integrating whole-exome and RNA sequencing. For this purpose, eight canine OSA cell lines and one matched pair of primary tumor and normal tissue were analyzed. Overall, cell lines revealed a mean tumor mutational burden of 9.6 mutations/Mb (range 3.9–16.8). Several known oncogenes and tumor suppressor genes, such as ALK, MYC, and MET, were prioritized as having a likely role in canine OSA. Mutations in eight genes, previously described as human OSA drivers and including TP53, PTCH1, MED12, and PI3KCA, were retrieved in our cell lines. When variants were cross-referenced with human OSA driver mutations, the E273K mutation of TP53 was identified in the Wall cell line and tumor sample. The transcriptome profiling detected two possible p53 inactivation mechanisms in the Wall cell line on the one hand, and in D17 and D22 on the other. Moreover, MET overexpression, potentially leading to MAPK/ERK pathway activation, was observed in D17 and D22 cell lines. In conclusion, our data provide the molecular characterization of a large number of canine OSA cell lines, allowing future investigations on potential therapeutic targets and associated biomarkers. Notably, the Wall cell line represents a valuable model to empower prospective in vitro studies both in human and in dogs, since the TP53 driver mutation was maintained during cell line establishment and was widely reported as a mutation hotspot in several human cancers.
Chymase Dependent Pathway of Angiotensin II Generation and Rapeseed Derived Peptides for Antihypertensive Treatment of Spontaneously Hypertensive Rats

The contribution of chymase, one of the enzymes responsible for angiotensin II generation in non-ACE pathway, remains unclear in the development of hypertension. The aim of the study was to investigate chymase inhibition as potential antihypertensive therapy in spontaneously hypertensive rats (SHR). To block chymase we employed chymostatin, a commercial inhibitor, and new analogues of rapeseed-derived peptides, VWIS and RIY. These simple and easy to obtain peptides not only block chymase, but also possess weak activity to inhibit ACE. This is a first attempt to evaluate the impact of chronic administration of selected inhibitors on blood pressure of SHR in two phases of hypertension. Male SHR (6 or 16 weeks old) were treated daily for two weeks with chymostatin (CH; 2 mg/kg/day), the peptides VWIS (12.5 mg/kg/day) or RIY (7.5 mg/kg/day); control groups received chymostatin solvent (0.15% DMSO in saline) or peptide solvent (saline). The substances were administered intravenously to conscious animals via a chronically cannulated femoral vein. Systolic blood pressure (SBP) was measured by telemetry. Metabolic parameters were measured weekly, and tissue samples were harvested after two weeks of treatment. None of the administered chymase inhibitors affected the development of hypertension in young rats. Only RIY exhibited beneficial properties when administered in the established phase of hypertension: SBP decreased from 165 ± 10 to 157 ± 7 mmHg while the excretion of nitric oxide metabolites increased significantly. The glomerulosclerosis index was lower after RIY treatment in both age groups (significant only in young rats 0.29 ± 0.05 vs 0.48 ± 0.04 in the control group; p < 0.05). Hence, it seems that peptide RIY exhibits some positive effect on renal morphology. The results obtained suggest that the peptide RIY may be a useful tool in the treatment of hypertension, especially in cases when ACE inhibitors are not effective.
Has COVID-19 Affected Cancer Screening Programs? A Systematic Review

Background Health care services across the world have been enormously affected by the onset of the coronavirus disease 2019 (COVID-19). Services in oncology have been curtailed because medical services have been focused on preventing the spread of the virus and maximizing the number of available hospital beds. The present study was designed to investigate the impact of COVID-19 on cancer screening. Methods Databases such as Medline, Web of Science Core Collection (Indexes = SCI-EXPANDED, SSCI, A & HCI Timespan) and Scopus were searched comprehensively for articles published until January 2021. The keywords used were COVID-19 and cancer screening, Articles dealing with cancer screening in the COVID-19 pandemic were included in the review. Results The review comprised 17 publications. The impact of COVID-19 was categorized into four dimensions: a significant decline in cancer screening and pathology samples, the cancer diagnosis rate, an increase in advanced cancers, mortality rate and years of life lost (YLLs). Conclusion Cancer screening programs have been clearly interrupted since the onset of the COVID-19 disease. The anticipated outcomes include delayed diagnosis and marked increases in the numbers of avoidable cancer deaths. Urgent policy interventions are needed to handle the backlog of routine diagnostic services and minimize the harmful effects of the COVID-19 pandemic on cancer patients.
Challenges Posed by Immune Responses to AAV Vectors: Addressing Root Causes

Host immune responses that limit durable therapeutic gene expression and cause clinically significant inflammation remain a major barrier to broadly successful development of adeno-associated virus (AAV)-based human gene therapies. In this article, mechanisms of humoral and cellular immune responses to the viral vector are discussed. A perspective is provided that removal of pathogen-associated molecular patterns in AAV vector genomes to prevent the generation of innate immune danger signals following administration is a key strategy to overcome immunological barriers.
Arabinogalactan Proteins in Plant Roots – An Update on Possible Functions

Responsiveness to environmental conditions and developmental plasticity of root systems are crucial determinants of plant fitness. These processes are interconnected at a cellular level with cell wall properties and cell surface signaling, which involve arabinogalactan proteins (AGPs) as essential components. AGPs are cell-wall localized glycoproteins, often GPI-anchored, which participate in root functions at many levels. They are involved in cell expansion and differentiation, regulation of root growth, interactions with other organisms, and environmental response. Due to the complexity of cell wall functional and regulatory networks, and despite the large amount of experimental data, the exact molecular mechanisms of AGP-action are still largely unknown. This dynamically evolving field of root biology is summarized in the present review.
The Palm oil from seed of Phoenix dactylifera (Oil of both Deglet Nour and Kentichi) as a natural antioxidants and Environment-Friendly inhibitors on the Corrosion of mild Steel in HCl 1M

The flora of Republic of Algeria comprises a lot of Palm species, including Phoenix dactylifera. In this work, we used the Palm oil from seed of Phoenix dactylifera (Oil of both Deglet Nour and Kentichi). The objective of this study is divided into two parts. Firstly, determine the antioxidant activity of Palm oil from seed of Phoenix dactylifera (Oil of both Deglet Nour and Kentichi) according to the DPPH radical scavenging assay to suggest it as a new potential source of natural antioxidants, secondly, study the effect of inhibiting Palm oil from seed of Phoenix dactylifera (Oil of both Deglet Nour and Kentichi) on corrosion of mild steel in hydrochloric acid by electrochemical methods. Furthermore, The DPPH scavenging activity of Oil of both Deglet Nour and Kentichi increased in the order, Deglet Nour Oil < Kentichi Oil < ascorbic acid. The results of the polarization curves show that the corrosion current density decreases 577.9 μA/cm 2 to 58μA/cm 2 and to 59.3 μA/cm 2 after addition of the inhibitor (oil of Deglet Nour and Kentichi respectively). The charge transfer resistance increases 21.69 ohm.cm 2 to 186.5 ohm.cm 2 and to 222.8 ohm.cm 2 in the electrochemical impedance spectrum after addition of oil of Deglet Nour and Kentichi respectively. The inhibition of the compound effect is attributed to the formation of a film on the surface of the steel.
Decitabine Sensitizes the Radioresistant Lung Adenocarcinoma to Pemetrexed Through Upregulation of Folate Receptor Alpha

Chemotherapy is the backbone of subsequent treatment for patients with lung adenocarcinoma (LUAD) exhibiting radiation resistance, and pemetrexed plays a critical role in this chemotherapy. However, few studies have assessed changes in the sensitivity of LUAD cells to pemetrexed under radioresistant circumstances. Therefore, the objectives of this study were to delineate changes in the sensitivity of radioresistant LUAD cells to pemetrexed and to elucidate the related mechanisms and then develop an optimal strategy to improve the cytotoxicity of pemetrexed in radioresistant LUAD cells. Our study showed a much lower efficacy of pemetrexed in radioresistant cells than in parental cells, and the mechanism of action was the significant downregulation of folate receptor alpha (FRα) by long-term fractionated radiotherapy, which resulted in less cellular pemetrexed accumulation. Interestingly, decitabine effectively reversed the decrease in FRα expression in radioresistant cells through an indirect regulatory approach. Thereafter, we designed a combination therapy of pemetrexed and decitabine and showed that the activation of FRα by decitabine sensitizes radioresistant LUAD cells to pemetrexed both in vitro and in xenografts. Our findings raised a question regarding the administration of pemetrexed to patients with LUAD exhibiting acquired radioresistance and accordingly suggested that a combination of pemetrexed and decitabine would be a promising treatment strategy.
A Systematic Review of Momentary Assessment Designs for Mood and Anxiety Symptoms

Background: Altering components of ecological momentary assessment (EMA) measures to better suit the purposes of individual studies is a common and oftentimes necessary step. Though the inherent flexibility in EMA has its benefits, no resource exists to provide an overview of the variability in how convergent constructs and symptoms have been assessed in the past. The present study fills that gap by examining EMA measurement design for mood and anxiety symptomatology. Methods: Various search engines were used to identify 234 relevant studies. Items administered, data collection schedules (i.e., beeps per day), response scales (i.e., Likert), data collection platforms (i.e., apps), and psychometric properties (i.e., reliability) were extracted. Results: Study designs varied greatly in all aspects across the identified papers. Over 4,600 extracted items were qualitatively analyzed, resulting in the identification of 12 themes. The most EMA items focused on affect, with categories such as “happiness” and “tension” appearing most frequently. We provide all of our data extraction in the format of an open-source database. Limitations: Despite our best attempts to include as much of the relevant literature as possible, this review and the accompanying database are not exhaustive, but can easily be built upon to include other, newer studies. Conclusions: The fact that the affect theme featured both positive and negative emotional constructs highlights the dichotomous focus on valence and affect within the literature surrounding anxious and depressive symptomatology. We hope that our database will act as a helpful design decision-making resource for researchers studying this kind of symptomatology in the future. Systematic Review Registration: PROSPERO (CRD42019139409).
New Item Selection Method Accommodating Practical Constraints in Cognitive Diagnostic Computerized Adaptive Testing: Maximum Deviation and Maximum Limitation Global Discrimination Indexes

Maximum deviation global discrimination index (MDGDI) is a new item selection method for cognitive diagnostic computerized adaptive testing that allows for attribute coverage balance. We developed the maximum limitation global discrimination index (MLGDI) from MDGDI, which allows for both attribute coverage balance and item exposure control. MLGDI can realize the attribute coverage balance and exposure control of the item. Our simulation study aimed to evaluate the performance of our new method against maximum global discrimination index (GDI), modified maximum GDI (MMGDI), standardized weighted deviation GDI (SWDGDI), and constraint progressive with SWDGDI (CP_SWDGDI). The results indicated that (1a) under the condition of realizing the attribute coverage balance, MDGDI had the highest attribute classification accuracy; (1b) when the selection strategy accommodated the practical constraints of the attribute coverage balance and item exposure control, MLGDI had the highest attribute classification accuracy; (2) adding the item exposure control mechanism to the item selection method reduces the classification accuracy of the attributes of the item selection method; and (3) compared with GDI, MMGDI, SWDGDI, CP_SWDGDI, and MDGDI, MLGDI can better achieve the attribute-coverage requirement, control item exposure rate, and attribute correct classification rate.
Excitation Conditions for Surface-Enhanced Hyper Raman Scattering With Biocompatible Gold Nanosubstrates

Surface enhanced hyper Raman scattering (SEHRS) can provide many advantages to probing of biological samples due to unique surface sensitivity and vibrational information complementary to surface-enhanced Raman scattering (SERS). To explore the conditions for an optimum electromagnetic enhancement of SEHRS by dimers of biocompatible gold nanospheres and gold nanorods, finite-difference time-domain (FDTD) simulations were carried out for a broad range of excitation wavelengths from the visible through the short-wave infrared (SWIR). The results confirm an important contribution by the enhancement of the intensity of the laser field, due to the two-photon, non-linear excitation of the effect. For excitation laser wavelengths above 1,000 nm, the hyper Raman scattering (HRS) field determines the enhancement in SEHRS significantly, despite its linear contribution, due to resonances of the HRS light with plasmon modes of the gold nanodimers. The high robustness of the SEHRS enhancement across the SWIR wavelength range can compensate for variations in the optical properties of gold nanostructures in real biological environments.
Long-Acting Metformin Vs. Metformin Immediate Release in Patients With Type 2 Diabetes: A Systematic Review

Background: Metformin, a commonly used antidiabetic medication, is available in both an immediate-release (IR) formulation and a long-acting formulation (metformin extended-release; XR). Objective: We performed a systematic review to compare the effectiveness, safety, and patient compliance and satisfaction between the metformin IR and XR formulations. Method: We searched for randomized control trials (RCTs) and observational studies comparing the effectiveness, safety, or patient compliance and satisfaction of metformin XR with metformin IR using the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases. Following report screening, data collection, and risk of bias assessment, we separately pooled data from RCTs and observational studies using the Grading of Recommendation Assessment, Development, and Evaluation approach to rate the quality of evidence. Result: We included five RCTs, comprising a total of 1,662 patients, and one observational study, comprising 10,909 patients. In the meta-analyses, no differences were identified in outcomes of effectiveness and safety between the two forms of metformin (including change in HbA1c: mean difference (MD), 0.04%, 95% confidence interval [CI], −0.05–0.13%, fasting blood glucose: MD, −0.03 mmol/L, 95% CI, −0.22–0.15 mmol/L, postprandial blood glucose: MD, 0.50 mmol/L, 95% CI, −0.71–1.72 mmol/L, adverse events of abdominal pain: relative risk (RR), 1.15, 95% CI, 0.57–2.33, all-cause death (RR, 3.02, 95% CI 0.12–73.85), any adverse events (RR, 1.14, 95% CI 0.97–1.34), any adverse events leading to treatment discontinuation: RR, 1.51, 95% CI, 0.82–2.8, any gastrointestinal adverse events: RR, 1.09, 95% CI, 0.93–1.29, diarrhea: RR, 0.82, 95% CI, 0.53–1.27, flatulence: RR, 0.43, 95% CI, 0.15–1.23, nausea: RR, 0.97, 95% CI, 0.64–1.47, severe adverse events: RR, 0.64, 95% CI, 0.28–1.42, and vomiting: RR, 1.46, 95% CI, 0.6–3.56). Data from both the RCTs and the observational study indicate mildly superior patient compliance with metformin XR use compared with metformin IR use; this result was attributable to the preference for once-daily administration with metformin XR. Conclusion: Our systematic review indicates that metformin XR and IR formulations have similar effectiveness and safety, but that metformin XR is associated with improved compliance to treatment.
Antibacterial potency and synergistic effect of certain plant extracts against food-borne diarrheagenic bacteria

In the present study, aqueous and ethanolic extracts of leaves of six commonly available medicinal plants, Balanites aegyptiaca (L.) Del. (Balanitaceae), Hyptis sauveolens Poit. (Lamiaceae), Lawsonia inermis L. (Lathyraceae), Leucas aspera L. (Lamiaceae), Lobelia nicotianaefolia Roth. ex. Roem. & Schult. (Lobeliaceae) and Phyllanthus madraspatana L. (Euphorbiaceae), individually and in combinations were tested in crude form for their antibacterial activity against five different diarrheagenic bacteria, Bacillus cereus, Staphylococcus aureus, Escherichia coli O157:H7 (enterohemorrhagic E. coli, EHEC), Salmonella enteritidis and Listeria monocytogenes. Cifroflaxacine (20 μg) was used as antimicrobial standard. The highest antimicrobial activity was recorded in both crude aqueous leaf extract (CALE) and crude ethanolic leaf extract (CELE) of L. nicotianaefolia when all the extracts were tested individually. The zone of inhibition (IZ) of 2.2 cm against S. aureus and S. enteritidis, 2.3 cm against B. cereus and L. monocytogenes were observed in CELE of L. nicotianaefolia. CALE and CELE of H. sauveolens and P. madraspatana when tested individually showed least IZ against test organisms (IZ, 0-1.2 cm). Synergistic activity of CALE and CELE of selected plant leaves, in combination of two, three, four, five and six against test organisms ranged from 0-2.8 cm zone of inhibition. The highest IZ of 2.8 cm was observed against S. aureus in CELE combination of B. aegyptiaca + L. nicotianaefolia. The IZ range of 2.6-2.8 was recorded for standard antibiotic, ciprofloxacin against test organisms. The combined or synergistic activity of CALE and of CELE also showed closer IZ to that of standard antibiotic, against food-borne diarrheagenic bacteria, there is a scope to develop effective combination of antimicrobial agents in purified form. _____________________________________________________________________________________________________________
Maxillary ameloblastic carcinoma: A diagnostic conundrum

Ameloblastic carcinoma (AC) is a rare malignant epithelial proliferation that is associated with an ameloblastoma or histologically resembles an ameloblastoma. It is considered to be an aggressive neoplasm that is locally invasive and spread to regional lymph nodes or distant sites. It requires aggressive surgical treatment, and regular follow-up, therefore, differs from ameloblastoma. Sometimes, ameloblastomas exhibit a mild-to-moderate degree of cytological atypia; hence, in such cases, a correlation should be established between the clinical, radiological and histopathological findings, thus detecting the aggressiveness of the tumor. Here, we present the case report of a 52-year-old male patient diagnosed as AC based on histopathological and immunohistochemical findings.
The Unifying Theory of Bootstrapping: The Collaboration of Multiple Language Acquisition Mechanisms

Scientists have long been exploring the possibility of Universal Grammar (UG), a linguistic gene that engenders our language acquisition process. What UG may comprise is debated: if semantics is innate, or syntax, or some other linguistic aspects. Moreover, no definitive evidence has surfaced to attest to its existence. Therefore, a first-language acquisition process without the prerequisite of UG is called for. In this paper, we tear apart the incompatibilities among different language acquisition hypotheses and combine them into a theory in which language learning does not require UG. We contend that a unification of the current hypotheses (i.e., pragmatic, prosodic, semantic, and syntactic bootstrapping) is substantial for first-language acquisition, and that scientists should be wary of oversimplifying matters with UG.
TRANSPORT PROCESSES IN THE LOW PRESSURE GAS DISCHARGE PLASMA

Plasma technologies for the film deposition and etching based on the ion flows application are intensively elaborated and used now. Some of the most important requirements imposed on the ion flows are homogeneity and monoenergeticity, what necessitate the analysis of processes of particles flow formation in existing devices as well as under designing the new plasma technology devices [1-5]. On the base of the simple mathematical model the transport processes in the low pressure gas discharge are considered. It was assumed that the gas discharge is in steady state regime. For the nonmagnetized plasma free fall mode for ions and electrons is supposed and free fall mode is assumed only for ions if a constant external magnetic field is applied. Consideration is treated in the framework of 2D two liquid hydrodynamic plasma model. PACS: 52.80. -s