Miracle-dz/UniFAR-FTUs huggingface dataset:
Residual Disease in Glioma Recurrence: A Dangerous Liaison with Senescence

Simple Summary Glioblastoma (GBM) is an aggressive and mostly incurable from of brain cancer. This is largely due to individual tumor cells invading the surrounding tissue, through which they evade surgical removal and reconstitute the tumor. Here, we define three distinct environments that GBM cells migrate into: the vascular, the neural, and the glial niches. These environments can nurture GBM recurrence through factors associated with a process called “senescence”; a cellular stress response which causes them to secrete mostly pro-tumorigenic factors. Senescence is especially relevant to late-stage brain cancer since it occurs mainly in aged people, who have senescent cells. Moreover, brain cells can become senescent in response to unresolved damage from chemo- and radio- therapies. As such, we summarize recent literature on brain senescence and discuss strategies to optimize and implement anti-senescence therapies aimed at overcoming recurrence and lethality from GBM. Abstract With a dismally low median survival of less than two years after diagnosis, Glioblastoma (GBM) is the most lethal type of brain cancer. The standard-of-care of surgical resection, followed by DNA-damaging chemo-/radiotherapy, is often non-curative. In part, this is because individual cells close to the resection border remain alive and eventually undergo renewed proliferation. These residual, therapy-resistant cells lead to rapid recurrence, against which no effective treatment exists to date. Thus, new experimental approaches need to be developed against residual disease to prevent GBM survival and recurrence. Cellular senescence is an attractive area for the development of such new approaches. Senescence can occur in healthy cells when they are irreparably damaged. Senescent cells develop a chronic secretory phenotype that is generally considered pro-tumorigenic and pro-migratory. Age is a negative prognostic factor for GBM stage, and, with age, senescence steadily increases. Moreover, chemo-/radiotherapy can provide an additional increase in senescence close to the tumor. In light of this, we will review the importance of senescence in the tumor-supportive brain parenchyma, focusing on the invasion and growth of GBM in residual disease. We will propose a future direction on the application of anti-senescence therapies against recurrent GBM.
Analysis of Rinsing Fluid during Negative Pressure Wound Therapy with Instillation: A Potential Monitoring Tool in Acute and Chronic Wound Treatment. A Pilot Study

Background: During negative pressure wound therapy (NPWT), open wounds are draped with a nontransparent sponge, making daily wound evaluation impossible. Sometimes, late or undetected bacterial infections and postoperative bleeding result in repetitive surgery, thus prolonging inpatient time. With the introduction of additional fluid instillation (NPWTi), the wound surface is rinsed, and bacteria, proteins and biomarkers are flushed into a collecting canister, which is later discarded. Methods: The aim of this pilot study was to analyze rinsing fluid samples (0.9% sodium chloride) from the NPWTi device in patients with acute and chronic wounds. In 31 consecutive patients a standardized laboratory analysis was performed to evaluate cellular composition and potassium, phosphate, lactate dehydrooxygenase, pH and total protein levels. Results: While there was an increase in the total cellular amount and the number of polymorphonuclear cells, the number of red blood cells (RBC) decreased after surgery. Potassium and pH showed no significant changes in the first three postoperative days, whereas total protein showed an undulant and partially significant course. Conclusion: We were able to quantify cellular metabolites by analyzing the rinsing fluid of NPWTi. We propose the analysis of this material as a novel and potentially promising tool to monitor wound status without removal of the dressing. The establishment of reference values might help to improve the NPWTi therapy.
Amyloid-Beta Induces Different Expression Pattern of Tissue Transglutaminase and Its Isoforms on Olfactory Ensheathing Cells: Modulatory Effect of Indicaxanthin

Herein, we assessed the effect of full native peptide of amyloid-beta (Aβ) (1-42) and its fragments (25-35 and 35-25) on tissue transglutaminase (TG2) and its isoforms (TG2-Long and TG2-Short) expression levels on olfactory ensheathing cells (OECs). Vimentin and glial fibrillary acid protein (GFAP) were also studied. The effect of the pre-treatment with indicaxanthin from Opuntia ficus-indica fruit on TG2 expression levels and its isoforms, cell viability, total reactive oxygen species (ROS), superoxide anion (O2−), and apoptotic pathway activation was assessed. The levels of Nestin and cyclin D1 were also evaluated. Our findings highlight that OECs exposure to Aβ(1-42) and its fragments induced an increase in TG2 expression levels and a different expression pattern of its isoforms. Indicaxanthin pre-treatment reduced TG2 overexpression, modulating the expression of TG2 isoforms. It reduced total ROS and O2− production, GFAP and Vimentin levels, inhibiting apoptotic pathway activation. It also induced an increase in the Nestin and cyclin D1 expression levels. Our data demonstrated that indicaxanthin pre-treatment stimulated OECs self-renewal through the reparative activity played by TG2. They also suggest that Aβ might modify TG2 conformation in OECs and that indicaxanthin pre-treatment might modulate TG2 conformation, stimulating neural regeneration in Alzheimer’s disease.
A DFT/ECP-Small Basis Set Modelling of Cisplatin: Molecular Structure and Vibrational Spectrum

A DFT conformational and vibrational analysis of a single molecule of cisplatin (cis-[Pt(NH3)2Cl2]) was performed by means of PW91 functional and LANL08 ECP basis set for the Pt atom. 3-21G and 3-21G* Basis sets were used for the remaining atoms. All the initially chosen conformations were found to converge to the global minimum conformation of C2v symmetry with H atoms lying in the coordination plane and pointing to the Cl atoms. The computational results were compared with the newest experimental structural data and with the vibrational spectroscopic data for cisplatin, obtained by other workers. The chosen level of theory was found to describe satisfactory the molecular structure (r. m. s. of the relative deviations ≤ 6%) and the harmonic vibrational frequencies (r. m. s. of the relative deviations ≤ 5%) of cisplatin.
The Association between TIF1 Family Members and Cancer Stemness in Solid Tumors

Simple Summary Stem cell-associated molecular features of solid tumors, collectively known as cancer stemness, are of great importance in the development, progression, and reoccurrence of cancer. Transcriptional and epigenetic dysregulation is significantly associated with cancer stemness. Here, we investigated the association between the Transcriptional Intermediary Factor 1 (TIF1) family members and cancer stemness in solid tumors. We aimed to evaluate the potential value of TIF1 members in predicting a stem-like cancer phenotype. Our results indicate that only TIF1β (also known as Tripartite Motif protein 28, TRIM28) high expression is consequently associated with a “stemness high” phenotype, regardless of the tumor type, resulting in a worse prognosis for cancer patients. The oncogenic signature of TRIM28HIGH tumors significantly reflects the enrichment of “stemness high” cancers with targets for c-Myc (MYC Proto-Oncogene). TRIM28-associated gene expression profiles are also robustly enriched with stemness markers. Our results demonstrate that the association between high TRIM28 expression and an enriched cancer stem cell-like phenotype is a common phenomenon across solid tumors. Abstract Cancer progression entails a gradual loss of a differentiated phenotype in parallel with the acquisition of stem cell-like features. Cancer de-differentiation and the acquisition of stemness features are mediated by the transcriptional and epigenetic dysregulation of cancer cells. Here, using publicly available data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and harnessing several bioinformatic tools, we characterized the association between Transcriptional Intermediary Factor 1 (TIF1) family members and cancer stemness in 27 distinct types of solid tumors. We aimed to define the prognostic value for TIF1 members in predicting a stem cell-like cancer phenotype and patient outcome. Our results demonstrate that high expression of only one member of the TIF1 family, namely TIF1β (also known as Tripartite Motif protein 28, TRIM28) is consequently associated with enriched cancer stemness across the tested solid tumor types, resulting in a worse prognosis for cancer patients. TRIM28 is highly expressed in higher grade tumors that exhibit stem cell-like traits. In contrast to other TIF1 members, only TIF1β/TRIM28-associated gene expression profiles were robustly enriched with stemness markers regardless of the tumor type. Our work demonstrates that TIF1 family members exhibit distinct expression patterns in stem cell-like tumors, despite their structural and functional similarity. Among other TIF1 members, only TRIM28 might serve as a marker of cancer stemness features.
Separation and Preconcentration of Cobalt Using a New Schiff Base Derivative on Amberlite XAD‐7

In this study, a new solid-phase extraction procedure has been developed for preconcentration and determination of Co ions in different water samples by flame atomic absorption spectrometry (FAAS). Cobalt was preconcentrated as N,N'-bis(pyridine-2-yl-methyl)benzene-1,4-diamine (Co-BPMBDA) from sample solutions using a column containing Amberlite XAD-7 and was determined. In order to achieve the best performance for the method, effects of several parameters such as pH, concentrations of ligand, sample flow rate, eluent, and matrix ions on the method efficiency were investigated. Under optimum conditions, the preconcentration factor was found to be 200 for 1000 mL waters samples. Detection limit based on the 3S b criterion was calculated as 0.24 μg/L for 100 mL of sample solution and relative standard deviation was found to be 1.8%. The method was applied to determine the trace amounts of cobalt in water samples.
The Role of Denosumab for Surgical Outcomes in Patients with Giant Cell Tumour of Bone: A Systematic Review

Background: The role of denosumab in patients with resectable giant cell tumour of bone remains unclear. We asked the following research question: for patients (aged ≥ 12 years) with resectable giant cell tumour of bone, what are the benefits and harms of denosumab compared with no denosumab in terms of (1) facilitation of surgery (operative time, blood loss), (2) disease recurrence, (3) pain control, (4) disease stability, and (5) adverse effects (e.g., malignant transformation, osteonecrosis of jaw, atypical femur fracture)? One previous systematic review addressed only one outcome—disease recurrence. Therefore, we undertook this new systematic review to address the above five outcomes. Methods: MEDLINE, EMBASE, PubMed, and Cochrane Database of Systematic Reviews databases were searched on June 30, 2020. Results: This systematic review included one previous systematic review and five comparative studies. Due to poor quality, non-randomized studies fraught with selection bias, it is difficult to determine if a significant difference exists in the outcomes for surgical giant cell tumour of bone with perioperative denosumab. There were no reported cases of adverse effects from denosumab. Conclusion: To date, there is insufficient evidence to understand the value of denosumab in the perioperative setting in patients with giant cell tumour of bone.
Highly Oxygenated Triterpenoids and Diterpenoids from Fructus Rubi (Rubus chingii Hu) and Their NF-kappa B Inhibitory Effects

During a phytochemical investigation of the unripe fruits of Rubus chingii Hu (i.e., Fructus Rubi, a traditional Chinese medicine named “Fu-Pen-Zi”), a number of highly oxygenated terpenoids were isolated and characterized. These included nine ursane-type (1, 2, and 4–10), five oleanane-type (3, 11–14), and six cucurbitane-type (15–20) triterpenoids, together with five ent-kaurane-type diterpenoids (21–25). Among them, (4R,5R,8R,9R,10R,14S,17S,18S,19R,20R)-2,19α,23-trihydroxy-3-oxo-urs-1,12-dien-28-oic acid (rubusacid A, 1), (2R*,4S*,5R*,8R*,9R*,10R*,14S*,17S*, 18S*,19R*,20R*)-2α,19α,24-trihydroxy-3-oxo-urs-12-en-28-oic acid (rubusacid B, 2), (5R,8R,9R,10R, 14S,17R,18S,19S)-2,19α-dihydroxy-olean-1,12-dien-28-oic acid (rubusacid C, 3), and (3S,5S,8S,9R, 10S,13R,16R)-3α,16α,17-trihydroxy-ent-kaur-2-one (rubusone, 21) were previously undescribed. Their chemical structures and absolute configurations were elucidated on the basis of spectroscopic data and electronic circular dichroism (ECD) analyses. Compounds 1 and 3 are rare naturally occurring pentacyclic triterpenoids featuring a special α,β-unsaturated keto-enol (diosphenol) unit in ring A. Cucurbitacin B (15), cucurbitacin D (16), and 3α,16α,20(R),25-tetrahydroxy-cucurbita-5,23- dien-2,11,22-trione (17) were found to have remarkable inhibitory effects against NF-κB, with IC50 values of 0.08, 0.61, and 1.60 μM, respectively.
Increased Stress Resistance and Lifespan in Chaenorhabditis elegans Wildtype and Knockout Mutants—Implications for Depression Treatment by Medicinal Herbs

Depression and anxiety disorders are widespread diseases, and they belong to the leading causes of disability and greatest burdens on healthcare systems worldwide. It is expected that the numbers will dramatically rise during the COVID-19 pandemic. Established medications are not sufficient to adequately treat depression and are not available for everyone. Plants from traditional medicine may be promising alternatives to treat depressive symptoms. The model organism Chaenorhabditis elegans was used to assess the stress reducing effects of methanol/dichlormethane extracts from plants used in traditional medicine. After initial screening for antioxidant activity, nine extracts were selected for in vivo testing in oxidative stress, heat stress, and osmotic stress assays. Additionally, anti-aging properties were evaluated in lifespan assay. The extracts from Acanthopanax senticosus, Campsis grandiflora, Centella asiatica, Corydalis yanhusuo, Dan Zhi, Houttuynia cordata, Psoralea corylifolia, Valeriana officinalis, and Withania somnifera showed antioxidant activity of more than 15 Trolox equivalents per mg extract. The extracts significantly lowered ROS in mutants, increased resistance to heat stress and osmotic stress, and the extended lifespan of the nematodes. The plant extracts tested showed promising results in increasing stress resistance in the nematode model. Further analyses are needed, in order to unravel underlying mechanisms and transfer results to humans.
Perceptual Learning beyond Perception: Mnemonic Representation in Early Visual Cortex and Intraparietal Sulcus

The ability to discriminate between stimuli relies on a chain of neural operations associated with perception, memory and decision-making. Accumulating studies show learning-dependent plasticity in perception or decision-making, yet whether perceptual learning modifies mnemonic processing remains unclear. Here, we trained human participants of both sexes in an orientation discrimination task, while using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to separately examine training-induced changes in working memory (WM) representation. fMRI decoding revealed orientation-specific neural patterns during the delay period in primary visual cortex (V1) before, but not after, training, whereas neurodisruption of V1 during the delay period led to behavioral deficits in both phases. In contrast, both fMRI decoding and disruptive effect of TMS showed that intraparietal sulcus (IPS) represented WM content after, but not before, training. These results suggest that training does not affect the necessity of sensory area in representing WM information, consistent with the sensory recruitment hypothesis in WM, but likely alters the coding format of the stored stimulus in this region. On the other hand, training can render WM content to be maintained in higher-order parietal areas, complementing sensory area to support more robust maintenance of information. SIGNIFICANCE STATEMENT There has been accumulating progresses regarding experience-dependent plasticity in perception or decision-making, yet how perceptual experience moulds mnemonic processing of visual information remains less explored. Here, we provide novel findings that learning-dependent improvement of discriminability accompanies altered WM representation at different cortical levels. Critically, we suggest a role of training in modulating cortical locus of WM representation, providing a plausible explanation to reconcile the discrepant findings between human and animal studies regarding the recruitment of sensory or higher-order areas in WM.
Correcting Susceptibility Artifacts of MRI Sensors in Brain Scanning: A 3D Anatomy-Guided Deep Learning Approach

Echo planar imaging (EPI), a fast magnetic resonance imaging technique, is a powerful tool in functional neuroimaging studies. However, susceptibility artifacts, which cause misinterpretations of brain functions, are unavoidable distortions in EPI. This paper proposes an end-to-end deep learning framework, named TS-Net, for susceptibility artifact correction (SAC) in a pair of 3D EPI images with reversed phase-encoding directions. The proposed TS-Net comprises a deep convolutional network to predict a displacement field in three dimensions to overcome the limitation of existing methods, which only estimate the displacement field along the dominant-distortion direction. In the training phase, anatomical T1-weighted images are leveraged to regularize the correction, but they are not required during the inference phase to make TS-Net more flexible for general use. The experimental results show that TS-Net achieves favorable accuracy and speed trade-off when compared with the state-of-the-art SAC methods, i.e., TOPUP, TISAC, and S-Net. The fast inference speed (less than a second) of TS-Net makes real-time SAC during EPI image acquisition feasible and accelerates the medical image-processing pipelines.
Diets within Environmental Limits: The Climate Impact of Current and Recommended Australian Diets

Planetary boundaries are an important sustainability concept, defining absolute limits for resource use and emissions that need to be respected to avoid major and potentially irreversible earth system change. To remain within the safe operating space for humanity, there is a need for urgent adoption of climate-neutral diets, which make no additional contribution to warming. In the first study of its kind, a new climate metric, the Global Warming Potential Star (GWP*), was used to assess greenhouse gas (GHG) emissions associated with 9341 Australian adult diets obtained from the Australian Health Survey. Dietary climate footprints averaged 3.4 kg CO2-equivelent per person per day, with total energy intake explaining around one quarter of the variation. Energy-dense and nutrient-poor discretionary foods contributed around one third. With lower climate footprint food choices, a diet consistent with current Australian dietary guidelines had a 42% lower climate footprint. Currently, it is not possible to define a climate-neutral dietary strategy in Australia because there are very few climate-neutral foods in the Australian food system. To bring Australian diets into line with the climate stabilization goals of the Paris Agreement, the most important need is for innovation across the agricultural and food processing industries to expand the range of climate-neutral foods available.
The genomic landscape of young and old lung cancer patients highlights age‐dependent mutation frequencies and clinical actionability in young patients

The aim of the study was to investigate age‐dependent tendency of genomic alterations in lung cancer, and also to examine mutational profiles and its association with clinical treatment outcomes in young adenocarcinoma patients. By studying 7858 lung cancer samples using targeted‐gene sequencing, we investigated genomic differences and clinical on‐treatment time (OTT) to different therapies between young (≤ 45 years) and old (> 45 years) patients. The age‐dependent trend test for genomic alterations in all patients revealed steady increases in tumor mutation burden and alterations in a number of genes with age, including KRAS, MET, CDKN2A, PIK3CA and MDM2, while the frequencies of ALK, ROS1 and RET fusions and ERBB2 mutations were decreasing. The highest rate of EGFR alterations was observed in the 45 ~ 50 years age group. Comparisons of young and old adenocarcinoma patients found that young patients were characterized by a higher prevalence of ALK, ROS1 and RET fusions, and ERBB2 exon‐20 insertions and EGFR exon‐19 deletions. Actionable mutations were highly prevalent in young adenocarcinoma patients, with 88% of patients harboring at least one actionable genetic alteration. First‐line therapies in EGFR‐positive patients (n = 979) by EGFR tyrosine kinase inhibitors or chemotherapy resulted in similar OTT between young and old patients. Somatic interaction analyses implied that young EGFR‐positive patients were more likely to also have PIK3CA, MET, TP53 and RB1 mutations than old patients. Lung cancer in young patients, and especially those with adenocarcinoma, exhibited different clinical features and genomic attributes compared to old patients, which should be considered for therapeutic decision‐making purposes.
Exceptional Mechanical Properties and Heat Resistance of Photocurable Bismaleimide Ink for 3D Printing

Photosensitive resins used in three-dimensional (3D) printing are characterized by high forming precision and fast processing speed; however, they often possess poor mechanical properties and heat resistance. In this study, we report a photocurable bismaleimide ink with excellent comprehensive performance for stereolithography (SLA) 3D printing. First, the main chain of bismaleimide with an amino group (BDM) was synthesized, and then, the glycidyl methacrylate was grafted to the amino group to obtain the bismaleimide oligomer with an unsaturated double bond. The oligomers were combined with reaction diluents and photo-initiators to form photocurable inks that can be used for SLA 3D printing. The viscosity and curing behavior of the inks were studied, and the mechanical properties and heat resistance were tested. The tensile strength of 3D-printed samples based on BDM inks could reach 72.6 MPa (166% of that of commercial inks), glass transition temperature could reach 155 °C (205% of that of commercial inks), and energy storage modulus was 3625 MPa at 35 °C (327% of that of commercial inks). The maximum values of T-5%, T-50%, and Tmax of the 3D samples printed by BDM inks reached 351.5, 449.6, and 451.9 °C, respectively. These photocured BDM inks can be used to produce complex structural components and models with excellent mechanical and thermal properties, such as car parts, building models, and pipes.
Lagos Bat Virus, an Under-Reported Rabies-Related Lyssavirus

Lagos bat virus (LBV), one of the 17 accepted viral species of the Lyssavirus genus, was the first rabies-related virus described in 1956. This virus is endemic to the African continent and is rarely encountered. There are currently four lineages, although the observed genetic diversity exceeds existing lyssavirus species demarcation criteria. Several exposures to rabid bats infected with LBV have been reported; however, no known human cases have been reported to date. This review provides the history of LBV and summarizes previous knowledge as well as new detections. Genetic diversity, pathogenesis and prevention are re-evaluated and discussed.