Miracle-dz/UniFAR-FTUs huggingface dataset:
SATB1-Mediated Upregulation of the Oncogenic Receptor Tyrosine Kinase HER3 Antagonizes MET Inhibition in Gastric Cancer Cells

MET-amplified gastric cancer cells are extremely sensitive to MET inhibition in vitro, whereas clinical efficacy of MET inhibitors is disappointing. The compensatory activation of other oncogenic growth factor receptors may serve as an underlying mechanism of resistance. In this study, we analyzed the role of HER receptors, in particular HER3 and its ligand heregulin, in this respect. This also included the chromatin-organizer protein SATB1, as an established regulator of HER expression in other tumor entities. In a panel of MET-amplified gastric carcinoma cell lines, cell growth under anchorage-dependent and independent conditions was studied upon inhibitor treatment or siRNA-mediated knockdown. Expression analyses were performed using RT-qPCR, FACS, and immunoblots. Signal transduction was monitored via antibody arrays and immunoblots. As expected, MET inhibition led to a growth arrest and inhibition of MAPK signaling. Strikingly, however, this was accompanied by a rapid and profound upregulation of the oncogenic receptor HER3. This finding was determined as functionally relevant, since HER3 activation by HRG led to partial MET inhibitor resistance, and MAPK/Akt signaling was even found enhanced upon HRG+MET inhibitor treatment compared to HRG alone. SATB1 was identified as mediator of HER3 upregulation. Concomitantly, SATB1 knockdown prevented upregulation of HER3, thus abrogating the HRG-promoted rescue from MET inhibition. Taken together, our results introduce the combined HER3/MET inhibition as strategy to overcome resistance towards MET inhibitors.
Attribute Supervised Probabilistic Dependent Matrix Tri-Factorization Model for the Prediction of Adverse Drug-Drug Interaction

Adverse drug-drug interaction (ADDI) becomes a significant threat to public health. Despite the detection of ADDIs is experimentally implemented in the early development phase of drug design, many potential ADDIs are still clinically explored by accidents, leading to a large number of morbidity and mortality. Several computational models are designed for ADDI prediction. However, they take no consideration of drug dependency, although many drugs usually produce synergistic effects and own highly mutual dependency in treatments, which contains underlying information about ADDIs and benefits ADDI prediction. In this paper, we design a dependent network to model the drug dependency and propose an attribute supervised learning model Probabilistic Dependent Matrix Tri-Factorization (PDMTF) for ADDI prediction. In particular, PDMTF incorporates two drug attributes, molecular structure and side effect, and their correlation to model the adverse interactions among drugs. The dependent network is represented by a dependent matrix, which is first formulated by the row precision matrix of the predicted attribute matrices and then regularized by the molecular structure similarities among drugs. Meanwhile, an efficient alternating algorithm is designed for solving the optimization problem of PDMTF. Experiments demonstrate the superior performance of the proposed model when compared with eight baselines and its two variants.
Infections and Immunotherapy in Lung Cancer: A Bad Relationship?

Infectious diseases represent a relevant issue in lung cancer patients. Bacterial and viral infections might influence the patients’ prognosis, both directly affecting the immune system and indirectly impairing the outcome of anticancer treatments, mainly immunotherapy. In this analysis, we aimed to review the current evidence in order to clarify the complex correlation between infections and lung cancer. In detail, we mainly explored the potential impact on immunotherapy outcome/safety of (1) bacterial infections, with a detailed focus on antibiotics; and (2) viral infections, discriminating among (a) human immune-deficiency virus (HIV), (b) hepatitis B/C virus (HBV-HCV), and (c) Sars-Cov-2. A series of studies suggested the prognostic impact of antibiotic therapy administration, timing, and exposure ratio in patients treated with immune checkpoint inhibitors, probably through an antibiotic-related microbiota dysbiosis. Although cancer patients with HIV, HBV, and HCV were usually excluded from clinical trials evaluating immunotherapy, some retrospective and prospective trials performed in these patient subgroups reported similar results compared to those described in not-infected patients, with a favorable safety profile. Moreover, patients with thoracic cancers are particularly at risk of COVID-19 severe outcomes and mortality. Few reports speculated about the prognostic implications of anticancer therapy, including immunotherapy, in lung cancer patients with concomitant Sars-Cov-2 infection, showing, to date, inconsistent results. The correlation between infectious diseases and immunotherapy remains to be further explored and clarified in the context of dedicated trials. In clinical practice, the accurate and prompt multidisciplinary management of lung cancer patients with infections should be encouraged in order to select the best treatment options for these patients, avoiding unexpected toxicities, while maintaining the anticancer effect.
Lack of GABARAP-Type Proteins Is Accompanied by Altered Golgi Morphology and Surfaceome Composition

GABARAP (γ-aminobutyric acid type A receptor-associated protein) and its paralogues GABARAPL1 and GABARAPL2 comprise a subfamily of autophagy-related Atg8 proteins. They are studied extensively regarding their roles during autophagy. Originally, however, especially GABARAPL2 was discovered to be involved in intra-Golgi transport and homotypic fusion of post-mitotic Golgi fragments. Recently, a broader function of mammalian Atg8s on membrane trafficking through interaction with various soluble N-ethylmaleimide-sensitive factor-attachment protein receptors (SNAREs) was suggested. By immunostaining and microscopic analysis of the Golgi network, we demonstrate the importance of the presence of individual GABARAP-type proteins on Golgi morphology. Furthermore, triple knockout (TKO) cells lacking the whole GABARAP subfamily showed impaired Golgi-dependent vesicular trafficking as assessed by imaging of fluorescently labelled ceramide. With the Golgi apparatus being central within the secretory pathway, we sought to investigate the role of the GABARAP-type proteins for cell surface protein trafficking. By analysing the surfaceome composition of TKOs, we identified a subset of cell surface proteins with altered plasma membrane localisation. Taken together, we provide novel insights into an underrated aspect of autophagy-independent functions of the GABARAP subfamily and recommend considering the potential impact of GABARAP subfamily proteins on a plethora of processes during experimental analysis of GABARAP-deficient cells not only in the autophagic context.
Reducing Iron Content in Infant Formula from 8 to 2 mg/L Does Not Increase the Risk of Iron Deficiency at 4 or 6 Months of Age: A Randomized Controlled Trial

Many infant formulas are fortified with iron at 8–14 mg/L whereas breast milk contains about 0.3 mg/L. Another major difference between breast milk and infant formula is its high concentration of lactoferrin, a bioactive iron-binding protein. The aim of the present study was to investigate how reducing the iron content and adding bovine lactoferrin to infant formula affects iron status, health and development. Swedish healthy full-term formula-fed infants (n = 180) were randomized in a double-blind controlled trial. From 6 weeks to 6 months of age, 72 infants received low-iron formula (2 mg/L) fortified with bovine lactoferrin (1.0 g/L) (Lf+), 72 received low-iron formula un-fortified with lactoferrin (Lf−) and 36 received standard formula with 8 mg of iron/L and no lactoferrin fortification as controls (CF). Iron status and prevalence of iron deficiency (ID) were assessed at 4 and 6 months. All iron status indicators were unaffected by lactoferrin. At 4 and 6 months, the geometric means of ferritin for the combined low-iron groups compared to the CF-group were 67.7 vs. 88.7 and 39.5 vs. 50.9 µg/L, respectively (p = 0.054 and p = 0.056). No significant differences were found for other iron status indicators. In the low-iron group only one infant (0.7%) at 4 months and none at 6 months developed ID. Conclusion: Iron fortification of 2 mg/L is an adequate level during the first half of infancy for healthy term infants in a well-nourished population. Adding lactoferrin does not affect iron status.
Sounds Stimulation on In Vitro HL1 Cells: A Pilot Study and a Theoretical Physical Model

Mechanical vibrations seem to affect the behaviour of different cell types and the functions of different organs. Pressure waves, including acoustic waves (sounds), could affect cytoskeletal molecules via coherent changes in their spatial organization and mechano-transduction signalling. We analyzed the sounds spectra and their fractal features. Cardiac muscle HL1 cells were exposed to different sounds, were stained for cytoskeletal markers (phalloidin, beta-actin, alpha-tubulin, alpha-actinin-1), and studied with multifractal analysis (using FracLac for ImageJ). A single cell was live-imaged and its dynamic contractility changes in response to each different sound were analysed (using Musclemotion for ImageJ). Different sound stimuli seem to influence the contractility and the spatial organization of HL1 cells, resulting in a different localization and fluorescence emission of cytoskeletal proteins. Since the cellular behaviour seems to correlate with the fractal structure of the sound used, we speculate that it can influence the cells by virtue of the different sound waves’ geometric properties that we have photographed and filmed. A theoretical physical model is proposed to explain our results, based on the coherent molecular dynamics. We stress the role of the systemic view in the understanding of the biological activity.
Left Atrial Strain Identifies Increased Atrial Ectopy in Patients with Beta-Thalassemia Major

Patients with beta-thalassemia major (β-ΤΜ) may develop cardiac arrhythmias through a multifactorial mechanism. The current study evaluated the association of cardiac structure and function on echocardiography with atrial ectopic burden on 24-hour tape recording in β-ΤΜ patients. This prospective study included consecutive β-ΤΜ patients. Demographic, laboratory, echocardiographic, cardiac magnetic resonance (CMR) T2* and 24-hour tape recording data were prospectively collected. The patients were classified according to the median value of premature atrial contractions (PACs) on 24-hour tape. In total, 50 β-TM patients (37.6 ± 9.1 years old, 50% male) were divided in 2 groups; PACs ≤ 24/day and > 24/day. Patients with PACs > 24/day were treated with blood transfusion for a longer period of time (39.0 ± 8.6 vs. 32.0 ± 8.9 years, p < 0.007), compared to their counterparts. Older age (OR: 1.121, 95% CI: 1.032–1.217, p = 0.007), longer duration of blood transfusion (OR:1.101, 95% CI:1.019–1.188, p = 0.014), larger LV end-diastolic diameter (OR: 4.522, 95% CI:1.009–20.280, p = 0.049), higher values of LA peak systolic strain (OR: 0.869, 95% CI: 0.783–0.964, p = 0.008), higher MV E/E′ average (OR: 1.407, 95% CI: 1.028–1.926, p = 0.033) and higher right ventricular systolic pressure (OR: 1.147, 95% CI: 1.039–1.266, p = 0.006) were univariably associated with PACs > 24/day. LA peak systolic strain remained significantly associated with PACs > 24/day after adjusting for the duration of blood transfusions or for CMR T2*. The multivariable model including blood transfusion duration and LA peak systolic strain was the most closely associated with PACs > 24/day. Receiver operating characteristic curve analysis identified a left atrial peak systolic strain of 31.5%, as the best cut-off value (83% sensitivity, 68% specificity) for prediction of PACs > 24/day. In β-TM patients, LA peak systolic strain was associated with the atrial arrhythmia burden independently to the duration of blood transfusions and CMR T2*.
Accumulation of Elements in Biodeposits on the Stone Surface in Urban Environment. Case Studies from Saint Petersburg, Russia

The pattern of elements accumulation in biodeposits formed by living organisms and extracellular products of their metabolism (biofouling, primary soils) on different bedrocks (of the monuments of Historical necropoleis in Saint Petersburg) were studied by a complex of biological and mineralogical methods (optical microscopy, SEM, EDX, XRD, ICP MS, XRFS). The content of 46 elements in biodeposits with various communities of microorganisms is determined. The model recreating the picture of the input and selective accumulation of elements in biodeposits on the stone surface in outdoor conditions is assumed. It is shown that the main contribution to the elemental composition of biodeposits is made by the environment and the composition of the microbial community. The contribution of leaching under the action of microbial metabolites of mineral grains, entering biodeposits from the environment, is significantly greater than that of the underlying rock.
Clinical Characteristics and Causative Pathogens of Infective Arthritis and Risk Factors for Gram-Negative Bacterial Infections

Background The aim of this study was to describe the clinical and microbiological characteristics of infective arthritis and to analyze risk factors for Gram-negative bacterial infections that cause infective arthritis. Materials and Methods Patients admitted between 2009 - 2018 with infective arthritis in a single-tertiary hospital were evaluated retrospectively. Results A total of 181 patients were enrolled in this study. Of them, 135 were native joint infection patients and 46 were prosthetic joint infection patients. The most common site of infective arthritis was the knee (63.6%), followed by the shoulder (17.7%), and the hip (9.9%). The most frequently identified microorganisms were Staphylococcus aureus (51.1%), followed by Streptococci sp. (21.1%), Enterobacteriaceae (8.4%), and coagulase-negative-Staphylococci (CNS; 8.4%). Infections due to Gram-negative bacteria and fungi made up 13.7% and 3.2% of all cases, respectively. Additionally, 20% and 4.2% of the cases involved methicillin-resistant S. aureus (MRSA) and MRCNS. We found that bacteriuria, infective arthritis in the hip, and steroid use at admission are independent risk factors for Gram-negative bacterial infections. Conclusion Infective arthritis with methicillin-resistant microorganisms reached up to about 25% in a single-tertiary hospital in Korea. In case of suspected urinary tract infection, infective arthritis of the hip joint, or steroid use at admission time among infective arthritis patients, empirical treatment covering Gram-negative microorganisms can be considered.
A New Paper-Based Microfluidic Device for Improved Detection of Nitrate in Water

In this paper, we report a simple and inexpensive paper-based microfluidic device for detecting nitrate in water. This device incorporates two recent developments in paper-based technology suitable for nitrate detection and has an optimized microfluidic design. The first technical advancement employed is an innovative fibrous composite material made up of cotton fibers and zinc microparticles that can be incorporated in paper-based devices and results in better nitrate reduction. The second is a detection zone with an immobilized reagent that allows the passage of a larger sample volume. Different acids were tested—citric and phosphoric acids gave better results than hydrochloric acid since this acid evaporates completely without leaving any residue behind on paper. Different microfluidic designs that utilize various fluid control technologies were investigated and a design with a folding detection zone was chosen and optimized to improve the uniformity of the signal produced. The optimized design allowed the device to achieve a limit of detection and quantification of 0.53 ppm and 1.18 ppm, respectively, for nitrate in water. This accounted for more than a 40% improvement on what has been previously realized for the detection of nitrate in water using paper-based technology.
COVID-19: A Global Challenge with Old History, Epidemiology and Progress So Far

Humans have witnessed three deadly pandemics so far in the twenty-first century which are associated with novel coronaviruses: SARS, Middle East respiratory syndrome (MERS), and COVID-19. All of these viruses, which are responsible for causing acute respiratory tract infections (ARTIs), are highly contagious in nature and/or have caused high mortalities. The recently emerged COVID-19 disease is a highly transmittable viral infection caused by another zoonotic novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Similar to the other two coronaviruses such as SARS-CoV-1 and MERS-CoV, SARS-CoV-2 is also likely to have originated from bats, which have been serving as established reservoirs for various pathogenic coronaviruses. Although, it is still unknown how SARS-CoV-2 is transmitted from bats to humans, the rapid human-to-human transmission has been confirmed widely. The disease first appeared in Wuhan, China, in December 2019 and quickly spread across the globe, infected 48,539,872 people, and caused 1,232,791 deaths in 215 countries, and the infection is still spreading at the time of manuscript preparation. So far, there is no definite line of treatment which has been approved or vaccine which is available. However, different types of potential vaccines and therapeutics have been evaluated and/or are under clinical trials against COVID-19. In this review, we summarize different types of acute respiratory diseases and briefly discuss earlier outbreaks of coronaviruses and compare their occurrence and pathogenicity with the current COVID-19 pandemic. Various epidemiological aspects of COVID-19 such as mode of spread, death rate, doubling time, etc., have been discussed in detail. Apart from this, different technical issues related to the COVID-19 pandemic including use of masks and other socio-economic problems associated with the pandemic have also been summarized. Additionally, we have reviewed various aspects of patient management strategies including mechanism of action, available diagnostic tools, etc., and also discussed different strategies for the development of effective vaccines and therapeutic combinations to deal with this viral outbreak. Overall, by the inclusion of various references, this review covers, in detail, the most important aspects of the COVID-19 pandemic.
The Prediction of Calorific Value of Carbonized Solid Fuel Produced from Refuse-Derived Fuel in the Low-Temperature Pyrolysis in CO2

The decrease in the calorific value of refuse-derived fuel (RDF) is an unintended outcome of the progress made toward more sustainable waste management. Plastics and paper separation and recycling leads to the overall decrease in waste’s calorific value, further limiting its applicability for thermal treatment. Pyrolysis has been proposed to densify energy in RDF and generate carbonized solid fuel (CSF). The challenge is that the feedstock composition of RDF is variable and site-specific. Therefore, the optimal pyrolysis conditions have to be established every time, depending on feedstock composition. In this research, we developed a model to predict the higher heating value (HHV) of the RDF composed of eight morphological refuse groups after low-temperature pyrolysis in CO2 (300–500 °C and 60 min) into CSF. The model considers cardboard, fabric, kitchen waste, paper, plastic, rubber, PAP/AL/PE (paper/aluminum/polyethylene) composite packaging pack, and wood, pyrolysis temperature, and residence time. The determination coefficients (R2) and Akaike information criteria were used for selecting the best model among four mathematical functions: (I) linear, (II) second-order polynomial, (III) factorial regression, and (IV) quadratic regression. For each RDF waste component, among these four models, the one best fitted to the experimental data was chosen; then, these models were integrated into the general model that predicts the HHV of CSF from the blends of RDF. The general model was validated experimentally by the application to the RDF blends. The validation revealed that the model explains 70–75% CSF HHV data variability. The results show that the optimal pyrolysis conditions depend on the most abundant waste in the waste mixture. High-quality CSF can be obtained from wastes such as paper, carton, plastic, and rubber when processed at relatively low temperatures (300 °C), whereas wastes such as fabrics and wood require higher temperatures (500 °C). The developed model showed that it is possible to achieve the CSF with the highest HHV value by optimizing the pyrolysis of RDF with the process temperature, residence time, and feedstock blends pretreatment.
The Microbiota–Gut–Brain Axis and Alzheimer’s Disease: Neuroinflammation Is to Blame?

For years, it has been reported that Alzheimer’s disease (AD) is the most common cause of dementia. Various external and internal factors may contribute to the early onset of AD. This review highlights a contribution of the disturbances in the microbiota–gut–brain (MGB) axis to the development of AD. Alteration in the gut microbiota composition is determined by increase in the permeability of the gut barrier and immune cell activation, leading to impairment in the blood–brain barrier function that promotes neuroinflammation, neuronal loss, neural injury, and ultimately AD. Numerous studies have shown that the gut microbiota plays a crucial role in brain function and changes in the behavior of individuals and the formation of bacterial amyloids. Lipopolysaccharides and bacterial amyloids synthesized by the gut microbiota can trigger the immune cells residing in the brain and can activate the immune response leading to neuroinflammation. Growing experimental and clinical data indicate the prominent role of gut dysbiosis and microbiota–host interactions in AD. Modulation of the gut microbiota with antibiotics or probiotic supplementation may create new preventive and therapeutic options in AD. Accumulating evidences affirm that research on MGB involvement in AD is necessary for new treatment targets and therapies for AD.
The Self-Enforcing Starch–Gluten System—Strain–Dependent Effects of Yeast Metabolites on the Polymeric Matrix

The rheological behaviour of dough during the breadmaking process is strongly affected by the accumulation of yeast metabolites in the dough matrix. The impact of metabolites in yeasted dough-like concentrations on the rheology of dough has not been characterised yet for process-relevant deformation types and strain rates, nor has the effect of metabolites on strain hardening behaviour of dough been analysed. We used fundamental shear and elongational rheometry to study the impact of fermentation on the dough microstructure and functionality. Evaluating the influence of the main metabolites, the strongest impact was found for the presence of expanding gas cells due to the accumulation of the yeast metabolite CO2, which was shown to have a destabilising impact on the surrounding dough matrix. Throughout the fermentation process, the polymeric and entangled gluten microstructure was found to be degraded (−37.6% average vessel length, +37.5% end point rate). These microstructural changes were successfully linked to the changing rheological behaviour towards a highly mobile polymer system. An accelerated strain hardening behaviour (+32.5% SHI for yeasted dough) was promoted by the pre-extension of the gluten strands within the lamella around the gas cells. Further, a strain rate dependency was shown, as a lower strain hardening index was observed for slow extension processes. Fast extension seemed to influence the disruption of sterically interacting fragments, leading to entanglements and hindered extensibility.