Miracle-dz/UniFAR-FTUs huggingface dataset:
Cancer Prevention by Natural Products Introduced into the Diet—Selected Cyclitols

Cancer is now the second leading cause of death worldwide. It is estimated that every year, approximately 9.6 million people die of oncologic diseases. The most common origins of malignancy are the lungs, breasts, and colorectum. Even though in recent years, many new drugs and therapeutic options have been introduced, there are still no safe, effective chemopreventive agents. Cyclitols seem poised to improve this situation. There is a body of evidence that suggests that their supplementation can decrease the incidence of colorectal cancer, lower the risk of metastasis occurrence, lower the proliferation index, induce apoptosis in malignant cells, enhance natural killer (NK) cell activity, protect cells from free radical damage, and induce positive molecular changes, as well as reduce the side effects of anticancer treatments such as chemotherapy or surgery. Cyclitol supplementation appears to be both safe and well-tolerated. This review focuses on presenting, in a comprehensive way, the currently available knowledge regarding the use of cyclitols in the treatment of different malignancies, particularly in lung, breast, colorectal, and prostate cancers.
New age water chillers with water as refrigerant

Vacuum-process technology producing chilled water needs no refrigerant of the conventional kind, but water from the process itself is used to generate cooling. This eye-catching novelty incorporates many of the considerations about the future of refrigerants: “ozone friendly”, no extra demands for safety measures or for skilful operators, no special requirements concerning the installation’s components, lower maintenance costs since leakages can be accommodated from the system. Vacuum-process technology may be used not only for production of chilled water but also for Binary Ice – pumpable suspension of minute ice crystals in an aqueous solution. This means that all the advantages related to a latent heat system may become available.
Preparation and Biological Evaluation of [99mTc]Tc-CNGU as a PSMA-Targeted Radiotracer for the Imaging of Prostate Cancer

Prostate-specific membrane antigen (PSMA) is a well-established biological target that is overexpressed on the surface of prostate cancer lesions. Radionuclide-labeled small-molecule PSMA inhibitors have been shown to be promising PSMA-specific agents for the diagnosis and therapy of prostate cancer. In this study, a glutamate-urea-based PSMA-targeted ligand containing an isonitrile (CNGU) was synthesized and labeled with 99mTc to prepare [99mTc]Tc-CNGU with a high radiochemical purity (RCP). The CNGU ligand showed a high affinity toward PSMA (Ki value is 8.79 nM) in LNCaP cells. The [99mTc]Tc-CNGU exhibited a good stability in vitro and hydrophilicity (log P = −1.97 ± 0.03). In biodistribution studies, BALB/c nude mice bearing LNCaP xenografts showed that the complex had a high tumor uptake with 4.86 ± 1.19% ID/g, which decreased to 1.74 ± 0.90% ID/g after a pre-injection of the selective PSMA inhibitor ZJ-43, suggesting that it was a PSMA-specific agent. Micro-SPECT imaging demonstrated that the [99mTc]Tc-CNGU had a tumor uptake and that the uptake was reduced in the image after blocking with ZJ-43, further confirming its PSMA specificity. All of the results in this work indicated that [99mTc]Tc-CNGU is a promising PSMA-specific tracer for the imaging of prostate cancer.
The Two TpsB-Like Proteins in Anabaena sp. Strain PCC 7120 Are Involved in Secretion of Selected Substrates

Cyanobacteria are important organisms for the ecosystem, considering their contribution to carbon fixation and oxygen production, while at the same time some species produce compounds that are toxic to their environment. As a consequence, cyanobacterial overpopulation might negatively impact the diversity of natural communities. ABSTRACT The outer membrane of Gram-negative bacteria acts as an initial diffusion barrier that shields the cell from the environment. It contains many membrane-embedded proteins required for functionality of this system. These proteins serve as solute and lipid transporters or as machines for membrane insertion or secretion of proteins. The genome of Anabaena sp. strain PCC 7120 codes for two outer membrane transporters termed TpsB1 and TpsB2. They belong to the family of the two-partner secretion system proteins which are characteristic of pathogenic bacteria. Because pathogenicity of Anabaena sp. strain PCC 7120 has not been reported, the function of these two cyanobacterial TpsB proteins was analyzed. TpsB1 is encoded by alr1659, while TpsB2 is encoded by all5116. The latter is part of a genomic region containing 11 genes encoding TpsA-like proteins. However, tpsB2 is transcribed independently of a tpsA gene cluster. Bioinformatics analysis revealed the presence of at least 22 genes in Anabaena sp. strain PCC 7120 putatively coding for substrates of the TpsB system, suggesting a rather global function of the two TpsB proteins. Insertion of a plasmid into each of the two genes resulted in altered outer membrane integrity and antibiotic resistance. In addition, the expression of genes coding for the Clp and Deg proteases is dysregulated in these mutants. Moreover, for two of the putative substrates, a dependence of the secretion on functional TpsB proteins could be confirmed. We confirm the existence of a two-partner secretion system in Anabaena sp. strain PCC 7120 and predict a large pool of putative substrates. IMPORTANCE Cyanobacteria are important organisms for the ecosystem, considering their contribution to carbon fixation and oxygen production, while at the same time some species produce compounds that are toxic to their environment. As a consequence, cyanobacterial overpopulation might negatively impact the diversity of natural communities. Thus, a detailed understanding of cyanobacterial interaction with the environment, including other organisms, is required to define their impact on ecosystems. While two-partner secretion systems in pathogenic bacteria are well known, we provide a first description of the cyanobacterial two-partner secretion system.
The essential oil composition of Phlomis bruguieri Desf. from Iran

The composition of the essential oil obtained from the dried flowering aerial parts of Phlomis bruguieri Desf. (Labiatae) was analysed by GC and GC–MS for the first time; 99 components were identified. The major constituents of the essential oil were germacrene D (23.6%), 4-hydroxy-4-methyl-2-pentanone (15.0%), α-pinene (6.8%) and β-caryophyllene (6.7%). Copyright © 2005 John Wiley & Sons, Ltd.
Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.
Impact of Pseudomonas aeruginosa Infection on Patients with Chronic Inflammatory Airway Diseases

Pseudomonas aeruginosa (P. aeruginosa) is a ubiquitous and opportunistic microorganism and is considered one of the most significant pathogens that produce chronic colonization and infection of the lower respiratory tract, especially in people with chronic inflammatory airway diseases such as asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and bronchiectasis. From a microbiological viewpoint, the presence and persistence of P. aeruginosa over time are characterized by adaptation within the host that precludes any rapid, devastating injury to the host. Moreover, this microorganism usually develops antibiotic resistance, which is accelerated in chronic infections especially in those situations where the frequent use of antimicrobials facilitates the selection of “hypermutator P. aeruginosa strain”. This phenomenon has been observed in people with bronchiectasis, CF, and the “exacerbator” COPD phenotype. From a clinical point of view, a chronic bronchial infection of P. aeruginosa has been related to more severity and poor prognosis in people with CF, bronchiectasis, and probably in COPD, but little is known on the effect of this microorganism infection in people with asthma. The relationship between the impact and treatment of P. aeruginosa infection in people with airway diseases emerges as an important future challenge and it is the most important objective of this review.
Long‐term outcomes in kidney transplant recipients with end‐stage kidney disease due to anti‐glomerular basement membrane disease

Anti‐glomerular basement membrane (GBM) disease causes rapidly progressive glomerulonephritis and end‐stage kidney disease (ESKD). Studies of post‐transplant outcomes in patients with ESKD due to anti‐GBM disease in the United States are lacking. To better characterize outcomes of transplant recipients with a history of anti‐GBM disease, we examined patient survival and graft survival among recipients with anti‐GBM disease compared with IgA nephropathy at a single center in the United States. We analyzed patient survival, graft survival, disease recurrence, and malignancy rates for kidney transplant recipients with ESKD due to biopsy‐proven anti‐GBM disease who underwent kidney transplantation at our center between 1994 and 2015. 26 patients with biopsy‐proven anti‐GBM disease and 314 patients with IgAN underwent kidney transplantation from 1994 to 2015. The incidence of graft loss was 6.2 per 100 person‐years for anti‐GBM disease, which was similar to IgAN (4.08 per 100 person‐years, p = .09). Patient mortality for anti‐GBM was 0.03 per 100 person‐years, similar to IgAN (0.02 per 100 person‐years, p = .12). Disease recurrence occurred in one of the 26 anti‐GBM patients. Four out of 26 patients (15%) developed malignancy, most commonly skin cancer. Long‐term graft and patient survival for patients with ESKD due to anti‐GBM was similar to IgAN after kidney transplantation.
Fiber Orientation and Concentration in an Injection-Molded Ethylene-Propylene Copolymer Reinforced by Hemp

This paper characterizes and analyzes the microstructures of injection-molded polypropylene parts reinforced with 20 wt% of hemp fibers in order to understand the process induced variations in thermomechanical properties. In-thickness fiber orientation and fiber content were determined by X-ray tomography along the flow. The fiber content along the flow path was also determined by direct fiber content measurements after matrix dissolution, showing an increase of 2%/100 mm for a 2.2 mm-thick plate due to fiber migration during the filling stage. A typical shell/core structure for fiber orientation in injection molding was observed, but with a very clear transition between the layer solidified under high shear rates and the core in which the fiber content was reduced by more than 50%. The orientation of hemp fibers is lower than the one of glass fibers, especially in thickness direction. However, the overall fiber orientation in the injection direction induces significant anisotropic thermomechanical properties, which cannot be explained by simple micromechanical models that consider isotropic mechanical properties for hemp fibers. These phenomena must be taken into account in process simulation codes for injection molding to better predict thermomechanical properties as well as part shrinkage and warpage to design molds.
Introduction to Infrared and Raman-Based Biomedical Molecular Imaging and Comparison with Other Modalities

Molecular imaging has rapidly developed to answer the need of image contrast in medical diagnostic imaging to go beyond morphological information to include functional differences in imaged tissues at the cellular and molecular levels. Vibrational (infrared (IR) and Raman) imaging has rapidly emerged among the molecular imaging modalities available, due to its label-free combination of high spatial resolution with chemical specificity. This article presents the physical basis of vibrational spectroscopy and imaging, followed by illustration of their preclinical in vitro applications in body fluids and cells, ex vivo tissues and in vivo small animals and ending with a brief discussion of their clinical translation. After comparing the advantages and disadvantages of IR/Raman imaging with the other main modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography/single-photon emission-computed tomography (PET/SPECT), ultrasound (US) and photoacoustic imaging (PAI), the design of multimodal probes combining vibrational imaging with other modalities is discussed, illustrated by some preclinical proof-of-concept examples.
Impact of Erythropoietin Production by Erythroblastic Island Macrophages on Homeostatic Murine Erythropoiesis

Erythropoietin (EPO) is an essential hormone for erythropoiesis, protecting differentiating erythroblasts against apoptosis. EPO has been largely studied in stress or pathological conditions but its regulatory role in steady state erythropoiesis has been less documented. Herein, we report production of EPO by bone marrow-derived macrophages (BMDM) in vitro, and its further enhancement in BMDM conditioned with media from apoptotic cells. Confocal microscopy confirmed EPO production in erythroblastic island (EBI)-associated macrophages, and analysis of mice depleted of EBI macrophages by clodronate liposomes revealed drops in EPO levels in bone marrow (BM) cell lysates, and decreased percentages of EPO-responsive erythroblasts in the BM. We hypothesize that EBI macrophages are an in-situ source of EPO and sustain basal erythropoiesis in part through its secretion. To study this hypothesis, mice were injected with clodronate liposomes and were supplied with exogenous EPO (1–10 IU/mouse) to evaluate potential rescue of the deficiency in erythroid cells. Our results show that at doses of 5 and 10 IU, EPO significantly rescues BM steady state erythropoiesis in mice deficient of macrophages. We propose existence of a mechanism by which EBI macrophages secrete EPO in response to apoptotic erythroblasts, which is in turn controlled by the numbers of erythroid precursors generated.
We need to keep a reproducible trace of facts, predictions, and hypotheses from gene to function in the era of big data

How do we scale biological science to the demand of next generation biology and medicine to keep track of the facts, predictions, and hypotheses? These days, enormous amounts of DNA sequence and other omics data are generated. Since these data contain the blueprint for life, it is imperative that we interpret it accurately. The abundance of DNA is only one part of the challenge. Artificial Intelligence (AI) and network methods routinely build on large screens, single cell technologies, proteomics, and other modalities to infer or predict biological functions and phenotypes associated with proteins, pathways, and organisms. As a first step, how do we systematically trace the provenance of knowledge from experimental ground truth to gene function predictions and annotations? Here, we review the main challenges in tracking the evolution of biological knowledge and propose several specific solutions to provenance and computational tracing of evidence in functional linkage networks.
An Updated Focus on Quadruplex Structures as Potential Therapeutic Targets in Cancer

Non-canonical, four-stranded nucleic acids secondary structures are present within regulatory regions in the human genome and transcriptome. To date, these quadruplex structures include both DNA and RNA G-quadruplexes, formed in guanine-rich sequences, and i-Motifs, found in cytosine-rich sequences, as their counterparts. Quadruplexes have been extensively associated with cancer, playing an important role in telomere maintenance and control of genetic expression of several oncogenes and tumor suppressors. Therefore, quadruplex structures are considered attractive molecular targets for cancer therapeutics with novel mechanisms of action. In this review, we provide a general overview about recent research on the implications of quadruplex structures in cancer, firstly gathering together DNA G-quadruplexes, RNA G-quadruplexes as well as DNA i-Motifs.
A π-conjugated polymer gelator from polyfluorene-based poly(tertiary alcohol) via the hydrogen-bonded supramolecular functionalization

The supramolecular approach of π-conjugated polymers imparts excellent self-assembly behaviour to construct organogels and simultaneously affords superstructured thin films, which allow for uncovering structure–function relationships. Herein, a polyfluorene-based poly(tertiary alcohol), poly(9-(4-(octyloxy)phenyl)-2,7-fluoren-9-ol) (PPFOH), has been synthesized to investigate the organic solvent effect on the gelation at room temperature. The driving force of hydrogen bonding and π–π stacking interactions in the aggregate processing of PPFOH has been investigated using nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and photoluminescence (PL). Aggregated structures of PPFOH in gelation solvents have been correlated with the characteristic emission peak at 440 nm in PL spectra. Large effects of the number molecular weight (Mn) on critical gel concentration (CGC) and green emissions of the organogels and nanostructured thin films have been observed. Finally, the emission colour of PPFOH from supramolecular thin films can be tuned flexibly from blue to yellow via selecting different types of solvent and Mn, which are promising approaches to control the optoelectronic functionalities of supramolecular π-conjugated polymers with potential applications in organic thin film electronics, optoelectronics and mechano-electronics.
Dedifferentiation of memory-related brain function as a potential early biomarker of Alzheimer's disease in asymptomatic older women: Results from the PREVENT-AD Cohort

Late-onset Alzheimer's disease (AD) disproportionately affects women compared to men. Episodic memory decline is one of the earliest and most pronounced deficits observed in AD. However, it remains unclear whether there are sex differences in episodic memory-related brain function in cognitively intact older adults at risk of developing AD. In the current study, we used task fMRI to test for sex differences in episodic memory-related brain activity and brain activity-behavior correlations in cognitively intact older adults with a family history of AD from the PREVENT-AD cohort study in Montreal, Canada (Mage=63.03 {+/-} 3.78; Meducation=15.41 {+/-} 3.40). Importantly, we tested women and men who were matched in age, body mass index, years of education, and proximity to the age of parental AD onset. We used data-driven task-based multivariate partial least squares (PLS) analysis to identify sex differences in brain activity during the successful encoding and retrieval of objects and their associated spatial context. We used behavior PLS to examine sex differences in the correlations between brain activity and memory performance at encoding and retrieval. Our results suggested no significant sex differences in behavioral performance on the memory task. Yet, we observed sex differences in task-related brain activity and in brain activity-behavior correlations during the encoding of object-location associative memories and object-only item memory, and the retrieval of object only item memories. Specifically, subsequent object-location associative retrieval associated with encoding related activation of caudate, cingulate, and middle occipital cortex in women and, additionally, of temporo-parietal regions in men. We also found male-specific activations in ventrolateral prefrontal cortex (PFC) and insula during associated with the encoding and retrieval of object-only information. Moreover, whereas activity in ventrolateral PFC, posterior cingulate, and inferior parietal regions during encoding supported subsequent performance in women, activity in these regions during retrieval supported object-location associative memory in men. Similarly, we found that activity in ventrolateral PFC, precuneus, parahippocampal, anterior cingulate, and occipital regions during retrieval supported general memory performance in women but object-only retrieval in men. Our findings suggest functional dedifferentiation of episodic memory-related brain activation and performance in women compared to men. Follow up analyses should test for sex differences in the relationship between brain activity patterns and performance longitudinally, in association with risk factors for AD development.
Retrospective development and evaluation of prognostic models for exacerbation event prediction in patients with Chronic Obstructive Pulmonary Disease using data self-reported to a digital health application

Background Self-reporting digital applications provide a way of remotely monitoring and managing patients with chronic conditions in the community. Leveraging the data collected by these applications in prognostic models could provide increased personalisation of care and reduce the burden of care for people who live with chronic conditions. This study evaluated the predictive ability of prognostic models for prediction of acute exacerbation events in people with Chronic Obstructive Pulmonary Disease using data self-reported to a digital health application. Methods Retrospective study evaluating the use of symptom and Chronic Obstructive Pulmonary Disease assessment test data self-reported to a digital health application (myCOPD) in predicting acute exacerbation events. We include data from 2,374 patients who made a total of 68,139 self-reports. We evaluated the degree to which the different variables self-reported to the application are predictive of exacerbation events and developed both heuristic and machine-learnt models to predict whether the patient will report an exacerbation event within three days of self-reporting to the application. The model's predictive ability was evaluated on self-reports from an independent set of patients. Findings Users self-reported symptoms and standard Chronic Obstructive Pulmonary Disease assessment tests display correlation with future exacerbation events. Both a baseline model (AUROC 0.655 (95 % CI: 0.689-0.676)) and a machine learnt model (AUROC 0.727 (95 % CI: 0.720-0.735)) showed moderate ability in predicting exacerbation events occurring within three days of a given self-report. While the baseline model obtained a fixed sensitivity and specificity of 0.551 (95 % CI: 0.508-0.596) and 0.759 (95 % CI: 0.752-0.767) respectively, the sensitivity and specificity of the machine-learnt model can be tuned by dichotomizing the continuous predictions it provides with different thresholds. Interpretation Data self-reported to healthcare applications designed to remotely monitor patients with Chronic Obstructive Pulmonary Disease can be used to predict acute exacerbation events with moderate performance. This could increase personalisation of care by allowing pre-emptive action to be taken to mitigate the risk of future exacerbation events. It is plausible future studies could improve the accuracy of these models by either the inclusion of symptom information recorded with greater granularity or including variables not considered in our study, for example vital signs, information on activity, local environmental data, and lifestyle information.