Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential DNA methylation following chemotherapy for breast cancer is associated with lack of memory improvement at one year

ABSTRACT The biological basis underlying cognitive dysfunction in women with early-stage breast cancer (BC) remains unclear, but could reflect gene expression changes that arise from the acquisition and long-term retention of soma-wide alterations in DNA methylation in response to chemotherapy. In this longitudinal study, we identified differences in peripheral methylation patterns present in women prior to treatment (T1) and 1 year after receiving chemotherapy (T4) and evaluated relationships among the differential methylation (DM) ratios with changes in cognitive function. A total of 58 paired (T1 and T4) blood specimens were evaluated. Methylation values were determined for DNA isolated from whole blood using a genome-wide array . Cognitive function was measured using the validated, computerized CNS Vital Signs platform. Relationships between methylation patterns and cognitive domain scores were compared using a stepwise linear regression analysis, with demographic variables as covariates. The symptom comparison analysis was restricted to 2,199 CpG positions showing significant methylation ratio changes between T1 and T4. The positions with DM were enriched for genes involved in the modulation of cytokine concentrations. Significant DM ratios were associated with memory domain (56 CpGs). Eight of the ten largest DM ratio changes associated with lack of memory improvement were localized to genes involved in either neural function (ECE2, PPFIBP2) or signalling processes (USP6NL, RIPOR2, KLF5, UBE2V1, DGKA, RPS6KA1). These results suggest that epigenetic changes acquired and retained for at least one year in non-tumour cells following chemotherapy may be associated with a lack of memory improvement following treatment in BC survivors.
Inland water bodies in China: Features discovered in the long-term satellite data

Significance Inland water bodies (WBs) provide essential ecosystem services for human society, yet their characteristics and changes over large areas remain elusive. We used unprecedented data layers derived from Landsat imagery to quantify and decipher the spatial distributions and contemporary changes of WBs in China. The results shed light on the characteristics (e.g., abundance and size-abundance and shoreline-area relationships) and spatiotemporal dynamics of WBs. This study highlights the importance of using appropriate long-term satellite data to reveal the true properties and dynamics of WBs over large areas, which is essential for developing theories and understanding the predominant impacts of human activities and climate change on water resources not only in China but also in other regions of the world. Water bodies (WBs), such as lakes, ponds, and impoundments, provide essential ecosystem services for human society, yet their characteristics and changes over large areas remain elusive. Here we used unprecedented data layers derived from all Landsat images available between 1984 and 2015 to understand the overall characteristics and changes of WBs between 2 epochs (i.e., 1984 to 1999 and 2000 to 2015) in China. Results show that the abundance estimate of WBs greater than 1 km2 and the total WB surface area were 0.3 to 1.5 times and 0.2 to 0.5 times more than the previous estimates, respectively. The size-abundance and shoreline-area relationships of WBs in China conformed to the classic power scaling law, in contradiction to most previous studies. WB changes with various occurrence probabilities show widespread coexistence of disappearance of existent and emergence of new WBs across China driven primarily by human activities and climate change. Our results highlight the importance of using appropriate long-term satellite data to reveal the true properties and dynamics of WBs over large areas, which is essential for developing scaling theories and understanding the relative impacts of human activities and climate change on water resources in the world.
Optimising treatment decision rules through generated effect modifiers: a precision medicine tutorial

Summary This tutorial introduces recent developments in precision medicine for estimating treatment decision rules. The objective of these developments is to advance personalised healthcare by identifying an optimal treatment option for each individual patient based on each patient's characteristics. The methods detailed in this tutorial define composite variables from the patient measures that can be viewed as ‘biosignatures’ for differential treatment response, which we have termed ‘generated effect modifiers’. In contrast to most machine learning approaches to precision medicine, these biosignatures are derived from linear and non-linear regression models and thus have the advantage of easy visualisation and ready interpretation. The methods are illustrated using examples from randomised clinical trials.
Nomograms and risk classification systems predicting overall and cancer‐specific survival in primary malignant cardiac tumor

Primary malignant cardiac tumors (PMCTs) are fatal, but up to now, there is still a lack of survival prediction model for prognosis evaluation. We developed nomograms to predict overall survival (OS) and cancer‐specific survival (CSS) for PMCTs by the Surveillance, Epidemiology, and End Result (SEER) database.
Efficient Interfacing of Partially Reconfigurable Instruction Set Extensions for Softcore CPUs on FPGAs

With the progress in silicon process technology, FPGA capacity raised by orders of magnitude and more focus in the research on run-time reconfigurable systems has been put on exchanging larger and more complex parts of the system. One of the reasons for this trend is a lack in techniques for integrating reconfigurable modules into a system. This means that it is not only required to place modules on an FPGA at run-time, it must also be ensured that these modules can communicate with the rest of the system. This might be communication with other partial modules as well as with the static system. The static system provides the logic that is required at any time, for example, a control CPU, a memory controller, and the interface to the FPGA configuration port. As running the logic placement and routing is not appropriate to be performed at run-time for any kind of complex module, it is common to provide modules as precompiled bitstreams that can be directly loaded to the FPGA fabric. While it is possible to manipulate minor parts of the configuration data at run-time (e.g., the placement coordinates [4]), the inner logic and routing of a module will be kept untouched. In order to provide communication to and from a reconfigurable module for a particular signal, the FPGA routing resources have to be constrained such that the same wire resources that cross the partial module border are used for each module at this position. Let us assume a system with several reconfigurable modules being connected to the backplane bus of a reconfigurable system over time. Then, the module bus signals that have to be routed across the border to the static system are required to use the same wire resources of the fabric among each particular module. For implementing reconfigurable systems, it requires therefore additional constraints that 1) separate reconfigurable resources from resources that are used by the static system and 2) location constraints on wires that are used to route signals across the border to a reconfigurable region. Such constraints are vendor tool specific, as HDL languages provide no constraints on routing or logic resources. For example, in VHDL, the only standardized synthesizable attribute is on the encoding of enumerated states, while all other attributes or constraints are not included in the language specification. Originally, FPGA vendors, such as Xilinx Inc., adapted established ASIC design techniques to allow customers to implement circuits on their devices. This ABSTRACT
Emergency myelopoiesis contributes to immune cell exhaustion and pulmonary vascular remodelling

Pulmonary hypertension (PH) secondary to chronic lung disease (World Health Organization Group 3 PH) is deadly, with lung transplant being the only available long‐term treatment option. Myeloid‐derived cells are known to affect progression of both pulmonary fibrosis and PH, although the mechanism of action is unknown. Therefore, we investigated the effect of myeloid cell proliferation induced by emergency myelopoiesis on development of PH and therapy directed against programmed death‐ligand 1 (PD‐L1), expressed by myeloid cells in prevention of pulmonary vascular remodelling.
A Pseudomonas aeruginosa type VI secretion system regulated by CueR facilitates copper acquisition

The type VI secretion system (T6SS) is widely distributed in Gram-negative bacteria, whose function is known to translocate substrates to eukaryotic and prokaryotic target cells to cause host damage or as a weapon for interbacterial competition. Pseudomonas aeruginosa encodes three distinct T6SS clusters (H1-, H2-, and H3-T6SS). The H1-T6SS-dependent substrates have been identified and well characterized; however, only limited information is available for the H2- and H3-T6SSs since relatively fewer substrates for them have yet been established. Here, we obtained P. aeruginosa H2-T6SS-dependent secretomes and further characterized the H2-T6SS-dependent copper (Cu2+)-binding effector azurin (Azu). Our data showed that both azu and H2-T6SS were repressed by CueR and were induced by low concentrations of Cu2+. We also identified the Azu-interacting partner OprC, a Cu2+-specific TonB-dependent outer membrane transporter. Similar to H2-T6SS genes and azu, expression of oprC was directly regulated by CueR and was induced by low Cu2+. In addition, the Azu-OprC-mediated Cu2+ transport system is critical for P. aeruginosa cells in bacterial competition and virulence. Our findings provide insights for understanding the diverse functions of T6SSs and the role of metal ions for P. aeruginosa in bacteria-bacteria competition.
Program Impact Pathways and Contexts: A Commentary on Theoretical Issues and Research Applications to Support the EsIAN Component of Mexico's Conditional Cash Transfer Program

ABSTRACT This commentary on the Integrated Strategy for Attention to Nutrition (EsIAN) journal supplement begins with a discussion about the challenges that implementation researchers confront with respect to analyzing complex impact pathways. We note that the research on the implementation of the EsIAN component of Mexico's conditional cash transfer program was based implicitly or explicitly on a program impact pathway approach, which used both quantitative and qualitative methods to examine bottlenecks in program implementation. We then identify 5 categories of contexts that affect the impact, implementation, and survival of intervention programs: 1) biological, 2) social-cultural, 3) delivery modalities and platforms, 4) bureaucratic, and 5) political. Each of these contexts presents theoretical and methodological challenges for investigators. In this commentary, we focus primarily on biological and social-cultural contexts, discussing the theoretical and methodological challenges the investigators faced and the research strategies they used to address them, which have produced a unique compilation of “learning by doing” studies. We also touch briefly on the political context in which the Prospera program research was conducted. We conclude with statements that highlight the exceptional value of the journal supplement, not only with respect to the analysis of the interventions the studies cover and the sustained examination of a long-term program but also as a major contribution to the literature in implementation science in nutrition.
In-depth comparison of cell-based methodological approaches to determine drug susceptibility of visceral Leishmania isolates

Monitoring the drug susceptibility of Leishmania isolates still largely relies on standard in vitro cell-based susceptibility assays using (patient-isolated) promastigotes for infection. Although this assay is widely used, no fully standardized/harmonized protocol is yet available hence resulting in the application of a wide variety of host cells (primary cells and cell lines), different drug exposure times, detection methods and endpoint criteria. Advocacy for standardization to decrease inter-laboratory variation and improve interpretation of results has already repeatedly been made, unfortunately still with unsatisfactory progress. As a logical next step, it would be useful to reach at least some agreement on the type of host cell and basic experimental design for routine amastigote susceptibility determination. The present laboratory study using different L. infantum strains as a model for visceral leishmaniasis species compared primary cells (mouse peritoneal exudate (PEC), mouse bone marrow derived macrophages and human peripheral blood monocyte derived macrophages) and commercially available cell lines (THP-1, J774, RAW) for either their susceptibility to infection, their role in supporting intracellular amastigote multiplication and overall feasibility/accessibility of experimental assay protocol. The major findings were that primary cells are better than cell lines in supporting infection and intracellular parasite multiplication, with PECs to be preferred for technical reasons. Cell lines require drug exposure of >96h with THP-1 to be preferred but subject to a variable response to PMA stimulation. The fast dividing J774 and RAW cells out-compete parasite-infected cells precluding proper assay read-out. Some findings could possibly also be applicable to cutaneous Leishmania strains, but this still needs cross-checking. Besides inherent limitations in a clinical setting, susceptibility testing of clinical isolates may remain problematic because of the reliance on patient-derived promastigotes which may exhibit variable degrees of metacyclogenesis and infectivity.
Development and Assessment of Nano-Technologies for Cancer Treatment: Cytotoxicity and Hyperthermia Laboratory Studies

Abstract Cancer treatment by magnetic hyperthermia offers numerous advantages, but for practical applications many variables still need to be adjusted before developing a controlled and reproducible cancer treatment that is bio-compatible (non-damaging) to healthy cells. In this work, Fe3O4 and CoFe2O4 were synthesized and systematically studied for the development of efficient therapeutic agents for applications in hyperthermia. The biocompatibility of the materials was further evaluated using HepG2 cells as biological model. Colorimetric and microscopic techniques were used to evaluate the interaction of magnetic nano-materials (MNMs) and HepG2 cells. Finally, the behavior of MNMs was evaluated under the influence of an alternating magnetic field (AMF), observing a more efficient temperature increment for CoFe2O4, a desirable behavior for biomedical applications since lower doses and shorter expositions to alternating magnetic field might be required. Graphical Abstract
Comparison of the eating behaviour and dietary consumption in older adults with and without visual impairment

Abstract Globally, a high prevalence of obesity and undernutrition has been reported in people with visual impairment (VI) who have reported multi-factorial obstacles that prevent them from achieving a healthy diet, such as having restricted shopping and cooking abilities. The present study is the first to investigate the relationship between VI and dietary consumption using a representative sample size, standardised methods to categorise VI and a detailed analysis of dietary consumption. Ninety-six participants with VI and an age-matched control group of fifty participants were recruited from across the UK. All participants were aged 50 years or over. The participants completed a 24-h food recall for a period of 3 d. The participants also answered questions about their abilities to shop for and cook food as well as their knowledge of healthy eating. The participants with VI in this sample consumed significantly fewer energy content and other nutrients than is recommended for their age group and when compared with an age-matched control group. The participants with VI mainly made food choices irrespective of nutritional value. The results of the present study highlight for the first time that a large proportion of older adults with VI in the UK are undernourished. These results suggest local and government-led initiatives should be implemented to support the diets of older adults in the UK, and these initiatives could include healthy eating workshops, café clubs or skills training and rehabilitation.
Efficiency of self-adhering flowable resin composite and different surface treatments in composite repair using a universal adhesive

Aims: The aim of this in vitro investigation was to evaluate the efficiency of self-adhering flowable resin composite (Vertise Flow, Kerr, Orange, CA, USA) and different surface treatments in the repair microtensile bond strength (μTBS) of aged nanofill resin composites using a universal adhesive. Materials and Methods: Aged substrates (×5000 thermocycling) were prepared using a nanofill (Filtek Ultimate; 3M ESPE) resin composite and randomly assigned to different surface treatments: (1) no treatment (control), (2) acid etching with 37% phosphoric acid, (3) Al2O3sandblasting, and (4) sandblasting with CoJet (3M ESPE). After surface treatment, specimens were further divided into two groups: no universal adhesive application and universal adhesive application. Vertise Flow was added to the substrates at 2-mm layer increments to a height of 5 mm and light cured. Restored specimens were sectioned to obtain 1.0-mm2 beams for μTBS testing. Data were analyzed with two-way analysis of variance and Tukey's honest significant difference tests (P < 0.05). Results: The lowest μTBS values were recorded in the control and acid etching groups with no universal adhesive application (P < 0.05). Universal adhesive application significantly increased the repair μTBS values of all surface treatments (P < 0.05), except CoJet treatment. There were no significant differences between Al2O3sandblasting, CoJet application, and acid etching groups with the universal adhesive application (P > 0.05). Conclusion: Vertise Flow can be used effectively in the repair of old nanofill resin composites. The usage of universal adhesive with prior acid etching to obtain acceptable repair performance would be the practical choice under clinical conditions.
Endothelial MT1‐MMP targeting limits intussusceptive angiogenesis and colitis via TSP1/nitric oxide axis

Pathological angiogenesis contributes to cancer progression and chronic inflammatory diseases. In inflammatory bowel disease, the microvasculature expands by intussusceptive angiogenesis (IA), a poorly characterized mechanism involving increased blood flow and splitting of pre‐existing capillaries. In this report, mice lacking the protease MT1‐MMP in endothelial cells (MT1iΔEC) presented limited IA in the capillary plexus of the colon mucosa assessed by 3D imaging during 1% DSS‐induced colitis. This resulted in better tissue perfusion, preserved intestinal morphology, and milder disease activity index. Combined in vivo intravital microscopy and lentiviral rescue experiments with in vitro cell culture demonstrated that MT1‐MMP activity in endothelial cells is required for vasodilation and IA, as well as for nitric oxide production via binding of the C‐terminal fragment of MT1‐MMP substrate thrombospondin‐1 (TSP1) to CD47/αvβ3 integrin. Moreover, TSP1 levels were significantly higher in serum from IBD patients and in vivo administration of an anti‐MT1‐MMP inhibitory antibody or a nonamer peptide spanning the αvβ3 integrin binding site in TSP1 reduced IA during mouse colitis. Our results identify MT1‐MMP as a new actor in inflammatory IA and a promising therapeutic target for inflammatory bowel disease.
Dendritic Cells Therapy with Cytokine-Induced Killer Cells and Activated Cytotoxic T Cells Attenuated Th2 Bias Immune Response

ABSTRACT The aim of this study The purpose of this study is to investigate whether the DC cells combined with CIK cells (DC/CIK) and DC activated cytotoxic T cells (DC-ACT) treatment can promote antitumor response and change the immune indicators by targeting the heterogeneous tumor cell populations at a system level. Methods In this study, 112 patients with cancer were assigned to the DC/CIK treatment and 116 patients received the DC-ACT therapy. We detected the lymphocyte subsets and other immune indicators pre- and post-treatment to evaluate the changes of patient’s immunity and compare the differences in immune status between two adoptive cellular immunotherapies. Results DC/CIK therapy elevated the percentage of CD3+ HLA-DR+ T cells, NK cells and several serological cytokines such as IL-2, IL-6 after cell infusion (p < .05). DC-ACT therapy could increase the total CD3 + T cells, CD8 + T cells, CD3+ HLA-DR+ cells and IL-12 cytokines after cell infusion (p < .05). The levels of IL-4/IFN-γ, IL-4/IL-12 and IL-6/IL-12 were reduced significantly in the DC-ACT group compared with DC/CIK group. These observations suggested that DC-ACT therapy has more dominance to induce Th1 cytokine response instead of skewing toward the Th2 cytokine profile based on the immunomodulatory properties. Conclusions These results indicated that DC, CIK, and DC-ACT cells exert anti-tumor activity through the different pathways. Thus, this work may provide valuable insights into the clinical curative effect evaluation of immunocyte therapy and the design of combined immunotherapeutic strategies for malignant tumors.
DNA Readout Viewer (DRV): visualization of specificity determining patterns of protein-binding DNA segments

Abstract Summary The sequence specific recognition of DNA by regulatory proteins typically occurs by establishing hydrogen bonds and non-bonded contacts between chemical sub-structures of nucleotides and amino acids forming the compatible interacting surfaces. The recognition process is also influenced by the physicochemical and conformational character of the target oligonucleotide motif. Although the role of these mechanisms in DNA-protein interactions is well-established, bioinformatical methods rarely address them directly, instead binding specificity is mostly assessed at nucleotide level. DNA Readout Viewer (DRV) aims to provide a novel DNA representation, facilitating in-depth view into these mechanisms by the concurrent visualization of functional groups and a diverse collection of DNA descriptors. By applying its intuitive representation concept for various DNA recognition related visualization tasks, DRV can contribute to unravelling the binding specificity factors of DNA-protein interactions. Availability and implementation DRV is freely available at https://drv.brc. hu. Supplementary information Supplementary data are available at Bioinformatics online.