Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of BCR-ABL1 Transcript Type on Response, Treatment-Free Remission Rate and Survival in Chronic Myeloid Leukemia Patients Treated with Imatinib

The most frequent BCR-ABL1-p210 transcripts in chronic myeloid leukemia (CML) are e14a2 and e13a2. Imatinib (IM) is the most common first-line tyrosine–kinase inhibitor (TKI) used to treat CML. Some studies suggest that BCR-ABL1 transcript types confer different responses to IM. The objective of this study was to correlate the expression of e14a2 or e13a2 to clinical characteristics, cumulative cytogenetic and molecular responses to IM, acquisition of deep molecular response (DMR) and its duration (sDMR), progression rate (CIP), overall survival (OS), and treatment-free remission (TFR) rate. We studied 202 CML patients, 76 expressing the e13a2 and 126 the e14a2, and correlated the differential transcript expression with the above-mentioned parameters. There were no differences in the cumulative incidence of cytogenetic responses nor in the acquisition of DMR and sDMR between the two groups, but the e14a2 transcript had a positive impact on molecular response during the first 6 months, whereas the e13a2 was associated with improved long-term OS. No correlation was observed between the transcript type and TFR rate.
Stereotactic Ablative Brachytherapy: Recent Advances in Optimization of Radiobiological Cancer Therapy

Simple Summary Emerging studies involving ablative brachytherapy with curative effect have been published, but the evidence was not comprehensively discussed. This study will provide an overview of stereotactic ablative brachytherapy, focusing on the advances in stereotactic ablative brachytherapy optimization, and provide insights on the future benefits of the combined application of stereotactic ablative brachytherapy with cancer immunotherapies. Abstract Brachytherapy (BT), a type of focal anti-cancer radiotherapy, delivers a highly focused radiation dose to localized tumors, sparing surrounding normal tissues. Recent technological advances have helped to increase the accuracy of BT and, thus, improve BT-based cancer treatment. Stereotactic ablative brachytherapy (SABT) was designed to improve the ablative effect of radiation, which was achieved via improved image guidance, and calculation of ablative dose, shorter treatment duration, and better organ preservation. Recently collected data characterized SABT as having the potential to cure various early-stage cancers. The method provides higher tumor control rate levels that were previously achievable only by surgical resection. Notably, SABT is suitable for application with unresectable malignancies. However, the pathological assessment of SABT irradiated tumors is limited due to difficulties in specimen acquisition. Prostate, lung, liver, and gynecological cancers are the most commonly reported SABT-treated malignancies. This study will give an overview of SABT, focusing on the advances in SABT optimization, and provide insights on the future benefits of the combined application of SABT with cancer immunotherapies.
Development of Multidrug Resistance in Acute Myeloid Leukemia Is Associated with Alterations of the LPHN1/GAL-9/TIM-3 Signaling Pathway

Simple Summary Latrophilin-1 is a latrotoxin receptor and is commonly found in the plasma membrane of neurons. This receptor has recently been identified in the plasma membrane of myeloid leukemia blasts but not in healthy leukocytes. We have shown that the development of drug resistance associated with ABCB1 overexpression leads to decreased regulation of latrophilin-1 in human acute myeloid leukemia cell lines. Here, we proved that latrophilin-1 expression also occurs in the myeloid blasts of patients newly diagnosed with myelodysplastic syndrome when ABCB1 is overexpressed. Furthermore, we provided the evidence that in case of ABCB1 overexpression in human acute myeloid leukemia cell lines, changes in the expression of latrophilin-1-regulated proteins occur that are thought to allow myeloid blasts to escape control of the immune system. All of the above changes in protein expression appear to be involved in the overall altered phenotype of neoplastic myeloid cells following ABCB1-mediated MDR development. Abstract P-glycoprotein (known as ABCB1 transporter) expression in myeloid blasts of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) leads to the commonly observed multidrug resistance. Overexpression of latrophilin-1 was detected in leukemic cells from AML patients. In a previous study, we showed that ABCB1 overexpression is associated with decreased latrophilin-1 expression in MOLM-13/VCR and SKM-1/VCR AML cell variants derived from MOLM-13 and SKM-1 cells by vincristine selection/adaptation. In the present study, we found that if ABCB1 overexpression occurs in myeloid blasts of newly diagnosed MDS patients, latrophilin-1 expression is attenuated. Latrophilin-1 may initiate TIM-3- and galectin-9-mediated immune escape. We demonstrated changes in the expression of both proteins by comparing ABCB1-positive cell variants (MOLM-13/VCR, SKM-1/VCR) with their ABCB1-negative counterparts. Galectin-9 was present in our cell lines in eight protein isoforms for which we identified the respective transcription variants resulting from alternative splicing, and we verified their structure by sequencing. The isoform profile of galectin-9 was different between ABCB1-positive and ABCB1-negative cell variants. The interaction partner of galectin-9 is CD44, and its expression was altered in the ABCB1-positive variants MOLM-13/VCR and SKM-1/VCR compared to their ABCB1-negative counterparts.
Research on the Fused Deposition Modeling of Polyether Ether Ketone

As a special engineering polymer, polyether ether ketone (PEEK) has been used widely due to its excellent mechanical properties, high thermal stability, and chemical resistance. Fused deposition modeling (FDM) is a promising process for fabricating PEEK parts. However, due to the semi-crystalline property and high melting point of PEEK, determining appropriate process parameters is important to reduce warpage deformation and improve the mechanical properties of PEEK. In this article, the influence of raster angle and infill density was determined by single factor experiment, which are the two most important parameters. The results showed that samples with 0°/90° raster angle and 50% infill density had the best comprehensive properties in terms of warpage deformation, tensile strength, and specific strength. Subsequently, based on the results above, the effects of printing speed, nozzle temperature, platform temperature, raster width, and layer thickness were analyzed by orthogonal experiment. The results indicated that platform temperature had the greatest impact on warpage deformation while printing speed and nozzle temperature were significant parameters on tensile strength. Through optimization, warpage deformation of the samples could be reduced to almost 0 and tensile strength could increase by 19.6% (from 40.56 to 48.50 MPa). This will support the development of FDM for PEEK.
Object Detection and Depth Estimation Approach Based on Deep Convolutional Neural Networks †

In this paper, we present a real-time object detection and depth estimation approach based on deep convolutional neural networks (CNNs). We improve object detection through the incorporation of transfer connection blocks (TCBs), in particular, to detect small objects in real time. For depth estimation, we introduce binocular vision to the monocular-based disparity estimation network, and the epipolar constraint is used to improve prediction accuracy. Finally, we integrate the two-dimensional (2D) location of the detected object with the depth information to achieve real-time detection and depth estimation. The results demonstrate that the proposed approach achieves better results compared to conventional methods.
Repurposing DPP-4 Inhibitors for Colorectal Cancer: A Retrospective and Single Center Study

Simple Summary Colorectal cancer is one of the most common causes and the leading cause of cancer deaths worldwide. Its poor prognosis highlights the urgent need for more effective treatments. Repurposing approved drugs is a promising strategy as preclinical screenings can be minimized. The aim of our retrospective study was to investigate the potential of Dipeptidyl-peptidase 4 (DPP4)-inhibitors, which are safe Food and Drug Association (FDA)-approved drugs for treating diabetes, in treating CRC patients. Our findings conclude that CRC patients with diabetes and treated with DPP4-inhibitors in our hospital during 2006–2015, their 5-year prognosis following curative resection was significantly better than those treated with metformin. We further showed that their prognosis was associated with immune cell population features that associated with better prognosis, and immune cell profile is a biomarker for predicting the prognosis of DPP4-inhibitors treated CRC patients. Abstract Background: There have been studies reporting the crucial roles of Dipeptidyl-peptidase 4 (DPP4) in colorectal cancer (CRC) initiation and progression, whereas DPP4-inhibitors are safe Food and Drug Association (FDA)-approved drugs for treating diabetes. This study aims to investigate the association between DPP4-inhibitor treatment and the prognosis of CRC patients. Methods: Clinical data of CRC patients with diabetes and the prescription of DPP4-inhibitors who had undergone curative surgery in our hospital between January 2006 and December 2015 were retrieved. Their survival data and immune cell population in circulatory blood were compared to those treated with metformin. Results: The DPP4-inhibitor patient group showed a significantly better 5-year disease-free survival (median DFS = 1733 days, 95% CI = 1596 to 1870 days) when compared to the metformin group (p = 0.030, median DFS = 1382 days, 95% CI = 1246 to 1518 days). 33 out of the 92 patients in the metformin group showed recurrence whereas only 3 of the 26 patients in the DPP4-inhibitor group showed recurrence (p = 0.033). Cox regression analysis demonstrated that DPP4-inhibitor application is a favorable factor associated with a lower risk of recurrence (Hazard ratio = 0.200, p = 0.035). Furthermore, our results suggested that the immune cell profile of CRC patients is a potential biomarker for response to DPP4-inhibitor treatment. Conclusion: This study demonstrated the association of DPP4-inhibitor treatment with a better prognosis of CRC patients.
Fiber Selection for Reinforced Additive Manufacturing

The purpose of this review is to survey, categorize, and compare the mechanical and thermal characteristics of fibers in order to assist designers with the selection of fibers for inclusion as reinforcing materials in the additive manufacturing process. The vast “family of fibers” is described with a Venn diagram to highlight natural, synthetic, organic, ceramic, and mineral categories. This review explores the history and practical uses of particular fiber types and explains fiber production methods in general terms. The focus is on short-cut fibers including staple fibers, chopped strands, and whiskers added to polymeric matrix resins to influence the bulk properties of the resulting printed materials. This review discusses common measurements for specific strength and tenacity in the textile and construction industries, including denier and tex, and discusses the proposed “yuri” measurement unit. Individual fibers are selected from subcategories and compared in terms of their mechanical and thermal properties, i.e., density, tensile strength, tensile stiffness, flexural rigidity, moisture regain, decomposition temperature, thermal expansion, and thermal conductivity. This review concludes with an example of the successful 3D printing of a large boat at the University of Maine and describes considerations for the selection of specific individual fibers used in the additive manufacturing process.
Mechanically Alloyed CoCrFeNiMo0.85 High-Entropy Alloy for Corrosion Resistance Coatings

High-entropy alloys could provide a solution for corrosion resistance due to their impressive properties. Solid-state processing of high purity Co, Cr, Fe, Ni and Mo metallic powders and consolidation resulted in a bulk material that was further machined into electro spark deposition electrodes. After the stainless steel substrate surface preparation, thin successive layers of the high-entropy alloy were deposited and Pull-Off testing was performed on the newly obtained coating, for a better understanding of the adhesion efficiency of this technique. Good adhesion of the coating to the substrate was proved by the test and no cracks or exfoliations were present. Corrosion resistance testing was performed in a liquid solution of 3.5 wt. % NaCl for 6 h at room temperature and the results obtained validated our hypothesis that CoCrFeNiMo0.85 high-entropy alloys could provide corrosion resistance when coating a stainless steel substrate.
Upregulated MUC2 Is an Unfavorable Prognostic Indicator for Rectal Cancer Patients Undergoing Preoperative CCRT

For locally advanced rectal cancer patients, introducing neoadjuvant concurrent chemoradiotherapy (CCRT) before radical resection allows tumor downstaging and increases the rate of anus retention. Since accurate staging before surgery and sensitivity prediction to CCRT remain challenging, a more precise genetic biomarker is urgently needed to enhance the management of such situations. The epithelial mucous barrier can protect the gut lumen, but aberrant mucin synthesis may defend against drug penetration. In this study, we focused on genes related to maintenance of gastrointestinal epithelium (GO: 0030277) and identified mucin 2 (MUC2) as the most significantly upregulated gene correlated with CCRT resistance through a public rectal cancer transcriptome dataset (GSE35452). We retrieved 172 records of rectal cancer patients undergoing CCRT accompanied by radical resection from our biobank. We also assessed the expression level of MUC2 using immunohistochemistry. The results showed that upregulated MUC2 immunoexpression was considerably correlated with the pre-CCRT and post-CCRT positive nodal status (p = 0.001 and p < 0.001), advanced pre-CCRT and post-CCRT tumor status (p = 0.022 and p < 0.001), vascular invasion (p = 0.015), and no or little response to CCRT (p = 0.006). Upregulated MUC2 immunoexpression was adversely prognostic for all three endpoints, disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS) (all p < 0.0001), at the univariate level. Moreover, upregulated MUC2 immunoexpression was an independent prognostic factor for worse DSS (p < 0.001), LRFS (p = 0.008), and MeFS (p = 0.003) at the multivariate level. Collectively, these results imply that upregulated MUC2 expression is characterized by a more advanced clinical course and treatment resistance in rectal cancer patients undergoing CCRT, revealing the potential prognostic utility of MUC2 expression.
How Machine Perfusion Ameliorates Hepatic Ischaemia Reperfusion Injury

The increasing disparity between the number of patients listed for transplantation and the number of suitable organs has led to the increasing use of extended criteria donors (ECDs). ECDs are at increased risk of developing ischaemia reperfusion injury and greater risk of post-transplant complications. Ischaemia reperfusion injury is a major complication of organ transplantation defined as the inflammatory changes seen following the disruption and restoration of blood flow to an organ—it is a multifactorial process with the potential to cause both local and systemic organ failure. The utilisation of machine perfusion under normothermic (37 degrees Celsius) and hypothermic (4–10 degrees Celsius) has proven to be a significant advancement in organ preservation and restoration. One of the key benefits is its ability to optimise suboptimal organs for successful transplantation. This review is focused on examining ischaemia reperfusion injury and how machine perfusion ameliorates the graft’s response to this.
Key Regulators of Sucrose Metabolism Identified through Comprehensive Comparative Transcriptome Analysis in Peanuts

Sucrose content is a crucial indicator of quality and flavor in peanut seed, and there is a lack of clarity on the molecular basis of sucrose metabolism in peanut seed. In this context, we performed a comprehensive comparative transcriptome study on the samples collected at seven seed development stages between a high-sucrose content variety (ICG 12625) and a low-sucrose content variety (Zhonghua 10). The transcriptome analysis identified a total of 8334 genes exhibiting significantly different abundances between the high- and low-sucrose varieties. We identified 28 differentially expressed genes (DEGs) involved in sucrose metabolism in peanut and 12 of these encoded sugars will eventually be exported transporters (SWEETs). The remaining 16 genes encoded enzymes, such as cell wall invertase (CWIN), vacuolar invertase (VIN), cytoplasmic invertase (CIN), cytosolic fructose-bisphosphate aldolase (FBA), cytosolic fructose-1,6-bisphosphate phosphatase (FBP), sucrose synthase (SUS), cytosolic phosphoglucose isomerase (PGI), hexokinase (HK), and sucrose-phosphate phosphatase (SPP). The weighted gene co-expression network analysis (WGCNA) identified seven genes encoding key enzymes (CIN, FBA, FBP, HK, and SPP), three SWEET genes, and 90 transcription factors (TFs) showing a high correlation with sucrose content. Furthermore, upon validation, six of these genes were successfully verified as exhibiting higher expression in high-sucrose recombinant inbred lines (RILs). Our study suggested the key roles of the high expression of SWEETs and enzymes in sucrose synthesis making the genotype ICG 12625 sucrose-rich. This study also provided insights into the molecular basis of sucrose metabolism during seed development and facilitated exploring key candidate genes and molecular breeding for sucrose content in peanuts.
Platelet and Erythrocyte Extravasation across Inflamed Corneal Venules Depend on CD18, Neutrophils, and Mast Cell Degranulation

Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the β2-integrin, CD18 (CD18hypo mice) shows reduced platelet extravasation with PMN extravasation apparently unaffected. To better define the role of CD18 on platelet extravasation, we focused on two relevant cell types expressing CD18: PMNs and mast cells. Following corneal abrasion in WT mice, we observed not only extravasated PMNs and platelets but also extravasated erythrocytes (RBCs). Ultrastructural observations of engorged limbal venules showed platelets and RBCs passing through endothelial pores. In contrast, injured CD18hypo mice showed significantly less venule engorgement and markedly reduced platelet and RBC extravasation; mast cell degranulation was also reduced compared to WT mice. Corneal abrasion in mast cell-deficient (KitW-sh/W-sh) mice showed less venule engorgement, delayed PMN extravasation, reduced platelet and RBC extravasation and delayed wound healing compared to WT mice. Finally, antibody-induced depletion of circulating PMNs prior to corneal abrasion reduced mast cell degranulation, venule engorgement, and extravasation of PMNs, platelets, and RBCs. In summary, in the injured cornea, platelet and RBC extravasation depends on CD18, PMNs, and mast cell degranulation.
On the Relationship between Hydrogen Bond Strength and the Formation Energy in Resonance-Assisted Hydrogen Bonds

Resonance-assisted hydrogen bonds (RAHB) are intramolecular contacts that are characterised by being particularly energetic. This fact is often attributed to the delocalisation of π electrons in the system. In the present article, we assess this thesis via the examination of the effect of electron-withdrawing and electron-donating groups, namely −F, −Cl, −Br, −CF3, −N(CH3)2, −OCH3, −NHCOCH3 on the strength of the RAHB in malondialdehyde by using the Quantum Theory of Atoms in Molecules (QTAIM) and the Interacting Quantum Atoms (IQA) analyses. We show that the influence of the investigated substituents on the strength of the investigated RAHBs depends largely on its position within the π skeleton. We also examine the relationship between the formation energy of the RAHB and the hydrogen bond interaction energy as defined by the IQA method of wave function analysis. We demonstrate that these substituents can have different effects on the formation and interaction energies, casting doubts regarding the use of different parameters as indicators of the RAHB formation energies. Finally, we also demonstrate how the energy density can offer an estimation of the IQA interaction energy, and therefore of the HB strength, at a reduced computational cost for these important interactions. We expected that the results reported herein will provide a valuable understanding in the assessment of the energetics of RAHB and other intramolecular interactions.
Lysophosphatidic acid receptor isoforms expression in prostate cancer cells is differentially regulated by the CYP17A1 inhibitor abiraterone and depends on the androgen receptor

Prostate cancer (PC) treatment with steroid synthesis inhibitor, abiraterone acetate (AA) provides substantial survival advantages in advanced PC therapy. Owing to AA's anti-proliferative efficacy, even in the absence of androgen receptor (AR), the molecular mode of action is suspected to be a result of simultaneously targeted cellular factors. The present study demonstrated a differentially regulated expression of proliferative lysophosphatidic acid receptor (LPAR) isoforms in androgen receptor AR-positive LNCaP cells incubated with AA. Since LPAR regulation in AR-negative PC-3 cells is unaffected, it could be assumed that AA’s anticancer activity on LPAR expression depends on AR signaling cascades.
Variability of Body Build and Physiological Spinal Curvatures of Young People in an Accelerated Longitudinal Study

The human body is characterized by the variability of the characteristics of body build, which is expressed in the instability of spinal curvatures, which change during ontogeny. This phenomenon leads to a phylogenetic evolution of the human body build and posture. The aim of the study was to assess the dynamics of the variability of traits and indices of body build and posture and their mutual relations. It was assumed that over the 10-year observation period, a significant variability and relationships will be observed between the characteristics of body build and posture in young adults. Between 2006 and 2016, 2154 women and men aged 19.6 ± 0.8 were examined (first-year students at the University of Economics in Katowice, Poland). Measurements of basic anthropometric measurements and angular values of lumbar lordosis and thoracic kyphosis were performed. The collected data were analysed statistically, and the intergroup and intragroup differences were evaluated (ANOVA with repeated measures). The dynamics of variability (by building time series) and absolute and single-base increments were determined. The body build of young men and women in the period of ontogenetic stabilization in the study group has changed statistically significantly over the decade. A prediction of the increases in body weight and hip circumference was recorded over a period of 10 years, especially in men. The characteristics of body posture have also undergone a significant progressive change. In women, thoracic kyphosis increased by 96.15%, whereas in men, lumbar lordosis decreased by 52.65%. Significant sexual differentiation was shown for such characteristics as body height, waist circumference and the angle of lumbar lordosis. The relationships between the characteristics of body build and posture were verified. There was a moderate relationship between the hip circumference and lumbar lordosis in women and a weak relationship between body height and the angle of thoracic kyphosis in men.