Search

For mechanical automobiles, elastomers are regarded as a common vibration damping material. The most widely used components are made of rubber, mostly because of their cost. PUR (rigid polyurethane) compounds are alternatives. This study presents the findings from studies on polyurethane materials in a specific hardness configuration. The hardness and fatigue tests received the most attention, and more crucially, the impact of the hardness value achieved on fatigue was investigated using both experimental and numerical methods. It was shown how a material with a specific stiffness, defined as 90ShA hardness, behaved significantly. All of the outcomes were contrasted with those of competitive materials, such rubbers, which had comparable hardness. PUR consistently demonstrated substantial fracture toughness.

The numerical and experimental examinations in the behavior of ARMOX 500 T steel plates of a standard thickness under blast loading are presented in this study. Furthermore, the dynamic reaction of the steel plate is crucial, particularly when subjected to blast loads produced by various explosive forms and at a certain stand-off distance (SoD). This study conducted experimental and numerical simulation tests on steel plates under the close-range air blast loads generated by 150 g TNT cylindrical explosives, which are the most widely used explosives in the military and engineering fields. In order to investigate the failure modes of steel plates, close-range air blast load experiments were conducted at a 400 mm SoD. Pressure gauges were positioned at equal distances, and the impact of these tests on the failure deformation and dynamic response of the steel plate was quantitatively examined. Ultimately, the properties of shock waves produced by cylindrical explosives were examined in order to ascertain how SoD and charge quantity affected the shock waves' spatial dispersion.

Waldenström macroglobulinemia (WM) is a rare indolent B-cell non-Hodgkin lymphoma with lymphoplasmacytic morphology, associated with immunoglobulin M (IgM) monoclonal gammopathy. The coexistence of WM and immunoglobulin light chain (AL) amyloidosis is an uncommon but well-described phenomenon. In patients suffering from IgM AL amyloidosis soft tissue involvement and neuropathy are more prevalent in comparison to non-IgM patients. We present a case of 82-year old female with WM and intercurrent IgM AL amyloidosis, presenting with massive amyloidomas of both lower extremities, without significant cardiac and renal involvement. The patient was refractory to several lines of treatment and finally started on zanubrutinib monotherapy, with rapid and sustained very good partial hematologic response (VGPR) and clinical improvement.

Horses have been companions of people for thousands of years. Areas in which humans use these animals include, for example, transport, participation in sports competitions, or during rehabilitation (hippotherapy). Unfortunately, injuries such as lower limb fracture very often require euthanasia due to the significant difficulties in conducting fracture therapy/repair. Therefore, there are still many possibilities for the improvement of existing treatments. The aim of the study was to conduct a numerical analysis enabling the prediction of bone union of the third metacarpal bone of a horse. The loading conditions and type of fracture were based on a pony weighing 120 kg; however, research on a live animal was not the purpose of this study. Numerical studies were carried out for three different methods of stabilization using bone plates in the Ansys program (lateral, anterior, and lateral–anterior stabilization). An algorithm based on the Carter model was used to predict bone union, while linear-coupled models were used to describe the behaviour of materials. The authors also performed dynamic analyses in the Abaqus/Explicit program to determine the maximum speed at which the horse could move so that the fracture would not deepen. For dynamic analyses, the authors used nonlinear models—Johnson–Cook in the case of the 316L surgical steel material and cortical bone. Material failure was described using the Johnson–Cook failure model for steel and the limit strain model for cortical bone. A series of numerical simulations allowed to determine the direction of bone union building, and the most favourable case of stabilization was determined.

Abstract Background The genomes of present-day non-Africans are composed of 1–3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50–60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations. Results The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19–1.54, P = 3.59 × 10–6), with a P-value close to a threshold that takes into account multiple testing. Conclusions Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.

Стаття представляє результати досліджень з впливу режимів тонкого боразонового шліфування на формування параметру шорсткості Ra циліндричних робочих поверхонь нових антифрикційних композитних деталей на основі утилізованих і регенерованих шліфувальних відходів швидкорізальної сталі Р6М5 з додаванням твердого мастила CaF2, що призначені для оснащення вузлів офсетних циліндрів друкарської техніки. Експерименти виконувались застосовуючи крупно- і дрібнозернисті боразонові круги на гумово-бакелітній GB1, бакелітній В1, керамічній К1 та металевій М1 зв’язці. Показано, що основні закономірності формування параметру шорсткості Ra співпадають при плоскому, круглому зовнішньому та внутрішньому боразоновому шліфуванні нових композиційних деталей. Виявлено, що на параметр шорсткості поверхні Ra суттєво впливають зернистість ріжучого інструменту, матеріал зв’язки боразонового кругу та режими тонкого боразонового шліфування. Показано, що, знаючи зернистість боразонового шліфувального кругу, можна розрахувати параметр шорсткості Ra і впевнитись у тому, що вибраний інструмент забезпечить вимоги до якості робочих поверхонь композитних деталей тертя. Мінімізація параметру шорсткості поверхні Ra до величин 0,215–0,375 мкм забезпечується використанням шліфувальних кругів з боразону Во зернистістю 14–28 мкм на гумово-бакелітній зв’язці за мінімальних режимах різання — поздовжньої подачі Vв, поперечної подачі Sпоп. і глибини різання t. Робочі поверхні нових самозмащувальних композитів, які оброблені за визначеними режимами тонкого боразонового шліфування, сприяють швидкому припрацьовуванню контактної пари через утворення на ділянках контакту самозмащувальних антизадирних плівок, що забезпечує мінімізацію інтенсивності зношування вузла. Одержані результати відкривають можливості для істотного поліпшення стабільності і надійності роботи важконавантажених вузлів тертя друкарської техніки, чому сприяють високі параметри якості поверхонь композитних деталей після боразонового тонкого шліфування.

This paper presents the possibility of using additional ballistic shields based on composite materials, which are applied to the body of a passenger car. A ballistic laminate made of Twaron T 750 aramid fabric with 5 mm thick and 2 mm thick magnetic foil was used. In the first stage, the mechanical parameters of the tested ballistic laminate system were determined in tensile tests. In field tests, the considered system was analyzed in terms of impact with a 9 × 19 mm FMJ Parabellum projectile, and then the results were numerically verified. The work was focused on the validation of numerical models. The appropriate correlation level of the numerical results was obtained with the fit, which was estimated at approximately 7%; furthermore, the results prove the correctness of this study’s research methodology.

The genetic factors of adult acute lymphoblastic leukemia (ALL) development are only partially understood. The Runt-Related Transcription Factor (RUNX) gene family play a crucial role in hematological malignancies, serving both a tumor suppressor and promoter function. The aim of this study was the assessment of relative RUNX1 and RUNX3 genes expression level among adult ALL cases and a geographically and ethnically matched control group. The relative RUNX1 and RUNX3 genes expression level was assessed by qPCR. The investigated group comprised 60 adult patients newly diagnosed with ALL. The obtained results were compared with a group of 40 healthy individuals, as well as clinical and hematological parameters of patients, and submitted for statistical analysis. ALL patients tend to have significantly higher RUNX1 gene expression level compared with controls. This observation is also true for risk group stratification where high-risk (HR) patients presented higher levels of RUNX1. A higher RUNX1 transcript level correlates with greater leukocytosis while RUNX3 expression is reduced in Philadelphia chromosome bearers. The conducted study sustains the hypothesis that both a reduction and increase in the transcript level of RUNX family genes may be involved in leukemia pathogenesis, although their interaction is complex. In this context, overexpression of the RUNX1 gene in adult ALL cases in particular seems interesting. Obtained results should be interpreted with caution. Further analysis in this research field is needed.

The authors of this paper focused their attention on developing numerical models of mechanical wave propagation along human tissue as a result of the application of the measuring head of the FibroScan® elastograph. The FibroScan® diagnostic device is used for diagnostic testing of liver fibrosis and steatosis. This examination is carried out using an in vivo method by directly applying the surface of the ultrasonic measuring probe to the patient’s skin at the site of the liver. The authors’ idea is to use this apparatus for non-invasive testing on the liver used for transplantation. In order to do this, the measuring head cap should be modified so that its application to the liver does not result in damage as a result of mechanical wave excitation. The purpose of the manuscript was to build numerical models of the liver and the tissues surrounding the liver. Then, the corresponding numerical simulations were carried out, the results of which corresponded to the mechanical–acoustic properties of the physical models of the tissues. The obtained results were validated on a set of commercial calibrated phantoms. High agreement of the numerical models was obtained.

To better characterize the heterogeneity of multiple myeloma (MM), we profiled plasma cells (PCs) and their B cell lymphopoiesis in the BM samples from patients with monoclonal gammopathy of undetermined significance, smoldering MM, and active MM by mass cytometry (CyTOF) analysis. Characterization of intra- and interneoplastic heterogeneity of malignant plasmablasts and PCs revealed overexpression of the MM SET domain (MMSET), Notch-1, and CD47. Variations in upregulation of B cell signaling regulators (IFN regulatory factor 4 [IRF-4], CXCR4, B cell lymphoma 6 [Bcl-6], c-Myc, myeloid differentiation primary response protein 88 [MYD88], and spliced X box-binding protein 1 [sXBP-1]) and aberrant markers (CD319, CD269, CD200, CD117, CD56, and CD28) were associated with different clinical outcomes in clonal PC subsets. In addition, prognosis was related to heterogeneity in subclonal expression of stemness markers, including neuroepithelial stem cell protein (Nestin), SRY-box transcription factor 2 (Sox2), Krüppel-like factor 4 (KLF-4), and Nanog. Furthermore, we have defined significantly elevated levels of MMSET, MYD88, c-Myc, CD243, Notch-1, and CD47 from hematopoietic stem cells to PCs in myeloma B cell lymphopoiesis, noted even in premalignant conditions, with variably modulated expression of B cell development regulators, including IRF-4, Bcl-2, Bcl-6, and sXBP-1; aberrant PC markers (such as CD52, CD44, CD200, CD81, CD269, CD117, and CXCR4); and stemness-controlling regulators, including Nanog, KLF-4, octamer-binding transcription factor 3/4 (Oct3/4), Sox2, and retinoic acid receptor α2 (RARα2). This study provides the rationale for precise molecular profiling of patients with MM by CyTOF technology to define disease heterogeneity and prognosis.

IntroductionFunctional single-nucleotide polymorphisms (SNPs) in genes regulating cellular uptake, elimination, and metabolism of xenobiotics may potentially influence the outcome of chronic myeloid leukemia (CML) patients treated with BCR-ABL1 tyrosine kinase inhibitors (TKI). Dasatinib, a second-generation TKI, is a substrate of the ABC-superfamily xenobiotic transporters ABCB1 (MDR1, Pg-P) and ABCG2 (BCRP). Pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3) are involved in the control of expression of ABCB1 and ABCG2.Aim of the studyIn this study, we assessed the impact of inherited variants in ABCB1, ABCG2, PXR, and CAR genes on dasatinib efficacy and toxicity in CML.Materials and methodsSixty-one tagging SNPs in ABCB1, ABCG2, PXR, and CAR genes were analyzed by real-time quantitative PCR with specific probes in 86 CML patients who failed imatinib therapy.ResultsWe found the associations between SNPs rs7787082 (ABCB1, OR = 0.2; 95% CI = 0.06-0.66, p = 0.008), rs12505410 (ABCG2, OR = 3.82; 95% CI = 1.38-10.55; p = 0.010), and rs3114018 (ABCG2, OR = 0.24; 95% CI = 0.08-0.71; p = 0.010) and the probability of achieving CCyR. Furthermore, progression-free survival (PFS) was significantly influenced by SNPs rs3732357 (HR = 0.2, 95% CI = 0.26-0.70; p = 0.001), rs3732360 (HR = 0.59; 95% CI = 0.38-0.93; p = 0.020), rs11917714 (HR = 0.58; 95% CI = 0.36-0.92; p = 0.020), and rs3732359 (HR = 0.57; 95% CI = 0.36-0.91; p = 0.024) in PXR; rs2307418 (HR = 2.02; 95% CI = 1.19-3.43; p = 0.048) in CAR; and rs2235023 (HR = 2.49; 95% CI = 1.13-5.50; p = 0.011) and rs22114102 (HR = 1.90; 95% CI = 1.00-3.63; p = 0.028) in ABCB1. Moreover, overall survival (OS) was impacted by rs3842 (HR = 1.84; 95% CI = 1.01-3.33; p = 0.012) and rs2235023 (HR = 2.28; 95% CI = 1.03 = 5.02; p = 0.027) in ABCB1, rs11265571 (HR = 1.59; 95% CI = 0.82-3.08; p = 0.037) and rs2307418 (HR = 73.68; 95% CI = 4.47-1215.31; p = 0.003) in CAR, and rs3732360 (HR = 0.64; 95% CI = 0.40 = 1.04; p = 0.049) in PXR. Taking into account the influence of the tested SNPs on treatment toxicity, we found a significant relationship between allele G of polymorphism in the ABCB1 rs7787082 (OR = 4.46; 95% CI = 1.38-14.39 p = 0.012) and hematological complications assuming the codominant gene inheritance model as well as a significant correlation between the presence of minor allele (G) of SNP rs2725256 in the ABCG2 gene (OR = 4.71; 95% CI = 1.20-18.47; p = 0.026) and the occurrence of non-hematological complications assuming a recessive gene inheritance model.ConclusionOur data suggest that inherited variants in the genes encoding for proteins involved in the transport of xenobiotics may modify the toxicity and efficacy of dasatinib therapy in CML patients.

Multi-layer fabrics are commonly used in ballistics shields with a lower bulletproof class to protect against pistol and revolver bullets. In order to additionally limit the dynamic deflection of the samples, layers reinforced with additional materials, including non-Newtonian fluids compacted by shear, are additionally used. Performing a wide range of tests in each case can be very problematic; therefore, there are many calculation methods that allow, with better or worse results, mapping of the behavior of the material in the case of impact loads. The search for simplified methods is very important in order to simplify the complexity of numerical fabric models while maintaining the accuracy of the results obtained. In this article, multi-layer composites were tested. Two samples were included in the elements subjected to shelling. In the first sample, the outer layers consisted of aramid fabrics in a laminate with a thermoplastic polymer matrix. The middle layer contained a non-Newtonian shear-thickening fluid enclosed in hexagonal (honeycomb) cells. The fluid was produced using polypropylene glycol and colloidal silica powder with a diameter of 14 µm in the proportions of 60/40. The backing plate was made using a 12-layer composite made of Twaron® para-aramid fabrics with a DCPD matrix—not yet used in a wide range of ballistics. Then, numerical simulations were carried out in the Abaqus/Explicit dynamic analysis. The Johnson–Cook constitutive strength model was used to describe the behavior of elastic–plastic materials constituting the elements of the projectiles. For the non-Newtonian fluid, a Up-Us EOS was used. The inner layers of the fabric were treated as an orthotropic material. Complete homogenization of the sample layers was carried out, thanks to which each layer was treated as a homogeneous continuum. As a parameter of fracture mechanics for shield components, the strain criterion was used with the smooth particles hydrodynamics method (SPH). Then, the results of simulations were compared with the results of the ballistic test for both samples placed next to each other, which resulted in the formation of a multi-layer composite in one ballistic test subjected to impact loads during firing with a 9 × 19 mm Parabellum FMJ projectile with an initial velocity of 370 ± 10 m/s. The results of numerical tests are very similar to the ballistic tests, which indicates the correct mapping of the process and the correct conduct of layer homogenization. The applied proportions of the components in the non-Newtonian fluid allowed a reduction in the deflection compared to previous studies. Additionally, the proposal to use a DCPD matrix allowed to obtain a much lower deflection value compared to other materials, which is a novelty in the field of production of ballistic shields.

Abstract Telomeres are involved in processes like cellular growth, chromosomal stability, and proper segregation to daughter cells. Telomere length measured in leukocytes (LTL) has been investigated in different cancer types, including multiple myeloma (MM). However, LTL measurement is prone to heterogeneity due to sample handling and study design (retrospective vs. prospective). LTL is genetically determined; genome-wide association studies identified 11 SNPs that, combined in a score, can be used as a genetic instrument to measure LTL and evaluate its association with MM risk. This approach has been already successfully attempted in various cancer types but never in MM. We tested the “teloscore” in 2407 MM patients and 1741 controls from the International Multiple Myeloma rESEarch (IMMeNSE) consortium. We observed an increased risk for longer genetically determined telomere length (gdTL) (OR = 1.69; 95% CI 1.36–2.11; P = 2.97 × 10−6 for highest vs. lowest quintile of the score). Furthermore, in a subset of 1376 MM patients we tested the relationship between the teloscore and MM patients survival, observing a better prognosis for longer gdTL compared with shorter gdTL (HR = 0.93; 95% CI 0.86–0.99; P = 0.049). In conclusion, we report convincing evidence that longer gdTL is a risk marker for MM risk, and that it is potentially involved in increasing MM survival.

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10−9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10−4−5.79 × 10−14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10−4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10−4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10−4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3− B cells, CD5+IgD− cells, IgM− cells, IgD−IgM− cells, and CD4−CD8− PBMCs (p = 4.9 × 10−4−8.6 × 10−4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27− cells (p = 9.3 × 10−4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3−, MCP-2−, and IL20-dependent pathways.

Abstract We investigated clinical associations of ficolins and mannose-binding lectin (MBL) in 157 patients suffering from acute myeloid leukaemia (AML). Concentrations of ficolin-1, ficolin-2, ficolin-3 and MBL (before chemotherapy) in serum were determined as were selected polymorphisms of the corresponding genes (FCN1, FCN2, FCN3 and MBL2). The control group (C) consisted of 267 healthy unrelated individuals. Median level of ficolin-1 in patients was lower (p 7 days) fever (p = 0.026). Genotyping indicated an association of G/G homozygosity (corresponding to FCN1 gene − 542 G > A polymorphism) with malignancy [p = 0.004, OR = 2.95, 95% CI (1.41–6.16)]. Based on ROC analysis, ficolin-1, -2 and -3 may be considered candidate supplementary biomarkers of AML. Their high potential to differentiate between patients from non-malignant controls but also from persons suffering from other haematological cancers (multiple myeloma and lymphoma) was demonstrated.

Although 21 pancreatic cancer susceptibility loci have been identified in individuals of European ancestry through genome-wide association studies (GWASs), much of the heritability of pancreatic cancer risk remains unidentified. A recessive genetic model could be a powerful tool for identifying additional risk variants. To discover recessively inherited pancreatic cancer risk loci, we performed a re-analysis of the largest pancreatic cancer GWAS, the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including 8,769 cases and 7,055 controls of European ancestry. Six single nucleotide polymorphisms (SNPs) showed associations with pancreatic cancer risk according to a recessive model of inheritance. We replicated these variants in 3,212 cases and 3,470 controls collected from the PANcreatic Disease ReseArch (PANDoRA) consortium. The results of the meta-analyses confirmed that rs4626538 (7q32.2), rs7008921 (8p23.2) and rs147904962 (17q21.31) showed specific recessive effects (p10−3), although none of the six SNPs reached the conventional threshold for genome-wide significance (p < 5×10−8). Additional bioinformatic analysis explored the functional annotations of the SNPs and indicated a possible relationship between rs36018702 and expression of the BCL2L11 and BUB1 genes, which are known to be involved in pancreatic biology. Our findings, while not conclusive, indicate the importance of considering non-additive genetic models when performing GWAS analysis. The SNPs associated with pancreatic cancer in this study could be used for further meta-analysis for recessive association of SNPs and pancreatic cancer risk and might be a useful addiction to improve the performance of polygenic risk scores.

This paper presents the results of a study of polyurethane rigid (PUR) elastomers in terms of the constitutive law identification, and analyses the effect of polyurethane elastomers’ hardness on fatigue properties. The research objects were PUR materials based on 4,4′-diphenylmethane diisocyanate (MDI) with the hardness of 80 ShA and 90 ShA, typically used in various industrial applications. Based on the performed experimental campaign under static and cyclic loading, the constitutive model proposed by Ogden is most appropriate. In addition, a hybrid numerical–experimental analysis (using FEM-DIC) of diabolo specimens’ behaviour is carried out in fatigue tests. Based on the performed fatigue test, it is worth noting that the energy approach describes the fatigue process synonymously compared to the displacement or strain approach. Finally, simple fatigue characteristics were analyzed and statistically validated for both PUR material configurations.

Genetic factors play an important role in the susceptibility to pancreatic cancer (PC). However, established loci explain a small proportion of genetic heritability for PC; therefore, more progress is needed to find the missing ones. We aimed at identifying single nucleotide polymorphisms (SNPs) affecting PC risk through effects on micro-RNA (miRNA) function. We searched in silico the genome for SNPs in miRNA seed sequences or 3 prime untranslated regions (3'UTRs) of miRNA target genes. Genome-wide association data of PC cases and controls from the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic Cancer Case–Control (PanC4) Consortium were re-analyzed for discovery, and genotyping data from two additional consortia (PanGenEU and PANDoRA) were used for replication, for a total of 14,062 cases and 11,261 controls. None of the SNPs reached genome-wide significance in the meta-analysis, but for three of them the associations were in the same direction in all the study populations and showed lower value of p in the meta-analyses than in the discovery phase. Specifically, rs7985480 was consistently associated with PC risk (OR = 1.12, 95% CI 1.07–1.17, p = 3.03 × 10−6 in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of UCHL3, a gene involved in PC progression. In conclusion, our results expand the knowledge of the genetic PC risk through miRNA-related SNPs and show the usefulness of functional prioritization to identify genetic polymorphisms associated with PC risk.

Clonal evolution drives treatment failure in multiple myeloma (MM). Here, we used a custom 372-gene panel to track genetic changes occurring during MM progression at different stages of the disease. A tumor-only targeted next-generation DNA sequencing was performed on 69 samples sequentially collected from 30 MM patients. The MAPK/ERK pathway was mostly affected with KRAS mutated in 47% of patients. Acquisition and loss of mutations were observed in 63% and 37% of patients, respectively. Four different patterns of mutation evolution were found: branching-, mutation acquisition-, mutation loss- and a stable mutational pathway. Better response to anti-myeloma therapy was more frequently observed in patients who followed the mutation loss—compared to the mutation acquisition pathway. More than two-thirds of patients had druggable genes mutated (including cases of heavily pre-treated disease). Only 7% of patients had a stable copy number variants profile. Consequently, a redistribution in stages according to R-ISS between the first and paired samples (R-ISS″) was seen. The higher the R-ISS″, the higher the risk of MM progression and death. We provided new insights into the genetics of MM evolution, especially in heavily pre-treated patients. Additionally, we confirmed that redefining R-ISS at MM relapse is of high clinical value.

The paper is devoted to studying the chemical elements distribution in the material’s structure depending on the manufacturing technological parameters and their effect on properties of a new self-lubricating antifriction composite based on powder nickel alloy EP975 with CaF2 solid lubricant for operation at temperature 800 °C and loads up to 5.0 MPa, in air. The study is focused on the features of alloying elements distribution in the composite matrix, which depends on the manufacturing technology. A uniform distribution of all alloying elements in the studied composite was shown. The chemical elements’ uniform distribution in the material is associated with one of the most important preparatory technological operations in the general manufacturing technology used. This is a technological operation of mixing powders with subsequent analysis of the finished mixture. The uniform distribution of chemical elements determines the uniform arrangement of carbides and intermetallics in the composite. General manufacturing technology, which includes the main operations, such as hot isostatic pressing technology and hardening heat treatment, contributed to the obtainment of a practically isotropic composite with almost the same properties in the longitudinal and transverse directions. Because of the composite’s structural homogeneity, without texturing, characteristics are isotropic. Improving the material’s structural homogeneity helps to keep its mechanical and anti-friction qualities stable at high temperatures and stresses in the air. The performed studies demonstrated the correctness of the developed manufacturing technology that was confirmed by the electron microscopy method, micro-X-ray spectral analysis, mechanical and tribological tests. The developed high-temperature antifriction composite can be recommended for severe operating conditions, such as friction units of turbines, gas pumping stations, and high-temperature units of foundry metallurgical equipment.

A prospective study of 312 patients [194 with multiple myeloma (MM) and 118 with lymphomas (LYMPH)] receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT) was conducted. Ficolins are innate immune defense factors, able to distinguish between “self” “abnormal self,” and “non-self” and contribute to the elimination of the last two by direct opsonization and/or initiation of complement activation via the lectin pathway. Concentrations of ficolin-1, ficolin-2, and ficolin-3 in serially taken serum samples were determined as were the polymorphisms of the corresponding (FCN1, FCN2, and FCN3) genes. Serum samples were collected before conditioning chemotherapy, before HSCT, and once weekly post-HSCT (four to five samples in total); some patients were also sampled at 1 and/or 3 months post-transplantation. The control group (C) consisted of 267 healthy unrelated individuals. Median ficolin-1 and ficolin-2 (but not ficolin-3) levels in MM patients' sera taken before chemotherapy were lower (and correspondingly frequencies of the lowest concentrations were higher) compared with controls. That appeared to be associated with the malignant disease itself rather than with post-HSCT complications (febrile neutropenia, infections accompanied, or not with bacteremia). Higher frequencies of the FCN1 genotype G/A-C/C-G/G (corresponding to polymorphisms at positions −542, −144, and +6658, respectively) and FCN2 gene heterozygosity for the −857 C>A polymorphism were found among patients diagnosed with MM compared with the C group. Furthermore, FCN2 G/G homozygosity (−557 A>G) was found more frequently and heterozygosity G/T at +6424 less frequently among LYMPH patients than among the healthy subjects. Heterozygosity for +1637delC mutation of the FCN3 gene was more common among patients diagnosed with lymphomas who experienced hospital infections. Although no evidence for an association of low ficolin-1 or ficolin-2 with infections during neutropenia following chemotherapy before HSCT was found, we observed a possible protective effect of ficolins during follow-up.

Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.

This article presents an analysis of the effectiveness of available numerical techniques in mapping the characteristic behavior of ballistic ceramics under projectile impact conditions. As part of the work, the ballistic tests were performed on the layered ceramic/steel composite armor and tested with the 7.62 × 39 mm, armor-piercing incendiary (API) BZ projectile. The experimental tests were then mapped using computer simulations. In numerical analyses, four different techniques were used to describe cubic ceramic tiles Al2O3 placed on the ARMOX 500T steel backing plate, i.e.,: the Finite Element Method without Erosion (FEM), Finite Element with erosion (FEM + Erosion), Smoothed Particles Hydrodynamics (SPH) and a hybrid method that converts finite elements to SPH particles after exceeding the defined failure criteria (FEM to SPH conversion). The effectiveness of the individual methods was compared in terms of quality (mapping of characteristic phenomena occurring during the penetration process), quantity (bulge height of the backing plate) and time needed to complete the calculations. On the basis of the results of the experiments and numerical simulations, it was noticed that the most accurate reproduction of the phenomenon of ballistic impact of AP projectiles on ceramic/steel composite armor can be obtained by using a hybrid method, incorporating the conversion of finite elements into SPH particles. This method should be used in cases where accuracy of the results is more important than the time required to complete the calculations. In other situations where the purpose of the calculation is not to determine, for example, the exact value of penetration depth but only to observe a certain trend, the FEM method with defined erosion criteria (variant 2), which is more than 10 times faster, can be successfully used.

Minimal residual disease (MRD) status is now considered as one of the most relevant prognostic factors in multiple myeloma (MM) while MRD negativity became an important endpoint in clinical trials. Here, we report the results of the first study evaluating the reproducibility of high-sensitivity flow cytometry MM MRD assessment in four laboratories in Poland. EuroFlow protocols for instrument setting standardization and sample preparation in MM MRD assessment were implemented in each laboratory. In the inter-laboratory reproducibility study, 12 bone marrow samples from MM patients were distributed and processed in participant laboratories. In the inter-operator concordance study, 13 raw data files from MM MRD measurements were analyzed by five independent operators. The inter-laboratory study showed high 95% overall concordance of results among laboratories. In the inter-operator study, 89% of MRD results reported were concordant, and the highest immunophenotype interpretation differences with regard to expression of CD27, CD45, CD81 were noticed. We confirmed the applicability and feasibility of the EuroFlow protocol as a highly sensitive method of MRD evaluation in MM. Results of our inter-center comparison study demonstrate that the standardization of MM MRD assessment protocols is highly desirable to improve quality and comparability of results within and between different clinical trials.

Plasma cell dyscrasias are a heterogeneous group of diseases characterized by the expansion of bone marrow plasma cells. Malignant transformation of plasma cells depends on the continuity of events resulting in a sequence of well-defined disease stages, from monoclonal gammopathy of undetermined significance (MGUS) through smoldering myeloma (SMM) to symptomatic multiple myeloma (MM). Evolution of a pre-malignant cell into a malignant cell, as well as further tumor progression, dissemination, and relapse, require development of multiple driver lesions conferring selective advantage of the dominant clone and allowing subsequent evolution under selective pressure of microenvironment and treatment. This process of natural selection facilitates tumor plasticity leading to the formation of genetically complex and heterogenous tumors that are notoriously difficult to treat. Better understanding of the mechanisms underlying tumor evolution in MM and identification of lesions driving the evolution from the premalignant clone is therefore a key to development of effective treatment and long-term disease control. Here, we review recent advances in clonal evolution patterns and genomic landscape dynamics of MM, focusing on their clinical implications.

Abstract. The introduction of new agents and management strategies over the past decade has resulted in a major step change in treatment outcomes with deepening responses and increased survival for patients with multiple myeloma. In daily clinical practice, healthcare professionals are now faced with challenges including, optimal treatment sequencing and changing treatment goals. In light of this, a group of experts met to discuss diagnostic and treatment guidelines, examine current clinical practice, and consider how new clinical trial data may be integrated into the management of multiple myeloma in the future.

A simple and prompt method to determine the mechanical properties of industrial multilayer extrusion polypropylene pipes for a gravity sewer network is suggested. The engineering formulas included for calculating the permissible thickness and relative position of a foam core in the pipes are based on a linear-elastic approximation and the rule of mixtures. The applicability of the approximation was justified experimentally during investigation of the effective tensile characteristics of single- and multilayer pipes and each layer specimen by using traditional tests and finite-element calculations. The results obtained were used to formulate engineering recommendations for calculations of this type.

Psoriasis (Ps), an autoimmune disease, and multiple myeloma (MM), a blood neoplasm, are characterized by immune dysregulation resulting from the imbalance between the effector and regulatory cells, including B regulatory (Breg) lymphocytes. Peripheral blood samples from 80 Ps patients, 17 relapsed/refractory MM patients before and after daratumumab (anti-CD38 monoclonal antibody) treatment, 23 healthy volunteers (HVs), and bone marrow samples from 59 MM patients were used in the study. Bregs were determined by flow cytometry using CD19, CD24, and CD38. Intracellular production of interleukin-10 (IL-10) was assessed by flow cytometry after CD40L, LPS, and CpG stimulation. IL-10 serum or plasma concentrations were tested using ELISA method. The percentage of CD19+CD24hiCD38hi Bregs was not different whereas the production of IL-10 in Bregs was significantly higher in Ps patients in comparison with HVs. The percentage of CD19+CD24hiCD38hi Bregs in MM patients was significantly higher than in HVs (p < 0.0001). The percentage of CD19+CD24hiCD38hi Bregs was significantly higher in MM patients with the ISS stage I (p = 0.0233) while IL-10 production in Bregs was significantly higher in ISS stage III (p = 0.0165). IL-10 serum or plasma concentration was significantly higher in Ps and MM patients when compared to HVs (p < 0.0001). Following the treatment with daratumumab the percentages of CD19+CD24hiCD38hi Bregs significantly decreased (p < 0.0003). Here, in the two opposite immune conditions, despite the differences in percentages of Bregs in Ps and MM we have identified some similarities in the IL-10 producing Bregs. Effective treatment of daratumumab besides the anti-myeloma effect was accompanied by the eradication of Bregs.

Finite element modeling of ballistic impact of inserts containing titanium structures were presented in the article. The inserts containing an additional layer made using additive manufacturing technology were analyzed. The layer was created from repetitive elements made without connections (adjacent cells were inseparable). Four variants of printed titanium structures were placed between layers of Twaron CT 750 aramid fabric to create ballistic inserts. In order to assess the ballistic resistance of the inserts, numerical simulations of ballistic impact phenomenon were carried out using LS-Dyna software. In the simulations the inserts were placed on a steel box filled with ballistic clay and were fired at with the 9 × 19 mm full metal jacket (FMJ) Parabellum projectile. The main aim of the work was to check the effectiveness of such solutions in soft ballistic protection applications and to select the most effective variant of 3D printed structure. Results of the numerical analysis showed a high potential for 3D printed structures made of titanium alloys to be used for bulletproof vest inserts. In all analyzed cases the projectile was stopped by the armor. In addition, thanks to the cooperation of adjacent cells, the projectile energy density was distributed over a large area, as evidenced by large volumes of hollows in the ballistic clay. The indentations in the ballistic clay obtained in the simulations were significantly lower than the acceptable value for the back face deformation (BFD) parameter required by international body armor standards.

This paper presents the results of research on ballistic panels made of polymer–matrix composites (PMCs). The analysis covers two types of composites produced by the authors based on high-density polyethylene (PEHD) and polypropylene (PP) reinforced with aramid fabric. Ballistic tests were carried out with the use of two types of projectile: 0.38 Special, and 9 × 19 Parabellum, which are characterized by different velocity and projectile energy. The study presents the X-ray computed tomography (XCT) analysis for structure assessment of ballistic panels and its impact behavior, further compared to the results of computer simulations conducted using the numerical analysis. The quality of the manufactured panels and their damage caused by a ballistic impact was assessed using a multi-scale geometry reconstruction. The mesoscale XCT allowed the internal composite geometry to be analyzed, as well as a unit cell of the representative volume element (RVE) model to be built. The RVE model was applied for homogenization and finite element (FEA) simulation of projectile penetration through the ballistic panel. The macroscale XCT investigation allowed for the quantitative description of the projectile’s impact on the degree of delamination and deformation of the panels’ geometry.

In this paper, the authors presented an analysis of the strengthening of the cumulative jet by the appropriate formation of the detonation wave front acting under the influence of high pressure on the liner. The analysis of the Polish ŁK cumulative charge was carried out using numerical methods in the ABAQUS program. Simulation studies were carried out on axial and peripheral initiations of the explosive cumulative liner. For this purpose, two types of cumulative charges were made with the same design parameters, differing only in the explosive detonation-initiation system. The impact of the elastomer insert on the focusing of the cumulative jet was verified. The influence of peripheral and axial initiation on a cumulative jet’s velocity was investigated. The authors proposed a new conical insert placed in the explosive between the pocket for the detonator and the liner, also changing the material of the cumulative liner. The smoothed-particle hydrodynamics method was used to describe the formation of a cumulative jet. The obtained results were verified experimentally, and they show that modification of the ŁK charge has a positive effect on jet amplification, with an inevitable collapse in the final stage of formation. The obtained results correlate with the literature’s data.

The paper presents the results of studies on the effects of shooting composite materials produced by pressure infiltration with the EN AW-7075 alloy as a matrix and reinforcement in the form of preforms made of α-Al2O3 particles. Composite materials were made with two reinforcement contents (i.e., 30% and 40% vol. of α-Al2O3 particles). The composites produced in the form of 12 mm thick plates were subjected to impact loads from a 7.62 × 39 FMJ M43 projectile fired from a Kalashnikov. The samples of composites with different contents of strengthening particles were subjected to detailed microscopic examination to determine the mechanism of destruction. The effect of a projectile impact on the microstructure of the material within the perforation holes was identified. There were radial cracks found around the puncture holes and brittle fragmentation of the front surfaces of the specimens. The change in the volume of the reinforcement significantly affected the inlet, puncture and outlet diameters. The observations confirmed that brittle cracking dominated the destruction mechanism and the crack propagation front ran mainly in the matrix material and along the boundaries of the α-Al2O3 particles. In turn, numerical tests were conducted to describe the physical phenomena occurring due to the erosion of a projectile hitting a composite casing. They were performed with the use of the ABAQUS program. Based on constitutive models, the material constants developed from the identification of material properties were modelled and the finite element was generated from homogenization in the form of a representative volume element (RVE). The results of microscopic investigations of the destruction mechanism and numerical investigations were combined. The conducted tests and analyses shed light on the application possibilities of aluminium composites reinforced with Al2O3 particles in the construction of add-on-armour protective structures.

We conducted a prospective study of 312 patients (194 with multiple myeloma, 118 with lymphomas) receiving high-dose conditioning chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT). Polymorphisms of MBL2 and MASP2 genes were investigated and serial measurements of serum concentrations of mannose-binding lectin (MBL), CL-LK collectin and MASP-2 as well as activities of MBL-MASP-1 and MBL-MASP-2 complex were made. Serum samples were taken before conditioning chemotherapy, before HSCT and once weekly after (totally 4-5 samples); in minority of subjects also 1 and/or 3 months post transplantation. The results were compared with data from 267 healthy controls and analyzed in relation to clinical data to explore possible associations with cancer and with chemotherapy-induced medical complications. We found a higher frequency of MBL deficiency-associated genotypes (LXA/O or O/O) among multiple myeloma patients compared with controls. It was however not associated with hospital infections or post-HSCT recovery of leukocytes, but seemed to be associated with the most severe infections during follow-up. Paradoxically, high MBL serum levels were a risk factor for prolonged fever and some infections. The first possible association of MBL2 gene 3′-untranslated region polymorphism with cancer (lymphoma) in Caucasians was noted. Heterozygosity for MASP2 gene +359 A>G mutation was relatively frequent in lymphoma patients who experienced bacteremia during hospital stay. The median concentration of CL-LK was higher in myeloma patients compared with healthy subjects. Chemotherapy induced marked increases in serum MBL and MASP-2 concentrations, prolonged for several weeks and relatively slighter decline in CL-LK level within 1 week. Conflicting findings on the influence of MBL on infections following chemotherapy of myeloma and lymphoma have been reported. Here we found no evidence for an association between MBL deficiency and infection during the short period of neutropenia following conditioning treatment before HSCT. However, we noted a possible protective effect of MBL during follow-up, and suspected that to be fully effective when able to act in combination with phagocytic cells after their recovery.

This paper discusses the general conditions relating to ballistic head protection, analyzing the risks that may occur on contemporary battlefields. A thorough literature review has enabled us to present development trends for helmets used in the largest armies in the world. The authors have focused on impacts to the helmet shell, overloading the entire helmet-protected head−neck system. The main objective of this study is to investigate the protective capability of a helmet shell when subjected to projectile−helmet contact, with contact curvature taken as being an indicator of the impact energy concentration. Blunt head trauma was estimated using backface deformation (BFD). The Wz.93 combat helmet was used for testing. Analytically, dependencies were derived to determine the scope of BFD. A five-parameter model of the helmet piercing process was adopted, thus obtaining the optimal BFD range. Verification of theoretical considerations was carried out on a specially developed research stand. In the ballistic tests, dynamic deflection of the helmet’s body was registered using a speed camera. On the impact testing stand, a fragment of the helmet was pierced, producing results in the low impact velocity range. Data have been presented on the appropriate graph in order to compare them with values specified in the relevant standard and existing literature. Our results correlate well with the norm and literature values.

We investigated HLA DRB1 correlations with chronic lymphocytic leukemia (B-CLL) outcome in 90 patients. Neither of the alleles was associated with B-CLL clinical characteristics or mortality. HLA DRB1*01 and HLA DRB1*02-null were associated with shorter overall survival (p=0.007, p=0.002). Our results suggest that HLA-restricted adaptive immunity influences CLL outcome.

In recent years, more and more emphasis has been placed on the use of home filtration systems as a coarse pre-filtration step. The PP (polypropylene) filter cartridge is one of the most common of these systems, with the role of retaining solid suspensions from drinking water. However, few studies have focused on the fouling analysis of PP cartridges using EDS (Energy-Dispersive X-ray Spectroscopy) analysis methods. Through this study, a clear and in-depth view of the structures and morphology of PP filter cartridges as well as their impurity retention capacities and their impact is provided with the help of an SEM (Scanning Electron Microscope) analyzer. To achieve these goals, it was necessary to establish a specialized preparation methodology for this type of material in order to analyze it using the SEM and, at the same time, determine the optimal setting of the SEM parameters (improved resolution, reduced acceleration voltage, reduced data acquisition time, etc.) depending on the analysis performed for the visualization and detailed characterization of surfaces. Based on the SEM-EDS analysis and characterization, an uneven distribution of impurities on the surface of the PP fibers was identified. The number of impurities varied according to the depth of the cartridge due to the sieving effect that occurred owing to the varied sizes and shapes of the impurities, but also the structural differences and pore sizes of the filter material. So, the most common chemical elements identified were Al, Si, Na, Cl, Ca, Fe, and S, having a predominantly higher intensity from the inside to the outside of the PP filter cartridge due to pressure forces and the uneven flow of filtered water. [ABSTRACT FROM AUTHOR]