Search

Introduction: Trimethyltin Chloride (TMT) is a neurotoxin that can kill neurons in the nervous system and activate astrocytes. This neurotoxin mainly damages the hippocampal neurons. After TMT injection, behavioral changes such as aggression and hyperactivity have been reported in animals along with impaired spatial and learning memory. Hence, TMT is a suitable tool for an experimental model of neurodegeneration. The present study aims to determine the palliative effects of Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs) on the hippocampi of rats damaged from TMT exposure. Methods: We assigned 28 male Wistar rats to the following groups: control, model, vehicle, and treatment. The groups received Intraperitoneal (IP) injections of 8 mg/kg TMT. After one week, stem cells were stereotactically injected into the CA1 of the right rats' hippocampi. Spatial memory was determined by the Morris Water Maze (MWM) test 6 weeks after cell transplantation. Finally, the rats' brains were perfused and stained by cresyl violet to determine the numbers of cells in the Cornus Ammonis (CA1) section of the hippocampus. We assessed the expressions of Glial Fibrillary Acidic Protein (GFAP) and Neuronal-specific Nuclear (NeuN) proteins in the right hippocampus by Western blot. Results: The MWM test showed that the treatment group had significantly higher traveled distances in the target quarter compared with the model and vehicle groups (P<0.05). Based on the result of cell count (Nissl staining), the number of cells increased in the treatment group compared with the model and vehicle groups (P<0.05). Western blot results showed up-regulation of GFAP and NeuN proteins in the model, vehicle, and treatment groups compared with the control group. Conclusion: Injection of BM-MSCs may lead to a behavioral and histological improvement in TMT-induced neurotoxicity by increasing the number of pyramidal neurons and improving memory. [ABSTRACT FROM AUTHOR]

Telomere biology disorder (TBD) can present within a wide spectrum of symptoms ranging from severe congenital malformations to isolated organ dysfunction in adulthood. Diagnosing TBD can be challenging given the substantial variation in symptoms and age of onset across generations. In this report, we present two families, one with a pathogenic variant in ZCCHC8 and another with a novel variant in TERC. In the literature, only one family has previously been reported with a ZCCHC8 variant and TBD symptoms. This family had multiple occurrences of pulmonary fibrosis and one case of bone marrow failure. In this paper, we present a second family with the same ZCCHC8 variant (p.Pro186Leu) and symptoms of TBD including pulmonary fibrosis, hematological disease, and elevated liver enzymes. The suspicion of TBD was confirmed with the measurement of short telomeres in the proband. In another family, we report a novel likely pathogenic variant in TERC. Our comprehensive description encompasses hematological manifestations, as well as pulmonary and hepatic fibrosis. Notably, there are no other reports which associate this variant to disease. The families expand our understanding of the clinical implications and genetic causes of TBD. [ABSTRACT FROM AUTHOR]

In our previous contributions we established a multiscale, multiphase material model for the simulation of cancellous bone with the novel idea of including the full coupling of mechanical, electric and magnetic effects, which could be used for example, for the early detection of osteoporosis. While our calculations have already shown promising results, our previous approach lacks very important aspects, strongly limiting the applicability of our findings. In this paper we extend our base model by considering the effect of a surrounding medium on our bone specimen, using improved boundary conditions and differentiating between cortical bone, bone marrow and spongy bone to better reflect the physiological properties of bone. We show numerical results and compare our calculations to our previous modeling. [ABSTRACT FROM AUTHOR]

Resident macrophages of various mammalian organs are characterized by several distinctive features in their gene expression profile and phenotype, including involvement in the regulation of organ functions, as well as reduced sensitivity to proinflammatory activation factors. The reasons for the formation of such a specific phenotype remain the subject of intensive research. Some papers emphasize the role of the origin of organ macrophages. Other studies indicate that monocytes that develop in the red bone marrow are also able to form resident macrophages with a phenotype characteristic of a particular organ, but this requires appropriate microenvironmental conditions. In this article, we studied the possibility of differentiation of monocyte‐derived macrophages into cells with a Kupffer‐like phenotype under the influence of the main stromal components of Kupffer cells macrophage niche: Ito cells, liver sinusoid endotheliocytes and hepatocyte growth factor (HGF). It was found that Kupffer cells are characterized by several features, including increased expression of transcription factors Spic and Id3, as well as MUP family genes, Clusterin and Ngp genes. In addition, Kupffer cells were characterized by a higher proliferative activity. The expression of marker genes of Kupffer cells (i.e. Id3, Spic, Marco and Timd4) increased in monocyte‐derived macrophages during coculture with Ito cells, liver sinusoid endothelial cells, macrophage colony–stimulating factor and HGF cells only by 3 days. However, the expression level of these genes was always higher in Kupffer cells. In addition, a complete coincidence of the expressed gene profile in monocyte‐derived macrophages and Kupffer cells did not occur even after 3 days of culturing. [ABSTRACT FROM AUTHOR]

Bone marrow lesion (BML) volume is a potential biomarker of knee osteoarthritis (KOA) as it is associated with cartilage degeneration and pain. However, segmenting and quantifying the BML volume is challenging due to the small size, low contrast, and various positions where the BML may occur. It is also time-consuming to delineate BMLs manually. In this paper, we proposed a fully automatic segmentation method for BMLs without requiring human intervention. The model takes intermediate weighted fat-suppressed (IWFS) magnetic resonance (MR) images as input, and the output BML masks are evaluated using both regular 2D Dice similarity coefficient (DSC) of the slice-level area metric and 3D DSC of the subject-level volume metric. On a dataset with 300 subjects, each subject has a sequence of 36 IWFS MR images approximately. We randomly separated the dataset into training, validation, and testing sets with a 70%/15%/15% split at the subject level. Since not every subject or image has a BML, we excluded the images without a BML in each subset. The ground truth of the BML was labeled by trained medical staff using a semi-automatic tool. Compared with the ground truth, the proposed segmentation method achieved a Pearson's correlation coefficient of 0.98 between the manually measured volumes and automatically segmented volumes, a 2D DSC of 0.68, and a 3D DSC of 0.60 on the testing set. Although the DSC result is not high, the high correlation of 0.98 indicates that the automatically measured BML volume is strongly correlated with the manually measured BML volume, which shows the potential to use the proposed method as an automatic measurement tool for the BML biomarker to facilitate the assessment of knee OA progression. [ABSTRACT FROM AUTHOR]

Background: In the past 40 years, China has experienced tremendous economic development, but the current situation of hematologists has rarely been reported. A landscape survey of human resources is essential for healthcare development and policy formulation in the future. Methods: The Chinese Society of Hematology initiated a survey of Chinese hematologists in mainland China for evaluating demographic and practice characteristics. Respondents were anonymous, and there were no limitations regarding their age, sex, etc. Results: Totally 2032 hematologists responded, with a median age bracket of 36–45 years. Respondents were well engaged into subspecialties, and 28.1% acquired doctorates of philosophy. Hematopoietic cell transplantation (HCT) centers have been established all over China. Higher-GDP regions reported more advantages, including bigger scale of transplant centers (P < 0.001), younger age structure (P = 0.039), better education qualifications (P = 0.001) and less turnover intentions (P = 0.004), despite of increased risk of medical disputes (P = 0.028). Although females accounted for 65.5% of hematologists, males were older (P < 0.001), and had more senior professional titles (P < 0.001), academic positions (P < 0.001), opportunities for continuing education (P < 0.001), and paper publishing in the recent two years (P = 0.001). For turnover intention, the higher GDP regions led to an independently reduced risk (HR = 0.673, 95%CI [0.482–0.940], P = 0.020), whereas medical disputes resulted in an increased the risk (HR = 2.037, 95%CI [1.513–2.743], P < 0.001). Considering the impact of the COVID-19 pandemic, majority of respondents believed that the decline in patient visits and delay in treatment was within 30%. 67.9% of respondents reported a decrease of the use of bone marrow as grafts but 18.8% reported an increase of cord blood units. 35.0% of the respondents switched their daily work to support the anti-epidemic medical activities. Conclusions: We concluded the discipline of hematology in China has flourished in recent years with a young workforce, while regional economic and gender disparities warrant further continuous optimization. Joint efforts against the impact of COVID-19 are needed in the post-pandemic era. [ABSTRACT FROM AUTHOR]

Fluorine-18 fluorodeoxyglucose ([18F]FDG) is nowadays the leading positron emission tomography (PET) tracer for routine clinical work-ups in hematological malignancies; however, it is limited by false positive findings. Notably, false positives can occur in inflammatory and infective cases or in necrotic tumors that are infiltrated by macrophages and other inflammatory cells. In this context, 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) has been shown to be a promising imaging biomarker of hematological malignant cell proliferation. In this review, a total of 15 papers were reviewed to collect literature data regarding the clinical application of [18F]FLT PET/CT in hematological malignancies. This imaging modality seems to be a suitable tool for noninvasive assessment of tumor grading, also showing a correlation with Ki-67 immunostaining. Moreover, [18F]FLT PET/CT demonstrated high sensitivity in detecting aggressive lymphoma lesions, especially when applying a standardized uptake value (SUV) cutoff of 3. At baseline, the potential of [18F]FLT imaging as a predictive tool is demonstrated by the low tracer uptake in patients with a complete response. However, its use is limited in evaluating bone diseases due to its high physiological uptake in bone marrow. Interim [18F]FLT PET/CT (iFLT) has the potential to identify high-risk patients with greater precision than [18F]FDG PET/CT, optimizing risk-adapted therapy strategies. Moreover, [18F]FLT uptake showed a greater ability to differentiate tumor from inflammation compared to [18F]FDG, allowing the reduction of false-positive findings and making the first one a more selective tracer. Finally, FLT emerges as a superior independent predictor of PFS and OS compared to FDG and ensures a reliable early response assessment with greater accuracy and predictive value. [ABSTRACT FROM AUTHOR]

A reduced incidence of graft versus host disease (GvHD) has been documented among Japanese allogeneic bone marrow transplantation (BMT) patients, as the Japanese are genetically more homogeneous than western populations. To clarify whether this ethnic difference affects the results of allogeneic peripheral blood stem cell transplantation (PBSCT), we conducted a nationwide survey to compare clinical outcomes of allogeneic PBSCT (n = 214) and BMT (n = 295) from a human leucocyte antigen- identical-related donor in Japanese patients. The cumulative incidence of grades II-IV acute GvHD was 374% for PBSCT and 320% for BMT. The cumulative incidence of extensive chronic GvHD at 1 year was significantly higher after PBSCT than BMT (42% vs. 27%; P < 001). The organ involvement patterns of GvHD were different between the two groups. By multivariate analyses, the incidence of chronic GvHD was significantly increased in PBSCT, whereas the stem cell source did not affect the incidence of acute GvHD, transplant-related mortality, relapse or survival. We concluded that Japanese PBSCT patients have an increased risk of chronic GvHD compared with BMT patients, but the incidence of acute GvHD was still lower than in western populations. Thus, the choice of haematopoietic stem cell source should be considered based on data for individual ethnic populations. [ABSTRACT FROM AUTHOR]

We reviewed eight cases that were diagnosed before 1995 with B-prolymphocytic leukaemia (B-PLL) harbouring t(11;14)(q13;q32) and/or cyclin D1 staining. Thirteen B-PLL patients without t(11;14) were selected as controls. Peripheral blood, bone marrow and histological sections were re-examined without cytogenetic information. Final diagnosis was made using morphology, cytogenetics, immunophenotype and immunohistochemistry. Clinical characteristics were similar for both groups except for younger age, male predominance and extranodal involvement in cases with t(11;14). CD5 was more frequently positive in the t(11;14)+ group (80%) than in the t(11;14)− group (31%). Surface membrane immunoglobulin was strongly expressed by all t(11;14)+ cases, but only 45% of t(11;14)− cases. Histopathological and cytological review of cases with t(11;14) showed an infiltrate with a mixture of cells, some resembling prolymphocytes and others with mantle cell lymphoma (MCL) morphology. Blood films of cases with t(11;14) showed features suggestive of B-PLL in three, and in others, a mixture of cells resembling MCL and nucleolated ones; none corresponded to the blastoid form of MCL. We suggest that ‘B-PLL’ with t(11;14) may represent a splenomegalic form of MCL evolving with leukaemia. These cases illustrate the importance of tissue diagnosis with cyclin D1 staining and fluorescence in situ hybridization analysis in B-cell leukaemia with prolymphocytic features. [ABSTRACT FROM AUTHOR]

Neoangiogenesis is an integral component of bone marrow myeloproliferation in patients with myelofibrosis with myeloid metaplasia (MMM). As extramedullary haematopoiesis is a constitutive feature of MMM, we studied spleen neoangiogenesis by a computerized image analysis in MMM patients. Compared with five normal subjects, spleen CD34-staining capillary vascular density (CVD) was 2·1–3·03 times higher than the upper range of normal in six of the 15 (40%) MMM patients. CD8-staining sinusoidal vascular density (SVD) was constantly normal or lesser than normal and was inversely correlated with CVD ( R = −0·53; P = 0·04). In MMM patients who did not receive cytoreductive or radiation therapy in the month before splenectomy ( n = 9), the CVD was a significant determinant of spleen size ( R = 0·88; P = 0·04). In MMM patients, the number of spleen CD34+ haematopoietic stem cells was increased from 1·2 to 98 times the upper limit of normal, and predicted the expansion of CVD ( R = 0·57; P = 0·03). A population of cells expressing the CD34+/CD133+/VEGFR-2+ angiopoietic phenotype was present in the blood and spleen of five of seven patients. These results document that neoangiogenesis is an integral component of spleen re-localization of haematopoietic stem cells and suggest a cellular mechanism for spleen neoangiogenesis. [ABSTRACT FROM AUTHOR]

Haematopoietic progenitor cells proliferate and develop predominantly when they adhere to bone marrow stromal cells such as osteoblasts. Therefore, changes in adhesion may be a common mechanism by which stem cells survive, mature and properly traffic between the bone marrow and the circulation. To characterize these adhesion molecules, we reduced the bone marrow cavity to a simple adhesion assay between KG1a (a CD34+ haematopoietic cell line) and osteosarcoma monolayers (MG-63 or SaOS-2). The data demonstrated that adhesion was mediated by cell-to-cell rather than cell-to-matrix contact, was sensitive to trypsin, calcium chelators and glycosylation inhibitors. Selective pretreatment attributed the constitutive binding to N-linked glycans on KG1a. When carboprocessing was inhibited later at the high mannose intermediate (via deoxymannojirimycin), adhesion was retained. Surprisingly, binding of KG1a to SaOS-2 increased past constitutive levels as doses of tunicamycin or deoxymannojirimycin dropped. Selective pretreatment suggested that this ‘inducible’ binding resides with molecule(s) on SaOS-2. If the terminal sialic acid was digested (via neuraminidase), this induced response was duplicated. These data, verified in primary cells, suggest that the initial tethering between blood and bone cells in this model is probably due to heavily glycosylated, rapidly processed protein(s) on both cell types. [ABSTRACT FROM AUTHOR]

With increasing aging population, osteoporosis has emerged as a public health problem worldwide. Epidemiological data reveal that the prevalence of osteoporosis in cold regions is high, and low temperatures may crucially affect bone mass. Recent studies have found that the transient receptor potential melastatin-8 (TRPM8) channel, a cold-sensitive ion channel, can sense cold environment, and can be activated in cold environment. It may play an antagonistic role in low temperature-induced bone mass reduction. Mechanistically, this function may be ascribed to the activation of TRPM8 channel proteins in human bone marrow mesenchymal stem cells (hBM-MSCs), which causes osteoblast differentiation and mineralization in the bone. TRPM8 channel on the surface of brown adipocytes participates in the thermogenesis in brown adipose tissue (BAT) and the regulation of whole-body energy balance to maintain bone homeostasis. TRPM8 may be involved in bone remodeling throughout life. This paper reviews recent research on the possible antagonistic mechanism of TRPM8 in signaling pathways related to low temperature-induced bone mass loss and assesses the possibility of TRPM8 as a molecular target for the prevention and treatment of low temperature-induced osteoporosis in cold regions. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple myeloma is the second most common hematological malignancy, and the majority of patients have osteolytic lesions by the time of diagnosis. Bone destruction increases the risk of fractures and spinal cord compression, reduces quality of life, and is associated with increased mortality. This paper focuses on current and novel medical and surgical treatment modalities and improvements in prevention and the treatment of therapy-related complications, in particular, medication-related osteonecrosis of the jaw. A special focus reviews new promising targets in the bone marrow microenvironment. Osteolytic bone disease is present in about 80% of patients with multiple myeloma at the time of diagnosis. Managing bone disease in patients with multiple myeloma is a challenge and requires a multi-faceted treatment approach with medication, surgery, and radiation. The established treatments with intravenous or subcutaneous antiresorptives can cause debilitating adverse events for patients, mainly osteonecrosis of the jaw, which, traditionally, has been difficult to manage. Now, oral surgery is recommended and proven successful in 60–85% of patients. Patients with spinal involvement may benefit from surgery in the form of vertebroplasty and kyphoplasty for pain relief, improved mobility, and reestablished sagittal balance, as well as the restoration of vertebral height. These procedures are considered safe, but the full therapeutic impact needs to be investigated further. Ixazomib, the first oral proteasome inhibitor, increases osteoblast differentiation, and recently published preliminary results in patients treated with Ixazomib maintenance have promisingly shown increased trabecular volume caused by prolonged bone formation activity. Other novel potential treatment strategies are discussed as well. [ABSTRACT FROM AUTHOR]

Monoclonal gammopathies (MG) are characterized by the proliferation of plasma cells that produce identical abnormal immunoglobulins (intact or some of their subunits). This abnormal immunoglobulin component is called monoclonal protein (M-protein), and is considered a biomarker of proliferative activity. The identification, characterization and measurement of M-protein is essential for the management of MG. We conducted a systematic review of the different tests and measurement methods used in the clinical laboratory for the study of M-protein in serum and urine, the biochemistry and hematology tests necessary for clinical evaluation, and studies in bone marrow, peripheral blood and other tissues. This review included literature published between 2009 and 2022. The paper discusses the main methodological characteristics and limitations, as well as the purpose and clinical value of the different tests used in the diagnosis, prognosis, monitoring and assessment of treatment response in MG. Included are methods for the study of M-protein, namely electrophoresis, measurement of immunoglobulin levels, serum free light chains, immunoglobulin heavy chain/light chain pairs, and mass spectrometry, and for the bone marrow examination, morphological analysis, cytogenetics, molecular techniques, and multiparameter flow cytometry. [ABSTRACT FROM AUTHOR]

Bone marrow fibrosis represents an important structural change in the marrow that interferes with some of its normal functions. The aetiopathogenesis of fibrosis is not well established except in its primary form. The present review consolidates current understanding of marrow fibrosis. We searched PubMed without time restriction using key words: bone marrow and fibrosis as the main stem against the terms: growth factors, cytokines and chemokines, morphology, megakaryocytes and platelets, myeloproliferative disorders, myelodysplastic syndrome, collagen biosynthesis, mesenchymal stem cells, vitamins and minerals and hormones, and mechanism of tissue fibrosis. Tissue marrow fibrosis-related papers were short listed and analysed for the review. It emerged that bone marrow fibrosis is the outcome of complex interactions between growth factors, cytokines, chemokines and hormones together with their facilitators and inhibitors. Fibrogenesis is initiated by mobilisation of special immunophenotypic subsets of mesenchymal stem cells in the marrow that transform into fibroblasts. Fibrogenic stimuli may arise from neoplastic haemopoietic or non-hematopoietic cells, as well as immune cells involved in infections and inflammatory conditions. Autoimmunity is involved in a small subset of patients with marrow fibrosis. Megakaryocytes and platelets are either directly involved or are important intermediaries in stimulating mesenchymal stem cells. MMPs, TIMPs, TGF-β, PDGRF, and basic FGF and CRCXL4 chemokines are involved in these processes. Genetic and epigenetic changes underlie many of these conditions. Highlights: Fibrosis of the marrow is always secondary to a primary event which may be clonal or non clonal. Megakaryocytes and platelets form the central arm in myelofibrosis. Haemopoietic stem cells, clonal or activated in various inflammatory processes, immune cells and megakaryocytes (clonal or activated) interact with mesenchymal stem cells of GLI+ and Lep+ subsets that differentiate into myofibroblasts, -fibroblasts and fibrocytes. At each of these steps different cytokines, vitamins, hormones and minerals interact to produce the fibrocollagenous matrix. TGF-β and CXCL4 are important growth factors and chemokines assist this process. PDGFα, VEGF, angiopoietin, bFGF-, BMP pathway and inflammatory/oxidative cytokine pathways and tissue oxygen sensing mechanism via HID1α are also involved in the process in specific cases. Vitamins, hormones, minerals, and protease/anti-protease balance finally determine the extent of fibrosis. Many signals converge to produce TGF-β that stimulates marrow fibrosis. There may be a healthy noradrenergic input to the marrow vasculature that prevents fibrosis. Epigenetic regulation of fibrosis is getting increasing attention for understanding the process and directing targeted therapy. Addressing these signals with various targeted therapies alone or in combination are being developed (e.g ruxolotinib in PMF) [ABSTRACT FROM AUTHOR]

Objective: Structural aberrations of 1p36 are very common in most hematologic malignancies. 1p36 consists of genes that are important in oncogenesis. The aim of this study was to define 1p36 abnormalities and their distributions within different hematologic malignancies. Materials and Methods: To achieve this goal, we retrospectively evaluated the cytogenetic results of our hematological cancer cases. Result: We found deletions or rearrangements of breakpoint 1p36 in 18 patients with various hematologic malignancies, including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), multiple myeloma (MM), chronic myeloid leukemia (CML), lymphoma, B cell acute lymphoblastic leukemia (B-ALL), idiopathic thrombocytopenic purpura (ITP) and aplastic anemia (AA). We observed t(1;3)(p36;p21) in one AML-M2 patient and t(1;3)(p36;q21) in two CML patients. Eight patients (1 MDS, 2 MM, 3 CML, 1 AML, and 1 AA) had translocations and rearrangements. One ITP patient had der(1)t(1;1)(p36;q21) and another CML patient had der(1)t(1;1)(p36;q12). We demonstrated several terminal deletions with different breakpoints between 1p11 and 1p36 in five patients, (2 MDS, 2 lymphomas, and 1 B cell acute lymphocytic leukemia). Conclusion: The 1p36 breakpoint is a hot spot for cancer-related chromosome rearrangements and is associated with poor prognosis. In order to emphasize the importance of 1p36 in hematologic malignancies it essential to build a large data pool on the subject. The distribution of breakpoints in 1p abnormalities in our series was remarkable, as 12 out of 18 1p breakpoints were 1p36. However, while 1p breakpoints aggregated on 1p36 in all translocations, there was only one 1p36 breakpoint in five deletions. With this paper, we contribute to the relevant literature by reporting our results. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the microRNA (miRNA) expressions of the corneal tissue after an alkaline burn and to compare the efficiency of adipose- and bone marrow-derived mesenchymal stem cells (MSCs) on expressions. Methods: Thirty-two rats were divided into 4 groups. No intervention was made in the control group. A chemical burn was created by applying 4 μL NaOH soaked in 6 mm filter paper to the right eye of each animal in the other groups. Whereas only subconjunctival 0.1 mL phosphate-buffered saline (PBS) was injected to in the group 1, 2 × 106 adipose- or bone marrow-derived MSC in 0.1 mL PBS was injected subconjunctivally to the animals in the remaining groups (groups 2 and 3, respectively). Tissue samples were collected for miRNA analysis on the third day after the burn. Results: When group 1 was compared with the control group, the expression of 3 of 93 miRNAs increased significantly, whereas the expression of 50 miRNAs decreased significantly. Significant changes in miRNA expressions were observed when group 1 was compared with groups 2 and 3. Although a significant change was observed in the expression of 6 miRNAs in the adipose-derived MSC group, it was found that the expression of 65 miRNAs significantly changed in the bone marrow-derived MSC group. Conclusion: This study shows that there are significant changes in some miRNA expressions after corneal alkaline burn and these changes can be reversed with the subconjunctival injection of MSCs. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study is to comparatively evaluate the anti-inflammatory and antiapoptotic effects of bone marrow and adipose-derived mesenchymal stem cells (MSCs) applied subconjunctivally after alkaline corneal burn. Methods: Thirty-two rats were divided into 4 groups and included in the study (n = 8). While no intervention was made in the control group, a chemical burn was created by applying 4 μL of NaOH soaked in 6 mm filter paper to the right eye of each subject in the other groups under general anesthesia. While only subconjunctival 0.1 mL phosphate-buffered saline (PBS) was injected to in the group 1, 2 × 106 adipose or bone marrow-derived MSC in 0.1 mL PBS was applied subconjunctivally to the subjects in the remaining groups (Group 2 and 3, respectively). Tissue samples were collected for histological analysis on the third day after the burn. Tissue samples were evaluated light microscopically and immunohistochemically stained for interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), caspase-3 (Cas-3), and CD68. Results: The IL-1β and TNF-α staining scores and the number of CD68- and Cas-3-positive stained cells were significantly lower in the groups given bone marrow and adipose-derived MSC compared to the alkaline burn group (P < 0.0001, for all parameters). Epithelial IL-1β and TNF-α staining scores were significantly lower in the bone marrow-derived MSC group compared to the adipose-derived MSC group (P < 0.0001, for all parameters). Conclusions: The presented study shows that both bone-marrow and adipose-derived MSCs support wound healing in the corneal tissue and strongly suppress the inflammation occured in the tissue. [ABSTRACT FROM AUTHOR]

Cluster failure time data are commonly encountered in survival analysis due to unobservable factors such as shared environmental conditions and genetic similarity. In such cases, careful attention needs to be paid to the correlation among the subjects within the same cluster. In addition, some diseases are curable due to the advancement of modern medical techniques. In this paper, we extend the frailty model based on Birnbaum–Saunders frailty distribution to incorporate the cure proportion. In addition, the marginal likelihood approach using Monte Carlo approximation and Expectation-Maximization algorithm are also developed for the determination of the maximum likelihood estimates of the parameters of the proposed model. An extensive simulation study is carried out to evaluate the performance of the proposed model and the methods of inference. Finally, the proposed model is applied to a real data set to analyse the effect of allogeneic and autologous bone marrow transplant treatment on acute lymphoblastic leukemia patients. [ABSTRACT FROM AUTHOR]

Background and Objective: Hairy cell leukemia (HCL) is a chronic lymphoproliferative disorder for which diagnosis is typically straightforward, based on bone marrow morphology and flow cytometry (FC) or immunohistochemistry. Nevertheless, variants present atypical expressions of cell surface markers, as is the case of CD5, for which the differential diagnosis can be more difficult. The aim of the current paper was to describe diagnosis of HCL with atypical CD5 expression, with an emphasis on FC. Methods: The detailed diagnostic methodology for HCL with atypical CD5 expression is presented, including differential diagnosis from other lymphoproliferative diseases with similar pathologic features, by FC analysis of the bone marrow aspirate. Results: Diagnosis of HCL by means of FC started by gating all events based on side scatter (SSC) versus CD45 and B lymphocytes were selected from the lymphocytes gate as CD45/CD19 positive. The gated cells were positive for CD25, CD11c, CD20, and CD103, while CD10 proved to be dim to negative. Moreover, cells positive for CD3, CD4, and CD8, the three pan-T markers, as well as CD19, showed a bright expression of CD5. The atypical CD5 expression is usually correlated with a negative prognosis and thus chemotherapy with cladribine should be initiated. Conclusion: HCL is an indolent chronic lymphoproliferative disorder and diagnosis is usually straightforward. However, atypical expression of CD5 renders its differential diagnosis more difficult, but FC is a useful tool that allows an optimal classification of the disease and allows initiation of timely satisfactory therapy. [ABSTRACT FROM AUTHOR]

The detection and classification of bone marrow (BM) cells is a critical cornerstone for hematology diagnosis. However, the low accuracy caused by few BM-cell data samples, subtle difference between classes, and small target size, pathologists still need to perform thousands of manual identifications daily. To address the above issues, we propose an improved BM-cell-detection algorithm in this paper, called YOLOv7-CTA. Firstly, to enhance the model's sensitivity to fine-grained features, we design a new module called CoTLAN in the backbone network to enable the model to perform long-term modeling between target feature information. Then, in order to cooperate with the CoTLAN module to pay more attention to the features in the area to be detected, we integrate the coordinate attention (CoordAtt) module between the CoTLAN modules to improve the model's attention to small target features. Finally, we cluster the target boxes of the BM cell dataset based on K-means++ to generate more suitable anchor boxes, which accelerates the convergence of the improved model. In addition, in order to solve the imbalance between positive and negative samples in BM-cell pictures, we use the Focal loss function to replace the multi-class cross entropy. Experimental results demonstrate that the best mean average precision (mAP) of the proposed model reaches 88.6%, which is an improvement of 12.9%, 8.3%, and 6.7% compared with that of the Faster R-CNN model, YOLOv5l model, and YOLOv7 model, respectively. This verifies the effectiveness and superiority of the YOLOv7-CTA model in BM-cell-detection tasks. [ABSTRACT FROM AUTHOR]

The analysis of left truncated and right censored data is very common in survival and reliability analysis. In lifetime studies patients are often subject to left truncation in addition to right censoring. For example, in bone marrow transplant studies based on International Bone Marrow Transplant Registry (IBMTR), the patients who die while waiting for the transplants will not be reported to the IBMTR. In this paper, we develop novel U-statistics under left truncation and right censoring. We prove the n -consistency of the proposed U-statistics. We derive the asymptotic distribution of the U-statistics using the counting process technique. As an application of the U-statistics, we develop a simple non-parametric test for testing the independence between time to failure and cause of failure in competing risks when the observations are subject to left truncation and right censoring. The finite sample performance of the proposed test is evaluated through a Monte Carlo simulation study. Finally, we illustrate our test procedure using the lifetime data of transformers. [ABSTRACT FROM AUTHOR]

Up‐front allogeneic haematopoietic stem cell transplantation (allo‐HSCT) after a reduced intensity conditioning regimen is the standard treatment in children with acquired severe aplastic anaemia (aSAA) and inherited bone marrow failure syndromes (iBMFs) in the presence of a healthy matched related donor (MRD). The paper by Alsultan et al. report the safety and efficacy of MRD HSCT conditioned with low‐dose cyclophosphamide, fludarabine and thymoglobulin in both aSAA and non‐Fanconi iBMFs, strengthening the concept of the pivotal role of immunosuppressive approach in allo‐HSCT for specific subgroups of non‐malignant diseases requiring a reduced risk of toxicities, offering the opportunity to discuss the essential points for achieving patients' long‐term survival after MRD HSCT in BMF. Commentary on: Alsultan et al. Human leucocyte antigen‐matched related haematopoietic stem cell transplantation using low‐dose cyclophosphamide, fludarabine and thymoglobulin in children with severe aplastic anaemia. Br J Haematol 2023;203:255‐263. [ABSTRACT FROM AUTHOR]

Since the discovery of mesenchymal stem cells (MSCs) in the 1970s, they have been widely used in the treatment of a variety of diseases because of their wide sources, strong differentiation potential, rapid expansion in vitro, low immunogenicity, and so on. At present, most of the related research is on mesoderm-derived MSCs (M-MSCs) such as bone marrow MSCs and adipose-derived MSCs. As a type of MSC, ectoderm-derived MSCs (E-MSCs) have a stronger potential for self-renewal, multidirectional differentiation, and immunomodulation and have more advantages than M-MSCs in some specific conditions. This paper analyzes the relevant research development of E-MSCs compared with that of M-MSCs; summarizes the extraction, discrimination and culture, biological characteristics, and clinical application of E-MSCs; and discusses the application prospects of E-MSCs. This summary provides a theoretical basis for the better application of MSCs from both ectoderm and mesoderm in the future. [ABSTRACT FROM AUTHOR]

The main aim of this work is to use a finite element technique (FEM) to gain understanding about the bone marrow biopsy (BMB) needle insertion process and needle-tissue interactions in the human iliac crest. A multi-layer iliac crest model consists of stratum corneum, dermis, epidermis, hypodermis, cortical, and cancellous bone has been established. This paper proposes a FE model that examines all phases of tissue deformation, including puncture, cutting, needle-tissue interaction, and various stress-strain values for BMB needle during interaction. The results explain the needle-tissue interface and show the potential of this technique to estimate bone damage and tissue deformation for multiple needle dimensions, coefficient of friction, and penetration speeds. The insertion and extraction force of conical-shaped needles in the multi-layered iliac crest model decreased by 18.92% and 37.5%, respectively, as the needle diameter reduced from 11 G to 20 G. It has also been found that the significant insertion motion raises the deformation of the tissue due to the augmented frictional forces but reduces the strain perpendicular to the penetration direction closer to the needle tip. The simulation outcomes are helpful for the optimal design of fine biopsy needles used to perform the bone marrow biopsies. [ABSTRACT FROM AUTHOR]

Objectives: Platelet-rich fibrin (PRF) and bone marrow mononuclear cells are potential scaffolds and cell sources for osteochondral regeneration. The main aim of this paper is to examine the effects of PRF scaffolds and autologous uncultured bone marrow mononuclear cells on osteochondral regeneration in rabbit knees. Materials and Methods: Three different types of PRF scaffolds were generated from peripheral blood (Ch-PRF and L-PRF) and bone marrow combined with uncultured bone marrow mononuclear cells (BMM-PRF). The histological characteristics of these scaffolds were assessed via hematoxylin–eosin staining, PicroSirius red staining, and immunohistochemical staining. Osteochondral defects with a diameter of 3 mm and depth of 3 mm were created on the trochlear groove of the rabbit's femur. Different PRF scaffolds were then applied to treat the defects. A group of rabbits with induced osteochondral defects that were not treated with any scaffold was used as a control. Osteochondral tissue regeneration was assessed after 2, 4, and 6 weeks by macroscopy (using the Internal Cartilage Repair Society score, X-ray) and microscopy (hematoxylin—eosin stain, safranin O stain, toluidine stain, and Wakitani histological scale, immunohistochemistry), in addition to gene expression analysis of osteochondral markers. Results: Ch-PRF had a heterogeneous fibrin network structure and cellular population; L-PRF and BMM-PRF had a homogeneous structure with a uniform distribution of the fibrin network. Ch-PRF and L-PRF contained a population of CD45-positive leukocytes embedded in the fibrin network, while mononuclear cells in the BMM-PRF scaffold were positive for the pluripotent stem cell-specific antibody Oct-4. In comparison to the untreated group, the rabbits that were given the autologous graft displayed significantly improved healing of the articular cartilage tissue and of the subchondral bone. Regeneration was gradually observed after 2, 4, and 6 weeks of PRF scaffold treatment, which was particularly evident in the BMM-PRF group. Conclusions: The combination of biomaterials with autologous platelet-rich fibrin and uncultured bone marrow mononuclear cells promoted osteochondral regeneration in a rabbit model more than platelet-rich fibrin material alone. Our results indicate that autologous platelet-rich fibrin scaffolds combined with uncultured bone marrow mononuclear cells applied in healing osteochondral lesions may represent a suitable treatment in addition to stem cell and biomaterial therapy. [ABSTRACT FROM AUTHOR]

Introduction : Myeloid sarcoma (previously chloroma or granulocytic sarcoma) is a very rare malignant neoplasm associated with myeloproliferative neoplasms. This type of tumour can be located anywhere outside the bone marrow. Aim: To describe the successful treatment and diagnostic of myeloid sarcoma. Case study: Retrospective case review. Results and discussion: This paper presents a case of myeloid sarcoma in a 50-year-old male. Patient presented due to pain lasting for 2 months in the left anterior axillary line region and a rapidly growing nodular lesion on the anterior chest wall. The lesion involved an extensive area of the ribs, causing rib destruction. Surgery was performed causing patients relief and chance of collecting histopathological tissue. Conclusions: In myeloid sarcoma patients, surgical treatment does not only bring relief in symptomatic patients but also provides material for histopathological examination, which is necessary to confirm the diagnosis. An important part of the diagnosis is the implementation of a wide panel of immunohistochemical tests. [ABSTRACT FROM AUTHOR]

Bone marrow studies currently provide a lot of valuable information in the diagnostics of hematological diseases including hematopoietic stem cells disorders. Our studies on low-molecular weight organic compounds in bone marrow stem cell niche in various pathogenic conditions, revealed relatively high variability of histamine levels in different groups of hematological diseases. It was also found that serotonin levels were significantly lower than those typically measured in peripheral blood as well as many have the influence on stem cells proliferative potential. This paper presents findings from quantitative and statistical analyses of histamine and serotonin levels. Bone marrow collected from patients undergoing routine diagnostic procedures for hematological diseases and receiving inpatient treatment were analyzed. Histamine and serotonin levels were measured using hydrophilic interaction liquid chromatography (HILIC) coupled with tandem mass spectrometry. Obtained data were analyzed statistically and correlated with the diagnosed groups of hematological diseases and the parameters of complete blood counts. Histamine was found in all tested samples, including those from patients without malignancy, and the reported levels were comparable to the reference values in blood. This observation allows us to assume that bone marrow cells can produce and accumulate histamine. Moreover, the statistical analysis revealed a significant relationship between histamine levels and diagnosed mastocytosis, and between histamine levels and myeloproliferative neoplasms. Different results were obtained for serotonin, and its concentrations in most cases were below the limit of quantification of the method used (< 0.2 ng/mL), which can only be compared to peripheral blood plasma. In a few cases, significantly higher serotonin levels were observed and it concerned diseases associated with an increased number of megakaryocytes in the bone marrow. [ABSTRACT FROM AUTHOR]

(1) Hematological malignancies are characterized by an immortalization, uncontrolled proliferation of blood cells and their differentiation block, followed by the loss of function. The primary goal in the treatment of leukemias is the elimination of rapidly proliferating leukemic cells (named blasts). However, chemotherapy, which removes proliferating blasts, also prevents the remaining immune cells from being activated. Acute leukemias affect elderly people, who are often not fit to survive aggressive chemotherapy. Therefore, there is a need of milder treatment, named differentiation therapy, which might simulate the immune system of the patient. 1,25-Dihydroxyvitamin D, or low-calcemic analogs of this compound, were proposed as supporting therapy in acute leukemias. (2) Bone marrow blasts from patients with hematological malignancies, and leukocytes from healthy volunteers were ex vivo exposed to 1,25-dihydroxyvitamin D, and then their genomes and transcriptomes were investigated. (3) Our analysis indicates that 1,25-dihydroxyvitamin D regulates in blood cells predominantly genes involved in immune response, such as CAMP (cathelicidin antimicrobial peptide), CP (ceruloplasmin), CXCL9 (C-X-C motif chemokine ligand 9), CD14 (CD14 molecule) or VMO1 (vitelline membrane outer layer 1 homolog). This concerns blood cells from healthy people, as well as blasts from patients with hematological malignancies. In addition, in one patient, 1,25-dihydroxyvitamin D significantly downregulated transcription of genes responsible for cell division and immortalization. (4) In conclusion, the data presented in this paper suggest that addition of 1,25-dihydroxyvitamin D to the currently available treatments would stimulate immune system, inhibit proliferation and reduce immortal potential of blasts. [ABSTRACT FROM AUTHOR]

The proportional subdistribution hazards (PSH) model is popularly used to deal with competing risks data. Censored quantile regression provides an important supplement as well as variable selection methods due to large numbers of irrelevant covariates in practice. In this paper, we study variable selection procedures based on penalized weighted quantile regression for competing risks models, which is conveniently applied by researchers. Asymptotic properties of the proposed estimators, including consistency and asymptotic normality of non-penalized estimator and consistency of variable selection, are established. Monte Carlo simulation studies are conducted, showing that the proposed methods are considerably stable and efficient. Real data about bone marrow transplant (BMT) are also analyzed to illustrate the application of the proposed procedure. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite increasing knowledge of the biological mechanisms leading to neoplastic transformation, the identification of various molecular targets for innovative drugs, refinements in supportive care, and the wider use of allogeneic transplants, the prognosis of acute myeloid leukemia (AML) remains dismal. In the last years, the role of the bone marrow microenvironment and of the immune system in favoring leukemic cell persistence has emerged both as a cause of treatment failure but also as a potential setting for novel therapies. The aim of the present paper is to review the biological evidence and clinical trials of immune-based treatments for AML. It is now well known that the bone marrow (BM) cell niche contributes to leukemogenesis, but emerging data support the role of the complex crosstalk between AML cells and the BM microenvironment to induce a permissive immune setting that protects leukemic stem cells (LSCs) from therapy-induced death, thus favoring disease persistence and eventual relapse. The identification of potential immune targets on AML cells and the modulation of the BM environment could lead to enhanced anti-leukemic effects of drugs, immune system reactivation, and the restoration of AML surveillance. Potential targets and effectors of this immune-based therapy could be monoclonal antibodies directed against LSC antigens such as CD33, CD123, and CLL-1 (either as direct targets or via several bispecific T-cell engagers), immune checkpoint inhibitors acting on different co-inhibitory axes (alone or in combination with conventional AML drugs), and novel cellular therapies such as chimeric antigen receptor (CAR) T-cells designed against AML-specific antigens. Though dozens of clinical trials, mostly in phases I and II, are ongoing worldwide, results have still been negatively affected by difficulties in the identification of the optimal targets on LSCs. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics which include genetics of adenoid cystic carcinoma, methylation estimate in breast cancer and effect of tumor cells on human bone-marrow.

Mammals have evolved several physiological mechanisms to cope with changes in ambient temperature. Particularly critical among them is the process of keeping the membrane of cells in a fluid phase to prevent metabolic dysfunction. In this paper, we examine variation in the fatty acid composition of bone marrow and muscle tissues in the cold-adapted caribou (Rangifer tarandus caribou) to determine whether there are systematic differences in fatty acid profiles between anatomical regions that could potentially be explained by thermal adaptation as influenced by cell function, including hematopoiesis. Our results indicate that the bone marrow and muscle tissues from the appendicular skeleton are more unsaturated than the same tissues in the axial skeleton, a finding that is consistent with physiological adaptation of the appendicular regions to thermal challenges. Because mechanisms of thermal adaptation appear to be widely shared among terrestrial mammals, we suggest that the same patterns may prevail in other species, possibly including humans. [ABSTRACT FROM AUTHOR]

The survival prediction of children undergoing hematopoietic stem-cell transplantation is essential for successful transplantation. However, the performance of current algorithms for predicting mortality in this patient group has not improved over recent decades. This paper proposes a new feature selection technique for survival prediction problems using the Mud Ring Algorithm (MRA). Experiments and tests were initially performed on 13 real datasets with varying occurrences to compare the suggested algorithm with other algorithms. After that, the constructed model classification performance was compared to other techniques using the bone marrow transplant children's dataset. Modern techniques were used to acquire their classification results, which were then compared to the suggested outcomes using a variety of well-known metrics, graphical tools, and diagnostic analysis. This investigation has demonstrated that our suggested approach is comparable and outperformed other methods in terms of results. In addition, the results showed that the constructed model enhanced prediction accuracy by up to 82.6% for test cases. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various research papers within the issue on topics including nuclear medicine, bone marrow and protection from radiations.

Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare variant of invasive urothelial carcinoma (UC) with aggressive behavior. Despite its prognosis being poorer than that of conventional UC, a median overall survival of approximately 2 years is ensured when it is treated with radical cystectomy (RC), and few patients die within a few months of RC. In this paper, we report the case of a patient with PUC who developed widespread bone metastasis only 6 weeks after RC, which resulted in death within 2 months postoperatively. [ABSTRACT FROM AUTHOR]

This paper considers the problem of comparing several means under the one-way Analysis of Variance (ANOVA) setup. In ANOVA, outliers and heavy-tailed error distribution can seriously hinder the treatment effect, leading to false positive or false negative test results. We propose a robust test of ANOVA using an M-estimator based on the density power divergence. Compared with the existing robust and non-robust approaches, the proposed testing procedure is less affected by data contamination and improves the analysis. The asymptotic properties of the proposed test are derived under some regularity conditions. The finite-sample performance of the proposed test is examined via a series of Monte-Carlo experiments and two empirical data examples—bone marrow transplant dataset and glucose level dataset. The results produced by the proposed testing procedure are favorably compared with the classical ANOVA and robust tests based on Huber's M-estimator and Tukey's MM-estimator. [ABSTRACT FROM AUTHOR]

Long bone breakage for bone marrow recovery is a commonly observed practice in Middle Palaeolithic contexts, regardless of the climatic conditions. While lithic technology is largely used to define cultural patterns in human groups, despite dedicating research by zooarchaeologists, for now butchering techniques rarely allowed the identification of clear traditions, notably for ancient Palaeolithic periods. In this paper, we test the hypothesis of butchery traditions among Neandertal groupsusing the bone assemblages from three sites in southwestern Europe. These sites are located in southeastern France and northern Italy and are dated to the Late Middle Palaeolithic: Abri du Maras (Marine Isotopic Stages (MIS) 4–3, Ardèche), Saint-Marcel (MIS 3, Ardèche), and Riparo Tagliente (MIS 4–3, Verona). The detection of culturally-induced patterns of bone breakage involves differentiating them from intuitively generated patterns. To tackle this issue, we used a zooarchaeological approach focusing on the percussion marks produced during the bone breakage process. Statistical analyses as the chi-square test of independence were employed to verify if percussion mark locations were randomly distributed, and if these distributions were different from the intuitive ones. For femurs and humeri, our results demonstrate that Neandertal groups occupying the Abri du Maras (levels 4.1 and 4.2) and the Saint-Marcel Cave (levels g and h) sites in France applied butchery traditions to recover yellow marrow. However, the traditions developed at each site were different. On the contrary, in Riparo Tagliente, in Italy, several groups or individuals of a same group did not share the same butchery traditions over time. Regarding the Abri du Maras and Saint Marcel Cave assemblages, our research demonstrates that Neandertal groups applied intense standardized bone breakage, far from the intuitive practice observed experimentally and related to bone density and/or skeletal morphology. These standardized patterns, which are systematic and counter-intuitive, can be interpreted as culturally induced for the Abri du Maras and Saint Marcel Cave. The diversity of Neandertal traditions should be considered by taking into account the butchery, in particular the practice of bone marrow extraction, and not only technological behaviours and types of tool kits. [ABSTRACT FROM AUTHOR]

Patients undergoing bone marrow transplantation or chemotherapy for cancer are profoundly immunosuppressed. They are at risk for both endogenous and exogenous infections and require enhanced protection from infection while in hospital. The aim of this narrative review was to determine the optimal design features of bone marrow transplant (BMT) units for reducing infection risk in these vulnerable patients. A literature search was performed on PubMed and other databases for documents published between January 2000 and October 2021. Keywords were: bone marrow transplant unit OR hematopoietic stem cell transplant unit OR haematology unit OR haemato-oncology unit AND design OR design guidelines OR design criteria OR ventilation specification OR HEPA filtration OR water outbreaks OR water system design. Guidelines and other papers pertaining to BMT unit design are discussed. Key design features identified from the literature to reduce infection risks include high efficiency particulate air filtration, positive-pressure ventilation, sufficient air changes and sealed rooms. The evidence for each of these parameters and other findings are discussed. We found no guidelines specific to water quality and control in BMT units. Guidelines on the various components of design were found, but no comprehensive guidance documents addressing all relevant aspects, such as ventilation, water, and other design features, were found. Literary publications and policy documents were combined and summarised to highlight key design features aimed at reducing infection risk in this vulnerable patient group. We propose the development of international guidance for the design of BMT units encompassing all components. [ABSTRACT FROM AUTHOR]

Megakaryocyte hyperplasia associated with myeloproliferative neoplasms commonly leads to abnormal bone tissue deposition in the bone marrow, known as osteosclerosis. In this study, we aimed to synthesize the known proteomics literature describing factors released by megakaryocytes and platelets and to examine if any of the secreted factors have a known ability to stimulate the bone-forming cells, osteoblasts. Using a systematic search of Medline, we identified 77 articles reporting on factors secreted by platelets and megakaryocytes. After a full-text screening and analysis of the studies, we selected seven papers that reported proteomics data for factors secreted by platelets from healthy individuals. From 60 proteins reported in at least two studies, we focused on 23 that contained a putative signal peptide, which we searched for a potential osteoblast-stimulatory function. From nine proteins with a positive effect on osteoblast formation and function, two extracellular matrix (ECM) proteins, secreted protein acidic and rich in cysteine (SPARC) and tissue inhibitor of metalloproteinase-1 (TIMP1), and three cellular proteins with known extracellular function, the 70-kDa heat shock protein (HSP70), thymosin-β4 (TB4), and super dismutase (SOD), were identified as hypothetical candidate molecules to be examined as potential mediators in mouse models of osteomyelofibrosis. Thus, careful analysis of prior literature can be beneficial in assisting the planning of future experimental studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cells travel to far away parts of the body before the original cancer can be detected. Breast cancer cells travel mainly to the bone marrow, where they are kept in a quiet, non-dividing, dormant state for many years by cells and proteins in the bone marrow. These metastatic cancer cells wake up at a steady rate over the years and result in incurable disease. This paper outlines how to study the interactions of cells that live in the bone marrow with cancer cells in the laboratory. We describe how to grow mixtures of a variety of bone marrow-residing cells to generate cell layers upon which cancer cells can be grown. Using this system, we can study their effects on cancer cell growth or dormancy and the biology of the interactions. With this approach, we can study how to either eliminate the cancer cells or prevent them from waking up. Cancers metastasize to the bone marrow before primary tumors can be detected. Bone marrow micrometastases are resistant to therapy, and while they are able to remain dormant for decades, they recur steadily and result in incurable metastatic disease. The bone marrow microenvironment maintains the dormancy and chemoresistance of micrometastases through interactions with multiple cell types and through structural and soluble factors. Modeling dormancy in vitro can identify the mechanisms of these interactions. Modeling also identifies mechanisms able to disrupt these interactions or define novel interactions that promote the reawakening of dormant cells. The in vitro modeling of the interactions of cancer cells with various bone marrow elements can generate hypotheses on the mechanisms that control dormancy, treatment resistance and reawakening in vivo. These hypotheses can guide in vivo murine experiments that have high probabilities of succeeding in order to verify in vitro findings while minimizing the use of animals in experiments. This review outlines the existing data on predominant stromal cell types and their use in 2D co-cultures with cancer cells. [ABSTRACT FROM AUTHOR]

Bone marrow (BM) is an organ responsible for crucial processes in living organs, e. g., hematopoiesis. In recent years, Organ-on-a-Chip (OoC) devices have been used to satisfy the need for in vitro systems that better mimic the phenomena occurring in the BM microenvironment. Given the growing interest in these systems and the diversity of developed devices, an integrative systematic literature review is required. We have performed this review, following the PRISMA method aiming to identify the main characteristics and assess the effectiveness of the devices that were developed to represent the BM. A search was performed in the Scopus, PubMed, Web of Science and Science Direct databases using the keywords (("bone marrow" OR "hematopoietic stem cells" OR "haematopoietic stem cells") AND ("organ in a" OR "lab on a chip" OR "microfluidic" OR "microfluidic*" OR ("bioreactor" AND "microfluidic*"))). Original research articles published between 2009 and 2020 were included in the review, giving a total of 21 papers. The analysis of these papers showed that their main purpose was to study BM cells biology, mimic BM niches, model pathological BM, and run drug assays. Regarding the fabrication protocols, we have observed that polydimethylsiloxane (PDMS) material and soft lithography method were the most commonly used. To reproduce the microenvironment of BM, most devices used the type I collagen and alginate. Peristaltic and syringe pumps were mostly used for device perfusion. Regarding the advantages compared to conventional methods, there were identified three groups of OoC devices: perfused 3D BM; co-cultured 3D BM; and perfused co-cultured 3D BM. Cellular behavior and mimicking their processes and responses were the mostly commonly studied parameters. The results have demonstrated the effectiveness of OoC devices for research purposes compared to conventional cell cultures. Furthermore, the devices have a wide range of applicability and the potential to be explored. [ABSTRACT FROM AUTHOR]

Background and purpose: Leukoerythroblastic reaction (LER) is characterized by the presence of immature erythroid cells and myeloid precursors (metamyelocytes, myelocytes, promyelocytes, myeloblasts, and blasts) as well as, exclusively in myelofibrotic disorders, teardrop cells in the peripheral blood (J Pathol Bacteriol, 42, 1936, 541; Semaine Med, 22, 1902, 373). Research on how to interpret LER and its meaning in clinical practice is scarce, and there is no consensus on the diagnostic criteria. We summarize the current evidence with the aim of clarifying the knowledge on this subject. Methods: We conducted a comprehensive search of the PubMed‐MEDLINE, EMBASE and ELSEVIER databases, the Cochrane Library, Google Scholar, and medical journals to identify relevant papers. Results: Our search identified 425 papers, of which, 35 (11 trials and 24 case reports) ultimately met the inclusion criteria. These showed two principal groups of diseases associated with leukoerythroblastosis (LEB), corresponding to solid and hematological malignancies. The other etiologies, in order of frequency, were hemolytic diseases, infection, and others, while hemorrhage was only reported in the trials group. Conclusion: The literature on LER is scarce and heterogeneous. The etiological factors of LER are diverse, and its presence in malignant disease is an indicator of disease progression and an adverse prognosis suggesting poor survival. In those cases where LER had neither hematological nor solid neoplasms, its manifestation, prognosis and its impact on our daily clinical practice are unknown. [ABSTRACT FROM AUTHOR]

Introduction: Bone marrow edema (BME) is one of the main imaging characteristics of juvenile idiopathic arthritis (JIA) in children and rheumatoid arthritis (RA) in adult. Previous studies have shown that BME occurred in approximately 64% of adults with RA and was a key predictor of poor prognosis. But BME with JIA has not been of great concern. Therefore, we evaluated the prevalence, characteristics, and prognosis of knee joint BME in children with JIA. Methods: In this retrospective study, we included children with JIA and knee joint involvement from January 2017 to December 2019. BME was evaluated according to the Juvenile Arthritis MRI Scoring system. Clinical characteristics were compared between the BME group and the non-BME group. The characteristics and prognosis of the BME were observed. Results: A total of 128 children with 136 knee joint MRI data were identified, with 37 knee joints (27.2%) having BME. BME has positive correlation with synovial hypertrophy (Rs = 0.562, p = 0.019). There were significant differences in age (p = 0.010) and disease duration (p = 0.013) between the BME and non-BME groups. BME was found to be more common in older children and the patients with long duration of disease. Locations with BME were the lateral tibial plateau (17/37, 45.9%), the lateral weight-bearing femur (16/37, 43.2%), the medial tibial plateau and the medial femoral condyle (both with 15/37, 40.5%), and the medial weight-bearing femur (12/37, 32.4%). The lateral femoral condyle and both the lateral and medial sides of the patella were rarely involved. Of the 15 BME joints with the MRI follow-up data (interval 6.5 ± 3.0 months), the lesions disappeared or improved within 12 months after the treatments in 13 (86.7%) joints. Conclusions: The prevalence of knee BME in JIA was 27.2%. There was positive correlation between BME and synovial hypertrophy. Older children and children with long disease duration had a higher risk for BME, which was commonly a late presentation and more likely involved the weight-bearing surfaces of the joint. The overall prognosis was satisfactory after the standard treatments. Key Points • To the best of our knowledge, this paper is the first one to investigate the MRI manifestation in JIA focus on knee BME sign. [ABSTRACT FROM AUTHOR]

Bone marrow mesenchymal stromal cells (MSCs) play a crucial role in the regulation of hematopoiesis. These cells affect the process through direct cell–cell contact, as well as releasing various trophic factors and extracellular vehicles (EVs) into the bone marrow microenvironment. MSC-derived EVs (MSC-EVs) are prominent intercellular communication tolls enriched with broad-spectrum bioactive factors such as proteins, cytokines, lipids, miRNAs, and siRNAs. They mimic some effects of MSCs by direct fusion with hematopoietic stem cells (HSC) membranes in the bone marrow (BM), thereby affecting HSC fate. MSC-EVs are attractive scope in cell-free therapy because of their unique capacity to repair BM tissue and regulate proliferation and differentiation of HSCs. These vesicles modulate the immune system responses and inhibit graft-versus-host disease following hematopoietic stem cell transplantation (HSCT). Recent studies have demonstrated that MSC-EVs play an influential role in the BM niches because of their unprecedented capacity to regulate HSC fate. Therefore, the existing paper intends to speculate upon the preconditioned MSC-EVs as a novel approach in HSCT. [ABSTRACT FROM AUTHOR]

Purpose: Meniscal allograft transplantation (MAT) has shown good promise in restoring normal knee joint biomechanics in a meniscal deficient patient. However, MRI appearance of the meniscal allograft is often questioned and raises concerns of its viability and function. This paper aims to introduce and validate a new scoring system for MAT MRI appearance at 12 months [MRI appearance in Meniscal Transplant Score (MIMS)], using key changes such as extrusion, meniscal signal change, loss of shape, synovitis and bone marrow oedema. Methods: A retrospective analysis of 10 patients from a single surgeon series was conducted. All MAT were performed with soft tissue fixation technique. MRI was performed at 12 months post-transplant with two independent consultant musculoskeletal radiologists and one experienced meniscal transplant surgeon scoring the images obtained. Interobserver agreement and intraclass correlation were measured. Results: Interobserver agreement between examiners on individual features of the MIMS was superior for tibial bone oedema, substantial for meniscal extrusion and femoral bone oedema, moderate for meniscal shape and synovitis, and fair for meniscal signal changes. Absolute agreement between raters found good reliability (ICC = 0.774; 95% 0.359, 0.960) for single measures and excellent reliability (ICC = 0.911; 95% 0.627, 0.986) for average measures. Conclusion: MIMS is a reliable method of evaluating the meniscal allograft transplant 12 months post-transplant. Further research with larger MAT cohort groups and patient reported outcome measures may be helpful to correlate its clinical significance and guide further management. Level of evidence: Level III. [ABSTRACT FROM AUTHOR]

Collagen quantity and integrity play an important role in understanding diseases such as myelofibrosis (MF). Label-free mid-infrared spectroscopic imaging (MIRSI) has the potential to quantify collagen while minimizing the subjective variance observed with conventional histopathology. Infrared (IR) spectroscopy with polarization sensitivity provides chemical information while also estimating tissue dichroism. This can potentially aid MF grading by revealing the structure and orientation of collagen fibers. Simultaneous measurement of collagen structure and biochemical properties can translate clinically into improved diagnosis and enhance our understanding of disease progression. In this paper, we present the first report of polarization-dependent spectroscopic variations in collagen from human bone marrow samples. We build on prior work with animal models and extend it to human clinical biopsies with a practical method for high-resolution chemical and structural imaging of bone marrow on clinical glass slides. This is done using a new polarization-sensitive photothermal mid-infrared spectroscopic imaging scheme that enables sample and source independent polarization control. This technology provides 0.5 µm spatial resolution, enabling the identification of thin (≈1 µm) collagen fibers that were not separable using Fourier Transform Infrared (FT-IR) imaging in the fingerprint region at diffraction-limited resolution (≈ 5 µm). Finally, we propose quantitative metrics to identify fiber orientation from discrete band images (amide I and amide II) measured under three polarizations. Previous studies have used a pair of orthogonal polarization measurements, which is insufficient for clinical samples since human bone biopsies contain collagen fibers with multiple orientations. Here, we address this challenge and demonstrate that three polarization measurements are necessary to resolve orientation ambiguity in clinical bone marrow samples. This is also the first study to demonstrate the ability to spectroscopically identify thin collagen fibers (≈1 µm diameter) and their orientations, which is critical for accurate grading of human bone marrow fibrosis. Graphical Abstract [ABSTRACT FROM AUTHOR]

In their paper the authors describe distinct transcriptomic changes associated to treatment response in core bone marrow biopsies from patients with acute myeloid leukaemia. This finding raises the possibility that stratifying patients for treatment according to their transcriptomic profiles could improve patients' response and prognosis. Commentary on: Treaba et al. Transcriptomics of AML core bone marrow biopsies reveals distinct therapy response‐specific osteo‐mesenchymal profiles. Br J Haematol 2023;200:740–754. [ABSTRACT FROM AUTHOR]

As a corridor for population movement out of Africa, the southern Levant is a natural laboratory for research exploring the dynamics of the Middle-to-Upper Paleolithic transition. Yet, the number of well-preserved sites dating to the initial millennia of the Early Upper Paleolithic (EUP; ∼45–30 ka) remains limited, restricting the resolution at which we can study the biocultural and techno-typological changes evidenced across the transition. With EUP deposits dating to 45–39 ka cal BP, Mughr el-Hamamah, Jordan, offers a key opportunity to expand our understanding of EUP lifeways in the southern Levant. Mughr el-Hamamah is particularly noteworthy for its large faunal assemblage, representing the first such assemblage from the Jordan Valley. In this paper, we present results from taxonomic and taphonomic analyses of the EUP fauna from Mughr el-Hamamah. Given broader debates about shifts in human subsistence across the Middle-to-Upper Paleolithic transition, we also assess evidence for subsistence intensification, focusing especially on the exploitation of gazelle and the use of small game. Taphonomic data suggest that the fauna was primarily accumulated by human activity. Ungulates dominate the assemblage; gazelle (Gazella sp.) is the most common taxa, followed by fallow deer (Dama mesopotamica) and goat (Capra sp.). Among the gazelle, juveniles account for roughly one-third of the sample. While the focus on gazelle and the frequency of juveniles are consistent with broader regional trends, evidence for the regular exploitation of marrow from gazelle phalanges suggests that the EUP occupants of Mughr el-Hamamah processed gazelle carcasses quite intensively. Yet, the overall degree of dietary intensification appears low—small game is rare and evidence for human capture of this game is more equivocal. As a whole, our results support a growing body of data showing gradual shifts in animal exploitation strategies across the Middle-to-Upper Paleolithic transition in the southern Levant. [ABSTRACT FROM AUTHOR]

Haematopoietic stem cell transplantation is a treatment modality that saves the health and lives of a growing number of patients around the world. In the majority of cases, the procedure is conducted to treat haematologic neoplasms, although it can also be used as a therapy for some non-haematooncological diseases. The progress that has been taking place in the field of haematopoietic stem cell transplantation involves the need for recruiting more and more potential unrelated bone marrow donors for allotransplantation. In Poland, the number of people registering as potential bone marrow donors has been continuously growing and in order to maintain this trend, it is necessary, above all, to consistently spread the noble idea of bone marrow donation and to raise Poles' awareness and knowledge about haematopoietic stem cell transplantation. Unfortunately, the situation caused by the severe acute respiratory syndrome coronavirus 2 pandemic limited the opportunities to act in public space and, as a consequence, it has become more difficult to achieve the objectives associated with recruiting new potential donors. The article provides a presentation of ethical and practical aspects associated with bone marrow donations as well as an overview of the legal situation concerning bone marrow donating and transplantation in Poland. The purpose of the paper is to also present some of the changes in transplantation procedures that have emerged as a consequence of the current epidemiological situation. The authors would like to emphasize the importance and the rightfulness of taking action that enables further development of transplantology. [ABSTRACT FROM AUTHOR]