Short Fragments Research Articles

Force-Induced Site-Specific Enzymatic Cleavage Probes Reveal That Serial Mechanical Engagement Boosts T Cell Activation.

The T cell membrane is studded with >104 T cell receptors (TCRs) that are used to scan target cells to identify short peptide fragments associated with viral infection or cancerous mutation. These peptides are presented as peptide-major-histocompatibility complexes (pMHCs) on the surface of virtually all nucleated cells. The TCR-pMHC complex forms at cell-cell junctions, is highly transient, and experiences mechanical forces. An important question in this area pertains to the role of the force duration in immune activation. Herein, we report the development of force probes that autonomously terminate tension within a time window following mechanical triggering. Force-induced site-specific enzymatic cleavage (FUSE) probes tune the tension duration by controlling the rate of a force-triggered endonuclease hydrolysis reaction. This new capability provides a method to study how the accumulated force duration contributes to T cell activation. We screened DNA sequences and identified FUSE probes that disrupt mechanical interactions with F > 7.1 piconewtons (pN) between TCRs and pMHCs. This rate of disruption, or force lifetime (τF), is tunable from tens of minutes down to 1.9 min. T cells challenged with FUSE probes with F > 7.1 pN presenting cognate antigens showed up to a 23% decrease in markers of early activation. FUSE probes with F > 17.0 pN showed weaker influence on T cell triggering further showing that TCR-pMHC with F > 17.0 pN are less frequent compared to F > 7.1 pN. Taken together, FUSE probes allow a new strategy to investigate the role of force dynamics in mechanotransduction broadly and specifically suggest a model of serial mechanical engagement boosting TCR activation.

Exploration of the Polymorphism Distribution of Bovine HMGA2 Gene in Worldwide Breeds and Its Associations with Ovarian Traits.

The high-mobility group AT-hook 2(HMGA2) gene has been widely studied in the context of cancer and animal growth. However, recently, several studies have uncovered its critical role in cell proliferation. A genome-wide association study (GWAS) further suggests that the HMGA2 gene is a candidate gene in fertility, indicating its connection not only to growth traits but also to reproduction, specifically ovarian traits. Thus, this study aimed to analyze the distribution of the HMGA2 gene in 54 bovine breeds worldwide, identify important short fragment variants (indels), and investigate the relationship between HMGA2 and ovarian development. The dataset included genotypic information from a bovine population of 634 individuals (n = 634). After genotyping and analyzing four selected loci, we found that one out of four loci, rs133750033 (P4-D22-bp), was polymorphic. Our results also reveal that this indel of HMGA2 is significantly associated with certain ovarian traits (p < 0.05). Specifically, it has connection with ovarian length (p = 0.004) and ovarian height (p = 0.026) during diestrus. Additionally, we discovered a higher expression of the HMGA2 gene in Asian cattle breeds. In summary, this study suggests that HMGA2 has the potential to serve as an animal fertility testing marker gene. Moreover, these findings contribute to a more promising outlook for the bovine industry.

Management of Nonunion of Distal Tibial Periarticular Fractures Using Ilizarov External Fixator

Nonunion of the periarticular distal tibial fractures is a challenging issue with limited options for treatment. The study aims to evaluate the outcomes of treatment of non-united periarticular distal tibial fractures using Ilizarov external fixation. A retrospective study included 16 patients with distal tibial fracture nonunion treated with Ilizarov fixator from 2014 to 2019 with a minimum 1-year follow-up after frame removal. Fibular plating was done in 8 cases and supplementary interfragmentary screws at the nonunion site in 5 cases. Primary or delayed bone graft was used in 11 patients. The ASAMI protocol was used to assess the bone and functional results. The American Orthopaedic Foot and Ankle Society (AOFAS) scale was used to assess the functional outcomes. Study included 9 males and 7 females, mean age of 47.4±14.1 years. 15 cases had previous surgeries for nonunion. 7 had active infection. duration of nonunion was 24.1±13.2 months. Mean duration of fixation was 5.7±1.0 months. Mean follow-up was 21.8±8.5 months. Mean AOFAS score improved from 52.4±3.7 preoperatively to 85.4±9.8 at the latest follow-up (P&lt;0.001). Finally, the infection was resolved, and union was achieved in all patients. Bone results were excellent in 3 cases and good in 13, whereas functional results were excellent in 6 cases, good in 8, fair in 1, and poor in 1. Ilizarov fixator is a reliable option for treating nonunion in the periarticular distal tibial fractures. It provides secure fixation for short distal fragments, especially with history of infection, those with bad skin conditions, previous failed internal fixation, and osteopenic bone. Level of Evidence: Level IV.

Recovering short DNA fragments from minerals and marine sediments: A comparative study evaluating lysis and isolation approaches

AbstractMarine sediments as excellent climate archives, contain among other biomolecules substantial amounts of extracellular DNA. Through mineral binding, some of the DNA remains protected from degradation which aids its preservation. While this pool of DNA represents genomic ecosystem fingerprints spanning over millions of years, the capability of current DNA extraction methods in recovering mineral‐bound DNA remains poorly understood. We evaluated current sedimentary DNA extraction approaches and their ability to recover short DNA fragments from artificially created DNA‐mineral complexes involving pure clay minerals or quartz, as well as from different types of natural marine sediments. We separately investigated lysis (DNA release) and isolation steps (purification of DNA) comparing five different lysis buffers across two commonly used DNA isolation approaches: silica magnetic beads and liquid‐phase organic extraction and purification. The choice of lysis buffer significantly impacted the amount of recovered mineral‐bound DNA and facilitated selective desorption of DNA fragments. High molarity EDTA and phosphate lysis buffers recovered on average an order of magnitude more DNA from clay minerals than other tested buffers, while both isolation approaches recovered comparable amounts of DNA. In marine sediments, however, liquid‐phase organic extraction caused inhibitory effects in subsequent downstream applications (e.g., PCR), across all assessed DNA extracts, while silica magnetic beads induced inhibition only in half of the tested DNA extracts. Thus, the isolation approach, together with the lysis buffer, played a decisive role in successful library preparation with lysis buffer choice ultimately impacting final library fragment distribution. With this study, we underscore the critical importance of lysis buffer selection to maximize the recovery of mineral‐bound DNA and show its profound impact on recovered fragment lengths in sedimentary DNA extractions, a crucial factor alongside existing isolation approaches in facilitating high‐quality DNA extracts for downstream analysis related to ancient environmental DNA research.

Cell-Free DNA Screening for Single-Gene Disorders.

In pregnancy, cell-free DNA (cfDNA) represents short fragments of placental DNA released into the maternal blood stream through natural cell death. Noninvasive prenatal screening with cfDNA is commonly used in pregnancy to screen for common aneuploidies. This technology continues to evolve, and laboratories now offer cfDNA screening for single-gene disorders. This article aims to review cfDNA screening for single-gene disorders including the technology, current syndromes for which screening may be offered, limitations, and current recommendations. Original research articles, review articles, laboratory white papers, and society guidelines were reviewed. Cell-free DNA screening for single-gene disorders is not currently recommended by medical societies. There may be a role in specific circumstances and only after comprehensive pretest counseling. It can be considered in the setting of some fetal ultrasound anomalies, and usually only after diagnostic testing is offered and declined. Given the limitations of using cfDNA screening for single-gene disorders, caution is recommended when considering these tests. It should only be offered with involvement of a reproductive genetic counselor, medical geneticist, or maternal fetal medicine specialist to ensure comprehensive counseling and appropriate utilization.

STROKES TO JAN BARSZCZEWSKI’S BIOGRAPHY: VISITING BRIDES OF CHRIST

The article comments the short fragment of Jan Barszczewski’s list to Julia Korsak. The circumstances of his visit in Spaso-Euphrosyne momastery of Polotsk in 1843 are revealed. The fates of Basilian nuns of Polotsk in new convent are reviewed. The personality of Barszczewski’s acquaintance Glyceria Szepielewicz is found out.

Extracellular Vesicles Slow Down Aβ(1-42) Aggregation by Interfering with the Amyloid Fibril Elongation Step.

Formation of amyloid-β (Aβ) fibrils is a central pathogenic feature of Alzheimer's disease. Cell-secreted extracellular vesicles (EVs) have been suggested as disease modulators, although their exact roles and relations to Aβ pathology remain unclear. We combined kinetics assays and biophysical analyses to explore how small (<220 nm) EVs from neuronal and non-neuronal human cell lines affected the aggregation of the disease-associated Aβ variant Aβ(1-42) into amyloid fibrils. Using thioflavin-T monitored kinetics and seeding assays, we found that EVs reduced Aβ(1-42) aggregation by inhibiting fibril elongation. Morphological analyses revealed this to result in the formation of short fibril fragments with increased thicknesses and less apparent twists. We suggest that EVs may have protective roles by reducing Aβ(1-42) amyloid loads, but also note that the formation of small amyloid fragments could be problematic from a neurotoxicity perspective. EVs may therefore have double-edged roles in the regulation of Aβ pathology in Alzheimer's disease.

Evaluation of whether there is residual polyp tissue after hysteroscopic morcellation at Cam and Sakura City Hospital: a retrospective cohort study

BackgroundIn polypectomy with mechanical hysteroscopic morcellators, the tissue removal procedure continues until no polyp tissue remains. The decision that the polypoid tissues were removed completely is made based on visual evaluation. In a situation where the polyp tissue was visually completely removed and no doubt that the polyp has been completely removed, short spindle-like tissue fragments on the polyp floor continue in most patients. There are no studies in the literature on whether visual evaluation provides adequate information at the cellular level in many patients in whom polypoid tissues have been determined to be completely removed. The aim of the present study was to analyze the pathological results of the curettage procedure, which was applied following the completion of polyp removal with operative hysteroscopy, and to evaluate whether there was residual polyp tissue in the short spindle-like tissue fragments that the mechanical hysteroscopic morcellator could not remove. The secondary aims of this study were to compare conventional loop resection hysteroscopy with hysteroscopic morcellation for the removal of endometrial polyps in terms of hemoglobin/hematocrit changes, polypectomy time and the amount of medium deficit.MethodsA total of 70 patients with a single pedunculate polypoid image of 1.5-2 cm, which was primarily visualized by office hysteroscopy, were included in the study. Patients who had undergone hysteroscopic polypectomy were divided into two groups according to the surgical device used: the morcellator group (n = 35, Group M) and the resectoscope group (n = 35, Group R). The histopathological results of hysteroscopic specimens and curettage materials of patients who had undergone curettage at the end of operative hysteroscopy were evaluated. In addition, the postoperative 24th hour Hb/HCT decrease amounts in percentage, the polypectomy time which was measured from the start of morcellation, and deficit differences were compared between groups.ResultsIn total, 7 patients in the morcellator group had residual polyp tissue detected in the full curettage material. The blood loss was lower in the morcellator group than in the resectoscope group (M, R; (-0.07 ± 0.08), (-0,11 ± 0.06), (p < 0.05), respectively). The deficit value of the morcellator group were higher (M, R; (500 ml), (300 ml), (p < 0.05), respectively). The polypectomy time was shorter in the morcellator group (M, R; mean (2.30 min), (4.6 min), (p < 0.05)).ConclusionsEven if the lesion is completely visibly removed during hysteroscopic morcellation, extra caution should be taken regarding the possibility of residual tissue. There is a need for new studies investigating the presence of residual polyp tissue.

Recognition of life-threatening arrhythmias by ECG scalograms

This work is devoted to the automatic classification of six classes of life-threatening arrhythmias using short ECG fragments of 2s-length. This task is extremely important for the detection of life-threatening arrhythmias with continuous monitoring. Especially dangerous are ventricular fibrillation and high-frequency heartbeat ventricular tachycardia. Timely detection of these dangerous disorders in the clinic allows doctors to effectively use electrical defibrillation, which saves the patient's life. A feature of our approach is the use of a unique technique for converting ECG signals into images (scalograms) using a continuous wavelet transform. For arrhythmia classification, the AlexNet neural network with a well-known deep learning architecture, which is commonly used in image classification tasks, is used. The experiments used data from the PhysioNet database, as well as synthesized ECG data obtained using the SMOTE method. The experimental results show that the proposed approach allows achieving an average accuracy of 98.7% for all classes, which exceeds the maximum accuracy estimates of 93.18% previously obtained by other researchers.

A macrophage-collagen fragment axis mediates subcutaneous adipose tissue remodeling in mice

Efficient removal of fibrillar collagen is essential for adaptive subcutaneous adipose tissue (SAT) expansion that protects against ectopic lipid deposition during weight gain. Here, we used mice to further define the mechanism for this collagenolytic process. We show that loss of collagen type-1 (CT1) and increased CT1-fragment levels in expanding SAT are associated with proliferation of resident M2-like macrophages that display increased CD206-mediated engagement in collagen endocytosis compared to chow-fed controls. Blockage of CD206 during acute high-fat diet-induced weight gain leads to SAT CT1-fragment accumulation associated with elevated inflammation and fibrosis markers. Moreover, these SAT macrophages' engagement in collagen endocytosis is diminished in obesity associated with elevated levels collagen fragments that are too short to assemble into triple helices. We show that such short fragments provoke M2-macrophage proliferation and fibroinflammatory changes in fibroblasts. In conclusion, our data delineate the importance of a macrophage-collagen fragment axis in physiological SAT expansion. Therapeutic targeting of this process may be a means to prevent pathological adipose tissue remodeling, which in turn may reduce the risk for obesity-related metabolic disorders.

Effect of peptides of trophoblastic Β1 glycoprotein on peripheral and local T-regulatory lymphocytes level in Wistar rats with allogeneous bone marrow cell transplantation

Objective. The range of peptide drugs is expanding, but no drug with immunosuppressive activity has yet been found. Considering the fact that the trophoblastic β1-glycoprotein (PSG) is a fetoplacental protein with immunosuppressive activity, short peptide fragments of this protein were studied in the formation of an immune response in a situation of allogeneic cell transplantation. To study the effect of PSG peptides (YECE, YQCE, YVCS, and YACS) on the levels of peripheral and local T-regulatory cells (Treg) during the formation of an immune response to the introduction of allogeneic bone marrow cells (BM) in a dynamic experiment on Wistar rats.&#x0D; Materials and methods. We used an original host-versus-graft model in male Wistar rats without preconditioning of recipients. Animals were injected with PSG peptide fragment composition against a background of allogeneic intraperitoneal transplantation of BM cells in a dynamic experiment, in which the following parameters were evaluated: the level of peripheral "true" Tregs (CD4+CD25+FOXP3+), CD4+CD25-FOXP3+ cells, and FOXP3 expression in mesenteric lymph nodes. Material was collected on days 3 and 21 of the experiment.&#x0D; Results. PSG peptide administration against a background of allogeneic BM cells was found to reduce the absolute and relative amount of Treg in the peripheral blood of rats on days 3 and 21 of the experiment. PSG peptides against the background of the introduction of allogeneic BM cells reduced the absolute and relative amounts of CD4+CD25-FOXP3+ cells on the day 3 of the experiment. The introduction of PSG peptides against the background of the introduction of BM cells resulted in a relative decrease in FOXP3 expression in the T zone of mesenteric lymph nodes on the day 21 of the experiment.&#x0D; Conclusions. Thus, the PSG peptides did not have the expected effect on the level of peripheral and local Treg cells; moreover, the presence of the peptides led to a decrease in the number of these cells.

The application of inverted lateral clavicle locking compression plate for medial clavicle fractures: biomechanical study and clinical implementation.

There has been no absolute consensus on the optimal implant for fixation of medial clavicle fracture. The purpose of the present study was to test the biomechanical efficacy of inverted lateral clavicle locking compression plate (LCP-LC) in fixation of this specific fracture location by finite element analysis. Transverse and comminuted medial clavicle fracture simulated models stabilized by three different devices including inverted LCP-LC, superior clavicle LCP (LCP-SC), and dual reconstruction (LCP-RP) with LCP-SC were investigated biomechanical performance under three loading conditions, i.e., axial compression, inferior bending, and axial torsion. EQV stress exhibited on implant and elastic strain at fracture site under inferior bending was greater than other loading cases. LCP-SC construct represented the greatest EQV stress and elastic strain. The inverted LCP-LC construct demonstrated lower EQV stress than the LCP-SC construct and was comparable to dual plating. Under axial compression and axial torsion, elastic strain produced from the inverted LCP-LC construct was comparable to dual plating, but greater than dual plating when subjected to inferior bending. By the results of FE analysis, inverted LCP-LC could be a potential application for fixation of clavicle fracture with short medial fragment.

Integration of Cell-Free DNA End Motifs and Fragment Lengths Can Identify Active Genes in Liquid Biopsies.

Multiple studies have shown that cell-free DNA (cfDNA) from cancer patients differ in both fragment length and fragment end motif (FEM) from healthy individuals, yet there is a lack of understanding of how the two factors combined are associated with cancer and gene transcription. In this study, we conducted cfDNA fragmentomics evaluations using plasma from lung cancer patients (n = 12) and healthy individuals (n = 7). A personal gene expression profile was established from plasma using H3K36me3 cell-free chromatin immunoprecipitation sequencing (cfChIP-seq). The genes with the highest expression displayed an enrichment of short cfDNA fragments (median = 19.99%, IQR: 16.94-27.13%, p < 0.0001) compared to the genes with low expression. Furthermore, distinct GC-rich FEMs were enriched after cfChIP. Combining the frequency of short cfDNA fragments with the presence of distinct FEMs resulted in an even further enrichment of the most expressed genes (median = 37.85%, IQR: 30.10-39.49%, p < 0.0001). An in vitro size selection of <150 bp cfDNA could isolate cfDNA representing active genes and the size-selection enrichment correlated with the cfChIP-seq enrichment (Spearman r range: 0.499-0.882, p < 0.0001). This study expands the knowledge regarding cfDNA fragmentomics and sheds new light on how gene activity is associated with both cfDNA fragment lengths and distinct FEMs.

EXPERIENCE OF THE SEGMENTAL BONE DEFECTS' TREATMENT FOR PATIENTS WITH COMBAT TRAUMA USING THE METHOD OF DISTRACTION OSTEOGENESIS

Upper and lower limb injuries resulting from battlefield trauma is a complex multidisciplinary problem. Efficacy of the treatment of segmental bone defects in patients with combat trauma is a subject of analysis for improving its results. Purpose. An analysis of the modern treatment strategies of the segmental bone defects in patients with battlefield trauma under conditions of distraction osteogenesis (based on data available in the literature and own clinical experience). Methods. Analytical review of scientific works and analysis of treatment results of 39 patients with segmental bone defects associated with battlefield trauma and treated using distraction osteogenesis were conducted. Results. Patients with segmental limbs defects require special attention of a multidisciplinary team of specialists to identify reconstructive opportunities to save the limb. Distraction osteogenesis — is an effective method of treating of segmental fractures and shortening of the limbs, infectious complications that led to bone defect formation. Bone transport with ring external fixator (ExFix) is considered as a classical method. Authors analyzed and illustrated with three clinical cases their own results of application of different distraction osteogenesis technique. Conclusions. Different types of ExFix can be applied independently or in combination with internal fixators. The use of an intramedullar nail along which distraction osteogenesis is carried out allows to provide better control of the axis of the limb and transported fragment, reduce the residence time in the ExFix, and, moreover, external fixation devices with a simpler configuration can be used. Transport along the plate allows to maintain proper axial relationships in the presence of short periarticular fragments and improve the quality of fixation but it also increases the risks of FRI and re-operations.

Integration of Rubus yellow net virus in the raspberry genome: A story centuries in the making

Rubus yellow net virus (RYNV) belongs to genus Badnavirus. Badnaviruses are found in plants as endogenous, inactive or activatable sequences, and/or in episomal (infectious and active) forms. To assess the state of RYNV in Rubus germplasm, we sequenced the genomes of various cultivars and mined eight raspberry whole genome datasets. Bioinformatics analysis revealed the presence of a diverse array of endogenous RYNV (endoRYNV) sequences that differ significantly in their structure; some lineages have nearly complete, yet non-functional genomes whereas others have rudimentary, short sequence fragments. We developed assays to genotype the main lineages as well as the only known episomal lineage present in the United States. This study discloses the widespread presence of endoRYNVs in commercial raspberries, likely because breeding efforts have focused on a limited pool of germplasm that harbored endoRYNVs.

Searching for Structure: Characterizing the Protein Conformational Landscape with Clustering-Based Algorithms.

The identification and characterization of the main conformations from a protein population are a challenging and inherently high-dimensional problem. Here, we evaluate the performance of the Secondary sTructural Ensembles with machine LeArning (StELa) double-clustering method, which clusters protein structures based on the relationship between the φ and ψ dihedral angles in a protein backbone and the secondary structure of the protein, thus focusing on the local properties of protein structures. The classification of states as vectors composed of the clusters' indices arising naturally from the Ramachandran plot is followed by the hierarchical clustering of the vectors to allow for the identification of the main features of the corresponding free energy landscape (FEL). We compare the performance of StELa with the established root-mean-squared-deviation (RMSD)-based clustering algorithm, which focuses on global properties of protein structures and with Combinatorial Averaged Transient Structure (CATS), the combinatorial averaged transient structure clustering method based on distributions of the φ and ψ dihedral angle coordinates. Using ensembles of conformations from molecular dynamics simulations of intrinsically disordered proteins (IDPs) of various lengths (tau protein fragments) or short fragments from a globular protein, we show that StELa is the clustering method that identifies many of the minima and relevant energy states around the minima from the corresponding FELs. In contrast, the RMSD-based algorithm yields a large number of clusters that usually cover most of the FEL, thus being unable to distinguish between states, while CATS does not sample well the FELs for long IDPs and fragments from globular proteins.

Synthesis of short DNA and RNA fragments by resonant acoustic mixing (RAM)

We demonstrate the first use of Resonant Acoustic Mixing (RAM) without bulk solvent for the synthesis of short oligonucleotide fragments.

Synthesis and performance evaluation of zinc oxide tubes/alginate microfibre composites for photodegradation of methylene blue: a novel reporting approach.

This research investigates the efficacy of zinc oxide (ZnO) tubes in decontaminating polluted water using a substrate-free hydrothermal synthesis process for ZnO tubes. The synthesized tubes are impregnated into calcium alginate microfibres, strategically chosen for their high surface area to enhance photocatalytic degradation performance and for practical handling during decontamination and subsequent collection, thereby preventing secondary contamination. Structural and morphological analyses, conducted using Scanning Electron Microscopy (SEM) and X-ray Diffraction (XRD), thoroughly characterize the properties of the ZnO tubes and the composite material. The efficacy of this composite is demonstrated through the photocatalytic degradation of methylene blue (MB), as a representative organic pollutant, resulting in an 88% degradation of MB after 5 hours of irradiation by a sun simulator. Cyclic tests exhibit consistent degradation levels in the first four cycles (81-89%), followed by a subsequent decrease to 72% in the fifth cycle, coinciding with the breakdown of the microfibres into shorter fragments. Innovatively, this study introduces an approach to reporting photocatalytic degradation results, utilizing normalized pollutant concentration plotted against irradiated energy instead of time, as energy encompasses irradiated power, time, and surface area. This reveals that the 88% degradation of MB is achieved by irradiating the sample with an approximately 18 kJ. Additionally, a new metric, Specific Energy Efficiency (SEE), is introduced. It expresses the ratio of degraded pollutant mass to the mass of photocatalytic active material per unit of irradiated energy, with the maximum and cumulative SEE in this study being 1.044 μg g-1 J-1 and 326 ng g-1 J-1, respectively. This research not only contributes to the understanding of ZnO tubes' efficiency in polluted water decontamination but also introduces valuable insights for standardized reporting in photocatalytic degradation studies.

Tumor targeted alpha particle therapy with an actinium-225 labelled antibody for carbonic anhydrase IX.

Selective antibody targeted delivery of α particle emitting actinium-225 to tumors has significant therapeutic potential. This work highlights the design and synthesis of a new bifunctional macrocyclic diazacrown ether chelator, H2MacropaSqOEt, that can be conjugated to antibodies and forms stable complexes with actinium-225. The macrocyclic diazacrown ether chelator incorporates a linker comprised of a short polyethylene glycol fragment and a squaramide ester that allows selective reaction with lysine residues on antibodies to form stable vinylogous amide linkages. This new H2MacropaSqOEt chelator was used to modify a monoclonal antibody, girentuximab (hG250), that binds to carbonic anhydrase IX, an enzyme that is overexpressed on the surface of cancers such as clear cell renal cell carcinoma. This new antibody conjugate (H2MacropaSq-hG250) had an average chelator to antibody ratio of 4 : 1 and retained high affinity for carbonic anhydrase IX. H2MacropaSq-hG250 was radiolabeled quantitatively with [225Ac]AcIII within one minute at room temperature with micromolar concentrations of antibody and the radioactive complex is stable in human serum for >7 days. Evaluation of [225Ac]Ac(MacropaSq-hG250) in a mouse xenograft model, that overexpresses carbonic anhydrase IX, demonstrated a highly significant therapeutic response. It is likely that H2MacropaSqOEt could be used to modify other antibodies providing a readily adaptable platform for other actinium-225 based therapeutics.

On-Chip Magnetic Extraction of Circulating Cell-Free DNA from Biological Samples.

In recent years, the analysis of circulating cell-free DNA (cfDNA) containing tumor-derived DNA has emerged as a noninvasive means for cancer monitoring and personalized medicine. However, the isolation of cfDNA from peripheral blood has remained a challenge due to the low abundance and high fragmentation of these molecules. Here, we present a dynamic Magnetic ExTRactiOn (METRO) protocol using microfluidic fluidized bed technology to isolate circulating cfDNA from raw biological materials such as undiluted serum. This protocol maximizes the surface area for DNA binding within the chip in order to capture short DNA fragments. It uses only a few μL of sample and reagents. The protocol can be automated, and it is fully compatible with sensitive DNA amplification methods such as droplet-based digital PCR (ddPCR).