Vertebrate centromeres in mitosis are functionally bipartite structures stabilized by cohesin.

Centromeres are scaffolds for the assembly of kinetochores that ensure chromosome segregation during cell division. How vertebrate centromeres obtain a three-dimensional structure to accomplish their primary function is unclear. Using super-resolution imaging, capture-C, and polymer modeling, we show that vertebrate centromeres are partitioned by condensins into two subdomains during mitosis. The bipartite structure is found in human, mouse, and chicken cells and is therefore a fundamental feature of vertebrate centromeres. Super-resolution imaging and electron tomography reveal that bipartite centromeres assemble bipartite kinetochores, with each subdomain binding a distinct microtubule bundle. Cohesin links the centromere subdomains, limiting their separation in response to spindle forces and avoiding merotelic kinetochore-spindle attachments. Lagging chromosomes during cancer cell divisions frequently have merotelic attachments in which the centromere subdomains are separated and bioriented. Our work reveals a fundamental aspect of vertebrate centromere biology with implications for understanding the mechanisms that guarantee faithful chromosome segregation.

Text mining and portal development for gene-specific publications on Alzheimer's disease and other neurodegenerative diseases.

BACKGROUND: Tremendous research efforts have been made in the Alzheimer's disease (AD) field to understand the disease etiology, progression and discover treatments for AD. Many mechanistic hypotheses, therapeutic targets and treatment strategies have been proposed in the last few decades. Reviewing previous work and staying current on this ever-growing body of AD publications is an essential yet difficult task for AD researchers. METHODS: In this study, we designed and implemented a natural language processing (NLP) pipeline to extract gene-specific neurodegenerative disease (ND) -focused information from the PubMed database. The collected publication information was filtered and cleaned to construct AD-related gene-specific publication profiles. Six categories of AD-related information are extracted from the processed publication data: publication trend by year, dementia type occurrence, brain region occurrence, mouse model information, keywords occurrence, and co-occurring genes. A user-friendly web portal is then developed using Django framework to provide gene query functions and data visualizations for the generalized and summarized publication information. RESULTS: By implementing the NLP pipeline, we extracted gene-specific ND-related publication information from the abstracts of the publications in the PubMed database. The results are summarized and visualized through an interactive web query portal. Multiple visualization windows display the ND publication trends, mouse models used, dementia types, involved brain regions, keywords to major AD-related biological processes, and co-occurring genes. Direct links to PubMed sites are provided for all recorded publications on the query result page of the web portal. CONCLUSION: The resulting portal is a valuable tool and data source for quick querying and displaying AD publications tailored to users' interested research areas and gene targets, which is especially convenient for users without informatic mining skills. Our study will not only keep AD field researchers updated with the progress of AD research, assist them in conducting preliminary examinations efficiently, but also offers additional support for hypothesis generation and validation which will contribute significantly to the communication, dissemination, and progress of AD research.

High-Density Glass Scintillators for Proton Radiography-Relative Luminosity, Proton Response, and Spatial Resolution.

Proton radiography is a promising development in proton therapy, and researchers are currently exploring optimal detector materials to construct proton radiography detector arrays. High-density glass scintillators may improve integrating-mode proton radiography detectors by increasing spatial resolution and decreasing detector thickness. We evaluated several new scintillators, activated with europium or terbium, with proton response measurements and Monte Carlo simulations, characterizing relative luminosity, ionization quenching, and proton radiograph spatial resolution. We applied a correction based on Birks's analytical model for ionization quenching. The data demonstrate increased relative luminosity with increased activation element concentration, and higher relative luminosity for samples activated with europium. An increased glass density enables more compact detector geometries and higher spatial resolution. These findings suggest that a tungsten and gadolinium oxide-based glass activated with 4% europium is an ideal scintillator for testing in a full-size proton radiography detector.

High-pressure studies of size dependent yield strength in rhenium diboride nanocrystals.

The superhard ReB2 system is the hardest pure phase diboride synthesized to date. Previously, we have demonstrated the synthesis of nano-ReB2 and the use of this nanostructured material for texture analysis using high-pressure radial diffraction. Here, we investigate the size dependence of hardness in the nano-ReB2 system using nanocrystalline ReB2 with a range of grain sizes (20-60 nm). Using high-pressure X-ray diffraction, we characterize the mechanical properties of these materials, including bulk modulus, lattice strain, yield strength, and texture. In agreement with the Hall-Petch effect, the yield strength increases with decreasing size, with the 20 nm ReB2 exhibiting a significantly higher yield strength than any of the larger grained materials or bulk ReB2. Texture analysis on the high pressure diffraction data shows a maximum along the [0001] direction, which indicates that plastic deformation is primarily controlled by the basal slip system. At the highest pressure (55 GPa), the 20 nm ReB2 shows suppression of other slip systems observed in larger ReB2 samples, in agreement with its high yield strength. This behavior, likely arises from an increased grain boundary concentration in the smaller nanoparticles. Overall, these results highlight that even superhard materials can be made more mechanically robust using nanoscale grain size effects.

Biomechanical phenotyping pipeline for stalk lodging resistance in maize.

Stalk lodging (structural failure crops prior to harvest) significantly reduces annual yields of vital grain crops. The lack of standardized, high throughput phenotyping methods capable of quantifying biomechanical plant traits prevents comprehensive understanding of the genetic architecture of stalk lodging resistance. A phenotyping pipeline developed to enable higher throughput biomechanical measurements of plant traits related to stalk lodging is presented. The methods were developed using principles from the fields of engineering mechanics and metrology and they enable retention of plant-specific data instead of averaging data across plots as is typical in most phenotyping studies. This pipeline was specifically designed to be implemented in large experimental studies and has been used to phenotype over 40,000 maize stalks. The pipeline includes both lab- and field-based phenotyping methodologies and enables the collection of metadata. Best practices learned by implementing this pipeline over the past three years are presented. The specific instruments (including model numbers and manufacturers) that work well for these methods are presented, however comparable instruments may be used in conjunction with these methods as seen fit.•Efficient methods to measure biomechanical traits and record metadata related to stalk lodging.•Can be used in studies with large sample sizes (i.e., > 1,000).

Diaphragmatic pacing for respiratory failure in children.

Diaphragm pacing is a ventilation strategy in respiratory failure. Most of the literature on pacing involves adults with common indications being spinal cord injury and amyotrophic lateral sclerosis (ALS). Previous reports in pediatric patients consist of case reports or small series; most describe direct phrenic nerve stimulation for central hypoventilation syndrome. This differs from adult reports that focus most commonly on spinal cord injuries and the rehabilitative nature of diaphragm pacing. This review describes the current state of diaphragm pacing in pediatric patients. Indications, current available technologies, surgical techniques, advantages, and pitfalls/problems are discussed.

Integrated-mode proton radiography with 2D lateral projections.

Integrated-mode proton radiography leading to water equivalent thickness (WET) maps is an avenue of interest for motion management, patient positioning, andin vivorange verification. Radiographs can be obtained using a pencil beam scanning setup with a large 3D monolithic scintillator coupled with optical cameras. Established reconstruction methods either (1) involve a camera at the distal end of the scintillator, or (2) use a lateral view camera as a range telescope. Both approaches lead to limited image quality. The purpose of this work is to propose a third, novel reconstruction framework that exploits the 2D information provided by two lateral view cameras, to improve image quality achievable using lateral views. The three methods are first compared in a simulated Geant4 Monte Carlo framework using an extended cardiac torso (XCAT) phantom and a slanted edge. The proposed method with 2D lateral views is also compared with the range telescope approach using experimental data acquired with a plastic volumetric scintillator. Scanned phantoms include a Las Vegas (contrast), 9 tissue-substitute inserts (WET accuracy), and a paediatric head phantom. Resolution increases from 0.24 (distal) to 0.33 lp mm-1(proposed method) on the simulated slanted edge phantom, and the mean absolute error on WET maps of the XCAT phantom is reduced from 3.4 to 2.7 mm with the same methods. Experimental data from the proposed 2D lateral views indicate a 36% increase in contrast relative to the range telescope method. High WET accuracy is obtained, with a mean absolute error of 0.4 mm over 9 inserts. Results are presented for various pencil beam spacing ranging from 2 to 6 mm. This work illustrates that high quality proton radiographs can be obtained with clinical beam settings and the proposed reconstruction framework with 2D lateral views, with potential applications in adaptive proton therapy.

Virtual reality applications in pediatric surgery.

Virtual reality modeling (VRM) is a 3-dimensional (3D) simulation. It is a powerful tool and has multiple uses and applications in pediatric surgery. Patient-specific 2-dimensional imaging can be used to generate a virtual reality model, which can improve anatomical perception and understanding, and can aid in preoperative planning for complex operations. VRM can also be used for realistic training and simulation. It has also proven effective in distraction for pediatric patients experiencing pain and/or anxiety. We detail the technical requirements and process required for VRM generation, the applications, and future directions.

Understanding How the Suppression of Insertion-Induced Phase Transitions Leads to Fast Charging in Nanoscale LixMoO2.

Fast-charging Li-ion batteries are technologically important for the electrification of transportation and the implementation of grid-scale storage, and additional fundamental understanding of high-rate insertion reactions is necessary to overcome current rate limitations. In particular, phase transformations during ion insertion have been hypothesized to slow charging. Nanoscale materials with modified transformation behavior often show much faster kinetics, but the mechanism for these changes and their specific contribution to fast-charging remain poorly understood. In this work, we combine operando synchrotron X-ray diffraction with electrochemical kinetics analyses to illustrate how nanoscale crystal size leads to suppression of first-order insertion-induced phase transitions and their negative kinetic effects in MoO2, a tunnel structure host material. In electrodes made with micrometer-scale particles, large first-order phase transitions during cycling lower capacity, slow charge storage, and decrease cycle life. In medium-sized nanoporous MoO2, the phase transitions remain first-order, but show a considerably smaller miscibility gap and shorter two-phase coexistence region. Finally, in small MoO2 nanocrystals, the structural evolution during lithiation becomes entirely single-phase/solid-solution. For all nanostructured materials, the changes to the phase transition dynamics lead to dramatic improvements in capacity, rate capability, and cycle life. This work highlights the continuous evolution from a kinetically hindered battery material in bulk form to a fast-charging, pseudocapacitive material through nanoscale size effects. As such, it provides key insight into how phase transitions can be effectively controlled using nanoscale size and emphasizes the importance of these structural dynamics to the fast rate capability observed in nanostructured electrode materials.

A supernumerary synthetic chromosome in Komagataella phaffii as a repository for extraneous genetic material.

BACKGROUND: Komagataella phaffii (Pichia pastoris) is a methylotrophic commercially important non-conventional species of yeast that grows in a fermentor to exceptionally high densities on simple media and secretes recombinant proteins efficiently. Genetic engineering strategies are being explored in this organism to facilitate cost-effective biomanufacturing. Small, stable artificial chromosomes in K. phaffii could offer unique advantages by accommodating multiple integrations of extraneous genes and their promoters without accumulating perturbations of native chromosomes or exhausting the availability of selection markers. RESULTS: Here, we describe a linear "nano"chromosome (of 15-25 kb) that, according to whole-genome sequencing, persists in K. phaffii over many generations with a copy number per cell of one, provided non-homologous end joining is compromised (by KU70-knockout). The nanochromosome includes a copy of the centromere from K. phaffii chromosome 3, a K. phaffii-derived autonomously replicating sequence on either side of the centromere, and a pair of K. phaffii-like telomeres. It contains, within its q arm, a landing zone in which genes of interest alternate with long (approx. 1-kb) non-coding DNA chosen to facilitate homologous recombination and serve as spacers. The landing zone can be extended along the nanochromosome, in an inch-worming mode of sequential gene integrations, accompanied by recycling of just two antibiotic-resistance markers. The nanochromosome was used to express PDI, a gene encoding protein disulfide isomerase. Co-expression with PDI allowed the production, from a genomically integrated gene, of secreted murine complement factor H, a plasma protein containing 40 disulfide bonds. As further proof-of-principle, we co-expressed, from a nanochromosome, both PDI and a gene for GFP-tagged human complement factor H under the control of PAOX1 and demonstrated that the secreted protein was active as a regulator of the complement system. CONCLUSIONS: We have added K. phaffii to the list of organisms that can produce human proteins from genes carried on a stable, linear, artificial chromosome. We envisage using nanochromosomes as repositories for numerous extraneous genes, allowing intensive engineering of K. phaffii without compromising its genome or weakening the resulting strain.

Case Report: Acute abdomen and large mesenteric mass as another face of multisystem inflammatory syndrome in an adolescent child: measure twice, act once!

Introduction: During the Covid-19 era, acute abdomen and mesenteric lymphadenopathy were encountered as frequent mimic of appendicitis. This phenomenon can further complicate the diagnosis of acute abdominal conditions, not solely due to bacterial or viral intestinal infections but also attributable to post-infectious acute inflammatory states resulting in either undertreatment of inflammatory conditions or unnecessary surgery. Case presentation: In this case study, we present the case of an 11-year-old female who initially presented with fever and right lower quadrant abdominal pain, raising concerns of appendicitis. However, upon further investigation, it was revealed that she harbored a sizable mesenteric mass. Subsequent biopsy results unveiled a significant necrotic mesenteric lymphadenitis. Notably, this patient fulfilled the criteria for Multisystem Inflammatory Syndrome in Children (MIS-C), a condition that manifested following persistent postoperative fever. Remarkably, the patient exhibited a highly favorable response to the treatment administered. This clinical scenario presents an atypical manifestation of MIS-C, as the patient displayed a substantial mesenteric mass alongside symptoms mimicking appendicitis, within the context of an acute abdomen. Conclusion: Clinicians should consider MIS-C and other post-infectious inflammatory conditions in mind when diagnosing acute abdominal cases. The presented case underscores the importance of recognizing atypical presentations of MIS-C that can mimic appendicitis, sometimes necessitating surgical resection of a large lymph node. We propose diagnostic flow chart to aid in the differentiation of acute bacterial appendicitis from MIS-C.

Escape of surgical smoke particles, comparing conventional and valveless trocar systems.

BACKGROUND: During minimal access surgery, surgical smoke is produced which can potentially be inhaled by the surgical team, leading to several health risks. This smoke can escape from the abdominal cavity into the operating room due to trocar leakage. The trocars and insufflator that are used during surgery influence gas leakage. Therefore, this study compares particle escape from a valveless (Conmed AirSeal iFS), and a conventional (Karl Storz Endoflator) system. MATERIALS AND METHODS: Using an in vitro model, a conventional and a valveless trocar system were compared. A protocol that simulated various surgical phases was defined to assess the surgical conditions and particle leakage. Insufflation pressures and instrument diameters were varied as these are known to affect gas leakage. RESULTS: The conventional trocar leaked during two distinct phases. Removal of the obturator caused a sudden release of particles. During instrument insertion, an average of 211 (IQR 111) particles per second escaped when using the 5 mm diameter instrument. With the 10 mm instrument, 50 (IQR 13) particles per second were measured. With the conventional trocar, a higher abdominal pressure increased particle leakage. The valveless trocar demonstrated a continuously high particle release during all phases. After the obturator was removed, particle escape increased sharply. Particle escape decreased to 1276 (IQR 580) particles per second for the 5 mm instrument insertion, and 1084 (IQR 630) particles per second for 10 mm instrument insertion. With the valveless trocar system, a higher insufflation pressure lowered particle escape. CONCLUSIONS: This study shows that a valveless trocar system releases more particles into the operating room environment than a conventional trocar. During instrument insertion, the leakage through the valveless system is 6 to 20 times higher than the conventional system. With a valveless trocar, leakage decreases with increasing pressure. With both trocar types leakage depends on instrument diameter.

The influence of prolonged instrument manipulation on gas leakage through trocars.

BACKGROUND: During laparoscopic surgery, CO2 insufflation gas could leak from the intra-abdominal cavity into the operating theater. Medical staff could therefore be exposed to hazardous substances present in leaked gas. Although previous studies have shown that leakage through trocars is a contributing factor, trocar performance over longer periods remains unclear. This study investigates the influence of prolonged instrument manipulation on gas leakage through trocars. METHODS: Twenty-five trocars with diameters ranging from 10 to 15 mm were included in the study. An experimental model was developed to facilitate instrument manipulation in a trocar under loading. The trocar was mounted to a custom airtight container insufflated with CO2 to a pressure of 15 mmHg, similar to clinical practice. A linear stage was used for prolonged instrument manipulation. At the same time, a fixed load was applied radially to the trocar cannula to mimic the reaction force of the abdominal wall. Gas leakage was measured before, after, and during instrument manipulation. RESULTS: After instrument manipulation, leakage rates per trocar varied between 0.0 and 5.58 L/min. No large differences were found between leakage rates before and after prolonged manipulation in static and dynamic measurements. However, the prolonged instrument manipulation did cause visible damage to two trocars and revealed unintended leakage pathways in others that can be related to production flaws. CONCLUSION: Prolonged instrument manipulation did not increase gas leakage rates through trocars, despite damage to some individual trocars. Nevertheless, gas leakage through trocars occurs and is caused by different trocar-specific mechanisms and design issues.

Hypo-Osmotic Stress and Pore-Forming Toxins Adjust the Lipid Order in Sheep Red Blood Cell Membranes.

Lipid ordering in cell membranes has been increasingly recognized as an important factor in establishing and regulating a large variety of biological functions. Multiple investigations into lipid organization focused on assessing ordering from temperature-induced phase transitions, which are often well outside the physiological range. However, particular stresses elicited by environmental factors, such as hypo-osmotic stress or protein insertion into membranes, with respect to changes in lipid status and ordering at constant temperature are insufficiently described. To fill these gaps in our knowledge, we exploited the well-established ability of environmentally sensitive membrane probes to detect intramembrane changes at the molecular level. Our steady state fluorescence spectroscopy experiments focused on assessing changes in optical responses of Laurdan and diphenylhexatriene upon exposure of red blood cells to hypo-osmotic stress and pore-forming toxins at room temperature. We verified our utilized experimental systems by a direct comparison of the results with prior reports on artificial membranes and cholesterol-depleted membranes undergoing temperature changes. The significant changes observed in the lipid order after exposure to hypo-osmotic stress or pore-forming toxins resembled phase transitions of lipids in membranes, which we explained by considering the short-range interactions between membrane components and the hydrophobic mismatch between membrane thickness and inserted proteins. Our results suggest that measurements of optical responses from the membrane probes constitute an appropriate method for assessing the status of lipids and phase transitions in target membranes exposed to mechanical stresses or upon the insertion of transmembrane proteins.

Experimental error analysis of biomechanical phenotyping for stalk lodging resistance in maize.

Stalk lodging destroys between 5 and 25% of grain crops annually. Developing crop varieties with improved lodging resistance will reduce the yield gap. Field-phenotyping equipment is critical to develop lodging resistant crop varieties, but current equipment is hindered by measurement error. Relatively little research has been done to identify and rectify sources of measurement error in biomechanical phenotyping platforms. This study specifically investigated sources of error in bending stiffness and bending strength measurements of maize stalks acquired using an in-field phenotyping platform known as the DARLING. Three specific sources of error in bending stiffness and bending strength measurements were evaluated: horizontal device placement, vertical device placement and incorrect recordings of load cell height. Incorrect load cell heights introduced errors as large as 130% in bending stiffness and 50% in bending strength. Results indicated that errors on the order of 15-25% in bending stiffness and 1-10% in bending strength are common in field-based measurements. Improving the design of phenotyping devices and associated operating procedures can mitigate this error. Reducing measurement error in field-phenotyping equipment is crucial for advancing the development of improved, lodging-resistant crop varieties. Findings have important implications for reducing the yield gap.

Disparities in care of pediatric, adolescent, and young adult patients with solid tumors: A systematic review.

BACKGROUND: Numerous studies have demonstrated a variety of social inequalities within pediatric and young adult patients with solid tumors. This systematic review examines and consolidates the existing literature regarding disparities in pediatric and young adult solid tumor oncology. PROCEDURE: A MeSH search was performed on the following databases: MEDLINE, PubMed, OvidSP Cochrane, Central, Embase, Cinhal, and Scopus. The systematic review was performed using Rayyan QCRI. RESULTS: Total 387 articles were found on the initial search, and 34 articles were included in final review. Twenty-seven studies addressed racial and ethnic disparities; 23 addressed socioeconomic disparities. Patients with Hispanic ethnicity, Black race, and lower socioeconomic status were more likely to present at later stages, have differences in treatments and higher mortality rates. CONCLUSION: This qualitative systematic review identified both racial and socioeconomic disparities in pediatric cancer patients across a variety of solid tumor types. Patients with Hispanic ethnicity, Black race, and lower socioeconomic status are associated with disparities in stage at presentation, treatment, and outcome. Characterization of existing disparities provides the evidence necessary to support changes at a systemic level.

In-Situ Measurement of Magnetoelectric Coupling and Strain Transfer in Multiferroic Nanocomposites of CoFe2O4 and Hf0.5Zr0.5O2 with Residual Porosity.

With increasing applications for voltage-controlled magnetism, the need to more fully understand magnetoelectric coupling and strain transfer in nanostructured multiferroic composites has also increased. Here, multiferroic nanocomposites were synthesized using block copolymer templating to create mesoporous cobalt ferrite (CFO), followed by partly filling the pores with ferroelectric zirconium-substituted hafnia (HZO) using atomic layer deposition (ALD) to produce a porous multiferroic composite with enhanced mechanical flexibility. Upon electrical poling of the nanocomposite, we observed large changes in the magnetization. These changes partly relaxed upon removing the electric field, suggesting a strain-mediated mechanism. Both the anisotropic strain transfer from HZO to CFO and the strain relaxation after the field was removed were confirmed using high-resolution X-ray diffraction measurements collected during in-situ poling. The in-situ observation of both anisotropic strain transfer and large magnetization changes allows us to directly characterize the strong multiferroic coupling that can occur in flexible, nanostructured composites.

Technical note: Comprehensive evaluations of gantry and couch rotation isocentricities for implementing proton stereotactic radiosurgery.

BACKGROUND: Mechanical accuracy should be verified before implementing a proton stereotactic radiosurgery (SRS) program. Linear accelerator (Linac)-based SRS systems often use electronic portal imaging devices (EPIDs) to verify beam isocentricity. Because proton therapy systems do not have EPID, beam isocentricity tests of proton SRS may still rely on films, which are not efficient. PURPOSE: To validate that our proton SRS system meets mechanical precision requirements and to present an efficient method to evaluate the couch and gantry's rotational isocentricity for our proton SRS system. METHODS: A dedicated applicator to hold brass aperture for proton SRS system was designed. The mechanical precision of the system was tested using a metal ball and film for 11 combinations of gantry and couch angles. A more efficient quality assurance (QA) procedure was developed, which used a scintillator device to replace the film. The couch rotational isocentricity tests were performed using orthogonal kV x-rays with the couch rotated isocentrically to five positions (0°, 315°, 270°, 225°, and 180°). At each couch position, the distance between the metal ball in kV images and the imaging isocenter was measured. The gantry isocentricity tests were performed using a cone-shaped scintillator and proton beams at five gantry angles (0°, 45°, 90°, 135°, and 180°), and the isocenter position and the distance of each beam path to the isocenter were obtained. Daily QA procedure was performed for 1 month to test the robustness and reproducibility of the procedure. RESULTS: The gantry and couch rotational isocentricity exhibited sub-mm precision, with most measurements within ±0.5 mm. The 1-month QA results showed that the procedure was robust and highly reproducible to within ±0.2 mm. The gantry isocentricity test using the cone-shaped scintillator was accurate and sensitive to variations of ±0.2 mm. The QA procedure was efficient enough to be completed within 30 min. The 1-month isocentricity position variations were within 0.5 mm, which demonstrating that the overall proton SRS system was stable and precise. CONCLUSION: The proton SRS Winston-Lutz QA procedure using a cone-shaped scintillator was efficient and robust. We were able to verify radiation delivery could be performed with sub-mm mechanical precision.

A direct and clean route to MXenes.

New, scalable methods synthesize two-dimensional carbide and nitride materials.

The semi-automated development of plant cell wall finite element models.

This study presents a methodology for a high-throughput digitization and quantification process of plant cell walls characterization, including the automated development of two-dimensional finite element models. Custom algorithms based on machine learning can also analyze the cellular microstructure for phenotypes such as cell size, cell wall curvature, and cell wall orientation. To demonstrate the utility of these models, a series of compound microscope images of both herbaceous and woody representatives were observed and processed. In addition, parametric analyses were performed on the resulting finite element models. Sensitivity analyses of the structural stiffness of the resulting tissue based on the cell wall elastic modulus and the cell wall thickness; demonstrated that the cell wall thickness has a three-fold larger impact of tissue stiffness than cell wall elastic modulus.