Outcomes of the early endoscopic-assisted suturectomy for treatment of multisuture craniosynostosis.

To present the outcomes and adverse events associated with the endoscopic-assisted, minimally invasive suturectomy in patients with multisuture synostosis. This retrospective cohort study included children < 65 days of age who underwent endoscopic-assisted suturectomy (EAS) for multisuture craniosynostosis at a single tertiary referral center from 2013 to 2021. The primary outcome was calvarial expansion, and the secondary outcome was adverse events. The pre- and post-operative 3-dimensional brain computed tomography (CT) scan was used to calculate the intracranial volume and cephalic index. During a period of 2 years, 10 infants (10-64 days) diagnosed with multisuture synostosis underwent single-stage EAS of every affected suture in our center. The coronal suture was the most prevalent involved suture among our cases. The mean age and weight of the patients were 39 ± 17.5 days and 4.39 ± 0.8 kg, respectively. The surgical procedure took 42 ± 17.4 min of time and caused 46 ± 25.4 mL of bleeding on average. Ninety percent of the operations were considered successful (n = 9) regarding calvarial expansion. There were two complications, one requiring an open vault surgery and one repairing a leptomeningeal cyst. In the eight patients who did not necessitate further interventions, the mean pre-operative intracranial volume was 643.3 ± 189.4 cm3. The follow-up results within the average of 38.9 months after surgery showed that as age increases, the intracranial volume also increased significantly (R: 0.6, P < 0.0001), which suggests continued skull growth in patients who underwent EAS. With the low rate of intra- or post-operative complications and promising results on revising the restricted skull sutures, EAS seems both a safe and effective therapeutic modality in patients with multisuture synostosis, especially if completed in the first months after birth.

A DNA methylation atlas of normal human cell types.

DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes1. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells2-5. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.

Evaluation of cell-free DNA approaches for multi-cancer early detection.

In the Circulating Cell-free Genome Atlas (NCT02889978) substudy 1, we evaluate several approaches for a circulating cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test by defining clinical limit of detection (LOD) based on circulating tumor allele fraction (cTAF), enabling performance comparisons. Among 10 machine-learning classifiers trained on the same samples and independently validated, when evaluated at 98% specificity, those using whole-genome (WG) methylation, single nucleotide variants with paired white blood cell background removal, and combined scores from classifiers evaluated in this study show the highest cancer signal detection sensitivities. Compared with clinical stage and tumor type, cTAF is a more significant predictor of classifier performance and may more closely reflect tumor biology. Clinical LODs mirror relative sensitivities for all approaches. The WG methylation feature best predicts cancer signal origin. WG methylation is the most promising technology for MCED and informs development of a targeted methylation MCED test.

Reducing salt intake: a systematic review and meta-analysis of behavior change interventions in adults.

CONTEXT: Prolonged high salt (sodium) intake can increase the risk of hypertension and cardiovascular disease. Behavioral interventions may help reduce sodium intake at the population level. OBJECTIVE: The effectiveness of behavior change interventions to reduce sodium intake in adults was investigated in this systematic review and meta-analysis. DATA SOURCE: The PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and EMBASE databases were searched. DATA EXTRACTION: Narrative synthesis and random-effects meta-analyses were used to determine intervention efficacy. A total of 61 trials (46 controlled trials and 15 quasi-experimental studies) were included. RESULTS: Behavior change interventions resulted in significant improvements in salt consumption behavior (eg, decrease in purchase of salty foods; increase in use of salt substitutes), leading to reductions in sodium intake as measured by urinary sodium in 32 trials (N = 7840 participants; mean difference, -486.19 mg/d [95%CI, -669.44 to -302.95]; P < 0.001; I2 = 92%) and dietary sodium in 19 trials (N = 3750 participants; mean difference -399.86 mg/d [95%CI, -581.51 to -218.20]; P < 0.001; I2 = 96%), equivalent to a reduction of >1 g of salt intake daily. Effects were not significantly different based on baseline sodium intakes, blood pressure status, disease status, the use of behavior change theories, or the main method of intervention delivery (ie, online vs face-to-face). CONCLUSION: Behavior change interventions are effective at improving salt consumption practices and appear to reduce salt intake by >1 g/d. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42020185639.

Remote immune processes revealed by immune-derived circulating cell-free DNA.

Blood cell counts often fail to report on immune processes occurring in remote tissues. Here, we use immune cell type-specific methylation patterns in circulating cell-free DNA (cfDNA) for studying human immune cell dynamics. We characterized cfDNA released from specific immune cell types in healthy individuals (N = 242), cross sectionally and longitudinally. Immune cfDNA levels had no individual steady state as opposed to blood cell counts, suggesting that cfDNA concentration reflects adjustment of cell survival to maintain homeostatic cell numbers. We also observed selective elevation of immune-derived cfDNA upon perturbations of immune homeostasis. Following influenza vaccination (N = 92), B-cell-derived cfDNA levels increased prior to elevated B-cell counts and predicted efficacy of antibody production. Patients with eosinophilic esophagitis (N = 21) and B-cell lymphoma (N = 27) showed selective elevation of eosinophil and B-cell cfDNA, respectively, which were undetectable by cell counts in blood. Immune-derived cfDNA provides a novel biomarker for monitoring immune responses to physiological and pathological processes that are not accessible using conventional methods.

Clinical correlates of circulating cell-free DNA tumor fraction.

BACKGROUND: Oncology applications of cell-free DNA analysis are often limited by the amount of circulating tumor DNA and the fraction of cell-free DNA derived from tumor cells in a blood sample. This circulating tumor fraction varies widely between individuals and cancer types. Clinical factors that influence tumor fraction have not been completely elucidated. METHODS AND FINDINGS: Circulating tumor fraction was determined for breast, lung, and colorectal cancer participant samples in the first substudy of the Circulating Cell-free Genome Atlas study (CCGA; NCT02889978; multi-cancer early detection test development) and was related to tumor and patient characteristics. Linear models were created to determine the influence of tumor size combined with mitotic or metabolic activity (as tumor mitotic volume or excessive lesion glycolysis, respectively), histologic type, histologic grade, and lymph node status on tumor fraction. For breast and lung cancer, tumor mitotic volume and excessive lesion glycolysis (primary lesion volume scaled by percentage positive for Ki-67 or PET standardized uptake value minus 1.0, respectively) were the only statistically significant covariates. For colorectal cancer, the surface area of tumors invading beyond the subserosa was the only significant covariate. The models were validated with cases from the second CCGA substudy and show that these clinical correlates of circulating tumor fraction can predict and explain the performance of a multi-cancer early detection test. CONCLUSIONS: Prognostic clinical variables, including mitotic or metabolic activity and depth of invasion, were identified as correlates of circulating tumor DNA by linear models that relate clinical covariates to tumor fraction. The identified correlates indicate that faster growing tumors have higher tumor fractions. Early cancer detection from assays that analyze cell-free DNA is determined by circulating tumor fraction. Results support that early detection is particularly sensitive for faster growing, aggressive tumors with high mortality, many of which have no available screening today.

A comprehensive characterization of the cell-free transcriptome reveals tissue- and subtype-specific biomarkers for cancer detection.

Cell-free RNA (cfRNA) is a promising analyte for cancer detection. However, a comprehensive assessment of cfRNA in individuals with and without cancer has not been conducted. We perform the first transcriptome-wide characterization of cfRNA in cancer (stage III breast [n = 46], lung [n = 30]) and non-cancer (n = 89) participants from the Circulating Cell-free Genome Atlas (NCT02889978). Of 57,820 annotated genes, 39,564 (68%) are not detected in cfRNA from non-cancer individuals. Within these low-noise regions, we identify tissue- and cancer-specific genes, defined as "dark channel biomarker" (DCB) genes, that are recurrently detected in individuals with cancer. DCB levels in plasma correlate with tumor shedding rate and RNA expression in matched tissue, suggesting that DCBs with high expression in tumor tissue could enhance cancer detection in patients with low levels of circulating tumor DNA. Overall, cfRNA provides a unique opportunity to detect cancer, predict the tumor tissue of origin, and determine the cancer subtype.

Green tea catechins and blood pressure: a systematic review and meta-analysis of randomised controlled trials.

PURPOSE: Although previous literature has reported that regular green tea consumption may improve blood pressure, the evidence from these studies is not consistent. The present study systematically reviewed randomised controlled trials and examined the effect of green tea consumption on blood pressure using meta-analysis. METHODS: Search of ProQuest, PubMed, Scopus and Cochrane Library (CENTERAL) was conducted, to identify eligible articles. Articles from 1995 to 2013 were included. A random-effect model was chosen to calculate the effect of combined trials. RESULT: Thirteen studies were included in the meta-analysis. Green tea consumption significantly changed systolic blood pressure, by -2.08 mm Hg (95% CI -3.06, -1.05), and diastolic blood pressure, by -1.71 mm Hg (95% CI -2.86, -0.56), compared to the control. Changes in lipid profile, blood glucose and body mass index were also assessed in the meta-analysis. A significant reduction was found in total cholesterol (-0.15 mmol/L [95% CI -0.27, -0.02]) and low-density lipoprotein cholesterol (-0.16 mmol/L [95% CI -0.22, -0.09]). Changes in other parameters did not reach statistical significance. Subgroup analysis suggested a greater reduction in both systolic and diastolic blood pressure in studies that included participants with a baseline mean systolic blood pressure of ≥ 130 mm Hg, and studies involving consuming green tea as an extract. CONCLUSION: The present meta-analysis suggests that green tea and its catechins may improve blood pressure, and the effect may be greater in those with systolic blood pressure ≥ 130 mm Hg. The meta-analysis also suggests that green tea catechins may improve total and low-density lipoprotein cholesterol.

Mass-producible and efficient optical antennas with CMOS-fabricated nanometer-scale gap.

Optical antennas have been widely used for sensitive photodetection, efficient light emission, high resolution imaging, and biochemical sensing because of their ability to capture and focus light energy beyond the diffraction limit. However, widespread application of optical antennas has been limited due to lack of appropriate methods for uniform and large area fabrication of antennas as well as difficulty in achieving an efficient design with small mode volume (gap spacing < 10nm). Here, we present a novel optical antenna design, arch-dipole antenna, with optimal radiation efficiency and small mode volume, 5 nm gap spacing, fabricated by CMOS-compatible deep-UV spacer lithography. We demonstrate strong surface-enhanced Raman spectroscopy (SERS) signal with an enhancement factor exceeding 108 from the arch-dipole antenna array, which is two orders of magnitude stronger than that from the standard dipole antenna array fabricated by e-beam lithography. Since the antenna gap spacing, the critical dimension of the antenna, can be defined by deep-UV lithography, efficient optical antenna arrays with nanometer-scale gap can be mass-produced using current CMOS technology.

Contact printing of compositionally graded CdS(x)Se(1-x) nanowire parallel arrays for tunable photodetectors.

Spatially composition-graded CdS(x)Se(1-x) (x = 0-1) nanowires are grown and transferred as parallel arrays onto Si/SiO(2) substrates by a one-step, directional contact printing process. Upon subsequent device fabrication, an array of tunable-wavelength photodetectors is demonstrated. From the spectral photoconductivity measurements, the cutoff wavelength for the device array, as determined by the bandgap, is shown to cover a significant portion of the visible spectrum. The ability to transfer a collection of crystalline semiconductor nanowires while preserving the spatially graded composition may enable a wide range of applications, such as tunable lasers and photodetectors, efficient photovoltaics, and multiplexed chemical sensors.

Fast, high-throughput creation of size-tunable micro/nanoparticle clusters via evaporative self-assembly in picoliter-scale droplets of particle suspension.

We report a fast, high-throughput method to create size-tunable micro/nanoparticle clusters via evaporative assembly in picoliter-scale droplets of particle suspension. Mediated by gravity force and surface tension force of a contacting surface, picoliter-scale droplets of the suspension are generated from a nanofabricated printing head. Rapid evaporative self-assembly of the particles on a hydrophobic surface leads to fast clustering of micro/nanoparticles and forms particle clusters of tunable sizes and controlled spacing. The evaporating behavior of the droplet is observed in real-time, and the clustering characteristics of the particles are understood based on the physics of evaporative-assembly. With this method, multiplex printing of various particle clusters with accurate positioning and alignment are demonstrated. Also, size-unifomity of the cluster arrays is thoroughly analyzed by examining the metallic nanoparticle cluster-arrays based on surface-enhanced Raman spectroscopy (SERS).

Optically- and thermally-responsive programmable materials based on carbon nanotube-hydrogel polymer composites.

A simple approach is described to fabricate reversible, thermally- and optically responsive actuators utilizing composites of poly(N-isopropylacrylamide) (pNIPAM) loaded with single-walled carbon nanotubes. With nanotube loading at concentrations of 0.75 mg/mL, we demonstrate up to 5 times enhancement to the thermal response time of the nanotube-pNIPAM hydrogel actuators caused by the enhanced mass transport of water molecules. Additionally, we demonstrate the ability to obtain ultrafast near-infrared optical response in nanotube-pNIPAM hydrogels under laser excitation enabled by the strong absorption properties of nanotubes. The work opens the framework to design complex and programmable self-folding materials, such as cubes and flowers, with advanced built-in features, including tunable response time as determined by the nanotube loading.

Roll-to-roll anodization and etching of aluminum foils for high-throughput surface nanotexturing.

A high-throughput process for nanotexturing of hard and soft surfaces based on the roll-to-roll anodization and etching of low-cost aluminum foils is presented. The process enables the precise control of surface topography, feature size, and shape over large areas thereby presenting a highly versatile platform for fabricating substrates with user-defined, functional performance. Specifically, the optical and surface wetting properties of the foil substrates were systematically characterized and tuned through the modulation of the surface texture. In addition, textured aluminum foils with pore and bowl surface features were used as zeptoliter reaction vessels for the well-controlled synthesis of inorganic, organic, and plasmonic nanomaterials, demonstrating yet another powerful potential use of the presented approach.

Radiation engineering of optical antennas for maximum field enhancement.

Optical antennas have generated much interest in recent years due to their ability to focus optical energy beyond the diffraction limit, benefiting a broad range of applications such as sensitive photodetection, magnetic storage, and surface-enhanced Raman spectroscopy. To achieve the maximum field enhancement for an optical antenna, parameters such as the antenna dimensions, loading conditions, and coupling efficiency have been previously studied. Here, we present a framework, based on coupled-mode theory, to achieve maximum field enhancement in optical antennas through optimization of optical antennas' radiation characteristics. We demonstrate that the optimum condition is achieved when the radiation quality factor (Q(rad)) of optical antennas is matched to their absorption quality factor (Q(abs)). We achieve this condition experimentally by fabricating the optical antennas on a dielectric (SiO(2)) coated ground plane (metal substrate) and controlling the antenna radiation through optimizing the dielectric thickness. The dielectric thickness at which the matching condition occurs is approximately half of the quarter-wavelength thickness, typically used to achieve constructive interference, and leads to ∼20% higher field enhancement relative to a quarter-wavelength thick dielectric layer.

A unified platform for optoelectrowetting and optoelectronic tweezers.

A platform capable of seamlessly unifying both optoelectrowetting and optoelectronic tweezers is presented. This enables the user to manipulate aqueous droplets (with electrowetting) as well as individual particles within those droplets (with dielectrophoresis). The device requires no photolithography and droplet/particle manipulation can occur continuously over the entire surface of the device. Droplet and 10 µm polystyrene particle speeds of up to 8 mm s(-1) and 60 µm s(-1), respectively, are demonstrated. Particle concentration within, and subsequent splitting of, a droplet is performed resulting in average concentration efficiencies of 93%. Serial concentration is also demonstrated resulting in exponentially increasing particle concentrations and a 10× concentration increase. Finally, the platform is used to select a single cell out of a cohort and subsequently encapsulate it in its own aqueous droplet.

Shape-controlled synthesis of single-crystalline nanopillar arrays by template-assisted vapor-liquid-solid process.

Highly regular, single-crystalline nanopillar arrays with tunable shapes and geometry are synthesized by the template-assisted vapor-liquid-solid growth mechanism. In this approach, the grown nanopillars faithfully reproduce the shape of the pores because during the growth the liquid catalyst seeds fill the space available, thereby conforming to the pore geometry. The process is highly generic for various material systems, and as an example, CdS and Ge nanopillar arrays with square, rectangular, and circular cross sections are demonstrated. In the future, this technique can be used to engineer the intrinsic properties of NPLs as a function of three independently controlled dimensional parameters--length, width and height.

Motile and non-motile sperm diagnostic manipulation using optoelectronic tweezers.

Optoelectronic tweezers was used to manipulate human spermatozoa to determine whether their response to OET predicts sperm viability among non-motile sperm. We review the electro-physical basis for how live and dead human spermatozoa respond to OET. The maximal velocity that non-motile spermatozoa could be induced to move by attraction or repulsion to a moving OET field was measured. Viable sperm are attracted to OET fields and can be induced to move at an average maximal velocity of 8.8 ± 4.2 µm s(-1), while non-viable sperm are repelled to OET, and are induced to move at an average maximal velocity of -0.8 ± 1.0 µm s(-1). Manipulation of the sperm using OET does not appear to result in increased DNA fragmentation, making this a potential method by which to identify viable non-motile sperm for assisted reproductive technologies.

Ordered arrays of dual-diameter nanopillars for maximized optical absorption.

Optical properties of highly ordered Ge nanopillar arrays are tuned through shape and geometry control to achieve the optimal absorption efficiency. Increasing the Ge materials filling ratio is shown to increase the reflectance while simultaneously decreasing the transmittance, with the absorbance showing a strong diameter dependency. To enhance the broad band optical absorption efficiency, a novel dual-diameter nanopillar structure is presented, with a small diameter tip for minimal reflectance and a large diameter base for maximal effective absorption coefficient. The enabled single-crystalline absorber material with a thickness of only 2 µm exhibits an impressive absorbance of ∼99% over wavelengths, λ = 300-900 nm. These results enable a viable and convenient route toward shape-controlled nanopillar-based high-performance photonic devices.

Phototransistor-based optoelectronic tweezers for dynamic cell manipulation in cell culture media.

Optoelectronic tweezers (OET), based on light-induced dielectrophoresis, has been shown as a versatile tool for parallel manipulation of micro-particles and cells (P. Y. Chiou, A. T. Ohta and M. C. Wu, Nature, 2005, 436, 370-372). However, the conventional OET device cannot operate in cell culture media or other high-conductivity physiological buffers due to the limited photoconductivity of amorphous silicon. In this paper, we report a new phototransistor-based OET (Ph-OET). Consisting of single-crystalline bipolar junction transistors, the Ph-OET has more than 500x higher photoconductivity than amorphous silicon. Efficient cell trapping of live HeLa and Jurkat cells in Phosphate Buffered Saline (PBS) and Dulbecco's Modified Eagle's Medium (DMEM) has been demonstrated using a digital light projector, with a cell transport speed of 33 microm/sec, indicating a force of 14.5 pN. Optical concentration of cells and real-time control of individually addressable cell arrays have also been realized. Precise control of separation between two cells has also been demonstrated. We envision a new platform for single cell studies using Ph-OET.