Pancreaticoduodenectomy after endoscopic ultrasound-guided lumen apposing metal stent (LAMS): A case series evaluating feasibility and short-term outcomes.

Introduction: Endoscopic ultrasound (EUS)-guided lumen-apposing metal stents (LAMS) represent a novel tool in therapeutic endoscopy. However, the presence of LAMS may dissuade surgeons from operations with curative-intent. We report three clinical scenarios with deployment of LAMS in patients that subsequently underwent pancreaticoduodenectomy (PD). Methods: Six patients identified from our IRB-approved pancreas cancer database had EUS-LAMS placement prior to PD. Patient, tumor, treatment-related variables, and outcomes are herein reported. Results: Two patients underwent a LAMS gastrojejunostomy (GJ) for duodenal obstruction. Another patient underwent LAMS choledochoduodenostomy (CDS) for malignant biliary obstruction. In three patients, a LAMS gastrogastrostomy or jejunogastrostomy was deployed post Roux-en-Y gastric bypass (RYGB) for a EUS-directed transgastric ERCP (EDGE) procedure. The hospital length of stay after LAMS placement was 0-3 days without morbidity. Patients subsequently proceeded to either classic PD (n = 5) or PPPD (n = 1). Interval from LAMS insertion to surgery ranged from 28 to 194 days. Mean PD operative time and EBL were 513 minutes and 560 mL, respectively. Post-PD hospital length of stay was 4-17 days. Clavien-Dindo IIIb morbidity required percutaneous drainage of intra-abdominal collections in two patients. In cases involving LAMS-GJ and CDS, the LAMS directly impacted the surgeon's preference not to perform pylorus preservation. Conclusions: In this case series, PD following EUS-LAMS was feasible with acceptable morbidity. Additional studies with larger patient populations are needed to evaluate LAMS as a bridge to PD with curative-intent.

Recent progress in DNA data storage based on high-throughput DNA synthesis.

DNA data storage has emerged as a solution for storing massive volumes of data by utilizing nucleic acids as a digital information medium. DNA offers exceptionally high storage density, long durability, and low maintenance costs compared to conventional storage media such as flash memory and hard disk drives. DNA data storage consists of the following steps: encoding, DNA synthesis (i.e., writing), preservation, retrieval, DNA sequencing (i.e., reading), and decoding. Out of these steps, DNA synthesis presents a bottleneck due to imperfect coupling efficiency, low throughput, and excessive use of organic solvents. Overcoming these challenges is essential to establish DNA as a viable data storage medium. In this review, we provide the overall process of DNA data storage, presenting the recent progress of each step. Next, we examine a detailed overview of DNA synthesis methods with an emphasis on their limitations. Lastly, we discuss the efforts to overcome the constraints of each method and their prospects.

Correction: Recent progress in DNA data storage based on high-throughput DNA synthesis.

[This corrects the article DOI: 10.1007/s13534-024-00386-z.].

Evolving Patterns of Hyperfluorescent Fundus Autofluorescence Accompany Retinal Atrophy in the Rat and Mimic Atrophic Age-Related Macular Degeneration.

PURPOSE: Complex two-dimensional (2D) patterns of hyperfluorescent short-wave fundus autofluorescence (FAF) at the border of geographic atrophy (GA) can predict its expansion in patients with late non-exudative "dry" AMD. However, preclinical models do not phenocopy this important feature of disease. We sought to describe the spatiotemporal changes in hyperfluorescent FAF patterns that occur following acute oxidative stress, potentially in association with GA expansion. METHODS: Sprague Dawley rats (n = 54) received systemic sodium iodate (25-45 mg/kg, n = 90 eyes) or saline (n = 18 eyes) and underwent serial full fundus imaging by confocal scanning laser ophthalmoscopy, including blue FAF and delayed near-infrared analysis. Composite images of the fundus were assembled, and the 2D patterns were described qualitatively and quantitatively. A subset of eyes underwent tissue analysis, and four underwent optical coherence tomography (OCT) imaging. RESULTS: Reproducibly changing, complex patterns of hyperfluorescent FAF emerge at the borders of toxin-induced damage; however, in the absence of GA expansion, they percolate inward within the region of retinal pigment epithelium loss, evolving, maturing, and senescing in situ over time. Unexpectedly, the late FAF patterns most closely resemble the diffuse tricking form of clinical disease. A five-stage classification system is presented. CONCLUSIONS: Longitudinal, full-fundus imaging of outer retinal atrophy in the rat eye identifies evolving, complex patterns of hyperfluorescent FAF that phenocopy aspects of disease. TRANSLATIONAL RELEVANCE: This work provides a novel tool to assess hyperfluorescent FAF in association with progressive retinal atrophy, a therapeutic target in late AMD.

Charge order textures induced by non-linear couplings in a half-doped manganite.

The self-organization of strongly interacting electrons into superlattice structures underlies the properties of many quantum materials. How these electrons arrange within the superlattice dictates what symmetries are broken and what ground states are stabilized. Here we show that cryogenic scanning transmission electron microscopy (cryo-STEM) enables direct mapping of local symmetries and order at the intra-unit-cell level in the model charge-ordered system Nd1/2Sr1/2MnO3. In addition to imaging the prototypical site-centered charge order, we discover the nanoscale coexistence of an exotic intermediate state which mixes site and bond order and breaks inversion symmetry. We further show that nonlinear coupling of distinct lattice modes controls the selection between competing ground states. The results demonstrate the importance of lattice coupling for understanding and manipulating the character of electronic self-organization and that cryo-STEM can reveal local order in strongly correlated systems at the atomic scale.

Image registration of low signal-to-noise cryo-STEM data.

Combining multiple fast image acquisitions to mitigate scan noise and drift artifacts has proven essential for picometer precision, quantitative analysis of atomic resolution scanning transmission electron microscopy (STEM) data. For very low signal-to-noise ratio (SNR) image stacks - frequently required for undistorted imaging at liquid nitrogen temperatures - image registration is particularly delicate, and standard approaches may either fail, or produce subtly specious reconstructed lattice images. We present an approach which effectively registers and averages image stacks which are challenging due to their low-SNR and propensity for unit cell misalignments. Registering all possible image pairs in a multi-image stack leads to significant information surplus. In combination with a simple physical picture of stage drift, this enables identification of incorrect image registrations, and determination of the optimal image shifts from the complete set of relative shifts. We demonstrate the effectiveness of our approach on experimental, cryogenic STEM datasets, highlighting subtle artifacts endemic to low-SNR lattice images and how they can be avoided. High-SNR average images with information transfer out to 0.72 Å are achieved at 300 kV and with the sample cooled to near liquid nitrogen temperature.

Insulator-to-Metal Transition at Oxide Interfaces Induced by WO3 Overlayers.

Interfaces between complex oxides constitute a unique playground for two-dimensional electron systems (2DESs), where superconductivity and magnetism can arise from combinations of bulk insulators. The 2DES at the LaAlO3/SrTiO3 interface is one of the most studied in this regard, and its origin is determined by the polar field in LaAlO3 as well as by the presence of point defects, like oxygen vacancies and intermixed cations. These defects usually reside in the conduction channel and are responsible for a decrease of the electronic mobility. In this work, we use an amorphous WO3 overlayer to obtain a high-mobility 2DES in WO3/LaAlO3/SrTiO3 heterostructures. The studied system shows a sharp insulator-to-metal transition as a function of both LaAlO3 and WO3 layer thickness. Low-temperature magnetotransport reveals a strong magnetoresistance reaching 900% at 10 T and 1.5 K, the presence of multiple conduction channels with carrier mobility up to 80 000 cm2 V-1 s-1, and quantum oscillations of conductance.

Ultrathin Epitaxial Barrier Layer to Avoid Thermally Induced Phase Transformation in Oxide Heterostructures.

Incorporating oxides with radically different physical and chemical properties into heterostructures offers tantalizing possibilities to derive new functions and structures. Recently, we have fabricated freestanding 2D oxide membranes using the water-soluble perovskite Sr3Al2O6 as a sacrificial buffer layer. Here, with atomic-resolution spectroscopic imaging, we observe that direct growth of oxide thin films on Sr3Al2O6 can cause complete phase transformation of the buffer layer, rendering it water-insoluble. More importantly, we demonstrate that an ultrathin SrTiO3 layer can be employed as an effective barrier to preserve Sr3Al2O6 during subsequent growth, thus allowing its integration in a wider range of oxide heterostructures.

Synthesis of freestanding single-crystal perovskite films and heterostructures by etching of sacrificial water-soluble layers.

The ability to create and manipulate materials in two-dimensional (2D) form has repeatedly had transformative impact on science and technology. In parallel with the exfoliation and stacking of intrinsically layered crystals, atomic-scale thin film growth of complex materials has enabled the creation of artificial 2D heterostructures with novel functionality and emergent phenomena, as seen in perovskite heterostructures. However, separation of these layers from the growth substrate has proved challenging, limiting the manipulation capabilities of these heterostructures with respect to exfoliated materials. Here we present a general method to create freestanding perovskite membranes. The key is the epitaxial growth of water-soluble Sr 3Al 2O 6 on perovskite substrates, followed by in situ growth of films and heterostructures. Millimetre-size single-crystalline membranes are produced by etching the Sr 3Al 2O 6 layer in water, providing the opportunity to transfer them to arbitrary substrates and integrate them with heterostructures of semiconductors and layered compounds.

Spontaneously occurring fundus findings observed using confocal scanning laser ophthalmoscopy in wild type Sprague Dawley rats.

PURPOSE: Non-invasive in vivo imaging is an increasingly used component of pre-clinical research. However, to reliably interpret data, it may be necessary to identify and document pre-existent findings prior to initiating long-term or intensive protocols, particularly where toxicity or efficacy is under investigation. Here we report here spontaneously occurring findings from the Sprague Dawley (SD) rat eye using multi-modal confocal scanning laser ophthalmoscopy (cSLO). METHODS: As part of ongoing studies, with the goal of excluding animals with abnormalities from further investigation, a total of 165 wild type SD rats (312 eyes) were assessed using cSLO imaging at baseline prior to initiating experiments to detect, describe, and determine the prevalence of spontaneous fundus findings. RESULTS: Using fundus autofluorescence (FAF) as the primary screening modality, over 30% of analyzed eyes possessed some fundus finding that differed from the normal composite reference image. Unexpectedly, 100% of eyes demonstrated a diffuse hyperfluorescent region in the posterior pole that was ultimately considered normal, and formed part of the reference. Evaluated by three independent reviewers, five groups of FAF abnormalities were defined, based primarily on shape and size of the lesion. Of these, the most extensive lesions were further analyzed using infrared reflectance (IR) and red free (RF) imaging. White light and autofluorescent microscopy of excised tissue confirmed that the extensive lesions were derived from abnormalities in both the isolated retina and posterior eyecups. CONCLUSIONS: Given the newly described hyperfluorescent glow that appears in all eyes, and the high basal rate of spontaneous lesions in the outbred SD rat, we suggest that investigators be aware of the variants of normal, and that baseline in vivo screening be considered prior to initiating intensive or expensive investigation.

Hydrophobically-modified poly(vinyl pyrrolidone) as a physically-associative, shear-responsive ophthalmic hydrogel.

The potential of hydrophobically-modified poly(vinyl pyrrolidone) as a shear-responsive, self-associative hydrogel for ophthalmic applications is demonstrated. Hydrophobic modification was achieved via random copolymerization of N-vinylpyrrolidone with N-vinylformamide, the latter of which can be hydrolyzed to expose a desired degree of reactive amine groups permitting grafting of alkyl chlorides of varying alkyl chain lengths. The resulting materials formed highly shear-responsive physical hydrogels, exhibiting tunable shear thinning over 4-5 decades of viscosity from infinite shear to zero shear conditions that facilitates lubrication upon blinking and/or facile injection or drop-based delivery to the anterior or posterior segments of the eye. Viscosity changes due to self-association over time can also be tuned by changing the length of the hydrophobe, with C18-grafted materials exhibiting prolonged thickening over several weeks to form extremely stiff hydrogels and shorter grafts equilibrating significantly faster but forming weaker gels. The hydrogels remained transparent even at very high polymer concentrations (20 wt%) and are demonstrated to facilitate controlled release of a model drug (doxorubicin). The polymers exhibit minimal cytotoxicity in vitro to human corneal epithelial cells and retinal pigment epithelial cells, particularly when lower molecular weight backbone polymers were used. In vivo assessments in rabbits indicated no significant conjunctival edema or redness, secretion, corneal opacity, or iris involvement upon anterior application. Following intravitreal injection in rat eyes, no opacification of the lens, cornea or vitreous, nor any morphological or functional change to the posterior segment was observed. Examination of wholemount tissues and histology demonstrated no adverse effect from the injection or deposition of material. As such, these shear-thinning materials offer potential for drug delivery in both the anterior and posterior segments or as a vitreal replacement that can be easily administered or removed.

Fundus autofluorescence (FAF) non-invasively identifies chorioretinal toxicity in a rat model of retinal pigment epithelium (RPE) damage.

INTRODUCTION: Traditional methods of pre-clinical ocular toxicology require that multiple cohorts of animals be sacrificed over time for terminal histological analysis. By contrast, in vivo techniques capable of following the same cohort prospectively have the potential to be efficient and cost-saving. We therefore asked if fundus autofluorescence (FAF), a non-invasive imaging technique, could detect damage to the posterior pole. Results were compared against electroretinography (ERG), another in vivo technique. The systemic toxin sodium iodate (NaIO3) was used to induce retinal pigment epithelium (RPE) damage. METHODS: FAF images (488/510nm excitation/emission) were obtained using a commercially available confocal scanning laser ophthalmoscope (cSLO; Heidelberg, HRAII) and were described qualitatively and quantitatively. NaIO3, over a dose range of 5 to 45mg/kg, or saline, was injected via tail vein in 6-10week old Sprague Dawley rats, and FAF images obtained at baseline and days 3, 7 and 14 thereafter and compared against the ERG response amplitude. RESULTS: Compared against baseline, there was no change in the FAF or ERG responses in the control, 5 or 15mg/kg NaIO3 groups. At 30mg/kg, responses fell into two groups. Half the animals developed small patches of abnormal FAF with modest reductions in the ERG amplitude; the other half developed large areas of damage and had severely reduced ERG responses. At 45mg/kg, all eyes developed extensive areas of abnormal FAF and the ERG was non- or minimally recordable. The en face size of the FAF patches was inversely correlated with the b-wave amplitude. DISCUSSION: This study demonstrates that FAF can detect chorioretinal toxicity in vivo in the rat eye, and that the findings correlate with the ERG. Such in vivo testing can enhance the detection of ocular toxicity.

Delayed near-infrared analysis permits visualization of rodent retinal pigment epithelium layer in vivo.

Patches of atrophy of the retinal pigment epithelium (RPE) have not been described in rodent models of retinal degeneration, as they have the clinical setting using fundus autofluorescence. We hypothesize that prelabeling the RPE would increase contrast and allow for improved visualization of RPE loss in vivo. Here, we demonstrate a new technique termed "delayed near-infrared analysis (DNIRA)" that permits ready detection of rat RPE, using optical imaging in the near-infrared (IR) spectrum with aid of indocyanine green (ICG) dye. Using DNIRA, we demonstrate a fluorescent RPE signal that is detected using confocal scanning laser ophthalmoscopy up to 28 days following ICG injection. This signal is apparent only after ICG injection, is dose dependent, requires the presence of the ICG filters (795/810 nm excitation/emission), does not appear in the IR reflectance channel, and is eliminated in the presence of sodium iodate, a toxin that causes RPE loss. Rat RPE explants confirm internalization of ICG dye. Together with normal retinal electrophysiology, these findings demonstrate that DNIRA is a new and safe noninvasive optical imaging technique for in vivo visualization of the RPE in models of retinal disease.

̀Spatial impulse response of a rectangular double curved transducer.

Calculation of the pressure field from transducers with both a convex and a concave surface geometry is a complicated assignment that often is accomplished by subdividing the transducer surface into smaller flat elements of which the spatial impulse response is known. This method is often applied to curved transducers because an analytical solution is unknown. In this work a semi-analytical algorithm for the exact solution to a first order in diffraction effect of the spatial impulse response of rectangular-shaped double curved transducers is presented. The solution and an approximation to it are investigated. The approximation reformulates the solution to an analytically integrable expression, which is computationally efficient to solve. Simulation results are compared to FIELD II simulations. Calculating the response from 200 different points yields a mean error for the different approximations ranging from 0.03% to 0.8% relative to a numerical solution for the spatial impulse response. It is also shown that the presented algorithm gives consistent results with FIELD II for a linear flat, a linear focused, and a convex nonfocused element. The solution involved a three-point Taylor expansion and gave an accuracy of 0.01%.

A nanoforest structure for practical surface-enhanced Raman scattering substrates.

A nanoforest structure for surface-enhanced Raman scattering (SERS) active substrates is fabricated and analyzed. The detailed morphology of the resulting structure can be easily controlled by modifying the process parameters such as initial gold layer thickness and etching time. The applicability of the nanoforest substrate as a label-free SERS immunosensor is demonstrated using influenza A virus subtype H1N1. Selective binding of the H1N1 surface antigen and the anti-H1 antibody is directly detected by the SERS signal differences. Simple fabrication and high throughput with strong in-plane hot-spots imply that the nanoforest structure can be a practical sensing component of a chip-based SERS sensing system.

A polydimethylsiloxane (PDMS) sponge for the selective absorption of oil from water.

We present a sugar-templated polydimethylsiloxane (PDMS) sponge for the selective absorption of oil from water. The process for fabricating the PDMS sponge does not require any intricate synthesis processes or equipment and it is not environmentally hazardous, thus promoting potential in environmental applications. The proposed PDMS sponge can be elastically deformed into any shape, and it can be compressed repeatedly in air or liquids without collapsing. Therefore, absorbed oils and organic solvents can be readily removed and reused by simply squeezing the PDMS sponge, enabling excellent recyclability. Furthermore, through appropriately combining various sugar particles, the absorption capacity of the PDMS sponge is favorably optimized.

Quantitative determination of arterial pulse wave velocity by non-interfering bioimpedance sensing.

Measurement of pulse wave velocity (PWV) in arteries is demonstrated with a novel measurement technique. Localized measurements are facilitated over arterial lengths below 10 cm on both the bicep and the wrist. Measurements do not interfere with the physiological state of the person or patient on which the measurement is performed. The scheme is based on impedance sensing utilizing novel conjugate impedances that eliminate destructive cross coupling between sets of electrodes. Initial measurements show that the test subject has a PWV of 8.0 +/- 0.1 m/s and 7.1 +/-0.2 on the wrist and bicep, respectively. The measurement distances were 8 cm and 5 cm, respectively.

Modeling transducer impulse responses for predicting calibrated pressure pulses with the ultrasound simulation program Field II.

Field II is a simulation software capable of predicting the field pressure in front of transducers having any complicated geometry. A calibrated prediction with this program is, however, dependent on an exact voltage-to-surface acceleration impulse response of the transducer. Such impulse response is not calculated by Field II. This work investigates the usability of combining a one-dimensional multilayer transducer modeling principle with the Field II software. Multilayer here refers to a transducer composed of several material layers. Measurements of pressure and current from Pz27 piezoceramic disks as well as pressure and intensity measurements in front of a 128 element commercial convex medical transducer are compared to the simulations. Results show that the models can predict the pressure from the piezoceramic disks with a root mean square (rms) error of 11.2% to 36.2% with a 2 dB amplitude decrease. The current through the external driving circuits are predicted within 8.6% to 36% rms error. Prediction errors of 30% and in the range of 5.8%-19.9% for the pressure and the intensity, respectively, are found when simulating the commercial transducer. It is concluded that the multilayer transducer model and the Field II software in combination give good agreement with measurements.