Clinicians' Prediction of Survival Is Most Useful for Palliative Care Referral.

Background: Timely palliative transition in patients with advanced cancer is essential for their improved quality of life and overall survival (OS). Most prognostic models have been developed focusing on weeks' survival. The current study aimed to compare the accuracies of several indicators, such as the Karnofsky Performance Scale (KPS), Clinicians' Prediction of Survival (CPS), and Edmonton Symptom Assessment System (ESAS), for predicting the survival of patients. Methods: Two hundred patients were enrolled at a single tertiary cancer center in South Korea between 2016 and 2019. We compared the discrimination of CPS versus KPS and ESAS total scores using the area under the receiver operating characteristic curve (AUROC) in 3-month and 6-month survival predictions. Results: The median age of patients was 66.0 years, and 128 (64%) were male. Two-thirds (66%) of the patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and 55.5% had a KPS of 80% or higher. The values of AUROC of CPS, KPS, and ESAS total score in 3-month survival prediction were 0.80 (95% confidence interval [CI]: 0.73-0.88), 0.71 (95% CI: 0.62-0.79), and 0.71 (95% CI: 0.62-0.81), respectively, whereas those in 6-month survival were 0.82 (95% CI: 0.76-0.88), 0.70 (95% CI: 0.63-0.78), and 0.63 (95% CI: 0.55-0.71), respectively. Conclusion: CPS showed the highest accuracy in predicting 3- and 6-month survival, whereas KPS had an acceptable accuracy. Experienced clinicians can rely on CPS to predict survival in months. We recommend the use of KPS with CPS to assist inexperienced clinicians.

Refractory solar lentigines successfully treated with 532-nm nanosecond Nd:YAG Vasculature Salvage Laser Surgery (VSLS) system: Case series.

BACKGROUND: Solar lentigo, a common epidermal hyperpigmented lesion found in sun-exposed areas, results from the proliferation of melanocytes and the accumulation of melanin. Although various treatments for solar lentigo have been explored, they often lead to complications, including prolonged erythema and post-inflammatory hyperpigmentation (PIH), posing significant concerns. OBJECTIVES AND METHODS: This study evaluated the safety and efficacy of the Vasculature Salvage Laser Surgery (VSLS) system. We treated six Korean patients, each with solar lentigo, in a single session using the 532-nm nanosecond neodymium-doped yttrium aluminum garnet (Nd:YAG) VSLS system, with follow-up periods ranging from 3 to 10 weeks. RESULTS: The treatment led to the complete removal of pigmented lesions in all patients without resulting in PIH, even in cases where previous laser treatments had failed. The only side effect observed was mild erythema, which resolved over the long term in most instances. CONCLUSIONS: The VSLS system emerges as a safe and effective treatment for pigmented lesions, including refractory solar lentigines. Nonetheless, additional studies are required to verify its long-term efficacy.

Targeted precision cryotherapy for acne vulgaris.

BACKGROUND: Acne vulgaris poses a significant dermatological challenge, necessitating alternative treatments due to limitations and side effects associated with current therapies. This pilot clinical trial investigated the feasibility and efficacy of precision cryotherapy for acne vulgaris. METHODS: A total of 20 volunteers underwent targeted precision cryotherapy using a carbon dioxide-based device. Treatment outcomes were assessed using various parameters, including Investigator Global Assessment (IGA) score, acne lesion count, erythema index (EI), global evaluation score, and participant satisfaction. Safety monitoring included adverse event reporting and physical examination. RESULTS: Precision cryotherapy demonstrated a significant reduction (90.25%) in the acne lesion count by week 4, with clinical improvement indicated by IGA score reduction (p < 0.001). The EI showed notable improvements at weeks 1, 2, and 4. The global evaluation score demonstrated a 75%-100% clinical improvement at Visit 4. Participants reported high satisfaction (6.75 ± 0.79) with the procedure. No adverse event or discomfort was reported. CONCLUSION: Precision cryotherapy effectively improved acne lesions, which was safe and satisfactory for participants. These findings suggest its potential as an alternative therapeutic modality, especially for populations with limited treatment options. Further research is needed to validate the results and explore underlying mechanisms.

Proximal High-Index Metamaterials based on a Superlattice of Gold Nanohexagons Targeting the Near-Infrared Band.

Plasmonic nanoparticles can be assembled into a superlattice, to form optical metamaterials, particularly targeting precise control of optical properties such as refractive index (RI). The superlattices exhibit enhanced near-field, given the sufficiently narrow gap between nanoparticles supporting multiple plasmonic resonance modes only realized in proximal environments. Herein, the planar superlattice of plasmonic Au nanohexagons (AuNHs) with precisely controlled geometries such as size, shape, and edge-gaps is reported. The proximal AuNHs superlattice realized over a large area with selective edge-to-edge assembly exhibited the highest-ever-recorded RI values in the near-infrared (NIR) band, surpassing the upper limit of the RI of the natural intrinsic materials (up to 10.04 at λ = 1.5 µm). The exceptionally enhanced RI is derived from intensified in-plane surface plasmon coupling across the superlattices. Precise control of the edge-gap of neighboring AuNHs systematically tuned the RI as confirmed by numerical analysis based on the plasmonic percolation model. Furthermore, a 1D photonic crystal, composed of alternating layers of AuNHs superlattices and low-index polymers, is constructed to enhance the selectivity of the reflectivity operating in the NIR band. It is expected that the proximal AuNHs superlattices can be used as new optical metamaterials that can be extended to the NIR range.

Air-through-precursor suction-augmented replica molding for fabrication of anisotropic microparticles in gas-impermeable molds.

Replica molding (REM) is a powerful technique for fabricating anisotropic microparticles. Current REM methods rely on the use of gas-permeable molds for defect-free castings and facile particle recovery. However, they often encounter limitations on either technical accessibility or producible particle diversity. While the use of gas-impermeable molds presents a promising solution to these challenges, particle production within such molds necessitates addressing two critical issues: precursor loading and particle recovery. This study introduces a REM methodology specifically tailored to enable the production of anisotropic microparticles within gas-impermeable molds. To address the issue of precursor loading, our approach incorporates the air-through-precursor suction method, employing a degassed polydimethylsiloxane block to effectively eliminate air bubbles trapped in microwells. Additionally, fluorosilane pretreatment of the mold surface, along with the polyvinyl alcohol film formation, significantly enhances particle recovery up to 249-fold while ensuring particle homogeneity. This methodology demonstrates high adaptability to various gas-impermeable molds and curing techniques. The practical feasibility is illustrated through the successful production of functional composite microparticles that can be effectively utilized for oxygen sensing and self-assembly, challenging in conventional REM.

Blood pressure control in diabetic kidney disease: a post-hoc analysis of the FANTASTIC trial.

BACKGROUND: The target blood pressure (BP) value is unclear for diabetic kidney disease (DKD). Therefore, we aimed to evaluate the effect of strict BP control or 'on treatment' BP on clinical outcomes in patients with DKD. METHODS: A post-hoc analysis of the prespecified secondary outcomes of the FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC) trial, a randomized multicenter double-blind phase III trial. Eligible patients were aged ≥ 19 years with DKD. We assigned 341 participants with DKD to BP control strategy (standard-systolic BP [SBP] < 140 mmHg versus strict-SBP < 130 mmHg). The outcome was the occurrence of cardiovascular events and renal events. Separate analyses were performed to compared the risk of outcome according to achieved average BP levels. RESULTS: A total of 341 participants were included in the analysis. Over a median follow-up of 2.8 years, cardiovascular/renal events were observed in 25 (7.3%) participants. Mean (SD) SBPs in the standard and strict BP control group were 140.2 (11.6) and 140.2 (11.9) mmHg, respectively. The strict BP control group did not show significantly reduced risk of cardiovascular/renal events (HR 1.32; 95% CI 0.60-2.92]). In the post-hoc analyses using achieved BP, achieved average SBP of 130-139 mmHg resulted in reduced risk of cardiovascular/renal events (HR 0.15; 95% CI 0.03-0.67) compared to achieved average SBP ≥ 140 mmHg, whereas further reduction in achieved average SBP < 130 mmHg did not impart additional benefits. CONCLUSION: In patients with DKD, targeting a SBP of less than 130 mmHg, as compared with less than 140 mmHg, did not reduce the rate of a composite of cardiovascular and renal events. Achieved SBP of 130-139 mmHg was associated with a decreased risk for the primary outcome in patients with DKD. TRIAL REGISTRATION: ClinicalTirals.gov Identifier: NCT02620306, registered December 3, 2015. ( https://clinicaltrials.gov/study/NCT02620306 ).

AP collagen peptides (APCPs) promote hair growth by activating the GSK-3ß/ß-catenin pathway and improve hair condition.

AP collagen peptides (APCPs) are enzymatically decomposed collagen peptides that contain tri-peptides such as glycine-proline-hydroxyproline. We found that APCPs increased the proliferation of both human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs). APCPs also stimulated the secretion of several growth factors, including IGFBP-6, PDGF-AB, PIGF and VEGF in hDPCs. Moreover, APCPs enhanced the phosphorylation of Akt(Ser473), GSK-3ß(Ser9) and ß-catenin(Ser675), indicating the activation of the GSK-3ß/ß-catenin signalling pathway. Ex vivo culture of human hair follicles (hHFs) tissue and in vivo patch assay revealed that APCPs promoted the elongation of hHFs and the induction of new hair shafts. In a mouse model, APCPs significantly promoted the transition from telogen to anagen phase and prolonged anagen phase, resulting in increased hair growth. APCPs also improved the thickness, amino acid content (cystine and methionine) and roughness of mouse hair. Taken together, these findings demonstrate that APCPs accelerate hair growth and contribute to overall hair health. Therefore, APCPs have the potential to be utilized as a food supplement and ingredient for preventing hair loss and maintaining hair health.

Factors related to accurate clinicians' prediction of survival: an international multicenter study in East Asia.

PURPOSE: Recent guidelines for prognostic evaluation recommend clinicians' prediction of survival (CPS) for survival prediction in patients with advanced cancer. However, CPS is often inaccurate and optimistic. Studies on factors associated with overestimation or underestimation of CPS are limited. We aimed to investigate the factors associated with the overestimation and underestimation of CPS in patients with far-advanced cancer. METHODS: The current study was a secondary analysis of an international multicenter prospective cohort study, which enrolled newly admitted patients with advanced cancer in palliative care units (PCUs) in Japan, Korea, and Taiwan from 2017 to 2018. We obtained the temporal CPS at enrollment and performed multivariate logistic regression analysis to identify the factors associated with "underestimation (less than 33% of actual survival)" and "overestimation (more than 33% of actual survival)." RESULTS: A total of 2571 patients were assessed and admitted in 37 PCUs between January 2017 and September 2018. Older age (adjusted odds ratio [aOR] 1.01; 95% confidence interval [CI] 1.01-1.02; P < 0.01) and reduced oral intake (aOR 0.68; 95% CI 0.51-0.89; P < 0.01) were identified as significant factors associated with underestimation. Dyspnea (aOR 1.28; 95% CI 1.06-1.54; P = 0.01) and hyperactive delirium (aOR 1.34; 95% CI 1.05-1.72; P = 0.02) were identified as significant factors associated with overestimation. CONCLUSION: Older age was related to underestimation, while dyspnea and hyperactive delirium were related to overestimation of CPS for patients with weeks of survival. However, reduced oral intake was less likely to lead to underestimation.

A clinical application for arterial coupling and histomorphometric comparison of internal mammary and thoracodorsal arteries for safe use.

BACKGROUND: In breast reconstruction, arterial coupling has been reported to be more favorable in the thoracodorsal artery (TDA) than the internal mammary artery (IMA). This technique may help overcome anastomosis in a small, deep space. Understanding the arteries' mechanical properties is crucial for breast reconstruction's safety and success. METHODS: Abdominal-based free flap breast reconstructions performed by a single surgeon between 2020 and 2022 were retrospectively analyzed. The patients were classified by microanastomosis technique (handsewn and coupler device) to compare the rate of vascular revision. Histomorphometric analysis of arterial coupling in TDA and IMA was performed in 10 fresh cadavers for comparing wall thickness and composition, including densities of elastic fiber, smooth muscle, and collagen. RESULTS: A total of 309 patients (339 reconstructed breasts) were included. There were 29 patients in the TDA handsewn group (A), 38 patients in the TDA coupler group (B), and 242 patients in the IMA handsewn group (C). The rates of arterial revision in groups A, B, and C were 0.00% (95%CI: 0.00%-11.03%), 2.5% (95%CI: 0.44%-12.88%), and 1.49% (95%CI: 0.58%-3.77%), respectively, with no statistically significant differences (p-value = .694). Histologically, the thickness of the tunica media and adventitia between IMA and TDA showed no significant difference. The density of elastic fiber was significantly higher in IMA (16.70%) than in TDA (0.79%) (p-value <.001). CONCLUSION: The histologic characteristics of TDA are more favorable for arterial coupling than those of IMA. Arterial coupling is a safe option in situations where TDA anastomosis must be performed through a narrow and deep incision.

Mortality of elderly patients with acute kidney injury undergoing continuous renal replacement therapy: is age a risk factor?

BACKGROUND: Whether advanced age is associated with poor outcomes of elderly patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is controversial. This study aimed to evaluate age effect and predictors for mortality in elderly AKI patients undergoing CRRT. METHODS: Data of 480 elderly AKI patients who underwent CRRT were retrospectively analyzed. Subjects were stratified into two groups according to age: younger-old (age, 65-74 years; n = 205) and older-old (age, ≥75 years; n = 275). Predictors for 28-day and 90-day mortality and age effects were analyzed using multivariable Cox regression analysis and propensity score matching. RESULTS: Urine output at the start of CRRT (adjusted hazard ratio [aHR], 0.99; 95% confidence interval [CI], 0.99-1.00; p = 0.04), operation (aHR, 0.53; 95% CI, 0.30-0.93; p = 0.03), and use of an intra-aortic balloon pump (aHR, 3.60; 95% CI, 1.18-10.96; p = 0.02) were predictors for 28-day mortality. Ischemic heart disease (aHR, 1.74; 95% CI, 1.02-2.98; p = 0.04) and use of a ventilator (aHR, 0.56; 95% CI, 0.36-0.89; p = 0.01) were predictors for 90-day mortality. The older-old group did not exhibit a higher risk for 28- day or 90-day mortality than the younger-old group in multivariable or propensity score-matched models. CONCLUSION: Advanced age was not a risk factor for mortality among elderly AKI patients undergoing CRRT, suggesting that advanced age should not be considered for therapeutic decisions in critically ill elderly patients with AKI requiring CRRT.

Efficient isolation of encoded microparticles in a degassed micromold for highly sensitive and multiplex immunoassay with signal amplification.

Multiplex detection of low-abundance protein biomarkers in biofluids can contribute to diverse biomedical fields such as early diagnosis and precision medicine. However, conventional techniques such as digital ELISA, microarray, and hydrogel-based assay still face limitations in terms of efficient protein detection due to issues with multiplexing capability, sensitivity, or complicated assay procedures. In this study, we present the degassed micromold-based particle isolation technique for highly sensitive and multiplex immunoassay with enzymatic signal amplification. Using degassing treatment of nanoporous polydimethylsiloxane (PDMS) micromold, the encoded particles are isolated in the mold within 5 min absorbing trapped air bubbles into the mold by air suction capability. Through 10 min of signal amplification in the isolated spaces by fluorogenic substrate and horseradish peroxidase labeled in the particle, the assay signal is amplified with one order of magnitude compared to that of the standard hydrogel-based assay. Using the signal amplification assay, vascular endothelial growth factor (VEGF) and chorionic gonadotropin beta (CG beta), the preeclampsia-related protein biomarkers, are quantitatively detected with a limit of detection (LoD) of 249 fg/mL and 476 fg/mL in phosphate buffer saline. The multiplex immunoassay is conducted to validate negligible non-specific detection signals and robust recovery rates in the multiplex assay. Finally, the VEGF and CG beta in real urine samples are simultaneously and quantitatively detected by the developed assay. Given the high sensitivity, multiplexing capability, and process simplicity, the presented particle isolation-based signal amplification assay holds significant potential in biomedical and proteomic fields.

The effect of preoperative botulinum toxin a injection on traction force during hernia repair: a prospective, single-blind study, intra-patient comparison using contralateral side as a control.

PURPOSE: Ventral hernias are a common complication of laparotomy, posing challenges particularly when primary fascial closure is unattainable. Although chemical component separation using preoperative botulinum toxin A (BTX) injections has emerged as a promising adjunct, objective evidence of its efficacy remains limited. This study aimed to objectively assess the effect of preoperative BTX on traction force during ventral hernia repair. METHODS: A prospective, single-blind study was conducted on patients with midline incisional hernias following liver transplantation. BTX was administered unilaterally, and the traction force required to medially advance the anterior rectus sheath was measured intraoperatively. Pre- and post-injection CT scans were analyzed for changes in hernia size and LAW muscle measurements. Statistical analyses were performed to evaluate traction force differences between BTX-injected and uninjected sides. RESULTS: Ten patients underwent hernia repair with primary fascial closure achieved in all cases. Comparison of pre- and post-injection CT scans showed no significant changes in hernia size. LAW muscle length increased by 1.8 cm, while thickness decreased by 0.2 cm. Intraoperative traction force measurements revealed a significant reduction on the BTX-injected side compared to the uninjected side (p < 0.0001). The traction force ratio on the BTX-injected to the uninjected side averaged 57%, indicating the efficacy of BTX in reducing tension. CONCLUSION: Preoperative BTX significantly reduces traction force during ventral hernia repair, highlighting its potential as an adjunctive therapy in complex cases. While challenges remain in patient selection and outcome assessment, BTX offers a promising avenue for enhancing abdominal wall reconstruction outcomes and reducing surgical complications.

Split fluorescent protein-mediated multimerization of cell wall binding domain for highly sensitive and selective bacterial detection.

Cell wall peptidoglycan binding domains (CBDs) of cell lytic enzymes, including bacteriocins, autolysins and bacteriophage endolysins, enable highly selective bacterial binding, and thus, have potential as biorecognition molecules for nondestructive bacterial detection. Here, a novel design for a self-complementing split fluorescent protein (FP) complex is proposed, where a multimeric FP chain fused with specific CBDs ((FP-CBD)n) is assembled inside the cell, to improve sensitivity by enhancing the signal generated upon Staphylococcus aureus or Bacillus anthracis binding. Flow cytometry shows enhanced fluorescence on the cell surface with increasing FP stoichiometry and surface plasmon resonance reveals nanomolar binding affinity to isolated peptidoglycan. The breadth of function of these complexes is demonstrated through the use of CBD modularity and the ability to attach enzymatic detection modalities. Horseradish peroxidase-coupled (FP-CBD)n complexes generate a catalytic amplification, with the degree of amplification increasing as a function of FP length, reaching a limit of detection (LOD) of 103 cells/droplet (approximately 0.1 ng S. aureus or B. anthracis) within 15 min on a polystyrene surface. These fusion proteins can be multiplexed for simultaneous detection. Multimeric split FP-CBD fusions enable use as a biorecognition molecule with enhanced signal for use in bacterial biosensing platforms.

Lipedema associated with Skin Hypoperfusion and Ulceration: Soft Tissue Debulking Improving Skin Perfusion.

Lipedema is a progressive connective tissue disease with enlargement of adipose tissue, fibrosis, fluid collection, and dermal thickening. Herein, we present a case of lipedema associated with skin hypoperfusion and ulceration in which soft tissue debulking with liposuction improved patients' symptoms. A 39-year-old female presented with asymmetric progressive initially unilateral lower limb swelling with severe pain with subsequent skin ulceration. Conservative management failed to improve her condition. After excluding other causes and detailed radiologic investigation, lipedema was diagnosed with an associated impaired skin perfusion. Trial of local wound care and compression therapy failed to improve the condition. Subsequent soft tissue debulking with circumferential liposuction and ulcer debridement and immediate compression showed dramatic improvement of the symptoms and skin perfusion. The unique nature of this case sheds light on lipedema as a loose connective tissue disease. Inflammation and microangiopathies explain the associated pain with hypoperfusion and ulceration being quite atypical and in part might be related to the large buildups of matrix proteins and sodium contents leading to fragility in microvessels with frequent petechiae and hematoma and subsequent tissue ischemia. Conservative measures like compression therapy plays a significant role in disease course. Surgical debulking with liposuction was shown to be efficacious in reducing the soft tissue load with improvement in limb pain, edema, circumference, and skin perfusion that was seen in our patient. Lipedema is a frequently misdiagnosed condition with disabling features. Skin involvement in lipedema with potential hypoperfusion was shown and it requires further investigation.

Stress hyperglycemia exacerbates inflammatory brain injury after stroke.

Post-stroke hyperglycemia occurs in 30% - 60% of ischemic stroke patients as part of the systemic stress response, but neither clinical evidence nor pre-clinical studies indicate whether post-stroke hyperglycemia affects stroke outcome. Here we investigated this issue using a mouse model of permanent ischemia. Mice were maintained either normoglycemic or hyperglycemic during the interval of 17 - 48 hours after ischemia onset. Post-stroke hyperglycemia was found to increase infarct volume, blood-brain barrier disruption, and hemorrhage formation, and to impair motor recovery. Post-stroke hyperglycemia also increased superoxide formation by peri-infarct microglia/macrophages. In contrast, post-stroke hyperglycemia did not increase superoxide formation or exacerbate motor impairment in p47 phox-/- mice, which cannot form an active superoxide-producing NADPH oxidase-2 complex. These results suggest that hyperglycemia occurring hours-to-days after ischemia can increase oxidative stress in peri-infarct tissues by fueling NADPH oxidase activity in reactive microglia/macrophages, and by this mechanism contribute to worsened functional outcome.

Real-Time Signal Analysis with Wider Dynamic Range and Enhanced Sensitivity in Multiplex Colorimetric Immunoassays Using Encoded Hydrogel Microparticles.

The simultaneous quantification of multiple proteins is crucial for accurate medical diagnostics. A promising technology, the multiplex colorimetric immunoassay using encoded hydrogel microparticles, has garnered attention, due to its simplicity and multiplex capabilities. However, it encounters challenges related to its dynamic range, as it relies solely on the colorimetric signal analysis of encoded hydrogel microparticles at the specific time point (i.e., end-point analysis). This necessitates the precise determination of the optimal time point for the termination of the colorimetric reaction. In this study, we introduce real-time signal analysis to quantify proteins by observing the continuous colorimetric signal change within the encoded hydrogel microparticles. Real-time signal analysis measures the "slope", the rate of the colorimetric signal generation, by focusing on the kinetics of the accumulation of colorimetric products instead of the colorimetric signal that appears at the end point. By developing a deep learning-based automatic analysis program that automatically reads the code of the graphically encoded hydrogel microparticles and obtains the slope by continuously tracking the colorimetric signal, we achieved high accuracy and high throughput analysis. This technology has secured a dynamic range more than twice as wide as that of the conventional end-point signal analysis, simultaneously achieving a sensitivity that is 4-10 times higher. Finally, as a demonstration of application, we performed multiplex colorimetric immunoassays using real-time signal analysis covering a wide concentration range of protein targets associated with pre-eclampsia.

α-Synuclein triggers cofilin pathology and dendritic spine impairment via a PrPC-CCR5 dependent pathway.

Cognitive dysfunction and dementia are critical symptoms of Lewy Body dementias (LBD). Specifically, alpha-synuclein (αSyn) accumulation in the hippocampus leading to synaptic dysfunction is linked to cognitive deficits in LBD. Here, we investigated the pathological impact of αSyn on hippocampal neurons. We report that either αSyn overexpression or αSyn pre-formed fibrils (PFFs) treatment triggers the formation of cofilin-actin rods, synapse disruptors, in cultured hippocampal neurons and in the hippocampus of synucleinopathy mouse models and of LBD patients. In vivo, cofilin pathology is present concomitantly with synaptic impairment and cognitive dysfunction. Rods generation prompted by αSyn involves the co-action of the cellular prion protein (PrPC) and the chemokine receptor 5 (CCR5). Importantly, we show that CCR5 inhibition, with a clinically relevant peptide antagonist, reverts dendritic spine impairment promoted by αSyn. Collectively, we detail the cellular and molecular mechanism through which αSyn disrupts hippocampal synaptic structure and we identify CCR5 as a novel therapeutic target to prevent synaptic impairment and cognitive dysfunction in LBD.

Autonomous Synthesis of Thin Film Materials with Pulsed Laser Deposition Enabled by In Situ Spectroscopy and Automation.

Autonomous systems that combine synthesis, characterization, and artificial intelligence can greatly accelerate the discovery and optimization of materials, however platforms for growth of macroscale thin films by physical vapor deposition techniques have lagged far behind others. Here this study demonstrates autonomous synthesis by pulsed laser deposition (PLD), a highly versatile synthesis technique, in the growth of ultrathin WSe2 films. By combing the automation of PLD synthesis and in situ diagnostic feedback with a high-throughput methodology, this study demonstrates a workflow and platform which uses Gaussian process regression and Bayesian optimization to autonomously identify growth regimes for WSe2 films based on Raman spectral criteria by efficiently sampling 0.25% of the chosen 4D parameter space. With throughputs at least 10x faster than traditional PLD workflows, this platform and workflow enables the accelerated discovery and autonomous optimization of the vast number of materials that can be synthesized by PLD.

Efficacy and Safety of PrabotulinumtoxinA in Subjects With Benign Masseteric Hypertrophy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Phase 3 Trial and Open-Label Extension Study.

BACKGROUND: Despite the widespread use of botulinum toxin (BTX) injection for the treatment of masseter muscle hypertrophy (MMH), there is no standard treatment option. OBJECTIVE: We report the efficacy and safety for BTX in MMH over a period of 48 weeks. METHODS: In double-blinded, placebo-controlled phase 3 trials, 180 patients (randomized 1:1) received treatment with placebo (normal saline) or prabotulinumtoxinA (48 units). Masseter muscle thickness (at maximal clenching and resting positions), 3D imaging analysis, and masseter muscle hypertrophy scale grades were analyzed at each time point. After the 24-week CORE study, all patients who met the same criteria of the CORE study at week 24 ( n = 114) received only prabotulinumtoxinA, regardless of previous treatment, for an additional 24 weeks (48 weeks in total) for the open-label extension study. RESULTS: The largest differences in mean and percent changes from baseline in masseter muscle thickness were observed at 12 weeks, and there were significant differences between the 2 groups at all time points (all p < .001). The effect was independent of the number of injections. No serious adverse event was observed. CONCLUSION: PrabotulinumtoxinA could effectively ameliorate MMH without major complications.

Selected Area Manipulation of MoS2 via Focused Electron Beam-Induced Etching for Nanoscale Device Editing.

We demonstrate direct-write patterning of single and multilayer MoS2 via a focused electron beam-induced etching (FEBIE) process mediated with the XeF2 precursor. MoS2 etching is performed at various currents, areal doses, on different substrates, and characterized using scanning electron and atomic force microscopies as well as Raman and photoluminescence spectroscopies. Scanning transmission electron microscopy reveals a sub-40 nm etching resolution and the progression of point defects and lateral etching of the consequent unsaturated bonds. The results confirm that the electron beam-induced etching process is minimally invasive to the underlying material in comparison to ion beam techniques, which damage the subsurface material. Single-layer MoS2 field-effect transistors are fabricated, and device characteristics are compared for channels that are edited via the selected area etching process. The source-drain current at constant gate and source-drain voltage scale linearly with the edited channel width. Moreover, the mobility of the narrowest channel width decreases, suggesting that backscattered and secondary electrons collaterally affect the periphery of the removed area. Focused electron beam doses on single-layer transistors below the etching threshold were also explored as a means to modify/thin the channel layer. The FEBIE exposures showed demonstrative effects via the transistor transfer characteristics, photoluminescence spectroscopy, and Raman spectroscopy. While strategies to minimize backscattered and secondary electron interactions outside of the scanned regions require further investigation, here, we show that FEBIE is a viable approach for selective nanoscale editing of MoS2 devices.