Targeted deletion of CD244 on monocytes promotes differentiation into anti-tumorigenic macrophages and potentiates PD-L1 blockade in melanoma.

BACKGROUND: In the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244. METHODS: To directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific CD244-deficient mice were generated using cre-lox recombination and challenged with B16F10 melanoma. The phenotype and function of tumor-infiltrating macrophages along with antigen-specific CD8 T cells were analyzed by flow cytometry and single cell RNA sequencing data analysis, and the molecular mechanism underlying anti-tumorigenic macrophage differentiation, antigen presentation, phagocytosis was investigated ex vivo. Finally, the clinical feasibility of CD244-negative monocytes as a therapeutic modality in melanoma was confirmed by adoptive transfer experiments. RESULTS: CD244fl/flLysMcre mice demonstrated a significant reduction in tumor volume (61% relative to that of the CD244fl/fl control group) 14 days after tumor implantation. Within tumor mass, CD244fl/flLysMcre mice also showed higher percentages of Ly6Clow macrophages, along with elevated gp100+IFN-γ+ CD8 T cells. Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Combining anti-PD-L1 antibody with CD244-/- bone marrow-derived macrophages markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with wild-type macrophages. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset revealed close association between CD244 and the inhibition of macrophage maturation and function. Furthermore, the presence of CD244-negative monocytes/macrophages significantly increased patient survival in primary and metastatic tumors. CONCLUSION: Our study highlights the novel role of CD244 on monocytes/macrophages in restraining anti-tumorigenic macrophage generation and tumor antigen-specific T cell response in melanoma. Importantly, our findings suggest that CD244-deficient macrophages could potentially be used as a therapeutic agent in combination with immune checkpoint inhibitors. Furthermore, CD244 expression in monocyte-lineage cells serve as a prognostic marker in cancer patients.

External Validation of Deep Learning-Based Cardiac Arrest Risk Management System for Predicting In-Hospital Cardiac Arrest in Patients Admitted to General Wards Based on Rapid Response System Operating and Nonoperating Periods: A Single-Center Study.

OBJECTIVES: The limitations of current early warning scores have prompted the development of deep learning-based systems, such as deep learning-based cardiac arrest risk management systems (DeepCARS). Unfortunately, in South Korea, only two institutions operate 24-hour Rapid Response System (RRS), whereas most hospitals have part-time or no RRS coverage at all. This study validated the predictive performance of DeepCARS during RRS operation and nonoperation periods and explored its potential beyond RRS operating hours. DESIGN: Retrospective cohort study. SETTING: In this 1-year retrospective study conducted at Yonsei University Health System Severance Hospital in South Korea, DeepCARS was compared with conventional early warning systems for predicting in-hospital cardiac arrest (IHCA). The study focused on adult patients admitted to the general ward, with the primary outcome being IHCA-prediction performance within 24 hours of the alarm. PATIENTS: We analyzed the data records of adult patients admitted to a general ward from September 1, 2019, to August 31, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Performance evaluation was conducted separately for the operational and nonoperational periods of the RRS, using the area under the receiver operating characteristic curve (AUROC) as the metric. DeepCARS demonstrated a superior AUROC as compared with the Modified Early Warning Score (MEWS) and the National Early Warning Score (NEWS), both during RRS operating and nonoperating hours. Although the MEWS and NEWS exhibited varying performance across the two periods, DeepCARS showed consistent performance. CONCLUSIONS: The accuracy and efficiency for predicting IHCA of DeepCARS were superior to that of conventional methods, regardless of whether the RRS was in operation. These findings emphasize that DeepCARS is an effective screening tool suitable for hospitals with full-time RRS, part-time RRS, and even those without any RRS.

Clonal Hematopoiesis and Acute Ischemic Stroke Outcomes.

OBJECTIVE: The effect of clonal hematopoiesis of indeterminate potential (CHIP) on the manifestation and clinical outcomes of acute ischemic stroke (AIS) has not been fully elucidated. METHODS: Patients with AIS were included from a prospective registry coupled with a DNA repository. Targeted next-generation sequencing on 25 genes that are frequently mutated in hematologic neoplasms was performed. The prevalence of CHIP was compared between patients with AIS and age-matched healthy individuals. A multivariate linear or logistic regression model was used to assess the association among CHIP and stroke severity, hemorrhagic transformation, and functional outcome at 90 days. RESULTS: In total, 380 patients with AIS (mean age = 67.2 ± 12.7 years; 41.3% women) and 446 age-matched controls (mean age = 67.2 ± 8.7 years; 31.4% women) were analyzed. The prevalence of CHIP was significantly higher in patients with AIS than in the healthy controls (29.0 vs 22.0%, with variant allele frequencies of 1.5%, p = 0.024). PPM1D was found to be most significantly associated with incident AIS (adjusted odds ratio [aOR] = 7.85, 95% confidence interval [CI] = 1.83-33.63, p = 0.006). The presence of CHIP was significantly associated with the initial National Institutes of Health Stroke Scale (NIHSS) score (ß = 1.67, p = 0.022). Furthermore, CHIP was independently associated with the occurrence of hemorrhagic transformation (65/110 clonal hematopoiesis positive [CH+] vs 56/270 CH negative [CH-], aOR = 5.63, 95% CI = 3.24-9.77, p < 0.001) and 90-day functional disability (72/110 [CH+] vs 99/270 [CH-], aOR = 2.15, 95% CI = 1.20-3.88, p = 0.011). INTERPRETATION: CH was significantly associated with incident AIS. Moreover, particularly, sequence variations in PPM1D, TET2, and DNMT3A represent a new prognostic factor for AIS. ANN NEUROL 2023;94:836-847.

Age-related Variations in Patterns of Patent Foramen Ovale-Stroke versus Other Cryptogenic Stroke.

INTRODUCTION: Patent Foramen Ovale (PFO)-stroke, a form of cryptogenic stroke, has certain identifying clinical and imaging features. However, data describing this stroke type remains inconsistent. This study examined the potential variations in PFO-stroke features, depending on age. METHODS: From a hospital registry, cryptogenic stroke patients were retrospectively selected, and PFO-strokes identified by the presence of >10 microembolic signals (MES) on transcranial doppler (TCD) saline agitation test. Cryptogenic strokes were grouped according to age (<70 as young, >70 as elderly). Clinical and imaging variables of PFO-strokes and non-PFO strokes were compared, with and without age considered. RESULTS: Of the 462 cryptogenic patients, 30.5% (141/462) were PFO-strokes, while majority (321/462) had no PFO. When cryptogenic strokes were analyzed by age, the significant difference was noted in the lesion number, pattern, and side. A single (72.8% vs 57.9%, p=0.020) and a small single lesion (51.1% vs 35.5%, p=0.039) were frequently seen in the younger PFO-strokes than the non-PFO counterpart, while mixed territory lesions identified the elderly PFO-strokes (30.6% vs 8.9%, p=0.001). A multivariate logistic regression analysis of PFO-strokes further showed that age was independently associated with lesion side (OR 1.12 (1.05-1.20), p<0.001) and lesion number (OR 1.06 (1.02-1.10), p=0.005). CONCLUSIONS: Incorporating age-specific imaging criteria in the identification of PFO-strokes may be of additional value. Further, PFO may remain contributory to the stroke risk in the elderly, in association with vascular risk factors.

Factors associated with the development of exudation in treatment-naive eyes with nonexudative macular neovascularization.

PURPOSE: To identify the predictive factors for development of exudation in patients with treatment-naïve nonexudative macular neovascularization (MNV). METHODS: We retrospectively analyzed 61 treatment-naïve patients with nonexudative MNV who had not received treatment for nonexudative MNV before the exudation developed. Baseline characteristics and changes in MNV were evaluated using multivariate modeling to determine the potential risk factors for exudative conversion. RESULTS: Exudation development was identified in 31.1% (19/61 eyes) of the study eyes during the 46.2 ± 8.2-month mean follow-up period. The mean period of development of exudation from the baseline was 21.5 ± 6.7 months. Multivariate Cox regression analysis identified that older age (hazard ratio [HR] of 1.380, 95% confidence interval [CI] 1.129-1.688, P = 0.008), larger MNV area at baseline (HR of 1.715, CI 1.288-2.308; P = 0.006), increase of MNV area by doubling (HR of 4.992, CI 1.932-9.246; P = 0.002), and retinal pigment epithelium (RPE) elevation more than 100 µm (HR of 1.017, CI 1.006-1.233; P = 0.015) were associated with increased risk of the development of exudation. CONCLUSION: Older age, larger MNV area, increasing MNV area, and higher RPE elevation were associated with an increased risk of exudative conversion in patients with treatment-naïve nonexudative MNV. Identifying these risk factors may be helpful in establishing treatment strategies and monitoring patients.

A comparative study of two presbyopia-correcting intraocular lenses combining bifocal and extended depth-of-focus profiles.

OBJECTIVE: To compare the visual performance of two presbyopia-correcting intraocular lenses (IOLs) that combine both bifocal and extended depth-of-focus profiles, Artis® Symbiose® Plus (Symbiose Plus; Cristalens Industrie, Lannion, France) and Tecnis® Synergy® (Synergy; Johnson & Johnson Vision, Santa Ana, CA, USA). METHODS: The medical records of patients with cataract bilaterally implanted with either Symbiose Plus or Synergy between January 2022 and January 2023 were assessed. The principal measures of postoperative findings included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near (40 and 33 cm) visual acuity (UNVA), objective optical quality (OOQ) parameters, distance-corrected defocus curve analysis, and surveys of subjective satisfaction. RESULTS: Total of 96 eyes from 48 patients were enrolled. Each group was equally composed of 24 patients, 48 eyes. There were no significant differences between the two groups on baseline characteristics. Both IOLs displayed excellent binocular UDVA, CDVA, and UNVA (40 and 33 cm) with no statistical difference (p = 0.467(UDVA), p = 0.584(CDVA), p = 0.096(40-cm UNVA), and p = 0.621(33-cm UNVA)). However, with regard to UIVA, the Synergy group showed significantly superior results (p < 0.001). In contrast, the Symbiose Plus group showed significantly better results on OOQ parameters and patient-reported quality of vision survey outcomes (both p < 0.001). CONCLUSIONS: Both IOLs provided a decent continuous range of vision from near to far distance.

Frequency of actionable secondary findings in 7472 Korean genomes derived from the National Project of Bio Big Data pilot study.

Exome and genome sequencing (ES/GS) in genetic medicine and research leads to discovering genomic secondary findings (SFs) unrelated to the purpose of the primary test. There is a lack of agreement to return the SF results for individuals undergoing the test. The aim of this study is to investigate the frequency of actionable secondary findings using GS data obtained from the rare disease study and the Korean Genome and Epidemiology Study (KoGES) in the National Project of Bio Big Data pilot study. Pathogenic (P) or likely pathogenic (LP) variants of 78 SF genes recommended by the American College of Medical Genetics and Genomics (ACMG) were screened in the rare disease study and KoGES. The pathogenicity of SF gene variants was determined according to the ACMG interpretation. The overall SF rate was 3.75% for 280 individuals with 298 P/LP variants of 41 ACMG SF genes which were identified among 7472 study participants. The frequencies of genes associated with cardiovascular, cancer, and miscellaneous phenotypes were 2.17%, 1.22%, and 0.58%, respectively. The most frequent SF gene was TTN followed by BRCA2. The frequency of actionable SFs among participants with rare disease and general population participants in the Korean population presented here will assist in reporting results of medically actionable SFs in genomic medicine.

Line spectroscopic reflectometry for rapid and large-area thickness measurement.

Thickness measurements in the range of 0.1-1 mm over large optically transparent layers are essential in various manufacturing applications. However, existing non-contact measurement methods, which typically measure a single point or a few points at a time, fall short in their suitability for inline area measurement. Here, we introduce line spectroscopic reflectometry (LSR), an approach that extends the point measurement of traditional SR to line measurement, enabling rapid thickness measurement over large areas. By combining line beam illumination and line spectroscopy, LSR can measure 2048 points simultaneously, thereby boosting the measurement speed by two thousand times. We detail the measurement principle and the optical design in the near-infrared regime, and demonstrate thickness measurements of single-layered and double-layered samples over a measurement line length of up to 68 mm. Furthermore, we showcase the inline area measurement capability of LSR through one-dimensional sample scanning, with measurement rates limited only by camera readout rates.

Simple and fast calibration method for phase-only spatial light modulators.

Phase-only spatial light modulators (SLMs) are widely used to engineer the phase of light in various applications. However, liquid-crystal-on-silicon SLMs have undesirable spatial variations in phase response and optical flatness across the SLM panel, which must be compensated for accurate phase control. Here, we introduce a simple and fast way to simultaneously extract these two types of SLM nonuniformities at single-pixel resolution using Twyman-Green interferometry without a piezoelectric transducer. By modulating the interference intensity via the SLM gray level, our approach requires N times fewer interferograms than typical N-step phase shift interferometry (PSI), while providing flatness correction as accurate as PSI. In practice, our calibration method works well with as few as 18 interferograms, which can be quickly acquired without concern for phase drift. We detail the calibration procedure and discuss the performance of our calibration.

Electrical noise in electrolytes: a theoretical perspective.

Seemingly unrelated experiments such as electrolyte transport through nanotubes, nano-scale electrochemistry, NMR relaxometry and surface force balance measurements, all probe electrical fluctuations: of the electric current, the charge and polarization, the field gradient (for quadrupolar nuclei) and the coupled mass/charge densities. The fluctuations of such various observables arise from the same underlying microscopic dynamics of the ions and solvent molecules. In principle, the relevant length and time scales of these dynamics are encoded in the dynamic structure factors. However, modelling the latter for frequencies and wavevectors spanning many orders of magnitude remains a great challenge to interpret the experiments in terms of physical processes such as solvation dynamics, diffusion, electrostatic and hydrodynamic interactions between ions, interactions with solid surfaces, etc. Here, we highlight the central role of the charge-charge dynamic structure factor in the fluctuations of electrical observables in electrolytes and offer a unifying perspective over a variety of complementary experiments. We further analyze this quantity in the special case of an aqueous NaCl electrolyte, using simulations with explicit ions and an explicit or implicit solvent. We discuss the ability of the standard Poisson-Nernst-Planck theory to capture the simulation results, and how the predictions can be improved. We finally discuss the contributions of ions and water to the total charge fluctuations. This work illustrates an ongoing effort towards a comprehensive understanding of electrical fluctuations in bulk and confined electrolytes, in order to enable experimentalists to decipher the microscopic properties encoded in the measured electrical noise.

Long Sleep Duration and Dissatisfaction with Sleep Quality Are Associated with Ischemic Stroke in Young Patients.

INTRODUCTION: Suboptimal sleep duration and poor sleep quality have been proposed to increase stroke risk. However, their significance in young ischemic stroke is unclear. We aimed to investigate the importance of sleep duration and quality on young ischemic stroke patients. METHODS: A multicenter matched case-control study was performed to evaluate under-recognized risk factors in young (<45 years) ischemic stroke patients in 8 tertiary hospitals in Korea. A total of 225 patients and 225 age- and sex-matched controls were enrolled in the same period. Detailed information about patients' demographics, socioeconomic state, and traditional and nontraditional risk factors including sleep-related factors were obtained using structured questionnaires. Risk of ischemic stroke was estimated using conditional logistic regression analysis. RESULTS: Although average sleep duration was similar in patients and controls, patients were more likely to have long (≥9 h) or extremely short (<5 h) sleep durations. In addition, the proportion of subjects with dissatisfaction with sleep quality was higher in patients than controls (66.2 vs. 49.3%, p < 0.001). In multivariable conditional logistic regression analysis, long sleep duration (OR: 11.076, 95% CI: 1.819-67.446, p = 0.009) and dissatisfaction with sleep quality (OR: 2.116, 95% CI: 1.168-3.833, p = 0.013) were independently associated with risk of ischemic stroke. CONCLUSIONS: Long sleep duration and dissatisfaction with sleep quality may be associated with increased risk of ischemic stroke in young adults. Improving sleep habit or quality could be important for reducing the risk of ischemic stroke.

Grand-canonical molecular dynamics simulations powered by a hybrid 4D nonequilibrium MD/MC method: Implementation in LAMMPS and applications to electrolyte solutions.

Molecular simulations in an open environment, involving ion exchange, are necessary to study various systems, from biosystems to confined electrolytes. However, grand-canonical simulations are often computationally demanding in condensed phases. A promising method [L. Belloni, J. Chem. Phys. 151, 021101 (2019)], one of the hybrid nonequilibrium molecular dynamics/Monte Carlo algorithms, was recently developed, which enables efficient computation of fluctuating number or charge density in dense fluids or ionic solutions. This method facilitates the exchange through an auxiliary dimension, orthogonal to all physical dimensions, by reducing initial steric and electrostatic clashes in three-dimensional systems. Here, we report the implementation of the method in LAMMPS with a Python interface, allowing facile access to grand-canonical molecular dynamics simulations with massively parallelized computation. We validate our implementation with two electrolytes, including a model Lennard-Jones electrolyte similar to a restricted primitive model and aqueous solutions. We find that electrostatic interactions play a crucial role in the overall efficiency due to their long-range nature, particularly for water or ion-pair exchange in aqueous solutions. With properly screened electrostatic interactions and bias-based methods, our approach enhances the efficiency of salt-pair exchange in Lennard-Jones electrolytes by approximately four orders of magnitude, compared to conventional grand-canonical Monte Carlo. Furthermore, the acceptance rate of NaCl-pair exchange in aqueous solutions at moderate concentrations reaches about 3% at the maximum efficiency.

Multi-Stage Network for Event-Based Video Deblurring with Residual Hint Attention.

Video deblurring aims at removing the motion blur caused by the movement of objects or camera shake. Traditional video deblurring methods have mainly focused on frame-based deblurring, which takes only blurry frames as the input to produce sharp frames. However, frame-based deblurring has shown poor picture quality in challenging cases of video restoration where severely blurred frames are provided as the input. To overcome this issue, recent studies have begun to explore the event-based approach, which uses the event sequence captured by an event camera for motion deblurring. Event cameras have several advantages compared to conventional frame cameras. Among these advantages, event cameras have a low latency in imaging data acquisition (0.001 ms for event cameras vs. 10 ms for frame cameras). Hence, event data can be acquired at a high acquisition rate (up to one microsecond). This means that the event sequence contains more accurate motion information than video frames. Additionally, event data can be acquired with less motion blur. Due to these advantages, the use of event data is highly beneficial for achieving improvements in the quality of deblurred frames. Accordingly, the results of event-based video deblurring are superior to those of frame-based deblurring methods, even for severely blurred video frames. However, the direct use of event data can often generate visual artifacts in the final output frame (e.g., image noise and incorrect textures), because event data intrinsically contain insufficient textures and event noise. To tackle this issue in event-based deblurring, we propose a two-stage coarse-refinement network by adding a frame-based refinement stage that utilizes all the available frames with more abundant textures to further improve the picture quality of the first-stage coarse output. Specifically, a coarse intermediate frame is estimated by performing event-based video deblurring in the first-stage network. A residual hint attention (RHA) module is also proposed to extract useful attention information from the coarse output and all the available frames. This module connects the first and second stages and effectively guides the frame-based refinement of the coarse output. The final deblurred frame is then obtained by refining the coarse output using the residual hint attention and all the available frame information in the second-stage network. We validated the deblurring performance of the proposed network on the GoPro synthetic dataset (33 videos and 4702 frames) and the HQF real dataset (11 videos and 2212 frames). Compared to the state-of-the-art method (D2Net), we achieved a performance improvement of 1 dB in PSNR and 0.05 in SSIM on the GoPro dataset, and an improvement of 1.7 dB in PSNR and 0.03 in SSIM on the HQF dataset.

A Pneumatically Controlled Prosthetic Socket for Transfemoral Amputees.

Amputees typically experience changes in residual limb volume in their daily lives. It causes an uncomfortable fit of the socket by applying high pressure on the sensitive area of the residual limb or by loosening the socket. In this study, we developed a transfemoral prosthetic socket for above-the-knee amputees that ensures a good socket fit by maintaining uniform and constant contact pressure despite volume changes in the residual limb. The socket has two air bladders in the posterior femoral region, and the pneumatic controller is located on the tibia of the prosthesis. The pneumatic system aims to minimize unstable fitting of the socket and improve walking performance by inflating or deflating the air bladder. The developed socket autonomously maintains the air pressure inside the prosthetic socket at a steady-state error of 3 mmHg or less by adjusting the amount of air in the air bladder via closed-loop control. In the clinical trial, amputee participants walked on flat and inclined surfaces. The displacement between the residual limb and socket during the gait cycle was reduced by up to 33.4% after air injection into the socket. The inflatable bladder increased the knee flexion angle on the affected side, resulting in increased stride length and gait velocity. The pneumatic socket provides a stable and comfortable walking experience not only when walking on flat ground but also on slopes.

SARS-CoV-2 Variant Screening Using a Virus-Receptor-Based Electrical Biosensor.

SARS-CoV-2 variants are of particular interest because they can potentially increase the transmissibility and virulence of COVID-19 or reduce the effectiveness of available vaccines. However, screening SARS-CoV-2 variants is a challenge because biosensors target viral components that can mutate. One promising strategy is to screen variants via angiotensin-converting enzyme 2 (ACE2), a virus receptor shared by all known SARS-CoV-2 variants. Here we designed a highly sensitive and portable COVID-19 screening biosensor based on the virus receptor. We chose a dual-gate field-effect transistor to overcome the low sensitivity of virus-receptor-based biosensors. To optimize the biosensor, we introduced a synthetic virus that mimics the important features of SARS-CoV-2 (size, bilayer structure, and composition). The developed biosensor successfully detected SARS-CoV-2 in 20 min and showed sensitivity comparable to that of molecular diagnostic tests (∼165 copies/mL). Our results indicate that a virus-receptor-based biosensor can be an effective strategy for screening infectious diseases to prevent pandemics.

Comparative Computational Analysis of Spike Protein Structural Stability in SARS-CoV-2 Omicron Subvariants.

The continuous emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with multiple spike (S) protein mutations pose serious threats to current coronavirus disease 2019 (COVID-19) therapies. A comprehensive understanding of the structural stability of SARS-CoV-2 variants is vital for the development of effective therapeutic strategies as it can offer valuable insights into their potential impact on viral infectivity. S protein mediates a virus' attachment to host cells by binding to angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain (RBD), and mutations in this protein can affect its stability and binding affinity. We analyzed S protein structural stability in various Omicron subvariants computationally. Notably, the S protein sequences analyzed in this work were obtained directly from our own sample collection. We evaluated the binding free energy between S protein and ACE2 in several complex forms. Additionally, we measured distances between the RBD of each chain in S protein to analyze conformational changes. Unlike most of the prior studies, we analyzed full-length S protein-ACE2 complexes instead of only RBD-ACE2 complexes. Omicron subvariants including BA.1, BA.2, BA.2.12.1, BA.4/BA.5, BA.2.75, BA.2.75_K147E, BA.4.6 and BA.4.6_N658S showed enhanced stability compared to wild type, potentially due to distinct S protein mutations. Among them, BA.2.75 and BA.4.6_N658S exhibited the highest and lowest level of stability, respectively.

High-dose rifamycins in the treatment of TB: a systematic review and meta-analysis.

BACKGROUND: There is growing interest in using high-dose rifamycin (HDR) regimens in TB treatment, but the safety and efficacy of HDR regimens remain uncertain. We performed a systematic review and meta-analysis comparing HDR to standard-dose rifamycin (SDR) regimens. METHODS: We searched MEDLINE, Embase, CENTRAL, Cochrane Database of Systematic Reviews and clinicaltrials.gov for prospective studies comparing daily therapy with HDRs to SDRs. Rifamycins included rifampicin, rifapentine and rifabutin. Our primary outcome was the rate of severe adverse events (SAEs), with secondary outcomes of death, all adverse events, SAE by organ and efficacy outcomes of 2-month culture conversion and relapse. This study was prospectively registered in the International Prospective Register of Systematic Reviews (CRD42020142519). RESULTS: We identified 9057 articles and included 13 studies with 6168 participants contributing 7930 person-years (PY) of follow-up (HDR: 3535 participants, 4387 PY; SDR: 2633 participants, 3543 PY). We found no significant difference in the pooled incidence rate ratio (IRR) of SAE between HDR and SDR (IRR 1.00, 95% CI 0.82 to 1.23, I 2=41%). There was no significant difference when analysis was limited to SAE possibly, probably or likely medication-related (IRR 1.07, 95% CI 0.82 to 1.41, I 2=0%); studies with low risk of bias (IRR 0.98, 95% CI 0.79 to 1.20, I 2=44%); or studies using rifampicin (IRR 1.00, 95% CI 0. 0.75-1.32, I 2=38%). No significant differences were noted in pooled outcomes of death, 2-month culture conversion and relapse. CONCLUSIONS: HDRs were not associated with a significant difference in SAEs, 2-month culture conversion or death. Further studies are required to identify specific groups who may benefit from HDR.

Enhanced Thermoelectric Power Factor in Carrier-Type-Controlled Platinum Diselenide Nanosheets by Molecular Charge-Transfer Doping.

2D transition metal dichalcogenides (TMDCs) have revealed great promise for realizing electronics at the nanoscale. Despite significant interests that have emerged for their thermoelectric applications due to their predicted high thermoelectric figure of merit, suitable doping methods to improve and optimize the thermoelectric power factor of TMDCs have not been studied extensively. In this respect, molecular charge-transfer doping is utilized effectively in TMDC-based nanoelectronic devices due to its facile and controllable nature owing to a diverse range of molecular designs available for modulating the degree of charge transfer. In this study, the power of molecular charge-transfer doping is demonstrated in controlling the carrier-type (n- and p-type) and thermoelectric power factor in platinum diselenide (PtSe2 ) nanosheets. This, combined with the tunability in the band overlap by changing the thickness of the nanosheets, allows a significant increase in the thermoelectric power factor of the n- and p-doped PtSe2 nanosheets to values as high as 160 and 250 µW mK-2 , respectively. The methodology employed in this study provides a simple and effective route for the molecular doping of TMDCs that can be used for the design and development of highly efficient thermoelectric energy conversion systems.

Publisher Correction: Oblique-plane single-molecule localization microscopy for tissues and small intact animals.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Oblique-plane single-molecule localization microscopy for tissues and small intact animals.

Single-molecule localization microscopy (SMLM), while well established for cultured cells, is not yet fully compatible with tissue-scale samples. We introduce single-molecule oblique-plane microscopy (obSTORM), which by directly imaging oblique sections of samples with oblique light-sheet illumination offers a deep and volumetric SMLM platform that is convenient for standard tissue samples and small intact animals. We demonstrate super-resolution imaging at depths of up to 66 µm for cells, Caenorhabditis elegans gonads, Drosophila melanogaster larval brain, mouse retina and brain sections, and whole stickleback fish.