The cytokine Meteorin-like inhibits anti-tumor CD8+ T cell responses by disrupting mitochondrial function.

Tumor-infiltrating lymphocyte (TIL) hypofunction contributes to the progression of advanced cancers and is a frequent target of immunotherapy. Emerging evidence indicates that metabolic insufficiency drives T cell hypofunction during tonic stimulation, but the signals that initiate metabolic reprogramming in this context are largely unknown. Here, we found that Meteorin-like (METRNL), a metabolically active cytokine secreted by immune cells in the tumor microenvironment (TME), induced bioenergetic failure of CD8+ T cells. METRNL was secreted by CD8+ T cells during repeated stimulation and acted via both autocrine and paracrine signaling. Mechanistically, METRNL increased E2F-peroxisome proliferator-activated receptor delta (PPARδ) activity, causing mitochondrial depolarization and decreased oxidative phosphorylation, which triggered a compensatory bioenergetic shift to glycolysis. Metrnl ablation or downregulation improved the metabolic fitness of CD8+ T cells and enhanced tumor control in several tumor models, demonstrating the translational potential of targeting the METRNL-E2F-PPARδ pathway to support bioenergetic fitness of CD8+ TILs.

Flat-surface-assisted and self-regulated oxidation resistance of Cu(111).

Oxidation can deteriorate the properties of copper that are critical for its use, particularly in the semiconductor industry and electro-optics applications1-7. This has prompted numerous studies exploring copper oxidation and possible passivation strategies8. In situ observations have, for example, shown that oxidation involves stepped surfaces: Cu2O growth occurs on flat surfaces as a result of Cu adatoms detaching from steps and diffusing across terraces9-11. But even though this mechanism explains why single-crystalline copper is more resistant to oxidation than polycrystalline copper, the fact that flat copper surfaces can be free of oxidation has not been explored further. Here we report the fabrication of copper thin films that are semi-permanently oxidation resistant because they consist of flat surfaces with only occasional mono-atomic steps. First-principles calculations confirm that mono-atomic step edges are as impervious to oxygen as flat surfaces and that surface adsorption of O atoms is suppressed once an oxygen face-centred cubic (fcc) surface site coverage of 50% has been reached. These combined effects explain the exceptional oxidation resistance of ultraflat Cu surfaces.

Sniper2L is a high-fidelity Cas9 variant with high activity.

Although several high-fidelity SpCas9 variants have been reported, it has been observed that this increased specificity is associated with reduced on-target activity, limiting the applications of the high-fidelity variants when efficient genome editing is required. Here, we developed an improved version of Sniper-Cas9, Sniper2L, which represents an exception to this trade-off trend as it showed higher specificity with retained high activity. We evaluated Sniper2L activities at a large number of target sequences and developed DeepSniper, a deep learning model that can predict the activity of Sniper2L. We also confirmed that Sniper2L can induce highly efficient and specific editing at a large number of target sequences when it is delivered as a ribonucleoprotein complex. Mechanically, the high specificity of Sniper2L originates from its superior ability to avoid unwinding a target DNA containing even a single mismatch. We envision that Sniper2L will be useful when efficient and specific genome editing is required.

Structural Asymmetry and Chiral-Induced Spin Selectivity in Chiral Palladium-Halide Semiconductors.

Chiral Pb-free metal-halide semiconductors (MHSs) have attracted considerable attention in the field of spintronics due to various interesting spin-related properties and chiral-induced spin selectivity (CISS) effect. Despite their excellent chemical and structural tunability, the material scope and crystal structure of Pb-free chiral MHSs exhibiting the CISS effect are still limited; chiral MHSs that have metal-halide structures of octahedra and tetrahedra are only reported. Here, we report a new class of chiral MHSs, of which palladium (Pd)-halides are formed in 1D square-pyramidal structures or 0D square-planar structures, with a general formula of ((R/S-MBA)2PdBr4)1-x((R/S-MBA)2PdCl4)x (MBA = methylbenzylammonium; x = 0, 0.25, 0.5, 0.75, and 1) for the first time. The crystals adopt the 1D helical chain of Pd-halide square-pyramid (for x = 0, 0.25, 0.5, and 0.75) and 0D structure of Pd-halide square-plane (for x = 1). All the Pd-halides are distorted by the interaction between the halide and the chiral organic ammonium and arranged in a noncentrosymmetric position. Circular dichroism (CD) for ((R/S-MBA)2PdBr4)1-x((R/S-MBA)2PdCl4)x indicates that chirality was transferred from chiral organic ammonium to Pd-halide inorganics. ((R-MBA)2PdBr4)1-x((R-MBA)2PdCl4)x (x = 0, 0.25, 0.5, and 0.75) shows a distortion index of 0.127-0.128, which is the highest value among the previously reported chiral MHSs to the best of our knowledge. We also find that (R/S-MBA)2Pd(Br1-xClx)4 crystals grow along the out-of-plane direction during spin coating and have high c-axis orientation and crystallinity, and (R/S-MBA)2Pd(Br1-xClx)4 (x = 0 and 0.5) crystals exhibit a CISS effect in polycrystalline bulk films. These results demonstrate the possibility of a new metal-halide series with square-planar structures or square-pyramidal structures for future spintronic applications.

Regional disparities and risk factors of mortality among patients at high risk of sudden cardiac death in emerging countries: a nonrandomized controlled trial.

BACKGROUND: Comprehensive data on patients at high risk of sudden cardiac death (SCD) in emerging countries are lacking. The aim was to deepen our understanding of the SCD phenotype and identify risk factors for death among patients at high risk of SCD in emerging countries. METHODS: Patients who met the class I indication for implantable cardioverter-defibrillator (ICD) implantation according to guideline recommendations in 17 countries and regions underrepresented in previous trials were enrolled. Countries were stratified by the WHO regional classification. Patients were or were not implanted with an ICD at their discretion. The outcomes were all-cause mortality and SCD. RESULTS: We enrolled 4222 patients, and 3889 patients were included in the analysis. The mean follow-up period was 21.6 ± 10.2 months. There were 433 (11.1%) instances of all-cause mortality and 117 (3.0%) cases of SCD. All-cause mortality was highest in primary prevention (PP) patients from Southeast Asia and secondary prevention (SP) patients from the Middle East and Africa. The SCD rates among PP and SP patients were both highest in South Asia. Multivariate Cox regression modelling demonstrated that in addition to the independent predictors identified in previous studies, both geographic region and ICD use were associated with all-cause mortality in patients with high SCD risk. Primary prophylactic ICD implantation was associated with a 36% (HR = 0.64, 95% CI 0.531-0.802, p < 0.0001) lower all-cause mortality risk and an 80% (HR = 0.20, 95% CI = 0.116-0.343, p < 0.0001) lower SCD risk. CONCLUSIONS: There was significant heterogeneity among patients with high SCD risk in emerging countries. The influences of geographic regions on patient characteristics and outcomes were significant. Improvement in increasing ICD utilization and uptake of guideline-directed medical therapy in emerging countries is urgent. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02099721.

High Open-Circuit Voltage Wide-Bandgap Perovskite Solar Cell with Interface Dipole Layer.

Wide-bandgap perovskite solar cells (PSCs) with high open-circuit voltage (Voc) represent a compelling and emerging technological advancement in high-performing perovskite-based tandem solar cells. Interfacial engineering is an effective strategy to enhance Voc in PSCs by tailoring the energy level alignments between the constituent layers. Herein, n-type quinoxaline-phosphine oxide-based small molecules with strong dipole moments is designed and introduce them as effective cathode interfacial layers. Their strong dipole effect leads to appropriate energy level alignment by tuning the work function of the Ag electrode to form an ohmic contact and enhance the built-in potential within the device, thereby improving charge-carrier transport and mitigating charge recombination. The organic interfacial layer-modified wide-bandgap PSCs exhibit a high Voc of 1.31 V (deficit of <0.44 V) and a power conversion efficiency (PCE) of 20.3%, significantly improved from the device without an interface dipole layer (Voc of 1.26 V and PCE of 16.7%). Furthermore, the hydrophobic characteristics of the small molecules contribute to improved device stability, retaining 95% of the initial PCE after 500 h in ambient air.

Suppression of Thermally Induced Surface Traps in Colloidal Quantum Dot Solids via Ultrafast Pulsed Light.

Thermal annealing (TA) of colloidal quantum dot (CQD) films is considered an important process for recent high-performing CQD solar cells (SCs) due to its beneficial effects on CQD solids, including enhanced electrical conductivity, denser packing of CQD films, and the removal of organic residues and solvents. However, the conventional TA for CQDs, which requires several  minutes, leads to hydroxylation and oxidation on the CQD surface, resulting in the formation of trap states and a subsequent decline in SC performance. To address these challenges, this study introduces a flashlight annealing (FLA) technique that significantly reduces the annealing time to the millisecond scale. Through the FLA approach, it successfully suppressed hydroxylation and oxidation, resulting in decreased trap states within the CQD solids while simultaneously preserving their charge transport properties. As a result, CQD SCs treated with FLA exhibited a notable improvement, achieving an open-circuit voltage of 0.66 V compared to 0.63 V in TA-treated devices, leading to an increase in power conversion efficiency from 12.71% to 13.50%.

Interfacial Triboelectricity Lights Up Phosphor-Polymer Elastic Composites: Unraveling the Mechanism of Mechanoluminescence in Zinc Sulfide Microparticle-Embedded Polydimethylsiloxane Films.

Composites comprising copper-doped zinc sulfide phosphor microparticles embedded in polydimethylsiloxane (ZnS:Cu-PDMS) have received significant attention over the past decade because of their bright and durable mechanoluminescence (ML); however, the underlying mechanism of this unique ML remains unclear. This study reports empirical and theoretical findings that confirm this ML is an electroluminescence (EL) of the ZnS:Cu phosphor induced by the triboelectricity generated at the ZnS:Cu microparticle-PDMS matrix interface. ZnS:Cu microparticles that exhibit bright ML are coated with alumina, an oxide with strong positive triboelectric properties; the contact separation between this oxide coating and PDMS, a polymer with strong negative triboelectric properties, produces sufficient interfacial triboelectricity to induce EL in ZnS:Cu microparticles. The ML of ZnS:Cu-PDMS composites varies on changing the coating material, exhibiting an intensity that is proportional to the amount of interfacial triboelectricity generated in the system. Finally, based on these findings, a mechanism that explains the ML of phosphor-polymer elastic composites (interfacial triboelectric field-driven alternating-current EL model) is proposed in this study. It is believed that understanding this mechanism will enable the development of new materials (beyond ZnS:Cu-PDMS systems) with bright and durable ML.

Efficient Polycrystalline Single-Cation Perovskite Light-Emitting Diodes by Simultaneous Intracrystal and Interfacial Defect Passivation.

Polycrystalline perovskite light-emitting diodes (PeLEDs) have shown great promise with high efficiency and easy processability. However, PeLEDs using single-cation polycrystalline perovskite emitters have demonstrated low efficiency due to defects within the grains and at the interfaces between the perovskite layer and the charge injection contact. Thus, simultaneous defect engineering of perovskites to suppress exciton loss within the grains and at the interfaces is crucial for achieving high efficiency in PeLEDs. Here, 1,8-octanedithiol which is a strong nucleophile, is used to increase the luminescence efficiency of a single-cation perovskite by suppressing non-radiative recombination within the grains of their polycrystalline emitter film as well as at their interface with an anode. The dithiol additive performs a multifunctional role in defect passivation, spatial confinement of excitons, and prevention of exciton quenching at the interface between the perovskite layer and the underlying hole-injection layer. Photoluminescence studies demonstrate that incorporating the dithiol additive significantly enhances the charge carrier dynamics in perovskites, resulting in an external quantum efficiency (EQE) of up to 23.46% even in a simplified PeLED that does not use a hole-injection layer. This represents the highest level of EQE achieved among devices utilizing polycrystalline single-cation perovskites.

iRhom2 deficiency reduces sepsis-induced mortality associated with the attenuation of lung macrophages in mice.

Sepsis has a high mortality rate and leads to multi-organ failure, including lung injury. Inactive rhomboid protease family protein (iRhom2) has been identified as accountable for the release of TNF-α, a crucial mediator in the development of sepsis. This study aimed to evaluate the role of iRhom2 in sepsis and sepsis-induced acute lung injury (ALI). TNF-α and IL-6 secretion in vitro by peritoneal macrophages from wild-type (WT) and iRhom2 knoukout (KO) mice was assessed by enzyme-linked immunosorbent assay. Cecal ligation and puncture (CLP)-induced murine sepsis model was used for in vivo experiments. To evaluate the role of iRhom2 deficiency on survival during sepsis, both WT and iRhom2 KO mice were monitored for 8 consecutive days following the CLP. For histologic and biochemical examination, the mice were killed 18 h after CLP. iRhom2 deficiency improved the survival of mice after CLP. iRhom2 deficiency decreased CD68+ macrophage infiltration in lung tissues. Multiplex immunohistochemistry revealed that the proportion of Ki-67+ CD68+ macrophages was significantly lower in iRhom2 KO mice than that in WT mice after CLP. Moreover, CLP-induced release of TNF-α and IL-6 in the serum were significantly inhibited by iRhom2 deficiency. iRhom2 deficiency reduced NF-kB p65 and IκBα phosphorylation after CLP. iRhom2 deficiency reduces sepsis-related mortality associated with attenuated macrophage infiltration and proliferation in early lung injury. iRhom2 may play a pivotal role in the pathogenesis of sepsis and early stage of sepsis-induced ALI. Thus, iRhom2 may be a potential therapeutic target for the management of sepsis and sepsis-induced ALI.

Association of temporal change in body mass index with sudden cardiac arrest in diabetes mellitus.

BACKGROUND: Underweight imposes significant burden on cardiovascular outcomes in patients with diabetes mellitus. However, less is known about the impact of serial change in body weight status measured as body mass index (BMI) on the risk of sudden cardiac arrest (SCA). This study investigated the association between SCA and temporal change in BMI among patients with diabetes mellitus. METHODS: Based on Korean National Health Insurance Service database, participants with diabetes mellitus who underwent health examination between 2009 and 2012 and had prior health examination data (four years ago, 2005-2008) were retrospectively analyzed. BMI was measured at baseline (2005-2008) and 4-year follow-up health examination (2009-2012). Patients were classified in four groups according to the body weight status and its temporal change: sustained non-underweight, sustained underweight, previous underweight, and newly developed underweight. Primary outcome was defined as occurrence of SCA. RESULTS: A total of 1,355,746 patients with diabetes mellitus were included for analysis, and SCA occurred in 12,554 cases. SCA was most common in newly developed underweight (incidence rate = 4.45 per 1,000 person-years), followed by sustained underweight (incidence rate = 3.90), previous underweight (incidence rate = 3.03), and sustained non-underweight (incidence rate = 1.34). Adjustment of covariates resulted highest risk of SCA in sustained underweight (adjusted hazard ratio = 2.60, 95% confidence interval [2.25-3.00], sustained non-underweight as a reference), followed by newly developed underweight (2.42, [2.15-2.74]), and previous underweight (2.12, [1.77-2.53]). CONCLUSIONS: In diabetes mellitus, sustained underweight as well as decrease in body weight during 4-year follow-up imposes substantial risk on SCA. Recovery from underweight over time had relatively lower, but yet increased risk of SCA. Both underweight and dynamic decrease in BMI can be associated with increased risk of SCA.

Pre-operative dual-time-point [18F]FET PET differentiates CDKN2A/B loss and PIK3CA mutation status in adult-type diffuse glioma: a single-center prospective study.

PURPOSE: While [18F]FET PET plays a complementary role in glioma imaging, it needs to be more comprehensively understood for improved characterization of glioma prior to surgery given the evolving landscape of molecular neuropathology. Thus, we investigated the utility of pre-operative dual-time-point [18F]FET PET in correlation with next-generation sequencing (NGS) data in patients with adult-type diffuse glioma (ADG). METHODS: Adult patients who were suspected to have primary glioma were prospectively recruited between June 2021 and January 2024. They underwent pre-operative dual-time-point static PET/CT at 20 min (early) and 80 min (delay) after [18F]FET injection. Semi-quantitative parameters of the hottest lesion (SUVmax) of tumour and the hottest lesion-to-normal brain ratio (TBRmax) were assessed from each summed image. Furthermore, the percentage changes (△) of SUVmax and TBRmax between two images were calculated. Histopathology of glioma was determined according to the 2021 WHO classification and NGS data. RESULTS: This study investigated a dozen genes in 76 patients, of whom 51 had isocitrate dehydrogenase (IDH)-wild-type glioblastoma, 13 had IDH-mutant astrocytoma, and 12 had IDH-mutant oligodendroglioma. Every tumour was [18F]FET-avid having TBRmax more than 1.6. Patients with CDKN2A/B loss had significantly higher values of SUVmax (5.7 ± 1.6 vs. 4.7 ± 1.3, p = 0.004; 5.0 ± 1.4 vs. 4.4 ± 1.2, p = 0.026) and TBRmax (6.5 ± 1.8 vs. 5.1 ± 1.7, p = 0.001; 5.3 ± 1.5 vs. 4.3 ± 1.3, p = 0.004) in both scans than patients without CDKN2A/B loss, even after adjustment for age, MRI enhancement, tumor grade and type of pathology. Furthermore, patients with PIK3CA mutation (16.2 ± 11.8 vs. 6.7 ± 11.6, p = 0.007) had significantly higher △SUVmax than patients without PIK3CA mutation, even after adjustment for age, MRI enhancement, tumor grade, and type of pathology. CONCLUSION: Among the dozen genes investigated in this prospective study in patients with ADG, we found out that CDKN2A/B loss and PIK3CA mutation status could be differentiated by pre-operative dual-time-point [18F]FET PET/CT.

Prospective longitudinal analysis of imaging-based spatiotemporal tumor habitats in glioblastoma, IDH-wild type: implication in patient outcome using multiparametric physiologic MRI.

BACKGROUND: Physiologic MRI-based tumor habitat analysis has the potential to predict patient outcomes by identifying the spatiotemporal habitats of glioblastoma. This study aims to prospectively validate the cut-off for tumor progression obtained from tumor habitat analysis based on physiologic MRI in ascertaining time-to-progression (TTP) and the site of progression in glioblastoma patients following concurrent chemoradiotherapy (CCRT). METHODS: In this prospective study (ClinicalTrials.gov ID: NCT02613988), we will recruit patients with IDH-wild type glioblastoma who underwent CCRT and obtained immediate post-operative and three serial post-CCRT MRI scans within a three-month interval, conducted using diffusion-weighted imaging and dynamic susceptibility contrast imaging. Voxels from cerebral blood volume and apparent diffusion coefficient maps will be grouped using k-means clustering into three spatial habitats (hypervascular cellular, hypovascular cellular, and nonviable tissue). The spatiotemporal habitats of the tumor will be evaluated by comparing changes in each habitat between the serial MRI scans (post-operative and post-CCRT #1, #2, and #3). Associations between spatiotemporal habitats and TTP will be analyzed using cox proportional hazard modeling. The site of progression will be matched with spatiotemporal habitats. DISCUSSION: The perfusion- and diffusion-derived tumor habitat in glioblastoma is expected to stratify TTP and may serve as an early predictor for tumor progression in patients with IDH wild-type glioblastoma. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02613988.

Assessment of imaging risks for recurrence after stereotactic radiosurgery for brain metastases (IRRaS-BM).

BACKGROUND: The identification of viable tumors and radiation necrosis after stereotactic radiosurgery (SRS) is crucial for patient management. Tumor habitat analysis involving the grouping of similar voxels can identify subregions that share common biology and enable the depiction of areas of tumor recurrence and treatment-induced change. This study aims to validate an imaging biomarker for tumor recurrence after SRS for brain metastasis by conducting tumor habitat analysis using multi-parametric MRI. METHODS: In this prospective study (NCT05868928), patients with brain metastases will undergo multi-parametric MRI before SRS, and then follow-up MRIs will be conducted every 3 months until 24 months after SRS. The multi-parametric MRI protocol will include T2-weighted and contrast-enhanced T1-weighted imaging, diffusion-weighted imaging, and dynamic susceptibility contrast imaging. Using k-means voxel-wise clustering, this study will define three structural MRI habitats (enhancing, solid low-enhancing, and nonviable) on T1- and T2-weighted images and three physiologic MRI habitats (hypervascular cellular, hypovascular cellular, and nonviable) on apparent diffusion coefficient maps and cerebral blood volume maps. Using RANO-BM criteria as the reference standard, via Cox proportional hazards analysis, the study will prospectively evaluate associations between parameters of the tumor habitats and the time to recurrence. The DICE similarity coefficients between the recurrence site and tumor habitats will be calculated. DISCUSSION: The tumor habitat analysis will provide an objective and reliable measure for assessing tumor recurrence from brain metastasis following SRS. By identifying subregions for local recurrence, our study could guide the next therapeutic targets for patients after SRS. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT05868928).

Surge of acute gastroenteritis outbreaks due to rising norovirus GII.4 transmission in Seoul childcare centers and kindergartens in 2022 compared to 2019-2021.

Noroviruses are the most common cause of acute gastroenteritis (AGE) outbreaks in childcare centers and kindergartens. Their high transmissibility is partly due to their genetic diversity. AGE outbreaks that occurred in Seoul childcare centers and kindergartens from 2019 to 2022 were investigated, and 68 epidemiological reports prepared by public health centers in Seoul were used for data collection. In the three quarters of 2022, there were 40 outbreaks of AGE in Seoul childcare centers and kindergartens, which exceeded the 35 total outbreaks that occurred during the previous three years. The proportion of childcare centers and kindergartens with AGE outbreaks among all facilities in Seoul increased from 12.6% in 2019 to 58.8% in 2022. Noroviruses were the most common pathogens responsible for AGE outbreaks in these cases. From 2019 to 2021, norovirus GII.2 was the predominant genotype, and GII.4 was detected in about 25% of cases. However, in 2022, GII.4 became predominant and was detected in about 79% of cases. The attack rate and infection source of AGE outbreaks from 2019 to 2021 were not significantly different from those in 2022. In conclusion, the number of AGE outbreaks in Seoul childcare centers and kindergartens increased significantly, primarily because of increased norovirus GII.4 transmission in 2022.

Atrial fibrillation and risk of sudden cardiac arrest in young adults.

AIMS: Evidence of an association between atrial fibrillation (AF) and sudden cardiac arrest (SCA) in young adults is limited. In this study, we aim to evaluate this association in a general population aged between 20 and 39 years. METHODS AND RESULTS: Young adults who underwent health check-ups between 2009 and 2012 were screened from a nationwide healthcare database in South Korea. A history of AF diagnosis before the health check-ups was identified based on the relevant International Classification of Diseases, 10th edition codes reported in the database. Associations between an established diagnosis of AF and the risk of SCA during follow-up were examined. A total of 6 345 162 young people were analysed with a mean follow-up duration of 9.4 years. The mean age was 30.9 ± 5.0 years, and 5875 (0.09%) individuals were diagnosed with AF. During follow-up, SCA occurred in 5352 (0.08%) individuals, and the crude incidence was 0.56 and 0.09 events per 1000 person-years for participants with and without AF, respectively. Individuals with AF had a 3.0-fold higher risk in a multivariate model adjusted for age, sex, lifestyle, anthropometric data, and medical comorbidities (adjusted hazard ratio 2.96, 95% confidence interval 1.99-4.41, P < 0.001). Both incident and prevalent AFs were associated with an increased risk of SCA, with no significant differences between the two groups. CONCLUSION: Atrial fibrillation was associated with a significantly higher risk of SCA developing in healthy young adults. Whether the rate or rhythm control influences the risk of SCA in young patients with AF remains to be examined.

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society .

RNA Remodeling Activity of DEAD Box Proteins Tuned by Protein Concentration, RNA Length, and ATP.

DEAD box RNA helicases play central roles in RNP biogenesis. We reported earlier that LAF-1, a DEAD box RNA helicase in C. elegans, dynamically interacts with RNA and that the interaction likely contributes to the fluidity of RNP droplets. Here we investigate the molecular basis of the interaction of RNA with LAF-1 and its human homolog, DDX3X. We show that both LAF-1 and DDX3X, at low concentrations, are monomers that induce tight compaction of single-stranded RNA. At high concentrations, the proteins are multimeric and dynamically interact with RNA in an RNA length-dependent manner. The dynamic LAF-1-RNA interaction stimulates RNA annealing activity. ATP adversely affects the RNA remodeling ability of LAF-1 by suppressing the affinity, dynamics, and annealing activity of LAF-1, suggesting that ATP may promote disassembly of the RNP complex. Based on our results, we postulate a plausible molecular mechanism underlying the dynamic equilibrium of the LAF-1 RNP complex.

Accelerated muscle mass estimation from CT images through transfer learning.

BACKGROUND: The cost of labeling to collect training data sets using deep learning is especially high in medical applications compared to other fields. Furthermore, due to variances in images depending on the computed tomography (CT) devices, a deep learning based segmentation model trained with a certain device often does not work with images from a different device. METHODS: In this study, we propose an efficient learning strategy for deep learning models in medical image segmentation. We aim to overcome the difficulties of segmentation in CT images by training a VNet segmentation model which enables rapid labeling of organs in CT images with the model obtained by transfer learning using a small number of manually labeled images, called SEED images. We established a process for generating SEED images and conducting transfer learning a model. We evaluate the performance of various segmentation models such as vanilla UNet, UNETR, Swin-UNETR and VNet. Furthermore, assuming a scenario that a model is repeatedly trained with CT images collected from multiple devices, in which is catastrophic forgetting often occurs, we examine if the performance of our model degrades. RESULTS: We show that transfer learning can train a model that does a good job of segmenting muscles with a small number of images. In addition, it was confirmed that VNet shows better performance when comparing the performance of existing semi-automated segmentation tools and other deep learning networks to muscle and liver segmentation tasks. Additionally, we confirmed that VNet is the most robust model to deal with catastrophic forgetting problems. CONCLUSION: In the 2D CT image segmentation task, we confirmed that the CNN-based network shows better performance than the existing semi-automatic segmentation tool or latest transformer-based networks.

Endoscopic decompression of severe post-tuberculosis kyphosis related ossification of the ligamentum flavum: case report and literature review.

PURPOSE: Spinal tuberculosis, if not promptly treated, can lead to kyphotic deformity, causing persistent neurological abnormalities and discomfort. Spinal cord compression can occur due to ossification of the ligamentum flavum (OLF) at the apex of kyphosis. Traditional surgical interventions, including osteotomy and fixation, pose challenges and risks. We present a case of thoracic myelopathy in a patient with post-tuberculosis kyphosis, successfully treated with biportal endoscopic spinal surgery (BESS). METHOD: A 73-year-old female with a history of untreated kyphosis presented with walking difficulties and lower limb pain. Imaging revealed a kyphotic deformity of 120° and OLF-induced cord compression at T8-9. UBE was performed under spinal anesthesia. Using the BESS technique, OLF was successfully removed with minimal damage to the stabilizing structures. RESULTS: The patient exhibited neurological improvement after surgery, walking on the first day without gait instability. Follow-up at 1 year showed no kyphosis progression or recurrence of symptoms. BESS successfully resolved the cord compression lesion with minimal blood loss and damage. CONCLUSION: In spinal tuberculosis-related OLF, conventional open surgery poses challenges. BESS emerges as an excellent alternative, providing effective decompression with reduced instrumentation needs, minimal blood loss, and preservation of surrounding structures. Careful patient selection and surgical planning are crucial for optimal outcomes in endoscopic procedures.