Androgen Deprivation Therapy and the Risk of Newly Developed Dry Eye Syndrome in Patients with Prostate Cancer: A Nationwide Nested Case-Control Study in the Republic of Korea.

Background: We aimed to evaluate the association between androgen deprivation therapy (ADT) and newly developed dry eye syndrome (DES) in patients with prostate cancer. Methods: A nested case-control study was conducted. From the nationwide claims database of the Republic of Korea, 125,005 patients were included in the final analysis. Cases were defined as those newly diagnosed with DES during follow-up, and 12,654 patients were identified. The cases were matched with controls in a ratio of 1:4. Odds ratios (ORs) for newly developed DES associated with ADT were estimated using conditional logistic regression. Results: After matching, 7499 cases and 29,996 controls were selected. ADT was associated with a reduced risk of newly developed DES in patients with prostate cancer compared to no ADT (OR = 0.875; 95% confidence interval, 0.825-0.927; p < 0.0001). An accumulated dose of ADT < 1 year was associated with a reduced risk of incidental DES (OR = 0.811; 95% CI, 0.751-0.875; p < 0.0001), and a duration of 1-2 years was also associated with a reduced risk (OR = 0.890; 95% CI, 0.802-0.986; p = 0.026). No association was observed with an ADT duration of ≥2 years. Conclusions: The use of ADT, especially for shorter durations (<2 years), was associated with a reduced risk of newly developed DES in S. Korean patients with prostate cancer.

Application of mesenchymal stem cells exosomes as nanovesicles delivery system in the treatment of breast cancer.

As people's living standards continue to improve and human life span expectancy increases, the incidence and mortality rates of breast cancer are continuously rising. Early detection of breast cancer and targeted therapy for different breast cancer subtypes can significantly reduce the mortality rate and alleviate the suffering of patients. Exosomes are extracellular vesicles secreted by various cells in the body. They participate in physiological and pathological responses by releasing active substances and play an important role in regulating intercellular communication. In recent years, research on exosomes has gradually expanded, and their special membrane structure and targetable characteristics are being increasingly applied in various clinical studies. Mesenchymal stem cells (MSCs)-derived exosomes play an important role in regulating the progression of breast cancer. In this review, we summarize the current treatment methods for breast cancer, the connection between MSCs, exosomes, and breast cancer, as well as the application of exosomes derived from MSCs from different sources in cancer treatment. We highlight how the rational design of modified MSCs-derived exosomes (MSCs-Exos) delivery systems can overcome the uncertainties of stem cell therapy and overcome the clinical translation challenges of nanomaterials. This work aims to promote future research on the application of MSCs-Exos in breast cancer treatment.

Mutations in starch BRANCHING ENZYME 2a suppress the traits caused by the loss of ISOAMYLASE1 in barley.

KEY MESSAGE: The hvbe2a mutations restore the starch-deficient phenotype caused by the hvisa1 and hvflo6 mutations in barley endosperm. The genetic interactions among starch biosynthesis genes can be exploited to alter starch properties, but they remain poorly understood due to the various combinations of mutations to be tested. Here, we isolated two novel barley mutants defective in starch BRANCHING ENZYME 2a (hvbe2a-1 and hvbe2a-2) based on the starch granule (SG) morphology. Both hvbe2a mutants showed elongated SGs in the endosperm and increased resistant starch content. hvbe2a-1 had a base change in HvBE2a gene, substituting the amino acid essential for its enzyme activity, while hvbe2a-2 is completely missing HvBE2a due to a chromosomal deletion. Further genetic crosses with barley isoamylase1 mutants (hvisa1) revealed that both hvbe2a mutations could suppress defects in endosperm caused by hvisa1, such as reduction in starch, increase in phytoglycogen, and changes in the glucan chain length distribution. Remarkably, hvbe2a mutations also transformed the endosperm SG morphology from the compound SG caused by hvisa1 to bimodal simple SGs, resembling that of wild-type barley. The suppressive impact was in competition with floury endosperm 6 mutation (hvflo6), which could enhance the phenotype of hvisa1 in the endosperm. In contrast, the compound SG formation induced by the hvflo6 hvisa1 mutation in pollen was not suppressed by hvbe2a mutations. Our findings provide new insights into genetic interactions in the starch biosynthetic pathway, demonstrating how specific genetic alterations can influence starch properties and SG morphology, with potential applications in cereal breeding for desired starch properties.

Two new species of the family Aoridae (Crustacea, Malacostraca, Amphipoda) from Korean waters.

Two new species of the family Aoridae, one from the genus Aoroides Walker, 1898, and other from the genus Grandidierella Coutière, 1904, are reported from Korean waters. Aoroidesgracilicrus sp. nov. is similar to A.longimerus in having numerous plumose setae on the basis and carpus of gnathopod 1. However, the new species can be distinguished from A.longimerus by the numerous plumose setae on the bases of pereopods 3 and 4 and the slender basis of pereopod 7. Grandidierellanaroensis sp. nov. is morphologically most similar to G.pseudosakaensis. However, the new species can be distinguished by the presence of small distal and proximal processes and a large middle process on the carpus of gnathopod 1, and the subovate propodus of gnathopod 1. Both new species are illustrated and compared to related species. A key to species in the family Aoridae from Korean waters is also provided.

Leveraging and learning from the long COVID experience: Translating telerehabilitation into practice.

BACKGROUND: Telerehabilitation, or the delivery of rehabilitation services through telehealth platforms, has existed since the late 1990 s. Telerehabilitation was characterized by unprecedented, exponential growth at the beginning of the novel coronavirus-2019 (COVID-19) pandemic. Medical systems sought to reduce the likelihood of disease transmission by using telerehabilitation to limit physical proximity during routine care. This dramatic change in how medical care was delivered forced many professions to adapt processes and practices. Following the change, debates sparked regarding the best path to move forward for the betterment of patients, clinicians, systems, and society. Long COVID has emerged as a complex chronic health condition arising from COVID-19. The unique needs and dynamic disease process of Long COVID has incentivized medical systems to create equitable ways for patients to safely access interdisciplinary care. OBJECTIVES: The purpose of this commentary is to describe what medical systems must consider when deploying high-quality telerehabilitation to deliver rehabilitation through asynchronous (e.g., text, portal) and synchronous modalities (e.g., phone or video). We highlight lessons learned to help guide decision-makers on key actions to support their patients and clinicians. METHODS: Not applicable. RESULTS: Not applicable. CONCLUSIONS: Key action steps from our lessons learned may be used to address complex chronic health conditions such as Long COVID and prepare for future challenges that may disrupt medical systems.

Macroscopic brain dynamics beyond contralateral primary motor cortex for movement prediction.

This study investigates the complex relationship between upper limb movement direction and macroscopic neural signals in the brain, which is critical for understanding brain-computer interfaces (BCI). Conventional BCI research has primarily focused on a local area, such as the contralateral primary motor cortex (M1), relying on the population-based decoding method with microelectrode arrays. In contrast, macroscopic approaches such as electroencephalography (EEG) and magnetoencephalography (MEG) utilize numerous electrodes to cover broader brain regions. This study probes the potential differences in the mechanisms of microscopic and macroscopic methods. It is important to determine which neural activities effectively predict movements. To investigate this, we analyzed MEG data from nine right-handed participants while performing arm-reaching tasks. We employed dynamic statistical parametric mapping (dSPM) to estimate source activity and built a decoding model composed of long short-term memory (LSTM) and a multilayer perceptron to predict movement trajectories. This model achieved a high correlation coefficient of 0.79 between actual and predicted trajectories. Subsequently, we identified brain regions sensitive to predicting movement direction using the integrated gradients (IG) method, which assesses the predictive contribution of each source activity. The resulting salience map demonstrated a distribution without significant differences across motor-related regions, including M1. Predictions based solely on M1 activity yielded a correlation coefficient of 0.42, nearly half as effective as predictions incorporating all source activities. This suggests that upper limb movements are influenced by various factors such as movement coordination, planning, body and target position recognition, and control, beyond simple muscle activity. All of the activities are needed in the decoding model using macroscopic signals. Our findings also revealed that contralateral and ipsilateral hemispheres contribute equally to movement prediction, implying that BCIs could potentially benefit patients with brain damage in the contralateral hemisphere by utilizing brain signals from the ipsilateral hemisphere. In conclusion, this study demonstrates that macroscopic activity from large brain regions significantly contributes to predicting upper limb movement. Non-invasive BCI systems would require a comprehensive collection of neural signals from multiple brain regions.

Comprehensive analysis of CXXX sequence space reveals that Saccharomyces cerevisiae GGTase-I mainly relies on a2X substrate determinants.

Many proteins undergo a post-translational lipid attachment, which increases their hydrophobicity, thus strengthening their membrane association properties or aiding in protein interactions. Geranylgeranyltransferase-I (GGTase-I) is an enzyme involved in a 3-step post-translational modification (PTM) pathway that attaches a 20-carbon lipid group called geranylgeranyl at the carboxy-terminal cysteine of proteins ending in a canonical CaaL motif (C-cysteine, a-aliphatic, L-often leucine, but can be phenylalanine, isoleucine, methionine, or valine). Genetic approaches involving 2 distinct reporters were employed in this study to assess Saccharomyces cerevisiae GGTase-I specificity, for which limited data exist, toward all 8,000 CXXX combinations. Orthogonal biochemical analyses and structure-based alignments were also performed to better understand the features required for optimal target interaction. These approaches indicate that yeast GGTase-I best modifies the Cxa[L/F/I/M/V] sequence that resembles but is not an exact match for the canonical CaaL motif. We also observed that minor modification of noncanonical sequences is possible. A consistent feature associated with well-modified sequences was the presence of a nonpolar a2 residue and a hydrophobic terminal residue, which are features recognized by mammalian GGTase-I. These results thus support that mammalian and yeast GGTase-I exhibit considerable shared specificity.

Cardiac Computed Tomography Identification of the Septal Vein-A Small Retrospective Study.

BACKGROUND: The advancement of medical interventions towards minimally invasive procedures highlights the crucial role of precise pre-procedural evaluation, particularly in catheter-based treatments for heart and cardiovascular conditions. This study investigates innovative techniques such as mitral loop cerclage (MLC) and transcatheter intramyocardial radiofrequency ablation (TIRA), emphasizing the importance of preprocedural cardiac CT scans for accurate anatomical guidance in these emerging therapies. PURPOSE: The objective of this study was to assess the cardiac cycle through examination of the proximal septal vein (ps) for mitral loop cerclage and the distal septal vein (ds) for transcatheter intramyocardial radiofrequency ablation. MATERIALS AND METHODS: Forty patients (mean age 59.4 ± 14.7 years) undergoing third-generation dual-source computed tomography (DSCT) for chest pain evaluation were enrolled. CT scans, utilizing dual-energy CT (DECT) with iopamidol and saline, encompassed the carina to the heart base. A noise-optimized linear blended image was reconstructed at 10% intervals throughout the cardiac cycle, and the presence of ps and ds in each phase was noted by two radiologists. RESULTS: This study identified ps in 62.5% and ds in 72.5% of patients, with both present in 45% of cases. The observation of septal veins occurred more frequently in the sequence of 70, 60, 40, 80, 30, 20, and 10% for ps, and 60, 70, 40, 80, 30, 90, 20, and 10% for ds, respectively. CONCLUSIONS: DECT in cardiac imaging is instrumental in assessing septal vein frequency. The 70% phase is optimal for MLC, while the 60% phase is preferred for TIRA.

Dual model transfer learning to compensate for individual variability in brain-computer interface.

BACKGROUND AND OBJECTIVE: Recent advancements in brain-computer interface (BCI) technology have seen a significant shift towards incorporating complex decoding models such as deep neural networks (DNNs) to enhance performance. These models are particularly crucial for sophisticated tasks such as regression for decoding arbitrary movements. However, these BCI models trained and tested on individual data often face challenges with limited performance and generalizability across different subjects. This limitation is primarily due to a tremendous number of parameters of DNN models. Training complex models demands extensive datasets. Nevertheless, group data from many subjects may not produce sufficient decoding performance because of inherent variability in neural signals both across individuals and over time METHODS: To address these challenges, this study proposed a transfer learning approach that could effectively adapt to subject-specific variability in cortical regions. Our method involved training two separate movement decoding models: one on individual data and another on pooled group data. We then created a salience map for each cortical region from the individual model, which helped us identify the input's contribution variance across subjects. Based on the contribution variance, we combined individual and group models using a modified knowledge distillation framework. This approach allowed the group model to be universally applicable by assigning greater weights to input data, while the individual model was fine-tuned to focus on areas with significant individual variance RESULTS: Our combined model effectively encapsulated individual variability. We validated this approach with nine subjects performing arm-reaching tasks, with our method outperforming (mean correlation coefficient, r = 0.75) both individual (r = 0.70) and group models (r = 0.40) in decoding performance. In particular, there were notable improvements in cases where individual models showed low performances (e.g., r = 0.50 in the individual decoder to r = 0.61 in the proposed decoder) CONCLUSIONS: These results not only demonstrate the potential of our method for robust BCI, but also underscore its ability to generalize individual data for broader applicability.

Normal value of neuron-specific enolase for predicting good neurological outcomes in comatose out-of-hospital cardiac arrest survivors.

Research on prognostic factors for good outcomes in out-of-hospital cardiac arrest (OHCA) survivors is lacking. We assessed whether normal levels of normal neuron-specific enolase (NSE) value would be useful for predicting good neurological outcomes in comatose OHCA survivors treated with targeted temperature management (TTM). This registry-based observational study with consecutive adult (≥18 years) OHCA survivors with TTM who underwent NSE measurement 48 hours after cardiac arrest was conducted from October 2015 to November 2022. Normal NSE values defined as the upper limit of the normal range by the manufacturer (NSE <16.3 µg/L) and guideline-suggested (NSE < 60 µg/L) were examined for good neurologic outcomes, defined as Cerebral Performance Categories ≤2, at 6 months post-survival. Among 226 OHCA survivors with TTM, 200 patients who underwent NSE measurement were enrolled. The manufacturer-suggested normal NSE values (<16.3 µg/L) had a specificity of 99.17% for good neurological outcomes with a very low sensitivity of 12.66%. NSE <60 µg/L predicted good outcomes with a sensitivity of 87.34% and specificity of 72.73%. However, excluding 14 poor-outcome patients who died from multi-organ dysfunction excluding hypoxic brain injury, the sensitivity and specificity of normal NSE values were 12.66% and 99.07% of NSE < 16.3 µg/L, and 87.34% and 82.24% of NSE < 60 µg/L. The manufacturer-suggested normal NSE had high specificity with low sensitivity, but the guideline-suggested normal NSE value had a comparatively low specificity for good outcome prediction in OHCA survivors. Our data demonstrate normal NSE levels can be useful as a tool for multimodal appropriation of good outcome prediction.

Advanced age and neurological recovery in elderly patients with out-of-hospital cardiac arrest treated with targeted temperature management: a nationwide population­based registry study 2016-2020.

The likelihood of neurological recovery after out-of-hospital cardiac arrest (OHCA) may be influenced by advanced age. This study aims to evaluate the impact of advanced age on neurological recovery in elderly OHCA survivors treated with targeted temperature management (TTM). This retrospective observational study, using a nationwide population-based OHCA registry, was conducted from January 2016 to December 2020. Non-traumatic elderly (≥ 65 years) comatose OHCA survivors treated with TTM were categorized according to age (65-69, 70-74, 75-79, and ≥ 80 years). Among 23,336 admitted OHCA patients, 3,398 were treated with TTM. Excluding 2,033 non-elderly patients, 1,365 were analyzed. Among the four groups, the rate of good neurological outcomes decreased by advanced age (24.2%, 16.1%, 11.4%, and 5.9%, respectively), which was also observed after subgroup analysis based on the initial shockable (40.6%, 31.5%, 28.6%, and 14.9%, respectively) and non-shockable rhythm (10.6%, 7.2%, 4.1%, and 3.4%, respectively). Multivariate analysis showed the adjusted odds ratio (aOR) for good neurological outcome decreased as age increased (65-69: reference, 70-74: aOR 0.70, 75-79: aOR 0.49, and ≥ 80 years: aOR 0.25). The optimal age cutoffs for good outcomes in elderly OHCA survivors with shockable and non-shockable rhythm were 77 and 72 years, respectively. The neurologic recovery rate in OHCA survivors treated with TTM gradually decreased with increasing age. However, even patients aged ≥ 80 years with shockable rhythm had a good neurologic outcome of 14.9% compared with patients aged 65-69 years with non-shockable rhythm (10.6%).

Deep learning-assisted inverse design of nanoparticle-embedded radiative coolers.

Radiative cooling is an energy-efficient technology without consuming power. Depending on their use, radiative coolers (RCs) can be designed to be either solar-transparent or solar-opaque, which requires complex spectral characteristics. Our research introduces a novel deep learning-based inverse design methodology for creating thin-film type RCs. Our deep learning algorithm determines the optimal optical constants, material volume ratios, and particle size distributions for oxide/nitride nanoparticle-embedded polyethylene films. It achieves the desired optical properties for both types of RCs through Mie Scattering and effective medium theory. We also assess the optical and thermal performance of each RCs.

A Military Audio Dataset for Situational Awareness and Surveillance.

Audio classification related to military activities is a challenging task due to the high levels of background noise and the lack of suitable and publicly available datasets. To bridge this gap, this paper constructs and introduces a new military audio dataset, named MAD, which is suitable for training and evaluating audio classification systems. The proposed MAD dataset is extracted from various military videos and contains 8,075 sound samples from 7 classes corresponding to approximately 12 hours, exhibiting distinctive characteristics not presented in academic datasets typically used for machine learning research. We present a comprehensive description of the dataset, including its acoustic statistics and examples. We further conduct a comprehensive sound classification study of various deep learning algorithms on the MAD dataset. We are also releasing the source code to make it easy to build these systems. The presented dataset will be a valuable resource for evaluating the performance of existing algorithms and for advancing research in the field of acoustic-based hazardous situation surveillance systems.

Visual Mental Imagery and Neural Dynamics of Sensory Substitution in the Blindfolded Subjects.

Although one can recognize the environment by soundscape substituting vision to auditory signal, whether subjects could perceive the soundscape as visual or visual-like sensation has been questioned. In this study, we investigated hierarchical process to elucidate the recruitment mechanism of visual areas by soundscape stimuli in blindfolded subjects. Twenty-two healthy subjects were repeatedly trained to recognize soundscape stimuli converted by visual shape information of letters. An effective connectivity method called dynamic causal modeling (DCM) was employed to reveal how the brain was hierarchically organized to recognize soundscape stimuli. The visual mental imagery model generated cortical source signals of five regions of interest better than auditory bottom-up, cross-modal perception, and mixed models. Spectral couplings between brain areas in the visual mental imagery model were analyzed. While within-frequency coupling is apparent in bottom-up processing where sensory information is transmitted, cross-frequency coupling is prominent in top-down processing, corresponding to the expectation and interpretation of information. Sensory substitution in the brain of blindfolded subjects derived visual mental imagery by combining bottom-up and top-down processing.

Evaluating protein prenylation of human and viral CaaX sequences using a humanized yeast system.

Prenylated proteins are prevalent in eukaryotic biology (∼1-2% of proteins) and are associated with human disease, including cancer, premature aging and infections. Prenylated proteins with a C-terminal CaaX sequence are targeted by CaaX-type prenyltransferases and proteases. To aid investigations of these enzymes and their targets, we developed Saccharomyces cerevisiae strains that express these human enzymes instead of their yeast counterparts. These strains were developed in part to explore human prenyltransferase specificity because of findings that yeast FTase has expanded specificity for sequences deviating from the CaaX consensus (i.e. atypical sequence and length). The humanized yeast strains displayed robust prenyltransferase activity against CaaX sequences derived from human and pathogen proteins containing typical and atypical CaaX sequences. The system also recapitulated prenylation of heterologously expressed human proteins (i.e. HRas and DNAJA2). These results reveal that substrate specificity is conserved for yeast and human farnesyltransferases but is less conserved for type I geranylgeranyltransferases. These yeast systems can be easily adapted for investigating the prenylomes of other organisms and are valuable new tools for helping define the human prenylome, which includes physiologically important proteins for which the CaaX modification status is unknown.

Infant Behaviors, Prenatal Cocaine Exposure, and Adult Intelligence.

Importance: Linking prenatal drug exposures to both infant behavior and adult cognitive outcomes may improve early interventions. Objective: To assess whether neonatal physical, neurobehavioral, and infant cognitive measures mediate the association between prenatal cocaine exposure (PCE) and adult perceptual reasoning IQ. Design, Setting, and Participants: This study used data from a longitudinal, prospective birth cohort study with follow-up from 1994 to 2018 until offspring were 21 years post partum. A total of 384 (196 PCE and 188 not exposed to cocaine [NCE]) infants and mothers were screened for cocaine or polydrug use. Structural equation modeling was performed from June to November 2023. Exposures: Prenatal exposures to cocaine, alcohol, marijuana, and tobacco assessed through urine and meconium analyses and maternal self-report. Main Outcomes and Measures: Head circumference, neurobehavioral assessment, Bayley Scales of Infant Development, Fagan Test of Infant Intelligence score, Wechsler Perceptual Reasoning IQ, Home Observation for Measurement of the Environment (HOME) score, and blood lead level. Results: Among the 384 mothers in the study, the mean (SD) age at delivery was 27.7 (5.3) years (range, 18-41 years), 375 of 383 received public assistance (97.9%) and 336 were unmarried (87.5%). Birth head circumference (standardized estimate for specific path association, -0.05, SE = 0.02; P = .02) and 1-year Bayley Mental Development Index (MDI) (standardized estimate for total of the specific path association, -0.05, SE = 0.02; P = .03) mediated the association of PCE with Wechsler Perceptual Reasoning IQ, controlling for HOME score and other substance exposures. Abnormal results on the neurobehavioral assessment were associated with birth head circumference (ß = -0.20, SE = 0.08; P = .01). Bayley Psychomotor Index (ß = 0.39, SE = 0.05; P < .001) and Fagan Test of Infant Intelligence score (ß = 0.16, SE = 0.06; P = .01) at 6.5 months correlated with MDI at 12 months. Conclusions and Relevance: In this cohort study, a negative association of PCE with adult perceptual reasoning IQ was mediated by early physical and behavioral differences, after controlling for other drug and environmental factors. Development of infant behavioral assessments to identify sequelae of prenatal teratogens early in life may improve long-term outcomes and public health awareness.

Androgen Deprivation Therapy and Newly Developed Neovascular Age-Related Macular Degeneration Risk in Patients with Prostate Cancer.

Background/Objectives: to evaluate the association between androgen deprivation therapy (ADT) and newly developed neovascular age-related macular degeneration (AMD) in patients with prostate cancer. Methods: We identified 228,803 men from the nationwide claims database in the Republic of Korea diagnosed with prostate cancer between 1 August 2009 and 31 December 2018 and followed until April 2021. Cases were defined as those newly diagnosed with neovascular AMD during follow-up. Cases were matched with controls based on age, index date, and follow-up duration, at a case-to-control ratio of 1:4. Adjusted odds ratios (aORs) of incident neovascular AMD associated with ADT were estimated using conditional logistic regression. Results: The main analysis included 1700 cases and 6800 controls, with a median follow-up of 3.42 years. ADT was associated with a reduced risk of incident neovascular AMD in patients with prostate cancer (aOR = 0.840; 95% confidence interval [CI], 0.743-0.951; p = 0.0058) in the multivariable analysis. A cumulative ADT duration less than 1 year was associated with a reduced risk of neovascular AMD (aOR = 0.727; 95% CI, 0.610-0.866; p = 0.0004); however, no association was observed when the duration of ADT was between 1 and 2 years (aOR = 0.862; 95% CI, 0.693-1.074; p = 0.1854) or more than 2 years (aOR = 1.009; 95% CI, 0.830-1.226; p = 0.9304). Conclusions: In patients with prostate cancer, medical castration for less than a year is associated with a reduced risk of incident neovascular AMD. These results suggest that androgens are involved in the pathogenesis of neovascular AMD.

Prmt7 is required for the osteogenic differentiation of mesenchymal stem cells via modulation of BMP signaling.

Arginine methylation, which is catalyzed by protein arginine methyltransferases (Prmts), is known to play a key role in various biological processes. However, the function of Prmts in osteogenic differentiation of mesenchymal stem cells (MSCs) has not been clearly understood. In the current study, we attempted to elucidate a positive role of Prmt7 in osteogenic differentiation. Prmt7-depleted C3H/10T1/2 cells or bone marrow mesenchymal stem cells (BMSCs) showed the attenuated expression of osteogenic specific genes and Alizarin red staining compared to the wild-type cells. Furthermore, we found that Prmt7 deficiency reduced the activation of bone morphogenetic protein (BMP) signaling cascade, which is essential for the regulation of cell fate commitment and osteogenesis. Taken together, our data indicate that Prmt7 plays important regulatory roles in osteogenic differentiation. [BMB Reports 2024; 57(7): 330-335].

Long-acting cilostazol versus isosorbide mononitrate for patients with vasospastic angina: a randomized controlled trial.

BACKGROUND: Cilostazol has a vasodilatory function that may be beneficial for patients with vasospastic angina (VSA). We conducted a randomized, open-label, controlled trial to compare the efficacy and safety of long-acting cilostazol and isosorbide mononitrate (ISMN) for VSA. METHODS: The study included patients with confirmed VSA between September 2019 and May 2021. Participants were randomly assigned to receive long-acting cilostazol (test group, 200 mg once daily) or conventional ISMN therapy (control group, 20 mg twice daily) for 4 weeks. The clinical efficacy and safety were evaluated using weekly questionnaires. RESULTS: Forty patients were enrolled in the study (long-acting cilostazol, n  = 20; ISMN, n  = 20). Baseline characteristics were balanced between the two groups. Long acting cilostazol showed better angina symptom control within the first week compared to ISMN [reduction of pain intensity score, 6.0 (4.0-8.0) vs. 4.0 (1.0-5.0), P  = 0.005; frequency of angina symptom, 0 (0-2.0) vs. 2.0 (0-3.0), P  = 0.027, respectively]. The rate of neurological adverse reactions was lower in the cilostazol group than in the ISMN group (headache or dizziness, 40 vs. 85%, P  = 0.009; headache, 30 vs. 70%, P  = 0.027). CONCLUSION: Long-acting cilostazol provided comparable control of angina and fewer adverse neurologic reactions within 4 weeks compared to ISMN. Long-acting cilostazol provides more intensive control of angina within 1 week, suggesting that it may be an initial choice for the treatment of VSA.

Comprehensive analysis of CXXX sequence space reveals that S. cerevisiae GGTase-I mainly relies on a2X substrate determinants.

Many proteins undergo a post-translational lipid attachment, which increases their hydrophobicity, thus strengthening their membrane association properties or aiding in protein interactions. Geranylgeranyltransferase-I (GGTase-I) is an enzyme involved in a three-step post-translational modification (PTM) pathway that attaches a 20-carbon lipid group called geranylgeranyl at the carboxy-terminal cysteine of proteins ending in a canonical CaaL motif (C - cysteine, a - aliphatic, L - often leucine, but can be phenylalanine, isoleucine, methionine, or valine). Genetic approaches involving two distinct reporters were employed in this study to assess S. cerevisiae GGTase-I specificity, for which limited data exists, towards all 8000 CXXX combinations. Orthogonal biochemical analyses and structure-based alignments were also performed to better understand the features required for optimal target interaction. These approaches indicate that yeast GGTase-I best modifies the Cxa[L/F/I/M/V] sequence that resembles but is not an exact match for the canonical CaaL motif. We also observed that minor modification of non-canonical sequences is possible. A consistent feature associated with well-modified sequences was the presence of a non-polar a2 residue and a hydrophobic terminal residue, which are features recognized by mammalian GGTase-I. These results thus support that mammalian and yeast GGTase-I exhibit considerable shared specificity.