Quantifying the Relationship Between Unilateral Induced Metamorphopsia and Stereopsis Impairment.

Purpose: To investigate the relationship between unilateral metamorphopsia, characterized by visual distortions in one eye, and impaired stereopsis. Methods: Utilizing both near and distance measurements through advanced testing systems, including 4K smartphones and an active shutter three-dimensional system, we simulated varying degrees of unilateral metamorphopsia in 30 healthy young adults aged between 21 and 29 years. Two types of contour-based stereotest symbols, lines and squares, were developed. Distortions were classified into six distinct patterns, each further divided into eight grades of severity. Participants were tasked with identifying visual targets, and their stereothresholds were determined under different conditions of induced distortion. Stereopsis was measured within a range of 2.9 to 1.0 log arcsec, at 0.2 log arcsec intervals. Stereopsis changes under different distortion scenarios were analyzed using the generalized estimating equations, with a sequential Bonferroni adjustment applied for pairwise comparisons. Results: A direct and quantifiable correlation was observed between the severity of metamorphopsia and reductions in stereopsis. As the degree of visual distortion increased, notably in both frequency and amplitude, there was a corresponding decline in stereopsis. This relationship held true in both near and distance measurements of stereopsis. Statistical analyses further reinforced these findings, highlighting a significant detrimental effect of distortion components on stereoacuity. Conclusions: The findings highlight the clinical significance of understanding the interplay between unilateral metamorphopsia and stereopsis. Early interventions in conditions leading to metamorphopsia might be critical to maintaining optimal stereopsis.

Metal-Assisted Carbohydrate Assembly.

The sequence-controlled assembly of nucleic acids and amino acids into well-defined superstructures constitutes one of the most revolutionary technologies in modern science. The elaboration of such superstructures from carbohydrates, however, remains elusive and largely unexplored on account of their intrinsic constitutional and configurational complexity, not to mention their inherent conformational flexibility. Here, we report the bottom-up assembly of two classes of hierarchical superstructures that are formed from a highly flexible cyclo-oligosaccharide─namely, cyclofructan-6 (CF-6). The formation of coordinative bonds between the oxygen atoms of CF-6 and alkali metal cations (i) locks a myriad of flexible conformations of CF-6 into a few rigid conformations, (ii) bridges adjacent CF-6 ligands, and (iii) gives rise to the multiple-level assembly of three extended frameworks. The hierarchical superstructures present in these frameworks have been shown to modulate their nanomechanical properties. This research highlights the unique opportunities of constructing convoluted superstructures from carbohydrates and should encourage future endeavors in this underinvestigated field of science.

The influence of simulated visual impairment on distance stereopsis.

The intricate interrelationships between visual acuity (VA) and stereopsis depend on an array of factors, incorporating the nature of vision impairment, its manifestation (monocular versus binocular), and the classification of stereopsis test symbols used. The objectives of this study were to methodically dissect these multifaceted interactions by simulating a diverse range of vision loss conditions. Thirty medical students with normal vision were subjected to simulated vision loss through opacification and blurring methodologies. Stereopsis was assessed at a distance using both contour-based and random-dot-based symbols under equal binocular and varied monocular VA conditions. In this study, opacification consistently affected stereopsis more than blurring at equivalent VA reductions. However, this difference was absent in contour-based symbols under binocular vision impairment conditions. Significant differences in stereopsis emerged between monocular and binocular vision within the opacification contour-based groups. These differences were less evident in the opacification and blurring groups using random-dot-based patterns. In terms of symbols, the contour-based test demonstrated superior results to the random-dot-based test, particularly under decreased VA. In sum, the method of VA reduction and the choice of stereogram significantly impact distance stereopsis outcomes. This understanding can guide clinical assessments of stereopsis in individuals with varying visual impairments.

A comparative study of stereopsis measurements: analyzing natural conditions versus dichoptic presentation using smartphones and ultraviolet printer technology.

Background: Accurate differentiation between stereopsis assessments in the natural and dichoptic presentation states has proven challenging with commercial stereopsis measurement tools. This study proposes a novel method to delineate these differences more precisely. Methods: We instituted two stereopsis test systems predicated on a pair of 4K smartphones and a modified Frisby Near Stereotest (FNS) version. Stereoacuity was evaluated both in the natural environment state (via the modified FNS) and the dichoptic state (via smartphones). Thirty subjects aged 20 to 28 years participated in the study with the best-corrected visual acuity (VA) of each eye no less than 0 logMAR and stereoauity of no worse than 40″. Varying degrees of monocular VA loss were induced using the fogging method, while this study does not explore conditions where the VA of both eyes is worse than 0 logMAR. Results: When the VA difference between the two eyes did not exceed 0.2 logMAR, the modified FNS produced lower stereoacuity values compared to the 4K smartphones (Wilcoxon signed-rank test: difference = 0 logMAR, Z = -3.879, P < 0.001; difference = 0.1 logMAR, Z = -3.478, P = 0.001; difference = 0.2 logMAR, Z = -3.977, P < 0.001). Conversely, no significant differences were observed when the binocular vision difference exceeded 0.2 logMAR (difference = 0.3 logMAR, Z = -1.880, P = 0.060; difference = 0.4 logMAR, Z = -1.784, P = 0.074; difference = 0.5 logMAR, Z = -1.812, P = 0.070). Conclusion: The findings suggest that stereoacuity values measurements taken in the natural environment state surpass those derived from the dichoptic presentation. However, the observed difference diminishes as stereopsis decreases, corresponding to an increase in induced anisometropia.

Cell death of alveolar lymphocytes and monocytes is negatively correlated with driving pressure and mechanical power in patients with acute respiratory distress syndrome.

BACKGROUND: Pathogenesis of acute respiratory distress syndrome (ARDS) involves immune cell death and removal from the injured lungs. ARDS severity is related to lung compliance. However, the correlation between the respiratory mechanics and alveolar immune cell death in patients with ARDS remains unclear. METHODS: Twenty-four patients with respiratory failure and ARDS were enrolled in the intensive care unit between November 2019 and November 2021. Neutrophil extracellular traps (NETs) and cell death of lymphocytes and monocytes in bronchoalveolar lavage fluid were detected on days 1 and 8. RESULTS: Lung compliance was positively correlated with the cell death percentage of alveolar CD4/CD8 lymphocytes and monocytes on day 8 (Pearson's correlation coefficient (r) = 0.554, p = 0.005; r = 0.422, p = 0.040; r = 0.569, p = 0.004, respectively). There was no association between lung compliance and the percentage of alveolar NETs on days 1 and 8. The cell death percentages of alveolar CD4/CD8 lymphocytes and monocytes were negatively correlated with driving pressure (DP) on days 1 (r = - 0.440, p = 0.032; r = - 0.613, p = 0.001; r = -0.557, p = 0.005, respectively) and 8 (r = - 0.459, p = 0.024; r = - 0.407, p = 0.048; r = - 0.607, p = 0.002, respectively). The cell death percentages of alveolar CD4/CD8 lymphocytes and monocytes were also negatively correlated with mechanical power (MP) on days 1 (r = - 0.558, p = 0.005; r = - 0.593, p = 0.002; r = - 0.571, p = 0.004, respectively) and 8 (r = - 0.539, p = 0.007; r = - 0.338, p = 0.107; r = - 0.649, p < 0.001, respectively). The percentage of alveolar NETs on days 1 and 8 was not associated with DP or MP. CONCLUSION: Patients with higher cell death rates of alveolar CD4/CD8 lymphocytes and monocytes exhibited lower DP and MP. Patients with less cell death of alveolar CD4/CD8 lymphocytes and monocytes required more DP or MP to maintain adequate ventilation.

Comparison of stereopsis thresholds measured with conventional methods and a new eye tracking method.

PURPOSE: Stereopsis is the ability to perceive depth using the slightly different views from two eyes. This study aims to conduct innovative stereopsis tests using the objective data outputted by eye tracking technology. METHODS: A laptop and an eye tracker were used to establish the test system. Anaglyphic glasses were employed to execute the stereopsis assessment. The test symbol employed was devised to emulate the quantitative measurement component of the Random Dot 3 Stereo Acuity Test. Sub-pixel technology was used to increase the disparity accuracy of test pages. The tested disparities were: 160″, 100″, 63″, 50″, 40″, 32″, 25″, 20″, 16″, and 12.5″. The test was conducted at a distance of 0.65m. Conventional and eye tracking stereopsis assessments were conducted on 120 subjects. Wilcoxon signed-rank test was used to test the difference, while the Bland-Altman method was used to test the consistency between the two methods. RESULTS: The Wilcoxon signed-rank test showed no significant difference between conventional and eye tracking thresholds of stereopsis (Z = -1.497, P = 0.134). There was a high level of agreement between the two methods using Bland- Altman statistical analysis (The 95 per cent limits of agreement were -0.40 to 0.47 log arcsec). CONCLUSIONS: Stereoacuity can be evaluated utilizing an innovative stereopsis measurement system grounded in eye tracking technology.

Spin-Frustrated Trisradical Trication of PrismCage.

Organic trisradicals featuring threefold symmetry have attracted significant interest because of their unique magnetic properties associated with spin frustration. Herein, we describe the synthesis and characterization of a triangular prism-shaped organic cage for which we have coined the name PrismCage6+ and its trisradical trication─TR3(•+). PrismCage6+ is composed of three 4,4'-bipyridinium dications and two 1,3,5-phenylene units bridged by six methylene groups. In the solid state, PrismCage6+ adopts a highly twisted conformation with close to C3 symmetry as a result of encapsulating one PF6- anion as a guest. PrismCage6+ undergoes stepwise reduction to its mono-, di-, and trisradical cations in MeCN on account of strong electronic communication between its 4,4'-bipyridinium units. TR3(•+), which is obtained by the reduction of PrismCage6+ employing CoCp2, adopts a triangular prism-shaped conformation with close to C2v symmetry in the solid state. Temperature-dependent continuous-wave and nutation-frequency-selective electron paramagnetic resonance spectra of TR3(•+) in frozen N,N-dimethylformamide indicate its doublet ground state. The doublet-quartet energy gap of TR3(•+) is estimated to be -0.08 kcal mol-1, and the critical temperature of spin-state conversion is found to be ca. 50 K, suggesting that it displays pronounced spin frustration at the molecular level. To the best of our knowledge, this example is the first organic radical cage to exhibit spin frustration. The trisradical trication of PrismCage6+ opens up new possibilities for fundamental investigations and potential applications in the fields of both organic cages and spin chemistry.

A Novel Deoxyribonuclease Low-Molecular-Weight Bacteriocin, Carocin S4, from Pectobacterium carotovorum subsp. carotovorum.

Pectobacterium carotovorum subsp. carotovorum (Pcc) is known to produce different types of bacteriocins, active protein substances that inhibit or kill related strains and are known to be induced by several factors. In this paper, we report the discovery, isolation, characterization, and functional analysis of Carocin S4, a novel low-molecular-weight bacteriocin (LMWB) from Pcc. A 2750 bp gene fragment was isolated from the chromosomal DNA of Pcc mutant strain rif-TO6, a rifampicin-resistant strain of TO6. The gene contains caroS4K and caroS4I within two open reading frames, which encode CaroS4K and CaroS4I, with molecular weights of about 90 kD and 10 kD, respectively. The unique characteristics of Carocin S4 were revealed after homology analysis with the previously discovered bacteriocins from Pcc. CaroS4K, which shares 23% and 85% homology with CaroS1K and CaroS3K, respectively, is also a deoxyribonuclease. However, unlike the two which can only hydrolyze genomic DNA, CaroS4K hydrolyzes both genomic and plasmid DNA. On the other hand, CaroS4K was found to be 90% homologous with CaroS2K but works differently in killing the target cell, as the latter is a ribonuclease. The optimal reaction temperature for CaroS4K to hydrolyze dsDNA is approximately 50 °C and requires the divalent metal ions Mg2+, Ca2+, and Zn2+ to catalyze its DNase activity. This study reveals another nuclease type of bacteriocin in Pcc, with CaroS4K and CaroS4I functioning as killer and immunity proteins, respectively.

Using sno-lncRNAs as potential markers for Prader-Willi syndrome diagnosis.

The genetic disorder Prader-Willi syndrome (PWS) is mainly caused by the loss of multiple paternally expressed genes in chromosome 15q11-q13 (the PWS region). Early diagnosis of PWS is essential for timely treatment, leading to effectively easing some clinical symptoms. Molecular approaches for PWS diagnosis at the DNA level are available, but the diagnosis of PWS at the RNA level has been limited. Here, we show that a cluster of paternally transcribed snoRNA-ended long noncoding RNAs (sno-lncRNAs, sno-lncRNA1-5) derived from the SNORD116 locus in the PWS region can serve as diagnostic markers. In particular, quantification analysis has revealed that 6,000 copies of sno-lncRNA3 are present in 1 µL whole blood samples from non-PWS individuals. sno-lncRNA3 is absent in all examined whole blood samples of 8 PWS individuals compared to 42 non-PWS individuals and dried blood samples of 35 PWS individuals compared to 24 non-PWS individuals. Further developing a new CRISPR-MhdCas13c system for RNA detection with a sensitivity of 10 molecules per µL has ensured sno-lncRNA3 detection in non-PWS, but not PWS individuals. Together, we suggest that the absence of sno-lncRNA3 represents a potential marker for PWS diagnosis that can be detected by both RT-qPCR and CRISPR-MhdCas13c systems with only microlitre amount of blood samples. Such an RNA-based sensitive and convenient approach may facilitate the early detection of PWS.

Macrocycle Self-Assembly Hydrogel for High-Efficient Oil-Water Separation.

Supramolecular hydrogels involved macrocycles have been explored widely in recent years, but it remains challenging to develop hydrogel based on solitary macrocycle with super gelation capability. Here, the construction of lantern[33 ]arene-based hydrogel with low critical gelation concentration (0.05 wt%), which can be used for efficient oil-water separation, is reported. The lantern[33 ]arenes self-assemble into hydrogen-bonded organic nanoribbons, which intertwine into entangled fibers to form hydrogel. This hydrogel which exhibits reversible pH-responsiveness characteristics can be coated on stainless-steel mesh by in situ sol-gel transformation. The resultant mesh exhibits excellent oil-water separation efficiency (>99%) and flux (>6 × 104 L m-2 h-1 ). This lantern[33 ]arene-based hydrogel not only sheds additional light on the gelation mechanisms for supramolecular hydrogels, but also extends the application of macrocycle-based hydrogels as functional interfacial materials.

Role of Changes in Driving Pressure and Mechanical Power in Predicting Mortality in Patients with Acute Respiratory Distress Syndrome.

Driving pressure (ΔP) and mechanical power (MP) are associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). We aimed to investigate which was better to predict mortality between changes in ΔP and MP. We reanalyzed data from a prospective observational cohort study of patients with ARDS in our hospital. Serial ΔP and MP values were calculated. The factors associated with survival were analyzed. Binary logistic regression showed that age (odds ratio (OR), 1.012; 95% confidence interval (CI), 1.003-1.022), Sequential Organ Failure assessment (SOFA) score (OR, 1.144; 95% CI, 1.086-1.206), trauma (OR, 0.172; 95% CI, 0.035-0.838), ΔP (OR, 1.077; 95% CI, 1.044-1.111), change in ΔP (OR, 1.087; 95% CI, 1.054-1.120), and change in MP (OR, 1.018; 95% CI, 1.006-1.029) were independently associated with 30-day mortality. Change in MP, change in ΔP, and SOFA scores were superior to ΔP in terms of the accuracy of predicting 30-day mortality. In conclusion, calculating change in ΔP is easy for respiratory therapists in clinical practice and may be used to predict mortality in patients with ARDS.

Attenuation of Ventilation-Enhanced Epithelial-Mesenchymal Transition through the Phosphoinositide 3-Kinase-γ in a Murine Bleomycin-Induced Acute Lung Injury Model.

Mechanical ventilation (MV) used in patients with acute lung injury (ALI) induces lung inflammation and causes fibroblast proliferation and excessive collagen deposition-a process termed epithelial-mesenchymal transition (EMT). Phosphoinositide 3-kinase-γ (PI3K-γ) is crucial in modulating EMT during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, EMT, and PI3K-γ remain unclear. We hypothesized that MV with or without bleomycin treatment would increase EMT through the PI3K-γ pathway. C57BL/6 mice, either wild-type or PI3K-γ-deficient, were exposed to 6 or 30 mL/kg MV for 5 h after receiving 5 mg/kg AS605240 intraperitoneally 5 days after bleomycin administration. We found that, after bleomycin exposure in wild-type mice, high-tidal-volume MV induced substantial increases in inflammatory cytokine production, oxidative loads, Masson's trichrome staining level, positive staining of α-smooth muscle actin, PI3K-γ expression, and bronchial epithelial apoptosis (p < 0.05). Decreased respiratory function, antioxidants, and staining of the epithelial marker Zonula occludens-1 were also observed (p < 0.05). MV-augmented bleomycin-induced pulmonary fibrogenesis and epithelial apoptosis were attenuated in PI3K-γ-deficient mice, and we found pharmacological inhibition of PI3K-γ activity through AS605240 (p < 0.05). Our data suggest that MV augmented EMT after bleomycin-induced ALI, partially through the PI3K-γ pathway. Therapy targeting PI3K-γ may ameliorate MV-associated EMT.

The effect of color vision resolution on intra-oral shade-selection accuracy.

BACKGROUND: Dentists must be able to identify subtle color changes as shade-matching is crucial in aesthetic dentistry. OBJECTIVE: To determine whether color discrimination ability is related to shade-matching accuracy among dentists. METHODS: The sensitivity of the normal-color vision population to different colors was investigated using Farnsworth Munsell 100 Hue (FM-100) test results. The FM-100 test was administered to 37 dentists at the Hospital of Stomatology, Jilin University. Sensitivity of dentists with normal-color vision to different colors was investigated using the FM-100 test. Participants were instructed to arrange color caps of various colors according to the gradual change in colors and the results were scored. Visual shade matching test using Vita 3D-MASTER shade guide was performed to determine shade-matching accuracy. The relationship between color discrimination ability and shade-matching accuracy was analyzed. The number of misplaced color caps in the FM-100 test was also calculated. RESULTS: The FM-100 test revealed that 16 and 21 participants had excellent and average color discrimination ability, respectively, and their shade-matching accuracies were 68.75% and 66.67%, respectively. No significant difference was observed in the shade-matching accuracy between the two groups. No significant correlation was observed between the color discrimination ability and shade-matching accuracy. In addition, the number of wrong color caps on the 43-63 color tray with the transition from blue-green to blue-purple was the highest according to Friedman's test. CONCLUSION: Color discrimination ability of dentists does not affect their visual shade-matching accuracy. Additionally, people with normal color vision are not sensitive to the transition from blue-green to blue-purple.

African Swine Fever Virus Cysteine Protease pS273R Inhibits Type I Interferon Signaling by Mediating STAT2 Degradation.

African swine fever virus (ASFV) is a large DNA virus that causes African swine fever (ASF), an acute and hemorrhagic disease in pigs with lethality rates of up to 100%. To date, how ASFV efficiently suppress the innate immune response remains enigmatic. In this study, we identified ASFV cysteine protease pS273R as an antagonist of type I interferon (IFN). Overexpression of pS273R inhibited JAK-STAT signaling triggered by type I IFNs. Mechanistically, pS273R interacted with STAT2 and recruited the E3 ubiquitin ligase DCST1, resulting in K48-linked polyubiquitination at K55 of STAT2 and subsequent proteasome-dependent degradation of STAT2. Furthermore, such a function of pS273R in JAK-STAT signaling is not dependent on its protease activity. These findings suggest that ASFV pS273R is important to evade host innate immunity. IMPORTANCE ASF is an acute disease in domestic pigs caused by infection with ASFV. ASF has become a global threat with devastating economic and ecological consequences. To date, there are no commercially available, safe, and efficacious vaccines to prevent ASFV infection. ASFV has evolved a series of strategies to evade host immune responses, facilitating its replication and transmission. Therefore, understanding the immune evasion mechanism of ASFV is helpful for the development of prevention and control measures for ASF. Here, we identified ASFV cysteine protease pS273R as an antagonist of type I IFNs. ASFV pS273R interacted with STAT2 and mediated degradation of STAT2, a transcription factor downstream of type I IFNs that is responsible for induction of various IFN-stimulated genes. pS273R recruited the E3 ubiquitin ligase DCST1 to enhance K48-linked polyubiquitination of STAT2 at K55 in a manner independent of its protease activity. These findings suggest that pS273R is important for ASFV to escape host innate immunity, which sheds new light on the mechanisms of ASFV immune evasion.

High-efficiency gold recovery by additive-induced supramolecular polymerization of ß-cyclodextrin.

Developing an eco-friendly, efficient, and highly selective gold-recovery technology is urgently needed in order to maintain sustainable environments and improve the utilization of resources. Here we report an additive-induced gold recovery paradigm based on precisely controlling the reciprocal transformation and instantaneous assembly of the second-sphere coordinated adducts formed between ß-cyclodextrin and tetrabromoaurate anions. The additives initiate a rapid assembly process by co-occupying the binding cavity of ß-cyclodextrin along with the tetrabromoaurate anions, leading to the formation of supramolecular polymers that precipitate from aqueous solutions as cocrystals. The efficiency of gold recovery reaches 99.8% when dibutyl carbitol is deployed as the additive. This cocrystallization is highly selective for square-planar tetrabromoaurate anions. In a laboratory-scale gold-recovery protocol, over 94% of gold in electronic waste was recovered at gold concentrations as low as 9.3 ppm. This simple protocol constitutes a promising paradigm for the sustainable recovery of gold, featuring reduced energy consumption, low cost inputs, and the avoidance of environmental pollution.

Correlative increasing expressions of KIF5b and Nav1.7 in DRG neurons of rats under neuropathic pain conditions.

Nav1.7, one of tetrodotoxin-sensitive voltage-gated sodium channels, mainly expressed in the small diameter dorsal root ganglion (DRG) neurons. The expression and accumulation on neuronal membrane of Nav1.7 increased following peripheral tissue inflammation or nerve injury. However, the mechanisms for membrane accumulation of Nav1.7 remained unclear. We report that KIF5b, a highly expressed member of the kinesin-1 family in DRGs, promoted the translocation of Nav1.7 to the plasma membrane in DRG neurons of the rat. Following nociceptive behaviors in rats induced by peripheral spared nerve injury (SNI), synchronously increased KIF5b and Nav1.7 expressions were observed in DRGs. Immunohistochemistry staining demonstrated the co-expressions of KIF5b and Nav1.7 in the same DRG neurons. Immunoprecipitation experiments further confirmed the interactions between KIF5b and Nav1.7. Moreover, intrathecal injections of KIF5b shRNA moderated the SNI-induced both mechanical and thermal hyperalgesia. The rescued analgesic effects also alleviated SNI-induced anxiety-like behaviors. In sum, KIF5b was required for the membrane localizations of Nav1.7, which suggests a novel mechanism for the trafficking of Nav1.7 involved in neuropathic pain.

Evaluating the relationship between induced aniseikonia and distance stereopsis.

Background: The impact of aniseikonia on stereopsis has been studied for decades, however, inconsistency which may be partly attributed to the method of inducing aniseikonia exists among these findings. This study aimed to induce overall and meridional aniseikonia using a three-dimensional (3D) computer and then evaluate the effect of induced aniseikonia on distance stereopsis using contour-based and random-dot-based patterns. Methods: A 3D laptop was used to produce all of the test symbols. Unlike the usual method of creating aniseikonia with size lenses, which would change not only the size but also the relative position of the test symbols in the two images as seen by the two eyes, a new test system was designed to evaluate the aniseikonia, which only modified the size while maintaining the relative position of the test symbols. This new method reduced the disparities induced by location changing of the paired test targets when inducing aniseikonia. Aniseikonia was induced overall or in one of the meridians. The induced meridional aniseikonia included 180°, 30°, 45°, 60°, and 90°, respectively. The range of induced aniseikonia was 0-30% with an increment of 5%. Results: Overall magnification affected stereopsis more than magnification in any one of the meridians. The stereoacuity differences between oblique meridians (30°, 45°, and 60°) were not significant until the aniseikonia increased up to 20%. The difference between 180°, 45°, and 90° was significant when the aniseikonia increased up to 10% in the contour-based test and over 20% in the random-dot-based test. The stereoacuity trend was improved gradually, coupled with the angle changing from 180º to 90º in the contour-based pattern, and deteriorated gradually in the random-dot-based pattern. Conclusions: Overall aniseikonia affected stereopsis more than meridional aniseikonia. The stereoacuity of the contour-based pattern was superior to that of the random-dot-based pattern in the 90° meridian, while the opposite result was obtained in the 180° meridian.

Combining Phenylalanine and Leucine Levels Predicts 30-Day Mortality in Critically Ill Patients Better than Traditional Risk Factors with Multicenter Validation.

In critically ill patients, risk scores are used; however, they do not provide information for nutritional intervention. This study combined the levels of phenylalanine and leucine amino acids (PLA) to improve 30-day mortality prediction in intensive care unit (ICU) patients and to see whether PLA could help interpret the nutritional phases of critical illness. We recruited 676 patients with APACHE II scores ≥ 15 or intubated due to respiratory failure in ICUs, including 537 and 139 patients in the initiation and validation (multicenter) cohorts, respectively. In the initiation cohort, phenylalanine ≥ 88.5 µM (indicating metabolic disturbance) and leucine < 68.9 µM (indicating malnutrition) were associated with higher mortality rate. Based on different levels of phenylalanine and leucine, we developed PLA scores. In different models of multivariable analyses, PLA scores predicted 30-day mortality independent of traditional risk scores (p < 0.001). PLA scores were then classified into low, intermediate, high, and very-high risk categories with observed mortality rates of 9.0%, 23.8%, 45.6%, and 81.8%, respectively. These findings were validated in the multicenter cohort. PLA scores predicted 30-day mortality better than APACHE II and NUTRIC scores and provide a basis for future studies to determine whether PLA-guided nutritional intervention improves the outcomes of patients in ICUs.