4D label-free proteomics analysis of oxygen-induced retinopathy with or without anti-VEGF treatment.

Oxygen-induced retinopathy (OIR) animal model is widely used for retinopathy of prematurity (ROP) researches. The purpose of this study was to identify proteins and related pathways of OIR with or without anti-vascular endothelial growth factor (VEGF) treatment, for use as biomarkers in diagnosing and treating ROP. Nine samples were subjected to proteomic analysis. Retina specimens were collected from 3 OIR mice, 3 OIR mice with anti-VEGF treatment and 3 normal mice (control group). Liquid chromatography-tandem mass spectrometry analysis was performed using the 4D label-free technique. Statistically significant differentially expressed proteins, gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representations, InterPro (IPR) and protein interactions were analyzed. In total, 4585 unique proteins were identified as differentially expressed proteins (DEPs). Enrichment analysis of the GO and KEGG indicated functional clusters related to peptide biosynthetic and metabolic process, cellular macromolecule biosynthetic process and nucleic acid binding in OIR group. For anti-VEGF treatment group, DEPs were clustered in DNA replication, PI3K/Akt signaling pathway and Jak/STAT signaling pathway. Proteomic profiling is useful for the exploration of molecular mechanisms of OIR and mechanisms of anti-VEGF treatment. These findings may be useful for identification of novel biomarkers for ROP pathogenesis and treatment.

Connectome-based prediction of decreased trust propensity in older adults with mild cognitive impairment: A resting-state functional magnetic resonance imaging study.

Trust propensity (TP) relies more on social than economic rationality to transform the perceived probability of betrayal into positive reciprocity expectations in older adults with normal cognition. While deficits in social rationality have been observed in older adults with mild cognitive impairment (MCI), there is limited research on TP and its associated resting-state functional connectivity (RSFC) mechanisms in this population. To measure TP and related psychological functions (affect, motivation, executive cognition, and social cognition), MCI (n = 42) and normal healthy control (NHC, n = 115) groups completed a one-shot trust game and additional assessments of related psychological functions. RSFC associated with TP was analyzed using connectome-based predictive modeling (CPM) and lesion simulations. Our behavioral results showed that the MCI group trusted less (i.e., had lower TP) than the NHC group, with lower TP associated with higher sensitivity to the probability of betrayal in the MCI group. In the MCI group, only negative CPM models (RSFC negatively correlated with TP) significantly predicted TP, with a high salience network (SN) contribution. In contrast, in the NHC group, positive CPM models (RSFC positively correlated with TP) significantly predicted TP, with a high contribution from the default mode network (DMN). In addition, the total network strength of the NHC-specific positive network was lower in the MCI group than in the NHC group. Our findings demonstrated a decrease in TP in the MCI group compared to the NHC group, which is associated with deficits in social rationality (social cognition, associated with DMN) and increased sensitivity to betrayal (affect, associated with SN) in a trust dilemma. In conclusion, our study contributes to understanding MCI-related alterations in trust and their underlying neural mechanisms.

Age-related intrinsic functional connectivity underlying emotion utilization.

Previous studies investigated the age-related positivity effect in terms of emotion perception and management, whereas little is known about whether the positivity effect is shown in emotion utilization (EU). If yes, the EU-related intrinsic functional connectivity and its age-associated alterations remain to be elucidated. In this study, we collected resting-state functional magnetic resonance imaging data from 62 healthy older adults and 72 undergraduates as well as their self-ratings of EU. By using the connectome-based predictive modeling (CPM) method, we constructed a predictive model of the positive relationship between EU self-ratings and resting-state functional connectivity. Lesion simulation analyses revealed that the medial-frontal network, default mode network, frontoparietal network, and subcortical regions played key roles in the EU-related CPM. Older subjects showed significantly higher EU self-ratings than undergraduates, which was associated with strengthened connectivity between the left dorsolateral prefrontal cortex and bilateral frontal poles, and between the left frontal pole and thalamus. A mediation analysis indicated that the age-related EU network mediated the age effect on EU self-ratings. Our findings extend previous research on the age-related "positivity effect" to the EU domain, suggesting that the positivity effect on the self-evaluation of EU is probably associated with emotion knowledge which accumulates with age.

Midfrontal theta phase underlies evidence accumulation and response thresholding in cognitive control.

Cognitive control involves evidence accumulation and response thresholding, but the neural underpinnings of these 2 processes are poorly understood. Based on recent findings that midfrontal theta phase coordinates the correlation between theta power and reaction time during cognitive control, this study investigated whether and how theta phase would modulate the relationships between theta power and evidence accumulation and response thresholding in human participants when they performed a flanker task. Our results confirmed the modulation of theta phase on the correlations between ongoing midfrontal theta power and reaction time under both conditions. Using hierarchical drift-diffusion regression modeling, we found that in both conditions, theta power was positively associated with boundary separation in phase bins with optimal power-reaction time correlations, whereas the power-boundary correlation decreased to nonsignificance in phase bins with reduced power-reaction time correlations. In contrast, the power-drift rate correlation was not modulated by theta phase, but by cognitive conflict. Drift rate was positively correlated with theta power for the bottom-up processing in the non-conflict condition, whereas it was negatively correlated with theta power for the top-down control to address conflict. These findings suggest that evidence accumulation is likely to be a phase-coordinated continuous process, whereas thresholding may be a phase-specific transient process.

Effects of engagement, persistence and adherence on cognitive training outcomes in older adults with and without cognitive impairment: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Limited understanding exists regarding the influences of engagement, persistence and adherence on the efficacy of cognitive training for age-related cognitive decline and neurodegenerative cognitive impairment. METHODS: This study conducted a meta-analysis of randomised controlled trials (RCTs). We systematically searched MEDLINE, PubMed, Web of Science, Embase and CINAHL databases from 1 January 2012 to 13 June 2023, and included RCTs assessing the effects of cognitive training in older adults, both with and without cognitive impairment. Hedges' g with a 95% confidence interval (CI) was used to synthesise cognitive training effect sizes on various neuropsychological tests. Subgroup analyses were conducted based on variables including engagement, persistence, adherence and cognitive conditions of normal cognition, mild cognitive impairment (MCI) or neurodegenerative dementia. RESULTS: This meta-analysis included 55 RCTs with 4,455 participants with cognitive conditions spanning normal cognition, MCI and neurodegenerative dementia. The mean age of participants was 73.9 (range: 65.7-84.5) years. Overall, cognitive training showed a significant cross-domain effect (Hedges' g = 0.286, 95% CI: 0.224-0.348). Training effects are significant when engagement or persistence rates exceed 60% or when adherence rates exceed 80%. Higher levels of persistence are required to achieve significant training effects in memory, visuospatial ability and reasoning than in executive function and attention and language. Higher persistence is also required for older adults with normal cognition to achieve significant training gains compared to those with cognitive impairment. CONCLUSIONS: This systematic review highlights the critical roles of engagement, persistence and adherence in augmenting the efficacy of cognitive training.

Quantitative optical coherence tomography angiography assessments in the fellow eyes of those with central serous chorioretinopathy.

BACKGROUND: To analyze the vessel density (VD) of the retina and choriocapillaris (CC) layer and the structure of the foveal avascular zone (FAZ) in the fellow eyes of central serous chorioretinopathy (CSC) patients by using optical coherence tomography angiography (OCTA). METHODS: This was a case-control study. Unilateral CSC patients and age-matched healthy subjects were recruited from the Affiliated Eye Hospital of Wenzhou Medical University between July 2016 and July 2021. All eyes were divided into three groups: acute CSC (aCSC), chronic CSC (cCSC), and healthy controls. Both aCSC and cCSC were again divided into two subgroups: the affected eyes and the fellow eyes. In this study, all parameters of VD and FAZ were measured by self-software of OCTA. RESULTS: A total of 231 eyes of 137 subjects were included, with 47 aCSC patients, 47 cCSC patients, and 43 healthy controls. In the fellow eyes of CSC, the retinal VD was significantly lower (all P < 0.05), and the FAZ was significantly larger (all P < 0.05) in the cCSC group than in healthy controls, while no difference was detected in the CC layer. There was no significant difference between the aCSC group and healthy controls in all OCTA parameters. In the affected eyes of CSC, the superficial retinal vessel density (SRVD) was significantly higher (all P < 0.05) in healthy controls than in the aCSC and cCSC groups, while the deep retinal vessel density (DRVD) was significantly lower (all P < 0.05) and the FAZ was larger (all P < 0.05) in the cCSC group than in the aCSC group and healthy controls. A liner regression equation was established: Y (BCVA, best corrected visual acuity) = 3.692-0.036✱X1 (DRVD-Fovea)-0.031✱X2 (FD-300, vessel density around the 300 µm width of the FAZ), R2 = 0.427. CONCLUSION: Based on OCTA measurements, this study revealed that the retinal microvascular network was impaired even in the fellow eyes of those with cCSC, which should arouse attention to the observation of unilateral CSC.

Improve the efficiency and accuracy of ophthalmologists' clinical decision-making based on AI technology.

BACKGROUND: As global aging intensifies, the prevalence of ocular fundus diseases continues to rise. In China, the tense doctor-patient ratio poses numerous challenges for the early diagnosis and treatment of ocular fundus diseases. To reduce the high risk of missed or misdiagnosed cases, avoid irreversible visual impairment for patients, and ensure good visual prognosis for patients with ocular fundus diseases, it is particularly important to enhance the growth and diagnostic capabilities of junior doctors. This study aims to leverage the value of electronic medical record data to developing a diagnostic intelligent decision support platform. This platform aims to assist junior doctors in diagnosing ocular fundus diseases quickly and accurately, expedite their professional growth, and prevent delays in patient treatment. An empirical evaluation will assess the platform's effectiveness in enhancing doctors' diagnostic efficiency and accuracy. METHODS: In this study, eight Chinese Named Entity Recognition (NER) models were compared, and the SoftLexicon-Glove-Word2vec model, achieving a high F1 score of 93.02%, was selected as the optimal recognition tool. This model was then used to extract key information from electronic medical records (EMRs) and generate feature variables based on diagnostic rule templates. Subsequently, an XGBoost algorithm was employed to construct an intelligent decision support platform for diagnosing ocular fundus diseases. The effectiveness of the platform in improving diagnostic efficiency and accuracy was evaluated through a controlled experiment comparing experienced and junior doctors. RESULTS: The use of the diagnostic intelligent decision support platform resulted in significant improvements in both diagnostic efficiency and accuracy for both experienced and junior doctors (P < 0.05). Notably, the gap in diagnostic speed and precision between junior doctors and experienced doctors narrowed considerably when the platform was used. Although the platform also provided some benefits to experienced doctors, the improvement was less pronounced compared to junior doctors. CONCLUSION: The diagnostic intelligent decision support platform established in this study, based on the XGBoost algorithm and NER, effectively enhances the diagnostic efficiency and accuracy of junior doctors in ocular fundus diseases. This has significant implications for optimizing clinical diagnosis and treatment.

HMOX1 as a therapeutic target associated with diabetic foot ulcers based on single-cell analysis and machine learning.

Diabetic foot ulcers (DFUs) are a serious chronic complication of diabetes mellitus and a leading cause of disability and death in diabetic patients. However, current treatments remain unsatisfactory. Although macrophages are associated with DFU, their exact role in this disease remains uncertain. This study sought to detect macrophage-related genes in DFU and identify possible therapeutic targets. Single-cell datasets (GSE223964) and RNA-seq datasets (GSM68183, GSE80178, GSE134431 and GSE147890) associated with DFU were retrieved from the gene expression omnibus (GEO) database for this study. Analysis of the provided single-cell data revealed the distribution of macrophage subpopulations in the DFU. Four independent RNA-seq datasets were merged into a single DFU cohort and further analysed using bioinformatics. This included differential expression (DEG) analysis, multiple machine learning algorithms to identify biomarkers and enrichment analysis. Finally, key results were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western bolt. Finally, the findings were validated using RT-qPCR and western blot. We obtained 802 macrophage-related genes in single-cell analysis. Differential expression analysis yielded 743 DEGs. Thirty-seven macrophage-associated DEGs were identified by cross-analysis of marker genes with macrophage-associated DEGs. Thirty-seven intersections were screened and cross-analysed using four machine learning algorithms. Finally, HMOX1 was identified as a potentially valuable biomarker. HMOX1 was significantly associated with biological pathways such as the insulin signalling pathway. The results showed that HMOX1 was significantly overexpressed in DFU samples. In conclusion, the analytical results of this study identified HMOX1 as a potentially valuable biomarker associated with macrophages in DFU. The results of our analysis improve our understanding of the mechanism of macrophage action in this disease and may be useful in developing targeted therapies for DFU.

Sirt1 Inhibits Atrial Fibrosis by Downregulating the Expression of the Transforming Growth Factor-ß1/Smad Pathway.

Background: Atrial fibrosis is an important factor leading to atrial fibrillation, and the transforming growth factor-ß1/Smad pathway is a key factor in inducing atrial fibrosis. Sirt1 is a member of the histone deacetylase (sirtuin) family, and recent studies have proven its cardioprotective effects. Objectives: This study explored the effect of Sirt1 on atrial fibrosis through the transforming growth factor-ß1/Smad pathway. Methods: We analyzed human right atrial appendage tissues and explored the relationship between Sirt1 and atrial fibrosis at the morphological, functional and molecular levels by Masson trichrome staining, immunofluorescence, real-time quantitative polymerase chain reaction and Western blot analysis. Rat atrial fibroblasts were extracted and treated by the Sirt1 agonist resveratrol, inhibitor sirtinol, and recombinant human transforming growth factor-ß1 protein. The expression levels of related proteins were detected by Western blot, and the effect on the migration of atrial fibroblasts was detected by wound healing assay. Results: We found that the expression of Sirt1 was reduced in the right atrial appendage tissues of patients with atrial fibrillation, and the degree of fibrosis was increased. In atrial fibroblasts, the activation of Sirt1 could inhibit the expression of transforming growth factor-ß1/Smad and reduce the development of fibrosis, while inhibiting Sirt1 reduced its inhibitory effect on the transforming growth factor-ß1/Smad pathway. Conclusions: These findings indicate that Sirt1 inhibits atrial fibrosis by downregulating the expression of the transforming growth factor-ß1/Smad pathway, and provide potential targets for the treatment of atrial fibrillation.

The connectome-based prediction of trust propensity in older adults: A resting-state functional magnetic resonance imaging study.

A recent neuropsychoeconomic model of trust propensity argues that an individual uses economic (executive functions) and social (social cognition) rationality strategies to transform the risk of treachery (affect) into positive expectations of reciprocity, promoting trust in another person. Previous studies have shown that the trust of older adults is associated with affect and social cognition. However, little is known about the intrinsic functional connectivity correlated with trust propensity or whether trust propensity is associated with executive functions in older adults. In this study, we examined the association between trust propensity (measured by a one-shot trust game [TG]), social preference (measured by a one-shot dictator game), and executive functions (measured by a battery of neuropsychological tests). We also performed connectome-based predictive modeling (CPM) and computational lesion analysis to identify the key large-scale resting-state functional connectivity (RSFC) underlying the prediction of trust propensity. Our behavioral results showed a lower trust propensity in older adults in our study than in younger adults in a previous meta-analysis. Furthermore, trust propensity was associated with social preference, but there was no significant relationship between trust propensity and executive functions. The neuroimaging results showed that the cingulo-opercular network (CON) and the default mode network (DMN), rather than the frontoparietal network (FPN), significantly contributed to the prediction of trust propensity in older adults. Our findings suggest that older adults rely less on economic rationality (executive functions, associated with FPN) in trust games. Rather, they are likely to depend more on social rationality (social cognition, associated with social preference and DMN) to resolve the risk of treachery (affect, associated with CON) in trust dilemmas. This study contributes to a better understanding of the neural underpinnings of older adults' trust propensity.

The impact of sarcopenia on the outcome of patients with left-sided colon and rectal cancer after curative surgery.

BACKGROUND: The impact of sarcopenia on the outcome of patients with left-sided colon and rectal cancer has not been exhaustively investigated. Thus, the present study was performed to evaluate the effect of sarcopenia on the outcome of patients with left-sided colon and rectal cancer. METHODS: Patients with pathologically diagnosed stage I, II and III left-sided colon or rectal cancer who had undergone curative surgery between January 2008 and December 2014 were retrospectively reviewed. The psoas muscle index (PMI) identified by 3D-image analysis of computed tomographic images was the criterion used to diagnose sarcopenia. The cut-off value recommended by Hamaguchi (PMI value < 6.36 cm2/m2 for men and < 3.92 cm2/m2 for women) was adopted to confirm the diagnosis of sarcopenia. According to the PMI, each patient was divided into the sarcopenia group (SG) or the nonsarcopenia group (NSG). Then, the SG was compared with the NSG in terms of postoperative outcomes. RESULTS: Among the 939 patients included, 574 (61.1%) were confirmed to have preoperative sarcopenia. Initially, it was demonstrated that the SG was not significantly different from the NSG in terms of most baseline characteristics except for a lower body mass index (BMI) (P < 0.001), a larger tumour size (P < 0.001) and more weight loss (more than 3 kg in the last three months) (P = 0.033). The SG had a longer hospital stay after surgery (P = 0.040), more intraoperative blood transfusions (P = 0.035), and higher incidence of anastomotic fistula (P = 0.027), surgical site infection (SSI) (P = 0.037) and hypoalbuminemia (P = 0.022), 30-day mortality (P = 0.042) and 90-day mortality (P = 0.041). The SG had significantly worse overall survival (OS) (P = 0.016) and recurrence-free survival (RFS) (P = 0.036) than the NSG. Subsequently, Cox regression analysis revealed that preoperative sarcopenia was an independent predictive factor for worse OS (P = 0.0211, HR = 1.367, 95% CI: 1.049-1.782) and RFS (P = 0.045, HR = 1.299, 95% CI: 1.006-1.677). CONCLUSION: Preoperative sarcopenia adversely affects the outcome of patients with left-sided colon and rectal cancer, and preoperative nutrition supplementation may help us improve their long-term and short-term outcomes.

EXCESSIVE GLIOSIS AFTER VITRECTOMY FOR THE HIGHLY MYOPIC MACULAR HOLE: A Spectral Domain Optical Coherence Tomography Study.

PURPOSE: To investigate different modes of foveal regeneration after the closure of idiopathic macular hole (IMH) or highly myopic macular hole (HMMH) by vitrectomy with internal limiting membranes peeling or flap techniques. METHODS: This retrospective observational study followed 47 IMH and 50 HMMH eyes for at least 6 months. Twenty four IMH and 25 HMMH eyes underwent internal limiting membrane peeling, whereas 23 IMH and 25 HMMH eyes received inverted internal limiting membrane flap technique. Spectral domain optical coherence tomography was used to analyze macular hole closure, foveal microstructures, and excessive gliosis as a foveal "peak-like" protuberance. RESULTS: A single procedure closed all IMH (n = 47). For HMMH, the inverted group (n = 25, 100%) closed more macular hole than the peeling group (n = 14, 56.00%) (P < 0.001). Excessive gliosis only occurred in the inverted group, and there was a significant difference (P = 0.005) in incidence between IMH (three in 23 eyes, 13.04%) and HMMH (13 in 25 eyes, 52.00%). The axial length more than 29.985 mm enhanced the risk of excessive gliosis. CONCLUSION: The inverted internal limiting membrane flap efficiently treated refractory MHs but was prone to cause excessive gliosis in highly myopic eyes. Excessive elongation of the globe (axial length > 29.985 mm) was linked to excessive gliosis growth.

Effect of Task-Oriented Biomechanical Perception-Balance Training on Motor Gait in Stroke Patients With Hemiplegia.

Objective: To investigate the effects of task-oriented biomechanical sensors-balance training on lower limb motor function and gait balance function in stroke patients with hemiplegia. Methods: Researchers divided 106 stroke patients with hemiplegia into observation and control groups. All received essential rehabilitation training treatment. The observation group's rehabilitation consisted of task-oriented biomechanical sensors-balance training. The modified Ashworth Scale score, FuGL-Meyer Motor Function Scale score, and other indicators measured the results of the two groups. Results: The Berg balance scale score and FuGL-Meyer Motor Function Scale score in the observation group were higher than in the control group (P < .05). The modified Ashworth Scale score of the triceps calf muscle in the observation group was significantly lower than that in the control group (P < .05). The observation group's step length, step frequency, maximum angle of hip extension, and knee flexion exceeded those of the control group. In contrast, the maximum angle of knee extension was smaller than those in the control group (P < .05). Conclusion: Basic rehabilitation training combined with task-oriented biomechanical perception-balance training can improve the lower limb motor function of stroke patients with hemiplegia.

Chewing Gum May Alleviate Degree of Thirst in Patients on Hemodialysis.

Background and Objectives: Fluid restriction commonly causes dry mouth in patients on hemodialysis (HD). The observed effects of chewing gum on the amount of saliva, interdialytic weight gain (IDWG), and degree of thirst in patients on HD have been inconsistent. We investigated whether chewing gum can modulate these three parameters in patients on HD. Materials and Methods: We used purposive sampling to enroll 37 patients on HD who were then randomly divided into the chewing gum group (n = 19) and the control (non-chewing gum) group (n = 18). The degree of thirst was assessed using a self-rated visual analog scale (VAS) and a summated xerostomia inventory (SXI), respectively. Results: The degree of thirst after dialysis was significantly lower in the chewing gum group than in the control group. The amount of saliva was higher in the chewing gum group than in the control group before dialysis, but the saliva amount was comparable between the groups after dialysis. Furthermore, the amount of saliva was not associated with IDWG in patients on HD before or after dialysis. Conclusions: Chewing gum may alleviate the feeling of thirst but may not affect the amount of saliva and IDWG in patients on HD. Therefore, we suggest that chewing gum may be a useful approach to improve dry mouth and thirst in patients on HD.

In situ Nucleation-Growth Strategy for Controllable Heterogeneous Supramolecular Polymerization of Liquid Crystalline Block Copolymers and Their Hierarchical Assembly.

The self-assembly morphologies of subunits are largely governed by thermodynamics, which plays a less important role in dimensional control. Particularly for one-dimensional assemblies from block copolymers (BCPs), the negligible energy difference between short and long ones imposes great challenges in length control. Herein, we report that by incorporating additional polymers to induce in situ nucleation and trigger the subsequent growth, controllable supramolecular polymerization driven by mesogenic ordering effect could be realized from liquid crystalline BCPs. The length of the resultant fibrillar supramolecular polymers (SP) is controlled by tuning the ratio between nucleating and growing components. Depending on the choice of BCPs, the SPs can be homopolymer-like, heterogeneous triblock, and even pentablock copolymer-like. More interestingly, with insoluble BCP as a nucleating component, amphiphilic SPs are fabricated, which can undergo spontaneous hierarchical assembly.

Packaged optofluidic microbottle resonator for high-sensitivity bidirectional magnetic field sensing.

We demonstrate a high-sensitivity bidirectional magnetic field sensor based on a packaged optofluidic microbottle resonator (OFMBR) filled with magnetic fluid (MF). The relationship between sensitivity and different wall thicknesses and radial modes of OFMBR is theoretically analyzed. Then the thin-wall OFMBR is fabricated by etching a capillary with the fusion discharge process. The OFMBR and tapered fiber is packaged with a portable and robust coupling configuration. By applying perpendicular or parallel magnetic field directions to the OFMBR, opposite refractive index responses of the MF can be obtained, with resonant wavelengths redshifted or blueshifted as the magnetic field intensity is increased. A magnetic field sensitivity of 98.23 pm/mT can be obtained by using the second-order radial mode when the magnetic field is perpendicular to the packaged OFMBR. When the magnetic field is parallel to the packaged OFMBR, the sensitivity is -304.80 pm/mT by using the third-order radial mode and the detection limit reaches 0.0656 mT. The proposed sensor has the advantages of easy fabrication, high sensitivity, and reliability, showing a great potential in bidirectional magnetic field application.

EFFICACY OF AIR TAMPONADE TREATMENT OF IDIOPATHIC MACULAR HOLES OF DIFFERENT DIAMETERS AND OF FOLLOW-UP INTRAVITREAL AIR TAMPONADE FOR PERSISTENT HOLES.

PURPOSE: To evaluate the efficacy of air tamponade in idiopathic macular hole (iMH) surgery and of an additional intravitreal air injection in the treatment of persistent holes. METHODS: Retrospective, observational case series. Sixty eyes of 60 patients with an iMH underwent phacoemulsification of cataract (when appropriate), pars plana vitrectomy, and internal limiting membrane peeling, followed by air tamponade. Eyes with persistent holes underwent an additional intravitreal air injection within 1 week after surgery. The iMH closure rate and the best-corrected visual acuity were evaluated. RESULTS: In all 30 eyes with an iMH diameter <400 µm, the iMH closed after the primary surgery; however, only 17 of 30 eyes with an iMH diameter of ≥400 µm closed after the primary surgery. For the 13 eyes with persistent holes, an additional intravitreal air injection resulted in successful hole closure. There was no significant difference in the best-corrected visual acuity at the final follow-up between the closed subgroup and the initially unclosed subgroup after closure. CONCLUSION: Pars plana vitrectomy combined with air tamponade effectively cured small iMHs. For large iMHs not closed after the primary surgery, an additional intravitreal air injection resulted in hole closure and achieved a good prognosis.

INTERNAL LIMITING MEMBRANE PEELING DISTORTS THE RETINAL LAYERS AND INDUCES SCOTOMA FORMATION IN THE PERIFOVEAL TEMPORAL MACULA.

PURPOSE: To determine whether internal limiting membrane peeling damages retinal function in patients with an idiopathic macular hole. METHODS: Retrospective case series. Forty-five eyes of 45 idiopathic macular hole patients who underwent vitrectomy with internal limiting membrane peeling with a minimum follow-up of 6 months. Each patient received a complete ophthalmological examination. The eyes were examined by microperimetry MP-3 in the central 20° visual field and optical coherence tomography angiography in the central 6 × 6 mm area. RESULTS: Six months after the surgery, macular hole closed in each patient. Retinal sensitivity decreased significantly in the perifoveal temporal ETDRS sector (from 24.97 ± 2.67-19.98 ± 5.68 dB, P = 0.001) but not in the other sectors. Six patients (13%) developed 24 scotomas, 62.5% presented in the perifoveal temporal sector. Anatomically, bumps in the outer nuclear layer were discovered concurrent with inner retinal dimples on B-scan images, predominantly (76.8%) in the perifoveal temporal sector, which have not been previously reported. The incidence of outer nuclear layer bumps was significantly higher in patients with scotomas than in those without (83% vs. 18%, P = 0.014). CONCLUSION: Internal limiting membrane peeling induced functional changes specifically in the perifoveal temporal macula. Distortion in the retinal layers is proposed to underly scotomas pathogenesis.

B2M gene expression shapes the immune landscape of lung adenocarcinoma and determines the response to immunotherapy.

Loss of the B2M gene is associated with tumour immune escape and resistance to immunotherapy. However, genetic alterations of the B2M gene are rare. We performed an integrative analysis of the mutational and transcriptional profiles of large cohorts of non-small-cell lung cancer (NSCLC) patients and found that epigenetic downregulation of B2M is common. B2M-low tumours exhibit a suppressive immune microenvironment characterized by reduced infiltration of immune cells of various lineages; in B2M-high tumours, more T and natural killer cells are present, but their activities are constrained by immune checkpoint molecules, indicating the diverse mechanisms of immune evasion. High levels of B2M mRNA, but not PD-L1, are correlated with an enhanced response to PD-1-based immunotherapy, suggesting its value for immunotherapy response prediction in solid tumours. Notably, a high tumour mutation burden (TMB) is associated with low B2M expression, which may explain the poor predictive value of the TMB in some situations. In syngeneic mouse models, genetic ablation of B2M in tumour cells causes resistance to PD-1-based immunotherapy, and B2M knockdown also diminishes the therapeutic efficacy. Moreover, forced expression of B2M in tumour models improves the response to immunotherapy, suggesting that B2M levels have significant impacts on treatment outcomes. Finally, we provide insight into the roles of transcription factors and KRAS mutations in B2M expression and the anticancer immune response. In conclusion, genetic and epigenetic regulation of B2M fundamentally shapes the NSCLC immune microenvironment and may determine the response to checkpoint blockade-based immunotherapy.

Beyond information rate, the capacity of cognitive control predicts response criteria in perceptual decision-making.

Recent studies indicate that higher capacity of cognitive control (CCC) represents higher processing efficiency (i.e., high accuracy with fast speed). However, the speed-accuracy tradeoff (SAT) exists ubiquitously in decision-making, and little is known about whether and how the CCC is associated with SAT and whether the CCC-SAT relationship would be affected by changes in information entropy. In this study, fifty-nine college students performed a majority function task in which accuracy and response speed were equally emphasized. A Bayesian-based hierarchical drift diffusion modeling method was used to estimate three parameters of boundary separation, drift rate, and nondecision time for each participant in this task. In addition, the CCC of each participant was estimated. The results showed that the CCC was positively correlated with the SAT represented by jointly increasing accuracy and reaction time (RT), which was modulated by the change in task-relevant information entropy. Multiple mediation analyses indicated that drift rate served as the key mediator in the positive CCC-accuracy relationship while boundary separation played the major mediating role in the positive CCC-RT relationship. These findings suggest that the CCC reflects not only the rate of information processing but also decision strategies for achieving current goals.