Unraveling Halogen Role in Two-Step Solution Growth of Organic-Inorganic Hybrid Mixed-Halide Perovskites: Guidelines of Fabricating Single-Phase Perovskites with Predictable Stoichiometry.

The challenge faced in optoelectronic applications of halide perovskites is their degradation. Minimizing material imperfections is critical to averting cascade degradation processes. Identifying causes of such imperfections is, however, hindered by mystified growth processes and is particularly urgent for mixed-halide perovskites because of inhomogeneity in growth and phase segregation under stresses. To unravel two-step solution growth of MAPbBr x I3-x , we monitored the evolution of Br composition and found that the construction of perovskite lattice is contributed by iodine from PbI2 substrate and Br from MABr solution with a 1:1 ratio rather than a 2:1 ratio originally thought. Kinetic analysis based on a derived three-stage model extracted activation energies of perovskite construction and anion exchange. This model is applicable to the growth of PbI2 reacting with a mixed solution of MABr and MAI. Two guidelines of fabricating single-phase MAPbBr x I3-x with predictable stoichiometry thus developed help strategizing protocols to reproducibly fabricate mixed-halide perovskite films tailored to specific optoelectronic applications.

Explanatory Role of Conversion Surgery as a Mediator of the Mortality Risk Difference Between Patients With Unresectable Metastatic Colorectal Cancer Treated With First-Line Anti-EGFR Agents Versus Bevacizumab.

INTRODUCTION: Bevacizumab and antiepidermal growth factor receptor-blocking (anti-EGFR) agents plus chemotherapy are first-line therapies for metastatic colorectal cancer (mCRC). Conversion surgery may improve outcomes; however, the extent to which it explains the difference in mortality rates among treatments is unclear. Herein, we aimed to assess the effects of conversion surgery on survival outcomes of patients with unresectable mCRC treated with bevacizumab and anti-EGFR agents. MATERIALS AND METHODS: This retrospective cohort study included patients with mCRC treated with bevacizumab and anti-EGFR agents as first-line therapy. We estimated the direct and indirect effects of treatments by comparing the mortality risk associated with targeted therapy type. Hazard ratios (HR) and the corresponding confidence intervals (CI) were estimated. Mediation analysis was used to estimate hazard ratio differences, and the proportion mediated. RESULTS: A total of 5,106 patients were included. The natural indirect effect of conversion surgery reduced mortality risk (HR: 0.95; 95% CI, 0.93-0.97), with a mediated proportion of 42% after propensity score adjustment. In subgroup analyses, KRAS wild-type (HR: 0.94; 95% CI: 0.91-0.97), left tumor sidedness (HR: 0.94; 95% CI, 0.91-0.96), and liver resection (HR: 0.95; 95% CI, 0.93-0.98) were associated with reduced risks of mortality. The controlled and total direct effects of targeted therapy were associated with reduced mortality risk in the anti-EGFR-treated group compared to those in the bevacizumab-treated group; however, this effect was not statistically significant. CONCLUSION: Conversion surgery may account for the difference in survival outcomes between users of the anti-EGFR agents and bevacizumab.

Selective depletion of tumor-infiltrating regulatory T cells with BAY 3375968, a novel Fc-optimized anti-CCR8 antibody.

Regulatory T cells (Tregs) are known to facilitate tumor progression by suppressing CD8+ T cells within the tumor microenvironment (TME), thereby also hampering the effectiveness of immune checkpoint inhibitors (ICIs). While systemic depletion of Tregs can enhance antitumor immunity, it also triggers undesirable autoimmune responses. Therefore, there is a need for therapeutic agents that selectively target Tregs within the TME without affecting systemic Tregs. In this study, as shown also by others, the chemokine (C-C motif) receptor 8 (CCR8) was found to be predominantly expressed on Tregs within the TME of both humans and mice, representing a unique target for selective depletion of tumor-residing Tregs. Based on this, we developed BAY 3375968, a novel anti-human CCR8 antibody, along with respective surrogate anti-mouse CCR8 antibodies, and demonstrated their in vitro mode-of-action through induction of potent antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) activities. In vivo, anti-mouse CCR8 antibodies effectively depleted Tregs within the TME primarily via ADCP, leading to increased CD8+ T cell infiltration and subsequent tumor growth inhibition across various cancer models. This monotherapeutic efficacy was significantly enhanced in combination with ICIs. Collectively, these findings suggest that CCR8 targeting represents a promising strategy for Treg depletion in cancer therapies. BAY 3375968 is currently under investigation in a Phase I clinical trial (NCT05537740).

Selective therapeutic efficacy of tyrosine kinase inhibitor sorafenib on the restoration of methylglyoxal-induced peritoneal fibrosis.

Peritoneal fibrosis, a common complication observed in long-term peritoneal dialysis patients, can gradually lead to ultrafiltration failure and the development of encapsulating peritoneal sclerosis. Although mechanisms of peritoneal fibrosis have been proposed, effective therapeutic options are unsatisfactory. Recently, several tyrosine kinase inhibitors have proven to be anti-fibrosis in rodent models. To assess the potential therapeutic effects of tyrosine kinase inhibitors on peritoneal fibrosis in the larger animal model, a novel porcine model of peritoneal fibrosis induced by 40 mM methylglyoxal in 2.5 % dialysate was established, and two different doses (20 mg/kg and 30 mg/kg) of sorafenib were given orally to evaluate their therapeutic efficacy in this study. Our results showed that sorafenib effectively reduced adhesions between peritoneal organs and significantly diminished the thickening of both the parietal and visceral peritoneum. Angiogenesis, vascular endothelial growth factor A production, myofibroblast infiltration, and decreased endothelial glycocalyx resulting from dialysate and methylglyoxal stimulations were also alleviated with sorafenib. However, therapeutic efficacy in ameliorating loss of mesothelial cells, restoring decreased ultrafiltration volume, and improving elevated small solutes transport rates was limited. In conclusion, this study demonstrated that sorafenib could potentially be used for peritoneal fibrosis treatment, but applying sorafenib alone might not be sufficient to fully rescue methylglyoxal-induced peritoneal defects.

Differential Diagnosis of OKC and SBC on Panoramic Radiographs: Leveraging Deep Learning Algorithms.

This study aims to determine whether it can distinguish odontogenic keratocyst (OKC) and simple bone cyst (SBC) based solely on preoperative panoramic radiographs through a deep learning algorithm. (1) Methods: We conducted a retrospective analysis of patient data from January 2018 to December 2022 at Pusan National University Dental Hospital. This study included 63 cases of OKC confirmed by histological examination after surgical excision and 125 cases of SBC that underwent surgical curettage. All panoramic radiographs were obtained utilizing the Proline XC system (Planmeca Co., Helsinki, Finland), which already had diagnostic data on them. The panoramic images were cut into 299 × 299 cropped sizes and divided into 80% training and 20% validation data sets for 5-fold cross-validation. Inception-ResNet-V2 system was adopted to train for OKC and SBC discrimination. (2) Results: The classification network for diagnostic performance evaluation achieved 0.829 accuracy, 0.800 precision, 0.615 recall, and a 0.695 F1 score. (4) Conclusions: The deep learning algorithm demonstrated notable accuracy in distinguishing OKC from SBC, facilitated by CAM visualization. This progress is expected to become an essential resource for clinicians, improving diagnostic and treatment outcomes.

Developing and validating a knowledge-based AI assessment system for learning clinical core medical knowledge in otolaryngology.

BACKGROUND: Clinical core medical knowledge (CCMK) learning is essential for medical trainees. Adaptive assessment systems can facilitate self-learning, but extracting experts' CCMK is challenging, especially using modern data-driven artificial intelligence (AI) approaches (e.g., deep learning). OBJECTIVES: This study aims to develop a multi-expert knowledge-aggregated adaptive assessment scheme (MEKAS) using knowledge-based AI approaches to facilitate the learning of CCMK in otolaryngology (CCMK-OTO) and validate its effectiveness through a one-month training program for CCMK-OTO education at a tertiary referral hospital. METHODS: The MEKAS utilized the repertory grid technique and case-based reasoning to aggregate experts' knowledge to construct a representative CCMK base, thereby enabling adaptive assessment for CCMK-OTO training. The effects of longitudinal training were compared between the experimental group (EG) and the control group (CG). Both groups received a normal training program (routine meeting, outpatient/operation room teaching, and classroom teaching), while EG received MEKAS for self-learning. The EG comprised 22 UPGY trainees (6 postgraduate [PGY] and 16 undergraduate [UGY] trainees) and 8 otolaryngology residents (ENT-R); the CG comprised 24 UPGY trainees (8 PGY and 16 UGY trainees). The training effectiveness was compared through pre- and post-test CCMK-OTO scores, and user experiences were evaluated using a technology acceptance model-based questionnaire. RESULTS: Both UPGY (z = -3.976, P < 0.001) and ENT-R (z = -2.038, P = 0.042) groups in EG exhibited significant improvements in their CCMK-OTO scores, while UPGY in CG did not (z = -1.204, P = 0.228). The UPGY group in EG also demonstrated a substantial improvement compared to the UPGY group in CG (z = -4.943, P < 0.001). The EG participants were highly satisfied with the MEKAS system concerning self-learning assistance, adaptive testing, perceived satisfaction, intention to use, perceived usefulness, perceived ease of use, and perceived enjoyment, rating it between an overall average of 3.8 and 4.1 out of 5.0 on all scales. CONCLUSIONS: The MEKAS system facilitates CCMK-OTO learning and provides an efficient knowledge aggregation scheme that can be applied to other medical subjects to efficiently build adaptive assessment systems for CCMK learning. Larger-scale validation across diverse institutions and settings is warranted further to assess MEKAS's scalability, generalizability, and long-term impact.

Comparative effectiveness of primary tumor resection versus chemotherapy in patients with asymptomatic unresectable metastatic colorectal cancer: a retrospective cohort study using the target trial emulation framework.

Patients who undergo primary tumor resection (PTR) reportedly have significantly higher overall survival (OS) than those who do not undergo this procedure. However, this result is only evident in past retrospective studies, and clinical trial results did not show the same trend. Thus, it remains unclear whether primary tumor resection effectively increases survival in patients with metastatic colorectal cancer (mCRC) across different study designs. We compared the OS of patients with asymptomatic unresectable mCRC who underwent PTR with that of those who did not. This retrospective cohort study was designed to be a target trial emulation of a randomized controlled trial (RCT) that would have compared the effectiveness of PTR versus non-PTR in patients with asymptomatic unresectable mCRC from 2009 to 2017. A systematic review and meta-analysis were conducted to compare the efficacy of PTR and non-PTR in patients with mCRC, and corresponding results were compared. This cohort included 1,132 patients for a per-protocol analysis. The PTR group had non-significantly longer survival (adjusted hazard ratio: 0.70, 95% confidence interval: 0.62-1.01) than the non-PTR group in our cohort. A meta-analysis including five RCTs (1,016 patients) and our cohort found that the PTR group did not have a significantly lower mortality rate than the non-PTR group. The results of this cohort study and previous RCTs suggest that PTR is not associated with improved survival compared to systemic chemotherapy combined with targeted therapy among asymptomatic unresectable mCRC patients. Therefore, routine PTR is not recommended in these patients.

Effect of Kinesiology Taping on Breast Cancer-Related Lymphedema: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: The objective of this systematic review and meta-analysis was to evaluate the impact of kinesiology taping on individuals suffering from breast cancer-related lymphedema. METHODS AND METHODS: We conducted a comprehensive search in PubMed, Cochrane Library, and Embase databases, spanning from their inception date to December 20, 2023, to identify pertinent studies. Inclusion criteria comprised studies that (1) enrolled participants diagnosed with breast cancer-related lymphedema; (2) implemented kinesiology taping as the intervention; (3) incorporated either complete decongestive therapy, exercise, or sham taping as the control treatment; and (4) included clinical measurements such as the severity of lymphedema, upper limb function assessment, quality of life, and perceived comfort. RESULTS: Information was extracted from 14 randomized controlled trials (RCTs). The analyses demonstrated statistically significant improvement, indicating a preference for kinesiology taping in the outcomes of upper limb functional assessment (standardized mean difference [SMD] = -0.88, 95% confidence interval [CI]: [-1.22, -0.55]), quality of life (SMD = 0.50, 95% CI: [0.16, 0.84]), and perceived comfort (SMD = 0.85, 95% CI: [0.34, 1.36]). CONCLUSION: The findings suggest that kinesiology taping could be considered a viable option for individuals dealing with breast cancer-related lymphedema. Nevertheless, acknowledging certain limitations within this study, further confirmation of its benefits necessitates additional larger-scale and better-designed RCTs.

Lithium nitrate salt-assisted CO2 absorption for the formation of corrosion barrier layer on AZ91D magnesium alloy.

Mg alloy corrosion susceptibility is a major issue that limits its wide industrial application in transport, energy and medical sectors. A corrosion-resistant layer containing crystalline MgCO3 was formed on the surface of AZ91D Mg alloy by Li salt loading and thermal CO2 treatment. Compared to the uncoated AZ91D surface, the surface layer exhibited up to a ∼15-fold increase in corrosion resistance according to the electrochemical results in 3.5 wt% NaCl solution and ∼32% decrease in wear rate compared to untreated AZ91D. The improved corrosion resistance is attributed to the formation of a <10 µm thick dense layer containing Mg, O, C and Li with crystalline MgCO3 phases. The initial step was to form a porous MgO layer on the surface of AZ91D Mg alloy, followed by loading an alkali metal salt (i.e., LiNO3) onto the MgO surface. The porous MgO surface was then reconstructed into a dense insulation layer containing Mg carbonate through CO2 absorption facilitated by molten Li salt during thermal CO2 treatment at 350 °C. As a potential method to utilize excessive CO2 for beneficial outcomes, the formation of the carbonate-containing film introduced in this study opens a new pathway for protecting various existing Mg alloys for diverse industrial applications.

A Nomogram Based on Conventional Ultrasound Radiomics for Differentiating Between Radial Scar and Invasive Ductal Carcinoma of the Breast.

ABSTRACT: We aimed to develop and validate a nomogram based on conventional ultrasound (CUS) radiomics model to differentiate radial scar (RS) from invasive ductal carcinoma (IDC) of the breast. In total, 208 patients with histopathologically diagnosed RS or IDC of the breast were enrolled. They were randomly divided in a 7:3 ratio into a training cohort (n = 145) and a validation cohort (n = 63). Overall, 1316 radiomics features were extracted from CUS images. Then a radiomics score was constructed by filtering unstable features and using the maximum relevance minimum redundancy algorithm and the least absolute shrinkage and selection operator logistic regression algorithm. Two models were developed using data from the training cohort: one using clinical and CUS characteristics (Clin + CUS model) and one using clinical information, CUS characteristics, and the radiomics score (radiomics model). The usefulness of nomogram was assessed based on their differentiating ability and clinical utility. Nine features from CUS images were used to build the radiomics score. The radiomics nomogram showed a favorable predictive value for differentiating RS from IDC, with areas under the curve of 0.953 and 0.922 for the training and validation cohorts, respectively. Decision curve analysis indicated that this model outperformed the Clin + CUS model and the radiomics score in terms of clinical usefulness. The results of this study may provide a novel method for noninvasively distinguish RS from IDC.

Study Protocol: Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project.

BACKGROUND: Objective and quantifiable markers are crucial for developing novel therapeutics for mental disorders by 1) stratifying clinically similar patients with different underlying neurobiological deficits and 2) objectively tracking disease trajectory and treatment response. Schizophrenia is often confounded with other psychiatric disorders, especially bipolar disorder, if based on cross-sectional symptoms. Awake and sleep EEG have shown promise in identifying neurophysiological differences as biomarkers for schizophrenia. However, most previous studies, while useful, were conducted in European and American populations, had small sample sizes, and utilized varying analytic methods, limiting comprehensive analyses or generalizability to diverse human populations. Furthermore, the extent to which wake and sleep neurophysiology metrics correlate with each other and with symptom severity or cognitive impairment remains unresolved. Moreover, how these neurophysiological markers compare across psychiatric conditions is not well characterized. The utility of biomarkers in clinical trials and practice would be significantly advanced by well-powered transdiagnostic studies. The Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project aims to address these questions through a large, multi-center cohort study involving East Asian populations. To promote transparency and reproducibility, we describe the protocol for the GRINS project. METHODS: The research procedure consists of an initial screening interview followed by three subsequent sessions: an introductory interview, an evaluation visit, and an overnight neurophysiological recording session. Data from multiple domains, including demographic and clinical characteristics, behavioral performance (cognitive tasks, motor sequence tasks), and neurophysiological metrics (both awake and sleep electroencephalography), are collected by research groups specialized in each domain. CONCLUSION: Pilot results from the GRINS project demonstrate the feasibility of this study protocol and highlight the importance of such research, as well as its potential to study a broader range of patients with psychiatric conditions. Through GRINS, we are generating a valuable dataset across multiple domains to identify neurophysiological markers of schizophrenia individually and in combination. By applying this protocol to related mental disorders often confounded with each other, we can gather information that offers insight into the neurophysiological characteristics and underlying mechanisms of these severe conditions, informing objective diagnosis, stratification for clinical research, and ultimately, the development of better-targeted treatment matching in the clinic.

Chromosome-level genome assemblies of 2 hemichordates provide new insights into deuterostome origin and chromosome evolution.

Deuterostomes are a monophyletic group of animals that includes Hemichordata, Echinodermata (together called Ambulacraria), and Chordata. The diversity of deuterostome body plans has made it challenging to reconstruct their ancestral condition and to decipher the genetic changes that drove the diversification of deuterostome lineages. Here, we generate chromosome-level genome assemblies of 2 hemichordate species, Ptychodera flava and Schizocardium californicum, and use comparative genomic approaches to infer the chromosomal architecture of the deuterostome common ancestor and delineate lineage-specific chromosomal modifications. We show that hemichordate chromosomes (1N = 23) exhibit remarkable chromosome-scale macrosynteny when compared to other deuterostomes and can be derived from 24 deuterostome ancestral linkage groups (ALGs). These deuterostome ALGs in turn match previously inferred bilaterian ALGs, consistent with a relatively short transition from the last common bilaterian ancestor to the origin of deuterostomes. Based on this deuterostome ALG complement, we deduced chromosomal rearrangement events that occurred in different lineages. For example, a fusion-with-mixing event produced an Ambulacraria-specific ALG that subsequently split into 2 chromosomes in extant hemichordates, while this homologous ALG further fused with another chromosome in sea urchins. Orthologous genes distributed in these rearranged chromosomes are enriched for functions in various developmental processes. We found that the deeply conserved Hox clusters are located in highly rearranged chromosomes and that maintenance of the clusters are likely due to lower densities of transposable elements within the clusters. We also provide evidence that the deuterostome-specific pharyngeal gene cluster was established via the combination of 3 pre-assembled microsyntenic blocks. We suggest that since chromosomal rearrangement events and formation of new gene clusters may change the regulatory controls of developmental genes, these events may have contributed to the evolution of diverse body plans among deuterostomes.

Perceived stress and influencing factors for the people at high risk to COVID-19 in centralized quarantine camps in Wenzhou, China.

BACKGROUND: This study was designed to assess stress levels and related factors during the coronavirus disease 2019 (COVID-19) epidemic among individuals in centralized quarantine camps in Wenzhou, China. METHODS: The survey was conducted using a questionnaire. The questionnaire included questions on sociodemographic characteristics, life events related to the COVID-19 and stressful situations, as well as Perceived Stress Scale-14. Participants included close contacts of patients with COVID-19 or at-risk individuals in quarantine camps. Multivariate logistic regression was used to analyze different factors affecting perceived stress. RESULTS: The prevalence of high stress among quarantine camp participants was 37.45%. Of the 881 respondents, 51.99% were concerned about the difficulty of controlling the epidemic, 46.20% were concerned about the health of themselves and their family members and 39.61% were concerned about not being able to leave their homes. Multivariate logistic regression analysis revealed statistically significant differences in the prevalence of stress among different groups for certain variables, including occupation, education level and knowledge of COVID-19 (all P < 0.05). Our study found that at-risk individuals and close contacts experienced high levels of stress in quarantine camps during the COVID-19 pandemic. CONCLUSIONS: These findings suggest that centralized quarantine policies should be adapted and optimized to minimize negative psychological effects on quarantined individuals.

Dietary inflammatory index, mediating biomarkers and incident frailty in Chinese community-dwelling older adults.

OBJECTIVES: Diet can modulate systemic inflammation, while inflammation is a critical contributory factor of frailty. However, longitudinal data on the association between dietary inflammatory index (DII) and frailty are limited, and the intermediate mechanisms remain unclear. This study aimed to examine the association between DII and incident frailty and the potential mediating roles of frailty-related biomarkers. DESIGN: Prospective cohort study. SETTING: The Mr. OS and Ms. OS (Hong Kong) study. PARTICIPANTS: A total of 3,035 community-dwelling men and women aged above 65 years without frailty at baseline were included. MEASUREMENTS: DII scores were calculated using the locally validated food frequency questionnaire. Incident frailty at year four was defined using the Fried frailty phenotype. Logistic regression was used to examine the association between DII and frailty onset. Mediation analysis was used to explore the mediating roles of frailty-related biomarkers in the DII-frailty association. RESULTS: During four years of follow-up, 208 individuals developed frailty. Compared with the lowest tertile of DII, the highest tertile was associated with an increased risk of incident frailty (OR: 1.82; 95% CI: 1.17-2.82; p = 0.008) after adjustment for relevant confounders. The DII-frailty association was significant in men but not in women. Furthermore, increasing serum homocysteine, decreasing serum folate, and reducing estimated glomerular filtration rate (eGFR) mediated 11.6%, 7.1%, and 9.6 % of the total relation between DII and frailty onset, respectively. CONCLUSION: In this cohort study, a pro-inflammatory diet was associated with a higher risk of frailty onset, mediated by homocysteine, folate, and renal function.

Decoding the Qu-aroma of medium-temperature Daqu starter by volatilomics, aroma recombination, omission studies and sensory analysis.

Qu-aroma is of great significance for evaluation the quality of Daqu starter. This study aimed to decode the Qu-aroma of medium-temperature Daqu (MT-Daqu) via "top-down" and "bottom-up" approaches. Firstly, 52 aroma descriptors were defined to describe the MT-Daqu aroma by quantitative descriptive analysis. Secondly, 193 volatile organic compounds (VOCs) were identified from 42 MT-Daqu samples by HS-SPME-GC-MS, and 43 dominant VOCs were screened out by frequence of occurrence or abundance. By Thin Film (TF)-SPME-GC-O-MS, 27 odors and 90 VOCs were detected in MT-Daqu mixture, and 14 odor-active VOCs were screened out by odor intensity. Thirdly, a five-level MT-Daqu aroma wheel was constructed by matching 52 aroma descriptors and 37 aroma-active VOCs. Finally, Qu-aroma of MT-Daqu was reconstructed with 37 aroma-active VOCs and evaluated by omission experiments. Hereinto, 26 key aroma-active VOCs were determined by OAV value ≥1, including isovaleric acid, 1-hexanol, isovaleraldehyde, 2-octanone, trimethylpyrazine, γ-nonalactone, 4-vinylguaiacol, etc.

Bletilla striata Polysaccharide-Containing Carboxymethyl Cellulose Bilayer Structure Membrane for Prevention of Postoperative Adhesion and Achilles Tendon Repair.

Postoperative tissue adhesion and poor tendon healing are major clinical problems associated with tendon surgery. To avoid postoperative adhesion and promote tendon healing, we developed and synthesized a membrane to wrap the surgical site after tendon suturing. The bilayer-structured porous membrane comprised an outer layer [1,4-butanediol diglycidyl ether cross-linked with carboxymethyl cellulose (CX)] and an inner layer [1,4-butanediol diglycidyl ether cross-linked with Bletilla striata polysaccharides and carboxymethyl cellulose (CXB)]. The morphology, chemical functional groups, and membrane structure were determined. In vitro experiments revealed that the CX/CXB membrane demonstrated good biosafety and biodegradability, promoted tenocyte proliferation and migration, and exhibited low cell attachment and anti-inflammatory effects. Furthermore, in in vivo animal study, the CX/CXB membrane effectively reduced postoperative tendon-peripheral tissue adhesion and improved tendon repair, downregulating inflammatory cytokines in the tendon tissue at the surgical site, which ultimately increased tendon strength by 54% after 4 weeks.

Diagnostic ability of macular nerve fiber layer thickness measured by swept-source optical coherence tomography in preperimetric glaucoma.

BACKGROUND: We evaluated the diagnostic ability of macula retinal nerve fiber layer (mRNFL) thickness in preperimetric glaucoma (PPG) patients. METHODS: This prospective study included 83 patients with PPG and 83 age- and refractive error-matched normal control subjects. PPG was defined as a localized RNFL defect corresponding to glaucomatous optic disc changes with a normal visual field test. We used spectral-domain (SD) optical coherence tomography (OCT) to measure the circumpapillary RNFL (cpRNFL) thickness and macular ganglion cell-inner plexiform layer (GCIPL) thickness. Swept-source (SS) OCT was used to measure cpRNFL thickness, macular ganglion cell layer + inner plexiform layer (IPL) thickness (GCL+), and macular ganglion cell layer + IPL+ mRNFL thickness (GCL++). The mRNFL thickness was defined as GCL++ minus GCL+. To evaluate the diagnostic power of each parameter, the area under the receiver operating characteristics curve (AUROC) was analyzed to differentiate PPG from the normal groups. RESULTS: Using SD-OCT, all GCIPL parameters and most cpRNFL parameters, except at the nasal and temporal quadrant, were significantly lower in PPG versus normal controls. PPG eyes had significantly smaller values than normal controls for all cpRNFL and GCL parameters measured by SS-OCT, except mRNFL at the superonasal area. The inferotemporal GCL++ had the largest AUROC value (0.904), followed by inferotemporal GCL+ (0.882), inferotemporal GCIPL thickness (0.871), inferior GCL++ (0.866), inferior cpRNFL thickness by SS-OCT (0.846), inferior cpRNFL thickness by SD-OCT (0.841), and inferotemporal mRNFL thickness (0.840). The diagnostic performance was comparable between inferotemporal mRNFL thickness and the best measures of GCL (inferotemporal GCL++, p = 0.098) and cpRNFL (inferior cpRNFL thickness by SS-OCT, p = 0.546). CONCLUSION: The diagnostic ability of mRNFL thickness was comparable to that of the best measures of cpRNFL and GCL analysis for eyes with PPG. Therefore, mRNFL thickness could be a new parameter to detect early structural changes in PPG.

Challenges with computing scalar and ad-hoc implicatures in Mandarin-speaking 4-8-year-old autistic children.

INTRODUCTION: Mixed findings have been reported about the computation of scalar or/and ad-hoc implicatures in primarily school-age autistic verbal children and adolescents: while some studies reported their struggles with both implicatures, others observed their strengths in computing scalar implicatures. This study extends the previous investigation by testing the derivation of scalar (including both number and quantifier) and ad-hoc implicatures of a younger group of Mandarin-speaking autistic 4-8-year-olds; moreover, we assess the biological, linguistic, and cognitive factors affecting children's implicature acquisition. METHODS: The participants included 22 4-8-year-old autistic verbal children (mean age = 67.64 months) and 19 typically developing (TD) children who did not significantly differ in age, receptive vocabulary, and non-verbal IQ. Both groups completed a computer-based Truth Value Judgment task, assessing their knowledge of scalar (involving the number 'three' and the quantifier 'some') and ad-hoc implicatures. We also examined whether their implicature computation was linked to age, receptive vocabulary, non-verbal IQ, and Theory of Mind (ToM). RESULTS: Compared with the TD controls, autistic children derived significantly fewer scalar and ad-hoc implicatures. Specifically, TD children successfully computed number and ad-hoc implicatures, contrasting to the bimodal distribution of their pragmatic vs. logical responses to quantifier implicatures. Though autistic children performed better with number implicatures slightly above the chance level, they had difficulties in computing quantifier and ad-hoc implicatures. Further, autistic children's knowledge of the number and ad-hoc implicatures was linked to their ToM skills. CONCLUSIONS: These findings underscore the overall delayed implicature knowledge of young autistic children, and their low sensitivity to the implicatures is related to the core ToM deficits. Furthermore, our data confirm the coherent pattern of the earlier acquisition of number over quantifier implicatures and illuminate the distinct mechanisms underlying the computation of scalar vs. ad-hoc implicatures.

A prospective study of psychological adjustment during and after forehead flap nasal reconstruction.

The psychological effects of staged nasal reconstruction with a forehead flap were prospectively investigated. Thirty-three patients underwent nasal reconstruction with forehead flaps between March 2017 and July 2020. Three questionnaires were used to assess psychosocial functioning before surgery (time 1), 1 week after forehead flap transfer (time 2), 1 week after forehead flap division (time 3), and after refinement procedures (time 4). The patients were categorized into three groups according to the severity of nasal defects. Between- and within-group comparisons were conducted. All patients reported increased satisfaction with their appearance during nasal reconstruction. For most patients, levels of distress and social avoidance were highest before reconstruction (time 1). Both levels decreased as reconstruction advanced, and were significantly improved by times 3 and 4. The stage of reconstruction had a greater effect on these levels than did severity of nasal defect. Nasal reconstruction with forehead flap is beneficial physically and psychologically. Psychological evaluation before and after surgery facilitates patient-surgeon interactions and further enhances outcomes.

Case report: Donor-derived CLL-1 chimeric antigen receptor T-cell therapy for relapsed/refractory acute myeloid leukemia bridging to allogeneic hematopoietic stem cell transplantation after remission.

Background: Explore the efficacy and safety of donor-derived CLL-1 chimeric antigen receptor T-cell therapy (CAR-T) for relapsed/refractory acute myeloid leukemia (R/R AML) bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) after remission. Case presentation: An adult R/R AML patient received an infusion of donor-derived CLL-1 CAR-T cells, and the conditioning regimen bridging to allo-HSCT was started immediately after remission on day 11 after CAR-T therapy upon transplantation. Then, routine post-HSCT monitoring of blood counts, bone marrow (BM) morphology, flow cytometry, graft-versus-host disease (GVHD) manifestations, and chimerism status were performed. Result: After CAR-T therapy, cytokine release syndrome was grade 1. On day 11 after CAR-T therapy, the BM morphology reached complete remission (CR), and the conditioning regimen bridging to allo-HSCT started. Leukocyte engraftment, complete donor chimerism, and platelet engraftment were observed on days +18, +23, and +26 post-allo-HSCT, respectively. The BM morphology showed CR and flow cytometry turned negative on day +23. The patient is currently at 4 months post-allo-HSCT with BM morphology CR, negative flow cytometry, complete donor chimerism, and no extramedullary relapse/GVHD. Conclusion: Donor-derived CLL-1 CAR-T is an effective and safe therapy for R/R AML, and immediate bridging to allo-HSCT after remission may better improve the long-term prognosis of R/R AML.