A prognostic model for triple-negative breast cancer patients with liver metastasis: A population-based study.

However, it is still difficult for clinicians to establish prognostic stratifications and therapeutic strategies because of the lack of tools for predicting the survival of triple-negative breast cancer patients with liver metastases (TNBC-LM). Based on clinical data from large populations, a sensitive and discriminative nomogram was developed and validated to predict the prognosis of TNBC patients with LM at initial diagnosis or at the later course. Introduction/background: Liver metastasis (LM) in TNBC patients is associated with significant morbidity and mortality. The objective of this study was to construct a clinical model to predict the survival of TNBC-LM patients. Materials and methods: Clinicopathologic data were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and the Fifth Affiliated Hospital of Sun Yat-Sen University (FAFSYU). Based on patients with newly diagnosed TNBC with LM (nTNBC-LM) from the SEER database, a predictive nomogram was established and validated. Its predictive effect on TNBC patients with LM at later disease course by enrolling TNBC patients from FAFSYU who developed LM later. The prognostic effect of different treatment for nTNBC-LM was further assessed. Results: A prognostic model was developed and validated to predict the prognosis of TNBC-LM patients. For LM patients diagnosed at the initial or later treatment stage, the C-index (0.712, 0.803 and 0.699 in the training, validation and extended groups, respectively) and calibration plots showed the acceptable prognostic accuracy and clinical applicability of the nomogram. Surgical resection on the primary tumour and chemotherapy were found to be associated with significantly better overall survival (OS). Conclusion: A sensitive and discriminative model was developed to predict OS in TNBC-LM patients both at and after initial diagnosis.

Distinct transcriptomes and autocrine cytokines underpin maturation and survival of antibody-secreting cells in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple autoantibody types, some of which are produced by long-lived plasma cells (LLPC). Active SLE generates increased circulating antibody-secreting cells (ASC). Here, we examine the phenotypic, molecular, structural, and functional features of ASC in SLE. Relative to post-vaccination ASC in healthy controls, circulating blood ASC from patients with active SLE are enriched with newly generated mature CD19-CD138+ ASC, similar to bone marrow LLPC. ASC from patients with SLE displayed morphological features of premature maturation and a transcriptome epigenetically initiated in SLE B cells. ASC from patients with SLE exhibited elevated protein levels of CXCR4, CXCR3 and CD138, along with molecular programs that promote survival. Furthermore, they demonstrate autocrine production of APRIL and IL-10, which contributed to their prolonged in vitro survival. Our work provides insight into the mechanisms of generation, expansion, maturation and survival of SLE ASC.

Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: A randomized non-inferiority trial.

PURPOSE: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts. DESIGN: Multicenter, randomized controlled, non-inferiority trial. METHODS: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications. RESULTS: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group. CONCLUSIONS: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life.

Assessing accuracy of resonances obtained with reassigned spectrograms from the "ground truth" of physical vocal tract models.

The reassigned spectrogram (RS) has emerged as the most accurate way to infer vocal tract resonances from the acoustic signal [Shadle, Nam, and Whalen (2016). "Comparing measurement errors for formants in synthetic and natural vowels," J. Acoust. Soc. Am. 139(2), 713-727]. To date, validating its accuracy has depended on formant synthesis for ground truth values of these resonances. Synthesis is easily controlled, but it has many intrinsic assumptions that do not necessarily accurately realize the acoustics in the way that physical resonances would. Here, we show that physical models of the vocal tract with derivable resonance values allow a separate approach to the ground truth, with a different range of limitations. Our three-dimensional printed vocal tract models were excited by white noise, allowing an accurate determination of the resonance frequencies. Then, sources with a range of fundamental frequencies were implemented, allowing a direct assessment of whether RS avoided the systematic bias towards the nearest strong harmonic to which other analysis techniques are prone. RS was indeed accurate at fundamental frequencies up to 300 Hz; above that, accuracy was somewhat reduced. Future directions include testing mechanical models with the dimensions of children's vocal tracts and making RS more broadly useful by automating the detection of resonances.

Early Diagnosis of Syndromic Congenital Cataracts in a Large Cohort of Congenital Cataracts.

PURPOSE: To explore the factors related to the diagnosis yield of syndromic congenital cataracts and describe the phenotype-genotype correlation in congenital cataract patients. DESIGN: Prospective cohort study. METHODS: Setting: the participants from underwent clinical examinations between 2021 and 2022. Facial and anterior eye segment photographs, pre- and postoperative ocular parameters, and medical and family histories were recorded. Bioinformatics analysis was performed using whole-exome sequencing data. Statistical and correlation analyses were performed using the basic characteristics, deep phenotype, and genotype data. PARTICIPANTS: 115 patients with unrelated congenital cataract. INTERVENTIONS: performing clinical examinations, whole-exome sequencing, and bioinformatics analysis for all participants. MAIN OUTCOMES AND MEASURES: factors related to the genetic diagnosis yield of syndromic congenital cataracts. RESULTS: Bilaterally asymmetrical cataracts were identified to be associated with syndromic congenital cataracts. The overall genetic diagnostic yield in the cohort was 72.2%. In total, 34.8% of the probands were early diagnosed with various syndromes with the help of genetic information. A phenotype-genotype correlation was detected for some genes and deep phenotypes. CONCLUSIONS: We highlight the importance of screening syndromic diseases in the patients with asymmetrical congenital cataracts. Application of whole-exome sequencing helps provide early diagnosis and treatment for the patients with syndromic congenital cataracts. This study also achieved a high genetic diagnostic yield, expanded the genotypic spectrum, and found phenotype-genotype correlations. A comprehensive analysis of cataract symmetricity, family history, and deep phenotypes makes the genotype prediction of some congenital cataract patients possible.

Surgical approach to and morphology of visually significant persistent pupillary membranes.

PURPOSE: To characterize the morphology of persistent pupillary membranes (PPMs) in pediatric patients and explore the corresponding surgical approaches. SETTING: Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. DESIGN: Prospective observational study. METHODS: Consecutive pediatric patients with PPMs who underwent surgery from April 2020 to July 2022 were included. PPM morphology was assessed and categorized according to its anatomic relationship with crystalline lens and distribution of iris strands. The surgical approaches for different morphologies of PPMs were described in detail. The visual outcome and operation-related complications were recorded. RESULTS: 31 eyes from 19 patients were included with the mean age of 7.2 years. 3 morphological variants of PPMs were observed: type I (51.6%, 16/31), a spider-like appearance and no adhesion to the anterior lens capsule (ALC); type II (38.7%, 12/31), a loose central adherence to the ALC and partially thick iris strands attached to the iris collarette; type III (9.7%, 3/31), a tight central adherence to the ALC and only silk-like iris strands. Surgeries were performed with a natural pupil size in type I, while dilated pupil in the other types. The adhesions between PPM and the ALC were separated by viscoelastic injection in type II and by discission needles in type III. The corrected distance visual acuity was significantly improved from 0.34 ± 0.18 logMAR preoperatively to 0.17 ± 0.09 logMAR postoperatively ( P < .001). No operation-related complications were observed during 9.5-month follow-up. CONCLUSIONS: PPMs were categorized into 3 types according to their different morphologies, which helped to determine the best surgical strategy.

Intraocular lens tilt and decentration in secondary ciliary sulcus implantation in paediatric eyes: A 3-year prospective study.

PURPOSE: The purpose of this study was to compare the tilt and decentration of one-piece anti-vaulting haptic intraocular lenses (IOL) and three-piece C-loop haptic IOLs in paediatric eyes undergoing secondary IOL implantation into the ciliary sulcus. METHODS: Paediatric aphakic patients receiving either one-piece anti-vaulting haptic or three-piece C-loop haptic IOL implants into the ciliary sulcus were enrolled in this prospective non-randomized interventional study and followed up for 3 years. IOL decentration and tilt were measured using Scheimpflug images. Preoperative and postoperative information, including demographic data and ocular biometric parameters and complications, were collected and analysed. RESULTS: Among 123 eyes of 79 paediatric patients, there were 72 eyes (58.54%) in the anti-vaulting haptic IOL group and 51 eyes (41.46%) in the C-loop haptic group. The anti-vaulting haptic IOL group had a lower incidence of clinically significant vertical IOL decentration than the C-loop haptic IOL group (23.88% vs. 43.14%, p = 0.037). No intergroup differences were observed in vertical or horizontal tilt or in horizontal decentration (all p > 0.05). One-piece anti-vaulting haptic IOL implantation was associated with a lower risk of clinically significant vertical decentration than three-piece C-loop haptic IOL implantation (odds ratio: 0.42, p = 0.037). There was a higher incidence of IOL dislocation in the C-loop haptic IOL group (15.22% vs. 4.17%, p = 0.046). CONCLUSIONS: In paediatric aphakic eyes undergoing secondary IOL implantation into the ciliary sulcus, one-piece anti-vaulting haptic IOLs can reduce the risk of clinically significant vertical IOL decentration compared with three-piece C-loop haptic IOLs and may favour long-term IOL positional stability.

Reopening the capsular bag by removing the capsular proliferative membrane to enable secondary in-the-bag intraocular lens implantation in pediatric aphakic eyes.

PURPOSE: To present a surgical technique for reopening the capsular bag in pediatric aphakia. SETTING: Zhongshan Ophthalmic Center, Guangzhou, China. DESIGN: Case series study. METHODS: Consecutive pediatric patients with bilateral aphakia requiring secondary intraocular lens (IOL) implantation between July 2021 and June 2022 were included. The diameter of the capsular proliferative membranous ring (PMR) and position of IOL implantation were documented. Various parameters of capsular bag opening during primary cataract removal and secondary surgery were also analyzed. RESULTS: 48 eyes were included with a mean follow-up of 8.1 ± 4.4 months. Using the surgical technique developed in this study, the capsular bag was successfully reopened with in-the-bag (ITB) implantation in 43 eyes (89.6%). ITB implantation was accomplished in all eyes with an outer diameter of PMR ≤5.5 mm and in 3 of 8 eyes (37.5%) with an outer diameter of PMR >5.5 mm. A positive correlation was observed between the primary and secondary anterior capsular opening diameters (ACODs) ( r = 0.422, P = .007) and the primary and secondary posterior capsular opening diameters (PCODs) ( r = 0.619, P < .001). The inner diameter of PMR was found to be positively correlated with secondary PCOD ( r = 0.728, P < .001) and the outer diameter with secondary ACOD ( r = 0.669, P < .001). CONCLUSIONS: This was a safe and effective surgical technique for pediatric secondary IOL implantation with maximum preservation of the peripheral capsule. Aphakic eyes with an outer diameter of PMR ≤5.5 mm are preferred for secondary ITB implantation.

Incidence of and risk factors for suspected and definitive glaucoma after bilateral congenital cataract surgery: a 5-year follow-up.

AIMS: To report the incidence and associated risk factors for developing suspected and definitive glaucoma after bilateral congenital cataract (CC) removal with a 5-year follow-up. METHODS: Secondary analysis of a prospective longitudinal cohort study. Bilateral CC patients who had undergone cataract surgery between January 2011 and December 2014 at Zhongshan Ophthalmic Centre were recruited. Suspected glaucoma was defined as persistent ocular hypertension requiring medical treatment. Definitive glaucoma was defined as accompanied by the progression of glaucomatous clinical features. According to postoperative lens status in 5 years follow-up: 130 eyes in the aphakia group; 219 in the primary intraocular lens (IOL) implantation group and 337 in the secondary IOL implantation group. The Kaplan-Meier survival and Cox regression analyses were used to explore the cumulative incidence and risk factors for suspected and definitive glaucoma. RESULTS: Three hundred fifty-one children (686 eyes) with bilateral CCs were enrolled in the study. The mean age at surgery was 1.82±2.08 years, and the mean follow-up duration was 6.26±0.97 years. Suspected and definitive glaucoma developed at a mean time of 2.84±1.75 years (range 0.02-7.33 years) postoperatively. The cumulative incidence of suspected and definitive glaucoma was 9.97% (35 of 351 patients), including 6.12% (42 eyes) for definitive glaucoma and 2.48% (17 eyes) for suspected glaucoma. Microcornea (HR 4.103, p<0.0001), CC family history (HR 3.285, p=0.001) and initial anterior vitrectomy (HR 2.365 p=0.036) were risk factors for suspected and definitive glaucoma. Gender, age at surgery, intraocular surgery frequency, length of follow-up and frequency of neodymium-doped yttrium aluminumaluminium garnet laser were non-statistically significant. Primary IOL implantation was a protective factor (HR 0.378, p=0.007). CONCLUSIONS: Identifying suspected and definitive glaucoma after bilateral CC surgery can lower the risk of secondary blindness in children. Patients with related risk factors need to pay more attention and thus reach early intervention and treatment during clinical practice. Primary IOL implantation may be a potential protective factor, need more clinical trials to be verified. TRIAL REGISTRATION NUMBER: NCT04342052.

Transient vacuolar changes of the crystalline lens in patients using a dispersive ophthalmic viscosurgical device.

AIM: To report the clinical prognosis and pathological findings of accidental lens vacuolar changes in eyes with intraoperative exposure to a dispersive ophthalmic viscosurgical device (OVD). METHODS: Two patients who developed transient lens vacuolar changes during uneventful persistent pupillary membrane (PPM) removal surgery were presented and followed up. This event was speculated to be associated with an intraoperative dispersive OVD DisCoVisc (hyaluronic acid 1.6%-chondroitin sulfate 4.0%) exposure. Then, to provide the pathological basis for our speculation, another four cataract patients were randomly exposed to different OVDs, and their anterior lens capsules were investigated with transmission electron microscopy (TEM). RESULTS: After months, the subcapsular vacuoles in both PPM cases were gradually disappeared without visual deterioration. For the cataract patients, similar lens changes were observed intraoperatively in those exposed to a dispersive DisCoVisc but not a cohesive OVD IVIZ (sodium hyaluronate gel 1.0%). In addition, marked ultrastructural changes, including chromatin condensation, extensive cytoplasmic vacuoles, and obvious intercellular space between lens epithelial cells in the anterior lens capsules of all eyes exposed to DisCoVisc, were observed by TEM. CONCLUSION: The lens vacuolar changes may be associated with a dispersive OVD exposure. Therefore, it is not preferable to use dispersive OVDs in patients with transparent lenses or without the intention of lens extraction. In addition, close follow-ups instead of immediate lens extraction are recommended for the occurrence of similar lens lesions.

Outcomes of Goniotomy With or Without Secondary Intraocular Lens Implantation in Pediatric Glaucoma Following Cataract Surgery: A Prospective Pilot Study.

PURPOSE: To report the outcomes of a 120-degree goniotomy (GT) with or without secondary intraocular lens (IOL) implantation in glaucoma following cataract surgery (GFCS). DESIGN: Prospective, observational study. METHODS: Pediatric patients with GFCS who underwent standalone 120-degree GT or 120-degree GT combined with secondary IOL implantation (GT+IOL) from March 2022 to August 2022 at the Zhongshan Ophthalmic Center were recruited. Primary outcomes were intraocular pressure (IOP) and the number of ocular hypotensive medications. A secondary outcome was the surgical success rate. Success was defined as a postoperative IOP within the range of 5-21 mm Hg. Complete and qualified successes were defined, as the above, without and with ocular hypotensive medications, respectively. RESULTS: Thirty-two eyes of 22 patients were included. The mean age at the time of GT was 68.5 ± 29.3 months. The mean follow-up duration was 12.2 ± 2.3 months (9-15 mo). Mean IOP decreased from 30.9 ± 4.8 mm Hg on 2 (interquartile range = 1) medications at baseline to 15.8 ± 3.6 mm Hg on 0 (interquartile range = 1.5) medication at the latest visit in all eyes. The overall complete and qualified success rates were 68.8% and 90.6%, respectively. There were no significant differences in IOP, number of medications, and complete and qualified success rates between the standalone GT and GT+IOL groups at the latest follow-up at 9 months postoperatively. CONCLUSIONS: To reduce the need for additional surgery, 120-degree GT was a safe and effective surgical treatment for GFCS in children, which could be combined with secondary IOL implantation in aphakic eyes with GFCS.

Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patients.

BACKGROUND: Cranio-lenticulo-sutural dysplasia (CLSD) is a rare dysmorphic syndrome characterized by skeletal dysmorphism, late-closing fontanels, and cataracts. CLSD is caused by mutations in the SEC23A gene (OMIM# 607812) and can be inherited in either an autosomal dominant or autosomal recessive pattern. To date, only four mutations have been reported to cause CLSD. This study aims to identify the disease-causing variants in a large cohort of congenital cataract patients, to expand the genotypic and phenotypic spectrum of CLSD, and to confirm the association between SEC23A and autosomal recessive CLSD (ARCLSD). METHODS: We collected detailed medical records and performed comprehensive ocular examinations and whole-exome sequencing (WES) on 115 patients with congenital cataracts. After suspecting that a patient may have CLSD based on the sequencing results, we proceeded to conduct transmission electron microscopy (TEM) on the cultured skin fibroblasts. The clinical validity of the reported gene-disease relationships for the gene and the disease was evaluated using the ClinGen gene curation framework. RESULTS: Two novel compound heterozygous variants (c.710A > C p.Asp237Ala, c.1946T > C p.Leu649Pro) of the SEC23A gene, classified as variant of uncertain significance, were identified in the proband with skeletal, cardiac, ocular, and hearing defects. The observation of typical distended endoplasmic reticulum cisternae further supported the diagnosis of CLSD. Application of the ClinGen gene curation framework confirmed the association between SEC23A and ARCLSD. CONCLUSION: This study expands the genotypic and phenotypic spectrum of CLSD, proposes TEM as a supplemental diagnostic method, and indicates that congenital cataracts are a typical sign of ARCLSD.

Refining and extending measures for fricative spectra, with special attention to the high-frequency rangea).

Fricatives have noise sources that are filtered by the vocal tract and that typically possess energy over a much broader range of frequencies than observed for vowels and sonorant consonants. This paper introduces and refines fricative measurements that were designed to reflect underlying articulatory and aerodynamic conditions These show differences in the pattern of high-frequency energy for sibilants vs non-sibilants, voiced vs voiceless fricatives, and non-sibilants differing in place of articulation. The results confirm the utility of a spectral peak measure (FM) and low-mid frequency amplitude difference (AmpD) for sibilants. Using a higher-frequency range for defining FM for female voices for alveolars is justified; a still higher range was considered and rejected. High-frequency maximum amplitude (Fh) and amplitude difference between low- and higher-frequency regions (AmpRange) capture /f-θ/ differences in English and the dynamic amplitude range over the entire spectrum. For this dataset, with spectral information up to 15 kHz, a new measure, HighLevelD, was more effective than previously used LevelD and Slope in showing changes over time within the frication. Finally, isolated words and connected speech differ. This work contributes improved measures of fricative spectra and demonstrates the necessity of including high-frequency energy in those measures.

Influence of Goniotomy Size on Treatment Safety and Efficacy for Primary Open-Angle Glaucoma: A Multicenter Study.

PURPOSE: To compare the efficacy and safety of 120-, 240-, and 360-degree goniotomy (GT) with or without phacoemulsification with intraocular lens implantation (PEI) for patients with primary open-angle glaucoma (POAG). DESIGN: Multicenter, retrospective, comparative, nonrandomized interventional study. METHODS: Patients diagnosed with POAG who underwent GT with or without PEI were included, and divided into 6 groups: 1) standalone 120-degree GT (120GT); 2) standalone 240-degree GT (240GT); 3) standalone 360-degree GT (360GT); 4) PEI + 120GT; 5) PEI + 240GT; and 6) PEI + 360GT. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. Success was defined as a postoperative IOP within the range of 6 to 18 mm Hg and a 20% reduction from baseline without further glaucoma surgery. Complete success and qualified success were defined as the above without and with ocular hypotensive medications, respectively. RESULTS: Three hundred eight eyes of 231 patients were included with a mean follow-up of 14.4 ± 8.6 months (6.0-48.0 months). There were no significant differences in the reductions in IOP and number of medications and cumulative survival probability for complete and qualified success rates among the 3 groups of standalone GT and PEI + GT. The 360GT group had the highest proportion of hyphema with or without PEI. CONCLUSIONS: 120GT, 240GT, and 360GT with or without PEI showed similar efficacy in reducing IOP and medications used in POAG. 360GT with or without PEI was more likely to cause hyphema compared with 120GT or 240GT. 120GT with or without PEI was sufficient for treating POAG with or without cataract..

Poor immunogenicity upon SARS-CoV-2 mRNA vaccinations in autoimmune SLE patients is associated with pronounced EF-mediated responses and anti-BAFF/Belimumab treatment.

Novel mRNA vaccines have resulted in a reduced number of SARS-CoV-2 infections and hospitalizations. Yet, there is a paucity of studies regarding their effectiveness on immunocompromised autoimmune subjects. In this study, we enrolled subjects naïve to SARS-CoV-2 infections from two cohorts of healthy donors (HD, n=56) and systemic lupus erythematosus (SLE, n=69). Serological assessments of their circulating antibodies revealed a significant reduction of potency and breadth of neutralization in the SLE group, only partially rescued by a 3rd booster dose. Immunological memory responses in the SLE cohort were characterized by a reduced magnitude of spike-reactive B and T cell responses that were strongly associated with poor seroconversion. Vaccinated SLE subjects were defined by a distinct expansion and persistence of a DN2 spike-reactive memory B cell pool and a contraction of spike-specific memory cTfh cells, contrasting with the sustained germinal center (GC)-driven activity mediated by mRNA vaccination in the healthy population. Among the SLE-associated factors that dampened the vaccine responses, treatment with the monoclonal antibody anti-BAFF/Belimumab (a lupus FDA-approved B cell targeting agent) profoundly affected the vaccine responsiveness by restricting the de novo B cell responses and promoting stronger extra-follicular (EF)-mediated responses that were associated with poor immunogenicity and impaired immunological memory. In summary, this study interrogates antigen-specific responses and characterized the immune cell landscape associated with mRNA vaccination in SLE. The identification of factors associated with reduced vaccine efficacy illustrates the impact of SLE B cell biology on mRNA vaccine responses and provides guidance for the management of boosters and recall vaccinations in SLE patients according to their disease endotype and modality of treatment.

SLE Antibody-Secreting Cells Are Characterized by Enhanced Peripheral Maturation and Survival Programs.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by multiple autoantibodies, some of which are present in high titers in a sustained, B cell-independent fashion consistent with their generation from long-lived plasma cells (LLPC). Active SLE displays high numbers of circulating antibody-secreting cells (ASC). Understanding the mechanisms of generation and survival of SLE ASC would contribute important insight into disease pathogenesis and novel targeted therapies. We studied the properties of SLE ASC through a systematic analysis of their phenotypic, molecular, structural, and functional features. Our results indicate that in active SLE, relative to healthy post-immunization responses, blood ASC contain a much larger fraction of newly generated mature CD19- CD138+ ASC similar to bone marrow (BM) LLPC. SLE ASC were characterized by morphological and structural features of premature maturation. Additionally, SLE ASC express high levels of CXCR4 and CD138, and molecular programs consistent with increased longevity based on pro-survival and attenuated pro-apoptotic pathways. Notably, SLE ASC demonstrate autocrine production of APRIL and IL-10 and experience prolonged in vitro survival. Combined, our findings indicate that SLE ASC are endowed with enhanced peripheral maturation, survival and BM homing potential suggesting that these features likely underlie BM expansion of autoreactive PC.

MIR34A modulates lens epithelial cell apoptosis and cataract development via the HK1/caspase 3 signaling pathway.

Cataracts are the leading cause of blindness in the world. Age is a major risk factor for cataracts, and with increasing aging, the burden of cataracts will grow, but the exact details of cataractogenesis remain unclear. A recent study showed that microRNA-34a (MIR34A) is involved in the development of cataracts, but the underlying pathogenesis remains obscure. Here, our results of microRNA target prediction showed that hexokinase 1 (HK1) is one of the genes targeted by MIR34A. Based on this finding, we focused on the function of MIR34A and HK1 in the progress of cataracts, whereby the human lens epithelial cell line SRA01/04 and mouse lens were treated with MIR34A mimics and HK1 siRNA. We found that HK1 mRNA is a direct target of MIR34A, whereby the high expression of MIR34A in the cataract lens suppresses the expression of HK1. In vitro, the upregulation of MIR34A together with the downregulation of HK1 inhibits the proliferation, induces the apoptosis of SRA01/04 cells, and accelerates the opacification of mouse lenses via the HK1/caspase 3 signaling pathway. In summary, our study demonstrates that MIR34A modulates lens epithelial cell (LEC) apoptosis and cataract development through the HK1/caspase 3 signaling pathway.

"Capsule drape wrap"-a new technology for iridoschisis management during phacoemulsification.

AIM: To introduce a new technique for iridoschisis management during phacoemulsification: "capsule drape wrap". METHODS: "Capsule drape wrap" technique was used for an 80-year-old man with idiopathic iridoschisis in the right eye during phacoemulsification. The inserted flexible nylon iris hooks to hold anterior capsule in place, the margin of the anterior capsule could act as drape wrap, tracking the fibrillary iris strands firmly from free floating and stabilizing the capsular bags simultaneously. RESULTS: The eye with iridoschisis was successfully treated. Iris fibrils remained immobile during the procedure, and despite the severity of iridoschisis, there were no intraoperative complications such as tear of the iris, hyphema, iris prolapse, loss of mydriasis, or rupture of the posterior lens capsule during phacoemulsification. The best-corrected visual acuity was increased by 0.1 (logMAR) 6mo after the surgery. CONCLUSION: "Capsule drape wrap" for iridoschisis is easily manageable, prevents further disruption to the loose iris fibers and ensures the stability of capsule-iris complex simultaneously, consequently minimizing the risk of surgical complications in phacoemulsification.

An acoustic study of Cantonese alaryngeal speech in different speaking conditions.

Esophageal (ES) speech, tracheoesophageal (TE) speech, and the electrolarynx (EL) are common methods of communication following the removal of the larynx. Our recent study demonstrated that intelligibility may increase for Cantonese alaryngeal speakers using clear speech (CS) compared to their everyday "habitual speech" (HS), but the reasoning is still unclear [Hui, Cox, Huang, Chen, and Ng (2022). Folia Phoniatr. Logop. 74, 103-111]. The purpose of this study was to assess the acoustic characteristics of vowels and tones produced by Cantonese alaryngeal speakers using HS and CS. Thirty-one alaryngeal speakers (9 EL, 10 ES, and 12 TE speakers) read The North Wind and the Sun passage in HS and CS. Vowel formants, vowel space area (VSA), speaking rate, pitch, and intensity were examined, and their relationship to intelligibility were evaluated. Statistical models suggest that larger VSAs significantly improved intelligibility, but slower speaking rate did not. Vowel and tonal contrasts did not differ between HS and CS for all three groups, but the amount of information encoded in fundamental frequency and intensity differences between high and low tones positively correlated with intelligibility for TE and ES groups, respectively. Continued research is needed to understand the effects of different speaking conditions toward improving acoustic and perceptual characteristics of Cantonese alaryngeal speech.