Evaluation of Optical Tracking to Distinguish Surgeon Experience During Endoscopic Stone Surgery.

Introduction and Objectives: Optical tracking (OT) has shown potential in assessing surgical skill but has yet to be evaluated for endoscopic urologic surgery. We sought to evaluate the potential for OT to distinguish expert and trainee surgeons during flexible ureteroscopy (fURS) for kidney stone treatment in both simulated and live surgical settings. Methods: We performed OT analysis of six surgeons performing stone localization during fURS in two settings. In the first setting, surgeons were tasked with fiducial localization in three separate kidney phantoms during fURS. In the second setting, surgeons performed stone localization via fURS in five separate patients. Surgeons were categorized as "expert" (n = 3, endourologist, average case volume of >100 fURS per year) or trainee (n = 3, trainee, <100 fURS per year). OT metrics were recorded for both settings using the Microsoft HoloLens 2© as the surgeons viewed the surgical monitor during fURS. Standard OT metrics of experts and trainees were compared, and included: area of eye gaze movement, gaze distance traveled, number of gaze fixation points, percentage of gaze fixation dwell time, and number of saccades. Results: In the simulated setting, the average time for stone localization was greater for trainees compared to experts (318 seconds vs 52 seconds, p < 0.01). Additionally, the mean area of eye gaze movements with area of interest (AOI) was greater for trainees compared to experts (1430 cm2 vs 1060 cm2, p < 0.01). The total gaze distance traveled was also greater for trainees compared to experts (1480 cm vs 730 cm, p < 0.01). In the live surgical setting, average time for stone localization was similar for trainees and experts (74 seconds vs 51 seconds, p = 0.05). The total area of eye gaze movements in AOI was greater for trainees compared to experts (700 cm2 vs 30 cm2, p < 0.01). Additionally, the total gaze distance traveled was greater for trainees compared to experts (14,000 cm vs 680 cm, p < 0.01). This suggests more varied and less point specific concentration on the surgical screen by trainees. There was no difference in percentage of gaze fixation dwell time and number of saccades between experts and trainees in either setting. Conclusions: OT analysis can objectively distinguish surgical experience between experts and trainee surgeons performing fURS in both simulated and live surgical settings. These findings may play a role in future surgical training and skills assessment.

Changing indications for and trends of keratoplasty in a tertiary comprehensive hospital in northern part of China from 2002 to 2021: a 20-year review.

OBJECTIVE: To investigate indications and surgical procedures of keratoplasty in a tertiary comprehensive hospital in northern part of China over a 20-year period. METHODS: All patients undergoing keratoplasty between January 1, 2002 to December 31, 2021 in a tertiary comprehensive hospital in northern part of China were retrospectively reviewed. The annual proportion of keratoplasty indications and surgical procedures was recorded and analyzed. RESULTS: A total of 8266 keratoplasty procedures were included. Leading indications were keratoleukoma (n = 2108, 25.50%), followed by regraft (n = 1453 ,17.58%), corneal endothelial dysfunction (n = 1085, 13.13%), and keratoconus (n = 922,11.15%). A decreasing trend was observed for keratoleukoma (P < 0.01) and an increasing trend for corneal endothelial dysfunction (P < 0.01), regraft (P = 0.012), corneal limbal dermoids (P < 0.01) and congenital corneal opacity (P < 0.01). From 2002 to 2021, the proportion of penetrating keratoplasty (PK) had decreased from 73.95% (2002 to 2006) to 53.49% (2017 to 2021). On contrary, anterior lamellar keratoplasty (ALK) (459-705, 26.05-31.96%, P = 0.034) and endothelial keratoplasty (EK) (0-321, 0.00-14.55%, P < 0.01) became more prevalent from 2002 to 2021. For cases with corneal endothelial dysfunction, EK became the preferred technique (74.72%) in the recent 5 years. CONCLUSION: Over the past 20 years, keratoleukoma and regraft have been the leading indications for keratoplasty. A noticeable shift in surgical preference from PK to DSAEK and ALK is evident, with key indications for keratoplasty including keratoleukoma, regraft, limbal dermoids, endothelial dysfunction, and keratoconus, respectively.

HIF1α Counteracts TGFß1-Driven TSP1 Expression in Endothelial Cells to Stimulate Angiogenesis in the Hypoxic Tumor Microenvironment.

Emerging evidence suggests that transforming growth factor ß1 (TGFß1) can inhibit angiogenesis, contradicting the coexistence of active angiogenesis and high abundance of TGFß1 in the tumor microenvironment. Here, we investigated how tumors overcome the anti-angiogenic effect of TGFß1. TGFß1 treatment suppressed physiological angiogenesis in chick chorioallantoic membrane and zebrafish models but did not affect angiogenesis in mouse hepatoma xenografts. The suppressive effect of TGFß1 on angiogenesis was recovered in mouse xenografts by a hypoxia-inducible factor 1α (HIF1α) inhibitor. In contrast, a HIF1α stabilizer abrogated angiogenesis in zebrafish, indicating that hypoxia may attenuate the anti-angiogenic role of TGFß1. Under normoxic conditions, TGFß1 inhibited angiogenesis by upregulating anti-angiogenic factor thrombospondin 1 (TSP1) in endothelial cells (ECs) via TGFß type I receptor (TGFßR1)-SMAD2/3 signaling. In a hypoxic microenvironment, HIF1α induced microRNA-145 (miR145) expression; miR145 abolished the inhibitory effect of TGFß1 on angiogenesis by binding and repressing SMAD2/3 expression and subsequently reducing TSP1 levels in ECs. Primary ECs isolated from human hepatocellular carcinoma (HCC) displayed increased miR145 and decreased SMAD3 and TSP1 compared to ECs from adjacent non-tumor livers. The reduced SMAD3 or TSP1 in ECs was associated with increased angiogenesis in HCC tissues. Collectively, this study identified that TGFß1-TGFßR1-SMAD2/3-TSP1 signaling in ECs inhibits angiogenesis. This inhibition can be circumvented by a hypoxia-HIF1α-miR145 axis, elucidating a mechanism by which hypoxia promotes angiogenesis.

Spatial and Single-Cell Transcriptomics Reveals the Regional Division of the Spatial Structure of MASH Fibrosis.

OBJECTIVE: To elucidate the regional distribution of metabolic dysfunction-associated steatohepatitis (MASH) fibrosis within the liver and to identify potential therapeutic targets for MASH fibrosis. METHODS: Liver sections from healthy controls, patients with simple steatosis and MASH patients were analysed using spatial transcriptomics integrated with single-cell RNA-seq. RESULTS: Spatial transcriptomics analysis of liver tissues revealed that the fibrotic region (Cluster 9) was primarily distributed in lobules, with some fibrosis also found in the surrounding area. Integration of the single-cell-sequencing data set (GSE189175) showed a greater proportion of inflammatory cells (Kupffer cells and T cells) and myofibroblasts in MASH. Six genes, showing high- or low-specific expression in Cluster 9, namely, ADAMTSL2, PTGDS, S100A6, PPP1R1A, ASS1 and G6PC, were identified in combination with pathology. The average expression levels of ADAMTSL2, PTGDS and S100A6 on the pathological HE staining map were positively correlated with the increase in the degree of fibrosis and aligned strongly with the distribution of fibrosis. ADAMTSL2+ myofibroblasts play a role in TNF signalling pathways and in the production of ECM structural components. Pseudotime analysis indicated that in the early stages of MASH, infiltration by T cells and Kupffer cells triggers a significant inflammatory response. Subsequently, this inflammation leads to the activation of hepatic stellate cells (HSCs), transforming them into myofibroblasts and promoting the development of liver fibrosis. CONCLUSION: This study is the first to characterise lineage-specific changes in gene expression, subpopulation composition, and pseudotime analysis in MASH fibrosis and reveals potential therapeutic targets for this condition.

Zero-shot prompt-based video encoder for surgical gesture recognition.

PURPOSE: In order to produce a surgical gesture recognition system that can support a wide variety of procedures, either a very large annotated dataset must be acquired, or fitted models must generalize to new labels (so-called zero-shot capability). In this paper we investigate the feasibility of latter option. METHODS: Leveraging the bridge-prompt framework, we prompt-tune a pre-trained vision-text model (CLIP) for gesture recognition in surgical videos. This can utilize extensive outside video data such as text, but also make use of label meta-data and weakly supervised contrastive losses. RESULTS: Our experiments show that prompt-based video encoder outperforms standard encoders in surgical gesture recognition tasks. Notably, it displays strong performance in zero-shot scenarios, where gestures/tasks that were not provided during the encoder training phase are included in the prediction phase. Additionally, we measure the benefit of inclusion text descriptions in the feature extractor training schema. CONCLUSION: Bridge-prompt and similar pre-trained + prompt-tuned video encoder models present significant visual representation for surgical robotics, especially in gesture recognition tasks. Given the diverse range of surgical tasks (gestures), the ability of these models to zero-shot transfer without the need for any task (gesture) specific retraining makes them invaluable.

Age-related analysis of corneal biomechanical parameters in healthy Chinese individuals.

To report the correlation between corneal biomechanical parameters and age in healthy Chinese individuals. This cross-sectional study was conducted on 864 eyes of 543 healthy participants. A comprehensive ophthalmic examination and corneal biomechanics examination using Corneal Visualization Scheimpflug Technology (Corvis ST) were conducted. Based on age, all participants were further divided into five age groups (n) as follows: group A, 11-20 years (105); group B, 21-30 years (112); group C, 31-40 years (113); group D, 41-50 years (100); and group E, > 50 years (113). Using Corvis ST, we examined 35 corneal biomechanical parameters and compared them across the different age groups. Spearman's correlation coefficients and stepwise multivariate linear regression models were used to investigate whether the corneal biomechanical parameters were related to demographic and ocular characteristics. A correlation analysis between the left and right eyes revealed that 13 parameters were significantly associated with eye differences. Among the 35 corneal biomechanical parameters, 28 exhibited significant differences across the age groups, with stiffness parameter at applanation 1(SPA1) showing an upward trend after the age of 30 and stress-strain index (SSI) demonstrates a statistically significant upward trend when comparing the five age groups in the study. Additionally, Spearman's correlation analysis and stepwise multivariate linear regression analysis revealed that 11 corneal biomechanical parameters were positively correlated with age and 10 were negatively correlated with age. Corvis biomechanical index (CBI) was significantly negatively correlated with intraocular pressure (IOP) and central corneal thickness (CCT), SSI was significantly positively correlated with age and IOP, and SPA1 were positively correlated with IOP and CCT. In conclusion, most corneal biomechanical parameters showed a significant correlation with age, with corneal stiffness progressively increasing alongside advancing age, IOP, or CCT.

BMAL1 deficiency provokes dry mouth and eyes by down-regulating ITPR2/3.

Secretory glands, responsible for tears and saliva production, play essential roles in maintaining ocular and oral well-being. Disruptions in gland secretion can arise from various factors, including rhythm disturbances associated with sleep disorders. However, the underlying mechanisms governing these disruptions remain largely unexplored. We demonstrate that BMAL1, a core component of the circadian system, plays a critical role in regulating secretory gland secretion. Loss of BMAL1 induces vacuolation and atrophy phenotypes in acinar cells, subsequently leading to cell apoptosis and gland hypofunction, but does not cause Sjogren's syndrome, which is characterized by localized inflammatory cell infiltration. Mechanically, BMAL1 directly modulates the transcription of ITPR2 and ITPR3, thereby altering the secretion of Lactoferrin and Lysozyme. Restoration of ITPR2 and ITPR3 expression in Bmal1-deficient rats effectively alleviated the symptoms of lacrimal and parotid glands secretory dysfunction and significantly reduced dry mouth and dry eye conditions in rhythm-disordered rats. These findings highlight the essential role of BMAL1 in regulating salivary and lacrimal gland secretion and suggest a novel therapeutic approach for treating dry mouth and dry eyes associated with rhythm disorders.

Comparison of upper eyelid pressure and ocular surface parameters in dry eye disease and benign essential Blepharospasm: A cross-sectional study.

PURPOSE: To compare the upper eyelid pressure (UEP) and ocular surface parameters between dry eye disease (DED) and DED coexisting with benign essential blepharospasm (BEB), exploring which parameters could assist in distinguishing between DED and BEB, as potential risk factors for DED with BEB. METHODS: All enrolled participants diagnosed with DED or DED coexisting with BEB were initially subjected to ocular surface disease index (OSDI) determination. Subsequently, the upper eyelid pressure was recorded using an innovative eyelid pressure measurement device, followed by a series of ocular surface examinations. The two groups were compared using the independent t-test and Mann-Whitney U test. A logistic regression analysis was performed to identify which parameters can predict the onset of blepharospasm. RESULTS: The BEB group achieved a higher upper eyelid pressure (101.9 ± 23.5mN vs 88.4 ± 18.1mN, P = 0.009), lower number of total blink (6.2 ± 4.2 vs 7.1 ± 4.1, P = 0.016), higher corneal fluorescein staining score (4.0 ± 1.9 vs 3.0 ± 1.7, P = 0.046), higher partial blink rate (0.9 ± 0.2 vs 0.5 ± 0.4, P = 0.000) and the lower grade of meibum expressibility (1 (1, 2) vs 2 (1, 3), P = 0.000) and meibum quality (1 (1, 1) vs 1 (1, 1), P = 0.033) compared with the DED group. The upper eyelid pressure (OR = 1.123), partial blink rate (OR = 0.014) and the grade of meibum expressibility (OR = 10.804) showed significant associations with BEB (P < 0.05). CONCLUSION: Despite similar OSDI scores, DED coexisting with BEB exhibited higher upper eyelid pressure, lower corneal fluorescein staining score, lower partial blink rate, more total blinks, lower grades of meibum expressibility, and lower meibum quality compared to DED alone. Among these, higher upper eyelid pressure, lower partial blink rate, and worse grade of meibum expressibility were identified as risk factors for BEB in DED.

Investigation of traditional Chinese medicine constitution in individuals afflicted by dry eye disease: A retrospective study.

The aim of this study is to explore the traditional Chinese medicine (TCM) constitution among individuals suffering from dry eye disease. Following the diagnostic criteria outlined in TFO DEWS II, a total of 114 patients with dry eye were included in this study. Based on the classification criteria for dry eye, the patients were categorized into 3 distinct dry eye subtypes. Each participant underwent a thorough clinical assessment for dry eye, and their TCM pattern manifestations were assessed using the "Traditional Chinese Medicine Questionnaire for Dry Eye." The Nine Constitutions Assessment Method was utilized for TCM pattern differentiation and classification. Spearman's correlation analysis was employed to investigate the associations between TCM constitution and dry eye subtypes, clinical indicators, and the relationships between TCM syndromes and dry eye subtypes. Among the 114 patients, the Qi-Stagnation constitution was the most common, with variations in constitution distribution among different dry eye subtypes. Significant correlations were observed between the Blood-Stasis, Yin-Deficiency, Qi-Deficiency, and Yang-Deficiency constitutions and 2, 4, 1, and 4 dry eye indicators, respectively. Spearman's analysis revealed that 5 out of 50 TCM syndromes were associated with mixed dry eye, 5 with evaporative dry eye, and 3 with aqueous tear deficiency dry eye. Further analysis, using lasso regression and binary unconditional logistic regression identified dizziness, lumbago, and weakness as influencing factors for both mixed-type and evaporative-type dry eye. In this study, we extensively examined the TCM constitution in individuals with dry eye, offering valuable insights and guiding future TCM-related research in the context of dry eye. Additionally, we established correlations between TCM syndrome patterns and dry eye indicators.

Heating-driven self-assembled glycyrrhizin nanomicelles loading bisdemethoxycurcumin: Preparation, characterization, and efficacy evaluation on experimental dry eye.

In this study, a simple but novel preparation method was developed by heating a mixture of dipotassium glycyrrhizinate (DG) and bisdemethoxycurcumin (BDMC) in aqueous solution, and a DG self-assembled nanomicelles-loading BDMC (named B@DNM) ophthalmic solution was successfully fabricated with this heating-driven process. AutoDock simulation analysis revealed that Pi-Alkyl hydrophobic interactions between BDMC and DG played important role in this self-assembled B@DNM. The optimized B@DNM, with a DG:BDMC mass ratio of 40:1 and heating time of 6 h, had a high encapsulation efficacy of 96.70 ± 0.13 % and particle sizes of 117.50 ± 6.07 nm. The apparent solubility of BDMC in B@DNM was significantly improved from bare BDMC (10.40 ± 0.16 µg/ml to 1405.60 ± 6.78 µg/ml) in artificial tears after 4 h incubation. B@DNM had great storage stability as an aqueous ophthalmic solution. B@DNM showed significantly improved in vitro antioxidant activity. Ex vivo hen's egg test-chorioallantoic membrane assay and long-term in vivo mouse eye tolerance evaluation showed that B@DNM had good ocular safety profiles. B@DNM showed improved in vivo corneal permeation profiles in the mouse eyes. Topical administration of B@DNM achieved a significantly improved efficacy on a mouse model of dry eye disease (DED), including accelerating corneal wound healing, restoring corneal sensitivity, and inhibiting corneal neovascularization. Regulation of the high mobility group box 1 signal pathway was involved in B@DNM's strong therapeutic effects. These findings demonstrate that heating is a simple method to prepare ocular nanoformulation with DG, and B@DNM might be a potential ocular drug for treating DED.

Factors influencing healthcare providers' behaviours in deprescribing: a cross-sectional study.

Introduction: Deprescribing serves as a pivotal measure to mitigate the drug-related problem due to polypharmacy. This study aimed to map the factors influencing healthcare providers' deprescribing decision using the Behaviour Change Wheel framework and develop an innovative conceptual model to support deprescribing practice. Methods: A cross-sectional online survey targeting doctors and pharmacists was conducted to assess the influence of various factors on healthcare providers' comfort in recommending deprescribing. The conceptual model was formulated, based on the existing deprescribing framework and the Behaviour Change Wheel. The model's robustness was scrutinised through Partial Least Squares Structural Equation Modeling (PLS-SEM), and model-fitting indices were employed to obtain the best-fit model. Results: A total of 736 responses were analysed with the final best-fit model consisting of 24 items in 5 constructs (R 2: 0.163; SRMR: 0.064; rho_c: 0.750-0.862; AVE: 0.509-0.627) and three independent factors. Based on the results, we proposed that deprescribing could be promoted through strategies aimed at enhancing healthcare providers internal capabilities such as knowledge levels, when patients' condition deteriorated and previous experiences with adverse events of drugs. Organisational support in providing such educational opportunities is important, with the empowerment of patient and healthcare providers through policy enhancements, guideline development, and effective communication. Conclusion: The deprescribing behaviours of healthcare professionals are influenced by an intricate interplay of patient, prescriber, and system factors. Enhancing deprescribing practices necessitates a comprehensive strategy that encompasses providers and patients' education, the development of structured deprescribing guidelines, the implementation of deprescribing support tools, and the enhancement of communication between healthcare providers.

Controlled aggregation of Pt/PtH/Rh/RhH doped silver superatomic nanoclusters into 16-electron supermolecules.

The assembly of discrete superatomic nanoclusters into larger constructs is a significant stride towards developing a new set of artificial/pseudo-elements. Herein, we describe a novel series of 16-electron supermolecules derived from the combination of discrete 8-electron superatomic synthons containing interstitial hydrides as vertex-sharing building blocks. The symmetric (RhH)2Ag33[S2P(OPr)2]17 (1) and asymmetric PtHPtAg32[S2P(OPr)2]17 (2) are characterized by ESI-MS, SCXRD, NMR, UV-vis absorption spectra, electrochemical and computational methods. Cluster 1 represents the first group 9-doped 16-electron supermolecule, composed of two icosahedral (RhH)@Ag12 8-electron superatoms sharing a silver vertex. Cluster 2 results from the assembly of two distinct icosahedral units, Pt@Ag12, and (PtH)@Ag12. In both cases, the presence of the interstitial hydrides is unprecedented. The stability of the supermolecules is investigated, and 2 spontaneously transforms into Pt2Ag33[S2P(OPr)2]17 (3) with thermal treatment. The lability of the hydride within the icosahedral framework in solution at low-temperature was confirmed by the VT-NMR.

Retrospective analysis of molecular characteristics, risk factors, and outcomes in carbapenem-resistant Klebsiella pneumoniae bloodstream infections.

BACKGROUND: Klebsiella pneumoniae (KP) is the second most prevalent Gram-negative bacterium causing bloodstream infections (BSIs). In recent years, the management of BSIs caused by KP has become increasingly complex due to the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP). Although numerous studies have explored the risk factors for the development of CRKP-BSIs, the mortality of patients with KP-BSIs, and the molecular epidemiological characteristics of CRKP, the variability in data across different populations, countries, and hospitals has led to inconsistent conclusions. In this single-center retrospective observational study, we utilized logistic regression analyses to identify independent risk factors for CRKP-BSIs and factors associated with mortality in KP-BSI patients. Furthermore, a risk factor-based prediction model was developed. CRKP isolates underwent whole-genome sequencing (WGS), followed by an evaluation of microbiological characteristics, including antimicrobial resistance and virulence genes, as well as epidemiological characteristics and phylogenetic analysis. RESULTS: Our study included a total of 134 patients with KP-BSIs, comprising 50 individuals infected with CRKP and 84 with carbapenem-susceptible Klebsiella pneumoniae (CSKP). The independent risk factors for CRKP-BSIs were identified as gastric catheterization (OR = 9.143; CI = 1.357-61.618; P = 0.023), prior ICU hospitalization (OR = 4.642; CI = 1.312-16.422; P = 0.017), and detection of CRKP in non-blood sites (OR = 8.112; CI = 2.130-30.894; P = 0.002). Multivariate analysis revealed that microbiologic eradication after 6 days (OR = 3.569; CI = 1.119-11.387; P = 0.032), high Pitt bacteremia score (OR = 1.609; CI = 1.226-2.111; P = 0.001), and inappropriate empirical treatment after BSIs (OR = 6.756; CI = 1.922-23.753; P = 0.003) were independent risk factors for the 28-day mortality in KP-BSIs. The prediction model confirmed that microbiologic eradication after 6.5 days and a Pitt bacteremia score of 4.5 or higher were significant predictors of the 28-day mortality. Bioinformatics analysis identified ST11 as the predominant CRKP sequence type, with blaKPC-2 as the most prevalent gene variant. CRKP stains carried multiple plasmid-mediated resistance genes along with some virulence genes. Phylogenetic analysis indicated the presence of nosocomial transmission of ST11 CRKP within the ICU. CONCLUSIONS: The analysis of risk factors for developing CRKP-BSIs and the association between KP-BSIs and 28-day mortality, along with the development of a risk factor-based prediction model and the characterization of CRKP strains, enhances clinicians' understanding of the pathogens responsible for BSIs. This understanding may help in the timely administration of antibiotic therapy for patients with suspected KP-BSIs, potentially improving outcomes.

More than meets the eye: Augmented reality in surgical oncology.

BACKGROUND AND OBJECTIVES: In the field of surgical oncology, there has been a desire for innovative techniques to improve tumor visualization, resection, and patient outcomes. Augmented reality (AR) technology superimposes digital content onto the real-world environment, enhancing the user's experience by blending digital and physical elements. A thorough examination of AR technology in surgical oncology has yet to be performed. METHODS: A scoping review of intraoperative AR in surgical oncology was conducted according to the guidelines and recommendations of The Preferred Reporting Items for Systematic Review and Meta-analyzes Extension for Scoping Reviews (PRISMA-ScR) framework. All original articles examining the use of intraoperative AR during surgical management of cancer were included. Exclusion criteria included virtual reality applications only, preoperative use only, fluorescence, AR not specific to surgical oncology, and study design (reviews, commentaries, abstracts). RESULTS: A total of 2735 articles were identified of which 83 were included. Most studies (52) were performed on animals or phantom models, while the remaining included patients. A total of 1112 intraoperative AR surgical cases were performed across the studies. The most common anatomic site was brain (20 articles), followed by liver (16), renal (9), and head and neck (8). AR was most often used for intraoperative navigation or anatomic visualization of tumors or critical structures but was also used to identify osteotomy or craniotomy planes. CONCLUSIONS: AR technology has been applied across the field of surgical oncology to aid in localization and resection of tumors.

Feasibility, safety and outcomes of conduction system pacing for bradycardia amongst the very elderly.

The impact of age (≥ 85 vs < 85 years) on clinical outcomes and pacemaker performance of conduction system pacing (CSP) compared to right ventricular pacing (RVP) were examined. Consecutive patients from a prospective, observational, multicenter study with pacemakers implanted for bradycardia were studied. The primary endpoint was a composite of heart failure (HF)-hospitalizations, pacing-induced cardiomyopathy requiring cardiac resynchronization therapy or all-cause mortality. Secondary endpoints were acutely successful CSP, absence of pacing-complications, optimal pacemaker performance defined as pacing thresholds < 2.5 V, R-wave amplitude ≥ 5 V and absence of complications, threshold stability (no increases of > 1 V) and persistence of His-Purkinje capture on follow-up. Among 984 patients (age 74.1 ± 11.2 years, 41% CSP, 16% ≥ 85 years), CSP was independently associated with reduced hazard of the primary endpoint compared to RVP, regardless of age-group (< 85 years: adjusted hazard ratio [AHR] 0.63, 95% confidence interval [CI] 0.40-0.98; ≥ 85 years: AHR 0.40, 95% CI 0.17-0.94). Among patients with CSP, age did not significantly impact the secondary endpoints of acute CSP success (86% vs 88%), pacing complications (19% vs 11%), optimal pacemaker performance (64% vs 69%), threshold stability (96% vs 96%) and persistent His-Purkinje capture (86% vs 91%) on follow-up (all p > 0.05). CSP improves clinical outcomes in all age-groups, without compromising procedural safety or pacemaker performance in the very elderly.

Ocular surface in patients with different degrees of myopia.

AIM: To investigate the clinical features of the ocular surface in patients with different degrees of myopia. METHODS: A cross-sectional study was conducted involving 122 participants with myopia in Beijing Tongren Hospital from February to June, 2023. After completing the Ocular Surface Disease Index (OSDI) score scale, measurements were taken for refraction, biometric parameters and ocular surface parameters. The prevalence, severity and related parameters of the dry eye among different groups based on axial length (AL) were compared. Correlation analysis was performed between ocular surface parameters and refraction/biometric measurement parameters. RESULTS: Statistically significant differences were observed in refractive error, corneal thickness, anterior chamber depth, and subfoveal choroidal thickness among the groups (all P<0.05). With the increase in AL, the incidence and severity of dry eye increased significantly (P<0.05). Moreover, the tear film break-up time (BUT) shortened (P<0.05), and the corneal fluorescein staining (CFS) points increased significantly (P<0.05). OSDI scores were positively correlated with AL and spherical equivalent (SE; both P<0.05); BUT was negatively correlated with AL, SE, and corneal astigmatism (AST; all P<0.05); Schirmer I test (SIT) results were negatively correlated with AL and SE (both P<0.05). CONCLUSION: AL elongation is a risk factor for dry eye onset in myopic participants. The longer the AL, the more severe the dry eye is, with the increased CFS spots and tear film instability. Additionally, SE and AST exhibit negative correlations with dry eye symptom scores and ocular surface parameters.

[Applications of native mass spectrometry and ultraviolet photodissociation in protein structure and interaction analysis].

Dynamic changes in the structures and interactions of proteins are closely correlated with their biological functions. However, the precise detection and analysis of these molecules are challenging. Native mass spectrometry (nMS) introduces proteins or protein complexes into the gas phase by electrospray ionization, and then performs MS analysis under near-physiological conditions that preserve the folded state of proteins and their complexes in solution. nMS can provide information on stoichiometry, assembly, and dissociation constants by directly determining the relative molecular masses of protein complexes through high-resolution MS. It can also integrate various MS dissociation technologies, such as collision-induced dissociation (CID), surface-induced dissociation (SID), and ultraviolet photodissociation (UVPD), to analyze the conformational changes, binding interfaces, and active sites of protein complexes, thereby revealing the relationship between their interactions and biological functions. UVPD, especially 193 nm excimer laser UVPD, is a rapidly evolving MS dissociation method that can directly dissociate the covalent bonds of protein backbones with a single pulse. It can generate different types of fragment ions, while preserving noncovalent interactions such as hydrogen bonds within these ions, thereby enabling the MS analysis of protein structures with single-amino-acid-site resolution. This review outlines the applications and recent progress of nMS and UVPD in protein dynamic structure and interaction analyses. It covers the nMS techniques used to analyze protein-small-molecule ligand interactions, the structures of membrane proteins and their complexes, and protein-protein interactions. The discussion on UVPD includes the analysis of gas-phase protein structures and interactions, as well as alterations in protein dynamic structures, and interactions resulting from mutations and ligand binding. Finally, this review describes the future development prospects for protein analysis by nMS and new-generation advanced extreme UV light sources with higher brightness and shorter pulses.

Clinical Characteristics and Outcomes of Generalized Myasthenia Gravis in Malaysia: A Single-Center Experience.

BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is clinically heterogeneous and can be classified into subgroups according to the clinical presentation, antibody status, age at onset, and thymic abnormalities. This study aimed to determine the clinical characteristics and outcomes of generalized MG (GMG) patients based on these subgroups. METHODS: Medical records of MG patients from 1976 to 2023 were reviewed retrospectively. Patients with pure ocular MG were excluded. Data on demographic, clinical characteristics, laboratory features, and outcomes were analyzed. RESULTS: This study included 120 GMG patients. There was a slight preponderance of female patients over male patients (male:female ratio=1:1.3), with the age at onset exhibiting a bimodal distribution. Female patients peaked at a lower age (21-30 years) whereas male patients peaked at a higher age (61-70 years). Most (92%, 105 of 114) patients had positive anti-acetylcholine receptor antibodies. Five patients were also tested for anti-muscle-specific tyrosine kinase antibodies, with two showing positivity. Thymectomy was performed in 62 (52%) patients, of which 30 had thymoma, 16 had thymic hyperplasia, 7 had an involuted thymus, and 6 had a normal thymus. There were significantly more female patients (68% vs. 45%, p=0.011) with early-onset disease (<50 years old) and thymic hyperplasia (33% vs. 0%, p<0.025). Most (71%) of the patients had a good outcome based on the Myasthenia Gravis Foundation of America postintervention status. GMG patients with early-onset disease had a significantly better outcome than patients with a late onset in univariate (58% vs. 37%, p=0.041) and multivariate (odds ratio=4.68, 95% confidence interval=1.17-18.64, p=0.029) analyses. CONCLUSIONS: Female patients with early-onset MG and thymic hyperplasia had significantly better outcomes, but only early-onset disease was independently associated with a good outcome. These findings are comparable with those of other studies.

Importance of Circadian Rhythms in the Ocular Surface.

Circadian rhythms are a ubiquitous feature throughout the organism. Accumulating evidence suggests that the dysfunction of circadian rhythms due to genetic mutations or environmental factors contributes to the genesis and progress of multiple diseases. The physiological homeostasis of the ocular surface, like any other tissue or organ, is also orchestrated by circadian rhythms. In this review, we summarize the molecular clocks and the expression of clock-controlled genes in the mammalian ocular surface. Based on the circadian expression of these genes, we conclude the diurnal oscillations of cellular biological activities in the mammalian ocular surface. Moreover, we evaluate the factors entraining circadian oscillators in the ocular surface. Finally, we further discuss the latest development of the close correlation between circadian rhythms and ocular health. Briefly, this review aimed to synthesize the previous studies to aid in understanding the importance of circadian rhythms in the ocular surface and the possible opportunities for circadian rhythm-based interventional strategies to restore the homeostasis of the ocular surface.

Gene expression signature for predicting homologous recombination deficiency in triple-negative breast cancer.

Triple-negative breast cancers (TNBCs) are a subset of breast cancers that have remained difficult to treat. A proportion of TNBCs arising in non-carriers of BRCA pathogenic variants have genomic features that are similar to BRCA carriers and may also benefit from PARP inhibitor treatment. Using genomic data from 129 TNBC samples from the Malaysian Breast Cancer (MyBrCa) cohort, we developed a gene expression-based machine learning classifier for homologous recombination deficiency (HRD) in TNBCs. The classifier identified samples with HRD mutational signature at an AUROC of 0.93 in MyBrCa validation datasets and 0.84 in TCGA TNBCs. Additionally, the classifier strongly segregated HRD-associated genomic features in TNBCs from TCGA, METABRIC, and ICGC. Thus, our gene expression classifier may identify triple-negative breast cancer patients with homologous recombination deficiency, suggesting an alternative method to identify individuals who may benefit from treatment with PARP inhibitors or platinum chemotherapy.