A Transdermal Prion-Bionics Supermolecule as a RAB3A Antagonist for Enhancing Facial Youthfulness.

The mechanism research of skin wrinkles, conducted on volunteers underwent high-intensity desk work and mice subjected to partial sleep deprivation, revealed a significant reduction in dermal thickness associated with the presence of wrinkles. This can be attributed to the activation of facial nerves in a state of hysteria due to an abnormally elevated interaction between SNAP25 and RAB3A proteins involved in the synaptic vesicle cycle (SVC). Facilitated by AI-assisted structural design, a refined peptide called RSIpep is developed to modulate this interaction and normalize SVC. Drawing inspiration from prions, which possess the ability to protect themselves against proteolysis and invade neighboring nerve cells through macropinocytosis, RSIpep is engineered to demonstrate a GSH-responsive reversible self-assembly into a prion-like supermolecule (RSIprion). RSIprion showcases protease resistance, micropinocytosis-dependent cellular internalization, and low adhesion with constituent molecules in the cuticle, thereby endowing it with the transdermic absorption and subsequent biofunction in redressing the frenzied SVC. As a facial mud mask, it effectively reduces periorbital and perinasal wrinkles in the human face. Collectively, RSIprion not only presents a clinical potential as an anti-wrinkle prion-like supermolecule, but also exemplifies a reproducible instance of bionic strategy-guided drug development that bestows transdermal ability upon the pharmaceutical molecule.

Association between low lung function and the increased risk of age-related macular degeneration: A population-based prospective cohort study.

Background: Low lung function is associated with an increased risk of age-related diseases. However, the relationship between age-related macular degeneration (AMD), the leading cause of blindness, and lung function remains unclear. We aimed to investigate whether low lung function increases the risk of AMD and the potential mechanisms behind this association. Methods: We conducted a prospective cohort analysis of 409 230 UK Biobank participants with completed lung function after excluding individuals with AMD. We used Cox proportional hazards models to estimate the risk of AMD incidence and mediation models to explore potential mechanisms driven by inflammatory markers, erythrocyte-related measures, and metabolites. Results: Overall, 6477 AMD cases were diagnosed across an average of 12.4 years of follow-up. Participants with low lung function had an increased risk of developing AMD compared to those with high lung function (forced vital capacity: adjusted hazard ratio (aHR) = 1.20 (95% confidence interval (CI) = 1.07-1.34); forced expiratory volume in one second: aHR = 1.32 (95% CI = 1.18-1.47); peak expiratory flow: aHR = 1.32 (95% CI = 1.20-1.45)). Inflammatory markers and erythrocyte-related measures mediated this relationship, acting as a pathway through which low lung function influenced AMD. The interactions of body mass index (BMI), sex, and smoking were significant and the effect of lung function on AMD was higher in men, obese, and smoking populations. Conclusions: The increased risk of AMD was associated with low lung function, with inflammatory and erythrocyte-related markers mediating this relationship. This suggests that improvements in lung function could reduce the risk of AMD, thereby promoting health and longevity.

Clinical and Molecular Characterization of AIPL1-Associated Leber Congenital Amaurosis/Early-Onset Severe Retinal Dystrophy.

PURPOSE: This study aimed to characterize the clinical features, genetic findings, and genotype-phenotype correlations of patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD) harboring biallelic AIPL1 pathogenic variants. DESIGN: Retrospective case series. METHODS: This study consecutively enrolled 51 patients from 47 families with a clinical diagnosis of LCA/EOSRD harboring disease-causing variants in the AIPL1 gene, from October 2021 to September 2023. Molecular genetic findings, medical history, and ophthalmic evaluation including visual acuity (VA), multimodal retinal imaging, and electrophysiologic assessment were reviewed. RESULTS: Of the 51 patients (32 with LCA and 19 with EOSRD), 27 (53%) were females, and age at last review ranged from 0.5 to 58.4 years. We identified 28 disease-causing AIPL1 variants, with 18 being novel. In patients with EOSRD, the mean (range) VA was 1.3 (0.7-2.7) logMAR and 1.3 (0.5-2.3) logMAR for right and left eyes respectively, with an average annual decline of 0.03 logMAR (R2 = 0.7547, P < .01). For patients with LCA, the VA ranged from light perception to counting fingers. Optical coherence tomography imaging demonstrated preservation of foveal ellipsoid zone in the 5 youngest EOSRD patients and 9 LCA children. Electroretinography showed severe cone-rod patterns in 78.6% (11/14) of patients with EOSRD, while classical extinguished pattern was documented in all patients with LCA available for the examination. The most common mutation was the nonsense variants of c.421C>T, with an allele frequency of 53.9%. All patients with EOSRD carried at least one missense mutation, of whom 13 identified with c.152A>G and 5 with c.572T>C. Twenty-six patients with LCA harbored two null AIPL1 variants, while 18 were homozygous for c.421C>T and 6 were heterozygous for c.421C>T with another loss-of-function variant. CONCLUSIONS: This study reveals distinct clinical features and variation spectrum between AIPL1-associated LCA and EOSRD. Patients harboring at least one nonnull mutation, especially c.152A>G and c.572T>C, were significantly more likely to have a milder EOSRD phenotype than those with two null mutations. Residual foveal outer retinal structure observed in the youngest proportion of patients suggests an early window for gene augmentation therapy.

Beyond stiffness: Multiscale viscoelastic features as biomechanical markers for assessing cell types and states.

Cell mechanics are pivotal in regulating cellular activities, diseases progression, and cancer development. However, the understanding of how cellular viscoelastic properties vary in physiological and pathological stimuli remains scarce. Here, we develop a hybrid self-similar hierarchical theory-microrheology approach to accurately and efficiently characterize cellular viscoelasticity. Focusing on two key cell types associated with livers fibrosis-the capillarized liver sinusoidal endothelial cells and activated hepatic stellate cells-we uncover a universal two-stage power-law rheology characterized by two distinct exponents, αshort and αlong. The mechanical profiles derived from both exponents exhibit significant potential for discriminating among diverse cells. This finding suggests a potential common dynamic creep characteristic across biological systems, extending our earlier observations in soft tissues. Using a tailored hierarchical model for cellular mechanical structures, we discern significant variations in the viscoelastic properties and their distribution profiles across different cell types and states from the cytoplasm (elastic stiffness E1 and viscosity η), to a single cytoskeleton fiber (elastic stiffness E2), and then to the cell level (transverse expansion stiffness E3). Importantly, we construct a logistic-regression-based machine-learning model using the dynamic parameters that outperforms conventional cell-stiffness-based classifiers in assessing cell states, achieving an area under the curve of 97% vs. 78%. Our findings not only advance a robust framework for monitoring intricate cell dynamics but also highlight the crucial role of cellular viscoelasticity in discerning cell states across a spectrum of liver diseases and prognosis, offering new avenues for developing diagnostic and therapeutic strategies based on cellular viscoelasticity.

Extracellular cold-inducible RNA-binding protein mediated neuroinflammation and neuronal apoptosis after traumatic brain injury.

Background: Extracellular cold-inducible RNA-binding protein (eCIRP) plays a vital role in the inflammatory response during cerebral ischaemia. However, the potential role and regulatory mechanism of eCIRP in traumatic brain injury (TBI) remain unclear. Here, we explored the effect of eCIRP on the development of TBI using a neural-specific CIRP knockout (KO) mouse model to determine the contribution of eCIRP to TBI-induced neuronal injury and to discover novel therapeutic targets for TBI. Methods: TBI animal models were generated in mice using the fluid percussion injury method. Microglia or neuron lines were subjected to different drug interventions. Histological and functional changes were observed by immunofluorescence and neurobehavioural testing. Apoptosis was examined by a TdT-mediated dUTP nick end labelling assay in vivo or by an annexin-V assay in vitro. Ultrastructural alterations in the cells were examined via electron microscopy. Tissue acetylation alterations were identified by non-labelled quantitative acetylation via proteomics. Protein or mRNA expression in cells and tissues was determined by western blot analysis or real-time quantitative polymerase chain reaction. The levels of inflammatory cytokines and mediators in the serum and supernatants were measured via enzyme-linked immunoassay. Results: There were closely positive correlations between eCIRP and inflammatory mediators, and between eCIRP and TBI markers in human and mouse serum. Neural-specific eCIRP KO decreased hemispheric volume loss and neuronal apoptosis and alleviated glial cell activation and neurological function damage after TBI. In contrast, eCIRP treatment resulted in endoplasmic reticulum disruption and ER stress (ERS)-related death of neurons and enhanced inflammatory mediators by glial cells. Mechanistically, we noted that eCIRP-induced neural apoptosis was associated with the activation of the protein kinase RNA-like ER kinase-activating transcription factor 4 (ATF4)-C/EBP homologous protein signalling pathway, and that eCIRP-induced microglial inflammation was associated with histone H3 acetylation and the α7 nicotinic acetylcholine receptor. Conclusions: These results suggest that TBI obviously enhances the secretion of eCIRP, thereby resulting in neural damage and inflammation in TBI. eCIRP may be a biomarker of TBI that can mediate the apoptosis of neuronal cells through the ERS apoptotic pathway and regulate the inflammatory response of microglia via histone modification.

Polyvinylpyrrolidone Assisted One-Pot Synthesis of Size-Tunable Cocktail Nanodrug for Multifunctional Combat of Cancer.

Background: The in vivo barriers and multidrug resistance (MDR) are well recognized as great challenges for the fulfillment of antitumor effects of current drugs, which calls for the development of novel therapeutic agents and innovative drug delivery strategies. Nanodrug (ND) combining multiple drugs with distinct modes of action holes the potential to circumvent these challenges, while the introduction of photothermal therapy (PTT) can give further significantly enhanced efficacy in cancer therapy. However, facile preparation of ND which contains dual drugs and photothermal capability with effective cancer treatment ability has rarely been reported. Methods: In this study, we selected curcumin (Cur) and doxorubicin (Dox) as two model drugs for the creation of a cocktail ND (Cur-Dox ND). We utilized polyvinylpyrrolidone (PVP) as a stabilizer and regulator to prepare Cur-Dox ND in a straightforward one-pot method. Results: The size of the resulting Cur-Dox ND can be easily adjusted by tuning the charged ratios. It was noted that both loaded drugs in Cur-Dox ND can realize their functions in the same target cell. Especially, the P-glycoprotein inhibition effect of Cur can synergistically cooperate with Dox, leading to enhanced inhibition of 4T1 cancer cells. Furthermore, Cur-Dox ND exhibited pH-responsive dissociation of loaded drugs and a robust photothermal translation capacity to realize multifunctional combat of cancer for photothermal enhanced anticancer performance. We further demonstrated that this effect can also be realized in 3D multicellular model, which possibly attributed to its superior drug penetration as well as photothermal-enhanced cellular uptake and drug release. Conclusion: In summary, Cur-Dox ND might be a promising ND for better cancer therapy.

The central retinal thickness and its related genotype in ABCA4-related retinopathy.

PURPOSE: To further explore the influence of genotype, including mutation type and structural domain, on the severity of macular atrophy, we measured the central retinal thickness (CRT) in patients with ABCA4-related retinopathy. METHODS: A total of 66 patients were included in the cohort. This was a retrospective investigation. The patients were tested using whole exon sequencing and ophthalmic exams, including slip lamp exams, best-corrected visual acuity, optical coherence tomography, fundus photo, and fundus autofluorescence. RESULTS: In this study, we discovered that mutations on nucleotide binding domains (NBD) lead to less CRT (45.00 ± 25.25µm, 95% CI: 31.54-58.46) had significantly less CRT than the others (89.75 ± 71.17µm, 95% CI: 30.25-149.25, p = 0.032), and could accelerate the rate of CRT decrease. CONCLUSIONS: Our study provides new perspectives in the understanding of ABCA4-related retinopathy.

Investigating Sea-Level Brain Predictors for Acute Mountain Sickness: A Multimodal MRI Study before and after High-Altitude Exposure.

BACKGROUND AND PURPOSE: Acute mountain sickness is a series of brain-centered symptoms that occur when rapidly ascending to high altitude. Predicting acute mountain sickness before high-altitude exposure is crucial for protecting susceptible individuals. The present study aimed to evaluate the feasibility of predicting acute mountain sickness after high-altitude exposure by using multimodal brain MR imaging features measured at sea level. MATERIALS AND METHODS: We recruited 45 healthy sea-level residents who flew to the Qinghai-Tibet Plateau (3650 m). We conducted T1-weighted structural MR imaging, resting-state fMRI, and arterial spin-labeling perfusion MR imaging both at sea level and high altitude. Acute mountain sickness was diagnosed for 5 days using Lake Louise Scoring. Logistic regression with Least Absolute Shrinkage and Selection Operator logistic regression was performed for predicting acute mountain sickness using sea-level MR imaging features. We also validated the predictors by using MR images obtained at high altitude. RESULTS: The incidence rate of acute mountain sickness was 80.0%. The model achieved an area under the receiver operating characteristic curve of 86.4% (sensitivity = 77.8%, specificity = 100.0%, and P < .001) in predicting acute mountain sickness At sea level, valid predictors included fractional amplitude of low-frequency fluctuations (fALFF) and degree centrality from resting-state fMRI, mainly distributed in the somatomotor network. We further learned that the acute mountain sickness group had lower levels of fALFF in the somatomotor network at high altitude, associated with smaller changes in CSF volume and higher Lake Louise Scoring, specifically relating to fatigue and clinical function. CONCLUSIONS: Our study found that the somatomotor network function detected by sea-level resting-state fMRI was a crucial predictor for acute mountain sickness and further validated its pathophysiologic impact at high altitude. These findings show promise for pre-exposure prediction, particularly for individuals in need of rapid ascent, and they offer insight into the potential mechanism of acute mountain sickness.

Effective removal of microplastics by filamentous algae and its magnetic biochar: Performance and mechanism.

In recent years, filamentous algae blooms and microplastics (MPs) pollution have become two major ecological and environmental problems in urban water systems. In order to solve these two problems at the same time, this study explored the loading capacity of MPs on fresh filamentous algae, and successfully synthesized magnetic filamentous algae biochar loading with Fe3O4 by hydrothermal method, with the purpose of removing MPs from water. The magnetic filamentous algal biochar was characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and so on. Experiments on adsorption kinetics, adsorption isotherms and optimum pH were carried out to explore the adsorption mechanism of MPs on magnetic filamentous algal biochar. The adsorption kinetics and adsorption isotherm models were evaluated, and the selection criterion for the appropriate model was determined by using the residual sum of squares (RSS) and Bayesian information criterion (BIC). Microscope images revealed that fresh filamentous algae could interact with MPs in the form of entanglement, adhesion and encapsulation. The average load of MPs in filamentous algae samples was 14.1 ± 5 items/g dry weight. The theoretical maximum adsorption capacities of polystyrene MPs (PS-MPs) by raw biochar (A500) and magnetic biochar with Fe3O4 (M2A500) were 176.99 mg/g and 215.58 mg/g, respectively. The adsorbent materials gave better reusability because they could be reused up to five times. Overall, these findings have provided new insights into the use of filamentous algae for in situ remediation of fluvial MPs pollution, as well as feasible strategies for the recycling of algal waste.

Exploring changes in brain function in IBD patients using SPCCA: a study of simultaneous EEG-fMRI.

Research on functional changes in the brain of inflammatory bowel disease (IBD) patients is emerging around the world, which brings new perspectives to medical research. In this paper, the methods of canonical correlation analysis (CCA), kernel canonical correlation analysis (KCCA), and sparsity preserving canonical correlation analysis (SPCCA) were applied to the fusion of simultaneous EEG-fMRI data from 25 IBD patients and 15 healthy individuals. The CCA, KCCA and SPCCA fusion methods were used for data processing to compare the results obtained by the three methods. The results clearly show that there is a significant difference in the activation intensity between IBD and healthy control (HC), not only in the frontal lobe (p < 0.01) and temporal lobe (p < 0.01) regions, but also in the posterior cingulate gyrus (p < 0.01), gyrus rectus (p < 0.01), and amygdala (p < 0.01) regions, which are usually neglected. The mean difference in the SPCCA activation intensity was 60.1. However, the mean difference in activation intensity was only 36.9 and 49.8 by using CCA and KCCA. In addition, the correlation of the relevant components selected during the SPCCA calculation was high, with correlation components of up to 0.955; alternatively, the correlations obtained from CCA and KCCA calculations were only 0.917 and 0.926, respectively. It can be seen that SPCCA is indeed superior to CCA and KCCA in processing high-dimensional multimodal data. This work reveals the process of analyzing the brain activation state in IBD disease, provides a further perspective for the study of brain function, and opens up a new avenue for studying the SPCCA method and the change in the intensity of brain activation in IBD disease.

Common dyadic coping and its congruence in couples facing breast cancer: The impact on couples' psychological distress.

OBJECTIVE: Psychological distress is prevalent in couples facing breast cancer. Couples often deal with breast cancer as a unit instead of as individuals. Couple's dyadic coping is important for their adjustment to breast cancer; however, little is known about how couple's coping congruence influences their distress. This study examined how common dyadic coping (CDC) and coping congruence impact psychological distress in couples facing breast cancer. METHODS: Baseline data were analyzed from 343 women with recently diagnosed early-stage breast cancer and their partners who participated in a randomized clinical trial. Psychological distress was indicated by depressed mood and state anxiety. Common dyadic coping was measured by a self-report scale. Coping congruence was assessed by the absolute difference between a woman's and her partner's CDC scores. RESULTS: Higher CDC scores were associated with lower psychological distress in both women and partners. In the CDC subscales, women who suffered less scored higher on open communication, sharing a positive outlook, and lower on avoidance coping. Partners who suffered less scored higher on open communication, sharing a positive outlook, spending time talking, and lower on avoidance coping. Greater congruence in CDC was associated with lower psychological distress in women and their partners. Congruence in sharing a positive outlook benefited both members of the dyad; congruence in avoidance coping significantly benefited patients; congruence in open communication significantly benefited partners. CONCLUSIONS: CDC and its congruence in specific areas have potential benefit to couple's psychological distress when facing breast cancer. Health care providers could consider enhancing couple's CDC and coping congruence to improve their adjustment.

Abnormal Amygdala Subregion Functional Connectivity in Patients with Crohn's Disease with or without Anxiety and Depression.

Objective: The aim of this study was to explore the resting-state functional connectivity (rsFC) of amygdala subregions in healthy controls (HCs) and in patients with Crohn's disease (CD) both with and without anxiety or depression. Materials and Methods: A total of 33 patients with CD and with anxiety or depression (CDad group), 31 patients with CD but without anxiety or depression (CDnad group), and 29 age-, sex-, and education level-matched HCs underwent functional magnetic resonance imaging. rsFC analysis was used to analyze the FC between the amygdala subregions and other areas of the brain. Results: Compared with the HC group, the CDad group demonstrated decreased rsFC between the right laterobasal subregion and the left hippocampus (P < .001) and right middle frontal gyrus (P < .001) and between the left superficial subregion and the left insula (P < .001). Compared with the HC group, the CDnad group demonstrated decreased rsFC between the left centromedial subregion and the left insula (P < .001). Compared with the CDnad group, the CDad group demonstrated decreased rsFC between the left centromedial subregion and the right precuneus (P < .001) and postcentral gyrus (P < .001), between the right laterobasal subregion and the left hippocampus (P < .001), and between the left superficial subregion and the right middle frontal gyrus (P < .001). Conclusions: There are significant FC changes in the amygdala subregions in patients with CD. These changes may be related to the disease itself or to the symptoms of anxiety and depression.

Refinement in Post-Operative Care for Orthopaedic Models: Implementing a Sheep Walking Cast (SWC) for Effective Tibial Fracture Management.

In the healthcare system, lower leg fractures remain relevant, incurring costs related to surgical treatment, hospitalization, and rehabilitation. The duration of treatment may vary depending on the individual case and its severity. Casting as a post-surgical fracture treatment is a common method in human and experimental veterinary medicine. Despite the high importance of sheep in preclinical testing materials for osteosynthesis, there is no standardised cast system ensuring proper stabilisation and functionality of hind limbs during the healing of tibia fractures or defects. Existing treatment approaches for tibial osteosynthesis in laboratory animal science include sling hanging, external fixators, or former Achilles tendon incision. These methods restrict animal movement for 4-6 weeks, limit species-typical behaviour, and impact social interactions. Our pilot study introduces a Standardised Walking Cast (SWC) for sheep, enabling immediate physiological movement post surgery. Seven Rhone sheep (female, 63.5 kg ± 6.45 kg) each with a single tibia defect (6 mm mechanical drilled defect) underwent SWC application for 4 weeks after plate osteosynthesis. The animals bore weight on their operated leg from day one, exhibiting slight lameness (grade 1-2 out of 5). Individual step lengths showed good uniformity (average deviation: 0.89 cm). Group housing successfully started on day three after surgery. Weekly X-rays and cast changes ensured proper placement, depicting the healing process. This study demonstrates the feasibility of using an SWC for up to 72 kg of body weight without sling hanging via ceiling mounting or external fixation techniques. Allowing species-typical movement and social behaviour can significantly improve the physiological behaviour of sheep in experiments, contributing to refinement.

Machine perfusion of the liver and in vivo animal models: A systematic review of the preclinical research landscape.

Machine perfusion (MP) is often referred to as one of the most promising advancements in liver transplantation research of the last few decades, with various techniques and modalities being evaluated in preclinical studies using animal models. However, low scientific rigor and subpar reporting standards lead to limited reproducibility and translational potential, hindering progress. This pre-registered systematic review (PROSPERO: CRD42021234667) aimed to provide a thematic overview of the preclinical research landscape on MP in liver transplantation using in vivo transplantation models and to explore methodological and reporting standards, using the ARRIVE (Animal Research: Reporting of In Vivo Experiments) score. In total 56 articles were included. Studies were evenly distributed across Asia, Europe, and the Americas. Porcine models were used in 57.1% of the studies, followed by rats (39.3%) and dogs (3.6%). In terms of graft type, 55.4% of the studies used donation after cardiac death grafts, while donation after brain death grafts accounted for 37.5%. Regarding MP modalities, the distribution was as follows: 41.5% of articles utilized hypothermic MP, 21.5% normothermic MP, 13.8% subnormothermic MP, and 16.9% utilized hypothermic oxygenated MP. The stringent documentation of ARRIVE elements concerning precise experimental execution, group size and selection, the choice of statistical methods, as well as adherence to the principles of the 3Rs, was notably lacking in the majority of publications, with less than 30% providing comprehensive details. Postoperative analgesia and antibiotics treatment were not documented in 82.1% of all included studies. None of the analyzed studies fully adhered to the ARRIVE Guidelines. In conclusion, the present study emphasizes the importance of adhering to reporting standards to promote reproducibility and adequate animal welfare in preclinical studies in machine perfusion. At the same time, it highlights a clear deficiency in this field, underscoring the need for further investigations into animal welfare-related topics.

Identification of the metaphyseal skeletal stem cell building trabecular bone.

Skeletal stem cells (SSCs) that are capable of self-renewal and multipotent differentiation contribute to bone development and homeostasis. Several populations of SSCs at different skeletal sites have been reported. Here, we identify a metaphyseal SSC (mpSSC) population whose transcriptional landscape is distinct from other bone mesenchymal stromal cells (BMSCs). These mpSSCs are marked by Sstr2 or Pdgfrb+Kitl-, located just underneath the growth plate, and exclusively derived from hypertrophic chondrocytes (HCs). These HC-derived mpSSCs have properties of self-renewal and multipotency in vitro and in vivo, producing most HC offspring postnatally. HC-specific deletion of Hgs, a component of the endosomal sorting complex required for transport, impairs the HC-to-mpSSC conversion and compromises trabecular bone formation. Thus, mpSSC is the major source of BMSCs and osteoblasts in bone marrow, supporting the postnatal trabecular bone formation.

Development of a common dyadic coping scale in couples facing breast cancer: the importance of open communication.

OBJECTIVE: Couples' joint coping is important in managing the impact of breast cancer. However, measures assessing couples' communication as a way of coping are insufficient. This study aimed to generate a self-report valid and reliable measure of couples' coping with a particular focus on communication. METHOD: We used baseline data of 343 couple dyads who participated in a randomized clinical trial targeting marital communication. Women were diagnosed with early-stage breast cancer in the past eight months; couples were married or in an intimate relationship for at least six months, could read and write English, and lived within 100 miles of the study center. An expert panel selected items with conceptual fit from the Mutuality and Interpersonal Sensitivity Scale (MIS) that was originally designed to evaluate marital communication about breast cancer. RESULTS: Exploratory and confirmatory factor analyses supported a 12-item measurement model with four factors: Keeping the communication open with each other about breast cancer (4 items), Sharing a positive outlook on breast cancer (2 items), Avoiding discussion of negative thoughts and feelings about breast cancer (3 items), and Spending sufficient time together talking about breast cancer (3 items). Reliability ranged from 0.76 to 0.87 for women and 0.70 to 0.83 for spouses. CONCLUSION: This new measure has potential application in clinical practice and future research to assess couple's joint coping efforts especially through communication.

Prevalence and optical coherence tomography analyses of outer retinal tubulations in Chinese population with inherited retinal diseases.

BACKGROUND: To investigate the prevalence of outer retinal tubulation (ORT) and its correlations with optical coherence tomography (OCT) parameters in Chinese population with inherited retinal diseases (IRDs). METHODS: This retrospective study enrolled consecutive patients identified with IRDs and referred for genetic testing between February 2016 and April 2021. Clinical characteristics from medical records and features of cross-sectional B-scans were reviewed and analysed. The associations of patient-specific and ocular features with the presence of ORT were evaluated using univariate and multivariate analyses. RESULTS: Two hundred and three patients (401 eyes) with a mean age of 49.7 ± 16.7 years were enrolled. ORT was observed in 41 eyes (10.2%), including 26 of 28 eyes (92.9%) with Bietti crystalline corneoretinal dystrophy (BCD), 14 of 338 eyes (4.1%) with retinitis pigmentosa (RP), and 1 of 26 eyes (3.8%) in eyes with cone-rod dystrophy. Eyes with ORT showed significantly worse visual acuity than those without ORT (P = 0.002). Multivariate analysis indicated that the presence of ORT was positively correlated with choroidal atrophy and inner nuclear layer (INL) cysts (P < 0.01). ORTs were detected more frequently in eyes with BCD than RP (P = 0.024), most of which located exclusively within the extrafoveal area. Large choroidal vessels were detected underneath the corresponding ORTs in both patients with BCD and RP. CONCLUSIONS: The prevalence of ORT varies among different IRDs phenotypes, with the highest prevalence in BCD. The presence of choroidal atrophy and INL cysts may be associated with an increased risk of ORT formation in patients with IRD.

GENETIC FACTORS AND CHARACTERISTICS ON SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY ARE ASSOCIATED WITH CHOROIDAL THICKNESS IN ABCA4 -RELATED RETINOPATHY.

PURPOSE: To investigate the possible correlation factors of choroidal thickness in ABCA4 -related retinopathy. METHODS: A total of 66 patients were included in the cohort. It is a retrospective, cross-sectional laboratory investigation. The patients were tested using whole-exon sequencing and ophthalmic examinations, including slit-lamp examinations, best-corrected visual acuity, spectral-domain optical coherence tomography, fundus photograph, and fundus autofluorescence. RESULTS: Besides demographic characteristics (age, onset age, duration), we selected genetic factors and ocular characteristics on spectral-domain optical coherence tomography as the candidates related to choroidal thickness. Mutation type (inframe mutation or premature termination codon), epiretinal membrane, retinal pigment epithelium- Bruch membrane integrity, and macular curvature changes were identified as related factors to choroidal thickness in ABCA4 -related retinopathy after the adjustment of Logistic LASSO regression. CONCLUSION: Mutation type, epiretinal membrane, retinal pigment epithelium-Bruch membrane integrity, and macular curvature changes are related factors to choroidal thinning. These findings could provide us a further understanding for the pathological process and clinical features of ABCA4 mutation.

Are immune checkpoint inhibitors ineffective in treating patients with head and neck squamous cell carcinoma aged 75 years or Older? A Meta-Analysis.

OBJECTIVES: The efficacy of immune checkpoint inhibitors (ICIs) is unclear in patients aged ≥ 75 years with head and neck squamous cell carcinoma (HNSCC). We conducted a systematic review and meta-analysis of randomized trials that compared ICIs with standard-of-care (SOC) therapy for recurrent/metastatic HNSCC. MATERIALS AND METHODS: PubMed, EMBASE, Web of Science, and ClinicalTrials.gov were searched for eligible trials. We evaluated the overall survival (OS) benefit of ICIs versus SOC according to patient age (<75 versus ≥ 75 years). The OS benefit was evaluated and compared between the age subgroups using hazard ratios (HRs). Data were pooled using a random-effects model. RESULTS: Five phase 3 trials involving 3437 patients were included. In patients aged ≥ 75 years (n = 207), ICIs did not improve OS compared to SOC (HR = 1.30, 95 % confidence interval [CI]: 0.93-1.81, P = 0.127). However, an improvement in OS was observed in patients aged < 75 years (n = 3230, HR = 0.90, 95 % CI: 0.83-0.99, P = 0.025). There is a significant difference in OS benefit between patients aged < 75 and ≥ 75 years (ratio of HR = 0.69, 95 % CI: 0.49-0.98, P = 0.036). Subgroup, meta-regression, and sensitivity analyses supported the reliability of the results. CONCLUSIONS: Given the small sample size, our findings showing no improvement in OS suggest a lack of evidence to support the use of ICIs in patients with recurrent/metastatic HNSCC aged ≥ 75 years. Therefore, prospective studies are needed to clarify their efficacy among this age group.

Complete genome sequence of carotenoid-producing Aestuariibaculum lutulentum L182T isolated from the tidal sediment.

Aestuariibaculum lutulentum L182T (= KCTC 92530T = MCCC 1K08065T) was isolated from the tidal sediment collected in Beihai, People's Republic of China. The genome was sequenced and consisted of a single chromosome with the size of 3,782,725 bp and DNA G + C content of 35.1%. Genomic annotations demonstrated that it encoded 12 rRNA genes, 56 tRNA genes and 3210 ORFs. The percentages of ORFs assigned to CAZy, COG, and KEGG databases were 5.5, 86.2 and 45.5%, respectively. Comparative genomic analysis indicated that the pan- and core-genomes of the genus Aestuariibaculum consisted of 4826 and 2257 orthologous genes, respectively. Carbohydrate-active enzyme annotations of the genus Aestuariibaculum genomes revealed that they shared three polysaccharide lyase (PL) families including PL1, PL22 and PL42. Meanwhile, one carotenoid biosynthetic gene cluster related to biosynthesizing flexixanthin was found in the genus Aestuariibaculum. Furthermore, the core-genome of the genus Aestuariibaculum showed that this genus played a role in cleaving pectate, degrading ulvan, and biosynthesizing carotenoids. This study is a complete genomic report of the genus Aestuariibaculum and broadens understandings of its ecological roles and biotechnological applications.