A novel infrared spectroscopy marker for assessing the postoperative infection risk in patients with upper urinary tract calculus.

The aim of this study is to evaluate the ability of infrared wavenumber of calculus to predict postoperative infection in patients with upper urinary tract calculus (UUTC), and to establish a predictive model based on this. From March 2018 to March 2023, 480 UUTC patients from Fujian Provincial Hospital were included in this study. The infrared-wavenumbers related infection score (IR-infection score) was constructed by univariate analysis, multicollinearity screening, and Lasso analysis to predict postoperative infection. Continually, the Delong test was used to compare the predictive power between the IR-infection score and traditional indicators. Afterward, we performed urine metagene sequencing and stone culture to prove the correlation between calculus toxicity and IR-infection score. Finally, logistic regression was used to build a nomogram. IR-infection score composed of four independent wavenumbers could precisely predict postoperative infection (AUCvalidation cohort = 0.707) and sepsis (AUCvalidation cohort = 0.824). IR-infection score had better predictive ability than commonly used clinical indicators. Moreover, metagenomics sequencing and calculus culture confirmed the correlation between IR-infection score and calculus toxicity (all P < 0.05). The nomogram based on the IR-infection score had high predictive power (all AUCs > 0.803). Our study first developed a novel infrared spectroscopy marker and nomogram, which can help urologists better predict postoperative infection in UUTC patients.

Assessing the Impact of Defacing Algorithms on Brain Volumetry Accuracy in MRI Analyses.

Background and Purpose: To ensure data privacy, the development of defacing processes, which anonymize brain images by obscuring facial features, is crucial. However, the impact of these defacing methods on brain imaging analysis poses significant concern. This study aimed to evaluate the reliability of three different defacing methods in automated brain volumetry. Methods: Magnetic resonance imaging with three-dimensional T1 sequences was performed on ten patients diagnosed with subjective cognitive decline. Defacing was executed using mri_deface, BioImage Suite Web-based defacing, and Defacer. Brain volumes were measured employing the QBraVo program and FreeSurfer, assessing intraclass correlation coefficient (ICC) and the mean differences in brain volume measurements between the original and defaced images. Results: The mean age of the patients was 71.10±6.17 years, with 4 (40.0%) being male. The total intracranial volume, total brain volume, and ventricle volume exhibited high ICCs across the three defacing methods and 2 volumetry analyses. All regional brain volumes showed high ICCs with all three defacing methods. Despite variations among some brain regions, no significant mean differences in regional brain volume were observed between the original and defaced images across all regions. Conclusions: The three defacing algorithms evaluated did not significantly affect the results of image analysis for the entire brain or specific cerebral regions. These findings suggest that these algorithms can serve as robust methods for defacing in neuroimaging analysis, thereby supporting data anonymization without compromising the integrity of brain volume measurements.

Association between phthalate exposure and sleep quality in pregnant women: Results from the Korean Children's Environmental Health Study with repeated assessment of exposure.

Background: Evidence linking environmental toxicants to sleep quality is growing; however, these associations during pregnancy remain unclear. We examined the associations of repeated measures of urinary phthalates in early and late pregnancy with multiple markers of sleep quality among pregnant women. Methods: The study population included 2324 pregnant women from the Korean Children's Environmental Health Study. We analyzed spot urine samples collected at two time points during pregnancy for exposure biomarkers of eight phthalate metabolites. We investigated associations between four summary phthalates (all phthalates: ∑Phthalates; di-(2-ethylhexyl) phthalate: ∑DEHP; phthalates from plastic sources: ∑Plastic; and antiandrogenic phthalates: ∑AA) and eight individual phthalates and self-reported sleep measures using generalized ordinal logistic regression and generalized estimating equations models that accounted for repeated exposure measurements. The models were adjusted for age, body mass index, education, gestational age, income, physical activity, smoking, occupation, chronic diseases, depression, and urinary cotinine levels. Results: Multiple individual phthalates and summary measures of phthalate mixtures, including ∑Plastic, ∑DEHP, ∑AA, and ∑Phthalates, were associated with lower sleep efficiency. To illustrate, every 1-unit log increase in ∑AA was associated with a reduction of sleep efficiency by 1.37 % (95% confidence interval [CI] = -2.41, -0.32). ∑AA and ∑Phthalates were also associated with shorter sleep duration and longer sleep latency. Associations between summary phthalate measures and sleep efficiency differed by urinary cotinine levels (P for subgroup difference < 0.05). Conclusions: Findings suggest that higher phthalate exposure may be related to lower sleep efficiency, shorter sleep duration, and prolonged sleep latency during pregnancy.

Prenatal and early-life air pollutant exposure and epigenetic aging acceleration.

BACKGROUND: This study investigated the association of prenatal and early childhood exposure to air pollution with epigenetic age acceleration (EAA) at six years of age using the Environment and Development of Children Cohort (EDC Cohort) MATERIALS & METHODS: Air pollution, including particulate matter [< 2.5 µm (PM2.5) and < 10 µm (PM10) in an aerodynamic diameter], nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and sulfur dioxide (SO2) were estimated based on the residential address for two periods: 1) during the whole pregnancy, and 2) for one year before the follow-up in children at six years of age. The methylation levels in whole blood at six years of age were measured, and the methylation clocks, including Horvath's clock, Horvath's skin and blood clock, PedBE, and Wu's clock, were estimated. Multivariate linear regression models were constructed to analyze the association between EAA and air pollutants. RESULTS: A total of 76 children in EDC cohort were enrolled in this study. During the whole pregnancy, interquartile range (IQR) increases in exposure to PM2.5 (4.56 µg/m3) and CO (0.156 ppm) were associated with 0.406 years and 0.799 years of EAA (Horvath's clock), respectively. An IQR increase in PM2.5 (4.76 µg/m3) for one year before the child was six years of age was associated with 0.509 years of EAA (Horvath's clock) and 0.289 years of EAA (Wu's clock). PM10 (4.30 µg/m3) and O3 (0.003 ppm) exposure in the period were also associated with EAA in Horvath's clock (0.280 years) and EAA in Horvath's skin and blood clock (0.163 years), respectively. CONCLUSION: We found that prenatal and childhood exposure to ambient air pollutants is associated with EAA among children. The results suggest that air pollution could induce excess biological aging even in prenatal and early life.

CRISPR/Cas13a-based genome editing for establishing the detection method of H9N2 subtype avian influenza virus.

Avian influenza virus (AIV) subtype H9N2 has significantly threatened the poultry business in recent years by having become the predominant subtype in flocks of chickens, ducks, and pigeons. In addition, the public health aspects of H9N2 AIV pose a significant threat to humans. Early and rapid diagnosis of H9N2 AIV is therefore of great importance. In this study, a new method for the detection of H9N2 AIV based on fluorescence intensity was successfully established using CRISPR/Cas13a technology. The Cas13a protein was first expressed in a prokaryotic system and purified using nickel ion affinity chromatography, resulting in a high-purity Cas13a protein. The best RPA (recombinase polymerase amplification) primer pairs and crRNA were designed and screened, successfully constructing the detection of H9N2 AIV based on CRISPR/Cas13a technology. Optimal concentration of Cas13a and crRNA was determined to optimize the constructed assay. The sensitivity of the optimized detection system is excellent, with a minimum detection limit of 10° copies/µL and didn't react with other avian susceptible viruses, with excellent specificity. The detection method provides the basis for the field detection of the H9N2 AIV.

In vitro Evaluation of DINCH-Plasticized Blood Bags for Red Blood Cell Storage with CPDA-1 Anticoagulant.

Introduction: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer commonly used in blood bags. Despite its protective effects on red blood cell (RBC) storage, concerns about its reproductive toxicity exist. This study investigated the in vitro quality of RBC concentrates stored in bags using di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) as an alternative plasticizer. Methods: Using a pool-and-split study design, we produced 20 matched homogenous quintets of RBC concentrates in two DINCH bags and three DEHP bags with citrate phosphate dextrose adenine (CPDA-1) anticoagulant. RBC storage quality was assessed weekly for 35 days. Results: On day 35, the median hemolysis levels in the DINCH bags (0.297-0.342%) were marginally higher (p < 0.05) than the DEHP bags (0.204-0.240%). All DINCH bags showed <0.8% hemolysis. RBCs in the DINCH bags showed increased mean corpuscular volume and decreased eosin 5' maleimide binding than in the DEHP bags. Higher pO2 and lower pCO2 levels in the DINCH bags indicated better gas permeability than in DEHP bags. Other metabolic parameters were comparable in both bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags. Conclusion: The quality of RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for nonleukoreduced RBC storage even without the use of next-generation additive solutions to improve RBC preservation quality.

A plasticizer is a chemical substance added to plastic to increase its flexibility. DEHP is a plasticizer that has been widely used in many products including plastic tubing and bags of medical devices. However, concerns about DEHP-related toxicity have been debated for many years. DEHP has been replaced with other plasticizers in many products, but it is still being used in blood bags due to its protective effect on RBC preservation. DINCH is an alternative plasticizer with a low toxicology profile. This study investigated the quality of RBC concentrates stored in blood bags using DINCH. Twenty sets of five RBC concentrates were produced using two DINCH bags and three DEHP bags with CPDA-1 anticoagulant, and the storage quality was assessed weekly for 35 days. On day 35, the median hemolysis levels in the DINCH bags (0.297­0.342%) were slightly increased than the DEHP bags (0.204­0.240%). However, all DINCH bags showed hemolysis lower than the regulatory limit of 0.8%. DINCH bags exhibited better gas permeability than DEHP bags. Compared to DEHP, DINCH exhibited considerably lower levels of plasticizer leaching into blood bags. Most of the other metabolic parameters were comparable in both bags. The quality of nonleukocyte-reduced RBC concentrates stored for 35 days in DINCH-plasticized blood bags with CDPA-1 is generally comparable to those in DEHP bags. Hence, DINCH can be a viable alternative to DEHP in blood bags for RBC storage, even without the use of next-generation additive solutions to improve RBC preservation quality.

Anti-contact protein-associated protein 2 antibody encephalitis in children: A case report.

BACKGROUND: Anti-contactin-associated protein-like 2 (CASPR2) antibody encephalitis is an autoimmune disorder characterized by the presence of antibodies against the voltage-gated potassium channel. This leads to neurological symptoms, such as seizures, cognitive decline, and neuropathic pain, primarily affecting the limbic system. The prognosis of this disorder varies among individuals. CASE SUMMARY: The patient, a girl aged nine years and nine months, underwent treatment for 14 to 21 d. The main clinical manifestations were vomiting and unclear consciousness, positive pathological signs, normal cranial computed tomography and magnetic resonance imaging, and abnormal electroencephalogram. The child was discharged after receiving immunoglobulin and hormone treatment. Subsequent follow-up over a period of 15 months after discharge, conducted through telephone and outpatient visits, showed no recurrence of symptoms. CONCLUSION: Anti-CASPR2 antibody autoimmune encephalitis in children is rare, mainly manifested as convulsions, mental abnormalities, cognitive impairment, and neuropathic pain, among others. Timely evaluation for autoimmune encephalitis antibodies is crucial, especially in cases of recurrent central nervous system involvement in children.

Menopausal stages and overactive bladder symptoms in middle-aged women: A cross-sectional study.

OBJECTIVE: To examine the prevalence of overactive bladder (OAB) according to menopausal stages in middle-aged women. DESIGN: Cross-sectional study. SETTING: Total Healthcare Center in South Korea. POPULATION: Middle-aged Korean women (n=3469, mean age, 49.5 ± 2.9 years). METHODS: Menopausal stages were defined according to the Stages of Reproductive Aging Workshop +10 criteria, and menopausal symptoms were assessed using the Korean version of Menopause-Specific Quality of Life (MENQOL). Logistic regression models were used to estimate prevalence ratios with 95% confidence intervals for OAB according to menopausal stage and to assess the associations with menopausal symptoms. MAIN OUTCOME MEASURES: OAB symptoms were evaluated using the Overactive Bladder Symptom Score (OABSS). RESULTS: The prevalence of OAB increased with menopausal stage; however, the multivariable-adjusted prevalence ratios for women in menopausal transition and postmenopausal stage were insignificant (ptrend = 0.160) compared to those for premenopausal women. Among individual OAB symptoms, the multivariable-adjusted prevalence ratios for nocturia increased with menopausal stage in a dose-response manner (ptrend = 0.005 for 1 time/day; ptrend < 0.001 for ≥2 times/day). The association between menopausal stages and nocturia occurring ≥2 times/day was evident in women without OAB and with relatively high MENQOL scores, vasomotor symptoms and difficulty sleeping. CONCLUSIONS: The prevalence of OAB, particularly nocturia, increased with menopausal stage, and the association was obvious in women with other menopausal symptoms. This finding underscores the importance of addressing nocturia as a potential menopausal symptom in middle-aged women. Further studies are required to understand the mechanisms linking OAB with menopausal symptoms in middle-aged women.

Associations between urinary level of bisphenol A, phthalates, 8-iso-prostaglandin-F2α, and emotional and behavioral problems among Chinese adolescents.

BACKGROUND: Emotional and behavioral problems (EBPs) of adolescents is a worldwide public health problem. Bisphenol A (BPA) and phthalate (PAEs) are prevalent and potentially toxic to human health. Therefore, this study aimed to investigate the associations between urinary level of BPA, PAEs, 8-iso-prostaglandin-F2α (8-iso-PGF2α), and EBPs. METHODS: A total of 865 Chinese adolescents were included in this study and EBPs was assessed using the Strengths and Difficulties Questionnaire (SDQ). Urinary concentrations of BPA and seven PAEs metabolites in adolescents were determined by high performance liquid chromatography-tandem mass spectrometry. Urinary 8-iso-PGF2α concentration was detected by enzyme-linked immunosorbent assay (ELISA). Spearman rank correlation analysis, multivariate logistic regression analysis, restricted cubic spline functions were used to explore the relationship between the levels of BPA, PAEs, 8-iso-PGF2α and EBPs. RESULTS: BPA and PAEs metabolites were positively associated with EBPs in Chinese adolescents. And the 8-iso-PGF2α was significantly non-linearly correlated with emotional symptoms, conduct problems, peer problems and total difficulties. Furthermore, 8-iso-PGF2α may partially mediate the association between BPA and PAEs exposure and EBPs. LIMITATIONS: This study was a cross-sectional study, the cause-effect relationship between BPA, PAEs exposure and EBPs could not be determined. A single spot urine sample for BPA and PAEs exposure characterization maybe could not represent their long-term exposure level. CONCLUSIONS: High exposure of BPA and PAEs are associated with EBPs, which may be partly mediated by oxidative stress among adolescents. The results of this study could provide certain ideas for subsequent related research.

Value of combining targeted emergency nursing with psychological nursing in children with febrile convulsions.

BACKGROUND: Febrile convulsions are a common pediatric emergency that imposes significant psychological stress on children and their families. Targeted emergency care and psychological nursing are widely applied in clinical practice, but their value and impact on the management of pediatric febrile convulsions are unclear. AIM: To determine the impact of targeted emergency nursing combined with psychological nursing on satisfaction in children with febrile convulsions. METHODS: Data from 111 children with febrile convulsions who received treatment at Nantong Maternal and Child Health Care Hospital between June 2021 and October 2022 were analyzed. The control group consisted of 44 children who received conventional nursing care and the research group consisted of 67 children who received targeted emergency and psychological nursing. The time to fever resolution, time to resolution of convulsions, length of hospital stays, Pittsburgh Sleep Quality Index, patient compliance, nursing satisfaction of the parents, occurrence of complications during the nursing process, and parental anxiety and depression were compared between the control and research groups. Parental anxiety and depression were assessed using the Hamilton Rating Scale for Depression (HAMD) and the Hamilton Rating Scale for Anxiety (HAMA). RESULTS: The fever resolution, convulsion disappearance, and hospitalization times were longer in the control group compared with the research group (P < 0.0001). The time to falling asleep, sleep time, sleep quality, sleep disturbance, sleep efficiency, and daytime status scores were significantly better in the research group compared with the control group (P < 0.0001). The HAMD and HAMA scores for parents of children in the research group were lower than the scores in the control group after nursing (P < 0.05). Compliance with treatment of children in the research group was higher than in the control group (P < 0.05). Parental satisfaction with nursing in the research group was higher than in the control group (P < 0.05). The total complication rate of children in the control group was higher than in the research group (P < 0.05). CONCLUSION: Combining psychological nursing with targeted emergency nursing improved the satisfaction of children's families and compliance with treatment and promoted early recovery of clinical symptoms and improvement of sleep quality.

EGFR Mutation and TKI Treatment Promote Secretion of Small Extracellular Vesicle PD-L1 and Contribute to Immunosuppression in NSCLC.

In Asian populations with non-small-cell lung cancer (NSCLC), EGFR mutations are highly prevalent, occurring in roughly half of these patients. Studies have revealed that individuals with EGFR mutation typically fare worse with immunotherapy. In patients who received EGFR tyrosine kinase inhibitor (TKI) treatment followed by anti-PD-1 therapy, poor results were observed. The underlying mechanism remains unclear. We used high-resolution flow cytometry and ELISA to detect the circulating level of small extracellular vesicle (sEV) PD-L1 in NSCLC individuals with EGFR mutations before and after receiving TKIs. The secretion amount of sEV PD-L1 of lung cancer cell lines with EGFR mutations under TKI treatment or not were detected using high-resolution flow cytometry and Western blotting. The results revealed that patients harboring EGFR mutations exhibit increased levels of sEV PD-L1 in circulation, which inversely correlated with the presence of CD8+ T cells in tumor tissues. Furthermore, tumor cells carrying EGFR mutations secrete a higher quantity of PD-L1-positive sEVs. TKI treatment appeared to amplify the levels of PD-L1-positive sEVs in the bloodstream. Mutation-induced and TKI-induced sEVs substantially impaired the functionality of CD8+ T cells. Importantly, our findings indicated that EGFR mutations and TKI therapies promote secretion of PD-L1-positive sEVs via distinct molecular mechanisms, namely the HRS and ALIX pathways, respectively. In conclusion, the increased secretion of PD-L1-positive sEVs, prompted by genetic alterations and TKI administration, may contribute to the limited efficacy of immunotherapy observed in EGFR-mutant patients and patients who have received TKI treatment.

The positive role of transforming growth factor-ß1 in ischemic stroke.

Ischemic stroke is one of the most disabling and fatal diseases around the world. The damaged brain tissues will undergo excessive autophagy, vascular endothelial cells injury, blood-brain barrier (BBB) impairment and neuroinflammation after ischemic stroke. However, there is no unified viewpoint on the underlying mechanism of brain damage. Transforming growth factor-ß1 (TGF-ß1), as a multi-functional cytokine, plays a crucial role in the intricate pathological processes and helps maintain the physiological homeostasis of brain tissues through various signaling pathways after ischemic stroke. In this review, we summarize the protective role of TGF-ß1 in autophagic flux, BBB, vascular remodeling, neuroinflammation and other aspects after ischemic stroke. Based on the review, we believe that TGF-ß1 could serve as a key target for treating ischemic stroke.

Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.

Background: Lung adenocarcinoma (LUAD) among never-smokers is a public health burden especially prevalent in East Asian (EAS) women. Polygenic risk scores (PRSs), which quanefy geneec suscepebility, are promising for straefying risk, yet have mainly been developed in European (EUR) populaeons. We developed and validated single-and mule-ancestry PRSs for LUAD in EAS never-smokers, using the largest available genome-wide associaeon study (GWAS) dataset. Methods: We used GWAS summary staesecs from both EAS (8,002 cases; 20,782 controls) and EUR (2,058 cases; 5,575 controls) populaeons, as well as independent EAS individual level data. We evaluated several PRSs approaches: a single-ancestry PRS using 25 variants that reached genome-wide significance (PRS-25), a genome-wide Bayesian based approach (LDpred2), and a mule-ancestry approach that models geneec correlaeons across ancestries (CT-SLEB). PRS performance was evaluated based on the associaeon with LUAD and AUC values. We then esemated the lifeeme absolute risk of LUAD (age 30-80) and projected the AUC at different sample sizes using EAS-derived effect-size distribueon and heritability esemates. Findings: The CT-SLEB PRS showed a strong associaeon with LUAD risk (odds raeo=1.71, 95% confidence interval (CI): 1.61, 1.82) with an AUC of 0.640 (95% CI: 0.629, 0.653). Individuals in the 95 th percenele of the PRS had an esemated 6.69% lifeeme absolute risk of LUAD. Comparison of LUAD risk between individuals in the highest and lowest 20% PRS quaneles revealed a 3.92-fold increase. Projeceon analyses indicated that achieving an AUC of 0.70, which approaches the maximized prediceon poteneal of the PRS given the esemated geneec variance, would require a future study encompassing 55,000 EAS LUAD cases with a 1:10 case-control raeo. Interpretations: Our study underscores the poteneal of mule-ancestry PRS approaches to enhance LUAD risk straeficaeon in never-smokers, parecularly in EAS populaeons, and highlights the necessary scale of future research to uncover the geneec underpinnings of LUAD.

Silicone oil migrating into the conjunctival space and orbit after surgery for an eye-penetrating injury: A case report.

BACKGROUND: We report a case of eye-penetrating injury in which a massive silicone oil migration into the patient's subconjunctival space and orbit occurred after vitrectomy. CASE SUMMARY: A 30-year-old male patient sought medical attention at Ganzhou People's Hospital after experiencing pain and vision loss in his left eye due to a nail wound on December 9, 2023. Diagnosis of penetrating injury caused by magnetic foreign body retention in the left eye and hospitalization for treatment. On December 9, 2023, pars plana vitrectomy was performed on the left eye for intraocular foreign body removal, abnormal crystal extraction, retinal photocoagulation. Owing to the discovery of retinal detachment at the posterior pole during surgery, silicone oil was injected to fill the vitreous body, following which upper conjunctival bubble-like swelling was observed. Postoperative orbital computed tomography (CT) review indicated migration of silicone oil to the subconjunctival space and orbit through a self-permeable outlet. On December 18, 2023, the patient sought treatment at the First Affiliated Hospital of Nanchang University, China. The patient presented with a pronounced foreign body sensation following left eye surgery. On December 20, 2023, the foreign body was removed from the left eye frame and an intraocular examination was conducted. The posterior scleral tear had closed, leading to termination of the surgical procedure following supplementary laser treatment around the tear. The patient reported a significant reduction in ocular surface symptoms just one day after surgery. Furthermore, a notable decrease in the migration of silicone oil was observed in orbital CT scans. CONCLUSION: The timing of silicone oil injection for an eye-penetrating injury should be carefully evaluated to avoid the possibility of silicone oil migration.

Association between work from home and health-related productivity loss among Korean employees.

Background: After the coronavirus disease 2019 pandemic, the widespread adoption of working from home, or teleworking, has prompted extensive research regarding its effects on work productivity and the physical and mental health of employees. In this context, our study aimed to investigate the association between working from home and health-related productivity loss (HRPL). Methods: An online survey was conducted with a sample of 1,078 workers. HRPL was estimated by the Work Productivity and Activity Impairment Questionnaire: General Health version. Workers that have been working from home in the last 6 months were categorized into the "work from home" group. Generalized linear models were used to compare the mean difference of HRPL between "work from home" and "commuters" group. Stratified analyses were conducted based on various factors including gender, age, income level, occupation, education level, previous diagnosis of chronic disease, presence of preschool children, living in studio apartment, living alone, commuting time, working hours and regular exercise. Results: The overall HRPL was higher in the "work from home" group than in the "commuters" group with a mean difference of 4.05 (95% confidence interval [CI]: 0.09-8.01). In the stratified analyses, significant differences were observed in workers with chronic diseases (mean difference: 8.23, 95% CI: 0.38-16.09), who do not live alone (mean difference: 4.84, 95% CI: 0.35-9.33), and workers that do not exercise regularly (mean difference: 4.96, 95% CI: 0.12-9.80). Conclusions: Working from home is associated with an increased HRPL in the Korean working population, especially among those with chronic diseases, those who do not live alone, and those who do not exercise regularly.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Overactive bladder and cognitive impairment in middle-aged women: A cross-sectional study.

BACKGROUND: Overactive bladder (OAB) is a common condition in middle-aged and older women. It has been reported to be potentially linked to cognitive decline, particularly in older adults. This study investigated the association between OAB symptoms and cognitive impairment in middle-aged women. MATERIALS AND METHODS: This cross-sectional study had a sample of 1652 women (mean age 49.3 ± 2.8 years) who were not taking medication for either urinary tract infection or OAB. OAB symptoms and cognitive function were evaluated by self-administered questionnaires: the Overactive Bladder Symptom Score and the Alzheimer's disease 8. Logistic regression models estimated prevalence ratios (PRs) with 95 % confidence intervals (CI) for cognitive impairment according to the presence/absence of OAB. Mediation analyses assessed the impact of poor sleep quality on this association. RESULTS: Cognitive impairment was more prevalent in women with OAB than in those without OAB (multivariable-adjusted PR: 1.88 [95 % CI: 1.52-2.24]). Women experiencing nocturia (≥twice a night), urinary urgency at least once a week, and urgency urinary incontinence at least once a week had multivariable-adjusted PRs (95 % CI) for cognitive impairment of 2.08 (1.50-2.65), 2.12 (1.66-2.58), and 1.75 (1.17-2.34), respectively. Poor sleep quality mediated 10.81 % [95 % CI: 4.55-19.44 %] of the relationship between OAB and cognitive impairment. CONCLUSIONS: Among middle-aged women not taking OAB medications, OAB symptoms were associated with cognitive impairment, partly because of poor sleep quality. Further research is needed to determine whether early screening of patients with OAB can help identify those susceptible to cognitive impairment associated with OAB medication and if preventive measures should be targeted at this group.

Cortex-to-caudate volume ratio as a predictor of cognitive decline in Alzheimer's disease and mild cognitive impairment.

BACKGROUND: Brain and cortical atrophy play crucial roles in supporting the clinical diagnosis of Alzheimer's disease (AD). This study hypothesized that the ratios of brain or cortical volume to subcortical gray matter structure volumes are potential imaging markers for cognitive alterations in AD dementia and amnestic mild cognitive impairment (aMCI). METHODS: Seventy-seven subjects diagnosed with AD dementia or aMCI underwent baseline neuropsychological testing, 2-year follow-up cognitive assessments, and high-resolution T1-weighted MRI scans. Total brain/cortical volume and subcortical gray matter structure volumes were automatically segmented and measured. Univariate and multiple linear regression analyses were conducted to determine the associations between volumetric ratios and interval changes in cognitive scores. RESULTS: The ratio of cortical volume to caudate volume showed the most significant association with changes in MoCA (B = 0.132, SE = 0.042, p = 0.002), MMSE (B = 0.140, SE = 0.040, p = 0.001), and CDR-SOB (B = -0.013, SE = 0.005, p = 0.007) scores over the 2-year follow-up period. These associations remained significant after adjusting for various covariates. Similar associations were observed for the ratios of cortical volume to putamen and globus pallidum volumes. CONCLUSIONS: The cortex-to-caudate volume ratio is significantly associated with cognitive decline in AD dementia and aMCI. This ratio may serve as a useful biomarker for monitoring disease progression and predicting cognitive outcomes. Our findings highlight the importance of considering the relative atrophy of cortical and subcortical structures in understanding AD pathology.

Effect of Domain Manipulation in the Staphylococcal Phage Endolysin, Endo88, on Lytic Efficiency and Host Range.

The bacteriophage endolysin Endo88 targeting Staphylococcus aureus PS88 consists of the CHAP and Amidase-2 enzymatic domains and one SH3b targeting domain. In this study, the effects of domain manipulations on Endo88 functionality were determined. Three truncated mutants of Endo88 (CHAP, CHAPAmidase and CHAPSH3) and two chimeras (CHAPAmidase-Cpl7Cpl7 and Endo88-Cpl7Cpl7) containing the Cpl7Cpl7 targeting domains of the streptococcal LambdaSa2-ECC endolysin were cloned in E. coli (pET28a), expressed, and then purified. Lytic efficiency and host range were assessed through plate lysis assays and turbidity reduction assays. Endo88 required all domains for maximum functionality, with activity detected against Staphylococcus aureus PS88 (host strain), S. aureus Mu50 (VISA), CoNS (Staphylococcus epidermidis and Staphylococcus hominis), and Enterococcus faecalis. The truncated constructs maintained the original host range but with reduced lytic efficiency. The Amidase-2 and SH3b domains are interdependent in maximizing functionality. The chimera constructs demonstrated reduced functionality, without activity against Streptococcus agalactiae in both assays. This study provides insights into domain function in a staphylococcal endolysin, which could enable the development of prospective engineered antimicrobials against multidrug-resistant pathogens.

Prognostic Value of a Multi-mRNA Signature for 1-Year All-Cause Death in Hospitalized Patients With Heart Failure With a Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction is a major global public health problem, while effective risk stratification tools are still lacking. We sought to construct a multi-mRNA signature to predict 1-year all-cause death. METHODS: We selected 30 patients with heart failure with preserved ejection fraction who died during 1-year follow-up and 30 who survived in the discovery set. One hundred seventy-one and 120 patients with heart failure with preserved ejection fraction were randomly selected as a test set and a validation set, respectively. We performed mRNA microarrays in all patients. RESULTS: We constructed a 5-mRNA signature for predicting 1-year all-cause death. The scores of the 5-mRNA signature were significantly associated with the 1-year risk of all-cause death in both the test set (hazard ratio, 2.72 [95% CI, 1.98-3.74]; P<0.001) and the validation set (hazard ratio, 3.95 [95% CI, 2.40-6.48]; P<0.001). Compared with a reference model, which included sex, ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) score, history of HF and NT-proBNP (N-terminal pro-B-type natriuretic peptide), the 5-mRNA signature had a better discrimination capability, with an increased area under the curve from 0.696 to 0.813 in the test set and from 0.712 to 0.848 in the validation set. A composite model integrating the 5-mRNA risk score and variables in the reference model demonstrated an excellent discrimination capability, with an area under the curve of 0.861 (95% CI, 0.784-0.939) in the test set and an area under the curve of 0.859 (95% CI, 0.755-0.963) in the validation set. The net reclassification improvement and integrated discrimination improvement indicated that the composite model significantly improved patient classification compared with the reference model in both sets (P<0.001). CONCLUSIONS: The 5-mRNA signature is a promising predictive tool for 1-year all-cause death and shows improved prognostic power over the established risk scores and NT-proBNP in patients with heart failure with preserved ejection fraction.