Temporary Gasserian ganglion stimulation utilizing SNM electrode in subacute herpetic trigeminal neuralgia.

Objective: Gasserian ganglion stimulation (GGS) is a neuromodulation technique that has been extensively applied in treating postherpetic trigeminal neuralgia. However, permanent implantation of GGS was preferred in most treatment approaches. Few studies have investigated temporary GGS for the treatment of acute/subacute herpetic trigeminal neuralgia. Moreover, previous research has reported lead dislocation when utilizing traditional electrodes, which was associated with poor pain relief. In GGS research, preventing the accidental displacement of lead following implantation has consistently been a primary objective. Methods: We report a case of a 70-year-old woman with subacute herpetic trigeminal neuralgia who underwent temporary GGS for 14 days utilizing a sacral neuromodulation (SNM) quadripolar-tined lead. Computed tomography-guided percutaneous foramen ovale (FO) puncture and temporary SNM electrode implantation were performed during the surgery. A telephone interview was conducted to record a 12-month follow-up. Results: At admission, zoster-related trigeminal pain severity was assessed to be 9/10 on the visual analog scale (VAS). After a 14-day GGS treatment, the pain assessed on the VAS score reduced to 1/10 at discharge but increased to 4/10 at the 12-month follow-up after surgery. Additionally, the anxiety level improved from 58 points to 35 points on the Self-Rating Anxiety Scale (SAS), and the depression level improved from 62 points to 40 points on the Self-Rating Depression Scale (SDS). The Physical Component Summary score of the 12-item Short-Form Health Survey (SF-12) increased from 33.9 to 47.0, and the Mental Component Summary (MCS) score of the SF-12 increased from 27.4 to 41.9. Conclusion: Temporary GGS might be a potentially effective treatment for subacute herpetic trigeminal neuralgia, and an SNM electrode might be a good choice for reducing the risk of dislocation.

Broadband stepped-frequency radar waveform generation by Fourier domain mode-locking period-one laser dynamics.

A stepped-frequency (SF) radar waveform generation method based on Fourier domain mode-locking (FDML) period-one laser dynamics is proposed and demonstrated. By fast controlling the optical injection strength of a semiconductor laser through electro-optical modulation, a broadband SF signal is generated. By further introducing an optoelectronic feedback loop with its round trip time delay matched with the temporal period of the SF signal, FDML is enabled through which the frequency stability, accuracy, and in-band signal-to-noise ratio are greatly improved. In the experiment, SF signals with a bandwidth of 6 GHz (12-18 GHz) and a frequency step of 150 MHz are generated. By comparing the qualities of signals generated with and without FDML, advantages of the proposed SF signal generation method are verified. Based on the proposed SF signal generation method, high-resolution inverse synthetic aperture radar (ISAR) imaging is also demonstrated, in which the 2D imaging resolution reaches 2.6 cm × 3.82 cm.

Assessing disparities through missing race and ethnicity data: results from a juvenile arthritis registry.

Introduction: Ensuring high-quality race and ethnicity data within the electronic health record (EHR) and across linked systems, such as patient registries, is necessary to achieving the goal of inclusion of racial and ethnic minorities in scientific research and detecting disparities associated with race and ethnicity. The project goal was to improve race and ethnicity data completion within the Pediatric Rheumatology Care Outcomes Improvement Network and assess impact of improved data completion on conclusions drawn from the registry. Methods: This is a mixed-methods quality improvement study that consisted of five parts, as follows: (1) Identifying baseline missing race and ethnicity data, (2) Surveying current collection and entry, (3) Completing data through audit and feedback cycles, (4) Assessing the impact on outcome measures, and (5) Conducting participant interviews and thematic analysis. Results: Across six participating centers, 29% of the patients were missing data on race and 31% were missing data on ethnicity. Of patients missing data, most patients were missing both race and ethnicity. Rates of missingness varied by data entry method (electronic vs. manual). Recovered data had a higher percentage of patients with Other race or Hispanic/Latino ethnicity compared with patients with non-missing race and ethnicity data at baseline. Black patients had a significantly higher odds ratio of having a clinical juvenile arthritis disease activity score (cJADAS10) of ≥5 at first follow-up compared with White patients. There was no significant change in odds ratio of cJADAS10 ≥5 for race and ethnicity after data completion. Patients missing race and ethnicity were more likely to be missing cJADAS values, which may affect the ability to detect changes in odds ratio of cJADAS ≥5 after completion. Conclusions: About one-third of the patients in a pediatric rheumatology registry were missing race and ethnicity data. After three audit and feedback cycles, centers decreased missing data by 94%, primarily via data recovery from the EHR. In this sample, completion of missing data did not change the findings related to differential outcomes by race. Recovered data were not uniformly distributed compared with those with non-missing race and ethnicity data at baseline, suggesting that differences in outcomes after completing race and ethnicity data may be seen with larger sample sizes.

Comparison of nanovesicles derived from Panax notoginseng at different size: physical properties, composition, and bioactivity.

Aim: Plant-derived nanovesicles have emerged as potential agents for combating tumors. In this study, we investigated the inhibitory effects of Panax notoginseng-derived nanovesicles (PnNVs) on the proliferation and migration of squamous cell carcinoma. Additionally, we explored the relationship between plant tuber size and the physical properties, composition and bioactivity of these nanovesicles. Methods: We isolated PnNVs from Panax notoginseng tubers of varying sizes: small-sized (s_PnNVs), medium-sized (m_PnNVs) and large-sized (l_PnNVs), and evaluated for size, potential, and morphology. Cellular uptake efficiency was assessed using confocal microscopy and flow cytometry. The ability of different PnNVs to inhibit oral squamous cell carcinoma cells was evaluated using plate cloning, CCK8 assay, and scratch healing assay. Off-target metabolomics was used to compare metabolic compounds of different PnNVs. Results: Our findings revealed that s_PnNVs exhibited lower potential but had the highest cellular uptake efficiency, whereas m_PnNVs were characterized by the smallest size and lowest cellular uptake efficiency. Notably, m_PnNVs demonstrated the most effective inhibition of squamous cell carcinoma growth and migration. Compositional analyses showed that PnNVs were rich in proteins and contained lower levels of RNA, with l_PnNVs having the highest protein content. Furthermore, untargeted metabolomics analysis revealed a significant increase in the expression of specific antitumour-related metabolites in m_PnNVs compared to s_PnNVs and l_PnNVs. Conclusion: Overall, our results underscore the influence of plant tuber size on the bioactivity of the nanovesicles from which they are derived, emphasizing its importance for experimental design and study reproducibility.

Synergistic promotion of nitrogen vacancies and single atomic dopants on Pt/C3N4 for photocatalytic hydrogen evolution.

C3N4 is widely applied in the synthesis of single-atom catalysts. However, understanding on the active site and the reaction mechanism is not fully in consensus. Especially, bare studies have considered the coordination environment of the single-atomic dopant and the effect of nitrogen vacancy on C3N4. In this study, we found that the presence of nitrogen vacancies promotes the activation of water and reduces the activation energy barrier for hydrogen generation. The results show that a synergistic effect between single-atom Pt and nitrogen vacancies enables the catalyst to achieve a superior hydrogen production rate of 3,890 µmol/g/h, which is 16.8 times higher than that of pristine C3N4. Moreover, the catalyst is also applicable for photocatalytic hydrogen production from seawater without significantly decreased hydrogen production rate. This study paves the way for the rational design and optimization of next-generation photocatalysts for sustainable energy applications, particularly in solar-driven hydrogen production.

Pleiotropic regulatory locus 1 maintains actin cytoskeleton integrity and cellular homeostasis to enable Arabidopsis root growth.

Cell functions are based on the integrity of actin filaments. The actin cytoskeleton is typically the target but also the source of signals. Arabidopsis PRL1 (Pleiotropic Regulatory Locus 1), regulates multiple cellular processes and physiological responses. However, the precise mechanisms underlying PRL1`s multiple functions are unclear. Here, we show that PRL1 maintains actin integrity and concomitant cellular homeostasis. The cortical actin cytoskeleton was de-polymerized in the prl1 mutant, causing the developmental root defect. Actin depolymerization, rather than reactive oxygen species (ROS) imbalance, constituted the fundamental cause of retarded root growth in prl1. ANAC085 upregulation by, and cooperation with, actin depolymerization triggered stele cell death in prl1 roots. Differential gene expression and alternative splicing defects resulting from actin depolymerization occurred independently in prl1. Our work establishes the cause-effect relationships between actin depolymerization and downstream stress-related signals, revealing a novel function of PRL1 and enhancing the understanding of PRL`s functional mechanisms.

First Report of Neofusicoccum yunnanense Causing Leaf Spot on Ivy in Yunnan Province, China.

Ivy (Hedera nepalensis var. sinensis (Tobl.) Rehd) is an evergreen root-climbing vine, widely cultivated in eastern Asia because of its ornamental, environmental, and medicinal value (Wu et al. 2019). In October 2023, the leaf spot symptom of Ivy was observed in the Kunming Botanical Garden in Yunnan Province, China (25.14°N, 102.75°E), and the disease incidence was up to 38% (76 of 200 leaves). Initially, dark-brown or black small spots appeared on the leaves. As the lesions progressed, their center emerged tawny, and the black halos were expanded around the lesions. In severe cases, small spots could link together to form leaf blight even resulting in blade death. In order to obtain pure isolates, 10 diseased leaves were collected and cut into 1 mm × 1 mm pieces, surface disinfected with 75 % ethanol for 30 s, followed by 3% NaClO for 3 min, and finally washed three times with sterilized water. The pieces were placed on the potato dextrose agar (PDA) media, which was incubated at 25°C for 3 days. Individual hyphal tips from the developing fungal colonies were placed on PDA and incubated for 5 to 10 days. Six strains (6 out of 10) were obtained with same colony morphology. Conidia were hyaline, unicellular, nonseptate, ellipsoidal or fusiform, thin walled, externally smooth and ranged from 15.0 to 22.0 (avg. 18.4) µm × 5.0 to 8.0 (avg. 7.2) µm (n=30). Morphological comparison proposed that the present fungi belonged to Neofusicoccum (Zhang et al. 2021). Two isolates (GUCC23-0141 and GUCC23-0142) were selected for multi-gene phylogenetic analyses. The PCR reaction of the internal transcribed spacer region (ITS), translation elongation factor 1-α (EF1-α), and ß-tubulin genes were run using primers ITS1/ ITS4 (White et al. 1990), EF1-728F/ EF1-986R (Carbone and Kohn 1999), and Bt2a/ Bt2b (Glass and Donaldson 1995). The accession numbers of DNA sequences of GUCC23-0141 and GUCC23-0142 are ITS: PP728109 and PP728110; TUB2: PP744490 and PP744491; and TEF1-α: PP744488 and PP744489. BLAST analysis showed 100% identity for ITS and TUB2, and 98.97% for TEF1-α with the Neofusicoccum yunnanense (CSF6142). Phylogenetic analyses also supported that our isolates kept a close relationship to N. yunnanense. Three one-year plants were used for pathogenicity test, two of which were inoculated with PDA plugs containing N. yunnanense and one of which was inoculated with blank PDA plugs and used as control. For each plant, three leaves were selected to conduct the test, whose surfaces were sterilized with 75% alcohol. All the leaves were covered with cotton moistened with sterilized water on top. All plants were placed in a greenhouse with 25℃ and 75% humidity. Few small black spots were observed at the inoculation site after 3 days, which were enlarged gradually after 7 days. However, control plants remained healthy. N. yunnanense was reisolated from the diseased tissues and identified based on morphological and molecular characteristics. On basis of pathogen identification and Koch's test, we proposed the leaf spot of Ivy caused by N. yunnanense. This was the first report about N. yunnanense causing the disease of Ivy. This result provides a theoretical basis for further research into the control of the disease. As an important ornamental plant, we should pay attention to the management of this disease.

Water Impact Dynamics and Mechanism Analysis of Polypropylene and Polypropylene/poly(ethylene-co-octene) Replica Surfaces with Nanowires under Low Temperature Conditions.

In this work, polypropylene (PP) and PP/poly(ethylene-co-octene) (PP/POE) blend replica surfaces with densely arranged nanowires are fabricated using a molding process. Morphology analysis shows that the nanowires on these replica surfaces have sharp tips and high aspect ratios. The droplet impact behaviors on the surfaces of the PP/POE blend replicas and PP replicas are investigated before and after freezing at -20 °C for 4 h. The height of the nanowires on the PP/POE blend replica surfaces is higher than that on the PP surface before and after freezing. The static wettability and droplet impact tests on the surfaces of PP/POE blend replicas and PP replica show that adding POE into the PP matrix can significantly increase the toughness of the nanowires on the PP/POE blend replica surfaces during the droplet impact at low temperatures. These investigations are favorable to broaden the practical applications of superhydrophobic surfaces in some severe environments.

Comparison of the Efficacy Between Standard Measurement-Base Care (MBC) and Enhanced MBC for Major Depressive Disorder: A Pilot Study.

Purpose: To validate the efficacy of enhanced measurement-based care against standard measurement-based care in patients with major depressive disorder. Patients and Methods: In this pilot study of an ongoing multicenter cluster randomized controlled trails, 160 patients diagnosed with major depressive disorder were enrolled from 2 mental health centers, with a plan to include 12 centers in total. One hundred patients engaged in a six-month evaluation using a technology-enhanced measurement-based care tool, including assessments of clinical symptoms, side effects, and functionality at baseline, two months, four months and six months. Simultaneously, the remaining 60 patients underwent standard paper-based measurement-based care, utilizing the same set of scales over the same six-month period, with assessments at the same time points. Results: Patients utilizing the enhanced measurement-based care tool demonstrated a significantly higher reduction rate in PHQ-9 scores compared to those using standard paper-based measurement-based care during the two-month follow-up. Additionally, a notable positive correlation was observed between the frequency of enhanced measurement-based care tool usage and the quality of life during the two-month follow-up. Conclusion: Enhanced measurement-based care has the effect of reducing depressive symptoms. Our study emphasized that using enhanced measurement-based care via smartphones is a feasible tool for patients with major depressive disorder. Our future study, including results from additional research centers, may further validate the effectiveness of enhanced measurement-based care.

A Pyroptosis-Inducing Arsenic(III) Nanomicelle Platform for Synergistic Cancer Immunotherapy.

Immunogenic cell death (ICD) could activate anti-tumor immune responses, which is highly attractive for improving cancer treatment effectiveness. Here, this work reports a multifunctional arsenic(III) allosteric inhibitor Mech02, which induces excessive accumulation of 1O2 through sensitized biocatalytic reactions, leading to cell pyroptosis and amplified ICD effect. After Mech02 is converted to Mech03, it could actualize stronger binding effects on the allosteric pocket of pyruvate kinase M2, further interfering with the anaerobic glycolysis pathway of tumors. The enhanced DNA damage triggered by Mech02 and the pyroptosis of cancer stem cells provide assurance for complete tumor clearance. In vivo experiments prove nanomicelle Mech02-HA NPs is able to activate immune memory effects and raise the persistence of anti-tumor immunity. In summary, this study for the first time to introduce the arsenic(III) pharmacophore as an enhanced ICD effect initiator into nitrogen mustard, providing insights for the development of efficient multimodal tumor therapy agents.

Response of soil moisture to rainfall following deep soil drying in China's hilly loess lands.

Deep soil drying is a physical soil phenomenon that has become increasingly characteristic to artificial afforestation on China's Loess Plateau. Current research is largely short of conclusive reports on soil moisture recovery following deep soil drying in afforested lands. In this study, a 10-m deep underground column was constructed at Pengyang Experimental Station in Ningxia. The CS650-CR1000 automatic soil moisture monitoring system and BLJW-4 small meteorological observation stations were used to respectively monitor soil moisture and meteorological conditions in the study area for the period 2014-2019. The local rainfall was classified and the characteristics of soil infiltration analyzed at both monthly and annual scales. The results showed that: i) Deep soil moisture recovery in the semi-arid Loess Plateau region depended mainly on 25-49.9 mm and >50 mm types of rainfall; together accounting for 35.44 % of the precipitation. ii) Deep soil moisture replenishment occurred mainly for the period from April to October. While this accounted for 30.13 % of the precipitation, evaporation loss accounted for 69.87 % of it. With increasing monthly rainfall (Pm), the variation in monthly infiltration depth (Zm) was quadratic in shape - where Zm = -0.0094 Pm2 + 3.7702 Pm (R2 = 0.9577). iii) At the annual scale, deep soil moisture replenishment was mainly driven by year-on-year infiltration water accumulation. This is because a single year precipitation infiltration was not enough to replenish deep soil moisture. The cumulative infiltration depth for 2014-2019 was 180, 260, 400, 700, 1000 > 1000 cm. It suggested that soil water infiltration and deep dry soil recovery occurred at different times under rainfed conditions in the semi-arid loess hills in China. This is key for in-depth studies of the hydrological process in dry soil regions.

Associations of personal PM2.5-bound heavy metals and heavy metal mixture with lung function: Results from a panel study in Chinese urban residents.

BACKGROUND: There are a few reports on the associations between fine particulate matter (PM2.5)-bound heavy metals and lung function. OBJECTIVES: To evaluate the associations of single and mixed PM2.5-bound heavy metals with lung function. METHODS: This study included 316 observations of 224 Chinese adults from the Wuhan-Zhuhai cohort over two study periods, and measured participants' personal PM2.5-bound heavy metals and lung function. Three linear mixed models, including the single constituent model, the PM2.5-adjusted constituent model, and the constituent residual model were used to evaluate the association between single metal and lung function. Mixed exposure models including Bayesian kernel machine regression (BKMR) model, weighted quantile sum (WQS) model, and Explainable Machine Learning model were used to assess the relationship between PM2.5-bound heavy metal mixtures and lung function. RESULTS: In the single exposure analyses, significant negative associations of PM2.5-bound lead, antimony, and cadmium with peak expiratory flow (PEF) were observed. In the mixed exposure analyses, significant decreases in forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC), maximal mid-expiratory flow (MMF), and forced expiratory flow at 75% of the pulmonary volume (FEF75) were associated with the increased PM2.5-bound heavy metal mixture. The BKMR models suggested negative associations of PM2.5-bound lead and antimony with lung function. In addition, PM2.5-bound copper was positively associated with FEV1/FVC, MMF, and FEF75. The Explainable Machine Learning models suggested that FEV1/FVC, MMF, and FEF75 decreased with the elevated PM2.5-bound lead, manganese, and vanadium, and increased with the elevated PM2.5-bound copper. CONCLUSIONS: The negative relationships were detected between PM2.5-bound heavy metal mixture and FEV1/FVC, MMF, as well as FEF75. Among the PM2.5-bound heavy metal mixture, PM2.5-bound lead, antimony, manganese, and vanadium were negatively associated with FEV1/FVC, MMF, and FEF75, while PM2.5-bound copper was positively associated with FEV1/FVC, MMF, and FEF75.

Role of N6-methyladenosine in tumor neovascularization.

Tumor neovascularization is essential for the growth, invasion, and metastasis of tumors. Recent studies have highlighted the significant role of N6-methyladenosine (m6A) modification in regulating these processes. This review explores the mechanisms by which m6A influences tumor neovascularization, focusing on its impact on angiogenesis and vasculogenic mimicry (VM). We discuss the roles of m6A writers, erasers, and readers in modulating the stability and translation of angiogenic factors like vascular endothelial growth factor (VEGF), and their involvement in key signaling pathways such as PI3K/AKT, MAPK, and Hippo. Additionally, we outline the role of m6A in vascular-immune crosstalk. Finally, we discuss the current development of m6A inhibitors and their potential applications, along with the contribution of m6A to anti-angiogenic therapy resistance. Highlighting the therapeutic potential of targeting m6A regulators, this review provides novel insights into anti-angiogenic strategies and underscores the need for further research to fully exploit m6A modulation in cancer treatment. By understanding the intricate role of m6A in tumor neovascularization, we can develop more effective therapeutic approaches to inhibit tumor growth and overcome treatment resistance. Targeting m6A offers a novel approach to interfere with the tumor's ability to manipulate its microenvironment, enhancing the efficacy of existing treatments and providing new avenues for combating cancer progression.

Rapid progress of an iris metastasis from esophageal cancer: a case report and review of literature.

This case report details a rare instance of rapid iris metastasis from esophageal cancer in a 59-year-old man. A literature review was conducted to explore recent advances in detecting, diagnosing, and treating intraocular metastatic malignancies. Positron emission tomography-computed tomography played a crucial role in identifying primary sites and systemic metastases. Local treatment combined with systemic therapy effectively reduced tumor size, preserved useful vision, and improved the patient's survival rate. A comparison was made of the characteristics of iris metastases from esophageal cancer and lung cancer, including age, gender, tumor characteristics, and treatment. The challenges associated with diagnosis and treatment are discussed, highlighting the implications for clinical practice.

Fighting ferroptosis: Protective effects of dexmedetomidine on vital organ injuries.

Vital organ injury is one of the leading causes of global mortality and socio-economic burdens. Current treatments have limited efficacy, and new strategies are needed. Dexmedetomidine (DEX) is a highly selective α2-adrenergic receptor that protects multiple organs by reducing inflammation and preventing cell death. However, its exact mechanism is not yet fully understood. Understanding the underlying molecular mechanisms of its protective effects is crucial as it could provide a basis for designing highly targeted and more effective drugs. Ferroptosis is the primary mode of cell death during organ injury, and recent studies have shown that DEX can protect vital organs from this process. This review provides a detailed analysis of preclinical in vitro and in vivo studies and gains a better understanding of how DEX protects against vital organ injuries by inhibiting ferroptosis. Our findings suggest that DEX can potentially protect vital organs mainly by regulating iron metabolism and the antioxidant defense system. This is the first review that summarizes all evidence of ferroptosis's role in DEX's protective effects against vital organ injuries. Our work aims to provide new insights into organ therapy with DEX and accelerate its translation from the laboratory to clinical settings.

The acoustic change complex evoked by location-change sounds in the elderly.

OBJECTIVE: We have shown that the acoustic change complex (ACC) can be elicited by changing the horizontal sound location in young individuals. In this study, we aimed to evaluate the application of ACC within the elderly and its relationship with behavioural results. DESIGN: The minimum audible angle (MAA), as well as onset cortical auditory evoked potentials (onset-CAEPs) and ACC elicited by the stimuli of location-change white noise (±45 to ±2 degrees) were recorded. Latencies and amplitudes were analysed using repeated-measures ANOVA. Pearson correlation analysis was conducted to examine the relationship between ACC and MAA. STUDY SAMPLE: Ten older adults with normal hearing (NH) and twenty with presbycusis. RESULTS: The ACC was effectively elicited with angular variations in elderly participants. The onset-CAEP N1 latency, ACC N1'-P2' amplitude, and N1' latency were all associated with the angle shifts, with the N1' latency being the most predictive factor for angle discrimination. The consistency between MAA and ACC made them complementary for the clinical evaluation of sound localisation. CONCLUSIONS: The utilisation of ACC, evoked by location-change sounds, presented a promising clinical objective measure for evaluating sound localisation abilities in the elderly.

Enhanced silicate weathering accelerates forest carbon sequestration by stimulating the soil mineral carbon pump.

Enhanced silicate rock weathering (ERW) is an emerging strategy for carbon dioxide removal (CDR) from the atmosphere to mitigate anthropogenic climate change. ERW aims at promoting soil inorganic carbon sequestration by accelerating geochemical weathering processes. Theoretically, ERW may also impact soil organic carbon (SOC), the largest carbon pool in terrestrial ecosystems, but experimental evidence for this is largely lacking. Here, we conducted a 2-year field experiment in tropical rubber plantations in the southeast of China to evaluate the effects of wollastonite powder additions (0, 0.25, and 0.5 kg m-2) on both soil organic and inorganic carbon at 0-10 cm depth. We found that ERW significantly increased the concentration of SOC and HCO3 -, but the increases in SOC were four and eight times higher than that of HCO3 - with low- and high-level wollastonite applications. ERW had positive effects on the accrual of organic carbon in mineral-associated organic matter (MAOM) and macroaggregate fractions, but not on particulate organic matter. Path analysis suggested that ERW increased MAOM mainly by increasing the release of Ca, Si, and Fe, and to a lesser extent by stimulating root growth and microbial-derived carbon inputs. Our study indicates that ERW with wollastonite can promote SOC sequestration in stable MOAM in surface soils through both the soil mineral carbon pump and microbial carbon pump. These effects may have been larger than the inorganic CDR during our experiment. We argue it is essential to account for the responses of SOC in the assessments of CDR by ERW.

Preliminary effects of risk-adapted PSA screening for prostate cancer after integrating PRS-specific and age-specific variation.

Background: Although the risk of prostate cancer (PCa) varies across different ages and genetic risks, it's unclear about the effects of genetic-specific and age-specific prostate-specific antigen (PSA) screening for PCa. Methods: Weighed and unweighted polygenic risk scores (PRS) were constructed to classify the participants from the PLCO trial into low- or high-PRS groups. The age-specific and PRS-specific cut-off values of PSA for PCa screening were determined with time-dependent receiver-operating-characteristic curves and area-under-curves (tdAUCs). Improved screening strategies integrating PRS-specific and age-specific cut-off values of PSA were compared to traditional PSA screening on accuracy, detection rates of high-grade PCa (Gleason score ≥7), and false positive rate. Results: Weighted PRS with 80 SNPs significantly associated with PCa was determined as the optimal PRS, with an AUC of 0.631. After stratifying by PRS, the tdAUCs of PSA with a 10-year risk of PCa were 0.818 and 0.816 for low- and high-PRS groups, whereas the cut-off values were 1.42 and 1.62 ng/mL, respectively. After further stratifying by age, the age-specific cut-off values of PSA were relatively lower for low PRS (1.42, 1.65, 1.60, and 2.24 ng/mL for aged <60, 60-64, 65-69, and ≥70 years) than high PRS (1.48, 1.47, 1.89, and 2.72 ng/mL). Further analyses showed an obvious interaction of positive PSA and high PRS on PCa incidence and mortality. Very small difference in PCa risk were observed among subgroups with PSA (-) across different age and PRS, and PCa incidence and mortality with PSA (+) significantly increased as age and PRS, with highest risk for high-PRS/PSA (+) in participants aged ≥70 years [HRs (95%CI): 16.00 (12.62-20.29) and 19.48 (9.26-40.96)]. The recommended screening strategy reduced 12.8% of missed PCa, ensured high specificity, but not caused excessive false positives than traditional PSA screening. Conclusion: Risk-adapted screening integrating PRS-specific and age-specific cut-off values of PSA would be more effective than traditional PSA screening.

Abnormal late postprandial glucagon response in type 1 diabetes is a function of differences in stimulated C-peptide concentrations.

Background: The functional changes in alpha cells in patients with type 1 diabetes (T1D) with different residual beta cell functions remain poorly elucidated. The study aimed to investigate the relationship between glucagon secretion and C-peptide levels and to explore the relationship between glucagon response and glucose increment in respond to a secretagogue in a steamed bread meal tolerance test (BMTT) in T1D. Methods: The study enrolled 43 adult patients with T1D and 24 healthy control subjects. Patients with T1D who underwent BMTT were divided into two groups based on peak C-peptide levels: C peptide low (CPL; C-peptide < 200 pmol/L; n=14) and high (CPH; C peptide ≥ 200 pmol/L; n=29). Plasma glucose, C-peptide, glucagon levels at 0, 30, 60, 120, and 180 min were measured. The glucagon response to the BMTT was defined by areas under the curve (AUC) as early (AUC0-30), late (AUC30-180), or total (AUC0-180) glucagon. Results: Compared to healthy individuals, fasting plasma glucagon was lower and postprandial plasma glucagon level was increased in patients with T1D. Glucagon levels after BMTT between the CPL and CPH group showed significant group by time interaction. Peak glucagon and glucagon at 60-180 min, total and late glucagon response were higher in CPL than CPH group, while fasting glucagon and early glucagon response adjusted for glucose were comparable between CPL and CPH group. The higher late glucagon response and late glucagon response adjusted for glucose were associated with lower peak C-peptide in T1D. The higher late glucagon response and lower peak C-peptide were associated with the higher value of ▵glucose at 180 min. Conclusion: Stimulated C-peptide levels affect the paradoxical increase in postprandial glucagon secretion in patients with T1D, especially late glucagon response. The exaggerated postprandial glucagon secretion further stimulates the elevation of postprandial glucose in patients with T1D.