Association between dietary vitamin C intake and migraine in adults: A cross-sectional study of the National Health and Nutrition Examination Survey.

BACKGROUND: Previous studies indicate that vitamin C may decrease the occurrence and intensity of migraines, but the evidence is restricted due to small sample sizes. This study aimed to determine the magnitude of the association between dietary vitamin C intake and migraine in the general population. METHODS: This cross-sectional study utilised data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004. Participants who had severe headaches or migraines in the past 3 months were classified as experiencing migraines. Dietary vitamin C intake was evaluated using the 24-h dietary recall system. Logistic regression models, restricted cubic spline (RCS) regression and stratified analyses were employed to assess the association between dietary vitamin C intake and migraine. RESULTS: The study included 4101 participants, of whom 702 (17.12%) experienced migraine. The study revealed an inverse association between dietary vitamin C intake and migraine (odds ratio [OR] = 0.89, 95% confidence intervals [CI] = 0.83-0.96, p = 0.002) after adjusting for demographic covariates, lifestyle covariates, laboratory tests, physical examinations, physical activity, dietary covariates and comorbidities. When vitamin C intake was categorised, the adjusted OR (95% CI) for migraine in Q4 (highest vitamin C intake) was 0.64 (95% CI = 0.49-0.84, p = 0.001) compared to Q1 (lowest vitamin C intake). The RCS regression showed a linear inverse relationship between dietary vitamin C intake and migraine (pnon-linearity = 0.449). The findings remained consistent, and no significant interactions were found among different groups. CONCLUSIONS: Dietary vitamin C intake was inversely associated with migraine, and a linear negative relationship was found between vitamin C intake and migraine.

Unimodular Multi-Input Multi-Output Waveform and Mismatch Filter Design for Saturated Forward Jamming Suppression.

Forward jammers replicate and retransmit radar signals back to generate coherent jamming signals and false targets, making anti-jamming an urgent issue in electronic warfare. Jamming transmitters work at saturation to maximize the retransmission power such that only the phase information of the angular waveform at the designated direction of arrival (DOA) is retained. Therefore, amplitude modulation of MIMO radar angular waveforms offers an advantage in combating forward jamming. We address both the design of unimodular MIMO waveforms and their associated mismatch filters to confront mainlobe jamming in this paper. Firstly, we design the MIMO waveforms to maximize the discrepancy between the retransmitted jamming and the spatially synthesized radar signal. We formulate the problem as unconstrained non-linear optimization and solve it using the conjugate gradient method. Particularly, we introduce fast Fourier transform (FFT) to accelerate the numeric calculation of both the objection function and its gradient. Secondly, we design a mismatch filter to further suppress the filtered jamming through convex optimization in polynomial time. The simulation results show that for an eight-element MIMO radar, we are able to reduce the correlation between the angular waveform and saturated forward jamming to -6.8 dB. Exploiting this difference, the mismatch filter can suppress the jamming peak by 19 dB at the cost of an SNR loss of less than 2 dB.

Association of dietary vitamin C intake with depression in adults: A cross-sectional study of NHANES from 2005 to 2020.

BACKGROUND: The aim of this study was to evaluate the association between dietary vitamin C intake and depression in adults. METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) during 2005 to 2020. Logistic regressions and restricted cubic spline (RCS) regression were used to assess the association between dietary vitamin C intake and depression. Additionally, we performed stratified and sensitivity analyses to evaluate the stability of the results. RESULTS: This study included 38,157 participants, with 3448 (9.04 %) of them experiencing depression. The vitamin C intake was negatively associated with depression after adjusting for all covariates (OR = 0.91, 95%CI: 0.88-0.94, P < 0.001). Similar inverse associations were observed when vitamin C intake was transformed into categorical variables. Individuals in higher quartiles of dietary vitamin C intake (Q2, Q3, and Q4) had lower odds ratios (ORs) compared to those in the lowest quartile (Q1), as indicated by adjusted ORs of 0.78 (95 % CI: 0.71-0.87, P < 0.001), 0.74 (95 % CI: 0.67-0.82, P < 0.001), and 0.73 (95 % CI: 0.65-0.81, P < 0.001), respectively. The RCS analysis found an L-shaped nonlinear relationship between dietary vitamin C intake and depression, after adjusting for all covariates (P for non-linearity<0.001). Consumption of vitamin C was inversely associated with depression (OR = 0.994, 95%CI: 0.993-0.996, P < 0.001) for intakes below 93.61 mg, but there was no association between dietary vitamin C intake and depression (P = 0.980) for intakes of 93.61 mg or higher. The inverse associations between vitamin C intake and depression remained robust in stratified and sensitivity analyses. LIMITATIONS: This study was a cross-sectional study, and therefore unable to establish a causal relationship between dietary vitamin C intake and depression. We are unable to fully eliminate the confounding effects resulted from other unmeasured or unknown factors. CONCLUSION: The study revealed a negative association between dietary vitamin C intake and depression, as well as an L-shaped nonlinear relationship between vitamin C intake and depression.

[Newborn screening, clinical features and genetic analysis for Citrin deficiency in Henan province].

OBJECTIVE: To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China. METHODS: A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired-t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. RESULTS: Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c.852_855delTATG, c.615+5G>A, c.550C>T and IVS16ins3kb were known pathogenic variants, whilst c.1111_1112delAT and c.837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis. CONCLUSION: The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c.852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.

Adverse events with pemigatinib in the real world: a pharmacovigilance study based on the FDA Adverse Event Reporting System.

BACKGROUND: To data, there is insufficient large-scale data on the adverse events (AEs) of pemigatinib. Consequently, we conducted a pharmacovigilance study utilizing the Food and Drug Administration Adverse Event Reporting System (FAERS) database to investigate these AEs. RESEARCH DESIGN AND METHODS: The OpenVigil 2.1 was used to extract AE data from the FAERS database. Proportional reporting ratio (PRR), reporting odds ratios (ROR), and bayesian analysis confidence propagation neural network (BCPNN) were used to assess the association between pemigatinib and AEs. The clinical importance of AE signals were prioritized using a rating scale. RESULTS: A total of 848 AE reports were retrieved from the FAERS database, and 421 AE reports were identified after the data cleaning process. After accounting for indication bias and removal of medication errors, 59 positive signals were finally included. The 59 positive signals emerged in 11 system organ classes (SOCs). Besides, 19 positive AEs were classified as moderate clinical priority, while 40 were deemed weak in terms of priority. 9 positive AEs were not included in the drug label. CONCLUSIONS: This study provided valuable evidence for clinicians to mitigate the risk of pemigatinib-related toxicities in the real world.

JAG1 Variants Confer Genetic Susceptibility to Thyroid Dysgenesis and Thyroid Dyshormonogenesis in 813 Congenital Hypothyroidism in China.

Background and Objective: Congenital hypothyroidism (CH) is indeed a prevalent neonatal endocrine disorder, affecting approximately 1 in 2000-3000 newborns worldwide, and 1 in 2400 newborns in China. Despite its high incidence, the genetic causes of CH, particularly those related to thyroid dysgenesis (TD), are still not well understood. However, previous studies have suggested that JAG1 may be a potential susceptibility gene for congenital thyroid defects. To explore the association between JAG1 and CH, we screened JAG1 variants in a large cohort of 813 CH patients. Methods: We performed genetic analysis of JAG1 using next-generation sequencing in 813 CH cases. The pathogenicity of the variants was assessed by bioinformatics softwares, protein sequence conservation analysis, and hydrophobic analysis. Further genetic analysis was conducted targeting 20 CH-related genes in these 25 JAG1 variant carriers. Results: We identified 10 pathogenic missense mutations (p.V45L, p.V272I, p.P552L, p.G610E, p.G852D, p.A891T, p.E1030K, p.R1060W, p.A1131T, p.P1174L) carried by 25 patients, the mutation rate of JAG1 in CH was 3.08%. Among these 25 patients, 16 with 1 variant, 6 with 2 variants, and the other 3 with 3 variants. Our findings indicated that JAG1 variants confer genetic susceptibility to both TD and DH, but with different inheritance models. JAG1 variants lead to TD mainly through monogenic model, while for DH cases, both monogenic mechanisms and oligogenic mechanisms play a pivotal role. Oligogenicity may contribute to the disease severity of DH. Conclusion: JAG1 is a shared genetic factor in TD and DH, with a detection rate of 3.08% in Chinese individuals with CH. A comparison between the oligogenic and monogenic groups suggests a gene dosage effect in CH. Patients with the same JAG1 mutation exhibit diverse clinical phenotypes, indicating complex mechanisms underlying phenotypic heterogeneity.

Pharmacovigilance study of BCR-ABL1 tyrosine kinase inhibitors: a safety analysis of the FDA adverse event reporting system.

BACKGROUND: With the increased use of BCR-ABL1 tyrosine kinase inhibitors (TKIs) in cancer patients, adverse events (AEs) have garnered considerable interest. We conducted this pharmacovigilance study to evaluate the AEs of BCR-ABL1 TKIs in cancer patients using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: To query AE reports from the FAERS database, we used OpenVigil 2.1. Descriptive analysis was then employed to describe the characteristics of TKIs-associated AE reports. We also utilized the disproportionality analysis to detect safety signals by calculating the proportional reporting ratio (PRR) and reporting odds ratios (ROR). RESULTS: From the FAERS database, a total of 85,989 AE reports were retrieved, with 3,080 significant AE signals identified. Specifically, imatinib, nilotinib, dasatinib, bosutinib, and ponatinib had significant AE signals of 1,058, 813, 232, 186, and 791, respectively. These significant signals were further categorized into 26 system organ classes (SOCs). The AE signals of imatinib and ponatinib were primarily associated with general disorders and administration site conditions. On the other hand, nilotinib, dasatinib, and bosutinib were mainly linked to investigations, respiratory, thoracic and mediastinal disorders, and gastrointestinal disorders, respectively. Notably, new signals of 245, 278, 47, 55, and 253 were observed in imatinib, nilotinib, dasatinib, bosutinib, and ponatinib, respectively. CONCLUSIONS: The results of this study demonstrated that AE signals differ among the five BCR-ABL1 TKIs. Furthermore, each BCR-ABL1 TKI displayed several new signals. These findings provide valuable information for clinicians aiming to reduce the risk of AEs during BCR-ABL1 TKI treatment.

Genetic analysis of isolated methylmalonic acidemia in Henan, China: c.1663G>A variant of MMUT prevalent in the Henan population.

BACKGROUND: Methylmalonic acidemia (MMA) is the most common organic acidemia in China, and isolated MMA accounts for approximately 30 % of all types of MMA. Common variants of the MMUT gene vary greatly around the world. The present study aims to determine the high-frequency and novel genetic variants of the MMUT gene in the Henan population of China and evaluate the prognosis of patients carrying the c.1663G>A (p.Ala555Thr) variant. METHODS: We performed next-generation sequencing for 41 patients with isolated MMA screened by tandem mass spectrometry (MS/MS) and analysed the genetic results. We also evaluated the prognosis of patients with the c.1663G>A variant. We used Jalview software for multispecies sequence alignment and Missense3D and DynaMut to predict the protein function of the detected novel variants. RESULTS: A total of 43 variants from 41 patients with isolated MMA were detected, of which c.1663G>A (14.63 %), c.729_730insTT (10.98 %), and c.1106G>A (8.53 %) are high-frequency variants of the MMUT gene in the Henan population. The patients carrying the c.1663G>A variant tended to be responsive to vitamin B12, have a low mortality rate. We also identified 5 novel variants (c.479C>T, c.811G>C, c.965T>A, c.1142G>A and c.1667C>T). CONCLUSION: The rare variant c.1663G>A is prevalent in the Henan population, and infants with this variant tend to have good prognosis. Our findings, especially novel variants, will help broaden the spectrum of genetic variants and facilitate clinical diagnosis and genetic counselling for affected families.

Pharmacovigilance Study of Infigratinib: A Safety Analysis of the FDA Adverse Event Reporting System.

BACKGROUND: Infigratinib is a fibroblast growth factor receptor (FGFR)-specifc tyrosine kinase inhibitor indicated for the treatment of patients with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma. However, few studies have been conducted to evaluated the safety of infigratinib in the real world. In this study, we conducted a pharmacovigilance study to evaluate the adverse events (AEs) of infigratinib by using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: OpenVigil 2.1 was employed to extract the FAERS database. Descriptive analysis was used to describe the characteristics of infigratinib-associated AE reports. Disproportionality analysis was performed by calculating the proportional reporting ratio (PRR), reporting odds ratios (ROR), and Bayesian analysis confidence propagation neural network (BCPNN) to detect positive signals. RESULTS: Our findings revealed 149 AE reports, among which 36 significant signals were identified. These significant AE signals were mainly observed in gastrointestinal disorders (N = 26, ROR = 26.03, PRR = 8.44, information component [IC] = 3.08) and skin and subcutaneous tissue disorders (N = 21, ROR = 92.13, PRR = 40.41, IC = 5.34). Notably, dehydration and skin exfoliation were unexpected AEs, but had relatively high signal intensities (ROR = 29.75, PRR = 26.64, IC = 4.74; ROR = 50.61, PRR = 45.24, IC = 5.50, respectively) despite not being listed on the drug label. Furthermore, our analysis showed that infigratinib dose differed statistically between severe and non-severe reports (113.82 ± 16.13 mg vs 125 ± 0.00 mg, t = - 4.28; p < 0.001). However, there were no significant differences in sex, age, and types of AEs between the two groups (p  = 0.06, p  = 0.86, and p = 0.93, respectively). CONCLUSIONS: These findings suggest that gastrointestinal and skin toxicities are the most common adverse reactions for infigratinib. It is important to recognize skin exfoliation and dehydration in clinical practice, as they are unexpected AEs. Additionally, our study indicates that infigratinib dose may correlate with an increased risk of AE severity, highlighting the need for dose adjustment of infigratinib when exposure to the drug is increased due to internal or external factors.

Cas9-mediated knockout of Ndrg2 enhances the regenerative potential of dendritic cells for wound healing.

Chronic wounds impose a significant healthcare burden to a broad patient population. Cell-based therapies, while having shown benefits for the treatment of chronic wounds, have not yet achieved widespread adoption into clinical practice. We developed a CRISPR/Cas9 approach to precisely edit murine dendritic cells to enhance their therapeutic potential for healing chronic wounds. Using single-cell RNA sequencing of tolerogenic dendritic cells, we identified N-myc downregulated gene 2 (Ndrg2), which marks a specific population of dendritic cell progenitors, as a promising target for CRISPR knockout. Ndrg2-knockout alters the transcriptomic profile of dendritic cells and preserves an immature cell state with a strong pro-angiogenic and regenerative capacity. We then incorporated our CRISPR-based cell engineering within a therapeutic hydrogel for in vivo cell delivery and developed an effective translational approach for dendritic cell-based immunotherapy that accelerated healing of full-thickness wounds in both non-diabetic and diabetic mouse models. These findings could open the door to future clinical trials using safe gene editing in dendritic cells for treating various types of chronic wounds.