Limb development genes underlie variation in human fingerprint patterns.

Fingerprints are of long-standing practical and cultural interest, but little is known about the mechanisms that underlie their variation. Using genome-wide scans in Han Chinese cohorts, we identified 18 loci associated with fingerprint type across the digits, including a genetic basis for the long-recognized "pattern-block" correlations among the middle three digits. In particular, we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice. Dynamic EVI1 expression during human development supports its role in shaping the limbs and digits, rather than influencing skin patterning directly. Trans-ethnic meta-analysis identified 43 fingerprint-associated loci, with nearby genes being strongly enriched for general limb development pathways. We also found that fingerprint patterns were genetically correlated with hand proportions. Taken together, these findings support the key role of limb development genes in influencing the outcome of fingerprint patterning.

Neofunctionalization of an OMT cluster dominates polymethoxyflavone biosynthesis associated with the domestication of citrus.

Polymethoxyflavones (PMFs) are a class of abundant specialized metabolites with remarkable anticancer properties in citrus. Multiple methoxy groups in PMFs are derived from methylation modification catalyzed by a series of hydroxylases and O-methyltransferases (OMTs). However, the specific OMTs that catalyze the systematic O-methylation of hydroxyflavones remain largely unknown. Here, we report that PMFs are highly accumulated in wild mandarins and mandarin-derived accessions, while undetectable in early-diverging citrus species and related species. Our results demonstrated that three homologous genes, CreOMT3, CreOMT4, and CreOMT5, are crucial for PMF biosynthesis in citrus, and their encoded methyltransferases exhibit multisite O-methylation activities for hydroxyflavones, producing seven PMFs in vitro and in vivo. Comparative genomic and syntenic analyses indicated that the tandem CreOMT3, CreOMT4, and CreOMT5 may be duplicated from CreOMT6 and contributes to the genetic basis of PMF biosynthesis in the mandarin group through neofunctionalization. We also demonstrated that N17 in CreOMT4 is an essential amino acid residue for C3-, C5-, C6-, and C3'-O-methylation activity and provided a rationale for the functional deficiency of OMT6 to produce PMFs in early-diverging citrus and some domesticated citrus species. A 1,041-bp deletion in the CreOMT4 promoter, which is found in most modern cultivated mandarins, has reduced the PMF content relative to that in wild and early-admixture mandarins. This study provides a framework for reconstructing PMF biosynthetic pathways, which may facilitate the breeding of citrus fruits with enhanced health benefits.

Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci.

Human ear morphology, a complex anatomical structure represented by a multidimensional set of correlated and heritable phenotypes, has a poorly understood genetic architecture. In this study, we quantitatively assessed 136 ear morphology traits using deep learning analysis of digital face images in 14,921 individuals from five different cohorts in Europe, Asia, and Latin America. Through GWAS meta-analysis and C-GWASs, a recently introduced method to effectively combine GWASs of many traits, we identified 16 genetic loci involved in various ear phenotypes, eight of which have not been previously associated with human ear features. Our findings suggest that ear morphology shares genetic determinants with other surface ectoderm-derived traits such as facial variation, mono eyebrow, and male pattern baldness. Our results enhance the genetic understanding of human ear morphology and shed light on the shared genetic contributors of different surface ectoderm-derived phenotypes. Additionally, gene editing experiments in mice have demonstrated that knocking out the newly ear-associated gene (Intu) and a previously ear-associated gene (Tbx15) causes deviating mouse ear morphology.

Interface Engineering with the Coupling of a 3D Porous Structure Enables MoP2-NiCoP Heterostructure Nanosheets for Enhanced Alkaline Hydrogen Evolution Reaction.

One of the crucial parts of the electrochemically focused energy conversion and storage system is the hydrogen evolution reaction. The further exploration of electrocatalysts made of nonprecious metals could help to bring the technology closer to industrialization. Here, we present an effective hydrogen evolution reaction (HER) electrocatalyst that employs hydrothermal and phosphorization steps to create three-dimensional (3D) porous MoP2-NiCoP heterostructure nanosheets on nickel foam (MoP2-NiCoP/NF). H2O-dissociation and H-adsorption were effectively achieved due to the distinctive interface engineering between NiCoP and MoP2, which functions as a channel for immediate electron transfer. Compared to the single-component MoP2 and NiCoP, the synergistic interaction between the heterogeneous components coupling and the 3D porous structure enables MoP2-NiCoP/NF to exhibit satisfactory catalytic activity with an ultralow overpotential of 50 mV at 10 mA cm-2, which is close to the commercial Pt/C catalyst in alkaline media. More importantly, it exhibits good stability, with the ability to be electrolyzed in 1.0 M KOH electrolyte for 24 h without a significant change in overpotential. This study offers directions for the design of low-cost, high-activity, transition metal phosphides (TMPs)-based HER catalyst alternatives for future practical applications.

Integrated Heterogeneous Engineering with the Vacancy Defect of Porous CoPv-MoxPv Nanosheets for an Accelerated Hydrogen Evolution Reaction.

Electrochemical water splitting is a possible way of realizing sustainable and clean hydrogen production but is challenging, because a highly active and durable electrocatalyst is essential. In this work, we integrated heterogeneous engineering and vacancy defect strategies to design and fabricate a heterostructure electrocatalyst (CoPv-MoxPv/CNT) with abundant phosphorus vacancies attached to carbon nanotubes (CNTs). The vacancy defects enabled the optimization of the electronic structure; thereby, the electron-rich low-valent metal sites enhanced the ability of nonmetallic P to capture proton H. Meanwhile, the heterogeneous interface between bimetallic phosphides and CNTs realized rapid electron transfer. In addition, the Co, Mo, and P active species in the electrocatalytic process exposed increased amounts of active sites featuring porous nanosheet structures, which facilitated the adsorption of reaction intermediates and thus enhanced the hydrogen evolution reaction performance. In particular, the optimized CoPv-MoxPv/CNT catalyst possesses an overpotential of 138 mV at a current density of 10 mA cm-2 and long-term stability for 24 h. This work offers insights and possibilities for the engineering and exploration of transition metal-based electrocatalysts through combining multiple synergistic strategies.

Genetic association between smoking and DLCO in idiopathic pulmonary fibrosis patients.

BACKGROUND: Observational studies have shown that smoking is related to the diffusing capacity of the lungs for carbon monoxide (DLCO) in individuals with idiopathic pulmonary fibrosis (IPF). Nevertheless, further investigation is needed to determine the causal effect between these two variables. Therefore, we conducted a study to investigate the causal relationship between smoking and DLCO in IPF patients using two-sample Mendelian randomization (MR) analysis. METHODS: Large-scale genome-wide association study (GWAS) datasets from individuals of European descent were analysed. These datasets included published lifetime smoking index (LSI) data for 462,690 participants and DLCO data for 975 IPF patients. The inverse-variance weighting (IVW) method was the main method used in our analysis. Sensitivity analyses were performed by MR‒Egger regression, Cochran's Q test, the leave-one-out test and the MR-PRESSO global test. RESULTS: A genetically predicted increase in LSI was associated with a decrease in DLCO in IPF patients [ORIVW = 0.54; 95% CI 0.32-0.93; P = 0.02]. CONCLUSIONS: Our study suggested that smoking is associated with a decrease in DLCO. Patients diagnosed with IPF should adopt an active and healthy lifestyle, especially by quitting smoking, which may be effective at slowing the progression of IPF.

Gamma-aminobutyric acid and glutamate/glutamine levels in the dentate nucleus and periaqueductal gray in new daily persistent headache: a magnetic resonance spectroscopy study.

BACKGROUND: Magnetic resonance spectroscopy (MRS) studies have indicated that the imbalance between gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels was the potential cause of migraine development. However, the changes in the GABA and Glx levels in patients with New daily persistent headache (NDPH) remain unclear. This study aimed to investigate the changes in GABA and Glx levels in the periaqueductal gray (PAG) and dentate nucleus (DN) in patients with NDPH using the MEGA-PRESS sequence. METHODS: Twenty-one NDPH patients and 22 age- and sex-matched healthy controls (HCs) were included and underwent a 3.0T MRI examination, using the MEGA-PRESS sequence to analyze GABA and Glx levels of PAG and DN. The correlations between these neurotransmitter levels and clinical characteristics were also analyzed. RESULTS: There were no significant differences in the GABA+/Water, GABA+/Cr, Glx/Water, and Glx/Cr levels in both PAG and DN between the two groups (all p > 0.05). Moderate-severe NDPH patients had lower levels of Glx/Water (p = 0.034) and Glx/Cr (p = 0.012) in DN than minimal-mild NDPH patients. In patients with NDPH, higher Glx/Water levels in the PAG (r=-0.471, p = 0.031, n = 21) and DN (r=-0.501, p = 0.021, n = 21) and higher Glx/Cr levels in DN (r=-0.483, p = 0.026, n = 21) were found to be correlated with lower Visual Analogue Scale scores. Additionally, a positive correlation was observed between the GABA+/Cr levels in the DN and the Generalized Anxiety Disorder-7 scores (r = 0.519, p = 0.039, n = 16). CONCLUSIONS: The results of this study indicated that the GABA and Glx levels in the PAG and DN may not be the primary contributor to the development of NDPH. The correlations between certain clinical scales and the neurotransmitter levels may be derived from the NDPH related symptoms.

White matter and cortical gray matter microstructural abnormalities in new daily persistent headache: a NODDI study.

BACKGROUND: New daily persistent headache (NDPH) is a rare primary headache with unclear pathogenesis. Neuroimaging studies of NDPH are limited, and controversy still exists. Diffusion tensor imaging (DTI) is commonly used to study the white matter. However, lacking specificity, the potential pathological mechanisms of white matter microstructural changes remain poorly understood. In addition, the intricacy of gray matter structures impedes the application of the DTI model. Here, we applied an advanced diffusion model of neurite orientation dispersion and density imaging (NODDI) to study the white matter and cortical gray matter microstructure in patients with NDPH. METHODS: This study assessed brain microstructure, including 27 patients with NDPH, and matched 28 healthy controls (HCs) by NODDI. The differences between the two groups were assessed by tract-based spatial statistics (TBSS) and surface-based analysis (SBA), focusing on the NODDI metrics (neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF)). Furthermore, we performed Pearson's correlation analysis between the NODDI indicators and clinical characteristics. RESULTS: Compared to HCs, patients with NDPH had a reduction of density and complexity in several fiber tracts. For robust results, the fiber tracts were defined as comprising more than 100 voxels, including bilateral inferior fronto-occipital fasciculus (IFOF), left superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), as well as right corticospinal tract (CST). Moreover, the reduction of neurite density was uncovered in the left superior and middle frontal cortex, left precentral cortex, and right lateral orbitofrontal cortex and insula. There was no correlation between the NODDI metrics of these brain regions and clinical variables or scales of relevance after the Bonferroni correction. CONCLUSIONS: Our research indicated that neurite loss was detected in both white matter and cortical gray matter of patients with NDPH.

The causal relationship between physical activity, sedentary time and idiopathic pulmonary fibrosis risk: a Mendelian randomization study.

BACKGROUND: Several observational studies have found that physical inactivity and sedentary time are associated with idiopathic pulmonary fibrosis (IPF) risk. However, the causality between them still requires further investigation. Therefore, our study aimed to investigate the causal effect of physical activity (PA) and sedentary time on the risk of IPF via two-sample Mendelian randomization (MR) analysis. METHODS: Multiple genome-wide association study (GWAS) data involving individuals of European ancestry were analyzed. The datasets encompassed published UK Biobank data (91,105-377,234 participants) and IPF data (2018 cases and 373,064 controls) from FinnGen Biobank. The inverse variance weighting (IVW) method was the primary approach for our analysis. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger regression, MR-PRESSO global test, and leave-one-out analysis. RESULTS: Genetically predicted self-reported PA was associated with lower IPF risk [OR = 0.27; 95% CI 0.09-0.82; P = 0.02]. No causal effects of accelerometry-based PA or sedentary time on the risk of IPF were observed. CONCLUSIONS: Our findings supported a protective relationship between self-reported PA and the risk for IPF. The results suggested that enhancing PA may be an effective preventive strategy for IPF.

Constructing a Functionalized Electrocatalyst of a Transition Metal Chalcogenide on Accordion-Like MXene to Boost the Hydrogen Evolution Reaction.

MXenes exhibit unique layered structures and excellent electrical conductivity, and their multiple surface termination groups are favorable for hosting impressive performance for electrochemical reactions. Therefore, a two-dimensional (2D) layered MXene-based catalyst may become a novel high-efficiency electrocatalyst to replace traditional noble metal electrocatalysts. In this work, a transition metal chalcogenide (MoS2/CuS) and MXene are combined to prepare a 2D electrocatalyst (MoS2/CuS/MXene) for the hydrogen evolution reaction (HER). MXene exhibited a large specific surface area in the shape of an accordion, which was very beneficial for the growth of nanomaterials. CuS/MXene promoted electron transfer and improved the exposed active site for HER. The exposed MoS2 edges exhibited a high chemical adsorption capacity, which is conducive to HER. Electrochemical tests reveal that the MoS2/CuS/MXene electrocatalyst can reduce the charge transfer resistance toward the HER and increase active sites for HER, leading to enhancing the catalytic performance. The MoS2/CuS/MXene electrocatalyst affords an efficient HER with a low overpotential (115 mV@10 mA cm-2). This work offers a new idea to create layered transition metal chalcogenide- and MXene-based electrocatalysts for HER.

Changes in gamma-aminobutyric acid and glutamate/glutamine levels in the right thalamus of patients with episodic and chronic migraine: A proton magnetic resonance spectroscopy study.

OBJECTIVE: To explore gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the right thalamus of patients with episodic migraine (EM) and chronic migraine (CM) and their effects on the chronification of migraine. BACKGROUND: Migraine affects approximately 1 billion people worldwide, with 2.5%-3% of people with EM progressing to CM each year. Magnetic resonance spectroscopy studies have revealed altered GABA and Glx levels in the thalamus of patients with migraine without aura, but these neurometabolic concentrations are underexplored in the thalamus of patients with CM. METHODS: In this cross-sectional study, patients with EM and CM were recruited. Mescher-Garwood point resolved spectroscopy sequence was used to acquire neurotransmitter concentrations in the right thalamus of patients with EM and CM and matched healthy controls (HCs). RESULTS: A total of 26 patients (EM, n = 11; CM, n = 15) and 16 age- and sex-matched HCs were included in the analysis. There were significantly lower GABA+/Water levels in the right thalamus of the CM group (mean ± standard deviation: 2.27 ± 0.4 [institutional units]) than that of the HC group (2.74 ± 0.4) (p = 0.026; mean difference [MD] = -0.5 [i.u.]), and lower Glx/Cr levels in the EM group (mean ± SD: 0.11 ± < 0.1) than in the HCs (0.13 ± < 0.1) and CM group (0.13 ± < 0.1) (p = 0.023, MD < -0.1, and p = 0.034, MD < -0.1, respectively). The GABA+/Glx ratio was lower in the CM group (mean ± SD: 0.38 ± 0.1) compared to the EM group (0.47 ± 0.1) (p = 0.024; MD = -0.1). The area under the curve for GABA+/Water levels in differentiating patients with CM from HCs was 0.83 (95% confidence interval 0.68, 0.98; p = 0.004). Correlation analyses within the migraine group revealed no significant correlation between metabolite concentration levels and headache characteristics after Bonferroni correction. CONCLUSION: Reduced GABA+/Water levels and imbalance of excitation/inhibition in the right thalamus may contribute to migraine chronification.

Normal glymphatic system function in patients with new daily persistent headache using diffusion tensor image analysis along the perivascular space.

OBJECTIVES: To investigate the glymphatic function in patients with new daily persistent headache (NDPH) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. BACKGROUND: NDPH, a rare and treatment-refractory primary headache disorder, is poorly understood. There is limited evidence to suggest that headaches are associated with glymphatic dysfunction. Thus far, no studies have evaluated glymphatic function in patients with NDPH. METHODS: In this cross-sectional study conducted in the Headache Center of Beijing Tiantan Hospital, patients with NDPH and healthy controls were enrolled. All participants underwent brain magnetic resonance imaging examinations. Clinical characteristics and neuropsychological evaluation were examined in patients with NDPH. ALPS indexes for both hemispheres were measured to determine the glymphatic system function in patients with NDPH and healthy controls. RESULTS: In total, 27 patients with NDPH (14 males, 13 females; age [mean ± standard deviation (SD)]: 36.6 ± 20.6) and 33 healthy controls (15 males, 18 females; age [mean ± SD]: 36.0 ± 10.8) were included in the analysis. No significant differences between groups were observed in the left ALPS index (1.583 ± 0.182 vs. 1.586 ± 0.175, mean difference = 0.003, 95% confidence interval [CI] of difference = -0.089 to 0.096, p = 0.942), or right ALPS index (1.578 ± 0.230 vs. 1.559 ± 0.206, mean difference = -0.027, 95% CI of difference = -0.132 to 0.094, p = 0.738). Additionally, ALPS indexes were not correlated with clinical characteristics or neuropsychiatric scores. CONCLUSION: No glymphatic dysfunction was detected in patients with NDPH by means of the ALPS method. Additional studies with larger samples are needed to confirm these preliminary findings and improve the understanding of glymphatic function in NDPH.

Micro-structural white matter abnormalities in new daily persistent headache: a DTI study using TBSS analysis.

BACKGROUND: New daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. The pathogenesis of NDPH remains unclear, and there are few white matter imaging studies related to NDPH. The purpose of this study was to investigate the micro-structural abnormalities of white matter in NDPH and provided insights into the pathogenesis of this disease based on tract-based spatial statistics (TBSS). METHODS: Twenty-one patients with NDPH and 25 healthy controls (HCs) were included in this study. T1 structural and diffusion magnetic resonance imaging (MRI) were acquired from all participants. Differences in the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) between patients with NDPH and HCs were investigated using TBSS analysis. RESULTS: Significantly decreased FA, increased MD and RD were found in patients with NDPH compared to HCs. White matter regions overlaid with decreased FA, increased MD and RD were found in 16 white matter tracts from the Johns Hopkins University ICBM-DTI-81 White-Matter Atlas and Johns Hopkins University White-Matter Tractography Atlas. Specifically, these white matter regions included the right anterior thalamic radiation (ATR), body of the corpus callosum (BCC), bilateral cingulum, left hippocampal cingulum (CGH), left corticospinal tract (CST), forceps major, fornix, left inferior fronto-occipital fasciculus (IFOF), bilateral inferior longitudinal fasciculus (ILF), left posterior limb of the internal capsule (PLIC), right retrolenticular part of the internal capsule (RPIC), splenium of the corpus callosum (SCC), right superior longitudinal fasciculus (SLF) and left uncinate fasciculus (UF). After Bonferroni correction, there were no correlations between the FA, MD, AD and RD values and the clinical characteristics of patients with NDPH (p > 0.05/96). CONCLUSION: The results of our research indicated that patients with NDPH might have widespread abnormalities in the white matter of the brain.

Brain structure and cortical activity changes of new daily persistent headache: multimodal evidence from MEG/sMRI.

BACKGROUND: New daily persistent headache (NDPH) is a rare but debilitating primary headache disorder that poses a significant burden on individuals and society. Despite its clinical importance, the underlying pathophysiological mechanisms of NDPH remain unclear. In this study, we aimed to investigate the brain structural changes and neural activity patterns in patients with NDPH using multimodal brain imaging analysis of structural magnetic resonance imaging (sMRI) combined with magnetoencephalography (MEG). METHODS: Twenty-eight patients with NDPH and 37 healthy controls (HCs) were recruited for this study, and their structural and resting-state data were collected by 3.0 Tesla MRI and MEG. We analyzed the brain morphology using voxel-based morphometry and source-based morphometry. In each brain region, MEG sensor signals from 1 to 200 Hz were analyzed using an adapted version of Welch's method. MEG source localization was conducted using the dynamic statistical parametric mapping, and the difference of source distribution between patients with NDPH and HCs was examined. RESULTS: Our results revealed significant differences in the regional grey matter volume, cortical thickness, and cortical surface area between the two groups. Specifically, compared with HCs, patients with NDPH showed a significant decrease in cortical thickness of the left rostral cortex in the middle frontal gyrus, decreased cortical surface area of the left fusiform gyrus, decreased grey matter volume of the left superior frontal gyrus and the left middle frontal gyrus, and increased grey matter volume of the left calcarine. Furthermore, the power of the whole brain, bilateral frontal lobes, and right temporal lobe in the NDPH group were higher than that in HCs in the ripple frequency band (80-200 Hz). Functional and structural analysis suggested that there were structural changes and abnormal high frequency cortical activity in both frontal and temporal lobes in patients with NDPH. CONCLUSION: Our findings indicated that patients with NDPH have abnormalities in brain morphology, such as cortical area, cortical thickness, and grey matter volume, accompanied by abnormal cortical neural activity. Brain structural changes in the frontotemporal cortex and abnormalities in cortical ripple activity may be involved in the pathogenesis of NDPH.

Hyperperfusion of bilateral amygdala in patients with chronic migraine: an arterial spin-labeled magnetic resonance imaging study.

BACKGROUND: Amygdala, an essential element of the limbic system, has served as an important structure in pain modulation. There is still a lack of clarity about altered cerebral perfusion of amygdala in migraine. This study aimed to investigate the perfusion variances of bilateral amygdala in episodic migraine (EM) and chronic migraine (CM) using multi-delay pseudo-continuous arterial spin-labeled magnetic resonance imaging (pCASL-MRI). METHODS: Twenty-six patients with EM, 55 patients with CM (33 CM with medication overuse headache (MOH)), and 26 age- and sex-matched healthy controls (HCs) were included. All participants underwent 3D multi-delay pCASL MR imaging to obtain cerebral perfusion data, including arrival-time-corrected cerebral blood flow (CBF) and arterial cerebral blood volume (aCBV). The CBF and aCBV values in the bilateral amygdala were compared among the three groups. Correlation analyses between cerebral perfusion parameters and clinical variables were performed. RESULTS: Compared with HC participants, patients with CM were found to have increased CBF and aCBV values in the left amygdala, as well as increased CBF values in the right amygdala (all P < 0.05). There were no significant differences of CBF and aCBV values in the bilateral amygdala between the HC and EM groups, the EM and CM groups, as well as the CM without and with MOH groups (all P > 0.05). In patients with CM, the increased perfusion parameters of bilateral amygdala were positively correlated with MIDAS score after adjustments for age, sex, and body mass index (BMI). CONCLUSION: Hyperperfusion of bilateral amygdala might provide potential hemodynamics evidence in the neurolimbic pain network of CM.

Increased glymphatic system activity in migraine chronification by diffusion tensor image analysis along the perivascular space.

BACKGROUND: Preliminary evidence suggests that several headache disorders may be associated with glymphatic dysfunction. However, no studies have been conducted to examine the glymphatic activity in migraine chronification. PURPOSES: To investigate the glymphatic activity of migraine chronification in patients with episodic migraine (EM) and chronic migraine (CM) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. METHODS: In this cross-sectional study, patients with EM, CM, and healthy controls (HCs) were included. All participants underwent a standard brain magnetic resonance imaging (MRI) examination. Bilateral DTI-ALPS indexes were calculated for all participants and compared among EM, CM, and HC groups. Correlations between the DTI-ALPS index and clinical characteristics were analyzed. RESULTS: A total of 32 patients with EM, 24 patients with CM, and 41 age- and sex-matched HCs were included in the analysis. Significant differences were found in the right DTI-ALPS index among the three groups (p = 0.011), with CM showing significantly higher values than EM (p = 0.033) and HCs (p = 0.015). The right DTI-ALPS index of CM group was significantly higher than the left DTI-ALPS index (p = 0.005). And the headache intensity was correlated to DTI-ALPS index both in the left hemisphere (r = 0.371, p = 0.011) and in the right hemisphere (r = 0.307, p = 0.038), but there were no correlations after Bonferroni correction. CONCLUSIONS: Glymphatic system activity is shown to be increased instead of impaired during migraine chronification. The mechanism behind this observation suggests that increased glymphatic activity is more likely to be a concomitant phenomenon of altered vascular reactivity associated with migraine pathophysiology rather than a risk factor of migraine chronification.

Alterations in regional homogeneity and multiple frequency amplitudes of low-frequency fluctuation in patients with new daily persistent headache: a resting-state functional magnetic resonance imaging study.

BACKGROUND: New daily persistent headache (NPDH) is a rare primary headache that is highly disabling. The pathophysiology of NDPH is still unclear, and we aimed to reveal the underlying mechanism of NDPH through functional magnetic resonance imaging (fMRI) analysis. METHODS: In this cross-sectional study, thirty patients with NDPH and 30 healthy controls (HCs) were recruited. The blood oxygen level-dependent (BOLD) sequences of all participants were obtained using the GE 3.0 T system. We performed ReHo, ALFF (conventional band: 0.01-0.08 Hz, slow-5: 0.01-0.027 Hz, slow-4: 0.027-0.073 Hz) and seed-based to the whole brain functional connectivity (FC) analysis in the NDPH and HC groups. The sex difference analysis of ReHo, ALFF, and FC values was conducted in the NDPH group. We also conducted Pearson's correlation analysis between ReHo, ALFF, FC values and clinical characteristics (pain intensity, disease duration, HIT-6, GAD-7, PHQ-9, and PSQI scores). RESULTS: Both increased ReHo (PFWE-corr = 0.012) and ALFF values (0.01-0.08 Hz, PFWE-corr = 0.009; 0.027-0.073 Hz, PFWE-corr =0.044) of the left middle occipital gyrus (MOG_L) were found in the NDPH group compared to the HC group. There was no significant difference in FC maps between the two groups. Compared to the HC group, no difference was found in ReHo (p = 0.284), ALFF (p = 0.246), and FC (p = 0.118) z scores of the MOG_L in the NDPH group. There was also no sex difference in ReHo (p = 0.288), ALFF (p = 0.859), or FC z score (p = 0.118) of the MOG_L in patients with NDPH. There was no correlation between ReHo, ALFF, FC z scores and clinical characteristics after Bonferroni correction (p < 0.05/18). CONCLUSIONS: Patients with NDPH may have abnormal activation of the visual system. Abnormal visual activation may occur mainly in higher frequency band of the classical band. No sex differences in brain activity were found in patients with NDPH.

Mapping the aberrant brain functional connectivity in new daily persistent headache: a resting-state functional magnetic resonance imaging study.

BACKGROUND AND PURPOSE: The pathogenesis of new daily persistent headache (NDPH) is not fully understood. We aim to map aberrant functional connectivity (FC) in patients with NDPH using resting-state functional magnetic resonance imaging (MRI). METHODS: Brain structural and functional MRI data were acquired from 29 patients with NDPH and 37 well-matched healthy controls (HCs) in this cross-sectional study. Region of interest (ROI) based analysis was used to compare FC between patients and HCs, with 116 brain regions in the automated anatomical labeling (AAL) atlas were defined as seeds. The correlations between aberrant FC and patients' clinical characteristics, and neuropsychological evaluation were also investigated. RESULTS: Compared with HCs, patients with NDPH showed increased FC in the left inferior occipital gyrus, right thalamus and decreased FC in right lingual gyrus, left superior occipital gyrus, right middle occipital gyrus, left inferior occipital gyrus, right inferior occipital gyrus, right fusiform gyrus, left postcentral gyrus, right postcentral gyrus, right thalamus and right superior temporal gyrus. There were no correlation between FC of these brain regions and clinical characteristics, neuropsychological evaluation after Bonferroni correction (p > 0.05/266). CONCLUSIONS: Patients with NDPH showed aberrant FC in multiple brain regions involved in perception and regulation of emotion and pain. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05334927.

Mapping brain functional networks topological characteristics in new daily persistent headache: a magnetoencephalography study.

BACKGROUND: The brain functional network topology in new daily persistent headache (NDPH) is not well understood. In this study, we aim to assess the cortical functional network topological characteristics of NDPH using non-invasive neural signal recordings. METHODS: Resting-state magnetoencephalography (MEG) was used to measure power fluctuations in neuronal oscillations from distributed cortical parcels in 35 patients with NDPH and 40 healthy controls (HCs). Their structural data were collected by 3T MRI. Functional connectivity (FC) of neural networks from 1 to 80 Hz frequency ranges was analyzed with topographic patterns and calculated network topological parameters with graph theory. RESULTS: In the delta (1-4 Hz) and beta (13-30 Hz) bands, the lateral occipital cortex and superior frontal gyrus FC were increased in NDPH groups compared to HCs. Graph theory analysis revealed that the NDPH had significantly increased global efficiency in the delta band and decreased nodal clustering coefficient (left medial orbitofrontal cortex) in the theta (4-8 Hz) band. The clinical characteristics had a significant correlation with network topological parameters. Age at onset of patients showed a positive correlation with global efficiency in the delta band. The degree of depression of patients showed a negative correlation with the nodal clustering coefficient (left medial orbitofrontal cortex) in the theta band. CONCLUSION: The FC and topology of NDPH in brain networks may be altered, potentially leading to cortical hyperexcitability. Moreover, medial orbitofrontal cortex is involved in the pathophysiological mechanism of depression in patients with NDPH. Increased FC observed in the lateral occipital cortex and superior frontal gyrus during resting-state MEG could serve as one of the imaging characteristics associated with NDPH.

Association of Helicobacter pylori and gastric atrophy with adenocarcinoma of the esophagogastric junction in Taixing, China.

Gastric atrophy caused by Helicobacter pylori infection was suggested to influence the risk of adenocarcinoma of the esophagogastric junction (AEGJ), however, the evidence remains limited. We aimed to examine the associations of H. pylori infection and gastric atrophy (defined using serum pepsinogen [PG] I to PGII ratio) with AEGJ risk, based on a population-based case-control study in Taixing, China (2010-2014), with 349 histopathologically confirmed AEGJ cases and 1859 controls. We explored the potential effect modification by H. pylori serostatus and sex on the association of serum PGs with AEGJ risk. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). H. pylori seropositivity was associated with an elevated AEGJ risk (OR = 1.95, 95% CI: 1.47-2.63). Neither CagA-positive nor VacA-positive strains dramatically changed this association. Gastric atrophy (PGI/PGII ratio ≤4) was positively associated with AEGJ risk (OR = 2.36, 95% CI: 1.72-3.22). The fully adjusted ORs for AEGJ progressively increased with the increasing levels of PGII (P-trend <.001). H. pylori showed nonsignificant effect modification (P-interaction = .385) on the association of gastric atrophy with AEGJ. In conclusion, H. pylori and gastric atrophy were positively associated with AEGJ risk. These results may contribute evidence to the ongoing research on gastric atrophy-related cancers and guide the prevention and control of AEGJ.