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Background: For a long time, the prevailing viewpoint suggests that shorter telomere contribute to chromosomal instability, which is a shared characteristic of both aging and cancer. The newest research presented that T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to some cancers. However, the relationship between genetically determined telomere length (TL) and immune cells remains unclear. Methods: The two‐sample Mendelian randomization analysis was conducted to elucidate the potential causal relationship. The genetic data of TL and immune cells were obtained from the Genome‐Wide Association Study. The inverse variance weighted (IVW) method was used to estimate the effects primarily and another four methods were as a supplement. Sensitivity analysis was used to test the results. Results: The IVW method showed a significant correlation between TL and the percentage of T cells in lymphocytes (odds ratio [OR]: 1.222, 95% confidence interval [CI]: 1.014–1.472, p =.035), indicating that shorter TL significantly increases the risk of low T cell percentage. Further analysis of T cell subsets indicated that shorter TL may primarily lead to a lower percentage of Natural Killer T cells (OR: 1.574, 95% CI: 1.281–1.935, p <.001). Analysis of B cell subsets revealed that shorter TL may be associated with a higher percentage of Naive‐mature B cells, and a lower percentage of Memory B cells. And the sensitivity analysis indicated the validity and robustness of our findings. Conclusion: In summary, our findings suggest that shorter TL may be associated with a decline in the percentage of T cell, as well as impediments in the differentiation of B cell, consequently leading to the onset of immunosenescence and immunodeficiency. The relevant mechanisms and potential therapeutic avenues still need further investigation. Shorter telomere length may be associated with a decline in the percentage of T cell, as well as impediments in the differentiation of B cell, consequently leading to the onset of immunosenescence and immunodeficiency. [ABSTRACT FROM AUTHOR]

Aims: To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short‐term intensive insulin therapy (SIIT) during study run‐in (prior to randomization) using a basal‐first insulin titration method. Materials and methods: This was exclusively an exploratory analysis of the 7‐ to 10‐day run‐in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once‐daily insulin glargine and three‐times‐daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre‐meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2‐hour postprandial blood glucose (PBG) targets. Results: Overall, 397 entered the run‐in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2‐hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2‐hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2‐hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia. Conclusions: Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to identify the prevalence of severe headache or migraine and the association between dietary thiamine and riboflavin intake with headache history using a large, nationally representative population sample. Background: Severe headache and migraine are common and disabling neurological disorders worldwide. Previous studies revealed that the B vitamin group, as an important nutrient of diet, can reduce migraine disability. Methods: We performed a cross‐sectional study of American adults surveyed in the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Information on headache history was collected in the Miscellaneous Pain section of the Questionnaire Data. Dietary intake data of thiamine and riboflavin were obtained by 24‐h dietary recall interview. Results: The present study included 13,439 participants and indicated that 2745/13,439 (21.6%) adults (aged ≥20 years) experienced severe headache or migraine in the past 3 months. Dietary thiamine intake was significantly inversely associated with severe headache or migraine (odds ratio [OR] = 0.93, 95% confidence interval [CI] = 0.88–1.00, p = 0.046). In the stratified analysis, the relationship was maintained in the female group (OR = 0.90, 95% CI = 0.82–0.98, p = 0.022), and the sex interaction term was significant (p = 0.020). However, no significant interaction was found between the age groups (p = 0.352). For dietary riboflavin, no significant negative association was observed between dietary riboflavin intake and headache history (OR = 0.98, 95% CI = 0.94–1.02, p = 0.367). After stratifying by sex or age, there remained no significant relationship between dietary riboflavin and migraine. Conclusions: We found that high intake of thiamine was significantly associated with lower odds of migraine, especially in females. In the future, more clinical studies are needed to confirm our conclusions, and additional experiments are needed to explore the possible mechanisms of prevention and treatment for migraine. [ABSTRACT FROM AUTHOR]

Except one little boy who received eculizumab treatment and had a good prognosis, the remaining three patients all presented with recurrent cerebral infarction and responded differently to antiplatelet therapy, which were detailed depicted in Table 1. Lost the ability to work for deteriorating weakness of the right limbs.Our patient42Female3 years66, 85, 67Dual antiplatelet therapy, prednisolone, washed red blood cell. In our case report, except the vasculitic moyamoya changes, the patient also presented with multiple cerebral infarction, pulmonary artery thrombosis, as well as intermuscular vein of the right lower extremity. [Extracted from the article]

Earthquake stress drop is an important source parameter that directly links to strong ground motion and fundamental questions in earthquake physics. Stress drop estimations may contain significant uncertainties due to such factors as variations in material properties and data limitations, which limit the applications of stress drop interpretations. Using a high‐resolution borehole network, we estimate stress drop for 4551 (M0‐4) earthquakes on the San Andreas Fault at Parkfield, California, between 2001 and 2016 using spectral decomposition and an improved stacking method. To evaluate the influence of spatiotemporal variations of material properties on stress drop estimations, we apply different strategies to account for spatial variations of velocity and attenuation changes, and divide earthquakes into three separate time periods to correct temporal variations of attenuation. These results show that appropriate corrections can significantly reduce the scatter in stress drop estimates, and decrease apparent depth and magnitude dependence. We find that insufficient bandwidth can cause systematic underestimation of stress drop estimates and increased scatter. The stress drop measurements from the high‐frequency borehole recordings exhibit complex stable spatial patterns with no clear correlation with the nature of fault slip, or the slip distribution of the 2004 M6 earthquake. Temporal variations are significantly smaller, less well resolved and varying spatially. They do not affect the long‐term stress drop spatial variations, suggesting local material properties may control the spatial heterogeneity of stress drop. Plain Language Summary: Earthquake stress drop (the change in shear stress before and after the earthquake) reflects the properties of the fault where earthquakes occur. Determining the scaling relationships between earthquake stress drop and magnitude enables us to predict the behavior of infrequent large earthquakes from the measurements of the more abundant small earthquakes. Measurement of stress drop is challenging, especially for small earthquakes. Different studies can obtain different stress drop values for the same earthquakes, leading to different interpretations. We use recordings from a high‐resolution borehole network in Parkfield, California to measure source parameters for small earthquakes. We examine the influence of data limitation (e.g., frequency bandwidth) and corrections for material properties on stress drop resolution. We find that if the bandwidth is too narrow, the resulting source parameters can be systematically underestimated with large scatter. Insufficient corrections of material properties can lead to biased interpretation of stress drop patterns and scaling relationships. Our final results show that the stress drops of earthquakes in Parkfield do not depend on magnitude or depth, but exhibit strong spatial variations that are stable with time. The 2004 M6 earthquake caused temporal variations of stress drop, and the temporal changes are different at different fault patches. Key Points: Borehole data and an improved spectral decomposition approach provide better constraints on estimates of corner frequency and stress dropFrequency bandwidth, and corrections for variable attenuation and velocity with depth most influence stress drop estimates and interpretationsSpatial pattern of stress drop is heterogeneous on a ∼1 km scale, and stable with time; temporal changes are smaller and spatially variable [ABSTRACT FROM AUTHOR]

We combine earthquake spectra from multiple studies to investigate whether the increase in stress drop with depth often observed in the crust is real, or an artifact of decreasing attenuation (increasing Q) with depth. In many studies, empirical path and attenuation corrections are assumed to be independent of the earthquake source depth. We test this assumption by investigating whether a realistic increase in Q with depth (as is widely observed) could remove some of the observed apparent increase in stress drop with depth. We combine event spectra, previously obtained using spectral decomposition methods, for over 50,000 earthquakes (M0 to M5) from 12 studies in California, Nevada, Kansas and Oklahoma. We find that the relative high‐frequency content of the spectra systematically increases with increasing earthquake depth, at all magnitudes. By analyzing spectral ratios between large and small events as a function of source depth, we explore the relative importance of source and attenuation contributions to this observed depth dependence. Without any correction for depth‐dependent attenuation, we find a systematic increase in stress drop, rupture velocity, or both, with depth, as previously observed. When we add an empirical, depth‐dependent attenuation correction, the depth dependence of stress drop systematically decreases, often becoming negligible. The largest corrections are observed in regions with the largest seismic velocity increase with depth. We conclude that source parameter analyses, whether in the frequency or time domains, should not assume path terms are independent of source depth, and should more explicitly consider the effects of depth‐dependent attenuation. Plain Language Summary: The stress release (or stress drop) during an earthquake provides information about the energy budget, and the slip and area of rupture, which are needed to investigate earthquake triggering and rupture dynamics. Stress drop is also an important element of seismic hazard forecasting since high stress drop earthquakes radiate more high frequency energy, resulting in stronger ground shaking. As depth increases in the earth, the stress on faults increases because of the increased weight of the rocks above. Therefore, many models predict that deeper earthquakes should have higher stress drops. Deeper earthquakes radiate more high frequency energy than shallow ones, and some studies have interpreted this as an increase in stress drop with depth. However, attenuation of seismic energy as the waves travel through the earth is also depth‐dependent, and this is rarely explicitly included in analyses. We perform a combined analysis of frequency spectra from over 50,000 previously studied earthquakes. We compare ratios of large to small magnitude earthquakes, from different depth ranges, to separate the effects of depth‐dependent source radiation from depth‐dependent attenuation. We find that depth‐dependent attenuation can have a first‐order effect and account for much of the previously reported apparent increase in stress drop with depth. Key Points: A stacked spectral ratio approach can separate depth dependence of source and path effectsAnalyses of spectral decomposition inversions suggest that previous reports of increase in stress drop with depth may be overstatedSource parameter analyses should explicitly include depth‐dependent attenuation models or empirical corrections [ABSTRACT FROM AUTHOR]

We calculate rupture directivity and velocity for earthquakes in three well‐recorded repeating sequences (2001–2016) on the San Andreas Fault at Parkfield using P waves from borehole recordings and the empirical Green's function method. The individual events in each sequence all show the same directivity; the largest magnitude sequence (M ~ 2.7, 8 events) ruptures unilaterally NW (at ~0.8Vs), the second sequence (M ~ 2.3, 9 events) ruptures unilaterally SE, and the smallest magnitude sequence (M ~ 2, 11 events) is less well resolved. The highly repetitive rupture suggests that geometry or material properties might control nucleation of small locked patches. The source spectra of the M ~ 2.7 sequence exhibit no detectable temporal variation. The smaller M sequences both exhibit a decrease in high‐frequency energy following the M6 earthquake that recovers with time. This could indicate a decrease in stress drop, an increase in attenuation, or a combination of the two, followed by gradual healing. Plain Language Summary: Sequences of small earthquakes with very similar seismograms have been observed on the San Andreas Fault at Parkfield and many other faults that are also observed to be creeping. The similarity of the seismograms suggests that these earthquakes represent repeating slip on overlapping pieces of fault. Under this assumption they have been used to investigate changes in slip conditions and the slip rate on major faults with time. To date, most studies have treated these repeating earthquakes as just points because most are too small and too poorly recorded to observe details of the rupture area or direction. Here we identify three exceptionally well‐recorded repeating sequences and are able to resolve the direction of rupture. All the earthquakes in one sequence propagate toward the NW, and all those in another propagate to the SW. The rupture velocities are similar to those of much larger earthquakes. This improved resolution of the earthquake sources will help constrain modeling of the rupture and hence our understanding of the factors that control earthquake nucleation and dynamics. Key Points: All individual earthquakes in a repeating sequence at Parkfield exhibit identical directivity, unaffected by 2004 M6One sequence (M ~ 2.7) ruptures to the NW and one (M ~ 2.5) to the SE, at ~0.8 × shear wave velocitySmallest magnitude sequences show most response to M6 earthquake, but we cannot fully distinguish between path and source effects [ABSTRACT FROM AUTHOR]

Introduction: Neuronal‐derived exosomal Aβ42, T‐tau, and P‐T181‐tau have been demonstrated to be biomarkers of Alzheimer's disease (AD). However, no study has assessed the association of Aβ42, T‐tau, and P‐T181‐tau between exosomes and CSF. Methods: This was a multicenter study with two‐stage design. The subjects included 28 AD patients, 25 aMCI patients, and 29 controls in the discovery stage; the results of which were confirmed in the validation stage (73 AD, 71 aMCI, and 72 controls). Results: The exosomal concentrations of Aβ42, T‐tau, and P‐T181‐tau in AD group were higher than those in aMCI and control groups (all P <.001). The level of each exosomal biomarker was highly correlated with that in CSF. Discussion: This study verified the agreement between CSF and blood exosomal biomarkers and confirmed that exosomal Aβ42, T‐tau, and P‐T181‐tau have the same capacity as those in CSF for the diagnosis of AD and aMCI. [ABSTRACT FROM AUTHOR]

Keywords: dissociative conversion disorder; functional movement disorders; parkinsonism; psychological parkinsonism EN dissociative conversion disorder functional movement disorders parkinsonism psychological parkinsonism 1097 1098 2 08/07/21 20210901 NES 210901 CONFLICTS OF INTEREST The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Certainly, some patients did present with combined FMDs and organic movement disorders, which is about 10%.9 Functional movement disorders still remain an enormous therapeutic challenge. [Extracted from the article]

Mutations in I DPM3 i lead to deficient -dystroglycan, so it is classified into dystroglycanopathies, which represent a group of muscular dystrophies with a wide spectrum ranging from mild limb-girdle muscular dystrophy to severe congenital muscular dystrophy with brain and eye abnormalities.[1] Till date, only three mutations of I DPM3 i (NM 153471), c.254T>A (p.Leu85Ser), c.41T>C (p.Leu14Pro) and a deletion, have been reported in five patients.[[1]] Mild and progressive limb-girdle muscular dystrophy was present in four patients, and isolated hyperCKemia was reported in one patient. Our patient showed hyperCKemia with developmental delay, epilepsy, intellectual impairment, and brain abnormality, indicating involvement of CNS. [Extracted from the article]

Aim Methods Results Conclusions To compare the efficacy and safety of a fixed‐ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with premixed insulin, insulin degludec plus insulin aspart (IDegAsp), in Chinese people with type 2 diabetes (T2D) suboptimally controlled with oral antidiabetic drug(s) (OADs).In Soli‐D, a 24‐week, multicentre, open‐label, study, insulin‐naïve adults were randomized 1:1 to once‐daily injections of iGlarLixi (n = 291) or IDegAsp (n = 291), with continued metformin ± sodium‐glucose co‐transporter‐2 inhibitors. The primary endpoint was non‐inferiority in HbA1c change from baseline to week 24. Key secondary endpoints included superiority in HbA1c change and body weight (BW) change at week 24. Hypoglycaemia rates were also assessed.At week 24, iGlarLixi showed non‐inferiority and superiority over IDegAsp in HbA1c reduction (least squares [LS] mean difference: −0.20 [95% confidence interval {CI}: –0.33, −0.07]; P < .001 for non‐inferiority; [97.5% CI: –0.35, −0.05]; P = .003 for superiority). iGlarLixi decreased BW and IDegAsp increased BW from baseline to week 24, with a statistically significant LS mean difference of −1.49 kg in favour of iGlarLixi (97.5% CI: –2.32, −0.66; P < .001). Event rates (per person‐year) for American Diabetes Association (ADA) Level 1, 2 or 3 hypoglycaemia were lower for iGlarLixi (1.90) versus IDegAsp (2.72) (relative risk: 0.71; 95% CI: 0.52, 0.98). No ADA Level 3 hypoglycaemia or unexpected safety findings were reported.In Chinese people with T2D suboptimally controlled with OADs, once‐daily iGlarLixi provided better glycaemic control with BW benefit and lower hypoglycaemia event rates versus IDegAsp. [ABSTRACT FROM AUTHOR]

Objective: Alzheimer's disease (AD) is the most common form of dementia characterized by memory loss at disease onset. The gene mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the frequent causes of AD. However, the clinical and genetic features of AD overlap with other neurodegenerative diseases. The present study aimed to identify the clinical and genetic characteristics in a Han Chinese AD cohort. Methods: Detailed clinical assessment was applied to all the patients. We screened amyloid precursor protein (APP), PSEN1, PSEN2, and microtubule‐associated protein tau (MAPT) genes were assessed in 83 sporadic AD patients by Sanger sequencing. A total of 25 probands from families with AD were subjected to next‐generation sequencing on 53 dementia‐associated genes to capture the target region, and Sanger sequencing was used to detect the variants in the DNA sequence. Results: PSEN1 p.L226R was found in an early‐onset AD (EOAD) family characterized by language impairment at disease onset, a novel probably pathogenetic variant (p.D534H) was identified in a frontal‐temporal dementia gene, TANK‐binding kinase 1 (TBK1) with a typical AD phenotype in a late‐onset AD (LOAD) family, and a PSEN2p.H169N mutation and two benign MAPT (p.Q230R and p.V48L) mutations were detected in three EOAD patients. Conclusions: Thus, five variants were identified in a Han Chinese cohort. In the present study, a novel, probably damaging FTLD gene TBK1variant with a typical AD phenotype was detected. Also, the phenotypic characteristics of PSEN1 p.L226R, a PSEN2pathogenic mutation, and two likely benign MAPT variants were described. Hence, screening for mutations in other dementia genes could be further explored in clinically diagnosed AD patients. Some gene mutations are associated with family Alzheimer's disease. In this work, we discovered five variants. We enrich the clinical phenotype and gene mutation database of AD. [ABSTRACT FROM AUTHOR]