Miracle-dz/UniFAR-FTUs huggingface dataset:
Utility estimations of different health states of patients with type I, II, and III spinal muscular atrophy in China: A mixed approach study with patient and proxy-reported data

Introduction Spinal muscular atrophy (SMA) is a rare autosomal-recessive neuromuscular disease. Health state utility values (HSUV) are used in health economic evaluation regarding the desirability of health outcomes such as a certain health state or change in health states over time. There is no utility data of Chinese patients with SMA. Materials and methods Vignettes were developed for 10 pediatric neurologists to value the utility of Chinese patients with Type I SMA. A mixed patient/proxy derived approach using EQ-5D-Y-3L, EQ-5D-3L, and CHU9D was adopted to estimate the HSUV data of patients with Type II and III SMA, including 112 patients and 301 caregivers. Result The utility of Type I SMA patients ranged from 0.19 to 0.72 with the health state improved from “permanent ventilation” to “walking”. The utility of children patients with Type II and III SMA derived from EQ-5D-Y-3L ranged from 0.33 to 0.82 while that derived from CHU9D ranged from 0.46 to 0.75. The utility of adult patients with Type II and III SMA measured by EQ-5D-3L ranged from 0.30 to 0.83. Conclusion The better health states the patients with SMA were in, the higher were the HSUV. The utilities derived from population with different age and disease subtypes were not statistically different when patients with SMA were in the same health states. We recommend further studies on the Chinese specific value set for EQ-5D-Y-3L and other PBMs for children to derive more robust utility data.
The prevalence of hypertension and its associated risk factors among older adults in Ghana

Background Hypertension is a worldwide health issue that primarily affects the elderly in our society. However, in comparison to the developed world, the prevalence of hypertension is higher in Sub-Saharan Africa. Objective This paper examines the prevalence of hypertension and its associated risk factors among older adults in Ghana. Methods Using the World Health Organization’s study on global AGEing and adult health (WHO SAGE) Wave 1 cross-sectional data collected via in-person structured interviews; paper and pencil interviews (PAPI) from ten administrative regions of Ghana using stratified multistage cluster design from respondents aged 50+ grouped by decade, this study analyzed a nationally representative sub-sample of 3,997 respondents employing binary logistic regression. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to estimate risk factors associated with hypertension (blood pressure ≥ 130/80 mm/Hg). Results There was a 53.72% hypertension prevalence rate among older adults. Hypertension prevalence tends to increase with increasing age. The prevalence of hypertension was associated with residency (B = −0.18, OR = 0.84, p < 0.017), with urban residents being more at risk of hypertension than rural residents. The prevalence of hypertension increased with overweight (B = 0.66, OR = 1.94, p < 0.001) and obesity (B = 0.82, OR = 2.28, p < 0.001). The amount of fruit and vegetable intake was insignificant but had an inverse relationship with hypertension prevalence. Conclusion This study has shown that demographic and lifestyle factors significantly affect and explain the hypertension risk among older adults. Medical factors, such as chronic diseases, were largely insignificant and accounted for less hypertension prevalence. Therefore, when interpreting test findings in clinical practice, such as hypertension, it is essential to consider demographic and lifestyle factors. In addition, health policies and primary interventions that seek to improve the standard of living, lifestyle, and wellbeing of older adults need to be critically considered moving forward to lower hypertension prevalence among older adults in Ghana.
Bianchi type-I cosmological models with perfect fluid in general relativity

Einstein's field equations with variable gravitational and cosmological con- stants are considered in the presence of perfect fluid for the Bianchi type-I universe by assuming that the cosmological term is proportional to R −m (R is a scale factor and m is a constant). A variety of solutions are presented. The physical significance of the respective cosmological models are also discussed.
Filamin A in platelets: Bridging the (signaling) gap between the plasma membrane and the actin cytoskeleton

Platelets are anucleate cells that are essential for hemostasis and wound healing. Upon activation of the cell surface receptors by their corresponding extracellular ligands, platelets undergo rapid shape change driven by the actin cytoskeleton; this shape change reaction is modulated by a diverse array of actin-binding proteins. One actin-binding protein, filamin A (FLNA), cross-links and stabilizes subcortical actin filaments thus providing stability to the cell membrane. In addition, FLNA binds the intracellular portion of multiple cell surface receptors and acts as a critical intracellular signaling scaffold that integrates signals between the platelet’s plasma membrane and the actin cytoskeleton. This mini-review summarizes how FLNA transduces critical cell signals to the platelet cytoskeleton.
Changes in the global, regional, and national burdens of NAFLD from 1990 to 2019: A systematic analysis of the global burden of disease study 2019

Background Understanding the burdens and trends of non-alcoholic fatty liver disease (NAFLD) is necessary for developing effective intervention strategies. In this study, Global Burden of Disease (GBD) 2019 study data were extracted and analyzed to elucidate trends of NAFLD. Methods The prevalence, incidence, disability-adjusted life year (DALY), and death rates of NAFLD in geographic populations worldwide from 1990 to 2019 were extracted from the GBD 2019 study data. The global temporal trend of NAFLD from 1990 to 2019 was evaluated using estimated annual percentage changes (EAPCs) and age-standardized rates. Results Globally, between 1999 and 2019, the age-standardized prevalence rate of NAFLD increased, with EAPCs of 0.77 [95% CI (0.69, 0.85)], whereas the DALY and Death rates decreased, with EAPCs of –0.82 [95% CI (–0.92, –0.71)], and –0.67 [95% CI (–0.76, –0.58)], respectively. Geographically, the age-standardized prevalence rate showed the most serious upward trend in high-income North America with an EAPC of 0.98 [95% CI (0.95, 1.02)], and the age-standardized incidence rate showed an upward trend in Central Asia with an EAPC of 3.17 [95% CI (2.2, 2.49)]. The most significant upward trend of DALY and death rates appeared in Eastern Europe, with EAPCs of 4.06 [95% CI (3.31, 4.82)], and 3.36 [95% CI (2.77, 3.96)], respectively. At the country level, the age-standardized rates showed an upward trend in Armenia, Belarus, and Republic of Korea. Regarding age groups, the percentage change of prevalence was the highest in the 40 to 44 group [0.29 (0.26, 0.34)] from 1990 to 2019; the percentage change of incidence was the highest in the 85 to 89 group [0.46 (0.12, 0.71)] from 1990 to 2019; the percentage change of DALY was the highest in the 80 to 84 group [0.25 (0.11, 0.39)] from 1990 to 2019; and the percentage change of death rate was the highest in the 15 to 19 group [0.36 (0.17, 0.60)] from 1990 to 2019. The percentage change of prevalence of liver cancer due to NASH was the highest in the group of 85 to 89, whereas those of incidence, DALY, and death were the highest in the group above 95 from 1990 to 2019. Regarding the sociodemographic index (SDI), the highest age-standardized prevalence, incidence, and Death rates of NAFLD occurred in middle-SDI countries, and the highest DALY rates of NAFLD occurred in low-SDI countries. Conclusion Global NAFLD burdens have increased since 1990. Our findings provide a reference for policymakers to reduce the burden of NAFLD, especially in middle and low-SDI countries.
The 2000HIV study: Design, multi-omics methods and participant characteristics

Background Even during long-term combination antiretroviral therapy (cART), people living with HIV (PLHIV) have a dysregulated immune system, characterized by persistent immune activation, accelerated immune ageing and increased risk of non-AIDS comorbidities. A multi-omics approach is applied to a large cohort of PLHIV to understand pathways underlying these dysregulations in order to identify new biomarkers and novel genetically validated therapeutic drugs targets. Methods The 2000HIV study is a prospective longitudinal cohort study of PLHIV on cART. In addition, untreated HIV spontaneous controllers were recruited. In-depth multi-omics characterization will be performed, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and metagenomics, functional immunological assays and extensive immunophenotyping. Furthermore, the latent viral reservoir will be assessed through cell associated HIV-1 RNA and DNA, and full-length individual proviral sequencing on a subset. Clinical measurements include an ECG, carotid intima-media thickness and plaque measurement, hepatic steatosis and fibrosis measurement as well as psychological symptoms and recreational drug questionnaires. Additionally, considering the developing pandemic, COVID-19 history and vaccination was recorded. Participants return for a two-year follow-up visit. The 2000HIV study consists of a discovery and validation cohort collected at separate sites to immediately validate any finding in an independent cohort. Results Overall, 1895 PLHIV from four sites were included for analysis, 1559 in the discovery and 336 in the validation cohort. The study population was representative of a Western European HIV population, including 288 (15.2%) cis-women, 463 (24.4%) non-whites, and 1360 (71.8%) MSM (Men who have Sex with Men). Extreme phenotypes included 114 spontaneous controllers, 81 rapid progressors and 162 immunological non-responders. According to the Framingham score 321 (16.9%) had a cardiovascular risk of >20% in the next 10 years. COVID-19 infection was documented in 234 (12.3%) participants and 474 (25.0%) individuals had received a COVID-19 vaccine. Conclusion The 2000HIV study established a cohort of 1895 PLHIV that employs multi-omics to discover new biological pathways and biomarkers to unravel non-AIDS comorbidities, extreme phenotypes and the latent viral reservoir that impact the health of PLHIV. The ultimate goal is to contribute to a more personalized approach to the best standard of care and a potential cure for PLHIV.
Seismicity and 3-D body-wave velocity models across the Hengill geothermal area, SW Iceland

We image shallow crustal structures and analyze seismicity patterns in the Hengill high-enthalpy geothermal area in SW Iceland, exploiting a temporary densification of the seismic network 2018 to 2020. Using a subset of 6,300 high-quality manually picked P- and S-phases, we compute a minimum 1-D model for the region. Our results suggest that the most consistent and accurate hypocenter locations are derived from a joint inversion of P and S arrival times for the Hengill area. We demonstrate that this minimum 1-D model in combination with SeisComP detection and location algorithms can be used to produce fully-automated yet high-quality earthquake catalogs. Our analysis established that both the induced and natural seismicity in the Hengill area occurs in several distinct, spatially constrained clusters. In production and injection areas, the depth of the clusters is at about 2 km, near the bottom of the production and injection wells. These are most likely triggered by the injection and induced by the production, respectively. Outside of these clusters, the seismicity is generally deeper, with the depth of the deepest seismicity indicating the brittle-ductile transition zone. This zone is encountered at about 4 km near the center of the Hengill volcanic area and deepens with increasing distance from its volcanic center, to about 7 km in the southernmost region. A spatial analysis of b-values shows slightly increased values in areas with numerous injection wells and slightly decreased values in production areas. Three-dimensional crustal imaging of VP, VS, VP/VS shows a SE-NW trending fast velocity that extends, at 1–3 km depth between the extinct Grensdalur volcanic center and the presently active Hengill volcanic center. The fastest velocities are found in the NW corner of the Grensdalur volcanic center coinciding with a gravity high and probably reflecting dense solidified magmatic intrusion(s). This trend coincides with traces of geothermal surface manifestations, a shallow lying low resistivity anomaly and an aero-magnetic low. All these anomalies are caused by high temperature at some point in the geological history of the area and are most likely due to migration of the crustal accretion and volcanic activity between the two volcanic centers. Below-average VP/VS ratios at similar depth, coincide with the main production field. We suggest that this anomaly is caused by the extensive fluid extraction, which lowers the pore-pressure in the field and consequently increases the steam dominated zone, leading to lower Vp/Vs ratios. Most of the earthquakes are within the Vp/Vs low and at the boundary of the high and low Vp/Vs anomalies, which might indicate a region of good permeability.
Comorbid depression and anxiety: Integration of insights from attachment theory and cognitive neuroscience, and their implications for research and treatment

COPYRIGHT © 2022 Rajkumar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Comorbid depression and anxiety: Integration of insights from attachment theory and cognitive neuroscience, and their implications for research and treatment
Effects of follicular output rate on cumulative clinical pregnancy rate and cumulative live birth rate in PCOS patients with different characteristics

Objective We aim to explore the effects of follicular output rate (FORT) on cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR) in polycystic ovary syndrome (PCOS) patients with different characteristics undergoing in vitro fertilization (IVF) treatment. Methods This retrospective study analyzed 454 patients with PCOS undergoing their first IVF cycle at our center from January 2016 to December 2020. FORT was calculated as pre-ovulatory follicle count (PFC) × 100/antral follicle count (AFC). Multivariate regression analyses were conducted to explore the relationships between FORT and CCPR and CLBR. Curve fitting and threshold effect analyses were established to find nonlinear relationships. Effect modification in different subgroups were examined by stratification analyses. Results Based on the FORT values, individuals were classified into the following three groups: low-FORT group, middle-FORT group and high-FORT group. Multivariate regression analyses revealed that FORT was an independent factor affecting the CCPR and CLBR significantly (OR = 1.015, 95% CI: 1.001, 1.030 and OR = 1.010, 95% CI:1.001, 1.020). Curve fitting and threshold effect analyses showed that the CCPR and CLBR had a positive correlation with FORT when the FORT was less than 70% (OR = 1.039, 95% CI: 1.013, 1.065 and OR = 1.024, 95% CI: 1.004, 1.044). Stratification analyses showed that the CLBR increased by 1.3% with each additional unit of FORT for patients with hyperandrogenic manifestations (OR = 1.013, 95% CI: 1.001, 1.025). Compared with the low-FORT group, in the high-FORT group, CCPR increased 1.251 times for patients with polycystic ovarian morphology, while CCPR and CLBR increased 1.891 times and 0.99 times for those with ovulation disorder, respectively (OR = 2.251, 95% CI: 1.008, 5.028 and OR = 2.891, 95% CI: 1.332, 6.323 and OR = 1.990, 95% CI: 1.133, 3.494). Conclusion In patients with PCOS, cumulative IVF outcomes have a positive correlation with FORT when the FORT is less than 70%. For PCOS patients with polycystic ovarian morphology, ovulation disorder or hyperandrogenic manifestations, a high FORT could be conductive to achieving better pregnancy outcomes.
Acquisition-dependent modulation of hippocampal neural cell adhesion molecules by associative motor learning

It is widely accepted that some types of learning involve structural and functional changes of hippocampal synapses. Cell adhesion molecules neural cell adhesion molecule (NCAM), its polysialylated form polysialic acid to NCAM (PSA-NCAM), and L1 are prominent modulators of those changes. On the other hand, trace eyeblink conditioning, an associative motor learning task, requires the active participation of hippocampal circuits. However, the involvement of NCAM, PSA-NCAM, and L1 in this type of learning is not fully known. Here, we aimed to investigate the possible time sequence modifications of such neural cell adhesion molecules in the hippocampus during the acquisition of a trace eyeblink conditioning. To do so, the hippocampal expression of NCAM, PSA-NCAM, and L1 was assessed at three different time points during conditioning: after one (initial acquisition), three (partial acquisition), and six (complete acquisition) sessions of the conditioning paradigm. The conditioned stimulus (CS) was a weak electrical pulse separated by a 250-ms time interval from the unconditioned stimuli (US, a strong electrical pulse). An acquisition-dependent regulation of these adhesion molecules was found in the hippocampus. During the initial acquisition of the conditioning eyeblink paradigm (12 h after 1 and 3 days of training), synaptic expression of L1 and PSA-NCAM was transiently increased in the contralateral hippocampus to the paired CS-US presentations, whereas, when the associative learning was completed, such increase disappeared, but a marked and bilateral upregulation of NCAM was found. In conclusion, our findings show a specific temporal pattern of hippocampal CAMs expression during the acquisition process, highlighting the relevance of NCAM, PSA-NCAM, and L1 as learning-modulated molecules critically involved in remodeling processes underlying associative motor-memories formation.
Perspectives on the basis of seizure-induced respiratory dysfunction

Epilepsy is an umbrella term used to define a wide variety of seizure disorders and sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in epilepsy. Although some SUDEP risk factors have been identified, it remains largely unpredictable, and underlying mechanisms remain poorly understood. Most seizures start in the cortex, but the high mortality rate associated with certain types of epilepsy indicates brainstem involvement. Therefore, to help understand SUDEP we discuss mechanisms by which seizure activity propagates to the brainstem. Specifically, we highlight clinical and pre-clinical evidence suggesting how seizure activation of: (i) descending inhibitory drive or (ii) spreading depolarization might contribute to brainstem dysfunction. Furthermore, since epilepsy is a highly heterogenous disorder, we also considered factors expected to favor or oppose mechanisms of seizure propagation. We also consider whether epilepsy-associated genetic variants directly impact brainstem function. Because respiratory failure is a leading cause of SUDEP, our discussion of brainstem dysfunction focuses on respiratory control.
Gut microbial indicators of metabolic health underlie age-related differences in obesity and diabetes risk among Native Hawaiians and Pacific Islanders

Native Hawaiians and Pacific Islanders (NHPIs) suffer from higher prevalence of and mortality to type 2 diabetes mellitus (T2DM) than any other major race/ethnic group in Hawaii. Health inequities in this indigenous population was further exacerbated by the SARS-CoV-2 pandemic. T2DM progression and medical complications exacerbated by COVID-19 are partially regulated by the gut microbiome. However, there is limited understanding of the role of gut bacteria in the context of inflammation-related diseases of health disparities including T2DM and obesity. To address these gaps, we used a community-based research approach from a cohort enriched with NHPI residents on the island of Oahu, Hawaii (N=138). Gut microbiome profiling was achieved via 16s rDNA metagenomic sequencing analysis from stool DNA. Gut bacterial capacity for butyrate-kinase (BUK)-mediated fiber metabolism was assessed using quantitative PCR to measure the abundance of BUK DNA and RNA relative to total bacterial load per stool sample. In our cohort, age positively correlated with hemoglobin A1c (%; R=0.39; P<0.001) and body mass index (BMI; R=0.28; P<0.001). The relative abundance of major gut bacterial phyla significantly varied across age groups, including Bacteroidetes (P<0.001), Actinobacteria (P=0.007), and Proteobacteria (P=0.008). A1c was negatively correlated with the relative levels of BUK DNA copy number (R=-0.17; P=0.071) and gene expression (R=-0.33; P=0.003). Interestingly, we identified specific genera of gut bacteria potentially mediating the effects of diet on metabolic health in this cohort. Additionally, α-diversity among gut bacterial genera significantly varied across T2DM and BMI categories. Together, these results provide insight into age-related differences in gut bacteria that may influence T2DM and obesity in NHPIs. Furthermore, we observed overlapping patterns between gut bacteria and T2DM risk factors, indicating more nuanced, interdependent interactions among these factors as partial determinants of health outcomes. This study adds to the paucity of NHPI-specific data to further elucidate the biological characteristics associated with pre-existing health inequities in this racial/ethnic group that is significantly underrepresented in biomedical research.
Severe early-onset manifestations of generalized arterial calcification of infancy (mimicking severe coarctation of the aorta) with ABCC6 gene variant — Case report and literature review

Introduction Generalized arterial calcification of infancy (GACI) is a rare cause of infantile heart failure and systemic hypertension with a poor prognosis, characterized by extensive calcification and proliferation of the intimal layer of large and medium sized arteries. Case report We present the first case report of successful surgical treatment of severe aortic arch obstruction by calcified plaques mimicking severe coarctation of the aorta and the outcome (of bisphosphonate therapy) in a newborn with GACI. Furthermore, we report the identification of a variant in ATP Binding Cassette Subfamily C, Member 6 (ABCC6) gene, possibly associated with severe early-onset manifestations of GACI. Conclusion This case report highlights the importance of considering GACI in an infant with heart failure, systemic hypertension, and evidence of increased echogenicity of the arterial vessels. We noted the favorable outcome in improving the aortic calcification in our patient after surgical treatment and bisphosphonates therapy. Early diagnosis and treatment improve the long-term prognosis. A better understanding of this rare genetic disease could lead to new therapeutic strategies.