Miracle-dz/UniFAR-FTUs huggingface dataset:
More Pronounced Hypercoagulable State and Hypofibrinolysis in Patients With Cirrhosis With Versus Without HCC

In patients with cirrhosis, particularly those with hepatocellular carcinoma (HCC), hypercoagulability may be associated with purported increased risks of portal vein thrombosis and cirrhosis progression. In this study, we extensively investigated hemostatic alterations potentially responsible for the thrombotic tendency in HCC, and evaluated whether such alterations were predictive of hepatic decompensation. Patients with cirrhosis at all stages were prospectively recruited and underwent an extensive hemostatic assessment, including all procoagulant factors and inhibitors, thrombin generation with and without thrombomodulin (TG), profibrinolytic and antifibrinolytic factors, and plasmin‐antiplasmin complex. In study part 1 (case control), we compared alterations of coagulation and fibrinolysis in patients with cirrhosis with versus without HCC. In study part 2 (prospective), the subgroup of patients with decompensated cirrhosis was followed for development of further decompensation, and predictors of outcome were assessed by multivariate analysis. One‐hundred patients were recruited (50 each with and without HCC). Severity of cirrhosis was comparable between groups. Median HCC volume was 9 cm3 (range: 5‐16). Compared with controls, patients with HCC demonstrated a significantly more prothrombotic hemostatic profile due to increased TG and reduced activation of fibrinolysis, independent of cirrhosis stage. During a median follow‐up of 175 days, 20 patients with decompensated cirrhosis developed further episodes of decompensation that were predicted by low FVII and high plasminogen activator inhibitor‐1 levels, independent of Model for End‐Stage Liver Disease score. Conclusion: Patients with cirrhosis with HCC have profound hyper‐coagulable changes that can account for their increased thrombotic tendency. In contrast, hypercoagulability in patients with decompensated cirrhosis is more likely a consequence of chronic liver disease rather than a driver for cirrhosis progression.
Synovial single-cell heterogeneity, zonation and interactions: a patchwork of effectors in arthritis

Abstract Despite extensive research, there is still no treatment that would lead to remission in all patients with rheumatoid arthritis as our understanding of the affected site, the synovium, is still incomplete. Recently, single-cell technologies helped to decipher the cellular heterogeneity of the synovium; however, certain synovial cell populations, such as endothelial cells or peripheral neurons, remain to be profiled on a single-cell level. Furthermore, associations between certain cellular states and inflammation were found; whether these cells cause the inflammation remains to be answered. Similarly, cellular zonation and interactions between individual effectors in the synovium are yet to be fully determined. A deeper understanding of cell signalling and interactions in the synovium is crucial for a better design of therapeutics with the goal of complete remission in all patients.
INPP5K and Atlastin-1 maintain the nonuniform distribution of ER–plasma membrane contacts in neurons

CIL-1 and ATLN-1 maintain the balance between ER tubules and sheets and prevent invasion of cortical ER sheets into the axon, contributing to the non-uniform distribution of neuronal ER-PM contacts. In neurons, the ER extends throughout all cellular processes, forming multiple contacts with the plasma membrane (PM) to fine-tune neuronal physiology. However, the mechanisms that regulate the distribution of neuronal ER-PM contacts are not known. Here, we used the Caenorhabditis elegans DA9 motor neuron as our model system and found that neuronal ER-PM contacts are enriched in soma and dendrite and mostly absent in axons. Using forward genetic screen, we identified that the inositol 5-phosphatase, CIL-1 (human INPP5K), and the dynamin-like GTPase, ATLN-1 (human Atlastin-1), help to maintain the non-uniform, somatodendritic enrichment of neuronal ER-PM contacts. Mechanistically, CIL-1 acts upstream of ATLN-1 to maintain the balance between ER tubules and sheets. In mutants of CIL-1 or ATLN-1, ER sheets expand and invade into the axon. This is accompanied by the ectopic formation of axonal ER-PM contacts and defects in axon regeneration following laser-induced axotomy. As INPP5K and Atlastin-1 have been linked to neurological disorders, the unique distribution of neuronal ER-PM contacts maintained by these proteins may support neuronal resilience during the onset and progression of these diseases.
Effects of maternal stress and/or anxiety interventions in the first 1000 days:Systematic review of reviews

ABSTRACT Objective Effective interventions are needed to mitigate effects of stress and anxiety from conception and up to two years postpartum (the first 1000 days), but it is unclear what works, for what populations and at what time points. This review aimed to synthesise evidence from existing reviews of the effects of stress and anxiety interventions. Methods A systematic review of systematic reviews was conducted. PsycINFO, CINAHL, MEDLINE and the Cochrane databases were searched (inception to January 2020). Reviews were eligible if they examined effects of interventions during the first 1000 days on women’s stress and/or anxiety. Extracted data were narratively synthesised. Review quality was assessed using existing recommendations including the AMSTAR tool . Results Thirty-four reviews were eligible for inclusion; 21 demonstrated high methodological quality. Cognitive behavioural therapy demonstrates some beneficial effects for anxiety across the first 1000 days for general and at-risk populations. Support-based interventions demonstrate effects for stress and anxiety for at-risk mothers in the postpartum. Music, yoga and relaxation demonstrate some effects for stress and anxiety, but studies are limited by high risk of bias. Conclusion Existing evidence is inconsistent. Cognitive behavioural therapy and support-based interventions demonstrate some benefits. Further methodologically and conceptually robust research is needed.
Pivotal role of video‐assisted thoracoscopic surgery in improving survival outcome of stage I non‐small cell lung cancer in day surgery patients

Lung cancer, the leading cause of cancer‐related deaths worldwide, has high morbidity rates. Video‐assisted thoracoscopic surgery (VATS) as day surgery makes surgical treatment ideally in time with the same quality of medical care. This study aimed to assess the safety of stage I NSCLC patients who underwent VATS at a day surgery center.
Beyond the beak: Brain size and allometry in avian craniofacial evolution

Birds exhibit an enormous variety of beak shapes. Such remarkable variation, however, has distracted research from other important aspects of their skull evolution, the nature of which has been little explored. Key aspects of avian skull variation appear to be qualitatively similar to those of mammals, encompassing variation in the degree of cranial vaulting, cranial base flexure, and the proportions and orientations of the occipital and facial regions. The evolution of these traits has been studied intensively in mammals under the Spatial Packing Hypothesis (SPH), an architectural constraint so‐called because the general anatomical organization and development of such skull parts makes them evolve predictably in response to changes in relative brain size. Such SPH predictions account for the different appearances of skull configurations across species, either in having longer or shorter faces, and caudally or ventrally oriented occiputs, respectively. This pattern has been morphometrically and experimentally proven in mammals but has not been examined in birds or other tetrapods, and so its generality remains unknown. We explored the SPH in an interspecific sample of birds using three‐dimensional geometric morphometrics. Our results show that the dominant trend of evolutionary variation in the skull of crown‐group birds can be predicted by the SPH, involving concomitant changes in the face, the cranial vault and the basicranium, and with striking similarities to craniofacial variation among mammals. Although craniofacial variation is significantly affected by allometry, these allometric effects are independent of the influence of the SPH on skull morphology, as are any effects of volumetric encephalization. Our results, therefore, validate the hypothesis that a general architectural constraint underlies skull homoplasy evolution of cranial morphology among avian clades, and possibly between birds and mammals, but they downplay encephalization and allometry as the only factors involved.
Intranasal Iloprost Prevents Tumors in a Murine Lung Carcinogenesis Model

Iloprost is a promising chemoprevention agent for lung cancer and this work describes a new delivery approach in vivo. Lung cancer chemoprevention with the prostacyclin analogue iloprost is the most promising approach to date for intercepting progression of premalignant lung lesions in former smokers. Previous preclinical studies of iloprost used oral delivery, but a study modeling delivery directly to the target organ was needed. In vivo and in vitro studies have identified gene expression changes following iloprost treatment, including increased e-cadherin and Ppargγ and decreased COX2 and vimentin. We used tumor counts and gene expression to demonstrate the effectiveness of intranasal delivery of iloprost in a murine model of premalignant adenomas. Intranasal delivery of iloprost reduced adenoma multiplicity 14 weeks after urethane exposure in FVB/N mice compared with untreated urethane controls. Intranasal iloprost reversed urethane-induced gene expression changes in tumors and whole lung. These results correspond to previous studies of oral iloprost and in vitro treatment of human bronchial epithelial cells. This study demonstrates that intranasal delivery of iloprost in a mouse model of lung premalignant lesions is effective chemoprevention. This will be an essential tool for exploring mechanisms and outcomes of iloprost chemoprevention, along with supporting ongoing clinical trials of inhaled iloprost chemoprevention. Prevention Relevance: Iloprost is a promising chemoprevention agent for lung cancer and this work describes a new delivery approach in vivo.
Maternal prenatal selenium levels and child risk of neurodevelopmental disorders: A prospective birth cohort study

Selenium (Se) is an essential trace element involved in various biological processes, including neurodevelopment. Available literature indicates that both Se deficiency and excess may be detrimental to health. It is also known that Se can cross the placenta from maternal to fetal circulation. To date, the role of maternal Se status in child long‐term neurodevelopment is largely unexplored. This study investigated the temporal and dose–response associations between maternal Se status and child risk of neurodevelopmental disorders including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). It consisted of 1550 mother–infant dyads from the Boston Birth Cohort. Maternal red blood cell (RBC) Se levels were measured in samples collected within 72 h of delivery (biomarker of third trimester Se status). Pediatric neurodevelopmental diagnoses were obtained from electronic medical records. Data analyses showed that maternal RBC Se levels were positively associated with child risk of developing ASD, with an adjusted odds ratio of 1.49 for ASD (95% CI: 1.09, 2.02) per IQR increase in Se. There was also a positive association between maternal Se and ADHD (OR: 1.29; 95% CI: 1.04, 1.56, per IQR increase in Se). These associations remained robust even after adjusting for pertinent covariables; and there was no significant interaction between Se and these covariables. Our findings suggest that prenatal exposure to high maternal Se levels may adversely affect child neurodevelopment. Our findings warrant further investigation; if confirmed, optimizing maternal prenatal Se levels may be necessary to maximize its health benefits while preventing undue risk.
Key stakeholder perspectives on obstacles to an autism-specific Medicaid waiver service delivery model.

BACKGROUND Children and youth with autism spectrum disorder have significant, multi-system needs that require supports, such as the autism waiver (AW) service delivery model. This study aimed to identify and describe characteristics of the AW, define obstacles and strengths in the provision of adequate services and provide recommendations for improving overall effectiveness. METHODS This mixed-methods exploratory study used an electronic survey to gain information and perceptions of AW provider agency directors (n = 27) and service coordinators (n = 30). RESULTS The key barriers reported were the shortage of qualified staff, inadequate staff training, complexity of cases or symptom severity of clients and lack of communication at multiple levels throughout the agency as well as with parents. CONCLUSIONS Recommendations include reinforcing the workforce through higher salaries, greater training and communication interventions. These strategies may reduce staff turnover and shortage, lighten the caseload, reduce the waitlist period and improve the effectiveness and responsiveness of AW services.
Radioembolization Versus Bland or Chemoembolization for Liver-Dominant Neuroendocrine Tumors: Is It an Either/Or Question?

Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; Department of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York; Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York City, New York; Department of Interventional Radiology, M.D. Anderson Cancer Center, Houston, Texas; Department of Gastrointestinal Medical Oncology, M.D. Anderson Cancer Center, Houston, Texas; Department of Gastrointestinal Oncology, Karmanos Cancer Center, Detroit, Michigan; and Department of Interventional Radiology, University of Pennsylvania, Philadelphia, Pennsylvania
Soluble Klotho and Incident Hypertension

Visual Abstract Background and objectives Hypertension is associated with significant morbidity and mortality despite effective antihypertensive therapies. Soluble klotho is a circulating protein that in preclinical studies is protective against the development of hypertension. There are limited studies of klotho and blood pressure in humans. Design, setting, participants, & measurements Within the Health, Aging, and Body Composition Study, a cohort of well-functioning older adults, soluble klotho was measured in serum. We evaluated the cross-sectional and longitudinal association between klotho and blood pressure, prevalent hypertension, incident hypertension, and BP trajectories. Analyses were adjusted for demographics, cardiovascular disease and kidney disease risk factors, and measures of mineral metabolism including calcium, phosphate, parathyroid hormone, 25(OH) vitamin D, and fibroblast growth factor 23. Results The median klotho concentration was 630 pg/ml (478–816, 25th to 75th percentile). Within the cohort, 2093 (76%) of 2774 participants had prevalent hypertension and 476 (70%) of the remaining 681 developed incident hypertension. There was no association between klotho and prevalent hypertension or baseline systolic BP, but higher klotho was associated with higher baseline diastolic BP (fully adjusted β=0.92 mmHg, 95% confidence interval, 0.24 to 1.60 mmHg, higher per two-fold higher klotho). Higher baseline serum klotho levels were significantly associated with a lower rate of incident hypertension (fully adjusted hazard ratio, 0.80; 95% confidence interval, 0.69 to 0.93 for every two-fold higher klotho). Higher klotho was also associated with lower subsequent systolic BP and diastolic BP (−0.16, 95% confidence interval, −0.31 to −0.01, mmHg lower systolic BP per year and −0.10, 95% confidence interval, −0.18 to −0.02, mmHg lower diastolic BP per year, for each two-fold higher klotho). Conclusions Higher klotho is associated with higher baseline diastolic but not systolic BP, a lower risk of incident hypertension, and lower BP trajectories during follow-up.
Engineering false smut resistance rice via host‐induced gene silencing of two chitin synthase genes of Ustilaginoidea virens

Rice false smut (RFS), caused by the pathogenic ascomycete fungus Ustilaginoidea virens (U. virens), is one of the severely devastating diseases worldwide (Sun et al., 2020; Zhang et al., 2014). U. virens infects rice flowers causing over 25% yield loss, also producing poisonous mycotoxins that threaten the health of humans and animals (Fan et al., 2016; Zhang et al., 2014). So far, rice varieties showing resistance to RFS are rarely mined and none resistant genes are genetically confirmed (Zhang et al., 2019). Host-induced gene silencing (HIGS) is a powerful strategy to control diseases, where small interference RNAs (siRNAs) are produced by plants to silence essential genes of pathogens. Application of HIGS to control fungal diseases is successfully reported in several crops (Hou and Ma, 2020). Here, we evaluated the potential of HIGS for engineering rice against RFS by silencing chitin synthase genes of U. virens.
A time‐course study of actively stained mouse brains: Diffusion tensor imaging parameters and connectomic stability over 1 year

While the application of diffusion tensor imaging (DTI), tractography, and connectomics to fixed tissue is a common practice today, there have been limited studies examining the effects of fixation on brain microstructure over extended periods. This mouse model time‐course study reports the changes of regional brain volumes and diffusion scalar parameters, such as fractional anisotropy, across 12 representative brain regions as measures of brain structural stability. The scalar DTI parameters and regional volumes were highly variable over the first 2 weeks after fixation. The same parameters were consistent over a 2–8‐week window after fixation, which means confounds from tissue stability over that scanning window were minimal. Quantitative connectomes were analyzed over the same time with extension out to 1 year. While there was some change in the scalar metrics at 1 year after fixation, these changes were sufficiently small, particularly in white matter, to support reproducible connectomes over a period ranging from 2‐weeks to 1‐year post‐fixation. These findings delineate a scanning period, during which brain volumes, diffusion scalar metrics, and connectomes are remarkably consistent.
Social groups constrain the spatiotemporal dynamics of wild sifaka gut microbiomes

Primates acquire gut microbiota from conspecifics through direct social contact and shared environmental exposures. Host behaviour is a prominent force in structuring gut microbial communities, yet the extent to which group or individual‐level forces shape the long‐term dynamics of gut microbiota is poorly understood. We investigated the effects of three aspects of host sociality (social groupings, dyadic interactions, and individual dispersal between groups) on gut microbiome composition and plasticity in 58 wild Verreaux's sifaka (Propithecus verreauxi) from six social groups. Over the course of three dry seasons in a 5‐year period, the six social groups maintained distinct gut microbial signatures, with the taxonomic composition of individual communities changing in tandem among coresiding group members. Samples collected from group members during each season were more similar than samples collected from single individuals across different years. In addition, new immigrants and individuals with less stable social ties exhibited elevated rates of microbiome turnover across seasons. Our results suggest that permanent social groupings shape the changing composition of commensal and mutualistic gut microbial communities and thus may be important drivers of health and resilience in wild primate populations.
Quantifying neural efficiency and neural capacity across the brain during a working memory task using a quadratic model of neural–cognitive relationships

Task‐based functional magnetic resonance imaging (MRI) neuroimaging for the study of cognitive neuroscience provides insight into how the brain responds to increasing cognitive demands. Theoretical models of neural–cognitive relationships define neural efficiency and neural capacity as two parameters to describe the rate of gain of brain activity and the upper limits of the increases, respectively. Although qualitatively well described, there are limited discussions and demonstrations of estimating these parameters from data. The current work presents a method using a quadratic equation model of cognitive demands. The methods were applied to 21 healthy young adults while engaging in four levels of the verbal n‐back working memory task (0, 1, 2 and 3‐back). Measures of the area under the curve captured both linear and curvilinear responses to quantify the locations and amounts of task‐related increases in brain activity. In addition, we calculated voxel‐wise maps of neural efficiency and neural capacity. Results showed increases in brain activation in regions typically involved in working memory. The relationships between increasing cognitive demands and brain activity also differed across the brain within and between individuals, as indicated by differential neural efficiency and neural capacity values. This approach provides tools for evaluating current theories about the relationships between brain activity and cognition. Neural efficiency and neural capacity provide physiological measures of brain activity, which will help evaluate how age, disease and intervention processes affect brain activity. Finally, all presented methods are readily applicable using standard current software packages for neuroimaging.
Myopalladin knockout mice develop cardiac dilation and show a maladaptive response to mechanical pressure overload

Myopalladin (MYPN) is a striated muscle-specific immunoglobulin domain-containing protein located in the sarcomeric Z-line and I-band. MYPN gene mutations are causative for dilated (DCM), hypertrophic, and restrictive cardiomyopathy. In a yeast two-hybrid screening, MYPN was found to bind to titin in the Z-line, which was confirmed by microscale thermophoresis. Cardiac analyses of MYPN knockout (MKO) mice showed the development of mild cardiac dilation and systolic dysfunction, associated with decreased myofibrillar isometric tension generation and increased resting tension at longer sarcomere lengths. MKO mice exhibited a normal hypertrophic response to transaortic constriction (TAC), but rapidly developed severe cardiac dilation and systolic dysfunction, associated with fibrosis, increased fetal gene expression, higher intercalated disc fold amplitude, decreased calsequestrin-2 protein levels, and increased desmoplakin and SORBS2 protein levels. Cardiomyocyte analyses showed delayed Ca2+ release and reuptake in unstressed MKO mice as well as reduced Ca2+ spark amplitude post-TAC, suggesting that altered Ca2+ handling may contribute to the development of DCM in MKO mice.