The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD)-related advanced fibrosis and cirrhosis in the United States population utilizing AGILE 3 + and AGILE 4 scores: analysis of the NHANES 2017-2018 cycle.

BACKGROUND: Studies attempted to estimate MASLD-related advanced fibrosis (AF) and cirrhosis (MC) prevalence utilized tests with low positive predictive value (PPV) which overestimates prevalence. AGILE3 + and 4 scores were developed to increase the PPV of both; respectively. In this study, we used these scores to assess the prevalence of AF and MC. METHODS: Participants aged ≥ 18 years with VCTE exam in the NHANES 2017-2018 cycle were included. We excluded pregnant women, patients with excessive alcohol intake, hepatitis B/C, and ALT or AST > 500 IU/L. MASLD was defined with CAP score > 248 dB/m. MASLD subjects with AGILE 3 + score of ≥ 0.68 and AGILE 4 score of ≥ 0.57 were considered to have advanced fibrosis and cirrhosis; respectively. AGILE 3 + of 0.45-0.67 and AGILE 4 of 0.25-0.57 were grey zone, whereas AGILE 3 + < 0.45 and AGILE 4 < 0.25 were considered a rule-out. RESULTS: 1244 subjects were included in the final analysis. The Median age was 53 (51.4-54.6) years, 55.6% were male, median BMI was 33.8 kg/m2 and 41.1% had T2DM. Based on AGILE 3+, 80.3% of the MASLD population were at low risk for AF and 11.5% were in grey zone. The prevalence of AF due to MASLD was 8.1% corresponding to 4.5 million Americans. Based on AGILE 4 score, 96.5% of the MASLD population were at low risk for cirrhosis and 2.4% were in the grey zone. The prevalence of MASLD-cirrhosis was 1.1% corresponding to 610,000 Americans. CONCLUSION: Our results suggest that approximately 4.5 million people in the U.S. have AF and 0.6 million have cirrhosis due to MASLD.

Racial and ethnic differences in uncontrolled diabetes mellitus among adults taking antidiabetic medication.

AIM: To examine whether racial and ethnic disparities in uncontrolled type 2 diabetes mellitus (T2DM) persist among those taking medication and after accounting for other demographic, socioeconomic, and health indicators. METHODS: Adults aged ≥20 years with T2DM using prescription diabetes medication were among participants assessed in a retrospective cohort study of the National Health and Nutrition Examination Survey 2007-2018. We estimated weighted sequential multivariable logistic regression models to predict odds of uncontrolled T2DM (HbA1c ≥ 8%) from racial and ethnic identity, adjusting for demographic, socioeconomic, and health indicators. RESULTS: Of 3649 individuals with T2DM who reported taking medication, 27.4% had uncontrolled T2DM (mean HgA1c 9.6%). Those with uncontrolled diabetes had a mean BMI of 33.8, age of 57.3, and most were non-Hispanic white (54%), followed by 17% non-Hispanic Black, and 20% Hispanic identity. In multivariable analyses, odds of uncontrolled T2DM among those with Black or Hispanic identities lessened, but persisted, after accounting for other indicators (Black OR 1.38, 97.5% CI: 1.04, 1.83; Hispanic OR 1.79, 97.5% CI 1.25, 2.57). CONCLUSIONS: Racial and ethnic disparities in T2DM control persisted among individuals taking medication. Future research might focus on developmental and epigenetic pathways of disparate T2DM control across racially and ethnically minoritized populations.

Sociodemographic disparities in GLP-1RA and SGLT2i use among US adults with type 2 diabetes: NHANES 2005-March 2020.

OBJECTIVE: Type 2 Diabetes (T2D) is a major cause of morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) are highly effective but underutilized. Our objective was to assess racial/ethnic and other sociodemographic disparities in GLP-1RA/SGLT2i use among US adults with T2D. METHODS: We conducted a retrospective analysis using the National Health and Nutrition Examination Survey from 2005-March 2020. Participants were adults with T2D taking ≥1 anti-diabetic medication, excluding pregnant women and adults with probable T1D. We performed univariate analyses to examine the characteristics of patients using GLP-1RA/SGLT2i and multivariable logistic regression to assess disparities in GLP-1RA/SGLT2i use after adjusting for other patient factors. RESULTS: Among 4777 people with T2D (representing >18 million US adults) taking ≥1 medication, GLP-1RA/SGLT2i usage increased from 1.4% in 2005-2006 to 13.3% in 2017-2020. In univariate analyses, patients using GLP-1RA/SGLT2i vs. other T2D drugs were more likely to be White than nonwhite (72% vs. 60%, p = .001), but in multivariable analysis there was no significant difference in GLP-1RA/SGLT2i use for nonwhite vs. White patients (aOR = 0.84, 95% CI [0.61, 1.16]). GLP-1RA/SGLT2i use was higher for patients who completed some college (aOR = 1.83, 95% CI [1.06, 3.15]) or above (aOR = 2.06, 95% CI [1.28, 3.32]) vs. high school or less, and for those with an income-poverty ratio ≥4 vs. <2 (aOR = 2.11, 95% CI [1.30, 3.42]). CONCLUSIONS: The use of GLP-1RA/SGLT2i drugs increased over time but remained low in March 2020. Higher education and income, but not race/ethnicity, were associated with GLP-1RA/SGLT2i use.

Manipulation of the Structure and Optoelectronic Properties through Bromine Inclusion in a Layered Lead Bromide Perovskite.

One of the great advantages of organic-inorganic metal halides is that their structures and properties are highly tuneable and this is important when optimizing materials for photovoltaics or other optoelectronic devices. One of the most common and effective ways of tuning the electronic structure is through anion substitution. Here, we report the inclusion of bromine into the layered perovskite [H3N(CH2)6NH3]PbBr4 to form [H3N(CH2)6NH3]PbBr4·Br2, which contains molecular bromine (Br2) intercalated between the layers of corner-sharing PbBr6 octahedra. Bromine intercalation in [H3N(CH2)6NH3]PbBr4·Br2 results in a decrease in the band gap of 0.85 eV and induces a structural transition from a Ruddlesden-Popper-like to Dion-Jacobson-like phase, while also changing the conformation of the amine. Electronic structure calculations show that Br2 intercalation is accompanied by the formation of a new band in the electronic structure and a significant decrease in the effective masses of around two orders of magnitude. This is backed up by our resistivity measurements that show that [H3N(CH2)6NH3]PbBr4·Br2 has a resistivity value of one order of magnitude lower than [H3N(CH2)6NH3]PbBr4, suggesting that bromine inclusion significantly increases the mobility and/or carrier concentration in the material. This work highlights the possibility of using molecular inclusion as an alternative tool to tune the electronic properties of layered organic-inorganic perovskites, while also being the first example of molecular bromine inclusion in a layered lead halide perovskite. By using a combination of crystallography and computation, we show that the key to this manipulation of the electronic structure is the formation of halogen bonds between the Br2 and Br in the [PbBr4]∞ layers, which is likely to have important effects in a range of organic-inorganic metal halides.

Prevalence of at-risk NASH and its association with metabolic syndrome in US adults with NAFLD, 2017-2018.

Patients with metabolic syndrome (MetS) have a higher risk for NASH and significant fibrosis. Presence of NASH and advanced fibrosis are associated with adverse outcomes in patients with NAFLD. Using a noninvasive method, we determined the prevalence of at-risk NASH and its association with MetS components in a large population-based analysis. We used the 2017-2018 National Health and Nutrition Examination Survey and included adults ≥18 years with NAFLD (controlled attenuation parameter ≥274 dB/m). Pregnancy, subjects with other causes of liver disease or missing data were excluded. FibroScan-AST (FAST) score was calculated using aspartate aminotransferase, liver stiffness measurement, and controlled attenuation parameter. Patients with a FAST score >0.35 were considered to have at-risk NASH, defined as NASH with NAFLD activity score ≥4 and fibrosis stage ≥2 on liver biopsy. The sample included 687 patients. The overall prevalence of at-risk NASH was 11.6% (95% CI: 8.8-15.1) and was higher in males than females (15.8% vs. 6.5%; p < 0.001). Subjects with comorbidities (diabetes mellitus, obesity, MetS, and insulin resistance) had between 1.3 and 1.7 times higher prevalence than the general population. Among MetS components, elevated glucose/diabetes, large waist circumference, and low HDL were independent risk factors for at risk-NASH. The number of MetS components was also important-one additional component increased the odds of at-risk NASH by 2 times. The FAST score had the highest correlation with alanine aminotransferase (r= 0.70; p < 0.001). We estimated ~9 million people in the US have at-risk NASH and may benefit from active surveillance and therapy.

Disease State Transition Probabilities Across the Spectrum of NAFLD: A Systematic Review and Meta-Analysis of Paired Biopsy or Imaging Studies.

BACKGROUND & AIMS: We conducted a meta-analysis to summarize the rates of progression to and regression of nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), and fibrosis in adults with nonalcoholic fatty liver disease (NAFLD). METHODS: We searched PubMed/Medline and 4 other databases from 1985 through 2020. We included observational studies and randomized controlled trials in any language that used liver biopsy or imaging to diagnose NAFLD in adults with a follow-up period ≥48 weeks. Rates were calculated as incident cases per 100 person-years and pooled using the random-effects Poisson distribution model. Heterogeneity was assessed using the I2 statistic. RESULTS: We screened 9744 articles and included 54 studies involving 26,738 patients. Among observational studies, 20% of healthy adults developed NAFL (incidence rate, 4.8/100 person-years) while 21% of people with fatty liver had resolution of NAFL (incidence rate, 2.4/100 person-years) after a median of approximately 4.5 years. In addition, 31% of patients developed NASH after 4.7 years (incidence rate, 7.4/100 person-years), whereas in 29% of those with NASH, resolution occurred after a median of 3.5 years (incidence rate, 5.1/100 person-years). Time to progress by 1 fibrosis stage was 9.9, 10.3, 13.3, and 22.2 years for F0, F1, F2, and F3, respectively. Time to regress by 1 stage was 21.3, 12.5, 20.4, and 40.0 years for F4, F3, F2, and F1, respectively. Rates estimated from randomized controlled trials were higher than those from observational studies. CONCLUSIONS: In our meta-analysis, progression to NASH was more common than regression from NASH. Rates of fibrosis progression were similar across baseline stage, but patients with advanced fibrosis were more likely to regress than those with mild fibrosis.

Simple diagnostic algorithm identifying at-risk nonalcoholic fatty liver disease patients needing specialty referral within the United States.

BACKGROUND: There is an urgent need to risk stratify patients with suspected nonalcoholic fatty liver disease (NAFLD) and identify those with fibrotic nonalcoholic steatohepatitis. This study aims to apply a simple diagnostic algorithm to identify subjects with at-risk NAFLD in the general population. AIM: To apply a simple diagnostic algorithm to identify subjects with at-risk NAFLD in the general population. METHODS: Adult subjects were included from the National Health and Nutrition Examination Survey database (2017-2018) if they had elevated alanine aminotransferase (ALT) and excluded if they had evidence of viral hepatitis or significant alcohol consumption. A fibrosis-4 (FIB4) cutoff of 1.3 differentiated patients with low risk vs high risk disease. If patients had FIB4 > 1.3, a FAST score < 0.35 ruled out advanced fibrosis. Patients with FAST > 0.35 were referred to a specialist. The same algorithm was applied to subjects with type 2 diabetes mellitus (T2DM). RESULTS: Three thousand six hundred and sixty-nine patients were identified who met all inclusion and exclusion criteria. From this cohort, 911 (28.6%) patients had elevated ALT of which 236 (22.9%) patients had elevated FIB4 scores ≥ 1.3. Among patients with elevated FIB4 score, 75 (24.4%) had elevated FAST scores, ruling in advanced fibrosis. This accounts for 2.0% of the overall study population. Applying this algorithm to 737 patients with T2DM, 213 (35.4%) patients had elevated ALT, 85 (37.9%) had elevated FIB4, and 42 (46.1%) had elevated FAST scores. This accounts for 5.7% of the population with T2DM. CONCLUSION: The application of this algorithm to identify at-risk NAFLD patients in need for specialty care is feasible and demonstrates that the vast majority of patients do not need subspecialty referral for NAFLD.

Synthesis, Structure, and Tunability of Zero-Dimensional Organic-Inorganic Metal Halides Utilizing the m-Xylylenediammonium Cation: MXD2PbI6, MXDBiI5, and MXD3Bi2Br12·2H2O.

Over the past decade, the efficiency of photovoltaic devices based on CH3NH3PbI3 have dramatically increased. This has driven research efforts in all areas, from the discovery of materials to film processing to long-term device stability studies. Here, we report the synthesis and structure of three new "zero dimensional" organic-inorganic metal halides which use the meta-xylylenediammonium (MXD) cation: MXD2PbI6, MXDBiI5, and (MXD)3Bi2Br12·2H2O. The different structures of the new materials lead to compounds with a range of band gaps with MXDBiI5 having the lowest at 2.15 eV. We have explored the tunabilty of MXDBiI5 through halide substitution by preparing a series of samples with composition MXDBiI5-x Br x and determined the halide content using energy dispersive X-ray spectroscopy. A large range of solid solution is obtained in MXDBiI5-x Br x , resulting in the formation of single-phase materials for bromine contents from x = 0 to 3.71 (iodine contents from 1.29 to 5). This highlights the fact that zero-dimensional organic-inorganic halides are highly tunable, in a similar manner to the higher-dimensional perovskite counterparts. Such new materials open up the opportunity for further studies of the physics and optoelectronic properties of these materials.

The prevalence of alcoholic and nonalcoholic fatty liver disease in adolescents and young adults in the United States: analysis of the NHANES database.

BACKGROUND: The prevalence of fatty liver disease is potentially increasing in adolescents and young adults (AYAs) due to the obesity and alcohol pandemics. The aim of this study was to assess the prevalence of alcohol-associated fatty liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) in a representative U.S. cohort utilizing transient elastography to directly measure hepatic steatosis and suspected fibrosis. METHODS: AYAs (age 15-39 years) with valid FibroScan® measurements in the National Health and Nutrition Examination Survey (NHANES) database (2017-2018) were included in the analyses. Those with viral hepatitis, pregnancy, or ALT/AST > 500 U/L were excluded. The population was divided into those with excessive alcohol consumption (ALQ130) and those without. Controlled attenuation parameter (CAP) score ≥ 248 dB/m was used to identify suspected ALD and NAFLD. In those with evidence of ALD, the following cutoffs of liver stiffness measurement (LSM) were used for suspected fibrosis: F ≥ F2 at LSM ≥ 7.5 kPa and F ≥ F3 at ≥ 9.5 kPa, respectively. In those with suspected NAFLD, the following LSM cutoffs were used: F ≥ F2 at 6.1 and F ≥ F3 at ≥ 7.1, respectively. Cutoffs were chosen based on published literature to maximize sensitivity. RESULTS: Comparing to those without, subjects with excessive alcohol consumption tended to be older (29.8 vs 28.5 years), have a higher BMI (29.3 vs 28.9 kg/m2), and be from a White ethnicity (65.3% vs. 55.4%). In subjects with excessive alcohol consumption, suspected ALD was present in 56.59% (95% CI 41.57-70.49). In those with suspected ALD, suspected significant fibrosis (F ≥ F2) was present in 12.3% (95% CI 4.74-28.34) and advanced fibrosis (F ≥ F3) was present in 6.31% (95% CI 0.69-39.55). Similarly, in subjects without excessive alcohol consumption, suspected NAFLD was present in 40.04% (36.64-43.54). In those with suspected NAFLD, suspected significant fibrosis (F ≥ F2) was present in 31.07% (27.25-35.16) and suspected advanced fibrosis (F ≥ F3) was present in 20.15% (16.05-24.99). CONCLUSION: A significant percentage of AYAs are at risk for ALD and NAFLD and a subset of these subjects is at risk for significant fibrosis. Efforts should focus on increasing awareness of the prevalence of ALD and NAFLD in this population and to mitigate modifiable risk factors.

Probing the structure-property-composition relationship in organic-inorganic tri-halide perovskites.

Here, we have synthesised a range of samples, with the formula (CH3NH3)1-2x(H3NC2H4NH3)xPbI3, with different levels of ethylenediammonium substitution to probe non-stoichiometry at the A-site of the perovskite. A single phase region was identified and is accompanied by a change in photophysical properties. The influence of aliovalent substitution with ethylenediammonium results in a decrease in HOMO level from -5.31 eV for x = 0 to -5.88 eV for x = 0.15.

Charge carrier localised in zero-dimensional (CH3NH3)3Bi2I9 clusters.

A metal-organic hybrid perovskite (CH3NH3PbI3) with three-dimensional framework of metal-halide octahedra has been reported as a low-cost, solution-processable absorber for a thin-film solar cell with a power-conversion efficiency over 20%. Low-dimensional layered perovskites with metal halide slabs separated by the insulating organic layers are reported to show higher stability, but the efficiencies of the solar cells are limited by the confinement of excitons. In order to explore the confinement and transport of excitons in zero-dimensional metal-organic hybrid materials, a highly orientated film of (CH3NH3)3Bi2I9 with nanometre-sized core clusters of Bi2I93- surrounded by insulating CH3NH3+ was prepared via solution processing. The (CH3NH3)3Bi2I9 film shows highly anisotropic photoluminescence emission and excitation due to the large proportion of localised excitons coupled with delocalised excitons from intercluster energy transfer. The abrupt increase in photoluminescence quantum yield at excitation energy above twice band gap could indicate a quantum cutting due to the low dimensionality.Understanding the confinement and transport of excitons in low dimensional systems will aid the development of next generation photovoltaics. Via photophysical studies Ni et al. observe 'quantum cutting' in 0D metal-organic hybrid materials based on methylammonium bismuth halide (CH3NH3)3Bi2I9.

Multilineage transduction of resident lung cells in vivo by AAV2/8 for α1-antitrypsin gene therapy.

In vivo gene delivery has long represented an appealing potential treatment approach for monogenic diseases such as α1-antitrypsin deficiency (AATD) but has proven challenging to achieve in practice. Alternate pseudotyping of recombinant adeno-associated virus (AAV) vectors is producing vectors with increasingly heterogeneous tropic specificity, giving researchers the ability to target numerous end-organs affected by disease. Herein, we describe sustained pulmonary transgene expression for at least 52 weeks after a single intratracheal instillation of AAV2/8 and characterize the multiple cell types transduced within the lung utilizing this approach. We demonstrate that lung-directed AAV2/8 is able to achieve therapeutic α-1 antitrypsin (AAT) protein levels within the lung epithelial lining fluid and that AAT gene delivery ameliorates the severity of experimental emphysema in mice. We find that AAV2/8 efficiently transduces hepatocytes in vivo after intratracheal administration, a finding that may have significance for AAV-based human gene therapy studies. These results support direct transgene delivery to the lung as a potential alternative approach to achieve the goal of developing a gene therapy for AATD.

An Exhaustive Symmetry Approach to Structure Determination: Phase Transitions in Bi2Sn2O7.

The exploitable properties of many materials are intimately linked to symmetry-lowering structural phase transitions. We present an automated and exhaustive symmetry-mode method for systematically exploring and solving such structures which will be widely applicable to a range of functional materials. We exemplify the method with an investigation of the Bi2Sn2O7 pyrochlore, which has been shown to undergo transitions from a parent γ cubic phase to ß and α structures on cooling. The results include the first reliable structural model for ß-Bi2Sn2O7 (orthorhombic Aba2, a = 7.571833(8), b = 21.41262(2), and c = 15.132459(14) Å) and a much simpler description of α-Bi2Sn2O7 (monoclinic Cc, a = 13.15493(6), b = 7.54118(4), and c = 15.07672(7) Å, ß = 125.0120(3)°) than has been presented previously. We use the symmetry-mode basis to describe the phase transition in terms of coupled rotations of the Bi2O' anti-cristobalite framework, which allow Bi atoms to adopt low-symmetry coordination environments favored by lone-pair cations.