Revisiting the complex time-varying effect of non-pharmaceutical interventions on COVID-19 transmission in the United States.

Introduction: Although the global COVID-19 emergency ended, the real-world effects of multiple non-pharmaceutical interventions (NPIs) and the relative contribution of individual NPIs over time were poorly understood, limiting the mitigation of future potential epidemics. Methods: Based on four large-scale datasets including epidemic parameters, virus variants, vaccines, and meteorological factors across 51 states in the United States from August 2020 to July 2022, we established a Bayesian hierarchical model with a spike-and-slab prior to assessing the time-varying effect of NPIs and vaccination on mitigating COVID-19 transmission and identifying important NPIs in the context of different variants pandemic. Results: We found that (i) the empirical reduction in reproduction number attributable to integrated NPIs was 52.0% (95%CI: 44.4, 58.5%) by August and September 2020, whereas the reduction continuously decreased due to the relaxation of NPIs in following months; (ii) international travel restrictions, stay-at-home requirements, and restrictions on gathering size were important NPIs with the relative contribution higher than 12.5%; (iii) vaccination alone could not mitigate transmission when the fully vaccination coverage was less than 60%, but it could effectively synergize with NPIs; (iv) even with fully vaccination coverage >60%, combined use of NPIs and vaccination failed to reduce the reproduction number below 1 in many states by February 2022 because of elimination of above NPIs, following with a resurgence of COVID-19 after March 2022. Conclusion: Our results suggest that NPIs and vaccination had a high synergy effect and eliminating NPIs should consider their relative effectiveness, vaccination coverage, and emerging variants.

Genetic Patterns of Selected Muscular Dystrophies in the Muscular Dystrophy Surveillance, Tracking, and Research Network.

Background and Objectives: To report the genetic etiologies of Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), congenital muscular dystrophy (CMD), and distal muscular dystrophy (DD) in 6 geographically defined areas of the United States. Methods: This was a cross-sectional, population-based study in which we studied the genes and variants associated with muscular dystrophy in individuals who were diagnosed with and received care for EDMD, LGMD, CMD, and DD from January 1, 2008, through December 31, 2016, in the 6 areas of the United States covered by the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). Variants of unknown significance (VUSs) from the original genetic test reports were reanalyzed for changes in interpretation. Results: Among 243 individuals with definite or probable muscular dystrophy, LGMD was the most common diagnosis (138 cases), followed by CMD (62 cases), DD (22 cases), and EDMD (21 cases). There was a higher proportion of male individuals compared with female individuals, which persisted after excluding X-linked genes (EMD) and autosomal genes reported to have skewed gender ratios (ANO5, CAV3, and LMNA). The most common associated genes were FKRP, CAPN3, ANO5, and DYSF. Reanalysis yielded more definitive variant interpretations for 60 of 144 VUSs, with a mean interval between the original clinical genetic test of 8.11 years for all 144 VUSs and 8.62 years for the 60 reclassified variants. Ten individuals were found to have monoallelic pathogenic variants in genes known to be primarily recessive. Discussion: This study is distinct for being an examination of 4 types of muscular dystrophies in selected geographic areas of the United States. The striking proportion of resolved VUSs demonstrates the value of periodic re-examinations of these variants. Such re-examinations will resolve some genetic diagnostic ambiguities before initiating repeat testing or more invasive diagnostic procedures such as muscle biopsy. The presence of monoallelic pathogenic variants in recessive genes in our cohort indicates that some individuals with muscular dystrophy continue to face incomplete genetic diagnoses; further refinements in genetic knowledge and diagnostic approaches will optimize diagnostic information for these individuals.

Associations Between Opioid Prescriptions and Use of Hospital-Based Services Among US Adults with Longstanding Physical Disability or Inflammatory Conditions Compared to Other Adults in the Medical Expenditure Panel Survey, 2010-2015.

Purpose: To investigate the association of filling opioid prescriptions with healthcare service utilization among a nationally representative sample of adults with disability. Materials and Methods: The Medical Expenditure Panel Survey (MEPS) for 2010-2015, Panels 15-19, was used to identify adults who were prescribed opioids during each two-year period. We examined the data for associations between opioid prescription filling and the number of emergency department (ED) visits and hospitalizations. The participants were grouped as those with inflammatory conditions or with longstanding physical disability, and a comparison group of those without these conditions. Results and conclusions: Opioid prescription filling differed among adults with inflammatory conditions and longstanding physical disability compared to the comparison group (44.93% and 40.70% vs 18.10%, respectively). For both groups of people with disability, the relative rates for an ED visit or hospitalization were significantly higher for those who filled an opioid prescription, compared to adults with the same conditions who did not fill an opioid prescription. People with a longstanding physical disability who filled an opioid prescription had the highest rate ratio of ED use and hospitalization. Results from this investigation demonstrate that opioid prescription filling among persons with inflammatory conditions and longstanding physical disabilities is associated with higher rates of ED visits and hospitalizations.

A Randomized Controlled Trial using Brief Educational Messages Directed to Adults with Intellectual Disability and Hypertension or their Helpers Reduces Hospital Stays.

PURPOSE: We assessed an educational intervention to reduce the number of emergency department (ED) and inpatient stays for cardiovascular diagnoses, among South Carolina adult Medicaid Members with intellectual and developmental disability and hypertension (Members). DESIGN: This Randomized Controlled Trial (RCT) included Members or the person who helped them with their medications (Helpers). Participants, who included Members and/or their Helpers, were randomly assigned to an Intervention or Control group. SETTING: South Carolina Department of Health and Human Services, which administers Medicaid, identified eligible Members. SAMPLE: 412 Medicaid Members - 214 Intervention (54 Members participating directly; 160 Helpers participating in lieu of Members) who received the messages about hypertension and surveys about knowledge and behavior and 198 Controls (62 Members; 136 Helpers) who only received surveys of knowledge and behavior. INTERVENTION: Educational intervention about hypertension included a flyer and monthly text or phone messages for one year. MEASURES: Input measures - characteristics of the Members; Outcome measures - hospital emergency department (ED) and inpatient visits for cardiovascular conditions. ANALYSIS: Quantile regression tested the association of Intervention/Control group status with ED and inpatient visits. We also estimated models using Zero-inflated Poisson (ZIP) models for sensitivity analysis. RESULTS: Participants in the Intervention group with highest baseline hospital use (top 20% ED; top 15% Inpatient) had significant reductions in Year 1 (.57 fewer ED and 2 fewer inpatient days) compared to the Control group. For ED visits, improvement continued in year two. CONCLUSION: The intervention reduced the frequency of cardiovascular disease-related ED visits and Inpatient days for participants in the Intervention group in the highest quantiles of hospital use, and the improvement was better for those who had a Helper.

Metabolism-Based Molecular Subtyping Endows Effective Ketogenic Therapy in p53-Mutant Colon Cancer.

Although targeting cancer metabolism is a promising therapeutic strategy, clinical success depends on accurate molecular and metabolic subtyping. Here, this study reports two metabolism-based molecular subtypes associated with the ketogenic treatment of colon cancer: glycolytic (glycolysis+ /ketolysis- ) and ketolytic (glycolysis+ /ketolysis+ ), which are manifested by distinct profiles of metabolic enzymes and mitochondrial dysfunction, and by different responses to ketone-containing interventions in vitro and in vivo. Notably, the glycolytic subtype is able to be transformed into the ketolytic subtype in p53-mutated tumors upon glucose limitation, rendering resistance to ketogenic therapy associated with upregulation of ketolytic enzymes, such as OXCT1 by mutant p53. The allosteric activator of mutant p53 effectively blocks the rewired molecular expression and the reprogrammed metabolism, leading to the suppression of tumor growth. The findings highlight the utility of metabolic subtyping to guide ketogenic therapy in colon cancer and identify mutant p53 as a synthetic lethality target for ketogenic treatment.

Artificial Intelligence-based Machine English-Assisted Translation in the Internet of Things Environment.

With the development of Internet of Things technology, the things that machines do instead of humans are becoming more and more complicated. Machine translation has developed rapidly in the past few decades, and the translation system has also been greatly improved. People's life and work are inseparable from machine translation, which brings a lot of convenience to people. But machine translation also has many flaws. Although machine translation can translate long texts in a very short time, its translation quality is quite poor, especially in the face of advanced English such as professional English, terminology, abbreviations, etc. To this end, machine English-assisted translation systems have been developed in recent years. Different from the working principle of machine English translation, machine English-assisted translation is a method of artificial intelligence + human-computer interaction. It uses convolutional neural networks and deep learning to translate words efficiently. The translator puts the original text and the translation into the machine database each time, and the machine can process some English terms, complex sentences, technical English, and other advanced English after continuous learning. Machine English-assisted translation can reduce repeated translations and greatly improve translation quality and translation efficiency. In this paper, the combination of artificial intelligence and machine English-assisted translation is compared with machine English translation, and comparative experiments are carried out by setting different matching degrees. Experiments show that the translation efficiency of machine English-assisted translation is much better than that of machine English translation. As the matching rate increases, the translation efficiency of machine English-assisted translation is higher. When the matching rate is greater than 80%, the translation efficiency is three times that of machine English translation. However, it is slightly insufficient in processing pure, simple statements. It highlights the advantages of machine English-assisted translation in terms of term translation and long complex sentences.

Salidroside attenuates myocardial ischemia/reperfusion injury via AMPK-induced suppression of endoplasmic reticulum stress and mitochondrial fission.

Ischemic heart disease (IHD) is the primary cause of death worldwide. Salidroside (Sal), the major active compound derived from Rhodiola rosea, is believed to have cardioprotective effects. AMP-activated protein kinase (AMPK), is a pivotal AMP-activated protein kinase in energy metabolism. Whether Sal plays an anti-endoplasmic reticulum stress/mitochondrial fission role through AMPK remains elusive. In this study, we established a myocardial ischemia/reperfusion (I/R) rat model. Rat hearts exposed to Sal with or without compound C were then subjected to I/R. Further, H9c2 cardiomyocytes were subjected to simulated ischemia/reperfusion (SIR) by hypoxia-reoxygenation. The rats and cardiomyocytes were pretreated with Sal, followed by Compound C and AMPK-siRNA to block AMPK activity. We found that Sal significantly ameliorated cardiac function, mitigated infarct size and serum content of lactate dehydrogenase and creatine kinase, improved mitochondrial function, and reduced mitochondrial fission and apoptosis. Furthermore, in cultured H9c2 cardiomyocytes, Sal increased the cell viability and inhibited SIR-induced myocardial apoptosis and mitochondrial fission. Furthermore, the translocation of Drp1 from the cytoplasm to mitochondria induced by salidroside was confirmed both in vivo and in vitro. However, the use of Compound C or AMPK siRNA to block AMPK activity leads to blockade of the protective effects of Sal. In summary, protects against myocardial I/R by activating the AMPK signaling pathway, inhibiting ER stress, and reducing mitochondrial fission and apoptosis.

Amide-Functionalized In-MOF for Effective Hydrocarbon Separation and CO2 Catalytic Fixation.

Energy saving and emission reduction have always been the goal of separation and catalysis pursued in industrial production. Metal-organic frameworks (MOFs) are leading porous crystal materials with unique advantages in these fields. Based on an amide-modified ligand 5-(ethyl oxamate)-isophthalic acid (H2EtL), a new porous indium-organic framework (Me2NH2)1.5[In1.5L2]·2DMF·2H2O (1) was synthesized and structurally characterized. The unique porous environment gives it dual functional advantages in separation and catalysis. At room temperature, 1 possesses excellent adsorption capacities for C2 hydrocarbons and CO2, showing good separation behaviors for C2 hydrocarbons/CO2 on CH4 and C2H2 on CO2, which is conducive to efficient purification of CH4 and C2H2 confirmed by the breakthrough experiment. Meanwhile, catalytic results indicate that 1 can be used as a good catalyst for effective fixation of CO2 under mild conditions to form cyclic carbonates.

Helpers help people with intellectual and developmental disabilities and hypertension to understand their condition and the need to adhere to anti-hypertensive medication.

BACKGROUND: Recent evidence suggests that many adults with intellectual and developmental disabilities (IDD) do not adequately manage hypertension (HTN) medication. Known risk factors for insufficient prescription filling include age, residential placement, and lack of caregiver support. This is a first report of a randomized intervention trial designed to analyze the relationship of a brief educational intervention with increased knowledge about HTN and improvement in prescription filling for anti-hypertensive medication. OBJECTIVE/HYPOTHESIS: The objective was to test whether an educational flyer and regular messages about HTN and the importance of refilling medication would improve scores on knowledge surveys. Participants were Medicaid members with HTN and IDD (Member) or caregivers (Helpers) who chose to participate on behalf of a Member. METHODS: Recruitment letters explained that either the Member or their Helper could participate (not both). Participants were randomly assigned to the Case or Comparison group, and both were comprised of Members and Helpers. Only Case participants received a flyer and monthly HTN education messages for one year, but all participants completed knowledge surveys at baseline, six, and 12 months. Linear regression and log-binomial models were used to compare responses between groups. RESULTS: Case Helpers had statistically significant improvements on HTN knowledge from baseline through the first year, compared to Comparison Members and Comparison Helpers. Regardless of group assignment, Helpers scored better on surveys than did Members. CONCLUSIONS: This study suggests that it is beneficial to explicitly include Helpers in health care instruction and in management of chronic disease for adults with IDD.

Acetylene Separation by a Ca-MOF Containing Accessible Sites of Open Metal Centers and Organic Groups.

Efficient separation of acetylene from a ternary acetylene-containing mixture is an important and vital task in petrochemical industry, which is difficult to achieve using a single material. Herein, a new Ca2+-based metal-organic framework (MOF) [Ca(dtztp)0.5(DMA)]·2H2O (1) was constructed using the N,O-donor ligand 2,5-di(2H-tetrazol-5-yl)terephthalic acid and the less-studied alkaline earth Ca2+ ions. The MOF shows a 3D honeycomb framework based on unique metal-carboxylate-azolate rod secondary building units. Owing to the presence of high-density organic hydrogen-bonding acceptors and open metal sites (OMSs), the activated MOF shows high adsorption capacity for C2H2 and selectivity for C2H2 over CO2, C2H4, C2H6, and CH4. Dynamic breakthrough experiments indicated the actual C2H2 separation potential of the MOF from binary (C2H2-C2H4 and C2H2-CO2) and ternary (C2H2-C2H4-CO2 and C2H2-C2H4-C2H6) mixtures. Simulations revealed that the synergistic interactions between the OMSs and N atoms in MOF and C2H2 molecules play an important role in the separation of C2H2.

Machine learning-based multimodal prediction of language outcomes in chronic aphasia.

Recent studies have combined multiple neuroimaging modalities to gain further understanding of the neurobiological substrates of aphasia. Following this line of work, the current study uses machine learning approaches to predict aphasia severity and specific language measures based on a multimodal neuroimaging dataset. A total of 116 individuals with chronic left-hemisphere stroke were included in the study. Neuroimaging data included task-based functional magnetic resonance imaging (fMRI), diffusion-based fractional anisotropy (FA)-values, cerebral blood flow (CBF), and lesion-load data. The Western Aphasia Battery was used to measure aphasia severity and specific language functions. As a primary analysis, we constructed support vector regression (SVR) models predicting language measures based on (i) each neuroimaging modality separately, (ii) lesion volume alone, and (iii) a combination of all modalities. Prediction accuracy across models was subsequently statistically compared. Prediction accuracy across modalities and language measures varied substantially (predicted vs. empirical correlation range: r = .00-.67). The multimodal prediction model yielded the most accurate prediction in all cases (r = .53-.67). Statistical superiority in favor of the multimodal model was achieved in 28/30 model comparisons (p-value range: <.001-.046). Our results indicate that different neuroimaging modalities carry complementary information that can be integrated to more accurately depict how brain damage and remaining functionality of intact brain tissue translate into language function in aphasia.

Constitutive overexpression of cytochrome P450 associated with imidacloprid resistance in Laodelphax striatellus (Fallén).

BACKGROUND: Imidacloprid is a principal insecticide for controlling rice planthoppers worldwide. Resistance to imidacloprid has been reported in a field population of Laodelphax striatellus. The present work was conducted to study the molecular mechanisms of imidacloprid resistance. RESULTS: An imidacloprid-resistant strain was produced by selecting a field population with imidacloprid for 24 generations. Piperonyl butoxide (PBO) showed a 1.70-fold synergistic effect. Enzyme activity assays were conducted, and cytochrome P450 monooxygenase showed 1.88-fold activity. The mRNA expression levels of 57 P450 genes were compared. Four CYP genes were found to be overexpressed and significantly different to the susceptible strain. Four strains were selected with imidacloprid for a short period, and the expression levels of ten identified detoxification genes were then compared. Only CYP353D1v2 overexpressed and was significantly different to the susceptible strain. Strong correlation was found between CYP353D1v2 expression levels and imidacloprid treatments. Additionally, gene-silencing RNAi via dsRNA feeding showed that depressing the expression of CYP353D1v2 could significantly enhance the sensitivity of L. striatellus to imidacloprid. CONCLUSION: Constitutive overexpression of four CYP genes was associated with imidacloprid resistance in long-term selection, and expression of CYP353D1v2 with imidacloprid resistance in short-term selection in L. striatellus.

Fluid intake of adults in four Chinese cities.

To investigate the fluid intake and knowledge on water and health in Chinese adults, and to provide a scientific basis for the development of adequate water intake values for people in China. A total of 1,483 adults aged 18-60 years were selected from four provincial capital cities using a multiple-stage random sampling method. The information on the amounts and types of daily fluid intake was collected using a 24-h fluid intake record for 7 consecutive days. Trained interviewers used a questionnaire to assess knowledge on water. The median of daily total fluid intake was 1,488 mL, with a wide range from 86 mL to 7,036 mL. Significant differences were found for fluid intake among the four cities. The medians of daily intakes of plain water, tea, and beverages were 786 mL, 109 mL, and 186 mL, respectively. Approximately 32% of the subjects drank less water than the amount recommended by the Chinese Nutrition Society (1,200 mL/day) and 71.6% of participants lacked knowledge of these recommendations. Moreover, 48.3% of them drank water only when they felt thirsty.

[Water intake sources analysis of adults in four cities of China in summer].

OBJECTIVE: To investigate the water intake sources of adults in the four cities of China in summer. METHODS: A total of 64 adults aged 18 - 60 yrs from the four cities (Beijing, Shanghai, Chengdu and Guangzhou) were selected using convenient sampling method. The information on amounts and types of daily drinking water was recorded by subjects for three consecutive days using a quantitative measurement. The food samples were collected by using duplicate portion method and the water content of food samples were determined. RESULTS: The median of daily total water intake of 63 subjects was 3045 ml, while daily total drinking water was 1600 ml, the median ratio of which accounting for 55.8% of total water intake. Water from food was 1157 ml, the median ratio of which accounting for 41.4% of total water intake. The median of daily total water intake (3566 ml) and the ratio of water from food (55.3%) of subjects in Chengdu was significantly higher than subjects in Guangzhou (2929 ml, 45.4%), Shanghai (2748 ml, 33.1%) and Beijing (2743 ml, 31.3%) (daily total water intake: χ² = 10.42, P = 0.015;the proportion of water: χ² = 28.48, P < 0.01). Daily total water intake in men (3302 ml) was significantly higher than that in women (2900 ml) (Z = 2.35, P = 0.019). CONCLUSION: Daily total water intake of subjects in summer was more than the current Chinese recommended total water intake (2200 ml), with the main part of drinking water and water from food.

Contribution of active site residues to substrate hydrolysis by USP2: insights into catalysis by ubiquitin specific proteases.

The ubiquitin-specific protease (USP) structural class represents the largest and most diverse family of deubiquitinating enzymes (DUBs). Many USPs assume important biological roles and emerge as potential targets for therapeutic intervention. A clear understanding of USP catalytic mechanism requires a functional evaluation of the proposed key active site residues. Crystallographic data of ubiquitin aldehyde adducts of USP catalytic cores provided structural details on the catalytic triad residues, namely the conserved Cys and His, and a variable putative third residue, and inferred indirect structural roles for two other conserved residues (Asn and Asp), in stabilizing via a bridging water molecule the oxyanion of the tetrahedral intermediate (TI). We have expressed the catalytic domain of USP2 and probed by site-directed mutagenesis the role of these active site residues in the hydrolysis of peptide and isopeptide substrates, including a synthetic K48-linked diubiquitin substrate for which a label-free, mass spectrometry based assay has been developed to monitor cleavage. Hydrolysis of ubiquitin-AMC, a model substrate, was not affected by the mutations. Molecular dynamics simulations of USP2, free and complexed with the TI of a bona fide isopeptide substrate, were carried out. We found that Asn271 is structurally poised to directly stabilize the oxyanion developed in the acylation step, while being structurally supported by the adjacent absolutely conserved Asp575. Mutagenesis data functionally confirmed this structural role independent of the nature (isopeptide vs peptide) of the bond being cleaved. We also found that Asn574, structurally located as the third member of the catalytic triad, does not fulfill this role functionally. A dual supporting role is inferred from double-point mutation and structural data for the absolutely conserved residue Asp575, in oxyanion hole formation, and in maintaining the correct alignment and protonation of His557 for catalytic competency.