Starch Assisted the ZnS Buffer Layer in Enhancing the Photoluminescence of ZnSe/ZnS:Mn/ZnS Quantum Dots for Detecting E. Coli and MRSA Bacteria Quickly.

In this study, we used a starch paste stabilizer to synthesize ZnSe: Mn/ZnS- Starch and ZnSe/ZnS: Mn/ZnS-starch quantum dot (QDs) in a non-toxic aqueous solvent. The -CH2-OH group of the starch paste promotes dispersibility and improves the compatibility of quantum dots with antibodies, its bonding is observed in the FTIR spectrum. Besides, the Mn-doped ZnS buffer shell with various concentrations (1, 3, 5, 7, and 9%) influence structure, optical, and photoluminescence of QDs properties were investigated in detail. The greatest luminescence intensity is achieved at a molar ratio of 3% Mn2+/Zn2+. Moreover, the ZnS: Mn buffer shell helps to enhance the fluorescence intensity and quantum yield (QY) of the ZnSe/ZnS: Mn/ZnS QDs, which are higher than ZnSe: Mn/ZnS-starch QDs. Through protein A and EDC bridging, ZnSe/ZnS:3%Mn/ZnS- Starch resulted in good signal and sensitivity, with no toxicity to E. coli O157:H7 and MRSA strains.

Skeletal muscle relaxant drug-drug-drug interactions and unintentional traumatic injury: Screening to detect three-way drug interaction signals.

AIM: The aim of this study was to identify skeletal muscle relaxant (SMR) drug-drug-drug interaction (3DI) signals associated with increased rates of unintentional traumatic injury. METHODS: We conducted automated high-throughput pharmacoepidemiologic screening of 2000-2019 healthcare data for members of United States commercial and Medicare Advantage health plans. We performed a self-controlled case series study for each drug triad consisting of an SMR base-pair (i.e., concomitant use of an SMR with another medication), and a co-dispensed medication (i.e., candidate interacting precipitant) taken during ongoing use of the base-pair. We included patients aged ≥16 years with an injury occurring during base-pair-exposed observation time. We used conditional Poisson regression to calculate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for injury with each SMR base-pair + candidate interacting precipitant (i.e., triad) versus the SMR-containing base-pair alone. RESULTS: Among 58 478 triads, 29 were significantly positively associated with injury; confounder-adjusted RRs ranged from 1.39 (95% CI = 1.01-1.91) for tizanidine + omeprazole with gabapentin to 2.23 (95% CI = 1.02-4.87) for tizanidine + diclofenac with alprazolam. Most identified 3DI signals are new and have not been formally investigated. CONCLUSION: We identified 29 SMR 3DI signals associated with increased rates of injury. Future aetiologic studies should confirm or refute these SMR 3DI signals.

Combined Gap-Polymerase Chain Reaction and Targeted Next-Generation Sequencing Improve α- and ß-Thalassemia Carrier Screening in Pregnant Women in Vietnam.

Vietnam has a high thalassemia burden. We collected blood samples from 5880 pregnant Vietnamese women during prenatal health checks to assess thalassemia carrier frequency using combined gap-polymerase chain reaction (gap-PCR) and targeted next-generation sequencing (NGS). Thalassemia carriers were identified with prevalence of 13.13% (772), including 7.82% (460) carriers of α-thalassemia (α-thal), 5.31% (312) carriers of ß-thalassemia (ß-thal), and 0.63% (37) concurrent α-/ß-thal carriers. Deletional mutations (368) accounted for 80.0% of α-thal carriers, of which, --SEA (Southeast Asian) (n = 254; 55.0%) was most prevalent, followed by the -α3.7 (rightward) (n = 66; 14.0%) and -α4.2 (leftward) (n = 45; 9.8%) deletions. Hb Westmead (HBA2: c.369C>G) (n = 53) and Hb Constant Spring (Hb CS or HBA2: c.427T>C) (in 28) are the two most common nondeletional α-globin variants, accounting for 11.5 and 6.0% of α-thal carriers. We detected 11 different ß-thal genotypes. Hb E (HBB: c.79G>A) (in 211) accounted for 67.6% of ß-thal carriers. The most common ß-thal genotypes were associated with mutations at codon 17 (A>T) (HBB: c.52A>T), codons 41/42 (-TTCT) (HBB: c.126_129delCTTT), and codon 71/72 (+A) (HBB: c.217_218insA) (prevalence 0.70%, 0.68%, and 0.2%, respectively). Based on mutation frequencies calculated in this study, estimates of 5021 babies in Vietnam are affected with clinically severe thalassemia annually. Our data suggest a higher thalassemia carrier frequency in Vietnam than previously reported. We established that combining NGS with gap-PCR creates an effective large-scale thalassemia screening method that can detect a broad range of mutations.

Genetic landscape of recessive diseases in the Vietnamese population from large-scale clinical exome sequencing.

Accurate profiling of population-specific recessive diseases is essential for the design of cost-effective carrier screening programs. However, minority populations and ethnic groups, including Vietnamese, are still underrepresented in existing genetic studies. Here, we reported the first comprehensive study of recessive diseases in the Vietnamese population. Clinical exome sequencing data of 4503 disease-associated genes obtained from a cohort of 985 Vietnamese individuals was analyzed to identify pathogenic variants, associated diseases and their carrier frequencies in the population. A total of 118 recessive diseases associated with 164 pathogenic or likely pathogenic variants were identified, among which 28 diseases had carrier frequencies of at least 1% (1 in 100 individuals). Three diseases were prevalent in the Vietnamese population with carrier frequencies of 2-12 times higher than in the world populations, including beta-thalassemia (1 in 23), citrin deficiency (1 in 31), and phenylketonuria (1 in 40). Seven novel pathogenic and two likely pathogenic variants associated with nine recessive diseases were discovered. The comprehensive profile of recessive diseases identified in this study enables the design of cost-effective carrier screening programs specific to the Vietnamese population.

Claims-Based Frailty and Outcomes: Applying an Aging Measure to Older Adults with Parkinson's Disease.

BACKGROUND: Frailty is a geriatric syndrome with negative health impacts not captured by comorbidity and disability alone. The prevalence of frailty in Parkinson's disease (PD) has been described, but data on frailty-associated outcomes are limited. OBJECTIVE: To describe the level of frailty and investigate the association between frailty and outcomes in a Medicare sample of persons diagnosed with PD. METHODS: We used the claims-based frailty index to assess frailty in a cohort of Medicare beneficiaries with PD in 2013. Frailty was categorized as non-frail/pre-frail, mildly frail, moderately frail, and severely frail. Adjusted logistic regression models examined the relationship between frailty and mortality, hospitalization, emergency department visits, and fall-related injuries through 2014. RESULTS: Of 62,786 beneficiaries with PD in 2013, 55.3% were frail. Frail individuals were more likely to be female, older, Black, metropolitan dwelling, without neurologist care, nursing facility residents, or multimorbid. The average daily levodopa equivalent dose initially increased, then decreased from the pre-frail to the severely frail groups. Compared to non-frail/pre-frail persons, severely frail persons had higher adjusted odds of 1-year mortality (AOR 2.74, 95% CI 1.98, 3.78), hospitalization (AOR 2.34, 95% CI 1.74, 3.14), emergency department visits (AOR 2.97, 95% CI 2.14, 4.13), and fall-related injury (AOR 1.43, 95% CI 0.90, 2.26). CONCLUSIONS: Frailty is common and differentially distributed among older adults with PD. Frailty in PD is associated with adverse health outcomes and death. Observational study analyses may benefit from adjustment for frailty; claims-based frailty surveillance may identify vulnerable PD patients in health system, registry, or administrative data. © 2021 International Parkinson and Movement Disorder Society.

Pharmacosafety of fluoroquinolone and macrolide antibiotics in the clinical care of patients with myasthenia gravis.

INTRODUCTION/AIMS: Anecdotal case reports have suggested a potential association of fluoroquinolones and macrolides with myasthenia gravis (MG) exacerbation, prompting warnings against the use of these drugs in this population. However, large-scale and reliable population-based data that demonstrate this association are lacking. This study aims to examine the association between outpatient treatment with fluoroquinolones or macrolides and MG-related hospitalization. METHODS: A retrospective cohort study consisting of adult MG patients was conducted using a large de-identified healthcare claims database. Antibiotic prescription claims were identified, and MG-related hospitalizations were assessed at 15, 30, and 90 days after the date of prescription. We used mixed effects survival regression with log-logistic distribution and independent covariance matrix to estimate odds ratios (ORs) of hospitalization for each potentially exacerbating antibiotic using beta-lactam as the reference and adjusting for covariates. RESULTS: Among 1556 MG patients receiving 894 fluoroquinolone prescriptions, 729 macrolide prescriptions, and 1608 beta-lactam prescriptions during the study period, there was no difference in 15, 30, or 90-day odds of MG-related hospitalization between fluoroquinolone or macrolide users compared to prescribed beta-lactams. However, estimates were higher for fluoroquinolones than macrolides, even after covariate adjustment (adjusted OR [aOR] 4.60, 95% confidence interval [CI] 0.55-38.57 for fluoroquinolones and OR 0.56, 95% CI 0.32-0.97 for macrolides, respectively, at 15 days). DISCUSSION: Fluoroquinolone and macrolide antibiotics are prescribed frequently to patients with MG. While statistical imprecision precludes a definitive conclusion, elevated ORs for fluoroquinolones raise the possibility of an underpowered association that merits further investigation.

Annual Prevalence of Use of Potentially Inappropriate Medications for Treatment of Affective Disorders in Parkinson's Disease.

OBJECTIVE: To examine the national prevalence of pharmacological treatment of affective disorders in older adults with Parkinson's disease (PD), and determine the prevalence and risk factors for receipt of an American Geriatrics Society Beers Criteria® defined potentially inappropriate medication (PIM) for affective disorder treatment. DESIGN: Cross-sectional analysis of 2014 Medicare data. SETTING: Research Identifiable File data from the Centers for Medicare and Medicaid Services. PARTICIPANTS: Individuals ≥65 years of age with PD whose inpatient, outpatient, and prescription care is administered through the U.S. Medicare Program. MEASUREMENTS: The 2014 prevalence of affective (i.e., depressive and anxiety) disorders was calculated. We assessed prescription fills for affective disorder treatment and classified prescriptions according to PIM status. Patient and clinician factors associated with PIM prescriptions were determined. RESULTS: Of 84,323 beneficiaries with PD, 15.1% had prevalent depression only, 7.5% had anxiety only, and 8.5% had comorbid depression and anxiety. Among those with depression only, 80.7% were treated in 2014 (12.8% of treated received at least one PIM). The annual treatment prevalence was 62.9% (75.9% PIM) and 93.1% (63.9% PIM) in the anxiety only and comorbid group, respectively. In most groups, PIM use was less likely among men and those with dementia; geriatricians were less likely to prescribe PIMs. CONCLUSION: Treatment of affective disorders in persons diagnosed with PD is high. PIM use is also common, particularly in persons with anxiety. Future research will quantify the potential effects of these PIMs on clinical and patient outcomes.

Low continuation of antipsychotic therapy in Parkinson disease - intolerance, ineffectiveness, or inertia?

BACKGROUND: Antipsychotics are used in Parkinson disease (PD) to treat psychosis, mood, and behavioral disturbances. Commonly used antipsychotics differ substantially in their potential to worsen motor symptoms through dopaminergic receptor blockade. Recent real-world data on the use and continuation of antipsychotic therapy in PD are lacking. The objectives of this study are to (1) examine the continuation of overall and initial antipsychotic therapy in individuals with PD and (2) determine whether continuation varies by drug dopamine receptor blocking activity. METHODS: We conducted a retrospective cohort study using U.S. commercially insured individuals in Optum 2001-2019. Adults aged 40 years or older with PD initiating antipsychotic therapy, with continuous insurance coverage for at least 6 months following drug initiation, were included. Exposure to pimavanserin, quetiapine, clozapine, aripiprazole, risperidone, or olanzapine was identified based on pharmacy claims. Six-month continuation of overall and initial antipsychotic therapy was estimated by time to complete discontinuation or switching to a different antipsychotic. Cox proportional hazards models evaluated factors associated with discontinuation. RESULTS: Overall, 38.6% of 3566 PD patients in our sample discontinued antipsychotic therapy after the first prescription, 61.4% continued with overall treatment within 6 months of initiation. Clozapine use was too rare to include in statistical analyses. Overall therapy discontinuation was more likely for those who initiated medications with known dopamine-receptor blocking activity (adjusted hazard ratios 1.76 [95% confidence interval 1.40-2.20] for quetiapine, 2.15 [1.61-2.86] for aripiprazole, 2.12 [1.66-2.72] for risperidone, and 2.07 [1.60-2.67] for olanzapine), compared with serotonin receptor-specific pimavanserin. Initial antipsychotic therapy discontinuation also associated with greater dopamine-receptor blocking activity medication use - adjusted hazard ratios 1.57 (1.28-1.94), 1.88 (1.43-2.46), 2.00 (1.59-2.52) and 2.03 (1.60-2.58) for quetiapine, aripiprazole, risperidone, and olanzapine, respectively, compared with pimavanserin. Similar results were observed in sensitivity analyses. CONCLUSIONS: Over one-third of individuals with PD discontinued antipsychotic therapy, especially if the initial drug has greater dopamine-receptor blocking activity. Understanding the drivers of antipsychotic discontinuation, including ineffectiveness, potentially inappropriate use, clinician inertia, patient adherence and adverse effects, is needed to inform clinical management of psychosis in PD and appropriate antipsychotic use in this population.

Frequency of and risk factors for potentially inappropriate medication use in Parkinson's disease.

BACKGROUND: impairments in neurotransmitter pathways put Parkinson's disease (PD) patients at risk for drug-disease interactions and adverse medication events. OBJECTIVE: to determine the prevalence and risk factors for potentially inappropriate medication (PIM) prescriptions, as defined by the 2015 Beers List, in PD. METHODS: cross-sectional analysis was conducted on 2014 Medicare beneficiaries with PD who had parts A, B and D coverage. The prevalence of PIM prescriptions for older adults was determined overall, and specifically for medications that can exacerbate motor symptoms or cognitive impairment in PD. Logistic regression models were constructed to determine the association between age, sex, race, geography and poverty with PIM prescriptions. RESULTS: the final sample included 458,086 beneficiaries. In 2014, 35.8% of beneficiaries with PD filled a prescription for at least one PIM for older adults. In total, 8.7% of beneficiaries received a PIM that could exacerbate motor symptoms and 29.0% received a PIM that could worsen cognitive impairment. After adjustment, in all models, beneficiaries who were younger, female, white, urban-dwelling and eligible for Medicaid benefits were more likely to receive a PIM. CONCLUSION: PIM prescriptions are not uncommon in PD, particularly for medications that can exacerbate cognitive impairment. Future research will examine underlying drivers of sex and other disparities in PIM prescribing. Additional studies are needed to understand the impact of PIMs on disease symptoms, healthcare utilisation and patient outcomes.

Stratifying patients using fast multiple kernel learning framework: case studies of Alzheimer's disease and cancers.

BACKGROUND: Predictive patient stratification is greatly emerging, because it allows us to prospectively identify which patients will benefit from what interventions before their condition worsens. In the biomedical research, a number of stratification methods have been successfully applied and have assisted treatment process. Because of heterogeneity and complexity of medical data, it is very challenging to integrate them and make use of them in practical clinic. There are two major challenges of data integration. Firstly, since the biomedical data has a high number of dimensions, combining multiple data leads to the hard problem of vast dimensional space handling. The computation is enormously complex and time-consuming. Secondly, the disparity of different data types causes another critical problem in machine learning for biomedical data. It has a great need to develop an efficient machine learning framework to handle the challenges. METHODS: In this paper, we propose a fast-multiple kernel learning framework, referred to as fMKL-DR, that optimise equations to calculate matrix chain multiplication and reduce dimensions in data space. We applied our framework to two case studies, Alzheimer's disease (AD) patient stratification and cancer patient stratification. We performed several comparative evaluations on various biomedical datasets. RESULTS: In the case study of AD patients, we enhanced significantly the multiple-ROIs approach based on MRI image data. The method could successfully classify not only AD patients and non-AD patients but also different phases of AD patients with AUC close to 1. In the case study of cancer patients, the framework was applied to six types of cancers, i.e., glioblastoma multiforme cancer, ovarian cancer, lung cancer, breast cancer, kidney cancer, and liver cancer. We efficiently integrated gene expression, miRNA expression, and DNA methylation. The results showed that the classification model basing on integrated datasets was much more accurate than classification model basing on the single data type. CONCLUSIONS: The results demonstrated that the fMKL-DR remarkably improves computational cost and accuracy for both AD patient and cancer patient stratification. We optimised the data integration, dimension reduction, and kernel fusion. Our framework has great potential for mining large-scale cohort data and aiding personalised prevention.

Does hospitalization for thromboembolism improve oral anticoagulant adherence in patients with atrial fibrillation?

BACKGROUND: It is not known how medication adherence changes after hospitalization for a sentinel thromboembolic event. OBJECTIVE: The purpose of this study was to examine the impact of hospitalization for ischemic stroke or thromboembolism on postdischarge adherence to oral anticoagulants in patients with atrial fibrillation. METHODS: We conducted a quasi-experimental pre-post observational study using a large U.S. commercial insurance health care claims database. Adult patients with atrial fibrillation taking oral anticoagulants with a random hospitalization for a nonbleeding-related reason occurring after the first observed oral anticoagulant prescription fill, with no other admissions within the preceding and following 6 months, were identified in Optum Clinformatics (Eden Prairie, MN) from 2009 to 2016. Adherence was estimated by the proportion of days covered within 6 and 12 months before and after hospitalization. Difference-in-difference analysis using a generalized linear model was employed to compare pre- and post-hospitalization proportions of days covered (PDCs) by reasons for hospitalization (i.e., ischemic stroke or thromboembolism vs. other nonbleeding-related reasons), adjusting for imbalanced baseline characteristics. RESULTS: Of the 21,400 individuals meeting inclusion criteria, 5.4% were hospitalized for ischemic stroke or thromboembolism and 94.6% for other nonbleeding-related reasons. Baseline characteristics were quite similar between groups, except for a few covariables such as age or CHA2DS2-VASc score. Minority race or ethnicity individuals had 0.7% lower overall PDC than whites (P = 0.006). After covariate adjustment, 6-month adherence declined by 1.1% less in individuals hospitalized for ischemic stroke or thromboembolism, compared with other nonbleeding reasons, although the difference was not statistically significant (P = 0.17). Similar results were observed for the 12-month window. CONCLUSION: This real-world study suggests that more effective strategies are needed to improve adherence to oral anticoagulant, particularly after a thromboembolic event.

Design, synthesis and evaluation of novel hybrids between 4-anilinoquinazolines and substituted triazoles as potent cytotoxic agents.

In this research several series of novel dioxygenated ring fused 4-anilinoquinazolines (10a-d) and 4-anilinoquinazoline-substituted triazole hybrid compounds (11-14) have been designed and synthesized. Their biological significance was highlighted by evaluating in vitro for anticancer activities, wherein several compounds displayed excellent activity specifically against three human cancer cell lines (KB, epidermoid carcinoma; HepG2, hepatoma carcinoma; SK-Lu-1, non-small lung cancer). Especially, compound 13a exhibited up to 100-fold higher cytotoxicity in comparison with erlotinib. Docking the most cytotoxic compounds (11d, 13a, 13b, and 14c) into the ATP binding site of different EGFR tyrosine kinase domains was perfomed to predict the analogous binding mode of these compounds to the EGFR targets.

Current applications, selection, and possible mechanisms of actions of synbiotics in improving the growth and health status in aquaculture: A review.

Synbiotics, a conjunction between prebiotics and probiotics, have been used in aquaculture for over 10 years. However, the mechanisms of how synbiotics work as growth and immunity promoters are far from being unraveled. Here, we show that a prebiotic as part of a synbiotic is hydrolyzed to mono- or disaccharides as the sole carbon source with diverse mechanisms, thereby increasing biomass and colonization that is established by specific crosstalk between probiotic bacteria and the surface of intestinal epithelial cells of the host. Synbiotics may indirectly and directly promote the growth of aquatic animals through releasing extracellular bacterial enzymes and bioactive products from synbiotic metabolic processes. These compounds may activate precursors of digestive enzymes of the host and augment the nutritional absorptive ability that contributes to the efficacy of food utilization. In fish immune systems, synbiotics cause intestinal epithelial cells to secrete cytokines which modulate immune functional cells as of dendritic cells, T cells, and B cells, and induce the ability of lipopolysaccharides to trigger tumor necrosis factor-α and Toll-like receptor 2 gene transcription leading to increased respiratory burst activity, phagocytosis, and nitric oxide production. In shellfish, synbiotics stimulate the proliferation and degranulation of hemocytes of shrimp due to the presence of bacterial cell walls. Pathogen-associated molecular patterns are subsequently recognized and bound by specific pattern-recognition proteins, triggering melanization and phagocytosis processes.

Cell type-selective disease-association of genes under high regulatory load.

We previously showed that disease-linked metabolic genes are often under combinatorial regulation. Using the genome-wide ChIP-Seq binding profiles for 93 transcription factors in nine different cell lines, we show that genes under high regulatory load are significantly enriched for disease-association across cell types. We find that transcription factor load correlates with the enhancer load of the genes and thereby allows the identification of genes under high regulatory load by epigenomic mapping of active enhancers. Identification of the high enhancer load genes across 139 samples from 96 different cell and tissue types reveals a consistent enrichment for disease-associated genes in a cell type-selective manner. The underlying genes are not limited to super-enhancer genes and show several types of disease-association evidence beyond genetic variation (such as biomarkers). Interestingly, the high regulatory load genes are involved in more KEGG pathways than expected by chance, exhibit increased betweenness centrality in the interaction network of liver disease genes, and carry longer 3' UTRs with more microRNA (miRNA) binding sites than genes on average, suggesting a role as hubs integrating signals within regulatory networks. In summary, epigenetic mapping of active enhancers presents a promising and unbiased approach for identification of novel disease genes in a cell type-selective manner.

Results of intraoperative neuromonitoring in thyroid surgery and preoperative vocal cord paralysis.

BACKGROUND: Systematic studies of intermittent intraoperative neuromonitoring (IONM) have shown that IONM enhances recurrent laryngeal nerve (RLN) identification via functional assessment, but does not significantly reduce rates of vocal cord (VC) paralysis (VCP). The reliability of functional nerve assessment depends on the preoperative integrity of VC mobility. The present study was therefore performed to analyze the validity of IONM in patients with pre-existing VC paralysis. METHODS: Of 8,128 patients, 285 (3.5 %) with preoperative VCP underwent thyroid surgery using standardized IONM of the RLN and vagus nerves (VNs). VC function was assessed by pre- and postoperative direct videolaryngoscopy. Quantitative parameters of IONM in patients with VCP were compared with IONM in patients with intact VC function. Clinical symptoms and surgical outcomes of patients with pre-existing VCP were analyzed. RESULTS: A total of 244 patients revealed negative, and 41 revealed positive IONM on the side of the VCP. VCP with positive IONM revealed significantly lower amplitudes of VN and RLN than intact VN (p = 0.010) and RLN (p = 0.011). Symptoms of patients with VCP included hoarseness (25 %), dyspnea (29 %), stridor (13 %), and dysphagia (13 %); 13 % were asymptomatic. New VCP occurred in five patients, ten needed tracheostomy for various reasons, and one patient died. CONCLUSIONS: Patients with pre-existing VCP revealed significantly reduced amplitude of ipsilateral VN and RLN, indicating retained nerve conductivity despite VC immobility. Preoperative laryngoscopy is therefore indispensable for reliable IONM and risk assessment, even in patients without voice abnormalities.

Efficient tensor decomposition-based filter pruning.

In this paper, we present CORING, which is short for effiCient tensOr decomposition-based filteR prunING, a novel filter pruning methodology for neural networks. CORING is crafted to achieve efficient tensor decomposition-based pruning, a stark departure from conventional approaches that rely on vectorized or matricized filter representations. Our approach represents a significant leap forward in the field by introducing tensor decompositions, specifically the HOSVD, which preserves the multidimensional nature of filters while providing a low-rank approximation, thus substantially reducing complexity. Furthermore, we introduce a versatile method for calculating filter similarity by using the low-rank approximation offered by the HOSVD. This obviates the need for using full filters or reshaped versions and enhances the overall efficiency and effectiveness of our approach. Extensive experimentation across diverse architectures and datasets spanning various vision tasks, including image classification, object detection, instance segmentation, and keypoint detection, validates CORING's prowess. Remarkably, it outperforms state-of-the-art methods in reducing MACs and parameters, consistently enhancing validation accuracy. Furthermore, we supplement our quantitative results with a comprehensive ablation study, providing substantial evidence of the efficiency of our tensor-based approach. Beyond quantitative outcomes, qualitative results vividly illustrate CORING's ability to retain essential features within pruned neural networks. Our code is available for research purposes.

Enhanced Network Compression Through Tensor Decompositions and Pruning.

Network compression techniques that combine tensor decompositions and pruning have shown promise in leveraging the advantages of both strategies. In this work, we propose enhanced Network cOmpRession through TensOr decompositions and pruNing (NORTON), a novel method for network compression. NORTON introduces the concept of filter decomposition, enabling a more detailed decomposition of the network while preserving the weight's multidimensional properties. Our method incorporates a novel structured pruning approach, effectively integrating the decomposed model. Through extensive experiments on various architectures, benchmark datasets, and representative vision tasks, we demonstrate the usefulness of our method. NORTON achieves superior results compared to state-of-the-art (SOTA) techniques in terms of complexity and accuracy. Our code is also available for research purposes.

Application of high-dimensional propensity score methods to the National Health and Aging Trends Study.

BACKGROUND: High-dimensional propensity scoring (HDPS) is a method for empirically identifying potential confounders within large healthcare databases such as administrative claims data. However, this method has not yet been applied to large national health surveys such as the National Health and Aging Trends Study (NHATS), an ongoing nationally representative survey of older adults in the U.S and important resource in gerontology research. METHODS: In this Research Practice article, we present an overview of HDPS and describe the specific data transformation steps and analytic considerations needed to apply it to national health surveys. We applied HDPS within NHATS to investigate the association between self-reported visual difficulty and incident dementia, comparing HDPS to conventional confounder selection methods. RESULTS: Among 7,207 dementia-free NHATS wave 1 respondents, 528 (7.3%) had self-reported visual difficulty. In an unadjusted discrete time proportional hazards model accounting for the complex survey design of NHATS, self-reported visual difficulty was strongly associated with incident dementia (OR 2.34, 95% CI: 1.95-2.81). After adjustment for standard investigator-selected covariates via inverse probability weighting, the magnitude of this association decreased, but evidence of an association remained (OR 1.44, 95% CI: 1.11-1.85). Adding 75 HDPS-prioritized variables to the investigator-selected propensity score model resulted in further attenuation of the association between visual impairment and dementia (OR 0.94, 95% CI: 0.70-1.23). CONCLUSIONS: HDPS can be successfully applied to national health surveys such as NHATS and may improve confounder adjustment. We hope developing this framework will encourage future consideration of HDPS in this setting.

Tight junction membrane proteins regulate the mechanical resistance of the apical junctional complex.

Epithelia must be able to resist mechanical force to preserve tissue integrity. While intercellular junctions are known to be important for the mechanical resistance of epithelia, the roles of tight junctions (TJs) remain to be established. We previously demonstrated that epithelial cells devoid of the TJ membrane proteins claudins and JAM-A completely lack TJs and exhibit focal breakages of their apical junctions. Here, we demonstrate that apical junctions fracture when claudin/JAM-A-deficient cells undergo spontaneous cell stretching. The junction fracture was accompanied by actin disorganization, and actin polymerization was required for apical junction integrity in the claudin/JAM-A-deficient cells. Further deletion of CAR resulted in the disruption of ZO-1 molecule ordering at cell junctions, accompanied by severe defects in apical junction integrity. These results demonstrate that TJ membrane proteins regulate the mechanical resistance of the apical junctional complex in epithelial cells.

Deprescribing medications among patients with multiple prescribers: A socioecological model.

Deprescribing is the intentional dose reduction or discontinuation of a medication. The development of deprescribing interventions should take into consideration important organizational, interprofessional, and patient-specific barriers that can be further complicated by the presence of multiple prescribers involved in a patient's care. Patients who receive care from an increasing number of prescribers may experience disruptions in the timely transfer of relevant healthcare information, increasing the risk of exposure to drug-drug interactions and other medication-related problems. Furthermore, the fragmentation of healthcare information across health systems can contribute to the refilling of discontinued medications, reducing the effectiveness of deprescribing interventions. Thus, deprescribing interventions must carefully consider the unique characteristics of patients and their prescribers to ensure interventions are successfully implemented. In this special article, an international working group of physicians, pharmacists, nurses, epidemiologists, and researchers from the United States Deprescribing Research Network (USDeN) developed a socioecological model to understand how multiple prescribers may influence the implementation of a deprescribing intervention at the individual, interpersonal, organizational, and societal level. This manuscript also includes a description of the concept of multiple prescribers and outlines a research agenda for future investigations to consider. The information contained in this manuscript should be used as a framework for future deprescribing interventions to carefully consider how multiple prescribers can influence the successful implementation of the service and ensure the intervention is as effective as possible.