Sensitive Target Research Articles

TransImg: A Translation Algorithm of Visible-to-Infrared Image Based on Generative Adversarial Network

Infrared images of sensitive targets are difficult to obtain and cannot meet the design and training needs of target detection and tracking algorithms for mobile platforms such as aircraft. This paper proposes an image translation algorithm TransImg, which can achieve visible light image translation to the infrared domain to enrich the dataset. First, the algorithm designed a generator structure consisting of a deep residual connected encoder and a region perception feature fusion module to enhance feature learning, thereby avoiding issues such as generating infrared images with insufficient details in the transfer task. Afterward, a multi-scale discriminator and a composite loss function were designed to further improve the transfer effect. Finally, an automatic mixed-precision training strategy was designed for the overall migration algorithm architecture to accelerate the training and generation of infrared images. Experiments have shown that the image translation algorithm TransImg has good algorithm accuracy, and the infrared image generated by visible light image translation has richer texture details, faster generation speed, and lower video memory consumption, and the performance exceeds the mainstream traditional algorithm, and the generated images can meet the requirements of target detection and tracking algorithms design and training for mobile platforms such as aircraft.

In silico models for the screening of human transthyretin disruptors

The use of New Approach Methodologies (NAMs), such as Quantitative Structure-Activity Relationship (QSAR) models, is highly recommended by international regulations to speed up hazard and risk assessment of Endocrine Disruptors, which are known to be linked to a wide spectrum of severe diseases on humans and wildlife. A very sensitive target for these chemicals is the thyroid hormone system, which plays a key role in regulating metabolic and cognitive functions. Several chemicals have been demonstrated to compete with the thyroid hormone thyroxine (T4) for binding to human thyroid hormone distributor protein transthyretin (hTTR). In this work, we generated three new datasets composed by T4-hTTR competing potencies of more than 200 heterogeneous chemicals measured by three different in vitro assays. These datasets were used for the development of new regression QSAR models. The best models were thoroughly validated by internal and external validation procedures. The mechanistic interpretation of the selected molecular descriptors provided information on structural features which are relevant to characterise hTTR binders, such as the presence of hydroxylated and halogenated aromatic rings. PCA analysis was used to rank the studied chemicals according to their increasing T4-hTTR competing potency. Hydroxylated and halogenated bicyclic aromatic compounds are ranked as the strongest hTTR binders. The new QSARs are useful to screen potential Thyroid Hormone System-Disrupting Chemicals (THSDCs), and to support the identification of sustainable alternatives to hazardous chemicals.

Integration of network pharmacology, metabolomics and lipidomics for clarifying the role of sphingolipid metabolism in the treatment of liver cancer by regorafenib

AimsRegorafenib, an FDA-approved drug for advanced primary liver cancer (PLC), could provide survival benefits for patients. However, markers for its therapeutic sensitivity are lacking. This study seeks to identify sensitive targets of regorafenib in PLC from the perspective of small molecular metabolites. Materials and methodsInitiated with network pharmacology (NP) to map regorafenib's target landscape and metabolic regulatory network in liver cancer. Subsequently, regorafenib's impact on hepatoma cells was evaluated by flow cytometry, western blotting (WB) and cell viability assay. Advanced metabolomics and lipidomics were employed to elucidate regorafenib's metabolic reprogramming effects in liver cancer. Metabolic enzyme expression was assessed by WB, immunohistochemical and immunofluorescence assays. Ultimately, mendelian randomization (MR) analysis was utilized to investigate the potential causality of sphingolipid metabolism in hepatic cancer. Key findingsRegorafenib was observed to inhibit hepatoma cell proliferation and cell cycle progression at G0/G1 phase, resulting in significant alterations in sphingolipid levels. It promoted the significant accumulation of 16:0 dihydroceramide (16:0 dhCer) by upregulating ceramide synthase 6 (CERS6) expression and inhibiting dihydroceramide desaturase 1 (DEGS1) activity. The MR analysis revealed that DEGS1 was a risk factor for the development and progression of liver cancer, while cumulative 16:0 dhCer was a protective factor. SignificanceSphingolipids, particularly dhCer and regulatory enzymes, may be potential sensitive markers of regorafenib in the treatment of liver cancer, providing new insights for enhancing the treated efficacy of regorafenib in liver cancer.

Prenatal exposure to low doses of benzophenone-3 elicits disruption of cortical vasculature in fetuses through perturbations in Wnt/β-catenin signaling correlating with depression-like behavior in offspring mice

Benzophenone-3 (BP-3), commonly used in personal care products, is routinely detected in environmental and human matrices. Evidence delineates a correlation between gestational BP-3 exposure and emotional and social disorders in children and adolescents. However, sensitive target cells and the mode of action underlying the early responses to environmentally relevant level of BP-3 exposure remain unclear. In this study, 0.3 and 3 mg/kg of BP-3 were administered to pregnant mice. Compared with the control group, the cortical blood vessel development process manifested the highest susceptibility to BP-3 exposure using transcriptomic sequencing at embryonic day 14 (E14). Notably, the diminution in vascular density and tight junction proteins presence was observed in the fetal cortex at E14, concomitant with the suppressed transcriptional activity of genes essential to angiogenesis and barrier formation. Strikingly, the investigation revealed that BP-3 exposure impeded vascular sprouting in aortic ring explants and neuroendothelial migration, implicating the Wnt/β-catenin signaling pathway. Moreover, BP-3 exposure compromised perivascular neural stem cell differentiation. Cortical vascular injury correlated with the exhibition of depression-like behavior in four-week postnatal progeny. These insights underscore the cerebrovasculature as an early sensitive target for low doses of BP-3 exposure, fostering the development of biomarkers and the establishment of the adverse outcome pathway framework for BP-3 hazard evaluation.

Molecular and in silico analyses for detection of Shiga toxin-producing Escherichia coli (STEC) and highly pathogenic enterohemorrhagic Escherichia coli (EHEC) using genetic markers located on plasmid, O Island 57 and O Island 71

BackgroundDue to the diversity of Shiga toxin-producing Escherichia coli (STEC) isolates, detecting highly pathogenic strains in foodstuffs is challenging. Currently, reference protocols for STEC rely on the molecular detection of eae and the stx1 and/or stx2 genes, followed by the detection of serogroup-specific wzx or wzy genes related to the top 7 serogroups. However, these screening methods do not distinguish between samples in which a STEC possessing both determinants are present and those containing two or more organisms, each containing one of these genes. This study aimed to evaluate ecf1, Z2098, Z2099, and nleA genes as single markers and their combinations (ecf1/Z2098, ecf1/Z2099, ecf1/nleA, Z2098/Z2099, Z2098/nleA, and Z2099/nleA) as genetic markers to detect potentially pathogenic STEC by the polymerase chain reaction (PCR) in 96 animal samples, as well as in 52 whole genome sequences of human samples via in silico PCR analyses.ResultsIn animal isolates, Z2098 and Z2098/Z2099 showed a strong association with the detected top 7 isolates, with 100% and 69.2% of them testing positive, respectively. In human isolates, Z2099 was detected in 95% of the top 7 HUS isolates, while Z2098/Z2099 and ecf1/Z2099 were detected in 87.5% of the top 7 HUS isolates.ConclusionsOverall, using a single gene marker, Z2098, Z2099, and ecf1 are sensitive targets for screening the top 7 STEC isolates, and the combination of Z2098/Z2099 offers a more targeted initial screening method to detect the top 7 STEC isolates. Detecting non-top 7 STEC in both animal and human samples proved challenging due to inconsistent characteristics associated with the genetic markers studied.

Interferon regulatory factor 1 mediated inhibition of Treg cell differentiation induces maternal-fetal immune imbalance in preeclampsia

The establishment and maintenance of a successful pregnancy rely heavily on maternal-fetal immune tolerance. Inflammatory and immune mechanisms during pregnancy bear a resemblance to those observed in tumor progression, with Treg cells exhibiting similar immunoregulatory functions in both contexts. Interferon regulatory factor 1 (IRF1) is implicated in modulating the immune milieu within tumors and influencing regulatory T (Treg) cell differentiation. However, the precise association between IRF1 and the onset of preeclampsia (PE) remains unclear. In our investigation, we identified trophoblasts as a significant source of IRF1 expression at the maternal-fetal interface through immunofluorescence analysis. Moreover, heightened levels of IRF1 expression were detected in both placental tissues and peripheral blood samples obtained from PE patients, concomitant with an imbalance in the Th17/Treg ratio. In the peripheral circulation, a notable inverse correlation was observed between IRF1 mRNA levels and Foxp3 mRNA, a transcription factor specific to Treg cells. IRF1 mRNA expression showed a positive association with systolic blood pressure and a negative association with serum albumin levels. Furthermore, co-culturing naïve T cells with supernatants from HTR-8/SV neo cells overexpressing IRF1 resulted in diminished differentiation of T cells into Treg cells. In summary, our study indicates elevated IRF1 expression in the peripheral blood and trophoblast cells of PE patients. Elevated IRF1 in trophoblast cells hinders the differentiation of maternal Treg cells, disrupting maternal-fetal immune tolerance and contributing to PE pathogenesis. Additionally, IRF1 expression correlates with disease severity, suggesting its potential as a novel sensitive target in PE.

Board reforms and managerial risk-taking incentives: evidence from Chinese central state-owned enterprises

PurposeThis paper examines the effect of board reforms on managerial risk-taking incentive provision in state-owned enterprises (SOEs) whose managers are undue risk-averse.Design/methodology/approachWe use the staggered implementation of board reforms in Chinese central government-controlled state-owned enterprises (CSOEs) as an exogenous shock to board governance. We collect data on board reforms for a set of pilot CSOEs during the period 2005 to 2020 from the State-owned Assets Supervision and Administration Commission (SASAC) website by hand. We use a generalized difference-in-difference (DID) design to test the effect of staggered board reform adoption on managerial risk-taking incentive provision.FindingsWe find a positive relationship between board reforms and risk-taking inventive provision, i.e. pay-performance sensitivity, promotion-performance sensitivity and performance target difficulty. The documented relationship is stronger when the value of risk-taking is higher. We also find that board reforms lead to greater risky but value-enhancing investments and that managerial risk-taking incentive provision acts as an important channel through which board reforms improve value-enhancing risk-taking.Originality/valueOur findings suggest that board reforms that improve board governance are effective in addressing risk-related agency conflicts in emerging markets. The findings also highlight the importance of managerial risk-taking incentive provision in inducing risky but value-enhancing investments.

The predictive value of TyG and lipid ratios on the development of complications and hyperuricemia in patients with type 2 diabetes mellitus.

Investigate the predictive value of TyG and lipid ratios on the development of complications and HUA in patients with T2DM. A retrospective cross-sectional study involving 9488 T2DM patients was conducted. They were divided into HUA and NUA group base on SUA level and divided into with and without complications groups according to the diagnosis of the endocrinologist. Necessary information and biochemical parameters were recorded during outpatient visit. TyG index and lipid ratios were calculated, and statistical analysis was carried out to correlate the calculated values and HUA using SPSS version 26.0 for Windows. TyG and lipid ratios were significantly higher in T2DM with HUA or with complications than those with NUA or without complications (p < 0.05). Regression analysis adjusting for confounding factors found TyG (adjusted OR = 1.54; 95% CI: 1.31-1.82; p < 0.05), TG/HDL-C (adjusted OR = 1.21; 95% CI: 1.04-1.40; p < 0.05) and TC/HDL (adjusted OR = 1.36; 95% CI: 1.17-1.57; p < 0.05) was risk factor of HUA in T2DM patients. TyG (adjusted OR = 1.21; 95% CI: 1.02-1.44; p < 0.05), TG/HDL (adjusted OR = 1.19; 95% CI: 1.03-1.38; p < 0.05) and Apo A/Apo B (adjusted OR = 1.41; 95% CI: 1.26-1.58; p < 0.05) was risk factor of complications in T2DM patients. TyG, TG/HDL-C, and TC/HDL can be used as early sensitive target in the occurrence of HUA in T2DM patients and TyG was the most influential risk factor. TyG, TG/HDL-C, and Apo A/Apo B can be used as early sensitive target in the occurrence of complications in T2DM patients and Apo A/Apo B was the most influential risk factor.

Long-lasting, UV shielding, and cellulose-based avermectin nano/micro spheres with dual smart stimuli-microenvironment responsiveness for Plutella xylostella control

The requirement to improve the efficiency of pesticide utilization has led to the development of sustainable and smart stimuli-responsive pesticide delivery systems. Herein, a novel avermectin nano/micro spheres (AVM@HPMC-Oxalate) with sensitive stimuli-response function target to the Lepidoptera pests midgut microenvironment (pH 8.0–9.5) was constructed using hydroxypropyl methylcellulose (HPMC) as the cost-effective and biodegradable material. The avermectin (AVM) loaded nano/micro sphere was achieved with high AVM loading capacity (up to 66.8 %). The simulated release experiment proved the rapid stimuli-responsive and pesticides release function in weak alkaline (pH 9) or cellulase environment, and the release kinetics were explained through release models and SEM characterization. Besides, the nano/micro sphere size made AVM@HPMC-Oxalate has higher foliar retention rate (1.6–2.1-fold higher than commercial formulation) which is beneficial for improving the utilization of pesticides. The in vivo bioassay proved that AVM@HPMC-Oxalate could achieve the long-term control of Plutella xylostella by extending UV shielding performance (9 fold higher than commercial formulation). After 3 h of irradiation, the mortality rate of P. xylostella treated by AVM@HPMC-Oxalate still up to 56.7 % ± 5.8 %. Moreover, AVM@HPMC-Oxalate was less toxic to non-target organisms, and the acute toxicity to zebrafish was reduced by 2-fold compared with AVM technical.

The CUPID neutrinoless double-beta decay experiment

Neutrinoless double-beta decay (0νββ) is a key process to address some of the major outstanding issues in particle physics, such as the lepton number conservation and the Majorana nature of the neutrino. The next-generation of experiments aims at covering the Inverted-Ordering region of the neutrino mass spectrum, with sensitivities on the half-lives greater than 1027 years. Among the exploited techniques, low-temperature calorimetry has proved to be a very promising one, and will keep its leading role in the future thanks to the CUPID experiment. CUPID will search for the neutrinoless double-beta decay of 100Mo. By deploying Li2MoO4 scintillating crystals enriched in 100Mo and cryogenic light detectors, CUPID will perform simultaneous readout of heat and light signals, allowing for particle identification, and thus a powerful rejection technique for α background. To meet the new sensitivity target, the CUORE readout system must be upgraded. The readout system for each channel will consist of a pre-amplifier, a Programmable Gain Amplifier (PGA), a low-pass filter (Bessel filter) and a Digital AcQuisition System (DAQ). Finally, there is a pulser to generate thermal stabilization energy in the crystals. The motivation and expected performance of the technical upgrades are described in the context of the goals of the CUPID experiment.

Antagonism of propofol anesthesia by alkyl-fluorobenzene derivatives

Despite their frequent use across many clinical settings, general anesthetics are medications with lethal side effects and no reversal agents. A fluorinated analogue of propofol has previously been shown to antagonize propofol anesthesia in tadpoles and zebrafish, but little further investigation of this class of molecules as anesthetic antagonists has been conducted. A 13-member library of alkyl-fluorobenzene derivatives was tested in an established behavioral model of anesthesia in zebrafish at 5 days post fertilization. These compounds were examined for their ability to antagonize propofol and two volatile anesthetics, as well as their interaction with the anesthetic-binding model protein apoferritin. Two compounds provided significant antagonism of propofol, and when combined, were synergistic, suggesting more than one antagonist sensitive target site. These compounds did not antagonize the volatile anesthetics, indicating some selectivity amongst general anesthetics. For the compounds with the most antagonistic potency, similarities in structure and binding to apoferritin may be suggestive of competitive antagonism; however, this was not supported by a Schild analysis. This is consistent with multiple targets contributing to general anesthesia, but whether these are physiologic antagonists or are antagonists at only some subset of the many anesthetic potential targets remains unclear, and will require additional investigation.

The Effects of Sevoflurane and Aβ Interaction on CA1 Dendritic Spine Dynamics and MEGF10-Related Astrocytic Synapse Engulfment.

General anesthetics may accelerate the neuropathological changes related to Alzheimer's disease (AD), of which amyloid beta (Aβ)-induced toxicity is one of the main causes. However, the interaction of general anesthetics with different Aβ-isoforms remains unclear. In this study, we investigated the effects of sevoflurane (0.4 and 1.2 maximal alveolar concentration (MAC)) on four Aβ species-induced changes on dendritic spine density (DSD) in hippocampal brain slices of Thy1-eGFP mice and multiple epidermal growth factor-like domains 10 (MEGF10)-related astrocyte-mediated synaptic engulfment in hippocampal brain slices of C57BL/6 mice. We found that both sevoflurane and Aβ downregulated CA1-dendritic spines. Moreover, compared with either sevoflurane or Aβ alone, pre-treatment with Aβ isoforms followed by sevoflurane application in general further enhanced spine loss. This enhancement was related to MEGF10-related astrocyte-dependent synaptic engulfment, only in AβpE3 + 1.2 MAC sevoflurane and 3NTyrAβ + 1.2 MAC sevoflurane condition. In addition, removal of sevoflurane alleviated spine loss in Aβ + sevoflurane. In summary, these results suggest that both synapses and astrocytes are sensitive targets for sevoflurane; in the presence of 3NTyrAβ, 1.2 MAC sevoflurane alleviated astrocyte-mediated synaptic engulfment and exerted a lasting effect on dendritic spine remodeling.

Astrocyte Mitochondria Are a Sensitive Target of PCB52 and its Human-Relevant Metabolites.

Polychlorinated biphenyls (PCBs) are industrial chemicals that are ubiquitously found in the environment. Exposure to these compounds has been associated with neurotoxic outcomes; however, the underlying mechanisms for such outcomes remain to be fully understood. Recent studies have shown that astrocytes, the most abundant glial cell type in the brain, are susceptible to PCB exposure as well as exposure to human-relevant metabolites of PCBs. Astrocytes are critical for maintaining healthy brain function due to their unique functional attributes and positioning within the neuronal networks in the brain. In this study, we assessed the toxicity of PCB52, one of the most abundantly found PCB congeners in outdoor and indoor air, and two of its human-relevant metabolites, on astrocyte mitochondria. We exposed C6 cells, an astrocyte cell line, to PCB52 or its human-relevant metabolites and found that all the compounds showed increased toxicity in galactose-containing media compared to that in the glucose-containing media, indicating the involvement of mitochondria in observed toxicity. Additionally, we also found increased oxidative stress upon exposure to PCB52 metabolites. All three compounds caused a loss of mitochondrial membrane potential, distinct changes in the mitochondrial structure, and impaired mitochondrial function. The hydroxylated metabolite 4-OH-PCB52 likely functions as an uncoupler of mitochondria. This is the first study to report the adverse effects of exposure to PCB52 and its human-relevant metabolites on the mitochondrial structure and function in astrocytes.

Understanding Kenyan policymakers' perspectives about the introduction of new maternal vaccines.

New vaccine policy adoption is a complex process, especially in low-and-middle-income countries (LMICs), requiring country policymakers to navigate challenges such as competing priorities, human and financial resource constraints, and limited logistical capacity. Since the Expanded Programme on Immunization's (EPI) beginning, most new vaccine introductions under this structure have not been aimed at adult populations. The majority of adult vaccines offered under the EPI are not typically tested among and tailored for pregnant persons, except those that are specifically recommended for pregnancy. Given that new maternal vaccines, including RSV and GBS vaccines, are on the horizon, it is important to understand what barriers may arise during the policy development and vaccine introduction process. In this study, we sought to understand information needs among maternal immunization policymakers and decision-makers in Kenya for new vaccine maternal policy adoption through in-depth interviews with 20 participants in Nakuru and Mombasa counties in Kenya. Results were mapped to an adapted version of an established framework by Levine et al., (2010) focused on new vaccine introduction in LMICs. Participants reported that the policy process for new maternal vaccine introduction requires substantial evidence as well as coordination among diverse stakeholders. Importantly, our findings suggest that the process for new maternal vaccines does not end with the adoption of a new policy, as intended recipients and various actors can determine the success of a vaccine program. Previous shortcomings, in Kenya, and globally during HPV vaccine introduction show the need to allocate adequate resources in education of communities given the sensitive target group. With maternal vaccines targeting a sensitive group - pregnant persons- in the pipeline, we are at an opportune time to understand how to ensure successful vaccine introduction with optimal acceptance and uptake, while also addressing vaccine hesitancy to increase population benefit.

An optical remote sensing image encryption algorithm for sensitive targets in sea-related scenes

An optical remote sensing image encryption algorithm for sensitive targets in sea-related scenes

Radiation Effects of Normal B-Lymphoblastoid Cells after Exposing Them to Low-Dose-Rate Irradiation from Tritium β-rays.

The effects of tritium at low doses and low dose rates have received increasing attention due to recent developments in fusion energy and the associated risks of tritium releases into the environment. Mitochondria have been identified as a potential candidate for studying the effects of low-dose/low-dose-rate radiation, with extensive experimental results obtained using X-ray irradiation. In this study, irradiation experiments were conducted on normal B-lymphoblastoid cells using HTO at varying doses. When compared to X-ray irradiation, no significant differences in cell viability induced by different doses were observed. However, the results of ATP levels showed a significant difference between the irradiated sample at a dose of 500 mGy by tritium beta-rays and the sham-irradiated sample, while the levels obtained with X-ray irradiation were almost identical to the sham-irradiated sample. In contrast, ATP levels for both tritium beta-rays and X-rays at a dose of 1.0 Gy showed minimal differences compared to the sham-irradiated sample. Furthermore, distinct effects at 500 mGy were also confirmed in both ROS levels and apoptosis results obtained through tritium beta-ray irradiation. This suggests that mitochondria might be a potential sensitive target for investigating the effects of tritium beta-ray irradiation.

The role of microglial TREM2 in development: A path toward neurodegeneration?

The nervous and the immune systems undergo a continuous cross talk, starting from early development and continuing throughout adulthood and aging. Defects in this cross talk contribute to neurodevelopmental and neurodegenerative diseases. Microglia are the resident immune cells in the brain that are primarily involved in this bidirectional communication. Among the microglial genes, trem2 is a key player, controlling the functional state of microglia and being at the forefront of many processes that require interaction between microglia and other brain components, such as neurons and oligodendrocytes. The present review focuses on the early developmental window, describing the early brain processes in which TREM2 is primarily involved, including the modulation of synapse formation and elimination, the control of neuronal bioenergetic states as well as the contribution to myelination processes and neuronal circuit formation. By causing imbalances during these early maturation phases, dysfunctional TREM2 may have a striking impact on the adult brain, making it a more sensitive target for insults occurring during adulthood and aging.

Development of an aptasensor for highly sensitive detection of cardiac troponin I using cobalt–nickel metal-organic framework (CoNi-MOF)

Objective and rationaleThis study aimed to develop a highly sensitive and selective single-stranded DNA (ssDNA) aptamer targeting cardiac troponin I (cTnI), a crucial biomarker for acute myocardial infarction (AMI). The objective was to fabricate a novel aptamer electrochemical sensor using a composite material of cobalt-nickel metal-organic framework (CoNi-MOF) on screen-printed carbon electrodes (SPCE), leveraging the composite's large surface area and excellent electrical conductivity alongside the aptamer's high affinity for cTnI. MethodsThe aptamer electrochemical sensor was fabricated using the CoNi-MOF composite on SPCE and characterized its properties. They conducted electrochemical measurements to assess the sensor's performance in detecting cTnI. The sensor's stability, reproducibility, and electro-catalytic activity were evaluated. ResultsThe sensor demonstrated linear detection of cTnI over a concentration range of 5–75 pg/mL, with a low limit of detection (LOD) of 13.2 pM. Remarkable stability and reproducibility were observed in cTnI detection. The sensor exhibited exceptional electro-catalytic activity, enabling accurate quantification of cTnI levels in various solutions. ConclusionsThis research presents a significant advancement towards the development of reliable, cost-effective, and easily deployable cTnI sensors for clinical applications. The sensor's versatility in detecting cTnI across different concentration ranges highlights its potential utility in diverse clinical settings, particularly for early detection and monitoring of cardiac conditions.

Neuropsychiatric Symptom Profile in Alzheimer's Disease and Their Relationship With Functional Decline

ObjectiveUnderstanding the course of individual neuropsychiatric symptoms (NPS) and their relationship with function is important for planning targeted interventions for preventing and delaying functional decline. This study aims to disentangle relative contributions of individual NPS on functional decline. MethodsLongitudinal study of 9,358 well-characterized participants with baseline diagnoses of Mild Cognitive Impairment or AD in the National Alzheimer's Coordinating Center Uniform Data Set. Function was measured using the Functional Assessment Questionnaire (FAQ). Clinician judgment of seven common behavioral symptoms were examined simultaneously: apathy-withdrawal, depressed mood, visual or auditory hallucinations, delusions, disinhibition, irritability, and agitation. ResultsApathy was the most common NPS at baseline (33.7%) and throughout follow-up, endorsed by clinicians in 63.7% of visits. Apathy was the most persistent with 36.7% of participants having clinician-endorsed apathy in ≥50% of their visits. Apathy strongly correlated with faster rate of functional decline. Compared to those who never had apathy, baseline FAQ was worse in those with intermittent or persistent/always apathy (intermittent: estimated coefficient ±SE=1.228±0.210, 95% CI=[0.817, 1.639]; persistent/always: 2.354±0.244 (95% CI=[1.876, 2.832], both p <0.001). Over time, rate of functional decline was faster in those with intermittent and persistent/always apathy (intermittent: 0.454±0.091, 95% CI=[0.276, 0.632]; persistent/always: 0.635±0.102, 95% CI=[0.436, 0.835], both p <0.001). Worse agitation, delusions, and hallucinations also correlated with functional decline, but magnitudes of the estimates were smaller. ConclusionIndividual NPS may be sensitive targets for tracking longitudinal change in function. The study raises awareness of the need for more comprehensive assessment of functional decline in AD patients with noncognitive symptoms.

The Crosswise Model for Surveys on Sensitive Topics: A General Framework for Item Selection and Statistical Analysis

When surveys contain direct questions about sensitive topics, participants may not provide their true answers. Indirect question techniques incentivize truthful answers by concealing participants’ responses in various ways. The Crosswise Model aims to do this by pairing a sensitive target item with a non-sensitive baseline item, and only asking participants to indicate whether their responses to the two items are the same or different. Selection of the baseline item is crucial to guarantee participants’ perceived and actual privacy and to enable reliable estimates of the sensitive trait. This research makes the following contributions. First, it describes an integrated methodology to select the baseline item, based on conceptual and statistical considerations. The resulting methodology distinguishes four statistical models. Second, it proposes novel Bayesian estimation methods to implement these models. Third, it shows that the new models introduced here improve efficiency over common applications of the Crosswise Model and may relax the required statistical assumptions. These three contributions facilitate applying the methodology in a variety of settings. An empirical application on attitudes toward LGBT issues shows the potential of the Crosswise Model. An interactive app, Python and MATLAB codes support broader adoption of the model.