Single-cell transcriptomics reveals subset-specific metabolic profiles underpinning the bronchial epithelial response to flagellin.

Airway epithelial cells represent the first line of defense against respiratory pathogens. Flagellin drives the motility of many mucosal pathogens and has been suggested as an immune enhancing adjunctive therapeutic in infections of the airways. This study leveraged single-cell RNA sequencing to determine cell-specific effects of flagellin in primary human bronchial epithelial cells growing in air-liquid interface. Seven cell clusters were identified, including ciliated cells, ionocytes, and several states of basal and secretory cells, of which only inflammatory basal cells and inflammatory secretory cells demonstrated a proportional increase in response to flagellin. Inflammatory secretory cells showed evidence of metabolic reprogramming toward aerobic glycolysis, while in inflammatory basal cells transcriptome profiles indicated enhanced oxidative phosphorylation. Inhibition of mTOR prevented the shift to glycolysis and reduced inflammatory gene transcription specifically in inflammatory secretory cells. These data demonstrate the functional heterogeneity of the human airway epithelium upon exposure to flagellin.

Understanding responses to multi-electrode epiretinal stimulation using a biophysical model.

Objective: Neural interfaces are designed to evoke specific patterns of electrical activity in populations of neurons by stimulating with many electrodes. However, currents passed simultaneously through multiple electrodes often combine nonlinearly to drive neural responses, making evoked responses difficult to predict and control. This response nonlinearity could arise from the interaction of many excitable sites in each cell, any of which can produce a spike. However, this multi-site activation hypothesis is difficult to verify experimentally. Approach: We developed a biophysical model to study retinal ganglion cell (RGC) responses to multi-electrode stimulation and validated it using data collected from ex vivo preparations of the macaque retina using a microelectrode array (512 electrodes; 30µm pitch; 10µm diameter). Results: First, the model was validated by reproducing essential empirical findings from single-electrode stimulation and recording, including spike waveforms over the electrode array and sigmoidal responses to injected current. Then, stimulation with two electrodes was modeled to test how the positioning of the electrodes relative to the cell affected the degree of response nonlinearity. Currents passed through pairs of electrodes positioned near the cell body or far from the axon (>40 µm) exhibited linear summation. Currents passed through pairs of electrodes close to the axon summed linearly when their locations along the axon were similar, and nonlinearly otherwise. Over a range of electrode placements, several distinct, localized spike initiation sites were observed, and the number of these sites covaried with the degree of response nonlinearity. Similar trends were observed for three-electrode stimuli. All of these trends were consistent with experimental observations. Significance: These findings support the multi-site activation hypothesis for nonlinear activation of neurons, providing a biophysical interpretation of previous experimental results and potentially enabling more efficient use of multi-electrode stimuli in future neural implants.

Ebola disease outbreak caused by the Sudan virus in Uganda, 2022: a descriptive epidemiological study.

BACKGROUND: Uganda has had seven Ebola disease outbreaks, between 2000 and 2022. On Sept 20, 2022, the Ministry of Health declared a Sudan virus disease outbreak in Mubende District, Central Uganda. We describe the epidemiological characteristics and transmission dynamics. METHODS: For this descriptive study, cases were classified as suspected, probable, or confirmed using Ministry of Health case definitions. We investigated all reported cases to obtain data on case-patient demographics, exposures, and signs and symptoms, and identified transmission chains. We conducted a descriptive epidemiological study and also calculated basic reproduction number (Ro) estimates. FINDINGS: Between Aug 8 and Nov 27, 2022, 164 cases (142 confirmed, 22 probable) were identified from nine (6%) of 146 districts. The median age was 29 years (IQR 20-38), 95 (58%) of 164 patients were male, and 77 (47%) patients died. Symptom onsets ranged from Aug 8 to Nov 27, 2022. The case fatality rate was highest in children younger than 10 years (17 [74%] of 23 patients). Fever (135 [84%] of 160 patients), vomiting (93 [58%] patients), weakness (89 [56%] patients), and diarrhoea (81 [51%] patients) were the most common symptoms; bleeding was uncommon (21 [13%] patients). Before outbreak identification, most case-patients (26 [60%] of 43 patients) sought care at private health facilities. The median incubation was 6 days (IQR 5-8), and median time from onset to death was 10 days (7-23). Most early cases represented health-care-associated transmission (43 [26%] of 164 patients); most later cases represented household transmission (109 [66%]). Overall Ro was 1·25. INTERPRETATION: Despite delayed detection, the 2022 Sudan virus disease outbreak was rapidly controlled, possibly thanks to a low Ro. Children (aged <10 years) were at the highest risk of death, highlighting the need for targeted interventions to improve their outcomes during Ebola disease outbreaks. Initial care-seeking occurred at facilities outside the government system, showing a need to ensure that private and public facilities receive training to identify possible Ebola disease cases during an outbreak. Health-care-associated transmission in private health facilities drove the early outbreak, suggesting gaps in infection prevention and control. FUNDING: None.

Fixational eye movements enhance the precision of visual information transmitted by the primate retina.

Fixational eye movements alter the number and timing of spikes transmitted from the retina to the brain, but whether these changes enhance or degrade the retinal signal is unclear. To quantify this, we developed a Bayesian method for reconstructing natural images from the recorded spikes of hundreds of retinal ganglion cells (RGCs) in the macaque retina (male), combining a likelihood model for RGC light responses with the natural image prior implicitly embedded in an artificial neural network optimized for denoising. The method matched or surpassed the performance of previous reconstruction algorithms, and provides an interpretable framework for characterizing the retinal signal. Reconstructions were improved with artificial stimulus jitter that emulated fixational eye movements, even when the eye movement trajectory was assumed to be unknown and had to be inferred from retinal spikes. Reconstructions were degraded by small artificial perturbations of spike times, revealing more precise temporal encoding than suggested by previous studies. Finally, reconstructions were substantially degraded when derived from a model that ignored cell-to-cell interactions, indicating the importance of stimulus-evoked correlations. Thus, fixational eye movements enhance the precision of the retinal representation.

Assessing sleep in primary brain tumor patients using smart wearables and patient-reported data: Feasibility and interim analysis of an observational study.

Background: Sleep-wake disturbances are common and disabling in primary brain tumor (PBT) patients but studies exploring longitudinal data are limited. This study investigates the feasibility and relationship between longitudinal patient-reported outcomes (PROs) and physiologic data collected via smart wearables. Methods: Fifty-four PBT patients ≥ 18 years wore Fitbit smart-wearable devices for 4 weeks, which captured physiologic sleep measures (eg, total sleep time, wake after sleep onset [WASO]). They completed PROs (sleep hygiene index, PROMIS sleep-related impairment [SRI] and Sleep Disturbance [SD], Morningness-Eveningness Questionnaire [MEQ]) at baseline and 4 weeks. Smart wearable use feasibility (enrollment/attrition, data missingness), clinical characteristics, test consistency, PROs severity, and relationships between PROs and physiologic sleep measures were assessed. Results: The majority (72%) wore their Fitbit for the entire study duration with 89% missing < 3 days, no participant withdrawals, and 100% PRO completion. PROMIS SRI/SD and MEQ were all consistent/reliable (Cronbach's alpha 0.74-0.92). Chronotype breakdown showed 39% morning, 56% intermediate, and only 6% evening types. Moderate-severe SD and SRI were reported in 13% and 17% at baseline, and with significant improvement in SD at 4 weeks (P = .014). Fitbit-recorded measures showed a correlation at week 4 between WASO and SD (r = 0.35, P = .009) but not with SRI (r = 0.24, P = .08). Conclusions: Collecting sleep data with Fitbits is feasible, PROs are consistent/reliable, > 10% of participants had SD and SRI that improved with smart wearable use, and SD was associated with WASO. The skewed chronotype distribution, risk and impact of sleep fragmentation mechanisms warrant further investigation. Trial Registration: NCT04 669 574.

The pregnancy rescue case versus typical abortion.

Hendricks' pregnancy rescue case (PRC) tries to show that abortion is typically morally wrong. I argue here that there are at least two morally relevant differences between the abortion in PRC and the typical abortion so that the latter isn't morally wrong even if the former is morally wrong. I develop five modifications to PRC to show that these two differences are morally important. First, in PRC we don't know whether the person gives informed consent to the abortion, nor does the medical professional who will perform the abortion, and so the abortion can't be performed because the patient gives informed consent to it. Second, not preventing the death of the fetus in PRC brings about the death of an additional fetus gestating in a separate pregnant person, whereas most abortions don't entail the termination of another's pregnancy.

Mapping environmental suitability changes for arbovirus mosquitoes in Southeast Asia: 1960-2020.

Spatial epidemiology recognizes the impact of environmental factors on human infectious diseases through disease vectors. The expansion of Aedes aegypti and Aedes albopictus raises concerns about health risks due to their changing distribution. However, current mosquito mapping methods have low spatial resolution and limited focus on long-term trends and factors. This study develops a high-resolution framework (500 m) to map mosquito distribution in Southeast Asia from 1960 to 2020. It includes a species distribution model, a spatial autocorrelation model, and a geographical detector model. The study produces Southeast Asia's first 500 m resolution map of mosquito suitability, revealing significant increases in mosquito suitability in most cities over the past 60 years. The analysis indicates a shift in high-suitability areas from coastal to inland regions, with nighttime land surface temperature playing a key role. These findings are crucial for regional risk assessments and mitigation strategies related to vector-borne diseases.

Organophosphorus S-adenosyl-L-methionine mimetics: synthesis, stability, and substrate properties.

S-Adenosyl-l-methionine (SAM)-mediated methylation of biomolecules controls their function and regulates numerous vital intracellular processes. Analogs of SAM with a reporter group in place of the S-methyl group are widely used to study these processes. However, many of these analogs are chemically unstable that largely limits their practical application. We have developed a new compound, SAM-P H , which contains an H-phosphinic group (-P(O)(H)OH) instead of the SAM carboxylic group. SAM-P H is significantly more stable than SAM, retains functional activity in catechol-O-methyltransferase and methyltransferase WBSCR27 reactions. The last is associated with Williams-Beuren syndrome. Rac-SAM-P H was synthesized chemically, while (R,S)-SAM-P H and its analogs were prepared enzymatically either from H-phosphinic analogs of methionine (Met-PH) or H-phosphinic analog of S-adenosyl-l-homocysteine (SAH-P H ) using methionine adenosyltransferase 2A or halide methyltransferases, respectively. SAH-P H undergoes glycoside bond cleavage in the presence of methylthioadenosine nucleosidase like natural SAH. Thus, SAM-P H and its analogs are promising new tools for investigating methyltransferases and incorporating reporter groups into their substrates.

Untwining the intertwined: a comprehensive review on differentiating pathologies of the shoulder and spine.

Background: The anatomic interplay and overlap between the cervical spine and the shoulder constitutes a challenge for shoulder and spine surgeons, as symptoms of spine and shoulder pathologies are often similar and may lead to entity misdiagnosis. Methods: PubMed, Cochrane, and Google Scholar (page 1-20) searches were updated to October 2023 in search of the qualified papers. Boolean Operators were used with a combination of the keywords "spine" OR "neck" And "Shoulder". Furthermore, reference lists from papers were also searched to find literature. Results: It is of pivotal importance to conduct comprehensive preoperative clinical investigation to appropriately evaluate and assess the source of the pathology and the leading causes behind it. Certain markers can help guide surgeons towards etiologies, and these include areas of pain and physical exam findings with the arm squeeze test having the highest sensitivity and specificity for diagnosing cervical radiculopathy. As for the shoulder, despite its low sensitivity, the Yergason test had the highest specificity for diagnosing subacromial impingement. Local anesthetic injection can help as well in the diagnostic approach. Moreover, the interplay between these anatomic locations is not solely related to preoperative diagnosis. Studies have shown that previous surgery for cervical spine pathology may negatively affect the outcomes of shoulder procedures like arthroplasties. Conclusion: Shoulder and spine surgeons should be wary and vigilant of accurately diagnosing the etiology of the presenting symptoms to ensure proper management and optimize prognosis.

Commensal-derived short-chain fatty acids disrupt lipid membrane homeostasis in Staphylococcus aureus.

The role of commensal anaerobic bacteria in chronic respiratory infections is unclear, yet they can exist in abundances comparable to canonical pathogens in vivo. Their contributions to the metabolic landscape of the host environment may influence pathogen behavior by competing for nutrients and creating inhospitable conditions via toxic metabolites. Here, we reveal a mechanism by which the anaerobe-derived short chain fatty acids (SCFAs) propionate and butyrate negatively affect Staphylococcus aureus physiology by disrupting branched chain fatty acid (BCFA) metabolism. In turn, BCFA impairment results in impaired growth, diminished expression of the agr quorum sensing system, as well as increased sensitivity to membrane-targeting antimicrobials. Altered BCFA metabolism also reduces S. aureus fitness in competition with Pseudomonas aeruginosa, suggesting that airway microbiome composition and the metabolites they produce and exchange directly impact pathogen succession over time. The pleiotropic effects of these SCFAs on S. aureus fitness and their ubiquity as metabolites in animals also suggests that they may be effective as sensitizers to traditional antimicrobial agents when used in combination.

The nutrient sensor CRTC and Sarcalumenin/thinman represent an alternate pathway in cardiac hypertrophy.

CREB-regulated transcription co-activator (CRTC) is activated by Calcineurin (CaN) to regulate gluconeogenic genes. CaN also has roles in cardiac hypertrophy. Here, we explore a cardiac-autonomous role for CRTC in cardiac hypertrophy. In Drosophila, CRTC mutants exhibit severe cardiac restriction, myofibrillar disorganization, fibrosis, and tachycardia. Cardiac-specific CRTC knockdown (KD) phenocopies mutants, and cardiac overexpression causes hypertrophy. CaN-induced hypertrophy in Drosophila is reduced in CRTC mutants, suggesting that CRTC mediates the effects. RNA sequencing (RNA-seq) of CRTC-KD and -overexpressing hearts reveals contraregulation of metabolic genes. Genes with conserved CREB sites include the fly ortholog of Sarcalumenin, a Ca2+-binding protein. Cardiac manipulation of this gene recapitulates the CRTC-KD and -overexpression phenotypes. CRTC KD in zebrafish also causes cardiac restriction, and CRTC KD in human induced cardiomyocytes causes a reduction in Srl expression and increased action potential duration. Our data from three model systems suggest that CaN-CRTC-Sarcalumenin signaling represents an alternate, conserved pathway underlying cardiac function and hypertrophy.

Role of the V2R-ßarrestin-Gßγ complex in promoting G protein translocation to endosomes.

Classically, G protein-coupled receptors (GPCRs) promote signaling at the plasma membrane through activation of heterotrimeric Gαßγ proteins, followed by the recruitment of GPCR kinases and ßarrestin (ßarr) to initiate receptor desensitization and internalization. However, studies demonstrated that some GPCRs continue to signal from internalized compartments, with distinct cellular responses. Both ßarr and Gßγ contribute to such non-canonical endosomal G protein signaling, but their specific roles and contributions remain poorly understood. Here, we demonstrate that the vasopressin V2 receptor (V2R)-ßarr complex scaffolds Gßγ at the plasma membrane through a direct interaction with ßarr, enabling its transport to endosomes. Gßγ subsequently potentiates Gαs endosomal translocation, presumably to regenerate an endosomal pool of heterotrimeric Gs. This work shines light on the mechanism underlying G protein subunits translocation from the plasma membrane to the endosomes and provides a basis for understanding the role of ßarr in mediating sustained G protein signaling.

Evaluation of Pain Catastrophizing Scale for surgical referral to pain psychology in patients undergoing spinal surgery.

Background: Chronic pain is an issue that affects over 100 million Americans daily. Acceptance and Commitment Therapy (ACT) has been found to be beneficial for patients with chronic pain by focusing provider efforts on teaching coping mechanisms for pain instead of eliminating the pain entirely. Current studies demonstrate that ACT significantly improves post-operative chronic pain scores and outcomes. Methods: The 200 patients chosen via random generator were collected and presented to (institution) orthopedic spine surgeons along with additional information such as the patients' history of present illness, Visual Analog Scale (VAS) scores, PROMIS-CAT Pain Interference scores, and status of opiate usage. Surgeons were blinded to the PCS cutoff scores. The (institution) orthopedic spine surgeons then identified which patients they would indicate for ACT and their reasoning. Pre-determined PCS score cut-offs were separately used to determine if a patient was indicated for ACT. Results: The effectiveness of this screening tool was based on the frequency at which the surgeons and PCS scores were complimentary. A department epidemiologist assisted in the analysis of the data with the use of a ROC curve. ROC Curve demonstrated an area under the curve of 0.7784 with a Sensitivity of 0.68 and a Specificity of 0.79. The cut point according to Youden's index is 35. The data showed that the PCS is moderately accurate in its ability to distinguish coinciding patients that the [institution] orthopedic spine surgeons referred for ACT. The adjusted cut-point indicates that patients above a PCS of 35 would be referred to ACT by the orthopedic spine surgeons while those below a PCS score of 35 would not be referred. Conclusions: Using the PCS, a referral with the department pain psychologist would occur by [institution] orthopedic spinal surgeons for patients that are deemed at-risk with a score of at least 35. The goal following this study is to perform future investigations regarding PCS and ACT with patients regarding chronic opioid use and postoperative outcomes. Patients who would be referred for help with chronic pain would be compared to PCS-referred patients and non-referred patients. Pre-operative ACT would be compared to patient outcomes post-operatively. The future aim is to use the cut-offs established in this study for experimental design to evaluate if PCS-referred patients have better pain management post-operatively as compared to the control and previously referred patients. Level of Evidence: Level III diagnostic study.

Hourly step recommendations to achieve daily goals for working and older adults.

BACKGROUND: The widespread use of physical activity trackers enables the collection of high-resolution health data, such as hourly step counts, to evaluate health promotion programmes. We aim to investigate how participants meet their daily step goals. METHODS: We used 24-h steps data from the National Steps ChallengeTM Season 3, wherein participants were rewarded with vouchers when achieving specified goals of 5000, 7500, and 10,000 steps per day. We extracted data from 3075 participants' including a total of 52,346 participant-days. We modelled the hourly step counts using a two-part model, in which the distribution for step counts was allowed to depend on the sum of step counts up to the previous hour and participant demographics. RESULTS: Participants have a mean age of 44.2 years (standard deviation = 13.9), and 40.4% are males. We show that on weekdays, the hourly mean step counts among participants aged 60 and above are higher than participants aged 30 to 59 from the start of the day till 6 p.m. We also find that participants who accumulate at least 7000 steps by 7 p.m. are associated with higher success of achieving 10,000 steps. CONCLUSIONS: We provide recommendations on the hourly targets to achieve daily goals, based on different participants' characteristics. Future studies could experimentally test if prompts and nudges at the recommended times of day could promote reaching step goals.

The National Steps Challenge^TM is a nationwide physical activity programme in Singapore that encourages participants to exercise more. We used daily step data from over 3000 adult participants to investigate how different types of participants met their daily step goals. We found that participants who had taken at least 7000 steps by 7 p.m. were more likely to achieve 10,000 steps by the end of the day. Based on our analysis, we propose specific recommendations for hourly targets based on characteristics such as age and sex. Our study provides a better understanding of the population's physical activity levels which will enable people to be given targeted recommendations based on their own characteristics that might facilitate them more easily meeting their exercise goals.

Gaze Scanning on Mid-Block Sidewalks by Pedestrians With Homonymous Hemianopia With or Without Spatial Neglect.

Purpose: The purpose of this study was to investigate gaze-scanning by pedestrians with homonymous hemianopia (HH) when walking on mid-block sidewalks. Methods: Pedestrians with right homonymous hemianopia (RHH), and left homonymous hemianopia (LHH) without and with left spatial neglect (LHSN) walked on city streets wearing a gaze-tracking system. Gaze points were obtained by combining head movement and eye-in-head movement. Mixed-effects regression models were used to compare horizontal gaze scan magnitudes and rates between the side of the hemi-field loss (BlindSide) and the seeing side (SeeingSide), among the three subject groups, and between mid-block walking and street crossing segments. Results: A total of 7021 gaze scans were obtained from 341 minutes of mid-block walking videos by 19 participants (6 with LHH, 7 with RHH, and 6 with LHSN). The average gaze magnitude and scanning rate in mid-block segments were significantly higher towards the BlindSide than the SeeingSide in LHH (magnitude larger by 1.9° (degrees), P = 0.006; scan rate higher by 4.2 scans/minute, P < 0.001) and RHH subjects (magnitude larger by 3.3°, P < 0.001; scan rate higher by 3.2 scans/minute, P = 0.002), but they were not significantly different in LHSN subjects. The scanning rate, in terms of scans/minute (mean, 95% confidence interval [CI]) was significantly lower in LHSN subjects (mean = 6.9, 95% CI = 5.6-8.7) than LHH (mean = 10.2, 95% CI = 8.0-13.1; P = 0.03) and RHH (mean = 11.1, 95% CI = 9.0-13.7; P = 0.007) subjects. Compared to street-crossings, the scan rate during the mid-block segments was lower by 3.5 scans/minute (P < 0.001) and the gaze magnitude was smaller by 3.8° (P < 0.001) over the 3 groups. Conclusions: Evidence of compensatory scanning suggests a proactive, top-down mechanism driving gaze in HH. The presence of spatial neglect (SN) appeared to negatively impact the top-down process.

Chatbot for Social Need Screening and Resource Sharing With Vulnerable Families: Iterative Design and Evaluation Study.

BACKGROUND: Health outcomes are significantly influenced by unmet social needs. Although screening for social needs has become common in health care settings, there is often poor linkage to resources after needs are identified. The structural barriers (eg, staffing, time, and space) to helping address social needs could be overcome by a technology-based solution. OBJECTIVE: This study aims to present the design and evaluation of a chatbot, DAPHNE (Dialog-Based Assistant Platform for Healthcare and Needs Ecosystem), which screens for social needs and links patients and families to resources. METHODS: This research used a three-stage study approach: (1) an end-user survey to understand unmet needs and perception toward chatbots, (2) iterative design with interdisciplinary stakeholder groups, and (3) a feasibility and usability assessment. In study 1, a web-based survey was conducted with low-income US resident households (n=201). Following that, in study 2, web-based sessions were held with an interdisciplinary group of stakeholders (n=10) using thematic and content analysis to inform the chatbot's design and development. Finally, in study 3, the assessment on feasibility and usability was completed via a mix of a web-based survey and focus group interviews following scenario-based usability testing with community health workers (family advocates; n=4) and social workers (n=9). We reported descriptive statistics and chi-square test results for the household survey. Content analysis and thematic analysis were used to analyze qualitative data. Usability score was descriptively reported. RESULTS: Among the survey participants, employed and younger individuals reported a higher likelihood of using a chatbot to address social needs, in contrast to the oldest age group. Regarding designing the chatbot, the stakeholders emphasized the importance of provider-technology collaboration, inclusive conversational design, and user education. The participants found that the chatbot's capabilities met expectations and that the chatbot was easy to use (System Usability Scale score=72/100). However, there were common concerns about the accuracy of suggested resources, electronic health record integration, and trust with a chatbot. CONCLUSIONS: Chatbots can provide personalized feedback for families to identify and meet social needs. Our study highlights the importance of user-centered iterative design and development of chatbots for social needs. Future research should examine the efficacy, cost-effectiveness, and scalability of chatbot interventions to address social needs.

Advancing Colorectal Cancer Detection With Blood-Based Tests: Qualitative Study and Discrete Choice Experiment to Elicit Population Preferences.

BACKGROUND: Colorectal cancer (CRC) is the second most deadly form of cancer, inducing an estimated 1.9 million incidence cases and 0.9 million deaths worldwide in 2020. Despite the availability of screening tests, their uptake remains suboptimal. However, blood-based tests that look for signs of cancer-specific markers in the body are increasingly available as an alternative for more invasive tests for cancer. Compared with existing tests, the benefits of blood-based tests for CRC include not needing pretest preparation, stool handling, and dietary or medication restrictions. OBJECTIVE: This study aims to explore the population's preferences for CRC screening tests, with a focus on blood-based tests, and investigate the factors influencing test uptake. METHODS: We used a mixed methods approach, combining semistructured interviews and a discrete choice experiment (DCE) survey. Interviews were analyzed using thematic analysis to identify salient attributes for CRC screening tests. These attributes informed the design of the DCE survey. The DCE data were analyzed using mixed logit and mixed-mixed multinomial logit models. RESULTS: Qualitative findings from 30 participants revealed that participants preferred blood-based tests due to their perceived low risk, minimal pain, and ease of sample collection. However, concerns about the test's lower accuracy were also expressed. The DCE survey was completed by 1189 participants. In the mixed logit model, participants demonstrated a stronger preference for blood-based tests over a 2-day stool-based test. The mixed-mixed multinomial logit model identified 2 classes, strong supporters and weak supporters, for CRC screening. Weak supporters, but not strong supporters, had a higher preference for blood-based tests. Women, ethnic Chinese, and people aged 40 to 60 years were more likely to be weak supporters. Both models highlighted the high influence of cost and test sensitivity on participants' preferences. Transitioning from a 2-day stool-based test to a blood-based test, assuming a national screening program at a base price of Singapore $5 (US $3.75), was estimated to have the potential to increase the relative uptake by 5.9% (95% CI 3.6%-8.2%). CONCLUSIONS: These findings contribute to our understanding of CRC screening preferences and provide insights into the factors driving test uptake. This study highlights the perceived advantages of blood-based tests and identifies areas of concern regarding their accuracy. Further research is needed to determine the actual increase in uptake rate when blood-based tests are made available.

Pilot study of a pedestrian collision detection test for a multisite trial of field expansion devices for hemianopia.

SIGNIFICANCE: Performance-based outcome measures are crucial for clinical trials of field expansion devices. We implemented a test simulating a real-world mobility situation, focusing on detection of a colliding pedestrian among multiple noncolliding pedestrians, suitable for measuring the effects of homonymous hemianopia and assistive devices in clinical trials. PURPOSE: In preparation for deploying the test in a multisite clinical trial, we conducted a pilot study to gather preliminary data on blind-side collision detection performance with multiperiscopic peripheral prisms compared with Fresnel peripheral prisms. We tested the hypothesis that detection rates for colliding pedestrians approaching on a 40° bearing angle (close to the highest collision risk when walking) would be higher with 100Δ oblique multiperiscopic (≈42° expansion) than 65Δ oblique Fresnel peripheral prisms (≈32° expansion). METHODS: Six participants with homonymous hemianopia completed the test with and without each type of prism glasses, after using them in daily mobility for a minimum of 4 weeks. The test, presented as a video on a large screen, simulated walking through a busy shopping mall. Colliding pedestrians approached from the left or the right on a bearing angle of 20 or 40°. RESULTS: Overall, blind-side detection was only 23% without prisms but improved to 73% with prisms. For multiperiscopic prisms, blind-side detection was significantly higher with than without prisms at 40° (88 vs. 0%) and 20° (75 vs. 0%). For Fresnel peripheral prisms, blind-side detection rates were not significantly higher with than without prisms at 40° (38 vs. 0%) but were significantly higher with prisms at 20° (94 vs. 56%). At 40°, detection rates were significantly higher with multiperiscopic than Fresnel prisms (88 vs. 38%). CONCLUSIONS: The collision detection test is suitable for evaluating the effects of hemianopia and prism glasses on collision detection, confirming its readiness to serve as the primary outcome measure in the upcoming clinical trial.

Evaluation of Xpert point-of-care assays for detection of HIV infection in persons using long-acting cabotegravir for pre-exposure prophylaxis.

Detection of HIV infection may be challenging in persons using long-acting cabotegravir (CAB-LA) pre-exposure prophylaxis (PrEP) due to viral suppression and reduced/delayed antibody production. We evaluated two point-of-care tests for detecting HIV infection in persons who received CAB-LA in the HPTN 083 trial. Samples were obtained from 12 participants who received CAB-LA and had delayed detection of HIV infection using HIV rapid tests and an antigen/antibody test (52 plasma samples; 18 dried blood spot [DBS] samples). Plasma samples were tested with the Xpert HIV-1 Viral Load XC test (Xpert VL-XC); DBS samples were tested with the total nucleic acid Xpert HIV-1 Qual XC test (Xpert Qual-XC). Results from these assays were compared to results from three reference, laboratory-based, plasma RNA assays (Aptima HIV-1 Qualitative assay [Aptima Qual]; Aptima HIV-1 Quant DX Assay [Aptima Quant]; cobas HIV-1/HIV-2 Qualitative Test [cobas]). HIV RNA was detected with all four plasma assays for all samples with viral loads (VLs) ≥ 200 copies/mL; the number of samples with VLs < 200 copies/mL with HIV RNA detected was: Xpert VL-XC: 19/26 (73.1%); Aptima Qual: 17/26 (65.4%); Aptima Quant: 17/26 (65.4%); and cobas: 12/21 (57.1%). The Xpert Qual-XC assay was positive for all DBS samples with VLs ≥ 200 copies/mL and 1/10 DBS with VLs < 200 copies/mL. The performance of the Xpert VL-XC assay was comparable to the reference assays for detecting HIV infection in these cases. The Xpert Qual-XC assay was less sensitive than plasma-based HIV RNA assays for detecting HIV in the setting of CAB-LA PrEP. IMPORTANCE: HIV RNA assays can detect HIV infections earlier than HIV rapid tests or Ag/Ab tests in persons using CAB-LA PrEP. Earlier HIV diagnosis could allow for earlier treatment initiation and reduced risk of INSTI resistance. POC tests may help detect HIV infection before CAB-LA administration and may be more accessible than laboratory-based assays in some settings. In this study, the POC Xpert VL-XC assay detected HIV RNA in most samples from individuals who received CAB-LA PrEP and had delayed detection of HIV infection with HIV rapid tests and an Ag/Ab test. The performance of this assay was similar to laboratory-based HIV RNA assays in this cohort. The POC Xpert Qual-XC assay detects both HIV RNA and DNA, with a higher viral load cutoff for RNA detection. This assay was negative for most lower viral load samples and did not offer an advantage for HIV screening in persons using CAB-LA PrEP.