bluuebunny/crossref_metadata_2025 huggingface dataset:
Signals from the TAFA4-PTEN-PU.1 axis alleviate nasal allergy by modulating the expression of FcεRI in mast cells
Authors: Zhou Caijie , Li Meihua , Liu Yu , Wang Xinxin , Zhang Shuang , Guan Li , Hong Jingyi , Zhou Wei , Wu Gaohui , Diao Weiliang , Huang Qinmiao , Yang Pingchang
Published: November 2022

The high-affinity IgE receptor, FcεRI, plays a key role in the antigen-induced mast cell activation. Regulations for FcεRI are not yet well understood. TAFA4 is a molecule derived from neuron tissues, and has immune regulation functions. This study aims to clarify the role of TAFA4 in the regulation of FcεRI expression in mast cells. Nasal secretions were collected from patients with allergic rhinitis (AR) and healthy control (HC) subjects. TAFA4 levels of nasal secretions were evaluated by ELISA. A mouse model AR was developed using ovalbumin as the specific antigen. Negative correlation between TAFA4 and tryptase levels in nasal secretions was observed. TAFA4 could suppress the antigen-related mast cell activation. TAFA4 modulated the transcription of Fcer1g (FcεRI γ gene) in mast cells. Signals from the TAFA4-PTEN-PU.1 axis restricted FcεRI expression in mast cells. Administration of TAFA4 attenuated experimental AR. TAFA4 suppressed the expression of FcεRI in mast cells of airway tissues. TAFA4 can down regulate the expression of FcεRI in mast cells to suppress experimental AR. The data suggest that TAFA4 has translation potential to be developed as an anti-allergy therapy.
Impact of Human Immunodeficiency Virus and Recreational Drugs on Cognitive Functions
Authors: Henrard Sophie , Trotta Nicola , Rovai Antonin , Coolen Tim , Slama Hichem , Bertels Julie , Puttaert Delphine , Goffard Jean-Christophe , Van Vooren Jean-Paul , Goldman Serge , De Tiège Xavier
Published: November 2022

Background

This prospective study characterizes the structural and metabolic cerebral correlates of cognitive impairments found in a preclinical setting that considers the lifestyle of young European men exposed to human immunodeficiency virus (HIV), including recreational drugs.

Methods

Simultaneous structural brain magnetic resonance imaging (MRI) and positron emission tomography using [18F]-fluorodeoxyglucose (FDG-PET) were acquired on a hybrid PET-MRI system in 23 asymptomatic young men having sex with men with HIV (HIVMSM; mean age, 33.6 years [range, 23–60 years]; normal CD4+ cell count, undetectable viral load). Neuroimaging data were compared with that of 26 young seronegative men under HIV preexposure prophylaxis (PrEPMSM), highly well matched for age and lifestyle, and to 23 matched young seronegative men (controls). A comprehensive neuropsychological assessment was also administered to the HIVMSM and PrEPMSM participants.

Results

HIVMSM had lower performances in executive, attentional, and working memory functions compared to PrEPMSM. No structural or metabolic differences were found between those 2 groups. Compared to controls, HIVMSM and PrEPMSM exhibited a common hypometabolism in the prefrontal cortex that correlated with the level of recreational drug use. No structural brain abnormality was found.

Conclusions

Abnormalities of brain metabolism in our population of young HIVMSM mainly relate to recreational drug use rather than HIV per se. A complex interplay between recreational drugs and HIV might nevertheless be involved in the cognitive impairments observed in this population.
Evaluating the Accuracy of Self-Collected Swabs for the Diagnosis of Mpox
Authors: Ubals Maria , Tarín-Vicente Eloy José , Oller Xènia , Mendoza Adrià , Alemany Andrea , Hernández-Rodríguez Águeda , Casañ Cristina , Rivero Ángel , Coll Pep , Cabrera José Miguel , Vall Martí , Agud-Dios Manuel , Gil-Cruz Elena , Paris de Leon Alexia , Marinero Aída Ramírez , Folgueira María Dolores , Meléndez María Ángeles , Buhiichyk Vira , Galván-Casas Cristina , Paredes Roger , Prat Nuria , Sala Farré Maria-Rosa , Bonet-Simó Josep Maria , Ortiz-Romero Pablo L , Clotet Bonaventura , Cardona Pere-Joan , Blanco Ignacio , Marks Michael , Suñer Clara , Mitjà Oriol ,   The Movie Group, Santos José Ramón , Bailón Lucía , Benet Susana , Andres Jorge Arroyo , Lozano Lorena Calderón , Hidalgo Yolanda Maltas , Perez Ramona Hervas , Romero Laura Clotet
Published: November 2022

We evaluated the accuracy of patient-collected skin lesions, oropharyngeal, and rectal swabs among 50 individuals enrolled in a study of mpox viral dynamics. We found that the performance of self-collected samples was similar to that of physician-collected samples, suggesting that self-sampling is a reliable strategy for diagnosing mpox.
A Translational Tool to Facilitate Use of Apolipoprotein B for Clinical Decision-Making
Authors: Cole Justine , Otvos James Dorian , Remaley Alan Thomas
Published: November 2022

Background

Despite recent large-scale discordance studies showing definitively that atherosclerotic cardiovascular disease (ASCVD) risk correlates better with apolipoprotein B (apoB) than with low-density lipoprotein cholesterol (LDL-C), the latter remains the recommended metric for guiding lipid-lowering treatment decisions in the United States. A major barrier to change, in this regard, is the lack of guideline-recommended apoB treatment targets. We developed a simple method to “translate” apoB values into population-equivalent LDL-C units, allowing apoB-based treatment decisions to be made using LDL-C targets.

Methods

Sequentially collected, population-based samples underwent standard lipid panel analysis and apoB testing by immunoassay. Those with triglycerides greater than 1000 mg/dl were excluded, leaving a study cohort of 15 153 individuals.

Results

Linear regression of calculated LDL-C values against percentile-equivalent apoB values yielded an equation to convert apoB into percentile-equivalent LDL-C units: [LDL-C equivalents = 1.38(apoB) – 29] (R2 = 0.999). The extent of discordance between LDL-C and apoB was examined in subgroups with similar LDL-C, ranging from very low (55–70 mg/dL) to very high (175–190 mg/dL). Among individuals with very low LDL-C, 40% had discordantly higher apoB, indicating higher ASCVD risk. Of those with very high LDL-C, 49% had discordantly lower apoB. Across the range, a minority of patients (25%–40%) had concordant levels of apoB, confirming that discordance between these biomarkers is highly prevalent. Similar results were found in discordance analysis between apoB and non-high-density lipoprotein cholesterol (HDL-C).

Conclusions

Providing visibility to discrepancies among LDL-C, non-HDL-C, and apoB should help to facilitate more rapid and widespread adoption of apoB for managing ASCVD risk.
Smartphone-based cardiac implantable electronic device remote monitoring: improved compliance and connectivity
Authors: Manyam Harish , Burri Haran , Casado-Arroyo Ruben , Varma Niraj , Lennerz Carsten , Klug Didier , Carr-White Gerald , Kolli Kranthi , Reyes Ignacio , Nabutovsky Yelena , Boriani Giuseppe
Published: November 2022

Aims

Remote monitoring (RM) is the standard of care for follow up of patients with cardiac implantable electronic devices. The aim of this study was to compare smartphone-based RM (SM-RM) using patient applications (myMerlinPulse™ app) with traditional bedside monitor RM (BM-RM).

Methods and results

The retrospective study included de-identified US patients who received either SM-RM or BM-RM capable of implantable cardioverter defibrillators or cardiac resynchronization therapy defibrillators (Abbott, USA). Patients in SM-RM and BM-RM groups were propensity-score matched on age and gender, device type, implant year, and month. Compliance with RM was quantified as the proportion of patients enrolling in the RM system (Merlin.net™) and transmitting data at least once. Connectivity was measured by the median number of days between consecutive transmissions per patient. Of the initial 9714 patients with SM-RM and 26 679 patients with BM-RM, 9397 patients from each group were matched. Remote monitoring compliance was higher in SM-RM; significantly more patients with SM-RM were enrolled in RM compared with BM-RM (94.4 vs. 85.0%, P < 0.001), similar number of patients in the SM-RM group paired their device (95.1 vs. 95.0%, P = 0.77), but more SM-RM patients transmitted at least once (98.1 vs. 94.3%, P < 0.001). Connectivity was significantly higher in the SM-RM, with patients transmitting data every 1.2 (1.1, 1.7) vs. every 1.7 (1.5, 2.0) days with BM-RM (P < 0.001) and remained better over time. Significantly more SM-RM patients utilized patient-initiated transmissions compared with BM-RM (55.6 vs. 28.1%, P < 0.001).

Conclusion

In this large real-world study, patients with SM-RM demonstrated improved compliance and connectivity compared with BM-RM.
The technique of balloon occlusion-assisted repair of a pseudoaneurysm originated from the side branch of an ascending aortic prosthetic graft via mini-thoracotomy
Authors: Handa Kazuma , Shijo Takayuki , Shimamura Kazuo , Miyagawa Shigeru
Published: November 2022

A 69-year-old woman underwent aortic root reimplantation and graft replacement of the ascending aorta 12 years ago. A pseudoaneurysm (2.5 cm × 3 cm) arising from the side branch of the ascending aortic prosthetic graft was incidentally detected on contrast-enhanced computed tomography. After endovascular balloon occlusion of the side branch through the left subclavian artery, the side branch was exposed via right mini-thoracotomy in the third intercostal space. After circumferential dissection, the side branch was ligated uneventfully. The patient was discharged home on postoperative day 7 without any complications.
Antigenic evolution of SARS-CoV-2 in immunocompromised hosts
Authors: Smith Cameron A , Ashby Ben
Published: November 2022

Objectives/aims: Prolonged infections of immunocompromised individuals have been proposed as a crucial source of new variants of SARS-CoV-2 during the COVID-19 pandemic. In principle, sustained within-host antigenic evolution in immunocompromised hosts could allow novel immune escape variants to emerge more rapidly, but little is known about how and when immunocompromised hosts play a critical role in pathogen evolution.

Materials and methods: Here, we use a simple mathematical model to understand the effects of immunocompromised hosts on the emergence of immune escape variants in the presence and absence of epistasis.

Conclusions: We show that when the pathogen does not have to cross a fitness valley for immune escape to occur (no epistasis), immunocompromised individuals have no qualitative effect on antigenic evolution (although they may accelerate immune escape if within-host evolutionary dynamics are faster in immunocompromised individuals). But if a fitness valley exists between immune escape variants at the between-host level (epistasis), then persistent infections of immunocompromised individuals allow mutations to accumulate, therefore, facilitating rather than simply speeding up antigenic evolution. Our results suggest that better genomic surveillance of infected immunocompromised individuals and better global health equality, including improving access to vaccines and treatments for individuals who are immunocompromised (especially in lower- and middle-income countries), may be crucial to preventing the emergence of future immune escape variants of SARS-CoV-2.
Left bundle branch area pacing in congenital heart disease
Authors: O’Connor Matthew , Riad Omar , Shi Rui , Hunnybun Dan , Li Wei , Jarman Julian W E , Foran John , Rinaldi Christopher A , Markides Vias , Gatzoulis Michael A , Wong Tom
Published: November 2022

Aims

Left bundle branch area pacing (LBBAP) has been shown to be effective and safe. Limited data are available on LBBAP in the congenital heart disease (CHD) population. This study aims to describe the feasibility and safety of LBBAP in CHD patients compared with non-CHD patients.

Methods and results

This is a single-centre, non-randomized observational study recruiting consecutive patients with bradycardia indication. Demographic data, ECGs, imaging, and procedural data including lead parameters were recorded. A total of 39 patients were included: CHD group (n = 13) and non-CHD group (n = 26). Congenital heart disease patients were younger (55 ± 14.5 years vs. 73.2 ± 13.1, P < 0.001). Acute success was achieved in all CHD patients and 96% (25/26) of non-CHD patients. No complications were encountered in either group. The procedural time for CHD patients was comparable (96.4 ± 54 vs. 82.1 ± 37.9 min, P = 0.356). Sheath reshaping was required in 7 of 13 CHD patients but only in 1 of 26 non-CHD patients, reflecting the complex and distorted anatomy of the patients in this group. Lead parameters were similar in both groups; R wave (11 ± 7 mV vs. 11.5 ± 7.5, P = 0.881) and pacing threshold (0.6 ± 0.3 V vs. 0.7 ± 0.3, P = 0.392). Baseline QRS duration was longer in the CHD group (150 ± 28.2 vs. 118.6 ± 26.6 ms, P = 0.002). Despite a numerically greater reduction in QRS and a similar left ventricular activation time (65.9 ± 6.2 vs. 67 ± 16.8 ms, P = 0.840), the QRS remained longer in the CHD group (135.5 ± 22.4 vs. 106.9 ± 24.7 ms, P = 0.005).

Conclusion

Left bundle branch area pacing is feasible and safe in CHD patients as compared to that in non-CHD patients. Procedural and fluoroscopy times did not differ between both groups. Lead parameters were satisfactory and stable over a short-term follow-up.
Opportunities for primary health care: a qualitative study of perinatal health and wellbeing during bushfire crises
Authors: Davis Deborah , Roberts Celia , Williamson Rebecca , Kurz Ella , Barnes Katelyn , Behie Alison M , Aroni Rosalie , Nolan Christopher J , Phillips Christine
Published: November 2022

Background

During the summer of 2019/2020, Australia experienced a catastrophic wildfire season that affected nearly 80% of Australians either directly or indirectly. The impacts of climate crisis on perinatal health have only recently begun to receive attention. The objective of this study was to understand experiences of perinatal women during the bushfire and smoke events of 2019–2020 regarding health, health care, and public health messaging.

Methods

Semistructured interviews were conducted by phone or web conferencing platforms with 43 participants living in the south-east of Australia who were either pregnant or who had recently had a baby during the 2019/2020 fires.

Results

The health impacts on participants of the fires, associated smoke, and evacuations for some, were both physical and psychological. Many participants sought information regarding how to protect their own health and that of their unborn/recently born children, but reported this difficult to find.

Conclusions

Pregnant women and new mothers exposed to bushfire events are a risk group for adverse physical and psychological outcomes. At the time of the 2019/2020 Australian bushfires, exposed women could not easily access evidence-based information to mitigate this risk. Family practitioners are well placed to provide pregnant women and new mothers with this sought-after information, but they need to be prepared well in advance of future similar events.
Effects of modified biochars on the shifts of short-chain fatty acid profile, iron reduction, and bacterial community in paddy soil
Authors: Liu Qian , Zhong Linrui , Hu Yingju , Fu Leiling , Hu Xingxin , Gu Yujing , Xie Qingqing , Liang Fangyi , Liu Qi , Lu Yue
Published: November 2022

Biochar is well known as an effective means for soil amendment, and modification on biochar with different methods could improve the benefits for environmental remediation. In this study, two modified biochars were generated with nitric acid (NBC) and hydrogen peroxide (OBC) pretreatment, and a control biochar was produced after washing with deionized water (WBC). The dynamics of short-chain fatty acids (SCFAs), iron concentration and bacterial community in rice paddy soil amended with different biochars or without adding biochar (CK) were studied during 70 days of anaerobic incubation. Compared to CK treatment, the accumulation of SCFAs was largely inhibited by the amendment of biochars. Besides, OBC and WBC increased the accumulation of Fe(II) at the initial stage of incubation. Via 16S rRNA gene sequencing, modified biochars caused significant response of bacterial community in comparison to WBC at Day 0–1, and three biochars favored bacterial α-diversity in the paddy soil at the end of the incubation. Interestingly, positive and negative correlations between NBC and several bacteria taxa (e.g. Geobacter, Fonticella and Clostridium) were observed. The study revealed that modified biochars had significant effects on the shifts of SCFAs, Fe(III) reduction and bacterial diversity, which provides fundamental information for future application of modified biochars in rice cropping ecosystem.
The relationship between zinc deficiency and infectious complications in patients with hepatitis B virus-related acute-on-chronic liver failure
Authors: Li Xinhua , Wang Lu , He Na , Zhang Yeqiong , Pang Jiahui , Wang Heping , Yu Meng , Mei Yongyu , Peng Liang , Xu Wenxiong
Published: November 2022

Background

The prevalence of zinc deficiency is high in patients with chronic liver disease, but few studies have hitherto explored the relationship between the serum zinc level and hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). This study aimed to assess the association between zinc deficiency and infectious complications, and model for end-stage liver disease (MELD) score in patients with HBV-related ACLF.

Methods

Patients with HBV-related ACLF from the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between January 2019 and December 2019 were retrospectively analysed in this study. Their demographic, clinical, and laboratory data were retrieved from the hospital information system and analysed. The Student’s t-test was used for normally distributed continuous variables between two groups and the Chi-square test was used for categorical data. Univariate and multivariate logistic regression analyses were applied to identify independent parameters.

Results

A total of 284 patients were included in this study, including 205 liver cirrhosis and 79 non-cirrhosis patients. The proportion of patients with zinc deficiency was the highest (84.5%), followed by subclinical zinc deficiency (14.1%) and normal zinc level (1.4%). Patients in the zinc deficiency group had a higher MELD score than the subclinical zinc deficiency or normal zinc group (P = 0.021). Age, total bilirubin, and serum zinc level were independent factors for infection (Ps < 0.05). The serum zinc level in patients without complications at admission was significantly higher than that in patients with complications (P = 0.004). Moreover, the serum zinc level in patients with prothrombin time activity (PTA) of <20% was significantly lower than that in patients with 20% ≤ PTA < 30% (P = 0.007) and that in patients with 30% ≤ PTA < 40% (P < 0.001).

Conclusions

Zinc deficiency is common in patients with HBV-related ACLF. Zinc deficiency is closely associated with infectious complications and MELD score in patients with HBV-related ACLF.
The Social Cost of Providing Care to Older Adults With and Without Dementia
Authors: Patterson Sarah E , Tate Ashley M , Hu Yi-Ling , Wang Jue (Jessie) , Schoeni Robert F , Choi HwaJung
Published: November 2022

Objectives

Social participation is known to enhance well-being. Caregiving responsibilities are more intense when caring for an older adult with than without dementia and may affect caregivers’ ability for social participation. We estimate social participation restrictions among caregivers for older persons with versus without dementia, variation within racial/ethnic group, and the mediating effect of care hours.

Methods

We use the 2017 National Health and Aging Trends Study (NHATS) and National Study of Caregiving (NSOC) to study family caregivers for older adults. We estimate the prevalence of social participation (e.g., visiting family/friends, religious activities, group/club activities, going out) that were important to the caregiver but missed due to caregiving. We use logistic models to test for differences in restrictions by the older adult’s dementia status overall and within race/ethnic group, adjusting for caregiver and care receiver characteristics.

Results

One-third of family caregivers for older adults with dementia reported restrictions due to caregiving, double the prevalence among caregivers of an older adult without dementia (33.3% vs 16.0%; p < .001). This doubling gap persisted in adjusted models (odds ratio [OR] = 2.4; p < .01) but mainly for White, non-Hispanic caregivers (OR = 3.2; p < .001). Substantially greater caregiving hours for people with versus without dementia was found (104 vs 60 hr per month), which is responsible for about 21% of the total difference in restrictions (p < .05).

Discussion

More time spent among caregivers of persons with versus without dementia may be an important factor undermining social participation, but hours only partially explain the gap. Future interventions should consider how to facilitate social participation among caregivers.
Predicted and observed impacts of COVID-19 lockdowns: two Health Impact Assessments in Scotland and Wales
Authors: Green Liz , Ashton Kathryn , Bellis Mark , Clements Timo , Douglas Margaret
Published: November 2022

Health Impact Assessment is a key approach used internationally to identify positive or negative impacts of policies, plans and proposals on health and well-being. In 2020, HIAs were undertaken in Scotland and Wales to identify the potential health and well-being impacts of the ‘stay at home’ and physical distancing measures implemented at the start of the coronavirus disease (COVID-19) pandemic. There is sparse evidence evaluating whether the impacts predicted in HIAs occur following policy implementation. This paper evaluates the impacts anticipated in the COVID-19 HIAs against actual observed trends. The processes undertaken were compared and predicted impacts were tabulated by population groups and main determinants of health. Routine data and literature evidence were collated to compare predicted and observed impacts. Nearly all health impacts anticipated in both HIAs have occurred in the direction predicted. There have been significant adverse impacts through multiple direct and indirect pathways including loss of income, social isolation, disruption to education and services, and psychosocial effects. This research demonstrates the value of prediction in impact assessment and fills a gap in the literature by comparing the predicted impacts identified within the HIAs with observed trends. Post-COVID-19 recovery should centre health and well-being within future policies and decisions. Processes like HIA can support this as part of a ‘health in all policies’ approach to improve the health and well-being of populations.
Reviving health promotion in South Australia: The role of ideas, actors and institutional forces
Authors: Musolino Connie , van Eyk Helen , Freeman Toby , Fisher Matt , MacDougall Colin , Williams Carmel , Baum Fran
Published: November 2022

Globally health promotion has remained marginalized while biomedical health systems have maintained and even increased their dominance. During 2019–2021 we drew on the local and historical knowledge of actors from multiple sectors through semi-structured interviews and focus groups, to assess the implications of the withdrawal of the state from health promotion in a suburban region of South Australia. Institutional theory enabled in-depth analysis of the ideas, actors, and institutional forces at play in the institutional field, and how these elements come together to maintain the dominance of medicine. We found that the ideas, actors and institutional forces supporting health promotion in the study region have weakened and fragmented. This has happened as biomedicine has increased its dominance in the region’s health system, mirroring international trends. The results point to a withdrawal of state and federal governments from health promotion, which has led to severe gaps in leadership and governance, and locally, to a decline in capacity and resources. The state health department reallocated resources to focus on individual behavioural change rather than more structural factors affecting health. While some activities aimed at the social determinants of health or community development strategies remained, these had minimal institutional support. The establishment of a state government wellbeing agency in 2020 prompted an exploration to determine whether the agency and the international wellbeing movement presents an opportunity for a revival of more comprehensive health promotion.
Community priorities for obesity prevention among low-income adults in Kuala Lumpur: a discrete choice experiment
Authors: Kocher Erica , Wood Dallas , Lim Shiang-Cheng , Jackson-Morris Angie , Kataria Ishu , Ngongo Carrie , Sham Zhi , Chandran Arunah , Nugent Rachel , Mustapha Feisul Idzwan
Published: November 2022

Non-communicable diseases and associated risk factors, such as obesity, are prevalent and increasing in Malaysia. To address this burden and the heightened vulnerability of low-income communities to these risk factors, the Better Health Programme Malaysia conducted a partial-profile discrete choice experiment (DCE) to inform the design of a community-based obesity-prevention programme. The DCE survey was conducted with community members (n = 1453) from three publicly supported low-cost, high-rise flat complexes in urban Kuala Lumpur. In the survey, community members were asked to choose between different sets of potential evidence-based interventions for obesity prevention. Their responses to these choice tasks were analysed to quantify preferences for these different health interventions using a random utility maximization model. Based on these results, we determined participants’ relative prioritization of the different options. The most preferred interventions were those that reduced the price of fruit and vegetables; altered cooking practices at restaurants and food vendors to reduce salt, sugar and oil; and offered reward incentives for completing online educational activities. Community members did not prioritize several evidence-based interventions, including changes to product placement or product labelling, suggesting that these effective approaches may be less familiar or simply not preferred by respondents. The DCE enabled the clear articulation of these community priorities for evidence-based interventions that focus on the supply and promotion of affordable healthy foods within the local food environment, as well as community demand for healthier food options.
ACR’s Connect and AI-LAB technical framework
Authors: Brink Laura , Coombs Laura P , Kattil Veettil Deepak , Kuchipudi Kashyap , Marella Sailaja , Schmidt Kendall , Nair Sujith Surendran , Tilkin Michael , Treml Christopher , Chang Ken , Kalpathy-Cramer Jayashree
Published: November 2022

Objective

To develop a free, vendor-neutral software suite, the American College of Radiology (ACR) Connect, which serves as a platform for democratizing artificial intelligence (AI) for all individuals and institutions.

Materials and Methods

Among its core capabilities, ACR Connect provides educational resources; tools for dataset annotation; model building and evaluation; and an interface for collaboration and federated learning across institutions without the need to move data off hospital premises.

Results

The AI-LAB application within ACR Connect allows users to investigate AI models using their own local data while maintaining data security. The software enables non-technical users to participate in the evaluation and training of AI models as part of a larger, collaborative network.

Discussion

Advancements in AI have transformed automated quantitative analysis for medical imaging. Despite the significant progress in research, AI is currently underutilized in current clinical workflows. The success of AI model development depends critically on the synergy between physicians who can drive clinical direction, data scientists who can design effective algorithms, and the availability of high-quality datasets. ACR Connect and AI-LAB provide a way to perform external validation as well as collaborative, distributed training.

Conclusion

In order to create a collaborative AI ecosystem across clinical and technical domains, the ACR developed a platform that enables non-technical users to participate in education and model development.
False-Positive Amphetamines in Urine Drug Screens: A 6-Year Review
Authors: Pope Jeffrey D , Drummer Olaf H , Schneider Hans G
Published: November 2022

Immunoassays are routinely used to provide rapid urine drug screening results in the clinical setting. These screening tests are prone to false-positive results and ideally require confirmation by mass spectrometry. In this study, we have examined a large number of urine specimens where drugs other than amphetamines may have caused a false-positive amphetamine immunoassay screening result. Urine drug screens (12,250) in a clinical laboratory that used the CEDIA amphetamine/ecstasy method were reviewed for false-positive results over a 6-year period (2015–2020). An additional 3,486 referred samples, for which confirmatory--mass spectrometry was requested, were also reviewed. About 86 in-house samples and 175 referral samples that were CEDIA false-positive screens were further analyzed by an LC–QTOF general unknown screen. Potential cross-reacting drugs were identified, and their molecular similarities to the CEDIA targets were determined. Commercial standards were also analyzed for cross-reactivity in the amphetamine/ecstasy CEDIA screen. Positive amphetamine results in 3.9% of in-house samples and 9.9% of referred tests for confirmatory analysis were false positive for amphetamines. Of these false-positive specimens, on average, 6.8 drugs were detected by the LC–QTOF screen. Several drugs were identified as possible cross-reacting drugs to the CEDIA amphetamine/ecstasy assay. Maximum common substructure scores for 70 potential cross-reacting compounds were calculated. This was not helpful in identifying cross-reacting drugs. False-positive amphetamine screens make up to 3.9–9.9% of positive amphetamine screens in the clinical laboratory. Knowledge of cross-reacting drugs may be helpful when mass spectrometry testing is unavailable.
Circadian regulation of the GLYCINE-RICH RNA-BINDING PROTEIN gene by the master clock protein CIRCADIAN CLOCK-ASSOCIATED 1 is important for plant innate immunity
Authors: Gao Min , Zhang Chong , Angel William , Kwak Owen , Allison Jessica , Wiratan Linda , Hallworth Amelia , Wolf Julie , Lu Hua
Published: November 2022

Recent studies have demonstrated the importance of temporal regulation of pathogen defense by the circadian clock. However, our understanding of the molecular basis underlying this role of the circadian clock is still in its infancy. We report here the mechanism by which the Arabidopsis master clock protein CCA1 regulates an output target gene GRP7 for its circadian expression and function in pathogen defense. Our data firmly establish that CCA1 physically associates with the GRP7 promoter via the predicted CCA1-binding motif, evening element (EE). A site-directed mutagenesis study showed that while individual EE motifs differentially contribute to robust circadian expression of GRP7, abolishing all four EE motifs in the proximal GRP7 promoter disrupts rhythmicity of GRP7 expression and results in misalignment of defense signaling mediated by GRP7 and altered pathogen responses. This study provides a mechanistic link of the circadian regulation of an output gene to its biological function in pathogen defense, underscoring the importance of temporal control of plant innate immunity.
Neuron-periphery mitochondrial stress communication in aging and diseases
Authors: Li Jiasheng , Cui Jimeng , Tian Ye
Published: November 2022

The nervous system is the central hub of the body, detecting environmental and internal stimuli to regulate organismal metabolism via communications to the peripheral tissues. Mitochondria play an essential role in neuronal activity by supplying energy, maintaining cellular metabolism, and buffering calcium levels. A variety of mitochondrial conditions are associated with aging and age-related neurological disorders. Beyond regulating individual neuron cells, mitochondria also coordinate signaling in tissues and organs during stress conditions to mediate systemic metabolism and enable organisms to adapt to such stresses. In addition, peripheral organs and immune cells can also produce signaling molecules to modulate neuronal function. Recent studies have found that mitokines released upon mitochondrial stresses affect metabolism and the physiology of different tissues and organs at a distance. Here, we summarize recent advances in understanding neuron-periphery mitochondrial stress communication and how mitokine signals contribute to the systemic regulation of metabolism and aging with potential implications for therapeutic strategies.
Estimating the warm dark matter mass from strong lensing images with truncated marginal neural ratio estimation
Authors: Anau Montel Noemi , Coogan Adam , Correa Camila , Karchev Konstantin , Weniger Christoph
Published: November 2022

Precision analysis of galaxy–galaxy strong gravitational lensing images provides a unique way of characterizing small-scale dark matter haloes, and could allow us to uncover the fundamental properties of dark matter’s constituents. Recently, gravitational imaging techniques made it possible to detect a few heavy subhaloes. However, gravitational lenses contain numerous subhaloes and line-of-sight haloes, whose subtle imprint is extremely difficult to detect individually. Existing methods for marginalizing over this large population of subthreshold perturbers to infer population-level parameters are typically computationally expensive, or require compressing observations into hand-crafted summary statistics, such as a power spectrum of residuals. Here, we present the first analysis pipeline to combine parametric lensing models and a recently developed neural simulation-based inference technique called truncated marginal neural ratio estimation (TMNRE) to constrain the warm dark matter halo mass function cut-off scale directly from multiple lensing images. Through a proof-of-concept application to simulated data, we show that our approach enables empirically testable inference of the dark matter cut-off mass through marginalization over a large population of realistic perturbers that would be undetectable on their own, and over lens and source parameter uncertainties. To obtain our results, we combine the signal contained in a set of images with Hubble Space Telescope resolution. Our results suggest that TMNRE can be a powerful approach to put tight constraints on the mass of warm dark matter in the multi-keV regime, which will be relevant both for existing lensing data and in the large sample of lenses that will be delivered by near-future telescopes.
Quality over quantity: Optimizing pulsar timing array analysis for stochastic and continuous gravitational wave signals
Authors: Speri Lorenzo , Porayko Nataliya K , Falxa Mikel , Chen Siyuan , Gair Jonathan R , Sesana Alberto , Taylor Stephen R
Published: November 2022

The search for gravitational waves using Pulsar Timing Arrays (PTAs) is a computationally expensive complex analysis that involves source-specific noise studies. As more pulsars are added to the arrays, this stage of PTA analysis will become increasingly challenging. Therefore, optimizing the number of included pulsars is crucial to reduce the computational burden of data analysis. Here, we present a suite of methods to rank pulsars for use within the scope of PTA analysis. First, we use the maximization of the signal-to-noise ratio as a proxy to select pulsars. With this method, we target the detection of stochastic and continuous gravitational wave signals. Next, we present a ranking that minimizes the coupling between spatial correlation signatures, namely monopolar, dipolar, and Hellings & Downs correlations. Finally, we also explore how to combine these two methods. We test these approaches against mock data using frequentist and Bayesian hypothesis testing. For equal-noise pulsars, we find that an optimal selection leads to an increase in the log-Bayes factor two times steeper than a random selection for the hypothesis test of a gravitational wave background versus a common uncorrelated red noise process. For the same test but for a realistic European PTA (EPTA) data set, a subset of 25 pulsars selected out of 40 can provide a log-likelihood ratio that is 89 % of the total, implying that an optimally selected subset of pulsars can yield results comparable to those obtained from the whole array. We expect these selection methods to play a crucial role in future PTA data combinations.
Stellar population analysis of MaNGA early-type galaxies: IMF dependence and systematic effects
Authors: Bernardi M , Sánchez H Domínguez , Sheth R K , Brownstein J R , Lane R R
Published: November 2022

We study systematics associated with estimating simple stellar population (SSP) parameters – age, metallicity [M/H], α-enhancement [α/Fe], and initial mass function (IMF) shape – and associated M*/L gradients, of elliptical slow rotators (E-SRs), fast rotators (E-FRs), and S0s from stacked spectra of galaxies in the MaNGA survey. These systematics arise from (i) how one normalizes the spectra when stacking; (ii) having to subtract emission before estimating absorption line strengths; (iii) the decision to fit the whole spectrum or just a few absorption lines; (iv) SSP model differences (e.g. isochrones, enrichment, IMF). The MILES+Padova SSP models, fit to the Hβ, 〈Fe〉, TiO2SDSS, and [MgFe] Lick indices in the stacks, indicate that out to the half-light radius Re: (a) ages are younger and [α/Fe] values are lower in the central regions but the opposite is true of [M/H]; (b) the IMF is more bottom-heavy in the center, but is close to Kroupa beyond about Re/2; (c) this makes M*/L about 2 × larger in the central regions than beyond Re/2. While the models of Conroy et al. return similar [M/H] and [α/Fe] profiles, the age and (hence) M*/L profiles can differ significantly even for solar abundances and a Kroupa IMF; different responses to non-solar abundances and IMF parametrization further compound these differences. There are clear (model independent) differences between E-SRs, E-FRs, and S0s: younger ages and less enhanced [α/Fe] values suggest that E-FRs and S0s are not SSPs, but relaxing this assumption is unlikely to change their inferred M*/L gradients significantly.
Host defense functions of the epididymal amyloid matrix
Authors: Myers Caitlyn , Hastert Mary Catherine , Cornwall Gail A
Published: November 2022

The epididymal lumen is an immunologically distinct environment. It maintains tolerance for the naturally antigenic spermatozoa to allow their maturation into functional cells while simultaneously defending against pathogens that can ascend the male tract and cause infertility. We previously demonstrated that a nonpathological amyloid matrix that includes several cystatin-related epididymal spermatogenic (CRES) subgroup family members is distributed throughout the mouse epididymal lumen but its function was unknown. Here, we reveal a role for the epididymal amyloid matrix in host defense and demonstrate that the CRES amyloids and CD-1 mouse epididymal amyloid matrix exhibit potent antimicrobial activity against bacterial strains that commonly cause epididymal infections in men. We show the CRES and epididymal amyloids use several defense mechanisms including bacterial trapping, disruption of bacterial membranes and promotion of unique bacterial ghost-like structures. Remarkably, these antimicrobial actions varied depending on the bacterial strain indicating CRES amyloids and the epididymal amyloids elicit strain-specific host defense responses. We also demonstrate that the CRES monomer and immature assemblies of the epididymal amyloid transitioned into advanced structures in the presence of bacteria, suggesting their amyloid-forming/shape-shifting properties allows for a rapid reaction to a pathogen and provides an inherent plasticity in their host defense response. Together, our studies reveal new mechanistic insight into how the male reproductive tract defends against pathogens. Future studies using a mouse model for human epididymitis are needed to establish the epididymal amyloid responses to pathogens in vivo. Broadly, our studies provide an example of why nature has maintained the amyloid fold throughout evolution.
Clinical utility of plasma cell-free DNA in gliomas
Authors: Carpenter Erica L , Bagley Stephen J
Published: November 2022

Noninvasive molecular profiling of tumors using plasma-based next-generation sequencing (NGS) is increasingly used to aid in diagnosis, treatment selection, and disease monitoring in oncology. In patients with glioma, however, the plasma cell-free DNA (cfDNA) tumor fraction, defined as the fractional proportion of circulating tumor-derived DNA (ctDNA) relative to total cfDNA, is especially low, in large part due to the blood-brain barrier. As a result, commercial plasma-based NGS assays, designed to screen for a small number of actionable genomic alterations, are not sensitive enough to guide the management of patients with glioma. As this has been long recognized in neuro-oncology, significant research efforts have been undertaken to improve the sensitivity of plasma ctDNA detection in patients with glioma and to understand the biology and clinical relevance of non-tumor-derived cfDNA, which makes up most of the total cfDNA pool. Here, we review key recent advances in the field of plasma cfDNA analysis in patients with glioma, including (1) the prognostic impact of pre-treatment and on-treatment total plasma cfDNA concentrations, (2) use of tumor-guided sequencing approaches to improve the sensitivity of ctDNA detection in the plasma, and (3) the emergence of plasma cfDNA methylomics for detection and discrimination of glioma from other primary intracranial tumors.
Liquid biopsy—from bench to bedside
Authors: Ray Amitava , Vohra Tarang K
Published: November 2022

Over the last decade, molecular markers have become an integral part in the management of Central Nervous System (CNS) tumors. Somatic mutations that identify and prognosticate tumors are also detected in the bio-fluids especially the serum and CSF; the sampling of which is known as liquid biopsy (LB). These tumor-derived biomarkers include plasma circulating tumor cells (CTCs), cell-free DNA (cf/ctDNAs), circulating cell-free microRNAs (cfmiRNAs), circulating extracellular vesicles, or exosomes (EVs), proteins, and tumor educated platelets. Established in the management of other malignancies, liquid biopsy is becoming an important tool in the management of CNS tumors as well. This review presents a snapshot of the current state of LB research its potential and the possible pitfalls.
Advances in molecular biomarkers and liquid biopsy in gliomas
Authors: Mathios Dimitrios , Phallen Jillian
Published: November 2022

There have been significant strides toward understanding the molecular landscape of brain cancer. These advances have been focused on analyses of the tumor microenvironment and have recently expanded to include liquid biopsies to identify molecular biomarkers noninvasively. Moving from tissue to liquid-based analyses of molecular biomarkers has been challenging and currently, there are no approved noninvasive tests that are clinically useful. However, the emerging field of molecular liquid biopsy assay development in the neuro-oncology space has great potential to revolutionize the detection and monitoring of patients with brain cancer.
The Impact of the Danish National Smoking Ban From 2007 on the Incidence of Eight Smoking-related Diseases: A Nationwide Register-based Interrupted Time Series Analysis
Authors: Jarlstrup Nanna Schneekloth , Thygesen Lau Caspar , Grønbæk Morten Klöcker , Rod Morten Hulvej , Tolstrup Janne Schurmann
Published: November 2022

Background

Previous research has documented the effect of comprehensive smoking bans on preventing various adverse health outcomes in the years post-ban. In 2007, Denmark implemented a national smoking ban that prohibited indoor smoking in workplaces and public settings, although only partial restrictions applied in specific premises such as small bars, one-person offices, and in psychiatric units. We tested the hypothesis that the implementation of the national smoking ban was associated with a decrease in incidence of smoking-related morbidity in the Danish population compared to the pre-ban period.

Methods

Interrupted time series analyses including the entire Danish population (≥30 years) was conducted. Information of hospitalizations and cause-specific mortality due to acute myocardial infarction, heart failure, hemorrhagic stroke, ischemic stroke, chronic obstructive pulmonary disease, cancer in bronchus and lung, cancer in lip, mouth, oral cavity, and pharynx, and bladder cancer were obtained from population-based registers. Poisson regression models accounting for seasonal variations and secular trends quantified immediate changes in incidence rates occurring at the time of the smoking ban as well as changes in the post-ban trend compared to pre-ban levels.

Results

Overall, we observed no consistent declines in incidence of cardiovascular diseases, chronic obstructive pulmonary disease, or the specific types of cancer in the post-ban period compared with the pre-ban period.

Conclusion

No consistent reduction in incidence of smoking-related diseases was observed after the smoking ban was introduced in Denmark. This probably reflects that the Danish smoking ban included several exemptions, resulting in a less comprehensive ban compared to those introduced in other countries.

Implications

In this study, we found that the Danish national smoking ban from 2007 did not consistently reduced the incidence of eight smoking-related outcomes in the post-ban period compared to pre-ban levels. We argue that due to the exemptions in the smoking ban, which for example allowed smoking in specific premises of the care and nursing sector, in one-person offices, and small bars, the ban was not sufficiently comprehensive to influence smoking behavior and thereof the incidence of smoking-related morbidity. Our findings highlight the importance of introducing comprehensive legislative measures to yield largest health benefits at a population level.