bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy of clinical predictions of prognosis at the end-of-life: evidence from routinely collected data in urgent care records
Authors: Orlovic M. , Droney J. , Vickerstaff V. , Rosling J. , Bearne A. , Powell M. , Riley J. , McFarlane P. , Koffman J. , Stone P.
Published: April 2023

Background

The accuracy of prognostication has important implications for patients, families, and health services since it may be linked to clinical decision-making, patient experience and outcomes and resource allocation. Study aim is to evaluate the accuracy of temporal predictions of survival in patients with cancer, dementia, heart, or respiratory disease.

Methods

Accuracy of clinical prediction was evaluated using retrospective, observational cohort study of 98,187 individuals with a Coordinate My Care record, the Electronic Palliative Care Coordination System serving London, 2010–2020. The survival times of patients were summarised using median and interquartile ranges. Kaplan Meier survival curves were created to describe and compare survival across prognostic categories and disease trajectories. The extent of agreement between estimated and actual prognosis was quantified using linear weighted Kappa statistic.

Results

Overall, 3% were predicted to live “days”; 13% “weeks”; 28% “months”; and 56% “year/years”. The agreement between estimated and actual prognosis using linear weighted Kappa statistic was highest for patients with dementia/frailty (0.75) and cancer (0.73). Clinicians’ estimates were able to discriminate (log-rank p < 0.001) between groups of patients with differing survival prospects. Across all disease groups, the accuracy of survival estimates was high for patients who were likely to live for fewer than 14 days (74% accuracy) or for more than one year (83% accuracy), but less accurate at predicting survival of “weeks” or “months” (32% accuracy).

Conclusion

Clinicians are good at identifying individuals who will die imminently and those who will live for much longer. The accuracy of prognostication for these time frames differs across major disease categories, but remains acceptable even in non-cancer patients, including patients with dementia. Advance Care Planning and timely access to palliative care based on individual patient needs may be beneficial for those where there is significant prognostic uncertainty; those who are neither imminently dying nor expected to live for “years”.
Psychological wellbeing of Australian community health service staff during the COVID-19 pandemic: a longitudinal cohort study
Authors: Holton Sara , Wynter Karen , Peeters Anna , Georgalas Alexandra , Yeomanson Ann , Rasmussen Bodil
Published: April 2023

Background

Hospital clinical staff have reported poor psychosocial wellbeing during the COVID-19 pandemic. Little is known about community health service staff who undertake various roles including education, advocacy and clinical services, and work with a range of clients. Few studies have collected longitudinal data. The aim of this study was to assess the psychological wellbeing of community health service staff in Australia during the COVID-19 pandemic at two time points in 2021.

Methods

A prospective cohort design with an anonymous cross-sectional online survey administered at two time points (March/April 2021; n = 681 and September/October 2021; n = 479). Staff (clinical and non-clinical roles) were recruited from eight community health services in Victoria, Australia. Psychological wellbeing was assessed using the Depression, Anxiety and Stress Scale (DASS-21) and resilience using the Brief Resilience Scale (BRS). General linear models were used to measure the effects of survey time point, professional role and geographic location on DASS-21 subscale scores, adjusting for selected sociodemographic and health characteristics.

Results

There were no significant differences in respondent sociodemographic characteristics between the two surveys. Staff’s mental health declined as the pandemic continued. Adjusting for dependent children, professional role, general health status, geographic location, COVID-19 contact status and country of birth; depression, anxiety and stress scores were significantly higher for respondents in the second survey than the first (all p < 0.001). Professional role and geographic location were not statistically significantly associated with scores on any of the DASS-21 subscales. Higher levels of depression, anxiety and stress were reported among respondents who were younger, and had less resilience or poorer general health.

Conclusions

The psychological wellbeing of community health staff was significantly worse at the time of the second survey than the first. The findings indicate that the COVID-19 pandemic has had an ongoing and cumulative negative impact on staff wellbeing. Staff would benefit from continued wellbeing support.
Evaluation of Ethiopia’s field epidemiology training program – frontline: perspectives of implementing partners
Authors: Kebebew Tolcha , Woldetsadik Mahlet A. , Barker Jordan , Cui Angelina , Abedi Aisha A. , Sugerman David E. , Williams Desmond E. , Turcios-Ruiz Reina M. , Takele Tariku , Zeynu Neima
Published: April 2023

Background

Field Epidemiology Training Program (FETP) has been adopted as an epidemiology and response capacity building strategy worldwide. FETP-Frontline was introduced in Ethiopia in 2017 as a three-month in-service training. In this study, we evaluated implementing partners’ perspectives with the aim of understanding program effectiveness and identifying challenges and recommendations for improvement.

Methods

A qualitative cross-sectional design was utilized to evaluate Ethiopia’s FETP-Frontline. Using a descriptive phenomenological approach, qualitative data were collected from FETP-Frontline implementing partners, including regional, zonal, and district health offices across Ethiopia. We collected data through in-person key informant interviews, using semi-structured questionnaires. Thematic analysis was conducted, assisted with MAXQDA, while ensuring interrater reliability by using the consistent application of theme categorization. The major themes that emerged were program effectiveness, knowledge and skills differences between trained and untrained officers, program challenges, and recommended actions for improvement. Ethical approval was obtained from the Ethiopian Public Health Institute. Informed written consent was obtained from all participants, and confidentiality of the data was maintained throughout.

Results

A total of 41 interviews were conducted with key informants from FETP-Frontline implementing partners. The regional and zonal level experts and mentors had a Master of Public Health (MPH), whereas district health managers were Bachelor of Science (BSc) holders. Majority of the respondents reflected a positive perception towards FETP-Frontline. Regional and zonal officers as well as mentors mentioned that there were observable performance differences between trained and untrained district surveillance officers. They also identified various challenges including lack of resources for transportation, budget constraints for field projects, inadequate mentorship, high staff turnover, limited number of staff at the district level, lack of continued support from stakeholders, and the need for refresher training for FETP-Frontline graduates.

Conclusions

Implementing partners reflected a positive perception towards FETP-Frontline in Ethiopia. In addition to scaling-up the program to reach all districts to achieve the International Health Regulation 2005 goals, the program also needs to consider addressing immediate challenges, primarily lack of resources and poor mentorship. Continued monitoring of the program, refresher training, and career path development could improve retention of the trained workforce.
Egg-laying by female Aedes aegypti shapes the bacterial communities of breeding sites
Authors: Mosquera Katherine D. , Martínez Villegas Luis Eduardo , Rocha Fernandes Gabriel , Rocha David Mariana , Maciel-de-Freitas Rafael , A. Moreira Luciano , Lorenzo Marcelo G.
Published: April 2023

Background

Aedes aegypti, the main arboviral mosquito vector, is attracted to human dwellings and makes use of human-generated breeding sites. Past research has shown that bacterial communities associated with such sites undergo compositional shifts as larvae develop and that exposure to different bacteria during larval stages can have an impact on mosquito development and life-history traits. Based on these facts, we hypothesized that female Ae. aegypti shape the bacteria communities of breeding sites during oviposition as a form of niche construction to favor offspring fitness.

Results

To test this hypothesis, we first verified that gravid females can act as mechanical vectors of bacteria. We then elaborated an experimental scheme to test the impact of oviposition on breeding site microbiota. Five different groups of experimental breeding sites were set up with a sterile aqueous solution of larval food, and subsequently exposed to (1) the environment alone, (2) surface-sterilized eggs, (3) unsterilized eggs, (4) a non-egg laying female, or (5) oviposition by a gravid female. The microbiota of these differently treated sites was assessed by amplicon-oriented DNA sequencing once the larvae from the sites with eggs had completed development and formed pupae. Microbial ecology analyses revealed significant differences between the five treatments in terms of diversity. In particular, between-treatment shifts in abundance profiles were detected, showing that females induce a significant decrease in microbial alpha diversity through oviposition. In addition, indicator species analysis pinpointed bacterial taxa with significant predicting values and fidelity coefficients for the samples in which single females laid eggs. Furthermore, we provide evidence regarding how one of these indicator taxa, Elizabethkingia, exerts a positive effect on the development and fitness of mosquito larvae.

Conclusions

Ovipositing females impact the composition of the microbial community associated with a breeding site, promoting certain bacterial taxa over those prevailing in the environment. Among these bacteria, we found known mosquito symbionts and showed that they can improve offspring fitness if present in the water where eggs are laid. We deem this oviposition-mediated bacterial community shaping as a form of niche construction initiated by the gravid female.
Third dose mRNA vaccination against SARS-CoV-2 reduces medical complaints seen in primary care: a matched cohort study
Authors: Methi Fredrik , Gran Jon Michael , Valberg Morten , Kinge Jonas Minet , Telle Kjetil , Magnusson Karin
Published: April 2023

Background

SARS-CoV-2 mRNA vaccination has been associated with both side effects and a reduction in COVID-related complaints due to the decrease in COVID-19 incidence. We aimed to investigate if individuals who received three doses of SARS-CoV-2 mRNA vaccines had a lower incidence of (a) medical complaints and (b) COVID-19-related medical complaints, both as seen in primary care, when compared to individuals who received two doses.

Methods

We conducted a daily longitudinal exact one-to-one matching study based on a set of covariates. We obtained a matched sample of 315,650 individuals aged 18–70 years who received the 3rd dose at 20–30 weeks after the 2nd dose and an equally large control group who did not. Outcome variables were diagnostic codes as reported by general practitioners or emergency wards, both alone and in combination with diagnostic codes of confirmed COVID-19. For each outcome, we estimated cumulative incidence functions with hospitalization and death as competing events.

Results

We found that the number of medical complaints was lower in individuals aged 18–44 years who received three doses compared to those who received two doses. The differences in estimates per 100,000 vaccinated were as follows: fatigue 458 less (95% confidence interval: 355–539), musculoskeletal pain 171 less (48–292), cough 118 less (65–173), heart palpitations 57 less (22–98), shortness of breath 118 less (81–149), and brain fog 31 less (8–55). We also found a lower number of COVID-19-related medical complaints: per 100,000 individuals aged 18–44 years vaccinated with three doses, there were 102 (76–125) fewer individuals with fatigue, 32 (18–45) fewer with musculoskeletal pain, 30 (14–45) fewer with cough, and 36 (22–48) fewer with shortness of breath. There were no or fewer differences in heart palpitations (8 (1–16)) or brain fog (0 (− 1–8)). We observed similar results, though more uncertain, for individuals aged 45–70 years, both for medical complaints and for medical complaints that were COVID-19 related.

Conclusions

Our findings suggest that a 3rd dose of SARS-CoV-2 mRNA vaccine administered 20–30 weeks after the 2nd dose may reduce the incidence of medical complaints. It may also reduce the COVID-19-related burden on primary healthcare services.
An archetypes approach to malaria intervention impact mapping: a new framework and example application
Authors: Bertozzi-Villa Amelia , Bever Caitlin A. , Gerardin Jaline , Proctor Joshua L. , Wu Meikang , Harding Dennis , Hollingsworth T. Deirdre , Bhatt Samir , Gething Peter W.
Published: April 2023

Background

As both mechanistic and geospatial malaria modeling methods become more integrated into malaria policy decisions, there is increasing demand for strategies that combine these two methods. This paper introduces a novel archetypes-based methodology for generating high-resolution intervention impact maps based on mechanistic model simulations. An example configuration of the framework is described and explored.

Methods

First, dimensionality reduction and clustering techniques were applied to rasterized geospatial environmental and mosquito covariates to find archetypal malaria transmission patterns. Next, mechanistic models were run on a representative site from each archetype to assess intervention impact. Finally, these mechanistic results were reprojected onto each pixel to generate full maps of intervention impact. The example configuration used ERA5 and Malaria Atlas Project covariates, singular value decomposition, k-means clustering, and the Institute for Disease Modeling’s EMOD model to explore a range of three-year malaria interventions primarily focused on vector control and case management.

Results

Rainfall, temperature, and mosquito abundance layers were clustered into ten transmission archetypes with distinct properties. Example intervention impact curves and maps highlighted archetype-specific variation in efficacy of vector control interventions. A sensitivity analysis showed that the procedure for selecting representative sites to simulate worked well in all but one archetype.

Conclusion

This paper introduces a novel methodology which combines the richness of spatiotemporal mapping with the rigor of mechanistic modeling to create a multi-purpose infrastructure for answering a broad range of important questions in the malaria policy space. It is flexible and adaptable to a range of input covariates, mechanistic models, and mapping strategies and can be adapted to the modelers’ setting of choice.
Application of mathematical modelling to inform national malaria intervention planning in Nigeria
Authors: Ozodiegwu Ifeoma D. , Ambrose Monique , Galatas Beatriz , Runge Manuela , Nandi Aadrita , Okuneye Kamaldeen , Dhanoa Neena Parveen , Maikore Ibrahim , Uhomoibhi Perpetua , Bever Caitlin , Noor Abdisalan , Gerardin Jaline
Published: April 2023

Background

For their 2021–2025 National Malaria Strategic Plan (NMSP), Nigeria’s National Malaria Elimination Programme (NMEP), in partnership with the World Health Organization (WHO), developed a targeted approach to intervention deployment at the local government area (LGA) level as part of the High Burden to High Impact response. Mathematical models of malaria transmission were used to predict the impact of proposed intervention strategies on malaria burden.

Methods

An agent-based model ofPlasmodium falciparumtransmission was used to simulate malaria morbidity and mortality in Nigeria’s 774 LGAs under four possible intervention strategies from 2020 to 2030. The scenarios represented the previously implemented plan (business-as-usual), the NMSP at an 80% or higher coverage level and two prioritized plans according to the resources available to Nigeria. LGAs were clustered into 22 epidemiological archetypes using monthly rainfall, temperature suitability index, vector abundance, pre-2010 parasite prevalence, and pre-2010 vector control coverage. Routine incidence data were used to parameterize seasonality in each archetype. Each LGA’s baseline malaria transmission intensity was calibrated to parasite prevalence in children under the age of five years measured in the 2010 Malaria Indicator Survey (MIS). Intervention coverage in the 2010–2019 period was obtained from the Demographic and Health Survey, MIS, the NMEP, and post-campaign surveys.

Results

Pursuing a business-as-usual strategy was projected to result in a 5% and 9% increase in malaria incidence in 2025 and 2030 compared with 2020, while deaths were projected to remain unchanged by 2030. The greatest intervention impact was associated with the NMSP scenario with 80% or greater coverage of standard interventions coupled with intermittent preventive treatment in infants and extension of seasonal malaria chemoprevention (SMC) to 404 LGAs, compared to 80 LGAs in 2019. The budget-prioritized scenario with SMC expansion to 310 LGAs, high bed net coverage with new formulations, and increase in effective case management rate at the same pace as historical levels was adopted as an adequate alternative for the resources available.

Conclusions

Dynamical models can be applied for relative assessment of the impact of intervention scenarios but improved subnational data collection systems are required to allow increased confidence in predictions at sub-national level.
The association of intimate partner violence and contraceptive use: a multi-country analysis of demographic and health surveys
Authors: Muluneh Muluken Dessalegn , Francis Lyn , Agho Kingsley , Stulz Virginia
Published: April 2023

Background

Intimate partner violence (IPV) affects millions of women each year and has been recognized as a leading cause of poor health, disability, and death among women of reproductive age. However, the existing studies about the association between IPV and contraceptive use have been found to be conflicting and relatively less studied, particularly in low and middle income countries, including Eastern Sub Saharan Africa (SSA). This study examines the relationship between IPV and contraceptive use in Eastern SSA countries.

Methods

The Demographic and Health Surveys (DHS) from 2014 to 2017 were a multi-stage cluster sample survey of 30,715 ever married (or cohabitating) women of reproductive age from six countries. The six Eastern SSA datasets were pooled and multivariable logistic regression using a hierarchical approach was performed to examine the association between IPV and contraceptive use after adjusting for women, partners, and household and health facility factors.

Result

Two thirds of women 67% [66.55, 67.88] were not using any modern contraceptive methods and almost half (48%) of the women had experienced at least one form of IPV from their partners. Our analysis showed a strong association with decreased odds of physical violence [adjusted odds ratios (aOR) = 0.72, 95%CI: 0.67, 0 0.78] among women not using any contraceptive methods. Other factors associated with women not using any contraceptive methods were older women (35–49 years), illiterate couples and women from poorest households. Women who had no access to any form of communication [aOR = 1.12, 95%CI: 1.08, 1.36], unemployed partner [aOR = 1.55, 95%CI: 1.23, 1.95] and women who travelled long distances to access health services [aOR = 1.16, 95%CI: 1.06, 1.26] significantly reported increased odds of not using any contraceptive methods.

Conclusion

Our study indicated that physical violence was negatively associated with not using any contraceptive method among married women in Eastern SSA countries. Tailored intervention messages to reduce IPV including physical violence among women not using contraceptive methods in East Africa should target those from low-socioeconomic groups especially, older women with no access to any form of communication, unemployed partners, and illiterate couples.
MicroRNA-19b-3p dysfunction of mesenchymal stem cell-derived exosomes from patients with abdominal aortic aneurysm impairs therapeutic efficacy
Authors: Zhang Yuxiao , Huang Xiaoran , Sun Tucheng , Shi Linli , Liu Baojuan , Hong Yimei , Fu Qing-Ling , Zhang Yuelin , Li Xin
Published: April 2023

Senescence of vascular smooth muscle cells (VSMCs) contributes to the formation of abdominal aortic aneurysm (AAA). Although mesenchymal stem cell exosomes (MSC-EXO) have been confirmed to restrict the development of AAA, their biological activity depends largely on the physiological state of the MSCs. This study aimed to compare the effects of adipose-derived MSC-EXO from healthy donors (HMEXO) and AAA patients (AMEXO) on senescence of VSMCs in AAA and explore the underlying mechanisms. An ApoE-/- mouse model of AAA was used to investigate the therapeutic effects of HMEXO, AMEXO or miR-19b-3p-AMEXO on AAA development. This in vitro model of AAA was established by treating VSMCs with Ang II (Angiotensin II). The senescence of VSMCs was determined by senescence-associated β-galactosidase (SA-β-gal) staining. The morphology of mitochondria in VSMCs was examined by MitoTracker staining. HMEXO exhibited superior capacity compared with AMEXO to inhibit VSMC senescence and attenuate AAA formation in Ang II–treated ApoE-/- mice. In vitro, both AMEXO and HMEXO inhibited Ang II-induced VSMC senescence via downregulation of mitochondrial fission. Notably, compared with HMEXO, the ability of AMEXO to inhibit VSMC senescence was significantly decreased. miRNA sequencing and the expression of miR-19b-3p was significantly decreased in AMEXO compared with HMEXO. Luciferase assay suggested that MST4 (Mammalian sterile-20-like kinase 4) is a potential target of miR-19b-3p. Mechanistically, miR-19b-3p in HMEXO ameliorated VSMC senescence by inhibiting mitochondrial fission via regulation of the MST4/ERK/Drp1 signaling pathway. Overexpression of miR-19b-3p in AMEXO improved their beneficial effect on AAA formation. Our study reveals that MSC-exosomal miR-19b-3p exerts protective effects against Ang II-induced AAA and VSMC senescence via regulation of the MST4/ERK/Drp1 pathway. The pathological state of AAA patients alters the miRNA components of AMEXO and impairs their therapeutic benefits.
Adherence to the World Health Organization’s physical activity recommendation in preschool-aged children: a systematic review and meta-analysis of accelerometer studies
Authors: Bourke Matthew , Haddara Ameena , Loh Aidan , Carson Valerie , Breau Becky , Tucker Patricia
Published: April 2023

Background

The World Health Organization (WHO) recommend that preschool-aged children should engage in 180 min of total physical activity (TPA) including 60 min of moderate-to-vigorous physical activity (MVPA) each day. No systematic reviews or meta-analyses have pooled adherence to the recommendation across multiple studies. This study aimed to estimate the prevalence of preschool-aged children achieving the WHO’s physical activity recommendation for young children, and determine if the prevalence differed between boys and girls.

Methods

Primary literature searches were conducted on six online databases and a machine learning assisted systematic review was used to identify relevant studies. Studies written in English reporting on the prevalence of children aged 3–5 years achieving overall WHO physical activity recommendation or the individual TPA or MVPA aspects of the recommendation measured using accelerometers were eligible for inclusion. Random effects meta-analysis was used to determine the prevalence of preschools achieving the overall WHO recommendation and the individual TPA and MVPA aspect of the recommendation, and to determine difference in prevalence between boys and girls.

Results

Forty-eight studies reporting on 20,078 preschool-aged children met the inclusion criteria. Based on the most commonly employed accelerometer cut-points across all aspects of the recommendation, 60% (95% Confidence Interval [CI] = 37%, 79%) of preschool-aged children adhered to the overall physical activity recommendation, 78% (95% CI = 38%, 95%) adhered to the TPA aspect of the recommendation, and 90% (95% CI = 81%, 95%) adhered to the MVPA aspect of the recommendation. There was substantial variability is prevalence estimates between different accelerometer cut-points. Girls were significantly less likely to achieve the overall recommendation and the MVPA aspect of the recommendation than boys were.

Conclusions

Although there was substantial variability in estimated prevalence of preschool-aged children adhering the WHO physical activity recommendation between various accelerometer cut-points, the weight of available evidence suggests that the majority of young children are adhering to the overall recommendation and the individual TPA and MVPA aspects of the recommendation. Large-scale, intercontinental surveillance studies are needed to further strengthen the evidence regarding the prevalence of preschool-aged children achieving physical activity recommendation globally.
A dominant variant in apoptosis-related gene XKR8 is relevant to hereditary auditory neuropathy
Authors: Chen Kaitian , Li Changwu , Dong Chang , Cen Xiaoqing , Wang Yueying , Liang Yue , Zhu Yuanping , Fang Shubin , Jiang Hongyan
Published: April 2023

Background

Auditory neuropathy is an unusual type of hearing loss. At least 40% of patients with this disease have underlying genetic causes. However, in many hereditary auditory neuropathy cases, etiology remains undetermined.

Methods

We collected data and blood samples from a four-generation Chinese family. After excluding relevant variants in known deafness-related genes, exome sequencing was conducted. Candidate genes were verified by pedigree segregation, transcript/protein expression in the mouse cochlea, and plasmid expression studies in HEK 293T cells. Moreover, a mutant mouse model was generated and underwent hearing evaluations; protein localization in the inner ear was also assessed.

Results

The clinical features of the family were diagnosed as auditory neuropathy. A novel variant c.710G > A (p.W237X) in apoptosis-related geneXKR8was identified. Genotyping of 16 family members confirmed the segregation of this variant with the deafness phenotype. BothXKR8mRNA and XKR8 protein were expressed in the mouse inner ear, predominantly in regions of spiral ganglion neurons; Moreover, this nonsense variant impaired the surface localization of XKR8 in cells. Transgenic mutant mice exhibited late-onset auditory neuropathy, and their altered XKR8 protein localization in the inner ear confirmed the damaging effects of this variant.

Conclusions

We identified a variant in theXKR8gene that is relevant to auditory neuropathy. The essential role ofXKR8in inner ear development and neural homeostasis should be explored.
Multiphase preclinical assessment of a novel device to locate unintentionally retained surgical sharps: a proof-of-concept study
Authors: Kang Hae Sung , Khoraki Jad , Gie Jessie , Duval Dielle , Haynes Susan , Siev Michael , Shah Jay , Kim Fernando , Mangino Martin , Procter Levi , Autorino Riccardo , Weprin Samuel
Published: April 2023

Background

Retained surgical sharps (RSS) is a “never event” that is preventable but may still occur despite of correct count and negative X-ray. This study assesses the feasibility of a novel device (“Melzi Sharps Finder®” or MSF) in effective detection of RSS.

Methods

The first study consisted of determination of the presence of RSS or identification of RSS in an ex-vivo model (a container with hay in a laparoscopic trainer box). The second study consisted of determining presence of RSS in an in-vivo model (laparoscopy in live adult Yorkshire pigs) with 3 groups: C-arm, C-arm with MSF and MSF. The third study used similar apparatus though with laparotomy and included 2 groups: manual search and MSF.

Results

In the first study, the MSF group had a higher rate of identification of a needle and decreased time to locate a needle versus control (98.1% vs. 22.0%, p < 0.001; 1.64 min ± 1.12vs. 3.34 min ± 1.28, p < 0.001). It also had increased accuracy of determining the presence of a needle and decreased time to reach this decision (100% vs. 58.8%, p < 0.001; 1.69 min ± 1.43 vs. 4.89 min ± 0.63, p < 0.001). In-the second study, the accuracy of determining the presence of a needle and time to reach this decision were comparable in each group (88.9% vs. 100% vs. 84.5%, p < 0.49; 2.2 min ± 2.2 vs. 2.7 min ± 2.1vs. 2.8 min ± 1.7, p = 0.68). In the third study, MSF group had higher accuracy in determining the presence of a needle and decreased time to reach this decision than the control (97.0% vs. 46.7%, p < 0.001; 2.0 min ± 1.5 vs. 3.9 min ± 1.4; p < 0.001). Multivariable analysis showed that MSF use was independently associated with an accurate determination of the presence of a needle (OR 12.1, p < 0.001).

Conclusions

The use of MSF in this study’s RSS models facilitated the determination of presence and localization of RSS as shown by the increased rate of identification of a needle, decreased time to identification and higher accuracy in determining the presence of a needle. This device may be used in conjunction with radiography as it gives live visual and auditory feedback for users during the search for RSS.
The impact of the COVID-19 pandemic on eating disorders risk and symptoms: a retrospective study
Authors: Straface Elisabetta , Jacobis Isabella Tarissi De , Capriati Teresa , Pretelli Italo , Grandin Annalisa , Mascolo Cristina , Vona Rosa , Gambardella Lucrezia , Cittadini Camilla , Villani Alberto , Marchili Maria Rosaria
Published: April 2023

Background

Social distancing and quarantine imposed by the authority during the COVID-19 pandemic caused restrictions, which had a negative impact on eating behavior, especially among adolescents. We proposed a retrospective study aimed to evaluate the effect of the COVID-19 pandemic on eating disorders risk and symptoms.

Methods

In this study, a group of 127 pediatric patients (117 females and 10 males) with eating disorders admitted to the Bambino Gesù Children’s Hospital of Rome (Italy), in the period between August 2019 and April 2021, was analyzed. All patient data were collected from patients’ electronic medical records.

Results

We found that 80.3% of patients were at the onset of eating disorders and that 26% of patients had familiarity for psychotic disorders. Often these patients had comorbidities and alterations in blood parameters such as leukocytopenia, neutropenia, hypovitaminosis and hormonal problems that could affect their future.

Conclusions

Our findings could provide a framework for developing clinical and educational interventions to mitigate the short- and long-term negative impact of the pandemic on adolescent future health.
Early non-invasive ventilation and high-flow nasal oxygen therapy for preventing endotracheal intubation in hypoxemic blunt chest trauma patients: the OptiTHO randomized trial
Authors: Carrié Cédric , Rieu Benjamin , Benard Antoine , Trin Kilian , Petit Laurent , Massri Alexandre , Jurcison Igor , Rousseau Guillaume , Tran Van David , Reynaud Salard Marie , Bourenne Jeremy , Levrat Albrice , Muller Laurent , Marie Damien , Dahyot-Fizelier Claire , Pottecher Julien , David Jean-Stéphane , Godet Thomas , Biais Matthieu
Published: April 2023

Background

The benefit–risk ratio of prophylactic non-invasive ventilation (NIV) and high-flow nasal oxygen therapy (HFNC-O2) during the early stage of blunt chest trauma remains controversial because of limited data. The main objective of this study was to compare the rate of endotracheal intubation between two NIV strategies in high-risk blunt chest trauma patients.

Methods

The OptiTHO trial was a randomized, open-label, multicenter trial over a two-year period. Every adult patients admitted in intensive care unit within 48 h after a high-risk blunt chest trauma (Thoracic Trauma Severity Score ≥ 8), an estimated PaO2/FiO2 ratio < 300 and no evidence of acute respiratory failure were eligible for study enrollment (Clinical Trial Registration: NCT03943914). The primary objective was to compare the rate of endotracheal intubation for delayed respiratory failure between two NIV strategies: i) a prompt association of HFNC-O2 and “early” NIV in every patient for at least 48 h with vs. ii) the standard of care associating COT and “late” NIV, indicated in patients with respiratory deterioration and/or PaO2/FiO2 ratio ≤ 200 mmHg. Secondary outcomes were the occurrence of chest trauma-related complications (pulmonary infection, delayed hemothorax or moderate-to-severe ARDS).

Results

Study enrollment was stopped for futility after a 2-year study period and randomization of 141 patients. Overall, 11 patients (7.8%) required endotracheal intubation for delayed respiratory failure. The rate of endotracheal intubation was not significantly lower in patients treated with the experimental strategy (7% [5/71]) when compared to the control group (8.6% [6/70]), with an adjusted OR = 0.72 (95%IC: 0.20–2.43), p = 0.60. The occurrence of pulmonary infection, delayed hemothorax or delayed ARDS was not significantly lower in patients treated by the experimental strategy (adjusted OR = 1.99 [95%IC: 0.73–5.89], p = 0.18, 0.85 [95%IC: 0.33–2.20], p = 0.74 and 2.14 [95%IC: 0.36–20.77], p = 0.41, respectively).

Conclusion

A prompt association of HFNC-O2 with preventive NIV did not reduce the rate of endotracheal intubation or secondary respiratory complications when compared to COT and late NIV in high-risk blunt chest trauma patients with non-severe hypoxemia and no sign of acute respiratory failure.

Clinical Trial Registration: NCT03943914, Registered 7 May 2019.
An optimized reverse β-oxidation pathway to produce selected medium-chain fatty acids in Saccharomyces cerevisiae
Authors: Garces Daza Fernando , Haitz Fabian , Born Alice , Boles Eckhard
Published: April 2023

Background

Medium-chain fatty acids are molecules with applications in different industries and with growing demand. However, the current methods for their extraction are not environmentally sustainable. The reverse β-oxidation pathway is an energy-efficient pathway that produces medium-chain fatty acids in microorganisms, and its use in Saccharomyces cerevisiae, a broadly used industrial microorganism, is desired. However, the application of this pathway in this organism has so far either led to low titers or to the predominant production of short-chain fatty acids.

Results

We genetically engineered Saccharomyces cerevisiae to produce the medium-chain fatty acids hexanoic and octanoic acid using novel variants of the reverse β-oxidation pathway. We first knocked out glycerolphosphate dehydrogenase GPD2 in an alcohol dehydrogenases knock-out strain (△adh1-5) to increase the NADH availability for the pathway, which significantly increased the production of butyric acid (78 mg/L) and hexanoic acid (2 mg/L) when the pathway was expressed from a plasmid with BktB as thiolase. Then, we tested different enzymes for the subsequent pathway reactions: the 3-hydroxyacyl-CoA dehydrogenase PaaH1 increased hexanoic acid production to 33 mg/L, and the expression of enoyl-CoA hydratases Crt2 or Ech was critical to producing octanoic acid, reaching titers of 40 mg/L in both cases. In all cases, Ter from Treponema denticola was the preferred trans-enoyl-CoA reductase. The titers of hexanoic acid and octanoic acid were further increased to almost 75 mg/L and 60 mg/L, respectively, when the pathway expression cassette was integrated into the genome and the fermentation was performed in a highly buffered YPD medium. We also co-expressed a butyryl-CoA pathway variant to increase the butyryl-CoA pool and support the chain extension. However, this mainly increased the titers of butyric acid and only slightly increased that of hexanoic acid. Finally, we also tested the deletion of two potential medium-chain acyl-CoA depleting reactions catalyzed by the thioesterase Tes1 and the medium-chain fatty acyl CoA synthase Faa2. However, their deletion did not affect the production titers.

Conclusions

By engineering the NADH metabolism and testing different reverse β-oxidation pathway variants, we extended the product spectrum and obtained the highest titers of octanoic acid and hexanoic acid reported in S. cerevisiae. Product toxicity and enzyme specificity must be addressed for the industrial application of the pathway in this organism.
Autonomic neuropathic symptoms in patients with diabetes: practical tools for screening in daily routine
Authors: de Azevedo Vieira Ana Raquel Souza , Porto-Dantas Lara Benigno , do Prado Romani Flaviene Alves , Carvalho Patrícia Souza , Pop-Busui Rodica , Pedrosa Hermelinda Cordeiro
Published: April 2023

Background

Diabetic autonomic neuropathy (DAN) is a frequent complication in people with diabetes whose screening is often neglected. This study aimed to evaluate DAN through practical tools in people with diabetes in a referral center for diabetes treatment.

Methods

DAN symptoms and severity were assessed using the Survey of Autonomic Symptoms (SAS) via digital application (app) in patients attended from June 1, 2021, to November 12, 2021. SAS scoring for DAN was performed using established validated cutoffs. The adhesive with cobalt salt color indicator (Neuropad™) was used as a measure of sudomotor dysfunction. Demographical and clinical data were also collected.

Results

Data from 109 participants, 66.9% T2DM, 73.4% female, with a median age of 54.00 (± 20.00) years, were analyzed. Symptomatic DAN was present in 69.7% of participants and was associated with older age (p = 0.002), higher HbA1c (p = 0.043), higher abdominal circumference (p = 0.019), higher BMI (p = 0.013), more likely to have metabolic syndrome (MS) with a 10-fold increased risk, and more frequent association with diabetic peripheral neuropathy (p = 0.005). Sudomotor dysfunction was found in 65 participants with positive Neuropad™ detected in 63.1% of them.

Conclusion

The use of SAS through an app proved to be a practical and easy-to-use instrument to document symptoms of DAN in busy clinical practice. The high frequency of symptoms draws attention to the importance of screening this underdiagnosed diabetes complication. The risk factors and comorbidities associated with symptomatic DAN highlight the patients’ phenotypes linked to MS that should be targeted for DAN evaluations in larger samples in the community.
An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients
Authors: Chen Jianhong , Long Mark D. , Sribenja Sirinapa , Ma Sung Jun , Yan Li , Hu Qiang , Liu Song , Khoury Thaer , Hong Chi-Chen , Bandera Elisa , Singh Anurag K. , Repasky Elizabeth A. , Bouchard Elizabeth G. , Higgins Michael , Ambrosone Christine B. , Yao Song
Published: April 2023

Background

Disadvantaged socioeconomic position (SEP), including lower educational attainment and household income, may influence cancer risk and outcomes. We hypothesized that DNA methylation could function as an intermediary epigenetic mechanism that internalizes and reflects the biological impact of SEP.

Methods

Based on tumor DNA methylation data from the Illumina 450 K array from 694 breast cancer patients in the Women’s Circle of Health Study, we conducted an epigenome-wide analysis in relation to educational attainment and household income. Functional impact of the identified CpG sites was explored in silico using data from publicly available databases.

Results

We identified 25 CpG sites associated with household income at an array-wide significance level, but none with educational attainment. Two of the top CpG sites, cg00452016 and cg01667837, were in promoter regions of NNT and GPR37, respectively, with multiple epigenetic regulatory features identified in each region. NNT is involved in β-adrenergic stress signaling and inflammatory responses, whereas GPR37 is involved in neurological and immune responses. For both loci, gene expression was inversely correlated to the levels of DNA methylation. The associations were consistent between Black and White women and did not differ by tumor estrogen receptor (ER) status.

Conclusions

In a large breast cancer patient population, we discovered evidence of the significant biological impact of household income on the tumor DNA methylome, including genes in the β-adrenergic stress and immune response pathways. Our findings support biological effects of socioeconomic status on tumor tissues, which might be relevant to cancer development and progression.
ADHD genetic burden associates with older epigenetic age: mediating roles of education, behavioral and sociodemographic factors among older adults
Authors: Arpawong Thalida E. , Klopack Eric T. , Kim Jung Ki , Crimmins Eileen M.
Published: April 2023

Background

Shortened lifespans are associated with having Attention Deficit Hyperactivity Disorder (ADHD), which is likely mediated by related behavioral and sociodemographic factors that are also associated with accelerated physiological aging. Such factors include exhibiting more depressive symptoms, more cigarette smoking, higher body mass index, lower educational attainment, lower income in adulthood, and more challenges with cognitive processes compared to the general population. A higher polygenic score for ADHD (ADHD-PGS) is associated with having more characteristic features of ADHD. The degree to which (1) the ADHD-PGS associates with an epigenetic biomarker developed to predict accelerated aging and earlier mortality is unknown, as are whether (2) an association would be mediated by behavioral and sociodemographic correlates of ADHD, or (3) an association would be mediated first by educational attainment, then by behavioral and sociodemographic correlates. We evaluated these relationships in a population-based sample from the US Health and Retirement Study, among N = 2311 adults age 50 and older, of European-ancestry, with blood-based epigenetic and genetic data. The ADHD-PGS was calculated from a prior genomewide meta-analysis. Epigenome-wide DNA methylation levels that index biological aging and earlier age of mortality were quantified by a blood-based biomarker called GrimAge. We used a structural equation modeling approach to test associations with single and multi-mediation effects of behavioral and contextual indicators on GrimAge, adjusted for covariates.

Results

The ADHD-PGS was significantly and directly associated with GrimAge when adjusting for covariates. In single mediation models, the effect of the ADHD-PGS on GrimAge was partially mediated via smoking, depressive symptoms, and education. In multi-mediation models, the effect of the ADHD-PGS on GrimAge was mediated first through education, then smoking, depressive symptoms, BMI, and income.

Conclusions

Findings have implications for geroscience research in elucidating lifecourse pathways through which ADHD genetic burden and symptoms can alter risks for accelerated aging and shortened lifespans, when indexed by an epigenetic biomarker. More education appears to play a central role in attenuating negative effects on epigenetic aging from behavioral and sociodemographic risk factors related to ADHD. We discuss implications for the potential behavioral and sociodemographic mediators that may attenuate negative biological system effects.
Environmental factors influencing detection efficiency of an acoustic telemetry array and consequences for data interpretation
Authors: Long Michael , Jordaan Adrian , Castro-Santos Theodore
Published: April 2023

Background

Acoustic telemetry is a commonly used technology to monitor animal occupancy and infer movement in aquatic environments. The information that acoustic telemetry provides is vital for spatial planning and management decisions concerning aquatic and coastal environments by characterizing behaviors and habitats such as spawning aggregations, migrations, corridors, and nurseries, among others. However, performance of acoustic telemetry equipment and resulting detection ranges and efficiencies can vary as a function of environmental conditions, leading to potentially biased interpretations of telemetry data. Here, we characterize variation in detection performance using an acoustic telemetry receiver array deployed in Wellfleet Harbor, Massachusetts, USA from 2015 to 2017. The array was designed to study benthic invertebrate movements and provided an in situ opportunity to identify factors driving variation in detection probability.

Results

The near-shore location proximate to environmental monitoring allowed for a detailed examination of factors influencing detection efficiency in a range-testing experiment. Detection ranges varied from < 50 to 1,500 m and efficiencies varied from 0 to 100% within those detection ranges. Detection efficiency was affected by distance, wind speed and direction, wave height and direction, water temperature, water depth, and water quality.

Conclusions

Performance of acoustic telemetry systems is strongly contingent on environmental conditions. Our study found that wind, waves, water temperature, water quality, and depth all affected performance to an extent that could seriously compromise a study if these effects were not taken into consideration. Other unmeasured factors may also be important, depending on the characteristics of each site. This information can help guide future telemetry study designs by helping researchers anticipate the density of receivers required to achieve study objectives. Researchers can further refine and document the reliability of their data by incorporating continuously deployed range-testing tags and prior knowledge on varying detection efficiency into movement and occupancy models.