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BioRxiv : the Preprint Server For... May 2024Chromosomal instability (CIN) is a hallmark of cancer that drives metastasis, immune evasion and treatment resistance. CIN results from chromosome mis-segregation events...
Chromosomal instability (CIN) is a hallmark of cancer that drives metastasis, immune evasion and treatment resistance. CIN results from chromosome mis-segregation events during anaphase, as excessive chromatin is packaged in micronuclei (MN), that can be enumerated to quantify CIN. Despite recent advancements in automation through computer vision and machine learning, the assessment of CIN remains a predominantly manual and time-consuming task, thus hampering important work in the field. Here, we present , a novel pipeline for automated and reliable quantification of MN of varying size, morphology and location from DNA-only stained images. In , single-cell crops are extracted from high-resolution microscopy images with the help of segmentation masks, which are then used to train a convolutional neural network (CNN) to output the number of MN associated with each cell. The pipeline was evaluated against manual single-cell level counts by experts and against routinely used MN ratio within the complete image. The classifier was able to achieve a weighted F1 score of 0.937 on the test dataset and the complete pipeline can achieve close to human-level performance on various datasets derived from multiple human and murine cancer cell lines. The pipeline achieved a root-mean-square deviation (RMSE) value of 0.0041, an R of 0.87 and a Pearson's correlation of 0.938 on images obtained at 10X magnification. We tested the approach in otherwise isogenic cell lines in which we genetically dialed up or down CIN rates, and also on a publicly available image data set (obtained at 100X) and achieved an RMSE value of 0.0159, an R of 0.90, and a Pearson's correlation of 0.951. Given the increasing interest in developing therapies for CIN-driven cancers, this method provides an important, scalable, and rapid approach to quantifying CIN on routinely obtained images. We release a GUI-implementation for easy access and utilization of the pipeline.
PubMed: 38854106
DOI: 10.1101/2024.05.24.595722 -
MedRxiv : the Preprint Server For... May 2024Sleep-wake disturbances frequently present in Veterans with mild traumatic brain injury (mTBI). These TBI-related sleep impairments confer significant burden and...
Feasibility and acceptability for LION, a fully remote, randomized clinical trial within the VA for light therapy to improve sleep in Veterans with and without TBI: An MTBI sponsored protocol: LION: A remote RCT protocol within VA.
Sleep-wake disturbances frequently present in Veterans with mild traumatic brain injury (mTBI). These TBI-related sleep impairments confer significant burden and commonly exacerbate other functional impairments. Therapies to improve sleep following mTBI are limited and studies in Veterans are even more scarce. In our previous pilot work, morning bright light therapy (MBLT) was found to be a feasible behavioral sleep intervention in Veterans with a history of mTBI; however, this was single-arm, open-label, and non-randomized, and therefore was not intended to establish efficacy. The present study, LION (light vs ion therapy) extends this preliminary work as a fully powered, sham-controlled, participant-masked randomized controlled trial (NCT03968874), implemented as fully remote within the VA (target n=120 complete). Randomization at 2:1 allocation ratio to: 1) active: MBLT (n=80), and 2) sham: deactivated negative ion generator (n=40); each with identical engagement parameters (60-min duration; within 2-hrs of waking; daily over 28-day duration). Participant masking via deception balanced expectancy assumptions across arms. Outcome measures were assessed following a 14-day baseline (pre-intervention), following 28-days of device engagement (post-intervention), and 28-days after the post-intervention assessment (follow-up). Primary outcomes were sleep measures, including continuous wrist-based actigraphy, self-report, and daily sleep dairy entries. Secondary/exploratory outcomes included cognition, mood, quality of life, circadian rhythm via dim light melatonin onset, and biofluid-based biomarkers. Participant drop out occurred in <10% of those enrolled, incomplete/missing data was present in <15% of key outcome variables, and overall fidelity adherence to the intervention was >85%, collectively establishing feasibility and acceptability for MBLT in Veterans with mTBI.
PubMed: 38853958
DOI: 10.1101/2024.05.30.24308195 -
Ophthalmology Jun 2024DRCR.net Protocol T data suggest the response to treatment among patients with diabetic macular edema (DME) may vary depending on baseline best-corrected visual acuity...
PURPOSE
DRCR.net Protocol T data suggest the response to treatment among patients with diabetic macular edema (DME) may vary depending on baseline best-corrected visual acuity (BCVA). We evaluated the efficacy of faricimab 6 mg versus aflibercept 2 mg over 2 years in patients with DME enrolled in faricimab phase 3 trials with baseline Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA ≤20/50.
DESIGN
YOSEMITE/RHINE were identically designed, multicenter, randomized, double-masked, active comparator-controlled, noninferiority trials.
PARTICIPANTS
Adults aged ≥18 years with center-involving macular edema secondary to type 1 or 2 diabetes.
METHODS
Patients were randomized to faricimab every 8 weeks (Q8W), faricimab per a personalized treat-and-extend-based regimen (T&E), or aflibercept Q8W. Post hoc subgroup analyses were conducted using the intent-to-treat population with baseline BCVA ≤20/50 (ETDRS letters <69).
MAIN OUTCOME MEASURES
Changes in ETDRS BCVA and central subfield thickness (CST) from baseline to years 1 and 2 were compared between treatment arms using mixed-model repeated measures analyses.
RESULTS
In YOSEMITE/RHINE, 220/217 patients in the faricimab Q8W; 220/219, faricimab T&E; and 219/214, aflibercept Q8W arms had baseline BCVA ≤20/50. In both trials, mean change in ETDRS BCVA was comparable between treatments at years 1 and 2. In YOSEMITE, adjusted mean (95% CI) change from baseline in CST (μm) at year 1 was greater with faricimab Q8W (-232.8 [-243.5, -222.1]) and faricimab T&E (-217.4 [-227.9, -206.9]) versus aflibercept Q8W (-190.4 [-200.9, -179.8]; P<0.0001 and P=0.0004, respectively). The pattern was similar in RHINE: faricimab Q8W, -214.2 (-225.3, -203.1); faricimab T&E, -206.6 (-217.4, -195.7); aflibercept Q8W, -186.6 (-197.7, -175.5); P=0.0006 and P=0.0116 for faricimab arms versus aflibercept, respectively. In both trials, change from baseline in CST at year 2 was greater with faricimab Q8W versus aflibercept. Median time to first CST <325 μm and first absence of intraretinal fluid was shorter in the faricimab arms versus aflibercept, with fewer injections on average.
CONCLUSIONS
In patients with DME and baseline ETDRS BCVA ≤20/50, faricimab treatment resulted in comparable visual acuity, greater reduction in retinal thickness, and fewer injections compared with aflibercept over 2 years of treatment.
PubMed: 38852921
DOI: 10.1016/j.ophtha.2024.05.025 -
Chemosphere Aug 2024The widespread presence of microplastics (MPs) in the air and their potential impact on human health underscore the pressing need to develop robust methods for...
The widespread presence of microplastics (MPs) in the air and their potential impact on human health underscore the pressing need to develop robust methods for quantifying their presence, particularly in the breathable fraction (<5 μm). In this study, Raman micro-spectroscopy (μRaman) was employed to assess the concentration of indoor airborne MPs >1 μm in four indoor environments (a meeting room, a workshop, and two apartments) under different levels of human activity. The indoor airborne MP concentration spanned between 58 and 684 MPs per cubic meter (MP m) (median 212 MP m, MPs/non-plastic ratio 0-1.6%), depending not only on the type and level of human activity, but also on the surface area and air circulation of the investigated locations. Additionally, we assessed in the same environments the filtration performance of a type IIR surgical facemask, which could overall retain 85.4 ± 3.9% of the MPs. We furthermore estimated a human MP intake from indoor air of 3415 ± 2881 MPs day (mostly poly-amide MPs), which could be decreased to 283 ± 317 MPs day using the surgical facemask. However, for the breathable fraction of MPs (1-5 μm), the efficiency of the surgical mask was reduced to 57.6%.
Topics: Air Pollution, Indoor; Microplastics; Humans; Environmental Monitoring; Air Pollutants; Spectrum Analysis, Raman; Masks
PubMed: 38851509
DOI: 10.1016/j.chemosphere.2024.142553 -
Lancet (London, England) Jun 2024After surgery for a broken ankle, patients are usually instructed to avoid walking for 6 weeks (delayed weight-bearing). Walking 2 weeks after surgery (early...
BACKGROUND
After surgery for a broken ankle, patients are usually instructed to avoid walking for 6 weeks (delayed weight-bearing). Walking 2 weeks after surgery (early weight-bearing) might be a safe and preferable rehabilitation strategy. This study aimed to determine the clinical and cost effectiveness of an early weight-bearing strategy compared with a delayed weight-bearing strategy.
METHODS
This was a pragmatic, multicentre, randomised, non-inferiority trial including 561 participants (aged ≥18 years) who received acute surgery for an unstable ankle fracture in 23 UK National Health Service (NHS) hospitals who were assigned to either a delayed weight-bearing (n=280) or an early weight-bearing rehabilitation strategy (n=281). Patients treated with a hindfoot nail, those who did not have protective ankle sensation (eg, peripheral neuropathy), did not have the capacity to consent, or did not have the ability to adhere to trial procedures were excluded. Neither participants nor clinicians were masked to the treatment. The primary outcome was ankle function measured using the Olerud and Molander Ankle Score (OMAS) at 4 months after randomisation, in the per-protocol population. The pre-specified non-inferiority OMAS margin was -6 points and superiority testing was included in the intention-to-treat population in the event of non-inferiority. The trial was prospectively registered with ISRCTN Registry, ISRCTN12883981, and the trial is closed to new participants.
FINDINGS
Primary outcome data were collected from 480 (86%) of 561 participants. Recruitment was conducted between Jan 13, 2020, and Oct 29, 2021. At 4 months after randomisation, the mean OMAS score was 65·9 in the early weight-bearing and 61·2 in the delayed weight-bearing group and adjusted mean difference was 4·47 (95% CI 0·58 to 8·37, p=0·024; superiority testing adjusted difference 4·42, 95% CI 0·53 to 8·32, p=0·026) in favour of early weight-bearing. 46 (16%) participants in the early weight-bearing group and 39 (14%) in the delayed weight-bearing group had one or more complications (adjusted odds ratio 1·18, 95% CI 0·80 to 1·75, p=0·40). The mean costs from the perspective of the NHS and personal social services in the early and delayed weight-bearing groups were £725 and £785, respectively (mean difference -£60 [95% CI -342 to 232]). The probability that early weight-bearing is cost-effective exceeded 80%.
INTERPRETATION
An early weight-bearing strategy was found to be clinically non-inferior and highly likely to be cost-effective compared with the current standard of care (delayed weight-bearing).
FUNDING
National Institute for Health and Care Research (NIHR), NIHR Barts Biomedical Research Centre, and NIHR Applied Research Collaboration Oxford and Thames Valley.
PubMed: 38848738
DOI: 10.1016/S0140-6736(24)00710-4 -
Heliyon Jun 2024Cocoa beans are susceptible to fungal contamination during processing and storage. The knowledge of the use of pesticides and post-harvest handling of cocoa beans among...
Cocoa beans are susceptible to fungal contamination during processing and storage. The knowledge of the use of pesticides and post-harvest handling of cocoa beans among farmers is of great importance for safe consumption. The study evaluated common cocoa production and post-harvest practices of farmers in selected study locations in South Western Nigeria. Primary data were collected through the administration of structured questionnaires, and interviews. The collected data were analyzed using inferential descriptive statistics. The results of 394 farmers showed that 52.9 % in Osun and 47.3 % in Oyo were primarily farmers by occupation, the rest had other ventures. The majority of cocoa farmers were men:83.6 % in Oyo State, 88.2 % in Osun state and 87.9 % in Ondo state. 28.6 % and 32.7 % of farmers were aged 51-60 in the Ondo and Oyo communities, respectively. Osun farming communities are dominated by young adults (51 %) of 31-50 years, followed by Ondo 40 % and36 % of farmers in Oyo State. Most cocoa farmers were married with 4-6 children as the most common household size in Osun (51 %), Ondo (60.4 %) and 49.1 % in Oyo State. The literacy level of farmers in cocoa communities was the highest in Oyo state where 47.3 % had tertiary education. Farmers in Oyo State had better knowledge of the dangers of pesticides than Ondo and Osun. However, ignorance of dangers in agrochemicals was higher among Osun farmers than in Ondo State. The highest (18 %) pesticide use during storage was recorded among Oyo farmers, while the least (11.0 %) was recorded among farmers in Ondo State. Pesticide usage was more abundant in Osun (50 %) during cocoa production than in the other study areas. The majority of farmers were positively disposed to make use of nose masks during agrochemical application, meanwhile, 69 %, 62 %, and 61 % of farmers used them already in Oyo, Ondo, and Osun states, respectively. Educational qualification (χ = 9.176, p = 0.027) of cocoa farmers was significantly related to knowledge of best practices. Farmers with higher education have a greater ability to receive and process information relating to global best practices in production, postharvest, and pesticide handling in cocoa. In conclusion, cocoa farmers' knowledge of processing, use of pesticides, and storage practices differed from one location to another. Intensive orientation and more enlightenment by extension workers against indiscriminate use of pesticides in cocoa plantations and stores must be consistently and continuously done.
PubMed: 38846000
DOI: 10.1016/j.heliyon.2024.e31724 -
PloS One 2024This cross-sectional study aimed to determine 1) whether German citizens' adherence to health professionals' recommendations and mandates regarding protective masks...
This cross-sectional study aimed to determine 1) whether German citizens' adherence to health professionals' recommendations and mandates regarding protective masks during the COVID-19 pandemic varied according to their political party affiliations, and 2) how behavioral cues provided by members of shared social groups, such as family and friends, influenced individual mask-wearing behavior. A quota-based sample of German voters (n = 330) consisting of 55 citizens whose voting intentions aligned with each of the country's six main political parties responded to an online questionnaire consisting of multiple-choice and open-ended questions. Univariate descriptive statistical analyses of quantitative data were conducted, and multiple regressions were performed to determine log odds and significant variations among group-based responses. A pragmatic inductive coding process was used to conduct a thematic analysis of qualitative data. Results indicated that those participants who expressed an intention to vote for the populist radical right party were the least likely to follow health experts' recommendations and the most likely to express anger and dissatisfaction over mask mandates. Prospective Left Party voters were the most likely to adhere to the advice of their doctors, while those associated with the Green Party were the most likely to adhere to the advice of public health experts. Most survey participants reported aligning their mask-wearing behavior with that of family and friends, with prospective CDU/CSU voters particularly likely to consider the mask-wearing behavior of family members. The results indicate that public health officials should consider how group-related factors influence public health compliance in order to encourage protective mask-wearing in the future.
Topics: Humans; COVID-19; Germany; Masks; Male; Female; Adult; Middle Aged; Cross-Sectional Studies; Politics; Surveys and Questionnaires; Social Identification; Pandemics; SARS-CoV-2; Aged; Cues
PubMed: 38843142
DOI: 10.1371/journal.pone.0302399 -
EJNMMI Physics Jun 2024The purpose of our study is to validate the robustness and accuracy of consensus contour in 2-deoxy-2-[ F]fluoro-D-glucose ( F-FDG) PET radiomic features.
PURPOSE
The purpose of our study is to validate the robustness and accuracy of consensus contour in 2-deoxy-2-[ F]fluoro-D-glucose ( F-FDG) PET radiomic features.
METHODS
225 nasopharyngeal carcinoma (NPC) and 13 extended cardio-torso (XCAT) simulated data were enrolled. All segmentation were performed with four segmentation methods under two different initial masks, respectively. Consensus contour (ConSeg) was then developed using the majority vote rule. 107 radiomic features were extracted by Pyradiomics based on segmentation and the intraclass correlation coefficient (ICC) was calculated for each feature between masks or among segmentation, respectively. In XCAT ICC between segmentation and simulated ground truth were also calculated to access the accuracy.
RESULTS
ICC varied with the dataset, segmentation method, initial mask and feature type. ConSeg presented higher ICC for radiomic features in robustness tests and similar ICC in accuracy tests, compared with the average of four segmentation results. Higher ICC were also generally observed in irregular initial masks compared with rectangular masks in both robustness and accuracy tests. Furthermore, 19 features (17.76%) had ICC ≥ 0.75 in both robustness and accuracy tests for any of the segmentation methods or initial masks. The dataset was observed to have a large impact on the correlation relationships between radiomic features, but not the segmentation method or initial mask.
CONCLUSIONS
The consensus contour combined with irregular initial mask could improve the robustness and accuracy in radiomic analysis to some extent. The correlation relationships between radiomic features and feature clusters largely depended on the dataset, but not segmentation method or initial mask.
PubMed: 38839641
DOI: 10.1186/s40658-024-00652-0 -
Veterinary Medicine International 2024This review delves into the historical context, current epidemiological landscape, genomics, and pathobiology of monkeypox virus (MPXV). Furthermore, it elucidates the... (Review)
Review
This review delves into the historical context, current epidemiological landscape, genomics, and pathobiology of monkeypox virus (MPXV). Furthermore, it elucidates the present vaccination status and strategies to curb the spread of monkeypox. Monkeypox, caused by the known as MPXV, is a zoonotic ailment. MPXV can be transmitted from person to person through respiratory droplets during prolonged face-to-face interactions. While many cases of monkeypox are self-limiting, vulnerable groups such as young children, pregnant women, and immunocompromised individuals may experience severe manifestations. Diagnosis predominantly relies on clinical presentations, complemented by laboratory techniques like RT-PCR. Although treatment is often not required, severe cases necessitate antiviral medications like tecovirimat, cidofovir, and brincidofovir. Vaccination, particularly using the smallpox vaccine, has proven instrumental in outbreak control, exhibiting an efficacy of at least 85% against mpox as evidenced by data from Africa. Mitigating transmission requires measures like wearing surgical masks, adequately covering skin lesions, and avoiding handling wild animals.
PubMed: 38836166
DOI: 10.1155/2024/8839830 -
BMJ Global Health Jun 2024During the COVID-19 pandemic, governments and health authorities faced tough decisions about infection prevention and control measures such as social distancing, face...
BACKGROUND
During the COVID-19 pandemic, governments and health authorities faced tough decisions about infection prevention and control measures such as social distancing, face masks and travel. Judgements underlying those decisions require democratic input, as well as expert input. The aim of this review is to inform decisions about how best to achieve public participation in decisions about public health and social interventions in the context of a pandemic or other public health emergencies.
OBJECTIVES
To systematically review examples of public participation in decisions by governments and health authorities about how to control the COVID-19 pandemic.
DESIGN
We searched Participedia and relevant databases in August 2022. Two authors reviewed titles and abstracts and one author screened publications promoted to full text. One author extracted data from included reports using a standard data-extraction form. A second author checked 10% of the extraction forms. We conducted a structured synthesis using framework analysis.
RESULTS
We included 24 reports (18 from Participedia). Most took place in high-income countries (n=23), involved 'consulting' the public (n=17) and involved public meetings (usually online). Two initiatives reported explicit support for critical thinking. 11 initiatives were formally evaluated (only three reported impacts). Many initiatives did not contribute to a decision, and 17 initiatives did not include any explicit decision-making criteria.
CONCLUSIONS
Decisions about how to manage the COVID-19 pandemic affected nearly everyone. While public participation in those decisions had the potential to improve the quality of the judgements and decisions that were made, build trust, improve adherence and help ensure transparency and accountability, few examples of such initiatives have been reported and most of those have not been formally evaluated. Identified initiatives did point out potential good practices related to online engagement, crowdsourcing and addressing potential power imbalance. Future research should address improved reporting of initiatives, explicit decision-making criteria, support for critical thinking, engagement of marginalised groups and decision-makers and communication with the public.
PROSPERO REGISTRATION NUMBER
358991.
Topics: Humans; COVID-19; Community Participation; Decision Making; SARS-CoV-2; Pandemics; Public Health
PubMed: 38830748
DOI: 10.1136/bmjgh-2023-014404