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Nevin Manimala Statistics

Imidacloprid reduces the mating success of males in bumblebees

Sci Total Environ. 2024 Apr 15:172525. doi: 10.1016/j.scitotenv.2024.172525. Online ahead of print.

ABSTRACT

Bumblebees play a vital role in both natural and agricultural environments, however there has been a noticeable decline in their populations. Pesticides, particularly neonicotinoids, are widely regarded as a substantial contributing factor to the decline in bumblebee populations, as evidenced by the detrimental impacts documented across many stages of their life cycle. Mating is vital for the population maintenance of bumblebees. Nevertheless, there is a scarcity of research conducted on the effects of pesticides on the mating process. In this study, we individually examined the impact of imidacloprid on the mating behavior of bumblebee males and queens. A competitive mating experiment was conducted to evaluate the effect on the competitive prowess of male individuals and the mate selection behavior of female individuals. The study revealed that the mating rate of bumblebees exposed to a concentration of 10 ppb of imidacloprid was 3 %. This finding demonstrated a statistically significant impact when compared to the control group, which exhibited a mating rate of 58 % in the normal mating experiment. Furthermore, in the competitive mating experiment, we found that the competitive mating success rate of treated males (1 %) was significantly lower than that of untreated males (35 %). Hence, it provides evidence that neonicotinoid imidacloprid negatively affects bumblebee mating success and cautions us to protect bumblebees from pesticide exposure to prevent a severe impact on their populations.

PMID:38631635 | DOI:10.1016/j.scitotenv.2024.172525

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Nevin Manimala Statistics

Unraveling the mechanisms of Sofosbuvir resistance in HCV NS3/4A protease: Structural and molecular simulation-based insights

Int J Biol Macromol. 2024 Apr 15:131629. doi: 10.1016/j.ijbiomac.2024.131629. Online ahead of print.

ABSTRACT

Current management of HCV infection is based on Direct-Acting Antiviral Drugs (DAAs). However, resistance-associated mutations, especially in the NS3 and NS5B regions are gradually decreasing the efficacy of DAAs. Among the most effective HCV NS3/4A protease drugs, Sofosbuvir also develops resistance due to mutations in the NS3 and NS5B regions. Four mutations at positions A156Y, L36P, Q41H, and Q80K are classified as high-level resistance mutations. The resistance mechanism of HCV NS3/4A protease toward Sofosbuvir caused by these mutations is still unclear, as there is less information available regarding the structural and functional effects of the mutations against Sofosbuvir. In this work, we combined molecular dynamics simulation, molecular mechanics/Generalized-Born surface area calculation, principal component analysis, and free energy landscape analysis to explore the resistance mechanism of HCV NS3/4A protease due to these mutations, as well as compare interaction changes in wild-type. Subsequently, we identified that the mutant form of HCV NS3/4A protease affects the activity of Sofosbuvir. In this study, the resistance mechanism of Sofosbuvir at the atomic level is proposed. The proposed drug-resistance mechanism will provide valuable guidance for the design of HCV drugs.

PMID:38631585 | DOI:10.1016/j.ijbiomac.2024.131629

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Analysis of X-ray irradiation effects on the mortality values and hemolymph immune cell composition of Apis mellifera and its parasite, Varroa destructor

J Invertebr Pathol. 2024 Apr 15:108109. doi: 10.1016/j.jip.2024.108109. Online ahead of print.

ABSTRACT

Varroa destructor is one of the most destructive enemies of the honey bee, Apis mellifera all around the world. Several control methods are known to control V. destructor, but the efficacy of several alternative control methods remains unexplored. Irradiation can be one of these unknown solutions but before practical application, the effectiveness, and the physiological effects of ionizing radiation on the host and the parasite are waiting to be tested. Therefore, the objective of our study was to investigate the effects of different doses (15, 50, 100, and 150 Gy) of high-energy X-ray irradiation through mortality rates and hemocyte composition changes in A. mellifera workers and record the mortality rates of the parasite. The mortality rate was recorded during short-term (12, 24, and 48 h) and long-term periods (3, 6, 12, 18, and 24d). The sensitivity of the host and the parasite in case of the higher doses of radiation tested (50, 100, and 150 Gy) been demonstrated by total mortality of the host and 90 % of its parasite has been observed on the 18th day after the irradiation. V. destructor showed higher sensitivity (1.52-times higher than the adult honey bee workers) at the lowest dose (15 Gy). A. mellifera hemocytes were influenced significantly by radiation dosage and the elapsed time after treatment. The higher radiation doses increased plasmatocyte numbers in parallel with the decrease in prohemocyte numbers. On the contrary, the numbers of granulocytes and oencoytes increased in the treated samples, but the putative effects of the different dosages on the recorded number of these hemocyte types could not be statistically proven. In summary, based on the outcome of our study X-ray irradiation can be deemed an effective tool for controlling phoretic V. destructor. However, further research is needed to understand the physiological response of the affected organisms.

PMID:38631557 | DOI:10.1016/j.jip.2024.108109

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Adiposity and cartilage lesions following ACL reconstruction

Osteoarthritis Cartilage. 2024 Apr 15:S1063-4584(24)01153-1. doi: 10.1016/j.joca.2024.04.004. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine if global, central, or peripheral adiposity is associated with prevalent and worsening cartilage lesions following anterior cruciate ligament reconstruction (ACLR).

METHODS: In 107 individuals one-year post-ACLR, adiposity was assessed globally (body mass index, BMI), centrally (waist circumference), and peripherally (knee subcutaneous adipose tissue thickness) from magnetic resonance imaging (MRI). Tibiofemoral and patellofemoral cartilage lesions were assessed from knee MRIs at 1- and 5-years post-ACLR. Poisson regression evaluated the relation of adiposity with prevalent and worsening tibiofemoral and patellofemoral cartilage lesions adjusting for age, sex, and activity level.

RESULTS: The prevalence ratios of adiposity with tibiofemoral (presence in 49%) and patellofemoral (44%) cartilage lesions ranged from 0.99 to 1.03. Adiposity was more strongly associated with longitudinal changes in tibiofemoral (worsening in 21%) and patellofemoral (44%) cartilage lesions. One-unit increase in global (kg/m2), central (cm), and peripheral (mm) adiposity was associated with a higher risk of worsening tibiofemoral cartilage lesions by 17% (risk ratios [95% CI]: 1.17 [1.09 to 1.23]), 5% (1.05 [1.02 to 1.08]), and 9% (1.09 [1.03 to 1.16]), and patellofemoral cartilage lesions by 5% (1.05 [1.00 to 1.12]) 2% (1.02 [1.00 to 1.04]) and 2% (1.02 [1.00 to 1.04]), respectively.

CONCLUSION: Greater adiposity was a risk factor for worsening cartilage lesions up to 5 years post-ACLR. Clinical interventions aimed at mitigating excess adiposity may be beneficial in preventive approaches for early post-traumatic OA.

PMID:38631554 | DOI:10.1016/j.joca.2024.04.004

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Ethnic Differences in Meat Consumption Attitudes, Norms and Behaviors: A Survey of White, South Asian and Black Ethnic Groups in the UK

Appetite. 2024 Apr 15:107359. doi: 10.1016/j.appet.2024.107359. Online ahead of print.

ABSTRACT

A reduction in meat consumption is necessary to mitigate negative impacts of climate change and adverse health outcomes. The UK has an increasingly multi-ethnic population, yet there is little research on meat consumption habits and attitudes among ethnic groups in the UK. We ran a survey (N=1014) with quota samples for ethnic groups and analyzed attitudes, behaviors and norm perceptions of White, South Asian and Black British respondents. Most respondents believe overconsumption of red and processed meat has negative impacts on health (73.3%) and the environment (64.3%).South Asian respondents were statistically significantly less likely to be meat eaters than White respondents (OR = .44, 95% CIs: .30-.65, t= -4.15, p= .000), while there was no significant difference between White and Black respondents (OR = 1.06, 95% CIs: .63-1.76, t= 0.21, p= .834). Both South Asian (OR = 2.76, 95% CIs: 1.89-4.03 t= 5.25, p= .000) and Black respondents (OR =2.09, 95% CIs: .1.30-3.35, t =3.06, p = .002) were significantly more likely to express being influenced by friends and family in their food choices than White respondents. South Asian (OR = 3.24 ,95% CIs: 2.17-4.84, t= 5.74, p= .000) and Black (OR = 2.02 ,95% CIs: 1.21-3.39, t= 2.69, p= .007) respondents were also both significantly more likely to report they would want to eat similarly to their friends and family than White respondents. Statistical analyses suggested some gender and socioeconomic differences across and among ethnic groups, which are reported and discussed. The differences in meat consumption behaviors and norm conformity between ethnic groups raises the prospect that interventions that leverage social norms may be more effective in South Asian groups than Black and White groups in the UK.

PMID:38631543 | DOI:10.1016/j.appet.2024.107359

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Toxicity evaluation of dose-escalation in hypofractionated regional nodal irradiation for breast cancer: a retrospective study

Int J Radiat Oncol Biol Phys. 2024 Apr 15:S0360-3016(24)00513-3. doi: 10.1016/j.ijrobp.2024.04.014. Online ahead of print.

ABSTRACT

PURPOSE: Regional nodal irradiation (RNI) to the axilla and supraclavicular area presents distinct toxicities, such as lymphedema and shoulder stiffness, compared to whole-breast irradiation. There is insufficient evidence on the safety of dose-escalation in hypofractionated RNI. We aimed to evaluate and compare toxicity rates in patients with breast cancer who received hypofractionated RNI with and without dose-escalation.

METHODS: We retrospectively analyzed 381 patients with breast cancer treated with hypofractionated RNI between March 2015 and February 2017. Patients received either the standard-dose to the regional nodal area (43.2 Gy/16 fx; 48.7 Gy3.5 EQD2, 2 Gy equivalent dose with α/β=3.5 Gy) or dose-escalation with a median dose of 54.8 Gy3.5 EQD2 (range, 51.7 – 60.9 Gy3.5 EQD2) depending on clinical and pathologic nodal stage. Toxicity rates of lymphedema and shoulder stiffness were assessed, and statistical analyses were conducted to identify associated factors.

RESULTS: The median follow-up time was 32.3 months (5.7 – 47.0 months). After radiotherapy, 71 (18.6%) patients developed lymphedema, and 48 (12.6%) developed shoulder stiffness. Patients who received dose-escalation exhibited significantly higher rates of lymphedema (32.1% vs. 14.8%; Odds Ratio (OR): 2.72, p=0.0004) and shoulder stiffness (23.8% vs. 9.4%; OR: 2.01, p=0.0205) compared to the standard-dose group. Moreover, dose-escalation showed a tendency to increase the severity of lymphedema and shoulder stiffness.

CONCLUSIONS: Patients who received dose-escalation in hypofractionated RNI face a higher risk of developing lymphedema and shoulder stiffness compared to those who received standard-dose hypofractionated RNI. Therefore, it is crucial to implement close and frequent monitoring for early detection, along with timely rehabilitation interventions for these patients.

PMID:38631540 | DOI:10.1016/j.ijrobp.2024.04.014

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Incorporating functional lung imaging (FLI) into radiation therapy planning in patients with lung cancer: A systematic review and meta-analysis

Int J Radiat Oncol Biol Phys. 2024 Apr 15:S0360-3016(24)00481-4. doi: 10.1016/j.ijrobp.2024.04.001. Online ahead of print.

ABSTRACT

PURPOSE: To provide an understanding of current FLI techniques, and their potential to improve dosimetry and outcomes for lung cancer patients receiving radiation therapy (RT).

METHODS: EMBASE, PubMed, and Cochrane Library were searched from 1990 until April 2023. Articles were included if they reported on FLI in one of: techniques, incorporation into RT planning for lung cancer, quantification of RT-related outcomes for lung cancer patients. Studies involving all RT modalities, including stereotactic body radiotherapy and particle therapy, were included. Meta-analyses were conducted to investigate differences in dose-function parameters between anatomical and functional RT planning techniques, as well as to investigate correlations of dose-function parameters with grade 2+ radiation pneumonitis (RP).

RESULTS: 178 studies were included in the narrative synthesis. We report on FLI modalities, dose-response quantification, functional lung (FL) definitions, FL avoidance techniques, and correlations between FL irradiation and toxicity. Meta-analysis results show that FL avoidance planning gives statistically significant absolute reductions of 3.22% to the fraction of well-ventilated lung receiving 20 Gy or more (vent-fV20), 3.52% to the fraction of well-perfused lung receiving 20 Gy or more (perf-fV20), 1.3 Gy to the mean dose to the well-ventilated lung (vent-fMLD), and 2.41 Gy to the mean dose to the well-perfused lung (perf-fMLD). Increases in the threshold value for defining FL are associated with decreases in functional parameters. For intensity-modulated radiation therapy and volumetric modulated arc therapy, avoidance planning results in a 13% rate of grade 2+ RP, which seems reduced compared to results from conventional planning cohorts. A trend of increased predictive ability for grade 2+ RP was seen in models using FL information, but was not statistically significant.

CONCLUSIONS: FLI shows promise as a method to spare FL during thoracic RT, but interventional trials related to FL avoidance planning are sparse. Such trials are critical to understanding the impact of FL avoidance planning on toxicity reduction and patient outcomes.

PMID:38631538 | DOI:10.1016/j.ijrobp.2024.04.001

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Reduction of ADC bias in diffusion MRI with deep learning-based acceleration: A phantom validation study at 3.0 T

Magn Reson Imaging. 2024 Apr 15:S0730-725X(24)00131-0. doi: 10.1016/j.mri.2024.04.018. Online ahead of print.

ABSTRACT

PURPOSE: Further acceleration of DWI in diagnostic radiology is desired but challenging mainly due to low SNR in high b-value images and associated bias in quantitative ADC values. Deep learning-based reconstruction and denoising may provide a solution to address this challenge.

METHODS: The effects of SNR reduction on ADC bias and variability were investigated using a commercial diffusion phantom and numerical simulations. In the phantom, performance of different reconstruction methods, including conventional parallel (SENSE) imaging, compressed sensing (C-SENSE), and compressed SENSE acceleration with an artificial intelligence deep learning-based technique (C-SENSE AI), was compared at different acceleration factors and flip angles using ROI-based analysis. ADC bias was assessed by Lin’s Concordance correlation coefficient (CCC) followed by bootstrapping to calculate confidence intervals (CI). ADC random measurement error (RME) was assessed by the mean coefficient of variation (CV¯) and non-parametric statistical tests.

RESULTS: The simulations predicted increasingly negative bias and loss of precision towards lower SNR. These effects were confirmed in phantom measurements of increasing acceleration, for which CCC decreased from 0.947 to 0.279 and CV¯ increased from 0.043 to 0.439, and of decreasing flip angle, for which CCC decreased from 0.990 to 0.063 and CV¯ increased from 0.037 to 0.508. At high acceleration and low flip angle, C-SENSE AI reconstruction yielded best denoised ADC maps. For the lowest investigated flip angle, CCC = {0.630, 0.771 and 0.987} and CV¯={0.508, 0.426 and 0.254} were obtained for {SENSE, C-SENSE, C-SENSE AI}, the improvement by C-SENSE AI being significant as compared to the other methods (CV: p = 0.033 for C-SENSE AI vs. C-SENSE and p < 0.001 for C-SENSE AI vs. SENSE; CCC: non-overlapping CI between reconstruction methods). For the highest investigated acceleration factor, CCC = {0.479,0.926,0.960} and CV¯={0.519,0.119,0.118} were found, confirming the reduction of bias and RME by C-SENSE AI as compared to C-SENSE (by trend) and to SENSE (CV: p < 0.001; CCC: non-overlapping CI).

CONCLUSION: ADC bias and random measurement error in DWI at low SNR, typically associated with scan acceleration, can be effectively reduced by deep-learning based C-SENSE AI reconstruction.

PMID:38631532 | DOI:10.1016/j.mri.2024.04.018

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Incorporating plan complexity into the statistical process control of volumetric modulated arc therapy pre-treatment verifications

Med Phys. 2024 Apr 17. doi: 10.1002/mp.17081. Online ahead of print.

ABSTRACT

BACKGROUND: Statistical process control (SPC) is a powerful statistical tool for process monitoring that has been highly recommended in healthcare applications, including radiation therapy quality assurance (QA). The AAPM TG-218 report described the clinical implementation of SPC for Volumetric Modulated Arc Therapy (VMAT) pre-treatment verifications, pointing out the need to adjust tolerance limits based on plan complexity. However, the quantification of plan complexity and its integration into SPC remains an unresolved challenge.

PURPOSE: The primary aim of this study is to investigate the incorporation of plan complexity into the SPC framework for VMAT pre-treatment verifications. The study explores and evaluates various strategies for this incorporation, discussing their merits and limitations, and provides recommendations for clinical application.

METHODS: A retrospective analysis was conducted on 309 VMAT plans from diverse anatomical sites using the PTW OCTAVIUS 4D device for QA measurements. Gamma Passing Rates (GPR) were obtained, and lower control limits were computed using both the conventional Shewhart method and three heuristic methods (scaled weighted variance, weighted standard deviations, and skewness correction) to accommodate non-normal data distributions. The ‘Identify-Eliminate-Recalculate’ method was employed for robust analysis. Eight complexity metrics were analyzed and two distinct strategies for incorporating plan complexity into SPC were assessed. The first strategy focused on establishing control limits for different treatment sites, while the second was based on the determination of control limits as a function of individual plan complexity. The study extensively examines the correlation between control limits and plan complexity and assesses the impact of complexity metrics on the control process.

RESULTS: The control limits established using SPC were strongly influenced by the complexity of treatment plans. In the first strategy, a clear correlation was found between control limits and average plan complexity for each site. The second approach derived control limits based on individual plan complexity metrics, enabling tailored tolerance limits. In both strategies, tolerance limits inversely correlated with plan complexity, resulting in all highly complex plans being classified as in control. In contrast, when plans were collectively analyzed without considering complexity, all the out-of-control plans were highly complex.

CONCLUSIONS: Incorporating plan complexity into SPC for VMAT verifications requires meticulous and comprehensive analysis. To ensure overall process control, we advocate for stringent control and minimization of plan complexity during treatment planning, especially when control limits are adjusted based on plan complexity.

PMID:38630979 | DOI:10.1002/mp.17081

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Glutamate Signaling in Patients With Parkinson Disease With REM Sleep Behavior Disorder

Neurology. 2024 May 14;102(9):e209271. doi: 10.1212/WNL.0000000000209271. Epub 2024 Apr 17.

ABSTRACT

BACKGROUND AND OBJECTIVES: Clinical heterogeneity of patients with Parkinson disease (PD) is well recognized. PD with REM sleep behavior disorder (RBD) is a more malignant phenotype with faster motor progression and higher nonmotor symptom burden. However, the neural mechanisms underlying this clinical divergence concerning imbalances in neurotransmitter systems remain elusive.

METHODS: Combining magnetic resonance (MR) spectroscopy and [11C]ABP688 PET on a PET/MR hybrid system, we simultaneously investigated two different mechanisms of glutamate signaling in patients with PD. Patients were grouped according to their RBD status in overnight video-polysomnography and compared with age-matched and sex-matched healthy control (HC) participants. Total volumes of distribution (VT) of [11C]ABP688 were estimated with metabolite-corrected plasma concentrations during steady-state conditions between 45 and 60 minutes of the scan following a bolus-infusion protocol. Glutamate, glutamine, and glutathione levels were investigated with single-voxel stimulated echo acquisition mode MR spectroscopy of the left basal ganglia.

RESULTS: We measured globally elevated VT of [11C]ABP688 in 16 patients with PD and RBD compared with 17 patients without RBD and 15 HC participants (F(2,45) = 5.579, p = 0.007). Conversely, glutamatergic metabolites did not differ between groups and did not correlate with the regional VT of [11C]ABP688. VT of [11C]ABP688 correlated with the amount of REM sleep without atonia (F(1,42) = 5.600, p = 0.023) and with dopaminergic treatment response in patients with PD (F(1,30) = 5.823, p = 0.022).

DISCUSSION: Our results suggest that patients with PD and RBD exhibit altered glutamatergic signaling indicated by higher VT of [11C]ABP688 despite unaffected glutamate levels. The imbalance of glutamate receptors and MR spectroscopy glutamate metabolite levels indicates a novel mechanism contributing to the heterogeneity of PD and warrants further investigation of drugs targeting mGluR5.

PMID:38630966 | DOI:10.1212/WNL.0000000000209271