Testing the causal impact of amyloidosis on total Tau using a genetically informative sample of adult male twins.

INTRODUCTION: The amyloid cascade hypothesis predicts that amyloid-beta (Aß) aggregation drives tau tangle accumulation. We tested competing causal and non-causal hypotheses regarding the direction of causation between Aß40 and Aß42 and total Tau (t-Tau) plasma biomarkers. METHODS: Plasma Aß40, Aß42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean = 67.0 years) using Simoa immunoassays. Genetically informative twin modeling tested the direction of causation between Aßs and t-Tau. RESULTS: No clear evidence that Aß40 or Aß42 directly causes changes in t-Tau was observed; the alternative causal hypotheses also fit the data well. In contrast, exploratory analyses suggested a causal impact of the Aß biomarkers on NFL. Separately, reciprocal causation was observed between t-Tau and NFL. DISCUSSION: Plasma Aß40 or Aß42 do not appear to have a direct causal impact on t-Tau. In contrast, Aß aggregation may causally impact NFL in cognitively unimpaired men in their late 60s.

Lifestyle and psychosocial associations with cognition at the cusp of midlife using twins and siblings.

INTRODUCTION: This study investigates the relationship between cognitive functioning and 59 modifiable and intrinsic factors at the cusp of midlife. METHODS: We analyzed data from 1221 participants in the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife; Mage = 33.20, %Female = 52.74). We assessed the impact of 59 factors on cognitive functioning using regularized regression and co-twin control models, controlling for earlier-life cognitive functioning and gray matter volume. RESULTS: Eight robust factors were identified, including education attainment, cognitive complexity, purpose-in-life, and smoking status. Twins reporting higher levels of cognitive complexity and purpose-in-life showed better cognitive performance than their cotwin, while smoking was negatively associated. Using meta-analytically derived effect size threshold, we additionally identified that twins experiencing more financial difficulty tend to perform less well compared with their cotwin. DISCUSSION: The findings highlight the early midlife link between cognitive functioning and lifestyle/psychological factors, beyond prior cognitive performance, brain status, genetic and familial confounders. Our results further highlight the potential of established adulthood as a crucial window for dementia prevention interventions targeting lifestyle and psychosocial factors. Highlights: Cog complexity(+), purpose-in-life(+) were associated with cognition in early midlife.Smoking(-) was also associated with cognition in early midlife.Results were consistent controlling for genetic and environmental confounds.Association between EA and cognition might be mostly genetic and familial confounded.

Effects from medications on functional biomarkers of aging in three longitudinal studies of aging in Sweden.

Antihypertensive, lipid-lowering, and blood glucose-lowering drugs have slowed down the aging process in animal models. In humans, studies are limited, have short follow-up times, and show mixed results. Therefore, this study aimed to estimate the effects of commonly used medications on functional aging, cognitive function, and frailty. We included information on individuals from three Swedish longitudinal population-based studies collected between 1986 and 2014. Our exposures were the 21 most used groups of medications among individuals aged 65 years and older in the Swedish population in 2022. Functional aging index (n = 1191), cognitive function (n = 1094), and frailty index (n = 1361) were the outcomes of interest. To estimate the medication effects, we used a self-controlled analysis, where each individual is his/her own control, thereby adjusting for all time-stable confounders. The analysis was additionally adjusted for time-varying confounders (chronological age, Charlson Comorbidity Index, smoking, body mass index, and the number of drugs). The participants were 65.5-82.8 years at the first in-person assessment. Adrenergics/inhalants (effect size = 0.089) and lipid-modifying agents/plain (effect size = 0.082) were associated with higher values of cognitive function (improvement), and selective calcium channel blockers with mainly vascular effects (effect size = -0.129) were associated with lower values of the functional aging index (improvement). No beneficial effects were found on the frailty index. Adrenergics/inhalants, lipid-modifying agents/plain, and selective calcium channel blockers with mainly vascular effects may benefit functional biomarkers of aging. More research is needed to investigate their clinical value in preventing adverse aging outcomes.

Epigenome-wide analysis of frailty: Results from two European twin cohorts.

Epigenetics plays an important role in the aging process, but it is unclear whether epigenetic factors also influence frailty, an age-related state of physiological decline. In this study, we performed a meta-analysis of epigenome-wide association studies in four samples drawn from the Swedish Adoption/Twin Study of Aging (SATSA) and the Longitudinal Study of Aging Danish Twins (LSADT) to explore the association between DNA methylation and frailty. Frailty was defined using the frailty index (FI), and DNA methylation levels were measured in whole blood using Illumina's Infinium HumanMethylation450K and MethylationEPIC arrays. In the meta-analysis consisting of a total of 829 participants, we identified 589 CpG sites that were statistically significantly associated with either the continuous or categorical FI (false discovery rate <0.05). Many of these CpGs have previously been associated with age and age-related diseases. The identified sites were also largely directionally consistent in a longitudinal analysis using mixed-effects models in SATSA, where the participants were followed up to a maximum of 20 years. Moreover, we identified three differentially methylated regions within the MGRN1, MIR596, and TAPBP genes that have been linked to neuronal aging, tumor growth, and immune functions. Furthermore, our meta-analysis results replicated 34 of the 77 previously reported frailty-associated CpGs at p < 0.05. In conclusion, our findings demonstrate robust associations between frailty and DNA methylation levels in 589 novel CpGs, previously unidentified for frailty, and strengthen the role of neuronal/brain pathways in frailty.

Interplay of body mass index and metabolic syndrome: association with physiological age from midlife to late-life.

Obesity and metabolic syndrome (MetS) share common pathophysiological characteristics with aging. To better understand their interplay, we examined how body mass index (BMI) and MetS jointly associate with physiological age, and if the associations changed from midlife to late-life. We used longitudinal data from 1,825 Swedish twins. Physiological age was measured as frailty index (FI) and functional aging index (FAI) and modeled independently in linear mixed-effects models adjusted for chronological age, sex, education, and smoking. We assessed curvilinear associations of BMI and chronological age with physiological age, and interactions between BMI, MetS, and chronological age. We found a significant three-way interaction between BMI, MetS, and chronological age on FI (p-interaction = 0·006), not FAI. Consequently, we stratified FI analyses by age: < 65, 65-85, and ≥ 85 years, and modeled FAI across ages. Except for FI at ages ≥ 85, BMI had U-shaped associations with FI and FAI, where BMI around 26-28 kg/m2 was associated with the lowest physiological age. MetS was associated with higher FI and FAI, except for FI at ages < 65, and modified the BMI-FI association at ages 65-85 (p-interaction = 0·02), whereby the association between higher BMI levels and FI was stronger in individuals with MetS. Age modified the MetS-FI association in ages ≥ 85, such that it was stronger at higher ages (p-interaction = 0·01). Low BMI, high BMI, and metabolic syndrome were associated with higher physiological age, contributing to overall health status among older individuals and potentially accelerating aging.

Significant enhancement in the cold emission characteristics of chemically synthesized super-hydrophobic zinc oxide rods by nickel doping.

The current article presents a huge enhancement in the field emission characteristics of zinc oxide (ZnO) micro/nanorods by nickel doping. The synthesis of pure and nickel-doped zinc oxide (ZnO) micro/nanorods was done by a simple low-temperature chemical method. Both the as-prepared pure and doped samples were analyzed by X-ray diffraction and electron microscopy to confirm the proper phase formation and the developed microstructure. UV-vis transmittance spectra helped in determining the band gap of the samples. Fourier-Transform Infrared Spectroscopy (FTIR) spectra showed the different bonds present in the sample, whereas X-ray Photoelectron Spectroscopy (XPS) confirmed the presence of nickel in the doped sample. Photoluminescence (PL) spectra showed that after doping, the band-to-band transition was affected, whereas defect-induced transition had increased significantly. After the nickel doping, contact angle measurement revealed a significant decrease in the sample's surface energy, leading to a remarkably high water contact angle (within the superhydrophobic region). Simulation through ANSYS suggested that the doped sample has the potential to function as an efficient cold emitter, which was also verified experimentally. The cold emission characteristics of the doped sample showed a significant improvement, with the turn-on field (corresponding to J = 1 µA cm-2) reduced from 5.34 to 2.84 V µm-1. The enhancement factor for the doped sample reached 3426, approximately 1.5 times higher compared to pure ZnO. Efforts have been made to explain the results, given the favorable band bending as well as the increased number of effective emission sites.

Longitudinal associations between use of antihypertensive, antidiabetic, and lipid-lowering medications and biological aging.

Aging is a major risk factor for many chronic diseases. This study aimed to examine the effects of antihypertensive, lipid-lowering, and antidiabetic drugs on biological aging. We included 672 participants and 2746 repeated measurements from the Swedish Adoption/Twin Study of Aging. Self-reported medicine uses were categorized into antidiabetic, antihypertensive, and lipid-lowering drugs. A total of 12 biomarkers for biological aging (BA biomarkers) were included as outcomes. Conditional generalized estimating equations were applied conditioning on individuals to estimate the drug effect on BA biomarker level within the same person when using or not using the drug. Chronological age, body mass index, smoking status, number of multiple medication uses, blood pressure, blood glucose level, and apoB/apoA ratio were adjusted for as covariates in the model. Overall, using antihypertensive drugs was associated with a decrease in one DNA-methylation age (PCGrimAge: beta = - 0.39, 95%CI = - 0.67 to - 0.12). When looking into drug subcategories, calcium channel blockers (CCBs) were associated with a decrease in several DNA-methylation ages (PCHorvathAge beta = - 1.28, 95%CI = - 2.34 to - 0.21; PCSkin&bloodAge beta = - 1.34, 95%CI = - 2.61 to - 0.07; PCPhenoAge beta = - 1.74, 95%CI = - 2.58 to - 0.89; PCGrimAge beta = - 0.57, 95%CI = - 0.96 to - 0.17) and in functional biological ages (functional age index beta = - 2.18, 95%CI = - 3.65 to - 0.71; frailty index beta = - 1.31, 95%CI = - 2.43 to - 0.18). However, the results within other drug subcategories were inconsistent. Calcium channel blockers may decrease biological aging captured by the BA biomarkers measured at epigenetic and functional level. Future studies are warranted to confirm these effects and understand the underlying biological mechanisms.

Soil nutrients and plant uptake parameters as related to greenhouse gas emissions.

Fertilizer and water management practices have short- and long-term effects on soil chemical and physical properties and, in turn, greenhouse gas (GHG) emissions. The goal of this 4-yr field study was to establish the relationships between soil properties, agronomic practices, and GHG (CO2 and N2 O) emissions under different fertilizer and water table management practices. There were two fertilizer treatments: inorganic fertilizer (IF) and a mix of solid cattle manure and inorganic fertilizer (SCM), combined with tile drainage(DR) and controlled drainage with subirrigation(CDS). The cropping system was a maize (Zea mays L.)-soybean [Glycine max (L.) Merr.] rotation. Nitrogen in biomass (BMN) and N in grain (GRN) were measured and used to calculate other plant N parameters. Nitrous oxide and CO2 fluxes were collected weekly, and their respective cumulative emissions were calculated. The results show that soil organic matter (OM), soil total carbon (C), and soil total nitrogen (N) were greater in SCM than IF by 23.7, 35.2, and 24.4%, respectively. Water table management did not significantly affect soil N and C. Increased CO2 emissions were witnessed under higher soil OM, soil total C, and total N. Plant N uptake parameters were negatively correlated with N2 O and CO2 emissions. Higher plant N uptake can reduce environmental pollution by limiting N2 O and CO2 emissions.

Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects.

Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects.

Effect of feeding of sorghum stover based complete feed blocks containing guar meal as protein supplement on reproductive efficiency, hormone profile and antioxidant status in Deccani ewes.

Guar meal (GM) can be considered as an alternative protein source for the livestock and has a potential value as a feed to animals with a high protein content ranging between 45-55%. A study was conducted to evaluate the effect of partial replacement of groundnut cake (GNC) with guar meal (GM) on reproductive efficiency, hormone profile, antioxidant status in Deccani ewes fed sorghum stover based complete feed blocks (SSCFB). Twenty-one non-pregnant Deccani ewes (b. wt. 23.34 ±0.40 kg; 2-4 years old and body condition score 2.51±0.56) were randomly divided into three groups to contain 7 animals each in a completely randomized design. Three dietary treatments viz. S1: conventional feeding (sorghum stover and concentrate mixture fed separately in 50:50 ratios to meet the requirement), S2: SSCFB with GNC as protein supplement in concentrate mixture and S3: SSCFB with GM replacing GNC nitrogen of S2 at 50% level. The ewes were synchronised for estrus with progesterone impregnated intravaginal sponges and naturally mated. The ewes were fed at the rate of 3.1 and 3.7% of their body weight from 1st day of experiment-to 108th day of gestation and from 108th day of gestation to till lambing, respectively. The replacement of 50% of GNC nitrogen with GM and densification of diet had no effect (P>0.05) on average DMI (g), antioxidant status, progesterone concentration, conception rate, non return rate, no of matings per service, lambing rate, body weights of lambs at birth, 15 and 30 days of age. GNC can be partially replaced by GM in the ewes diet without any adverse effect on reproductive parameters, antioxidant status, progesterone concentration and weight of lambs.

Independent and joint effects of body mass index and metabolic health in mid- and late-life on all-cause mortality: a cohort study from the Swedish Twin Registry with a mean follow-up of 13 Years.

BACKGROUND: There is robust evidence that in midlife, higher body mass index (BMI) and metabolic syndrome (MetS), which often co-exist, are associated with increased mortality risk. However, late-life findings are inconclusive, and few studies have examined how metabolic health status (MHS) affects the BMI-mortality association in different age categories. We, therefore, aimed to investigate how mid- and late-life BMI and MHS interact to affect the risk of mortality. METHODS: This cohort study included 12,467 participants from the Swedish Twin Registry, with height, weight, and MHS measures from 1958-2008 and mortality data linked through 2020. We applied Cox proportional hazard regression with age as a timescale to examine how BMI categories (normal weight, overweight, obesity) and MHS (identification of MetS determined by presence/absence of hypertension, hyperglycemia, low HDL, hypertriglyceridemia), independently and in interaction, are associated with the risk of all-cause mortality. Models were adjusted for sex, education, smoking, and cardiovascular disease. RESULTS: The midlife group included 6,252 participants with a mean age of 59.6 years (range = 44.9-65.0) and 44.1% women. The late-life group included 6,215 participants with mean age 73.1 years (65.1-95.3) and 46.6% women. In independent effect models, metabolically unhealthy status in midlife increased mortality risks by 31% [hazard ratio 1.31; 95% confidence interval 1.12-1.53] and in late-life, by 18% (1.18;1.10-1.26) relative to metabolically healthy individuals. Midlife obesity increased the mortality risks by 30% (1.30;1.06-1.60) and late-life obesity by 15% (1.15; 1.04-1.27) relative to normal weight. In joint models, the BMI estimates were attenuated while those of MHS were less affected. Models including BMI-MHS categories revealed that, compared to metabolically healthy normal weight, the metabolically unhealthy obesity group had increased mortality risks by 53% (1.53;1.19-1.96) in midlife, and across all BMI categories in late-life (normal weight 1.12; 1.01-1.25, overweight 1.10;1.01-1.21, obesity 1.31;1.15-1.49). Mortality risk was decreased by 9% (0.91; 0.83-0.99) among those with metabolically healthy overweight in late-life. CONCLUSIONS: MHS strongly influenced the BMI-mortality association, such that individuals who were metabolically healthy with overweight or obesity in mid- or late-life did not carry excess risks of mortality. Being metabolically unhealthy had a higher risk of mortality independent of their BMI.

Long-term associations of cigarette smoking in early mid-life with predicted brain aging from mid- to late life.

BACKGROUND AND AIMS: Smoking is associated with increased risk for brain aging/atrophy and dementia. Few studies have examined early associations with brain aging. This study aimed to measure whether adult men with a history of heavier smoking in early mid-life would have older than predicted brain age 16-28 years later. DESIGN: Prospective cohort observational study, utilizing smoking pack years data from average age 40 (early mid-life) predicting predicted brain age difference scores (PBAD) at average ages 56, 62 (later mid-life) and 68 years (early old age). Early mid-life alcohol use was also evaluated. SETTING: Population-based United States sample. PARTICIPANTS/CASES: Participants were male twins of predominantly European ancestry who served in the United States military between 1965 and 1975. Structural magnetic resonance imaging (MRI) began at average age 56. Subsequent study waves included most baseline participants; attrition replacement subjects were added at later waves. MEASUREMENTS: Self-reported smoking information was used to calculate pack years smoked at ages 40, 56, 62, and 68. MRIs were processed with the Brain-Age Regression Analysis and Computation Utility software (BARACUS) program to create PBAD scores (chronological age-predicted brain age) acquired at average ages 56 (n = 493; 2002-08), 62 (n = 408; 2009-14) and 68 (n = 499; 2016-19). FINDINGS: In structural equation modeling, age 40 pack years predicted more advanced age 56 PBAD [ß = -0.144, P = 0.012, 95% confidence interval (CI) = -0.257, -0.032]. Age 40 pack years did not additionally predict PBAD at later ages. Age 40 alcohol consumption, but not a smoking × alcohol interaction, predicted more advanced PBAD at age 56 (ß = -0.166, P = 0.001, 95% CI = -0.261, -0.070) with additional influences at age 62 (ß = -0.115, P = 0.005, 95% CI = -0.195, -0.036). Age 40 alcohol did not predict age 68 PBAD. Within-twin-pair analyses suggested some genetic mechanism partially underlying effects of alcohol, but not smoking, on PBAD. CONCLUSIONS: Heavier smoking and alcohol consumption by age 40 appears to predict advanced brain aging by age 56 in men.

Associations between depression and cardiometabolic health: A 27-year longitudinal study.

BACKGROUND: Clarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems. METHODS: The study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse ('baseline') and the longitudinal Vietnam Era Twin Study of Aging ('follow-up'). Depression symptoms were assessed at baseline [mean age 41.42 years (s.d. = 2.34)] using the Diagnostic Interview Schedule, Version III, Revised. The onset of eight cardiometabolic conditions (atrial fibrillation, diabetes, erectile dysfunction, hypercholesterolemia, hypertension, myocardial infarction, sleep apnea, and stroke) was assessed via self-reported doctor diagnosis at follow-up [mean age 67.59 years (s.d. = 2.41)]. RESULTS: Total depression symptoms were longitudinally associated with incident diabetes (OR 1.29, 95% CI 1.07-1.57), erectile dysfunction (OR 1.32, 95% CI 1.10-1.59), hypercholesterolemia (OR 1.26, 95% CI 1.04-1.53), and sleep apnea (OR 1.40, 95% CI 1.13-1.74) over 27 years after controlling for age, alcohol consumption, smoking, body mass index, C-reactive protein, and polygenic risk for specific health conditions. In sensitivity analyses that excluded somatic depression symptoms, only the association with sleep apnea remained significant (OR 1.32, 95% CI 1.09-1.60). CONCLUSIONS: A history of depression symptoms by early midlife is associated with an elevated risk for subsequent development of several self-reported health conditions. When isolated, non-somatic depression symptoms are associated with incident self-reported sleep apnea. Depression symptom history may be a predictor or marker of cardiometabolic risk over decades.

Does treatment sequence affect outcomes in patients with metaplastic breast cancer?

INTRODUCTION: We compared characteristics and outcomes by treatment sequence among patients with metaplastic breast cancer (MBC), an aggressive subtype. METHODS: Women ≥18 years old with newly diagnosed Stage I-III MBC from 2003 to 2018 who received any treatment in our health system were identified. Unadjusted overall survival (OS) was estimated with the Kaplan-Meier method; the log-rank test was used to compare survival differences between recipients of neoadjuvant (NACT) and adjuvant chemotherapy (ACT). RESULTS: Of the 91 MBC patients identified, 60 received chemotherapy. NACT recipients (n = 20, median age 46.5 y) were younger than ACT recipients (n = 40, median age 60.5 y, p < 0.001) but similar with regards to race and radiation receipt. There was no significant OS difference between NACT and ACT recipients (log-rank p = 0.15), which remained true when patients were stratified by age (≥50 y vs < 50 y). CONCLUSIONS: Among MBC patients, NACT recipients were younger than ACT recipients, but there was no survival difference by treatment sequence.

Mutations and structural variations in Catechol-O-methyltransferase gene of patients exhibiting chronic persistent surgical pain. / Mutaciones y variaciones estructurales en el gen catecol-O-metiltransferasa de los pacientes que exhiben dolor quirúrgico persistente crónico.

OBJECTIVES: Mutations in the exon 4 of the COMT gene are associated with chronic persistent surgical pain (CPSP). Especially COMT mutated allele G472A (Val158Met) associated with CPSP patients is reported in different ethnic population. The purpose of this study is to evaluate the prevalence of genetic mutations and structural variations in exon 4 of COMT that can be related to the appearance of CPSP in patients under sternotomy. MATERIALS AND METHODS: One hundred patients with American Society of Anesthesiologists (ASA) physical status grades i, ii and iii, who underwent sternotomy procedures, were selected to assess the development and magnitude of the CPSP evaluated with pain questionaries' at the end of three months after surgery. This was correlated with COMT allele presence. The exon 4 of COMT gene (that contains the G472A allele) was studied. The polymerase chain reaction (PCR) products were sequenced and mutated sequences were deposited in GenBank®. The structural analysis of COMT was performed using ProCheck® and distortions of three-dimensional tertiary structural orientation was evaluated with root-mean-square deviation (RMSD) score. RESULTS: Genetic analysis carried out through PCR showed 220 bp amplicons. The 25% of patients with CPSP showed a Numeric Rating Scale (NRS) > 4 pain score. The 20% of these patients have known Val158Met mutation, 5% of patients showed novel mutations c.382C>G, c.383G>C, p.(Arg128Ala). The mutations in COMT gene contributed major structural variations in COMT leading to the formation of inactive COMT that correlates with CPSP. CONCLUSION: The results of the present study showed that both novel and previously reported mutations in COMT gene has strong association with CPSP.

Possible mechanism of bamboo shoots (Bambusa balcooa) induced thyroid disruption - An in vitro study.

Endemic goitre and associated iodine deficiency disorders (IDDs) are a major concern in public health even in the period of post salt iodization in many regions. Among others the consumption of cyanogenic plants found responsible for the persistence of such diseases. Bamboo shoots (BS) is one such cyanogenic plant food that caused disruption of certain thyroid hormone synthesizing regulatory element as has already been reported in our earlier study. In this investigation the possible mechanism of thyrocytes disruption along with interruption of thyroid hormone biosynthesis by BS has been worked out. Commonly consumed BS, Bambusa Balcooa Roxb (BBR) water extract was analysed by GC MS; three doses below IC50 were administered to thyrocytes in culture with and without iodine. Expressions of thyroglobulin (Tg), pendrin (PDS) and monocarboxylate transporter 8 (MCT8) were evaluated in thyrocytes with cell cycle analysis, reactive oxygen species (ROS) generation, DNA oxidation and apoptotic regulation through Bax, Bcl-2 and p53. Phytochemical analysis of BBR extract revealed the presence of precursors and metabolic end products of cyanogenic glycosides. Dose dependent decrease in expression of Tg and PDS with concomitant decrease in gene expression of these with MCT8 were observed. Increased ROS, DNA oxidation and associated imbalance were found through increased Bax and p53 with decreased Bcl-2 that perturbed thyrocytes cell cycle. Cyanogenic constituents of BBR generates ROS associated oxidative changes in thyrocytes with DNA damage and oxidation and cell cycle disruption followed by inhibition of thyroid hormone synthesizing regulatory elements; addition of extra iodine showed partial prevention.

The role of transoral fine needle aspiration in expediting diagnosis and reducing risk in head and neck cancer patients in the coronavirus disease 2019 (COVID-19) era: a single-institution experience.

OBJECTIVE: The global coronavirus disease 2019 (COVID-19) pandemic has necessitated rapid alterations to diagnostic pathways for head and neck cancer patients that aim to reduce risk to patients (exposure to the hospital environment) and staff (aerosol-generating procedures). Transoral fine needle aspiration cytology offers a low-risk means of rapidly diagnosing patients with oral cavity or oropharyngeal lesions. The technique was utilised in selected patients at our institution during the pandemic. The outcomes are considered in this study. METHOD: Diagnostic outcomes were retrospectively evaluated for a series of patients undergoing transoral fine needle aspiration cytology of oral cavity and oropharyngeal lesions during the COVID-19 pandemic. RESULTS: Five patients underwent transoral fine needle aspiration cytology, yielding lesional material in 100 per cent, with cell blocks providing additional information. In one case, excision biopsy of a lymphoproliferative lesion was required for final diagnosis. CONCLUSION: Transoral fine needle aspiration cytology can provide rapid diagnosis in patients with oral cavity and oropharyngeal lesions. Whilst limitations exist (including tolerability and lesion location), the technique offers significant advantages pertinent to the COVID-19 era, and could be employed in the future to obviate diagnostic surgery in selected patients.

Machine learning for predicting greenhouse gas emissions from agricultural soils.

Machine learning (ML) models are increasingly used to study complex environmental phenomena with high variability in time and space. In this study, the potential of exploiting three categories of ML regression models, including classical regression, shallow learning and deep learning for predicting soil greenhouse gas (GHG) emissions from an agricultural field was explored. Carbon dioxide (CO2) and nitrous oxide (N2O) fluxes, as well as various environmental, agronomic and soil data were measured at the site over a five-year period in Quebec, Canada. The rigorous analysis, which included statistical comparison and cross-validation for the prediction of CO2 and N2O fluxes, confirmed that the LSTM model performed the best among the considered ML models with the highest R coefficient and the lowest root mean squared error (RMSE) values (R = 0.87 and RMSE = 30.3 mg·m-2·hr-1 for CO2 flux prediction and R = 0.86 and RMSE = 0.19 mg·m-2·hr-1 for N2O flux prediction). The predictive performances of LSTM were more accurate than those simulated in a previous study conducted by a biophysical-based Root Zone Water Quality Model (RZWQM2). The classical regression models (namely RF, SVM and LASSO) satisfactorily simulated cyclical and seasonal variations of CO2 fluxes (R = 0.75, 0.71 and 0.68, respectively); however, they failed to reasonably predict the peak values of N2O fluxes (R < 0.25). Shallow ML was found to be less effective in predicting GHG fluxes than other considered ML models (R < 0.7 for CO2 flux and R < 0.3 for estimating N2O fluxes) and was the most sensitive to hyperparameter tuning. Based on this comprehensive comparison study, it was elicited that the LSTM model can be employed successfully in simulating GHG emissions from agricultural soils, providing a new perspective on the application of machine learning modeling for predicting GHG emissions to the environment.