Miracle-dz/UniFAR-FTUs huggingface dataset:
Adenomyotic Lesions Are Induced in the Mouse Uterus after Exposure to NSAID and EE2 Mixtures at Environmental Doses

The aim of this study was to assess the long-term effect of exposure to environmentally relevant doses of non-steroidal anti-inflammatory drugs (NSAIDs; ibuprofen, and diclofenac) and 17β-ethinylestradiol (EE2) on the mouse uterus. NSAID-EE2 mixtures were administered in the drinking water from gestational day 8 until 8 weeks post-birth (i.e., during embryo development, lactation, puberty, and sexual maturity). The incidence of adenomyosis lesions (presence of endometrial glands in the inner myometrium) increased up to 60% in the uterus of 8-week-old exposed females (F1) and to 85% in F2 females (exposed father). Histological analysis revealed aberrant proliferation and apoptosis, vacuolization of epithelial cells, and increased incidence of abnormal glands in the luminal and glandular epithelium in F1 and F2 uteri. Moreover, myofibroblast proportion (alpha-smooth muscle actin (α-SMA) expression analysis) and collagen expression (Picrosirius red stain; a fibrosis hallmark) were increased in F1 and F2 endometrium. Connexin-43 was aberrantly distributed in the endometrial stroma and glands of F1 and F2 uteri. Conversely, uterine 17β-estradiol and progesterone levels were not affected in F1 and F2 females. These findings demonstrated that in mice, chronic exposure to NSAID and EE2 mixtures at environmental doses intergenerationally affects uterine physiology, particularly the endometrium. It may serve as a model to study the pathophysiology of human adenomyosis.
Health and Quality of Life Outcomes

Background: Little is known about the Quality of Life (QOL) in parents of children with developmental diseases as compared to other severe neurological or psychiatric disorders. Aims of the present study were: to evaluate QOL in parents of children affected by Pervasive Development Disorder (PDDs), Cerebral Palsy (CP) or Mental Retardation (MR) as compared to a control group (CG); to evaluate QOL of parents of patients with different types of PDDs, namely Autistic Disorder (AD), High Function Autism/Asperger Syndromes (HFA/AS) and Pervasive Developmental Disorder Not Otherwise Specified (PPD-NOS); and to compare the level of impairment in QOL of mothers and fathers within PDDs, CP, MR groups and between AD, HFA/ AS, PDD-NOS sub-groups. Methods: The sample consisted of 212 parents (115 mothers and 97 fathers) of 135 children or adolescents affected by PDDs, MR or CP. An additional sample of 77 parents (42 mothers and 35 fathers) of 48 healthy children was also included and used as a control group. QOL was assessed by the WHOQOL-BREF questionnaire. Results: Compared with parents of healthy children, parents in the PDDs group reported impairment in physical activity (p = 0.0001) and social relationships (p = 0.0001) and worse overall perception of their QOL (p = 0.0001) and health (p = 0.005). Scores in the physical (p = 0.0001), psychological (p = 0.0001) and social relationships domains (p = 0.0001) and in the physical (p = 0.0001) and social relationships (p = 0.0001) domains were lower compared to the MR group CP group respectively. Little differences were observed between MR, CP and control groups. The level of impairment of physical (p = 0.001) and psychological (p = 0.03) well-being were higher in mothers than in fathers in the PDDs and CP groups respectively; in the other groups, and across all the other domains of QQL impairment was similar. There were no statistically significant differences in the scores between the AD, HFA/AS and PDD-NOS sub-groups, but parents in the HFA/AS sub-group seemed to display a lower QOL compared to the AD sub-group. Conclusion: Parents of children with PDDs seem to display a higher burden, probably for a combination of environmental and genetic factors. Within this group of parents also those of HFA or AS people have higher stress. These finding must be taken into account in policy making to provide better and more specific supports and interventions for this group of diseases. Published: 27 April 2007 Health and Quality of Life Outcomes 2007, 5:22 doi:10.1186/1477-7525-5-22 Received: 17 October 2006 Accepted: 27 April 2007 This article is available from: http://www.hqlo. com/content/5/1/22 © 2007 Mugno et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Arsenic in groundwater of West Bengal: Implications from a field study

This publication presents results of an interdisciplinary field study assessing the contribution of biological and inorganic processes in the mobilisation and accumulation of arsenic in groundwater of the Bengal Delta Plain, West Bengal. Investigations were focussed on the distribution of arsenic in sediments and shallow groundwater of two representative study sites. All results were combined in an effort to develop a conceptional model describing the mobility of arsenic in West Bengal aquifers.
Mechanistic models of humoral kinetics following COVID-19 vaccination

Introduction: Future COVID-19 vaccine programmes need to take into account the variable responses elicited by different vaccines and their waning protection over time. Existing descriptions of antibody response to COVID-19 vaccination convey limited information about the mechanisms of antibody production and maintenance. Methods: We describe the antibody dynamics elicited by COVID-19 vaccination with two biologically-motivated mathematical models of antibody production by plasma cells and subsequent decay. We fit the models using Markov Chain Monte Carlo to seroprevalence data from 14,602 uninfected individuals collected via the primary care network in England between May 2020 and September 2022. We ensure our models are structurally and practically identifiable when using anti- body data alone. We analyse the effect of age, vaccine type, number of doses, and the interval between doses on antibody production and longevity of response. Results: We find evidence that individuals over 35 years of age who received a second dose of ChAdOx1-S generate a persistent antibody response suggestive of long-lived plasma cell induction, while individuals that receive two doses of BNT162b2, or one dose of either vaccine do not. We also find that plasamblast productive capacity, the likely driver of short-term antibody responses, is greater in younger people than older people ([≤] 4.5 fold change in point estimates), people vaccinated with two doses than people vaccinated with one dose ([≤] 12 fold change), and people vaccinated with BNT162b2 than people vaccinated with ChAdOx1-S ([≤] 440 fold change). The effect of age on antibody dynamics is more pronounced in people vaccinated with BNT162b2 than people vaccinated with ChAdOx1-S. We find the half-life of an antibody to be between 23 - 106 days. Conclusion: Routinely-collected seroprevalence data are a valuable source of information for characterising within-host mechanisms of antibody production and persistence. Extended sampling and linking seroprevalence data to outcomes would allow for powerful conclusions about how humoral kinetics protect against disease.
HDAC9‐mediated calmodulin deacetylation induces memory impairment in Alzheimer's disease

Abstract Aims Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. AD pathology involves protein acetylation. Previous studies have mainly focused on histone acetylation in AD, however, the roles of nonhistone acetylation in AD are less explored. Methods The protein acetylation and expression levels were detected by western blotting and co‐immunoprecipitation. The stoichiometry of acetylation was measured by home‐made and site‐specific antibodies against acetylated‐CaM (Ac‐CaM) at K22, K95, and K116. Hippocampus‐dependent learning and memory were evaluated by using the Morris water maze, novel object recognition, and contextual fear conditioning tests. Results We showed that calmodulin (CaM) acetylation is reduced in plasma of AD patients and mice. CaM acetylation and its target Ca2+/CaM‐dependent kinase II α (CaMKIIα) activity were severely impaired in AD mouse brain. The stoichiometry showed that Ac‐K22, K95‐CaM acetylation were decreased in AD patients and mice. Moreover, we screened and identified that lysine deacetylase 9 (HDAC9) was the main deacetylase for CaM. In addition, HDAC9 inhibition increased CaM acetylation and CaMKIIα activity, and hippocampus‐dependent memory in AD mice. Conclusions HDAC9‐mediated CaM deacetylation induces memory impairment in AD, HDAC9, or CaM acetylation may become potential therapeutic targets for AD.
Mechanistic role of alpha oscillations in a computational model of working memory

Brain oscillations are believed to be involved in the different operations necessary to manipulate information during working memory tasks. We propose a mechanistic role for the observed inhibition effect of the alpha rhythm based on its interference with the theta rhythm. Using the Lisman-Idiart model for multi-item working memory, we show that the interaction between these two oscillations is capable of creating a long lasting destructive interference that prevents the cyclic reactivation of neuronal ensembles and, as a consequence, memory maintenance. Additionally, to ensure robustness we propose a modular version of the model and implement oscillations as traveling waves. Using this model, we show that the interactions between theta and gamma determine the allocation of multiple memories in distinct modules, while the interference between theta and alpha disrupts the maintenance of the information already stored in them. The effect of alpha in erasing or blocking storage is robust and seems fairly independent of frequency, as long as it stays within the alpha range. This model helps us to understand why the alpha and theta oscillations, which have close frequency bands, could have opposite roles in working memory.
Same-day versus rapid ART initiation in HIV-positive individuals presenting with symptoms of tuberculosis: Protocol for an open-label randomized non-inferiority trial in Lesotho and Malawi

Background In absence of contraindications, same-day initiation (SDI) of antiretroviral therapy (ART) is recommended for people testing HIV-positive who are ready to start treatment. Until 2021, World Health Organization (WHO) guidelines considered the presence of TB symptoms (presumptive TB) a contraindication to SDI due to the risk of TB-immune reconstitution inflammatory syndrome (TB-IRIS). To reduce TB-IRIS risk, ART initiation was recommended to be postponed until results of TB investigations were available, and TB treatment initiated if active TB was confirmed. In 2021, the WHO guidelines changed to recommending SDI even in the presence of TB symptoms without awaiting results of TB investigations based on the assumption that TB investigations often unnecessarily delay ART initiation, increasing the risk for pre-ART attrition from care, and noting that the clinical relevance of TB-IRIS outside the central nervous system remains unclear. However, this guideline change was not based on conclusive evidence, and it remains unclear whether SDI of ART or TB test results should be prioritized in people with HIV (PWH) and presumptive TB. Design and methods SaDAPT is an open-label, pragmatic, parallel, 1:1 individually randomized, non-inferiority trial comparing two strategies for the timing of ART initiation in PWH with presumptive TB (“ART first” versus “TB results first”). PWH in Lesotho and Malawi, aged 12 years and older (re)initiating ART who have at least one TB symptom (cough, fever, night sweats or weight loss) and no signs of intracranial infection are eligible. After a baseline assessment, participants in the “ART first” arm will be offered SDI of ART, while those in the “TB results first” arm will be offered ART only after active TB has been confirmed or refuted. We hypothesize that the “ART first” approach is safe and non-inferior to the “TB results first” approach with regard to HIV viral suppression (<400 copies/ml) six months after enrolment. Secondary outcomes include retention in care and adverse events consistent with TB-IRIS. Expected outcomes SaDAPT will provide evidence on the safety and effects of SDI of ART in PWH with presumptive TB in a pragmatic clinical trial setting. Trial registration The trial has been registered on clinicaltrials.gov (NCT05452616; July 11 2022).
Synchronous monitoring of brain‐heart electrophysiology using heart rate variability coupled with rapid quantitative electroencephalography in orthostatic hypotension patients with α‐synucleinopathies: Rapid prediction of orthostatic hypotension and preliminary exploration of brain stimulation thera

Abstract Background In α‐synucleinopathies, the dysfunction of the autonomic nervous system which typically manifests as orthostatic hypotension (OH) often leads to severe consequences and poses therapeutic challenges. This study aims to discover the brain‐cardiac electrophysiological changes in OH patients with α‐synucleinopathies using the rapid quantitative electroencephalography (qEEG) coupled with heart rate variability (HRV) technique to identify rapid, noninvasive biomarkers for early warning and diagnosis, as well as shed new light on complementary treatment approaches such as brain stimulation targets. Methods In this study, 26 subjects of α‐synucleinopathies with OH (α‐OH group), 21 subjects of α‐synucleinopathies without OH (α‐NOH group), and 34 healthy controls (control group) were included from September 2021 to August 2023 (NCT05527067). The heart rate‐blood pressure variations in supine and standing positions were monitored, and synchronization parameters of seated resting‐state HRV coupled with qEEG were collected. Time‐domain and frequency‐domain of HRV measures as well as peak frequency and power of the brainwaves were extracted. Differences between these three groups were compared, and correlations between brain‐heart parameters were analyzed. Results The research results showed that the time‐domain parameters such as MxDMn, pNN50, RMSSD, and SDSD of seated resting‐state HRV exhibited a significant decrease only in the α‐OH group compared to the healthy control group (p < 0.05), while there was no significant difference between the α‐NOH group and the healthy control group. Several time‐domain and frequency‐domain parameters of seated resting‐state HRV were found to be correlated with the blood pressure changes within the first 5 min of transitioning from supine to standing position (p < 0.05). Differences were observed in the power of beta1 waves (F4 and Fp2) and beta2 waves (Fp2 and F4) in the seated resting‐state qEEG between the α‐OH and α‐NOH groups (p < 0.05). The peak frequency of theta waves in the Cz region also showed a difference (p < 0.05). The power of beta2 waves in the Fp2 and F4 brain regions correlated with frequency‐domain parameters of HRV (p < 0.05). Additionally, abnormal electrical activity in the alpha, theta, and beta1 waves was associated with changes in heart rate and blood pressure within the first 5 min of transitioning from supine to standing position (p < 0.05). Conclusion Rapid resting‐state HRV with certain time‐domain parameters below normal levels may serve as a predictive indicator for the occurrence of orthostatic hypotension (OH) in patients with α‐synucleinopathies. Additionally, the deterioration of HRV parameters correlates with synchronous abnormal qEEG patterns, which can provide insights into the brain stimulation target areas for OH in α‐synucleinopathy patients.
A cost-effectiveness analysis of a South African pregnancy support grant

Poverty among expectant mothers often results in sub-optimal maternal nutrition and inadequate antenatal care, with negative consequences on child health outcomes. South Africa has a child support grant that is available from birth to those in need. This study aims to determine whether a pregnancy support grant, administered through the extension of the child support grant, would be cost-effective compared to the existing child support grant alone. A cost-utility analysis was performed using a decision-tree model to predict the incremental costs (ZAR) and disability-adjusted life years (DALYs) averted by the pregnancy support grant over a 2-year time horizon. An ingredients-based approach to costing was completed from a governmental perspective. The primary outcome was the incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were performed. The intervention resulted in a cost saving of R13.8 billion ($930 million, 95% CI: ZAR3.91 billion ‐ ZAR23.2 billion/ $1.57 billion ‐ $264 million) and averted 59,000 DALYs (95% CI: -6,400–110,000), indicating that the intervention is highly cost-effective. The primary cost driver was low birthweight requiring neonatal intensive care, with a disaggregated incremental cost of R31,800 ($2,149) per pregnancy. Mortality contributed most significantly to the DALYs accrued in the comparator (0.68 DALYs). The intervention remained the dominant strategy in the sensitivity analyses. The pregnancy support grant is a highly cost-effective solution for supporting expecting mothers and ensuring healthy pregnancies. With its positive impact on child health outcomes, there is a clear imperative for government to implement this grant. By investing in this program, cost savings could be leveraged. The implementation of this grant should be given high priority in public health and social policies.
Developing and validating a survival prediction model for NSCLC patients through distributed learning across three countries

Please cite this article as: Jochems A, Deist TM, El Naqa I, Kessler M, Mayo C, Reeves J, Jolly S, Matuszak M, Haken RT, van Soest J, Oberije C, Faivre-Finn C, Price G, de Ruysscher D, Lambin P, Dekker A, Developing and validating a survival prediction model for NSCLC patients through distributed learning across three countries, International Journal of Radiation Oncology • Biology • Physics (2017), doi: 10.1016/j.ijrobp. 2017.04. 021.
Influence of COVID-19 pandemic on pregnancy and fertility preferences among the residents of the United Arab Emirates (UAE)

Background The coronavirus disease 2019 (COVID-19) significantly impacted the lifestyles of millions of people, with new challenges arising as the pandemic progresses. However, little attention has been given to issues like fertility intentions and pregnancy planning during COVID-19. Consequently, we aimed to investigate the influence of the pandemic on pregnancy and fertility decisions among the residents of the United Arab Emirates (UAE). Methods We surveyed UAE residents of reproductive age between November 2021 to June 2022 via the Google Forms platform and collected data on demographics, associated health conditions, COVID-19 infections, as well as plans for pregnancy and fertility intentions. We presented data through descriptive statistics (frequencies and percentages) and used Pearson’s χ2 test to compare the characteristics of participants who reported that the COVID-19 pandemic has influenced their fertility preferences with those who reported that it had not. Results Overall, 564 participants completed the survey, of whom 115 (20.4%) stated that the COVID-19 pandemic had influenced their fertility preferences. Meanwhile, 234 (41.5%) reported previous history of COVID-19 infection; regarding post-COVID-19 infection symptoms, 53 (22.6%) reported decreased libido and 40 (17%) reported trouble in conceiving a baby. Participants who were ≤30 years of age were less likely to be influenced by the COVID-19 pandemic on their decision on fertility compared to those >30 years of age. Factors like education, income, chronic health conditions, and previous history of COVID-19 infection or vaccination did not have any significant effect on the COVID-19 pandemic influence on fertility preferences. Conclusions The COVID-19 pandemic has brought in new challenges which could affect fertility and this needs to be studied further for planning effective measures.
Dynamic nonlinear CO2 emission effects of urbanization routes in the eight most populous countries

A dynamic STIRPAT model used in the current study is based on panel data from the eight most populous countries from 1975 to 2020, revealing the nonlinear effects of urbanization routes (percentage of total urbanization, percentage of small cities and percentage of large cities) on carbon dioxide (CO2) emissions. Using “Dynamic Display Unrelated Regression (DSUR)” and “Fully Modified Ordinary Least Squares (FMOLS)” regressions, the outcomes reflect that percentage of total urbanization and percentage of small cities have an incremental influence on carbon dioxide emissions. However, square percentage of small cities and square percentage of total urbanization have significant adverse effects on carbon dioxide (CO2) emissions. The positive relationship between the percentage of small cities, percentage of total urbanization and CO2 emissions and the negative relationship between the square percentage of small cities, square percentage of total urbanization and CO2 emissions legitimize the inverted U-shaped EKC hypothesis. The impact of the percentage of large cities on carbon dioxide emissions is significantly negative, while the impact of the square percentage of large cities on carbon dioxide emissions is significantly positive, validating a U-shaped EKC hypothesis. The incremental effect of percentage of small cities and percentage of total urbanization on long-term environmental degradation can provide support for ecological modernization theory. Energy intensity, Gross Domestic Product (GDP), industrial growth and transport infrastructure stimulate long-term CO2 emissions. Country-level findings from the AMG estimator support a U-shaped link between the percentage of small cities and CO2 emissions for each country in the entire panel except the United States. In addition, the Dumitrescu and Hulin causality tests yield a two-way causality between emission of carbon dioxide and squared percentage of total urbanization, between the percentage of the large cities and emission of carbon dioxide, and between energy intensity and emission of carbon dioxide. This study proposes renewable energy options and green city-friendly technologies to improve the environmental quality of urban areas.
Associations between impulsivity and fecal microbiota in individuals abstaining from methamphetamine

Abstract Introduction Methamphetamine (MA) abuse is a major public problem, and impulsivity is both a prominent risk factor and a consequence of addiction. Hence, clarifying the biological mechanism of impulsivity may facilitate the understanding of addiction to MA. The microbiota–gut–brain axis was suggested to underlie a biological mechanism of impulsivity induced by MA. Methods We therefore recruited 62 MA addicts and 50 healthy controls (HCs) to investigate the alterations in impulsivity and fecal microbiota and the associations between them in the MA group. Thereafter, 25 MA abusers who abstained from MA for less than 3 months were followed up for 2 months to investigate the relationship between impulsivity and microbiota as abstinence became longer. 16S rRNA sequencing was conducted for microbiota identification. Results Elevated impulsivity and dysbiosis characterized by an increase in opportunistic pathogens and a decrease in probiotics were identified in MA abusers, and both the increased impulsivity and disrupted microbiota tended to recover after longer abstinence from MA. Impulsivity was related to microbiota, and the effect of MA abuse on impulsivity was mediated by microbiota. Conclusion Our findings potentially highlighted the importance of abstention and implicated the significant role of the microbiota–gut–brain axis in the interrelationship between microbiota and behaviors, as well as the potential of microbiota as a target for intervention of impulsivity.