Miracle-dz/UniFAR-FTUs huggingface dataset:
Cross-fitted instrument: A blueprint for one-sample Mendelian randomization

Bias from weak instruments may undermine the ability to estimate causal effects in instrumental variable regression (IVR). We present here a simple solution for handling weak instrument bias by introducing a new type of instrumental variable called ‘cross-fitted instrument’ (CFI). CFI splits the data at random and estimates the impact of the instrument on the exposure in each partition. The estimates are then used to perform an IVR on each partition. We adapt CFI to Mendelian randomization (MR) and term this adaptation ‘Cross-Fitting for Mendelian Randomization’ (CFMR). A major advantage of CFMR is its use of all the available data to select genetic instruments, as opposed to traditional two-sample MR where a large part of the data is only used for instrument selection. Consequently, CFMR has the potential to enhance the power of MR in a meta-analysis setting by enabling an unbiased one-sample MR to be performed in each cohort prior to meta-analyzing the results across all the cohorts. In a similar fashion, CFMR enables a cross-ethnic MR analysis by accounting for ethnic heterogeneity, which is particularly important in consortia-led meta-analyses where the participating cohorts might be of different ethnicities. To our knowledge, there are currently no MR approach that can account for such heterogeneity. Finally, CFMR enables the application of MR to exposures that are rare or difficult to measure, which would normally preclude their analysis in the regular two-sample MR setting. Key messages We develop a new method to enable an unbiased one-sample Mendelian Randomization. The new method provides the same power as the standard two-sample Mendelian Randomization approach and does not require summary statistics from a genome-wide association study in an independent cohort. Our approach enables a cross-ethnic instrumental variable regression to account for heterogeneity in a sample consisting of multiple ethnicities.
Cinnamomum Species: Bridging Phytochemistry Knowledge, Pharmacological Properties and Toxicological Safety for Health Benefits

The genus Cinnamomum includes a number of plant species largely used as food, food additives and spices for a long time. Different traditional healing systems have used these plants as herbal remedies to cure diverse ailments. The aim of this comprehensive and updated review is to summarize the biodiversity of the genus Cinnamomum, its bioactive compounds, the mechanisms that underlie the pharmacological activities and molecular targets and toxicological safety. All the data in this review have been collected from databases and recent scientific literature including Web of Science, PubMed, ScienceDirect etc. The results showed that the bioactive compounds of Cinnamomum species possess antimicrobial, antidiabetic, antioxidant, anti-inflammatory, anticancer and neuroprotective effects. The preclinical (in vitro/in vivo) studies provided the possible molecular mechanisms of these action. As a novelty, recent clinical studies and toxicological data described in this paper support and confirm the pharmacological importance of the genus Cinnamomum. In conclusion, the obtained results from preclinical studies and clinical trials, as well as reduced side effects provide insights into future research of new drugs based on extracts and bioactive compounds from Cinnamomum plants.
Polymeric polyelectrolytes obtained from renewable sources for biodiesel wastewater treatment by dual-flocculation

Biodiesel wastewater generally contains high levels of oils, soaps and glycerol residues. This needs wastewater treatment. In this study, the biodiesel wastewater treatment was tested (industrial wastewater (EFID) and laboratory wastewater (EFLB) from biodiesel) by performing flocculation and dual-flocculation with renewable polymers. Tannin and cationic hemicellulose (CH) were used as cationic flocculant, and cellulose acetate sulfate (CAS) was used as an anionic flocculant. Polyacrylamide (PAM) was used as a reference anionic flocculant for result efficiencies analysis obtained with CAS (renewable source flocculant). The treatment efficacy in wastewater was evaluated by: turbidity removal, sludge volume formed, chemical oxygen demand (COD) and total suspended solids (TSS). The obtained sludge was studied using thermogravimetric analysis (TG). The dual-flocculation application condition of the 25% proportion of tannin (T) and 75% proportion of cationic hemicelluloses (i.e., T25/CH75) showed EFLB turbidity removal of 89.1% and 89.5% for CAS and PAM additions respectively, and for EFID of 67% and 41% for CAS and PAM additions respectively. The dual-flocculation performance suggested that the polyelectrolytes obtained from renewable sources can be used for treating biodiesel wastewater.
Highly Sensing Properties Sensors Based on Ce-doped ZnO and SnO2 Nanoparticles to Ethanol Gas

The detection of different types of gases and quantification of their precisely concentration have wide applications in different fields like domestic gas alarms, medical diagnostic equipment, industrial safety, environmental pollution, military field and food industry [Papadopoulos et al (1996), Wang C et al (2009), Wetchakun et al (2011), Brudzewski et al (2012), Mielle et al (2001) and Fleming (2001)]. With numerous industries that utilize or produce ethanol, it is apparent that reliable methods are needed Abstract
Genetic determinism of phage-bacteria coevolution in natural populations

Coevolution between bacteriophage (or phage) and their bacterial host is thought to be key for the coexistence of these antagonists. Recent studies have revealed the major role of mobile genetic elements in the emergence of phage resistant hosts but how phage escape these defenses in the wild remained to be explored. Here we show a striking parallel in phage evolving counter defenses to host defenses in natural population. We established a large collection of phages and their bacterial hosts and we explored the genetic structure of their interaction. We find that clearly delineated genomic clusters of phage are specific for distinct clades within a bacterial species, Vibrio crassostreae, yet while all phages can adsorb, only a subset of hosts are killed due to intracellular defense mechanisms. Host genomes contain multiple mobile defense genes and susceptibility to phage is negatively correlated with genome size. Phages also display extensive gene content variation, but their genome size remains conserved. We show that this gene content variation in hosts and phage is due to rapid turnover of genes involved in defense and escape, and that by exchanging anti-defense genes, phages irreversibly switch host. This could be indicative of co-evolution following the matching-allele-model of specificity and the spatial and temporal variability of phage infectivity further suggests that negative-frequency dependent selection drives phage-vibrio coevolutionary dynamics. We propose a “pan-escape system” that can be shared among phages by homologous recombination within a population that infects a bacterial host.
A Modified Comprehensive Grading System for Murine Knee Osteoarthritis: Scoring the Whole Joint as an Organ

Objective This study aimed to develop a comprehensive but easy to apply histologic grading system to score osteoarthritic changes in the whole knee joint for both spontaneous and posttraumatic osteoarthritis (OA) mouse models. Methods The new OA grading scheme was developed based on extensive literature review and the authors’ experience in mouse OA models with relatively long periods of observation (up to 24 months of age or 24-week post-surgery). Semi-quantitative assessments of the histopathologic OA changes were applied to all four quadrants of the knee. Grading elements per quadrant were defined as follows: cartilage (0-7) including three new grading elements for early- and late-stage OA, respectively; osteophyte (0-2) covering chondro-osteophytes in both outer and inner joint margins; subchondral bone (0-2) containing subchondral bone thickening and destruction; synovitis (0-2) comprised of both synovial plica and intercondylar notch; and peri-articular tissues (0-2) highlighting ectopic chondrogenesis and ossification in the knee capsule, ligament, and musculature. Results Statistical analyses showed that the new grading system had high intra- and inter-observer reproducibility (Pearson’s correlation coefficients r >0.9) for both experienced and novice scorers. Sensitivity and reliability analyses confirmed the ability of the new system to detect minimal OA progression between two timepoints with a two-week interval and to accurately identify tissue-specific OA severity within the knee joint. Conclusions The comprehensive histologic grading system presented here covers all-stage osteoarthritic changes in all major knee joint tissues of mice, which enable us to score OA severity for the whole joint reproducibly and accurately without software-assisted time-consuming measurements.
Simultaneous Brain, Brainstem and Spinal Cord

1) Anaesthesia, Pain & Critical Care Sciences, School of Physiology, Pharmacology & 6 Neuroscience, Biomedical Sciences Building, University of Bristol, Bristol, BS8 1TD, UK. 7 2) Clinical Research and Imaging Centre, School of Psychological Science, University of 8 Bristol, Bristol, BS8 1TU, UK 9 3) Medical Physics, University Hospitals Bristol & Weston NHS Trust, Bristol, BS2 8HW, 10 UK. 11 4) Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, 12 King's College London, London, SE5 8AF, UK. 13 5) Wellcome Wolfson Brain Imaging Centre, School of Psychology, Lawrence Stenhouse 14 Building, University of East Anglia, Norwich, NR4 7TJ, UK. 15 6) Department of Anesthesiology, University of California San Diego, 9500 Gilman Dr, La 16 Jolla, CA 92093, USA. 17
The role of elections as drivers of tropical deforestation

Tropical forests support immense biodiversity and provide essential ecosystem services for billions of people. Despite this value, tropical deforestation continues at a high rate. Emerging evidence suggests that elections can play an important role in shaping deforestation, for instance by incentivising politicians to allow increased utilisation of tropical forests in return for political support and votes. Nevertheless, the role of elections as a driver of deforestation has not been comprehensively tested at broad geographic scales. Here, we created an annual database from 2001 to 2018 on political elections and forest loss for 55 tropical nations and modelled the effect of elections on deforestation. In total, 1.5 million km2 of forest was lost during this time period, and the rate of deforestation increased in 37 (67%) of the analysed countries. Deforestation was significantly lower in years with presidential or lower chamber elections compared to non-election years, which is in contrast to previous local-scale studies. Moreover, deforestation was significantly higher in presidential or lower chamber elections that are competitive (i.e. when the opposition can participate in elections and has a legitimate chance to gain governmental power) compared to uncompetitive elections. Our results document a pervasive loss of tropical forests and suggest that competitive elections are potential drivers of deforestation. We recommned that organisations monitoring election transparency and fairness should also monitor environmental impacts such as forest loss, habitat destruction and resource exploitation. This would benefit the tracking of potential illegal vote buying with natural resources.
OMRT-3. Longitudinal analysis of diffuse glioma reveals cell state dynamics at recurrence associated with changes in genetics and the microenvironment

To interrogate the factors driving therapy resistance in diffuse glioma, we collected and analyzed RNA and/or DNA sequencing data from temporally separated tumor pairs of 292 adult patients with IDH-wild-type or IDH-mutant glioma. Tumors recurred in distinct manners that were dependent on IDH mutation status and attributable to changes in histological feature composition, somatic alterations, and microenvironment interactions. Hypermutation and acquired CDKN2A deletions associated with an increase in proliferating stem-like malignant cells at recurrence in both glioma subtypes, reflecting active tumor growth. IDH-wild-type tumors were more invasive at recurrence, and their malignant cells exhibited increased expression of neuronal signaling programs that reflected a possible role for neuronal interactions in promoting glioma progression. Mesenchymal transition was associated with the presence of a specific myeloid cell state defined by unique ligand-receptor interactions with malignant cells. Collectively, our results uncover recurrence-associated changes that could be targetable to shape disease progression following initial diagnosis.
The influence of vitality forms on action perception and motor response

During the interaction with others, action, speech, and touches can communicate positive, neutral, or negative attitudes. Offering an apple can be gentle or rude, a caress can be kind or rushed. These subtle aspects of social communication have been named vitality forms by Daniel Stern. Although they characterize all human interactions, to date it is not clear whether vitality forms expressed by an agent may affect the action perception and the motor response of the receiver. To this purpose, we carried out a psychophysics study aiming to investigate how perceiving different vitality forms can influence cognitive and motor tasks performed by participants. In particular, participants were stimulated with requests made through a physical contact or vocally and conveying rude or gentle vitality forms, and then they were asked to estimate the end of a passing action observed in a monitor (action estimation task) or to perform an action in front of it (action execution task) with the intention to pass an object to the other person presented in the video. Results of the action estimation task indicated that the perception of a gentle request increased the duration of a rude action subsequently observed, while the perception of a rude request decreased the duration of the same action performed gently. Additionally, during the action execution task, accordingly with the perceived vitality form, participants modulated their motor response.
Double Empathy: Why Autistic People Are Often Misunderstood

Autism affects how someone makes sense of the world around them. About 1–2% of people are autistic. You might have an autistic classmate or family member, or maybe you are autistic. Autistic people might communicate differently than people who are not autistic. This means that it can be difficult for other people to understand what autistic people are trying to say or what they mean. We tend to think that people who are not autistic might be more successful at understanding other people, but in fact, autistic people may be better understood by other autistic people. We will examine and explain some research that has explored how autistic and non-autistic people communicate with each other and explore how this research fits with a theory called the double empathy problem. Understanding what makes interaction comfortable and easy for different people can help us all understand each other better.
The Regulation of Adipose Triglyceride Lipase-Mediated Lipolysis in Avian Species: the Role of Comparative Gene Identification-58

ii Dedication . v Acknowledgments. vi Vita . viii List of Tables . xii List of Figures . xiii List of Abbreviations . xvi Chapter 1:Introduction . 1 1.1 Aims . 3 Chapter 2: Review of the Literature . 4 2.1 Adipose Tissue . 4 2.2 Obesity . 5 2.3 Considerations for Adipose Tissue in Livestock Production . 7 2.4 Adipose Tissue Lipolysis . 8 2.5 Hormone-sensitive Lipase . 9 2.5. 1 Regulation of HSL . 11 x 2.6 Monoglyceride Lipase . 13 2.7 Adipose Triglyceride Lipase . 14 2.7. 1 Regulation of ATGL . 16 2.7. 1.1 Transcriptional Regulation.16 2.7. 1.2 Post-translational Regulation . 17 2.8 Pathogenesis of Mutations in ATGL and CGI-58 . 21 Chapter 3: Cloning of comparative gene identification-58 (CGI-58) in avian species and investigation of its developmental and nutritional regulation in chicken adipose tissue . 24 3.1 Abstract . 24 3.2 Introduction . 25 3.3 Materials and Methods . 27 3.4 Results . 31 3.5 Discussion . 33 3.6 Acknowledgments.37 Chapter 4: Acute up-regulation of adipose triglyceride lipase (ATGL) by dexamethasone in chicken adipose tissue . 46 4.1 Abstract . 46 4.2 Introduction . 47 4.3 Materials and Methods . 48 4.4 Results . 52 4.5 Discussion . 54 4.6 Acknowledgements . 58
Corrigendum

May CD and Fletcher R. The development and application of a protocol for the writing, assessing, and validating of a corpus of relationship-focused text messages for new and expecting fathers. Health Informatics Journal 2017; DOI: 10.1177/1460458217704249 The funding statement of this article was not wholly correct. The correct funding statement is given below. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research reported in this paper was funded by beyondblue with donations from the Movember Foundation. The subsequent versions of the article have been corrected.
Trypanosoma brucei PolIE suppresses telomere recombination

Telomeres are essential for genome integrity and stability. In T. brucei that causes human African trypanosomiasis, the telomere structure and telomere proteins also influence the virulence of the parasite, as its major surface antigen involved in the host immune evasion is expressed exclusively from loci immediately upstream of the telomere repeats. However, telomere maintenance mechanisms are still unclear except that telomerase-mediated telomere synthesis is a major player. We now identify PolIE as an intrinsic telomere complex component. We find that depletion of PolIE leads to an increased amount of telomere/subtelomere DNA damage, an elevated rate of antigenic variation, and an increased amount of telomere T-circles and C-circles, indicating that PolIE suppresses telomere recombination and helps maintain telomere integrity. In addition, we observe much longer telomere G-rich 3’ overhangs in PolIE-depleted cells, which is not dependent on telomerase. Furthermore, the level of telomere DNA synthesis is slightly increased in PolIE-depleted cells, which is dependent on telomerase. Therefore, we identify PolIE as a major player for telomere maintenance in T. brucei.
World Cancer Day 2021 - Perspectives in Pediatric and Adult Neuro-Oncology

Significant advances in our understanding of the molecular genetics of pediatric and adult brain tumors and the resulting rapid expansion of clinical molecular neuropathology have led to improvements in diagnostic accuracy and identified new targets for therapy. Moreover, there have been major improvements in all facets of clinical care, including imaging, surgery, radiation and supportive care. In selected cohorts of patients, targeted and immunotherapies have resulted in improved patient outcomes. Furthermore, adaptations to clinical trial design have facilitated our study of new agents and other therapeutic innovations. However, considerable work remains to be done towards extending survival for all patients with primary brain tumors, especially children and adults with diffuse midline gliomas harboring Histone H3 K27 mutations and adults with isocitrate dehydrogenase (IDH) wild-type, O6 guanine DNA-methyltransferase gene (MGMT) promoter unmethylated high grade gliomas. In addition to improvements in therapy and care, access to the advances in technology, such as particle radiation or biologic therapy, neuroimaging and molecular diagnostics in both developing and developed countries is needed to improve the outcome of patients with brain tumors.
Decoding the silence: Neural bases of zero pronoun resolution in Chinese

Chinese is one of many languages that can drop subjects. We report an fMRI study of language comprehension processes in these “zero pronoun” cases. The fMRI data come from Chinese speakers who listened to an audiobook. We conducted both univariate GLM and multivariate pattern analysis (MVPA) on these data time-locked to each verb with a zero pronoun subject. We found increased left middle temporal gyrus activity for zero pronouns compared to overt subjects, suggesting additional effort searching for an antecedent during zero pronoun resolution. MVPA further revealed that the intended referent of a zero pronoun seems to be physically represented in the Precuneus and the Parahippocampal Gyrus shortly after its presentation. This highlights the role of memory and discourse-level processing in resolving referential expressions, including unspoken ones, in naturalistic language comprehension.
Crop loss identification at field parcel scale using satellite remote sensing and machine learning

Identifying crop loss at field parcel scale using satellite images is challenging: first, crop loss is caused by many factors during the growing season; second, reliable reference data about crop loss are lacking; third, there are many ways to define crop loss. This study investigates the feasibility of using satellite images to train machine learning (ML) models to classify agricultural field parcels into those with and without crop loss. The reference data for this study was provided by Finnish Food Authority (FFA) containing crop loss information of approximately 1.4 million field parcels in Finland covering about 3.5 million ha from 2000 to 2015. This reference data was combined with Normalised Difference Vegetation Index (NDVI) derived from Landsat 7 images, in which more than 80% of the possible data are missing. Despite the hard problem with extremely noisy data, among the four ML models we tested, random forest (with mean imputation and missing value indicators) achieved the average AUC (area under the ROC curve) of 0.688 ± 0.059 over all 16 years with the range [0.602, 0.795] in identifying new crop-loss fields based on reference fields of the same year. To our knowledge, this is one of the first large scale benchmark study of using machine learning for crop loss classification at field parcel scale. The classification setting and trained models have numerous potential applications, for example, allowing government agencies or insurance companies to verify crop-loss claims by farmers and realise efficient agricultural monitoring.
Fine-scale quantification of GC-biased gene conversion intensity in mammals

GC-biased gene conversion (gBGC) is a molecular evolutionary force that favours GC over AT alleles irrespective of their fitness effect. Quantifying the variation in time and across genomes of its intensity is key to properly interpret patterns of molecular evolution. In particular, the existing literature is unclear regarding the relationship between gBGC strength and species effective population size, Ne. Here we analysed the nucleotide substitution pattern in coding sequences of closely related species of mammals, thus accessing a high resolution map of the intensity of gBGC. Our maximum likelihood approach shows that gBGC is pervasive, highly variable among species and genes, and of strength positively correlated with Ne in mammals. We estimate that gBGC explains up to 60% of the total amount of synonymous AT→GC substitutions. We show that the fine-scale analysis of gBGC-induced nucleotide substitutions has the potential to inform on various aspects of molecular evolution, such as the distribution of fitness effects of mutations and the dynamics of recombination hotspots.