Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple drivers of the COVID-19 spread: role of climate, international mobility, and region-specific conditions

The novel Coronavirus Disease 2019 (COVID-19) has spread quickly across the globe. Here, we evaluated the role of climate (temperature and precipitation), region-specific susceptibility (BCG vaccination, malaria infection, and elderly population) and international traveller population (human mobility) in shaping the geographical patterns of COVID-19 cases across 1,055 countries/regions, and examined the sequential shift of multiple drivers of the accumulated cases from December, 2019 to April 12, 2020. The accumulated numbers of COVID-19 cases (per 1 million population) were well explained by a simple regression model. The explanatory power (R2) of the model increased up to > 70% in April 2020 as the COVID-19 spread progressed. Climate, host mobility, and host susceptibility largely explained the variance of the COVID-19 cases (per 1 million population), and their explanatory power improved as the pandemic progressed; the relative importance of host mobility and host susceptibility have been greater than that of climate. The number of days from outbreak onset showed greater explanatory power in the earlier stages of COVID-19 spread but rapidly lost its influence. Our findings demonstrate that the COVID-19 pandemic is deterministically driven by climate suitability, cross-border human mobility, and region-specific susceptibility. The present distribution of COVID-19 cases has not reached an equilibrium and is changing daily, especially in the Southern Hemisphere. Nevertheless, the present results, based on mapping the spread of COVID-19 and identifying multiple drivers of this outbreak trajectory, may contribute to a better understanding of the COVID-19 disease transmission risk and the measures against long-term epidemic.
5-Hydroxytryptamine Receptors and Tardive Dyskinesia in Schizophrenia

Background Tardive dyskinesia (TD) is a common side effect of antipsychotic treatment. This movement disorder consists of orofacial and limb-truncal components. The present study is aimed at investigating the role of serotonin receptors (HTR) in modulating tardive dyskinesia by genotyping patients with schizophrenia. Methods A set of 29 SNPs of genes of serotonin receptors HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B, and HTR6 was studied in a population of 449 Caucasians (226 females and 223 males) with verified clinical diagnosis of schizophrenia (according to ICD-10: F20). Five SNPs were excluded because of low minor allele frequency or for not passing the Hardy-Weinberg equilibrium test. Affinity of antipsychotics to 5-HT2 receptors was defined according to previous publications. Genotyping was carried out with SEQUENOM Mass Array Analyzer 4. Results Statistically significant associations of rs1928040 of HTR2A gene in groups of patients with orofacial type of TD and total diagnosis of TD was found for alleles, and a statistical trend for genotypes. Moreover, statistically significant associations were discovered in the female group for rs1801412 of HTR2C for alleles and genotypes. Excluding patients who used HTR2A, respectively, HTR2C antagonists changed little to the associations of HTR2A polymorphisms, but caused a major change of the magnitude of the association of HTR2C variants. Due to the low patient numbers, these sub-analyses did not have significant results. Conclusion We found significant associations in rs1928040 of HTR2A and for rs1801412 of X-bound HTR2C in female patients. The associations were particularly related to the orofacial type of TD. Excluding patients using relevant antagonists particularly affected rs1801412, but not rs1928040-related associations. This suggest that rs1801412 is directly or indirectly linked to the functioning of HTR2C. Further study of variants of the HTR2C gene in a larger group of male patients who were not using HTR2C antagonists is necessary in order to verify a possible functional role of this receptor.
High Throughput Screening for New Fungal Polyester Hydrolyzing Enzymes

There is a strong need for novel and more efficient polyester hydrolyzing enzymes in order to enable the development of more environmentally friendly plastics recycling processes allowing the closure of the carbon cycle. In this work, a high throughput system on microplate scale was used to screen a high number of fungi for their ability to produce polyester-hydrolyzing enzymes. For induction of responsible enzymes, the fungi were cultivated in presence of aliphatic and aromatic polyesters [poly(1,4-butylene adipate co terephthalate) (PBAT), poly(lactic acid) (PLA) and poly(1,4-butylene succinate) (PBS)], and the esterase activity in the culture supernatants was compared to the culture supernatants of fungi grown without polymers. The results indicate that the esterase activity of the culture supernatants was induced in about 10% of the tested fungi when grown with polyesters in the medium, as indicated by increased activity (to >50 mU/mL) toward the small model substrate para-nitrophenylbutyrate (pNPB). Incubation of these 50 active culture supernatants with different polyesters (PBAT, PLA, PBS) led to hydrolysis of at least one of the polymers according to liquid chromatography-based quantification of the hydrolysis products terephthalic acid, lactic acid and succinic acid, respectively. Interestingly, the specificities for the investigated polyesters varied among the supernatants of the different fungi.
Fear of Recurrence Affects Health-Related Quality of Life in Thyroid Cancer Patients

BACKGROUND The number of new cases of differentiated thyroid cancer, the most common endocrine cancer, has been increasing over the past several years. A diagnosis of cancer has many significant implications to patients, including concerns about death and the need for strong chemotherapy drugs that cause one to lose their hair. While thyroid cancer patients usually need to undergo surgery, the majority of patients do well and have an excellent prognosis. The risk of death due to differentiated thyroid cancer is very low and very few patients require strong chemotherapy drugs. Despite this, previous studies have shown that thyroid cancer patients have decreased health-related quality of life (HRQoL) compared to the general population, and surprisingly similar to that of patients with more aggressive cancers. This study evaluated changes in HRQoL over time and the factors at diagnosis that may predict HRQoL at one-year follow up.
The Emerging Role of Myeloid-Derived Suppressor Cells in the Glioma Immune Suppressive Microenvironment

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid progenitor and precursor cells at different stages of differentiation, which play an important role in tumor immunosuppression. Glioma is the most common and deadliest primary malignant tumor of the brain, and ample evidence supports key contributions of MDSCs to the immunosuppressive tumor microenvironment, which is a key factor stimulating glioma progression. In this review, we summarize the source and characterization of MDSCs, discuss their immunosuppressive functions, and current approaches that target MDSCs for tumor control. Overall, the review provides insights into the roles of MDSC immunosuppression in the glioma microenvironment and suggests that MDSC control is a powerful cellular therapeutic target for currently incurable glioma tumors.
Light Up the Brain: The Application of Optogenetics in Cell-Type Specific Dissection of Mouse Brain Circuits

The exquisite intricacies of neural circuits are fundamental to an animal’s diverse and complex repertoire of sensory and motor functions. The ability to precisely map neural circuits and to selectively manipulate neural activity is critical to understanding brain function and has, therefore been a long-standing goal for neuroscientists. The recent development of optogenetic tools, combined with transgenic mouse lines, has endowed us with unprecedented spatiotemporal precision in circuit analysis. These advances greatly expand the scope of tractable experimental investigations. Here, in the first half of the review, we will present applications of optogenetics in identifying connectivity between different local neuronal cell types and of long-range projections with both in vitro and in vivo methods. We will then discuss how these tools can be used to reveal the functional roles of these cell-type specific connections in governing sensory information processing, and learning and memory in the visual cortex, somatosensory cortex, and motor cortex. Finally, we will discuss the prospect of new optogenetic tools and how their application can further advance modern neuroscience. In summary, this review serves as a primer to exemplify how optogenetics can be used in sophisticated modern circuit analyses at the levels of synapses, cells, network connectivity and behaviors.
Precision Medicine and the Role of Biomarkers of Radiotherapy Response in Breast Cancer

Radiotherapy remains an important treatment modality in nearly two thirds of all cancers, including the primary curative or palliative treatment of breast cancer. Unfortunately, largely due to tumor heterogeneity, tumor radiotherapy response rates can vary significantly, even between patients diagnosed with the same tumor type. Although in recent years significant technological advances have been made in the way radiation can be precisely delivered to tumors, it is proving more difficult to personalize radiotherapy regimens based on cancer biology. Biomarkers that provide prognostic or predictive information regarding a tumor's intrinsic radiosensitivity or its response to treatment could prove valuable in helping to personalize radiation dosing, enabling clinicians to make decisions between different treatment options whilst avoiding radiation-induced toxicity in patients unlikely to gain therapeutic benefit. Studies have investigated numerous ways in which both patient and tumor radiosensitivities can be assessed. Tumor molecular profiling has been used to develop radiosensitivity gene signatures, while the assessment of specific intracellular or secreted proteins, including circulating tumor cells, exosomes and DNA, has been performed to identify prognostic or predictive biomarkers of radiation response. Finally, the investigation of biomarkers related to radiation-induced toxicity could provide another means by which radiotherapy could become personalized. In this review, we discuss studies that have used these methods to identify or develop prognostic/predictive signatures of radiosensitivity, and how such assays could be used in the future as a means of providing personalized radiotherapy.
Automated Home-Cage Testing as a Tool to Improve Reproducibility of Behavioral Research?

Over the past few years, an intense discussion about the reproducibility of scientific findings in various life science disciplines arose (e.g., Baker, 2016; Scannell and Bosley, 2016; Voelkl and Würbel, 2016). Thereby, particular attention has been given to animal research, where irreproducibility prevalence rates have been estimated to range between 50 and 90% (Prinz et al., 2011; Collins and Tabak, 2014; Freedman et al., 2015). Highlighted under the umbrella term of the “reproducibility crisis,” mostly failures in the planning and conduct of animal experiments have been criticized to lead to invalid and hence irreproducible findings. To counteract these trends, animal scientists have repeatedly emphasized the need for a rethinking of current methodologies, mainly targeting aspects of the experimental design, but also of the reporting and publishing standards (see e.g., ARRIVE guidelines, Kilkenny et al., 2010; TOP guidelines, Nosek et al., 2016; du Sert et al., 2018; PREPARE guidelines, Smith et al., 2018). However, as demonstrated by an already 20 years-old study, the use of thoroughly planned and well-reported protocols does not automatically lead to perfect reproducibility: In this study, three laboratories found remarkably different results when comparing the behavior of eightmouse strains in a battery of six conventionally carried out behavioral paradigms (Crabbe et al., 1999). It was hypothesized that “specific experimenters performing the testing were unique to each laboratory and could have influenced behavior of the mice. The experimenter in Edmonton, for example, was highly allergic tomice and performed all tests while wearing a respirator—a laboratory-specific (and uncontrolled) variable. ” Following on from these thoughts, the importance of the experimenter as an uncontrollable background factor in the study of behavior moved into focus (e.g., Chesler et al., 2002a,b). Concomitantly, the use of automated test systems was promoted as a tool to reduce the experimenter’s influence and to improve the accuracy and reproducibility of behavioral data (e.g., Spruijt and DeVisser, 2006). Against this background, the present opinion paper aims at (1) briefly discussing the role of the experimenter in animal studies, (2) investigating the advantages and disadvantages of automated test systems, (3) exploring the potential of automation for improving reproducibility, and (4) proposing an alternative strategy for systematically integrating the experimenter as a controlled variable in the experimental design. In particular, I will argue that systematic variation of personnel rather than rigorous homogenization of experimental conditionsmight benefit the external validity, and hence the reproducibility of behavioral data.
The Construction of Biomimetic Cementum Through a Combination of Bioskiving and Fluorine-Containing Biomineralization

Despite tremendous attention is given to the construction of biomimetic cementum for regeneration of tooth cementum, the lack of recapitulating the composition and hierarchical structure of cementum often leads to the poor performance of constructed materials. How to highly mimic the sophisticated composition and hierarchy of cementum remains a longstanding challenge in constructing the biomimetic cementum. Inspired by cementum formation process, a novel construction approach via a combination of bioskiving and fluorine-containing biomineralization is developed in this study. The alternative collagen lamellae (ACL) that can highly mimic the rotated plywood structure of cementum collagen matrix is fabricated via bioskiving. Followed by biomineralization in the amorphous calcium phosphate (ACP) solution with different concentration of fluorine, a series of biomimetic cementum is constructed. Screened by physicochemical characterization, the biomimetic cementum with the composition and hierarchical structure highly similar to human cementum is selected. Through in vitro biological assay, this biomimetic cementum is proven to significantly promote the adhesion, proliferation, and cementogenic differentiation of periodontal ligament cells (PDLCs). Furthermore, in vivo study demonstrates that biomimetic cementum could induce cementogenesis. This biomimetic cementum constructed via combinatory application of bioskiving and fluorine-containing biomineralization stands as a promising candidate for achieving cementum regeneration.
Effects of Light on Secondary Metabolites in Selected Leafy Greens: A Review

In contrast to the primary metabolism, responsible for essential synthesis mechanisms and mass balance in plants, the secondary metabolism is not of particular importance for each cell but for the plant organism as its whole. Most of these metabolites show antioxidant properties and are beneficial for human health. In order to affect accumulation of those metabolites, light is an essential factor. It is possible to select various combinations of light intensity and light quality to address corresponding photoreceptors and synthesis. However, the plethora of additional variables considering environmental conditions such as temperature, relative humidity or cultivation method complicate defining specific “light recipes”. This review summarizes experiments dealing with consumable leafy greens such as lettuce or basil and the enhancement of three selected metabolites – anthocyanins, carotenoids and flavonols.
Association of Carotid Atherosclerosis With Lipid Components in Asymptomatic Low-Income Chinese: A Population-Based Cross-Sectional Study

Intima-media thickness is a non-invasive arterial marker of early-stage atherosclerosis. Identifying carotid plaque is a superior surrogate endpoint for assessing atherosclerotic lesions. The aim of this study was to investigate the association of carotid intima-media thickness (CIMT) and carotid plaque with lipids among asymptomatic low-income rural residents in China. A total of 3,789 people aged ≥45 years without a history of stroke or cardiovascular disease were recruited to this study. B-mode ultrasonography was performed to measure CIMT and identify carotid plaque for early identification of atherosclerosis. Multivariate analysis was used to assess the association of blood lipid levels with atherosclerosis. The mean CIMT across our cohort was 567 μm. A linear regression analysis showed that low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were risk factors for early-stage atherosclerosis; however, high-density lipoprotein cholesterol and triglycerides protected against early-stage atherosclerosis after adjusting for potential risk factors (P < 0.001). Carotid plaque risk increased by 24 and 62% for each 1-mmol/L increase in TC and LDL-C (P < 0.001). These findings suggest that it is vital to manage and control the dyslipidemia standard levels in China, especially among rural residents, in order to reduce the burden of cardiovascular diseases.
XRCC1 Is a Promising Predictive Biomarker and Facilitates Chemo-Resistance in Gallbladder Cancer

Gallbladder cancer is a relatively uncommon human malignant tumor with an extremely poor prognosis. Currently, no biomarkers can accurately diagnose gallbladder cancer and predict patients’ prognosis. XRCC1 is involved in tumorigenesis, progression, and chemo-resistance of several human cancers, but the role of XRCC1 in gallbladder cancer is never reported. In this study, we investigated the expression of XRCC1 and its clinicopathological and prognostic significance in gallbladder cancer, and explored the biological role of XRCC1 in gallbladder cancer cells. We found that XRCC1 was significantly up-regulated in gallbladder cancer in protein and mRNA levels. Positive XRCC1 expression was correlated with aggressive clinicopathological features and was an independent poor prognostic factor in gallbladder cancer. The ROC curves suggested that XRCC1 expression had potential clinicopathological diagnostic value in gallbladder cancer. In vitro, XRCC1 was overexpression in CD133+GBC-SD cells compared to GBC-SD cells. In functional experiment, XRCC1 knockdown had a non-significant impact on proliferation, migration, invasion, and apoptosis of CD133+GBC-SD cells. But, XRCC1 knockdown could significantly improve the sensitivity of CD133+GBC-SD cells to 5-Fluorouracil via promoting cell necrosis and apoptosis. Thus, this study indicates that XRCC1 may be a promising predictive biomarker of gallbladder cancer and a potential therapeutic target for gallbladder cancer.
Cystic Fibrosis Patients Infected With Epidemic Pseudomonas aeruginosa Strains Have Unique Microbial Communities

Pseudomonas aeruginosa is the archetypal cystic fibrosis (CF) pathogen. However, the clinical course experienced by infected individuals varies markedly. Understanding these differences is imperative if further improvements in outcomes are to be achieved. Multiple studies have found that patients infected with epidemic P. aeruginosa (ePA) strains may have a worse clinical prognosis than those infected with unique, non-clonal strains. Additionally, the traditionally uncultured CF lung bacterial community (i.e., CF microbiome) may further influence the outcome. We sought to identify if these two important variables, not identified through routine culture, associate and together may contribute to disease pathogenesis. Patients were classified as being infected with Prairie Epidemic ePA (PES) or a non-clonal strain, unique PA strains (uPA), through a retrospective assessment of a comprehensive strain biobank using a combination of PFGE and PES-specific PCR. Patients were matched to age, sex, time-period controls and sputum samples from equivalent time periods were identified from a sputum biobank. Bacterial 16S rRNA gene profiling and Pseudomonas qPCR was used to characterize the respiratory microbiome. We identified 31 patients infected with PES and matched them with uPA controls. Patients infected with PES at baseline have lower microbial diversity (P = 0.02) and higher P. aeruginosa relative abundance (P < 0.005). Microbial community structure was found to cluster by PA strain type, although it was not the main determinant of community structure as additional factors were also found to be drivers of CF community structure. Communities from PES infected individuals were enriched with Pseudomonas, Streptococcus and Prevotella OTUs. The disproportionate disease experienced by ePA infected CF patients may be mediated through a combination of pathogen-pathogen factors as opposed to strictly enhanced virulence of infecting P. aeruginosa strains.
CRISPR/Cas9 Gene Editing of Gluten in Wheat to Reduce Gluten Content and Exposure—Reviewing Methods to Screen for Coeliac Safety

Ingestion of gluten proteins (gliadins and glutenins) from wheat, barley and rye can cause coeliac disease (CD) in genetically predisposed individuals. The only remedy is a strict and lifelong gluten-free diet. There is a growing desire for coeliac-safe, whole-grain wheat-based products, as consumption of whole-grain foods reduces the risk of chronic diseases. However, due to the large number of gluten genes and the complexity of the wheat genome, wheat that is coeliac-safe but retains baking quality cannot be produced by conventional breeding alone. CD is triggered by immunogenic epitopes, notably those present in α-, γ-, and ω-gliadins. RNA interference (RNAi) silencing has been used to down-regulate gliadin families. Recently, targeted gene editing using CRISPR/Cas9 has been applied to gliadins. These methods produce offspring with silenced, deleted, and/or edited gliadins, that overall may reduce the exposure of patients to CD epitopes. Here we review methods to efficiently screen and select the lines from gliadin gene editing programs for CD epitopes at the DNA and protein level, for baking quality, and ultimately in clinical trials. The application of gene editing for the production of coeliac-safe wheat is further considered within the context of food production and in view of current national and international regulatory frameworks.
Fetal Membranes and Associated Complications in Dairy Animals: A Review

Fetal membrane is temporary organ that feeds the fetus intrauterine. It also permits transfer of oxygen and nutrients from mother to fetus and release of carbon dioxide and waste products from fetus. Placenta is partly maternal and partly embryonic in origin. Actual mixing of maternal and fetal blood is not possible due to placental membrane. After conception uterine contraction and tonicity decreases to retain blastocyst in situ position in uterus. Protein factors like blastokinin, trophoblastin has role in maternal recognition of pregnancy (MRP). Placenta of dairy animals is polycotyledonary and non-deciduate type. Prevention of RFM includes reducing stress, improving comfort and balance ration during transition period. Proper exercise, Vitamins (Vitamin A, E and Selenium), minerals along with infection control are common factors which control post-parturient problems including retention of placenta. Use of ecbolic, collagenase, antibiotics, herbal preparation and hormones are common practice used by farmers and farms with very positive effect i.e., reducing infertility.