Miracle-dz/UniFAR-FTUs huggingface dataset:
Schizophrenia-An Overview.

Importance Schizophrenia is a common, severe mental illness that most clinicians will encounter regularly during their practice. This report provides an overview of the clinical characteristics, epidemiology, genetics, neuroscience, and psychopharmacology of schizophrenia to provide a basis to understand the disorder and its treatment. This educational review is integrated with a clinical case to highlight how recent research findings can inform clinical understanding. Observations The first theme considered is the role of early-life environmental and genetic risk factors in altering neurodevelopmental trajectories to predispose an individual to the disorder and leading to the development of prodromal symptoms. The second theme is the role of cortical excitatory-inhibitory imbalance in the development of the cognitive and negative symptoms of the disorder. The third theme considers the role of psychosocial stressors, psychological factors, and subcortical dopamine dysfunction in the onset of the positive symptoms of the disorder. The final theme considers the mechanisms underlying treatment for schizophrenia and common adverse effects of treatment. Conclusions and Relevance Schizophrenia has a complex presentation with a multifactorial cause. Nevertheless, advances in neuroscience have identified roles for key circuits, particularly involving frontal, temporal, and mesostriatal brain regions, in the development of positive, negative, and cognitive symptoms. Current pharmacological treatments operate using the same mechanism, blockade of dopamine D2 receptor, which contribute to their adverse effects. However, the circuit mechanisms discussed herein identify novel potential treatment targets that may be of particular benefit in symptom domains not well served by existing medications.
Examining associations between two different jumping to conclusions scores with positive schizotypy and recent distress

ABSTRACT Introduction: Jumping to conclusions is associated with delusions. It is unclear whether positive schizotypy, which refers to delusion-like and hallucination-like symptoms, is associated with jumping to conclusions. Relatedly, the relative validity of two jumping to conclusions scores, extreme responding and draws to decision, is unclear, particularly whether extreme responding (responding after one or two draws) reflects the same bias as decreased draws to decision on non-extreme responding trials. Methods: Extreme positive schizotypy individuals with increased psychosis risk (n = 69) and controls (n = 95) completed the Probabilistic Reasoning Task and reported on recent distress, which was previously associated with jumping to conclusions. We calculated extreme responding, draws to decision (number of draws), and draws to decision/non-extreme responding (number of draws on trials with three or more draws). Results: Positive schizotypy was associated with extreme responding, but not draws to decision/non-extreme responding. Furthermore, draws to decision and draws to decision/non-extreme responding were associated with recent distress, whereas extreme responding was not. Conclusion: Positive schizotypy was specifically associated with extreme responding and not draws to decision/non-extreme responding, which suggests that the nature of extreme responding and of draws to decision might be different. This could have relevance for assessing and treating jumping to conclusions.
CONSTANS-FKBP12 interaction contributes to modulate photoperiodic flowering in Arabidopsis.

Flowering time is a key process in plant development. Photoperiodic signals play a crucial role in the floral transition in Arabidopsis thaliana and CONSTANS (CO) protein has a central regulatory function that is tightly regulated at the transcriptional and post-translational levels. CO protein stability depends on a light-driven proteasome process that optimizes its accumulation in the evening to promote the production of the florigen FLOWERING LOCUS T (FT) and induce seasonal flowering. To further investigate the posttranslational regulation of CO protein we have dissected its interactome network employing in vivo and in vitro assays and molecular genetics approaches. The immunophilin FKBP12 has been identified as a CO interactor in Arabidopsis that regulates its accumulation and activity. FKBP12-CO interact through the CCT domain, affecting CO stability and function. fkbp12 insertion mutants show a delay in flowering time, while FKBP12 overexpression accelerates flowering, and these phenotypes can be directly related to a change in FT protein accumulation. The interaction is conserved between the Chlamydomonas algal orthologues CrCO-CrFKBP12, revealing an ancient regulatory step in photoperiod regulation of plant development.
Squeezing Dynamic Mechanism of High-Viscosity Droplet and its Application for Adhesive Dispensing in Sub-Nanoliter Resolution

The dispensing resolution of high-viscosity liquid is essential for adhesive micro-bonding. In comparison with the injection technique, the transfer printing method appears to be promising. Herein, an analytical model was developed to describe the dynamic mechanism of squeezing-and-deforming a viscous droplet between plates in a transfer printing process: as the distance between plates decreases, the main constituents of contact force between the droplet and substrate can be divided into three stages: surface tension force, surface tension force and viscous force, and viscous force. According to the above analysis, the transfer printing method was built up to dispense high-viscosity adhesives, which replaced the geometric parameters, utilized the critical contact force to monitor the adhesive droplet status, and served as the criterion to trigger the liquid-bridge stretching stage. With a home-made device and a simple needle-stamp, the minimum dispensed amount of 0.05 nL (93.93 Pa·s) was achieved. Moreover, both the volume and the contact area of adhesive droplet on the substrate were approximately linear to the critical contact force. The revealed mechanism and proposed method have great potential in micro-assembly and other applications of viscous microfluidics.
hiPSCs Derived Cardiac Cells for Drug and Toxicity Screening and Disease Modeling: What Micro- Electrode-Array Analyses Can Tell Us

Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) have been intensively used in drug development and disease modeling. Since iPSC-cardiomyocyte (CM) was first generated, their characterization has become a major focus of research. Multi-/micro-electrode array (MEA) systems provide a non-invasive user-friendly platform for detailed electrophysiological analysis of iPSC cardiomyocytes including drug testing to identify potential targets and the assessment of proarrhythmic risk. Here, we provide a systematical overview about the physiological and technical background of micro-electrode array measurements of iPSC-CM. We introduce the similarities and differences between action- and field potential and the advantages and drawbacks of MEA technology. In addition, we present current studies focusing on proarrhythmic side effects of novel and established compounds combining MEA systems and iPSC-CM. MEA technology will help to open a new gateway for novel therapies in cardiovascular diseases while reducing animal experiments at the same time.
Boosting Recombinant Inclusion Body Production—From Classical Fed-Batch Approach to Continuous Cultivation

State of the art microbial recombinant protein production is regularly performed in fed-batch based cultivations. However, these cultivations suffer from highly time-dependent changes in productivity and product quality, leading to high variations in the downstream process. Continuous biomanufacturing offers the possibility of a time independent process, boosting the time-space-yield of the recombinantly produced protein and further reducing costs for production, also as downstream gets more predictive. In the current work, the continuous production of a pharmaceutically relevant protein in form of an inclusion body in E. coli BL21(DE3) was investigated in single vessel cultivations by varying dilution rates using glycerol as carbon source, inducer (lactose or IPTG) and respective inducer concentrations. Attempts to increase low specific productivities observed in single vessel continuous cultivations, led to the establishment of a continuously operated cascade of two stirred tank reactors to spatially separate biomass formation from recombinant protein production. Process performance was substantially improved compared to a single vessel chemostat culture, as specific productivity and space-time yield were boosted using an optimized cascaded process by about a factor of 100. This study shows the potential of a two-stage continuous process as promising alternative to benchmark fed-batch processes achieving constant inclusion body production at a time-independent level.
Serum neurofilament levels correlate with retinal nerve fiber layer thinning in multiple sclerosis

Background: Serum neurofilament light chain (sNfL) levels and peripapillary retinal nerve fiber layer (pRNFL) are both emerging biomarkers of neuro-axonal damage in multiple sclerosis (MS). However, data on the relation between sNfL and pRNFL are scarce. Objective: We aimed to determine the relation of sNfL levels with pRNFL thinning in a large cohort of relapsing–remitting (RR) MS patients. Methods: We identified 80 patients from a prospective, 3-year observational study on retinal changes in RRMS with annual blood samples available. sNfL levels were measured using single-molecule array (SimoaTM) assay. Annualized loss of pRNFL (aLpRNFL) was determined by individual linear regression models. Correlations between single and repeated sNfL levels and aLpRNFL were analyzed using multivariate linear regression and mixed-effect models. Results: After correction for sex, age, and baseline sNfL, an sNfL increase of 10 pg/mL was associated with an aLpRNFL of −0.7 µm (95% confidence interval (CI): (−1.3, −0.2), p < 0.001). Patients with ⩾2 sNfL measurements >75th percentile displayed higher aLpRNFL (2.2 µm, standard deviation (SD) 0.6) compared to patients with no sNfL measure >75th percentile (0.4 µm, SD 0.2, p < 0.001). Between 15% and 20% of the aLpRNFL variance could be predicted from sNfL levels. Conclusion: sNfL levels contribute to the prediction of retinal thinning in patients with RRMS, strengthening its value as a biomarker of neuro-axonal damage.
The causality of borrowing: Lexical loans in Eurasian languages

All languages borrow words from other languages. Some languages are more prone to borrowing, while others borrow less, and different domains of the vocabulary are unequally susceptible to borrowing. Languages typically borrow words when a new concept is introduced, but languages may also borrow a new word for an already existing concept. Linguists describe two causalities for borrowing: need, i.e., the internal pressure of borrowing a new term for a concept in the language, and prestige, i.e., the external pressure of borrowing a term from a more prestigious language. We investigate lexical loans in a dataset of 104 concepts in 115 Eurasian languages from 7 families occupying a coherent contact area of the Eurasian landmass, of which Indo-European languages from various periods constitute a majority. We use a cognacy-coded dataset, which identifies loan events including a source and a target language. To avoid loans for newly introduced concepts in languages, we use a list of lexical concepts that have been in use at least since the Chalcolithic (4000–3000 BCE). We observe that the rates of borrowing are highly variable among concepts, lexical domains, languages, language families, and time periods. We compare our results to those of a global sample and observe that our rates are generally lower, but that the rates between the samples are significantly correlated. To test the causality of borrowing, we use two different ranks. Firstly, to test need, we use a cultural ranking of concepts by their mobility (of nature items) or their labour intensity and “distance-from-hearth” (of culture items). Secondly, to test prestige, we use a power ranking of languages by their socio-cultural status. We conclude that the borrowability of concepts increases with increasing mobility (nature), and with increased labour intensity and “distance-from-hearth” (culture). We also conclude that language prestige is not correlated with borrowability in general (all languages borrow, independently of prestige), but prestige predicts the directionality of borrowing, from a more prestigious language to a less prestigious one. The process is not constant over time, with a larger inequality during the ancient and modern periods, but this result may depend on the status of the data (non-prestigious languages often remain unattested). In conclusion, we observe that need and prestige compete as causes of lexical borrowing.
Impact of cooking and heating fuel use on acute respiratory health of preschool children in South Africa.

Dependence on polluting fuels (wood, coal, crop residues, animal dung, paraffin) for cooking and heating exposes costless women and young children in developing countries to elevated air pollution concentration indoors. This study explored the connection between polluting fuel use for cooking and heating with childhood(<5years) acute lower respiratory infections (LRIs) in South Africa. Analysis is based on data from 4 679 children living in 2 651 households collected during the 1998 South African Demographic and Health Surtey. Cases were defined as those who experienced cough accompanied by short, rapid breathing during the two weeks prior to the survey. Logistic regression was applied to estimate the odds of suffering from acute LRI among children from households using polluting fuels in combination with electricity or liquid petroleum gas/natural gas for cooking and heating relative to those using electricity or liquid petroleum gas/natural gas exclusively, after controlling for potentially confounding .
Derivation of All Attitude Error Governing Equations for Attitude Filtering and Control

This article presents the full analytical derivations of the attitude error kinematics equations. This is done for several attitude error representations, obtaining compact closed-forms expressions. Attitude error is defined as the rotation between true and estimated orientations. Two distinct approaches to attitude error kinematics are developed. In the first, the estimated angular velocity is defined in the true attitude axes frame, while in the second, it is defined in the estimated attitude axes frame. The first approach is of interest in simulations where the true attitude is known, while the second approach is for real estimation/control applications. Two nonlinear kinematic models are derived that are valid for arbitrarily large rotations and rotation rates. The results presented are expected to be broadly useful to nonlinear attitude estimation/control filtering formulations. A discussion of the benefits of the derived error kinematic models is included.
Individuals who do and do not perceive difficulties adhering to a diet for diabetes mellitus, their quality of life and glycaemic control

Opinion regarding the successful management of insulin dependent diabetes mellitus (IDDM) has identified nutrition as a key player. Whilst important, diet has also been highlighted as one of the most difficult aspects of the regimen, by both individuals with IDDM and health workers. Current dietetic recommendations for the nutritional management of individuals with IDDM include, the normalisation of plasma glucose and the promotion of patient well being. This study aimed to determine if any significant difference in quality of life (QOL) and glycaemic control existed between groups of individuals with IDDM, who perceive their diet difficult to adhere to and those who perceive adherence easy. Nineteen individuals, all clients of a diabetes education centre and aged 1830 years, volunteered to participate. The Diabetes Control and Complications Trial QOL questionnaire and the SF-36 were used to assess QOL. Glycaemic control was assessed via a non fasting blood sample to determine HbAlc. Finally a question was used to divide the nineteen subjects into three groups, based on their perception of adherence difficulties. The three groups were those that found adherence difficult (A), neither difficult or easy (B) and easy (C). QOL and glycaemic control comparisons were then made for the two most polarised groups (A and C). Of the nineteen subjects, ten perceived no difficulty, seven perceived neither difficulty or ease, and only two subjects perceived any difficulty with adherence to their diet. The ages of the subjects, duration of IDDM and the sample selection process was believed to contribute to the afore mentioned distribution. Statistical analysis comparing glycaemic control and QOL results between the groups was restricted by the small size of group A. The two subjects in group A displayed incompatible results for glycaemic control and QOL, both compared to one another and to the mean of group C. The QOL tools were practical and simple to work with and it is recommended to continue the study utilising the current method, with modifications to the sample selection process.
ApoE (Apolipoprotein E) in Brain Pericytes Regulates Endothelial Function in an Isoform-Dependent Manner by Modulating Basement Membrane Components.

OBJECTIVE The ε4 allele of the APOE gene (APOE4) is the strongest genetic risk factor for Alzheimer disease when compared with the common ε3 allele. Although there has been significant progress in understanding how apoE4 (apolipoprotein E4) drives amyloid pathology, its effects on amyloid-independent pathways, in particular cerebrovascular integrity and function, are less clear. Approach and Results: Here, we show that brain pericytes, the mural cells of the capillary walls, differentially modulate endothelial cell phenotype in an apoE isoform-dependent manner. Extracellular matrix protein induction, tube-like structure formation, and barrier formation were lower with endothelial cells cocultured with pericytes isolated from apoE4-targeted replacement mice compared with those from apoE3-TR mice. Importantly, aged apoE4-targeted replacement mice had decreased extracellular matrix protein expression and increased plasma protein leakages compared with apoE3-TR mice. CONCLUSIONS ApoE4 impairs pericyte-mediated basement membrane formation, potentially contributing to the cerebrovascular effects of apoE4.
Carbohydrate-Based Chiral Iodoarene Catalysts: A Survey through the Development of an Improved Catalyst Design

Iodoarene catalysts can be applied in versatile reactions, for instance in the construction of complex chiral molecules via dearomatization of simple aromatic compounds. Recently, we reported the synthesis of the first carbohydrate-based chiral iodoarene catalysts and their application in asymmetric catalysis. Here we describe the synthesis of some new and improved catalysts. An account on how we got to the improved catalyst design, as well as the X-ray structure of one of the carbohydrate-based iodoarenes, is given.
Impact of Menopausal Hormone Formulations on Pituitary-Ovarian Regulatory Feedback.

Changes in pituitary-ovarian hormones across the menopausal transition have multiple physiological consequences. However, little is known about how the major types of post-menopausal hormone therapy (HT) affect pituitary-ovarian hormonal relationships. This study evaluated these relationships in recently menopausal women (52.45± 2.49 years of age) in the Kronos Early Estrogen Prevention Study (KEEPS) who were compliant to randomized, double-blinded treatment with oral conjugated equine estrogen (o-CEE, n=109), transdermal 17β-estradiol (t-E2, n=107), or placebo (n=146). Androstenedione, testosterone, 17β-estradiol, estrone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) were measured in serum prior to (baseline) and 48 months after randomization to treatment. Descriptive summaries of hormone levels were performed, and multiple regression analyses were used to examine the effects of o-CEE , t-E2, and placebo on these hormone levels at 48 months adjusting for baseline levels. A network analysis examined the covariance of changes in hormone levels over the 48 months within treatment groups. As expected, at 48 months of treatment, hormone levels differed between women in the two active treatment groups compared to placebo, and network analysis indicated stronger relationships among hormone levels in the t-E2 and o-CEE groups as compared to placebo. Associations among testosterone, 17β-estradiol, FSH and LH differed between the o-CEE group compared to t-E2 and placebo groups. Thus, two common HT regimens differentially alter pituitary-ovarian hormone levels, altering feedback cycles and inter-hormonal associations in recently menopausal women. These interactions provide the basis for future studies investing the impact of hormonal modulation of aging including cognitive decline in women.
The Many Faces of Follicular Variant of Papillary Thyroid Carcinoma

This article reviews the various morphologic presentations of follicular variant of papillary carcinoma. Most of these can be diagnosed with ease; however, there exists a subgroup which has generated recent controversy in the literature. We present our views based on our experience with the cytologic and histologic diagnosis and clinical follow-up of these tumors, and propose a scheme to assist in their diagnosis and appropriate clinical management.
Lithium-associated hypothyroidism and potential for reversibility after lithium discontinuation: Findings from the LiSIE retrospective cohort study

Background: The association between lithium and thyroid dysfunction has long been known. However, it remains unknown if lithium-associated hypothyroidism is reversible once lithium treatment has been stopped. Aims: To determine whether lithium-associated hypothyroidism was reversible in patients who subsequently discontinued lithium. Methods: A retrospective cohort study in the Swedish region of Norrbotten into the effects and side- effects of lithium treatment and other drugs for relapse prevention (Lithium – Study into Effects and Side Effects). For this particular study, we reviewed medical records between 1997 and 2015 of patients with lithium-associated hypothyroidism who had discontinued lithium. Results: Of 1340 patients screened, 90 were included. Of these, 27% had overt hypothyroidism at the start of thyroid replacement therapy. The mean delay from starting lithium to starting thyroid replacement therapy was 2.3 years (SD 4.7). In total, 50% of patients received thyroid replacement therapy within 10 months of starting lithium. Of 85 patients available for follow-up, 41% stopped thyroid replacement therapy after lithium discontinuation. Only six patients reinstated thyroid replacement therapy subsequently. Of these, only one had overt hypothyroidism. Conclusions: Lithium-associated hypothyroidism seems reversible in most patients once lithium has been discontinued. In such cases, thyroid replacement therapy discontinuation could be attempted much more often than currently done. Based on the limited evidence of our study, we can expect hypothyroidism to recur early after thyroid replacement therapy discontinuation, if at all.