Miracle-dz/UniFAR-FTUs huggingface dataset:
Mouse Lines with Cre-Mediated Recombination in Retinal Amacrine Cells

Abstract Amacrine cells (ACs) are the most diverse neuronal cell type in the vertebrate retina. Yet little is known about the contribution of ACs to visual processing and retinal disease. A major challenge in evaluating AC function is genetic accessibility. A classic tool of mouse genetics, Cre-mediated recombination, can provide such access. We have screened existing genetically-modified mouse strains and identified multiple candidates that express Cre-recombinase in subsets of retinal ACs. The Cre-expressing mice were crossed to fluorescent-reporter mice to assay Cre expression. In addition, a Cre-dependent fluorescent reporter plasmid was electroporated into the subretinal space of Cre strains. Herein, we report three mouse lines (Tac1::IRES-cre, Camk2a-cre, and Scx-cre) that express Cre recombinase in sub-populations of ACs. In two of these lines, recombination occurred in multiple AC types and a small number of other retinal cell types, while recombination in the Camk2a-cre line appears specific to a morphologically distinct AC. We anticipate that these characterized mouse lines will be valuable tools to the community of researchers who study retinal biology and disease.
Selective publication of antidepressant trials and its influence on apparent efficacy: Updated comparisons and meta-analyses of newer versus older trials

Background Valid assessment of drug efficacy and safety requires an evidence base free of reporting bias. Using trial reports in Food and Drug Administration (FDA) drug approval packages as a gold standard, we previously found that the published literature inflated the apparent efficacy of antidepressant drugs. The objective of the current study was to determine whether this has improved with recently approved drugs. Methods and findings Using medical and statistical reviews in FDA drug approval packages, we identified 30 Phase II/III double-blind placebo-controlled acute monotherapy trials, involving 13,747 patients, of desvenlafaxine, vilazodone, levomilnacipran, and vortioxetine; we then identified corresponding published reports. We compared the data from this newer cohort of antidepressants (approved February 2008 to September 2013) with the previously published dataset on 74 trials of 12 older antidepressants (approved December 1987 to August 2002). Using logistic regression, we examined the effects of trial outcome and trial cohort (newer versus older) on transparent reporting (whether published and FDA conclusions agreed). Among newer antidepressants, transparent publication occurred more with positive (15/15 = 100%) than negative (7/15 = 47%) trials (OR 35.1, CI95% 1.8 to 693). Controlling for trial outcome, transparent publication occurred more with newer than older trials (OR 6.6, CI95% 1.6 to 26.4). Within negative trials, transparent reporting increased from 11% to 47%. We also conducted and contrasted FDA- and journal-based meta-analyses. For newer antidepressants, FDA-based effect size (ESFDA) was 0.24 (CI95% 0.18 to 0.30), while journal-based effect size (ESJournals) was 0.29 (CI95% 0.23 to 0.36). Thus, effect size inflation, presumably due to reporting bias, was 0.05, less than for older antidepressants (0.10). Limitations of this study include a small number of trials and drugs—belonging to a single class—and a focus on efficacy (versus safety). Conclusions Reporting bias persists but appears to have diminished for newer, compared to older, antidepressants. Continued efforts are needed to further improve transparency in the scientific literature.
Short-term, but not long-term, beneficial effects of concomitant benzodiazepine use on clinical course in patients with schizophrenia

This study aims to examine possible differences in the effect on the course characteristics of the disease in cases of no use, short-term use and long-term use of benzodiazepines in patients with schizophrenia. In this retrospective observational study, the sample comprised patients with schizophrenia who were admitted to our psychiatric clinics from January 2015 to January 2019. Patients were also retrospectively tracked from the date of the first admission during the specified time until the end of the observation period (24 months) for clinical course characteristics. Data for 1710 patients with schizophrenia were included in the analyses. Patients with short-term benzodiazepines use had fewer psychiatric hospitalizations and shorter lengths of stay at psychiatric services than patients with no use or long-term use. Rates of antipsychotic drug discontinuation and suicidal behavior were also significantly lower among short-term benzodiazepines users than among those with no use or long-term use. In conclusion, our study indicates that short-term benzodiazepines use is associated with a better clinical course in patients with schizophrenia. Future studies should evaluate the effects of different benzodiazepines use patterns on disease prognosis with longer-term follow-up and prospective methodology and should concomitantly examine psychopathological variables.
Test niezależności chi-kwadrat i jego zastosowanie w interpretacji wyników badań klinicznych The chi-square independence test and its application in the clinical researches

Streszczenie Praca ma na celu krotkie i praktyczne omowienie zasad stosowania testu χ 2 , bez ktorego nie moze obyc sie analiza statystyczna ogromnej wiekszości publikowanych prac medycznych. W badaniach klinicznych bardzo czesto ma sie do czynienia z cechami niemierzalnymi, jakościowymi – chorzy klasyfikowani są pod wzgledem roznych kategorii. Typowymi zmiennymi tego rodzaju są: plec, wystepowanie określonej choroby czy zaszeregowanie chorych w roznych skalach – skali zaawansowania dlawicy piersiowej opracowanej przez Kanadyjskie Towarzystwo Kardiologiczne (ang. Canadian Cardiovascular Society – CCS), skali sluzącej do klasyfikacji ciezkości objawow niewydolności krązenia zaproponowanej przez Nowojorskie Towarzystwo Kardiologiczne (ang. New York Heart Association – NYHA) czy klasyfikacji Killipa-Kimballa opracowanej do oceny niewydolności serca w świezym zawale mieśnia sercowego. Czesto interesujący jest wplyw jednej cechy jakościowej na drugą ceche tego samego typu, np. wplywu plci na czestośc wystepowania danej choroby lub na rozklad punktacji CCS/NYHA w populacji chorych. W takim przypadku nalezy posluzyc sie odpowiednim aparatem obliczeniowym i testem statystycznym. Najcześciej stosowanym testem w takiej sytuacji jest opracowany w 1900 r. przez Karla Pearsona test niezalezności χ 2 . Sluzy on do weryfikacji hipotezy zerowej (H 0 ) – o braku roznic istotnych statystycznie miedzy rozpatrywanymi cechami. Obszar stosowalności tego testu obejmuje nie tylko analize czestości wystepowania cech jakościowych, ale rowniez analize zgodności cech ilościowych oraz przypadki badania zalezności cechy jakościowej od ilościowej. Analizowanie danych z wykorzystaniem testu χ 2 nie sprawia wiekszych problemow – pod warunkiem, ze badacz posiadl podstawową wiedze z zakresu statystyki. Nawet nie bedąc ekspertem w tej dziedzinie, lekarz prowadzący badania naukowe moze stac sie świadomym uzytkownikiem pakietu staty
Non-invasive imaging as the cornerstone of cardiovascular precision medicine.

AIMS To provide an overview of the role of cardiovascular (CV) imaging in facilitating and advancing the field of precision medicine in CV disease. METHODS AND RESULTS Non-invasive CV imaging is essential to accurately and efficiently phenotype patients with heart disease, including coronary artery disease (CAD) and heart failure (HF). Various modalities, such as echocardiography, nuclear cardiology, cardiac computed tomography (CT), cardiovascular magnetic resonance (CMR), and invasive coronary angiography, and in some cases a combination, can be required to provide sufficient information for diagnosis and management. Taking CAD as an example, imaging is essential for the detection and functional assessment of coronary stenoses, as well as for the quantification of cardiac function and ischaemic myocardial damage. Furthermore, imaging may detect and quantify coronary atherosclerosis, potentially identify plaques at increased risk of rupture, and guide coronary interventions. In patients with HF, imaging helps identify specific aetiologies, quantify damage, and assess its impact on cardiac function. Imaging plays a central role in individualizing diagnosis and management and to determine the optimal treatment for each patient to increase the likelihood of response and improve patient outcomes. CONCLUSIONS Advances in all imaging techniques continue to improve accuracy, sensitivity, and standardization of functional and prognostic assessments, and identify established and novel therapeutic targets. Combining imaging with artificial intelligence, machine learning and computer algorithms, as well as with genomic, transcriptomic, proteomic, and metabolomic approaches, will become state of the art in the future to understand pathologies of CAD and HF, and in the development of new, targeted therapies.
Antiepileptic Drug Tiagabine Does Not Directly Target Key Cardiac Ion Channels Kv11.1, Nav1.5 and Cav1.2

Tiagabine is an antiepileptic drug used for the treatment of partial seizures in humans. Recently, this drug has been found useful in several non-epileptic conditions, including anxiety, chronic pain and sleep disorders. Since tachycardia—an impairment of cardiac rhythm due to cardiac ion channel dysfunction—is one of the most commonly reported non-neurological adverse effects of this drug, in the present paper we have undertaken pharmacological and numerical studies to assess a potential cardiovascular risk associated with the use of tiagabine. A chemical interaction of tiagabine with a model of human voltage-gated ion channels (VGICs) is described using the molecular docking method. The obtained in silico results imply that the adverse effects reported so far in the clinical cardiological of tiagabine could not be directly attributed to its interactions with VGICs. This is also confirmed by the results from the isolated organ studies (i.e., calcium entry blocking properties test) and in vivo (electrocardiogram study) assays of the present research. It was found that tachycardia and other tiagabine-induced cardiac complications are not due to a direct effect of this drug on ventricular depolarization and repolarization.
Fuzzy Insurance

Abstract Fuzzy set theory is a recently developed field of mathematics, that introduces sets of objects whose boundaries are not sharply defined. Whereas in ordinary Boolean algebra an element is either contained or not contained in a given set, in fuzzy set theory the transition between membership and non-membership is gradual. The theory aims at modelizing situations described in vague or imprecise terms, or situations that are too complex or ill-defined to be analysed by conventional methods. This paper aims at presenting the basic concepts of the theory in an insurance framework. First the basic definitions of fuzzy logic are presented, and applied to provide a flexible definition of a “preferred policyholder” in life insurance. Next, fuzzy decision-making procedures are illustrated by a reinsurance application, and the theory of fuzzy numbers is extended to define fuzzy insurance premiums.
Upregulation of Neural Cell Adhesion Molecule 1 and Excessive Migration of Purkinje Cells in Cerebellar Cortex

Purkinje cells (PCs) are large GABAergic projection neurons of the cerebellar cortex, endowed with elaborate dendrites that receive a multitude of excitatory inputs. Being the only efferent neuron of the cerebellar cortex, PCs project to cerebellar nuclei and control behaviors ranging from movement to cognition and social interaction. Neural cell adhesion molecule 1 (NCAM1) is widely expressed in the embryonic and postnatal development of the brain and plays essential roles in neuronal migration, axon pathfinding and synapse assembly. However, despite its high expression levels in cerebellum, little is known to date regarding the role(s) of NCAM1 in PCs development. Among other aspects, elucidating how the expression of NCAM1 in PCs could impact their postnatal migration would be a significant achievement. We analyzed the Acp2 mutant mouse (nax: naked and ataxia), which displays excessive PC migration into the molecular layer, and investigated how the excessive migration of PCs along Bergmann glia could correlate to NCAM1 expression pattern in early postnatal days. Our Western blot and RT-qPCR analysis of the whole cerebellum show that the protein and mRNA of NCAM1 in wild type are not different during PC dispersal from the cluster stage to monolayer formation. However, RT-qPCR analysis from FACS-based isolated PCs shows that Ncam1 is significantly upregulated when PCs fail to align and instead overmigrate into the molecular layer. Our results suggest two alternative interpretations: (1) NCAM1 promotes excessive PC migration along Bergmann glia, or (2) NCAM1 upregulation is an attempt to prevent PCs from invading the molecular layer. If the latter scenario proves true, NCAM1 may play a key role in PC monolayer formation.
Editorial: Adaptation of Trees to Climate Change: Mechanisms Behind Physiological and Ecological Resilience and Vulnerability

1 Research Unit Environmental Simulation, Institute of Biochemical Plant Pathology, Helmholtz Zentrum München, Oberschleißheim, Germany, Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio, Finland, 3 Institute of Meteorology and Climate Research—Atmospheric Environmental Research, Karlsruhe Institute of Technology KIT, Garmisch-Partenkirchen, Germany, 4 Institute for Sustainable Plant Protection (IPSP)-National Research Council (CNR), Turin, Italy, College of Forest Resources and Environmental Science, Michigan Technological University,
In-Person and Remote Workshops for People With Neurocognitive Disorders: Recommendations From a Delphi Panel

Workshops using arts and board games are forms of non-pharmacological intervention widely employed in seniors with neurocognitive disorders. However, clear guidelines on how to conduct these workshops are missing. The objective of the Art and Game project (AGAP) was to draft recommendations on the structure and content of workshops for elderly people with neurocognitive disorders and healthy seniors, with a particular focus on remote/hybrid workshops, in which at least a part of the participants is connected remotely. Recommendations were gathered using a Delphi methodology. The expert panel (N = 18) included experts in the health, art and/or board games domains. They answered questions via two rounds of web-surveys, and then discussed the results in a plenary meeting. Some of the questions were also shared with the general public (N = 101). Both the experts and the general public suggested that organizing workshops in a hybrid format (some face-to-face sessions, some virtual session) is feasible and interesting for people with neurocognitive disorders. We reported guidelines on the overall structure of workshops, practical tips on how to organize remote workshops, and a SWOT analysis of the use of remote/hybrid workshops. The guidelines may be employed by clinicians to decide, based on their needs and constraints, what interventions and what kind of workshop format to employ, as well as by researcher to standardize procedures to assess the effectiveness of non-pharmacological treatments for people with neurocognitive disorders.
Assessing Smoothness of Arm Movements With Jerk: A Comparison of Laterality, Contraction Mode and Plane of Elevation. A Pilot Study

Measuring the quality of movement is a need and a challenge for clinicians. Jerk, defined as the quantity of acceleration variation, is a kinematic parameter used to assess the smoothness of movement. We aimed to assess and compare jerk metrics in asymptomatic participants for 3 important movement characteristics that are considered by clinicians during shoulder examination: dominant and non-dominant side, concentric and eccentric contraction mode, and arm elevation plane. In this pilot study, we measured jerk metrics by using Xsens® inertial measurement units strapped to the wrists for 11 different active arm movements (ascending and lowering phases): 3 bilateral maximal arm elevations in sagittal, scapular and frontal plane; 2 unilateral functional movements (hair combing and low back washing); and 2 unilateral maximal arm elevations in sagittal and scapular plane, performed with both arms alternately, right arm first. Each arm movement was repeated 3 times successively and the whole procedure was performed 3 times on different days. The recorded time series was segmented with semi-supervised algorithms. Comparisons involved the Wilcoxon signed rank test (p < 0.05) with Bonferroni correction. We included 30 right-handed asymptomatic individuals [17 men, mean (SD) age 31.9 (11.4) years]. Right jerk was significantly less than left jerk for bilateral arm elevations in all planes (all p < 0.05) and for functional movement (p < 0.05). Jerk was significantly reduced during the concentric (ascending) phase than eccentric (lowering) phase for bilateral and unilateral right and left arm elevations in all planes (all p < 0.05). Jerk during bilateral arm elevation was significantly reduced in the sagittal and scapular planes versus the frontal plane (both p < 0.01) and in the sagittal versus scapular plane (p < 0.05). Jerk during unilateral left arm elevation was significantly reduced in the sagittal versus scapular plane (p < 0.05). Jerk metrics did not differ between sagittal and scapular unilateral right arm elevation. Using inertial measurement units, jerk metrics can well describe differences between the dominant and non-dominant arm, concentric and eccentric modes and planes in arm elevation. Jerk metrics were reduced during arm movements performed with the dominant right arm during the concentric phase and in the sagittal plane. Using IMUs, jerk metrics are a promising method to assess the quality of basic shoulder movement.
Role of Digital Economy in Rebuilding and Sustaining the Space Governance Mechanisms

The need for sustainable corporate governance has gained the interests of researchers for a while now and it has been found as a very significant component of successful organizational operations. The current paper has examined the role of sustainable corporate governance in achieving sustainable economic space along with measuring the indirect impact of technological innovation and IT governance on the whole process. This paper has followed the quantitative-positivism approach to measure the hypotheses developed in the study. The population considered in this study are the managers currently employed in the corporate sector in China (N = 310). The data is analyzed using the Smart-PLS 3.3. 3 software for checking the data for preliminary screening and the measurement of hypotheses. The findings of the study show that the three components of sustainable corporate governance, i.e., concern for employees, sustainable corporate governance awareness, and the environmental aspects have a significant as well as a positive effect on technological innovation and hence on the sustainable economic space. Similarly, the study has recorded a significant moderating effect of IT governance on the relationship of technological innovation and the sustainable economic space. Overall, it can be seen that corporate governance, innovative technology, and a sustainable digital economy share a reciprocal relationship. Where corporate governance helps as a supporting force to keep both innovation and sustainability in action. Whereas IT governance provides enhanced communication and delivery of public services, business, and advanced human capital. The study will be of high advantage for the corporate sector in China for devising and modifying their policies that consider the employee’s concerns for the governance mechanisms prevailing at priority in the organizations. Further, it will be interesting for the organizations to incorporate the IT governance mechanism in their technological innovations for achieving a sustainable economic space.
Elevation of Clavibacter michiganensis subsp. californiensis to species level as Clavibacter californiensis sp. nov., merging and re-classification of Clavibacter michiganensis subsp. chilensis and Clavibacter michiganensis subsp. phaseoli as Clavibacter chilensis sp. nov. based on complete genome i

The Gram-positive Clavibacter genus is currently divided into seven species (C. michiganensis, C. nebraskensis, C. capsici, C. sepedonicus, C. tessellarius, C. insidiosus and C. zhangzhiyongii) and three subspecies (C. michiganensis subsp. californiensis, C. michiganensis subsp. chilensis and C. michiganensis subsp. phaseoli). Recent studies have indicated that the taxonomic rank of the subspecies must be re-evaluated. In this research, we assessed the taxonomy position of the three C. michiganensis subspecies and clarified the taxonomic nomenclature of other 75 Clavibacter strains. The complete genomes of the type strains of the three Clavibacter subspecies, type strain of C. tessellarius and C. nebraskensis A6096 were sequenced using PacBio RSII technology. Application of whole-genome-based computational approaches such as average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH), multi-locus sequence analysis (MLSA) of seven housekeeping genes (acnA, atpD, bipA, icdA, mtlD, recA and rpoB), phylogenomic tree reconstructed from 1,028 core genes, and ANI-based phylogeny pinpointed conclusive evidence to raise C. michiganensis subsp. californiensis to the species status. These results led us to propose the establishment of C. californiensis sp. nov. as a species with its type strain C55ᵀ (=CFBP 8216ᵀ=ATCC BAA-2691ᵀ). Moreover, the orthologous and in-silico dot plot analyses, along with the aforementioned bioinformatic strategies, revealed a high degree of homology between C. michiganensis subsp. chilensis and C. michiganensis subsp. phaseoli. Based on these outcomes, we proposed to combine both subspecies into a single taxon and elevate its rank to the species level as C. chilensis sp. nov., with ZUM3936ᵀ (= ATCC BAA-2690ᵀ = CFBP 8217ᵀ) as the type strain.
Dying for information

The use of variable message signs (VMS) could help mitigate risks to highway safety. The use of mobile devices in vehicles leads to driver distraction, and providing real-time information via integrated VMS systems can stop drivers from taking their eyes off the road to look at their device screens. At present, many highways lack real-time information on display, and it is necessary to improve VMS systems to provide information comparable to that which drivers are able to access on mobile devices.