Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of different gene addition strategies to modify placental derived-mesenchymal stromal cells to produce FVIII

Introduction Placenta-derived mesenchymal cells (PLCs) endogenously produce FVIII, which makes them ideally suited for cell-based fVIII gene delivery. We have previously reported that human PLCs can be efficiently modified with a lentiviral vector encoding a bioengineered, expression/secretion-optimized fVIII transgene (ET3) and durably produce clinically relevant levels of functionally active FVIII. The objective of the present study was to investigate whether CRISPR/Cas9 can be used to achieve location-specific insertion of a fVIII transgene into a genomic safe harbor, thereby eliminating the potential risks arising from the semi-random genomic integration inherent to lentiviral vectors. We hypothesized this approach would improve the safety of the PLC-based gene delivery platform and might also enhance the therapeutic effect by eliminating chromatin-related transgene silencing. Methods We used CRISPR/Cas9 to attempt to insert the bioengineered fVIII transgene “lcoET3” into the AAVS1 site of PLCs (CRISPR-lcoET3) and determined their subsequent levels of FVIII production, comparing results with this approach to those achieved using lentivector transduction (LV-lcoET3) and plasmid transfection (Plasmid-lcoET3). In addition, since liver-derived sinusoidal endothelial cells (LSECs) are the native site of FVIII production in the body, we also performed parallel studies in human (h)LSECs). Results PLCs and hLSECs can both be transduced (LV-lcoET3) with very high efficiency and produce high levels of biologically active FVIII. Surprisingly, both cell types were largely refractory to CRISPR/Cas9-mediated knockin of the lcoET3 fVIII transgene in the AAVS1 genome locus. However, successful insertion of an RFP reporter into this locus using an identical procedure suggests the failure to achieve knockin of the lcoET3 expression cassette at this site is likely a function of its large size. Importantly, using plasmids, alone or to introduce the CRISPR/Cas9 “machinery”, resulted in dramatic upregulation of TLR 3, TLR 7, and BiP in PLCs, compromising their unique immune-inertness. Discussion Although we did not achieve our primary objective, our results validate the utility of both PLCs and hLSECs as cell-based delivery vehicles for a fVIII transgene, and they highlight the hurdles that remain to be overcome before primary human cells can be gene-edited with sufficient efficiency for use in cell-based gene therapy to treat HA.
Reference genes identification for qRT-PCR normalization of gene expression analysis in Cucumis sativus under Meloidogyne incognita infection and Pseudomonas treatment

qRT-PCR is a common and key technical means to study gene expression in biological research. However, reliability and accuracy of quantification by qRT-PCR is entirely dependent on the identification of appropriate reference genes. Cucumber as an economical vegetable is widely cultivated worldwide and is subject to serious nematode infection, especially from M. incognita. Plant could employ beneficial soil bacteria in the rhizosphere to enhance plant adaptability to various stresses. In this study, the optimal reference genes in cucumber under M. incognita stress and Pseudomonas treatment were calculated and confirmed. A total of thirteen candidate reference genes were identified across three different treatments. Of these, geNorm, NormFinder and BestKeeper programs combined RefFinder software identified EF1 and UBI are the most suitable reference gene in the root knot and whole root of cucumber infected M. incognita, respectively, and CACS is the most suitable reference gene in the whole root of cucumber treated by Pseudomonas. The work first validated the most suitable reference genes for the normalization gene expression in cucumber by nematode infected or Pseudomonas inoculated, and these results would facilitate the further research on M. incognita or Pseudomonas soil rhizosphere microbe interaction with cucumber.
Evaluation of the effect of a gel made with amniotic fluid formulation on the healing of diabetic foot ulcers: A triple-blind clinical trial

Aim The aim of this study was to evaluate the effect of a gel made with amniotic fluid (AF) formulation on wound healing in diabetic foot ulcers. Methods This clinical trial was performed on 92 type 2 diabetic patients referring to the Diabetes Clinic of Golestan Hospital of Ahvaz, southwest of Iran in 2019–2020. Patients were randomly divided into three groups of intervention and one placebo group. The wounds of the three intervention groups were dressed with gauze impregnated with an AF formulation gel while wounds of the control group were dressed with plain gauze without any topical agent. Chi-square tests and generalized estimating equations (GEE) with a significance level of 0.05 were used to analyze the data. Results At the end of the eighth week of intervention, there was a statistically significant difference among the four groups in terms of wound grade, wound color, condition of the tissues surrounding the wound, the overall condition of the wound, and the duration of wound healing (P < 0.05). Conclusions Based on our experience with the patients in the present study, we believe that AF represents a useful and safe option for the treatment of chronic diabetic foot ulcers. Clinical trial registration https://en.irct. ir/trial/51551, Identifier: IRCT20201010048985N1.
Overview of global publications on machine learning in diabetic retinopathy from 2011 to 2021: Bibliometric analysis

Purpose To comprehensively analyze and discuss the publications on machine learning (ML) in diabetic retinopathy (DR) following a bibliometric approach. Methods The global publications on ML in DR from 2011 to 2021 were retrieved from the Web of Science Core Collection (WoSCC) database. We analyzed the publication and citation trend over time and identified highly-cited articles, prolific countries, institutions, journals and the most relevant research domains. VOSviewer and Wordcloud are used to visualize the mainstream research topics and evolution of subtopics in the form of co-occurrence maps of keywords. Results By analyzing a total of 1147 relevant publications, this study found a rapid increase in the number of annual publications, with an average growth rate of 42.68%. India and China were the most productive countries. IEEE Access was the most productive journal in this field. In addition, some notable common points were found in the highly-cited articles. The keywords analysis showed that “diabetic retinopathy”, “classification”, and “fundus images” were the most frequent keywords for the entire period, as automatic diagnosis of DR was always the mainstream topic in the relevant field. The evolution of keywords highlighted some breakthroughs, including “deep learning” and “optical coherence tomography”, indicating the advance in technologies and changes in the research attention. Conclusions As new research topics have emerged and evolved, studies are becoming increasingly diverse and extensive. Multiple modalities of medical data, new ML techniques and constantly optimized algorithms are the future trends in this multidisciplinary field.
Possible northern persistence of Siebold’s beech, Fagus crenata, at its northernmost distribution limit on an island in Japan Sea: Okushiri Island, Hokkaido

Siebold’s beech, Fagus crenata, is widely distributed across the Japanese Archipelago and islands in Japan Sea. Similar to the northern limit of the geographical distribution of F. crenata on the mainland of Hokkaido, the northern limit of the distribution of F. crenata on islands in the Japan Sea is observed on Okushiri Island (ca 42°N). To understand the genetic relationships of F. crenata on Okushiri Island, we examined chloroplast (cp) DNA haplotypes and 11 nuclear microsatellite (SSR) loci among 1,838 individuals from 44 populations from Okushiri Island, mainland Hokkaido, and the northern part of the Tohoku region on Honshu Island. We identified 2 cpDNA haplotypes, which represent not only populations on the Japan Sea coast but also those on the Pacific coast and this suggested the Okushiri Island populations might not be formed by single colonization. Genetic diversity of the Okushiri Island populations of nuclear SSR was not lower than the mainland and the STRUCTURE analysis revealed the Okushiri Island individuals were admixed between Hokkaido and Tohoku clusters. Approximate Bayesian computation inferred that divergence between Tohoku and Hokkaido, and admixture between two populations which generated Okushiri populations occurred before the last glacial maximum (LGM), that is, 7,890 (95% hyper probability density (HPD): 3,420 – 9,910) and 3,870 (95% HPD: 431– 8,540) generations ago, respectively. These inferences were well supported by a geological history which suggested an isolation of Okushiri Island from Hokkaido started prior to the Middle Pleistocene. We discuss the possible persistence of F. crenata during the last glacial maximum on northern islands in the Japan Sea such as Okushiri Island.
Rostro-caudal networks for sound processing in the primate brain

Sound is processed in primate brains along anatomically and functionally distinct streams: this pattern can be seen in both human and non-human primates. We have previously proposed a general auditory processing framework in which these different perceptual profiles are associated with different computational characteristics. In this paper we consider how recent work supports our framework.
Predictors in language proficiency of young children with presumed developmental language disorder within the setting of early language intervention

Introduction In the Netherlands, early language intervention is offered to children with presumed Developmental Language Disorder (DLD). The intervention is a combination of group language intervention, individual speech and language therapy and parent-implemented language intervention. During the intervention, some children show more language progress than others. It is unclear what might explain this variation. In this study, we therefore explored to what extent child, parental, and treatment factors were predictive for receptive and expressive language outcomes of young children with presumed DLD during early language intervention. Methods Four multiple regression analyses were conducted with four child factors [pre-test receptive syntax, behavior (internalizing and externalizing), non-verbal cognitive ability and gender], one parental factor (parental stress) and one treatment factor (treatment duration) as predictors and receptive and expressive language post-test scores as outcomes. For each language post-test, the corresponding pre-test language measure was also added. Data of 183 children with presumed DLD were included. Results Receptive syntax problems were an important predictor of expressive language outcomes. Findings also showed a longer treatment duration to be a predictor of progress in expressive vocabulary. Internalizing behavior, externalizing behavior, non-verbal cognitive ability, gender and parental stress did not contribute to predicting language outcomes. Lower pre-intervention language scores led to lower corresponding post-intervention language scores. Conclusions Professionals may need to be aware that children with receptive problems may be indicative of more pervasive impairment and that it can be more difficult to improve their language problems. In fact, children with receptive language problems may need both more and different approaches. The finding that the level of the pre-intervention score has an essential influence on language outcomes underlines the importance of early diagnosis and early intervention, to prevent language problems increasing.
Neem Plus Garlic Oils Biopesticide Formulation: Safe and Efficient in Watermelon Pest Management

Summary To investigate the impact of a novel biopesticide formulation (neem plus garlic oil emulsion - NGOE) in watermelon production, field trials were laid in the early- and late-cropping season of 2020. Watermelon seeds (var. Sweet Sangria F1) were sown in 36 plots which were grouped into 4 replicates of 9 treatments. Data collected include densities of leaf beetles, spiders and Apis mellifera L. (bees) using a modified Grizzly 2500/8 leaf blower-vac. All data were subjected to variance analysis after appropriate transformation. Results showed that the most efficient treatment with respect to leaf beetles was 0.125% Magicforce® - Lambda-cyhalothrin 15g/L + Dimethoate 300 g/L (MF) + 5% NGOE in the early-crop, and 0.25% MF in the late-crop. Assessment of change in population densities revealed that 0.25% MF, followed by 0.125% MF + 5% NGOE was most suppressive of A. mellifera in the early-crop. Corresponding ordering in the late-crop was: 0.25% MF followed by 0.125% MF + 3% NGOE. While treatment with NGOE suppressed ants by 27.99 – 56.21%, 0.25% MF did it by 45.49 – 63.51%. Similar trend was observed with respect to ant and spider densities. Though 0.125% MF + 5% NGOE treated plots consistently produced the highest number of fruits, followed by 0.25% MF, statistical analyses showed that except for 1% NGOE, other insecticide treatments were comparable in the late-, but not in the early-crop. While the effectiveness of Magicforce® in suppressing pest and improving yield of watermelon was highlighted, the potential of neem plus garlic oils formulation in managing pests of watermelon while relatively favouring the activities of beneficial arthropods, and improving yield was clearly noticeable.
Myth: Children Raised in Similar Ways Have Similar Personalities

Oddly, many people claim to believe this misconception while simultaneously recognizing that they are nothing like their siblings (often followed by a “thank goodness! ”). Exploring the claim provides an opportunity to discuss issues involving nature and nurture in developmental and personality psychology. Concepts include the value of using a variety of research methods to address complex issues, the nature of interactions, reciprocal determinism, and deriving advice from research findings.
SYSTEMATIC EVALUATION OF CONTROL STRATEGIES FOR IMPROVING 1 TRAFFIC CONGESTION IN MIXED-AUTONOMY TRAFFIC 2

1 We design a testbed for evaluating and comparing the performance of automated vehicles (AVs) 2 control strategies for reducing traffic congestion and improving the energy efficiency in mixed 3 autonomy traffic. The system includes a microscopic traffic simulator along with specific test 4 scenarios derived from real-world trajectory data representing different traffic conditions. We equip 5 the system with a set of desired KPIs and evaluation metrics that serve as the basis on which we 6 compare and rank the controllers. We present a use case of the system by implementing and 7 comparing a few control strategies ranging from classical to deep reinforcement learning (DRL) 8 based controllers. Our comparison results show that the controllers can achieve an increase of 9 up to 19 . 15% in the average speed and an improvement of up to 25 . 39% in the fuel efficiency of 10 the platoon, compared to the baseline of fully human-driven traffic. Through these experiments we 11 illustrate the capabilities of the system in allowing for detailed and fair comparison between control 12 strategies of different nature on a wide range of scenarios with flexible configurations. Finally, the 13 system architecture allows for easy integration of additional control strategies in the future. This 14 aims to promote continues development in the field and to allow input from the broader research 15 community. 16
Flask from Scratch-A Learning Platform for the Flask Web Framework

The audience for beginner programming is expanding as more and more people have a growing interest in the subject due to its high applicability and growing job sector in the modern world. Students are being exposed to the world of programming at a younger age than ever before. Thus, the popularity of engaging tools to learn the abstract concepts of programming has grown phenomenally in recent years. There are various beginner-friendly programming environments; two of particular relevance are: 1. Scratch from the MIT Media Lab, and 2. Pytch produced in TCD and is intended to follow on to Scratch for introducing Python. In this research work, we consider a potential follow-on environment to Pytch and provide a new learning platform for users to explore web application development in a platform designed to leverage existing knowledge gained in Scratch and Pytch. ‘Flask from Scratch’ is a fully-browser based online learning platform to teach web app development using the Pythonic web framework called Flask. The proposed service is intended to be used as part of an educational framework for beginners who are moving on from simple introductory programming environments and want to start building more practical web applications but want a low barrier to entry. The new online environment would enable students to quickly jump into the Flask framework without any complex setups and provide guided tutorials to learn the crucial concepts of Flask and web application development in general.
The Association of Depression With QT Duration: A Comparison Between Individuals Younger or Older Than 65 Years

ABSTRACT Objective The electrocardiogram-derived corrected QT (QTc) interval is an indicator of cardiac autonomic activity that has been proposed as a biological measure to investigate the interplay between depression and cardiovascular diseases. This study assesses whether depression is associated with a longer QTc interval across age groups. Methods Assessment of depressive symptoms was performed in 1637 participants of the cross-sectional Corinthia study with the Zung Self-Rating Depression Scale in those younger than 65 years (group 1) and with the Geriatric Depression Scale in elderly individuals (≥65 years, group 2). The QT interval was obtained from electrocardiogram recordings and corrected for heart rate (QTc). Results Individuals in group 1 with depression were predominantly women and had a higher prevalence of coronary artery disease and diabetes mellitus. Group 1 individuals with depression had longer QTc duration (no depression versus depression, 389.3 [27.0] versus 401.1 [32.9] milliseconds; p < .001) and percentage of abnormal QTc (no depression versus depression, 2.0% versus 10.8%; p = .001) compared with those without depression. Elderly individuals (group 2) had similar values of QTc and percentage of abnormal QTc irrespective of depression status. Even after adjustment for known QT-prolonging factors, the presence of depression in younger individuals was associated with an increased QTc by 11.1 milliseconds and with an approximately 10.6-fold higher prevalence of abnormal QTc duration. Conclusions Depression was associated with a longer QTc interval especially in individuals younger than 65 years. These findings may indicate an interrelationship between depression and autonomic dysregulation as potential risk factors for cardiovascular disease and sudden cardiac death.
Molecular gas in the starburst nucleus of M82

High-resolution interferometric observations of the CO(1-0) emission from the central one arcmin region of the peculiar galaxy M82 are presented. The observations show that the molecular gas can be divided into two components: a high concentration in the central 700 pc x 200 pc and extended regions that may be shell-like and filamentary in structure. The properties of the interstellar medium in the nuclear region of M82 implied by these and other observations are discussed, and the implications of the observations for star formation in M82 and other galaxies are considered. 76 references.
NHS staff wellbeing: Why investing in organisational and management practices makes business sense

4 Executive Summary . 8 The issue of concern . 8 What did we find? 8 Key points for policymakers . 9 Introduction . 10 Background . 11 Concerns in the NHS and primary care . 11 Why invest in workplace wellbeing? 12 Current guidance . 12 Why this review? 13 Positionality of the topic specialists . 14 Structure of the report . 14 Part 1: Mental health and wellbeing in the NHS . 15 The mental health and wellbeing of NHS Staff.15 What were the effects of the pandemic on the mental health and wellbeing of NHS staff? 16 Monitoring staff mental health . 19 Summary and comment . 19 Part 2: Building the case . 21 Staff wellbeing and organisational outcomes . 21 NHS staff absence rates . 21 Staff turnover in the NHS . 21 The impact of HR practices . 22 The importance of staff engagement . 22 The effect of staff wellbeing on patient outcomes . 23 Quality of care and patient satisfaction . 23 Medical errors . 23 Infection and mortality rates . 24 Summary and comment . 25 Part 3: Estimating the costs of poor health and wellbeing . 26 Cost of staff absence to the NHS . 26 Cost of staff presenteeism to the NHS . 27
Interface Formation in a Partially Miscible Polymer Blend

We have directly measured the interface formation and diffusion between two partially miscible polymers, SCPE and PMMA, using Rutherford backscattering spectrometry, as the temperature was varied from the glass transition into the two-phase region. As the temperature was increased, the interfacial width for a given diffusion time increased sharply, attaining a maximum value approximately 25 °C above the lower critical solution temperature and then dropped abruptly. The results are briefly discussed within the framework of the extended Flory-Huggins theory wherein nonlocal terms are included in the free energy.
Refining Black Hole Physics to Obtain Planck’s Constant from Information Shared from Cosmological Cycle to Cycle (Avoiding Super-Radiance)

Padmanabhan elucidated the concept of super radiance in black hole physics which would lead to loss mass of a black hole, and loss of angular momentum due to space-time infall of material into a black hole. As Padmanabhan explained it, to avoid super radiance, and probable break down of black holes, from in fall, one would need in fall material frequency, divided by mass of particles undergoing in fall in the black hole to be greater than the angular velocity of the black hole event horizon in question. We should keep in mind we bring this model up to improve the chance that Penrose’s conformal cyclic cosmology will allow for retention of enough information for preservation of Planck’s constant from cycle to cycle, as a counterpart to what we view as unacceptable reliance upon the LQG quantum bounce and its tetrad structure to preserve memory. In addition, we are presuming that at the time of z = 20 in red shift that there would be roughly about the same order of magnitude of entropy as number of operations in the electro weak era, and that the number of operations in the z = 20 case is close to the entropy at redshift z = 0. Finally, we have changed Λ with the result that after redshift = 20; there is a rapid collapse to the present-day vacuum energy value i.e. by z = 12 the value of the cosmological constant, Λ likely being the same, today, as for what it was when z = 12. And z = 12 is the redshift value about when Galaxies form.