Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Interactomes of Genes Showing Association with Type-2 Diabetes and Its Intermediate Phenotypic Traits Point towards Adipo-Centric Mechanisms in Its Pathophysiology

The pathogenic mechanisms causing type 2 diabetes (T2D) are still poorly understood; a greater awareness of its causation can lead to the development of newer and better antidiabetic drugs. In this study, we used a network-based approach to assess the cellular processes associated with protein–protein interaction subnetworks of glycemic traits—HOMA-β and HOMA-IR. Their subnetworks were further analyzed in terms of their overlap with the differentially expressed genes (DEGs) in pancreatic, muscle, and adipose tissue in diabetics. We found several DEGs in these tissues showing an overlap with the HOMA-β subnetwork, suggesting a role of these tissues in β-cell failure. Many genes in the HOMA-IR subnetwork too showed an overlap with the HOMA-β subnetwork. For understanding the functional theme of these subnetworks, a pathway-to-pathway complementary network analysis was done, which identified various adipose biology-related pathways, containing genes involved in both insulin secretion and action. In conclusion, network analysis of genes showing an association between T2D and its intermediate phenotypic traits suggests their potential role in beta cell failure. These genes enriched the adipo-centric pathways and were expressed in both pancreatic and adipose tissue and, therefore, might be one of the potential targets for future antidiabetic treatment.
Adenoviral Vectors Meet Gene Editing: A Rising Partnership for the Genomic Engineering of Human Stem Cells and Their Progeny

Gene editing permits changing specific DNA sequences within the vast genomes of human cells. Stem cells are particularly attractive targets for gene editing interventions as their self-renewal and differentiation capabilities consent studying cellular differentiation processes, screening small-molecule drugs, modeling human disorders, and testing regenerative medicines. To integrate gene editing and stem cell technologies, there is a critical need for achieving efficient delivery of the necessary molecular tools in the form of programmable DNA-targeting enzymes and/or exogenous nucleic acid templates. Moreover, the impact that the delivery agents themselves have on the performance and precision of gene editing procedures is yet another critical parameter to consider. Viral vectors consisting of recombinant replication-defective viruses are under intense investigation for bringing about efficient gene-editing tool delivery and precise gene-editing in human cells. In this review, we focus on the growing role that adenoviral vectors are playing in the targeted genetic manipulation of human stem cells, progenitor cells, and their differentiated progenies in the context of in vitro and ex vivo protocols. As preamble, we provide an overview on the main gene editing principles and adenoviral vector platforms and end by discussing the possibilities ahead resulting from leveraging adenoviral vector, gene editing, and stem cell technologies.
Trajectories of fatigue among stroke patients from the acute phase to 18 months post-injury: A latent class analysis

Introduction Post-stroke fatigue (PSF) is a common symptom affecting 23–75% of stroke survivors. It is associated with increased risk of institutionalization and death, and it is of many patients considered among the worst symptoms to cope with after stroke. Longitudinal studies focusing on trajectories of fatigue may contribute to understanding patients’ experience of fatigue over time and its associated factors, yet only a few have been conducted to date. Objectives To explore whether subgroups of stroke survivors with distinct trajectories of fatigue in the first 18 months post stroke could be identified and whether these subgroups differ regarding sociodemographic, medical and/or symptom-related characteristics. Materials and methods 115 patients with first-ever stroke admitted to Oslo University Hospital or Buskerud Hospital were recruited and data was collected prospectively during the acute phase and at 6, 12 and 18 months post stroke. Data on fatigue (both pre- and post-stroke), sociodemographic, medical and symptom-related characteristics were collected through structured interviews, standardized questionnaires and from the patients’ medical records. Growth mixture modeling (GMM) was used to identify latent classes, i.e., subgroups of patients, based on their Fatigue Severity Scales (FSS) scores at the four time points. Differences in sociodemographic, medical, and symptom-related characteristics between the latent classes were evaluated using univariate and multivariable ordinal regression analyses. Results and their significance Using GMM, three latent classes of fatigue trajectories over 18 months were identified, characterized by differing levels of fatigue: low, moderate and high. The mean FSS score for each class remained relatively stable across all four time points. In the univariate analyses, age <75, pre-stroke fatigue, multiple comorbidities, current depression, disturbed sleep and some ADL impairment were associated with higher fatigue trajectories. In the multivariable analyses, pre-stroke fatigue (OR 4.92, 95% CI 1.84–13.2), multiple comorbidities (OR 4,52,95% CI 1.85–11.1) and not working (OR 4.61, 95% CI 1.36–15,7) were the strongest predictor of higher fatigue trajectories The findings of this study may be helpful for clinicians in identifying patients at risk of developing chronic fatigue after stroke.
ADHD and Judgments of Impulsivity in Rule Violations

Abstract Participants with ADHD (n = 45) and participants without ADHD (n = 130, total n = 175) judged hypothetical moral and conventional rule violations that varied the impulsivity of the act, the ADHD diagnosis, and the gender of the actor in order to examine (1) social reasoning about impulsiveness and (2) whether participants infer impulsiveness from the characteristics of the actor, including gender and ADHD-status. Moral violations were judged more negatively than conventional violations, even when they were impulsive. The characteristics of the actor influenced judgments in that participants judged boys’ behavior as more acceptable, as having less control, and as deserving of less punishment compared to girls. In addition, actors who were described as having ADHD were judged overall more positively. Participants with ADHD judged that all actors should receive similar punishment, regardless of the actor’s ADHD diagnosis, while participants without ADHD judged actors with ADHD should receive less punishment than those without.
Comprehensive core stability intervention and coordination of care in acute and subacute stroke rehabilitation—a pilot study

Abstract Purpose: To investigate the feasibility and preliminary effects of new intervention emphasising core stability training integrated in functional activity (I-CoreDIST), supported by clinical Skype sessions to coordinate between health care levels among acute stroke patients. Methods: A baseline-, 4- and 12-week post-test design, including 13 individuals with acute stroke who received I-CoreDIST 5–6 day/week for 30–60 min as inpatients and three times a week as outpatients, for a total of 12 weeks. Primary outcomes: Trunk Impairment Scale-Norwegian Version (TIS-NV) and Swedish Postural Assessment Scale for Stroke-Norwegian Version (SwePASS-NV). Secondary outcomes: The Mini-BESTest, 10-m Walk Test, 2-min Walk Test, ActiGraphWgt3X-BT monitors and Questback. Linear mixed models and non-parametric tests were used for the analysis. Results: The TIS-NV demonstrated significant within-group improvements: mean difference 2.36 points at 4 weeks (p = .006) and 5.09 points at 12 weeks (p < .000) compared to baseline. The SwePASS-NV showed significant within-group improvements compared to baseline: mean difference 6.91 points at 4 weeks (p = .005) and 9.64 points at 12 weeks (p < .000). The secondary outcomes showed significant within-group improvements at 12 weeks. The Skype sessions are valuable but not applicable prior to discharge. Conclusions: I-CoreDIST is feasible, indicate effects, and Skype sessions should be re-scheduled. Randomised controlled trials are warranted.
An attributional process model of workplace gossip.

Despite the ubiquity of gossip in the workplace, the management literature offers a limited understanding of its consequences for gossip senders. To understand whether gossiping is beneficial or detrimental for the gossip sender, it is necessary to consider the perspective of gossip recipients and their response to gossip. We develop a typology of gossip that characterizes archetypal patterns of interpreting gossip. We then draw from attribution theory to develop a multilevel process model of workplace gossip that focuses on how the gossip recipient's attributions of a gossip episode shape the gossip recipient's subsequent response and behaviors. In addition to the valence and work-relatedness dimensions of gossip that comprise the typology, we examine credibility and the status of the gossip target as fundamental features of the gossip episode that jointly affect the gossip recipient's attributions. At the episodic level, the process of deciphering the gossip sender's motives influences the subsequent reciprocation of gossip. Depending on the locus of causality attributed to the gossip episode, gossip also contributes to the perceived trustworthiness of the gossip sender and the gossip recipient's cooperation with or social undermining of the gossip sender over time. The proposed model suggests that the potential benefits or social consequences of gossip for the gossip sender depend on the characteristics of the gossip and the context of the gossip episode that serve as inputs to the gossip recipient's attributional process. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
MLIR Loop Optimizations for High-Level Synthesis: A Case Study

High-Level Synthesis (HLS) tools automatically translate code from a general-purpose programming language (typically C or C++) into a hardware description language (HDL) such as Verilog or VHDL, significantly reducing the hardware design productivity gap. HLS benefits from the same compiler optimizations that identify instruction, memory, and data parallelism for general-purpose processors. However, they also need to consider specific needs of low-level circuit design, such as the notion of time, synchronous and asynchronous logic, and wiring delays. Because of the mismatch between hardware abstractions and general-purpose programming languages, HLS tools often require the addition of pragma directives in the input code to guide hardware generation.
High-risk areas of leprosy in Brazil between 2001-2015.

OBJECTIVES to identify high-risk areas of leprosy in Brazil from 2001 to 2015. METHODS this is an ecological study of spatial analysis based on Brazilian municipalities. Spatial scan statistics were used to identify spatial clustering and measure the relative risk from the annual detection rate of new cases of leprosy. By criterion based on the Gini index, only secondary clusters were considered. RESULTS spatial scan statistics detected 26 clusters, in which the detection rate was 59.19 cases per 100 thousand inhabitants, while in the remainder of the country it was 11.76. Large part of the cluster area is located in the Legal Amazon. These groups included only 21.34% of the total population, but 60.40% of the new cases of the disease. CONCLUSIONS Leprosy remains concentrated in some areas, showing the need for control programs to intensify actions in these municipalities.
Towards Physiologically and Tightly Regulated Vectored Antibody Therapies

Cancers represent highly significant health issues and the options for their treatment are often not efficient to cure the disease. Immunotherapy strategies have been developed to modulate the patient’s immune system in order to eradicate cancerous cells. For instance, passive immunization consists in the administration at high doses of exogenously produced monoclonal antibodies directed either against tumor antigen or against immune checkpoint inhibitors. Its main advantage is that it provides immediate immunity, though during a relatively short period, which consequently requires frequent injections. To circumvent this limitation, several approaches, reviewed here, have emerged to induce in vivo antibody secretion at physiological doses. Gene delivery vectors, such as adenoviral vectors or adeno-associated vectors, have been designed to induce antibody secretion in vivo after in situ cell modification, and have driven significant improvements in several cancer models. However, anti-idiotypic antibodies and escape mutants have been detected, probably because of both the continuous expression of antibodies and their expression by unspecialized cell types. To overcome these hurdles, adoptive transfer of genetically modified B cells that secrete antibodies either constitutively or in a regulated manner have been developed by ex vivo transgene insertion with viral vectors. Recently, with the emergence of gene editing technologies, the endogenous B cell receptor loci of B cells have been modified with the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated endonuclease (Cas-9) system to change their specificity in order to target a given antigen. The expression of the modified BCR gene hence follows the endogenous regulation mechanisms, which may prevent or at least reduce side effects. Although these approaches seem promising for cancer treatments, major questions, such as the persistence and the re-activation potential of these engineered cells, remain to be addressed in clinically relevant animal models before translation to humans.
Dynamics, a Powerful Component of Current and Future in Silico Approaches for Protein Design and Engineering

Computational prediction has become an indispensable aid in the processes of engineering and designing proteins for various biotechnological applications. With the tremendous progress in more powerful computer hardware and more efficient algorithms, some of in silico tools and methods have started to apply the more realistic description of proteins as their conformational ensembles, making protein dynamics an integral part of their prediction workflows. To help protein engineers to harness benefits of considering dynamics in their designs, we surveyed new tools developed for analyses of conformational ensembles in order to select engineering hotspots and design mutations. Next, we discussed the collective evolution towards more flexible protein design methods, including ensemble-based approaches, knowledge-assisted methods, and provable algorithms. Finally, we highlighted apparent challenges that current approaches are facing and provided our perspectives on their further development.
Natural microalgal cultivation systems using primary effluent and excess sludge

ABSTRACT Microalgae have been recently cultivated using resources from wastewater treatment plants, including nutrients, CO2, and heat. In the present study, we focused on the natural cultivation of total microalgae rather than specific microalgae, for which culture conditions and the cultivation environment are difficult to prepare. Natural microalgal cultivation systems using 380-L raceway tanks were operated outdoors for 8 months and the effects of the culture substrate were investigated. The cultivation substrate was the primary effluent with or without excess sludge. The results showed that when diluted excess sludge was added to the substrate, microalgal biomass increased more than when the substrate contained only primary effluent. Additionally, the wastewater suspended matter and water quality were removed, reaching low levels. Microalgal culture systems using excess sludge showed higher organic acid content, higher biochemical methane potential, and higher efficiency in producing more microalgal biomass than wastewater treatment plant systems that did not use excess sludge. GRAPHICAL ABSTRACT
“Many wasted months”: Stakeholders’ perspectives about waiting for speech-language pathology services

Abstract Purpose: High demand for speech-language pathology services is reflected in long waiting lists. Waiting can be active or passive and has implications for stakeholders, including consumers, professionals, and organisations. The present study explored experiences and perspectives regarding waiting for speech-language pathology services through analysis of stakeholders’ written submissions to an Australian Government Senate Inquiry. Method: Written submissions (n = 337) were screened for terms related to waiting. Included submissions (n = 133) were written by organisations (36.8%), speech-language pathologists (29.3%), parents (27.8%), individuals with communication and/or swallowing difficulties (5.3%), and others. Result: Inductive thematic analysis identified three themes. (1) Duration. Consistently described as long. (2) Consequences. Consumers’ consequences included: burden on physical health, finances, time, emotional wellbeing, and relationships, reduced continuity of care, and increased intervention needs. Professional consequences included: stress and burnout impacting job satisfaction, and reduced effectiveness. Societal consequences included: social and ethical burden, and a drain on health and legal systems. (3) Actions. Consumers advocated and sought alternatives (e.g. threats to harm their child, relocation to a capital city), professionals implemented service delivery and policy actions, and organisations lacked effective system-wide strategies. Conclusion: Existing services did not appear to meet stakeholders’ needs. Action is needed to improve speech-language pathology waiting lists and access to services, and minimise possible consequences for stakeholders.
Development of a Simple Reversible-Flow Method for Preparation of Micron-Size Chitosan-Cu(II) Catalyst Particles and Their Testing of Activity

A simple flow system employing a reversible-flow syringe pump was employed to synthesize uniform micron-size particles of chitosan-Cu(II) (CS-Cu(II)) catalyst. A solution of chitosan and Cu(II) salt was drawn into a holding coil via a 3-way switching valve and then slowly pumped to drip into an alkaline solution to form of hydrogel droplets. The droplets were washed and dried to obtain the catalyst particles. Manual addition into the alkaline solution or employment of flow system with a vibrating rod, through which the end of the flow line is inserted, was investigated for comparison. A sampling method was selected to obtain representative samples of the population of the synthesized particles for size measurement using optical microscopy. The mean sizes of the particles were 880 ± 70 µm, 780 ± 20 µm, and 180 ± 30 µm for the manual and flow methods, without and with the vibrating rod, respectively. Performance of the flow methods, in terms of rate of droplet production and particle size distribution, are discussed. Samples of 180 µm size CS-Cu(II) particles were tested for catalytic reduction of 0.5 mM p-nitrophenol to p-aminophenol by 100-fold excess borohydride. The conversion was 98% after 20 min, whereas without the catalyst there was only 14% conversion.
Molecular Routes to Specific Identification of the Lactobacillus Casei Group at the Species, Subspecies and Strain Level

The genus Lactobacillus includes, among others, Lactobacillus casei, Lactobacillus paracasei and Lactobacillus rhamnosus, species that are collectively referred to as the Lactobacillus casei group. Many studies have shown that strains belonging to this group may decrease lactose intolerance, the effects of inflammatory bowel disease, diarrhea, constipation, food allergies and even colon cancer. Moreover, evidences exists of positive effects of these bacteria on mucosal immunity and blood cholesterol level. Because of their beneficial influence on human health, many of them are used as food additives and probiotic pharmaceuticals. It should be stressed that health-promoting properties are not attributed at the species level, but to specific strains. Therefore, procedures are necessary to allow specific identification at each phylogenetic level—genus, species and strain. In this paper we present a practical overview of molecular methods for the identification and differentiation of L. casei bacteria. The research included 30 bacterial strains belonging to three species: L.casei, L. paracasei and L. rhamnosus. Among the tested procedures were genus- and species-specific PCR, multiplex-PCR, Real-Time HRM analysis, RFLP-PCR, rep-PCR, RAPD-PCR, AFLP-PCR, and proteomic methods such as MALDI-TOF MS typing and SDS-PAGE fingerprinting. The obtained results showed that multiplex-PCR and MALDI-TOF MS turned out to be the most useful methods to identify the tested bacteria at the species level. At the strain level, the AFLP-PCR method showed the highest discriminatory power. We hope that the presented results will allow for the easy selection of an appropriate procedure, depending on the experiment conducted and the equipment capabilities of any given laboratory.
Transcriptomic analysis of polyketide synthases in a highly ciguatoxic dinoflagellate, Gambierdiscus polynesiensis and low toxicity Gambierdiscus pacificus, from French Polynesia

Marine dinoflagellates produce a diversity of polyketide toxins that are accumulated in marine food webs and are responsible for a variety of seafood poisonings. Reef-associated dinoflagellates of the genus Gambierdiscus produce toxins responsible for ciguatera poisoning (CP), which causes over 50,000 cases of illness annually worldwide. The biosynthetic machinery for dinoflagellate polyketides remains poorly understood. Recent transcriptomic and genomic sequencing projects have revealed the presence of Type I modular polyketide synthases in dinoflagellates, as well as a plethora of single domain transcripts with Type I sequence homology. The current transcriptome analysis compares polyketide synthase (PKS) gene transcripts expressed in two species of Gambierdiscus from French Polynesia: a highly toxic ciguatoxin producer, G. polynesiensis, versus a non-ciguatoxic species G. pacificus, each assembled from approximately 180 million Illumina 125 nt reads using Trinity, and compares their PKS content with previously published data from other Gambierdiscus species and more distantly related dinoflagellates. Both modular and single-domain PKS transcripts were present. Single domain β-ketoacyl synthase (KS) transcripts were highly amplified in both species (98 in G. polynesiensis, 99 in G. pacificus), with smaller numbers of standalone acyl transferase (AT), ketoacyl reductase (KR), dehydratase (DH), enoyl reductase (ER), and thioesterase (TE) domains. G. polynesiensis expressed both a larger number of multidomain PKSs, and larger numbers of modules per transcript, than the non-ciguatoxic G. pacificus. The largest PKS transcript in G. polynesiensis encoded a 10,516 aa, 7 module protein, predicted to synthesize part of the polyether backbone. Transcripts and gene models representing portions of this PKS are present in other species, suggesting that its function may be performed in those species by multiple interacting proteins. This study contributes to the building consensus that dinoflagellates utilize a combination of Type I modular and single domain PKS proteins, in an as yet undefined manner, to synthesize polyketides.
Aging in Times of the COVID-19 Pandemic: Avoiding Ageism and Fostering Intergenerational Solidarity

1School of Social Work, Bar Ilan University, Ramat Gan, Israel. 2Department of Psychology, University of Toronto, Ontario, Canada. 3Department of Human Development and Family Studies, Colorado State University, Fort Collins. 4Social and Behavioral Sciences Department, Yale School of Public Health, New Haven, Connecticut. 5Department of Psychology, North Carolina State University, Raleigh. 6Department of Psychology, Friedrich-Schiller-University Jena, Germany. 7German Centre of Gerontology, Berlin, Germany. 8Network of Aging Research, Heidelberg University, Germany.