Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of molecular diagnostic approaches for the detection and differentiation of the intestinal protist Blastocystis sp. in humans

Blastocystis is the most commonly found intestinal protist in the world. Accurate detection and differentiation of Blastocystis including its subtypes (arguably species) are essential to understand its epidemiology and role in human health. We compared (i) the sensitivity of conventional PCR (cPCR) and qPCR in a set of 288 DNA samples obtained from stool samples of gut-healthy individuals, and (ii) subtype diversity as detected by next-generation sequencing (NGS) versus Sanger sequencing. Real-time PCR resulted in more positive samples than cPCR, revealing high fecal load of Blastocystis based on the quantification curve in most samples. In subtype detection, NGS was largely in agreement with Sanger sequencing but showed higher sensitivity for mixed subtype colonization within one host. This fact together with use of the combination of qPCR and NGS and obtaining information on the fecal protist load will be beneficial for epidemiological and surveillance studies.
Air entrapment as a potential cause of early subcutaneous implantable cardioverter defibrillator malfunction: a systematic review of the literature

Abstract Aims Air entrapment (AE) has been reported as a potential cause of early inappropriate shocks (ISs) following subcutaneous implantable cardioverter defibrillator (S-ICD) implantation, but a cause–effect relationship is not always evident. This systematic review aims to analyse this phenomenon concerning implantation techniques, electrogram (EGM) features, radiologic findings, and patient management. Methods and results A systematic search was conducted using PubMed, Embase, and Google Scholar databases following the PRISMA guidelines to obtain all available literature data since 2010 on S-ICD malfunctions possibly due to AE. The final analysis included 54 patients with AE as a potential cause of S-ICD malfunction. Overall, the aggregate incidence of this condition was 1.2%. Of ICD malfunctions possibly due to AE, 93% were ISs, and 95% were recorded within the first week following implantation. Radiologic diagnosis of AE was confirmed in 28% of the entire study cohort and in 68% of patients in whom this diagnostic examination was reported. At the time of device malfunction, EGMs showed artefacts, baseline drift, and QRS voltage reduction in 95, 76, and 67% of episodes, respectively. Management included ICD reprogramming or testing, no action (observation), and invasive implant revision in 57, 33, and 10% of patients, respectively. No recurrences occurred during follow-up, irrespective of management performed. Conclusions Device malfunction possibly due to AE may occur in ∼1% of S-ICD recipients. Diagnosis is strongly suggested by early occurrence, characteristic EGM features, and radiologic findings. Non-invasive management, principally device reprogramming, appears to be effective in most patients.
Using Attachment and Biobehavioral Catch-up with young children with developmental delays: A multiple-baseline trial of attachment, sensitivity, and cortisol

The Attachment and Biobehavioral Catchup intervention potentially offsets psychosocial risks facing dyads in which children have intellectual disability or developmental delays. In this single-case multiple-baseline study the efficacy of this intervention was tested across three such South African families. Maternal sensitivity, attachment security, and child affect regulation were measured weekly during a baseline and intervention period, using the Ainsworth Maternal Sensitivity Scales, Attachment Q-sort and salivary cortisol, respectively. Furthermore, post-intervention interviews invited parents’ and intervenors’ evaluations of the intervention. Visual analysis broadly indicated improvement in maternal sensitivity and attachment security across subjects over time following the introduction of the intervention, although randomisation tests were not statistically significant. Effects on affect regulation were not clearly observed and may have been influenced by case-specific variables. Parent-participants and intervenors also identified particularly helpful contributions from the intervention. Findings underscore the importance of individual-level effects evaluation, especially when implementing interventions outside the original population.
Genomic signatures of the evolution of a diurnal lifestyle in Strigiformes

Abstract Understanding the targets of selection associated with changes in behavioral traits represents an important challenge of current evolutionary research. Owls (Strigiformes) are a diverse group of birds, most of which are considered nocturnal raptors. However, a few owl species independently adopted a diurnal lifestyle in their recent evolutionary history. We searched for signals of accelerated rates of evolution associated with a diurnal lifestyle using a genome-wide comparative approach. We estimated substitution rates in coding and noncoding conserved regions of the genome of seven owl species, including three diurnal species. Substitution rates of the noncoding elements were more accelerated than those of protein-coding genes. We identified new, owl-specific conserved noncoding elements as candidates of parallel evolution during the emergence of diurnality in owls. Our results shed light on the molecular basis of adaptation to a new niche and highlight the importance of regulatory elements for evolutionary changes in behavior. These elements were often involved in the neuronal development of the brain.
Efficient extracellular production of recombinant proteins in E. coli via enhancing expression of dacA on the genome

Abstract D, D-carboxypeptidase DacA plays an important role in the synthesis and stabilization of Escherichia coli cell wall peptidoglycan. The production level of extracellular recombinant proteins in E. coli can be enhanced by high D, D-carboxypeptidase activity. Construction of expression systems under optimal promoters is one of the main strategies to realize high protein production in E. coli. In this study, the promoter PdacA-3 from DacA on the genome of E. coli BL21 (DE3) was verified to be efficient for recombinant green fluorescent protein using the plasmid mutant pET28a-PdacA with PdacA-3. Meanwhile, the promoter PdacA-3 was engineered to increase the production level of proteins via inserting one or two Shine–Dalgarno (SD) sequences between the promoter PdacA-3 and the target genes. The expression level of dacA on the genome was increased by the improved transcription of the engineered promoters (especially after inserting one additional SD sequence). The engineered promoters increased cell membrane permeabilities to significantly enhance the secretion production of extracellular recombinant proteins in E. coli. Among them, the extracellular recombinant amylase activities in E. coli BL21::1SD-pET28a-amyK and E. coli BL21::2SD-pET28a-amyK were increased by 2.0- and 1.6-fold that of the control (E. coli BL21-pET28a-amyK), respectively. Promoter engineering also affected the morphology and growth of the E. coli mutants. It was indicated that the engineered promoters enhanced the expression of dacA on the genome to disturb the synthesis and structural stability of cell wall peptidoglycans.
Inhibition of vascular endothelial growth factor alleviates neovascular retinopathy with regulated neurotrophic/proinflammatory cytokines through the modulation of DBI‐TSPO signaling

Diazepam binding inhibitor (DBI)‐translocator protein (18kDa) (TSPO) signaling in the retina was reported to possess coordinated macroglia‐microglia interactions. We investigated DBI‐TSPO signaling and its correlation with vascular endothelial growth factor (VEGF), neurotrophic or inflammatory cytokines in neovascular retinopathy, and under hypoxic conditions. The vitreous expression of DBI, VEGF, nerve growth factor (NGF), and interleukin‐1beta (IL‐1β) were examined in proliferative diabetic retinopathy (PDR) patients with or without anti‐VEGF therapy and nondiabetic controls. Retinal DBI‐TSPO signaling and the effect of the anti‐VEGF agent were evaluated in a mouse model of oxygen‐induced retinopathy (OIR). Interactions between Müller cell‐derived VEGF and DBI, as well as cocultured microglial cells under hypoxic conditions, were studied, using Western blot, real‐time RT‐PCR, enzyme‐linked immunosorbent assay (ELISA), flow cytometry, and immunofluorescent labeling. Results showed that vitreous levels of DBI, VEGF, NGF, and IL‐1β were significantly higher in PDR patients compared with controls, which further changed after anti‐VEGF therapy. A statistical association was found between vitreous DBI and VEGF, NGF, IL‐1β, and age. The application of the anti‐VEGF agent in the OIR model induced retinal expression of DBI and NGF, and attenuated inflammation and microglial cell activation. Inhibition of Müller cell‐derived VEGF could increase its DBI expression under hypoxic conditions, while the DBI‐TSPO signaling pathway is essential for anti‐VEGF agents exerting anti‐inflammatory and neuroprotective effects, as well as limiting inflammatory magnitude, promoting its neurotrophin production and anti‐inflammatory (M2) polarization in microglial cells. These findings suggest the beneficial effect of anti‐VEGF therapy on inflammation and neurotrophy of retinal glial cells through modulation of the DBI‐TSPO signaling pathway.
Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: The DEBBRAH trial

Abstract Background Trastuzumab deruxtecan (T-DXd) has shown durable antitumor activity in pretreated patients with HER2-positive advanced breast cancer (ABC), but its efficacy has not yet been evaluated in patients with active brain metastases (BMs). DEBBRAH aims to assess T-DXd in patients with HER2-positive or HER2-low ABC and central nervous system involvement. Methods This ongoing, five-cohort, phase II study (NCT04420598) enrolled patients with pretreated HER2-positive or HER2-low ABC with stable, untreated, or progressing BMs, and/or leptomeningeal carcinomatosis. Here, we report findings from HER2-positive ABC patients with non-progressing BMs after local therapy (n = 8; cohort 1), asymptomatic untreated BMs (n = 4; cohort 2), or progressing BMs after local therapy (n = 9; cohort 3). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days. The primary endpoint was 16-week progression-free survival (PFS) for cohort 1 and intracranial objective response rate (ORR-IC) for cohorts 2 and 3. Results As of October 20, 2021, 21 patients received T-DXd. In cohort 1, 16-week PFS rate was 87.5% (95%CI, 47.3-99.7; P < .001). ORR-IC was 50.0% (95%CI, 6.7-93.2) in cohort 2 and 44.4% (95%CI, 13.7-78.8; P < .001) in cohort 3. Overall, the ORR-IC in patients with active BMs was 46.2% (95%CI, 19.2-74.9). Among patients with measurable intracranial or extracranial lesions at baseline, the ORR was 66.7% (12 out of 18 patients; 95%CI, 41.0-86.7), 80.0% (95%CI, 28.4-99.5) in cohort 1, 50.0% (95%CI, 6.7-93.2) in cohort 2, and 66.7% (95%CI, 29.9-92.5) in cohort 3. All responders had partial responses. The most common adverse events included fatigue (52.4%; 4.8% grade ≥3), nausea (42.9%; 0% grade ≥3), neutropenia (28.6%; 19% grade ≥3), and constipation (28.6%; 0% grade ≥3). Two (9.5%) patients suffered grade 1 interstitial lung disease/pneumonitis. Conclusions T-DXd showed intracranial activity with manageable toxicity and maintained the quality of life in pretreated HER2-positive ABC patients with stable, untreated, or progressing BMs. Further studies are needed to validate these results in larger cohorts.
The pharmacotherapeutic management of comorbid bipolar disorder and alcohol use disorder

ABSTRACT Introduction Comorbidity of bipolar disorder (BD) and alcohol use disorder (AUD) is very frequent resulting in detrimental outcomes, including increased mortality. Diagnosis of AUD in BD and vice versa is often delayed as symptoms of one disorder mimic and obscure the other one. Evidence for pharmacotherapies for people with comorbid BD and AUD remains limited, and further proof-of-concept studies are urgently needed. Areas covered This paper explores the currently available pharmacotherapies for AUD, BD and their usefulness for comorbid BD and AUD. It also covers to some degree the epidemiology, diagnosis, and potential common neurobiological traits of comorbid BD and AUD. Expert opinion The authors conclude that more controlled studies are needed before evidence-based guidance can be drawn up for clinician’s use. Since there are no relevant pharmacological interactions, approved medications for AUD can also be used safely in BD. For mood stabilization, lithium should be considered first in adherent persons with BD and comorbid AUD. Alternatives include valproate, lamotrigine, and some atypical antipsychotics, with partial D2/D3 receptor agonism possibly being beneficial in AUD, too.
Nonsuicidal self‐injury and rumination: A meta‐analysis

Abstract Trait rumination is the tendency to overthink and focus on negative emotions and events and is related to a number of psychological disorders and maladaptive behaviors including nonsuicidal self‐injury (NSSI). The purpose of this study was to conduct a meta‐analysis of the relationship between trait rumination and NSSI behaviors. Results from 60 samples showed small effect sizes between trait rumination and NSSI engagement, NSSI frequency, and the number of methods used to self‐injure in cross‐sectional samples. Results from 13 samples showed small effect sizes between trait rumination and NSSI engagement and NSSI frequency in longitudinal samples. Moderator analyses indicated that this relationship is similar whether the type of rumination is depressive or not and is generally consistent across different ages, genders, and ethnicities. These results help clarify the role of trait rumination as a risk factor for NSSI.
Sox9 and Lef1 regulate the fate and behavior of airway glandular progenitors in response to injury.

Cartilaginous airways of larger mammals and the mouse trachea contain at least three well-established stem cell compartments including basal cells (BC) of the surface airway epithelium (SAE) and ductal and myoepithelial cells of the submucosal glands (SMG). Here we demonstrate that glandular Sox9-expressing progenitors capable of SAE repair decline with age in mice. Notably, Sox9-lineage glandular progenitors produced basal and ciliated cells in the SAE, but failed to produce secretory cells. Lef1 was required for glandular Sox9 lineage contribution to SAE repair and its deletion significantly reduced proliferation following injury. By contrast, in vivo deletion of Sox9 enhanced proliferation in both SAE and SMG progenitors shortly following injury, but these progenitors failed to proliferate in vitro in the absence of Sox9, similar to that previously shown for Lef1 deletion. In cystic fibrosis ferret airways, Sox9 expression inversely correlated with Ki67 proliferative marker expression in SMG and the SAE. Using in vitro and ex vivo models, we demonstrate that Sox9 is extinguished as glandular progenitors exit ducts and proliferate on the airway surface and that Sox9 is required for migration and proper differentiation of SMG, but not SAE, progenitors. We propose a model whereby Wnt/Lef1 and Sox9 signals differentially regulate the proliferative and migratory behavior of glandular progenitors, respectively.
Development of PARcific Approach: Participatory Action Research Methodology for Collectivist Health Research

This article explores the evolution of a novel approach designed to advance qualitative methods in cross-cultural health research. This methodology was developed by synthesising several research methods and involved in-depth stakeholder consultation with participants of a Pacific-based nursing and midwifery health leadership program. Many of these participants played a crucial role in creating, exploring and evaluating several research methods and implementing and evaluating this co-designed research methodology. Starting with a Participatory Action Research framework, the research methodology evolved as it was informed by the local Pacific methodologies (in particular Talanoa and Kakala frameworks), where researchers, co-researchers and participants alike, working from within their own collectivist/individualist paradigms, negotiated cultural differences. Finally, a methodological framework of ‘best practice’ for future health research methods was developed for use with capacity building research. The new methodology could provide a foundation for future co-designed cross-cultural research in collectivist cultures.
GCKIII kinases in lipotoxicity: Roles in NAFLD and beyond

Nonalcoholic fatty liver disease (NAFLD) is defined by excessive accumulation of lipid droplets within hepatocytes. The STE20‐type kinases comprising the germinal center kinase III (GCKIII) subfamily – MST3, MST4, and STK25 – decorate intrahepatocellular lipid droplets and have recently emerged as critical regulators of the initiation and progression of NAFLD. While significant advancement has been made toward deciphering the role of GCKIII kinases in hepatic fat accumulation (i.e., steatosis) as well as the aggravation of NAFLD into its severe form nonalcoholic steatohepatitis (NASH), much remains to be resolved. This review provides a brief overview of the recent studies in patient cohorts, cultured human cells, and mouse models, which have characterized the function of MST3, MST4, and STK25 in the regulation of hepatic lipid accretion, meta‐inflammation, and associated cell damage in the context of NAFLD/NASH. We also highlight the conflicting data and emphasize future research directions that are needed to advance our understanding of GCKIII kinases as potential targets in the therapy of NAFLD and its comorbidities. Conclusions: Several lines of evidence suggest that GCKIII proteins govern the susceptibility to hepatic lipotoxicity and that pharmacological inhibition of these kinases could mitigate NAFLD development and aggravation. Comprehensive characterization of the molecular mode‐of‐action of MST3, MST4, and STK25 in hepatocytes as well as extrahepatic tissues is important, especially in relation to their impact on carcinogenesis, to fully understand the efficacy as well as safety of GCKIII antagonism.
Real life long‐term efficacy and safety of ixekizumab in moderate‐to‐severe psoriasis: A 192 weeks multicentric retrospective study—IL PSO (Italian landscape psoriasis)

Psoriasis is one of the commonest inflammatory skin diseases determining a very high impact on patients' quality of life and daily activities and relationships. Several biologic therapies have been approved through the years for the treatment of moderate‐to‐severe plaque psoriasis, and efficacy and safety profile have been analyzed in clinical trials. Ixekizumab is an immunoglobulin G subclass 4 monoclonal antibody that selectively targets and binds IL‐17A with high specificity and affinity. Inhibiting IL‐17A activity, ixekizumab reduces and turns down levels of inflammation, resulting in the clinical improvement of the disease. Long‐term efficacy and safety profile of ixekizumab have been investigated and reported in the UNCOVER trials, but in literature there are only few studies based on real life experience. We present the efficacy and safety profile of ixekizumab in a cohort of 779 patients affected by moderate‐to‐severe plaque psoriasis and treated with ixekizumab in 11 Italian dermatology hospitals, with a follow‐up of care until 192 weeks.
Genetic Variation in Reproductive Investment Across an Ephemerality Gradient in Daphnia pulex

Abstract Species across the tree of life can switch between asexual and sexual reproduction. In facultatively sexual species, the ability to switch between reproductive modes is often environmentally dependent and subject to local adaptation. However, the ecological and evolutionary factors that influence the maintenance and turnover of polymorphism associated with facultative sex remain unclear. We studied the ecological and evolutionary dynamics of reproductive investment in the facultatively sexual model species, Daphnia pulex. We found that patterns of clonal diversity, but not genetic diversity varied among ponds consistent with the predicted relationship between ephemerality and clonal structure. Reconstruction of a multi-year pedigree demonstrated the coexistence of clones that differ in their investment into male production. Mapping of quantitative variation in male production using lab-generated and field-collected individuals identified multiple putative quantitative trait loci (QTL) underlying this trait, and we identified a plausible candidate gene. The evolutionary history of these QTL suggests that they are relatively young, and male limitation in this system is a rapidly evolving trait. Our work highlights the dynamic nature of the genetic structure and composition of facultative sex across space and time and suggests that quantitative genetic variation in reproductive strategy can undergo rapid evolutionary turnover.
Platelet TAU is Associated with Changes in Depression and Alzheimer's Disease.

BACKGROUND Platelets (thrombocytes) are small anuclear cells that play an important role in blood clotting. They are activated and dysfunctional in brain disorders, such as Alzheimer's disease (AD) and depression. Platelets express the amyloid-precursor protein (APP) and release beta-amyloid40 into the blood. Recent evidence reports that platelets also express the microtubule-associated protein tau. In this study, we further characterized the molecular appearance of tau and examined its alterations in patients with neurocognitive impairment. METHODS Platelets were isolated from patients with AD, mild cognitive impairment (MCI) or depression and compared to healthy controls. Subsequently, FACS analysis was employed to characterize platelets for platelet surface P-selectin (CD62P). In order to enhance the detection levels, samples were pooled (15 samples per group) and analyzed by Lumipulse Assay, Western blots, and mass spectrometry. RESULTS Tau is expressed in human platelets and tau levels were decreased in platelets isolated from patients with AD and depression. Additionally, phospho-tau-181 was slightly increased in patients with depression. We show that tau is highly fragmented (20-40 kDa) in the platelet extracts using Western blot analysis. The mass spectrometry data did not show a clear identification of tau in the pooled platelet samples. CONCLUSIONS Our data reveal that tau is found in platelets, possibly in a highly fragmented form. Tau levels may be used as a potential diagnostic approach to differentiate AD and depression from healthy controls.
Correlation of quantitative polymerase chain reaction with clinical characteristics of patients with viral retinitis

Purpose: To evaluate the correlation of quantitative real-time polymerase chain reaction (qRT-PCR) to the clinical characteristics of patients with viral retinitis.Methods: Retrospective case series. Results: Aqueous or vitreous samples of 20 out of 35 eyes showed qRT-PCR positivity for virus etiology (57.14%). Cytomegalovirus (CMV) was most commonly identified in nine eyes (45%). The mean DNA copy number was 2,68,339.65 copies/mL (range: 90–3205397). DNA copy number significantly correlated with the extent of clinical involvement (P = 0.013); however, there was no correlation between DNA copy number and presenting visual acuity (P = 0.31), macular involvement (P = 0.675), optic nerve involvement (P = 0.14), and development of retinal detachment (P = 0.73). There was a significant correlation between the number of DNA copies and the timing of sampling (P = 0.0005). Samples taken earlier in the course of the disease had higher viral copies than later ones. Conclusion: qRT-PCR is useful in confirming a viral etiology in over 50% of cases of suspected viral retinitis. It correlates well with the extent of clinical involvement and timing of sampling.