Miracle-dz/UniFAR-FTUs huggingface dataset:
On-clamp versus off-clamp robotic partial nephrectomy: A systematic review and meta-analysis

Background: The debate on the pros and cons of robot-assisted partial nephrectomy performed with (on-clamp) or without (off-clamp) renal artery clamping is ongoing. The aim of this meta-analysis is to summarize the available evidence on the comparative studies assessing the outcomes of these two approaches. Material and methods: A systematic review of the literature on PubMed, ScienceDirect®, and Embase® was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement (PRISMA). Only comparative and case-control studies were submitted to full-text assessment and meta-analysis. RevMan 5.3 software was used. Results: From the initial retrieval of 1937 studies, 15 fulfilling inclusion criteria were selected and provided 2075 patients for analysis (702 off-clamp, 1373 on-clamp). Baseline tumor’s features showed a significant difference in size (weighted mean difference: –0.58 cm; 95% confidence interval: [–1.06, –0.10]; p = 0.02) and R.E. N.A. L. score (weighted mean difference: –0.53; 95% confidence interval: [–0.81, –0.25]; p = 0.0002), but not in the exophytic property, the location, and the PADUA score. Pooled analysis revealed shorter operative time (p = 0.02) and higher estimated blood loss (p = 0.0002) for the off-clamp group. Overall complication and transfusion rates were similar, while higher major complication rate was observed in the on-clamp approach (5.6% vs 1.9%, p = 0.03). No differences in oncological outcomes were found. Finally, functional outcomes (assessed by estimated glomerular filtration rate at early postoperative, 3 month, 6 month, and last available follow-up) were not statistically different. Conclusion: This meta-analysis shows that off-clamp robot-assisted partial nephrectomy is reserved to smaller renal masses. Under such conditions, no differences with the on-clamp approach emerged.
Temporal Changes in the Cross-Sectional Associations between Cannabis Use, Suicidal Ideation, and Depression in a Nationally Representative Sample of Canadian Adults in 2012 Compared to 2002

Background: With the recent legalization of nonmedical cannabis in Canada, it is important to document previous associations between cannabis use and major depressive episode and suicidal ideation, as well as the extent to which these associations have changed over time. Methods: This study uses pooled data from the 2002 and 2012 Canadian Community Health Survey’s Mental Health Component, which are repeated cross-sectional surveys of nationally representative samples of Canadians 15 to 60 years of age (n = 43,466). Binary logistic regression was performed, applying weighting and bootstrapping, to examine the association between at least monthly use of cannabis and past 12-month suicidal ideation and major depressive episode (MDE). Results: At least monthly nonmedical cannabis use was associated with an increased odds of MDE and suicidal ideation, and both associations strengthened in 2012 compared to 2002. Canadians using cannabis at least once a month in 2012 had 1.59 (95% confidence interval [CI], 1.11 to 2.27) times the odds of experiencing suicidal ideation and 1.55 (95% CI, 1.12 to 2.13) times the odds of experiencing MDE compared to those who used cannabis at least once a month in 2002. This temporal change remained after controlling for other substance use. Conclusions: Monthly cannabis use was consistently related to both suicidal ideation and MDE, and these associations were stronger in 2012 compared to 2002. The findings of this study provide a baseline for the association between cannabis use and suicide and depression in the Canadian population that should be reevaluated now that nonmedical cannabis has been legalized.
Mammalian tolerance to humans is predicted by body mass: evidence from long-term archives.

Humans are implicated as a major driver of species extinctions from the Late Pleistocene to the present. However, our predictive understanding of human-caused extinction remains poor due to the restricted temporal and spatial scales at which this process is typically assessed, and the risks of bias due to "extinction filters" resulting from a poor understanding of past species declines. We develop a novel continent-wide dataset containing country-level last-occurrence records for 30 European terrestrial mammals across the Holocene (c.11,500 years to present), an epoch of relative climatic stability that captures major transitions in human demography. We analyze regional extirpations against a high-resolution database of human population density (HPD) estimates to identify species-specific tolerances to changing HPD through the Holocene. Mammalian thresholds to HPD scale strongly with body mass, with larger-bodied mammals experiencing regional population losses at lower HPDs than smaller-bodied mammals. Our analysis enables us to identify levels of tolerance to HPD for different species, and therefore has wide applicability for determining biotic vulnerability to human impacts. This ecological pattern is confirmed across wide spatiotemporal scales, providing insights into the dynamics of prehistoric extinctions and the modern biodiversity crisis, and emphasizing the role of long-term archives in understanding human-caused biodiversity loss. This article is protected by copyright. All rights reserved.
Response‐adapted therapy for the treatment of children with newly diagnosed high risk Hodgkin lymphoma (AHOD0831): a report from the Children’s Oncology Group

The AHOD0831 study for paediatric patients with high risk Hodgkin lymphoma tested a response‐based approach designed to limit cumulative alkylator exposure and reduce radiation volumes. Patients (Stage IIIB/IVB) received two cycles of ABVE‐PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide). Rapid early responders [RER, no positron emission tomography (PET) activity above mediastinal blood pool] were consolidated with 2 cycles of ABVE‐PC. Slow early responders (SER) received 2 cycles of ifosfamide/vinorelbine and 2 cycles of ABVE‐PC. Radiotherapy was administered to sites of initial bulk and/or SER. By intent‐to‐treat analysis, 4‐year second event‐free survival (EFS; freedom from second relapse or malignancy) was 91·9% [95% confidence interval (CI): 86·1–95·3%], below the projected baseline of 95% (P = 0·038). Five‐year first EFS and overall survival (OS) rates are 79·1% (95% CI: 71·5–84·8%) and 95% (95% CI: 88·8–97·8%). Eight of 11 SER patients with persistent PET positive lesions at the end of chemotherapy had clinical evidence of active disease (3 biopsy‐proven, 5 with progressive disease or later relapses). Although this response‐directed approach did not reach the ambitiously high pre‐specified target for second EFS, EFS and OS rates are comparable with results of recent trials despite the reduction in radiotherapy volumes from historical involved fields. Persistent PET at end of chemotherapy identifies a cohort at an especially high risk for relapse/early progression.
Transcriptional Regulation of Abscission Zones

Precise and timely regulation of organ separation from the parent plant (abscission) is consequential to improvement of crop productivity as it influences both the timing of harvest and fruit quality. Abscission is tightly associated with plant fitness as unwanted organs (petals, sepals, filaments) are shed after fertilization while seeds, fruits, and leaves are cast off as means of reproductive success or in response to abiotic/biotic stresses. Floral organ abscission in Arabidopsis has been a useful model to elucidate the molecular mechanisms that underlie the separation processes, and multiple abscission signals associated with the activation and downstream pathways have been uncovered. Concomitantly, large-scale analyses of omics studies in diverse abscission systems of various plants have added valuable insights into the abscission process. The results suggest that there are common molecular events linked to the biosynthesis of a new extracellular matrix as well as cell wall disassembly. Comparative analysis between Arabidopsis and soybean abscission systems has revealed shared and yet disparate regulatory modules that affect the separation processes. In this review, we discuss our current understanding of the transcriptional regulation of abscission in several different plants that has improved on the previously proposed four-phased model of organ separation.
Nucleoside dimers analogues with a 1,2,3-triazole linkage: conjugation of floxuridine and thymidine provides novel tools for cancer treatment. Part II

Abstract The fluorinated nucleoside dimers with a 1,2,3-triazole linkage are novel compounds within the field of bioorganic chemistry. We report on the synthesis and properties of two groups of nucleoside dimers analogs possessing a different arrangement of the 1,4-disubstituted 1,2,3-triazole linkage. Based on analysis of the 3JHH, 3JH1′C2, and 3JH1′C6 we estimated conformational preferences of sugar part and orientation around glycosidic bond. These compounds show moderate anticancer activity, with cytostatic studies in three different cancer cell lines.
Familial history of heart disease and increased risk for elevated troponin in apparently healthy individuals

Family history of heart disease (FH‐HD) is associated with an increase drisk of subsequent HD. High sensitive cardiac troponin T (hs‐cTnT) is arecognized biomarker of myocyte injury even in HD free patients. We examined the association between FH‐HD and hs‐cTnT in apparently healthy individuals.
Maintenance of homeostatic plasticity at the Drosophila neuromuscular synapse requires continuous IP3-directed signaling

Synapses and circuits rely on neuroplasticity to adjust output and meet physiological needs. Forms of homeostatic synaptic plasticity impart stability at synapses by countering destabilizing perturbations. The Drosophila melanogaster larval neuromuscular junction (NMJ) is a model synapse with robust expression of homeostatic plasticity. At the NMJ, a homeostatic system detects impaired postsynaptic sensitivity to neurotransmitter and activates a retrograde signal that restores synaptic function by adjusting neurotransmitter release. This process has been separated into temporally distinct phases, induction and maintenance. One prevailing hypothesis is that a shared mechanism governs both phases. Here, we show the two phases are separable. Combining genetics, pharmacology, and electrophysiology, we find that a signaling system consisting of PLCβ, inositol triphosphate (IP3), IP3 receptors, and Ryanodine receptors is required only for the maintenance of homeostatic plasticity. We also find that the NMJ is capable of inducing homeostatic signaling even when its sustained maintenance process is absent. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
Perceived physical health in obsessive-compulsive disorder: a protocol for a systematic review and meta-analysis

Introduction Obsessive-compulsive disorder (OCD) is a mental health condition associated with severe impairment in a variety of quality of life domains, an increased physical health burden, and a higher risk of general medical conditions and mortality compared with the general population. While there is a large amount of literature on psychological quality of life, a systematic review of perceived physical health in OCD is lacking. A quantitative summary might suggest that policy makers also focus the evaluation on perceived physical health and develop new strategies also aimed at this outcome. The current paper presents a protocol for the first systematic review and meta-analysis aimed at summarising perceived physical health in OCD by specifically examining perceived physical health status, bodily pain and role limitations due to physical problems in patients with OCD compared with controls. The review will also investigate potential demographic and clinical moderators of perceived physical health status (age, gender, OCD severity, publication date, methodological quality). Methods and analysis A systematic review and meta-analysis will be conducted according to PRISMA guidelines. Studies will be included if using a clinical group with a current primary diagnosis of OCD established by international standardised criteria, if measuring perceived physical health status, and if using screened or community participants as controls. No publication date or language restriction will be applied. An online systematic search of electronic databases (Scopus, PubMed, PsycINFO, EMBASE, Cochrane Library), and examination of conference proceedings and theses/dissertations will be conducted by independent reviewers. Risk of bias will be assessed through the Newcastle-Ottawa Scale. Ethics and dissemination The current review does not require ethics approval. The results will be disseminated through publications in peer-reviewed journals. PROSPERO registration number 2018 CRD42018106194.
Signaling Cascade through DC-ASGPR Induces Transcriptionally Active CREB for IL-10 Induction and Immune Regulation

Key Points DC-ASGPR induces IL-10 expression mainly through the activation of ERK/p90RSK/CREB. DC-ASGPR–induced Akt/GSK-3/β-catenin activation contributes to IL-10 induction. DC-ASGPR can play an important role in controlling host immune responses. The types and magnitude of Ag-specific immune responses can be determined by the functional plasticity of dendritic cells (DCs). However, how DCs display functional plasticity and control host immune responses have not been fully understood. In this study, we report that ligation of DC–asialoglycoprotein receptor (DC-ASGPR), a C-type lectin receptor (CLR) expressed on human DCs, resulted in rapid activation of Syk, followed by PLCγ2 and PKCδ engagements. However, different from other Syk-coupled CLRs, including Dectin-1, signaling cascade through DC-ASGPR did not trigger NF-κB activation. Instead, it selectively activated MAPK ERK1/2 and JNK. Rapid and prolonged phosphorylation of ERK1/2 led to sequential activation of p90RSK and CREB, which consequently bound to IL10 promoter and initiated cytokine expression. In addition, DC-ASGPR ligation activated Akt, which differentially regulated the activities of GSK-3α/β and β-catenin and further contributed to IL-10 expression. Our observations demonstrate that DC-ASGPR induces IL-10 expression via an intrinsic signaling pathway, which provides a molecular explanation for DC-ASGPR–mediated programing of DCs to control host immune responses.
The protective effect of neighbourhood social cohesion on adolescent mental health following stressful life events

Abstract Background Exposure to stressful life events is an established risk factor for the development of adolescent mental disorder. Growing evidence also suggests that neighbourhood social environments, including strong social cohesion, could have a protective effect on mental health. However, little is known about how neighbourhood social cohesion may buffer against the effects of stressful life events on adolescent mental health. Our aim was to assess whether neighbourhood social cohesion modifies the association between stressful life events and adolescent mental health outcomes. Methods Data were drawn from a nationally-representative prospective sample of Canadian adolescents, including 5183 adolescents aged 12/13 years at T1 and 14/15 years at T2. Caregivers reported neighbourhood social cohesion at T1, and exposure to stressful life events between T1 and T2. Symptoms of mental health and behaviour problems were self-reported by adolescents at T1 and T2. Multivariable logistic regression was used to determine whether the relationship between stressful life events and outcomes was modified by neighbourhood social cohesion. Results Associations between stressful life events and adolescent outcomes were statistically significantly lower in neighbourhoods with greater social cohesion for: depression/anxiety (high cohesion OR = 0.98 v. low cohesion OR = 3.11), suicidal ideation (ORhigh = 1.30 v. ORlow = 5.25), aggression/conduct disorder (ORhigh = 1.09 v. ORlow = 4.27), and property offence (ORhigh = 1.21 v. ORlow = 4.21). Conclusions Greater neighbourhood social cohesion appeared to buffer the effects of stressful life events on several domains of adolescent mental health. This potentially presents a target for public health intervention to improve adolescent mental health and behavioural outcomes.
Exercise induces region‐specific remodeling of astrocyte morphology and reactive astrocyte gene expression patterns in male mice

Astrocytes are essential mediators of many aspects of synaptic transmission and neuroplasticity. Exercise has been demonstrated to induce neuroplasticity and synaptic remodeling, such as through mediating neurorehabilitation in animal models of neurodegeneration. However, the effects of exercise on astrocytic function, and how such changes may be relevant to neuroplasticity remain unclear. Here, we show that exercise remodels astrocytes in an exercise‐ and region‐dependent manner as measured by GFAP and SOX9 immunohistochemistry and morphological analysis in male mice. Additionally, qRT‐PCR analysis of reactive astrocyte gene expression showed an exercise‐induced elevation in brain regions known to be activated by exercise. Taken together, these data demonstrate that exercise actively modifies astrocyte morphology and drives changes in astrocyte gene expression and suggest that astrocytes may be a central component to exercise‐induced neuroplasticity and neurorehabilitation.
Heterogeneity in surface sensing suggests a division of labor in Pseudomonas aeruginosa populations

The second messenger signaling molecule cyclic diguanylate monophosphate (c-di-GMP) drives the transition between planktonic and biofilm growth in many bacterial species. Pseudomonas aeruginosa has two surface sensing systems that produce c-di-GMP in response to surface adherence. Current thinking in the field is that once cells attach to a surface, they uniformly respond by producing c-di-GMP. Here, we describe how the Wsp system generates heterogeneity in surface sensing, resulting in two physiologically distinct subpopulations of cells. One subpopulation has elevated c-di-GMP and produces biofilm matrix, serving as the founders of initial microcolonies. The other subpopulation has low c-di-GMP and engages in surface motility, allowing for exploration of the surface. We also show that this heterogeneity strongly correlates to surface behavior for descendent cells. Together, our results suggest that after surface attachment, P. aeruginosa engages in a division of labor that persists across generations, accelerating early biofilm formation and surface exploration.
Stimuli, presentation modality, and load‐specific brain activity patterns during n‐back task

Working memory (WM) refers to a set of cognitive processes that allows for the temporary storage and manipulation of information, crucial for everyday life skills. WM deficits are present in several neurological, psychiatric, and neurodevelopmental disorders, thus making the full understanding of its neural correlates a key aspect for the implementation of cognitive training interventions. Here, we present a quantitative meta‐analysis focusing on the underlying neural substrates upon which the n‐back, one of the most commonly used tasks for WM assessment, is believed to rely on, as highlighted by functional magnetic resonance imaging and positron emission tomography findings. Relevant published work was scrutinized through the activation likelihood estimate (ALE) statistical framework in order to generate a set of task‐specific activation maps, according to n‐back difficulty. Our results confirm the known involvement of frontoparietal areas across different types of n‐back tasks, as well as the recruitment of subcortical structures, cerebellum and precuneus. Specific activations maps for four stimuli types, six presentation modalities, three WM loads and their combination are provided and discussed. Moreover, functional overlap with resting‐state networks highlighted a strong similarity between n‐back nodes and the Dorsal Attention Network, with less overlap with other networks like Salience, Language, and Sensorimotor ones. Additionally, neural deactivations during n‐back tasks and their functional connectivity profile were examined. Clinical and functional implications are discussed in the context of potential noninvasive brain stimulation and cognitive enhancement/rehabilitation programs.
Immune Correlates of Herpes Zoster in People Living with HIV on Effective Antiretroviral Therapy.

Background Herpes zoster (HZ) has high morbidity in people living with HIV (PLHIV). We investigated immunologic factors that correlated with the development of HZ in PLHIV with controlled HIV replication on antiretroviral therapy (ART). Methods PLHIV who developed HZ on ART (cases), with undetectable plasma HIV RNA, and CD4 counts ≥200 cells/µL were matched 1:1 to controls by CD4 count, age, sex, race and duration of ART. VZV-specific T cells and circulating regulatory T cells (Treg) were measured by flow cytometry before and after HZ. Differences between cases and controls were assessed by paired t-tests and longitudinal changes by Wilcoxon signed rank test. Results HZ cases (N=31) had higher CD4+FOXP3+CD25+% Treg prior to HZ compared to 31 controls. After VZV ex-vivo restimulation, cases had lower T cell responses, including CD8+Perforin+% cytotoxic T lymphocytes (CTL), CD4+IL10+% and CD4+TGFβ+% compared with controls. Overall, Treg negatively correlated with VZV-specific Th1 responses. However, although Treg decreased over time on ART in HZ cases, VZV-CTL were stable and did not increase even after HZ. Conclusions Increased circulating Treg and decreased VZV-specific T cell immune responses were associated with the risk of HZ in PLHIV. The kinetics of Treg over time, but not of VZV-CTL, paralleled the natural history of HZ, whose incidence decreases over time on effective ART.