Miracle-dz/UniFAR-FTUs huggingface dataset:
Association between opioid agonist therapy and testing, treatment uptake, and treatment outcomes for hepatitis C infection among people who inject drugs: A systematic review and meta-analysis.

BACKGROUND People who inject drugs (PWID) experience barriers to accessing testing and treatment for hepatitis C virus (HCV) infection. Opioid agonist therapy (OAT) may provide an opportunity to improve access to HCV care. This systematic review assessed the association of OAT and HCV testing, treatment, and treatment outcomes among PWID. METHODS Bibliographic databases and conference presentations were searched for studies assessing the association between OAT and HCV testing, treatment, and treatment outcomes [direct-acting antiviral (DAA) therapy only] among people who inject drugs (in the past year). Meta-analysis was used to pool estimates. RESULTS Among 9,877 articles identified, 22 studies conducted in Australia, Europe, North America, and Thailand were eligible and included. Risk of bias was serious in 21 studies and moderate in one study. Current/recent OAT was associated with an increased odds of recent HCV antibody testing [4 studies; odds ratio (OR), 1.80; 95% CI:1.36, 2.39), HCV RNA testing among those who were HCV antibody positive (2 studies; OR, 1.83; 95% CI:1.27, 2.62), and DAA treatment uptake among those who were HCV RNA positive (7 studies; OR 1.53; 95% CI: 1.07, 2.20). There was insufficient evidence of an association between OAT and treatment completion (9 studies) or sustained virologic response following DAA therapy (9 studies). CONCLUSIONS Opioid agonist therapy can increase linkage to HCV care, including uptake of HCV testing and treatment among PWID. This supports the scale-up of OAT as part of strategies to enhance HCV treatment to further HCV elimination efforts.
Perspectives of Nunavut patients and families on their cancer and end of life care experiences

ABSTRACT The present study arose from a recognition among service providers that Nunavut patients and families could be better supported during their care journeys by improved understanding of people’s experiences of the health-care system. Using a summative approach to content analysis informed by the Piliriqatigiinniq Model for Community Health Research, we conducted in-depth interviews with 10 patients and family members living in Nunavut communities who experienced cancer or end of life care. Results included the following themes: difficulties associated with extensive medical travel; preference for care within the community and for family involvement in care; challenges with communication; challenges with culturally appropriate care; and the value of service providers with strong ties to the community. These themes emphasise the importance of health service capacity building in Nunavut with emphasis on Inuit language and cultural knowledge. They also underscore efforts to improve the quality and consistency of communication among health service providers working in both community and southern referral settings and between service providers and the patients and families they serve.
The Aspergillus fumigatus Secretome Alters the Proteome of Pseudomonas aeruginosa to Stimulate Bacterial Growth: Implications for Co-infection

The growth of Pseudomonas aeruginosa increased exponentially when exposed to the culture filtrates produced by Aspergillus fumigatus and by co-cultures of A. fumigatus and P. aeruginosa in a nutrient-poor, nitrate-rich medium. Qualitative proteomic analysis of the A. fumigatus culture filtrates identified several secreted proteases and peptidases, including known human allergens. LFQ proteomics performed on P. aeruginosa exposed to the culture filtrates identified changes in several pathways and processes including an increase in outer-membrane proteins and stress response proteins. Graphical Abstract Highlights Pseudomonas aeruginosa growth increases in Aspergillus fumigatus culture filtrates. A. fumigatus culture filtrates are characterized by a range of peptidases and proteases. LFQ proteomics characterizes the response of P. aeruginosa to A. fumigatus culture filtrates. A. fumigatus creates an environment for P. aeruginosa to proliferate. Individuals with cystic fibrosis are susceptible to co-infection by Aspergillus fumigatus and Pseudomonas aeruginosa. Despite the persistence of A. fumigatus in the cystic fibrosis lung P. aeruginosa eventually predominates as the primary pathogen. Several factors are likely to facilitate P. aeruginosa colonization in the airways, including alterations to the microbial environment. The cystic fibrosis airways are hypoxic, nitrate-rich environments, and the sputum has higher amino acid concentrations than normal. In this study, significant growth proliferation was observed in P. aeruginosa when the bacteria were exposed to A. fumigatus culture filtrates (CuF) containing a high nitrate content. Proteomic analysis of the A. fumigatus CuF identified a significant number of environment-altering proteases and peptidases. The molecular mechanisms promoting bacterial growth were investigated using label-free quantitative (LFQ) proteomics to compare the proteome of P. aeruginosa grown in the A. fumigatus CuF and in CuF produced by a P. aeruginosa-A. fumigatus co-culture, to that cultured in P. aeruginosa CuF. LFQ proteomics revealed distinct changes in the proteome of P. aeruginosa when cultured in the different CuFs, including increases in the levels of proteins involved in denitrification, stress response, replication, amino acid metabolism and efflux pumps, and a down-regulation of pathways involving ABC transporters. These findings offer novel insights into the complex dynamics that exist between P. aeruginosa and A. fumigatus. Understanding the molecular strategies that enable P. aeruginosa to predominate in an environment where A. fumigatus exists is important in the context of therapeutic development to target this pathogen.
A Qualitative study assessing organisational readiness to implement caregiver support programmes in Ontario, Canada

Objective To qualitatively explore factors affecting implementation of caregiver support programmes in healthcare institutions in a regional stroke system. Design A qualitative descriptive study with the Ontario Stroke System (OSS) was conducted. Data were collected through focus groups and in-depth interviews. Transcripts were coded and analysed using inductive thematic analysis. Setting Regional Stroke System, Ontario, Canada. Participants OSS stakeholders including medical directors, executives, programme directors, education coordinators, rehabilitation and community and long-term care specialists, primary care leaders and healthcare professionals. Intervention Not applicable. Main outcome measures Data collection explored perceptions of the need for caregiver support programmes and factors that may affect their implementation. Results Four focus groups (n=43) and 29 interviews were completed. Analyses identified themes related to (1) evidence that a caregiver programme will improve health and health system outcomes, (2) personnel requirements, (3) barriers associated with current billing and referral processes and (4) integration with current practice and existing workflow processes. Conclusions Implementation strategies to adopt caregiver programmes into clinical practice should incorporate evidence and consider personnel and existing workflow processes.
Single-entity approach to investigate surface charge enhancement in magnetoelectric nanoparticles induced by AC magnetic field stimulation.

Magneto-electric nanoparticles (MENPs), composed of a piezoelectric shell and a ferromagnetic core, exhibited enhanced cell-uptake and controlled drug release due to the enhanced localized electric field (surface charge/potential) and the generation of acoustics, respectively, on applying alternating current (AC)-magnetic (B)-field stimulation. This research, for the first time, implements an electrochemical single-entity approach to probe AC B-field induced strain mediated surface potential enhancement on MENP surface. The surface potential changes at the single-NP level can be probed by the open circuit potential changes of the floating carbon nanoelectrode (CNE) during the MENP-CNE collision events. The results confirmed that the AC B-field (60 Oe) stimulation caused localized surface potential enhancement of MENP. This observation is associated with the presence of a piezoelectric shell whereas magnetic nanoparticles were found unaffected under identical stimulation.
Collector Channels: Role and Evaluation in Schlemm’s Canal Surgery

ABSTRACT Objectives 1) To elucidate the role of collector channels in the aqueous humor outflow pathway 2) To suggest anatomic and functional methods of imaging collector channels in-vitro and in-vivo and 3) To discuss the role of such imaging modalities in the surgical management of glaucoma. Methods A thorough literature search was conducted on databases for studies published in English regarding the available methods to determine the role of collecting channels in normal and glaucomatous patients and to assess their patency. Results Intraocular pressure (IOP) exists as a balance between aqueous humor production and aqueous humor outflow. Collector channels are an essential anatomical constituent of the distal portion of the conventional aqueous humor outflow pathway. There are different surgical options for glaucoma management and with the recent advances in Schlemm’s canal-based surgeries, collector channel’s patency became a key factor in determining the optimum management for the glaucomatous eye. The advent of anatomic imaging methods has improved the ability to visualize collector channel morphology in-vitro, including swept-source optical coherence tomography (SS-OCT), spectral domain optical coherence tomography (SD-OCT), micro-computed tomography (micro CT), new immunohistochemistry techniques and scanning electron microscopy. The recent advent of real-time assessment of collector channel patency (including evaluation of episcleral venous outflow, observation of episcleral venous fluid wave, and tracer studies utilizing fluorescein, indocyanine green, and trypan blue) has been validated by the aforementioned anatomic imaging modalities. Conclusions New modalities of in-vitro and in-vivo studies of collector channels provide promise to aid in the assessment of collector channel patency and individualization of surgical management for glaucoma patients.
Analytical validation of the Immunoscore and its associated prognostic value in patients with colon cancer

Background New and fully validated tests need to be brought into clinical practice to improve the estimation of recurrence risk in patients with colon cancer. The aim of this study was to assess the analytical performances of the Immunoscore (IS) and show its contribution to prognosis prediction. Methods Immunohistochemical staining of CD3+ and CD8+ T cells on adjacent sections of colon cancer tissues were quantified in the core of the tumor and its invasive margin with dedicated IS modules integrated into digital pathology software. Staining intensity across samples collected between 1989 and 2016 (n=595) was measured. The accuracy of the IS workflow was established by comparing optical and automatic counts. Analytical precision of the IS was evaluated within individual tumor block on distant sections and between eligible blocks. The IS interlaboratory reproducibility (n=100) and overall assay precision were assessed (n=3). Contribution of the IS to prediction of recurrence based on clinical and molecular parameters was determined (n=538). Results Optical and automatic counts for CD3+ or CD8+ were strongly correlated (r=0.94, p<0.001 and r=0.92, p<0.001, respectively). CD3 and CD8 staining intensities were not altered by the age of the tumor block over a period of 30 years. Neither the position of tested tissue sections within a tumor block nor the selection of the tissue blocks affected the IS. Reproducibility of the IS was not affected by multiple variables (eg, antibody lots, DAB revelation kits, immunohistochemistry automates and operators). Interassay repeatability of the IS was 100% and interlaboratory reproducibility between two testing centers was 93%. Finally, in a case series of patients with stage II–III colon cancer, the relative proportion of variance for time to recurrence was greatest for the IS (53% of prognostic variability) in a model that included IS, T-stage, microsatellite instability status and total number of lymph nodes. Conclusion IS is a robust and validated clinical assay leveraging immune scoring to predict recurrence risk of patient with localized colon cancer. The strong and independent prognostic value of IS should pave the way for it use in clinical practice.
Repurposing of cefpodoxime proxetil as potent neuroprotective agent through computational prediction and in vitro validation

Abstract In recent reports, NR2B-NMDA receptor antagonists showed more research value because of its strong targeting ability and less side effects potential. In 2016, EVT-101 was reported to bind in an almost entirely new binding region of this target. Whether strikingly different binding modes can improve targeting and reduce side effects is worth studying. In our preliminary work, we explored the binding patterns of ifenprodil and EVT-101, found the key amino acids and summarized the pharmacophores, hoping to find such antagonists that target the two binding modes simultaneously. In this study, we developed a scalable virtual screening workflow in the FDA-approved drugs library to identify novel NR2B-NMDAR antagonists based on the combination of two pharmacophores. Cefpodoxime proxetil (5) was identified as the hit compound, and it was found for the first time that 5 might have neuroprotective activity as a NR2B-NMDAR antagonist. This result interested us to make further study, the ligand-receptor interactions modeled by molecular docking studies showed that the compound could perfectly merge both the pharmacophore characteristics of ifenprodil and EVT-101 at the binding cavity between the ATDs of GluN1 and GluN2B. The accuracy of molecular docking results and binding stability of ligand-receptor complexes were validated through 100 ns molecular dynamics simulation and binding free energy calculation. Afterwards, MTT assay (49.8%±0.1%, 5 μM) on NMDA injured SH-SY5Y cells and evidence of the effect on attenuating Ca2+ influx induced by NMDA were applied to validate the computational results, further investigation showed that 5 could suppress the NR2B upregulation induced by NMDA. Communicated by Ramaswamy H. Sarma
Physical and elemental analysis of Middle East sands from recent combat zones

Abstract Objective: The lungs are uniquely exposed to the external environment. Sand and dust exposures in desert regions are common among deployed soldiers. A significant number of Veterans deployed to the Middle East report development of respiratory disorders and diseases. Materials and methods: Sand collected from Fallujah, Iraq and Kandahar, Afghanistan combat zones was analyzed and compared to a sand sample collected from an historic United States (U.S.) battle region (Fort Johnson, James Island, SC, Civil War battle site). Sand samples were analyzed to determine the physical and elemental characteristics that may have the potential to contribute to development of respiratory disease. Results: Using complementary scanning electron microscopy (SEM) imaging and analysis, and inductively coupled plasma mass spectrometry (ICP-MS), it was determined that Iraq sand contained elevated levels of calcium and first row transition metals versus Afghanistan and U.S. sand. Iraq sand particle texture was smooth and round, and particles were considerably smaller than Afghanistan sand. Afghanistan sand was elevated in rare earth metals versus Iraq or U.S. sands and had sharp edge features and larger particle size than Iraq sand. Conclusions: These data demonstrate significant differences in Iraq and Afghanistan sand particle size and characteristics. Middle East sands contained elevated levels of elements that have been associated with respiratory disease versus control site sand, suggesting the potential of sand/dust storm exposure to promote adverse respiratory symptoms. Data also demonstrate the potential for variation based on geographical region or site of exposure. The data generated provide baseline information that will be valuable in designing future exposure studies.
Pharmacological treatment of acute-phase anorexia nervosa: Evidence from randomized controlled trials

Background: Anorexia nervosa (AN) is the psychiatric disorder with the highest mortality rate, with a standard mortality ratio of 5.86. Despite the large use of psychotropic drugs in the clinical setting, Food and Drug Administration has not approved any psychoactive treatment for AN. Aims: The aim of this study was to perform an updated systematic review and meta-analysis of published randomized controlled trials (RCTs) investigating psychopharmacological treatment in acute-phase AN. Methods: The present paper follows the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. An extensive literature search was performed. All RCTs enrolling patients with acute-phase AN, comparing at least one psychotropic drug with another drug, placebo, treatment-as-usual or no treatment were included. The main outcome was the effect of psychoactive drugs on body mass index (BMI); data on psychopathological outcomes were also collected when available. Results: A total of 19 RCTs met all specified criteria. Of these, 11 were excluded from quantitative analyses. Of the eight studies included in the meta-analyses, five reported data on BMI, showing no significant difference between olanzapine and placebo for weight recovery. No significant result was found for AN psychopathology, depressive and anxious symptoms for any of the molecules studied. Conclusions: RCTs published in this field display methodological biases, low sample sizes and short follow-up periods. Further research efforts are needed in this field as no evidence has been demonstrated for the use of any psychotropic drug in acute-phase AN neither for weight recovery, nor for comorbid psychiatric symptoms.
An acoustic methodology for selecting highly dissipative probes for ultra-sensitive DNA detection.

The objective of this work is to present a methodology for the selection of nanoparticles such as liposomes to be used as acoustic probes for the detection of very low concentrations of DNA. Liposomes, applied in the past as mass-amplifiers and detected through frequency measurement, are employed in the current work as probes for energy dissipation enhancement. Since the dissipation signal is related to the structure of the sensed nano-entity, a systematic investigation of the geometrical features of the liposome/DNA complex was carried out. We introduce the parameter of dissipation capacity by which several sizes of liposome and DNA structures were compared with respect to their ability to dissipate acoustic energy at the level of a single molecule/particle. Optimized 200 nm liposomes anchored to a dsDNA chain led to an improvement of the limit of detection (LoD) by 3 orders of magnitude when compared to direct DNA detection, with the new LoD being 1.2 fmol (or 23 fg/μl or 2 pM). Dissipation monitoring was also shown to be 8 times more sensitive than the corresponding frequency response. The high versatility of this new methodology is demonstrated in the detection of genetic biomarkers down to 1-2 target copies in real samples such as blood. This study offers new prospects in acoustic biosensing detection with potential use in real world diagnostics.
Cyclophilin D palmitoylation and permeability transition: a new twist in the tale of myocardial ischaemia-reperfusion injury.

F1-ATPase subunit of the PTP and enhances pore opening and calcium efflux at reperfusion, thus leading to greater myocardial damage and in-creased infarct size. Mutation of C202 to a serine (S) results in no possible modification by S-nitrosylation, S-palmitoylation but also S-oxidation and trans-genic mice have significantly reduced infarct size and enhanced functional recovery as a result.
Playing the hare or the tortoise in parasitoids: could different oviposition strategies have an influence in host partitioning in two Aphidius species?

In this paper, we compare the host selection behaviours of two parasitoids, Aphidius rhopalosiphi and Aphidius picipes, in order to analyse whether behavioural adaptations to the defensive behaviour of their host (the grain aphid Sitobion avenae) could, in part, be responsible for the simultaneous presence of both species in cereal fields. The oviposition behaviour of A. picipes differed from that of A. rhopalosiphi by including a number of ‘fluttering wings’ sequences followed by immobility. It resulted in a 44 times longer host-handling time for A. picipes than for A. rhopalosiphi. Hosts attacked by A. picipes exhibited fewer defensive behaviours than hosts attacked by A. rhopalosiphi. A. picipes and A. rhopalosiphi rejected respectively 0% and 53% of unparasitized hosts presenting cornicle secretions, one of the defensive means of aphids. Furthermore, A. picipes females rejected 100% of the hosts that were already parasitized, whereas A. rhopalosiphi was previously described to reject only 20 to 40% of such hosts. Such differences could be explained by the way the two species deal with the aphid defensive behaviour. Field analyses, showed that A. rhopalosiphi was already present in wheat fields in early April whereas A. picipes appeared later and only achieved a low level of parasitism. However, when both species were present simultaneously, they shared the same resource.
The well-being of medical students: A biopsychosocial approach

Objective: Mental health problems among medical students have been widely reported, but the predisposing and perpetuating factors and biological concomitants are poorly understood. Adopting a biopsychosocial approach, we studied well-being in a group of Australian medical students, focusing on sleep, autonomic and immune mechanisms, as well as mental, social and physical well-being, health-related behaviours, and daily functioning. Methods: Fourth-year medical students (N = 151) completed comprehensive assessments, including laboratory-based and nocturnal autonomic monitoring via ambulatory bioharness, a psychiatric diagnostic interview, and questionnaires assessing sleep quality and psychosocial and physical well-being. A blood sample was taken to quantify the inflammatory marker C-reactive protein. Sleep, mood and activity was additionally monitored daily for 7 days. Results: A sizable minority of students reported diminished physical, mental and psychosocial well-being. We also found concerning levels of sleep disturbance and social and occupational impairment in a subset of students. The strong co-occurrence of problems across symptom domains supported a biopsychosocial interdependence of health and well-being states. Maladaptive coping behaviours were apparent, notably hazardous alcohol consumption, which was associated with a clinically significant elevation in C-reactive protein levels (> 3 mg/L). We documented, for the first time, significantly diminished nocturnal heart rate variability in medical students with a mental health diagnosis. Nocturnal heart rate variability was strongly associated with sleep quality, daytime autonomic stress reactivity, as well as occupational and social functioning. Conclusion: Well-being is a multifaceted phenomenon firmly interlinked with sleep, autonomic and immune function, health behaviours and functional outcomes. Our novel findings supported a key role for nocturnal autonomic function in promoting sleep quality and mental well-being. Interventions could focus on sleep hygiene and health behaviours as a buffer for well-being and teach more adaptive strategies for coping with the stresses of medical training.