Miracle-dz/UniFAR-FTUs huggingface dataset:
Patient-Reported Nonadherence with Glaucoma Therapy

Abstract Purpose: Effective glaucoma therapy relies to a great extent on the patients' ability to regularly self-administer eye drops. This study aimed to assess self-reported nonadherence and to identify potential barriers to adherence in glaucoma patients. Methods: Participants completed a 16-item questionnaire, designed to examine nonadherence rate and assess the therapy experience. Inclusion criteria stipulated treatment duration of at least 1 year. Nonadherence was defined as missing ≥5% of the prescribed pressure-lowering eye drops doses. Results: In total, 201 glaucoma patients aged 24–88 years were included. Mean treatment duration was 9.4 years. Nonadherence was reported by 30.3% of participants and 69.7% were reported to be adherent. Individuals who experienced side effects reported higher levels of nonadherence than those who did not (37.6% vs. 18.4%; P = 0.004). Eye drops with preservatives were used by 84.1% of participants, 11.9% were on combined preservative and preservative-free treatment, and 4.0% on preservative-free medication only. Self-reported nonadherence levels were 32.0%, 25.0%, and 12.5%, respectively, for each of these groups. Men reported higher rates of nonadherence than women (36.8% vs. 24.5%; P = 0.066). Age, social status, history of migration, severity of disease, and fear of blindness were not associated with significant differences in nonadherence levels. Conclusions: Nonadherence with glaucoma therapy is a significant barrier to therapeutic success for approximately one-third of patients. Nonadherence may be reduced if side effects are avoided. Preservative-free products may provide adherence benefits. The patient experience should be a key consideration when selecting appropriate treatments, to reduce nonadherence and optimize outcomes.
ATP-Binding Cassette (ABC) Transporter Genes Involved in Pyrethroid Resistance in the Malaria Vector Anopheles sinensis: Genome-Wide Identification, Characteristics, Phylogenetics, and Expression Profile

background: The ATP-binding cassette (ABC) transporters family is one of the largest families of membrane proteins existing in all living organisms. Pyrethroid resistance has become the largest unique obstacle for mosquito control worldwide. ABC transporters are thought to be associated with pyrethroid resistance in some agricultural pests, but little information is known for mosquitoes. Herein, we investigated the diversity, location, characteristics, phylogenetics, and evolution of ABC transporter family of genes in the Anopheles sinensis genome, and identified the ABC transporter genes associated with pyrethroid resistance through expression profiles using RNA-seq and qPCR. Results: 61 ABC transporter genes are identified and divided into eight subfamilies (ABCA-H), located on 22 different scaffolds. Phylogenetic and evolution analyses with ABC transporters of A. gambiae, Drosophila melanogaster, and Homo sapiens suggest that the ABCD, ABCG, and ABCH subfamilies are monophyly, and that the ABCC and ABCG subfamilies have experienced a gene duplication event. Both RNA-seq and qPCR analyses show that the AsABCG28 gene is uniquely significantly upregulated gene in all three field pyrethroid-resistant populations (Anhui, Chongqing, and Yunnan provinces) in comparison with a laboratory-susceptible strain from Jiangsu province. The AsABCG28 is significantly upregulated at 12-h and 24-h after deltamethrin exposure in three-day-old female adults. Conclusion: This study provides the information frame for ABC transporter subfamily of genes, and lays an important basis for the better understanding and further research of ABC transporter function in insecticide toxification. The AsABCG28 gene is associated with pyrethroid detoxification, and it functions at later period in the detoxification process for xenobiotics transportation.
Cysteine Cathepsins and Their Extracellular Roles: Shaping the Microenvironment

For a long time, cysteine cathepsins were considered primarily as proteases crucial for nonspecific bulk proteolysis in the endolysosomal system. However, this view has dramatically changed, and cathepsins are now considered key players in many important physiological processes, including in diseases like cancer, rheumatoid arthritis, and various inflammatory diseases. Cathepsins are emerging as important players in the extracellular space, and the paradigm is shifting from the degrading enzymes to the enzymes that can also specifically modify extracellular proteins. In pathological conditions, the activity of cathepsins is often dysregulated, resulting in their overexpression and secretion into the extracellular space. This is typically observed in cancer and inflammation, and cathepsins are therefore considered valuable diagnostic and therapeutic targets. In particular, the investigation of limited proteolysis by cathepsins in the extracellular space is opening numerous possibilities for future break-through discoveries. In this review, we highlight the most important findings that establish cysteine cathepsins as important players in the extracellular space and discuss their roles that reach beyond processing and degradation of extracellular matrix (ECM) components. In addition, we discuss the recent developments in cathepsin research and the new possibilities that are opening in translational medicine.
Sketching the Power of Machine Learning to Decrypt a Neural Systems Model of Behavior

Uncovering brain-behavior mechanisms is the ultimate goal of neuroscience. A formidable amount of discoveries has been made in the past 50 years, but the very essence of brain-behavior mechanisms still escapes us. The recent exploitation of machine learning (ML) tools in neuroscience opens new avenues for illuminating these mechanisms. A key advantage of ML is to enable the treatment of large data, combing highly complex processes. This essay provides a glimpse of how ML tools could test a heuristic neural systems model of motivated behavior, the triadic neural systems model, which was designed to understand behavioral transitions in adolescence. This essay previews analytic strategies, using fictitious examples, to demonstrate the potential power of ML to decrypt the neural networks of motivated behavior, generically and across development. Of note, our intent is not to provide a tutorial for these analyses nor a pipeline. The ultimate objective is to relate, as simply as possible, how complex neuroscience constructs can benefit from ML methods for validation and further discovery. By extension, the present work provides a guide that can serve to query the mechanisms underlying the contributions of prefrontal circuits to emotion regulation. The target audience concerns mainly clinical neuroscientists. As a caveat, this broad approach leaves gaps, for which references to comprehensive publications are provided.
Predicting Risk of Recurrent Acute Kidney Injury: A Systematic Review

Background: Although the epidemiology of acute kidney injury (AKI) has been well described, less is known about recurrent AKI (r-AKI). We undertook a systematic review to identify incidence, risk factors, and outcomes of r-AKI. Methods: MEDLINE, EMBASE, CINAHL, Cochrane, Web of Science were searched, from inception to December 2017, for quantitative studies on adults with AKI, where follow-up included reporting of r-AKI. Two reviewers independently identified studies and assessed study quality. Summary: From 2,824 citations, 10 cohort studies met inclusion criteria (total patients n = 538,667). There were 2 distinct set of studies; 4 studies assessed r-AKI within the same hospital admission (most were intensive care unit [ICU] patients) and 6 studies assessed postdischarge r-AKI. The median percentage of people developing r-AKI within the same hospital admission was 23.4% (IQR 20.3–27.2%) and postdischarge r-AKI was 31.3% (IQR 26.4–33.7%). A higher Acute Physiology and Chronic Health Evaluation score was associated with increased risk of r-AKI within the same hospital admission in ICU patients. Cardiovascular disease and AKI severity were associated with increased risk of postdischarge r-AKI. R-AKI (within same admission and postdischarge) was associated with worse survival. It was not possible to pool results due to methodological differences across studies, such as varying definitions for AKI and r-AKI, varying length of follow-up and effect measures. Key messages: More representative population-based studies with robust assessment of predictors and consensus definition of r-AKI are needed to identify risk factors and develop risk stratification tools to reduce recurrence and improve outcomes. Systematic Review Registration: CRD42017082668.
Chatbots and Conversational Agents in Mental Health: A Review of the Psychiatric Landscape

Objective: The aim of this review was to explore the current evidence for conversational agents or chatbots in the field of psychiatry and their role in screening, diagnosis, and treatment of mental illnesses. Methods: A systematic literature search in June 2018 was conducted in PubMed, EmBase, PsycINFO, Cochrane, Web of Science, and IEEE Xplore. Studies were included that involved a chatbot in a mental health setting focusing on populations with or at high risk of developing depression, anxiety, schizophrenia, bipolar, and substance abuse disorders. Results: From the selected databases, 1466 records were retrieved and 8 studies met the inclusion criteria. Two additional studies were included from reference list screening for a total of 10 included studies. Overall, potential for conversational agents in psychiatric use was reported to be high across all studies. In particular, conversational agents showed potential for benefit in psychoeducation and self-adherence. In addition, satisfaction rating of chatbots was high across all studies, suggesting that they would be an effective and enjoyable tool in psychiatric treatment. Conclusion: Preliminary evidence for psychiatric use of chatbots is favourable. However, given the heterogeneity of the reviewed studies, further research with standardized outcomes reporting is required to more thoroughly examine the effectiveness of conversational agents. Regardless, early evidence shows that with the proper approach and research, the mental health field could use conversational agents in psychiatric treatment.
The Effect of Probiotic Yogurt on Glycemic Control in Type 2 Diabetes or Obesity: A Meta-Analysis of Nine Randomized Controlled Trials

Probiotic yogurt is suggested as a nutritional approach in type 2 diabetes (T2D) and obesity. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the effects of probiotic yogurt on glycemic outcomes in T2D or obesity. The databases used to search for RCTs included Medline and Scopus. The RCTs were eligible if outcomes included selected glycemic markers. In nine eligible trials, 237 and 235 subjects were in treatment (probiotic yogurt) and control (mostly conventional yogurt) groups, respectively. There was no significant difference for pooled unstandardized mean difference (USMD) hemoglobin A1c (HbA1c) by probiotic yogurt compared with the control in T2D (USMD: −0.366; 95% CI: −0.755, 0.024, p = 0.066) and obesity (USMD: 0.116, 95% CI: −0.007, 0.238, p = 0.065). Similarly, there were no effects of probiotic yogurt on fasting blood glucose, fasting insulin, or insulin resistance (estimated by homeostatic model assessment of insulin resistance (HOMA-IR)) in either T2D or obesity. In conclusion, the present meta-analysis has not demonstrated the benefits of consuming probiotic compared with conventional yogurt for improving glucose control in patients with diabetes or obesity. Larger trials are needed to verify the benefits of probiotic and/or conventional yogurt or other probiotic fermented milk (e.g., kefir) on glycemic markers in patients with diabetes and obesity.
Sensory retraining of the leg after stroke: systematic review and meta-analysis

Objective: This systematic review aimed to investigate the effects of interventions intended for retraining leg somatosensory function on somatosensory impairment, and secondary outcomes of balance and gait, after stroke. Data sources: Databases searched from inception to 16 January 2019 included Cochrane Library, PubMed, MEDLINE, CINAHL, EMBASE, PEDro, PsycINFO, and Scopus. Reference lists of relevant publications were also manually searched. Review methods: All types of quantitative studies incorporating interventions that intended to improve somatosensory function in the leg post stroke were retrieved. The Quality Assessment Tool for Quantitative Studies was used for quality appraisal. Standardised mean differences were calculated and meta-analyses were performed using preconstructed Microsoft Excel spreadsheets. Results: The search yielded 16 studies, comprising 430 participants, using a diverse range of interventions. In total, 10 of the included studies were rated weak in quality, 6 were rated moderate, and none was rated strong. Study quality was predominantly affected by high risk of selection bias, lack of blinding, and the use of somatosensory measures that have not been psychometrically evaluated. A significant heterogeneous positive summary effect size (SES) was found for somatosensory outcomes (SES: 0.52; 95% confidence interval (CI): 0.04 to 1.01; I2 = 74.48%), which included joint position sense, light touch, and two-point discrimination. There was also a significant heterogeneous positive SES for Berg Balance Scale scores (SES: 0.62; 95% CI: 0.10 to 1.14; I2 = 59.05%). Gait SES, mainly of gait velocity, was not significant. Conclusion: This review suggests that interventions used for retraining leg somatosensory impairment after stroke significantly improved somatosensory function and balance but not gait.
Quiet standing: The Single Inverted Pendulum model is not so bad after all

In the study of balance and postural control the (Single) Inverted Pendulum model (SIP) has been taken for a long time as an acceptable paradigm, with the implicit assumption that only ankle rotations are relevant for describing and explaining sway movements. However, more recent kinematic analysis of quiet standing revealed that hip motion cannot be neglected at all and that ankle-hip oscillatory patterns are characterized by complex in-phase and anti-phase interactions, suggesting that the SIP model should be substituted by a DIP (Double Inverted Pendulum) model. It was also suggested that DIP control could be characterized as a kind of optimal bi-axial active controller whose goal is minimizing the acceleration of the global CoM (Center of Mass). We propose here an alternative where active feedback control is applied in an intermittent manner only to the ankle joint, whereas the hip joint is stabilized by a passive stiffness mechanism. The active control impulses are delivered to the ankle joint as a function of the delayed state vector (tilt rotation angle + tilt rotational speed) of a Virtual Inverted Pendulum (VIP), namely a pendulum that links the ankle to the CoM, embedded in the real DIP. Simulations of such DIP/VIP model, with the hybrid control mechanism, show that it can reproduce the in-phase/anti-phase interaction patterns of the two joints described by several experimental studies. Moreover, the simulations demonstrate that the DIP/VIP model can also reproduce the measured minimization of the CoM acceleration, as an indirect biomechanical consequence of the dynamic interaction between the active control of the ankle joint and the passive control of the hip joint. We suggest that although the SIP model is literally false, because it ignores the ankle-hip coordination, it is functionally correct and practically acceptable for experimental studies that focus on the postural oscillations of the CoM.
Anticoagulant therapy for acute venous thrombo-embolism in cancer patients: A systematic review and network meta-analysis

Background Low-molecular-weight heparin (LMWH) is usually recommended for the treatment of cancer-associated thrombosis (CAT) but this treatment requires burdensome daily injections. We did a systematic review to compare the efficacy and safety of direct oral anticoagulants (DOAC), vitamin K antagonists (VKA) and LMWH in patients with CAT. Methods We searched Pubmed, Embase and CENTRAL for randomised controlled trials comparing DOAC, VKA and LMWH in patients with CAT. Pairwise and network meta-analyses were computed for venous thromboembolism (VTE) recurrence and bleeding complications. Results We identified 14 studies, including 4,661 patients. In pairwise comparison, DOAC were superior to LMWH to prevent VTE recurrence (HR 0.63; 95% CI 0.42–0.96) and LMWH was superior to VKA (HR 0.53; 95% CI 0.40–0.70). The rate of major bleeding was higher with DOAC compared to LMWH (HR 1.78; 95% CI 1.11–2.87). In the network meta-analysis, DOAC had a lower, but non-significant, rate of VTE recurrence compared to LMWH (HR 0.74; 95% CI 0.54–1.01). Both DOAC (HR 0.42; 95% CI 0.29–0.61) and LMWH (HR 0.57; 95% CI 0.44–0.75) were associated with lower rates of recurrence compared to VKA. No significant difference in major bleeding rate was observed in the network meta-analysis. Inconsistency was observed between pairwise and network meta-analysis comparisons for major bleeding. Conclusions DOAC are effective to prevent VTE recurrence in patients with CAT but are associated with an increased risk of bleeding compared to LMWH. The choice of anticoagulant should be personalised, taking into account the patient’s bleeding risk, including cancer site, and patient’s values and preferences.
Particle‐attached microorganism oxidation of ammonia in a hypereutrophic urban river

To elucidate the importance and mechanisms of particle‐attached microorganisms on ammonia oxidation, we conducted a controlled simulation experiment with samples collected from the Shunao River, an ammonia‐rich hypereutrophic urban river in eastern China. The effects of particle concentration, ammonia concentration, organic carbon source and concentration, dissolved oxygen concentration, and pH were investigated on ammonia transformation rate (ammonia removal rate and NO2− + NO3− accumulation rate) and abundance of particle‐attached ammonia‐oxidizing bacteria (AOB) and archaea (AOA). All these factors significantly influenced ammonia transformation rates. Our results provided direct evidence that microorganisms attached on riverine suspended particles were associated with ammonia oxidation. Sequencing revealed that the AOA genus Nitrososphaera, and the AOB genus Nitrosomonas were the most dominant in particle‐attached ammonia‐oxidizing microbial communities. Further analysis showed that AOB communities had higher species richness and diversity compared with AOA communities. Additionally, AOB amoA genes were ~10–100 times more abundant than AOA amoA genes, and AOB abundance was more strongly correlated with ammonia transformation rates than AOA abundance in most experiments, indicating that particle‐attached AOB were more important than AOA in the hypereutrophic urban river. This study adds to our knowledge of particle‐attached microorganism oxidation of ammonia.
Shared decision-making about cardiovascular disease medication in older people: a qualitative study of patient experiences in general practice

Objectives To explore older people’s perspectives and experiences with shared decision-making (SDM) about medication for cardiovascular disease (CVD) prevention. Design, setting and participants Semi-structured interviews with 30 general practice patients aged 75 years and older in New South Wales, Australia, who had elevated CVD risk factors (blood pressure, cholesterol) or had received CVD-related lifestyle advice. Data were analysed by multiple researchers using Framework analysis. Results Twenty eight participants out of 30 were on CVD prevention medication, half with established CVD. We outlined patient experiences using the four steps of the SDM process, identifying key barriers and challenges: Step 1. Choice awareness: taking medication for CVD prevention was generally not recognised as a decision requiring patient input; Step 2. Discuss benefits/harms options: CVD prevention poorly understood with emphasis on benefits; Step 3. Explore preferences: goals, values and preferences (eg, length of life vs quality of life, reducing disease burden vs risk reduction) varied widely but generally not discussed with the general practitioner; Step 4. Making the decision: overall preference for directive approach, but some patients wanted more active involvement. Themes were similar across primary and secondary CVD prevention, different levels of self-reported health and people on and off medication. Conclusions Results demonstrate how older participants vary widely in their health goals and preferences for treatment outcomes, suggesting that CVD prevention decisions are preference sensitive. Combined with the fact that the vast majority of participants were taking medications, and few understood the aims and potential benefits and harms of CVD prevention, it seems that older patients are not always making an informed decision. Our findings highlight potentially modifiable barriers to greater participation of older people in SDM about CVD prevention medication and prevention in general.
Targeting the mDia Formin-Assembled Cytoskeleton Is an Effective Anti-Invasion Strategy in Adult High-Grade Glioma Patient-Derived Neurospheres

High-grade glioma (HGG, WHO Grade III–IV) accounts for the majority of adult primary malignant brain tumors. Failure of current therapies to target invasive glioma cells partly explains the minimal survival advantages: invasive tumors lack easily-defined surgical margins, and are inherently more chemo- and radioresistant. Much work centers upon Rho GTPase-mediated glioma invasion, yet downstream Rho effector roles are poorly understood and represent potential therapeutic targets. The roles for the mammalian Diaphanous (mDia)-related formin family of Rho effectors have emerged in invasive/metastatic disease. mDias assemble linear F-actin to promote protrusive cytoskeletal structures underlying tumor cell invasion. Small molecule mDia intramimic (IMM) agonists induced mDia functional activities including F-actin polymerization. mDia agonism inhibited polarized migration in Glioblastoma (WHO Grade IV) cells in three-dimensional (3D) in vitro and rat brain slice models. Here, we evaluate whether clinically-relevant high-grade glioma patient-derived neuro-sphere invasion is sensitive to formin agonism. Surgical HGG samples were dissociated, briefly grown as monolayers, and spontaneously formed non-adherent neuro-spheres. IMM treatment dramatically inhibited HGG patient neuro-sphere invasion, both at neuro-sphere embedding and mid-invasion assay, inducing an amoeboid morphology in neuro-sphere edge cells, while inhibiting actin- and tubulin-enriched tumor microtube formation. Thus, mDia agonism effectively disrupts multiple aspects of patient-derived HGG neuro-sphere invasion.