Miracle-dz/UniFAR-FTUs huggingface dataset:
Visual hallucinations in neurological and ophthalmological disease: pathophysiology and management

Visual hallucinations are common in older people and are especially associated with ophthalmological and neurological disorders, including dementia and Parkinson’s disease. Uncertainties remain whether there is a single underlying mechanism for visual hallucinations or they have different disease-dependent causes. However, irrespective of mechanism, visual hallucinations are difficult to treat. The National Institute for Health Research (NIHR) funded a research programme to investigate visual hallucinations in the key and high burden areas of eye disease, dementia and Parkinson’s disease, culminating in a workshop to develop a unified framework for their clinical management. Here we summarise the evidence base, current practice and consensus guidelines that emerged from the workshop. Irrespective of clinical condition, case ascertainment strategies are required to overcome reporting stigma. Once hallucinations are identified, physical, cognitive and ophthalmological health should be reviewed, with education and self-help techniques provided. Not all hallucinations require intervention but for those that are clinically significant, current evidence supports pharmacological modification of cholinergic, GABAergic, serotonergic or dopaminergic systems, or reduction of cortical excitability. A broad treatment perspective is needed, including carer support. Despite their frequency and clinical significance, there is a paucity of randomised, placebo-controlled clinical trial evidence where the primary outcome is an improvement in visual hallucinations. Key areas for future research include the development of valid and reliable assessment tools for use in mechanistic studies and clinical trials, transdiagnostic studies of shared and distinct mechanisms and when and how to treat visual hallucinations.
Napsin-A Expression, a Reliable Immunohistochemical Marker for Diagnosis of Ovarian and Endometrial Clear Cell Carcinomas

Background & Objective: Clear cell carcinomas (CCC) differ from other types of ovarian and endometrial carcinomas in biology, behavior and response to chemotherapy. Histopathologic diagnosis may be challenging in some situations which necessitates immunohistochemistary (IHC) assessment. In this study we investigated the diagnostic utility of Napsin-A in diagnosis of ovarian and endometrial CCCs. Methods: Ovarian and endometrial CCC samples from 2013 to 2018 in 3 general and women’s hospital in Tehran were re-evaluated by 2 expert pathologists. Forty-two samples were included as case and 42 non-clear cell carcinomas (Non-CCC) of ovary and endometrium were selected as control group. Based on IHC study tumors with sum intensity and percentage score ≥2 (at least 1+ staining in more than 1% of tumor cells) were considered positive. Results: The prevalence of endometrial and ovarian CCC in the case group were 15 and 27 respectively. The tumors in the control group included 22 cases of endometrioid, 2 high grade papillary serous carcinoma (HGSC) of endometrium, 6 endometrioid and 12 HGSC of ovary. Napsin-A positivity was observed in 35 (83%) of CCCs while 7 (17%) samples including 3 out of 15 endometrial and 4 out of 27 ovarian CCCs were Napsin-A negative. No positive reaction was seen in control group. The overall accuracy, specifity and sensitivity of Napsin-A for diagnosis of ovarian and endometrial CCCs were 83%, 100% and 83%, respectively. Sensitivity for ovarian and endometrial CCCs were 85% and 80%, orderly. Conclusion: Napsin-A is an accurate and reliable marker for distinction of CCCs from non-CCCs in ovary and endometrium. A panel of antibodies may yield the highest diagnostic accuracy.
Parental Efficacy and Control Questionnaire in Hematopoietic Stem Cell Transplant: Preliminary Validation.

OBJECTIVE Develop and evaluate the preliminary validity of a self-report measure of parents' treatment-related efficacy and control, Parental Efficacy and Control Questionnaire-Hematopoietic Stem Cell Transplant (PECQ-HCT), in a pediatric HCT sample. METHODS Participants included 185 parents of children (≤12 years old) receiving HCT participating in a larger, longitudinal study. Parents completed the PECQ-HCT as well as measures of social problem-solving skills, collective family efficacy, family beliefs, and parental distress. RESULTS Exploratory factor analysis results indicated that a 37-item four-factor model was the best fitting and most theoretically sound, χ2(df = 1,596) = 14,089.95, p < . 01, comparative fit index = 0.92, Tucker-Lewis Index = 0.90, and root mean square error of approximation = 0.07. Preliminary subscale scores demonstrated adequate internal consistency as well as good content and criterion-related validity. CONCLUSIONS If replicated using a confirmatory factor analysis in a separate sample, these findings suggest that the four-factor PECQ-HCT measure may be useful for measuring HCT-related parental efficacy and perceived control.
End-to-End Automatic Pronunciation Error Detection Based on Improved Hybrid CTC/Attention Architecture

Advanced automatic pronunciation error detection (APED) algorithms are usually based on state-of-the-art automatic speech recognition (ASR) techniques. With the development of deep learning technology, end-to-end ASR technology has gradually matured and achieved positive practical results, which provides us with a new opportunity to update the APED algorithm. We first constructed an end-to-end ASR system based on the hybrid connectionist temporal classification and attention (CTC/attention) architecture. An adaptive parameter was used to enhance the complementarity of the connectionist temporal classification (CTC) model and the attention-based seq2seq model, further improving the performance of the ASR system. After this, the improved ASR system was used in the APED task of Mandarin, and good results were obtained. This new APED method makes force alignment and segmentation unnecessary, and it does not require multiple complex models, such as an acoustic model or a language model. It is convenient and straightforward, and will be a suitable general solution for L1-independent computer-assisted pronunciation training (CAPT). Furthermore, we find that in regards to accuracy metrics, our proposed system based on the improved hybrid CTC/attention architecture is close to the state-of-the-art ASR system based on the deep neural network–deep neural network (DNN–DNN) architecture, and has a stronger effect on the F-measure metrics, which are especially suitable for the requirements of the APED task.
Morphological evaluation of polysaccharide content and collagen composition during cutaneous wound healing in the Sunda porcupine (Hystrix javanica)

Wound healing in the Sunda porcupine is believed to occur quickly, although the wound is large and severe. Wound enclosure involves many processes to restore the lost or damaged skin structure where conjugated polysaccharide-protein and collagen, as the main components deposited in wound tissue to restore it. The aim of this study was to evaluate alteration of polysaccharide contents and collagen in untreated full-thickness wound healing in the thoracodorsal and lumbosacral regions in the Sunda porcupines. Histological analysis was performed by periodic acid Schiff, alcian blue pH 2.5, picrosirius red staining method and Low Vacuum Scanning Electron Microscope (LV-SEM) imaging to obtain the fundamental data of healing process. Wound healing began with re-epithelization followed by progressive wound contraction with 4 overlapping stages in about 30–50 days until the wound closed (21–30 days in thoracodorsal and 30–50 days in lumbosacral). Neutral polysaccharide was more widely distributed compared to the acid polysaccharide in almost all stages of wound healing. The ratio of collagen I to III appeared to be higher in the thoracodorsal region than the lumbosacral region during healing process. LV-SEM imaging showed changes in connective tissue structure in the wound border and granulation tissue which appeared abundant and mixed of thin and thick fiber. In conclusion, cutaneous full thickness wound healing in the Sunda porcupine occurred faster in the thoracodorsal region, which might be correlated to the role of neutral polysaccharide and a high ratio of collagen I to III.
Glaucoma medication adherence in an adult population in Nigeria

Introduction: Glaucoma is a common and potentially blinding condition, which can be managed with the use of appropriate medication therapy. For the medication to be effective, there has to be strict adherence to drug regimen. However, this is not usually the case for many glaucoma patients. The aim of this study was to identify the barriers and facilitators related to glaucoma medication adherence among an adult population. Materials and Methods: Forty-nine participants who had been diagnosed with glaucoma and had been on glaucoma medications for at least a year were recruited and interviewed. They were aged between 18 and 70 years with a mean age of 54 years. The one-on-one in-depth interviews were recorded using an audio recorder. Data obtained were transcribed and analysed using rank ordering to determine the degree of importance. Results: Results identified eight barriers to drug adherence among which were finance/cost of medication (195), forgetfulness (160) and side effects of drops (155). Other barriers were difficulty with drop administration (143), busy schedule (130) and non-availability of eye drops (122) among others. Facilitators identified included fear of blindness (185), desire for improved vision (152) and knowledge about the disease (112). Other facilitators were convenience of eye drop schedule (99), availability of drops (91) and use of alarms (89) among others. Conclusion: Understanding these factors would help eye care practitioners to advice their patients better and greatly slow down the progression of the disease.
Sensing Senses: Optical Biosensors to Study Gustation

The five basic taste modalities, sweet, bitter, umami, salty and sour induce changes of Ca2+ levels, pH and/or membrane potential in taste cells of the tongue and/or in neurons that convey and decode gustatory signals to the brain. Optical biosensors, which can be either synthetic dyes or genetically encoded proteins whose fluorescence spectra depend on levels of Ca2+, pH or membrane potential, have been used in primary cells/tissues or in recombinant systems to study taste-related intra- and intercellular signaling mechanisms or to discover new ligands. Taste-evoked responses were measured by microscopy achieving high spatial and temporal resolution, while plate readers were employed for higher throughput screening. Here, these approaches making use of fluorescent optical biosensors to investigate specific taste-related questions or to screen new agonists/antagonists for the different taste modalities were reviewed systematically. Furthermore, in the context of recent developments in genetically encoded sensors, 3D cultures and imaging technologies, we propose new feasible approaches for studying taste physiology and for compound screening.
Comparison of Gaseous Ubiquitin Ion Structures obtained from a Solid and Solution Matrix Using Ion Mobility Spectrometry-Mass Spectrometry.

RATIONALE Examining surface protein conformations, and especially achieving this with spatial resolution, is an important goal. The recently discovered ionization processes offer spatial-resolution measurements similar to MALDI and produce charge states similar to ESI extending higher-mass protein applications directly from surfaces on high-performance mass spectrometers. Studying a well-interrogated protein by ion mobility spectrometry-mass spectrometry (IMS-MS) to access effects on structures using a solid vs solvent matrix may provide insights. METHODS Ubiquitin was studied by IMS-MS using new ionization processes with commercial and homebuilt ion sources and instruments (Waters SYNAPT-G2(S) and homebuilt 2m drift-tube instrument; MSTM sources). Mass-to-charge and drift-time (td )-measurements are compared for ubiquitin ions obtained by inlet and vacuum ionization using laserspray ionization (LSI), matrix- (MAI) and solvent-assisted ionization (SAI), respectively, and compared with those from ESI under conditions that are most comparable. RESULTS Using the same solution conditions with SYNAPT G2(S) instruments, td -distributions of various ubiquitin charge states of MAI, LSI, and SAI are similar to those from ESI using a variety of solvents, matrices, extraction voltages, a laser, and temperature only, showing subtle differences in more compact features within the elongated distribution of structures. However, on a homebuilt drift-tube instrument, within the elongated distribution of structures, both similar and different td -distributions are observed for ubiquitin ions obtained by MAI and ESI. MAI generated ions are frequently narrower in their td -distributions. CONCLUSIONS Direct comparisons between ESI and the new ionization methods operational directly from surfaces, suggest that the protein in its solution structure prior to exposure to the ionization event is either captured (frozen out) at the time of crystallization, or that the protein in the solid matrix is associated with sufficient solvent to maintain the solution structure, or, alternatively, that the observed structures are those related to what occurs in the gas phase with ESI- or MAI-generated ions and not with the solution structures.
Environmental Monitoring of PAHs Exposure, Biomarkers and Vital Status in Coke Oven Workers

A follow-up study of a cohort of workers from a coke plant compared with a control group from the same industrial area was conducted in 2019. The recruitment and environmental and biomarker measurements were performed during 1993/1994. The environmental concentrations of polycyclic aromatic hydrocarbons (PAH), B(a)P, pyrene and nitro-PAH were measured. Personal data were collected via an individual semi-structured questionnaire by a trained physician. All biomarkers were measured after a specific blood drawing for every test. Significant risks (ORs) were observed for nitro-PAH (≥0.12 µg/m3) [OR = 7.96 (1.01–62.82)], urinary 1-hydroxypyrene (1-OHpy) (≥0.99 µmoles/moles of creatinine) [OR = 11.71 (1.47–92.90)], PAH DNA adducts (P32) (≥2.69 adducts/108 nucleotides) [OR = 5.46 (1.17–25.58)], total nitro-PAH hemoglobin adducts (≥161.68 fg/µg of Hb) [OR = 5.92 (1.26–27.86)], sister chromatid exchange (SCE) with TCR (≥377.84 SCE/cell chromosomes) [OR = 13.06 (3.95–93.10)], sister chromatid exchange with T (≥394.72 total SCE) [OR = 13.06 (3.95–93.10)], and sister chromatid exchange with X (≥8.19 mean SCE) [OR = 13.06 (3.95–93.10)]. Significant risk of death for all causes and chromosomal aberrations (48 h) (OR = 7.19 [1.19–43.44]) or micronuclei in culture at 48 h (OR = 3.86 [1.04–14.38]) were also found.
Effects of Microwave-Assisted Opuntia humifusa Extract in Inhibiting the Impacts of Particulate Matter on Human Keratinocyte Skin Cell

Particulate matter (PM) is one of the most important factors causing serious skin diseases, due to its generation of reactive oxygen species (ROS) over the course of long-term exposure. As a source of natural antioxidants, Opuntia humifusa (O. humifusa) is a potential candidate for the design of advanced formulations to prevent PM’s harmful effects. Unfortunately, its high viscosity does not allow it to be utilized in these formulations. In this present study, a new approach to the extract of O. humifusa using high-power microwave treatment, namely microwave-assisted O. humifusa extract (MA-OHE), was investigated. The results indicated that MA-OHE not only is a reasonable viscosity extract, but also enhances O. humifusa’s antioxidant properties. Additionally, this study also found that MA-OHE exhibited outstanding antioxidant and anti-inflammatory activities in eliminating PM’s effects, due to suppression of AhR degradation, ROS production, and COX-2 and MMP-9 expression in HaCaT keratinocytes. It is believed that MA-OHE is a potential cosmeceutical ingredient that could be utilized to prevent PM-induced skin oxidative stress and inflammation.
Physical prognostic factors predicting outcome following anterior cruciate ligament reconstruction: protocol for a systematic review

Introduction Injuries of the anterior cruciate ligament (ACL) are a common musculoskeletal complication and can cause significant reduction in patient function and quality of life. Many undergo ACL reconstruction, with high-quality rehabilitation key to successful outcome. Knowledge of physical prognostic factors, such as quadriceps strength, is crucial to inform rehabilitation and has important implications for outcome following ACL reconstruction. However, these factors predicting outcome are poorly defined. Therefore, the aim of this systematic review is to establish physical prognostic factors predictive of outcome in adults following ACL reconstruction. Outcome will be subdivided into two groups of outcome measures, patient-reported and performance-based. Physical prognostic factors of interest will reflect a range of domains and may be modifiable/non-modifiable. Results will help decide most appropriate management and assist in planning and tailoring preoperative and postoperative rehabilitation. Methods and analysis This systematic review protocol is reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. MEDLINE, CINAHL and EMBASE databases, key journals and grey literature will be searched from inception to July 2019. Prospective cohort studies including participants aged ≥16 years who have undergone ACL reconstruction will be included, with articles focusing on multi-ligament reconstructions and ACL repair surgery, or not published in English excluded. Two independent reviewers will conduct searches, assess study eligibility, extract data, assess risk of bias (Quality in Prognostic Studies tool) and quantify overall quality of evidence (modified Grading of Recommendations, Assessment, Development and Evaluation guidelines). If possible, a meta-analysis will be conducted, otherwise a narrative synthesis will ensue focusing on prognostic factors, risk of bias of included studies and strength of association with outcomes. Ethics and dissemination Findings will be published in a peer-reviewed journal, presented at conferences and locally to physiotherapy departments. Ethical approval is not required for this systematic review. PROSPERO registration number CRD42019127732.
Defining how multiple lipid species interact with inward rectifier potassium (Kir2) channels

Significance Ion channels form pores that allow for the selective transport of ions across cell membranes, generating electrical signals in response to a variety of signals. Inward rectifier potassium (Kir) channels in particular are regulated by direct interactions with the complex mixture of lipids that are present in eukaryotic cell membranes. However, the molecular details of these concurrent lipid interactions with Kir channels are not clear and difficult to access via experimental methods. Here, we simulate the Kir2.2 channel in a complex lipid mixture to explore how anionic phospholipids and cholesterol dynamically organize around the membrane protein. In particular we demonstrate a synergy between binding interactions of different anionic phospholipid species which are known to activate Kir channels. Protein–lipid interactions are a key element of the function of many integral membrane proteins. These potential interactions should be considered alongside the complexity and diversity of membrane lipid composition. Inward rectifier potassium channel (Kir) Kir2.2 has multiple interactions with plasma membrane lipids: Phosphatidylinositol (4, 5)-bisphosphate (PIP2) activates the channel; a secondary anionic lipid site has been identified, which augments the activation by PIP2; and cholesterol inhibits the channel. Molecular dynamics simulations are used to characterize in molecular detail the protein–lipid interactions of Kir2.2 in a model of the complex plasma membrane. Kir2.2 has been simulated with multiple, functionally important lipid species. From our simulations we show that PIP2 interacts most tightly at the crystallographic interaction sites, outcompeting other lipid species at this site. Phosphatidylserine (PS) interacts at the previously identified secondary anionic lipid interaction site, in a PIP2 concentration-dependent manner. There is interplay between these anionic lipids: PS interactions are diminished when PIP2 is not present in the membrane, underlining the need to consider multiple lipid species when investigating protein–lipid interactions.
Vasculoprotective Effects of Vildagliptin. Focus on Atherogenesis

Vildagliptin is a representative of Dipeptidyl Peptidase-4 (DPP-4) inhibitors, antihyperglycemic drugs, approved for use as monotherapy and combination therapy in type 2 diabetes mellitus. By inhibiting enzymatic decomposition, DPP-4 inhibitors increase the half-life of incretins such as GLP-1 (Glucagon-like peptide-1) and GIP (Gastric inhibitors polypeptide) and prolong their action. Some studies present results suggesting the anti-sclerotic and vasculoprotective effects of vildagliptin reaching beyond glycemic control. Vildagliptin is able to limit inflammation by suppression of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway and proinflammatory agents such as TNF-α (tumor necrosis factor α), IL-1β (Interleukin-1β), and IL-8 (Interleukin 8). Moreover, vildagliptin regulates lipid metabolism; attenuates postprandial hypertriglyceridemia; and lowers serum triglycerides, apolipoprotein B, and blood total cholesterol levels. This DPP-4 inhibitor also reduces macrophage foam cell formation, which plays a key role in atheromatous plaque formation and stability. Vildagliptin reduces vascular stiffness via elevation of nitric oxide synthesis, improves vascular relaxation, and results in reduction in both systolic and diastolic blood pressure. Treatment with vildagliptin lowers the level of PAI-1 presenting possible antithrombotic effect. By affecting the endothelium, inflammation, and lipid metabolism, vildagliptin may affect the development of atherosclerosis at its various stages. The article presents a summary of the studies assessing vasculoprotective effects of vildagliptin with special emphasis on atherogenesis.
Multicentre study: reliability and repeatability of Scheimpflug system measurement in keratoconus

Purpose To assess the repeatability and reliability of the most important tomographic parameters for characterising keratoconus measured with a Pentacam HR (high resolution). Methods Overall, 230 eyes in 158 patients with keratoconus were analysed. We performed five consecutive corneal tomography examinations for each eye with a Pentacam HR in patients with keratoconus. Study eyes were classified into three groups depending on the maximum posterior elevation (max_BFS_post): grade 1 for cases of keratoconus with a max_BFS_post of 40 µm; grade 2 for those with a max_BFS_post of between 41 and 75 µm and grade 3 for those with a max_BFS_post of over 75 µm. We calculated the intraclass correlation coefficients (ICCs) and repeatability limits of parameters from tomography and aberrometry. Results All the parameters were found to have excellent ICCs (0.9). The repeatability limits for the key parameters were higher than 0.5D for the power parameters, 20° for the axis of corneal astigmatism and 10 µm for the thinnest corneal thickness. Further, we obtained repeatability limits of above 0.1 µm for the aberrometry values and overall greater than 15° for the coma axis. All the values increase with the severity of keratoconus, except for that of the coma axis which falls with keratoconus grade. Conclusions The reliability indicated by ICCs supports the view that the Pentacam HR is useful for the diagnosis of keratoconus. The repeatability limits suggest that new criteria should be established for monitoring progression taking into account the real measurements that can be made using this system.