Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of quantitative measurements of central nervous system tumour consistency and the associated preoperative imaging findings

Abstract Purpose: Central nervous system (CNS) tumour consistency is one of the factors determining the difficulty of surgery for such lesions. We measured the consistency of surgically excised CNS tumour specimens using a hardness meter. The purpose of this study was to identify imaging parameters that reflect tumour consistency by comparing preoperative imaging findings with CNS tumour consistency measurements. Material and methods: Of 175 consecutive patients with CNS tumours who underwent surgery at our hospital between October 2012 and October 2018, 127 were included in this study (those whose specimens were difficult to measure were excluded). CNS tumour consistency was measured immediately after surgical excision using a hardness meter and compared with preoperative T1-weighted, T2-weighted (T2WI), fluid attenuated inversion recovery (FLAIR), diffusion-weighted imaging, gadolinium-enhanced magnetic resonance imaging, plain computed tomography (CT), and contrast-enhanced CT findings. Tumour consistency was also subjectively classified by the surgeon into soft, hard, or very hard. Results: The intracranial meningiomas were harder than the metastatic tumours and gliomas (p = 0.03 and p = 0.03, respectively). Among the intracranial meningiomas, the tumours that exhibited high intensity on T2WI were softer than those that displayed isointensity or low intensity (p < 0.001 and p < 0.001, respectively), and the isointense tumours were softer than the low intensity tumours (p = 0.02). Among the metastatic tumours, the tumours that exhibited high intensity on T2WI were softer than those that displayed isointensity or low intensity (p < 0.001 and p < 0.001, respectively). Among the intracranial meningiomas and metastatic tumours, significant correlations were detected between the T2WI findings and subjective tumour consistency according to the surgeon or quantitative tumour consistency (p = 0.01 and p = 0.03, respectively). Conclusions: The preoperative T2WI findings of intracranial meningiomas and metastatic tumours were significantly correlated with quantitatively measured tumour consistency and subjectively evaluated tumour consistency. Therefore, we concluded that T2WI findings are useful for preoperatively predicting the consistency of such tumours.
Impact of pharmacist-led home medicines review services on drug-related problems among the elderly population: a systematic review

OBJECTIVES To address and elucidate the impact of pharmacist-led home medicines review (HMR) services on identifying drug-related problems (DRPs) among the elderly population in home care settings. METHODS A comprehensive systematic search was performed using electronic scientific databases such as PubMed, Scopus, Embase, and Web of Science for studies published between January 1, 2008 and December 31, 2018, pertaining to HMR services by pharmacists for identifying DRPs. RESULTS In total, 4,292 studies were retrieved from the searches, of which 24 were excluded as duplicates. Titles and abstracts were screened for the remaining 4,268 studies, of which 4,239 were excluded due to the extraneous nature of the titles and/or abstracts. Subsequently, 29 full-text articles were assessed, and 19 were removed for lacking the outcome of interest and/or not satisfying the study’s inclusion criteria. Finally, 10 studies were included in the review; however, publication bias was not assessed, which is a limitation of this study. In all studies, pharmacists identified a highly significant amount of DRPs through HMR services. The most common types of DRPs were potential drug-drug interactions, serious adverse drug reactions, need for an additional drug, inappropriate medication use, non-adherence, untreated indications, excessive doses, and usage of expired medications. CONCLUSIONS HMR is a novel extended role played by pharmacists. The efficiency of such programs in identifying and resolving DRPs could minimize patients’ health-related costs and burden, thereby enhancing the quality of life and well-being among the elderly.
The origins and functions of hepatic polyploidy

ABSTRACT Polyploid cells contain more than two homologous sets of chromosomes. The original observations of liver polyploidy date back to the 1940s, but functional roles for polyploid cells are still unclear. Liver polyploidy may influence regeneration, stress response, and cancer, although little evidence has established direct causal links between polyploidy and these biological phenotypes. In this review, we will introduce broad concepts about polyploidy including its distribution in nature and how polyploids form in normal and pathological situations. Then we will examine recent discoveries that have begun to clarify functionality and disease relevance of liver polyploidy. Finally, we will discuss implications and future directions of research about polyploidy in the liver.
Nitric Oxide Regulates Mitochondrial Fatty Acid Metabolism Through Reversible Protein S-Nitrosylation

S-nitrosylation increases the catalytic efficiency of an enzyme critical to fatty acid β-oxidation. Altering Metabolism Through S-Nitrosylation Derivatives of the gasotransmitter nitric oxide can be covalently linked to cysteine residues through a process called S-nitrosylation. Using mass spectrometry, Doulias et al. identified S-nitrosylated proteins in multiple mouse tissues, including the liver. Many of the S-nitrosylated proteins had roles in metabolic processes that occur in mitochondria, such as β-oxidation of fatty acids. S-nitrosylation of VLCAD [very long chain acyl–coenzyme A (CoA) dehydrogenase], an enzyme in the liver that catalyzes the first committed step in fatty acid β-oxidation, improved its catalytic efficiency in vitro, which would be expected to increase fatty acid metabolism and decrease hepatic steatosis, or the accumulation of fat and triglycerides in the liver. Mice used as a model for obesity (ob/ob mice) spontaneously develop hepatic steatosis, and treatment of ob/ob mice with GSNO, a compound that releases nitric oxide, reduced liver triglyceride concentrations and fatty deposits in the liver. Thus, these results implicate S-nitrosylation in the regulation of the activity of several metabolic enzymes. Cysteine S-nitrosylation is a posttranslational modification by which nitric oxide regulates protein function and signaling. Studies of individual proteins have elucidated specific functional roles for S-nitrosylation, but knowledge of the extent of endogenous S-nitrosylation, the sites that are nitrosylated, and the regulatory consequences of S-nitrosylation remains limited. We used mass spectrometry–based methodologies to identify 1011 S-nitrosocysteine residues in 647 proteins in various mouse tissues. We uncovered selective S-nitrosylation of enzymes participating in glycolysis, gluconeogenesis, tricarboxylic acid cycle, and oxidative phosphorylation, indicating that this posttranslational modification may regulate metabolism and mitochondrial bioenergetics. S-nitrosylation of the liver enzyme VLCAD [very long chain acyl–coenzyme A (CoA) dehydrogenase] at Cys238, which was absent in mice lacking endothelial nitric oxide synthase, improved its catalytic efficiency. These data implicate protein S-nitrosylation in the regulation of β-oxidation of fatty acids in mitochondria.
A Comparison of Differential Item Functioning Detection Methods in Cognitive Diagnostic Models

As a class of discrete latent variable models, cognitive diagnostic models have been widely researched in education, psychology, and many other disciplines. Detecting and eliminating differential item functioning (DIF) items from cognitive diagnostic tests is of great importance for test fairness and validity. A Monte Carlo study with varying manipulated factors was carried out to investigate the performance of the Mantel-Haenszel (MH), logistic regression (LR), and Wald tests based on item-wise information, cross-product information, observed information, and sandwich-type covariance matrices (denoted by Wd, WXPD, WObs, and WSw, respectively) for DIF detection. The results showed that (1) the WXPD and LR methods had the best performance in controlling Type I error rates among the six methods investigated in this study and (2) under the uniform DIF condition, when the item quality was high or medium, the power of WXPD, WObs, and WSw was comparable with or superior to that of MH and LR, but when the item quality was low, WXPD, WObs, and WSw were less powerful than MH and LR. Under the non-uniform DIF condition, the power of WXPD, WObs, and WSw was comparable with or higher than that of LR.
Ultrasound Microbubbles for Diagnosis and Treatment of Cardiovascular Diseases

Abstract Ultrasound (US) imaging of heart and major arteries and veins is among the most frequently used diagnostic techniques applied in humans. Conventional cardiovascular US sessions include anatomical B-mode and functional M-, pulsed-wave- and Doppler mode, which have their limitations in both precise cardiac chambers' delineation and small vessel imaging. The introduction of contrast-enhanced US, employing microbubble suspensions as contrast agent, has enabled a better delineation of heart chambers, the visualization of myocardial microvasculature, and the atherosclerotic plaque neovascularization. Moreover, specific disease-related molecular tracers have been developed by modifying the microbubbles with targeting ligands directed to biological markers exposed to the luminal side of the blood vessels. Microbubble functionalization has enabled in vivo molecular US imaging of various stages of atherosclerosis, from plaque initiation to plaque vulnerability, and neointima formation following revascularization procedures. Furthermore, oscillating microbubbles have been used to mechanically dissolve thrombus material and may act as carriers of drugs and nucleic acids that are released locally by US pulses. This review article summarizes recent advances in functional and molecular US images and discusses therapeutic applications of microbubbles. The addressed topics include an overview on microbubble formats, microbubble detection methods, molecular targets of cardiovascular diseases, and the use of microbubbles for thrombolysis and drug delivery.
A Step-by-Step Guide to Building a Complex Care Coordination Program in a Small Setting

Children with medical complexity comprise a growing population that stresses existing models of pediatric care. This report will describe a care support project that delivered shared plans of care to providers and families of children with medical complexity. This program was built around carefully constructed care support teams where each member had clearly defined roles and responsibilities. The teams worked collaboratively to improve provider communication, create SMART (Specific, Measurable, Assignable, Realistic, and Timely) goals, and perform task tracking. This process created a scaffolding to support community physicians, allowing patients to remain in their local medical homes and to access services closer to home and reducing hospital admissions and emergency room overutilization.
Role of homocysteine in the treatment of Parkinson's disease

The saga of harmful administration of levodopa (LD) in the treatment of Parkinson’s disease (PD) resulted from outcomes of animal trials and cell culture studies. They were initiated after the clinical observation of onset of motor complications related to the short plasma half-life of the drug in PD patients. This discussion only partially considered a further aspect, which is associated with the long-term administration of LD. Chronic LD intake increases homocysteine plasma levels. This may support progression of the disease due to concomitant onset of neuropsychiatric symptoms and comorbidities (i.e., vascular disease). In the periphery, therapeutic approaches for this LD-mediated homocysteine increase are vitamin supplementation (i.e., folic acid or application of LD with an inhibitor of catechol-O-methyltransferase [COMT]). In the brain, a blood–brain trespassing precursor of folic acid or a centrally acting COMT inhibitor may represent hypothetical therapeutic approaches. This COMT inhibitor should be applied together with an oxidative stress reducing monoamine oxidase-B inhibitor, in order to force central dopamine metabolism further down via the methylation path. However, this may turn out to be a double-edged sword, since the inhibition of O-methylation with the COMT inhibitor may hypothetically contribute to increased N-methylation. Thus, endogenous tetrahydroisoquinolines may be transformed to neurotoxic N-methylated tetrahydroisoquinolines. These neurotoxic compounds were observed in cerebrospinal fluid and plasma of long-term LD-treated PD patients. They have a structure similar to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine or its ion 1-methyl-4-phenylpyridinium, both of which are known to induce PD-like motor symptoms.
Quality and use of trauma histories obtained from psychiatric outpatients through mandated inquiry.

OBJECTIVE A growing awareness of the sequelae of trauma has prompted clinical and administrative mandates that psychiatric assessments must include inquiry about whether patients have experienced trauma or abuse. This study was designed to assess how a trauma history obtained through mandated inquiry is recorded and how it is used in diagnostic formulation and treatment planning. METHODS Histories of physical and sexual abuse and other trauma were reviewed in the charts of 180 outpatients receiving psychotherapy at an urban teaching hospital clinic. The extent and variety of traumatic experiences and the quality of clinicians' assessment of trauma histories were measured by a rating instrument developed for the study. RESULTS Mandated inquiry led to the detection of histories of traumatic experiences for 72 patients (40 percent). The recognition of trauma did not trigger appropriate evaluation. Only 11 percent of clinicians mentioned posttraumatic stress disorder symptoms. Only one in ten charts of patients with histories of trauma contained diagnostic assessments or treatment plans that adequately incorporated the trauma history as a factor in the patient's presentation for treatment. CONCLUSIONS Although mandated inquiry led to the detection of substantial abuse and trauma, this information was rarely used in assessment and treatment planning. Implementation of mandated inquiry should be accompanied by relevant education and supervision to ensure that clinicians understand the diagnostic and treatment implications of past trauma.
A seed motif for target RNA capture enables efficient immune defence by a type III-B CRISPR-Cas system

ABSTRACT CRISPR-Cas systems provide an adaptive defence against foreign nucleic acids guided by small RNAs (crRNAs) in archaea and bacteria. The Type III CRISPR systems are reported to carry RNase, RNA-activated DNase and cyclic oligoadenylate (cOA) synthetase activity, and are significantly different from other CRISPR systems. However, detailed features of target recognition, which are essential for enhancing target specificity remain unknown in Type III CRISPR systems. Here, we show that the Type III-B Cmr-α system in S. islandicus generates two constant lengths of crRNA independent of the length of the spacer. Either mutation at the 3ʹ-end of crRNA or target truncation greatly influences the target capture and cleavage by the Cmr-α effector complex. Furthermore, we found that cleavage at the tag-proximal site on the target RNA by the Cmr-α RNP complex is delayed relative to the other sites, which probably provides Cas10 more time to function as a guard against invaders. Using a mutagenesis assay in vivo, we discovered that a seed motif located at the tag-distal region of the crRNA is required by Cmr1α for target RNA capture by the Cmr-α system thereby enhancing target specificity and efficiency. These findings further refine the model for immune defence of Type III-B CRISPR-Cas system, commencing on capture, cleavage and regulation.
Measurement of arterial stiffness and vascular aging in community pharmacies—The ASINPHAR@2action project

The ASINPHAR@2action project aims at raising awareness to arterial stiffness (AS) and early vascular aging (EVA) through a community pharmacy–based intervention. This preliminary analysis is focused on the analysis of the proportion of participants with increased AS and the identification of its main determinants. We performed an observational cross‐sectional study of participants enrolled in 11 community pharmacies in Portugal, between April and November 2017. Blood pressure (BP) and arterial function parameters were measured with a validated device. Clinical and demographic information was gathered, as well as the estimation of global cardiovascular risk, health‐related quality of life, and dietary profile. Cholesterol and glycaemia were taken from a recent laboratory bulletin. The cohort includes 658 participants with a mean age of 57.3 ± 16.3 years, 66% women. Brachial BP was 126.6 ± 16.4 mm Hg and 79.9 ± 11.5 mm Hg, and central BP was 115.8 ± 15.4 mm Hg and 81.2 ± 11.6 mm Hg, respectively, for systolic and diastolic BP. Mean pulse wave velocity (PWV) was 8.5 ± 2.3 m/s, and the augmentation index was 23.6 ± 15.6%. The proportion of participants with increased AS was 19.8%. The overall best‐fitting model for AS included age, gender, aortic PP, visceral fat, HDL cholesterol, AIx@75, total vascular resistance, hypertension, and diabetes, corresponding to an AUC of 0.910 (CI: 0.883, 0.937; P < 0.001) in the ROC curve analysis. The preliminary results of this pioneering large‐scale study measuring arterial function in community pharmacies provide the grounds for the operationalization of subclinical target organ damage screening in pharmacies, as a strategy to improve cardiovascular risk monitoring and to promote adherence to treatment.
The Effect of Endoplasmic Reticulum Stress on Neurotoxicity Caused by Inhaled Anesthetics

BACKGROUND: The mechanisms by which inhaled anesthetics cause neurotoxicity are not well clarified. Exposure to inhaled anesthetics induces a release of Ca2+ from the endoplasmic reticulum (ER) into the cytosol. Aberrant Ca2+ mobilization may alter the protein-folding environment in the ER, causing ER stress. Binding immunoglobulin protein (BiP) is an ER chaperone that is critical to ER functions. Because ER stress leads to cellular dysfunction and apoptotic cell death, leading to diverse human disorders such as neurodegenerative diseases, we hypothesized ER stress may play a role in neurotoxicity caused by inhaled anesthetics. METHODS: We investigated the relationship between ER stress and neurodegeneration caused by inhaled anesthetics by using knock-in mice expressing a mutant BiP and neuronal culture cells. Neuronal culture cells and mutant BiP pregnant mice were exposed to 3% sevoflurane. The levels of BiP and C/EBP homologous protein (CHOP), a transcription factor related to cell death during ER stress, were evaluated by Western blot in neuronal cells and fetal brains delivered by cesarean delivery. Cell death in the fetal brains was evaluated with TUNEL staining. Statistical significance was assessed using unpaired t test and analysis of variance followed by multiple comparison tests. RESULTS: Sevoflurane exposure enhanced the expression of BiP and CHOP significantly in neuronal culture cells. A chemical chaperone that assisted ER functions reduced the expression of CHOP induced by sevoflurane exposure. In an in vivo study, we observed that an enhanced expression of CHOP and significantly more apoptotic cells in the brains of homozygous mutant BiP fetuses compared with the wild type. Mouse embryonic fibroblasts derived from the mutant BiP mice also exhibited enhanced levels of CHOP and cleaved caspase-3 after sevoflurane exposure. CONCLUSIONS: Sevoflurane exposure may cause ER stress, which is tolerated to some extent in wild-type cells. When this tolerance is limited, like in cells with mutant BiP, the exposure leads to cell death in the brain, suggesting that ER stress may partially mediate neurotoxicity caused by inhaled anesthetics. This study suggests that patients with certain conditions sensitive to ER stress such as ischemia, hypoxia, developing brain, or neurodegenerative diseases may be vulnerable to inhaled anesthetics.
Evaluation of Neuroanatomy Web Resources for Undergraduate Education: Educators’ and Students’ Perspectives

Despite the development of novel teaching strategies and the abundance of adjunct teaching web resources, students and early career physicians have continuously reported difficulties in learning and clinically applying neuroanatomy. Differences in instructional design of these resources, the lack of assessment of their capacity to meet intended educational goals, and a poor understanding of the user’s perspective may have hindered their success in increasing understanding and retention of neuroanatomical knowledge. To decipher the limitations of existing web resources, an online search for neuroanatomy web resources was performed and distilled through a strict filtration rubric. A selection of resources were analyzed by a panel of educators and rated using Likert scales, focusing on the identification of features influencing their usefulness in learning the anatomy of the spinal pathways. The top three ranked web resources were subsequently evaluated by a panel of medical and neuroscience students to assess how specific features aided in their learning of the subject. This detailed analysis has identified features of neuroanatomy web resources that are valued by both educators and users with regard to instructional design. One resource was rated highest by end users and educators on a series of Likert scale questions in terms of clarity of explanation, step‐wise teaching design, summarization of information, control of instructional‐pace, integration with neurophysiology, neuroradiology and clinical correlates, deployment of a wide array of pedagogical tools, and factors for visualizing neuroanatomical inter‐relationships. These results have provided a novel user perspective on the influence of specific elements of neuroanatomy web resources to improve instructional design and enhance learner performance.