Miracle-dz/UniFAR-FTUs huggingface dataset:
Diffuse Midline Gliomas with Histone H3‐K27M Mutation: A Series of 47 Cases Assessing the Spectrum of Morphologic Variation and Associated Genetic Alterations

Somatic mutations of the H3F3A and HIST1H3B genes encoding the histone H3 variants, H3.3 and H3.1, were recently identified in high‐grade gliomas arising in the thalamus, pons and spinal cord of children and young adults. However, the complete range of patients and locations in which these tumors arise, as well as the morphologic spectrum and associated genetic alterations remain undefined. Here, we describe a series of 47 diffuse midline gliomas with histone H3‐K27M mutation. The 25 male and 22 female patients ranged in age from 2 to 65 years (median = 14). Tumors were centered not only in the pons, thalamus, and spinal cord, but also in the third ventricle, hypothalamus, pineal region and cerebellum. Patients with pontine tumors were younger (median = 7 years) than those with thalamic (median = 24 years) or spinal (median = 25 years) tumors. A wide morphologic spectrum was encountered including gliomas with giant cells, epithelioid and rhabdoid cells, primitive neuroectodermal tumor (PNET)‐like foci, neuropil‐like islands, pilomyxoid features, ependymal‐like areas, sarcomatous transformation, ganglionic differentiation and pleomorphic xanthoastrocytoma (PXA)‐like areas. In this series, histone H3‐K27M mutation was mutually exclusive with IDH1 mutation and EGFR amplification, rarely co‐occurred with BRAF‐V600E mutation, and was commonly associated with p53 overexpression, ATRX loss (except in pontine gliomas), and monosomy 10.
An Institutional and Ecological Analysis of the Healthcare Environment in Korea: Focus on Institutional Logics, Actors, and Governance structures

【The primary goal of our study was to investigate the vast transformations of the healthcare sector in Korea during the past half century. Official data reported in the Korean statistical yearbooks and secondary data suggested by previous studies were used for institutional analysis of healthcare environment. Information on hospital released by the Korean Hospital Association was also used for ecological analysis. Institutional analysis: We identified three distinctive eras based primarily on changes in institutional logics, institutional actors, and governance structures : 'professional dominance (1952-1976)', 'government involvement (1977-1999)', and 'coexistence of competing institutional logics (2000-present)'. During the first era, physician association supported by Korean government comprised the primary governance regime. During the second era, the government became a major actor as a regulator and purchaser in health care sector, introducing of the 'mandatory national health insurance'. During the third era, making healthcare system sustainable and providing health care efficiently was overarching goals although it was hard to find a single central logic dominating this period. Ecological analysis: Evidence from the analysis of hospital population suggested that the expansion of the bed capacity was made from different processes, shifting from the ecological process in 1980s to the adaptive process in 1990s. And Korean hospitals had changed following both 'directional process' and 'stabilizing process' over time. Based on our results, we concluded that more studies to compare more organizational populations other than hospitals and to empirically test the effects of institutional changes on organizational changes and vice-versa, need to be conducted. 】
Relationship among Plasma Homocysteine, Folate, Vitamin B12 and Nutrient Intake and Neurocognitive Function in the Elderly

This study examined the relationship among plasma homocysteine, folate, and vitamin B12 levels and neurocognitive function in 118 community-dwelling elderly subjects (mean age, 75.1 ± 6.7 years). The Mini-Mental State Examination (MMSE-KC) was used to screen and assess neurocognitive function in the participants. Dietary intake data including the use of dietary supplements were obtained using the 24-hour recall method by well-trained interviewers. Plasma folate and vitamin B12 concentrations were analyzed by radioimmunoassay, and homocysteine was assessed by a high performance liquid chromatography-fluorescence method. The proportions of participants with suboptimal levels of plasma folate (＜ 3 ng/mL), vitamin B12 (＜ 221 pmol/mL), and homocysteine (＞ 15 μmol/L) were 16.1%, 5.9%, and 21.2%, respectively. A multiple regression analysis showed that plasma homocysteine was negatively associated with plasma folate and vitamin B12 levels. The MMSE-KC test scores were significantly associated with plasma homocysteine and fo late, but not with vitamin B12, after adjusting for age, gender, body mass index, living with spouse, education, current smoking, energy intake, and chronic diseases such as hypertension, diabetes, thyroid disease, dyslipidemia, stroke, and cardiovascular disease. A general linear model adjusted for covariates revealed that MMSE-KC test scores increased from the lowest to the highest quartiles of vitamin B1, vitamin B2, vitamin B6, vitamin B12, and vitamin C intake (p for trend = 0.012, 0.039, 0.014, 0.046, 0.026, respectively). These results indicate that the problem of folate inadequacy and hyperhomocysteinemia are highly prevalent among community-dwelling elderly people and that dietary intake of the B vitamins and vitamin C is positively associated with cognitive function scores. (Korean J Nutr 2011; 44(6): 498 ~ 506)
Midluteal Progesterone: A Marker of Treatment Outcomes in Couples With Unexplained Infertility

Context Adequate luteal phase progesterone exposure is necessary to induce endometrial changes required for a successful pregnancy outcome. The relationship between low midluteal progesterone concentration and the outcome of live birth in ovarian stimulation with intrauterine insemination (OS-IUI) treatments is not defined. Objective To determine the level of midluteal progesterone portending a low chance of live birth after OS-IUI in couples with unexplained infertility. Design and Setting Secondary analyses of data from a prospective, randomized, multicenter clinical trial that determined pregnancy outcomes following OS-IUI with clomiphene citrate, letrozole, or gonadotropins for couples with unexplained infertility. Participants Couples (n = 900) underwent 2376 OS-IUI cycles during the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation clinical trial. Main Outcome Measures Live birth as it relates to midluteal progesterone level and thresholds below which no live births occur by treatment group. Results Thresholds for non-live birth cycles were similar for clomiphene (14.4 ng/mL) and letrozole (13.1 ng/mL) yet were lower for gonadotropin (4.3 ng/mL) treatments. A midluteal progesterone level >10th percentile specific for each treatment group independently was associated with greater odds for a live birth in all OS-IUI cycles (adjusted OR: 2.17; 95% CI: 1.05, 4.48). Conclusions During OS-IUI, a low midluteal progesterone level was associated with a low probability of live birth. Thresholds differed by medication, with the lowest threshold for gonadotropin. Several pathophysiologic mechanisms may account for low progesterone levels. Refinement of the predictive range associated with particular ovarian stimulation medications during treatment of unexplained infertility may improve accuracy.
Exocytosis and Spreading of Normal and Aberrant α‐Synuclein

It is now established that α‐synuclein can be physiologically secreted to the extracellular space. In this sense, mechanisms that govern the secretion of the protein may be of importance in the initiation and progress of synucleinopathies. It is possible that increased secretion may aid the formation of toxic seeds extracellularly. Alternatively, reduced presence of extracellular α‐synuclein due to impaired secretion may increase the intracellular load and trigger intracellular seeding. Once outside, α‐synuclein can exert various paracrine actions on neighboring cells again by mechanisms that have not been fully elucidated. It has been demonstrated that, when applied extracellularly, α‐synuclein species can induce multiple neurotoxic and inflammatory responses, and aid the transmission of pathology between neurons. Still, the exact mechanism(s) by which secreted α‐synuclein affects the homeostasis of other neurons is still not well understood. A portion of α‐synuclein has been shown to be associated with the surface and lumen of exosomes which can transfer it to the surrounding cells, and potentially trigger seeding. Interestingly, increased exosome release has been linked to pathological situations of lysosomal dysfunction as observed in Parkinson's disease (PD). However, the possibility that the observed α‐synuclein pathology spread is attributable to the passive diffusion of the initial injected α‐synuclein strains cannot be excluded. Importantly, most of the studies that have so far addressed the role of extracellular α‐synuclein have not employed naturally secreted forms of the protein. It is plausible that deregulation in the normal processing of secreted α‐synuclein may aid the formation of “toxic” species and as such it may also be a causative risk factor for PD. In this capacity, elucidation of the underlying mechanisms that regulate the protein‐levels of extracellular α‐synuclein becomes essential. Such mechanisms could involve its proteolytic clearance from the extracellular milieu.
Cerebral Hypoperfusion and the Energy Deficit in Alzheimer's Disease

There is a perfusion deficit in Alzheimer's disease (AD), commencing in the precuneus and spreading to other parts of the cerebral cortex. The deficit anticipates the development of dementia, contributes to brain damage, and is caused by both functional and structural abnormalities of the cerebral vasculature. Most of the abnormalities are probably secondary to the accumulation of Aβ but the consequent hypoperfusion may, in turn, increase Aβ production. In the early stages of disease, abnormalities that cause vasoconstriction predominate. These include cholinergic vascular denervation, inhibition of endothelial nitric oxide synthase, increased production of endothelin‐1 production and possibly also of angiotensin II. Patients with AD also have an increased prevalence of structural disease of cerebral microvessels, particularly CAA and capillary damage, and particularly in the later stages of disease these are likely to make an important contribution to the cerebral hypoperfusion. The metabolic abnormalities that cause early vascular dysfunction offer several targets for therapeutic intervention. However, for intervention to be effective it probably needs to be early. Prolonged cerebral hypoperfusion may induce compensatory circulatory changes that are themselves damaging, including hypertension and small vessel disease. This has implications for the use of antihypertensive drugs once there is accumulation of Aβ within the brain.
Effect of an exercise program on risk factors of falls in elderly women

The aim of this study was to verify the benefits of an exercise program on functional capacity and balance in elderly community. A longitudinal study was conducted with 11 female subjects with mean age 77 (SD = 13) years. All individuals were evaluated at the beginning and at the end of the study by 'Berg' Balance Scale and 'Timed Up and Go' Test. Initially, the participants answered a questionnaire about the socio-demographics aspects, health conditions, falls and physical activity practice. Then, the subjects were submitted to a program of exercises for balance, strengthening and stretching muscles. The results of the 'Berg' Scale ranged from 46 to 56 points before the intervention, and from 50 to 56, after the intervention (p = 0.01). Individuals older than 75 years old had a better improvement (p = 0.04). In the 'Timed Up and Go' Test the percentage of improvement was 8.2% ( = 13.1; SD= 11.7). The exercise program showed a positive effect in improving risk factors of falls in the elderly community.
Stratification of astrocytes in healthy and diseased brain

Astrocytes, a subtype of glial cells, come in variety of forms and functions. However, overarching role of these cell is in the homeostasis of the brain, be that regulation of ions, neurotransmitters, metabolism or neuronal synaptic networks. Loss of homeostasis represents the underlying cause of all brain disorders. Thus, astrocytes are likely involved in most if not all of the brain pathologies. We tabulate astroglial homeostatic functions along with pathological condition that arise from dysfunction of these glial cells. Classification of astrocytes is presented with the emphasis on evolutionary trails, morphological appearance and numerical preponderance. We note that, even though astrocytes from a variety of mammalian species share some common features, human astrocytes appear to be the largest and most complex of all astrocytes studied thus far. It is then an imperative to develop humanized models to study the role of astrocytes in brain pathologies, which is perhaps most abundantly clear in the case of glioblastoma multiforme.
5‐Chloroindole: a potent allosteric modulator of the 5‐HT3 receptor

The 5‐HT3 receptor is a ligand‐gated ion channel that is modulated allosterically by various compounds including colchicine, alcohols and volatile anaesthetics. However the positive allosteric modulators (PAMs) identified to date have low affinity, which hinders investigation because of non‐selective effects at pharmacologically active concentrations. The present study identifies 5‐chloroindole (Cl‐indole) as a potent PAM of the 5‐HT3 receptor.
Oral Appliances for the Treatment of Snoring and Obstructive Sleep Apnea

Background: Removable oral appliances are employed to treat obstructive sleep apnea and snoring. In this review we summarize the current state of the art of this therapy. Methods: We performed a systematic review of the medical literature on the effectiveness, side effects and practical aspects of oral appliance therapy for sleep-disordered breathing. Results: Several randomized, controlled trials demonstrate the improvement of symptoms and sleep-related breathing disturbances in obstructive sleep apnea and snoring by oral appliances that advance the mandible. Side effects are common but usually transient and rarely severe. Conclusions: Mandibular advancement devices are a valuable treatment modality for obstructive sleep apnea and snoring. Dental and medical examinations at regular intervals and polysomnographic follow-up are important during long-term treatment to avoid potential adverse effects and to assure continued effectiveness.
Sex‐based differences in cardiac ischaemic injury and protection: therapeutic implications

Ischaemic heart disease (IHD) is the most frequent cause of mortality among men and women. Many epidemiological studies have demonstrated that premenopausal women have a reduced risk for IHD compared with their male counterparts. The incidence of IHD in women increases after menopause, suggesting that IHD is related to declining oestrogen levels. Experimental observations have confirmed the results of epidemiological studies investigating sex‐specific differences in cardiac tolerance to ischaemia. Female sex appears also to favourably influence cardiac remodelling after ischaemia/reperfusion injury. Furthermore, sex‐related differences in ischaemic tolerance of the adult myocardium can be influenced by interventions during the early phases of ontogenetic development. Detailed mechanisms of these sex‐related differences remain unknown; however, they involve the genomic and non‐genomic effects of sex steroid hormones, particularly the oestrogens, which have been the most extensively studied. Although the protective effects of oestrogen have many potential therapeutic implications, clinical trials have shown that oestrogen replacement in postmenopausal women may actually increase the incidence of IHD. The results of these trials have illustrated the complexity underlying the mechanisms involved in sex‐related differences in cardiac tolerance to ischaemia. Sex‐related differences in cardiac sensitivity to ischaemia/reperfusion injury may also influence therapeutic strategies in women with acute coronary syndrome. Women undergo coronary intervention less frequently and a lower proportion of women receive evidence‐based therapy compared with men. Although our understanding of this important topic has increased in recent years, there is an urgent need for intensive experimental and clinical research to develop female‐specific therapeutic strategies. Only then we will be able to offer patients better evidence‐based treatment, a better quality of life and lower mortality.
Comparison of ultra‐fast 2D and 3D ligand and target descriptors for side effect prediction and network analysis in polypharmacology

Some existing computational methods are used to infer protein targets of small molecules and can therefore be used to find new targets for existing drugs, with the goals of re‐directing the molecule towards a different therapeutic purpose or explaining off‐target effects due to multiple targeting. Inherent limitations, however, arise from the fact that chemical analogy is calculated on the basis of common frameworks or scaffolds and also because target information is neglected. The method we present addresses these issues by taking into account 3D information from both the ligand and the target.
Does female disadvantage mean lower access to food

The literature on gender differentials in nutrition demonstrates that the calorie intake of females is generally as adequate as that of males at all ages. Female disadvantage in micronutrient intake is, however, frequent. Pregnant and lactating women are disadvantaged relative to both men and other women. In South Asia there is evidence that boys are advantaged over girls in food intake at some ages, but the evidence for male advantage in access to health care is far stronger. The authors argue that nutrition interventions are best targeted when the incidence of female disadvantage is better understood and, similarly, that interventions to improve women's status should be focused on objectives other than calorie intake in most communities. However, standards for measuring adequacy incorporate norms for female body size and physical activity that may uncritically accept the notion that females are more physically passive. Maintaining adequacy by these standards could perpetuate low levels of female functioning.
Engendering biased signalling from the calcium‐sensing receptor for the pharmacotherapy of diverse disorders

The human calcium‐sensing receptor (CaSR) is widely expressed in the body, where its activity is regulated by multiple orthosteric and endogenous allosteric ligands. Each ligand stabilizes a unique subset of conformational states, which enables the CaSR to couple to distinct intracellular signalling pathways depending on the extracellular milieu in which it is bathed. Differential signalling arising from distinct receptor conformations favoured by each ligand is referred to as biased signalling. The outcome of CaSR activation also depends on the cell type in which it is expressed. Thus, the same ligand may activate diverse pathways in distinct cell types. Given that the CaSR is implicated in numerous physiological and pathophysiological processes, it is an ideal target for biased ligands that could be rationally designed to selectively regulate desired signalling pathways in preferred cell types.
Designing, developing, and testing a mobile health reservation system in the Egyptian context

The main subject of the research study is the implementation of m-health reservation system at the Arab Academy for Science, Technology and Maritime Transport (AASTMT), Egypt. The AASTMT was selected as a case university that offers health services to both staff members and students. The proposed system is based on the current electronic medical records of the academy’s staff at the clinic. The study tries to answer the research question: ‘What are the main usability problems that affect user experience with regards to m-health reservation system? ’ In order to answer the research question, usability test was developed and tested on two phases, where respondents were asked to actually reserve an appointment at the academy’s clinic and to perform typical tasks using an iPhone 3G. The experimental evaluation was carried out at a controlled laboratory environment. The experiment was recorded, analysed, and conclusions were derived.
Investigation of connexin 43 uncoupling and prolongation of the cardiac QRS complex in preclinical and marketed drugs

Prolongation of the cardiac QRS complex is linked to increased mortality and may result from drug‐induced inhibition of cardiac sodium channels (hNaV1.5). There has been no systematic evaluation of preclinical and marketed drugs for their additional potential to cause QRS prolongation via gap junction uncoupling.
Composition of the bacterial biota in slime developed in two machines at a Canadian paper mill.

During the process of papermaking by pulp and paper plants, a thick and viscous deposits, termed slime, is quickly formed around the paper machines, which can affect the papermaking process. In this study, we explored the composition of the bacterial biota in slime that developed on shower pipes from 2 machines at a Canadian paper mill. Firstly, the composition was assessed for 12 months by DNA profiling with polymerase chain reaction coupled with denaturing gradient gel electrophoresis. Except for short periods (2-3 months), clustered analyses showed that the bacterial composition of the slime varied substantially over the year, with less than 50% similarity between the denaturing gradient gel electrophoresis profiles. Secondly, the screening of 16S rRNA gene libraries derived from 2 slime samples showed that the most abundant bacteria were related to 6 lineages, including Chloroflexi, candidate division OP10, Clostridiales, Bacillales, Burkholderiales, and the genus Deinococcus. Finally, the proportion of 8 bacterial lineages, such as Deinococcus sp. , Meiothermus sp. , and Chloroflexi, was determined by the Catalyzed Reporter Deposition-Fluorescence In Situ Hybridization in 2 slime samples. The results showed a high proportion of Chloroflexi, Tepidimonas spp. , and Schlegelella spp. in the slime samples.
Survey of Upper-Extremity Prosthesis Users in Sweden and the United Kingdom

A sample of 156 users of upper-limb prostheses from three fitting centers in Sweden and the United Kingdom participated in a survey that focused on user satisfaction. The survey was conducted via postal questionnaire. It included questions to record demographic data and prostheses type and usage. Respondents were asked to assess their level of satisfaction with their prostheses and were invited to comment on potential improvements to their current devices. The sample was heterogeneous with respect to the type of limb loss, principle type of prosthesis, and subject gender and age. Ratings of comfort, cosmetics, function, and maintenance revealed a high level of satisfaction with the current generation of prostheses. Separate analysis of responses from users of cosmetic and electric prostheses showed that both groups are concerned about the prostheses’ appearance. Users of electric prostheses particularly expressed a desire for improved functionality. Respondents requested lighter, more reliable and more anthropomorphic devices, quiet operation, wide range of grip shapes, and intuitive control.