Takshan/R1 huggingface dataset:
Spatial panorama of malaria prevalence in Africa under climate change and interventions scenarios.

BACKGROUND: Malaria is highly sensitive to climatic variables and is strongly influenced by the presence of vectors in a region that further contribute to parasite development and sustained disease transmission. Mathematical analysis of malaria transmission through the use and application of the value of the basic reproduction number (R0) threshold is an important and useful tool for the understanding of disease patterns. METHODS: Temperature dependence aspect of R0 obtained from dynamical mathematical network model was used to derive the spatial distribution maps for malaria transmission under different climatic and intervention scenarios. Model validation was conducted using MARA map and the Annual Plasmodium falciparum Entomological Inoculation Rates for Africa. RESULTS: The inclusion of the coupling between patches in dynamical model seems to have no effects on the estimate of the optimal temperature (about 25 °C) for malaria transmission. In patches environment, we were able to establish a threshold value (about α = 5) representing the ratio between the migration rates from one patch to another that has no effect on the magnitude of R0. Such findings allow us to limit the production of the spatial distribution map of R0 to a single patch model. Future projections using temperature changes indicated a shift in malaria transmission areas towards the southern and northern areas of Africa and the application of the interventions scenario yielded a considerable reduction in transmission within malaria endemic areas of the continent. CONCLUSIONS: The approach employed here is a sole study that defined the limits of contemporary malaria transmission, using R0 derived from a dynamical mathematical model. It has offered a unique prospect for measuring the impacts of interventions through simple manipulation of model parameters. Projections at scale provide options to visualize and query the results, when linked to the human population could potentially deliver adequate highlight on the number of individuals at risk of malaria infection across Africa. The findings provide a reasonable basis for understanding the fundamental effects of malaria control and could contribute towards disease elimination, which is considered as a challenge especially in the context of climate change.
Seizures and disturbed brain potassium dynamics in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts.

OBJECTIVE: Loss of function of the astrocyte-specific protein MLC1 leads to the childhood-onset leukodystrophy "megalencephalic leukoencephalopathy with subcortical cysts" (MLC). Studies on isolated cells show a role for MLC1 in astrocyte volume regulation and suggest that disturbed brain ion and water homeostasis is central to the disease. Excitability of neuronal networks is particularly sensitive to ion and water homeostasis. In line with this, reports of seizures and epilepsy in MLC patients exist. However, systematic assessment and mechanistic understanding of seizures in MLC are lacking. METHODS: We analyzed an MLC patient inventory to study occurrence of seizures in MLC. We used two distinct genetic mouse models of MLC to further study epileptiform activity and seizure threshold through wireless extracellular field potential recordings. Whole-cell patch-clamp recordings and K+ -sensitive electrode recordings in mouse brain slices were used to explore the underlying mechanisms of epilepsy in MLC. RESULTS: An early onset of seizures is common in MLC. Similarly, in MLC mice, we uncovered spontaneous epileptiform brain activity and a lowered threshold for induced seizures. At the cellular level, we found that although passive and active properties of individual pyramidal neurons are unchanged, extracellular K+ dynamics and neuronal network activity are abnormal in MLC mice. INTERPRETATION: Disturbed astrocyte regulation of ion and water homeostasis in MLC causes hyperexcitability of neuronal networks and seizures. These findings suggest a role for defective astrocyte volume regulation in epilepsy. Ann Neurol 2018;83:636-649.
Seasonal Incidence of Acute Coronary Syndrome and Its Features.

Introduction: Acute coronary syndrome (ACS) is one of the most common health problems in the world and the leading cause of death. Goal: The goals of this study are to determine: ACS type, risk factors, incidence and the seasonal distribution of occurrence Spring/Summer, Autumn/Winter, ACS incidence by age and gender, and complications (post-infarction angina and heart failure) and fatal outcomes of ACS per season. Material and methodology: This study is designed as retrospective-prospective and analytical, which included 250 patients hospitalized in the Intensive Cardiac care unit of the Clinic for heart disease, blood vessels and rheumatism in the period from June 2013 to July 2014. It was assumed that there is the influence of the seasons on the incidence and characteristics of ACS. Material used were the medical records and data from the history of illness. Results: The most common type of ACS was ST elevation myocardial infarction (STEMI), without statistical significant difference between seasons. Presence of risk factors is not significantly different between seasons, with the hypertension as the most common risk factor for ACS during both seasons. The highest incidence of ACS was recorded in December during the winter season, while the lowest incidence was recorded in March. The occurrence of ACS during the Spring/Summer, Autumn/Winter was different according to age, with more frequent occurrence of ACS in older patients during the winter months. ACS complications (postinfaction angina and cardiac insufficiency) were also statistically different between seasons (p=0.048). Fatal ACS is more often recorded during the season Autumn/Winter compared to Spring/Summer season (p=0.001). Conclusion: The results suggest seasonal meteorological impact on the incidence, complications and outcomes of ACS, so there is a necessity that patients adapt their lifestyle and health professionals to improve the ACS treatment.
Emerging variants of methicillin-resistant Staphylococcus aureus genotypes in Kuwait hospitals.

BACKGROUND: Frequent changes in the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) occurring worldwide demand regular surveillance to study their composition and distribution in healthcare facilities. We investigated the genotypic characteristics of MRSA obtained in Kuwait hospitals to better understand their clonal distribution. MATERIALS AND METHODS: A total of 1,327 MRSA isolates obtained from clinical samples in 13 Kuwait hospitals from 1 January to 31 December 2016 were investigated using antibiogram, SCCmec typing, spa typing and DNA microarray. RESULTS: The isolates belonged to six SCCmec types with the majority belonging to type IV (658; 49.5%) and type V (355; 26.7%). Two hundred and sixty-one spa types were identified with spa types t688, t304, t860, t127, t044, t311, t002, t223, t267, t019, t3841, t005, t084, t852, and t657 constituting 51.0% (n = 677) of the isolates. Among the 1,327 MRSA isolates, 102 (7.68%) isolates were identified as novel variants of internationally recognized MRSA clones. These 102 isolates were investigated further and belonged to 14 clonal complexes (CCs) with CC361 (32; 32.3%), CC30 (15; 14.7%), CC22 (13; 12.7%) and CC1 (11, 10.7%) as the dominant CCs. Eighty-one (79.4%) of the novel isolates harbored SCCmec IV or V+fusC composite genetic elements. Four isolates (3.9%) harbored unusual combinations of ccr and mec complexes comprising of CC6-MRSA [IV+fusC+ccrC], CC97-MRSA [V/VT+fusC+ccrAB2], CC121-MRSA [V/VT+fusC+ccrB4] and CC1-MRSA-pseudoSCCmec [class B mec+fusc+ccrAB1]. Forty-six (45.1%) of these isolates were positive for PVL and 89 (87.2%) were resistant to fusidic acid mediated by fusC. CONCLUSIONS: The study showed the emergence of novel variants of previously recognized MRSA genotypes with unusual genetic characteristics including high prevalence of PVL and fusidic acid resistance in Kuwait hospitals. This has added to the dynamic lists of known variations in MRSA genomes which can impose serious challenges for infection control and treatment of MRSA infections.
The presence of human mesenchymal stem cells of renal origin in amniotic fluid increases with gestational time.

BACKGROUND: Established therapies for managing kidney dysfunction such as kidney dialysis and transplantation are limited due to the shortage of compatible donated organs and high costs. Stem cell-based therapies are currently under investigation as an alternative treatment option. As amniotic fluid is composed of fetal urine harboring mesenchymal stem cells (AF-MSCs), we hypothesized that third-trimester amniotic fluid could be a novel source of renal progenitor and differentiated cells. METHODS: Human third-trimester amniotic fluid cells (AFCs) were isolated and cultured in distinct media. These cells were characterized as renal progenitor cells with respect to cell morphology, cell surface marker expression, transcriptome and differentiation into chondrocytes, osteoblasts and adipocytes. To test for renal function, a comparative albumin endocytosis assay was performed using AF-MSCs and commercially available renal cells derived from kidney biopsies. Comparative transcriptome analyses of first, second and third trimester-derived AF-MSCs were conducted to monitor expression of renal-related genes. RESULTS: Regardless of the media used, AFCs showed expression of pluripotency-associated markers such as SSEA4, TRA-1-60, TRA-1-81 and C-Kit. They also express the mesenchymal marker Vimentin. Immunophenotyping confirmed that third-trimester AFCs are bona fide MSCs. AF-MSCs expressed the master renal progenitor markers SIX2 and CITED1, in addition to typical renal proteins such as PODXL, LHX1, BRN1 and PAX8. Albumin endocytosis assays demonstrated the functionality of AF-MSCs as renal cells. Additionally, upregulated expression of BMP7 and downregulation of WT1, CD133, SIX2 and C-Kit were observed upon activation of WNT signaling by treatment with the GSK-3 inhibitor CHIR99201. Transcriptome analysis and semiquantitative PCR revealed increasing expression levels of renal-specific genes (e.g., SALL1, HNF4B, SIX2) with gestational time. Moreover, AF-MSCs shared more genes with human kidney cells than with native MSCs and gene ontology terms revealed involvement of biological processes associated with kidney morphogenesis. CONCLUSIONS: Third-trimester amniotic fluid contains AF-MSCs of renal origin and this novel source of kidney progenitors may have enormous future potentials for disease modeling, renal repair and drug screening.
Identifying the best sleep measure to screen clinical insomnia in a psychiatric population.

BACKGROUND: Insomnia symptoms are highly prevalent among patients with psychiatric disorders, and this mandates the need to identify the best self-administered sleep measure to screen for clinical insomnia among them. METHODS: A total of 400 psychiatric outpatients completed the Pittsburgh Sleep Quality Index, Insomnia Severity Index (ISI), Epworth Sleepiness Scale, Flinders Fatigue Scale, Functional Outcomes of Sleep Questionnaire, and Dysfunctional Beliefs and Attitudes about Sleep Scale in a cross-sectional study. The sensitivity, specificity, positive, and negative predictive values of these six sleep scales were assessed and compared in relation to both ICD-10 and DSM-5 insomnia disorder status established using the interviewer-administered Brief Insomnia Questionnaire. RESULTS: Receiver operator characteristic curves with the area under the curve (AUC) revealed the ISI to be the most accurate measure to discriminate cases and non-cases on both ICD-10 (AUC = 0.88, 95% CI = 0.84-0.92) and DSM-5 (AUC = 0.82, 95% CI = 0.78-0.86) criteria with "good" accuracy. The cut-off scores of ≥14 and ≥ 11 for the ISI provided optimal sensitivity and specificity for the detection of ICD-10 and DSM-5 insomnia, respectively. DISCUSSION: With the new calling from DSM-5 to treat sleep symptoms in the presence of a co-existing mental condition, early detection of psychiatric patients with clinically significantly insomnia using a simple but accurate self-report sleep measure becomes important. Our study suggests that the ISI could be used as a potential screening tool for comorbid insomnia disorder in patients with mental disorders.
Association of seasonal viral acute respiratory infection with pneumococcal disease: a systematic review of population-based studies.

OBJECTIVE: Animal and in vitro studies suggest that viral acute respiratory infection (VARI) can predispose to pneumococcal infection. These findings suggest that the prevention of VARI can yield additional benefits for the control of pneumococcal disease (PD). In population-based studies, however, the evidence is not in accordance, possibly due to a variety of methodological challenges and problems in these studies. We aimed to summarise and critically review the methods and results from these studies in order to inform future studies. METHODS: We conducted a systematic review of population-based studies that analysed the association between preceding seasonal VARI and subsequent PD. We searched MEDLINE, Embase and Global Health databases using tailored search strategies. RESULTS: A total of 28 studies were included. After critically reviewing the methodologies and findings, 11 studies did not control for seasonal factors shared by VARI and PD. This, in turn, could lead to an overestimation of the association between the two illnesses. One case-control study was limited by its small sample size (n case=13). The remaining 16 studies that controlled for seasonal factors suggested that influenza and/or respiratory syncytial virus (RSV) infections were likely to be associated with the subsequent occurrence of PD (influenza: 12/14 studies; RSV: 4/5 studies). However, these 16 studies were unable to conduct individual patient data-based analyses. Nevertheless, these studies suggested the association between VARI and subsequent PD was related to additional factors such as virus type and subtype, age group, comorbidity status, presentation of PD and pneumococcal serotype. CONCLUSIONS: Population-based studies do not give consistent support for an association between preceding seasonal VARI and subsequent PD incidence. The main methodological challenges of existing studies include the failure to use individual patient data, control for seasonal factors of VARI and PD, or include other factors related to the association (eg, virus, age, comorbidity and pneumococcal serotype).
Culture bag systems for clinical applications of adult human neural crest-derived stem cells.

INTRODUCTION: Facing the challenging treatment of neurodegenerative diseases as well as complex craniofacial injuries such as those common after cancer therapy, the field of regenerative medicine increasingly relies on stem cell transplantation strategies. Here, neural crest-derived stem cells (NCSCs) offer many promising applications, although scale up of clinical-grade processes prior to potential transplantations is currently limiting. In this study, we aimed to establish a clinical-grade, cost-reducing cultivation system for NCSCs isolated from the adult human nose using cGMP-grade Afc-FEP bags. METHODS: We cultivated human neural crest-derived stem cells from inferior turbinate (ITSCs) in a cell culture bag system using Afc-FEP bags in human blood plasma-supplemented medium. Investigations of viability, proliferation and expression profile of bag-cultured ITSCs were followed by DNA-content and telomerase activity determination. Cultivated ITSCs were introduced to directed in vitro differentiation assays to assess their potential for mesodermal and ectodermal differentiation. Mesodermal differentiation was determined using an enzyme activity assay (alkaline phosphatase, ALP), respective stainings (Alizarin Red S, Von Kossa and Oil Red O), and RT-PCR, while immunocytochemistry and synaptic vesicle recycling were applied to assay neuroectodermal differentiation of ITSCs. RESULTS: When cultivated within Afc-FEP bags, ITSCs grew three-dimensionally in a human blood plasma-derived matrix, thereby showing unchanged morphology, proliferation capability, viability and expression profile in comparison to three dimensionally-cultured ITSCs growing in standard cell culture plastics. Genetic stability of bag-cultured ITSCs was further accompanied by unchanged telomerase activity. Importantly, ITSCs retained their potential to differentiate into mesodermal cell types, particularly including ALP-active, Alizarin Red S-, and Von Kossa-positive osteogenic cell types, as well as adipocytes positive in Oil Red O assays. Bag culture further did not affect the potential of ITSCs to undergo differentiation into neuroectodermal cell types coexpressing β-III-tubulin and MAP2 and exhibiting the capability for synaptic vesicle recycling. CONCLUSIONS: Here, we report for the first time the successful cultivation of human NCSCs within cGMP-grade Afc-FEP bags using a human blood plasma-supplemented medium. Our findings particularly demonstrate the unchanged differentiation capability and genetic stability of the cultivated NCSCs, suggesting the great potential of this culture system for future medical applications in the field of regenerative medicine.
Core elements to understand and improve coping with Parkinson's disease in patients and family carers: A focus group study.

AIMS: The aim of this study were: (1) To explore the meaning that coping with Parkinson's disease has for patients and family carers; (2) To suggest the components of an intervention focused on enhancing their coping with the disease. BACKGROUND: Adapting to Parkinson's disease involves going through many difficult changes; however, it may improve quality of life in patients and family carers. One of the key aspects for facilitating the psychosocial adjustment to Parkinson's disease is the strengthening of coping skills. DESIGN: A sequential explanatory mixed methods study was carried out. Findings from the qualitative phase are presented. METHODS: Data were collected in May 2014 through three focus groups: one of people with Parkinson's disease (n = 9), one of family carers (n = 7) and one of healthcare professionals (n = 5). All focus groups were digitally recorded and transcribed verbatim and content analysis was independently carried out by two researchers. FINDINGS: The participants coincided in highlighting that coping with Parkinson's disease helped the patient and the family carer in their search for balance; and it implied a transformation in their lives. To aid the process of coping with Parkinson's disease, a multifaceted intervention is proposed. CONCLUSION: Coping with Parkinson's disease is a complex process for both patients and family carers and it should therefore be considered a standard service in healthcare policies aimed at this group. The proposed intervention constitutes a nursing tool which has great potential to improve the quality of life in Parkinson's disease and in other long-term conditions.
Interventions and working relationships of voluntary organisations for diabetes self-management: A cross-national study.

BACKGROUND: Diabetes has become a challenging health priority globally. Given the tensions of financially burdened health systems in Europe the mobilisation of community resources like voluntary organisations and community groups is seen as a health policy strategy to sustain the management of long-term conditions like diabetes. However, little is known about how this is happening in practice in Europe. OBJECTIVES: To explore diabetes self-management interventions undertaken or promoted by voluntary organisations and community groups in Europe; and describe the types of working relationships between these organisations, European health systems and users when implementing diabetes self-management programmes in different areas. DESIGN: A mixed method study (survey/qualitative interviews) was undertaken. This research formed part of a European project (7th Framework programme of the European Commission) exploring the link between resources, like community organisations, and peoples' capacities to manage long-term conditions. SETTINGS: Six European countries (Bulgaria, Greece, Norway, Spain, the Netherlands and the United Kingdom) participated in the study. Three areas: deprived urban area, a relatively affluent urban area and a deprived rural area were purposefully selected. PARTICIPANTS: Through a purposeful sample and bottom up strategies 749 representatives of voluntary organisations and community groups were recruited from the geographical areas above. Organisations with at least three members, existing for at least one year that could provide information or other type of support directly or indirectly relevant to patients with diabetes were included. METHODS: Participants completed a 15 item questionnaire for the survey (n=749) and a voice recorded semi structured interview (n=300). Data collection focused on the type of activities and roles developed to promote health, and relationships and communication channels between organisations, health services and users. Descriptive and comparative statistical and qualitative content analyses were used. RESULTS: Participants perceived they had better reach of people with health needs than health providers, filled the administration gaps left in their capacity to deal with basic diabetes practical needs, humanized care, and acted as mediators between services and communities. There were significant differences between countries in relation to the types of activities (p-value<0.001), roles (p-value<0.001) and funding sources (p-value<0.001) of organisations concerning diabetes self-management. In non-affluent countries organisations tend to promote social activities twice more often. CONCLUSIONS: Community and voluntary organisations provide complimentary and on-going support in diabetes management. This involves a shift from focusing on the illness to also longing for social cohesion, sense of community and wellbeing in diabetes health practices and policies.
Landmark-based evaluation of a deformable motion correction for DCE-MRI of the liver.

PURPOSE: Annotation of meaningful landmark ground truth on DCE-MRI is difficult and laborious. Motion correction methods applied to DCE-MRI of the liver are thus mostly evaluated using qualitative or indirect measures. We propose a novel landmark annotation scheme that facilitates the generation of landmark ground truth on larger clinical datasets. METHODS: In our annotation scheme, landmarks are equally distributed over all time points of all available dataset cases and annotated by multiple observers on a per-pair basis. The scheme is used to annotate 26 DCE-MRI of the liver. A subset of the ground truth is used to optimize parameters of a deformable motion correction. Several variants of the motion correction are evaluated on the remaining cases with respect to distances of corresponding landmarks after registration, deformation field properties, and qualitative measures. RESULTS: A landmark ground truth on 26 cases could be generated in under 12 h per observer with a mean inter-observer distance below the mean voxel diagonal. Furthermore, the landmarks are spatially well distributed within the liver. Parameter optimization significantly improves the performance of the motion correction, and landmark distance after registration is 2 mm. Qualitative evaluation of the motion correction reflects the quantitative results. CONCLUSIONS: The annotation scheme makes a landmark-based evaluation of motion corrections for hepatic DCE-MRI practically feasible for larger clinical datasets. The comparably large number of cases enables both optimization and evaluation of motion correction methods.