Miracle-dz/UniFAR-FTUs huggingface dataset:
Diffeomorphic susceptibility artifact correction of diffusion-weighted magnetic resonance images

Diffusion-weighted magnetic resonance imaging is a key investigation technique in modern neuroscience. In clinical settings, diffusion-weighted imaging and its extension to diffusion tensor imaging (DTI) are usually performed applying the technique of echo-planar imaging (EPI). EPI is the commonly available ultrafast acquisition technique for single-shot acquisition with spatial encoding in a Cartesian system. A drawback of these sequences is their high sensitivity against small perturbations of the magnetic field, caused, e.g., by differences in magnetic susceptibility of soft tissue, bone and air. The resulting magnetic field inhomogeneities thus cause geometrical distortions and intensity modulations in diffusion-weighted images. This complicates the fusion with anatomical T1- or T2-weighted MR images obtained with conventional spin- or gradient-echo images and negligible distortion. In order to limit the degradation of diffusion-weighted MR data, we present here a variational approach based on a reference scan pair with reversed polarity of the phase- and frequency-encoding gradients and hence reversed distortion. The key novelty is a tailored nonlinear regularization functional to obtain smooth and diffeomorphic transformations. We incorporate the physical distortion model into a variational image registration framework and derive an accurate and fast correction algorithm. We evaluate the applicability of our approach to distorted DTI brain scans of six healthy volunteers. For all datasets, the automatic correction algorithm considerably reduced the image degradation. We show that, after correction, fusion with T1- or T2-weighted images can be obtained by a simple rigid registration. Furthermore, we demonstrate the improvement due to the novel regularization scheme. Most importantly, we show that it provides meaningful, i.e. diffeomorphic, geometric transformations, independent of the actual choice of the regularization parameters.
Is it safe to use lamotrigine during pregnancy? A prospective comparative observational study.

BACKGROUND Lamotrigine is a second-generation antiepileptic drug, also used as a mood stabilizer. Published data on its use in human pregnancy are largely derived from pregnancy registries. Pregnancy experience in most studies has been reassuring. However, data from the North American Antiepileptic Drug Pregnancy Registry suggested an increased risk for oral clefts. The primary objective of the study was to evaluate the rate of major anomalies after lamotrigine exposure during pregnancy compared with pregnancies of women counseled for nonteratogenic exposure (NTE). METHODS Callers who contacted the Israeli Teratology Information Service regarding lamotrigine treatment or NTE during pregnancy between 1997 and 2008 were prospectively followed-up. RESULTS The rate of major congenital anomalies was similar between 218 lamotrigine exposed pregnancies (208 in the first trimester) and 865 NTE-pregnancies. There was no case of oral cleft in the lamotrigine-exposed group. The median lamotrigine dose in the beginning of pregnancy was 200 mg/d. The dose was increased during pregnancy in 29%. The majority of women in the cohort (82%) were treated for neurologic indications, while 18% for psychiatric disorders. Monotherapy was taken by 72%. CONCLUSION The data available, thus far, on lamotrigine monotherpy-exposed pregnancies are encouraging. However, further studies are needed to determine with greater certainty the overall risk for major anomalies, as well as the specific risk for oral clefts. Based on the current and previously published data, lamotrigine, seems a reasonable alternative for pregnant women when clinically indicated. Birth Defects Research 109:1196-1203, 2017. © 2017 Wiley Periodicals, Inc.
Thought suppression and suicidal ideation: preliminary evidence in support of a robust association

Background: The suppression of unwanted thoughts appears to contribute to the development and maintenance of emotional disorders. This report tested the thought suppression paradigm in relation to suicidal ideation. Based on the ironic process theory, we hypothesized that the suppression of unwanted thoughts, especially suicidal thoughts, would associate with a higher frequency and a greater intensity of suicidal ideation. Methods: Study 1 examined cross‐sectional associations between self‐reported thought suppression and the frequency of suicidal ideation in a nonclinical sample of 166 undergraduate students. Study 2 extended cross‐sectional findings in an inpatient sample of 71 suicidal adolescents. Study 3 examined prospective associations between suicidal thought suppression and increases in self‐reported suicidal ideation over a 4‐week period in a separate nonclinical sample of 118 undergraduate students. Results: Findings across studies support a robust association between thought suppression and suicidal ideation, even controlling for general depressive symptoms. Participants in Studies 1 and 2 who endorsed greater tendencies toward suppression of thoughts, especially suicidal thoughts (Study 2), displayed higher concurrent levels of suicidal ideation. Participants in Study 3 who endorsed greater baseline tendencies toward suppression of suicidal thoughts displayed an increase in the severity of suicidal ideation over time. Conclusions: Suppression of suicidal thoughts may represent 1 mechanism contributing to the persistence of suicidal ideation. Clinicians may wish to explore patients' reactions to suicidal ideation and consider acceptance‐oriented strategies among patients who attempt to control unwanted suicidal thoughts. Depression and Anxiety, 2009. © 2008 Wiley‐Liss, Inc.
Predictors of employment status change over 2 years in people with schizophrenia living in Europe

SUMMARY Aim – To examine the associations of job acquisition and loss in a representative, prospective community sample of people with schizophrenia living in the UK, France and Germany. Method – A representative sample of twelve hundred and eight people with schizophrenia were recruited from selected secondary mental health services in the U.K, France and Germany and followed up for 2 years. Information on demographic details, psychotic symptoms and work status was collected. Results – The odds of getting jobs were increased by being resident in Marseille, Leipzig, Hemer and Heilbronn and by a higher regional general population employment rate. The odds were reduced by living in Lyon, a later illness onset, a longer length of illness, a continuous illness course and more severe negative psychotic symptoms. Previous vocational training reduced the odds of losing employment, whilst living in Lyon or Leipzig, harmful use of alcohol and more positive psychotic symptoms at baseline all increased the odds. Conclusions – In addition to illness related factors, area of residence and local labour market conditions appear to be important in explaining employment status change in people with schizophrenia. Declaration of Interest: All authors declare there are no conflicts of interest. This study was funded by grants from Lundbeck A/S and from the German Federal Ministry of Education and Research.
Predictors of hip fractures in elderly men

To assess the influence on the risk of hip fractures in men of medical conditions associated with secondary osteoporosis or with an increased likelihood of falling, we conducted a population‐based nested case‐control study among the 232 Rochester, Minnesota, men with an initial hip fracture due to moderate trauma in 1965–1989 and an equal number of age‐matched control men from the general population. Information on selected medical and surgical conditions and certain behavioral risk factors prior to fracture (or comparable index date for controls) was obtained from inpatient and outpatient medical records in the community that averaged over 36 years in duration. After adjusting for age, obesity, and inactivity, disorders linked with secondary osteoporosis were associated with a 2‐fold increase in the risk of hip fracture in men (odds ratio [OR] 2.3; 95% confidence interval [CI] 1.3–4.3), while conditions linked with an increased risk of falling were associated with almost a 7‐fold increase in risk (OR 6.9; 95% CI 3.3–14.8). These factors together appeared to account for about 72% of the hip fractures in men. Increased attention must be paid to these conditions which, in aggregate, are very common in elderly men and lead to a substantial increase in the risk of hip fracture with its devastating sequelae of death, disability, and cost.
Specific Cell‐Mediated Responses to Bacterial Antigens and Clinical Correlations in Reactive Arthritis, Reiter's Syndrome and Ankylosing Spondylitis

In 2 cases of ReA seen during the acute phase and shown serologically to be due to Y. enterocolitica 0:3, the LT test showed a marked response using as antigen a freeze dried preparation of the causative organism. The test result correlated with the activity of the disease when repeated during a flare in the 1st case, and during remission in both. Patients with ReA/RS in general showed a significantly higher response to the yersinia and klebsiella antigens tested when compared to AS, suggesting an overall difference in cell-mediated immunity to these enteric bacteria. AS cases reacted significantly less than controls to K. pneumoniae under suboptimal conditions. K. pneumoniae was shown to enhance the LT response to yersinia, possibly through an adjuvant effect. This was found with AS, ReA and in controls, though whether it is of relevance in the etiopathogenesis of AS or ReA/RS remains far from clear. Acute non-traumatic synovitis of the knee, occurring de novo, or in association with psoriasis, inflammatory bowel disease, or as part of RS, may be accompanied by evidence of heightened reactivity to streptococci both by blood and synovial fluid mononuclear cells. In 1 case with serological evidence of streptococcal infection and erythema nodosum, these changes were found to parallel disease activity. ReA can, it appears, follow recent streptococcal infection, and be associated with B27.
Regional Study of Care for the Dying: methods and sample characteristics

The Regional Study of Care for the Dying (RSCD) was established in 1990 with the dual aims of providing district health authorities with an audit of local services for the dying, and of addressing questions about experiences of people dying from cancer, effectiveness of hospice care, and needs of, and appropriate service provision for, people dying from causes other than cancer. The survey methods are described in this paper, together with the characteristics and representativeness of the sample. An interview survey was conducted of family or others who knew about the last year of life of a random sample of people who died in 1990. It was based upon methods used in nationally representative surveys by Cartwright in 1969, and Cartwright and Seale in 1987. The setting was 20 district health authorities, who paid for local data collection. Approximately 270 deaths were randomly sampled in each district: 5375 deaths were sampled in total. As cancer patients are the focus of most services for the dying, cancer deaths were sampled disproportionately (54%). Interviews were obtained for 69% (3696) of the sample. The response rate varied significantly by cause of death, age and social class of deceased, and the degree of deprivation of the district. There were small, but statistically significant, differences in cause of death and age between those deaths for whom interviews were obtained and national figures for deaths occurring in 1990. The discussion addresses key issues in the study, including responses from ethical committees, response rate and quality of data. The survey has been successful, both in providing districts with information on local services, and in obtaining a large, broadly representative, sample of deaths, thus enabling many outstanding questions about the needs of dying patients and their families, and about appropriate service provision, to be addressed.
Future artificial pancreas technology for type 1 diabetes: what do users want?

BACKGROUND The primary focus of artificial pancreas (AP) research has been on technical achievements, such as time in range for glucose levels or prevention of hypoglycemia. Few studies have attempted to ascertain the expectations of users of AP technology. SUBJECTS AND METHODS Persons with type 1 diabetes and parents of children with type 1 diabetes were invited to take part in an online survey concerning future use and expectations of AP technology. The survey was advertised via Twitter, Facebook, and DiabetesMine, plus advocacy groups and charities including INPUT, Diabetes UK, and the Diabetes Research and Wellness Foundation. Quantitative responses were categorized on a 5-point Likert scale. Free text responses were analyzed using content analysis. RESULTS Two hundred sixty-six surveys were completed over a 1-month period. Two hundred forty participants indicated they were highly likely to use a fully automated 24-h AP. Approximately half of the respondents indicated they would be likely to use a device that only functioned overnight. Size, visibility, and lack of effectiveness were the top reasons for not wanting an AP. Despite perceived potential downsides, participants expressed a strong need for a device that will help minimize the burden of disease, help facilitate improved psychosocial functioning, and improve quality of life. CONCLUSIONS The views of people who would use an AP are crucial in the development of such devices to ensure they are fit for use alongside biomedical and engineering excellence. Without this, it is unlikely that an AP will be sufficiently successful to meet the needs of users and to achieve their ultimate goals.
Disruption of Endocrine Rhythms in Sleeping Sickness With Preserved Relationship Between Hormonal Pulsatility and the REM-NREM Sleep Cycles

In human African trypanosomiasis (sleeping sickness), sleep and wake episodes are sporadically distributed throughout the day and the night. To determine whether these sleep disturbances affect the 24-h hormone profiles and the normal relationships between hormone pulsatility and sleep stages, poly-graphic sleep recordings and concomitant hormone profiles were obtained in 6 African patients with sleeping sickness and in 5 healthy African subjects selected from Abidjan on the Ivory Coast. Polysomnographic recordings were continuous, and blood was taken every 10 min throughout the 24-h period. Plasma was analyzed for cortisol, prolactin, and plasma renin activity (PRA). The 24-h rhythm of cortisol, considered to be an endogenous circadian rhythm, was attenuated in all of the patients except one. However, as in normal subjects, slow wave sleep (SWS) remained associated with the declining phases of the cortisol secretory episodes. Prolactin and PRA profiles, which are strongly influenced by the sleep-wake cycle, did not manifest the nocturnal increase normally associated with the sleep period; instead, they reflected a sporadic distribution of the sleep and wake episodes throughout the 24-h period. In patients with sleeping sickness as in normal subjects, rapid eye movement (REM) sleep began during the descending phases of prolactin pulses. In both groups, PRA reflected the sleep stage distribution with non REM (NREM) sleep occurring during the ascending phases and REM sleep during the descending phases of the PRA oscillations. However, in sleeping sickness patients, the marked sleep fragmentation often did not allow sufficient time for PRA to increase significantly, as is normally the case in subjects with regular NREM-REM sleep cycles. These results demonstrate that, together with the disruption of the sleep-wake cycle, there are profound differences in the temporal organization of the 24-h hormone profiles in humans with African trypanosomiasis. However, the relationship between hormonal pulses and specific sleep stages persists, indicating the existence of a robust link between hormonal release and the internal sleep structure.
Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma.

BACKGROUND Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Our recent findings indicated that microvessel density (count or grade) in invasive breast carcinoma (a measure of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. PURPOSE This study was designed to further define the relationship of microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma. METHODS In a prospective, blinded study of 165 consecutive patients, the microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen. Using light microscopy, we counted microvessels per 200x field in the most active areas of neovascularization and graded microvessel density. These findings were correlated, by univariate and multivariate analyses, with overall and relapse-free survival, axillary node status, and other prognostic indicators (median follow-up, 51 months). RESULTS There was a highly significant (P < or = .001) association of microvessel density with overall survival and relapse-free survival in all patients, including node-negative and node-positive subsets. All patients with breast carcinomas having more than 100 microvessels per 200x field experienced tumor recurrence within 33 months of diagnosis, compared with less than 5% of the patients with breast carcinoma having 33 or fewer microvessels per 200x field. Moreover, microvessel density was the only statistically significant predictor of overall survival among node-negative women (P < .001). Only microvessel density (P < .001) and histologic grade (P = .04) showed statistically significant correlations with relapse-free survival in the node-negative subset. CONCLUSIONS Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma (I or II by International Union Against Cancer criteria). IMPLICATIONS Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are at high risk for having occult metastasis at presentation. These patients could then be given systemic adjuvant therapy.
Chronic exposure to sub‐lethal beta‐amyloid (Aβ) inhibits the import of nuclear‐encoded proteins to mitochondria in differentiated PC12 cells*

Studies on amyloid beta (Aβ|), the peptide thought to play a crucial role in the pathogenesis of Alzheimer’s disease, have implicated mitochondria in Aβ‐mediated neurotoxicity. We used differentiated PC12 cells stably transfected with an inducible green fluorescent protein (GFP) fusion protein containing an N′‐terminal mitochondrial targeting sequence (mtGFP), to examine the effects of sub‐lethal Aβ on the import of nuclear‐encoded proteins to mitochondria. Exposure to sub‐lethal Aβ25–35 (10 μmol/L) for 48 h inhibited mtGFP import to mitochondria; average rates decreased by 20 ± 4%. Concomitant with the decline in mtGFP, cytoplasmic mtGFP increased significantly while mtGFP expression and intramitochondrial mtGFP turnover were unchanged. Sub‐lethal Aβ1–42 inhibited mtGFP import and increased cytoplasmic mtGFP but only after 96 h. The import of two endogenous nuclear‐encoded mitochondrial proteins, mortalin/mtHsp70 and Tom20 also declined. Prior to the decline in import, mitochondrial membrane potential (mmp), and reactive oxygen species levels were unchanged in Aβ‐treated cells versus reverse phase controls. Sustained periods of decreased import were associated with decreased mmp, increased reactive oxygen species, increased vulnerability to oxygen‐glucose deprivation and altered mitochondrial morphology. These findings suggest that an Aβ‐mediated inhibition of mitochondrial protein import, and the consequent mitochondrial impairment, may contribute to Alzheimer’s disease.
Prediction of interface residues in protein–protein complexes by a consensus neural network method: Test against NMR data

The number of structures of protein–protein complexes deposited to the Protein Data Bank is growing rapidly. These structures embed important information for predicting structures of new protein complexes. This motivated us to develop the PPISP method for predicting interface residues in protein–protein complexes. In PPISP, sequence profiles and solvent accessibility of spatially neighboring surface residues were used as input to a neural network. The network was trained on native interface residues collected from the Protein Data Bank. The prediction accuracy at the time was 70% with 47% coverage of native interface residues. Now we have extensively improved PPISP. The training set now consisted of 1156 nonhomologous protein chains. Test on a set of 100 nonhomologous protein chains showed that the prediction accuracy is now increased to 80% with 51% coverage. To solve the problem of over‐prediction and under‐prediction associated with individual neural network models, we developed a consensus method that combines predictions from multiple models with different levels of accuracy and coverage. Applied on a benchmark set of 68 proteins for protein–protein docking, the consensus approach outperformed the best individual models by 3–8 percentage points in accuracy. To demonstrate the predictive power of cons‐PPISP, eight complex‐forming proteins with interfaces characterized by NMR were tested. These proteins are nonhomologous to the training set and have a total of 144 interface residues identified by chemical shift perturbation. cons‐PPISP predicted 174 interface residues with 69% accuracy and 47% coverage and promises to complement experimental techniques in characterizing protein–protein interfaces. Proteins 2005. © 2005 Wiley‐Liss, Inc.