Miracle-dz/UniFAR-FTUs huggingface dataset:
Robust Automated Detection of Microstructural White Matter Degeneration in Alzheimer’s Disease Using Machine Learning Classification of Multicenter DTI Data

Diffusion tensor imaging (DTI) based assessment of white matter fiber tract integrity can support the diagnosis of Alzheimer’s disease (AD). The use of DTI as a biomarker, however, depends on its applicability in a multicenter setting accounting for effects of different MRI scanners. We applied multivariate machine learning (ML) to a large multicenter sample from the recently created framework of the European DTI study on Dementia (EDSD). We hypothesized that ML approaches may amend effects of multicenter acquisition. We included a sample of 137 patients with clinically probable AD (MMSE 20.6±5.3) and 143 healthy elderly controls, scanned in nine different scanners. For diagnostic classification we used the DTI indices fractional anisotropy (FA) and mean diffusivity (MD) and, for comparison, gray matter and white matter density maps from anatomical MRI. Data were classified using a Support Vector Machine (SVM) and a Naïve Bayes (NB) classifier. We used two cross-validation approaches, (i) test and training samples randomly drawn from the entire data set (pooled cross-validation) and (ii) data from each scanner as test set, and the data from the remaining scanners as training set (scanner-specific cross-validation). In the pooled cross-validation, SVM achieved an accuracy of 80% for FA and 83% for MD. Accuracies for NB were significantly lower, ranging between 68% and 75%. Removing variance components arising from scanners using principal component analysis did not significantly change the classification results for both classifiers. For the scanner-specific cross-validation, the classification accuracy was reduced for both SVM and NB. After mean correction, classification accuracy reached a level comparable to the results obtained from the pooled cross-validation. Our findings support the notion that machine learning classification allows robust classification of DTI data sets arising from multiple scanners, even if a new data set comes from a scanner that was not part of the training sample.
Kainate receptors in the hippocampus

Kainate receptors (KARs) consist of a family of ionotropic glutamate receptors composed of the combinations of five subunits, GluK1–GluK5. Although KARs display close structural homology with AMPA receptors, they serve quite distinct functions. A great deal of our knowledge of the molecular and functional properties of KARs comes from their study in the hippocampus. This review aims at summarising the functions of KARs in the regulation of the activity of hippocampal synaptic circuits at the adult stage and throughout development. We focus on the variety of roles played by KARs in physiological conditions of activation, at pre‐ and postsynaptic sites, in different cell types and through either metabotropic or ionotropic actions. Finally, we present some of the few attempts to link the role of KARs in the regulation of local hippocampal circuits to the behavioural functions of the hippocampus in health and diseases.
Interventions for treating proximal humeral fractures in adults.

BACKGROUND Proximal humeral fractures are common yet management varies widely. In particular, the role and timing of any surgical intervention have not been clearly defined. OBJECTIVES To collate and evaluate the scientific evidence supporting the various methods used for treating proximal humeral fractures. SEARCH STRATEGY We searched the Cochrane Musculoskeletal Injuries Group trials register, MEDLINE, PubMed, the Cochrane Controlled Trials Register, CINAHL, the National Research Register and bibliographies of trial reports. The search was completed in July 2000. SELECTION CRITERIA All randomised studies pertinent to the treatment of proximal humeral fractures were selected. DATA COLLECTION AND ANALYSIS Independent quality assessment and data extraction were performed by two reviewers. Although quantitative data from trials are presented, trial heterogeneity prevented pooling of results. MAIN RESULTS Nine randomised trials were included. All were small trials; the largest study involved only 85 patients. Bias in these trials could not be ruled out. Six trials evaluated conservative treatment, two compared surgery with conservative treatment and one compared two surgical techniques. In the 'conservative' group there was very limited evidence indicating that the type of bandage used made any difference in terms of time to fracture union and the functional end result. However, an arm sling was generally more comfortable than a body bandage. There was some evidence that mobilisation at one week instead of three weeks alleviated pain in the short term without compromising long term outcome. Two trials provided some evidence that patients, when given sufficient instruction to pursue an adequate physiotherapy programme, could generally achieve a satisfactory outcome if allowed to exercise without supervision. Operative reduction improved fracture alignment in two trials. However, in one trial, surgery was associated with a greater risk of complication, and did not result in improved shoulder function. Fracture fixation of severe injuries was associated with a high rate of re-operation in one trial, comparing tension-band wiring fixation with hemi-arthroplasty. REVIEWER'S CONCLUSIONS Only tentative conclusions can be drawn from the available randomised trials, which do not provide robust evidence for many of the decisions which need to be made in contemporary fracture management. It is unclear whether operative intervention, even for specific fracture types, will produce consistently better long term outcomes. There is a need for good quality evidence for the management of these fractures.
Patients with irritable bowel syndrome: health status and use of health care services.

BACKGROUND The reason for consulting a physician is more related to illness behaviour than to the severity of complaints. Yet, little is known about the course of complaints, the health care seeking behaviour, and psychosocial factors influencing these items in patients with irritable bowel syndrome (IBS) attending the general practitioner (GP). AIM To study health status, lifestyle, and use of health care services of patients with IBS in order to indicate problem areas accessible for intervention strategies. METHOD Structured interviews of 53 patients with IBS aged 15 years and older compared with a general population of 12,975 in the same age range, all drawn from the Dutch National survey of Morbidity and Intervention in General Practice. RESULTS Patients with IBS revealed a lower grade of education (P < 0.001), poorer health (P < 0.001), a higher mean complaint score (8.3 versus 4.0, P < 0.001), a higher score on the General Health Questionnaire (P < 0.001), a higher score on the biographic problem list (BIOPRO, 2.3 versus 1.4, P < 0.001), and more absence from work (32% versus 18% in two months, P < 0.01). Patients with IBS consulted the family physician (1.6 versus 0.8 in three months, P < 0.001), the physical therapist (30% versus 15% in one year, P < 0.001), and the alternative therapist (32% versus 15% in five years, P < 0.001) more often than those without. CONCLUSIONS The study shows an excess of comorbidity, psychosocial problems, use of health care services, and absence owing to disease in patients with IBS. Special guidelines and training of GPs to apply a more integral approach may reduce the cost of health care and may lead to a more favourable course in patients with IBS.
Epidemiology and Clinical Characteristics of Respiratory Infections Due to Adenovirus in Children Living in Milan, Italy, during 2013 and 2014

To evaluate the predominant human adenovirus (HAdV) species and types associated with pediatric respiratory infections, nasopharyngeal swabs were collected from otherwise healthy children attending an emergency room in Milan, Italy, due to a respiratory tract infection from January 1 to February 28 of two subsequent years, 2013 and 2014. The HAdVs were detected using a respiratory virus panel fast assay (xTAG RVP FAST v2) and with a HAdV-specific real-time polymerase chain reaction; their nucleotides were sequenced, and they were tested for positive selection. Among 307 nasopharyngeal samples, 61 (19.9%) tested positive for HAdV. HAdV was the only virus detected in 31/61 (50.8%) cases, whereas it was found in association with one other virus in 25 (41.0%) cases and with two or more viruses in 5 (8.2%) cases. Human Enterovirus/human rhinovirus and respiratory syncytial virus were the most common co-infecting viral agents and were found in 12 (19.7%) and 7 (11.5%) samples, respectively. Overall, the HAdV strain sequences analyzed were highly conserved. In comparison to HAdV-negative children, those infected with HAdV had a reduced frequency of lower respiratory tract involvement (36.1% vs 55.2%; p = 0.007), wheezing (0.0% vs 12.5%; p = 0.004), and hospitalization (27.9% vs 56.1%; p<0.001). Antibiotic therapy and white blood cell counts were more frequently prescribed (91.9% vs 57.1%; p = 0.04) and higher (17,244 ± 7,737 vs 9,565 ± 3,211 cells/μL; p = 0.04), respectively, in children infected by HAdV-C than among those infected by HAdV-B. On the contrary, those infected by HAdV-B had more frequently lower respiratory tract involvement (57.1% vs 29.7%) but difference did not reach statistical significant (p = 0.21). Children with high viral load were absent from child care attendance for a longer period of time (14.5 ± 7.5 vs 5.5 ± 3.2 days; p = 0.002) and had higher C reactive protein levels (41.3 ± 78.5 vs 5.4 ± 9.6 μg/dL; p = 0.03). This study has shown that HAdV infections are diagnosed more commonly than usually thought and that HAdVs are stable infectious agents that do not frequently cause severe diseases. A trend toward more complex disease in cases due to HAdV species C and in those with higher viral load was demonstrated. However, further studies are needed to clarify factors contributing to disease severity to understand how to develop adequate preventive and therapeutic measures.
Immune Responses to Broad-Spectrum Antibiotic Treatment and Fecal Microbiota Transplantation in Mice

Compelling evidence demonstrates the pivotal role of the commensal intestinal microbiota in host physiology and the detrimental effects of its perturbations following antibiotic treatment. Aim of this study was to investigate the impact of antibiotics induced depletion and subsequent restoration of the intestinal microbiota composition on the murine mucosal and systemic immunity. To address this, conventional C57BL/6j mice were subjected to broad-spectrum antibiotic treatment for 8 weeks. Restoration of the intestinal microbiota by peroral fecal microbiota transplantation (FMT) led to reestablishment of small intestinal CD4+, CD8+, and B220+ as well as of colonic CD4+ cell numbers as early as 7 days post-FMT. However, at d28 following FMT, colonic CD4+ and B220+ cell numbers were comparable to those in secondary abiotic (ABx) mice. Remarkably, CD8+ cell numbers were reduced in the colon upon antibiotic treatment, and FMT was not sufficient to restore this immune cell subset. Furthermore, absence of gut microbial stimuli resulted in decreased percentages of memory/effector T cells, regulatory T cells, and activated dendritic cells in the small intestine, colon, mesenteric lymph nodes (MLN), and spleen. Concurrent antibiotic treatment caused decreased cytokine production (IFN-γ, IL-17, IL-22, and IL-10) of CD4+ cells in respective compartments. These effects were, however, completely restored upon FMT. In summary, broad-spectrum antibiotic treatment resulted in profound local (i.e., small and large intestinal), peripheral (i.e., MLN), and systemic (i.e., splenic) changes in the immune cell repertoire that could, at least in part, be restored upon FMT. Further studies need to unravel the distinct molecular mechanisms underlying microbiota-driven changes in immune homeostasis subsequently providing novel therapeutic or even preventive approaches in human immunopathologies.
Estimating Bacterial Diversity in Scirtothrips dorsalis (Thysanoptera: Thripidae) via Next Generation Sequencing

Abstract The last 2 decades have produced a better understanding of insect-microbial associations and yielded some important opportunities for insect control. However, most of our knowledge comes from model systems. Thrips (Thysanoptera: Thripidae) have been understudied despite their global importance as invasive species, plant pests and disease vectors. Using a culture and primer independent next-generation sequencing and metagenomics pipeline, we surveyed the bacteria of the globally important pest, Scirtothrips dorsalis Hood. The most abundant bacterial phyla identified were Actinobacteria and Proteobacteria and the most abundant genera were Propionibacterium, Stenotrophomonas, and Pseudomonas. A total of 189 genera of bacteria were identified. The absence of any vertically transferred symbiont taxa commonly found in insects is consistent with other studies suggesting that thrips primarilly acquire resident microbes from their environment. This does not preclude a possible beneficial/intimate association between S. dorsalis and the dominant taxa identified and future work should determine the nature of these associations.
Axonal GABAA Receptors Increase Cerebellar Granule Cell Excitability and Synaptic Activity

We report that activation of GABAA receptors on cerebellar granule cell axons modulates both transmitter release and the excitability of the axon and soma. Axonal GABAA receptors depolarize the axon, increasing its excitability and causing calcium influx at axonal varicosities. GABA-mediated subthreshold depolarizations in the axon spread electrotonically to the soma, promoting orthodromic action potential initiation. When chloride concentrations are unperturbed, GABA iontophoresis elicits spikes and increases excitability of parallel fibers, indicating that GABAA receptor-mediated responses are normally depolarizing. GABA release from molecular layer interneurons activates parallel fiber GABAA receptors, and this, in turn, increases release probability at synapses between parallel fibers and molecular layer interneurons. These results describe a positive feedback mechanism whereby transmission from granule cells to Purkinje cells and molecular layer interneurons will be strengthened during granule cell spike bursts evoked by sensory stimulation.
The Effects of Bazedoxifene on Bone, Glucose, and Lipid Metabolism in Postmenopausal Women With Type 2 Diabetes: An Exploratory Pilot Study

Background Selective estrogen receptor modulators (SERMs) decrease homocysteine and cross-linking of pentosidine and reduce low-density lipoprotein cholesterol (LDL-C), and they are expected to improve bone quality and atherosclerosis. Therefore, the potential effects of bazedoxifene on bone (bone resorption, bone formation, and bone quality), as well as on glucose and lipid metabolism markers, were examined in Japanese postmenopausal women with type 2 diabetes mellitus (T2DM). Methods Eligible patients received 20 mg of bazedoxifene tablets once daily and were followed up for 12 weeks. Bone resorption markers including tartrate-resistant acid phosphatase 5b (TRACP-5b), bone formation markers and bone quality markers such as homocysteine and serum pentosidine, total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and HbA1c were all measured. Results Twenty patients completed this study. All bone resorption markers decreased significantly 4 weeks after bazedoxifene treatment. In particular, TRACP-5b decreased significantly at 12 weeks (median percent change: -20.6%), and the minimum significant change (MSC) achievement rate of TRACP-5b was 65%. Bazedoxifene also decreased bone formation markers. However, bazedoxifene did not improve bone quality markers. LDL-C, HDL-C, and non-HDL-C were decreased, but TG was unchanged. Glucose metabolism was not changed after bazedoxifene treatment. In a subgroup analysis, the group of patients in whom the percent change in TRACP-5b exceeded the MSC had no change in pentosidine levels at 12 weeks. However, in the group of patients in whom the percent change in TRACP-5b did not exceed the MSC, pentosidine levels tended to increase. Conclusions Bazedoxifene may improve bone resorption markers and LDL-C without affecting glucose metabolism in Japanese postmenopausal women with T2DM.
Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis

Although there have been significant advances in understanding the clinical and biochemical features of primary biliary cirrhosis (PBC), there is still a paucity of data on the usefulness of biomarkers as prognostic indicators. This is particularly important at the time of initial diagnosis. Indeed, the widespread use of antimitochondrial antibody testing has led to an earlier diagnosis of asymptomatic PBC and it is difficult to predict which patients will experience a benign versus a rapidly progressive course. To address this issue, we examined a unique population of 127 newly diagnosed patients with PBC during a 15‐year period of observation that began in January 1990. Sera from these patients were analyzed for antimitochondrial, antinuclear, and anti–smooth muscle antibodies, and immunoblotting was performed for nuclear pore complex (NPC). The patients were then followed up longitudinally using biochemical liver function tests. No patient was under any medical therapy for PBC at the time of the initial sera collection. Data were analyzed based not only on the clinical features, but also the Mayo score and specific outcome measures, including time to death, need for liver transplantation, and complication free survival. Among patients with early disease, bilirubin increased to >2 mg/dL in the anti‐NPC(+) patients (26% vs. 5%, P = .019). Anti‐NPC antibodies remained stable or slightly increased over the period of observation. In conclusion, anti‐NPC identifies patients likely to experience an unfavorable clinical course and more rapid disease progression. (HEPATOLOGY 2006;43:1135–1144.)
Global Egr1-miRNAs Binding Analysis in PMA-Induced K562 Cells Using ChIP-Seq

Although much is known about microRNAs' regulation in gene expression and their contributions in cell fate, to date, globally lineage-(cell-) specific identification of the binding events between a transcription factor and its targeting microRNA genes is still waiting for elucidation. In this paper, we performed a ChIP-Seq experiment to find the targeting microRNA genes of a transcription factor, Egr1, in human erythroleukemia cell line K562. We found Egr1 binding sites near the promoters of 124 distinct microRNA genes, accounting for about 42% of the miRNAs which have high-confidence predicted promoters (294). We also found EGR1 bind to another 63 pre-miRNAs. We chose 12 of the 187 microRNAs with Egr1 binding sites to perform ChIP-PCR assays and the positive binding signal from ChIP-PCR confirmed the ChIP-Seq results. Our experiments provide the first global binding profile between Egr1 and its targeting microRNA genes in PMA-treated K562 cells, which may facilitate the understanding of pathways controlling microRNA biology in this specific cell line.
Fibrosing alveolitis in patients with rheumatoid arthritis as assessed by high resolution computed tomography, chest radiography, and pulmonary function tests

BACKGROUND Fibrosing alveolitis (FA) is a common and serious complication of rheumatoid arthritis (RA). Before the availability of high resolution computed tomographic (HRCT) scanning, it was difficult to diagnose accurately without recourse to biopsy. Prospective studies have reported a prevalence of interstitial lung disease (ILD) of 19–44%. The term ILD used by these authors encompasses a variety of appearances on HRCT scans. This prospective study used HRCT scanning to determine the true prevalence of FA in hospital outpatients with RA, and to study associated clinical characteristics. METHODS One hundred and fifty consecutive patients with RA were selected from a hospital outpatient department, irrespective of the presence or absence of chest disease. All underwent a detailed clinical assessment, chest HRCT scanning, and conventional chest radiography within 4 weeks of full pulmonary function tests. RESULTS Seventy percent of patients were current or reformed cigarette smokers. Twenty eight (19%) had FA, most frequently of reticular pattern, and 12 of this group (43%) also had emphysematous bullae. None of the previously suggested risk factors for developing FA were confirmed. Fifty four percent of patients with HRCT evidence of FA had bilateral basal chest crackles, 82% had a reduced carbon monoxide transfer factor (Tlco), 14% had restrictive pulmonary function tests, and 14% had bilateral chest radiographic signs of FA. CONCLUSIONS HRCT evidence of FA was present in 19% of hospital outpatients with RA. Abnormalities on chest examination or on full pulmonary function tests, even without restrictive changes or chest radiographic abnormalities, should prompt physicians to request a chest HRCT scan when investigating dyspnoea in patients with RA.
The use of nuclear medicine techniques in the emergency department

Nuclear medicine techniques have received little attention in the practice of emergency medicine, yet radionuclide imaging can provide valuable and unique information in the management of acutely ill patients. In this review, emphasis is placed on the role of these techniques in patients with bone injuries, non-traumatic bone pain and in those with pleuritic chest pain. New developments such as single photon emission computed tomography (SPECT) in myocardial infarction are outlined and older techniques such as scrotal scintigraphy are reviewed. Radionuclide techniques are discussed in a clinical context and in relation to alternative imaging modalities or strategies that may be available to the emergency medicine physician. Aspects of a 24 hour nuclear medicine service are considered.
Lactate and Acrylate Metabolism by Megasphaera elsdenii under Batch and Steady-State Conditions

ABSTRACT The growth of Megasphaera elsdenii on lactate with acrylate and acrylate analogues was studied under batch and steady-state conditions. Under batch conditions, lactate was converted to acetate and propionate, and acrylate was converted into propionate. Acrylate analogues 2-methyl propenoate and 3-butenoate containing a terminal double bond were similarly converted into their respective saturated acids (isobutyrate and butyrate), while crotonate and lactate analogues 3-hydroxybutyrate and (R)-2-hydroxybutyrate were not metabolized. Under carbon-limited steady-state conditions, lactate was converted to acetate and butyrate with no propionate formed. As the acrylate concentration in the feed was increased, butyrate and hydrogen formation decreased and propionate was increasingly generated, while the calculated ATP yield was unchanged. M. elsdenii metabolism differs substantially under batch and steady-state conditions. The results support the conclusion that propionate is not formed during lactate-limited steady-state growth because of the absence of this substrate to drive the formation of lactyl coenzyme A (CoA) via propionyl-CoA transferase. Acrylate and acrylate analogues are reduced under both batch and steady-state growth conditions after first being converted to thioesters via propionyl-CoA transferase. Our findings demonstrate the central role that CoA transferase activity plays in the utilization of acids by M. elsdenii and allows us to propose a modified acrylate pathway for M. elsdenii.