Miracle-dz/UniFAR-FTUs huggingface dataset:
Fat intake in patients newly diagnosed with type 2 diabetes: a 4-year follow-up study in general practice.

BACKGROUND Although treatment targets for the consumption of dietary fat in patients with type 2 diabetes mellitus are well accepted, little is known about the actual fat consumption by newly diagnosed patients or the dietary adjustments that they make in the following years. AIMS To measure fat intake in patients with type 2 diabetes in general practice at diagnosis, shortly after dietary consultation, and after 4 years. DESIGN OF STUDY A prospective cohort study. SETTING Thirty-three general practices in The Netherlands. METHOD One hundred and forty-four patients with newly diagnosed type 2 diabetes were referred to a dietician, and fat consumption (the main outcome measure) was assessed with a 104-item food frequency questionnaire at diagnosis, 8 weeks following diagnosis, and after 4 years. Reference values for fat consumption were obtained from an age-matched sample of a population-based survey. RESULTS At diagnosis, total energy intake was 10.6 MJ/day and cholesterol intake was 300 mg/day. Total fat consumption was 40.9% of energy intake, with saturated fatty acids 15.0%, monounsaturated fatty acids 14.3%, and polyunsaturated fatty acids 9.2% of energy intake. All levels, except for polyunsaturated fatty acids, were significantly unfavourable compared with those for the general population. After 8 weeks, consumption of saturated fatty acids had decreased to a lower level than in the general population and all other levels measured were similar to those for the general population. After 4 years there was a slight increase in the consumption of total fat and monounsaturated fatty acids, but cholesterol and saturated fatty acid consumption had decreased further. CONCLUSIONS Patients with newly diagnosed type 2 diabetes have an unfavourable fat consumption at diagnosis. They adapt to a more desirable consumption shortly after diagnosis, and this improved dietary behaviour is sustained for 4 years. Recommendations regarding consumption of total and saturated fat are, in contrast to those for cholesterol, not met by patients in general practice.
THE SECOND COMPONENT OF HUMAN COMPLEMENT: ITS ISOLATION, FRAGMENTATION BY C'1 ESTERASE, AND INCORPORATION INTO C'3 CONVERTASE

A method has been described for the purification and isolation of the second component of complement (C'2) from human serum. The protein is a β1-globulin with an approximate molecular weight of 117,000. Immunochemical analysis using a variety of specific antisera, including a monospecific antiserum to the isolated protein, indicate that the C'2 protein represents a heretofore unrecognized human serum constituent. Isolated C'2 contained 2 x 109 "effective molecules" per microgram and 1000 hemolytically active C'2 molecules were required to produce a single hemolytically effective C'2 site on erythrocytes undergoing immune cytolysis. C'1 esterase treatment of C'2 resulted in reduction of both its electrophoretic mobility and its molecular size, the latter observation indicating fragmentation of the molecule. Direct evidence was presented for the physical presence of C'2 as an integral part of the enzyme C'3 convertase.
Changes in auditory P300 event‐related potentials and brainstem evoked potentials in diabetes mellitus

To investigate the influence of diabetes mellitus on higher cognitive functions electrophysiologically, we studied auditory P300 event‐related potentials (P300) in 40 NIDDM patients, taking into account wave I‐V latencies (I‐V) in auditory brainstem evoked potentials, clinical parameters and head MRI findings. Compared with 20 controls, diabetics had significantly longer P300 and I‐V latencies. P300 latencies in diabetics correlated with neither I‐V. HbA1, blood glucose levels, nor disease duration. Of the 13 diabetics investigated neuroradiologically, four had lacunar infarcts with prolonged electrophysiological values. The remaining nine had normal MRI scans, but their physiological parameters were still significantly longer than those of controls. These findings suggest that NIDDM can independently alter higher cognitive and the central auditory pathway functions. Our data also suggest that these alterations occur regardless of the recent metabolic derangement and disease duration. Cerebrovascular ischemia, if present, also appears to contribute in part to cognitive alterations.
Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia

Differentiating agents have been proposed to overcome the impaired cellular differentiation in acute myeloid leukemia (AML). However, only the combinations of all-trans retinoic acid or arsenic trioxide with chemotherapy have been successful, and only in treating acute promyelocytic leukemia (also called AML3). We show that iron homeostasis is an effective target in the treatment of AML. Iron chelating therapy induces the differentiation of leukemia blasts and normal bone marrow precursors into monocytes/macrophages in a manner involving modulation of reactive oxygen species expression and the activation of mitogen-activated protein kinases (MAPKs). 30% of the genes most strongly induced by iron deprivation are also targeted by vitamin D3 (VD), a well known differentiating agent. Iron chelating agents induce expression and phosphorylation of the VD receptor (VDR), and iron deprivation and VD act synergistically. VD magnifies activation of MAPK JNK and the induction of VDR target genes. When used to treat one AML patient refractory to chemotherapy, the combination of iron-chelating agents and VD resulted in reversal of pancytopenia and in blast differentiation. We propose that iron availability modulates myeloid cell commitment and that targeting this cellular differentiation pathway together with conventional differentiating agents provides new therapeutic modalities for AML.
Limited Model Antigen Expression by Transgenic Fungi Induces Disparate Fates during Differentiation of Adoptively Transferred T Cell Receptor Transgenic CD4+ T Cells: Robust Activation and Proliferation with Weak Effector Function during Recall

ABSTRACT CD4+ T cells are the key players of vaccine resistance to fungi. The generation of effective T cell-based vaccines requires an understanding of how to induce and maintain CD4+ T cells and memory. The kinetics of fungal antigen (Ag)-specific CD4+ T cell memory development has not been studied due to the lack of any known protective epitopes and clonally restricted T cell subsets with complementary T cell receptors (TCRs). Here, we investigated the expansion and function of CD4+ T cell memory after vaccination with transgenic (Tg) Blastomyces dermatitidis yeasts that display a model Ag, Eα-mCherry (Eα-mCh). We report that Tg yeast led to Eα display on Ag-presenting cells and induced robust activation, proliferation, and expansion of adoptively transferred TEa cells in an Ag-specific manner. Despite robust priming by Eα-mCh yeast, antifungal TEa cells recruited and produced cytokines weakly during a recall response to the lung. The addition of exogenous Eα-red fluorescent protein (RFP) to the Eα-mCh yeast boosted the number of cytokine-producing TEa cells that migrated to the lung. Thus, model epitope expression on yeast enables the interrogation of Ag presentation to CD4+ T cells and primes Ag-specific T cell activation, proliferation, and expansion. However, the limited availability of model Ag expressed by Tg fungi during T cell priming blunts the downstream generation of effector and memory T cells.
Prototypical Networks for Few-shot Learning

We propose Prototypical Networks for the problem of few-shot classification, where a classifier must generalize to new classes not seen in the training set, given only a small number of examples of each new class. Prototypical Networks learn a metric space in which classification can be performed by computing distances to prototype representations of each class. Compared to recent approaches for few-shot learning, they reflect a simpler inductive bias that is beneficial in this limited-data regime, and achieve excellent results. We provide an analysis showing that some simple design decisions can yield substantial improvements over recent approaches involving complicated architectural choices and meta-learning. We further extend Prototypical Networks to zero-shot learning and achieve state-of-the-art results on the CU-Birds dataset.
Selective inhibition of proteolytic enzymes in an in vivo mouse model for experimental metastasis.

Peptide aldehyde transition state analogue inhibitors of serine and cysteine proteases have been used to selectively inhibit proteases for which prior evidence supports a role in tumor cell metastasis. These enzymes include cathepsin B, urokinase plasminogen activator (PA), and thrombin. The inhibition constants of the peptidyl aldehyde inhibitors show that they are highly selective for a particular targeted serine or cysteine protease. The inhibitors are introduced by i.p. injection or by miniosmotic pumps into syngeneic C57BL/6 mice also given injections of B16-F10 melanoma cells, and the number of metastatic foci in the lung was determined. While the injection protocol gave an initially high but changing in vivo concentration of inhibitor over time, the minipump implant gave a constant steady state concentration of inhibitor over 5-7 days. Minipump infusion of leupeptin (acetylleucylleucylargininal), a strong inhibitor of cathepsin B at a steady state plasma concentration 1000-fold greater than its Ki(cathepsin B), gave no significant decrease in lung colonization by the B16 tumor cells. Ep475, a stoichiometric irreversible peptide inhibitor of cathepsin B-like proteases, also did not significantly inhibit metastatic foci formation. Introduction of selective inhibitors of urokinase PA, tert-butyloxycarbonylglutamylglycyl-argininal and H-glutamylglycylargininal at concentrations near its Ki, produced no significant decrease in mouse lung colonization. The selective thrombin inhibitor D-phenylalanylprolylargininal infused to a steady state concentration 100-fold greater than its Ki dramatically increased B16 melanoma colonization of mouse lung. The results indicate that neither secreted cathepsin B-like nor urokinase PA have roles in B16 colonization of mouse lung, while thrombin may have a role in preventing metastasis. These experiments do not eliminate roles for a cathepsin B-like enzyme or urokinase PA in the initial steps of the metastatic process.
Nitric oxide regulates synaptic transmission between spiny projection neurons

Significance The function of the basal ganglia relies on striatal spiny projecting neurons (SPNs). Axon collaterals of these GABAergic neurons form connections with other SPNs as a means of a feedback inhibition circuit. The mechanisms that regulate neurotransmission at these local synapses remain poorly understood. In this paper, neurotransmission at SPN collaterals is found to be regulated by the gaseous neurotransmitter nitric oxide, which activates a signal-transduction cascade that transcriptionally regulates vesicular GABA transporter specifically at axon collaterals. These findings illustrate a previously unidentified role for nitric oxide in striatal learning and action selection. Recurrent axon collaterals are a major means of communication between spiny projection neurons (SPNs) in the striatum and profoundly affect the function of the basal ganglia. However, little is known about the molecular and cellular mechanisms that underlie this communication. We show that intrastriatal nitric oxide (NO) signaling elevates the expression of the vesicular GABA transporter (VGAT) within recurrent collaterals of SPNs. Down-regulation of striatal NO signaling resulted in an attenuation of GABAergic signaling in SPN local collaterals, down-regulation of VGAT expression in local processes of SPNs, and impaired motor behavior. PKG1 and cAMP response element-binding protein are involved in the signal transduction that transcriptionally regulates VGAT by NO. These data suggest that transcriptional control of the vesicular GABA transporter by NO regulates GABA transmission and action selection.
DAMS: Data Aggregation using Mobile Sink in Wireless Sensor Networks

WSNs consist of resource constrained sensor nodes that monitor the physical environment and transmit their data to the Sink through multi-hop communication. Mobile sinks are used to reduce the number of hops the data travels and thereby reducing the overall energy consumption. In this paper we propose Data Aggregation using Mobile Sink (DAMS) protocol that allows the mobile sink to collect data from WSNs where path of the mobile sink is not known apriori. The mobile sink halts at a point in the network and broadcasts an aggregate query. The average path length of a data packet is a constant in DAMS and hence it can withstand node failures. The performance analysis shows that DAMS incurs less energy consumption and improved packet delivery ratio in comparison to SinkTrail [1].
Laryngeal Changes during Exercise and Exercise-Induced Asthma

Exercise-induced asthma is defined as bronchospasm within the distal airways initiated by exercise. Whether the larynx responds to produce an exacerbation or alleviation of symptoms during an attack has never been evaluated. Thirty subjects were tested, including 15 normals and 15 with exercise-induced asthma. Laryngeal response to exercise was determined by measuring the area of the glottic aperture before, during, and after exercise. The glottis was visualized with a flexible laryngoscope and video images were recorded during monitoring of respirations. Asthma was induced in subjects by having them exercise on an ergometer for 10 minutes while breathing dry air at 10°C. Measurements were subsequently made from recorded images and relative glottic areas were compared between groups. Our data quantify the normal physiologic response of the larynx to exercise and demonstrate a substantial laryngeal contribution to asthma induced by exercise.
Cavovarus Foot Realignment to Treat Anteromedial Ankle Arthrosis

Background: Adult patients with cavovarus feet were seen with symptomatic anteromedial ankle arthrosis and, frequently, lateral hindfoot instability. Static and dynamic realignment was performed to redistribute joint contact pressures and restore stability. Methods: Thirteen patients with fixed cavovarus feet (6 neurogenic, 7 idiopathic; 6 with hindfoot instability, 7 without) and mild to moderate anteromedial ankle arthrosis were treated by osteotomies and tendon transfers but no lateral ligament reconstruction. Anteromedial cheilectomy of the ankle was added to increase dorsiflexion and alleviate anteromedial impingement. Results: Failure occurred in 2 patients, who required additional procedures. The remaining 11 patients improved from preoperative 45 to 71 points (American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale score) at the latest follow-up (average 84 months). Ankle dorsiflexion improved 7 degrees on average. There was no recurrent hindfoot instability and no progression of anteromedial ankle arthrosis over time. Conclusion: Cavovarus foot realignment with anteromedial ankle cheilectomy reliably improved patients’ symptoms related to ankle arthrosis, restored lateral hindfoot stability, and stabilized the extent of anteromedial ankle arthrosis when talar varus tilt was reduced. Level of Evidence: Level IV, retrospective case series.
Exercise for the Treatment of Depression

Depression is a common mental disorder that presents with depressed mood, loss of interest or pleasure, feel- ings of guilt or low self-worth, disturbed sleep and/or appetite, low energy, and poor concentration. Depression is a wide- spread and often chronic condition. Lifetime prevalence estimates for major depressive disorder are approximately 15% to 20%; 1-year prevalence estimates are 5% to 10%. Moreover, depression is characterized by high rates of relapse: 22% to 50% of patients suffer recurrent episodes within 6 months after recovery. Depression is associated with a high incidence of co-morbid somatic illness. Individuals suffering from major depression run a higher relative risk of coronary heart disease, type 2 diabetes and osteoporosis compared with the general popula- tion. In general, depressed individuals exhibit a less active life-style and have a reduced cardio-respiratory fitness in com- parison with the general population. Strong evidence demonstrates that lack of physical activity is associated with an un- healthier body mass and composition, and a biomarker risk profile for cardiovascular disease, type 2 diabetes, and osteo- porosis. A growing body of evidence suggests that exercise is an effective treatment for depression. For mild to moderate depression the effect of exercise may be comparable to antidepressant medication and psychotherapy; for severe depres- sion exercise seems to be a valuable complementary therapy to the traditional treatments. Exercise training not only im- proves depression, but also produces 'positive side effects' on depression associated physical diseases and cognitive de- cline. We identified the meta-analyses in the area of exer- cise/physical activity and depression from 1998 until 2008. Relevant studies were identified by searching PubMed, Med- line, Sport Discus, and PsycInfo. Terms used in the search were 'depression', 'clinical depression', 'depressive symp- toms', 'exercise', 'physical activity', 'meta-analysis'. We also identified the meta-analyses and single-studies on the theme depression as an independent risk factor for develop- ment of coronary heart disease, type 2 diabetes and osteopo- rosis. All studies that investigated the role of exercise in the association among depression and these diseases were in- cluded. Finally, literature was also identified by citation tracking using reference lists from selected papers.
Difference threshold test for M-ary orthogonal FSK signaling in Rayleigh fading channels

We present the difference threshold test (DTT) for M-ary orthogonal frequency shift keying (FSK) signaling in Rayleigh flat fading channels. The proposed DTT declares an erasure whenever the difference between the largest and the second largest energy detector output does not exceed a fixed threshold. We show that the DTT is an approximation of the Bayesian erasure test, but provides almost the same performance as the Bayesian erasure test. For (7,3) and (31,15) Reed-Solomon (RS)-coded systems, the DTT provides power gains of 0.8 dB and 0.4 dB over the ratio threshold test (RTT), respectively. We prove that the limiting performance of the DTT approaches that of the RTT for very large M.
Positron Emission Tomography and Single-Photon Emission Computed Tomography in Neurology

ABSTRACTPurpose of Review: Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are now available for routine clinical applications in neurology. This article discusses their diagnostic use in dementia, brain tumors, epilepsy, parkinsonism, cerebrovascular disease, and traumatic brain injury.Recent Findings: Neuromolecular imaging, also known as nuclear neurology, involves clinical imaging of both basal regional physiology (perfusion, metabolism, and transport mechanisms) and specific neurochemical physiology (currently, only the dopamine transporter). This article serves as an introduction to neuromolecular imaging, reviewing the literature supplemented by the author’s experience.Summary: Neurologic PET and SPECT are no longer restricted to the research realm. These modalities have high diagnostic accuracy.
A Candida albicans CRISPR system permits genetic engineering of essential genes and gene families

CRISPR simplifies genetic engineering of the human fungal pathogen Candida albicans. Candida albicans is a pathogenic yeast that causes mucosal and systematic infections with high mortality. The absence of facile molecular genetics has been a major impediment to analysis of pathogenesis. The lack of meiosis coupled with the absence of plasmids makes genetic engineering cumbersome, especially for essential functions and gene families. We describe a C. albicans CRISPR system that overcomes many of the obstacles to genetic engineering in this organism. The high frequency with which CRISPR-induced mutations can be directed to target genes enables easy isolation of homozygous gene knockouts, even without selection. Moreover, the system permits the creation of strains with mutations in multiple genes, gene families, and genes that encode essential functions. This CRISPR system is also effective in a fresh clinical isolate of undetermined ploidy. Our method transforms the ability to manipulate the genome of Candida and provides a new window into the biology of this pathogen.
The Effects of Foreknowledge and Task-Set Shifting as Mirrored in Cue- and Target-Locked Event-Related Potentials

The present study examined the use of foreknowledge in a task-cueing protocol while manipulating sensory updating and executive control in both, informatively and non-informatively pre-cued trials. Foreknowledge, sensory updating (cue switch effects) and task-switching were orthogonally manipulated in order to address the question of whether, and to which extent, the sensory processing of cue changes can partly or totally explain the final task switch costs. Participants responded faster when they could prepare for the upcoming task and if no task-set updating was necessary. Sensory cue switches influenced cue-locked ERPs only when they contained conceptual information about the upcoming task: frontal P2 amplitudes were modulated by task-relevant cue changes, mid-parietal P3 amplitudes by the anticipatory updating of stimulus-response mappings, and P3 peak latencies were modulated by task switching. Task preparation was advantageous for efficient stimulus-response re-mapping at target-onset as mirrored in target N2 amplitudes. However, N2 peak latencies indicate that this process is faster for all repeat trials. The results provide evidence to support a very fast detection of task-relevance in sensory (cue) changes and argue against the view of task repetition benefits as secondary to purely perceptual repetition priming. Advanced preparation may have a stronger influence on behavioral performance and target-locked brain activity than the local effect of repeating or switching the task-set in the current trial.
Efficacy of risperidone treatment for psychoses associated with schizophrenia, schizoaffective disorder, bipolar disorder, or senile dementia in 11 geriatric patients: a case series.

BACKGROUND Clinical trials of risperidone, a recently approved novel antipsychotic, included elderly healthy patients, but more data are needed on the effects of risperidone in this population, especially those with comorbid medical illnesses. METHOD Risperidone was used to treat 11 elderly hospitalized patients between 61 and 79 years of age who manifested signs of psychoses related to schizophrenia, schizoaffective disorder, bipolar disorder, or senile dementia. All patients had been treated previously with classic antipsychotics. Response was assessed by clinical observation of the patients' behavior. RESULTS Eight patients responded to treatment, 1 did not respond, and 2 had treatment discontinued because of hypotension or dizziness. Positive and negative symptoms decreased markedly in 7 of the responding patients. Four patients had preexisting extrapyramidal symptoms (EPS) and symptoms of tardive dyskinesia that also decreased in response to risperidone treatment. In addition, 4 patients were able to discontinue anti-parkinsonian medications, and 2 were able to discontinue antihypertensive medications. Side effects related to blockade of dopamine, histamine, and serotonin were negligible. No adverse consequences occurred when electroconvulsive therapy, carbamazepine, or lithium was given concurrently. CONCLUSION The reduction of both positive and negative symptoms of schizophrenia and the lack of significant EPS, tardive dyskinesia, sedation, and anticholinergic side effects indicate that risperidone is a safe and effective medication for the elderly.