Miracle-dz/UniFAR-FTUs huggingface dataset:
Deep Structured Energy Based Models for Anomaly Detection

In this paper, we attack the anomaly detection problem by directly modeling the data distribution with deep architectures. We propose deep structured energy based models (DSEBMs), where the energy function is the output of a deterministic deep neural network with structure. We develop novel model architectures to integrate EBMs with different types of data such as static data, sequential data, and spatial data, and apply appropriate model architectures to adapt to the data structure. Our training algorithm is built upon the recent development of score matching \cite{sm}, which connects an EBM with a regularized autoencoder, eliminating the need for complicated sampling method. Statistically sound decision criterion can be derived for anomaly detection purpose from the perspective of the energy landscape of the data distribution. We investigate two decision criteria for performing anomaly detection: the energy score and the reconstruction error. Extensive empirical studies on benchmark tasks demonstrate that our proposed model consistently matches or outperforms all the competing methods.
Novel application of stereotactic ablative radiotherapy using CyberKnife® for early-stage renal cell carcinoma in patients with pre-existing chronic kidney disease: Initial clinical experiences

The treatment of renal cell carcinoma (RCC) in patients diagnosed with chronic kidney disease (CKD) requires particular care in order to preserve the remaining renal function. The present study aimed to investigate the potential of a novel nephron-sparing treatment, which is capable of targeting tumors embedded deep within tissues. The present study analyzed three patients, with pre-existing CKD and multiple comorbidities, who were successfully treated for stage I RCC using the CyberKnife® stereotactic ablative radiotherapy (SABR) system. The total prescribed dose was 40 Gy in five fractions administered over five consecutive days. Treatment efficiency was determined using computed tomography scans of the tumors and periodic measurements of the glomerular filtration rate over a period of 12–40 months. Local control, defined as a radiologically stable condition, was achieved in all patients. Lung metastasis was observed in one patient nine months after SABR; however, the side-effects were generally mild and self-limiting. One patient developed renal failure 26 months after SABR, while the severity of CKD was only marginally altered in the other two patients and renal failure did not occur. In conclusion, in the present study, SABR with CyberKnife® was observed to be well tolerated in the patients, with an acceptable acute toxicity effect. Therefore, it may represent a potential therapeutic option for patients with early-stage RCC who have previously been diagnosed with CKD, but for whom other nephron-sparing treatments are contraindicated.
Myocyte Turnover in the Aging Human Heart

Rationale: The turnover of cardiomyocytes in the aging female and male heart is currently unknown, emphasizing the need to define human myocardial biology. Objective: The effects of age and gender on the magnitude of myocyte regeneration and the origin of newly formed cardiomyocytes were determined. Methods and Results: The interaction of myocyte replacement, cellular senescence, growth inhibition, and apoptosis was measured in normal female (n=32) and male (n=42) human hearts collected from patients 19 to 104 years of age who died from causes other than cardiovascular diseases. A progressive loss of telomeric DNA in human cardiac stem cells (hCSCs) occurs with aging and the newly formed cardiomyocytes inherit short telomeres and rapidly reach the senescent phenotype. Our data provide novel information on the superior ability of the female heart to sustain the multiple variables associated with the development of the senescent myopathy. At all ages, the female heart is equipped with a larger pool of functionally competent hCSCs and younger myocytes than the male myocardium. The replicative potential is higher and telomeres are longer in female hCSCs than in male hCSCs. In the female heart, myocyte turnover occurs at a rate of 10%, 14%, and 40% per year at 20, 60, and 100 years of age, respectively. Corresponding values in the male heart are 7%, 12%, and 32% per year, documenting that cardiomyogenesis involves a large and progressively increasing number of parenchymal cells with aging. From 20 to 100 years of age, the myocyte compartment is replaced 15 times in women and 11 times in men. Conclusions: The human heart is a highly dynamic organ regulated by a pool of resident hCSCs that modulate cardiac homeostasis and condition organ aging.
Clinical evaluation of the microscopic-observation drug-susceptibility assay for detection of tuberculosis.

BACKGROUND There is an urgent need for low-cost methods for rapid, accurate detection of Mycobacterium tuberculosis in clinical specimens. The microscopic-observation drug-susceptibility (MODS) assay is a relatively low-cost and simple liquid culture method that has been proposed for use in resource-limited environments. METHODS This prospective study evaluated the performance of the MODS assay for detection of M. tuberculosis in persons undergoing evaluation for pulmonary tuberculosis in Brazil and Honduras. Respiratory specimens were evaluated using smear microscopy, culture on Lowenstein-Jensen medium, and culture using the MODS assay. A subset of specimens was also cultured using the Mycobacterial Growth Indicator Tube (MGIT) 960 automated system (Becton Dickinson). A study subject was considered to have tuberculosis if at least 1 culture on Lowenstein-Jensen medium was positive for M. tuberculosis. FINDINGS A total of 1639 respiratory specimens obtained from 854 study subjects were analyzed. On a per-subject basis, MODS sensitivity was 97.5% (95% confidence interval [CI], 95.7-98.6), and specificity was 94.4% (95% CI, 93.1-95.2). Median times to detection were 21 days (interquartile range [IQR], 17-25 days) and 7 days (IQR, 5-10) for culture on Lowenstein-Jensen medium and for the MODS assay, respectively (P<.01). For 64 specimens cultured using the MGIT 960 automated system, median time to growth was similar for the MODS assay (7 days; IQR, 7-10 days) and the MGIT 960 automated system (8 days; IQR, 6-11.5 days; P=.16). The percentage of contaminated cultures was lower for the MODS assay than for culture on Lowenstein-Jensen medium (3.8% vs. 5.8%; P<.01). CONCLUSIONS The MODS assay is a relatively simple test whose good performance characteristics for detection of pulmonary tuberculosis may make it suitable for resource-limited environments.
Impaired Development of CD4 CD25 Regulatory T Cells in the Absence of STAT1: Increased Susceptibility to Autoimmune Disease

Type I and II interferons (IFNs) exert opposing effects on the progression of multiple sclerosis, even though both IFNs use the signal transducer and activator of transcription 1 (STAT1) as a signaling mediator. Here we report that STAT1-deficient mice expressing a transgenic T cell receptor against myelin basic protein spontaneously develop experimental autoimmune encephalomyelitis with dramatically increased frequency. The heightened susceptibility to this autoimmune disease appears to be triggered by a reduced number as well as a functional impairment of the CD4 CD25 regulatory T cells in STAT1-deficient animals. Adoptive transfer of wild-type regulatory T cells into STAT1-deficient hosts is sufficient to prevent the development of autoimmune disease. These results demonstrate an essential role of STAT1 in the maintenance of immunological self-tolerance.
Anti-predator defence drives parallel morphological evolution in flea beetles

Complex morphological or functional traits are frequently considered evolutionarily unique and hence useful for taxonomic classification. Flea beetles (Alticinae) are characterized by an extraordinary jumping apparatus in the usually greatly expanded femur of their hind legs that separates them from the related Galerucinae. Here, we examine the evolution of this trait using phylogenetic analysis and a time-calibrated tree from mitochondrial (rrnL and cox1) and nuclear (small subunits and large subunits) genes, as well as morphometrics of femora using elliptic Fourier analysis. The phylogeny strongly supports multiple independent origins of the metafemoral spring and therefore rejects the monophyly of Alticinae, as defined by this trait. Geometric outline analysis of femora shows the great plasticity of this structure and its correlation with the type and diversity of the metafemoral springs. The recognition of convergence in jumping apparatus now resolves the long-standing difficulties of Galerucinae–Alticinae classification, and cautions against the value of trait complexity as a measure of taxonomic significance. The lineage also shows accelerated species diversification rates relative to other leaf beetles, which may be promoted by the same ecological factors that also favour the repeated evolution of jumping as an anti-predation mechanism.
Factors Affecting Tropical Tree Damage and Survival after Catastrophic Wind Disturbance

The structure and dynamics of cyclone‐prone tropical forests are driven in part by variation in tree species resistance to and survival after wind‐induced structural damage. We determined the factors associated with tree damage and 3‐yr survival following Category 5 Cyclone Olaf on the Polynesian island of Ta'u, American Samoa. Despite sustaining a high rate of severe damage (34.6% of all trees snapped, 23.0% uprooted), system resilience was high with 74.3 percent stem survival overall and an annual mortality rate of 7.9 percent compared with 2.1 percent in nearby undisturbed late successional forest. Three‐yr survival rate of trees sustaining severe damage was 63.1 percent, compared to about 89 percent for trees sustaining only branch loss or defoliation. Three‐yr survival differed according to damage type, 78.5 percent after snapping vs. 38.4 percent after uprooting. Species differed widely in resistance to and survival after snapping and uprooting. Several species and individual traits were associated with the probability of snapping or uprooting; however, wood density was the only species trait consistently, and negatively, associated with the probability of sustaining either damage type. Survival after snapping was negatively associated with the proportion of the tree snapped off, which was determined by individual tree architecture. Species growth rate was negatively associated with survival after uprooting, indicating the importance of shade tolerance for survival after uprooting. Thus, whereas species traits seemed to exclusively underpin resistance to and survival after uprooting, they only partly accounted for snapping resistance, and did not determine the intensity of snap damage or survival after snapping. Our results highlight the importance of considering each damage type separately when considering ecological trade‐offs.
Levetiracetam monotherapy in Alzheimer patients with late‐onset seizures: a prospective observational study

Levetiracetam (LEV) monotherapy was investigated in 25 patients with advanced Alzheimer's disease (AD) and new‐onset epileptic seizures in a prospective open‐label study. At a daily dose of 1000–1500 mg, 72% were seizure‐free for at least one year; 16% discontinued for untolerability; 8% were unresponsive; 4% were lost to follow‐up. These results suggest the need for controlled studies to confirm if LEV can be a first‐choice drug in AD.
Alcohol Use and Frailty Risk among Older Adults over 12 Years: The Health and Retirement Study

ABSTRACT Objectives: The primary goal was to examine the relationship between alcohol use and frailty, a variable characterizing late-life decline, in a national, longitudinal survey of older adults living in the United States. Methods: The sample drawn from the Health and Retirement Study included 9,499 stroke-free participants over age 65 in 2000. The sample was 59.1% female, and had a mean age of 74.25 years (SD = 6.99). Follow-up data was from 2004, 2008, and 2012. Frailty was defined phenotypically using the Paulson-Lichtenberg Frailty Index (PLFI). Alcohol use was measured via self-report. Control variables included age, race, education, socio-economic status (SES), depressive symptomatology, medical burden score, body mass index (BMI), and partner status. With abstinent participants as the reference group, logistic regressions were conducted to determine prevalent frailty at 2000, and Cox’s proportional hazard models were utilized to determine time to incident frailty over a 12-year period. Results: Results revealed that age, depressive symptomatology, and medical burden score were significant positive correlates of prevalent and incident frailty (p < .05) for both males and females. Logistic regressions revealed that consumption of 1–7 alcoholic drinks per week was associated with reduced prevalent frailty (OR = .49, p < .001) for females. Survival analysis results reveal that compared with nondrinkers, males and females who reportedly consumed 1–7 drinks per week had a decreased probability of incident frailty (HR = .78–081, p < .05). Conclusions: Findings suggest that moderate alcohol use confers reduced frailty risk for both older men and women. Future research should examine the mechanism(s) relating alcohol consumption and frailty. Clinical Implications: Findings support extant literature suggesting some healthcare benefits may be associated with moderate drinking.
Regulation of FLOWERING LOCUS T by a MicroRNA in Brachypodium distachyon[C][W]

This work identifies a Pooideae-specific microRNA that posttranscriptionally regulates the florigen gene FT under different daylength conditions in Brachypodium distachyon, revealing one mechanism in the complex but precise genetic regulatory pathways for flowering time control in plants. The highly conserved florigen gene FLOWERING LOCUS T (FT) functions at the core of the flowering pathways. Extensive studies have examined the transcriptional regulation of FT; however, other layers of FT regulation remain unclear. Here, we identified miR5200 a Pooideae-specific microRNA that is expressed in leaves and targets Brachypodium distachyon FT orthologs for mRNA cleavage. miR5200 was abundantly expressed in plants grown under short-day (SD) conditions but was dramatically repressed in plants transferred to long-day (LD) conditions. We also found that the epigenetic chromatin status, specifically the levels of histone methylation marks, at miR5200 precursor loci changed in response to daylength. Moreover, artificial interruption of miR5200 activity by target mimicry in B. distachyon altered flowering time in SD but not in LD conditions, suggesting that miR5200 functions in photoperiod-mediated flowering time regulation. Together, these findings illustrate a posttranscriptional regulation mechanism of FT and provide insights into understanding of the multiple concerted pathways for flowering time control in plants.
Allotopic expression of mitochondrial-encoded genes in mammals: achieved goal, undemonstrated mechanism or impossible task?

Mitochondrial-DNA diseases have no effective treatments. Allotopic expression—synthesis of a wild-type version of the mutated protein in the nuclear-cytosolic compartment and its importation into mitochondria—has been proposed as a gene-therapy approach. Allotopic expression has been successfully demonstrated in yeast, but in mammalian mitochondria results are contradictory. The evidence available is based on partial phenotype rescue, not on the incorporation of a functional protein into mitochondria. Here, we show that reliance on partial rescue alone can lead to a false conclusion of successful allotopic expression. We recoded mitochondrial mt-Nd6 to the universal genetic code, and added the N-terminal mitochondrial-targeting sequence of cytochrome c oxidase VIII (C8) and the HA epitope (C8Nd6HA). The protein apparently co-localized with mitochondria, but a significant part of it seemed to be located outside mitochondria. Complex I activity and assembly was restored, suggesting successful allotopic expression. However, careful examination of transfected cells showed that the allotopically-expressed protein was not internalized in mitochondria and that the selected clones were in fact revertants for the mt-Nd6 mutation. These findings demonstrate the need for extreme caution in the interpretation of functional rescue experiments and for clear-cut controls to demonstrate true rescue of mitochondrial function by allotopic expression.
Preventive Ablation Strategies in a Biophysical Model of Atrial Fibrillation Based on Realistic Anatomical Data

Ablation strategies to prevent episodes of paroxysmal atrial fibrillation (AF) have been subject to many clinical studies. The issues mainly concern pattern and transmurality of the lesions. This paper investigates ten different ablation strategies on a multilayered 3-D anatomical model of the atria with respect to 23 different setups of AF initiation in a biophysical computer model. There were 495 simulations carried out showing that circumferential lesions around the pulmonary veins (PVs) yield the highest success rate if at least two additional linear lesions are carried out. The findings compare with clinical studies as well as with other computer simulations. The anatomy and the setup of ectopic beats play an important role in the initiation and maintenance of AF as well as the resulting therapy. The computer model presented in this paper is a suitable tool to investigate different ablation strategies. By including individual patient anatomy and electrophysiological measurement, the model could be parameterized to yield an effective tool for future investigation of tailored ablation strategies and their effects on atrial fibrillation.
Impact of a nutritional formula enriched in fish oil and micronutrients on pressure ulcers in critical care patients.

BACKGROUND Pressure ulcers are an important source of morbidity and suffering for patients and a formidable burden on caregivers. OBJECTIVES To assess the impact of a feeding formula enriched with fish oil on healing of preexisting pressure ulcers and serum levels of C-reactive protein in critical care patients. METHODS Adult patients with pressure ulcers grade II or higher were randomly allocated to receive either a formula enriched with fish oil or an isocaloric control formula. Wound healing was assessed by using the Pressure Ulcer Scale for Healing tool on days 7, 14, and 28. Blood levels of C-reactive protein were measured on days 0, 7, and 14. RESULTS Baseline demographics did not differ between the study (n = 20) and the control (n = 20) groups. The mean score on the ulcer healing tool increased significantly (P = .02) from day 0 to day 28 in the control group (from 9.25 [SD, 2.12] to 10.75 [SD, 3.41]) compared with the study group (from 9.10 [SD, 2.84] to 9.40 [SD, 3.72]). Mean levels of C-reactive protein decreased significantly (P= .02) from day 0 to day 14 in the study group (from 191 [SD, 104.4] mg/L to 111.7 [SD, 97.8] mg/L) compared with the control group (from 145 [SD, 90] mg/L to 139 [SD, 62] mg/L). CONCLUSION Administration of a feeding formula enriched with fish oil was associated with decreased progression of pressure ulcers and a decrease in blood concentrations of C-reactive protein.
Mechanisms of Tissue Uptake and Retention in Zotarolimus-Coated Balloon Therapy

Background— Drug-coated balloons are increasingly used for peripheral vascular disease, and, yet, mechanisms of tissue uptake and retention remain poorly characterized. Most systems to date have used paclitaxel, touting its propensity to associate with various excipients that can optimize its transfer and retention. We examined zotarolimus pharmacokinetics. Methods and Results— Animal studies, bench-top experiments, and computational modeling were integrated to quantify arterial distribution after zotarolimus-coated balloon use. Drug diffusivity and binding parameters for use in computational modeling were estimated from the kinetics of zotarolimus uptake into excised porcine femoral artery specimens immersed in radiolabeled drug solutions. Like paclitaxel, zotarolimus exhibited high partitioning into the arterial wall. Exposure of intimal tissue to drug revealed differential distribution patterns, with zotarolimus concentration decreasing with transmural depth as opposed to the multiple peaks displayed by paclitaxel. Drug release kinetics was measured by inflating zotarolimus-coated balloons in whole blood. In vivo drug uptake in swine arteries increased with inflation time but not with balloon size. Simulations coupling transmural diffusion and reversible binding to tissue proteins predicted arterial distribution that correlated with in vivo uptake. Diffusion governed drug distribution soon after balloon expansion, but binding determined drug retention. Conclusions— A large bolus of zotarolimus releases during balloon inflation, some of which pervades the tissue, and a fraction of the remaining drug adheres to the tissue–lumen interface. As a result, the duration of delivery modulates tissue uptake where diffusion and reversible binding to tissue proteins determine drug transport and retention, respectively.
Nonnormality and Finite Precision Arithmetic in PowerMethod

The Power Method is the simplest algorithm for computing eigenvalues and eigenvec-tors, yet its behaviour when subjected to rounding error and when the matrix is highly nonnormal has never been examined comprehensively. The Power Method deenes a dy-namical system on a sphere. Many eeects of nonnormality on the algorithm in both exact and nite precision arithmetic can easily be translated into dynamical phenomena. We analyse exhaustively the method for 2 2 matrices where, despite the apparent simplicity , complex behaviour is possible. Many results can be generalised to n dimensions. In particular, we are able to show that chaotic motion is impossible in exact arithmetic, in contrast to the Rayleigh Quotient Iteration.
Incidence of Liver Injury After Beginning Antiretroviral Therapy with Efavirenz or Nevirapine

Abstract Objective: To compare the incidence and define the risk factors associated with liver toxicity in patients beginning treatment with nevirapine (NVP) and efavirenz (EFZ). Method: This was a retrospective chart review of all HIV-infected patients starting any antiretroviral regimen containing at least two nucleoside analogues plus either NVP or EFZ between January 1998 and January 2000. Liver toxicity was defined as an increase in transaminase levels 5-fold above the upper limits of normal if they were normal at baseline or 3.5-fold above baseline levels if they werepreviously elevated. Results: Out of 298 patients included in the study, 162 received NVP and 136 EFZ. Overall, 75% were men, and 45% were coinfected with the hepatitis C virus (HCV). Median (interquartile range) time on follow-up was 10 (6-12) months. Liver toxicity was more frequently associated with NVP (12%) than with EFZ (4%) (p = .016). Overall, it was first recognized at a median time of 5.5 months (2.7-9.2) on therapy, with no differences between treatment arms. Both univariate and multivariate analyses identified the use of NVP, HCV coinfection, alcohol abuse, and female gender as independent risk factors for liver toxicity. Conclusion: Liver damage is three times more common in patients receiving NVP than in those taking EFZ. In both groups of patients, it is recognized late, after an average of 5.5 months on therapy. Coinfection with HCV, alcohol abuse, and female gender increase the risk for developing liver toxicity with both drugs.