Miracle-dz/UniFAR-FTUs huggingface dataset:
An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers: the atherosclerosis risk in communities study.

BACKGROUND There has been interest in recent years in whether additional, and in particular novel, risk factors or blood markers, such as C-reactive protein, can enhance existing coronary heart disease (CHD) prediction models. METHODS Using a series of case-cohort studies, the prospective Atherosclerosis Risk in Communities (ARIC) Study assessed the association of 19 novel risk markers with incident CHD in 15,792 adults followed up since 1987-1989. Novel markers included measures of inflammation, endothelial function, fibrin formation, fibrinolysis, B vitamins, and antibodies to infectious agents. Change in the area under the receiver operating characteristic curve (AUC) was used to assess the additional contribution of novel risk markers to CHD prediction beyond that of traditional risk factors. RESULTS The basic risk factor model, which included traditional risk factors (age, race, sex, total and high-density lipoprotein cholesterol levels, systolic blood pressure, antihypertensive medication use, smoking status, and diabetes), predicted CHD well, as evidenced by an AUC of approximately 0.8. The C-reactive protein level did not add significantly to the AUC (increase in AUC of 0.003), and neither did most other novel risk factors. Of the 19 markers studied, lipoprotein-associated phospholipase A(2), vitamin B(6), interleukin 6, and soluble thrombomodulin added the most to the AUC (range, 0.006-0.011). CONCLUSIONS Our findings suggest that routine measurement of these novel markers is not warranted for risk assessment. On the other hand, our findings reinforce the utility of major, modifiable risk factor assessment to identify individuals at risk for CHD for preventive action.
Yeast AP-1 like transcription factors (Yap) and stress response: a current overview

Yeast adaptation to stress has been extensively studied. It involves large reprogramming of genome expression operated by many, more or less specific, transcription factors. Here, we review our current knowledge on the function of the eight Yap transcription factors (Yap1 to Yap8) in Saccharomyces cerevisiae, which were shown to be involved in various stress responses. More precisely, Yap1 is activated under oxidative stress, Yap2/Cad1 under cadmium, Yap4/Cin5 and Yap6 under osmotic shock, Yap5 under iron overload and Yap8/Arr1 by arsenic compounds. Yap3 and Yap7 seem to be involved in hydroquinone and nitrosative stresses, respectively. The data presented in this article illustrate how much knowledge on the function of these Yap transcription factors is advanced. The evolution of the Yap family and its roles in various pathogenic and non-pathogenic fungal species is discussed in the last section.
3D Holographic Imaging and Trapping for Non-Invasive Cell Identification and Tracking

Real-time high-throughput identification, screening, characterization, and processing of biological specimen is of great interest to a host of areas spanning from cell biology and medicine to security and defense. Much like human biometrics, microorganisms exhibit natural signatures that can be used for identification. In this paper, we first overview two optical techniques, namely digital holographic microscopy and holographic optical tweezers which can non-invasively image, manipulate, and identify microorganisms in three dimensions. The two methods bear similarities in their optics and implementation. Thus, we have proposed a new approach to identification of micro/nano organisms and cells by combining the two methods of digital holographic microscopy and holographic optical tweezers which can be integrated into a single compact hardware. The proposed system can simultaneously sense, control, identify, and track cells and microorganisms in three dimensions. New possibilities that arise from the proposed method are discussed.
A novel high-torque-density and wide-speed-range hub motor for electric vehicle propulsion

This article proposes a novel hub motor, which uses variable electromagnetic (EM) gearing to leverage torque and rotation speed when necessary. Depending on driving conditions, the motor can select a high EM gear ratio or a low EM gear ratio to either increase torque or to increase speed. The technology requires combination of a pole-changeable phase winding and geometry-variable stator profile. The performance of the motor is evaluated and compared with other traditional motors.
Transplantation of Mature Photoreceptors in Rodents With Retinal Degeneration

Purpose To demonstrate survival and integration of mature photoreceptors transplanted with the retinal pigment epithelium (RPE). Methods Full-thickness retina with attached RPE was harvested from healthy adult rats. Grafts were implanted into two rat models of retinal degeneration, Royal College of Surgeons (RCS) and S334ter-3. Survival of the host and transplanted retina was monitored using optical coherence tomography (OCT) for up to 6 months. The retinal structure and synaptogenesis between the host and transplant was assessed by histology and immunohistochemistry. Results OCT and histology demonstrated a well-preserved photoreceptor layer with inner and outer segments, while the inner retinal layers of the transplant largely disappeared. Grafts, including RPE, survived better than without and the transplanted RPE appeared as a monolayer integrated with the native one. Synaptogenesis was observed through sprouting of new dendrites from the host bipolar cells and synaptic connections forming with cells of the transplant. However, in many samples, a glial fibrillary acidic protein–positive membrane separated the host retina and the graft. Conclusions Presence of RPE in the graft improved the survival of transplanted photoreceptors. Functional integration between the transplant and the host retina is likely to be further enhanced if formation of a glial seal could be prevented. Transplantation of the mature photoreceptors with RPE may be a practical approach to restoration of sight in retinal degeneration. Translational Relevance This approach to restoration of sight in patients with photoreceptor degeneration can be rapidly advanced to clinical testing. In patients with central scotoma, autologous transplantation of the peripheral retina can be an option.
The Evaluation of Attention Deficit/ Hyperactivity Disorder in Family Medicine Residency Programs

Background: Previous studies have highlighted great variability in how primary care physicians arrive at the diagnosis of Attention Deficit/ Hyperactivity Disorder (ADHD) and their frequent use of unreliable methods. This study examines how physicians in family medicine residency programs evaluate for ADHD in light of the 2000 American Academy of Pediatrics ADHD Practice guidelines. Methods: A 55-item survey was sent to 17 military and 17 civilian family medicine residency programs. Two hundred and thirty-five physicians participated. Descriptive statistics and chi-square analysis was performed. Results: Only 22% of physicians are familiar with the AAP guidelines and only 12.9% of respondents screen for ADHD. 70% of physicians use a child’s behavior in the office and 53% use a child’s response to stimulants to arrive at a diagnosis. Conclusions: Four years after publication of the practice guidelines, few physicians incorporate them into their practice. A majority of physicians still use unreliable methods in diagnosing ADHD.
Thickness, Cross‐Sectional Areas and Depth of Invasion in the Prognosis of Cutaneous Melanoma

CuTANEous melanoma is a most unpredictable lesion. The marked variation in prognosis is probably a function of many variables, one of which is the size of the tumor. Though there is a roughly inverse relationship between the diameter of the lesion and survival,5 very small lesions have recurred or metastasized. One possible reason for the lack of reliability of tumor size in estimating prognosis may be that studies to date have considered size in only two diamensions and have neglected tumor volume. Two melanomas can have the same diameter but differ greatly in thickness because of variation in either depth of invasion or degree of protrusion from the surface of the skin or both. A recent study 2 has shown that prognosis correlates well with staging of the depth of invasion, but there have been no studies relating survival to tumor volume. To measure tumor volume it is necessary to know the surface area of the tumor, but in this retrospective study we only know the maximal diameters of the lesions. By measuring the maximal thickness of the lesions we can calculate the maximal crosssectional area, which should be roughly proportional to the volume of the tumor. The depth of invasion was also studied using the criteria for staging of Clark et al.2 to see if maximal cross-sectional area, thickness, stage of invasion, or a combination of these can be of value in assessing the prognosis of cutaneous melanoma. A total of 98 lesions were so studied.
A DNA telomerase vaccine for canine cancer immunotherapy

Telomerase reverse transcriptase (TERT) is highly expressed in more than 90% of canine cancer cells and low to absent in normal cells. Given that immune tolerance to telomerase is easily broken both naturally and experimentally, telomerase is an attractive tumor associated antigen for cancer immunotherapy. Indeed, therapeutic trials using human telomerase peptides have been performed. We have developed an immunogenic yet catalytically inactive human telomerase DNA construct that is in clinical trials with patients presenting solid tumors. Paralleling this human construct, we have developed a canine telomerase DNA vaccine, called pDUV5. When administered intradermally to mice combined with electrogene transfer, pDUV5 induced canine TERT specific cytotoxic T-cells as measured by IFN-γ ELISpot assay. Intradermal vaccination of healthy dogs with 400 μg of pDUV5 generated strong, broad and long lasting TERT specific cellular immune responses. In vitro immunization with cTERT peptides revealed the maintenance of cTERT specific T-cells in PBMCs from tumor bearing dogs showing that this repertoire was not depleted. This study highlights the potential of pDUV5 as a cancer vaccine and supports its evaluation for the treatment of spontaneous canine tumors.
Endogenous estrogens as carcinogens through metabolic activation.

A common thread linking the main risks for developing breast cancer in women is cumulative, excessive exposure to estrogen. The standard paradigm to account for this association focuses on increased cell proliferation caused by estrogen through estrogen receptor-mediated signal transduction accompanied by increased probability for mutation to occur during DNA synthesis. This chapter provides an overview of the mounting evidence, provided from cell culture and whole animal experimental studies, in support of a role for the oxidative metabolites of estrogen, in particular, the catechol estrogens, in the development of estrogen carcinogenesis. This provides a paradigm for how estrogens may contribute to the development of human breast cancer. The chapters that follow will fill in the details. Evidence shows that the catechols themselves are signaling molecules that work through the estrogen receptor. In addition, upon further oxidation, the catechols can give rise to reactive quinones capable of forming direct adducts with glutathione and purines in DNA and of redox cycling to generate reactive oxygen species that can cause oxidative damage. Estradiol and estrone, as well as their 4-hydroxy catechols, are carcinogenic in the Syrian golden hamster kidney, and ethinyl estradiol is a strong promoter of hepatocarcinogenesis in the rat. Increased oxidative DNA damage has been detected in target tissues after estrogen treatment in both animal model systems. Furthermore, several recent molecular epidemiologic studies have found that a polymorphism associated with a low-activity form of catechol-O-methyltransferase, an enzyme involved in the inactivation of catechol estrogens, is associated with an increased risk for developing breast cancer. The increased risk is observed in certain women, although the studies are not consistent on which subgroup of women (e.g., premenopausal or postmenopausal) is at increased risk, and one study detected no increased risk. Reasons for such discrepancies are discussed in light of factors, such as genetic polymorphisms and environmental/lifestyle susceptibility factors, which control the tissue-specific balance within cells among the estrogen metabolites. It is concluded that such factors will have to be identified through additional mechanistic studies and that, as they are identified, they can be incorporated into future molecular epidemiologic studies designed to determine their actual impact on cancer risk in human populations.
Ocular Autoimmune Systemic Inflammatory Infectious Study – Report 3: Posterior and Panuveitis

ABSTRACT Purpose: To report the pattern of posterior and panuveitis at a tertiary referral center in Singapore. Methods: Subgroup retrospective analysis of 334 new posterior and panuveitis cases, from the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) database. Descriptive analysis was performed and visual outcome and complications were reported. Results: The etiology for posterior uveitis and panuveitis was infectious in 162 patients (48.5%), non-infectious in 144 patients (43.1%), and idiopathic in 28 patients (8.4%). More patients with bilateral disease had a non-infectious etiology (n = 82, 50.9%) (p = 0.012). The most common complication was epiretinal membrane (n = 20, 12.3%) for the infectious group and cystoid macular edema (n = 12, 8.3%) for the non-infectious group. Conclusions: The proportion of etiologies in our cohort varies from other studies. Understanding the variations and demographic associations allows the diagnosis and management of posterior and panuveitis to be further improved.
Preventing HIV infection among adolescents: evaluation of a school-based education program.

BACKGROUND This article reports the results of the impact of a school-based HIV prevention intervention on students' knowledge, attitudes, and behavior related to HIV infection. METHODS Seventeen schools within six Colorado school districts were assigned to either intervention or comparison conditions. Students in 10 schools received a 15-session, skills-based HIV prevention curriculum implemented by trained teachers. A total of 2,844 students completed at least one survey during the study period; surveys were matched using demographic questions, yielding a cohort of 979 students who had baseline and 6-month follow-up data. RESULTS Intervention students exhibited greater knowledge about HIV and greater intent to engage in safer sexual practices than the comparison students. Among sexually active students at the 6-month follow-up, intervention students reported fewer sexual partners within the past 2 months, greater frequency of using condoms, and greater intentions to engage in sex less frequently and to use a condom when having sex. Intervention students were also more likely to believe that teens their age who engage in HIV risk behaviors are vulnerable to infection. The intervention neither delayed the onset nor decreased the frequency of sexual intercourse and the frequency of alcohol and other drug use before sex by the 6-month follow-up assessment. CONCLUSIONS The results suggest that skills-based risk reduction programs can have an effect on student behavior. Among sexually active students, evidence suggests that school-based interventions can reduce behavior associated with risk of HIV infection.
Clinical research challenges in rare genetic diseases in Brazil

Abstract Rare diseases are defined as conditions with a prevalence of no more than 6.5 per 10,000 people. Although each rare disease individually affects a small number of people, collectively, the 6,000 to 8,000 rare conditions (80% of them with genetic cause) affect around 8% of the world’s population. Research about the natural history and underlying pathophysiological mechanisms of rare diseases, as well as clinical trials with new drugs, are important and necessary to develop new strategies for the treatment of these conditions. This report describes the experience of a clinical research group working with rare diseases in a reference center for lysosomal diseases in Brazil (Medical Genetics Service, Hospital de Clínicas de Porto Alegre). The activities of this research group enabled its participation in several international multicenter clinical research protocols related to the natural history or therapy development for rare genetic diseases. This participation has allowed the development of personal skills and institutional facilities for clinical research. The clinical research developed in our center has raised the quality of the medical assistance provided to non-clinical research patients in addition to enabling early access to new therapies to many patients with orphan conditions.
Leukoencephalomyelopathy in cats linked to abnormal fatty acid composition of the white matter of the spinal cord and of irradiated dry cat food

Abstract Four outbreaks of leukoencephalomyelopathy in colonies of SPF cats on a long‐term diet of irradiated dry cat food were observed in the Netherlands between 1989 and 2001. As a primary defect in myelin formation was suspected to be the cause of the disease and myelin consists mainly of lipids and their fatty acids, we investigated the fatty acid composition of the white matter of the spinal cord of affected and control cats and of irradiated and non‐irradiated food. The irradiated food had low levels of alpha‐linolenic acid compared to linoleic acid as well as a high total omega‐6:omega‐3 ratio of 7:1 in the irradiated and of 2:1 in the non‐irradiated food. The white matter of the spinal cord showed low levels of linoleic acid and absence of alpha‐linolenic acid in affected cats as well as absence of lignoceric and nervonic acid in both affected and control cats. These abnormalities in fatty acid composition of the white matter of the spinal cord may reflect an increased need for alpha‐linolenic acid as a substrate for longer chain omega‐3 fatty acids to compose myelin and thus indicate a particular species sensitivity to dietary deficiency in omega‐3 polyunsaturated fatty acids, particularly alpha‐linolenic acid in cats. Our findings indicate that abnormalities in fatty acid metabolism in myelin play an essential role in the pathogenesis of this acquired form of leukoencephalomyelopathy in cats.
Genome-wide identification, characterisation and expression profiling of the ubiquitin-proteasome genes in Biomphalaria glabrata

BACKGROUND Biomphalaria glabrata is the major species used for the study of schistosomiasis-related parasite-host relationships, and understanding its gene regulation may aid in this endeavor. The ubiquitin-proteasome system (UPS) performs post-translational regulation in order to maintain cellular protein homeostasis and is related to several mechanisms, including immune responses. OBJECTIVE The aims of this work were to identify and characterise the putative genes and proteins involved in UPS using bioinformatic tools and also their expression on different tissues of B. glabrata. METHODS The putative genes and proteins of UPS in B. glabrata were predicted using BLASTp and as queries reference proteins from model organism. We characterised these putative proteins using PFAM and CDD software describing the conserved domains and active sites. The phylogenetic analysis was performed using ClustalX2 and MEGA5.2. Expression evaluation was performed from 12 snail tissues using RPKM. FINDINGS 119 sequences involved in the UPS in B. glabrata were identified, which 86 have been related to the ubiquitination pathway and 33 to proteasome. In addition, the conserved domains found were associated with the ubiquitin family, UQ_con, HECT, U-box and proteasome. The main active sites were lysine and cysteine residues. Lysines are responsible and the starting point for the formation of polyubiquitin chains, while the cysteine residues of the enzymes are responsible for binding to ubiquitin. The phylogenetic analysis showed an organised distribution between the organisms and the clades of the sequences, corresponding to the tree of life of the animals, for all groups of sequences analysed. The ubiquitin sequence was the only one with a high expression profile found in all libraries, inferring its wide range of performance. MAIN CONCLUSIONS Our results show the presence, conservation and expression profile of the UPS in this mollusk, providing a basis and new knowledge for other studies involving this system. Due to the importance of the UPS and B. glabrata, this work may influence the search for new methodologies for the control of schistosomiasis.
Primer on US Food and Nutrition Policy and Public Health: Food Sustainability.

This section of the Primer on US Food andNutrition Policy and Public Health deals with agricultural sustainability, which determines the type of nutrition, and therefore health outcomes, thatwill be offered to Americans threatened by food insecurity (Brownell et al., p. 988) and to 30 million schoolchildren (Schwartz et al., p. 989). The farm bill is the most important vehicle for agricultural policy and a key opportunity to diversify US agriculture, make it sustainable, improve nutrition, andmeet public health goals. The recent farm bill offered a mixed bag for public and environmental health, but genuine reform will require new political coalitions to champion agricultural policy that is good for people and the planet.
MR imaging of meniscal contusion in the knee.

OBJECTIVE We describe focal abnormal signal of the meniscus in the knees of six patients who had a history of acute trauma to the knee. This signal abuts the articular surface of the meniscus on MR imaging but does not meet criteria for a meniscal tear or degeneration. CONCLUSION Acute trauma to the knee may cause an abnormal signal in the meniscus that does not meet the previously described criteria for a meniscal tear or an intrasubstance degeneration. This abnormal signal could be misinterpreted as a tear because of its contact with the articular surface; this signal is seen most often in our series in the setting of an anterior cruciate ligament tear with adjacent bone contusions. We suggest that this signal may be due to a contusion of the meniscus and that the signal may resolve over time in some patients.
Signal Transduction in Ribosome Biogenesis: A Recipe to Avoid Disaster

Energetically speaking, ribosome biogenesis is by far the most costly process of the cell and, therefore, must be highly regulated in order to avoid unnecessary energy expenditure. Not only must ribosomal RNA (rRNA) synthesis, ribosomal protein (RP) transcription, translation, and nuclear import, as well as ribosome assembly, be tightly controlled, these events must be coordinated with other cellular events, such as cell division and differentiation. In addition, ribosome biogenesis must respond rapidly to environmental cues mediated by internal and cell surface receptors, or stress (oxidative stress, DNA damage, amino acid depletion, etc.). This review examines some of the well-studied pathways known to control ribosome biogenesis (PI3K-AKT-mTOR, RB-p53, MYC) and how they may interact with some of the less well studied pathways (eIF2α kinase and RNA editing/splicing) in higher eukaryotes to regulate ribosome biogenesis, assembly, and protein translation in a dynamic manner.