Miracle-dz/UniFAR-FTUs huggingface dataset:
Human immunodeficiency virus type 1 pol gene mutations in an AIDS patient treated with multiple antiretroviral drugs

Multiple mutations were found in the human immunodeficiency virus pol gene following treatment of an AIDS patient with antiretroviral drugs. After approximately 2.5 years of monthly alternating therapy with 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC), most of the pol sequences amplified from the patient's peripheral blood mononuclear cell DNA contained known AZT resistance mutations at codons 41, 67, and 215 and a putative ddC resistance mutation at codon 69 as well as other novel mutations. These mutations persisted for 6 months after the patient was switched to 2',3'-dideoxyinosine monotherapy. Mutations known to be associated with 2',3'-dideoxyinosine resistance did not occur during this time. Antiviral susceptibility testing of point mutants, introduced into the genetic background of laboratory strain NL4-3, showed that the codon 41 mutation antagonized ddC resistance when present with the codon 69 mutation. However, this antagonism was not found with a chimeric mutant containing the patient's pol gene sequence from codons 25 to 218, implying that other mutations compensated for the antagonism. Thus, alternating therapy with AZT and ddC resulted in the selection of viruses resistant to both drugs.
Estimating the risk of importation of foot-and-mouth disease into Europe

The opinions of a number of recognised world experts on foot-and-mouth disease (FMD) were sought in order to answer key questions relating to the importation of the disease into European countries from countries outside Europe. In addition, their opinions were sought on where in Europe a primary outbreak of FMD was most likely to occur and the number of outbreaks likely to occur within European countries in the next five years. The Balkans group of countries was considered to be the most likely group within Europe to have a primary outbreak of FMD and also most likely to have the highest number of primary outbreaks. Turkey was considered to be the country outside Europe which was most likely to be the source of an outbreak within Europe as a whole, and the illegal importation of livestock was considered to be the most likely route of introduction of FMD into Europe. Results specific to the Islands group of countries, which included the UK and Ireland, suggested that this group was likely to have a mean of one primary outbreak of FMD in the five years from September 2000, and that the importation of foodstuffs by people entering those countries from Turkey was the most likely source of an outbreak.
Intraplatelet serotonin in patients with diabetes mellitus and peripheral vascular disease

Abstract Intraplatelet serotonin (5‐HT) content was determined in 23 patients with type I (insulin‐dependent) diabetes mellitus (IDDM), 23 patients with type II (non‐insulin‐dependent) diabetes mellitus (NIDDM), 29 patients with peripheral vascular disease (PVD) and 34 age‐matched normal subjects. Intraplatelet 5‐HT content in normal subjects showed an age‐related decline (r=–0·45; P < 0·008), as has been previously demonstrated. The median 5‐HT content in platelets of the young normal subjects was 4·36 (range: 3·62–6·79) nmol 10‐9platelets, while that in the elderly normal subjects was 3·87 (range: 2·8–6·0) nmol 10‐9platelets and that in young+elderly subjects was 4·05 (range: 2·8–6·8) nmol 10‐9platelets. The median intraplatelet 5‐HT content was significantly lower (P < 0·002) in IDDM patients: 3·0 (range 1·3–6·3), NIDDM patients: 2·5 (range 1·7–5·8), PVD patients: 2·42 (range 0·94–4·98) nmol 10‐9platelets than that in all young+elderly healthy subjects. The presence of hypertension in DM patients caused a small but significant (P < 0·05) decrease in intraplatelet 5‐HT content, whilst its presence had no effect in PVD patients. In a smaller study, it was established that NIDDM and PVD patients have significantly (P < 0·002) greater plasma 5‐HT concentrations than controls. Insulin‐dependent diabetes mellitus patients had greater plasma 5‐HT concentrations but this did not achieve statistical significance despite a 66% increment in its value. We conclude that the diminished 5‐HT content in platelets and the increased plasma levels may reflect enhanced release of 5‐HT by hyperactive platelets. This increase in plasma 5‐HT may contribute to the pathogenesis of atherosclerosis and vasospasm.
Mathematical model to simulate the cellular dynamics of infection with human herpesvirus‐6 in EBV‐negative infectious mononucleosis

Acute infection with human herpesvirus‐6 induces physiological cell proliferation in persons without major immune deficiency. It thus can serve as a parameter to validate a mathematical model designed to simulate cell proliferation under physiological and pathological conditions. Such a mathematical model is presented to simulate various cell changes of the T‐cell immune system during the course of HHV‐6 infection. Model development follows several steps, beginning with a basic model containing physiological T‐cell pools to the introduction of infectious stimuli in the final model. A search algorithm designed to optimize the system parameters, as well as initial variables of the model, is presented. The results of simulation runs for acute HHV‐6 infection of the final computational model correspond well to the data, as documented in human patients; they suggest that the computational model presented for the simulation of T‐cell levels in a given viral infection may well serve as a tool for similar studies of other viral infections, including those that lead to cellular aplasia or neoplasia. J. Med. Virol. 71:569–577, 2003. © 2003 Wiley‐Liss, Inc.
Effects of voluntary contraction on descending volleys evoked by transcranial stimulation in conscious humans

1 The spinal volleys evoked by single transcranial magnetic or electric stimulation over the cerebral motor cortex were recorded from a bipolar electrode inserted into the cervical epidural space of three conscious human subjects. These volleys were termed direct (D) and indirect (I) waves according to their latency. 2 We measured the size and number of volleys elicited by magnetic stimulation at various intensities with subjects at rest and during 20 or 100 % maximum contraction of the contralateral first dorsal interosseous muscle (FDI). Surface EMG activity was also recorded. 3 Electrical stimulation evoked a D‐wave volley. Magnetic stimulation at intensities up to about 15 % of stimulator output above threshold evoked only I‐waves. At higher intensities, a D‐wave could be seen in two of the three subjects. 4 At all intensities tested, voluntary contraction increased the number and size of the I‐waves, particularly during maximum contractions. However, there was only a small effect on the threshold for evoking descending activity. Voluntary contraction produced large changes in the size of EMG responses recorded from FDI. 5 Because the recorded epidural activity is destined for muscles other than the FDI, it is impossible to say to what extent increased activity contributes to voluntary facilitation of EMG responses. Indeed, our results suggest that the main factor responsible for enhancing EMG responses in the transition from rest to activity is likely to be increased excitability of spinal motoneurones, rather than increases in the corticospinal volley. The latter may be more important in producing EMG facilitation at different levels of voluntary contraction.
NK depletion results in increased CCL22 secretion and Treg levels in Lewis Lung Carcinoma via the accumulation of CCL22‐secreting CD11b+CD11c+ cells

Tumor‐induced immune suppression involves the accumulation of suppressive infiltrates in the tumor microenvironment such as regulatory T‐cells (Tregs). Previous studies demonstrated that NK‐dependant increases in CCL22 secretion selectively recruit Tregs toward murine lungs bearing Lewis Lung Carcinoma (LLC). To extend the in vitro studies, the present studies utilized in vivo depletion of NK cells to ascertain the contribution of NK‐derived CCL22 toward total CCL22 and subsequent Treg levels in both normal and LLC‐bearing lungs. However, NK depletion had the unexpected effect of increasing both CCL22 secretion and Treg levels in the lungs of NK‐depleted LLC‐bearing mice. This was concurrent with an increase in tumor burden. Flow cytometry and a series of both immunomagnetic and FACS isolations were used to identify the CCL22‐producing cellular fractions in LLC‐bearing lungs. A novel CD11b+CD11c+ cell population was identified that accumulates in large numbers in NK‐depleted LLC‐bearing lung tissue. These CD11b+CD11c+ cells secreted large amounts of CCL22 that may overcompensate for the loss of NK‐derived CCL22 in the lungs of NK‐depleted LLC‐bearing mice. Taken together, these data suggest that NK cells play both a positive and negative role in the regulation of CCL22 secretion and, in turn, the recruitment of Tregs toward LLC‐bearing lungs.
CORONARY ARTERY DISEASE RISK FACTORS IN DRIVING VERSUS OTHER OCCUPATIONS

INTRODUCTION: The link between occupational factors and coronary artery diseases (CAD) has been studied and confirmed in many countries. Conditions associated with driving such as stress, and factors such as long working hours and the environment can increase the risk of CAD. In this study, we measured potential CAD risk factors in bus and taxi drivers and compared them with a control group. METHODS: 135 taxi drivers, 194 bus drivers and 121 non-drivers (control group) were evaluated for CAD risk factors, i.e. age, body mass index (BMI>24), cigarette smoking, hypertension, high-density and low-density lipoprotein cholesterol (HDL, LDL), triglyceride >200, blood sugar >126 and familiar history of CAD. Univariate and multivariate logistic regression tests were used to distinguish major risk factors. RESULTS: Taxi drivers have an increased risk of hypertension compared with the control group (odds ratio: crude=5.94, adjusted=9.09; P<0001). Cigarette smoking in taxi and bus drivers was 1.4 (P<0.3) and 3.24 (P<0001) times greater than the control group, respectively. The risk of increased LDL and decreased HDL in bus drivers was 4.38 and 5.28 (P<0001) times greater than the control group, respectively. The risk of obesity, high blood sugar and high triglyceride was not significantly different among the groups. CONCLUSIONS: Driving is an independent risk factor for hypertension. Known CAD risk factors are also higher in drivers.
Comparable Efficacies of the Antimicrobial Peptide Human Lactoferrin 1-11 and Gentamicin in a Chronic Methicillin-Resistant Staphylococcus aureus Osteomyelitis Model

ABSTRACT The therapeutic efficacy of an antimicrobial peptide, human lactoferrin 1-11 (hLF1-11), was investigated in a model of chronic methicillin-resistant Staphylococcus aureus (MRSA) (gentamicin susceptible) osteomyelitis in rabbits. We incorporated 50 mg hLF1-11/g or 50 mg gentamicin/g cement powder into a calcium phosphate bone cement (Ca-P) and injected it into the debrided tibial cavity, creating a local drug delivery system. The efficacy of hLF1-11 and gentamicin was compared to that of a sham-treated control (plain bone cement) (n = 6) and no treatment (infected only) (n = 5). The results were evaluated by microbiology, radiology, and histology. MRSA was recovered from all tibias in both control groups (n = 11). On the other hand, hLF1-11 and gentamicin significantly reduced the bacterial load. Furthermore, no growth of bacteria was detected in five out of eight and six out of eight specimens of the hLF1-11- and gentamicin-treated groups, respectively. These results were confirmed by a significant reduction of the histological disease severity score by hLF1-11 and gentamicin compared to both control groups. The hLF1-11-treated group also had a significantly lower radiological score compared to the gentamicin-treated group. This study demonstrates the efficacy of hLF1-11 incorporated into Ca-P bone cement as a possible therapeutic strategy for the treatment of osteomyelitis, showing efficacy comparable to that of gentamicin. Therefore, the results of this study warrant further preclinical investigations into the possibilities of using hLF1-11 for the treatment of osteomyelitis.
The emotional wellbeing of lay HIV counselling and testing counsellors

The HIV testing, treatment and care programme of the South African public healthcare system depends on HIV counselling and testing (HCT) that is primarily delivered by lay counsellors. Lay counsellors are expected to educate clients about HIV/AIDS, advocate behaviour change, convey test results and support those infected and affected to cope with the emotional and social challenges associated with HIV/AIDS. This research focuses on the emotional wellbeing of lay HCT counsellors because this influences the quality of services they provide. A mixed methods approach was used. The emotional wellbeing, level of burnout, depression and coping style of 50 lay HCT counsellors working at the City of Tshwane clinics were assessed. Additionally, five focus group discussions were conducted. The results showed that HCT counsellors reported average emotional wellbeing, high levels of emotional exhaustion and depression. They had a sense of personal accomplishment and positive coping skills. The results revealed that they may have difficulty dealing with clients’ emotional distress without adequate training and supervision. This creates a dilemma for service delivery. In the light of the important role they play in service delivery, the role of the lay HCT counsellor needs to be reconsidered. HCT should develop as a profession with specific training and supervision to develop their emotional competencies to conduct effective counselling sessions.
Functional implications of the morphology of spinal ventral horn neurons of the cat

When Ramon y Cajal (’09) published his book “Histologie du Systeme Nerveux de l’Homme et des VertebrCs,” the anatomy of the nervous system was intimately fused with physiology in a single discipline, often supported by clinical contributions, that led to a homogeneous course of research. Progressive specialization and refinements of investigative methods mainly of the physiological ones produced an unavoidable separation of the discipline, which has frequently induced an unnatural difficulty of communication and dangerous distortion of interpretations not only as to the reciprocal results, but also as to the limits of research pertaining to the various branches of neurology. In recent years, the progress of neurophysiological methods has permitted physiologists to postulate patterns of organization in the nervous system of such a variety and complexity as to give serious trouble to morphologists called to support or to criticize them. The necessity for better morphological control appears evident and the present paper must be regarded as providing critical revision of the anatomical data on which the function of some spinal mechanisms may be postulated.
Rac1 Mediates Type I Collagen-dependent MMP-2 Activation

Cell migration and proteolysis are two essential processes during tumor invasion and metastasis. Matrix metalloproteinase (MMP)-2 (type IV collagenase; gelatinase A), is implicated in tumor metastasis as well as in primary tumor growth. The Rho family of small GTPases regulates the dynamics of actin cytoskeleton associated with cell motility. In this report, we provide evidence that Rac1, one member of Rho-related small GTPases, is a mediator of MMP-2 activation in HT1080 fibrosarcoma cells cultured in three-dimensional collagen gel (3D-col) and that MMP-2 activation is required for Rac1-promoted cell invasion through collagen barrier. Stable expression of dominant negative (Rac1V12N17) and constitutively active Rac1 (Rac1V12), respectively, in HT1080 cells demonstrates that Rac1 promoted cell invasiveness across type I collagen and collagen-dependent MMP-2 activation. Active Rac1 is sufficient to induce MMP-2 activation in cells cultured in fibrin gel, an extracellular matrix component that does not support MMP-2 activation. The Rac1-dependent MMP-2 activation occurred in a cell-associated fashion and required MMP activities. Because the cell membrane-mediated MMP-2 activation requires MT1-MMP and low amount of issue inhibitor of matrix metalloproteinase-2 (TIMP-2), their expression was examined. Rac1 modulated MT1-MMP mRNA level and the accumulation of a 43-kDa form of MT1-MMP protein, in correlation with MMP-2 activation profile. However, TIMP-2 expression was independent of Rac1 activity. The coordinate modulation of MMP-2 activity and MT1-MMP expression/processing by Rac1 is consistent with cell collagenolytic activity. The C-terminal hemopexin-like domain of MMP-2, which interferes with the cell membrane activation of MMP-2, reduced Rac1-promoted cell invasiveness as monitored by collagen invasion assay. These results suggest that collagen-dependent MMP-2 activation and MT1-MMP expression/processing contribute to Rac-promoted tumor cell invasion through interstitial collagen barrier.
A Century of Evidence on Trend-Following Investing

In this article, the authors study the performance of trend-following investing across global markets since 1880, extending the existing evidence by more than 100 years using a novel data set. They find that in each decade since 1880, time-series momentum has delivered positive average returns with low correlations to traditional asset classes. Further, time-series momentum has performed well in 8 out of 10 of the largest crisis periods over the century, defined as the largest drawdowns for a 60/40 stock/bond portfolio. Lastly, the authors find that time-series momentum has performed well across different macro environments, including recessions and booms, war and peace, high- and low-interest-rate regimes, and high- and low-inflation periods.
Expression of TRAG‐3 in breast cancer

Dear Sir, Breast cancer is the leading cause of cancer-related deaths in women worldwide yearly. Although surgical treatment, adjuvant therapies with hormones and chemotherapy have been used for the treatment of breast cancer, new therapeutic approaches are needed to reduce its high recurrence rate. Immunotherapy aimed at recruiting the host’s immune system to identify and destroy aberrant tumor cells maybe a useful method. Furthermore, successful development of immunotherapeutic breast cancer vaccines hinges on the identification of appropriate target antigens, especially the cancer/testis antigen. Taxol resistance-associated gene-3 (TRAG-3) is a novel cancer/testis antigen2 initially discovered when comparing ovarian cell line SKOV-3 to SKOV-3TR by differential display in the search for new genes.3 This antigen is highly expressed in melanoma2 and nonsmall cell lung carcinoma.4 We report for the first time to our knowledge that TRAG-3 also is overexpressed in most human breast cancer, which suggests TRAG-3 could be a potential target for immunotherapy in breast cancer. Thirty-four tumor samples and one normal breast tissue sample were collected during routine surgery performed at Southwest Hospital, Chongqing, China. The median age of the patients was 51 years. Histologic examination of the tumors revealed 8 invasive lobular carcinoma, 2 carcinoma simplex, 2 medullary carcinoma and 22 invasive ductal carcinoma according to the WHO classification of cancer. RT-PCR was used to analyze the TRAG-3 mRNA expression in the breast cancer tissue specimens (Table I). Total RNA was prepared from frozen tissues with TRIzol Reagent (GIBCO, Carlsbad, CA) according to the manufacturer’s protocol. The commercially synthesized primers were sense 5 -
Height Distributions of Scots Pine Sapling Stands Affected by Retained Tree and Edge Stand Competition

The paper focused on the height structure of Scots pine saplings affected by (1) retained solitary pine trees or (2) a pine-dominated edge stand. The study material in (1) and (2) consisted of ten separate regeneration areas in southern Finland. In (1) 2-m radius study plots were located at 1, 3, 6 and 10 m distances from 10 systematically selected, solitary retained trees in each stand. In (2) the study plots were systematically located within 20 m from the edge stand. Competition of the individual trees was modelled using ecological field theory. The 24th and 93rd sample percentiles were used for estimating the height distribution using the two-parameter Weibull function. The models incorporated the effect of varying advanced tree competition on the predicted percentiles. Competition free dominant height was used as a driving variable for the developmental phase. Competition resulted in retarded height development within a radius of about 6 m from the retained tree, while it extended up to roughly half of the dominant height of the edge stand. The height distribution without external competition was relatively symmetrical, but increasing competition resulted in a more peaked and skewed distribution. Slight differences were found between northern sunny and southern shaded stand edges, while the least retarded height occurred at the north-western edge receiving morning sunlight. Kolmogorov-Smirnov goodness-of-fit tests showed acceptable and equal fit for both data sets; 2% and 8% of the distributions did not pass the test at the alpha 0.1 level when the Weibull distribution was estimated with the observed or predicted percentiles, respectively.
The epidemiology of canine and feline dermatophytoses in southern Italy

A total of 424 animals (268 dogs and 156 cats) with skin lesions (alopecia and peripheral scaling) were examined from January 1999 to December 2002. Of the 424 samples examined, 99 (23.3%) yielded a positive culture and, in particular, 20.5% of the dog samples and 28.2% of the cat samples. Microsporum canis was the most common dermatophyte isolated from dogs and cats (77.7%), followed by geophilic dermatophyte species (M. gypseum, Trichophyton terrestre). Young dogs and cats, especially those younger than 1 year, showed a statistically significant higher prevalence of M. canis infection than older animals. No statistically significant association was found between infection and sex in cats, while male dogs were more affected by dermatophytes. Among breeds, Yorkshire terriers showed the highest positivity (50%) caused mainly by M. canis (46.6%), while no differences were noticed for cats. A significantly higher prevalence of positive samples was registered in summer and in autumn for cats. The presence of dermatophytes was not associated with itching. The diagnostic value of Wood's lamp fluorescence and microscopic examination proved to be scarce compared with fungal cultures as only 45.5% of the 77 samples that tested positive for M. canis at the cultural examination was positive under Wood's lamp florescence and 53.2% at microscopic examination.
Loneliness and Sexual Risk Behavior in Gay Men

This study examined loneliness in a sample of gay men and its association with unprotected anal intercourse, social support, instability of self-esteem, intimacy, and coping. A sample of 470 urban gay men completed a self-administered questionnaire. Participants scored high on Loneliness in comparison to other samples. Measures of Intimacy, Social Support, Instability of Self-esteem, monogamous relationship status, and use of Avoidance Coping predicted 58.5% of the variance in Loneliness scores. Both social and psychological variables appear to be important for understanding loneliness in this population. Men who had unprotected anal intercourse with nonprimary partners during the previous six months scored higher on Loneliness than other participants, but those who did so with primary partners scored the lowest Episodes of unprotected anal intercourse with nonprimary partners might have been Avoidance strategies to help participants cope with loneliness or other negative affect.