Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti‐apoptotic role of TWIST and its association with Akt pathway in mediating taxol resistance in nasopharyngeal carcinoma cells

TWIST, a basic helix‐loop‐helix transcription factor, has been reported to be associated with development and progression of human cancer. Recently, over expression of TWIST is found in cancer patients with shorter survival and poor response to chemotherapy. Previously, we found that upregulation of TWIST was responsible for the development of acquired resistance to taxol in a nasopharyngeal carcinoma (NPC) cell line, HNE1‐T3 (Wang et al., Oncogene, 2004;24:274). In this study, we investigated the underlying molecular mechanisms responsible for the TWIST‐mediated taxol resistance. By comparison of the parental HNE1 and its derivative HNE1‐T3 cell lines, we found that the resistance to taxol in HNE1‐T3 cells was associated with suppression of taxol‐induced apoptosis evidenced by decreased expression of Bak and Bax and increased Bcl‐2, as well as inhibition of PARP and caspase cleavage and DNA ladder formation. However, there was no correlation between taxol sensitivity and alterations on G2/M cell cycle distribution, suggesting that the TWIST‐induced taxol resistance is mediated through protection against apoptosis but not mitotic arrest. Analysis of additional 8 NPC cell lines showed that upregulation of TWIST was associated with resistance to microtubule disrupting agents, especially taxol, and inactivation of TWIST through small RNA interference led to increased sensitivity to taxol‐induced cell death. Subsequent studies also demonstrated that the TWIST‐mediated taxol resistance may be regulated through its positive involvement with the Akt pathway. Our findings suggest an underlying molecular mechanism responsible for the TWIST‐mediated chemodrug resistance and suggest a target for overcoming taxol resistance in cancer cells. © 2007 Wiley‐Liss, Inc.
Viral infections of the central nervous system in Spain: A prospective study

The aim of the study was to determine the incidence of viruses causing aseptic meningitis, meningoencephalitis, and encephalitis in Spain. This was a prospective study, in collaboration with 17 Spanish hospitals, including 581 cases (CSF from all and sera from 280): meningitis (340), meningoencephalitis (91), encephalitis (76), febrile syndrome (7), other neurological disorders (32), and 35 cases without clinical information. CSF were assayed by PCR for enterovirus (EV), herpesvirus (herpes simplex [HSV], varicella‐zoster [VZV], cytomegalovirus [CMV], Epstein–Barr [EBV], and human herpes virus‐6 [HHV‐6]), mumps (MV), Toscana virus (TOSV), adenovirus (HAdV), lymphocytic choriomeningitis virus (LCMV), West Nile virus (WNV), and rabies. Serology was undertaken when methodology was available. Amongst meningitis cases, 57.1% were characterized; EV was the most frequent (76.8%), followed by VZV (10.3%) and HSV (3.1%; HSV‐1: 1.6%; HSV‐2: 1.0%, HSV non‐typed: 0.5%). Cases due to CMV, EBV, HHV‐6, MV, TOSV, HAdV, and LCMV were also detected. For meningoencephalitis, 40.7% of cases were diagnosed, HSV‐1 (43.2%) and VZV (27.0%) being the most frequent agents, while cases associated with HSV‐2, EV, CMV, MV, and LCMV were also detected. For encephalitis, 27.6% of cases were caused by HSV‐1 (71.4%), VZV (19.1%), or EV (9.5%). Other positive neurological syndromes included cerebellitis (EV and HAdV), seizures (HSV), demyelinating disease (HSV‐1 and HHV‐6), myelopathy (VZV), and polyradiculoneuritis (HSV). No rabies or WNV cases were identified. EVs are the most frequent cause of meningitis, as is HSV for meningoencephalitis and encephalitis. A significant number of cases (42.9% meningitis, 59.3% meningoencephalitis, 72.4% encephalitis) still have no etiological diagnosis. J. Med. Virol. 85:554–562, 2013. © 2012 Wiley Periodicals, Inc.
Durable HIV-1 Suppression with Indinavir after Failing Lamivudine-Containing Double Nucleoside Therapy: A Randomized Controlled Trial

Objective To assess the durability of the antiretroviral effect in plasma and cerebrospinal fluid (CSF) of antiviral therapy intensification, produced by the addition of indinavir from week 12 onwards to the original regimen of zidovudine/lamivudine or stavudine/lamivudine, after 72 weeks of follow-up using an ultrasensitive HIV-1 RNA assay. To assess CSF concentrations of indinavir at week 48. Design In a prospectively, randomized, open, single-centre study, antiretroviral-naive patients (CD4 cell count ≥200 cells/μl and a plasma HIV-1 RNA level ≥10000 copies/ml) were assigned to a combination of zidovudine/lamivudine or stavudine/lamivudine. Indinavir could be added to the double nucleoside analogue regimen from week 12 or thereafter in case the plasma HIV RNA level was insufficiently suppressed (>500 copies/ml). Results Forty-seven patients were enrolled (23 stavudine/lamivudine and 24 zidovudine/lamivudine), of whom 33 completed a follow-up of 72 weeks. Indinavir was added in 89% (42/47) of the patients. Only one discontinuation occurred due to virological failure. At week 72, the median plasma HIV-1 RNA levels in the zidovudine/lamivudine group had decreased from 4.80 log10 copies/ml to <500 copies/ml in 100% of patients and <50 copies/ml in 86.6% of the patients. In the stavudine/lamivudine group the plasma HIV-1 RNA decreased from 4.98 log10 copies/ml at baseline to <500 copies/ml in 100% of patients and <50 copies/ml in 66.7% of the patients. On an intent-to-treat basis these figures were 54.2 and 52.2% for zidovudine/lamivudine and stavudine/lamivudine, respectively, for the 50 copies/ml assay. The median CD4 cell count increased from 315 cells/μl, with 150 cells/μl in the zidovudine/lamivudine arm, and from 290 cells/μl, with 310 cells/μl in the stavudine/lamivudine arm (P=0.0001). However, the percentage of CD4 cells did not differ in each group. In the zidovudine/lamivudine group 9/10 and 5/5, and in the stavudine/lamivudine group 11/11 and 6/6 had a CSF HIV-1 RNA level <50 copies/ml at week 12 and 48, respectively. The CSF indinavir concentration ranged from 50 to 170 ng/ml. Conclusion The long-term HIV-1 suppression observed in this study is remarkable, as adding a single antiretroviral agent to a failing regimen goes against current notions of adequate therapy.
Obstructive Sleep Apnea Syndrome in Two Subjects with Down Syndrome: Continuous Positive Airway Pressure Contribution on Exercise Tolerance

In subjects with Down syndrome the obstructive sleep apnea is the cause of many disorders (cognitive and cardiovascular disorders, premature exhaustion, increase of daytime sleepiness). The standard treatment in the obstructive sleep apnea is continuous positive airway pressure, which eliminates the respiratory events, allows recovery of a satisfactory quality of sleep, and suppresses daytime sleepiness and cognitive dysfunction. The aim of this study was to verify the effects of continuous positive airway pressure on aerobic performance, as well as on hormonal and metabolic parameters during exercise, in two young adults with Down syndrome and with obstructive sleep apnea, treated or not, after an interval of 5 years. The main result observed is the beneficial effect on the ability to achieve a longer submaximal exercise with higher intensity in subject receiving the treatment. Obstructive sleep apnea syndrome treatment in people with Down syndrome could improve aerobic capacity and reduce daytime sleepiness.
Comparative ultrastructure and cytochemistry of the avian pineal organ

The breeding of birds is expected to solve problems of nourishment for the growing human population. The function of the pineal organ synchronizing sexual activity and environmental light periods is important for successful reproduction. Comparative morphology of the avian pineal completes data furnished by experiments on some frequently used laboratory animals about the functional organization of the organ. According to comparative histological data, the pineal of vertebrates is originally a double organ (the “third” and the “fourth eye”). One of them often lies extracranially, perceiving direct solar radiation, and the other, located intracranially, is supposed to measure diffuse brightness of the environment. Birds have only a single pineal, presumably originating from the intracranial pineal of lower vertebrates. Developing from the epithalamus, the avian pineal organ histologically seems not to be a simple gland (“pineal gland”) but a complex part of the brain composed of various pinealocytes and neurons that are embedded in an ependymal/glial network. In contrast to organs of “directional view” that develop large photoreceptor outer segments (retina, parietal pineal eye of reptiles) in order to decode two‐dimensional images of the environment, the “densitometer”‐like pineal organ seems to increase their photoreceptor membrane content by multiplying the number of photoreceptor perikarya and developing follicle‐like foldings of its wall during evolution (“folded retina”). Photoreceptor membranes of avian pinealocytes can be stained by antibodies against various photoreceptor‐specific compounds, among others, opsins, including pineal opsins. Photoreceptors immunoreacting with antibodies to chicken pinopsin were also found in the reptilian pineal organ. Similar to cones and rods representing the first neurons of the retina in the lateral eye, pinealocytes of birds posses an axonal effector process which terminates on the vascular surface of the organ as a neurohormonal ending, or forms ribbon‐containing synapses on pineal neurons. Serotonin is detectable immunocytochemically on the granular vesicles accumulated in neurohormonal terminals. Pinealocytic perikarya and axon terminals also bind immunocytochemically recognizable excitatory amino acids. Peripheral autonomic fibers entering the pineal organ through its meningeal cover terminate near blood vessels. Being vasomotor fibers, they presumably regulate the blood supply of the pineal tissue according to the different levels of light‐dependent pineal cell activity. Microsc. Res. Tech. 53:12–24, 2001. © 2001 Wiley‐Liss, Inc.
Phase I study of MORAb-003, a humanized anti-folate receptor-alpha monoclonal antibody, in platinum resistant ovarian cancer.

5027 Background: Folate receptor alpha (FRA) is over-expressed in the majority of epithelial ovarian cancers (EOC) but largely absent from normal tissue. MORAb-003 (M3) is a humanized monoclonal antibody (MAb) to FRA. Binding of M3 to FRA can prevent phosphorylation of substrates specific for the Lyn kinase; suppress proliferation of cells over-expressing FRA; mediate FRA-positive tumor cell killing via antibody-dependent cellular and complement-dependent mechanisms; and suppress tumor growth in vivo of FRA-expressing tumors in rodent xenograft models. Toxicology studies in non-human primates found no evidence of toxicity with M3 at supra-pharmacological doses. This open-label, multiple-infusion, first-in-human, dose-escalation trial evaluates the safety, pharmacokinetics (PK), and antitumor activity of M3 in patients with platinum-resistant EOC. METHODS Sequential cohorts of patients receive four weekly infusions at escalating dose levels of M3, from 12.5 mg/m2 to 100 mg/m2. Human anti-human antibody (HAHA) and PK analyses are performed. Eligible patients have EOC that relapsed < 6 months after platinum-based therapy, acceptable organ function, Karnofsky Performance Status ≥ 70%, and measurable disease by GOG-RECIST criteria. Patients undergo pulmonary function testing (PFT) at baseline, and at end of study. RESULTS To date, 7 women have been treated with M3: 3 at the 12.5 mg/m2 dose, 3 at 25 mg/m2, and 1 at 37.5 mg/m2. Median age was 60. Neither dose limiting toxicity nor HAHA has been observed. Grade 1 rash occurred in 1 patient. Grade 1/2 fever following drug administration occurred in 2 patients. Grade 2 FEV1 decrease was observed in a patient with likely pulmonary lymphangitic metastasis. One subject at 25 mg/m2 had radiographically stable disease. At low doses, the PK analysis demonstrated the half-life to be shorter than anticipated based on animal studies, possibly due to tumor binding. Radiolableled imaging studies are underway to determine the distribution of M3. CONCLUSIONS The FRA-specific MAb MORAb-003 appears to be well tolerated in patients with EOC. Enrollment continues and updated results will be presented. No significant financial relationships to disclose.
Longitudinal Follow-Up of Biochemical Markers of Fatigue Throughout a Sporting Season in Young Elite Rugby Players

Abstract Alaphilippe, A, Mandigout, S, Ratel, S, Bonis, J, Courteix, D and Duclos, M. Longitudinal follow-up of biochemical markers of fatigue throughout a sporting season in young elite rugby players. J Strength Cond Res 26(12): 3376–3384, 2012—The aims of this study were to evaluate links between biochemical markers and competition and training conditions, overtraining questionnaire scores, and anthropometric characteristics of young elite rugby players and to identify evolving profiles of fatigue during the sports season. Twelve elite rugby players were included in the study. The tests were carried out every 15 days over the course of one sporting season from July until March, including the interseason. Changes in body composition parameters, blood biochemistry, and scores on various questionnaires were examined. The majority of the biochemical parameters and subjective variables showed significant variations over time. There were significant positive correlations between overtraining scores and alanine amino transferase (ALAT; r = 0.24, p < 0.05) and creatine phosphokinase (CK; r = 0.3, p < 0.01) levels. In addition, game time was significantly correlated with changes in CK (r = 0.46, p < 0.01), whereas difficult training sessions were significantly correlated with changes in both CK (r = 0.27, p < 0.05) and ALAT (r = 0.33, p < 0.01). We suggest that regular monitoring of these biochemical parameters may provide important information for the coach on the fatigue of rugby players and their perceived difficulty of training.
The Association Between Physical Activity, Productivity, and Health Care Utilization Among Employees in Brazil

Objective: To document the relationship between physical activity, absenteeism, presenteeism, health care utilization, and morbidity among Brazilian automotive workers. Methods: Eligible employees (N = 620) completed a questionnaire. Univariate correlations, multivariate logistic regression, and Pearson's product-moment correlation coefficient were used. Results: Work absenteeism was associated with physical activity at work (OPA) (odds ratio, [OR] = 1.63, 95% confidence interval [CI] = 1.31 to 2.02) and leisure physical activity time excluding sport (OR = 0.73, 95% CI = 0.58 to 1.00). Health care utilization was associated with OPA (OR = 1.25, 95% CI = 0.99 to 1.58) and leisure physical activity time excluding sport (OR = 0.76, 95% CI = 0.57 to 1.02). Presenteeism showed an indirect relationship with OPA (r = 0.099, P = 0.014). Referred morbidity was associated with OPA (OR = 1.3, 95% CI = 1.06 to 1.61) and sports during leisure time (OR = 0.67, 95% CI = 0.54 to 0.82). Conclusions: Physical activity components seem to have differential relationships to the studied outcomes. Associations measured indicate negative impacts of OPA on absenteeism, health care utilization, and morbidity, although overall physical activity did not show these relationships.
[Extrapulmonary tuberculosis: a review of 102 cases in Pereira, Colombia].

Introduccion. La tuberculosis continua siendo un problema de salud publica en el mundo. Es necesario conocer su magnitud en cada institucion, la oportunidad en el diagnostico y la utilizacion de recursos. Objetivo. Determinar las localizaciones y caracterizar la tuberculosis extrapulmonar desde el punto de vista epidemiologico, clinico, microbiologico, de diagnostico y de costos hospitalarios de los pacientes egresados en un hospital estatal de III nivel. Materiales y metodos. Estudio descriptivo retrospectivo realizado entre el 2000 y el 2004 mediante la revision de historias clinicas y archivos de laboratorio de pacientes egresados con diagnostico de tuberculosis extrapulmonar del Hospital Universitario San Jorge de Pereira, Colombia. Resultados. Se encontraron 102 casos, con promedio de edad de 31,6 anos, de los cuales el 62,7% correspondia a hombres. El 70,6% procedia del area urbana y el 59,6% presento sintomas clinicos mayores a los 15 dias de evolucion. La forma mas frecuente de presentacion fue la pleural, con 47 casos, seguida de la meningea con 19, la ganglionar con 13, la peritoneal con 5, la miliar con 4, la genitourinaria con 4, la faringea con 4, la articular con 3, la osea con 2 y la pericardica con 1 caso. Los metodos de diagnostico mas utilizados fueron la biopsia en 68 casos (66,6%), el clinico en 28 (27,4%). Por medio de baciloscopia con coloracion de Zielh Neelsen, se diagnostico el 3,9%, y con el cultivo de Mycobacterium tuberculosis, el 5,8%. El tiempo de estancia hospitalaria promedio fue de 13 dias y el costo promedio fue de $5'784.603 por caso. Fallecieron 15 pacientes, de los cuales el 60% se asocio con sida, y 53,3% con meningitis. Conclusion. Las localizaciones mas frecuentes fueron la pleural, la meningea y la ganglionar. El principal metodo de diagnostico fue la biopsia. La estancia prolongada se relaciono con demora en el diagnostico y sida. La mortalidad fue mayor en los casos de sida y localizacion meningea.
The Ethical Foundation of Analytic Action

A fter Schafer and Lacan, Renik (1993a,b) and Friedman (1993, 2007), and, more or less, the entire relational tradition (Harris 2011), it is by now a commonplace to say that psychoanalysts are interested in their own activity—that is, our activity, what we are doing with our patients, what we, as analysts, say, feel, and imagine. Analysts have grasped the ways in which their internal worlds shape, illuminate, or constrain engagement with, and perhaps the very emergence of, the patient’s subjective experience. Analysands talk in the hope we will receive their message generatively, openly, all the while taking the risk that we might misrecognize, not hear, and fail to witness what they want us to recognize, hear, and witness. This risk involves, as Shulman (2016) says, “a bid for utmost intimacy” (p. 706); the emotional stakes are high. In this context, it is no wonder we care deeply about how we act and why we act as we do. This is why what we concern ourselves with is
Selective white cell apheresis reduces relapse rates in patients with IBD at significant risk of clinical relapse

Background: We assessed whether selective granulocyte and monocyte/macrophage adsorption apheresis maintained clinical remission in asymptomatic inflammatory bowel disease (IBD) patients at significant risk of clinical relapse. Methods: Sixty asymptomatic patients (age 18–70 years) with IBD (in clinical remission) with fecal calprotectin over 250 &mgr;g/g (which defines those at risk of clinical relapse with >80% specificity and sensitivity) were recruited for this open‐label, prospective, randomized, controlled study. Twenty‐nine underwent selective leukocytapheresis, undergoing 5, once weekly, out‐patient sessions. Thirty‐one had unchanged maintenance treatment and acted as controls. Follow‐up for a clinical relapse was 6 months. The secondary outcome variable was the time to relapse. Results: The number of patients who remained in clinical remission at 6 months was significantly lower in controls (32.3%) than in the apheresis (72.4%) group (P = 0.0023, Fisher's exact test). The time to first relapse was significantly earlier in the control group (99 ± 73 days) as compared with the apheresis group (161 ± 44 days) (log‐rank test; P = 0.0004). Mild and transient headache was reported by 16 of the 29 (55%) for up to 3 hours, but no serious side effects were observed. Conclusions: This study represents a new approach to the treatment of IBD by targeting a group of asymptomatic patients for treatment who are at significant risk of relapse based on high fecal calprotectin concentrations. Selective leukocytapheresis significantly reduced the number of, and increased the time to, clinical relapse in these patients without serious side effects.
Spatial relationship between the hepatic artery and portal vein based on the fusion image of CT angiography and CT arterial portography: the left hemiliver.

OBJECTIVE The objective of our study was to clarify the hepatic artery anatomy of the left hemiliver using the fusion image of CT angiography (CTA) and CT arterial portography. MATERIALS AND METHODS CTA and CT arterial portography were performed on a 64-MDCT scanner in 144 patients. All images were transferred to a workstation for 3D analysis using the multiimage fusion mode. We classified the left hepatic artery (LHA) and middle hepatic artery (MHA) as type L when only the LHA was present, type MB when a medial branch from the LHA was present, type LM when both the LHA and MHA were present, and type M when only the MHA was present. The hepatic artery was classified into infraportal and supraportal groups on the basis of its relationship with the laterosuperior branch of the left portal vein. We also classified the branching pattern of the arteries to each segment. Pattern 1 was defined as when the LHA divided into the laterosuperior segment artery (A2), which then divided into the lateroinferior segment artery (A3) and medial segment artery (A4). Pattern 2 was defined as when the LHA divided into A3, which then divided into A2 and A4. Pattern 3 was defined as when the LHA divided into A4, which then divided into A2 and A3. Pattern 4 was defined as when the LHA divided into A2, A3, and A4 simultaneously. RESULTS The prevalence of each type was as follows: type L (n = 37, 25.7%), type MB (n = 44, 30.6%), type LM (n = 53, 36.8%), and type M (n = 6, 4.2%). The number of cases classified as infraportal was 54 (37.5%) and supraportal, 73 (50.7%). The cases classified by branching pattern were as follows: pattern 1, 26 cases (18.0%); pattern 2, eight (5.6%); pattern 3, 93 (64.5%); and pattern 4, 13 (9.0 %). CONCLUSION Three-dimensional fusion images based on CTA and CT arterial portography can show the various anatomic patterns of the left hemiliver hepatic artery in relation to the left portal vein.
Microinjection of plasmid DNA encoding the A surface antigen of Paramecium tetraurelia restores the ability to regenerate a wild-type macronucleus

Strain d48 of Paramecium tetraurelia contains the A i-antigen gene in the micronucleus, but the gene is lost when micronuclear products develop into the macronucleus. It has recently been shown that when injected into d48, macronucleoplasm from the wild type transforms d48 cells to wild type. It is shown here that wild-type cytoplasm can also bring about transformation, with a marked stage-specific sensitivity for both donor and recipient. It was also found that a plasmid containing the cloned A gene could transform d48 to wild type. Injection of nucleoplasm from animals in the vegetative stage of the cell cycle into the cytoplasm of recipients at various stages of autogamy caused high-frequency transformation of cells able to express the A serotype both before and after the next autogamy. Injection of nucleoplasm into vegetative macronuclei produced over 70% transformants able to express the A serotype after the next autogamy. The ability of nucleoplasm to transform was acquired at the second cell cycle after autogamy and was maintained throughout the vegetative stage. When cytoplasm was obtained from donors during autogamy and injected into the cytoplasm of recipients 1 to 2 h after the sensitive period, quite high frequencies of stable revertants were found when tested both before and after the next autogamy. Cells that were injected into the macronucleus with the cloned A plasmid expressed the A serotype after five fissions in over 20% of the lines and maintained this ability through successive fissions; all transformants except one stably expressed the A serotype even after the next autogamy.