Miracle-dz/UniFAR-FTUs huggingface dataset:
Acute promyelocytic leukaemia:a review

Acute promyelocytic leukaemia (APL) is characterised by the fusion gene transcript PML-RAR-α and is now the most frequently curable acute leukaemia in adults if promptly diagnosed and adequately treated. The clinical presentation is associated with a haemorrhagic diathesis and the blasts almost always have Auer rods. Poor prognostic factors include older age, elevated white blood cell count, low platelet count, and CD56 expression. The introduction of all-trans retinoic acid (ATRA), which leads to the differentiation of leukaemic blasts into mature granulocytes has been the major breakthrough in the treatment of APL. Induction treatment with concurrent ATRA and chemotherapy leads to a rapid resolution of the characteristic life-threatening coagulopathy, high complete remission rates and excellent survival rates, compared to chemotherapy alone. However, treatment with ATRA is associated with the retinoic acid syndrome (RAS), which is a major toxicity and may lead to mortality. The role of cytarabine as a part of initial induction regimen remains unclear. After achievement of complete remission (CR), there is a definitive role of maintenance therapy with ATRA with or without low-dose chemotherapy. In relapsed patients, arsenic trioxide is considered the treatment of choice. However, the best postremission treatment for patients with second CR remains unknown. With the continued improvement in the field of stem cell transplantation, it may play an important role in the few patients with relapsed/refractory disease or those in second CR.
Running Title : Candidate genes in the Diabetes Prevention Program

1 The Biostatistics Center, George Washington University, Rockville, Maryland, USA; 2 Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA; 3 Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA; Departments of 4 Medicine and 10 Genetics, Harvard Medical School, Boston, Massachusetts, USA; 5 Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA; 6 Genetic Epidemiology & Clinical Research Group, Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University Hospital, Umeå, Sweden and Department of Clinical Sciences, Lund University, Malmö, Sweden; 7 Department of Medicine, Division of Endocrinology, Diabetes & Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA; 8 Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, USA; 9 Geriatrics Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland, USA; and 11 Diabetes Research Center (Diabetes Unit), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
Effects of isovolemic resuscitation with hemoglobin-based oxygen carrier Hemoglobin glutamer-200 (bovine) on systemic and mesenteric perfusion and oxygenation in a canine model of hemorrhagic shock: a comparison with 6% hetastarch solution and shed blood.

OBJECTIVE To study Hemoglobin glutamer-200 bovine (Hb-200), 6% hetastarch (HES) and shed whole blood (WB) resuscitation in canine hemorrhagic shock. STUDY DESIGN Prospective laboratory investigation. Animals Twelve adult dogs [29 +/- 1 kg (mean +/- SD)]. METHODS Anesthetized dogs were instrumented for recording systemic and mesenteric hemodynamic parameters and withdrawal of arterial, mixed and mesenteric venous blood, in which hematological, oxygenation, blood gas and acid-bases variables were determined. Recordings were made before [baseline (BL)], after 1 hour of hypovolemia and immediately and 3 hours post-resuscitation with 30 mL kg(-1) of either Hb-200, HES, or WB. RESULTS Blood withdrawal (average 34 +/- 2 mL kg(-1)) caused significant hemodynamic changes, metabolic acidosis and hyperlactatemia characteristic for hemorrhagic shock. Only WB transfusion restored all variables. Hemoglobin glutamer-200 bovine infusion returned most hemodynamic parameters including cardiac output and mesenteric arterial blood flow to BL but increased mean arterial pressure above BL (p < 0.05). However, Hb-200 failed to restore total Hb and arterial oxygen content (CaO2), leaving systemic (DO2I) and mesenteric O2 delivery (DO2Im) below BL (p < 0.05). Nevertheless, acid-base variables recovered completely after Hb-200 resuscitation, and met-hemoglobin (Met-Hb) levels increased (p < 0.05). Hetastarch resuscitation returned hemodynamic variables to or above BL but further decreased total Hb and CaO2, preventing recovery of sDO2I and mDO2I (p < 0.05). Thus, systemic and mesenteric O2 extraction stayed above BL (p < 0.05) while acid-base variables recovered to BL, although slower than in Hb-200 and WB groups (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE Resuscitation with Hb-200 seemed to resolve metabolic acidosis and lactatemia more rapidly than HES, but not WB; yet it is not superior to HES in improving DO2I and DO2Im. The hyperoncotic property of solutions like Hb-200 that results in rapid volume expansion with more homogenous microvascular perfusion and the ability to facilitate diffusive O2 transfer accelerating metabolic recovery may be the key mechanisms underlying their beneficial effects as resuscitants.
Development of a novel drug release system, time-controlled explosion system (TES). I. Concept and design.

A novel controlled drug release system. Time-Controlled Explosion System (TES) has been developed. TES has a four-layered spherical structure, which consists of core, drug, swelling agent and water insoluble polymer membrane. TES is characterized by a rapid drug release with a precisely programmed lag time; i.e. expansion of the swelling agent by water penetrating through the outer membrane, destruction of the membrane by stress due to swelling force and subsequent rapid drug release. For establishing the concept and development strategy, TES was designed using metoprolol and polystyrene balls (size: 3.2 mm in diameter) as a model drug and core particles. Among the polymers screened, low-substituted hydroxypropylcellulose (L-HPC) and ethylcellulose (EC) were selected for a swelling agent and an outer water insoluble membrane, respectively. The release profiles of metoprolol from the system were not affected by the pH of the dissolution media. Lag time was controlled by the thickness of the outer EC membrane; thus, a combination of TES particles possessing different lag times could offer any desired release profile of the model compound, metoprolol.
Assessing 'stage of change' in current and former smokers.

AIMS The concept of 'stage of change' is widely used by researchers and clinicians in the field of smoking cessation. Our aim was to assess the validity of three staging questionnaires and of the concept of 'stage of change' itself. SETTING AND PARTICIPANTS Survey on the Internet in 1025 ever smokers, retest after 8 days in 318 people (31%), follow-up after 32 days in 451 people (44%). MEASUREMENTS Three measures of 'stage of change'. FINDINGS Participants (83-93%) were classified in the same stage by all pairs of questionnaires, and 15% changed stage during an interval of 8 days. Including quit attempts in the 'preparation' stage had a large impact on stage distributions, because 18-24% of smokers who had decided to quit in the next 30 days were downgraded to the 'contemplation' stage as they had not made a quit attempt in the previous year. The 'action' stage included 5-7% of occasional smokers. Quit attempts during the past 7 days and 30 days were better predictors of smoking cessation than quit attempts during the past 12 months. Baseline stage and a continuous measure of intention predicted smoking abstinence at follow-up. CONCLUSIONS These results reflect theoretical and methodological problems with the concept of stage of change. 'Stage' covers four different variables: current behaviour, quit attempts, intention to change and time since quitting. These variables are combined in a somewhat haphazard manner, none of them is measured comprehensively, and intention and time are continuous variables categorized by arbitrary cutpoints. Measuring each of these four variables independently may be preferable to using an incomplete mix of these elements.
Combination Therapy With Molecular Hydrogen and Hyperoxia in a Murine Model of Polymicrobial Sepsis

ABSTRACT Sepsis is the most common cause of death in intensive care units. Some studies have found that hyperoxia may be beneficial to sepsis. However, the clinical use of hyperoxia is hindered by concerns that it could exacerbate organ injury by increasing free radical formation. Recently, it has been suggested that molecular hydrogen (H2) at low concentration can exert a therapeutic antioxidant activity and effectively protect against sepsis by reducing oxidative stress. Therefore, we hypothesized that combination therapy with H2 and hyperoxia might afford more potent therapeutic strategies for sepsis. In the present study, we found that inhalation of H2 (2%) or hyperoxia (98%) alone improved the 14-day survival rate of septic mice with moderate cecal ligation and puncture (CLP) from 40% to 80% or 70%, respectively. However, combination therapy with H2 and hyperoxia could increase the 14-day survival rate of moderate CLP mice to 100% and improve the 7-day survival rate of severe CLP mice from 0% to 70%. Moreover, moderate CLP mice showed significant organ damage characterized by the increases in lung myeloperoxidase activity, lung wet-to-dry weight ratio, protein concentration in bronchoalveolar lavage, serum biochemical parameters (alanine aminotransferase, aspartate aminotransferase, creatinine, and blood urea nitrogen), and organ histopathological scores (lung, liver, and kidney), as well as the decrease in PaO2/FIO2 ratio at 24 h, which was attenuated by either H2 or hyperoxia alone. However, combination therapy with H2 and hyperoxia had a more beneficial effect against lung, liver, and kidney damage of moderate or severe CLP mice. Furthermore, we found that the beneficial effect of this combination therapy was associated with the decreased levels of oxidative product (8-iso-prostaglandin F2&agr;), increased activities of antioxidant enzymes (superoxide dismutase and catalase) and anti-inflammatory cytokine (interleukin 10), and reduced levels of proinflammatory cytokines (high-mobility group box 1 and tumor necrosis factor &agr;) in serum and tissues. Therefore, combination therapy with H2 and hyperoxia provides enhanced therapeutic efficacy via both antioxidant and anti-inflammatory mechanisms and might be potentially a clinically feasible approach for sepsis.
Anatomical distribution of estrogen target cells in the avian CNS: A comparison with the mammalian CNS

The distribution of labeled cells was investigated in the brain of the ring dove one hour after administration of 3H‐estradiol. Major areas of concentration of labeled cells were found in (1) the preoptico‐strial region: nucleus preopticus medialis and nucleus interstitialis of the dorsal olfactory projection, (2) the basal hypothalamic region: nucleus hypothalamicus posterior medialis and nucleus inferior, (3) the amygdaloid region: nucleus taeniae and adjacent portions of the archistriatum, and (4) the midbrain: substantia grisea surrounding the nucleus mesencephalicus lateralis, pars dorsalis. The findings support the phylogenetic homologies between the avian nucleus interstitialis of the stria dorsal olfactory projection and the mammalian nucleus interstitialis of the stria terminalis, the avian nucleus hypothalamicus posterior medialis and the mammalian nucleus ventromedialis hypothalami, as well as the avian nucleus inferior and the mammalian nucleus infundibularis‐premammillaris ventralis. The results also suggest that the nucleus taeniae and adjacent portions of the archistriatum correspond to the nucleus medialis and other more differentiated labeled areas of the mammalian amygdala.
Dynamics of the inflammatory response after murine spinal cord injury revealed by flow cytometry

Spinal cord injury (SCI) triggers a robust inflammatory response that contributes in part to the secondary degeneration of spared tissue. Here, we use flow cytometry to quantify the inflammatory response after SCI. Besides its objective evaluation, flow cytometry allows for levels of particular markers to be documented that further aid in the identification of cellular subsets. Analyses of blood from SCI mice for CD45 (common leukocyte antigen), CD11b (complement receptor‐3), Gr‐1 (neutrophil/monocyte marker), and CD3 (T‐cell marker) revealed a marked increase in circulating neutrophils (CD45high:Gr‐1high) at 12 hr compared with controls. Monocyte density in blood increased at 24 hr, and in contrast, lymphocyte numbers were significantly decreased. Mirroring the early increase in neutrophils within the blood, flow analysis of the spinal cord lesion site revealed a significant (P < 0.01) and maintained increase in blood‐derived leukocytes (CD45high:CD11bhigh) from 12 to 96 hr compared with sham‐injured and naive controls. Importantly, this technique clearly distinguishes blood‐derived neutrophils (CD45:Gr‐1high:F4/80negative) and monocyte/macrophages (CD45high) from resident microglia (CD45low) and revealed that the majority of the blood‐derived infiltrate were neutrophils. Our results highlight an assumed, but previously uncharacterized, marked and transient increase in leukocyte populations in blood early after SCI followed by the orchestrated invasion of neutrophils and monocytes into the injured cord. In contrast to mobilization of neutrophils, SCI induces lymphopenia that may contribute negatively to the overall outcome after spinal cord trauma. © 2008 Wiley‐Liss, Inc.
Cost-effectiveness evaluation of a home blood pressure monitoring program.

OBJECTIVES To evaluate the health system cost of a home blood pressure monitoring (HBPM) program versus usual care in an integrated healthcare system. STUDY DESIGN This cost-effectiveness analysis was based upon a previously completed randomized controlled trial of 348 hypertensive patients, in which mean systolic blood pressure (BP) was lowered 21 versus 8 mm Hg in the HBPM and usual care groups, respectively, and BP control was achieved in 54% versus 35% of patients (P < .001). METHODS This analysis compared direct costs from the health plan perspective, including clinic visits, e-mail and telephone encounters, laboratory tests, medications, hospitalizations, and emergency department visits between the 2 groups. Primary outcomes were the incremental hypertension care-related cost of HBPM per mm Hg lowering of systolic BP per patient, per additional BP controlled, and per life-year gained. RESULTS Median hypertension-related cost per patient over 6 months was $455 in the HBPM group and $179 for usual care (P < .001). This increase was attributable to additional e-mail and telephone encounters, greater antihypertensive medication use, additional laboratory monitoring, and the BP monitor. Median total cost per patient was $1530 and $1283 for the HBPM and usual care groups, respectively (P = .034). The HBPM program increased hypertension-related expenditures by $20.50 per mm Hg lowering of systolic BP, $1331 per additional patient achieving BP control at 6 months, and $3330 per life-year gained. CONCLUSIONS The HBPM program requires investment in outpatient encounters, medications, and laboratory monitoring, but produces significantly improved BP control.
ImAble system for upper limb stroke rehabilitation

ImAble is an integrated upper limb (UL) exercise system comprising three devices (Able-B, Able-M and Able-X) targeting UL rehabilitation using computer games and virtual reality (VR). The system can be tailored to different levels of ability and strength, depending on the presentation of the stroke. Results from pilot testing and case studies indicate a therapeutic benefit for both movement outcome and patient motivation.
The Modified Tardieu Scale for the measurement of elbow flexor spasticity in adult patients with hemiplegia

Primary objective: To investigate the inter-rater reliability of the Modified Tardieu Scale (MTS) in the measurement of elbow flexor muscle spasticity in patients with adult hemiplegia. Research design: A cross-sectional study to examine the agreement between two raters on elbow flexor muscle spasticity using Modified Tardieu Scale. Interventions: Not applicable. Methods and procedures: Thirty patients (21 men, nine women) with an age range of 21–79 years (mean = 54.9; SD = 15.7) were tested. Two inexperienced raters assessed the elbow flexor muscle spasticity in the affected side during the same session. The order of assessments by the two raters was randomized. The main outcome measure was dynamic component of spasticity (R2–R1). Reliability was also calculated for MTS scores, angle of muscle reaction (R1), and passive range of motion (R2). Main outcomes and results: The ICC for R2–R1 was 0.72. The ICC for MTS scores, R1 and R2 were 0.74, 0.74 and 0.56, respectively. Conclusions: The Modified Tardieu Scale did not provide acceptable high inter-rater reliability in the measurement of muscle spasticity in patients with hemiplegia when used by raters of limited experience.
Role of Central Amygdala Neuronal Ensembles in Incubation of Nicotine Craving

The craving response to smoking-associated cues in humans or to intravenous nicotine-associated cues in adult rats progressively increases or incubates after withdrawal. Here, we further characterized incubation of nicotine craving in the rat model by determining whether this incubation is observed after adolescent-onset nicotine self-administration. We also used the neuronal activity marker Fos and the Daun02 chemogenetic inactivation procedure to identify cue-activated neuronal ensembles that mediate incubation of nicotine craving. We trained adolescent and adult male rats to self-administer nicotine (2 h/d for 12 d) and assessed cue-induced nicotine seeking in extinction tests (1 h) after 1, 7, 14, or 28 withdrawal days. In both adult and adolescent rats, nicotine seeking in the relapse tests followed an inverted U-shaped curve, with maximal responding on withdrawal day 14. Independent of the withdrawal day, nicotine seeking in the relapse tests was higher in adult than in adolescent rats. Analysis of Fos expression in different brain areas of adolescent and adult rats on withdrawal days 1 and 14 showed time-dependent increases in the number of Fos-positive neurons in central and basolateral amygdala, orbitofrontal cortex, ventral and dorsal medial prefrontal cortex, and nucleus accumbens core and shell. In adult Fos–lacZ transgenic rats, selective inactivation of nicotine-cue-activated Fos neurons in central amygdala, but not orbitofrontal cortex, decreased “incubated” nicotine seeking on withdrawal day 14. Our results demonstrate that incubation of nicotine craving occurs after adolescent-onset nicotine self-administration and that neuronal ensembles in central amygdala play a critical role in this incubation. SIGNIFICANCE STATEMENT The craving response to smoking-associated cues in humans or to intravenous nicotine-associated cues in adult rats progressively increases or incubates after withdrawal. It is currently unknown whether incubation of craving also occurs after adolescent-onset nicotine self-administration. The brain areas that mediate such incubation are also unknown. Here, we used a rat model of incubation of drug craving, the neuronal activity marker Fos, and the Daun02 chemogenetic inactivation method to demonstrate that incubation of nicotine craving is also observed after adolescent-onset nicotine self-administration and that neuronal ensembles in the central nucleus of the amygdala play a critical role in this incubation in adult rats.
An investigation of the impact of mobility on the protocol performance in wireless sensor networks

Mobility has introduced a new dimension to the wireless research areas such as IP mobility management protocols and wireless ad hoc networks. In this paper we take a closer look at the issues related to the mobility in wireless sensor networks (WSNs). The aim of this work is to identify improvements that can be obtained considering mobility, recognize its research challenges. We describe different levels of mobility in WSNs and highlight the effect of the mobility on the performance of WSN protocols.
Apocynin Attenuates Cerebral Infarction after Transient Focal Ischaemia in Rats

This study investigated whether inhibition of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase attenuates cerebral infarction after transient focal ischaemia in rats. Focal ischaemia (1.5 h) was produced in male Sprague-Dawley rats (250 − 280 g) by middle cerebral artery occlusion. Some rats also received treatment with 50 mg/kg apocynin, a NADPH oxidase inhibitor, by intraperitoneal injection 30 min prior to reperfusion. Two hours after reperfusion, brains were harvested to measure NADPH oxidase activity and superoxide levels. After 24 h, the remaining brains were harvested to investigate infarct size. NADPH oxidase activity and superoxide level were all augmented 2 h after reperfusion compared with controls. Apocynin treatment significantly reduced NADPH oxidase activity and superoxide levels. Cerebral infarct size was significantly smaller in the apocynin-treated group compared with those undergoing ischaemia/reperfusion alone. These results indicate that inhibition of NADPH oxidase attenuates cerebral infarction after transient focal ischaemia in rats, suggesting that inhibition of NADPH oxidase may provide a therapeutic strategy for ischaemic stroke.
Influence of non-inherited maternal HLA-DR antigens on susceptibility to rheumatoid arthritis

OBJECTIVE It has recently been observed that non-inherited maternal DR4 antigens (NIMAs) of DR4 negative rheumatoid arthritis (RA) patients were increased compared with non-inherited paternal DR4 antigens (NIPAs). The aim of this study was to determine the prevalence of non-inherited DR4 antigens and DRB1 alleles in parents of RA patients. METHODS HLA-DR serology and DRB1 typing was performed in 97 RA patients and their parents. NIMA and NIPA frequencies were compared, stratified according to the presence of DR4 and/or the shared epitope (SE). RESULTS In DR4 negative patients, NIMA DR4 was increased compared with NIPA DR4 (OR 3.10, 95% CI 0.76, 12.70). When combined with results from a previous study this increase was significant (OR 3.65, 95% CI 1.29, 10.31). The NIMA effect of SE positive DR4 subtypes in this study (OR 4.73, 95% CI 0.94, 23.8) was stronger than the NIMA effect of combined SE positive DRB1 alleles (OR 2.19 95% CI 0.36, 13.22). CONCLUSIONS The association between non-inherited maternal HLA-DR4 alleles and the susceptibility to RA was observed in two independent populations.