Miracle-dz/UniFAR-FTUs huggingface dataset:
Bradykinin‐induced nociceptor sensitization to heat is mediated by cyclooxygenase products in isolated rat skin

Bradykinin can excite C‐polymodal nociceptors and sensitize them to heat and it can also enhance prostaglandin synthesis, but it is unclear whether these effects are causally related. The role of cyclooxygenase products was investigated using two enantiomers of the cyclooxygenase inhibitor flurbiprofen of which S(+)‐ is more potent than R(–)‐flurbiprofen. Single‐unit activity was recorded from mechano‐heat‐sensitive, polymodal C‐fibers in the isolated rat skin‐saphenous nerve preparation. Bradykinin pretreatment (10 µm, 5 min) induced a 219 ± 26% increase in the number of spikes evoked by noxious heat stimulation and a drop in the heat threshold by 5.2 ± 0.6 °C in a fully reproducible manner. S(+)‐flurbiprofen (1 µm) abolished the bradykinin‐induced heat sensitization but did not alter the unconditioned heat response itself. Under R(–)‐flurbiprofen (1 µm) bradykinin still induced a significant heat sensitization which was reduced by 33 ± 21% (P = 0.11) of its previous extent; this effect may be due to the limited purity of the enantiomer preparation or to a cyclooxygenase‐independent action of flurbiprofen. The heat sensitization suppressed by S(+)‐flurbiprofen could be significantly restored (to 43 ± 12%) by addition of PGE2 plus PGI2 (10 µm both) to bradykinin. Neither S(+)‐ nor R(–)‐flurbiprofen had an influence on the magnitude of the excitatory effect of bradykinin. It is concluded that (i) cyclooxygenase products are the main mediators of nociceptor sensitization to heat following bradykinin treatment in the isolated rat skin; (ii) PGE2/I2 are essential but perhaps not the only relevant cyclooxygenase products involved and (iii) neither S(+)‐ nor R(–)‐flurbiprofen inhibit the unconditioned noxious heat response and the excitatory bradykinin response of the polymodal C‐nociceptors.
A phase Ib trial of IPI-926, a hedgehog pathway inhibitor, plus gemcitabine in patients with metastatic pancreatic cancer.

213 Background: IPI-926 is a novel, natural product-derived small molecule that targets the Hedgehog (Hh) pathway by inhibiting smoothened. In preclinical models of pancreatic cancer, repressing activation of the Hh pathway diminishes tumor-associated desmoplasia and improves chemotherapy delivery. METHODS This is the final report of the Phase 1b portion of a Phase 1b/2 trial evaluating the safety and efficacy of IPI-926 plus gemcitabine. Eligible patients (pts) with untreated metastatic pancreatic cancer and ECOG status 0-1 were administered oral IPI-926 daily (QD) for 28-day cycles, in 3 to 6 pt dose cohorts. Gemcitabine (1,000 mg/m2) was administered IV weekly for 3 weeks with 1 week off. DLTs were evaluated during Cycle 1. RESULTS 16 pts (median age 69 years; range 58-86) were enrolled at IPI-926 doses of 110, 130 or 160 mg QD (single agent MTD). Pts received a median of 5 cycles (1-13). Two pts remain on trial. No IPI-926-related serious AEs have been observed. One DLT of Grade 3 AST increase was observed (130 mg dose cohort) and was asymptomatic; it resolved with dose interruption, and did not recur with dose reduction. The most common AEs occurring were fatigue (75% total, 6% ≥ Grade 3), thrombocytopenia (63%, 25%), anemia (56%, 13%), nausea (50%, 0%), diarrhea (44%, 0%), vomiting (44%, 0%), peripheral edema (44%, 0%), pyrexia (44%, 0%), and AST increase (44%, 13%). Dose reductions of IPI-926 occurred in 3 (19%) pts. Dose reductions of gemcitabine occurred in 11 (69%) pts, primarily for thrombocytopenia (9 pts). One pt (6%) discontinued due to an AE (microangiopathic hemolytic anemia). Five (31%) radiographic partial responses were observed (1/3 at 110 mg, 2/6 at 130 mg, 2/7 at 160 mg). Median progression-free survival is > 7 months. 74% of pts were alive 6 months after study entry. CONCLUSIONS IPI-926 plus gemcitabine is well tolerated in pts with untreated metastatic pancreatic cancer, with evidence of activity and no unexpected toxicity. Complete Phase 1b data, including final overall survival, will be presented. Clinical evaluation of this combination continues in the randomized, double-blind, placebo-controlled Phase 2 portion of the trial.
Recurrent herpes simplex type 2 virus (Mollaret) meningitis.

Mollaret meningitis is a rare form of meningitis that is recurrent, aseptic, mild, and self-limiting. When initially described by Mollaret, this form of aseptic meningitis had no identifiable infecting agent. [1][1] New sophisticated diagnostic tools have now identified Herpes simplex type 2 virus as
Flow cytometric measurement of intracellular Th1 and Th2 cytokine production by human villous and extravillous cytotrophoblast.

A wide variety of cytokines are present at the maternal-fetal interface, but the extreme cellular complexity of the placenta has made it difficult to determine which cytokines are produced by which cells. Hence novel flow cytometric methods have been applied to determine intracellular cytokine production by specific cell-types in placental cell suspensions. Cell suspensions were prepared from first and third trimester chorionic villi and third trimester amniochorion by enzymatic digestion and Percoll density gradient centrifugation. After overnight incubation in the presence of monensin, cells were fixed, permeabilized and labelled with antibodies for villous cytotrophoblast (cytokeratin+, MHC class I-), extravillous cytotrophoblast (cytokeratin+, MHC class 1+) and leucocytes (CD45+). These cell types were further characterized by their expression of EGFR (proliferative cytotrophoblast) and c-erbB2 (invasive cytotrophoblast). Production of IL-4, IL-10, TNF-alpha, IFN-gamma and IL-12 was determined by simultaneous labelling with the appropriate monoclonal antibodies. Only IL-4 was detected consistently in all samples of cytotrophoblast. IL-10 was not detected but IL-10 mRNA was demonstrated in third trimester chorionic villus digests by RT-PCR. Although IL-4 secretion has not been demonstrated, these data suggest that, in vivo there may be a "Th2 type cytokine bias" orchestrated by the trophoblast. It is proposed that other cytokines (including IL-10 and TNF-alpha) are produced by decidual leukocytes, and not cytotrophoblast, at the maternal-fetal interface.
Extended Regimens of the Contraceptive Vaginal Ring: A Randomized Trial

Objective: To compare the bleeding patterns and tolerability of 3 different extended ring regimens with those of the standard 28-day cycle with 21 days of contraceptive vaginal ring use followed by 7 ring-free days. Methods: Following a run-in 28-day ring cycle, women were randomized to 1 of 4 regimens: monthly (28-day cycle), every other month (49-day cycle), every third month (91-day cycle), or continuous (364-day cycle). Treatment duration was 1 year. Daily bleeding diary, interval visit questionnaire, and examination data were collected. Results: A total of 561 women were enrolled, 429 were subsequently randomized, and 289 (67.4%) women completed the entire year. All schedules were well tolerated and acceptable to women, but study completion rates were higher for the shorter cycles. Bleeding days were reduced with postponement of the withdrawal bleeding (ring-free) week, but spotting days increased. For example, women using the continuous or 364-day ring cycle reported a median of zero bleeding days but 10–12 days of spotting during the first 3 months of extended use. Unscheduled bleeding during ring use was the lowest with the traditional 28-day cycle. Adverse events, blood pressure, body weight, and laboratory findings were comparable over the 4 treatment groups. Conclusion: The combination vaginal contraceptive ring can be used for extended cycles to alter the bleeding schedule. Women willing to tolerate some spotting might choose the longer extensions to have fewer menstrual periods. Level of Evidence: I
Single-Layer Dual-Band Dual-Linear-Polarization Reflectarray Antenna with Different Beams for Each Band

A novel single-layer unit cell structure is proposed to design a dual-band dual-linearpolarization reflectarray antenna with different beams for X and Ku bands. The unit cell structure is composed of a circular ring and two cross bow-tie structures combined by a circular patch. Five tunable geometric parameters can be optimized to achieve the required phase distributions of the reflectarray antenna with independent radiation patterns for each band which is a challenge for singlelayer linearly polarized reflectarrays. Besides, the proposed unit cell structure has the ability to meet the demand of dual-polarization applications. A 301-element center-fed reflectarray with an octagon-shape aperture operating at X and Ku bands is designed, manufactured and measured to verify the dual-band performance of the proposed unit cell. The measured results show that the object of achieving different beams at different frequencies is realized with good radiation patterns at both designed frequencies. Besides, the similar radiation patterns for both linear polarizations are also achieved at both bands.
Lung cancer and exposure to arsenic in rural Bangladesh

Background: Arsenic is a known carcinogen but the risk of lung cancer from the widespread contamination of drinking water in rural Bangladesh has not been estimated. Objectives: To determine whether estimated exposure of villagers in Bangladesh to arsenic in drinking water differed between those with lung cancer and those with non-malignant lesions. Methods: Data were obtained from 7286 subjects who underwent lung biopsy in 2003–2006 at a diagnostic centre taking referrals from throughout Bangladesh. Analysis was limited to 5372 people living in villages for the last 10 years who reported using tube well water. Of these, 3223 with a primary lung tumour were enrolled as cases and 1588 with non-malignant lesions as referents in an unmatched analysis. Arsenic exposure was estimated by average concentrations for each of 64 districts. Logistic regression was used to test the effects of age, arsenic and smoking on risk and to investigate relationship to cell type. Results: Male cases were older than referents and more likely to smoke, to smoke >20 units/day and to smoke bidi—small, hand-rolled cigarettes. Odds ratios for lung cancer increased steadily with mean arsenic concentration, but the confidence interval excluded 1.0 only at concentrations >100 μg/l (OR 1.45, 95% CI 1.16 to 1.80). This trend was seen only in smokers where the increased risk at >100 μg/l was 1.65 (95% CI 1.25 to 2.18). A similar trend was seen in women smokers. Squamous cell lung cancer was more frequent in smokers and, having adjusted for smoking, in districts with arsenic concentrations >100 μg/l. Conclusions: Among Bangladeshis who smoke, those whose drinking water is contaminated with arsenic at concentrations >100 μg/l are at increased risk of lung cancer. With high levels of exposure misclassification and short latency of exposure, the study cannot estimate or exclude the likely long term risk in non-smokers and at lower arsenic concentrations.
Papulonodular Mucinosis Associated with Subacute Cutaneous Lupus erythematosus

Mucin deposition is a common histopathologic finding in lupus erythematosus (LE) but is rarely present in sufficient quantity to produce clinically apparent skin lesions. Until now, fewer than 40 cases of papulonodular mucinosis associated with LE have been reported in the literature, and it was associated with either systemic LE or discoid LE. For the first time, to our knowledge, we describe 2 patients with subacute cutaneous LE who presented with papulonodular mucinosis as a major clinical manifestation of their disease.
Large‐scale neurocognitive networks and distributed processing for attention, language, and memory

Cognition and comportment are subserved by interconnected neural networks that allow high‐level computational architectures including parallel distributed processing. Cognitive problems are not resolved by a sequential and hierarchical progression toward predetermined goals but instead by a simultaneous and interactive consideration of multiple possibilities and constraints until a satisfactory fit is achieved. The resultant texture of mental activity is characterized by almost infinite richness and flexibility. According to this model, complex behavior is mapped at the level of multifocal neural systems rather than specific anatomical sites, giving rise to brain‐behavior relationships that are both localized and distributed. Each network contains anatomically addressed channels for transferring information content and chemically addressed pathways for modulating behavioral tone. This approach provides a blueprint for reexploring the neurological foundations of attention, language, memory, and frontal lobe function.
Right-sided laparoscopic live-donor nephrectomy: Is reluctance still justified?

Background. Laparoscopic donor nephrectomy (LDN) of the right kidney is performed with great reluctance because of the shorter renal vein and possible increased incidence of venous thrombosis. Methods. In this retrospective, clinical study, right LDN and left LDN were compared. Between December 1997 and May 2001, 101 LDN were performed. Seventy-three (72%) right LDN were compared with 28 (28%) left LDN for clinical characteristics, operative data, and graft function. Results. There were no significant differences between the two groups regarding conversion rate, complications, hospital stay, thrombosis, graft function, and graft survival. Operating time was significantly shorter in the right LDN group (218 vs. 280 min). Conclusion. In this study, right LDN was not associated with a higher number of complications, conversions, or incidence of venous thrombosis compared with the left LDN. Thus, reluctance toward right LDN is not justified, and therefore, right LDN should not be avoided.
Utility of thermal image sharpening for monitoring field‐scale evapotranspiration over rainfed and irrigated agricultural regions

The utility of a thermal image sharpening algorithm (TsHARP) in providing fine resolution land surface temperature data to a Two‐Source‐Model for mapping evapotranspiration (ET) was examined over two agricultural regions in the U.S. One site is in a rainfed corn and soybean production region in central Iowa. The other lies within the Texas High Plains, an irrigated agricultural area. It is concluded that in the absence of fine (sub‐field scale) resolution thermal data, TsHARP provides an important tool for monitoring ET over rainfed agricultural areas. In contrast, over irrigated regions, TsHARP applied to kilometer‐resolution thermal imagery is unable to provide accurate fine resolution land surface temperature due to significant sub‐pixel moisture variations that are not captured in the sharpening procedure. Consequently, reliable estimation of ET and crop stress requires thermal imagery acquired at high spatial resolution, resolving the dominant length‐scales of moisture variability present within the landscape.
Lichen Planus in Childhood: A Report of 17 Patients

Abstract: Lichen planus is a dermatosis of unknown origin with a very limited frequency in children. Over a period of one and a half years we observed 17 cases of childhood lichen planus. The classic form of the disease as seen in adults was the most common in these children; unlike adults, however, mucosal and nail involvement was uncommon. The natural history of the disease was similar to that in adults.
Intermittent positive pressure respiration as a treatment in severe respiratory distress syndrome.

Since the initial work of Donald and Lord (1953) and Donald, Kerr, and MacDonald (1958), there have been several reported survivals ofinfants with the respiratory distress syndrome (RDS) treated by assisted ventilation (Benson, Celander, Haglund, Nilsson, Paulsen, and Renck, 1958; Stahlman, Young, and Payne, 1962; Delivoria-Papadopoulos and Swyer, 1963; Heese, Wittmann, and Malan, 1963). Previous work in our unit (Delivoria-Papadopoulos and Swyer, 1964) demonstrated the possibility of reversing at least temporarily the biochemical changes of terminal asphyxia in patients dying with RDS. The purpose of this study was to gain further information regarding criteria for initiating assisted ventilation and its technique in relation to the clinical features and course of the disease.
Quantitative Comparison of the Transient Rescue Effects of Neurotrophic Factors on Axotomized Motoneurons In Vivo

A reproducible neuronal degeneration induced by nerve lesion in neonatal rats or mice provides a convenient in vivo assay for testing the survival‐promoting activity of putative growth factors on motoneurons. The goal of this study was to compare the rescue effects of the four known neurotrophins [nerve growth factor (NGF), brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3) and neurotrophin‐4 (NT‐4)] and two of the cytokines [ciliary neurotrophic factor (CNTF) and leukaemia inhibitory factor (LIF)] in one particular experimental model of spinal motoneuron degeneration at two different survival times. The sciatic nerve was cut in neonatal rats and the factors were applied onto the nerve stump; bovine serum albumin was used in controls. Simultaneous application of the retrograde tracer fluoro‐gold made it possible to count motoneurons specifically in the sciatic pool. One week after lesion, the neurotrophins BDNF, NT‐3 and NT‐4, but not NGF, equally enhanced motoneuron survival compared to controls; their effects were significantly better than those of the cytokines. However, the rescue from cell death was only transitory because a great number of the motoneurons died during the second week after nerve lesion. Additional BDNF and/or CNTF supplied by repeated subcutaneous injections (1 mg/ml) over 2 weeks could not prevent this delayed motoneuron loss. These results suggest that still other factors or alternative routes of administration may be required for permanent rescue of the lesioned immature motoneurons.
Sample Dimensions Influence Strength and Crystal Plasticity

When a crystal deforms plastically, phenomena such as dislocation storage, multiplication, motion, pinning, and nucleation occur over the submicron-to-nanometer scale. Here we report measurements of plastic yielding for single crystals of micrometer-sized dimensions for three different types of metals. We find that within the tests, the overall sample dimensions artificially limit the length scales available for plastic processes. The results show dramatic size effects at surprisingly large sample dimensions. These results emphasize that at the micrometer scale, one must define both the external geometry and internal structure to characterize the strength of a material.
A High-Linearity Wideband Power Amplifier With Cascaded Third-Order Analog Predistorters

A high-linearity wideband analog predistortion power amplifier (PA) is presented. The memory effects of the PA are reduced by a high drain bias voltage as well as a wide bias line and several decoupling capacitors. The simple cascaded third-order analog predistorters (CTAPDs) are used to cancel the third- and fifth-order intermodulations (IM3s and IM5s) of the low-memory PA. For verification, the 45 W class-AB PA is implemented and tested using a two-tone signal and a four-carrier wideband code division multiple access (WCDMA) signals at 2.14 GHz. From the measured results, the low-memory PA with the CTAPDs delivers significant IM3 and IM5 cancellation and superior ACLR improvement.
Long‐term beneficial effect of protease inhibitors on the intrinsic apoptosis of peripheral blood mononuclear cells in HIV‐infected patients

Viral suppression by antiretroviral therapy (ART) inhibits HIV‐induced apoptosis and CD4 T‐cell loss. It has been suggested that protease inhibitors (PIs) have nonviral antiapoptotic effects by maintaining mitochondrial integrity. Long‐term clinical effects of PI‐based ART on mitochondrial toxicity and lymphocyte apoptosis beyond viral suppression have not been exploited to date.
Predictors of Relapse of Methicillin-Resistant Staphylococcus aureus Bacteremia after Treatment with Vancomycin

ABSTRACT The risk factors for relapse of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia after vancomycin treatment are unknown. Diversilab typing was used to classify recurrent bacteremia as relapse or reinfection. Bacteremia for >7 days and staphylococcal cassette chromosome mec element (SCCmec) type II were independently associated with relapse of MRSA bacteremia after vancomycin treatment.
Nematodes of armadillos in Paraguay: a description of a new species Aspidodera esperanzae (Nematoda: Aspidoderidae).

Twelve species of nematodes comprising 9 genera were recovered from the gastrointestinal tract of 2 Euphractus sexcinctus and 2 Dasypus novemcinctus captured in the Department of San Pedro, Paraguay. All armadillos were infected with 1 or more species of nematode. The following nematodes were recovered: Mazzia mazzia, Spirura guianensis, Trichohelix tuberculata, Ancylostoma sp. , Moennigia complexus, Moennigia pintoi, Ascaris dasypodina, Cruzia tentaculata, Aspidodera fasciata, Aspidodera scoleciformis, Aspidodera esperanzae n. sp. , and Heterakinae gen. sp. This report describes a new species of the Aspidodera nematode, Aspidodera esperanzae n. sp. , the first species to be reported bearing cephalic cordons made up of 7 longitudinal loops in the subfamily of Aspidoderinae. This study also documents a new host record for S. guianensis and shows a new geographical distribution in Paraguay for M. mazzia, S. guianensis, T. tuberculata, M. complexus, and M. pintoi.
Mendelian randomization studies: using naturally randomized genetic data to fill evidence gaps

Purpose of review Mendelian randomization studies have the potential to transform our understanding of cardiovascular medicine by generating naturally randomized data that can fill evidence gaps when a randomized trial would be either impossible or impractical to conduct. Here, we review recent Mendelian randomization studies evaluating the effect of low-density lipoprotein cholesterol (LDL-C) on the risk of coronary heart disease (CHD). Recent findings Mendelian randomization studies consistently demonstrate that LDL-C is causally associated with the risk of CHD. Furthermore, exposure to genetically mediated lower LDL-C appears to be associated with a much greater than expected reduction in CHD risk, thus suggesting that LDL-C has a cumulative effect on the risk of CHD. In addition, genetically mediated lower LDL-C is log-linearly associated with the risk of CHD and the effect of polymorphisms in multiple different genes on the risk of CHD is remarkably consistent when measured per unit lower LDL-C. Summary The naturally randomized genetic evidence suggests that LDL-C has a causal and cumulative effect on the risk of CHD, and that the clinical benefit of exposure to lower LDL-C is determined by the absolute magnitude of exposure to lower LDL-C independent of the mechanism by which LDL-C is lowered.