Miracle-dz/UniFAR-FTUs huggingface dataset:
Transient Receptor Potential Vanilloid 4–Mediated Disruption of the Alveolar Septal Barrier: A Novel Mechanism of Acute Lung Injury

Disruption of the alveolar septal barrier leads to acute lung injury, patchy alveolar flooding, and hypoxemia. Although calcium entry into endothelial cells is critical for loss of barrier integrity, the cation channels involved in this process have not been identified. We hypothesized that activation of the vanilloid transient receptor potential channel TRPV4 disrupts the alveolar septal barrier. Expression of TRPV4 was confirmed via immunohistochemistry in the alveolar septal wall in human, rat, and mouse lung. In isolated rat lung, the TRPV4 activators 4α-phorbol-12,13-didecanoate and 5,6- or 14,15-epoxyeicosatrienoic acid, as well as thapsigargin, a known activator of calcium entry via store-operated channels, all increased lung endothelial permeability as assessed by measurement of the filtration coefficient, in a dose- and calcium-entry dependent manner. The TRPV antagonist ruthenium red blocked the permeability response to the TRPV4 agonists, but not to thapsigargin. Light and electron microscopy of rat and mouse lung revealed that TRPV4 agonists preferentially produced blebs or breaks in the endothelial and epithelial layers of the alveolar septal wall, whereas thapsigargin disrupted interendothelial junctions in extraalveolar vessels. The permeability response to 4α-phorbol-12,13-didecanoate was absent in TRPV4−/− mice, whereas the response to thapsigargin remained unchanged. Collectively, these findings implicate TRPV4 in disruption of the alveolar septal barrier and suggest its participation in the pathogenesis of acute lung injury.
Tree mortality from fires, bark beetles, and timber harvest during a hot and dry decade in the western United States (2003–2012)

High temperatures and severe drought contributed to extensive tree mortality from fires and bark beetles during the 2000s in parts of the western continental United States. Several states in this region have greenhouse gas (GHG) emission targets and would benefit from information on the amount of carbon stored in tree biomass killed by disturbance. We quantified mean annual tree mortality from fires, bark beetles, and timber harvest from 2003–2012 for each state in this region. We estimated tree mortality from fires and beetles using tree aboveground carbon (AGC) stock and disturbance data sets derived largely from remote sensing. We quantified tree mortality from harvest using data from US Forest Service reports. In both cases, we used Monte Carlo analyses to track uncertainty associated with parameter error and temporal variability. Regional tree mortality from harvest, beetles, and fires (MORTH+B+F) together averaged 45.8 ± 16.0 Tg AGC yr−1 (±95% confidence interval), indicating a mortality rate of 1.10 ± 0.38% yr−1. Harvest accounted for the largest percentage of MORTH+B+F (∼50%), followed by beetles (∼32%), and fires (∼18%). Tree mortality from harvest was concentrated in Washington and Oregon, where harvest accounted for ∼80% of MORTH+B+F in each state. Tree mortality from beetles occurred widely at low levels across the region, yet beetles had pronounced impacts in Colorado and Montana, where they accounted for ∼80% of MORTH+B+F. Tree mortality from fires was highest in California, though fires accounted for the largest percentage of MORTH+B+F in Arizona and New Mexico (∼50%). Drought and human activities shaped regional variation in tree mortality, highlighting opportunities and challenges to managing GHG emissions from forests. Rising temperatures and greater risk of drought will likely increase tree mortality from fires and bark beetles during coming decades in this region. Thus, sustained monitoring and mapping of tree mortality is necessary to inform forest and GHG management.
Factors regulating quiescent stem cells: insights from the intestine and other self‐renewing tissues

Long‐lived and self‐renewing adult stem cells (SCs) are essential for homeostasis in a wide range of tissues and can include both rapidly cycling and quiescent (q)SC populations. Rapidly cycling SCs function principally during normal tissue maintenance and are highly sensitive to stress, whereas qSCs exit from their quiescent state in response to homeostatic imbalance and regenerative pressure. The regulatory mechanisms underlying the quiescent state include factors essential for cell cycle control, stress response and survival pathways, developmental signalling pathways, and post‐transcriptional modulation. Here, we review these regulatory mechanisms citing observations from the intestine and other self‐renewing tissues.
Change of serum phosphate level and clinical outcome of hypophosphatemia in massive burn patient

BACKGROUND Hypophosphatemia is relatively common phenomenon in patients with massive burn injury. Therefore, we check serum phosphate level routinely and try to supply phosphate in a timely manner. The purpose of this study was to investigate the change of the serum phosphate level of early postburn period and the impact of hypophosphatemia on the prognosis of patients. METHODS A total of 227 patients with burn injury were reviewed retrospectively. We performed analysis of serum phosphate level within 20 days from burn injury. RESULTS Patients’ mean (SD) age was 47.0 (14.1) years, and mean (SD) percentage of total body surface area burned were 47.7 (21.9). Severe hypophosphatemia (phosphate < 1.0 mg/dL) was observed in 35 patients (15.8%), and moderate hypophosphatemia (1.0 ⩽ phosphate < 2.0 mg/dL) was found in 115 patients (50.6%). Therefore, overall incidence of hypophosphatemia was 66.4%. There was no significant difference in serum phosphate level with survival, total body surface area burned, and mechanical ventilation. Age (odds ratio [OR], 3.180; 95% confidence interval [CI], 1.025–9.871; p = 0.045), total body surface area burned (OR, 20.934; 95% CI, 6.845–64.024; p = 0.000), and mechanical ventilation (OR, 5.581; 95% CI, 2.380–13.085; p = 0.002) were independently associated with mortality. However, serum phosphate level (OR, 0.828; 95% CI, 0.275–2.495; p = 0.737) does not have a statistical significance. CONCLUSION Although multiple studies have evaluated the efficacy and safety of phosphate repletion regimens, the effect on mortality and morbidity is not well reported. However, our results show that patients with massive burn injury have high incidence of hypophosphatemia, and hypophosphatemia can result in many complications. Therefore, routine check and supply of phosphate can be suggested in patients with massive burn injury. LEVEL OF EVIDENCE Prognostic study, level II.
Prepared patients: internet information seeking by new rheumatology patients.

OBJECTIVE To investigate to what extent and why new rheumatology patients access medical information online prior to first appointments and secondarily to ask whether they discuss information gained from the Internet with physicians. METHODS Research was conducted in a teaching rheumatology clinic with a nonrandom sample of 120 English-speaking adults presenting for first appointments in rheumatology. Quantitative and qualitative data were gained in pre- and postappointment patient surveys and interviews, including online information gathering prior to first appointment, demographics, health status, information usage in patient-physician interactions, and satisfaction. Data were analyzed for significant relationships across variables and for qualitative insights into quantitative outcome measures. RESULTS Of all patients, 87.5% looked up their symptoms or suspected condition prior to their first appointment and 62.5% of all patients sought that information on the Internet. Only 20% of online information seekers discussed that information with their physicians. Age and sex were significant predictors of Internet information seeking. Physician and patient appointment satisfaction was significantly higher when Internet information was discussed; however, most patients did not discuss their information seeking because they primarily feared being perceived as challenging their physician. CONCLUSION The majority of patients research their conditions online prior to initial appointments, but are unlikely to discuss that research with physicians even though discussion is related to higher satisfaction. Physicians may want to consider strategies for enabling communication about online research.
Analytical models for information propagation in vehicle-to-vehicle networks

There has been increasing interest in information infrastructures based on vehicle-to-vehicle communications. Proposed network architectures have unique characteristics that distinguish them from other systems. We present analytical models to study spatial propagation of information in a highly mobile vehicle-to-vehicle ad-hoc network. We show that information propagation depends on vehicle traffic characteristics, e.g., the vehicle density, average vehicle speed and relative speed among vehicles. Simulations validate these models and highlight the need to include other vehicle traffic models.
Are psychotropic medications associated with differences in baseline neurocognitive assessment scores for young athletes? A pilot study

Abstract Objectives. Baseline and post-concussive neurocognitive testing is useful in managing concussed athletes. The Concussion in Sport Group has postulated that the use of psychotropic medications is a modifying factor in the management of sport-related concussion. About 7% of US adolescents are prescribed psychotropics in a given year. Our aim was to investigate whether psychotropic medication use or psychiatric illness is associated with differences in baseline neurocognitive test scores. Methods. From 2007 to 2012, over 7000 athletes underwent pre-participation baseline neurocognitive testing using the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery. Following application of inclusion and exclusion criteria, athletes’ self-reported medication lists were reviewed and: 1) classified as psychotropic or not and 2) subclassified. Group subclassification yielded: 1) use of any psychotropic medication, 2) psychostimulant use, 3) antidepressant use and 4) self-reported history of depression and/or anxiety without psychotropic use. Each group was matched, by sex, age, body mass index, education level and concussion history with athletes who were not reportedly prescribed psychotropic medications or did not report a depression/anxiety history, respectively. Each group’s baseline ImPACT scores were compared to matched controls. Results. The use of prescribed psychotropic medications without regard to subclass had no effect on baseline ImPACT composite scores among athletes ages 13–25. However, athletes reportedly prescribed psychostimulants displayed significantly lower visual motor speed scores (32.8 vs 37.1, p = 0.030) and slower reaction times (0.65 vs 0.60, p = 0.044) than non-users. In contrast, antidepressant users displayed significantly faster reaction times (0.58 vs 0.61, p = 0.029). Those reporting a history of depression/anxiety, not treated with psychotropics, displayed significantly lower visual memory (70.4 vs 75.2, p = 0.010) and higher symptom scores (8.83 vs 4.72, p = 0.005). Conclusions. This pilot study suggests that self-reported psychotropic medications are associated with differences in baseline ImPACT test scores, which appear dependent on medication subclass. Our preliminary results support the inclusion of psychotropic medications, specifically psychostimulants and antidepressants, as well as history of depression/anxiety as potential concussion modifiers.
Does Compensation Impact on Employee Engagement? Evidence from Telecom Sector of Pakistan

Explanatory study was conducted to check the impact of compensation on employee engagement. A survey questionnaire was adopted and validated through pilot data (α=0.821). Convenience sampling was used to select the employees from middle and upper managerial levels of telecom sector of Pakistan. Overall 300 questionnaires were distributed, out of which 234 return back with 78% response rate. After the analysis has been done it was found that compensation is the determinant of employee engagement (r2=0.087), thus having a significant positive impact on employee engagement.
Severe and selective deficiency of interferon‐γ‐producing invariant natural killer T cells in patients with myelodysplastic syndromes

Summary. Here we show that patients with myelodysplastic syndromes (MDS) have a severe deficiency of glycolipid reactive Vα24+/Vβ11+ natural killer T (NKT) cells, but not NK cells or CD4+ or CD8+ T cells. Neither the blood nor marrow of MDS patients had detectable interferon‐γ‐producing NKT cells in response to the NKT ligand, α‐galactosyl ceramide, although influenza‐virus‐specific effector T‐cell function was preserved. This severe and selective deficiency of an important immune regulatory cell may contribute to the pathogenesis of MDS.
The Vulvovaginal Symptoms Questionnaire: a questionnaire for measuring vulvovaginal symptoms in postmenopausal women

Objective This study aims to develop a Vulvovaginal Symptoms Questionnaire (VSQ) to determine the symptoms, emotions, life impact, and sexual impact of vulvovaginal symptoms on postmenopausal women. Methods We developed a questionnaire that focuses on vulvovaginal symptoms based on modifications to Skindex-16, a validated questionnaire for measuring the impact of skin disease. We recruited postmenopausal women seeking routine gynecologic care to test the psychometric properties of the VSQ. Test-retest reliability was assessed 2 to 4 weeks after their initial recruitment and measured using intraclass coefficients. Four distinct a priori scales of the VSQ were developed: symptoms, emotions, life impact, and sexual impact. Confirmatory factor analysis was performed to verify the four a priori scales by evaluating the goodness of fit of a final confirmatory factor analysis model. The internal consistency of the scales was assessed by calculating Cronbach’s &agr; coefficients. Results The VSQ is a 21-item written questionnaire with four scales: symptoms, emotions, life impact, and sexual impact. One hundred twenty postmenopausal women participated in the psychometric validation of the VSQ. The test-retest reliability measured by intraclass coefficients was 0.75, 0.60, 0.55, and 0.65 for the symptoms, emotions, life impact, and sexual impact scales, respectively. The goodness of fit of the confirmatory factor response model was confirmed. The Cronbach’s &agr; coefficients were 0.76, 0.87, 0.83, and 0.82 for the respective scales. Conclusions The VSQ is a reliable and internally consistent instrument for measuring vulvovaginal symptoms in postmenopausal women.
G-protein signaling modulator 1 deficiency accelerates cystic disease in an orthologous mouse model of autosomal dominant polycystic kidney disease

Polycystic kidney diseases are the most common genetic diseases that affect the kidney. There remains a paucity of information regarding mechanisms by which G proteins are regulated in the context of polycystic kidney disease to promote abnormal epithelial cell expansion and cystogenesis. In this study, we describe a functional role for the accessory protein, G-protein signaling modulator 1 (GPSM1), also known as activator of G-protein signaling 3, to act as a modulator of cyst progression in an orthologous mouse model of autosomal dominant polycystic kidney disease (ADPKD). A complete loss of Gpsm1 in the Pkd1V/V mouse model of ADPKD, which displays a hypomorphic phenotype of polycystin-1, demonstrated increased cyst progression and reduced renal function compared with age-matched cystic Gpsm1+/+ and Gpsm1+/− mice. Electrophysiological studies identified a role by which GPSM1 increased heteromeric polycystin-1/polycystin-2 ion channel activity via Gβγ subunits. In summary, the present study demonstrates an important role for GPSM1 in controlling the dynamics of cyst progression in an orthologous mouse model of ADPKD and presents a therapeutic target for drug development in the treatment of this costly disease.
Effect of unilateral noise exposure on the tonotopic distribution of spontaneous activity in the cochlear nucleus and inferior colliculus in the cortically intact and decorticate rat

Effects of unilateral noise exposure on spontaneous activity (SA) in the anteroventral and dorsal cochlear nuclei (AVCN and DCN) and the central nucleus of the inferior colliculus (ICc) were studied in cortically intact and decorticate rats. SA was measured 1 week following exposure using uptake of 14C‐labeled 2‐deoxyglucose (2DG) in quiet. Optical density (OD) measurements were obtained in low‐ and high‐frequency (LF and HF) areas of each nucleus. We refer to the ipsilateral AVCN and DCN (side of the noise‐exposed ear) and the contralateral ICc as direct nuclei and to their opposite side counterparts as indirect nuclei. Noise exposure altered the tonotopic profile of SA in the direct pathway by causing a decrease in the ratio of HF OD to LF OD (HF/LF ratio). In intact animals, the decreased HF/LF ratio was due to decreased HF OD. In decorticate animals, it was due to decreased HF OD and increased LF OD, the latter occurring mainly in the DCN and ICc. Decorticate‐intact differences may reflect corticofugal feedback inhibition. Lesion of the dorsal acoustic stria caused a substantial decrement of SA in the contralateral ICc. Furthermore, strong positive correlations between HF/LF ratios in the DCN, AVCN, and contralateral ICc suggest that the cochlear nucleus is a major contributor to SA in the ICc. Noise exposure had opposite and weaker effects on 2DG uptake in the indirect pathway that were attributed to crossed inhibition. Noise‐induced changes in the tonotopic profile of SA may represent a neural correlate of tinnitus. J. Comp. Neurol. 490:391–413, 2005. © 2005 Wiley‐Liss, Inc.
Granulocyte colony-stimulating factor in severe chemotherapy-induced afebrile neutropenia.

BACKGROUND Randomized trials of colony-stimulating factors in febrile patients with neutropenia after chemotherapy have not consistently shown clinical benefit. Nevertheless, the use of colony-stimulating factors to treat patients with chemotherapy-induced neutropenia is widespread. METHODS We performed a randomized, double-blind, placebo-controlled trial of granulocyte colony-stimulating factor (G-CSF) in afebrile outpatients with severe chemotherapy-induced neutropenia. We measured the number of days of neutropenia, rate of hospitalization, number of days in the hospital, number of days the patient received parenteral antibiotics, and number of culture-positive infections. RESULTS We randomly assigned 138 patients to receive G-CSF (n=71) or placebo (n=67). The median time to an absolute neutrophil count of at least 500 per cubic millimeter was significantly shorter for patients who received G-CSF (two days, vs. four days for the patients given placebo). However, there was no effect on the rate of hospitalization, number of days in the hospital, duration of treatment with parenteral antibiotics, or number of culture-positive infections. CONCLUSIONS Routine therapeutic application of G-CSF in afebrile patients with severe neutropenia can reduce the duration of neutropenia, but this does not appear to provide practical clinical benefit.
Methods to estimate genetic components of variance for quantitative traits in family studies

The aim of this paper was to compare several methods of estimating the genetic components of a quantitative trait in familial data. The Expectation and Maximization (E‐M) algorithm, the Newton‐Raphson method, and the scoring method were compared for estimating polygenic and environmental effects on nuclear families. We also compared scoring and quasilikelihood (QL) methods when a linked genetic marker was available to estimate effects from a major gene. Generally, all procedures performed similarly in estimating polygenic and environmental variance components. The E‐M algorithm yielded more precise estimators when heritability was low. The scoring method was much faster than the other methods and yielded slightly more precise estimates of mean effects but slightly less precise estimates of the variance components. Estimates of major gene effects were not affected by the number of alleles at the trait locus. For these relatively large sample sizes, QL and scoring had similar precision, but QL took 32 times longer than scoring. Finally, we compared the results of applying these methods to data from the Bogalusa Heart Study. Results showed larger imprecision when the QL method was applied, consistent with earlier studies that showed decreased precision of quasilikelihood compared with maximum likelihood in moderately small sample sizes. Genet. Epidemiol. 17:64–76, 1999. © 1999 Wiley‐Liss, Inc.
The effect of depression treatment on elderly patients' preferences for life-sustaining medical therapy.

OBJECTIVE This study was undertaken 1) to test the hypothesis that remission of depression results in an increase in desire for life-sustaining medical therapy and 2) to characterize patients whose desire for life-sustaining treatment increases substantially following depression therapy. METHOD Elderly patients, suffering from major depression, were interviewed on admission to a psychiatric inpatient unit and at discharge about their desire for specific medical therapies in their current state of health and in two hypothetical scenarios of medical illness. A psychiatrist rated the impact of depressive thinking on the subject's response to these questions. Forty-three subjects completed the study, and 24 were in remission from depression at the time of discharge. RESULTS In the majority of patients, remission of depression did not result in an increase in desire for life-sustaining medical therapy. However, a clinically evident increase in desire for life-sustaining medical therapies followed treatment of depression in subjects (N = 11 [26%]) who had been initially rated as more severely depressed, more hopeless, and more likely to overestimate the risks and to underestimate the benefits of treatment. CONCLUSIONS In major depression of mild to moderate severity, a patient's desire to forgo life-sustaining medical treatment is unlikely to be altered by depression treatment. On the other hand, severely depressed patients, particularly those who are hopeless, overestimate the risks of treatment, or underestimate the benefits of treatment, should be encouraged to defer advance treatment directives. In these patients decisions about life-sustaining therapy should be discouraged until after treatment of the depression.
A polysilicon base bipolar transistor

We have made PNP bipolar transistors consisting of n and p type polysilicon layers on a 0.01 ohm-cm p type substrate. The object of making this device was to study minority carrier transport through the n polysilicon, although we have also succeeded in making transistors with current gains greater than 5. Preliminary results indicate strong recombination in the bulk base polysilicon, with diffusion lengths less than 40nm. The base region nearest or within, the single crystal substate is much more transparent to minority carriers. In addition, the polysilicon seems to block minority carrier injection from the substrate.