Miracle-dz/UniFAR-FTUs huggingface dataset:
Does pre-hospital ventilation effect outcome after significant brain injury?

Traumatic brain injury has a devastating impact on society, utilizing many resources and disproportionately affecting the young. Recent evidence demonstrates the early care of the brain injured patient impacts patient outcomes. While prevention of systolic hypotension and hypoxia are mainstays of prehospital management of the injured patient ventilatory management performed in the prehospital environment has recently been shown to impact outcomes. Hypocapnea from hyperventilation has been shown in several trials to cause deleterious effects from cerebral vasoconstriction and ischemia. The importance of balancing the prevention of both hypocapnea and hypercapnea has led to the idea of a target ventilation range for arterial carbon dioxide tension, the ideal way to achieve this balance in the prehospital setting remains elusive. This article reviews the background, physiologic effects, impact on outcomes, and implications for prehospital care of prehospital ventilation.
Clinical significance of acanthosis nigricans in children and adolescents with obesity induced metabolic complications

Purpose : This study investigated the clinical significance of AN in children and adolescents with obesity induced metabolic complications. Methods : Forty-nine patients who had obesity induced metabolic complications were participated in this cross-sectional study. Obesity induced metabolic complications are as follows: hypertension, dyslipidemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), nonalcoholic steatohepatitis (NASH), homeostasis model assessment of insulin resistance (HOMA-IR)>3.16. Clinical characteristics, such as, age, percentage-weight-for-height (PWH), pubertal status, blood pressure (BP), fasting plasma insulin level, fasting and post-oral glucose tolerance test 2-hour glucose levels, liver function test, lipid profile, HOMA-IR were compared according to the presence of AN. Results : Sixty-five percent of patients had AN, 57.1% NASH, 57.1% dyslipidemia, 55.1% hypertension, 46.9% IFG, 24.5% HOMA-IR>3.16 and 16.2% IGT. The patients who were moderately to severely obese with AN had higher incidence of IGT and HOMA-IR>3.16. The patients with AN had significantly higher diastolic BP (79.4±6.9 vs 75.4±5.6 mmHg), fasting levels of plasma insulin (10.6±6.0 vs 6.2±5.4 μIU/mL), HOMA-IR index (2.6±1.4 vs 1.4±1.3) and PWH (42.4±13.0 vs 34.3±1.8%). The increasing tendency for the presence of AN was significantly related to the cumulative number of obesity induced metabolic complications. Binary logistic regression analysis revealed that the presence of AN was significantly associated with fasting plasma insulin level, PWH and IFG. Conclusion : AN could be useful as a clinical surrogate of obesity induced metabolic complications.
Reproductive risk factors and endometrial cancer: the European Prospective Investigation into Cancer and Nutrition

Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full‐term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7–8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis.
Actin cytoskeleton regulates functional anchorage-migration switch during T-cadherin-induced phenotype modulation of vascular smooth muscle cells

ABSTRACT Vascular smooth muscle cell (SMC) switching between differentiated and dedifferentiated phenotypes is reversible and accompanied by morphological and functional alterations that require reconfiguration of cell-cell and cell-matrix adhesion networks. Studies attempting to explore changes in overall composition of the adhesion nexus during SMC phenotype transition are lacking. We have previously demonstrated that T-cadherin knockdown enforces SMC differentiation, whereas T-cadherin upregulation promotes SMC dedifferentiation. This study used human aortic SMCs ectopically modified with respect to T-cadherin expression to characterize phenotype-associated cell-matrix adhesion molecule expression, focal adhesions configuration and migration modes. Compared with dedifferentiated/migratory SMCs (expressing T-cadherin), the differentiated/contractile SMCs (T-cadherin-deficient) exhibited increased adhesion to several extracellular matrix substrata, decreased expression of several integrins, matrix metalloproteinases and collagens, and also distinct focal adhesion, adherens junction and intracellular tension network configurations. Differentiated and dedifferentiated phenotypes displayed distinct migrational velocity and directional persistence. The restricted migration efficiency of the differentiated phenotype was fully overcome by reducing actin polymerization with ROCK inhibitor Y-27632 whereas myosin II inhibitor blebbistatin was less effective. Migration efficiency of the dedifferentiated phenotype was diminished by promoting actin polymerization with lysophosphatidic acid. These findings held true in both 2D-monolayer and 3D-spheroid migration models. Thus, our data suggest that despite global differences in the cell adhesion nexus of the differentiated and dedifferentiated phenotypes, structural actin cytoskeleton characteristics per se play a crucial role in permissive regulation of cell-matrix adhesive interactions and cell migration behavior during T-cadherin-induced SMC phenotype transition.
Alcohol consumption‐associated breast cancer incidence and potential effect modifiers: the Japan Public Health Center‐based Prospective Study

Epidemiological studies have evaluated whether the impact of alcohol intake on breast cancer risk is modified by use of exogenous estrogens, folate intake, body weight and smoking status, but results have been inconsistent. Further, effect modification by intake of isoflavones and alcohol‐induced facial flushing, which are prevalent in Asian populations, have not been investigated. We investigated the association between alcohol intake and breast cancer risk and whether the association is modified by these factors among 50,757 premenopausal and postmenopausal women (aged 40–69 years) in the population‐based Japan Public Health Center‐based Prospective Study. Alcohol consumption and other related factors were assessed using self‐reported questionnaires. Through to the end of 2006, 572 patients were identified. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated by hazard ratios derived from Cox proportional hazards regression models. Compared with never‐drinkers, regular alcohol drinkers (>150 g of ethanol/week) had a higher risk of the development of breast cancer; the multivariable‐adjusted RRs were 1.75 (95% CI = 1.16–2.65; ptrend = 0.035) for overall, 1.78 (95% CI = 1.09–2.90) for premenopausal and 1.21 (95% CI = 0.53–2.75) for postmenopausal women. There was no statistical evidence for effect modification by menopausal status, use of exogenous estrogens, intakes of isoflavone and folate, body weight, alcohol‐induced facial flushing or smoking (All pinteractions ≥ 0.15). Excessive alcohol intake was associated with an increase in the risk of breast cancer in this population. There was no statistical evidence for effect modification.
P‐glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2) Localize in the Microvessels Forming the Blood‐Tumor Barrier in Ependymomas

Ependymomas are neuroepithelial tumors that arise from the ependymal layer bordering the cerebral ventricles and spinal canal. Intracranial ependymoma represents a major encephalic tumor in children, while spinal ependymoma develops more frequently in adults. To understand the pharmacoresistance that characterizes this tumoral entity, we analyzed the level of expression and localization of three major efflux transport proteins with a multidrug resistance function, P‐glycoprotein, multidrug resistance‐related protein 1 (MRP1) and breast cancer resistance protein (BCRP), in a series of 25 ependymomas from both children and adults. Real‐time‐PCR analysis showed that all three genes were expressed in all tumors, with no apparent correlation between the level of expression and either age or tumor grade. The MRP1 transcript was expressed at a significantly higher level in spinal tumors than in intracranial tumors. The expression of the proteins corresponding to these genes was confirmed by Western blot analysis. In an immunohistochemical study, P‐glycoprotein and BCRP were shown to be associated with the tumoral vessels, where they presented a luminal localization, a prerequisite for their efflux drug activity into the blood. These data indicate that a biochemical, transporter‐dependent blood–tumor barrier may exist in ependymomas, which may reduce the tumoral bioavailability of lipophilic and amphiphilic anticancer drugs.
A Novel Function of MicroRNA Let‐7d in Regulation of Galectin‐3 Expression in Attention Deficit Hyperactivity Disorder Rat Brain

In this study we investigated the locomotor activity and non‐selective attention in spontaneously hypertensive rats (SHR) with control Wistar–Kyoto (WKY) rats, which were employed as an attention deficit hyperactivity disorder (ADHD) model. In open‐field test and làt maze, SHR rats were found to be much more spontaneously active than WKY rats. As compared with WKY rats, a lower level of galectin‐3 was observed in SHR brain prefrontal cortex (PFC), which was the major affected brain area of ADHD. Through miRNA microarray screening, rno‐let‐7d was noted to be solely upregulated in SHR PFC. Interestingly, rno‐let‐7d had a binding site at galectin‐3 mRNA and was shown to regulate galectin‐3 3′ untranslated region (UTR) directly. Mutation of galectin‐3 3′UTR by one nucleotide of the seed sequence prevented rno‐let‐7d regulation of the 3′ UTR completely. Although rno‐let‐7d did not directly regulate tyrosine hydroxylase (TH) 3′UTR, the level of galectin‐3 was important for cAMP response element binding protein, the major transcript factor for TH gene. Either overexpression or downexpression of galectin‐3 could result in modulation of TH expression in both PC12H and PC12L cells. In conclusion, our data suggested a novel function of rno‐let‐7d in regulation of galectin‐3 and in ADHD development. Rno‐let‐7d, which is increased in the PFC of SHR brain, negatively regulated galectin‐3, which is coupled with TH expression regulation.
Epidermal growth factor receptor expression affects the efficacy of the combined application of saponin and a targeted toxin on human cervical carcinoma cells

Cervical cancer is the second most common cancer in women worldwide. Targeting the epidermal growth factor receptor (EGFR) is a very promising approach since it is overexpressed in about 90% of cervical tumors. Here, we quantified the toxic effect of SE, a targeted toxin consisting of epidermal growth factor (EGF) as targeting moiety and the plant toxin saporin‐3, on 3 common human cervical carcinoma cell lines (HeLa, CaSki and SiHa) and recently established lines (PHCC1 and PHCC2) from 2 different individuals. A human melanocytic and a mouse cell line served as negative control. Additionally, we combined SE with saponinum album, a saponin composite from Gypsophila paniculata, which exhibited synergistic properties in previous studies. The cell lines, except for SiHa cells, revealed high sensitivity to SE with 50% cell survival in the range of 5–24.5 nM. The combination with saponin resulted in a remarkable enhancement of cytotoxicity with enhancement factors ranging from 9,000‐fold to 2,500,000‐fold. The cytotoxicity of SE was clearly target receptor specific since free EGF blocks the effect and saporin‐3 alone was considerably less toxic. For all cervical carcinoma cell lines, we evinced a clear correlation between EGFR expression and SE sensitivity. Our data indicate a potential use of targeted toxins for the treatment of cervical cancer. In particular, the combination with saponins is a promising approach since efficacy is drastically improved.
Correlation of Polydispersed Prion Protein and Characteristic Pathology in the Thalamus in Variant Creutzfeldt‐Jakob Disease: Implication of Small Oligomeric Species

The vacuolation, neuronal loss and gliosis that characterize human prion disease pathology are accompanied by the accumulation of an aggregated, insoluble and protease‐resistant form (termed PrPSc) of the host‐encoded normal cellular prion protein (PrPC). In variant Creutzfeldt‐Jakob disease the frontal cortex and cerebellum exhibit intense vacuolation and the accumulation of PrPSc in the form of amyloid plaques and plaque‐like structures. In contrast the posterior thalamus is characterized by intense gliosis and neuronal loss, but PrPSc plaques are rare and vacuolation is patchy. We have used sucrose density gradient centrifugation coupled with conformation dependent immunoassay to examine the biochemical properties of the PrPSc that accumulates in these different brain regions. The results show a greater degree of PrPSc polydisperal in thalamus compared with frontal cortex or cerebellum, including a subpopulation PrPSc molecules in the thalamus that have sedimentation properties resembling those of PrPC. Much effort has focused on identifying aspects of PrPSc biochemistry that distinguish between different forms of human prion disease and contribute to differential diagnosis. Here we show that PrPSc sedimentation properties, which can depend on aggregation state, correlate with, and may underlie the distinct neurodegenerative processes occurring in different regions of the variant Creutzfeldt‐Jakob disease brain.
Reduction of transforming growth factor‐β type II receptor is caused by the enhanced ubiquitin‐dependent degradation in human renal cell carcinoma

Although dysregulation of transforming growth factor‐β (TGF‐β) signaling is implicated in renal carcinogenesis, its precise mechanism is unknown in renal cell carcinoma (RCC). In our study, we investigated Smad‐mediated TGF‐β signaling pathway and its regulatory mechanisms in surgical samples from patients with RCC. We found that immunoreactivity for nuclear phosphorylated Smad2 was significantly decreased in RCC compared to normal renal tissues, thereby TGF‐β signaling was suggested to be attenuated in RCC tissues. In accordance with the result, transcriptional downregulation of Smad4 and post‐transcriptional downregulation of TGF‐β type II receptor (TβR‐II) were frequently found in RCC tissues compared to normal renal tissues. Next, to clarify the reason why the protein level of TβR‐II was decreased in RCC, we investigated the activities of degradation and ubiquitination of TβR‐II. We found that both proteasome‐mediated degradation and ubiquitination of TβR‐II were markedly enhanced in RCC tissues. Moreover, we found that the level of Smad‐ubiquitination regulatory factor 2 (Smurf2), the E3 ligase for TβR‐II, was increased in RCC tissues of the patients with higher clinical stages compared to the normal tissues and was inversely correlated with the level of TβR‐II. Our results suggest that the low TβR‐II protein level is due to augmented ubiquitin‐dependent degradation via Smurf2 and might be involved in the attenuation of TGF‐β signaling pathway in RCC.
ALDH1A1 is a Marker of Astrocytic Differentiation during Brain Development and Correlates with Better Survival in Glioblastoma Patients

Glioblastoma is the most common malignant brain tumor and patients usually succumb to their disease within 2 years. Aldehyde dehydrogenase 1A1 (ALDH1A1) has been suggested as a marker for cancer stem cells that is associated with poor prognosis in human gliomas. However, little is known about the expression and the function of ALDH1A1 in early stages of brain development. We analyzed ALDH1A1 expression in developing and mature central nervous system (CNS) as well as in 93 cases of primary glioblastomas. Surprisingly, ALDH1A1 was absent in the stem cell niches at varying stages of CNS development, but strong ALDH1A1 expression was observed in mature astrocytes coexpressing GFAP and S100. There were 92 out of 93 glioblastomas (99%) that showed ALDH1A1 protein expression in up to 49% of tumor cells. The majority of these cells co‐expressed GFAP, but not established stem cell markers such as Nestin, OLIG2 or SOX2. Finally, strong expression of ALDH1A1 correlated with a significantly better survival of the patients and proved to be an independent prognostic marker in our series (P < 0.01). In contrast to other published data, we therefore provide evidence for ALDH1A1 as a marker of astrocytic differentiation during brain development and of better prognosis in patients suffering from primary glioblastoma.
Proteomic analysis of native cerebellar iFGF14 complexes

ABSTRACT Intracellular Fibroblast Growth Factor 14 (iFGF14) and the other intracellular FGFs (iFGF11-13) regulate the properties and densities of voltage-gated neuronal and cardiac Na+ (Nav) channels. Recent studies have demonstrated that the iFGFs can also regulate native voltage-gated Ca2+ (Cav) channels. In the present study, a mass spectrometry (MS)-based proteomic approach was used to identify the components of native cerebellar iFGF14 complexes. Using an anti-iFGF14 antibody, native iFGF14 complexes were immunoprecipitated from wild type adult mouse cerebellum. Parallel control experiments were performed on cerebellar proteins isolated from mice (Fgf14−/−) harboring a targeted disruption of the Fgf14 locus. MS analyses of immunoprecipitated proteins demonstrated that the vast majority of proteins identified in native cerebellar iFGF14 complexes are Nav channel pore-forming (α) subunits or proteins previously reported to interact with Nav α subunits. In contrast, no Cav channel α or accessory subunits were revealed in cerebellar iFGF14 immunoprecipitates. Additional experiments were completed using an anti-PanNav antibody to immunoprecipitate Nav channel complexes from wild type and Fgf14−/− mouse cerebellum. Western blot and MS analyses revealed that the loss of iFGF14 does not measurably affect the protein composition or the relative abundance of Nav channel interacting proteins in native adult mouse cerebellar Nav channel complexes.
Unilateral renal agenesis in a neonate with congenital diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) is a rare and severe disorder with a high mortality rate among infants. Unilateral renal agenesis (URA) is a relatively common congenital urinary malformation. Here, we present the case of a newborn infant with left CDH associated with ipsilateral renal agenesis. The male patient was born weighing 3.850 g through normal spontaneous vaginal delivery at 38 weeks and 6 days of gestational age at a maternity hospital. He was transferred to our neonatal intensive care unit due to respiratory distress with tachypnea, grunting and cyanosis after birth. A chest radiography indicated parts of the bowel in the thoracic cavity, consistent with CDH. Renal ultrasonography indicated no kidney structure on the left side and a 5.6 cm right kidney with normal echogenicity. Repair of the diaphragmatic hernia was performed three days after birth. Most of the colon, small bowel, stomach and spleen were located in the left pleural cavity, but the left kidney was not seen. Subsequent dimercaptosuccinic acid scintigraphy indicated non-visualized functional cortical uptake in the left kidney on day 13 after birth. Thus, we report the successful treatment of a patient with CDH accompanied by URA.
Postural Compensations and Subjective Complaints Due to Backpack Loads and Wear Time in Schoolchildren

Purpose: This study investigated the effects of carrying weighted backpacks of up to 20% of body weight on the posture and pain complaints of elementary-school children. Methods: Craniovertebral, forward trunk lean and pelvic tilt angles were measured from sagittal photographs of 62 children (8-11 years old) before and after walking while carrying backpacks containing 10%, 15%, or 20% of body weight. Pain severity after a 6-minute walk with the loaded backpack was recorded. Subjective complaints of pain were assessed using a visual analog scale after walking. Results: Repeated-measures ANOVA revealed statistically significant differences in postural angles and increased complaints of pain after walking with increased backpack loads. Conclusion: These results indicate that typical backpack loads create worsening postural changes due to backpack loads and time spent carrying those loads, putting children at increased risk for injury and pain, the latter of which is a strong predictor for back pain in adulthood.
Job Activities and Respiratory Symptoms Among Farmworkers in North Carolina

ABSTRACT Respiratory health is an important component of the ability to perform physically demanding work. The authors assessed respiratory symptom prevalence among Latino farmworkers engaged in crop production, and investigated work activities as risk factors for respiratory symptoms. During June to September 2008, 122 farmworkers completed up to 3 questionnaires. The authors estimated associations between work activities and wheezing symptoms using alternating logistic regression, controlling for age and smoking. At the first data collection, 29 (24%) farmworkers reported ever wheezing and 10 (8%) reported wheezing within the past month. Though not statistically significant, the odds of wheezing were elevated for individuals who reported performing tobacco-related work in the last 3 days. The odds were decreased among individuals who reported harvesting activities (odds ratio: 0.3, 95% confidence interval: 0.1, 1.0). Among Latino farmworkers, respiratory symptoms may be associated with work activities.