Miracle-dz/UniFAR-FTUs huggingface dataset:
Ultrasound-guided femoral dialysis access placement: a single-center randomized trial.

BACKGROUND AND OBJECTIVES Insertion of dialysis catheters (DCs) is a prerequisite for successful initiation of hemodialysis. We attempted to determine if ultrasonography-guided (USG) insertion was superior and safer than the anatomical landmark-guided technique (ALT) for the femoral vein (FV). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a randomized prospective study on 110 patients requiring FV DCs in a tertiary care hospital. Patients were randomized into two groups: USG and ALT. Data were collected on demography, operator experience, and side of insertion. The USG group had their catheters inserted under USG guidance, whereas the ALT group had their DC inserted by ALT. Outcome measures included successful insertion of DC, number of attempts, and complications. RESULTS Both groups were comparable regarding age and gender of patients, operator experience, and the side of catheterization. The overall success rate was 89.1%, with 80% using ALT and 98.2% under USG guidance (P = 0.002). First attempt success rate was 54.5% in the ALT group as compared with 85.5% in the USG group (P = 0.000). The complication rate was 18.2% in the ALT group and 5.5% in the USG group (P = 0.039). The odds ratio (OR) for complications with two or more attempts was 10.73 with a relative risk (RR) of 3.2. The OR for successful insertion using USG was 13.5 (95% CI: 1.7 to 108.7). CONCLUSIONS USG significantly improves success rate, reduces number of attempts, and decreases the incidence of complications related to FV DC insertion.
Reduced retinoids and retinoid receptors' expression in pancreatic cancer: A link to patient survival

Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers in the world. All‐trans retinoic acid (ATRA) is the major physiologically active form of vitamin A, regulating expression of many genes. Disturbances of vitamin A metabolism are prevalent in some cancer cells. The main aim of this work was to investigate deeply the components of retinoid signaling in PDAC compared to in the normal pancreas and to prove the clinical importance of retinoid receptor expression. For the study, human tumor tissues obtained from PDAC patients and murine tumors from the orthotopic Panc02 model were used for the analysis of retinoids, using high performance liquid chromatography mass spectrometry and real‐time RT‐PCR gene expression analysis. Survival probabilities in univariate analysis were estimated using the Kaplan–Meier method and the Cox proportional hazards model was used for the multivariate analysis. In this work, we showed for the first time that the ATRA and all‐trans retinol concentration is reduced in PDAC tissue compared to their normal counterparts. The expression of RARα and β as well as RXRα and β are down‐regulated in PDAC tissue. This reduced expression of retinoid receptors correlates with the expression of some markers of differentiation and epithelial‐to‐mesenchymal transition as well as of cancer stem cell markers. Importantly, the expression of RARα and RXRβ is associated with better overall survival of PDAC patients. Thus, reduction of retinoids and their receptors is an important feature of PDAC and is associated with worse patient survival outcomes. © 2014 Wiley Periodicals, Inc.
Static magnetic field measurements in residences in relation to resonance hypotheses of interactions between power‐frequency magnetic fields and humans

Bowman et al. used epidemiologic data to test a model in which subjects were classified as being “in‐resonance” or “not‐in‐resonance” for 60‐Hz magnetic‐field exposures depending on single static magnetic‐field measurements at the centers of their bedrooms. A second paper by Swanson concluded that a single static magnetic‐field measurement is insufficient to meaningfully characterize a residential environment. The main objective of this study was to investigate exposure‐related questions raised by these two papers in two U.S. data sets, one containing single spot measurements of static magnetic fields at two locations in homes located in eight states, and the other repeated spot measurements (seven times during the course of one year) of the static magnetic fields at the centers of bedrooms and family rooms and on the surfaces of beds in 51 single‐family homes in two metropolitan areas. Using Bowman's criterion, bedrooms were first classified as being in‐resonance or not‐in‐resonance based on the average of repeated measurements of the static magnetic field measured on the bed where the presumed important exposure actually occurred. Bedrooms were then classified a second time using single spot measurements taken at the centers of bedrooms, centers of family rooms, or on the surfaces of beds, as would be done in the typical epidemiologic study. The kappa statistics characterizing the degree of concordance between the first (on‐bed averages) and second (spot measurements) methods of assessing resonance status were 0.44, 0.33, and 0.67, respectively. This level of misclassification could significantly affect the results of studies involving the determination of resonance status. Bioelectromagnetics 22:294–305, 2001. © 2001 Wiley‐Liss, Inc.
Unemployment Effects of the German Minimum Wage in an Equilibrium Job Search Model

We structurally estimate an equilibrium search model using German administrative data and use this for counterfactual analyses of a uniform minimum wage. The model with worker and firm heterogeneity does not restrict the sign of employment effects a priori and allows for different job offer arrival rates for the employed and the unemployed. We find that unemployment is a non-monotonic function of the minimum wage level. Effects differ strongly by labour market segment. Cross-segment variation of the estimated effects is mostly driven by firm productivity levels rather than by search frictions or the opportunity cost of employment.
Utilisation of specialist care in patients with incurable rectal cancer. A population-based study from Western Norway

Introduction. About 25% of patients with rectal cancer have incurable disease at the time of diagnosis. In the current study from Western Norway (population of 981 000) we focused on the utilisation of specialist care in patients with primarily incurable rectal cancer. Patients and methods. Between 1997 and 2002, 1 167 patients were diagnosed with rectal cancer, of whom 297 (25%) had incurable disease, according to consecutive and prospective reporting to the Norwegian Colorectal Cancer Registry. Consumption of specialist care facilities was studied with regard to outpatient contacts, hospital admissions, and various treatment modalities. Data were analysed with regard to age, sex, marital status, type of residence, and geographical access to hospital facilities. Data were available for 287 patients (97%). Results. The median age was 77 years. Elderly patients (>77 years) more often lived in nursing homes without a spouse. About 60% of the patients were treated with major surgery, chemotherapy or radiotherapy, either alone or in combination. Of those who did not receive such treatment, 87% were elderly. Oncological treatment, either alone or combined with surgery, predicted increased hospital admissions and outpatient contacts. Age >77 years predicted fewer hospital admissions. Survival varied statistically significantly with the various treatment modalities, and was highest for major resections combined with oncological treatment. The majority of the patients living at home died in hospitals (54%) and only 26% died in their homes, while two-thirds of residents of nursing homes died there. Discussion. Patients with primary incurable rectal cancer are heterogeneous with regard to their needs of treatment. While younger patients receive extensive tumour-related treatment, elderly patients are most commonly treated according to their symptoms. Prospective studies of the effect of various treatment options on the ease of symptoms and improved quality of life in unselected populations are needed.
Bötzinger neurons project towards bulbospinal neurons in the rostral ventrolateral medulla of the rat

Sympathetic nerve activity often fluctuates with the respiratory cycle, but the central neurons that impose this respiratory modulation have not been conclusively identified. In the present study, we used intracellular recording and dye‐filling to identify expiratory neurons in the Bötzinger complex. Our aim was to see if Bötzinger neurons project towards putative cardiovascular neurons in the rostral ventrolateral medulla. In the first series of experiments, histochemistry and immunohistochemistry were used to reveal the labelled Bötzinger neurons and neurons immunoreactive for tyrosine hydroxylase. Two out of four Bötzinger neurons had axon varicosities that were closely apposed to tyrosine hydroxylase‐immunoreactive neurons with cell bodies located within 0.6 mm caudal to the facial nucleus (three and five close appositions, respectively). In a second series of studies, rats were injected with cholera toxin B into the intermediolateral cell column of the spinal cord 4–7 days before the electrophysiological recording. Eight of the fourteen labelled Bötzinger neurons had a direct projection towards cholera toxin B‐labelled neurons in the rostral ventrolateral medulla. Close appositions were found on both somata and proximal dendrites (5 ± 2 close appositions/neuron, n=8). The present study supports the idea that a direct projection from Bötzinger neurons to presympathetic neurons in the rostral medulla plays a role in the respiratory modulation of sympathetic nerve activity. J. Comp. Neurol. 388:23–31, 1997. © 1997 Wiley‐Liss, Inc.
Role of Brain and Peripheral Angiotensin II in Hypertension and Altered Arterial Baroreflex Programmed during Fetal Life in Rat

Intrauterine programming of hypertension is associated with evidence of increased renin-angiotensin system (RAS) activity. The current study was undertaken to investigate whether arterial baroreflex and blood pressure variability are altered in a model of in utero programming of hypertension secondary to isocaloric protein deprivation and whether activation of the RAS plays a role in this alteration. Pregnant Wistar rats were fed a normal-protein (18%) or low-protein (9%) diet during gestation, which had no effect on litter size, birth weight, or pup survival. Mean arterial blood pressure (MABP; 126 ± 3 mm Hg 9%versus 108 ± 4 mm Hg 18%; p < 0.05) and blood pressure variability were significantly greater in the adult offspring of the 9% protein–fed mothers. Arterial baroreflex control of heart rate, generated by graded i.v. infusion of phenylephrine and nitroprusside, was significantly shifted toward higher pressure; i.v. angiotensin-converting enzyme inhibitor normalized MABP and shifted the arterial baroreflex curve of the 9% offspring toward lower pressure without affecting the 18% offspring. For examining whether brain RAS is also involved in programming of hypertension, angiotensin-converting enzyme inhibitor and losartan (specific AT1 receptor antagonist) were administered intracerebroventricularly; both significantly reduced MABP of the 9% but not the 18% offspring. Autoradiographic receptor binding studies demonstrated an increase in brain AT1 expression in the subfornical organ and the vascular organ of the lamina terminalis in the 9% offspring. These data demonstrate a major tonic role of brain and peripheral RAS on hypertension associated with antenatal nutrient deprivation.
Proteolytic stress: A unifying concept for the etiopathogenesis of Parkinson's disease

The etiopathogenesis of Parkinson's disease (PD) has been elusive. Recently, several lines of evidence have converged to suggest that defects in the ubiquitin‐proteasome system and proteolytic stress underlie nigral pathology in both familial and sporadic forms of the illness. In support of this concept, mutations in α‐synuclein that cause the protein to misfold and resist proteasomal degradation cause familial PD. Similarly, mutations in two enzymes involved in the normal function of the ubiquitin‐proteasome system, parkin and ubiquitin C‐terminal hydrolase L1, are also associated with hereditary PD. Furthermore, structural and function defects in 26/20S proteasomes with accumulation and aggregation of potentially cytotoxic abnormal proteins have been identified in the substantia nigra pars compacta of patients with sporadic PD. Thus, a defect in protein handling appears to be a common factor in sporadic and the various familial forms of PD. This hypothesis may also account for the vulnerability of the substantia nigra pars compacta in PD, why the disorder is age related, and the nature of the Lewy body. It has also facilitated the development of experimental models that recapitulate the behavioral and pathological features of PD, and hopefully will lead to the development of novel neuroprotective therapies for the disorder. Ann Neurol 2003;53 (suppl 3):S73–S86
Growth Arrest-Specific 6 Enhances the Suppressive Function of CD4+CD25+ Regulatory T Cells Mainly through Axl Receptor

Background. Growth arrest-specific (Gas) 6 is one of the endogenous ligands of TAM receptors (Tyro3, Axl, and Mertk), and its role as an immune modulator has been recently emphasized. Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are essential for the active suppression of autoimmunity. The present study was designed to investigate whether Tregs express TAM receptors and the potential role of Gas6-TAM signal in regulating the suppressive function of Tregs. Methods. The protein and mRNA levels of TAM receptors were determined by using Western blot, immunofluorescence, flow cytometry, and RT-PCR. Then, TAM receptors were silenced using targeted siRNA or blocked with specific antibody. The suppressive function of Tregs was assessed by using a CFSE-based T cell proliferation assay. Flow cytometry was used to determine the expression of Foxp3 and CTLA4 whereas cytokines secretion levels were measured by ELISA assay. Results. Tregs express both Axl and Mertk receptors. Gas6 increases the suppressive function of Tregs in vitro and in mice. Both Foxp3 and CTLA-4 expression on Tregs are enhanced after Gas6 stimulation. Gas6 enhances the suppressive activity of Tregs mainly through Axl receptor. Conclusion. Gas6 has a direct effect on the functions of CD4+CD25+Tregs mainly through its interaction with Axl receptor.
Responses of pigeon horizontal semicircular canal afferent fibers. I. Step, trapezoid, and low-frequency sinusoid mechanical and rotational stimulation.

1. The horizontal semicircular canals of anesthetized (barbiturate/ketamine) pigeons were stimulated by rotational and by mechanical stimulation. 2. The mechanical stimulation consisted of making a small (less than 1 mm) fistula in the lateral part of the bony horizontal semicircular canal and, after inserting a probe coupled to a piezoelectric micropusher through the fistula, providing controlled indentation of the exposed membranous horizontal semicircular duct. 3. Extracellular action potentials from single horizontal semicircular canal primary afferent (HCA) fibers were recorded during sinusoidal rotational and during step, ramp, and sinusoidal mechanical stimulation. 4. The mean spontaneous discharge rate of 160 horizontal canal afferents was 86 +/- 4 (SE) spikes/s. This rate was not significantly different from that reported previously for pigeon HCA fibers recorded with the horizontal canal intact (i.e., no fistula introduced). 5. Sinusoidal mechanical indentation of the horizontal semicircular duct produced clearly entrained action potentials on 36 HCA fibers for a range of peak displacements from +/- 0.5 to +/- 30 microns. Action potentials were never modulated on afferents (n greater than 100) identified as innervating the anterior and posterior semicircular canals or the otolith organs during mechanical stimulation of the horizontal semicircular canal, even for displacements as large as 30 microns. 6. Intensity functions relating peak firing frequency (spikes per second) and peak probe displacement (micrometers) for 1.0-Hz sinusoidal mechanical stimulation were linear over the range 1.0-5.0 microns. The most sensitive units (6/36, 17%) showed response saturation as the stimulus magnitude was extended to 7 microns and beyond. 7. In 15 of 36 units, both mechanical and rotational sinusoidal stimulation (1.0 Hz) were applied to the same unit. The duct indentation magnitudes were 1.0, 2.5, 5.0, and 7.0 microns and the rotational velocities were 5, 10, and 20 deg/s. The constant of proportionality found to equate the peak response produced by rotational to that elicited by mechanical stimulation was 7.0 deg.sec-1/1.0 microns. 8. Bode plots and best-fit transfer functions of the frequency response (0.05-10.0 Hz) of 14 HCAs exposed to both mechanical and rotational stimulation were nearly identical. 9. Parameters for best-fit transfer functions, responses to step, and trapezoidal duct displacements were in excellent agreement with previous rotational studies carried out using the pigeon. 10. Although the mechanisms by which focal identation of the horizontal membranous duct produce responses have not yet been determined, primary afferent responses using this method of stimulation are directly comparable with rotatory stimulation. (ABSTRACT TRUNCATED AT 400 WORDS)
Ventilatory strategies and supportive care in acute respiratory distress syndrome

While antiviral therapy is an important component of care in patients with the acute respiratory distress syndrome (ARDS) following influenza infection, it is not sufficient to ensure good outcomes, and additional measures are usually necessary. Patients usually receive high levels of supplemental oxygen to counteract the hypoxemia resulting from severe gas exchange abnormalities. Many patients also receive invasive mechanical ventilation for support for oxygenation, while in resource‐poor settings, supplemental oxygen via face mask may be the only available intervention. Patients with ARDS receiving mechanical ventilation should receive lung‐protective ventilation, whereby tidal volume is decreased to 6 ml/kg of their predicted weight and distending pressures are maintained ≤30 cm H2O, as well as increased inspired oxygen concentrations and positive end‐expiratory pressure (PEEP) to prevent atelectasis and support oxygenation. While these measures are sufficient in most patients, a minority develop refractory hypoxemia and may receive additional therapies, including prone positioning, inhaled vasodilators, extracorporeal membrane oxygenation, recruitment maneuvers followed by high PEEP, and neuromuscular blockade, although recent data suggest that this last option may be warranted earlier in the clinical course before development of refractory hypoxemia. Application of these “rescue strategies” is complicated by the lack of guidance in the literature regarding implementation. While much attention is devoted to these strategies, clinicians must not lose sight of simple interventions that affect patient outcomes including head of bed elevation, prophylaxis against venous thromboembolism and gastrointestinal bleeding, judicious use of fluids in the post‐resuscitative phase, and a protocol‐based approach to sedation and spontaneous breathing trials.
Clumping Factor B Promotes Adherence of Staphylococcus aureus to Corneocytes in Atopic Dermatitis

ABSTRACT Staphylococcus aureus skin infection is a frequent and recurrent problem in children with the common inflammatory skin disease atopic dermatitis (AD). S. aureus colonizes the skin of the majority of children with AD and exacerbates the disease. The first step during colonization and infection is bacterial adhesion to the cornified envelope of corneocytes in the outer layer, the stratum corneum. Corneocytes from AD skin are structurally different from corneocytes from normal healthy skin. The objective of this study was to identify bacterial proteins that promote the adherence of S. aureus to AD corneocytes. S. aureus strains from clonal complexes 1 and 8 were more frequently isolated from infected AD skin than from the nasal cavity of healthy children. AD strains had increased ClfB ligand binding activity compared to normal nasal carriage strains. Adherence of single S. aureus bacteria to corneocytes from AD patients ex vivo was studied using atomic force microscopy. Bacteria expressing ClfB recognized ligands distributed over the entire corneocyte surface. The ability of an isogenic ClfB-deficient mutant to adhere to AD corneocytes compared to that of its parent clonal complex 1 clinical strain was greatly reduced. ClfB from clonal complex 1 strains had a slightly higher binding affinity for its ligand than ClfB from strains from other clonal complexes. Our results provide new insights into the first step in the establishment of S. aureus colonization in AD patients. ClfB is a key adhesion molecule for the interaction of S. aureus with AD corneocytes and represents a target for intervention.
GPNMB enhances bone regeneration by promoting angiogenesis and osteogenesis: Potential role for tissue engineering bone

Bone regeneration is a coordinated process involving the connection between blood vessels and bone cells. Glycoprotein non‐metastatic melanoma protein B (GPNMB) is known to be vital in bone formation. However, the effect of GPNMB on bone regeneration and the underlying molecular mechanism are still undefined. Fibroblast growth factor receptor (FGFR)‐mediating signaling is pivotal in bone formation and angiogenesis. Therefore, we assessed GPNMB function as a communicating molecule between osteoblasts and angiogenesis, and the possible correlation with FGFR‐1 signaling. Recombinant GPNMB dose‐dependently increased the differentiation of human bone marrow stromal cells (hBMSCs) into osteoblasts, as well as the mRNA levels of osteoblasts marker alkaline phosphatase (ALP) and osteocalcin (OCN). Furthermore, these increases depended on the activation of FGFR‐1 signaling, as pretreatment with FGFR‐1 siRNA or its inhibitor SU5402 dramatically dampened GPNMB‐induced osteogenesis. Additionally, GPNMB triggered dose‐dependently the proliferation and migration of human umbilical vein endothelial cells (hUVECs), FGFR‐1 phosphorylation, as well as capillary tube and vessels formation in vitro and in vivo. Blocking FGFR‐1 signaling dampened GPNMB‐induced angiogenic activity. Following construction of a rodent cranial defect model, scaffolds delivering GPNMB resulted in an evident increase in blood vessels and new bone formation; however, combined delivery of GPNMB and SU5402 abated these increase in defect sites. Taken together, these results suggest that GPNMB stimulates bone regeneration by inducing osteogenesis and angiogenesis via regulating FGFR‐1 signaling. Consequently, our findings will clarify a new explanation about how GPNMB induces bone repair, and provide a potential target for bone regeneration therapeutics and bone engineering. J. Cell. Biochem. 114: 2729–2737, 2013. © 2013 Wiley Periodicals, Inc.