Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for electronic gap-driven metal-semiconductor transition in phase-change materials

Phase-change materials are functionally important materials that can be thermally interconverted between metallic (crystalline) and semiconducting (amorphous) phases on a very short time scale. Although the interconversion appears to involve a change in local atomic coordination numbers, the electronic basis for this process is still unclear. Here, we demonstrate that in a nearly vacancy-free binary GeSb system where we can drive the phase change both thermally and, as we discover, by pressure, the transformation into the amorphous phase is electronic in origin. Correlations between conductivity, total system energy, and local atomic coordination revealed by experiments and long time ab initio simulations show that the structural reorganization into the amorphous state is driven by opening of an energy gap in the electronic density of states. The electronic driving force behind the phase change has the potential to change the interconversion paradigm in this material class.
The target plasma concentration of propofol required to place laryngeal mask versus cuffed oropharyngeal airway.

UNLABELLED To determine the target plasma concentration of propofol required to place either a laryngeal mask airway (LMA) or a cuffed oropharyngeal airway (COPA), we started a continuous target-controlled infusion of propofol in 60 ASA physical status I or II unpremedicated patients scheduled for minor orthopedic surgery with peripheral nerve block. The target plasma concentration of propofol was initially set at 2 microg/mL. When the effect-site calculated concentration of propofol was equal to the plasma concentration according to the computer simulation, the target plasma concentration was increased by 0.5-microg/mL steps until successful placement of either the LMA (n = 30) or the COPA (n = 30). The mean target plasma concentration of propofol required to place a LMA was 4.3 +/- 0.8 microg/mL compared with 3.2 +/- 0.6 microg/mL to place a COPA (P < 0.001). To successfully place the airways in 95% of patients, the target plasma concentration of propofol had to be increased up to 4 microg/mL for the COPA and 6 microg/mL for the LMA. We conclude that placing a LMA in healthy, unpremedicated patients requires target plasma concentrations of propofol higher than those required for placing a COPA. IMPLICATIONS We evaluated the use of target-controlled infusion of propofol to place extratracheal airways in this prospective, randomized study and demonstrated that the target plasma concentration of propofol required to successfully place a laryngeal mask in >95% of healthy, unpremedicated patients is 6 microg/mL, compared with 4 microg/mL to place a cuffed oropharyngeal airway.
Variation in tibial functionality and fracture susceptibility among healthy, young adults arises from the acquisition of biologically distinct sets of traits

Physiological systems like bone respond to many genetic and environmental factors by adjusting traits in a highly coordinated, compensatory manner to establish organ‐level function. To be mechanically functional, a bone should be sufficiently stiff and strong to support physiological loads. Factors impairing this process are expected to compromise strength and increase fracture risk. We tested the hypotheses that individuals with reduced stiffness relative to body size will show an increased risk of fracturing and that reduced strength arises from the acquisition of biologically distinct sets of traits (ie, different combinations of morphological and tissue‐level mechanical properties). We assessed tibial functionality retrospectively for 336 young adult women and men engaged in military training, and calculated robustness (total area/bone length), cortical area (Ct.Ar), and tissue‐mineral density (TMD). These three traits explained 69% to 72% of the variation in tibial stiffness (p < 0.0001). Having reduced stiffness relative to body size (body weight × bone length) was associated with odds ratios of 1.5 (95% confidence interval [CI], 0.5–4.3) and 7.0 (95% CI, 2.0–25.1) for women and men, respectively, for developing a stress fracture based on radiography and scintigraphy. K‐means cluster analysis was used to segregate men and women into subgroups based on robustness, Ct.Ar, and TMD adjusted for body size. Stiffness varied 37% to 42% among the clusters (p < 0.0001, ANOVA). For men, 78% of stress fracture cases segregated to three clusters (p < 0.03, chi‐square). Clusters showing reduced function exhibited either slender tibias with the expected Ct.Ar and TMD relative to body size and robustness (ie, well‐adapted bones) or robust tibias with reduced residuals for Ct.Ar or TMD relative to body size and robustness (ie, poorly adapted bones). Thus, we show there are multiple biomechanical and thus biological pathways leading to reduced function and increased fracture risk. Our results have important implications for developing personalized preventative diagnostics and treatments.
Pregabalin: an antiepileptic agent useful for neuropathic pain.

PURPOSE The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of pregabalin are reviewed. SUMMARY Pregabalin is the first drug to receive approved labeling from the Food and Drug Administration (FDA) for the treatment of painful diabetic neuropathy and postherpetic neuralgia and is the first antiepileptic agent to receive FDA-approved labeling since 1999. Pregabalin is the pharmacologically active S-enantiomer of racemic 3-isobutyl gamma-aminobutyric acid. Pregabalin has demonstrated efficacy in the management of neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and as adjunctive therapy for adult patients with partial onset seizures. Its exact mechanism of action is unknown. Pregabalin is rapidly absorbed and exhibits linear pharmacokinetics after oral administration. The lack of hepatic metabolism and lack of interaction with cytochrome P-450 isoenzymes explain the absence of drug interactions with pregabalin. Several clinical studies have demonstrated pregabalin's efficacy for each of the FDA-approved indications, with dizziness and somnolence reported as the most common adverse events. Pregabalin has been designated as a Schedule V controlled substance because of its potential for abuse and dependence. The starting dosage for patients with neuropathic pain associated with diabetic peripheral neuropathy is 50 mg three times daily and may be increased to 300 mg daily within one week based on efficacy and tolerability. The starting dosage for patients with partial-onset seizures is 75 mg twice daily or 50 mg three times daily and may be increased to 600 mg daily based on individual response and tolerability. CONCLUSION Pregabalin may be beneficial for the treatment of neuropathic pain or partial-onset seizures in patients who do not respond to conventional treatments or cannot tolerate their adverse effects.
Regional Collaborations as a Tool for Quality Improvements in Surgery: A Systematic Review of the Literature

Background:A systematic review of the literature identifying regional collaborations in surgical practice examining practices related to quality improvement. Methods:The MEDLINE, EMBASE, and Cochrane Library databases, were searched for published reports of regional collaborations in the surgical community relating to initiatives to enhance quality improvement, quality of care, patient safety, knowledge transfer, or communities of practice. Results:Seven collaborative initiatives met the inclusion criteria and were included in the systematic review of the evidence. Motivations for initiating collaborations were often in response to external demands for performance data. Changes in the processes of clinical care and improvements in clinical outcomes were reported on the basis of the collaborative efforts. Significant improvements in clinical outcomes such as decreases in mortality rates, lower duration of postoperative intubations, and fewer surgical-site infections were reported. Quality improvement process measures were also reported to be improved across all of the collaborative initiatives. Success factors included (a) the establishment of trust among health professionals and health institutions; (b) the availability of accurate, complete, relevant data; (c) clinical leadership; (d) institutional commitment; and (e) the infrastructure and methodological support for quality management. Conclusions:A community of practice framework incorporating the success elements described in the systematic review of the literature can be used as a valuable model for collaboration amongst surgeons and healthcare organizations to improve quality of care and foster continuing professional development.
Electromigration: Void Dynamics

The detailed knowledge of the void evolution is helpful to understand and interpret traditional electromigration (EM) lifetime experiments. As void formation and subsequent evolution is highly dynamic, an in situ observation experiment was employed using an SEM allowing for void detection down to a few nanometers in diameter. For void nucleation, it has been suggested that due to the large anisotropy in modulus in Cu, incompatible grain boundaries can act as stress concentrators for both stress-induced and EM-induced voiding. In addition, during growth, the shape change and migration have been associated with the microstructure. To better understand void formation and evolution, we examined the Cu microstructure using EBSD during the experiment without interruption. We tested interconnects consisting of Cu-based damascene (M1) drift type structures, capped with SiCN. Void formation could be confirmed to be associated with features such as incompatible grain boundaries in some instances. In other cases, triple points and grain boundary/sidewall intersections were found as void nucleation sites. Void growth and migration is found strongly correlated with the driving current density. We show conditions under which void migration takes place or is suppressed. In particular, a critical current density of approximately 10 mA/μm2 is observed, below which no void migration occurs. At current densities of 15 mA/μm2 and above, all voids migrated at a net drift velocity proportional to the current density. Independent of migration, all voids are observed to grow at rates consistent with published data for a mixed near bamboo microstructure and interface diffusion.
Combining three antibodies nullifies feedback-mediated resistance to erlotinib in lung cancer

Triple antibody targeting of multiple receptors subverts the resistance induced by single-agent therapies in lung cancer. Triple teaming cancer Patients with lung cancer that is driven by mutant epidermal growth factor receptor (EGFR) are resistant to EGFR-targeted kinase inhibitors, such as erlotinib. Mancini et al. found that resistance may be overcome by inhibiting erlotinib-induced feedback activation of other EGFR family members and the receptor tyrosine kinase MET. In culture and in mice, combining the three antibodies targeting three different EGFR family members inhibited the growth of tumor cells that survived treatment with erlotinib or a single antibody targeting only EGFR. Thus, attacking triple targets subverts the resistance-mediating network rewiring induced by single-agent therapies. Despite initial responses to targeted kinase inhibitors, lung cancer patients presenting with primary epidermal growth factor receptor (EGFR) mutations acquire resistance, often due to a second-site mutation (T790M). However, clinical trials found no survival benefits in patients treated with a monoclonal antibody (mAb) to EGFR that should block activation of the mutated receptor and thus bypass resistance to molecules that target the catalytic or ATP-binding site. Using cell lines with the T790M mutation, we discovered that prolonged exposure to mAbs against only the EGFR triggered network rewiring by (i) stimulating the extracellular signal–regulated kinase (ERK) pathway; (ii) inducing the transcription of HER2 (human epidermal growth factor receptor 2) and HER3, which encode other members of the EGFR family, and the gene encoding HGF, which is the ligand for the receptor tyrosine kinase MET; and (iii) stimulating the interaction between MET and HER3, which promoted MET activity. Supplementing the EGFR-specific mAb with those targeting HER2 and HER3 suppressed these compensatory feedback loops in cultured lung cancer cells. The triple mAb combination targeting all three receptors prevented the activation of ERK, accelerated the degradation of the receptors, inhibited the proliferation of tumor cells but not of normal cells, and markedly reduced the growth of tumors in mice xenografted with cells that were resistant to combined treatment with erlotinib and the single function-blocking EGFR mAb. These findings uncovered feedback loops that enable resistance to treatment paradigms that use a single antibody and indicate a new strategy for the treatment of lung cancer patients.
FL‐926‐16, a novel bioavailable carnosinase‐resistant carnosine derivative, prevents onset and stops progression of diabetic nephropathy in db/db mice

The advanced glycation end products (AGEs) participate in the pathogenesis of diabetic nephropathy (DN) by promoting renal inflammation and injury. L‐carnosine acts as a quencher of the AGE precursors reactive carbonyl species (RCS), but is rapidly inactivated by carnosinase. In this study, we evaluated the effect of FL‐926‐16, a carnosinase‐resistant and bioavailable carnosine derivative, on the onset and progression of DN in db/db mice.
The Melbourne Family Grief Study, II: Psychosocial morbidity and grief in bereaved families.

OBJECTIVE The aim of this study was to describe the intensity of grief, the psychosocial morbidity, and the coping patterns in members of families classified according to a typology of family functioning comprising supportive, conflict-resolving, intermediate, sullen, and hostile classes. METHOD One hundred fifteen families were assessed longitudinally 6 weeks (time 1), 6 months (time 2), and 13 months (time 3) after the death of a parent (constituting 670 individual responses) on measures of grief intensity, psychological state, social adjustment, and family coping. A previously described typology of perceptions of family functioning was applied. Repeated measures multivariate analysis of variance based on both individuals and families and post hoc comparisons of significant results were undertaken. RESULTS Sullen families displayed the most intense grief and the most severe psychosocial morbidity. Well-functioning families (supportive and conflict-resolving) resolved their grief and adjusted more adaptively than their dysfunctional counterparts (intermediate, sullen, and hostile families). There were no cluster-by-time interactions. The clusters accounted for 15.7% of the variance in depression (Beck Depression Inventory) and 27.9% of the variance in social functioning (Social Adjustment Scale). Well-functioning families used more family coping strategies (Family Crisis Oriented Personal Evaluation Scales). CONCLUSIONS More intense grief and greater psychosocial morbidity are found in sullen, hostile, and intermediate bereaved families than in the more adaptive supportive and conflict-resolving types. At-risk families are identifiable and could be treated preventively to reduce morbidity.
The Proximal Convoluted Tubule is a Target for the Uroguanylin-regulated Natriuretic Response

Objectives and Methods: Guanylin and uroguanylin are peptides synthesized in the intestine and kidney that are postulated to have both paracrine and endocrine functions, forming a potential enteric-renal link to coordinate salt ingestion with natriuresis. To explore the in vivo role of guanylin and uroguanylin in the regulation of sodium excretion, we used gene-targeted mice in which the uroguanylin, guanylin or the peptide receptor guanylate cyclase C gene expression had been ablated. Results: Metabolic balance studies demonstrated that there was impaired excretion of a sodium load in uroguanylin (but not in guanylin or guanylate cyclase C) knockout mice. Uroguanylin-dependent natriuresis occurred without an increase in circulating prouroguanylin. A distinct morphological phenotype was present in the proximal convoluted tubules of uroguanylin knockout animals after an enteral salt loading. Marked vacuolization of the proximal convoluted tubule epithelial cells was observed by using light and electron microscopy. There was also a change in the distribution of the sodium hydrogen exchanger 3 (NHE3) after an enteral salt loading. In wild-type animals, there was a partial redistribution of NHE3 from the villus fraction to the less accessible submicrovillus membrane compartment, but this effect was less apparent in uroguanylin knockout animals, presumably resulting in greater Na+/H+ exchange. Conclusions: Together, these findings further establish a role for uroguanylin in fluid homeostasis and support a role for uroguanylin as an integral component of a signaling mechanism that mediates changes in Na+ excretion in response to an enteral salt loading. Proximal tubular NHE3 activity is a possible target for uroguanylin-mediated changes in Na+ excretion.
Early multitherapy including a protease inhibitor for human immunodeficiency virus type 1-infected infants

Background. To assess tolerance and efficacy of early multitherapy including a protease inhibitor for infants perinatally infected with HIV. Methods. Observational study of tolerance and clinical and immunovirologic evolution in HIV-infected infants treated before the age of 1 year in the French Perinatal Study. Results. Thirty-one infants were included. The median age was 3.7 months at initiation of multitherapy. Clinical stage was C (n = 8), B (n = 5) or A/N (n = 18). The median HIV RNA viral load was 5.8 log copies/ml, and the median CD4 cell percentage was 29%. Median follow-up of treatment was 27 months. Of 31 infants 15 experienced mild to moderate adverse events. No infant had clinical or immunologic progression. The median change in viral load was −2.7 log copies/ml after 3 months, −2.0 log after 12 months and −1.7 log after 24 months of treatment. The proportion of infants with a viral load below 500 copies/ml decreased from 53% at 6 months to 18% at 24 months of treatment. The virologic response was not correlated with viral load at baseline. However, the slope of the viral load decrease during the first month of treatment was predictive of the virologic response at 3 and 6 months. Fourteen infants with a viral load of >500 copies/ml after 6 months of treatment displayed viruses with antiretroviral resistance mutations in reverse transcriptase and/or protease genes. Conclusions. Despite the absence of clinical or immunologic progression, the high frequency of virologic failure associated with genotypic resistance reveals the difficulties associated with implementing antiretroviral multitherapy in infants. Suboptimal doses of protease inhibitor could be a factor contributing to treatment failure.
Effects of intravenous lipopolysaccharide infusion on glucose and insulin dynamics in horses with equine metabolic syndrome.

OBJECTIVE To test the hypothesis that glucose and insulin dynamics during endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS). ANIMALS 6 healthy adult mares and 6 horses with EMS. PROCEDURES Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline insulin-modified frequently sampled IV glucose tolerance tests were performed 27 hours before and then repeated at 0.5 and 21 hours after infusion. Results were assessed via minimal model analysis and area under the curve values for plasma glucose and serum insulin concentrations. RESULTS Lipopolysaccharide infusion decreased insulin sensitivity and increased area under the serum insulin concentration curve (treatment × time) in both healthy and EMS-affected horses, compared with findings following saline solution administration. The magnitude of increase in area under the plasma glucose curve following LPS administration was greater for the EMS-affected horses than it was for the healthy horses. Horses with EMS that received LPS or saline solution infusions had decreased insulin sensitivity over time. CONCLUSIONS AND CLINICAL RELEVANCE Glucose and insulin responses to endotoxemia differed between healthy horses and horses with EMS, with greater loss of glycemic control in EMS-affected horses. Horses with EMS also had greater derangements in glucose and insulin homeostasis that were potentially stress induced. It may therefore be helpful to avoid exposure of these horses to stressful situations.
Effects of β-conglycinin on growth performance, immunoglobulins and intestinal mucosal morphology in piglets

One of the main causes of allergic reactions in young animals is β-conglycinin, an antigenic glycoprotein found in soya beans. Therefore, the objective of the study was to investigate the effects of a prior immunisation with β-conglycinin on growth performance, serum immunoglobulin levels and intestinal histology in piglets. Forty piglets (7 d of age) were randomly divided into four groups of ten piglets each. Piglets of Groups Im and Im+S were immunised twice by hypodermic injection with β-conglycinin at 500 μg/kg body weight (BW) at day 7 and 21 of age. At day 23, Groups Im+S and S were intramuscularly injected with 5000 μg β-conglycinin per kg BW. The piglets of Group C received a physiological saline solution by hypodermic injection. All piglets were weaned at the age of 23 d and blood samples were taken on days 7, 21 and 35. At the end of the trial, five piglets per group were slaughtered and the intestine was collected for evaluating mucosal histology. Compared to Group C, in Group S the average daily gain (ADG), feed intake and gain:feed ratio were decreased (p < 0.01), and serum levels of IgG and IgE were increased (p < 0.01). Furthermore, in this group the structure of duodenal and jejunal mucosa was severely damaged. But in Groups Im and Im+S the ADG was increased (p < 0.05), serum IgE levels were decreased (p < 0.01) and the intestinal mucosa was not damaged. The results suggest that prior immunisation with β-conglycinin can increase ADG and serum IgG levels and decrease serum IgE levels. Therefore, this method is also potentially able to protect the structural integrity of the intestinal mucosal epithelia and alleviate allergic reactions in piglets.