Miracle-dz/UniFAR-FTUs huggingface dataset:
Defining the "edge of the envelope": patient selection in treating complex sellar-based neoplasms via transsphenoidal versus open craniotomy.

OBJECT Endonasal approaches have become the gold standard intervention for many anterior and middle skull base tumors. The authors aimed to define some of the existing limitations of these approaches by reviewing their experience with complex sellar region tumors that were initially considered for both transsphenoidal and open skull base approaches and were thus deemed tumors at "the edge of the envelope. " METHODS Between April 2008 and April 2010, 250 transsphenoidal operations were performed at Brigham and Women's Hospital. All cases were retrospectively reviewed to identify patients with complex sellar region tumors that were initially considered for, or soon thereafter required, an open craniotomy as the definitive treatment. The anatomical tumor characteristics that posed limitations to performing safe and effective endonasal skull base operations were reviewed. RESULTS Thirteen cases exemplifying some of the existing limitations to achieving optimal surgical outcomes via transsphenoidal-based approaches are presented. The following 8 factors are separately discussed that repeatedly limited the extent of resection, increased the risk of the operation, and contributed to perioperative complications: significant suprasellar extension, lateral extension, retrosellar extension, brain invasion with edema, firm tumor consistency, involvement or vasospasm of the arteries of the circle of Willis, and encasement of the optic apparatus or invasion of the optic foramina. CONCLUSIONS Although the ability to approach and resect complex tumors using endonasal skull base techniques has evolved dramatically in recent years, several inherent tumor characteristics mandate extensive preoperative consideration. In selected cases these characteristics may lend support to selecting an open craniotomy as the initial operation.
Antibodies to a Synthetic Peptide Corresponding to a Ser‐40‐Containing Segment of Tyrosine Hydroxylase: Activation and Immunohistochemical Localization of Tyrosine Hydroxylase

Abstract: A peptide corresponding to position 32‐47 in tyrosine hydroxylase was synthesized (TH‐16) and polyclonal antibodies against this peptide were raised in rabbits (anti‐TH‐16). The effects of anti‐TH‐16 on modulation of tyrosine hydroxylase activity were investigated. Anti‐TH‐16 enhanced the enzymatic activity in a concentration‐dependent manner, and the antigen TH‐16 inhibited the stimulatory activity of the antiserum in a concentration‐dependent manner. The activated enzyme had a lower Kmapp for the cofactor 2‐amino‐4‐hydroxy‐6‐methyl‐5,6,7,8‐tetrahydropterin and a higher Vmax app than the nonactivated enzyme. Anti‐TH‐16 was characterized further by its ability to immunoprecipitate the enzyme activity by labeling tyrosine hydroxylase after Western blotting and by immunohistochemical labeling of cate‐cholaminergic neurons. Anti‐TH‐16 did not block activation of tyrosine hydroxylase by phosphorylation catalyzed by cyclic AMP‐dependent protein kinase. Exposure of the enzyme to anti‐TH‐16 and subsequent phosphorylation of the enzyme resulted in a greater activation of the enzyme than the sum of activation produced by these two treatments separately. However, the activation was less than additive when the enzyme was first phosphorylated and subsequently exposed to anti‐TH‐16. The present study demonstrates the utility of anti‐TH‐16 in investigating the molecular aspects of the enzyme activation.
Serum adiponectin levels in adults with Prader-Willi syndrome are independent of anthropometrical parameters and do not change with GH treatment.

OBJECTIVE Obesity and growth hormone (GH) deficiency are common in Prader-Willi syndrome (PWS) and these patients are at risk of metabolic diseases in adult life and of reduced life span. Low adiponectin values are associated with obesity and the metabolic syndrome. We therefore found it of interest to measure adiponectin levels in PWS. PATIENTS AND METHODS 17 adults, nine men and eight women, 17 to 32 years of age, with a mean body mass index (BMI) of 35+/-3.2 kg/m2 participated. All had clinical PWS. They were randomized to treatment with placebo or GH (Genotropin) for six months, and subsequently all received GH for 12 months. At baseline, serum total adiponectin levels in the PWS patients were compared with 25 lean and 34 obese controls. Body composition and various metabolic parameters, including adiponectin, were studied every six months in the PWS group. RESULTS Serum adiponectin levels in PWS subjects were significantly lower (P<0.001) compared with lean and significantly higher (P<0.001) compared with obese controls. In PWS patients, no correlation was found between adiponectin and anthropometrical parameters or measures of insulin sensitivity (e.g. fasting insulin and insulin sensitivity as estimated by the homeostasis model assessment), or between adiponectin and IGF binding protein-1 or IGF-I. Adiponectin did not change during GH intervention. CONCLUSION In this study of adults with PWS serum total adiponectin levels were higher than in controls with simple obesity and were independent of anthropometrical parameters. In accordance with this the metabolic syndrome is not necessarily present in all PWS patients. Correction of GH deficiency had no effect on serum adiponectin levels.
One-dimensional steady-state photorefractive screening solitons.

We study one-dimensional steady-state photorefractive screening solitons in a bulk strontium barium niobate crystal. We compare measurements and calculations of the soliton properties and find good agreement for relations between the profile, width and intensity of the soliton, the applied voltage and material parameters. We find the solitons stable against perturbations both in the plane and perpendicular to the plane of the soliton for intensities large compared to the background intensity.
Jitter simulation and measurement of an all-digital clock generator with dynamic frequency counting loop

This paper presents a jitter simulation technique with Verilog hardware description language for an all-digital clock generator with dynamic frequency counting (DFC) loop. The Verilog simulation environment was selected for its high simulation speed, the direct relationship between the simulated and the built circuit. An all-digital clock generator has been fabricated in TSMC 0.35 mum 2P4M CMOS process to measure the jitter performance. The proposed jitter simulation with probabilistic distribution function has been successfully validated based on chip measurements.
A survey of dissociation, boundary-thinness, and psychological wellbeing in spiritualist mental mediumship

The purpose of this study was to explore the personality and psychological wellbeing of Spiritualist mental mediums compared to nonmedium Spiritualists. A total of 159 Spiritualists (mediums = 80, nonmediums = 79) participated in a nationwide cross-sectional survey and completed measures of dissociation, boundary-thinness, psychological wellbeing, fantasy-proneness, and personality. Mediums scored significantly higher than nonmediums on psychological wellbeing, t = 3.80, p <. 001, and reported lower psychological distress, t = 3.25, p = . 001, but no significant differences were found between the groups on dissociation or boundary-thinness. Secondary analyses revealed significant differences for extraversion, t = 2.01, p = . 046, neuroticism, t = 3.59, p = <. 001, and openness to experience, t = 3.21, p = . 002, but not for fantasy-proneness, agreeableness, or conscientiousness. Findings suggest that mediumship is not associated with a reported incidence of dissociative experiences or pathology. Results are discussed in relation to previous research that has proposed the mediumship role may serve a therapeutic function
T1 Slope and Degenerative Cervical Spondylolisthesis

Study Design. Retrospective analysis. Objective. The main objectives of this study were to analyze and compare cervical sagittal parameters, including the T1 slope, in a population of 45 patients with degenerative cervical spondylolisthesis (DCS) and to compare these patients with a control group of asymptomatic population. Summary of Background Data. Sagittal balance in the cervical spine is as important as the pelvic incidence and is related to the concept of T1 slope. Compared with degenerative lumbar spondylolisthesis, there are few studies evaluating DCS, and characteristic changes of the cervical sagittal parameters (including T1 slope) in patients with DCS are not well studied. Methods. We identified 45 patients with DCS (5.8%) from a database of 767 patients, using cervical radiograph in a standing position. All had radiograph and computed tomographic scan at the same time. Cervical sagittal parameters were analyzed on computed tomographic scan in a standardized supine position. The following cervical sagittal parameters were measured: T1 slope, neck tilt, thoracic inlet angle, and cervical lordosis (C2–C7 angle). The DCS group was compared with a control group of 45 asymptomatic age- and sex-matched adults to the DCS group, who were studied in a recently published study. Results. Of our initial group of 767 patients, 45 with anterolisthesis (5.8%) were included for this study. The T1 slope was significantly greater for DCS (26.06° ± 7.3°) compared with the control group (22.32° ± 7.0°). No significant difference of the neck tilt, thoracic inlet angle, and C2–C7 angle was seen between the DSC group and the control group. Therefore, the T1 slope of the DSC group was significantly greater than that of the control group (P < 0.005). Conclusion. The DCS group was characterized by a greater T1 slope than the control group; therefore, we suggest that a high T1 slope may be a predisposing factor in developing DCS. Level of Evidence: 3
Association between cytochrome P450 2D6 genotype and harm avoidance

Genetic polymorphisms within the serotonergic and dopaminergic neurotransmitter systems may be associated with heightened harm avoidance and novelty seeking. It is also conceivable that polymorphisms in enzymes that mediate the metabolism of endogenous amines within the brain may influence these components of temperament. The CYP2D6 enzyme is expressed at low levels in the brain, and has been shown to mediate the formation of the neurotransmitters serotonin and dopamine from trace amines. Some 5–10% of Caucasians are CYP2D6 deficient due to inactivating mutations in the CYP2D6 gene, and are termed poor metabolizers (PMs). In this study, we investigated whether temperament varied significantly between PMs and CYP2D6 extensive metabolizers (EMs) using the Temperament and Character Inventory (TCI). CYP2D6 genotypes were determined for 121 depressed patients. Of these patients, 113 were inferred from genotype as being EMs and eight as PMs. A significant difference in temperament was observed between inferred CYP2D6 EM and PM individuals. CYP2D6 PMs had significantly lower harm avoidance scores (P = 0.003) than EMs. Furthermore, analysis of the harm avoidance sub‐scales revealed that the CYP2D6 PMs scored significantly lower on “fear of uncertainty” (P < 0.001), fatigability (P = 0.009), and shyness (P = 0.038) than EMs, but did not differ significantly from EMs on the worry/pessimism sub‐scale. No significant difference in character scores was detected between inferred CYP2D6 EMs and PMs. Our findings suggest that the CYP2D6 polymorphism may impact on personality, and one potential mechanism for this would be by influencing the generation of endogenous neurotransmitters in the brain. © 2004 Wiley‐Liss, Inc.
Ricin: structure, mode of action, and some current applications

Ricin is an abundant protein component of Ricinus communis seeds (castor beans) that is exquisitely toxic to mammalian cells. It consists of an enzymic polypeptide that catalyzes the N‐glycosidic cleavage of a specific adenine residue from 28S ribosomal RNA, joined by a single disulfide bond to a galactose (cell)‐binding lectin. The enzymatic activity renders ribosomes containing depurinated 28S RNA incapable of protein synthesis. The bipartite molecular structure of ricin allows it to bind to the mammalian cell surface, enter via endocytic uptake, and deliver the catalytically active polypeptide into the cell cytosol where it irreversibly inhibits protein synthesis causing cell death. Because of its cytotoxic potency, modified ricin is being used for the selective killing of unwanted cells and for the toxigenic ablation of cell lineages in transgenic organisms. —Lord, J. M. , Roberts, L. M. , Robertus, J. D. Ricin: structure, mode of action, and some current applications. FASEB J. 8: 201‐208; 1994.
Early Gastric Cancer: Clinical Characteristics and Results of Surgery

Background: Early gastric cancer (EGC) is associated with better prognosis than advanced cancer of the stomach. Unfortunately, EGC accounts for a minority of operated gastric cancers in Europe. The aim of this study was to evaluate the clinical characteristics of EGC and the outcome after surgery. Methods: The study group comprised 94 EGC patients having undergone surgery at Helsinki University Central Hospital between April 1983 and July 2007. Results: The overall 5-year survival rate of EGC patients was 92.4%. Tumor location in the upper part of the stomach and mixed histological type impaired the prognosis (p = 0.043 and 0.008, respectively). The probability of lymph node metastasis was significantly higher when the tumor infiltrated gastric submucosa rather than mucosa (p = 0.012). Existence of lymph node or distant metastases decreased the survival rates (both p < 0.001). Total gastrectomy, pancreatic resection, and extended D2 lymph node dissection increased the complication rate, but did not have effect on survival. Conclusion: The overall prognosis of EGC is favorable. The survival rates of EGC decreased when the tumor was located in the upper part of the stomach or was of mixed histological type, or the patient had lymph node or distant metastasis.
The Grounded Theory Review (2012), Volume 11, Issue 2 Deciphering Unwritten Rules

The aim of this study was to develop a classic grounded theory of patients, relatives and nurses in palliative cancer care. Data from three earlier studies conducted in palliative care were analyzed. “Deciphering unwritten rules” emerged as the pattern of behavior through which patients, relatives and nurses are dealing with the uncertainty of how to act and behave in palliative cancer care. Deciphering means finding out what the rules mean and trying to interpret them and this can be done consciously or unnoticed. Deciphering unwritten rules involves the strategies figuring out, deliberating, maneuvering and evaluating. This theory demonstrates the complexities of palliative care and the importance of knowledge, counseling and resources for all involved.
Lung function and exercise gas exchange in chronic heart failure.

BACKGROUND The ventilatory response to exercise in patients with chronic heart failure (HF) is greater than normal for a given metabolic rate. The objective of the present study was to determine the mechanism(s) for the high ventilatory output in patients with chronic HF. METHODS AND RESULTS Centers in Germany, Italy, Japan, and the United States participated in this study. Each center contributed studies on patients and normal subjects of similar age and sex. One hundred thirty patients with chronic HF and 52 healthy subjects participated. Spirometric and breath-by-breath gas exchange measurements were made during rest and increasing cycle exercise. Arterial blood was sampled for measurement of pH, PaCO2, PaO2, and lactate during exercise in 85 patients. Resting forced expiratory volume in 1 second (FEV1) and vital capacity (VC) were proportionately reduced at all levels of impairment. Patients with more severe HF had greater tachypnea and a smaller tidal volume (VT) at a given exercise expired volume per unit time (VE). This was associated with an expiratory flow pattern characteristic of lung restriction. VE and VCO2 as a function of VO2 were increased during exercise in HF patients. The increases were greater the lower the peak VO2 per kilogram of body weight. The ratio of VD (physiological dead space) to VT and the difference between arterial and end tidal PCO2 at peak VO2 also increased inversely with peak VO2/kg. In contrast, the difference between alveolar and arterial PO2 and PaCO2 were both normal, on average, at peak VO2 regardless of the level of impairment. The more severe the exercise limitation, the higher the lactate and the lower the HCO3- at a given VO2, although pH was tightly regulated. CONCLUSIONS The increase in VE in chronic HF patients is caused by an increase in VD/VT due to high ventilation/perfusion mismatching, an increase in VCO2 relative to VO2 resulting from HCO3- buffering of lactic acid, and a decrease in PaCO2 due to tight regulation of arterial pH. With regard to the excessive VE in HF patients, the increases in VD/VT and VCO2 relative to VO2 are more important as the patient becomes more exercise limited. Regional hypoperfusion but not hypoventilation typifies lung gas exchange in HF. This and other mechanisms might account for the restrictive changes leading to exercise tachypnea in HF patients.
Ein Hybridansatz zur Interaktion mit Retrievalsystemen

Zusammenfassung Gangige Retrievalsysteme nutzen qualitative oder quantitative Ansatze, um das subjektive Ahnlichkeitsempfinden der Nutzer bzw. ihre Praferenzen bezuglich einer Anfrage zu formulieren. Die beiden Ansatze treten dabei meist getrennt auf. Vertreter qualitativer Ansatze sehen quantitative Ansatze, die Ergebnismengen auf Basis numerischer Score-Werte und Gewichtungen erzeugen und damit eine Totalordnung generieren, meist als Spezialisierung ihrer Methoden. Die vorgestellte Arbeit versucht, die Vorzuge beider Methoden zu verbinden, um dem Nutzer eine vereinfachte Interaktion wahrend des Relevance Feedbacks mit dem Retrievalsystem zu bieten, ohne auf die hohere Ausdifferenzierung der Ergebnismenge quantitativer Ansatze verzichten zu mussen. Die Interaktion mit dem System geschieht dabei allein auf Basis der Angabe von intuitiv verstandlichen Praferenzpaaren, die wiederum eine Halbordnung bilden. Hierbei muss angemerkt werden, dass die Angabe einer Praferenz≥ immer auf einzelnen Paaren der Ergebnismenge geschieht und nicht mittels abstrakter Praferenzen, deren konkrete Angabe gerade im Feld des Multimedia Retrievals schwierig erscheint. Diese nutzerdefinierte Halbordnung stellt die Grundlage fur ein maschinelles Lernverfahren auf Basis einer nicht-linearen Optimierung dar, welches aus den speziellen Praferenzen allgemeingultige Gewichtungen fur die Anfrage generiert. Erste Ergebnisse experimenteller Untersuchungen zeigen, dass der vorgestellte Ansatz gut einsetzbar ist und weiterverfolgt werden sollte.
Oligodendrocyte differentiation is increased in transferrin transgenic mice

Transferrin (Tf), the iron transport glycoprotein found in biological fluids of vertebrates, is synthesized mainly by hepatocytes. Tf is also synthesized by oligodendrocytes (Ol), and several lines of evidence indicate that brain Tf could be involved in myelinogenesis. Because Tf is postnatally expressed in the brain, we sought to investigate whether Tf could intervene in Ol differentiation. For this purpose, we analyzed transgenic mice overexpressing the complete human Tf gene in Ol. We show that the hTf transgene was expressed only from 5 days postpartum onward. In the brain of 14‐day‐old transgenic mice, the DM‐20 mRNA level was decreased, whereas the PLP, MBP, CNP, and MAG mRNA levels were increased. We counted a higher proportion of Ol expressing the O4 (Ol‐specific antigens) and PLP in brain cells cultured from transgenic mice. These results support the idea that overexpressing Tf in the brain accelerates the oligodendrocyte lineage maturation. Accordingly, by NMR imaging acquisition of diffusion tensor in hTf transgenic mice, we observed early maturation of the cerebellum and spinal cord and more myelination in the corpus callosum. In addition, hTf overexpression led to an increase in Sox10 mRNA and protein. Increases in Sox10 and in Tf expression occur simultaneously during brain development. The Olig1 mRNA level also increased, but long after the rise of hTf and Sox10. The Olig2 mRNA level remained unchanged in the brain of transgenic mice. Our findings suggest that Tf could influence oligodendrocyte progenitor differentiation in the CNS. © 2006 Wiley‐Liss, Inc.
Learning to use the S.1 knowledge engineering tool

Abstract It is often claimed that it is easy to write expert systems. This claim was examined by monitoring experienced programmers learning to use the S.I knowledge engineering tool. Their achievements and difficulties were examined using a framework that has emerged from previous research into novices learning to use standard programming languages. Even though the experienced programmers all had several years' experience of programming in more than one standard language, there were similarities between their difficulties in learning to use S.I and the difficulties of complete novices learning to program in standard languages. The experienced programmers were however able to overcome their initial difficulties fairly quickly, but it is argued that complete novices would not find it so easy to do so. Also the experienced programmers did take time to develop a repertoire of schemeta for representing different kinds of factual, judgemental and procedural knowledge. It was concluded that in S.1, as with other programming languages and softwares tools, it is easy to learn how to do simple things, but difficult, even for experienced programmers to learn how to do more complex things. No criticism of S.1 is implied. S.1 was found to be a suitable vehicle for introducing non-trivial knowledge engineering concepts, and we believe that similar difficulties would occur in learning to use other knowledge engineering tools.
Potent Strategy To Inhibit HIV-1 by Binding both gp120 and gp41

ABSTRACT The development of an anti-HIV microbicide is critical in the fight against the spread of HIV. It is shown here that the covalent linking of compounds that bind gp120 with compounds that bind gp41 can inhibit HIV entry even more potently than individual inhibitors or noncovalent combinations. The most striking example involves griffithsin, a potent HIV inhibitor that binds to the surface of HIV gp120. While griffithsin inhibits HIV Env-mediated fusion in a CCR5-tropic cell-cell fusion assay with a 50% inhibitory concentration (IC50) of 1.31 ± 0.87 nM and the gp41-binding peptide C37 shows an IC50 of 18.2 ± 7.6 nM, the covalently linked combination of griffithsin with C37 (Griff37) has an IC50 of 0.15 ± 0.05 nM, exhibiting a potency 8.7-fold greater than that of griffithsin alone. Similarly, in CXCR4-tropic cell-cell fusion assays, Griff37 is 5.2-fold more potent than griffithsin alone. In viral assays, both griffithsin and Griff37 inhibit HIV replication at midpicomolar levels, but the linked compound Griff37 is severalfold more potent than griffithsin alone against both CCR5- and CXCR4-tropic virus strains. Another example of this strategy is the covalently linked combination of peptide C37 with a variant of the gp120-binding peptide CD4M33 (L. Martin et al., Nat. Biotechnol. 21:71-76, 2003). Also, nuclear magnetic resonance (NMR) spectra for several of these compounds are shown, including, to our knowledge, the first published NMR spectrum for griffithsin.