HEIDI: an experiment-management platform enabling high-throughput fragment and compound screening.

The Swiss Light Source facilitates fragment-based drug-discovery campaigns for academic and industrial users through the Fast Fragment and Compound Screening (FFCS) software suite. This framework is further enriched by the option to utilize the Smart Digital User (SDU) software for automated data collection across the PXI, PXII and PXIII beamlines. In this work, the newly developed HEIDI webpage (https://heidi.psi.ch) is introduced: a platform crafted using state-of-the-art software architecture and web technologies for sample management of rotational data experiments. The HEIDI webpage features a data-review tab for enhanced result visualization and provides programmatic access through a representational state transfer application programming interface (REST API). The migration of the local FFCS MongoDB instance to the cloud is highlighted and detailed. This transition ensures secure, encrypted and consistently accessible data through a robust and reliable REST API tailored for the FFCS software suite. Collectively, these advancements not only significantly elevate the user experience, but also pave the way for future expansions and improvements in the capabilities of the system.

Transversity Distributions and Tensor Charges of the Nucleon: Extraction from Dihadron Production and Their Universal Nature.

We perform the first global quantum chromodynamics (QCD) analysis of dihadron production for a comprehensive set of data in electron-positron annihilation, semi-inclusive deep-inelastic scattering, and proton-proton collisions, from which we extract simultaneously the transversity distributions of the nucleon and π^{+}π^{-} dihadron fragmentation functions. We incorporate in our fits known theoretical constraints on transversity, namely, its small-x asymptotic behavior and the Soffer bound. We furthermore show that lattice-QCD results for the tensor charges can be successfully included in the analysis. This resolves the previously reported incompatibility between the tensor charges extracted from dihadron production data and lattice QCD. We also find agreement with results for the transversity and tensor charges obtained from measurements on single-hadron production. Overall, our work demonstrates for the first time the universal nature of all available information for the transversity distributions and the tensor charges of the nucleon.

Number Density Interpretation of Dihadron Fragmentation Functions.

We present a new quantum field-theoretic definition of fully unintegrated dihadron fragmentation functions (DiFFs) as well as a generalized version for n-hadron fragmentation functions. We demonstrate that this definition allows certain sum rules to be satisfied, making it consistent with a number density interpretation. Moreover, we show how our corresponding so-called extended DiFFs that enter existing phenomenological studies are number densities and also derive their evolution equations. Within this new framework, DiFFs extracted from experimental measurements will have a clear physical meaning.

Isovector EMC Effect from Global QCD Analysis with MARATHON Data.

We report the results of a Monte Carlo global QCD analysis of unpolarized parton distribution functions (PDFs), including for the first time constraints from ratios of ^{3}He to ^{3}H structure functions recently obtained by the MARATHON experiment at Jefferson Lab. Our simultaneous analysis of nucleon PDFs and nuclear effects in A=2 and A=3 nuclei reveals the first indication for an isovector nuclear EMC effect in light nuclei. We find that while the MARATHON data yield relatively weak constraints on the F_{2}^{n}/F_{2}^{p} neutron to proton structure function ratio and on the d/u PDF ratio, they suggest an enhanced nuclear effect on the d-quark PDF in the bound proton, questioning the assumptions commonly made in nuclear PDF analyses.

A decision support tool for the detection of pancreatic cancer in general practice: A modified Delphi consensus.

BACKGROUND/OBJECTIVES: Diagnosis of pancreatic cancer is often delayed, contributing to patient and family distress and leading to worse survival. We aimed to develop a decision support tool to support primary care providers to identify patients that should undergo investigations for pancreatic cancer, and to recommend initial diagnostic pathways. METHODS: A modified Delphi process, including a series of three surveys, was undertaken to ascertain clinical expert opinion on which combinations of signs, symptoms and risk factors should be included in a tool for the early identification of pancreatic cancer. A group of clinical specialists finalised the development of the tool during a focus group meeting. RESULTS: The tool presents individual or combinations of signs, symptoms, and risk factors in three tiers which direct the urgency of investigation. Tier 1 includes 5 clinical presentation and risk factors clusters that indicate the need for urgent investigation of the pancreas. A further five clusters are included as Tier 2 aiming to elimate other causes and reduce the time to investigating the pancreas. Tier 3 includes a list of non-specific signs, symptoms and risk factors that indicate the need to consider pancreatic cancer as a potential diagnosis, but without specific recommendations for investigation. CONCLUSIONS: Prospective validation studies are now required prior to implementation in the primary care setting. Implementation into primary care practice and as an educational resource may facilitate rapid diagnosis and improve outcomes such as distress and survival.

Continuous coloured light altered human brain haemodynamics and oxygenation assessed by systemic physiology augmented functional near-infrared spectroscopy.

Exposure to artificial coloured light is unavoidable in our modern life, but we are only just beginning to understand the impact of coloured light on human physiology. The aim of the present study was to determine effects of coloured light exposure on human systemic and brain physiology using systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS). We measured changes in haemoglobin concentrations and tissue oxygen saturation in the left and right prefrontal cortices (L-PFC, R-PFC) by fNIRS, and also recorded skin conductance (SC), partial pressure of end-tidal CO2 (PETCO2), and heart-rate variability variables. 17 healthy adults (median age: 29 years, range: 25-65 years, 6 women) were exposed to blue, red, green, or yellow light for 10 minutes. Pre-light and post-light conditions were in darkness. In the L-PFC the yellow evoked a brain activation. SC and PETCO2 did not change during any of the coloured light exposures, but SC increased and PETCO2 decreased for all colours (except green) in the post-light period. Changes in L-PFC haemoglobin concentration were also observed during the post-light period but have to be interpreted with care, because heart rate and SC increased while PETCO2 decreased. The detected effects are potentially of high relevance for choosing room lighting and may possibly be applied therapeutically.

Physiological Effects of Continuous Colored Light Exposure on Mayer Wave Activity in Cerebral Hemodynamics: A Functional Near-Infrared Spectroscopy (fNIRS) Study.

We are increasingly exposed to colored light, but its impact on human physiology is not yet extensively investigated. In the present study we aimed to determine the effects of colored light on human cerebral Mayer wave activity (MWA). We measured oxy- ([O2Hb]), deoxy- ([HHb]), total hemoglobin ([tHb]) concentrations and tissue oxygen saturation (StO2) by functional near-infrared spectroscopy (fNIRS) in the left and right pre-frontal cortex (L-PFC, R-PFC) of 17 subjects (median age: 29 years, 6 women). In a randomized crossover design subjects were exposed to blue, red, green, and yellow LED light for 10 min. Pre-light (8 min, baseline) and post-light (15 min, recovery) conditions were darkness. MWA was calculated from band-pass filtered fNIRS signals (~0.08-0.12 Hz). The medians from the last 3 min of each period (baseline, light exposure, recovery) were statistically analyzed. MWA was increased during red and green light vs. baseline and after blue light exposure in recovery in the L-PFC. MWA differed depending on the chosen frequency range, filter design, and type of signals to analyze (raw intensity, hemoglobin signal from multi-distance method or modified Beer-Lambert law, or within hemoglobin signals).

Simulation of Preterm Neonatal Brain Metabolism During Functional Neuronal Activation Using a Computational Model.

We present a computational model of metabolism in the preterm neonatal brain. The model has the capacity to mimic haemodynamic and metabolic changes during functional activation and simulate functional near-infrared spectroscopy (fNIRS) data. As an initial test of the model's efficacy, we simulate data obtained from published studies investigating functional activity in preterm neonates. In addition we simulated recently collected data from preterm neonates during visual activation. The model is well able to predict the haemodynamic and metabolic changes from these observations. In particular, we found that changes in cerebral blood flow and blood pressure may account for the observed variability of the magnitude and sign of stimulus-evoked haemodynamic changes reported in preterm infants.

Cilengitide--exceptional pseudopolymorphism of a cyclic pentapeptide.

Cilengitide (Cil) represents a cyclic pentapeptide, cyclo-(Arg-Gly-Asp-D-Phe-N-MeVal). Existence of an anhydrate form (A1) and a tetrahydrate form Cil1(H2O)4 has been observed. Surprisingly the anhydrate form proved to be more stable in aqueous environment compared to the tetrahydrate form. Assessment of thermodynamic stability has been carried out by competitive slurry experiments as well as by investigation of thermodynamic solubility. The lower solubility of the anhydrate form A1 can be explained by the hydrogen bonding motifs within the crystal structures. The tetrahydrate form Cil1(H2O)4 represents a special manifestation of a class of non-stoichiometric water-alcohol solvates Cil1(H2O)x(alcohol)y where methanol and ethanol can substitute water molecules in the crystal lattice of the tetrahydrate form leading to the hydrate-solvate systems Cil1(H2O)x(methanol)y named S1 and Cil1(H2O)x(ethanol)y named S2 with x ⩽ 4, y ⩽ 1 and y ⩽ 2-0.5x. The non-stoichiometric water alcohol solvates exhibit a higher solubility compared to the anhydrate form but convert rapidly to the anhydrate form in aqueous environments. Accordingly, the better soluble non-stoichiometric water alcohol solvates cannot be obtained by crystallization from aqueous media. However slurries or crystallization from solvent mixtures containing methanol and ethanol represent a means to obtain the highly soluble pseudo-polymorphs S1 and S2 and to circumvent formation of the low soluble anhydrate form A1.

Orbital tumors: operative and therapeutic strategies.

The term "orbital tumors" includes diverse benign or malignant space-occupying lesions of the orbit, often leading to dystopia of the eyeball, motility disturbances, diplopia, visual field defects, and sometimes a complete loss of vision. Removing these tumors in a limited surgical field is challenging. Therefore, the preservation of function is a primary concern. We retrospectively reviewed 671 patients with orbital tumors from October 1999 to June 2014. Diagnosis on referral, presenting symptoms, radiological records, histology of the primary tumor or orbital metastasis, and treatment choice were analyzed. Among the 671 orbital tumors, 40% were accessed anteriorly, 36% via an orbitotomy with temporary osteotomy, and 23.9% underwent an orbital exenteration. As an illustration of the operative strategies with subsequent reconstructions, a distinction was made among the main indication groups: (1) function-preserving therapy for retrobulbar tumors, (2) malignant tumors of the conjunctiva and the eyelids, (3) exenteration of the orbit and subsequent reconstruction, and (4) operative and therapeutic strategy for orbital metastases. Adequate preoperative use of modern imaging techniques and thorough planning of the operation are crucial. Accurate histopathological diagnosis is crucial for planning appropriate therapeutic and surgical interventions. New innovative treatment concepts and surgical techniques arise from the close cooperation of related disciplines such as ophthalmology and neurosurgery. Although an orbital exenteration in patients with eyelid and conjunctival carcinomas can now often be avoided, eye-preserving treatment for locally advanced carcinomas of the conjunctiva and eyelid must be attempted. For extensive orbital malignancies, orbital exenteration is curative. In this context, primary closure of the orbit can improve the patient's quality of life and avoid subsequent complications. Concerning orbital metastasis, early diagnosis can preserve function and fulfil the esthetic demands of the patients. In palliative tumor disease, operative procedures such as orbital decompression or tumor debulking can reduce patient complaints and contribute to improved quality of life.

[Extensive dermoid cyst occupying almost the entire floor of the mouth in a juvenile patient]. / Ausgedehnte Dermoidzyste nahezu des gesamten Mundbodens bei einer jugendlichen Patientin.

This article presents a case report of a 15-year-old female patient with an substantial swelling of the floor of the mouth and the submandibular region with impairment of deglutition and speech. Descriptions of the diagnostic and operative procedures are given. The histological examination revealed the typical pattern of a dermoid cyst but such dimensions are rare. Complete removal is necessary to prevent fulminant inflammation and disorders of function; furthermore the risk of a malignant transformation is seldom but present.

Dihadron fragmentation functions for large invariant mass.

Using perturbative quantum chromodynamics, we compute dihadron fragmentation functions for a large invariant mass of the dihadron pair. The main focus is on the interference fragmentation function H(1)(∢), which plays an important role in spin physics of the nucleon. Our calculation also reveals that H(1)(∢) and the Collins fragmentation function have closely related underlying dynamics. By considering semi-inclusive deep-inelastic scattering, we further show that collinear factorization in terms of dihadron fragmentation functions and collinear factorization in terms of single-hadron fragmentation functions provide the same result in the region of intermediate invariant mass.

Factors that predict bleeding following endoscopic mucosal resection of large colonic lesions.

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) for large colonic laterally spreading tumors (LSTs) is a safe, efficacious, and cost-effective treatment. The most common serious complication is delayed bleeding, which reduces these advantages, but consensus guidelines for large-polyp EMR do not exist. PATIENTS AND METHODS: Data from two large prospective intention-to-treat studies of EMR for colonic LSTs 20 mm or greater in size were analyzed. Data collection was comprehensive, and included patient and lesion characteristics. EMR technique and cessation of anticoagulant and antiplatelet therapy was standardized. Clinically significant delayed bleeding was defined as that requiring hospital admission. RESULTS: EMR was performed on 302 lesions in 288 patients. There was clinically significant delayed bleeding in 21 cases (7 %). Ten underwent colonoscopy. One required angiography. One required surgery after perforation following hemostatic clip placement. There were no deaths. Risk factors for bleeding on multivariate analysis were right colon location [adjusted odds ratio (OR) 4.4, P = 0.01], use of aspirin (OR 6.3, P = 0.005), and age (OR per decade of age 1.70). All bleeds occurred before aspirin was restarted. Patient characteristics, including ASA grade and co-morbidity type, were not predictive. Despite requiring more complex EMR, larger lesion size ( P = 0.2), multiple excisions rather than en bloc resection ( P = 0.1), polyp morphology ( P = 0.2), and previous attempts ( P = 0.5), were not associated with increased risk. CONCLUSIONS: Proximal lesion location is a highly significant risk for clinically significant delayed bleeding following colonic EMR, and this knowledge could form the basis of a targeted therapeutic trial. Recent aspirin use also increases bleeding risk--specific consensus guidelines in this area are required for colonic EMR.

Partonic pole matrix elements for fragmentation.

A model-independent analysis of collinear three-parton correlation functions for fragmentation is performed. By investigating their support properties it is shown, in particular, that the so-called partonic pole matrix elements vanish. This sheds new light on the understanding of transverse single spin asymmetries in various hard semi-inclusive reactions. Moreover, it gives additional strong evidence for the universality of transverse-momentum-dependent fragmentation functions.

Introduction of a ketogenic diet in young infants.

The ketogenic diet is a rational treatment for pyruvate dehydrogenase complex deficiency (McKusick 312170) and GLUT1 deficiency syndrome (McKusick 138140). An increasing number of patients are diagnosed in early infancy, but few data are available on the introduction of a ketogenic diet in this age group. GLUT1 deficiency syndrome was suspected in four infants presenting with seizures and unexplained hypoglycorrhachia. A ketogenic diet was introduced at 6-28 weeks of age. Ketosis was initiated by fasting, monitored by bedside blood glucose and 3-hydroxybutyrate determinations, and was maintained successfully using supplemented carbohydrate-free infant formula and emulgated triglycerides. All patients developed ketosis within 24 h. 3-Hydroxybutyrate concentrations available at the bedside correlated inversely with the base excess. At glucose levels < or = 40 mg/dl patients remained asymptomatic in the presence of ketones. The ketogenic formula was tolerated well, parental compliance was good, and all patients remained seizure-free on the diet. GLUT1 deficiency was confirmed in two patients; the diet was discontinued in the other two patients. In one infant, failure to thrive on medium-chain triglycerides was effectively reversed using long-chain triglycerides. Urine dipstick analyses failed to detect ketosis in another infant. Adverse effects of the diet were limited to renal stones in one patient. The ketogenic diet can be introduced and maintained successfully in young infants using long-chain fat emulsion. Monitoring 3-hydroxybutyrate at the bedside was useful for metabolic control and superior to urine dipstick analysis. Seizure control was effective and adverse effects were limited, but evaluation of the long-term effects of the ketogenic diet in this age group must await ongoing studies.

Comparison of cytochrome P450 2A6 polymorphism frequencies in Caucasians and African-Americans using a new one-step PCR-RFLP genotyping method.

CYP2A6 (cytochrome P450 2A6), which was first identified as the human coumarin 7-hydroxylase, is the most important enzyme in nicotine C-oxidation. The enzyme also metabolically activates the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in vitro. Polymorphisms in the CYP2A6 gene may thus impact on both smoking behavior and lung cancer susceptibility. Several different genotyping methods have been reported with conflicting results in the frequencies of CYP2A6 polymorphic variants. Thus we decided to perform a sequence analysis of the entire CYP2A6 gene. Sequencing confirmed the published CYP2A6 cDNA sequence. However, intron sequences differed considerably from the reported sequence of the CYP2A6*3 (v2) variant. Our analyses revealed that parts of introns shared homologies with the published sequence of CYP2A13. Based on our sequence data we developed a one step protocol for specific amplification of exon 3 of CYP2A6. The resulting PCR product can be used directly for restriction endonuclease digestion with XcmI and DdeI to determine the frequencies of the reported variant alleles CYP2A6*2 and CYP2A6*3. In a population of 305 African-Americans and 145 Caucasians, we found allele frequencies of 0.003 (2/610) for CYP2A6*2 and 0 (0/610) for CYP2A6*3 in African-Americans and allele frequencies of 0.014 (4/290) and 0 (0/290) in Caucasians. We conclude that both alleles are considerably less frequent in populations than previously reported.

A placebo-controlled comparison of the effects on sexual functioning of bupropion sustained release and fluoxetine.

BACKGROUND: Many antidepressants are associated with sexual dysfunction, a side effect that may lead to patients' dissatisfaction and noncompliance with treatment. OBJECTIVE: This study compared the efficacy, tolerability, and effects on sexual functioning of bupropion sustained release (bupropion SR) and the selective serotonin reuptake inhibitor fluoxetine. METHODS: In this multicenter, randomized, double-blind, double-dummy, parallel-group study, patients with recurrent major depression were treated with bupropion SR 150 to 400 mg/d, fluoxetine 20 to 60 mg/d, or placebo for up to 8 weeks. Depression and sexual-functioning status were assessed by site-specific trained investigators at weekly clinic visits; tolerability was assessed primarily by monitoring adverse events. RESULTS: Four hundred fifty-six patients participated in the study, 150 receiving bupropion SR, 154 fluoxetine, and 152 placebo. The majority of patients in each group completed the study (63% each, bupropion SR [n = 94] and fluoxetine [n = 97]; 67%, placebo [n = 102]). Bupropion SR and fluoxetine were similarly effective in the treatment of depressive symptoms. Beginning at week 2 and continuing throughout the study, significantly more fluoxetine-treated patients experienced orgasm dysfunction than did patients receiving bupropion SR or placebo (P < 0.001); similar results were seen in patients defined as clinical responders (> or =50% decrease from baseline in 21-item Hamilton Rating Scale for Depression [HAM-D] total score) (P < 0.001) and in those experiencing remission of depression (HAM-D total score <8) (P < 0.05). At various time points, worsened sexual functioning, sexual desire disorder, sexual arousal disorder, and dissatisfaction with sexual functioning in those satistied at baseline were more frequently associated with fluoxetine treatment than with bupropion SR or placebo. Both active treatments were well tolerated. CONCLUSIONS: Bupropion SR and fluoxetine were similarly effective and well tolerated in the treatment of depression. Fluoxetine, however, was more frequently associated with sexual dysfunction compared with bupropion SR. Bupropion SR may be an appropriate initial choice for the treatment of depression in patients concerned about sexual functioning.

Two telomerase reverse transcriptases (TERTs) expressed in Candida albicans.

The human pathogenic yeast Candida albicans contains two telomerase reverse transcriptase (TERT) genes. CaTERT1 and CaTERT2 appear either to be two alleles of the same gene or two entirely different genes that encode 867-residue proteins that differ by five amino acids. Both TERTs have a calculated pI of 9.5 and a M(r) of 100.9 kDa and are the smallest TERTs identified to date. Both genes appear to be expressed. Based on sequence similarity between CaTERT1 and the Saccharomyces cerevisiae orthologue Est2p, we suggest a revised alignment for motif E of Est2p. The identification of these TERT genes provides the first opportunity to study telomerase in an important human pathogen.