bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of medicines used to treat gastrointestinal diseases on the pharmacokinetics of coadministered drugs: a PEARRL Review
Authors: Litou Chara , Effinger Angela , Kostewicz Edmund S , Box Karl J , Fotaki Nikoletta , Dressman Jennifer B 
Published: July 2018

Abstract

Objectives
Drugs used to treat gastrointestinal diseases (GI drugs) are widely used either as prescription or over-the-counter (OTC) medications and belong to both the 10 most prescribed and 10 most sold OTC medications worldwide. The objective of this review article is to discuss the most frequent interactions between GI and other drugs, including identification of the mechanisms behind these interactions, where possible.

Key findings
Current clinical practice shows that in many cases, these drugs are administered concomitantly with other drug products. Due to their metabolic properties and mechanisms of action, the drugs used to treat gastrointestinal diseases can change the pharmacokinetics of some coadministered drugs. In certain cases, these interactions can lead to failure of treatment or to the occurrence of serious adverse events. The mechanism of interaction depends highly on drug properties and differs among therapeutic categories. Understanding these interactions is essential to providing recommendations for optimal drug therapy.

Summary
Interactions with GI drugs are numerous and can be highly significant clinically in some cases. While alterations in bioavailability due to changes in solubility, dissolution rate, GI transit and metabolic interactions can be (for the most part) easily identified, interactions that are mediated through other mechanisms, such as permeability or microbiota, are less well-understood. Future work should focus on characterising these aspects.
In-line derivative spectroscopy as a promising application to a small-scale in vitro transfer model in biorelevant supersaturation and precipitation testing
Authors: Jede Christian , Wagner Christian , Kubas Holger , Weber Christian , Weitschies Werner 
Published: July 2018

Abstract

Objectives
Dissolution testing of poorly soluble and precipitating drugs is of great importance for pharmaceutical industry. As offline HPLC analytics is time-consuming and labour-intensive, the development of suitable in-line analytics to measure drug concentration allows better predictions of drug dissolution and precipitation. The purpose of this study was to develop an in-line derivative spectroscopic method which facilitates drug concentration measurements in suspensions without additional sample preparation.

Methods
Solubility, dissolution and precipitation of ketoconazole were analysed using derivative spectroscopy and HPLC.

Key findings
Results of solubility and dissolution experiments were highly comparable. Due to higher sampling frequency and lack of sample preparations, supersaturation in a pH-shift experiment was more accurately captured by UV in-line analytics. The application of a prefiltration step and flow-through cuvettes facilitates implementation of in-line derivative spectroscopy into an in vitro transfer model with changing UV-active media and high supersaturation in highly turbid samples.

Conclusions
Although the application of derivative spectroscopy has been described previously, the approach described herein is novel and well-suited for the application in an automated in vitro transfer model. Moreover, it represents a promising tool for drug substance characterisation, candidate selection and formulation development.
Employment and fiscal policy in a Marxian model
Authors: Thompson Stephen 
Published: July 2018

AbstractThis article presents a simple formalization of Marx's circuit of capital framework, but with some modern additions: a public sector, an investment function that shifts over time in reaction to disequilibria, and a ‘wage curve’ linking income distribution to the size of the reserve army of labor. The dynamics can gravitate toward either a low‐employment trajectory in which public spending has expansionary long‐run effects, or a high‐employment trajectory characterized by a profit squeeze. The stability of the different trajectories depends on the investment function.
Demonstration of differences in colonic volumes, transit, chyme consistency, and response to psyllium between healthy and constipated subjects using magnetic resonance imaging
Authors: Major G. , Murray K. , Singh G. , Nowak A. , Hoad C. L. , Marciani L. , Silos‐Santiago A. , Kurtz C. B. , Johnston J. M. , Gowland P. , Spiller R. 
Published: July 2018

AbstractBackgroundIn functional gastrointestinal disorders a lack of objective biomarkers limits evaluation of underlying mechanisms. We aimed to demonstrate the utility of magnetic resonance imaging for this task using psyllium, an effective constipation treatment, in patients and controls.MethodsTwo crossover studies: (i) adults without constipation (controls, n = 9) took three treatments in randomized order for 6 days – maltodextrin (placebo), psyllium 3.5 g t.d.s and 7 g t.d.s., (ii) adults with chronic constipation (patients, n = 20) took placebo and psyllium 7 g t.d.s. for 6 days. MRI was performed fasting and postprandially on day 6. Measurements included small bowel and ascending colon water content, colonic volume, transit time, and MR relaxometry (T1, T2) to assess colonic chyme. Stool water percentage was measured.Results7 g psyllium t.d.s. increased fasting colonic volumes in controls from median 372 mL (IQR 284‐601) to 578 mL (IQR 510‐882), and in patients from median 831 mL (IQR 745‐934) to 1104 mL (847‐1316), P < .05. Mean postprandial small bowel water was higher in controls and patients after 7 g psyllium t.d.s. vs placebo. Whole gut transit was slower in patients than controls (P < .05). T1 of the descending colon chyme (fasting) was lower in patients (213 ms, 176‐420) than controls (440 ms, 352‐884, P < .05) on placebo, but increased by 7 g psyllium t.d.s. (590 ms, 446‐1338), P < .001. Descending colon T1 correlated with baseline stool water content and stool frequency on treatment.Conclusions and InferencesMRI measurements can objectively demonstrate the mode of action of therapy targeting intestinal fluid content in constipation.
Effect of attention bias modification on event‐related potentials in patients with irritable bowel syndrome: A preliminary brain function and psycho‐behavioral study
Authors: Tayama J. , Saigo T. , Ogawa S. , Takeoka A. , Hamaguchi T. , Inoue K. , Okamura H. , Yajima J. , Matsudaira K. , Fukudo S. , Shirabe S. 
Published: July 2018

AbstractBackgroundAttention bias modification normalizes electroencephalographic abnormalities in alpha and beta power percentages related to attention in patients with irritable bowel syndrome (IBS). Yet, it is unknown whether ABM contributes to the normalization of event‐related potentials (ERP) in these patients. We hypothesized that ERP related to attention deficit would be normalized after ABM implementation in individuals with IBS.MethodsThirteen patients with IBS and 10 control subjects completed a 2‐month intervention that included five ABM sessions. Each session included 128 trials, resulting in a total of 640 trials during the study period. Event‐related potentials were measured at the first and fifth sessions. As per the international 10‐20 system for electroencephalographic electrode placement, right parietal P4 was evaluated to measure the attention component of facial expression processing.Key ResultsA group comparison of P100 latency at P4 revealed that latencies were significantly different between groups in session 1 (IBS vs control, 108 ± 8 vs 97 ± 14; t = −2.51, P = .0203). This difference was absent in session 5 (94 ± 11 vs 93 ± 11, respectively; t = −0.397, P = .6954, r = .09), indicating an effect of ABM in the IBS group.Conclusions and inferencesAttention bias modification may have clinical utility for normalizing brain function and specifically attentional abnormalities in patients with IBS.
Regional gastrointestinal pH profile is altered in patients with type 1 diabetes and peripheral neuropathy
Authors: Wegeberg A.‐M. L. , Brock C. , Brock B. , Farmer A. D. , Hobson A. R. , Semler J. R. , Scott S. M. 
Published: July 2018

AbstractBackgroundGastrointestinal (GI) symptoms, such as nausea and bloating, are common in people with type 1 diabetes (T1DM). Autonomic dysfunction can lead to changes in the GI secreto‐motor function which can be associated with GI symptom development. We hypothesized that regional pH profiles in T1DM differs from health and would be associated with objective physiological/clinical markers.MethodsForty‐seven T1DM with confirmed diabetic sensory peripheral neuropathy and 41 healthy age‐matched subjects underwent standardized wireless motility capsule testing. T1DM completed the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale. Disease duration, glycemic control, insulin usage, and 24‐hour heart rate variability testing were evaluated.Key ResultsIn comparison to healthy subjects, gastric, and large bowel median pH were lower in T1DM (1.8 ± 1.6 vs 2.9 ± 1.5, P = 0.001 and 6.7 ± 0.6 vs 7.0 ± 0.5, P = 0.003, respectively). Additionally, change in pH across the pylorus was lower while change in pH across the ileocecal junction was higher in T1DM (5.2 ± 1.5 vs 5.8 ± 0.5, P = 0.003 and 1.8 ± 0.4 vs 1.3 ± 0.4, P < 0.0001, respectively). No difference was found in small bowel median pH. Gastric median pH was associated with small bowel transit time (r = 0.30, P = 0.049). Change in pH across the pylorus was negatively associated with fasting glycose (r = −0.35, P = 0.027). Small bowel median pH was associated with nausea (r = 0.42, P = 0.005) and small bowel transit time (r = 0.48, P = 0.0007). Large bowel median pH was associated with nausea (r = 0.35, P = 0.018) and the total GCSI score (r = 0.34, P = 0.023).Conclusions and InferencesThe GI pH profile in T1DM with DSPN is different from healthy subjects. Changes in pH profile may have important therapeutic implications and influence pharmacotherapeutic bioavailability.
Three Arguments to Think that Faith Does Not Entail Belief
Authors: Howard‐Snyder Daniel 
Published: July 2018

AbstractOn doxastic theories of propositional faith, necessarily, S has faith that p only if S believes that p. On nondoxastic theories of propositional faith, it's false that, necessarily, S has faith that p only if S believes that p. In this article, I defend three arguments for nondoxastic theories of faith and I respond to published criticisms of them.
Fundamental differences in starch synthesis in the maize leaf, embryo, ovary and endosperm
Authors: Boehlein Susan K. , Shaw Janine R. , Boehlein Timothy J. , Boehlein Emily C. , Hannah L. Curtis 
Published: July 2018

SummaryEnzymological and starch analyses of various ADP‐glucose pyrophosphorylase (AGPase) null mutants point to fundamental differences in the pathways for starch synthesis in the maize leaf, embryo, ovary and endosperm. Leaf starch is synthesized via the AGPase encoded by the small and large subunits shown previously to be expressed at abundant levels in the leaf, whereas more than one AGPase isoform functions in the embryo and in the ovary. Embryo starch content is also dependent on genes functioning in the leaf and in the endosperm. AGPase encoded by shrunken‐2 and brittle‐2 synthesizes ~75% of endosperm starch. The gene, agpsemzm, previously shown to encode the small subunit expressed in the embryo, and agpllzm, the leaf large subunit gene, are here shown to encode the endosperm, plastid‐localized AGPase. Loss of this enzyme does not reduce endosperm starch. Rather, the data suggest that AGPase‐independent starch synthesis accounts for ~25% of endosperm starch. Three maize genes encode the small subunit of the AGPase. Data here show that the triple mutant lacking all three small subunits is lethal in early seed development but can be viable in both male and female gametes. Seed and plant viability is restored by any one of the three small subunit genes, including one previously thought to function only in the cytosol of the endosperm. Data herein also show the functionality of a fourth gene encoding the large subunit of this enzyme. Although adenosine diphosphate glucose pyrophosphorylase is shown here to be essential for maize viability, strong evidence for starch synthesis in the endosperm that is independent of this enzyme is also presented. Starch synthesis is distinct in the maize embryo, ovary, leaf and endosperm, and is coordinated among the various tissues.
Protocol for the first clinical trial to investigate safety and efficacy of corneal xenotransplantation in patients with corneal opacity, corneal perforation, or impending corneal perforation
Authors: Choi Hyuk Jin , Yoon Chang Ho , Hyon Joon Young , Lee Hyung Keun , Song Jong‐Suk , Chung Tae‐Young , Mo Hyojung , Kim Jaeyoung , Kim Jae‐eun , Hahm Bong‐Jin , Yang Jaeseok , Park Wan Beom , Kim Mee Kum 
Published: July 2018

AbstractBackgroundXenotransplantation using fresh porcine corneas has been suggested as a feasible alternative to overcome the shortage of human donor corneas. Successful long‐term survival of grafts without evidence of xenozoonosis in clinically applicable pig‐to‐non‐human primate corneal transplantation model has brought researchers close to human clinical trials. Accordingly, we aimed to prepare a clinical trial protocol to conduct the first corneal xenotransplantation.MethodsWe developed the clinical trial protocol based on international consensus statement on conditions for undertaking clinical trials of corneal xenotransplantation developed by the International Xenotransplantation Society. Detailed contents of the protocol have been modified with reference to comments provided by ophthalmologists and multidisciplinary experts, including an infectionist, an organ transplantation specialist, a clinical pharmacologist, a neuropsychiatrist, a laboratory medicine doctor, and a microbiologist.ResultsTwo patients with bilateral legal corneal blindness (best‐corrected visual acuity ≤20/200 in the better eye and ≤20/1000 in the candidate eye) or with (impending) corneal perforation will be enrolled. During the screening period, participants and their family members will have two separate deep consideration periods before signing informed consent forms. Each patient will undergo corneal xenotransplantation using fresh corneas from Seoul National University miniature pigs. Commercially available immunosuppressants will be administered and systemic infection prophylaxis will be performed according to the program schedule. After transplantation, each patient will be monitored at a specialized clinic to investigate safety up to 2 years and efficacy up to 1 year.ConclusionsA detailed clinical trial protocol for the first corneal xenotransplantation reflecting the global guidelines is provided.
Multiple Evolutionarily Conserved Domains of Cap2 Are Required for Promoter Recruitment and Iron Homeostasis Gene Regulation
Authors: Srivastav Manjit Kumar , Agarwal Neha , Natarajan Krishnamurthy 
Published: July 2018

Iron is an essential micronutrient for living cells.
Candida albicans
, the predominant human fungal pathogen, thrives under diverse environments with vastly different iron levels in the mammalian host. Therefore, to tightly control iron homeostasis,
C. albicans
has evolved a set of transcriptional regulators that cooperate to either upregulate or downregulate transcription of iron uptake genes or iron utilization genes. Cap2/Hap43, a critical transcriptional regulator, contains multiple conserved protein domains. In this study, we carried out mutational analyses to identify the functional roles of the conserved protein domains in Cap2. Our results show that the bZIP, HAP4L, and the C-terminal domain are each required for Cap2 transcriptional activity. Thus, Cap2 employs multiple, disparate protein domains for regulation of iron homeostasis in
C. albicans
.
Partially-static data as free extension of algebras
Authors: Yallop Jeremy , von Glehn Tamara , Kammar Ohad 
Published: July 2018

Partially-static data structures are a well-known technique for improving binding times. However, they are often defined in an ad-hoc manner, without a unifying framework to ensure full use of the equations associated with each operation.
We present a foundational view of partially-static data structures as free extensions of algebras for suitable equational theories, i.e. the coproduct of an algebra and a free algebra in the category of algebras and their homomorphisms. By precalculating these free extensions, we construct a high-level library of partially-static data representations for common algebraic structures. We demonstrate our library with common use-cases from the literature: string and list manipulation, linear algebra, and numerical simplification.
Copper Chelation as Targeted Therapy in a Mouse Model of Oncogenic BRAF-Driven Papillary Thyroid Cancer
Authors: Xu MengMeng , Casio Michael , Range Danielle E. , Sosa Julie A. , Counter Christopher M. 
Published: July 2018

Abstract
Purpose: Sixty percent of papillary thyroid cancers (PTC) have an oncogenic (V600E) BRAF mutation. Inhibitors of BRAF and its substrates MEK1/2 are showing clinical promise in BRAFV600E PTC. PTC progression can be decades long, which is challenging in terms of toxicity and cost. We previously found that MEK1/2 require copper (Cu) for kinase activity and can be inhibited with the well-tolerated and economical Cu chelator tetrathiomolybdate (TM). We therefore tested TM for antineoplastic activity in BRAFV600E-positive PTC.
Experimental Design: The efficacy of TM alone and in combination with current standard-of-care lenvatinib and sorafenib or BRAF and MEK1/2 inhibitors vemurafenib and trametinib was examined in BRAFV600E-positive human PTC cell lines and a genetically engineered mouse PTC model.
Results: TM inhibited MEK1/2 kinase activity and transformed growth of PTC cells. TM was as or more potent than lenvatinib and sorafenib and enhanced the antineoplastic activity of sorafenib and vemurafenib. Activated ERK2, a substrate of MEK1/2, overcame this effect, consistent with TM deriving its antineoplastic activity by inhibiting MEK1/2. Oral TM reduced tumor burden and vemurafenib in a BrafV600E-positive mouse model of PTC. This effect was ascribed to a reduction of Cu in the tumors. TM reduced P-Erk1/2 in mouse PTC tumors, whereas genetic reduction of Cu in developing tumors trended towards a survival advantage. Finally, TM as a maintenance therapy after cessation of vemurafenib reduced tumor volume in the aforementioned PTC mouse model.
Conclusions: TM inhibits BRAFV600E-driven PTC through inhibition of MEK1/2, supporting clinical evaluation of chronic TM therapy for this disease. Clin Cancer Res; 24(17); 4271–81. ©2018 AACR.
Protagoras’ Homo-Mensura Doctrine and Literary Interpretation in Certamen Homeri et Hesiodi
Authors: Osorio Peter 
Published: July 2018

Abstract
Taking a cue from the interpretive difficulties faced by Socrates and his interlocutors in Plato’s Theaetetus as they struggle to determine the meaning of Protagoras’ homo-mensura doctrine (HM), I argue that Protagoras, or early Protagoreans, used HM to speak on the relativity of literary criticism. For evidence I adduce an overlooked passage of the anonymous Certamen Homeri et Hesiodi, which contains an ethical formulation of HM. This formulation of HM, compatible with the portrait of Protagoras from Theaetetus, explains the concern for literary interpretation latent in two sections of the Certamen. From the evidence in the Certamen, we may infer that HM was directly related to Protagorean education in civic virtue, part of which included a study of how to read and listen to texts.
Adolescent-led strategies within the home to promote healthy eating and physical activity
Authors: Foley Bridget C , Mihrshahi Seema , Shrewsbury Vanessa A , Shah Smita 
Published: July 2018

Objectives: This study aimed to identify barriers, facilitators and potential intervention strategies for adolescents to use within the home to promote healthy eating and active living. Design: Cross-sectional design using semi-structured discussion groups. Setting: Peer leaders (aged 15–16 years) from five secondary schools in Sydney, Australia, were invited to participate. Methods: In groups of four to nine, peer leaders completed a worksheet focused on three priority behaviours: eating breakfast daily, avoiding sugary drinks and being physically active. Each group discussed, identified and recorded barriers, facilitators and opportunities where they could act as agents of healthy lifestyle change in their homes. The worksheets and field notes were reviewed, analysed and coded into emergent themes. Results: All peer leaders ( n = 77; 51% girls) attending school on the day of the discussion groups participated in this study. They identified a variety of barriers and facilitators for each of the priority behaviours. From the adolescent-generated strategies, such as not having sugary drinks in the fridge, making a routine and cooking or being active with the whole family, three main themes emerged: ‘improving time management’, ‘using social activities to engage family members’ and ‘changing access and availability’. Conclusion: The strategies suggested by peer leaders in this study add to the limited literature of potential low-intensity interventions which young people can use to enable healthy lifestyle change in their home environment.
Resource dependence patterns, goal change, and social value in nonprofit organizations: does goal change matter in nonprofit management?
Authors: Seo JungWook 
Published: July 2018

Resource acquisition is an important factor for the survival and success of nonprofit organizations. Nonprofit organizations are not free from the demands of potential funders and they experience involuntary goal changes in competitive environments. This article investigates the relationships among resource dependence patterns (resource dependency, resource competitiveness, and resource diversity), goal change, and social value in nonprofit organizations. The findings suggest that competition for financial resources (resource competitiveness) is positively associated with goal change in nonprofit organizations. Goal change in an environment of high resource competitiveness has a negative effect on social value. On the other hand, the empirical findings show that a diversified or balanced revenue structure (high resource diversity) helps nonprofit organizations to maintain their social value. Points for practitioners This study shows that frequent goal change can damage social value in the nonprofit sector. This can be interpreted as indicating that the involvement of external stakeholders makes it difficult to attain social value in that the demands of potential donors are a major cause of goal change in nonprofit organizations. To alleviate this problem, a nonprofit organization should try to reduce its dependency on one or a few financial resources for its autonomy and social value. In the mid- and long-term view, nonprofit organizations should enhance their financial independence in order to ensure their survival and success, as well as to improve their social value.