bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antifungal treatment in haematological and oncological patients: Need for quality assessment in routine care
Authors: Lachenmayr Sarah J. , Berking Sophie , Horns Heidi , Strobach Dorothea , Ostermann Helmut , Berger Karin 
Published: March 2018

SummaryInvasive fungal infections in haematological and oncological patients have a major impact on morbidity, mortality and treatment costs. Therefore, rational use of antifungal agents is important for optimal patient care and resource use. The study's objective was to analyse antifungal usage in a German tertiary teaching hospital, department of haematology and oncology, to evaluate quality of antifungal treatment and to assess the need for an antifungal stewardship programme. This retrospective observational study included patients ≥18 years receiving systemic antifungals for prophylaxis or therapy of invasive fungal infection between January and June 2016. Appropriateness of antifungal prescriptions was evaluated in accordance with guidelines of the German Society of Haematology and Oncology (DGHO) and drug labelling. In total, 104/1278 (8.1%) patients received antifungals. One hundred seventy‐one antifungals were prescribed: 48 for prophylaxis, 104 for empirical and 19 for targeted therapy. In 127 (74.3%) prescriptions, indication was appropriate, and in 132 (77.2%), choice of drug. Antifungals were correctly dosed in 131 prescriptions (76.6%). Thirty‐four antifungals (20.0%) were co‐administrated with interacting drugs (5 mild to moderate, 29 severe interactions). Results of this analysis demonstrate that use of systemic antifungals in routine care differs in a substantial number of patients from guideline and labelling recommendations. To optimise antifungal use, the implementation of antifungal stewardship programmes seems to be justified.
Expression profile of pattern recognition receptors in skeletal muscle of SOD1(G93A) amyotrophic lateral sclerosis (ALS) mice and sporadic ALS patients
Authors: Lehmann S. , Esch E. , Hartmann P. , Goswami A. , Nikolin S. , Weis J. , Beyer C. , Johann S. 
Published: March 2018

AimsAmyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons and progressive muscle wasting. Inflammatory processes, mediated by non‐neuronal cells, such as glial cells, are known to contribute to disease progression. Inflammasomes consist of pattern recognition receptors (PRRs), apoptosis‐associated speck‐like protein (ASC) and caspase 1 and are essential for interleukin (IL) processing and a rapid immune response after tissue damage. Recently, we described inflammasome activation in the spinal cord of ALS patients and in SOD1(G93A) ALS mice. Since pathological changes in the skeletal muscle are early events in ALS, we hypothesized that PRRs might be abnormally expressed in muscle fibre degeneration.MethodsWestern blot analysis, real‐time PCR and immunohistochemistry were performed with muscle tissue from presymptomatic and early‐symptomatic male SOD1(G93A) mice and with muscle biopsies of control and sporadic ALS (sALS) patients. Analysed PRRs include nucleotide‐binding oligomerization domain‐like (NOD‐like) receptor protein 1 (NLRP1), NLR protein 3 (NLRP3), NLR family CARD domain‐containing 4 (NLRC4) and absent in melanoma 2. Additionally, expression levels of ASC, caspase 1, interleukin 1 beta (IL1β) and interleukin 18 (IL18) were evaluated.ResultsExpression of PRRs and ASC was detected in murine and human tissue. The PRR NLRC4, caspase 1 and IL1β were significantly elevated in denervated muscle of SOD1(G93A) mice and sALS patients. Furthermore, levels of caspase 1 and IL1β were already increased in presymptomatic animals.ConclusionOur findings suggest that increased inflammasome activation may be involved in skeletal muscle pathology in ALS. Furthermore, elevated levels of NLRC4, caspase 1 and IL1β reflect early changes in the skeletal muscle and may contribute to the denervation process.
A case of late‐onset Krabbe disease which showed subacute progression of spastic paresis with bilateral spinal cord lesions
Authors: Mitsutake Akihiko , Matsukawa Takashi , Ishiura Hiroyuki , Mitsui Jun , Taira Kenichiro , Tokushige Shin‐ichi , Iwata Atsushi , Terao Yasuo , Shimizu Jun , Sakai Norio , Tsuji Shoji 
Published: March 2018

AbstractWe report a 16‐year‐old boy with the late‐onset form of Krabbe disease. The patient had been free of neuromuscular diseases until he showed subacute progression of spastic paraparesis at age 15. There was no evident peripheral neuropathy. Magnetic resonance imaging (MRI) of the brain and the spinal cord showed T2‐weighted high‐intensity lesions along the bilateral pyramidal tract from the internal capsule to the lumbar cord. Bilateral pyramidal tract involvement raised the possibility of late‐onset Krabbe disease. A markedly reduced galactocerebrosidase activity and a homozygous known pathogenic mutation in the GALC gene confirmed the diagnosis. This case was unique in that the progression was subacute and the lesions from the cervical to the lumbar cord were clearly shown by MRI.
Egogram characteristics in Japanese patients with Parkinson's disease
Authors: Shinoda Tomomi , Nakashita Satoko , Hamada Mao , Hirono Kanako , Ito Mariko , Miyagi Tomo , Namihira Yukihiro , Tokashiki Takashi , Kashihara Kenichi , Nakashima Kenji , Maeda Tetsuya 
Published: March 2018

AbstractBackgroundPersonality has been investigated as a possible onset risk factor for Parkinson's disease (PD). Recently, personality has attracted increasing attention because certain non‐motor aspects may be associated with patients’ personality and deterioration of their quality of life. The Tokyo University Egogram version II (TEGII) is a reliable questionnaire for assessing personality in Japanese people, but few studies have reported personality assessments in Japanese PD patients.AimTo clarify the clinical utility of the TEGII for evaluating personality in Japanese PD.MethodsPatients were consecutively enrolled in four medical centers throughout Japan, and their personality was evaluated using the TEGII. Personality is described in terms of five ego‐states: critical parent (CP), nurturing parent (NP), adult (A), free child (FC), and adapted child (AP). The scores for each ego‐state and the egogram patterns describe personality characteristics. We statistically analyzed our data and compared the results with standardized data from a Japanese cohort.ResultsWe enrolled 133 PD patients. The mean scores ± SDs of the five ego‐states were CP: 11.4 ± 4.5, NP: 14.5 ± 4.2, A: 10.5 ± 4.8, FC: 11.1 ± 4.7, and AC: 9.5 ± 5.2. NP scores were significantly higher than the others (P < 0.001), and the NP dominant pattern (15.8%) was most frequent.ConclusionThe NP dominant pattern, which illustrates a thoughtful, obliging and kind personality, is characteristic of Japanese PD patients. The TEGII is a simple clinical tool for evaluating personality in PD and can be used to evaluate changes in patients over time.
20 year trends in renal disease mortality in Ghana: A review of autopsies
Authors: Adjei David N , Adu Dwomoa , Quayson Solomon E , Kardaun Jan WPF , Erskine Isaac J , Lartey Isaac S , Agyemang Charles 
Published: March 2018

ABSTRACTAimData on the changing levels in renal morbidity and mortality are scant globally. We sought to assess trends in renal disease mortality and attributable causes over a 20 year period in Ghana.MethodsA retrospective analysis of 20 year autopsy records of the Pathology Departments of leading teaching hospitals in Ghana, (Korle‐Bu Teaching Hospital (KBTH) in Accra and Komfo Anokye Teaching Hospital (KATH) in Kumasi) from January 1994 to December 2013. Data comprising autopsies from in‐patients, community cases and coroners’ cases were used. We defined primary cause of death as death directly due to renal disease and secondary cause of death as death in which renal disease was a comorbid or contributing factor.ResultsOver the period, there were a total of 94 309 deaths, of which 5608 were attributed to renal disease (5.9/100). Mortality rate remained fairly the same from 1994 to 2009 (5.0%), but doubled from 2010 to 2013 (10.8%). Similar trends were observed among males and females during the same period. However, males had slightly higher mortality rates (6.6%; 95% CI: 46.1%–6.8%) compared to females (5.6%; 95% CI: 5.4%–5.8%; P = 0.271). The major leading attributable causes of renal disease death include end stage renal disease 45.0% and acute pyelonephritis accounting for 20.9% of the cases. Hypertensive heart disease accounted for 30.0% of all secondary cause of death while congestive heart disease and septicaemia accounted for 13.0% and 12.0%, respectively.ConclusionsWe observed marked increase in the renal disease mortality rate during the last few years predominantly driven by chronic and infectious related renal diseases as a main cause, and hypertensive heart disease and congestive heart failure as the main secondary causes. Measures geared towards prevention, treatment and managing such conditions may impact on the reduction of renal disease mortality rate among Ghanaian populations.
Renal regeneration after acute kidney injury
Authors: Coelho Silvia , Cabral Guadalupe , Lopes José A , Jacinto António 
Published: March 2018

Summary at a GlanceThis review focuses on the short and long term clinical risk factors that contribute to progression to chronic renal disease following acute insult. The probability of patient recovery, taking into consideration the aetiology of disease, and the cellular, molecular and immune response that determines tissue regeneration are discussed in detail.
Heart rate variability characteristics of patients with irritable bowel syndrome and associations with symptoms
Authors: Polster A. , Friberg P. , Gunterberg V. , Öhman L. , Le Nevé B. , Törnblom H. , Cvijovic M. , Simren M. 
Published: March 2018

AbstractBackgroundDisturbed brain‐gut interactions are assumed to be of importance for symptom generation in patients with irritable bowel syndrome (IBS). The autonomic nervous system (ANS) is part of the bidirectional brain‐gut communication, but previous studies in IBS show diverging results. We aimed to identify subgroups of IBS patients with distinct ANS characteristics differentiating them from healthy controls (HC), and to study associations between ANS status and symptoms.MethodsHeart rate variability (HRV) was measured in IBS patients and HC (Holter monitoring: supine and standing positions with controlled respiration and ambulatory 24‐hour period). Frequency (5 minutes, supine, standing) and time domains (24 hours, day, night) were analyzed. Validated questionnaires were used to measure gastrointestinal and psychological symptoms in patients. Patients and HC were compared on a univariate and multivariate level (principal component analysis [PCA] and orthogonal partial least squares discriminatory analysis (OPLS‐DA)).Key ResultsWe analyzed 158 IBS patients (Rome III) and 39 HC. Patients differed significantly from HC in HRV parameters during daytime and in standing position. In the PCA, a majority of patients overlapped with HC, but the weighted means differed (P < .01). A subset of patients (n = 30; 19%) with an aberrant global HRV profile was identified through PCA and OPLS‐DA; these patients reported more severe symptoms of frequent (P < .05) and loose stools (P = .03), as well as urgency (P = .01).Conclusions and InferencesAltered ANS function was demonstrated in patients with IBS, and this might be of particular relevance for symptoms in a subset of the patients.
Radar plots: A novel modality for displaying disparate data on the efficacy of eluxadoline for the treatment of irritable bowel syndrome with diarrhea
Authors: Brenner D. M. , Dove L. S. , Andrae D. A. , Covington P. S. , Gutman C. , Chey W. D. 
Published: March 2018

AbstractBackgroundPatients with irritable bowel syndrome with diarrhea (IBS‐D) experience a range of abdominal and bowel symptoms; successful management requires alleviation of this constellation of symptoms. Eluxadoline, a locally active mixed μ‐ and κ‐opioid receptor agonist and δ‐opioid receptor antagonist, is approved for the treatment of IBS‐D in adults based on the results of 2 Phase 3 studies. Radar plots can facilitate comprehensive, visual evaluation of diverse but interrelated efficacy endpoints.MethodsTwo double‐blind, placebo‐controlled, Phase 3 trials (IBS‐3001 and IBS‐3002) randomized patients meeting Rome III criteria for IBS‐D to twice‐daily eluxadoline 75 or 100 mg or placebo. Radar plots were prepared showing pooled Weeks 1‐26 response rates for the primary efficacy composite endpoint (simultaneous improvement in abdominal pain and stool consistency), stool consistency, abdominal pain, urgency‐free days, and adequate relief, and change from baseline to Week 26 in IBS‐D global symptom score, abdominal discomfort, abdominal pain, abdominal bloating, and daily number of bowel movements.Key ResultsThe studies enrolled 2428 patients. Eluxadoline increased Weeks 1‐26 responder proportions vs placebo for the composite endpoint, stool consistency, abdominal pain, urgency‐free days, and adequate relief. Changes from baseline to Week 26 in IBS‐D global symptom score, abdominal discomfort, abdominal pain, abdominal bloating, and number of bowel movements were greater with eluxadoline vs placebo.Conclusions and InferencesData presentation in radar plot format facilitates interpretation across multiple domains, demonstrating that eluxadoline treatment led to improvements vs placebo across 13 endpoints representing the range of symptoms experienced by patients with IBS‐D.
High temporal resolution gastric emptying breath tests in mice
Authors: Miller K. E. , Bajzer Ž. , Hein S. S. , Phillips J. E. , Syed S. , Wright A. M. , Cipriani G. , Gibbons S. J. , Szurszewski J. H. , Farrugia G. , Ordog T. , Linden D. R. 
Published: March 2018

AbstractBackgroundGastric emptying is a complex physiological process regulating the division of a meal into smaller partitions for the small intestine. Disrupted gastric emptying contributes to digestive disease, yet current measures may not reflect different mechanisms by which the process can be altered.MethodsWe have developed high temporal resolution solid and liquid gastric emptying breath tests in mice using [13C]‐octanoic acid and off axis‐ integrated cavity output spectroscopy (OA‐ICOS). Stretched gamma variate and 2‐component stretched gamma variate models fit measured breath excretion data.Key ResultsThese assays detect acceleration and delay using pharmacological (7.5 mg/kg atropine) or physiological (nutrients, cold exposure stress, diabetes) manipulations and remain stable over time. High temporal resolution resolved complex excretion curves with 2 components, which was more prevalent in mice with delayed gastric emptying following streptozotocin‐induced diabetes. There were differences in the gastric emptying of Balb/c vs C57Bl6 mice, with slower gastric emptying and a greater occurrence of two‐phase gastric emptying curves in the latter strain. Gastric emptying of C57Bl6 could be accelerated by halving the meal size, but with no effect on the occurrence of two‐phase gastric emptying curves. A greater proportion of two‐phase gastric emptying was induced in Balb/c mice with the administration of PYY (8‐80 nmol) 60 min following meal ingestion.Conclusions and InferencesCollectively, these results demonstrate the utility of high temporal resolution gastric emptying assays. Two‐phase gastric emptying is more prevalent than previously reported, likely involves intestinal feedback, but contributes little to the overall rate of gastric emptying.
Different perception of chronic constipation between patients and gastroenterologists
Authors: Bellini M. , Gambaccini D. , Salvadori S. , Bocchini R. , Pucciani F. , Bove A. , Alduini P. , Battaglia E. , Bassotti G. 
Published: March 2018

AbstractBackgroundThere is a certain number of subjects that consider themselves to be constipated (self diagnosed constipation; SDC). The Rome Criteria separate FC from IBS‐C, but some SDC patients do not meet the Rome criteria (no Rome Constipation; NRC). Our aims were to evaluate the percentage of SDC subjects with a diagnosis of FC and IBS‐C and to compare demographic and clinical features, symptoms, and quality of life in the different SDC groups (FC, IBS‐C, NRC).MethodsDuring a 2‐month period, 934 patients and 980 accompanying persons (AP) were asked to complete a survey. The presence of FC or IBS‐C was assessed. SDC subjects were invited to record the stool consistency (Bristol scale) and to fill in the Constipation Severity Index (CSI), obstructed defecation syndrome (ODS) and patient assessment of constipation‐quality of life (PAC‐QoL). The use of laxatives and enemas was evaluated.Key ResultsThe probability of the ROME III criteria being present was higher in SDC compared with no‐SDC (OR 20.5). NRC was present in 13.5% of the SDC. In the patients’ group the agreement between a diagnosis of Rome III and SDC was good (K 0.62), whereas in the AP it was moderate (K 0.56). NRC showed lower mean values of ODS, CSI and PAC‐QoL, higher Bristol scale and a lower use of laxatives and enemas compared to IBS‐C and FC. No differences were found between IBS‐C and FC.Conclusions and InferencesThe Rome III criteria identify subjects with a greater clinical impact, but separation of FC and IBS‐C does not seem justified.
Gastrointestinal dysmotility: A qualitative exploration of the journey from symptom onset to diagnosis
Authors: Twist K. , Ablett J. , Wearden A. , Paine P. , Vasant D. , Lal S. , Peters S. 
Published: March 2018

AbstractBackgroundGastrointestinal dysmotility (GID) covers a spectrum of disorders disrupting enteric neuromuscular co‐ordination which, when severe, causes intractable gastrointestinal symptoms and malnutrition and is a recognized cause of chronic intestinal failure. To date, no study has provided an in‐depth account of the experiences of patients with severe GID and their psychosocial needs. This study aimed to explore patients’ experiences from symptom onset and the process of seeking and receiving a diagnosis. It specifically explored the psychological effect of this process and the effect on relationships.MethodsParticipants (n = 20, mean age = 47.9, female n = 16, parenteral nutrition = 13) were recruited from a UK center with tertiary Neurogastroenterology and Intestinal Failure services. A qualitative exploratory design with semi‐structured in‐depth interviews was used. Data were analyzed using thematic analysis.Key ResultsSignificant delays were experienced in obtaining a diagnosis. Participants reported having their mental health questioned and felt that they had to fight to prove their symptoms had a physical basis to access appropriate treatment. Although a diagnosis helped legitimize symptoms, the condition remained poorly understood by participants themselves, relatives, and health professionals. Participants discussed the impact that “feeling delegitimized” and the “lack of coherent understanding of GID” had on their relationships and mental health.Conclusions & InferencesThe distressing experience of GID symptoms are compounded by a delay in validating symptoms and lack of coherent understanding. More knowledge of GID is needed by health professionals to speed up diagnosis and offer more coherent information. The psychological impact of a GID diagnosis should be acknowledged early to help facilitate adjustment.
Aphid (Myzus persicae) feeding on the parasitic plant dodder (Cuscuta australis) activates defense responses in both the parasite and soybean host
Authors: Zhuang Huifu , Li Juan , Song Juan , Hettenhausen Christian , Schuman Meredith C. , Sun Guiling , Zhang Cuiping , Li Jing , Song Dunlun , Wu Jianqiang 
Published: March 2018

Summary

Dodders (Cuscuta spp.) are shoot holoparasites, whose haustoria penetrate host tissues to enable fusion between the parasite and host vascular systems, allowing Cuscuta to extract water, nutrients and other molecules from hosts. Aphids are piercing–sucking herbivores that use specialized stylets to feed on phloem sap. Aphids are known to feed on Cuscuta, but how Cuscuta and its host plant respond to aphids attacking the parasite was unknown.

Phytohormone quantification, transcriptomic analysis and bioassays were performed to determine the responses of Cuscuta australis and its soybean (Glycine max) hosts to the feeding of green peach aphid (GPA; Myzus persicae) on C. australis.

Decreased salicylic acid levels and 172 differentially expressed genes (DEGs) were found in GPA‐attacked C. australis, and the soybean hosts exhibited increased jasmonic acid contents and 1015 DEGs, including > 100 transcription factor genes. Importantly, GPA feeding on C. australis increased the resistance of the soybean host to subsequent feeding by the leafworm Spodoptera litura and soybean aphid Aphis glycines, resulting in 21% decreased leafworm mass and 41% reduced aphid survival rate.

These data strongly suggest that GPA feeding on Cuscuta induces a systemic signal, which is translocated to hosts and activates defense against herbivores.
Class C ARFs evolved before the origin of land plants and antagonize differentiation and developmental transitions in Marchantia polymorpha
Authors: Flores‐Sandoval Eduardo , Eklund D. Magnus , Hong Syuan‐Fei , Alvarez John P. , Fisher Tom J. , Lampugnani Edwin R. , Golz John F. , Vázquez‐Lobo Alejandra , Dierschke Tom , Lin Shih‐Shun , Bowman John L.  
Published: March 2018

Summary

A plethora of developmental and physiological processes in land plants is influenced by auxin, to a large extent via alterations in gene expression by AUXIN RESPONSE FACTORs (ARFs). The canonical auxin transcriptional response system is a land plant innovation, however, charophycean algae possess orthologues of at least some classes of ARF and AUXIN/INDOLE‐3‐ACETIC ACID (AUX/IAA) genes, suggesting that elements of the canonical land plant system existed in an ancestral alga.

We reconstructed the phylogenetic relationships between streptophyte ARF and AUX/IAA genes and functionally characterized the solitary class C ARF, MpARF3, in Marchantia polymorpha.

Phylogenetic analyses indicate that multiple ARF classes, including class C ARFs, existed in an ancestral alga. Loss‐ and gain‐of‐function MpARF3 alleles result in pleiotropic effects in the gametophyte, with MpARF3 inhibiting differentiation and developmental transitions in multiple stages of the life cycle. Although loss‐of‐function Mparf3 and Mpmir160 alleles respond to exogenous auxin treatments, strong miR‐resistant MpARF3 alleles are auxin‐insensitive, suggesting that class C ARFs act in a context‐dependent fashion.

We conclude that two modules independently evolved to regulate a pre‐existing ARF transcriptional network. Whereas the auxin‐TIR1‐AUX/IAA pathway evolved to repress class A/B ARF activity, miR160 evolved to repress class C ARFs in a dynamic fashion.