bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral amoxicillin‐clavulanate for treating diabetic foot infections
Authors: Gariani Karim , Lebowitz Dan , Kressmann Benjamin , von Dach Elodie , Sendi Parham , Waibel Felix , Berli Martin , Huber Tanja , Lipsky Benjamin A. , Uçkay Ilker 
Published: February 2019

AimTo assess amoxicillin‐clavulanate (AMC) for the oral therapy of diabetic foot infections (DFIs), especially for diabetic foot osteomyelitis (DFO).MethodsWe performed a retrospective cohort analysis among 794 DFI episodes, including 339 DFO cases.ResultsThe median duration of antibiotic therapy after surgical debridement (including partial amputation) was 30 days (DFO, 30 days). Oral AMC was prescribed for a median of 20 days (interquartile range, 12‐30 days). The median ratio of oral AMC among the entire antibiotic treatment was 0.9 (interquartile range, 0.7‐1.0). After a median follow‐up of 3.3 years, 178 DFIs (22%) overall recurred (DFO, 75; 22%). Overall, oral AMC led to 74% remission compared with 79% with other regimens (χ2‐test; P = 0.15). In multivariate analyses and stratified subgroup analyses, oral AMC resulted in similar clinical outcomes to other antimicrobial regimens, when used orally from the start, after an initial parenteral therapy, or when prescribed for DFO.ConclusionsOral AMC is a reasonable option when treating patients with DFIs and DFOs.
Ocular drift reflects volitional action preparation
Authors: Watanabe Masayuki , Okada Ken‐ichi , Hamasaki Yuta , Funamoto Mari , Kobayashi Yasushi , MacAskill Michael , Anderson Tim 
Published: February 2019

AbstractHuman cognitive behavior is predictive rather than reflexive because of volitional action preparation. Recent studies have shown that the covert process of volitional action preparation can be decoded from overt fixational eye movements of fixational/microsaccades and pupil dilation. Ocular drift, the slowest fixational eye movements, is also under the active neural control, but its relationship with cognitive behavior is unknown. Here, we examined whether ocular drift also reflects volitional action preparation. We analyzed ocular drift while adult humans maintained fixation on a central visual stimulus as they prepared to generate a volitional saccade. We adopted the antisaccade paradigm in which subjects generate a targeting saccade toward the opposite direction of a peripheral visual stimulus. Our findings are the following five points. First, ocular drift was slower when subjects prepared for targeting saccade initiation than when such preparation was unnecessary. Second, ocular drift was slowed down with elapsed time from fixation initiation, which was associated with the facilitation of targeting saccade initiation. Third, ocular drift was further slowed on correct antisaccade trials than when subjects failed to suppress targeting saccades toward peripheral stimuli. Fourth, such correlation with antisaccade performance was observed immediately after fixation initiation in ocular drift, but it emerged more slowly in the other fixational eye movements. Fifth, subjects with unstable fixation because of faster ocular drift had poorer antisaccade performance. We suggest that fixation stability measured by ocular drift can be used to decode the covert process of volitional action preparation along with the other fixational eye movements.
Cerebrospinal fluid changes following epileptic seizures unrelated to inflammation
Authors: Süße M. , Saathoff N. , Hannich M. , von Podewils F. 
Published: February 2019

Background and purposeAnalyzing cerebrospinal fluid (CSF) is crucial in the diagnostic workup of epileptic seizures to rule out autoimmunity or infections as the underlying cause. Therefore, the description of post‐ictal changes in CSF is essential to differentiate between negligible and etiopathologically relevant changes in the CSF profile.MethodsA retrospective analysis of 247 patients newly diagnosed with epileptic seizures and CSF analysis during diagnostic workup was conducted. Patients with possible or definitive autoimmune or infectious encephalitis were excluded. CSF results were evaluated for associations with seizure types, seizure etiology and electroencephalography (EEG) findings.ResultsAn increased cell count (>4/μL) was found in 4% (n = 10), increased lactate concentration (>2.5 mmol/L) in 28% (n = 70), increased total protein (>500 mg/L) in 51% (n = 125) and a dysfunction of the blood–brain barrier in 29% (n = 71) of patients. Intrathecal immunoglobulin G production was observed in 5% (n = 12) of patients. Higher lactate concentrations were found in seizures with motor onset (P = 0.02) compared with those with non‐motor onset. Patients with generalized slow activity on EEG had significantly higher lactate values (P = 0.01) and albumin quotient (P = 0.05) than those with normal EEG.ConclusionsCompared with mild pleocytosis and immunoglobulin synthesis, elevated lactate and total protein concentrations as well as blood–brain barrier dysfunction are frequently found following epileptic seizures. Our data suggest that seizure semiology might impact CSF profiles. The highest lactate concentrations were found following motor‐onset seizures. Our findings may help clinicians to avoid over‐interpretation of minor CSF changes; however, the exclusion of alternative causes should always be carefully considered, taking into account further clinical features.
No evidence for a BRD2 promoter hypermethylation in blood leukocytes of Europeans with juvenile myoclonic epilepsy
Authors: Schulz Herbert , Ruppert Ann‐Kathrin , Zara Federico , Madia Francesca , Iacomino Michele , S. Vari Maria , Balagura Ganna , Minetti Carlo , Striano Pasquale , Bianchi Amedeo , Marini Carla , Guerrini Renzo , Weber Yvonne G. , Becker Felicitas , Lerche Holger , Kapser Claudia , Schankin Christoph J. , Kunz Wolfram S. , Møller Rikke S. , Oliver Karen L. , Bellows Susannah T. , Mullen Saul A. , Berkovic Samuel F. , Scheffer Ingrid E. , Caglayan Hande , Ozbek Ugur , Hoffmann Per , Schramm Sara , Tsortouktzidis Despina , Becker Albert J. , Sander Thomas 
Published: February 2019

SummaryJuvenile myoclonic epilepsy (JME) is a common syndrome of genetic generalized epilepsies (GGEs). Linkage and association studies suggest that the gene encoding the bromodomain‐containing protein 2 (BRD2) may increase risk of JME. The present methylation and association study followed up a recent report highlighting that the BRD2 promoter CpG island (CpG76) is differentially hypermethylated in lymphoblastoid cells from Caucasian patients with JME compared to patients with other GGE subtypes and unaffected relatives. In contrast, we found a uniform low average percentage of methylation (<4.5%) for 13 CpG76‐CpGs in whole blood cells from 782 unrelated European Caucasians, including 116 JME patients, 196 patients with genetic absence epilepsies, and 470 control subjects. We also failed to confirm an allelic association of the BRD2 promoter single nucleotide polymorphism (SNP) rs3918149 with JME (Armitage trend test, P = 0.98), and we did not detect a substantial impact of SNP rs3918149 on CpG76 methylation in either 116 JME patients (methylation quantitative trait loci [meQTL], P = 0.29) or 470 German control subjects (meQTL, P = 0.55). Our results do not support the previous observation that a high DNA methylation level of the BRD2 promoter CpG76 island is a prevalent epigenetic motif associated with JME in Caucasians.
The protective effect of acute pantoprazole pretreatment on renal ischemia/reperfusion injury in rats
Authors: Kohansal Parichehr , Rajai Nazanin , Dehpour Ahmad Reza , Rashidian Amir , Shafaroodi Hamed 
Published: February 2019

AbstractRenal ischemia/reperfusion injury (IRI), which occurs in many pathological conditions, is associated with high rate of morbidity and mortality. Activation of inflammatory responses and oxidative stress contribute to induce organ damage following IRI. Pantoprazole, a proton pump inhibitor, which is mostly prescribed for gastroesophageal reflux disease (GERD) has been shown to exert anti‐inflammation effects. In order to evaluate the effects of pantoprazole on renal ischemia/reperfusion injury, four different doses of pantoprazole (4.5, 9, 18, and 36 mg/kg) were administered 30 min before the induction of IRI in male Wistar rats. Serum concentration of creatinine and blood urea nitrogen (BUN) were measured to assess renal function. Histopathological changes, malondialdehyde (MDA) level and toll‐like receptor 4 (TLR‐4) expression in renal tissue were determined and compared to control group. The results revealed that pretreatment with 18 and 36 mg/kg of pantoprazole leads to the significant decline in serum creatinine and BUN levels and the severity of necrosis grade in comparison with control group (P < 0.05). Pantoprazole also reduced the MDA level and TLR‐4 expression in renal tissue. In summary, pantoprazole attenuates renal injury following ischemia/reperfusion. This effect is mediated partially through inhibition of oxidative stress and TLR‐4 signaling pathway.
Human THO coordinates transcription termination and subsequent transcript release from the HSP70 locus
Authors: Katahira Jun , Ishikawa Hiroki , Tsujimura Kakeru , Kurono Sadamu , Hieda Miki 
Published: February 2019

AbstractA multiprotein complex, THO/TREX, couples the transcription, 3′‐end formation and nuclear export of mRNAs. In this study, we report that crucial factors for mRNA processing, such as XRN2, DDX5/DDX17 and CstF64, are copurified with human THO (hTHO). Using chromatin immunoprecipitation, we found increased cross‐linking of XRN2 and CstF64 to the RNA polymerase II (RNAP II) pause site of the HSPA1A gene upon down‐regulation of THOC5, a metazoan‐specific component of hTHO. As observed in THOC5‐depleted cells, knockdown of XRN2 blocked HSP70 transcript release and increased the amount of CstF64 at the pause site. In addition, our data indicate that DDX5/DDX17 is also required for HSP70 transcript release. As the degradation of read‐through transcripts, but not cleavage at polyadenylation sites per se, was hindered upon THOC5 or DDX5/DDX17 down‐regulation, these factors appear to influence transcriptional termination. Interestingly, over‐expression of RNase H suppressed the accumulation of HSP70 transcripts in nuclear foci in THOC5‐ or DDX5/DDX17‐depleted cells. Thus, we propose a model in which hTHO, along with DDX5/DDX17, restricts the formation of R‐loops, thereby facilitating the XRN2‐mediated transcriptional termination and release of the mature transcript from the HSPA1A locus.
Distribution of emphysema and fibrosis in idiopathic pulmonary fibrosis with coexisting emphysema
Authors: Kinoshita Yoshiaki , Watanabe Kentaro , Ishii Hiroshi , Kushima Hisako , Fujita Masaki , Nabeshima Kazuki 
Published: February 2019

AimsCombined pulmonary fibrosis and emphysema (CPFE) is a syndrome that results from tobacco smoking. Emphysema and fibrosis in CPFE patients have been considered to exist separately, with emphysema in the upper lobes and interstitial pneumonia in the lower lobes. The aim of this study was to examine the intrapulmonary distribution of fibrosis and emphysema in clinically diagnosed patients with idiopathic pulmonary fibrosis (IPF) and coexisting emphysema.Methods and resultsAmong IPF patients (n = 40) who had been autopsied or pneumonectomised for lung transplantation from 1993 to 2018, we retrospectively selected patients with IPF and coexisting emphysema (n = 19) on the basis of the appearance on chest computed tomography (IPF patients with emphysema). We then histologically determined the intrapulmonary distribution of emphysema and fibrosis in the upper lobes and the lower lobes separately. In 15 of the 19 IPF patients with emphysema (79%), fibrosis and emphysema coexisted in the upper lobes and the lower lobes. No patients showed emphysema exclusively in the upper lobes and fibrosis exclusively in the lower lobes.ConclusionsIn the autopsied and pneumonectomised specimens of IPF patients with emphysema, craniocaudal separation of emphysema and fibrosis (emphysema in the upper lobes and interstitial pneumonia in the lower lobes) was histologically rare; coexistence or collision of fibrosis and emphysema in each lobe was common.
Validation of a predictive method for sunscreen formula evaluation using gene expression analysis in a Chinese reconstructed full‐thickness skin model
Authors: Liu Y. , Wang R. , He X. , Dai H. , Betts R. J. , Marionnet C. , Bernerd F. , Planel E. , Wang X. , Nocairi H. , Cai Z. , Qiu J. , Ding C. 
Published: February 2019

AbstractObjectiveThis study aimed to establish a predictive in vitro method for assessing the photoprotective properties of sunscreens using a reconstructed full‐thickness skin model.Materials and MethodsA full‐thickness skin model reconstructed with human fibroblasts and keratinocytes isolated from Chinese skin was exposed to daily UV radiation (DUVR). We examined the transcriptomic response, identifying genes for which expression was modulated by DUVR in a dose‐dependent manner. We then validated the methodology for efficacy evaluation of different sunscreens formulas.ResultsThe reconstructed skin model was histologically consistent with human skin, and upon DUVR exposure, the constituent fibroblasts and keratinocytes exhibited transcriptomic alterations in pathways associated with oxidative stress, inflammation and extracellular matrix remodelling. When used to evaluate sunscreen protection on the model, the observed level of protection from UV‐induced gene expression was consistent with the corresponding protection factors determined clinically and allowed for statistical ranking of sunscreen efficacy.ConclusionsWithin this study we show that quantification of gene modulation within the reconstructed skin model is a biologically relevant approach with sensitivity and predictability to evaluate photoprotection products.
Nuclear receptor hormone receptor 39 is required for locust moulting by regulating the chitinase and carboxypeptidase genes
Authors: Zhao X.‐M. , Qin Z.‐Y. , Zhang J. , Yang Y. , Jia P. , Yang Q. , Ma E.‐B. , Zhang J.‐Z. 
Published: February 2019

AbstractThe nuclear receptor‐mediated 20‐hydroxyecdysone (20E) signalling pathway plays crucial roles in insects by initiating and regulating moulting and metamorphosis. In the present study, we identified and characterized a cDNA encoding a putative nuclear receptor protein (Locusta migratoria hormone receptor 39, LmHR39) based on L. migratoria transcriptomics data. Reverse‐transcription quantitative PCR (RT‐qPCR) revealed that LmHR39 shows low‐level expression in the early days of fifth‐instar nymphs, and peak expression occurs on day 5, which is followed by a decrease before ecdysis. LmHR39 transcription could be induced by 20E in vivo and was significantly suppressed by knocking down the expression of the L. migratoria ecdysone receptor gene and early‐late gene LmHR3. After RNA interference of LmHR39 with double‐stranded RNA (dsRNA), 85% of the insects showed abnormal morphology, with curly wings after moulting and delayed eclosion time. Haematoxylin and eosin staining indicated that apolysis of the integument and wing pad cuticle in the dsLmHR39‐treated insects was delayed compared to that in the dsRNA for green fluorescent protein‐injected control. Furthermore, RNA‐sequencing and RT‐qPCR analysis showed the expression level of carboxypeptidase genes (Carboxypeptidase A (CPA) and Carboxypeptidase M (CPM)) and chitin degrading genes (LmChitinase5 (LmCHT5) and LmChitinase10 (LmCHT10)) dramatically declined in the dsLmHR39‐treated insects, implying that the LmHR39‐mediated 20E signalling pathway is involved in the regulation of carboxypeptidase genes (CPA and CPM) and chitinase genes (LmCHT5 and LmCHT10), and participated in apolysis of the integument and wing pads during locust moulting.
Is there a role for proton pump inhibitor prophylaxis in haematology patients?
Authors: Leitinger Emma , Hui Lisa , Grigg Andrew 
Published: February 2019

AbstractWhile proton pump inhibitors (PPI) are widely prescribed as prophylaxis in selected haematology inpatient and outpatients, an informal survey of haematology units around Australia found wide variations in the specific indications for their use. This is consistent with a literature review which showed a paucity of robust evidence to support their use, specifically in chemotherapy‐induced mucositis, thrombocytopenia or administration of high dose glucocorticosteroids in the absence of additional risk factors. Rationalising PPI prescribing is clinically important from both a cost and safety perspective, given the emerging evidence of adverse events associated with prolonged PPI administration. A review of prescribing practices at our institution over a 14‐month period found that approximately 60% of myeloma, lymphoma and autograft patients received PPI prophylaxis during and beyond chemotherapy without an accepted indication. We encourage institutions to review their PPI prescribing practices with the intent of rationalising their use, and to conduct studies aiming to fill the substantial gaps in our knowledge.
Reply to Woltsche N. et al. Managing adverse effects by dose reduction during routine treatment of locally advanced basal cell carcinoma with the hedgehog inhibitor vismodegib: a single‐centre experience
Authors: Scalvenzi M. , Costa C. , Cappello M. , Villani A. 
Published: February 2019

Linked article: This article is commented on by N. Woltsche et al., pp. e144–e145 in this issue. To view this article visit https://doi.org/10.1111/jdv.15367.
Defining and measuring ‘eczema control’: an international qualitative study to explore the views of those living with and treating atopic eczema
Authors: Howells L. , Thomas K.S. , Sears A.V. , Nasr I. , Wollenberg A. , Schuttelaar M.L.A. , Romeijn G.L.E. , Paller A.S. , Mueller K. , Doytcheva K. , Kataoka Y. , Daguze J. , Barbarot S. , von Kobyletzki L.B. , Beckman L. , Ratib S. , Cowdell F. , Santer M. , Chalmers J.R. ,   the long‐term control of eczema working group for the HOME initiative
Published: February 2019

AbstractBackgroundAtopic eczema (also known as eczema) is a chronic, inflammatory skin condition that often afflicts patients’ health and well‐being. The Harmonising Outcome Measures for Eczema (HOME) initiative recommends that ‘long‐term control of eczema’ is measured in all clinical trials 3 months or longer in duration. However, little has been published on what eczema control means to those living with or treating atopic eczema.ObjectivesTo (i) develop understanding of what eczema control means to patients, carers and clinicians and (ii) explore the feasibility and acceptability of different ways of measuring eczema control in the long term.MethodsOnline focus groups explored patients/carers experiences in the UK, the United States, the Netherlands, France, Sweden and Japan, and an international online survey gathered views of clinicians. The framework method was used to analyse the focus groups, and thematic analysis was used to analyse survey data. All findings were integrated into a theoretical framework to create overarching themes that cut across these diverse groups.ResultsEight focus groups with patients (16 years+) and eight groups with carers of children took place (N = 97). Sixty‐two people took part in the survey. Eczema control was described as a multifaceted construct involving changes in disease activity, the treatment and management of the condition and psychological, social and physical functioning. Patient/carer measurement allows personal accounts and frequent measurement, whilst clinician measurement was deemed less subjective. The burden on patients/carers and issues for analysing and interpreting data should be considered.ConclusionsThis study formed the basis of judging the content validity and feasibility of measurement instruments/methods to assess control of eczema in clinical trials. This online approach to an international qualitative study is an example of how core outcome set developers with limited resources can engage with multiple stakeholder groups on an international basis to inform consensus meeting discussions.
Applications of reflection‐contrast microscopy, including the sensitive detection of the results ofin situhybridisation a review
Authors: PLOEM JOHAN 
Published: February 2019

SummaryThe observation with RCM of the reflection from reaction products produced by nonisotopicin situhybridisation and a peroxidase staining, has recently facilitated the identification of single copy genes. RCM also reveals light microscope structures in stained ultrathin (0.1 μm) epon and lowicryl sections. In such preparations no out‐of‐focus blur can be observed. Confocal optics are thus not needed to obtain high‐quality images of ultrathin sections at the highest conventional light microscope optical resolution, and with higher image‐contrast than can be obtained by classical absorption microscopy. Such RCM images provide the same type of information as confocal scanning microscope images. A sequential ultrathin section of the same microscopic specimen can be examined with electron microscopy for a simple and accurate (CLEM) procedure. For some applications RCM can replace (CLSM).Lay DescriptionWith reflection contrast microscopy (RCM), a microscope image can be observed if micromirror‐like reflecting substances are present in the reaction product of cytochemical stains. Using an antiflex objective for RCM, the reflected incident light from the stained microscope specimen can be observed with only a small amount of unwanted stray‐light in the image background. Stray‐light is caused by reflection of incident light from the surface of the lenses in the microscope objective and in the microscope tube (using a 50% beam splitter for epi‐illumination). Several authors who compared RCM with bright‐field and fluorescence microscopy, found RCM to be a sensitive microscope method in many applications. It has been reported that RCM, usingin situhybridisation methods, can detect DNA sequences in single copy genes. In the literature is mentioned that single copy genes have an estimated mass of less than a trillionth of a gram of DNA. From stained ultrathin microscope sections with less than 0.1 μm thickness, multicoloured images with a high image contrast, optimal resolution and no out‐of‐focus blur can be observed with RCM. To achieve this, RCM uses an antiflex microscope objective, with a quarter‐wave plate mounted on the front lens in combination with a polarising filter cube inserted in the epi‐illuminator. RCM can also make use of oblique illumination, for a further increase of the image‐contrast and the resolution of the microscope image. A central stop has then to be inserted in the aperture plane of an epi‐illuminator.