bluuebunny/crossref_metadata_2025_split huggingface dataset:
Percutaneous venting gastrostomy/gastrojejunostomy for malignant bowel obstruction: a qualitative study
Authors: Singh Curry Rebecca , Evans Elizabeth , Raftery Anne-Marie , Hiscock Julia , Poolman Marlise 
Published: October 2019

ObjectiveMalignant bowel obstruction (MBO) is a complication of advanced malignancy and is associated with a short prognosis. MBO can infrequently be reversed by surgery or stenting. The focus of treatment is usually symptomatic management, of which percutaneous venting gastrostomy/gastrojejunostomy (PVG) is one consideration. There is little data considering the impact of PVG on quality of life; we therefore aimed to explore this.MethodsWe identified patients with a PVG inserted for MBO and those who consented to participate were interviewed. The interviews were audio recorded, transcribed and analysed using Framework. Alongside patient interviews, a data collection tool was designed and used to record patient demographics and medical information, enabling us to contextualise individual patients’ experiences.Results11 patients were interviewed and 10 patients’ data were analysed (1 patient withdrew). No patients regretted having a PVG and many benefitted symptomatically and psychosocially. Challenges encountered included practical issues, pain and PVG tube complications.ConclusionsThe analysis provided a detailed insight into the impact of PVG insertion and demonstrated that each patient’s experience is shaped by a complex interplay of individual factors, thereby highlighting the need to improve referral criteria and individualise patient selection. Other service improvements include enhancing information provision for patients and training for healthcare professionals, thus aiming to mitigate the challenges experienced. Our study is the first in-depth exploration of patients’ experiences of PVG at a tertiary cancer centre. Ensuring that the insights from this study are fed back to guide future service provision is critical in enhancing future patient experiences.
Accuracy of automated identification of delayed diagnosis of pediatric appendicitis and sepsis in the ED
Authors: Michelson Kenneth A , Buchhalter Lillian C , Bachur Richard G , Mahajan Prashant , Monuteaux Michael C , Finkelstein Jonathan A 
Published: October 2019

BackgroundDelayed diagnoses of serious emergency conditions can lead to morbidity in children, but are challenging to identify and measure. We developed and piloted an automated tool for identifying delayed diagnosis of two serious conditions commonly seen in the ED using administrative data.MethodsWe identified cases with a final diagnosis of appendicitis or sepsis in a freestanding children’s hospital from 2008 to 2018, with any hospital ED encounter within the preceding 7 days. Two investigators reviewed a subset of these cases using the electronic health records (EHR) to determine if there was a delayed diagnosis and interrater reliability was assessed using the intraclass correlation coefficient (ICC). An automated tool was applied to the same cases to assess its positive predictive value (PPV) to identify those with a delayed diagnosis, using the manual chart review as the gold standard. The tool used number of days since visit, presence of a related diagnosis on the initial visit, and whether or not the patient was discharged.ResultsPrevious ED encounters preceded 91/3703 (2.5%) appendicitis cases and 159/1754 (9.1%) sepsis cases; 78 cases of each were sampled for review. In manual review, 73.4% and 22.8% were thought to have delayed diagnoses; reviewer agreement was excellent (appendicitis ICC 0.77, 95% CI 0.62 to 0.86 and sepsis ICC 0.77, 95% CI 0.43 to 0.89). The PPVs of the automated tool for determination of delayed diagnosis for appendicitis within 1, 3 or 7 days were 96.2%, 95.1% and 93.6%, respectively. For sepsis, the PPVs were 71.4%, 63.6% and 41.2% within 1, 3 or 7 days, respectively.ConclusionsThis automated tool performed well compared with expert EHR review. Performance was stronger for appendicitis. Further tool refinement could improve performance.
Caesarean section delivery and childhood obesity: evidence from the growing up in New Zealand cohort
Authors: Masukume Gwinyai , McCarthy Fergus P , Russell Jin , Baker Philip N , Kenny Louise C , Morton Susan MB , Khashan Ali S 
Published: October 2019

BackgroundEpidemiological studies have reported conflicting results in the association between Caesarean section (CS) birth and childhood obesity. Many of these studies had small sample sizes, were unable to distinguish between elective/planned and emergency CS, and did not adjust for the key confounder maternal pre-pregnancy body mass index (BMI). We investigated the association between CS delivery, particularly elective/planned and childhood obesity, using the Growing Up in New Zealand prospective longitudinal cohort study.MethodsPregnant women planning to deliver their babies on the New Zealand upper North Island were invited to participate. Mode of delivery was categorised into spontaneous vaginal delivery (VD) (reference), assisted VD, planned CS and emergency CS. The main outcome was childhood obesity defined according to the International Obesity Taskforce criteria at age 24 and 54 months. Multinomial logistic regression and mixed-effects linear regression models were fitted with associations adjusted for several potential confounders.ResultsOf the 6599 infants, 1532 (23.2%) were delivered by CS. At age 24 months, 478 (9.3%) children were obese. There was a statistically significant association between planned CS adjusted relative risk ratio (aRRR=1.59; (95% CI 1.09 to 2.33)) and obesity but not for emergency CS (aRRR=1.27; (95% CI 0.89 to 1.82)). At age 54 months there was no association between planned CS (aRRR=0.89; (95% CI 0.54 to 1.45)) and obesity as well as for emergency CS (aRRR=1.19; (95% CI 0.80 to 1.77)). At all-time points those born by planned CS had a higher mean BMI (adjusted mean difference=0.16; (95% CI 0.00 to 0.31), p=0.046).ConclusionsPlanned CS was an independent predictor of obesity in early childhood. This suggests that birth mode influences growth, at least in the short term. This association occurred during a critical phase of human development, the first 2 years of life, and if causal might result in long-term detrimental cardiometabolic changes.
Hypersensitive adverse drug reactions to glucosamine and chondroitin preparations in Australia between 2000 and 2011
Authors: Hoban Claire , Byard Roger , Musgrave Ian 
Published: October 2019

AbstractPurpose of the studyThis study investigates spontaneous adverse drug reactions (ADRs) to glucosamine and chondroitin in the Australian population between 2000 and 2011, with a primary focus on hypersensitivity reactions.Study designCase reports of ADR to glucosamine and chondroitin sent to the Therapeutic Goods Administration between 2000 and 2011 were obtained and analysed. The demographic information and severity of the ADR were recorded for individual ADR cases. These reactions were classified according to the Brown et al grading system for generalised hypersensitivity reactions. This included mild hypersensitivity reactions (generalised erythema, urticaria and angioedema) through to moderate hypersensitivity reactions (wheeze, nausea, vomiting, dizziness (presyncope), diaphoresis, chest or throat tightness and abdominal pain), and more severe reactions (hypotension, confusion and collapse).ResultsIn this study of 366 ADRs to glucosamine and chondroitin preparations, 71.85% of cases (n=263) were found to have hypersensitivity reactions. Of these 263 cases, 92 cases were classified as mild (eg, pruritus, urticaria and lip oedema), 128 cases classified as moderate (such as dyspnoea, nausea and abdominal pain), and 43 cases classified as severe (including amnesia, gait disturbance, somnolence and hypotension). It is not clear whether the patients involved had a known shellfish allergy or underlying atopy.ConclusionResults of this investigation support the need for clear labelling on glucosamine and chondroitin preparations to raise awareness of possible adverse events for those predisposed to allergy or atopy in response to shellfish.
Ovine infectious keratoconjunctivitis in sheep: the farmer's perspective
Authors: Williams Helen J , Duncan Jennifer S , Fisher Sarah Nichol , Coates Amy , Stokes Jessica Eleanor , Gillespie Amy 
Published: October 2019

The objective of this study was to gather current, farmer‐reported data on the frequency of occurrence, risk factors and treatment practices for the sheep eye disease, ovine infectious keratoconjunctivitis (OIKC).A questionnaire regarding eye disease in sheep was completed by 135 farmers from four livestock markets. Most farmers (87%) had observed OIKC in their flock, 88% of these within the last 2 years.Farmers reported observing most cases in the winter months (51%) and fewest in the summer (10%). They proposed housing and forage feeding from racks as factors associated with OIKC.A variety of treatment protocols were used by farmers. The three most popular treatments used were: cloxacillin eye ointment, intramuscular oxytetracycline injection and topical tetracycline spray applied to the eye. Only 62% of treatments were considered very effective by the farmers, with no difference in farmer perceived efficacy between these three most commonly used treatments (p=0.6).Farmers used 15 different terms to describe a photograph of a sheep with OIKC, including many colloquial terms. We hypothesise that this could result in communication problems between veterinary surgeons and farmers.
Equine uveitis in the UK: a retrospective study (2008–2018)
Authors: Malalana Fernando , Ireland Jo L , Pinchbeck Gina , McGowan Cathy M 
Published: October 2019

BackgroundUveitis appears to be less prevalent in the UK compared with other parts of the world and studies characterising the disease in the UK are lacking. The objectives of this retrospective study were to describe acute and recurrent cases presenting for management of uveitis in a referral hospital on the North West of England and compare the signalment of horses presenting with uveitis with the equine hospital population during the same period.MethodsMedical records of horses presented to the referral Equine Hospital, University of Liverpool with signs of uveitis between 2008 and 2018 were reviewed and clinical details extracted.ResultsSeventy horses presented with uveitis; 33 were classified as acute and 37 as recurrent cases. Sixteen of the horses were affected bilaterally. More bilateral cases were classified as recurrent than acute (P=0.04). No differences in age or sex were noted between acute and recurrent cases, or between cases and the general hospital population. Warmbloods and Appaloosas were over‐represented when compared with the general hospital population (P<0.001). Twenty‐one horses (30 per cent, 95 per cent CI 20.5 to 41.4) underwent surgery for the control of the uveitis. Fourteen of the 70 horses (20.0 per cent, 95 per cent CI 12.3 to 30.8) underwent enucleation.ConclusionWhile relatively uncommon in the UK, uveitis can affect horses from a relatively young age. The disease appears to have a relatively higher frequency than expected in Warmbloods and Appaloosas. It is more likely that a recurrent case will have both eyes affected.
GABAA receptor currents in the dorsal motor nucleus of the vagus in females: influence of ovarian cycle and 5α-reductase inhibition
Authors: Littlejohn Erica L. , Espinoza Liliana , Lopez Monica M. , Smith Bret N. , Boychuk Carie R. 
Published: October 2019

The dorsal motor nucleus of the vagus (DMV) contains the preganglionic motor neurons important in the regulation of glucose homeostasis and gastrointestinal function. Despite the role of sex in the regulation of these processes, few studies examine the role of sex and/or ovarian cycle in the regulation of synaptic neurotransmission to the DMV. Since GABAergic neurotransmission is critical to normal DMV function, the present study used in vitro whole cell patch-clamping to investigate whether sex differences exist in GABAergic neurotransmission to DMV neurons. It additionally investigated whether the ovarian cycle plays a role in those sex differences. The frequency of phasic GABAA receptor-mediated inhibitory postsynaptic currents in DMV neurons from females was lower compared with males, and this effect was TTX sensitive and abolished by ovariectomy (OVX). Amplitudes of GABAergic currents (both phasic and tonic) were not different. However, females demonstrated significantly more variability in the amplitude of both phasic and tonic GABAA receptor currents. This difference was eliminated by OVX in females, suggesting that these differences were related to reproductive hormone levels. This was confirmed for GABAergic tonic currents by comparing females in two ovarian stages, estrus versus diestrus. Female mice in diestrus had larger tonic current amplitudes compared with those in estrus, and this increase was abolished after administration of a 5α-reductase inhibitor but not modulation of estrogen. Taken together, these findings demonstrate that DMV neurons undergo GABAA receptor activity plasticity as a function of sex and/or sex steroids. NEW & NOTEWORTHY Results show that GABAergic signaling in dorsal vagal motor neurons (DMV) demonstrates sex differences and fluctuates across the ovarian cycle in females. These findings are the first to demonstrate that female GABAA receptor activity in this brain region is modulated by 5α-reductase-dependent hormones. Since DMV activity is critical to both glucose and gastrointestinal homeostasis, these results suggest that sex hormones, including those synthesized by 5α-reductase, contribute to visceral, autonomic function related to these physiological processes.
Spontaneous action potentials in retinal horizontal cells of goldfish (Carassius auratus) are dependent upon L-type Ca2+ channels and ryanodine receptors
Authors: Country Michael W. , Campbell Benjamin F. N. , Jonz Michael G. 
Published: October 2019

Horizontal cells (HCs) are interneurons of the outer retina that undergo graded changes in membrane potential during the light response and provide feedback to photoreceptors. We characterized spontaneous Ca2+-based action potentials (APs) in isolated goldfish ( Carassius auratus) HCs with electrophysiological and intracellular imaging techniques. Transient changes in intracellular Ca2+ concentration ([Ca2+]i) were observed with fura-2 and were abolished by removal of extracellular Ca2+ or by inhibition of Ca2+ channels by 50 µM Cd2+ or 100 µM nifedipine. Inhibition of Ca2+ release from stores with 20 µM ryanodine or 50 µM dantrolene abolished Ca2+ transients and increased baseline [Ca2+]i. This increased baseline was prevented by blocking L-type Ca2+ channels with nifedipine, suggesting that Ca2+-induced Ca2+ release from stores may be needed to inactivate membrane Ca2+ channels. Caffeine (3 mM) increased the frequency of Ca2+ transients, and the store-operated channel antagonist 2-aminoethyldiphenylborinate (100 μM) counteracted this effect. APs were detected with voltage-sensitive dye imaging (FluoVolt) and current-clamp electrophysiology. In current-clamp recordings, regenerative APs were abolished by removal of extracellular Ca2+ or in the presence of 5 mM Co2+ or 100 µM nifedipine, and APs were amplified with 15 mM Ba2+. Collectively, our data suggest that during APs Ca2+ enters through L-type Ca2+ channels and that Ca2+ stores (gated by ryanodine receptors) contribute to the rise in [Ca2+]i. This work may lead to further understanding of the possible role APs have in vision, such as transitioning from light to darkness or modulating feedback from HCs to photoreceptors. NEW & NOTEWORTHY Horizontal cells (HCs) are interneurons of the outer retina that provide inhibitory feedback onto photoreceptors. HCs respond to light via graded changes in membrane potential. We characterized spontaneous action potentials in HCs from goldfish and linked action potential generation to a rise in intracellular Ca2+ via plasma membrane channels and ryanodine receptors. Action potentials may play a role in vision, such as transitioning from light to darkness, or in modulating feedback from HCs to photoreceptors.
Mutual information analysis of neural representations of speech in noise in the aging midbrain
Authors: Zan Peng , Presacco Alessandro , Anderson Samira , Simon Jonathan Z. 
Published: October 2019

Younger adults with normal hearing can typically understand speech in the presence of a competing speaker without much effort, but this ability to understand speech in challenging conditions deteriorates with age. Older adults, even with clinically normal hearing, often have problems understanding speech in noise. Earlier auditory studies using the frequency-following response (FFR), primarily believed to be generated by the midbrain, demonstrated age-related neural deficits when analyzed with traditional measures. Here we use a mutual information paradigm to analyze the FFR to speech (masked by a competing speech signal) by estimating the amount of stimulus information contained in the FFR. Our results show, first, a broadband informational loss associated with aging for both FFR amplitude and phase. Second, this age-related loss of information is more severe in higher-frequency FFR bands (several hundred hertz). Third, the mutual information between the FFR and the stimulus decreases as noise level increases for both age groups. Fourth, older adults benefit neurally, i.e., show a reduction in loss of information, when the speech masker is changed from meaningful (talker speaking a language that they can comprehend, such as English) to meaningless (talker speaking a language that they cannot comprehend, such as Dutch). This benefit is not seen in younger listeners, which suggests that age-related informational loss may be more severe when the speech masker is meaningful than when it is meaningless. In summary, as a method, mutual information analysis can unveil new results that traditional measures may not have enough statistical power to assess. NEW & NOTEWORTHY Older adults, even with clinically normal hearing, often have problems understanding speech in noise. Auditory studies using the frequency-following response (FFR) have demonstrated age-related neural deficits with traditional methods. Here we use a mutual information paradigm to analyze the FFR to speech masked by competing speech. Results confirm those from traditional analysis but additionally show that older adults benefit neurally when the masker changes from a language that they comprehend to a language they cannot.
Malondialdehyde and Uric Acid as Predictors of Adverse Outcome in Patients with Chronic Heart Failure
Authors: Romuk Ewa , Wojciechowska Celina , Jacheć Wojciech , Zemła-Woszek Aleksandra , Momot Alina , Buczkowska Marta , Rozentryt Piotr 
Published: October 2019

In chronic heart failure (HF), some parameters of oxidative stress are correlated with disease severity. The aim of this study was to evaluate the importance of oxidative stress biomarkers in prognostic risk stratification (death and combined endpoint: heart transplantation or death). In 774 patients, aged 48-59 years, with chronic HF with reduced ejection fraction (median: 24.0 (20-29)%), parameters such as total antioxidant capacity, total oxidant status, oxidative stress index, and concentration of uric acid (UA), bilirubin, protein sulfhydryl groups (PSH), and malondialdehyde (MDA) were measured. The parameters were assessed as predictive biomarkers of mortality and combined endpoint in a 1-year follow-up. The multivariate Cox regression analysis was adjusted for other important clinical and laboratory prognostic markers. Among all the oxidative stress markers examined in multivariate analysis, only MDA and UA were found to be independent predictors of death and combined endpoint. Higher serum MDA concentration increased the risk of death by 103.0% (HR=2.103; 95% CI (1.330-3.325)) and of combined endpoint occurrence by 100% (HR=2.000; 95% CI (1.366-2.928)) per μmol/L. Baseline levels of MDA in the 4th quartile were associated with an increased risk of death with a relative risk (RR) of 3.64 (95% CI (1.917 to 6.926), p<0.001) and RR of 2.71 (95% CI (1.551 to 4.739), p<0.001) for the occurrence of combined endpoint as compared to levels of MDA in the 1st quartile. Higher serum UA concentration increased the risk of death by 2.1% (HR=1.021; 95% CI (1.005-1.038), p<0.001) and increased combined endpoint occurrence by 1.4% (HR=1.014; 95% CI (1.005-1.028), p<0.001), for every 10 μmol/L. Baseline levels of UA in the 4th quartile were associated with an increased risk for death with a RR of 3.21 (95% CI (1.734 to 5.931)) and RR of 2.73 (95% CI (1.560 to 4.766)) for the occurrence of combined endpoint as compared to the levels of UA in the 1st quartile. In patients with chronic HF, increased MDA and UA concentrations were independently related to poor prognosis in a 1-year follow-up.
Tumor Vessel Normalization, Immunostimulatory Reprogramming, and Improved Survival in Glioblastoma with Combined Inhibition of PD-1, Angiopoietin-2, and VEGF
Authors: Di Tacchio Mariangela , Macas Jadranka , Weissenberger Jakob , Sommer Kathleen , Bähr Oliver , Steinbach Joachim P. , Senft Christian , Seifert Volker , Glas Martin , Herrlinger Ulrich , Krex Dietmar , Meinhardt Matthias , Weyerbrock Astrid , Timmer Marco , Goldbrunner Roland , Deckert Martina , Scheel Andreas H. , Büttner Reinhard , Grauer Oliver M. , Schittenhelm Jens , Tabatabai Ghazaleh , Harter Patrick N. , Günther Stefan , Devraj Kavi , Plate Karl H. , Reiss Yvonne 
Published: October 2019

Abstract
Glioblastoma (GBM) is a non-T-cell–inflamed cancer characterized by an immunosuppressive microenvironment that impedes dendritic cell maturation and T-cell cytotoxicity. Proangiogenic cytokines such as VEGF and angiopoietin-2 (Ang-2) have high expression in glioblastoma in a cell-specific manner and not only drive tumor angiogenesis and vascular permeability but also negatively regulate T-lymphocyte and innate immune cell responses. Consequently, the alleviation of immunosuppression might be a prerequisite for successful immune checkpoint therapy in GBM. We here combined antiangiogenic and immune checkpoint therapy and demonstrated improved therapeutic efficacy in syngeneic, orthotopic GBM models. We observed that blockade of VEGF, Ang-2, and programmed cell death protein-1 (PD-1) significantly extended survival compared with vascular targeting alone. In the GBM microenvironment, triple therapy increased the numbers of CTLs, which inversely correlated with myeloid-derived suppressor cells and regulatory T cells. Transcriptome analysis of GBM microvessels indicated a global vascular normalization that was highest after triple therapy. Our results propose a rationale to overcome tumor immunosuppression and the current limitations of VEGF monotherapy by integrating the synergistic effects of VEGF/Ang-2 and PD-1 blockade to reinforce antitumor immunity through a normalized vasculature.