bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health workers’ perspectives of a mobile health tool to improve diagnosis and management of paediatric acute respiratory illnesses in Uganda: a qualitative study
Authors: Ellington Laura Elizabeth , Najjingo Irene , Rosenfeld Margaret , Stout James W , Farquhar Stephanie A , Vashistha Aditya , Nekesa Bridget , Namiya Zaituni , Kruse Agatha J , Anderson Richard , Nantanda Rebecca 
Published: July 2021

ObjectivesMobile health tools have potential to improve the diagnosis and management of acute lower respiratory illnesses (ALRI), a leading cause of paediatric mortality worldwide. The objectives were to evaluate health workers’ perceptions of acceptability, usability and feasibility of Acute Lower Respiratory Illness Treatment and Evaluation (ALRITE), a novel mobile health tool to help frontline health workers diagnose, treat and provide education about ALRI in children <5 years.DesignA qualitative study including semistructured interviews with health facility administrators and focus groups with primary care health workers.SettingTwo federally funded Ugandan primary care health facilities, one peri-urban and one rural.ParticipantsWe enrolled 3 health administrators and 28 health workers (clinical officers and nurses).InterventionThe ALRITE smartphone application was developed to help frontline health workers adhere to ALRI guidelines and differentiate wheezing illnesses from pneumonia in children under 5 years of age. ALRITE contains a simple decision tree, a partially automated respiratory rate counter, educational videos and an adapted respiratory assessment score to determine bronchodilator responsiveness. We performed a demonstration of ALRITE for participants at the beginning of interviews and focus groups. No participant had used ALRITE prior.ResultsThemes impacting the potential implementation of ALRITE were organised using individual-level, clinic-level and health-system level determinants. Individual-level determinants were acceptability and perceived benefit, usability, provider needs and provider–patient relationship. Clinic-level determinants were limited resources and integration within the health centre. Systems-level determinants included medication shortages and stakeholder engagement.ConclusionsIncorporation of these themes will ready ALRITE for field testing. Early engagement of end users provides insights critical to the development of tailored mHealth decision support tools.
Effect of power Doppler and digital subtraction techniques on the comparison of myocardial contrast echocardiography with SPECT
Authors: Haluska B , Case C , Short L , Anderson J , Marwick T H 
Published: July 2021

OBJECTIVETo compare the accuracy and feasibility of harmonic power Doppler and digitally subtracted colour coded grey scale imaging for the assessment of perfusion defect severity by single photon emission computed tomography (SPECT) in an unselected group of patients.DESIGNCohort study.SETTINGRegional cardiothoracic unit.PATIENTS49 patients (mean (SD) age 61 (11) years; 27 women, 22 men) with known or suspected coronary artery disease were studied with simultaneous myocardial contrast echo (MCE) and SPECT after standard dipyridamole stress.MAIN OUTCOME MEASURESRegional myocardial perfusion by SPECT, performed with 99mTc tetrafosmin, scored qualitatively and also quantitated as per cent maximum activity.RESULTSNormal perfusion was identified by SPECT in 225 of 270 segments (83%). Contrast echo images were interpretable in 92% of patients. The proportion of normal MCE by grey scale, subtracted, and power Doppler techniques were respectively 76%, 74%, and 88% (p < 0.05) at > 80% of maximum counts, compared with 65%, 69%, and 61% at < 60% of maximum counts. For each technique, specificity was lowest in the lateral wall, although power Doppler was the least affected. Grey scale and subtraction techniques were least accurate in the septal wall, but power Doppler showed particular problems in the apex. On a per patient analysis, the sensitivity was 67%, 75%, and 83% for detection of coronary artery disease using grey scale, colour coded, and power Doppler, respectively, with a significant difference between power Doppler and grey scale only (p < 0.05). Specificity was also the highest for power Doppler, at 55%, but not significantly different from subtracted colour coded images.CONCLUSIONSMyocardial contrast echo using harmonic power Doppler has greater accuracy than with grey scale imaging and digital subtraction. However, power Doppler appears to be less sensitive for mild perfusion defects.
Incremental shuttle walk test in the assessment of patients for heart transplantation
Authors: Lewis M E , Newall C , Townend J N , Hill S L , Bonser R S 
Published: July 2021

OBJECTIVETo compare the incremental shuttle walk test (ISWT) with treadmill exercise testing (TT) derived measurement of peak oxygen consumption (peak Vo2) in patients undergoing assessment for cardiac transplantation.DESIGNProspective comparison. All investigations occurred during a single period of admission for transplant assessment.SETTINGSingle UK cardiothoracic transplantation unit.PATIENTS25 patients recruited (21 men). Mean age was 53 years.INTERVENTIONSPatients underwent two TT of peak Vo2 using the modified Naughton protocol and three (one practice) ISWT. Investigations were performed on consecutive days.MAIN OUTCOME MEASURESMain outcome measures were repeatability of TT and ISWT assessments; relation between peak Vo2 and distance walked in the ISWT; and receiver operating characteristic (ROC) analysis to establish a distance walked in the ISWT that predicted which patients would have a peak Vo2 greater than 14 ml/min/kg.RESULTSBoth the ISWT and the TT were highly reproducible. Following the first practice walk, mean (SD) ISWT distances were 400.0 (146) m (ISWT2) and 401.3 (129) m (ISWT3),r = 0.90, p < 0.0001. Mean peak Vo2 by TT was 15.2 (4.4) ml/kg/min (TT1) and 15.0 (4.4) ml/kg/min (TT2), r = 0.83, p < 0.0001. The results revealed a strong correlation between distance covered in the ISWT and peak Vo2obtained during TT (r = 0.73, p = 0.0001). ROC analysis showed that a distance walked of 450 m allowed the selection of patients with a peak Vo2 of over 14 ml/min/kg.CONCLUSIONSThis work confirms the utility of the ISWT in the assessment of exercise capacity in patients with severe heart failure undergoing assessment for cardiac transplantation. ISWT may provide a widely applicable surrogate measure for peak Vo2 estimation in this population. Shuttle distance walked may therefore allow the convenient, serial assessment of patients with heart failure before referral for transplantation.
Abnormalities of right ventricular long axis function after atrial repair of transposition of the great arteries
Authors: Derrick G P , Josen M , Vogel M , Henein M Y , Shinebourne E A , Redington A N 
Published: July 2021

BACKGROUNDWhile volume derived global indices of right ventricle (RV) function are frequently abnormal after the Mustard procedure, the mechanism for these abnormalities is poorly understood. RV muscle fibres are predominantly arranged longitudinally and thus indices derived in the long axis may better describe RV function.METHODS20 survivors of the Mustard operation were studied (age 7.8–37.3 years, median 14.2 years). Long axis recordings from the apical four chamber view were obtained with the M mode cursor positioned through the lateral angle of the tricuspid valve annulus. M mode traces were recorded on paper and later digitised to derive total atrioventricular ring excursion, peak lengthening rate, and peak shortening rate. These data were averaged and compared with control data for the normal RV and left ventricle (LV).RESULTSRV total atrioventricular ring excursion was lower than that for the RV (p < 0.0001) or LV (p < 0.005) of controls. Peak lengthening rate was lower than the normal RV (p < 0.0001) and LV (p < 0.0001) rates. Furthermore, peak shortening rate was less than that of normal RV (p < 0.0001) and normal LV (p < 0.005) controls.CONCLUSIONSystemic RV long axis function is notably reduced compared with that of either the normal subpulmonary RV or the systemic LV. This presumably reflects the response of the predominantly longitudinally arranged myocardial fibres to increased afterload. However, such measurements may provide a more sensitive marker for progressive changes in global function during long term follow up.
Magnesium causes nitric oxide independent coronary artery vasodilation in humans
Authors: Teragawa H , Kato M , Yamagata T , Matsuura H , Kajiyama G 
Published: July 2021

OBJECTIVETo determine how magnesium affects human coronary arteries and whether endothelium derived nitric oxide (EDNO) is involved in the coronary arterial response to magnesium.DESIGNQuantitative coronary angiography and Doppler flow velocity measurements were used to determine the effects of the nitric oxide synthase inhibitorNG-monomethyl-L-arginine (L-NMMA) on magnesium induced dilation of the epicardial and resistance coronary arteries.SETTINGHiroshima University Hospital a tertiary cardiology centre.PATIENTS17 patients with angiographically normal coronary arteries.INTERVENTIONSMagnesium sulfate (MgSO4) (0.02 mmol/min and 0.2 mmol/min) was infused for two minutes into the left coronary ostium before and after intracoronary infusion of L-NMMA.MAIN OUTCOME MEASURESDiameter of the proximal and distal segments of the epicardial coronary arteries and coronary blood flow.RESULTSAt a dose of 0.02 mmol/min, MgSO4 did not affect the coronary arteries. At a dose of 0.2 mmol/min, MgSO4 caused coronary artery dilation (mean (SEM) proximal diameter 3.00 (0.09) to 3.11 (0.09) mm; distal 1.64 (0.06) to 1.77 (0.07) mm) and increased coronary blood flow (79.3 (7.5) to 101.4 (9.9) ml/min, p < 0.001 vbaseline for all). MgSO4 increased the changes in these parameters after the infusion of L-NMMA (p < 0.001v baseline).CONCLUSIONSMagnesium dilates both the epicardial and resistance coronary arteries in humans. Furthermore, the coronary arterial response to magnesium is dose dependent and independent of EDNO.
GCH1 induces immunosuppression through metabolic reprogramming and IDO1 upregulation in triple-negative breast cancer
Authors: Wei Jin-Li , Wu Si-Yu , Yang Yun-Song , Xiao Yi , Jin Xi , Xu Xiao-En , Hu Xin , Li Da-Qiang , Jiang Yi-Zhou , Shao Zhi-Ming 
Published: July 2021

PurposeRegulatory T cells (Tregs) heavily infiltrate triple-negative breast cancer (TNBC), and their accumulation is affected by the metabolic reprogramming in cancer cells. In the present study, we sought to identify cancer cell-intrinsic metabolic modulators correlating with Tregs infiltration in TNBC.Experimental designUsing the RNA-sequencing data from our institute (n=360) and the Molecular Taxonomy of Breast Cancer International Consortium TNBC cohort (n=320), we calculated the abundance of Tregs in each sample and evaluated the correlation between gene expression levels and Tregs infiltration. Then, in vivo and in vitro experiments were performed to verify the correlation and explore the underlying mechanism.ResultsWe revealed that GTP cyclohydrolase 1 (GCH1) expression was positively correlated with Tregs infiltration and high GCH1 expression was associated with reduced overall survival in TNBC. In vivo and in vitro experiments showed that GCH1 increased Tregs infiltration, decreased apoptosis, and elevated the programmed cell death-1 (PD-1)-positive fraction. Metabolomics analysis indicated that GCH1 overexpression reprogrammed tryptophan metabolism, resulting in L-5-hydroxytryptophan (5-HTP) accumulation in the cytoplasm accompanied by kynurenine accumulation and tryptophan reduction in the supernatant. Subsequently, aryl hydrocarbon receptor, activated by 5-HTP, bound to the promoter of indoleamine 2,3-dioxygenase 1 (IDO1) and thus enhanced the transcription of IDO1. Furthermore, the inhibition of GCH1 by 2,4-diamino-6-hydroxypyrimidine (DAHP) decreased IDO1 expression, attenuated tumor growth, and enhanced the tumor response to PD-1 blockade immunotherapy.ConclusionsTumor-cell-intrinsic GCH1 induced immunosuppression through metabolic reprogramming and IDO1 upregulation in TNBC. Inhibition of GCH1 by DAHP serves as a potential immunometabolic strategy in TNBC.
Home dampness, current allergic diseases, and respiratory infections among young adults
Authors: Kilpeläinen M , Terho E O , Helenius H , Koskenvuo M 
Published: July 2021

BACKGROUNDThe relation between home dampness and respiratory symptoms among adults is well confirmed, but data on specific allergic diseases and respiratory infections is more limited. Individual factors that may enhance susceptibility to the effects of home dampness are mainly unknown.METHODSThe association between home dampness and current physician diagnosed asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, common colds, and bacterial respiratory infections was studied in a questionnaire survey of 10 667 Finnish first year university students aged 18–25 years. The dampness categories analysed were visible mould and visible mould or damp stains or water damage during the last year. In multivariate analyses adjustment was made for parental education, active and passive smoking, type and place of residence, pets, and wall to wall carpets. The interaction effect of atopic heredity and dampness was investigated.RESULTSVisible mould or damp stains or water damage was reported by 15.0% of the respondents. In multivariate models there was a positive association between home dampness and current asthma, allergic rhinitis, and atopic dermatitis, as well as common colds ⩾4 times per year and other respiratory infections, but not between home dampness and allergic conjunctivitis. The strongest association was found between exposure to visible mould and asthma (OR 2.21, 95% CI 1.48 to 3.28) and common colds (OR 1.49, 95% CI 1.18 to 1.87). The risk of current asthma in damp homes was highest among subjects with atopic heredity.CONCLUSIONSThe risk of current asthma, allergic rhinitis, and atopic dermatitis was higher in damp homes. Of the respiratory infections, the risk of common colds was most clearly increased.
Enhanced survival of lung granulocytes in an animal model of asthma: evidence for a role of GM-CSF activated STAT5 signalling pathway
Authors: Turlej R K , Fiévez L , Sandersen C F , Dogné S , Kirschvink N , Lekeux P , Bureau F 
Published: July 2021

BACKGROUNDAs granulocyte/macrophage colony stimulating factor (GM-CSF) mediated delay of granulocyte apoptosis contributes to the accumulation of inflammatory cells at the site of inflammation in many diseases, we sought to determine whether asthma is also associated with a GM-CSF dependent increase in lung granulocyte survival. Moreover, because GM-CSF mediates its effects through activation of signal transducer and activator of transcription 5 (STAT5), we also investigated the potential role of STAT5 in allergic inflammation.METHODSBlood granulocytes were recovered from six healthy and six heaves affected horses, a model of asthma. Lung granulocytes were obtained by bronchoalveolar lavage (BAL) from the same horses. Granulocytes were cultured in the presence or absence of anti-GM-CSF receptor antibodies for different times and apoptosis was determined using the Annexin-V/propidium iodide detection method. Nuclear protein extracts from cultured granulocytes were analysed for STAT5 binding activity by electrophoretic mobility shift assay.RESULTSBAL fluid granulocytes from heaves affected horses demonstrated a significant delay in apoptosis compared with blood granulocytes from the same horses and blood and BAL fluid granulocytes from healthy horses. Conversely, the rate of apoptosis in blood granulocytes from healthy and heaves affected horses was comparable. The enhanced survival of BAL fluid granulocytes from affected horses was suppressed in the presence of antibodies directed against GM-CSF receptors. Increased levels of active STAT5 were found in BAL fluid granulocytes from heaves affected horses and were markedly reduced after treatment with anti-GM-CSF receptor antibodies.CONCLUSIONSThese data indicate that granulocyte survival is enhanced in the lung of heaves affected horses and suggest a role for a GM-CSF activated STAT5 pathway in delaying apoptosis of lung granulocytes in this model of asthma.
Aerosolised iloprost improves pulmonary haemodynamics in patients with primary pulmonary hypertension receiving continuous epoprostenol treatment
Authors: Petkov V , Ziesche R , Mosgoeller W , Schenk P , Vonbank K , Stiebellehner L , Raderer M , Brunner Ch , Kneussl M , Block L H 
Published: July 2021

BACKGROUNDContinuous intravenous treatment with epoprostenol significantly improves pulmonary haemodynamics and survival in patients with primary pulmonary hypertension (PPH). Its beneficial effect, however, may be blunted due to adverse effects such as catheter sepsis and systemic hypotension. Recent investigations have shown that inhaled iloprost is effective in the treatment of PPH. Based on their different pharmacokinetics, we hypothesised that the combination of intravenous epoprostenol and inhaled iloprost would be more efficacious than epoprostenol alone during acute testing in patients with PPH.METHODSThe effect of a single dose of inhaled iloprost (30 μg total over 15 minutes) on pulmonary haemodynamics was examined in eight patients with PPH (initial non-responders to nitric oxide) who had considerable adverse effects during treatment with epoprostenol.RESULTSThe combination of inhaled iloprost and intravenous epoprostenol significantly improved mean pulmonary artery pressure (MPAP), cardiac index (CI), mixed venous oxygen saturation (Svo2), and systemic arterial oxygen pressure (Pao2) compared with epoprostenol treatment alone. Mean systemic arterial pressure (MSAP) and pulmonary capillary wedge pressure (PCWP) remained unchanged.CONCLUSIONSThe pulmonary vasoreactivity shown by additional iloprost inhalation during effective epoprostenol treatment suggests that an improvement of treatment for pulmonary hypertension may be possible by combining vasoactive substances.
Excited states of holographic superconductors with backreaction
Authors: Wang Yong-Qiang , Li Hong-Bo , Liu Yu-Xiao , Zhong Yin 
Published: July 2021

AbstractIn this paper we investigate the model of the anti-de Sitter gravity coupled to a Maxwell field and a free, complex scalar field, and construct a fully back-reacted holographic model of superconductor with excited states. With the fixed charge q, there exist a series of excited states of holographic superconductor with the corresponding critical chemical potentials. The condensates as functions of the temperature for the two operators $${\mathcal {O}}_1$$

O
1

and $${\mathcal {O}}_2$$

O
2

of excited states are also studied. For the optical conductivity in the excited states, we find that there exist the additional peaks in the imaginary and real parts of the conductivity. Moreover, the number of peaks corresponding to n-th excited state is equal to n.
Dependence of charge-exchange efficiency on cooling water temperature of a beam transport line
Authors: Yamamoto Kazami , Hatakeyama Shuichiro , Saha Pranab Kumar , Moriya Katsuhiro , Okabe Kota , Yoshimoto Masahiro , Nakanoya Takamitsu , Fujirai Kosuke , Yamazaki Yoshio , Suganuma Kazuaki 
Published: July 2021

AbstractThe 3-GeV Rapid Cycling Synchrotron at the Japan Proton Accelerator Research Complex supplies a high-intensity proton beam for neutron experiments and to the Main Ring synchrotron. Various parameters are monitored to achieve a stable operation, and it was found that the oscillations of the charge-exchange efficiency and cooling water temperature were synchronized. We evaluated the orbit fluctuations at the injection point using a beam current of the injection dump, which is proportional to the number of particles that miss the foil and fail in the charge exchange, and profile of the injection beam. The total width of the fluctuations was approximately 0.072 mm. This value is negligible from the user operation viewpoint as our existing beam position monitors cannot detect such a small signal deviation. This displacement corresponds to a 1.63 × 10− 5 variation in the dipole magnetic field. Conversely, the magnetic field variation in the L3BT dipole magnet, which was estimated by the temperature change directly, is 4.08 × 10− 5. This result suggested that the change in the cooling water temperature is one of the major causes of the efficiency fluctuation.
Global models for radio-frequency ion thrusters
Authors: Dietz Patrick , Reeh Andreas , Keil Konstantin , Holste Kristof , Probst Uwe , Klar Peter J. , Volkmar Chris 
Published: July 2021

AbstractThe emerging “new space” age strengthens the importance of rapid development and qualification procedures of electric engines and their peripheral devices. A key element is the reliable simulation of the thrusters and their supply units on short time scales. Global models seem to be well suited for this purpose. In this article, three variants of global models are presented and validated by comparison with experimental results. All models show excellent agreement with experiment, illustrating the strength of this modeling approach. Future developments of radio-frequency ion thrusters can be significantly accelerated with the help of these global models.
Statins for Prostate Cancer: When and How Much?
Authors: Murtola Teemu J. , Siltari Aino 
Published: July 2021

Abstract

Statins have plausible biological effects against prostate cancer cells and are associated with improved disease-specific mortality. In current randomized placebo-controlled trial, low-dose atorvastatin caused no difference in relapses after radical prostatectomy in Asian men. Future trials should study higher statin doses at later disease stages with survival as the endpoint.
See related article by Jeong et al., p. 5004
Genetic Screens Identify a Context-Specific PI3K/p27Kip1 Node Driving Extrahepatic Biliary Cancer
Authors: Falcomatà Chiara , Bärthel Stefanie , Ulrich Angelika , Diersch Sandra , Veltkamp Christian , Rad Lena , Boniolo Fabio , Solar Myriam , Steiger Katja , Seidler Barbara , Zukowska Magdalena , Madej Joanna , Wang Mingsong , Öllinger Rupert , Maresch Roman , Barenboim Maxim , Eser Stefan , Tschurtschenthaler Markus , Mehrabi Arianeb , Roessler Stephanie , Goeppert Benjamin , Kind Alexander , Schnieke Angelika , Robles Maria S. , Bradley Allan , Schmid Roland M. , Schmidt-Supprian Marc , Reichert Maximilian , Weichert Wilko , Sansom Owen J. , Morton Jennifer P. , Rad Roland , Schneider Günter , Saur Dieter 
Published: July 2021

AbstractBiliary tract cancer ranks among the most lethal human malignancies, representing an unmet clinical need. Its abysmal prognosis is tied to an increasing incidence and a fundamental lack of mechanistic knowledge regarding the molecular basis of the disease. Here, we show that the Pdx1-positive extrahepatic biliary epithelium is highly susceptible toward transformation by activated PIK3CAH1047R but refractory to oncogenic KrasG12D. Using genome-wide transposon screens and genetic loss-of-function experiments, we discover context-dependent genetic interactions that drive extrahepatic cholangiocarcinoma (ECC) and show that PI3K signaling output strength and repression of the tumor suppressor p27Kip1 are critical context-specific determinants of tumor formation. This contrasts with the pancreas, where oncogenic Kras in concert with p53 loss is a key cancer driver. Notably, inactivation of p27Kip1 permits KrasG12D-driven ECC development. These studies provide a mechanistic link between PI3K signaling, tissue-specific tumor suppressor barriers, and ECC pathogenesis, and present a novel genetic model of autochthonous ECC and genes driving this highly lethal tumor subtype.Significance:We used the first genetically engineered mouse model for extrahepatic bile duct carcinoma to identify cancer genes by genome-wide transposon-based mutagenesis screening. Thereby, we show that PI3K signaling output strength and p27Kip1 function are critical determinants for context-specific ECC formation.This article is highlighted in the In This Issue feature, p. 2945