bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seeking diagnostic and prognostic biomarkers for childhood bacterial pneumonia in sub-Saharan Africa: study protocol for an observational study
Authors: Valim Clarissa , Olatunji Yekin Ajauoi , Isa Yasir Shitu , Salaudeen Rasheed , Golam Sarwar , Knol Edward F , Kanyi Sheriffo , Jammeh Abdoulie , Bassat Quique , de Jager Wilco , Diaz Alejandro A , Wiegand Roger C , Ramirez Julio , Moses Marsha A , D’Alessandro Umberto , Hibberd Patricia L , Mackenzie Grant A 
Published: September 2021

IntroductionClinically diagnosed pneumonia in children is a leading cause of paediatric hospitalisation and mortality. The aetiology is usually bacterial or viral, but malaria can cause a syndrome indistinguishable from clinical pneumonia. There is no method with high sensitivity to detect a bacterial infection in these patients and, as result, antibiotics are frequently overprescribed. Conversely, unrecognised concomitant bacterial infection in patients with malarial infections occur with omission of antibiotic therapy from patients with bacterial infections. Previously, we identified two combinations of blood proteins with 96% sensitivity and 86% specificity for detecting bacterial disease. The current project aimed to validate and improve these combinations by evaluating additional biomarkers in paediatric patients with clinical pneumonia. Our goal was to describe combinations of a limited number of proteins with high sensitivity and specificity for bacterial infection to be incorporated in future point-of-care tests. Furthermore, we seek to explore signatures to prognosticate clinical pneumonia.Methods and analysisPatients (n=900) aged 2–59 months presenting with clinical pneumonia at two Gambian hospitals will be enrolled and classified according to criteria for definitive bacterial aetiology (based on microbiological tests and chest radiographs). We will measure proteins at admission using Luminex-based immunoassays in 90 children with definitive and 160 with probable bacterial aetiology, and 160 children classified according to the prognosis of their disease. Previously identified diagnostic signatures will be assessed through accuracy measures. Moreover, we will seek new diagnostic and prognostic signatures through machine learning methods, including support vector machine, penalised regression and classification trees.Ethics and disseminationEthics approval has been obtained from the Gambia Government/Medical Research Council Unit The Gambia Joint Ethics Committee (protocol 1616) and the institutional review board of Boston University Medical Centre (STUDY00000958). Study results will be disseminated to the staff of the study hospitals, in scientific seminars and meetings, and in publications.Trial registration numberH-38462.
Continuation versus discontinuation of aspirin-based antiplatelet therapy for perioperative bleeding and ischaemic events in adults undergoing neurosurgery: protocol for a systematic review and meta-analysis
Authors: Wang Xinyan , Wang Xinxin , Yu Yun , Han Ruquan 
Published: September 2021

IntroductionAntiplatelet therapy is commonly used in primary or secondary prevention of atherosclerotic and thrombotic diseases, such as coronary artery disease, transient ischaemic attack or stroke. Recent studies noted that antiplatelet therapy should be continued perioperatively in patients at high risk of thrombosis and low bleeding risk in orthopaedic, spinal or urological surgery. However, evidence in neurosurgery is lacking. Thus, we aim to conduct a systematic review and meta-analysis to assess whether the continuous use of antiplatelet drugs in neurosurgery increases the risk of perioperative bleeding.Methods and analysisWe will search PubMed, Cochrane Central Register of Controlled Trials and Embase using a strategy that combines the terms aspirin, bleeding/ischaemic and neurosurgery. Two reviewers will independently screen all identified abstracts for eligibility and evaluate the risk of bias of the included studies using the Cochrane risk of bias tool for randomised controlled studies and the Newcastle-Ottawa Scale for observational studies (including cohort studies, case–control studies, case series). Discrepancies will be resolved by consultation with a third researcher. We will conduct a systematic review and meta-analysis. If evidence suggests moderate statistical or clinical heterogeneity, we plan to investigate this heterogeneity by performing subgroup analyses and sensitivity analysis.Ethics and disseminationNo ethics approval will be sought as no original data will be collected for this review. Findings will be disseminated through peer-reviewed publication and conference presentations.PROSPERO registration numberCRD42020202590.
Inflammation and nutrition-based biomarkers in the prognosis of oesophageal cancer: a systematic review and meta-analysis
Authors: Jiang Yan , Xu Dian , Song Huan , Qiu Beibei , Tian Dan , Li Zhongqi , Ji Ye , Wang Jianming 
Published: September 2021

BackgroundAccumulating literature has shown the predictive values of inflammation and nutrition-based biomarkers in the prognosis of oesophageal cancer but with inconsistent findings.MethodWe performed a meta-analysis to systematically evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), C reactive protein-to-albumin ratio (CAR), systemic inflammation index (SII), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS) and modified Glasgow Prognostic Score (mGPS) in oesophageal cancer. The outcome indicators include the overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS). We applied pooled HR, sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the curve together with 95% CI to estimate the predictive accuracy.ResultsA total of 72 studies, including 22 260 patients, were included in the meta-analysis. Elevated NLR, PLR CAR, SII, GPS, mGPS and decreased LMR and PNI were associated with poor OS of oesophageal cancer. A high level of NLR, PLR and GPS was related to poor DFS. A high level of NLR and GPS was related to poor CSS. The summarised AUC of CAR (0.72, 95% CI: 0.68 to 0.75) and mGPS (0.75, 95% CI: 0.71 to 0.78) surpassed any other indicators.ConclusionsClinical indicators such as NLR, PLR, LMR, PNI, SII, CAR, GPS and mGPS have the moderate predictive ability in OS, DFS and CSS of oesophageal cancer. The pretreatment level of CAR and mGPS showed an outstanding prediction value in 5-year OS for oesophageal cancer.
What was the impact of the first wave of COVID-19 on the delivery of care to children and adults with congenital heart disease? A qualitative study using online forums
Authors: Wray Jo , Pagel Christina , Chester Adrian H , Kennedy Fiona , Crowe Sonya 
Published: September 2021

ObjectivesGlobally, healthcare systems have been stretched to the limit by the COVID-19 pandemic. Significant changes have had to be made to the way in which non-COVID-19-related care has been delivered. Our objective was to understand, from the perspective of patients with a chronic, life-long condition (congenital heart disease, CHD) and their parents/carers, the impact of COVID-19 on the delivery of care, how changes were communicated and whether healthcare providers should do anything differently in a subsequent wave of COVID-19 infections.Design and settingQualitative study involving a series of asynchronous discussion forums set up and moderated by three patient charities via their Facebook pages.ParticipantsPatients with CHD and parents/carers of patients with CHD.Main outcome measuresQualitative responses to questions posted on the discussion forums.ResultsThe forums ran over a 6-week period and involved 109 participants. Following thematic analysis, we identified three themes and 10 subthemes related to individual condition-related factors, patient-related factors and health professional/centre factors that may have influenced how patients and parents/carers experienced changes to service delivery as a result of COVID-19. Specifically, respondents reported high levels of disruption to the delivery of care, inconsistent advice and messaging and variable communication from health professionals, with examples of both excellent and very poor experiences of care reported. Uncertainty about follow-up and factors related to the complexity and stability of their condition contributed to anxiety and stress.ConclusionsThe importance of clear, consistent communication cannot be over-estimated. Our findings, while collected in relation to patients with CHD, are not necessarily specific to this population and we believe that they reflect the experiences of many thousands of people with life-long conditions in the UK. Recommendations related to communication, service delivery and support during the pandemic may improve patients’ experience of care and, potentially, their outcomes.
Association of anthropometric indices of obesity with hypertension among public employees in northern Ethiopia: findings from a cross-sectional survey
Authors: Saif-Ur-Rahman KM , Chiang Chifa , Weldegerima Gebremariam Lemlem , Haregot Hilawe Esayas , Hirakawa Yoshihisa , Aoyama Atsuko , Yatsuya Hiroshi 
Published: September 2021

ObjectivesThe burden of hypertension is increasing in low-income countries, including Ethiopia. Obesity is widely known to be associated with hypertension, but different anthropometric indices of obesity might differ in association with hypertension, which is largely unknown in northern Ethiopia.DesignData from our previous cross-sectional epidemiological survey were statistically analysed.SettingPublic employees in the regional capital city in northern Ethiopia.ParticipantsThe data of 1380 participants (823 men and 557 non-pregnant women) aged 25 and 64 years were analysed.Outcome measuresThe presence of hypertension was the outcome measure and multivariable-adjusted logistic regression analyses were used to investigate the association of body mass index (BMI), waist circumference, and waist–hip ratio in men and women separately. The area under the curve (AUC) for three anthropometric indices for discriminating hypertension was also obtained. Separate analyses were conducted for waist circumference and waist–hip ratio analyses further adjusted for BMI.ResultsBMI was linearly associated with hypertension in men (OR for 1 SD increase in BMI 1.45, p=0.001) and women (OR for 1 SD increase in BMI 1.41, p=0.01). The association of waist circumference was independent of BMI both in men (OR for 1 SD increase in waist circumference: 1.74, p=0.002) and women (OR for 1 SD increase in waist circumference: 1.57, p=0.029). The association of waist–hip ratio with hypertension adjusted for BMI was significant in men (OR for 1 SD increase in the waist–hip ratio: 1.46, p<0.001), but was weak and non-significant in women. The AUC for BMI was 0.64 in men and 0.67 in women, while AUC for waist circumference was 0.69 both in men and women.ConclusionsWaist circumference was associated with hypertension independent of BMI among public employees in northern Ethiopia.
Phase II study of pembrolizumab in refractory esophageal cancer with correlates of response and survival
Authors: de Klerk Leonie K , Patel Anuj K , Derks Sarah , Pectasides Eirini , Augustin Jeremy , Uduman Mohamed , Raman Nihal , Akarca Fahire G , McCleary Nadine J , Cleary James M , Rubinson Douglas A , Clark Jeffrey W , Fitzpatrick Bridget , Brais Lauren K , Cavanaugh Megan E , Rode Amanda J , Jean Melissa G , Lizotte Patrick H , Nazzaro Matthew J , Severgnini Mariano , Zheng Hui , Fuchs Charles S , Enzinger Peter C , Bass Adam J 
Published: September 2021

BackgroundImmune checkpoint inhibitors have revolutionized cancer treatment, but the benefits in refractory patients with esophageal cancer have been modest. Predictors of response as well as new targets for novel therapeutic combinations are needed. In this phase 2 clinical trial, we tested single-agent pembrolizumab in patients with advanced esophageal cancer, who received at least one prior line of therapy.MethodsPembrolizumab 200 mg every 3 weeks was tested in 49 patients with refractory esophageal cancer: 39 with adenocarcinoma and 10 with esophageal squamous cell carcinoma. Major endpoints were radiological response by Immune-related Response Evaluation Criteria In Solid Tumors and survival. Tumor samples were evaluated for programmed cell death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), and immune contexture by both NanoString mRNA expression analysis and flow cytometry. Peripheral blood mononuclear cells and a panel of circulating chemokines were also analyzed.ResultsThe overall response rate (ORR) was 8% (4 of 49 patients; 95% CI 2.3% to 19.6%). Median overall survival (OS) was 5.8 months (95% CI 4.0 to 9.5). ORR and OS were not associated with histology. For PD-L1-positive patients, ORR was 13.3% (95% CI 1.7% to 40.5%) and median OS was 7.9 months (95% CI 4.7 to 15.5). A trend toward improved OS was observed in seven patients with a TMB ≥10 mut/Mb (p=0.086). Tumors with a PD-L1 Combined Positive Score ≥1 showed enrichment of LAG3 (p=0.005) and IDO1 (p=0.04) gene expression. Baseline levels of circulating CXCL10, interleukin 2 (IL2) receptor α (IL2RA) and IL6 were associated with survival: CXCL10 favorably, (HR 0.37, p=0.002 (progression-free survival); HR 0.55, p=0.018 (OS)); IL2RA and IL6 unfavorably (HR 1.57, p=0.020 for IL6 (OS); HR 2.36, p=0.025 for IL2RA (OS)).ConclusionsPembrolizumab monotherapy was modestly effective in refractory esophageal cancer. Circulating CXCL10 at baseline appeared to be a robust predictor of response. Other T cell exhaustion markers are upregulated in PD-L1-positive patients, suggesting that immunotherapy combinations such as anti-LAG3/programmed cell death protein 1 (PD-1) or anti-IDO1/PD-1 may be of promise in refractory esophageal cancer.
Loss of host tissue transglutaminase boosts antitumor T cell immunity by altering STAT1/STAT3 phosphorylation in ovarian cancer
Authors: Sima Livia Elena , Chen Siqi , Cardenas Horacio , Zhao Guangyuan , Wang Yinu , Ivan Cristina , Huang Hao , Zhang Bin , Matei Daniela 
Published: September 2021

BackgroundTissue transglutaminase (TG2), an enzyme overexpressed in cancer cells, promotes metastasis and resistance to chemotherapy. Its distinct effects in cancer versus the host compartments have not been elucidated.MethodsHere, by using a TG2-/-syngeneic ovarian cancer mouse model, we assessed the effects of TG2 deficiency in the host tissues on antitumor immunity and tumor progression. Multicolor flow cytometry was used to phenotype immune cell populations in the peritoneal environment. Cancer cells recovered from malignant ascites were characterized by RNA sequencing, proliferation, and apoptosis assays.ResultsWe observed that host TG2 loss delayed tumor growth and ascites accumulation and caused increased infiltration of CD8+T cells and decreased numbers of myeloid cells in the peritoneal fluid. Tumor antigen-specific CD8+T cell cytotoxic responses were enhanced in ascites from TG2-/-versus TG2+/+mice and CD8+T cell depletion caused accelerated ascites accumulation in TG2-/-mice. CD8+T cells from tumor-bearing TG2-/-mice displayed an effector T cell phenotype, differentiated toward effector memory (Tem). Mechanistically, absence of TG2 augmented signals promoting T cell activation, such as increased cytokine-induced STAT1 and attenuated STAT3 phosphorylation in T cells. Additionally, immune-suppressive myeloid cell populations were reduced in the peritoneal milieu of TG2-/-tumor-bearing mice. In response to the more robust immune response caused by loss of TG2, cancer cells growing intraperitoneally exhibited an interferon-γ(IFN-γ) responsive gene signature and underwent apoptosis. In human specimens, stromal, not tumor, TG2 expression correlated indirectly with numbers of tumor-infiltrating lymphocytes.ConclusionsCollectively, our data demonstrate decreased tumor burden, increased activation and effector function of T cells, and loss of immunosuppressive signals in the tumor microenvironment of TG2-/-mice. We propose that TG2 acts as an attenuator of antitumor T cell immunity and is a new immunomodulatory target.
A Sub-1 V Bulk-Driven Rail to Rail Dynamic Voltage Comparator with Enhanced Transconductance
Authors: Joseph George M. , Hameed T. A. Shahul 
Published: September 2021

Reduced voltage head room availability for input signal swing is one of the major bottlenecks in the design of circuits operating with low supply voltages which attracts investigations leading to improvement in the input signal dynamic range of such circuits. Employing bulk-driven MOSFETs (BDMOS) at the input section of the circuit is a popular technique used for increasing the input dynamic range, but the smaller bulk transconductance of the bulk-driven MOSFET degrades the performance of the circuit in comparison with that of a conventional gate-driven counterpart. A double tail voltage comparator employing BDMOS technique offering rail-to-rail input dynamic range and capable of operating at sub-1[Formula: see text]V power supply is presented in this paper. A transconductance improvement scheme is employed for the first time in the literature for a voltage comparator to overcome the major drawbacks associated with the reduced bulk transconductance of BDMOS input transistors and double tail topology permits low voltage operation. The performance parameters of the proposed voltage comparator are comparable to that of conventional gate-driven comparators, with an additional advantage of rail-to-rail input dynamic range. Pre-layout and post-layout simulations were performed in Cadence Virtuoso suite with gpdk 90[Formula: see text]nm library at power supply as low as 0.6[Formula: see text]V. The worst case delay of the proposed circuit is 0.71[Formula: see text]ns and the worst case power consumption of the circuit is 15[Formula: see text]uW. The circuit consumes a silicon area of 33[Formula: see text]μm[Formula: see text]46[Formula: see text]μm. An analytical model of the transconductance enhancement technique and delay of the proposed comparator are also presented.
Large deviation principles for a 2D stochastic Allen–Cahn–Navier–Stokes driven by jump noise
Authors: Tachim Medjo Theodore 
Published: September 2021

In this paper, we derive a large deviation principle for a stochastic 2D Allen–Cahn–Navier–Stokes system with a multiplicative noise of Lévy type. The model consists of the Navier–Stokes equations for the velocity, coupled with a Allen–Cahn system for the order (phase) parameter. The proof is based on the weak convergence method introduced in [A. Budhiraja, P. Dupuis and V. Maroulas, Variational representations for continuous time processes, Ann. Inst. Henri Poincar Probab. Stat. 47(3) (2011) 725747].
Immediate effects of manual hyperinflation on cardiorespiratory function and sputum clearance in mechanically ventilated pediatric patients: A randomized crossover trial
Authors: Luadsri Tawatchai , Boonpitak Jaturon , Pongdech-Udom Kultida , Sukpom Patnuch , Chidnok Weerapong 
Published: September 2021

Background: In developing countries, lower respiratory tract infection is a major cause of death in children, with severely ill patients being admitted to the critical-care unit. While physical therapists commonly use the manual hyperinflation (MHI) technique for secretion mass clearance in critical-care patients, its efficacy has not been determined in pediatric patients. Objective: This study investigated the effects of MHI on secretion mass clearance and cardiorespiratory responses in pediatric patients undergoing mechanical ventilation. Methods: A total of 12 intubated and mechanically ventilated pediatric patients were included in this study. At the same time of the day, the patients received two randomly ordered physical therapy treatments (MHI with suction and suction alone) from a trained physical therapist, with a washout period of 4[Formula: see text]h provided between interventions. Results: The MHI treatment increased the tidal volume [[Formula: see text]; 1.2[Formula: see text]mL/kg (95% CI, 0.8–1.5)] and static lung compliance [[Formula: see text]; 3.7[Formula: see text]mL/cmH2O (95% CI, 2.6–4.8)] immediately post-intervention compared with the baseline ([Formula: see text]). Moreover, the MHI with suction induced higher [Formula: see text] [1.4[Formula: see text]mL/kg (95% CI, 0.8–2.1)] and [Formula: see text] [3.4[Formula: see text]mL/cmH2O (95% CI, 2.1–4.7)] compared with the suction-alone intervention. In addition, the secretion mass [0.7[Formula: see text]g (95% CI, 0.6–0.8)] was greater in MHI with suction compared with suction alone ([Formula: see text]). However, there was no difference in peak inspiratory pressure, mean airway pressure, respiratory rate, heart rate, blood pressure, mean arterial blood pressure or oxygen saturation ([Formula: see text]) between interventions. Conclusions: MHI can improve [Formula: see text], [Formula: see text] and secretion mass without inducing adverse hemodynamic effects upon the pediatric patients requiring mechanical ventilation.
Simultaneous Electrochemical Detection of Ascorbic Acid, Dopamine and Uric Acid Using the Composite Materials of Fe3O4 and Nitrogen Self-Doped Sunflower Plate-Derived Carbon
Authors: Gao Panpan , Huang Yaqi , Zhang Yaoyao , Sun Qiaoqian , Ruan Shaojie , Yin Wei , Pu Hongchen , Yin Miao , Fa Huanbao 
Published: September 2021

A simple pyrolysis, activation and hydrothermal method was utilized to synthesize composite materials (Fe3O4/SFP) of ferroferric oxide and nitrogen self-doped sunflower plate-derived carbon for the simultaneous electrochemical sensing of ascorbic acid (AA), dopamine (DA) and uric acid (UA). The Fe3O4/SFP had synergistic catalytic effect on target molecules, and the oxidation peak potential of AA, DA and UA was well distinguished in the differential pulse voltammetry determination. Under the optimal conditions, the linear response ranges of AA, DA and UA are 3–150[Formula: see text][Formula: see text]M, 5–450[Formula: see text][Formula: see text]M and 15–1200[Formula: see text][Formula: see text]M, respectively. The detection limits of AA, DA and UA ([Formula: see text]/[Formula: see text]) are 1.0[Formula: see text][Formula: see text]M, 0.4[Formula: see text][Formula: see text]M and 1.48[Formula: see text][Formula: see text]M, respectively, and the sensitivity is 1.87[Formula: see text][Formula: see text] (3–20[Formula: see text][Formula: see text]M) and 0.64[Formula: see text][Formula: see text] (20–150[Formula: see text][Formula: see text]M) for AA, 3.90[Formula: see text][Formula: see text] (5–20[Formula: see text][Formula: see text]M) and 1.21[Formula: see text][Formula: see text] (20–450[Formula: see text][Formula: see text]M) for DA and 1.12[Formula: see text][Formula: see text] (15–100[Formula: see text][Formula: see text]M) and 0.31[Formula: see text][Formula: see text] (100–1200[Formula: see text][Formula: see text]M) for UA. In addition, satisfactory results have been obtained for the determination of AA, DA and UA in normal human serum, which provides a new research direction for the construction of electrochemical sensors in the future.