bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of treatment effect modification by biomarkers measured pre- and post-randomization in the presence of non-monotone missingness
Authors: Zhuang Yingying , Huang Ying , Gilbert Peter B 
Published: September 2020

Summary
In vaccine studies, an important research question is to study effect modification of clinical treatment efficacy by intermediate biomarker-based principal strata. In settings where participants entering a trial may have prior exposure and therefore variable baseline biomarker values, clinical treatment efficacy may further depend jointly on a biomarker measured at baseline and measured at a fixed time after vaccination. This makes it important to conduct a bivariate effect modification analysis by both the intermediate biomarker-based principal strata and the baseline biomarker values. Existing research allows this assessment if the sampling of baseline and intermediate biomarkers follows a monotone pattern, i.e., if participants who have the biomarker measured post-randomization would also have the biomarker measured at baseline. However, additional complications in study design could happen in practice. For example, in a dengue correlates study, baseline biomarker values were only available from a fraction of participants who have biomarkers measured post-randomization. How to conduct the bivariate effect modification analysis in these studies remains an open research question. In this article, we propose approaches for bivariate effect modification analysis in the complicated sampling design based on an estimated likelihood framework. We demonstrate advantages of the proposed method over existing methods through numerical studies and illustrate our method with data sets from two phase 3 dengue vaccine efficacy trials.
‘Inspiring Conversations’: A Comparative Analysis of the Involvement of Experts by Experience in Italian and Scottish Social Work Education
Authors: Cabiati Elena , Levy Susan 
Published: September 2020

Abstract
The involvement of service users and carers, Experts by Experience (EBE), in social work education at the Catholic University of Milan, Italy, and the University of Dundee, Scotland, is rooted and connected epistemologically and pedagogically. Differences emerge in how these roots are manifest in the models of EBE involvement adopted in the two universities. This article explores these similarities and differences through discussion of the different models of EBE involvement in use at the two European universities, and thus provides a comparative European insight into approaches, experiences and impact of EBE involvement in social work education. The authors contextualise the pedagogy and core values underpinning EBE involvement and introduce the concept of ‘inspiring conversations’. The comparative analysis is centred on five areas of EBE involvement in social work education: context and types of involvement; recruitment of EBE; roles and responsibilities of EBE; resource implications; and impact and outcomes of involvement. The article calls for a focus on ‘Coherence’, ‘Prudence’ and ‘Sustainability’ as a foundation for other universities to enhance their social work programmes through cultivating EBE involvement to co-create knowledge to inform future innovative practice.
Quality Assessment of Sitopaladi Churna Using High-Performance Liquid Chromatography Coupled with Multivariate Analysis
Authors: Patel Nikunj D , Prajapati Prajesh N , Kanaki Niranjan S 
Published: September 2020

Abstract
“Sitopaladi churna,” a well-known formulation of Ayurveda, is prescribed to treat the disease like Bronchitis, Pneumonia, allergic conditions, viral infection of the respiratory tract and as a natural antioxidant. A novel method based on reversed-phase high-performance liquid chromatography (RP-HPLC) coupled to photodiode array detector was established and validated for sitopaladi churna. Here, HPLC fingerprints data obtained for 28 samples including standard sample were then treated to chemometric analysis like principal component analysis and hierarchical clustering analysis for further analysis to evaluate the differences in market samples of sitopaladi churna. Additionally, one major marker compound, piperine was quantified and it also facilitated for relative retention time. The simulative mean spectrum was also generated. The validation results showed that the developed method was simple, precise and stable. Thus, the developed chromatographic method adjoined with multivariate analysis can be used as an efficient and practical approach for quality assessment of sitopaladi churna.
Diagnostic Value of Clinical Features to Distinguish Enteric Fever From Other Febrile Illnesses in Bangladesh, Nepal, and Pakistan
Authors: Aiemjoy Kristen , Tamrakar Dipesh , Saha Shampa , Naga Shiva R , Yu Alexander T , Longley Ashley , Date Kashmira , Hemlock Caitlin , Qamar Farah N , Saha Samir K , Luby Stephen P , Garrett Denise O , Andrews Jason R , Bogoch Isaac I 
Published: September 2020

Abstract

Background
Enteric fever, a bacterial infection caused by Salmonella enterica serotypes Typhi and Paratyphi A, frequently presents as a nonlocalizing febrile illness that is difficult to distinguish from other infectious causes of fever. Blood culture is not widely available in endemic settings and, even when available, results can take up to 5 days. We evaluated the diagnostic performance of clinical features, including both reported symptoms and clinical signs, of enteric fever among patients participating in the Surveillance for Enteric Fever in Asia Project (SEAP), a 3-year surveillance study in Bangladesh, Nepal, and Pakistan.

Methods
Outpatients presenting with ≥3 consecutive days of reported fever and inpatients with clinically suspected enteric fever from all 6 SEAP study hospitals were eligible to participate. We evaluated the diagnostic performance of select clinical features against blood culture results among outpatients using mixed-effect regression models with a random effect for study site hospital. We also compared the clinical features of S. Typhi to S. Paratyphi A among both outpatients and inpatients.

Results
We enrolled 20 899 outpatients, of whom 2116 (10.1%) had positive blood cultures for S. Typhi and 297 (1.4%) had positive cultures for S. Paratyphi A. The sensitivity of absence of cough was the highest among all evaluated features, at 65.5% (95% confidence interval [CI], 55.0–74.7), followed by measured fever at presentation at 59.0% (95% CI, 51.6–65.9) and being unable to complete normal activities for 3 or more days at 51.0% (95% CI, 23.8–77.6). A combined case definition of 3 or more consecutive days of reported fever and 1 or more of the following (a) either the absence of cough, (b) fever at presentation, or (c) 3 or more consecutive days of being unable to conduct usual activity--yielded a sensitivity of 94.6% (95% CI, 93.4–95.5) and specificity of 13.6% (95% CI, 9.8–17.5).

Conclusions
Clinical features do not accurately distinguish blood culture–confirmed enteric fever from other febrile syndromes. Rapid, affordable, and accurate diagnostics are urgently needed, particularly in settings with limited or no blood culture capacity.
Modifiable Risk Factors for the Emergence of Ceftolozane-tazobactam Resistance
Authors: Tamma Pranita D , Beisken Stephan , Bergman Yehudit , Posch Andreas E , Avdic Edina , Sharara Sima L , Cosgrove Sara E , Simner Patricia J 
Published: September 2020

Abstract

Background
Ceftolozane-tazobactam (TOL-TAZ) affords broad coverage against Pseudomonas aeruginosa. Regrettably, TOL-TAZ resistance has been reported. We sought to identify modifiable risk factors that may reduce the emergence of TOL-TAZ resistance.

Methods
Twenty-eight consecutive patients infected with carbapenem-resistant P. aeruginosa isolates susceptible to TOL-TAZ, treated with ≥72 hours of TOL-TAZ , and with P. aeruginosa isolates available both before and after TOL-TAZ exposure between January 2018 and December 2019 in Baltimore, Maryland, were included. Cases were defined as patients with at least a 4-fold increase in P. aeruginosa TOL-TAZ MICs after exposure to TOL-TAZ. Independent risk factors for the emergence of TOL-TAZ resistance comparing cases and controls were investigated using logistic regression. Whole genome sequencing of paired isolates was used to identify mechanisms of resistance that emerged during TOL-TAZ therapy.

Results
Fourteen patients (50%) had P. aeruginosa isolates which developed at least a 4-fold increase in TOL-TAZ MICs(ie, cases). Cases were more likely to have inadequate source control (29% vs 0%, P = .04) and were less likely to receive TOL-TAZ as an extended 3-hour infusion (0% vs 29%; P = .04). Eighty-six percent of index isolates susceptible to ceftazidime-avibactam (CAZ-AVI) had subsequent P. aeruginosa isolates with high-level resistance to CAZ-AVI, after TOL-TAZ exposure and without any CAZ-AVI exposure. Common mutations identified in TOL-TAZ resistant isolates involved AmpC, a known binding site for both ceftolozane and ceftazidime, and DNA polymerase.

Conclusions
Due to our small sample size, our results remain exploratory but forewarn of the potential emergence of TOL-TAZ resistance during therapy and suggest extending TOL-TAZ infusions may be protective. Larger studies are needed to investigate this association.
Primary HPV and Molecular Cervical Cancer Screening in US Women Living With Human Immunodeficiency Virus
Authors: Strickler Howard D , Keller Marla J , Hessol Nancy A , Eltoum Isam-Eldin , Einstein Mark H , Castle Philip E , Massad L Stewart , Flowers Lisa , Rahangdale Lisa , Atrio Jessica M , Ramirez Catalina , Minkoff Howard , Adimora Adaora A , Ofotokun Igho , Colie Christine , Huchko Megan J , Fischl Margaret , Wright Rodney , D’Souza Gypsyamber , Leider Jason , Diaz Olga , Sanchez-Keeland Lorraine , Shrestha Sadeep , Xie Xianhong , Xue Xiaonan , Anastos Kathryn , Palefsky Joel M , Burk Robert D 
Published: September 2020

Abstract

Background
Primary human papillomavirus (HPV) screening (PHS) utilizes oncogenic human papillomavirus (oncHPV) testing as the initial cervical cancer screening method and typically, if positive, additional reflex-triage (eg, HPV16/18-genotyping, Pap testing). While US guidelines support PHS usage in the general population, PHS has been little studied in women living with HIV (WLWH).

Methods
We enrolled n = 865 WLWH (323 from the Women’s Interagency HIV Study [WIHS] and 542 from WIHS-affiliated colposcopy clinics). All participants underwent Pap and oncHPV testing, including HPV16/18-genotyping. WIHS WLWH who tested oncHPV[+] or had cytologic atypical squamous cells of undetermined significance or worse (ASC-US+) underwent colposcopy, as did a random 21% of WLWH who were oncHPV[−]/Pap[−] (controls). Most participants additionally underwent p16/Ki-67 immunocytochemistry.

Results
Mean age was 46 years, median CD4 was 592 cells/µL, 95% used antiretroviral therapy. Seventy WLWH had histologically-determined cervical intraepithelial neoplasia grade 2 or greater (CIN-2+), of which 33 were defined as precancer (ie, [i] CIN-3+ or [ii] CIN-2 if concurrent with cytologic high grade squamous intraepithelial lesions [HSILs]). PHS had 87% sensitivity (Se) for precancer, 9% positive predictive value (PPV), and a 35% colposcopy referral rate (Colpo). “PHS with reflex HPV16/18-genotyping and Pap testing” had 84% Se, 16% PPV, 30% Colpo. PHS with only HPV16/18-genotyping had 24% Colpo. “Concurrent oncHPV and Pap Testing” (Co-Testing) had 91% Se, 12% PPV, 40% Colpo. p16/Ki-67 immunochemistry had the highest PPV, 20%, but 13% specimen inadequacy.

Conclusions
PHS with reflex HPV16/18-genotyping had fewer unnecessary colposcopies and (if confirmed) could be a potential alternative to Co-Testing in WLWH.
Healthcare Utilization Patterns for Acute Febrile Illness in Bangladesh, Nepal, and Pakistan: Results from the Surveillance for Enteric Fever in Asia Project
Authors: Andrews Jason R , Vaidya Krista , Saha Shampa , Yousafzai Mohammad Tahir , Hemlock Caitlin , Longley Ashley , Aiemjoy Kristen , Yu Alexander T , Bogoch Isaac I , Tamrakar Dipesh , Date Kashmira , Saha Samir K , Garrett Denise O , Luby Stephen P , Qamar Farah 
Published: September 2020

Abstract

Background
Characterizing healthcare-seeking patterns for acute febrile illness is critical for generating population-based enteric fever incidence estimates from facility-based surveillance data.

Methods
We used a hybrid model in the Surveillance for Enteric Fever in Asia Project (SEAP) to assess incidence of enteric fever at 6 study hospitals in 3 countries. We recruited individuals presenting to the hospitals and obtained blood cultures to evaluate for enteric fever. For this analysis, we undertook cluster random household surveys in Dhaka, Bangladesh (2 sites); Karachi, Pakistan; Kathmandu, Nepal; and Kavrepalanchok, Nepal between January 2017 and February 2019, to ascertain care-seeking behavior for individuals with 1) fever for ≥3 consecutive days within the past 8 weeks; or 2) fever resulting in hospitalization within the past year. We also collected data about disease severity and household demographics and assets. We used mixed-effect multivariable logistic regression models to identify determinants of healthcare seeking at study hospitals and determinants of culture-confirmed enteric fever.

Results
We enrolled 31 841 households (53 926 children) in Bangladesh, 25 510 households (84 196 children and adults) in Nepal, and 21 310 households (108 031 children and adults) in Pakistan. Children &lt;5 years were most likely to be taken to the study hospitals for febrile illness at all sites. Household wealth was positively correlated with healthcare seeking in 4 of 5 study sites, and at least one marker of disease severity was positively associated with healthcare seeking in 3 of 5 catchment areas. Wealth and disease severity were variably predictive of blood culture-confirmed enteric fever.

Conclusions
Age, household wealth, and disease severity are important determinants of healthcare seeking for acute febrile illness and enteric fever risk in these communities, and should be incorporated into estimation models for enteric fever incidence.
Challenges to the International Institutional Order
Authors: Dai Xinyuan 
Published: September 2020

Abstract
Witnessing power shifts among major countries in the world, scholars and policymakers alike are confronted with crucial questions about the international institutional order: Do power shifts expedite the collapse of the order? Who are its major challengers, and why? This article tackles these issues, drawing on rationalist theories of international institutions that include both realist and neoliberal thinking. I analyse how the making of the international institutional order, along with its evolution, informs us of the sources of challenges to that order. Accordingly, I explain why the country most powerful in making the international institutional order—thus the apparent beneficiary of that order—ends up nursing so many grievances against it. I illustrate this thesis in the areas of collective security, international trade, and democracy promotion. This article contributes to important debates on global governance and raises policy implications for the rewriting of international rules.
Tyrosine kinase inhibitor-induced hypertension—marker of anti-tumour treatment efficacy or cardiovascular risk factor?
Authors: Ptinopoulou Anastasia G. , Sprangers Ben 
Published: September 2020

Abstract
Tyrosine kinase receptor inhibitors (TKIs) are a relatively new class of targeted anti-cancer agents with vascular endothelial growth factor signalling pathway–inhibiting properties. Hypertension is recognized as one of the most common adverse effects of this anti-angiogenic therapy and is the consequence of reduced production of vasodilatory nitric oxide and reduced prostacyclin production as well as increased production of vasoconstrictive endothelin-1. TKI-induced hypertension is dose dependent and it has been suggested as a marker of treatment effectiveness. In this issue, Saito et al. report the incidence of treatment-related hypertension in patients treated with lenvatinib, a newer TKI, for non-resectable hepatocellular carcinoma. The authors demonstrate that a subset of TKI-treated patients develop fluid retention 3 weeks after treatment initiation as a consequence of lower urinary sodium excretion and thus provides insights into the pathogenesis of blood pressure elevation in the second phase. These findings contribute to a better understanding of TKI-associated hypertension and help in choosing the most appropriate antihypertensive agents in this setting. Active control of hypertension may help more patients benefit from longer TKI therapy, possibly resulting in better cancer outcomes.
Nomenclature for kidney function and disease—executive summary and glossary from a Kidney Disease: Improving Global Outcomes (KDIGO) consensus conference
Authors: Levey Andrew S , Eckardt Kai-Uwe , Dorman Nijsje M , Christiansen Stacy L , Cheung Michael , Jadoul Michel , Winkelmayer Wolfgang C 
Published: September 2020

Abstract
The worldwide burden of kidney disease is rising, but public awareness remains limited, underscoring the need for more effective communication by stakeholders in the kidney health community. Despite this need for clarity, the nomenclature for describing kidney function and disease lacks uniformity. In June 2019, Kidney Disease: Improving Global Outcomes (KDIGO) convened a consensus conference with the goal of standardizing and refining the nomenclature used in the English language to describe kidney function and disease, and of developing a glossary that could be used by journals in scientific publications. Guiding principles of the conference were that the revised nomenclature should be patient-centred, precise, and consistent with nomenclature used in the KDIGO guidelines. Conference attendees reached general consensus on the following recommendations: (i) to use ‘kidney’ rather than ‘renal’ or ‘nephro’ when referring to kidney disease and kidney function; (ii) to use ‘kidney failure’ with appropriate descriptions of the presence or absence of symptoms, signs, and treatment rather than ‘end-stage’ kidney disease; (iii) to use the KDIGO definition and classification of acute kidney diseases and disorders (AKD) and acute kidney injury (AKI) rather than alternative descriptions to define and classify the severity of AKD and AKI; (iv) to use the KDIGO definition and classification of chronic kidney disease (CKD) rather than alternative descriptions to define and classify the severity of CKD; and (v) to use specific kidney measures, such as albuminuria or decreased glomerular filtration rate, rather than ‘abnormal or reduced kidney function’ to describe alterations in kidney structure and function. A proposed five-part glossary contains specific items for which there was general agreement. Conference attendees acknowledged limitations of the recommendations and glossary but considered that standardizing scientific nomenclature is essential for improving communication.
Digging into the Genomic Past of Swiss Honey Bees by Whole-Genome Sequencing Museum Specimens
Authors: Parejo Melanie , Wragg David , Henriques Dora , Charrière Jean-Daniel , Estonba Andone 
Published: September 2020

AbstractHistorical specimens in museum collections provide opportunities to gain insights into the genomic past. For the Western honey bee, Apis mellifera L., this is particularly important because its populations are currently under threat worldwide and have experienced many changes in management and environment over the last century. Using Swiss Apis mellifera mellifera as a case study, our research provides important insights into the genetic diversity of native honey bees prior to the industrial-scale introductions and trade of non-native stocks during the 20th century—the onset of intensive commercial breeding and the decline of wild honey bees following the arrival of Varroa destructor. We sequenced whole-genomes of 22 honey bees from the Natural History Museum in Bern collected in Switzerland, including the oldest A. mellifera sample ever sequenced. We identify both, a historic and a recent migrant, natural or human-mediated, which corroborates with the population history of honey bees in Switzerland. Contrary to what we expected, we find no evidence for a significant genetic bottleneck in Swiss honey bees, and find that genetic diversity is not only maintained, but even slightly increased, most probably due to modern apicultural practices. Finally, we identify signals of selection between historic and modern honey bee populations associated with genes enriched in functions linked to xenobiotics, suggesting a possible selective pressure from the increasing use and diversity of chemicals used in agriculture and apiculture over the last century.
Potential for Standardization and Automation for Pathology and Endoscopy in Inflammatory Bowel Disease
Authors: Syed Sana , Stidham Ryan W 
Published: September 2020

Abstract
Automated image analysis methods have shown potential for replicating expert interpretation of histology and endoscopy images, which traditionally require highly specialized and experienced reviewers. Inflammatory bowel disease (IBD) diagnosis, severity assessment, and treatment decision-making require multimodal expert data interpretation and integration, which could be significantly aided by applications of machine learning analyses. This review introduces fundamental concepts of machine learning for imaging analysis and highlights research and development of automated histology and endoscopy interpretation in IBD. Proof-of-concept studies strongly suggest that histologic and endoscopic images can be interpreted with similar accuracy as knowledge experts. Encouraging results support the potential of automating existing disease activity scoring instruments with high reproducibility, speed, and accessibility, therefore improving the standardization of IBD assessment. Though challenges surrounding ground truth definitions, technical barriers, and the need for extensive multicenter evaluation must be resolved before clinical implementation, automated image analysis is likely to both improve access to standardized IBD assessment and advance the fundamental concepts of how disease is measured.