bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Methyl-β-Cyclodextrin on the Interaction of Fluoroquinolones with Human Serum Albumin
Authors: Yakupova L. R. , Kopnova T. Yu. , Skuredina A. A. , Kudryashova E. V. 
Published: March 2022

Abstract—
The influence of the structure of fluoroquinolones (on the example of ciprofloxacin and levofloxacin) and their complexation with methyl-β-cyclodextrin on the interaction of the drug with human serum albumin was studied. It was found that the binding of the drug molecule with albumin is significantly affected by the structure of fluoroquinolone, as well as the presence of methyl-β-cyclodextrin. It was discovered that of the two fluoroquinolones, the more hydrophobic ciprofloxacin molecule interacts more strongly with the protein, using circular dichroism and fluorescence spectroscopy methods. It has also been shown that binding of albumin to the drug causes quenching of protein fluorescence, and this effect is more pronounced for ciprofloxacin. The complexation of fluoroquinolones with methyl-β-cyclodextrin leads to a change in the interaction of fluoroquinolones with the protein: in the case of complexes, more pronounced interactions are observed for levofloxacin. The results obtained will help to bring the use of fluoroquinolones to a new level in clinical practice, by creating new highly effective drugs with improved properties.
Economic evaluations of health system strengthening activities in low-income and middle-income country settings: a methodological systematic review
Authors: Hendrix Nathaniel , Kwete Xiaoxiao , Bolongaita Sarah , Megiddo Itamar , Memirie Solomon Tessema , Mirkuzie Alemnesh H , Nonvignon Justice , Verguet Stéphane 
Published: March 2022

ObjectiveHealth system strengthening (HSS) activities should accompany disease-targeting interventions in low/middle-income countries (LMICs). Economic evaluations provide information on how these types of investment might best be balanced but can be challenging. We conducted a systematic review to evaluate how researchers address these economic evaluation challenges.MethodsWe identified studies about economic evaluation of HSS activities in LMICs using a two-stage approach. First, we conducted a broad search to identify areas where economic evaluations of HSS activities were being conducted. Next, we selected specific interventions for more targeted literature review. We extracted study characteristics using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Finally, we summarised authors’ modelling decisions using a framework that examines how models are developed to emphasise generalisability, precision, or realism.FindingsOur searches produced 1978 studies, out of which we included 36. Most studies used data from prospective trials and calculated cost-effectiveness directly from these trial inputs, rather than using simulation methods. As a group, these studies primarily emphasised precision and realism over generalisability, meaning that their results were best suited to specific settings.ConclusionsThe number of included studies was small. Our findings suggest that most economic evaluations of HSS do not leverage methods like sensitivity analyses or inputs from literature review that would produce more generalisable (but potentially less precise) results. More research into how decision-makers would use economic evaluations to define the expansion path to strengthening health systems would allow for conceptualising impactful work on the economic value of HSS.
Multicomponent stretching and rubber band strengthening exercises do not reduce overuse shoulder injuries: a cluster randomised controlled trial with 579 handball athletes
Authors: Achenbach Leonard , Huppertz Gunnar , Zeman Florian , Weber Johannes , Luig Patrick , Rudert Maximilian , Krutsch Werner 
Published: March 2022

ObjectivesHandball is associated with a high risk of overuse shoulder injury. This study investigated if an injury prevention programme effectively reduces overuse injury to the throwing shoulder of handball athletes.Methods61 men’s and women’s handball teams (u-19 and senior athletes) were cluster-randomised into an intervention and a control group in the 2019–2020 season. Players of the intervention group regularly carried out an injury prevention programme. Both groups documented overuse shoulder injuries via an online questionnaire every second week. The primary endpoint was the prevalence of overuse injury to the throwing shoulder. Secondary endpoints were the influence of compliance on the primary endpoint and intensity of overuse shoulder symptoms measured by a shortened, handball-specific Western Ontario Shoulder Index (WOSI).Results31 teams (295 players) in the intervention group and 30 teams (284 players) in the control group were included for analyses. The overall questionnaire response rate was 61%. The average prevalence of overuse shoulder injury did not significantly differ between the intervention group (n=109, 38.4% (95% CI 32.9% to 44.2%)) and the control group (n=106, 35.9% (95% CI 30.7% to 41.6%), p=0.542). Compliance with the intervention programme did not significantly affect overuse shoulder injury (p=0.893). Using generalised estimating equations for WOSI, the estimated mean for the intervention group was 44.6 points (95% CI 42.0 to 47.1) and 47.6 points for the control group (95% CI 44.9 to 50.3, p=0.111).ConclusionsA multicomponent exercise programme using rubber bands and stretching did not significantly reduce the prevalence or symptoms of overuse throwing shoulder injury in handball athletes of both sexes. Randomised controlled study; level of evidence I.Trial registration numberISRCTN99023492.
Smartphone detection of atrial fibrillation using photoplethysmography: a systematic review and meta-analysis
Authors: Gill Simrat , Bunting Karina V , Sartini Claudio , Cardoso Victor Roth , Ghoreishi Narges , Uh Hae-Won , Williams John A , Suzart-Woischnik Kiliana , Banerjee Amitava , Asselbergs Folkert W , Eijkemans MJC , Gkoutos Georgios V , Kotecha Dipak 
Published: March 2022

ObjectivesTimely diagnosis of atrial fibrillation (AF) is essential to reduce complications from this increasingly common condition. We sought to assess the diagnostic accuracy of smartphone camera photoplethysmography (PPG) compared with conventional electrocardiogram (ECG) for AF detection.MethodsThis is a systematic review of MEDLINE, EMBASE and Cochrane (1980–December 2020), including any study or abstract, where smartphone PPG was compared with a reference ECG (1, 3 or 12-lead). Random effects meta-analysis was performed to pool sensitivity/specificity and identify publication bias, with study quality assessed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) risk of bias tool.Results28 studies were included (10 full-text publications and 18 abstracts), providing 31 comparisons of smartphone PPG versus ECG for AF detection. 11 404 participants were included (2950 in AF), with most studies being small and based in secondary care. Sensitivity and specificity for AF detection were high, ranging from 81% to 100%, and from 85% to 100%, respectively. 20 comparisons from 17 studies were meta-analysed, including 6891 participants (2299 with AF); the pooled sensitivity was 94% (95% CI 92% to 95%) and specificity 97% (96%–98%), with substantial heterogeneity (p<0.01). Studies were of poor quality overall and none met all the QUADAS-2 criteria, with particular issues regarding selection bias and the potential for publication bias.ConclusionPPG provides a non-invasive, patient-led screening tool for AF. However, current evidence is limited to small, biased, low-quality studies with unrealistically high sensitivity and specificity. Further studies are needed, preferably independent from manufacturers, in order to advise clinicians on the true value of PPG technology for AF detection.
The vaccine-site microenvironment: impacts of antigen, adjuvant, and same-site vaccination on antigen presentation and immune signaling
Authors: Meneveau Max O , Kumar Pankaj , Lynch Kevin T , Patel Sapna P , Slingluff Craig L 
Published: March 2022

BackgroundA goal of cancer vaccines is to induce strong T cell responses to tumor antigens, but the delivery method, schedule, and formulation of cancer vaccines have not yet been optimized. Adjuvants serve to increase the immune response against vaccine antigens. However, little is known about the impact of adjuvants plus antigen and their delivery schedule on the immunologic milieu in the vaccine-site microenvironment (VSME). We hypothesized that antigen processing and presentation may occur directly in the VSME, that adding the toll-like receptor 3 (TLR3) agonist polyICLC (pICLC) would enhance markers of immune activation, and that the immune signatures would be enhanced further by repeated vaccination in the same skin site rather than after multiple vaccines in different skin locations.MethodsUsing RNA sequencing, we evaluated VSME biopsies from patients undergoing subcutaneous/intradermal peptide vaccination against melanoma, with incomplete Freund’s adjuvant (IFA) with or without pICLC. Differential gene expression analyses and gene set enrichment analyses were performed using R. False discovery rate corrected p values <0.05 were considered significant.ResultsWe found that addition of peptide antigens to IFA enhanced antigen presentation pathways and a tertiary lymphoid structure gene-signature locally at the VSME. Addition of pICLC to IFA + peptide induced an immunologically favorable VSME 1 week after injection but had little impact on the VSME after three injections, compared with IFA + peptide alone. Repeated same-site injection of IFA + peptide antigens induced a VSME with more dendritic cell activation, Th1 dominance, and TLR adaptor protein gene expression than that induced by injections at different, rotating skin locations.ConclusionsThese data suggest that the vaccine-site itself may be a critically important location contributing to vaccine immunity rather than just the draining lymph node, that IFA induces a favorable VSME with TLR agonist being most beneficial early in the vaccine course, and that same-site injections lead to persistent stimulation of immune pathways that may be beneficial in eliciting antigen specific T cell expansion.
Phase 2 trial of T-cell activation using MVI-816 and pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC)
Authors: McNeel Douglas G , Eickhoff Jens C , Wargowski Ellen , Johnson Laura E , Kyriakopoulos Christos E , Emamekhoo Hamid , Lang Joshua M , Brennan Mary Jane , Liu Glenn 
Published: March 2022

BackgroundWe previously reported a trial using a DNA vaccine encoding prostatic acid phosphatase (MVI-816, pTVG-HP), given over 12 weeks concurrently or sequentially with pembrolizumab, in patients with mCRPC. We report the final analysis of this trial following two additional treatment arms in which patients with mCRPC continued concurrent treatment until progression.Materials and methodsPatients with mCRPC were treated with MVI-816 and pembrolizumab every 3 weeks (arm 3, n=20) or MVI-816 every 2 weeks and pembrolizumab every 4 weeks (arm 4, n=20). The primary objectives were safety, 6-month progression-free survival (PFS), median time to radiographic progression, and objective response rates. Secondary objectives included immunological evaluations.ResultsIn 25 patients with measurable disease, there were no complete response and one confirmed partial response in a patient who subsequently found to have an MSIhitumor. 4/40 patients (10%) had a prostate-specific antigen decline >50%. The estimated overall radiographic PFS rate at 6 months was 47.2% (44.4% arm 3, 61.5% arm 4). Accounting for all off-study events, overall median time on treatment was 5.6 months (95% CI: 5.4 to 10.8 months), 5.6 months for arm 3 and 8.1 months for arm 4 (p=0.64). Thirty-two per cent of patients remained on trial beyond 6 months without progression. Median overall survival was 22.9 (95% CI: 16.2 to 25.6) months. One grade 4 event (hyperglycemia) was observed. Immune-related adverse events (irAEs) >grade 1 were observed in 42% of patients overall. Interferon-γ and/or granzyme B immune response to prostatic acid phosphatase was detected in 2/20 patients in arm 3 and 6/20 patients in arm 4. Plasma cytokines associated with immune activation and CD8+ T-cell recruitment were augmented at weeks 6 and 12. The development of irAE was significantly associated with a prolonged time on treatment (HR=0.42, p=0.003). Baseline DNA homologous recombination repair mutations were not associated with longer time to progression.ConclusionsFindings here demonstrate that combining programmed cell death 1 blockade with MVI-816 is safe, can augment tumor-specific T cells, and can result in a favorable 6-month disease control rate. Correlative studies suggest T-cell activation by vaccination is critical to the mechanism of action of this combination. Future randomized clinical trials are needed to validate these findings.Trial registration numberNCT02499835.
Does the presence of conspecifics facilitate exploratory behaviour in a cichlid fish (Etroplus suratensis)?
Authors: Sommer-Trembo C. , Oliver C. , Wolf L. , Garcia C. , Salzburger W. 
Published: March 2022

Abstract
Animals confronted with any kind of novelty show behavioural responses driven by avoidance and exploration. The expression of both tendencies is modulated by anxiety. Especially in group-living animals, the presence of conspecifics can reduce anxiety in novel situations and hence increase exploratory tendency. Such intensified behavioural responses triggered by the social environment of an individual are called social facilitation. Here, we tested for social facilitation on the exploratory tendency of group-living juvenile Green chromide cichlid fish (Etroplus suratensis) by assessing each individual twice in an open field test: once alone and once together with a conspecific. Contrary to our expectations, we found no difference in exploratory behaviour between the groups. However, our results suggest that changes in exploratory tendency across the two treatments were highly individual, both in extent and direction, and are likely driven by the presence of the conspecific and the focal individual’s own behavioural type.
Jan van der Goes
Authors: van den Bel Martijn M. 
Published: March 2022

Abstract
This article tries to demonstrate that the former governor of Essequibo, Jan van der Goes, was also the Indian prince called Vandergoes met by the English, French, and Dutch in the early second half of the seventeenth century at Cayenne. This hypothesis is supported by detailed information on the career of Jan van der Goes derived from the general meetings of the Zeeland Chamber of the WIC and by appearances of the aforementioned Vandergoes in various European documents. In addition, the incorporation of this Dutchman among the Arecarets reveals a particular Amerindian adaptation to colonization along the Wild Coast.
Miracles in Writing: Obstetric Intercessions, Scribal Relics, and Jesuit News in the Early Modern Global Cult of Ignatius of Loyola
Authors: Greenwood Jonathan E. 
Published: March 2022

Abstract
The reputation of Ignatius of Loyola (c.1491–1556), the founder of the Society of Jesus, as a miracle-worker grew during the 1590s, which included his aid in childbirth through handwritten relics. This article examines obstetric miracles associated with Ignatius in the early modern world prior to his canonization in 1622. Through his letters and signature, Ignatius rescued women and their offspring during dangerous and near-fatal deliveries; delayed certain neonatal mortalities long enough for a baptism to occur; and allowed the delivery of a dead fetus to save the mother’s life. While the claims had no bearing on the official declaration of his sainthood, the attributed miracles are emblematic of the concentric and transoceanic nature of his cult. Information and material pathways contributed to the promulgation of the founder’s sanctity in the confines of women in labor and childbirth that had their own patron saints for centuries.
In the Shadow of Francis Xavier: Martyrdom and Colonialism in the Jesuit Asian Missions
Authors: Cañeque Alejandro 
Published: March 2022

Abstract
This article focuses on the violent deaths of the Jesuit missionaries Rodolfo Acquaviva, Marcello Mastrilli, and Diego Luis de San Vítores, who were killed in the course of their evangelical endeavors in India, Japan, and the Mariana Islands, respectively. It elucidates the ways in which the figure of St. Francis Xavier intersected with the Jesuit ideal of martyrdom, while situating the three martyred Jesuits within the history of Iberian imperialism and colonialism. Xavier became the dominant Jesuit image of apostolic sanctity, and he greatly energized the evangelical zeal of many Jesuits, eager to missionize in distant East Asia. At the same time, the Jesuit evangelical impulse in the early modern period became closely intertwined with the desire for martyrdom. In their efforts to create saintly figures of the three slain missionaries, Jesuit authors would establish a special connection between St. Francis Xavier and the martyred Jesuits, Mastrilli and San Vítores being described as almost perfect replicas of the saint, even though Xavier never experienced martyrdom.
A Comparison of Land Surface Phenology in the Northern Hemisphere Derived from Satellite Remote Sensing and the Community Land Model
Authors: Li Xiaolu , Melaas Eli , Carrillo Carlos M. , Ault Toby , Richardson Andrew D. , Lawrence Peter , Friedl Mark A. , Seyednasrollah Bijan , Lawrence David M. , Young Adam M. 
Published: March 2022

Abstract
Large-scale changes in the state of the land surface affect the circulation of the atmosphere and the structure and function of ecosystems alike. As global temperatures increase and regional climates change, the timing of key plant phenophase changes are likely to shift as well. Here we evaluate a suite of phenometrics designed to facilitate an “apples to apples” comparison between remote sensing products and climate model output. Specifically, we derive day-of-year (DOY) thresholds of leaf area index (LAI) from both remote sensing and the Community Land Model (CLM) over the Northern Hemisphere. This systematic approach to comparing phenologically relevant variables reveals appreciable differences in both LAI seasonal cycle and spring onset timing between model simulated phenology and satellite records. For example, phenological spring onset in the model occurs on average 30 days later than observed, especially for evergreen plant functional types. The disagreement in phenology can result in a mean bias of approximately 5% of the total estimated Northern Hemisphere NPP. Further, while the more recent version of CLM (v5.0) exhibits seasonal mean LAI values that are in closer agreement with satellite data than its predecessor (CLM4.5), LAI seasonal cycles in CLM5.0 exhibit poorer agreement. Therefore, despite broad improvements for a range of states and fluxes from CLM4.5 to CLM5.0, degradation of plant phenology occurs in CLM5.0. Therefore, any coupling between the land surface and the atmosphere that depends on vegetation state might not be fully captured by the existing generation of the model. We also discuss several avenues for improving the fidelity between observations and model simulations.
LainePoiss®—A Lightweight and Ice-Resistant Wave Buoy
Authors: Alari Victor , Björkqvist Jan-Victor , Kaldvee Valdur , Mölder Kristjan , Rikka Sander , Kask-Korb Anne , Vahter Kaimo , Pärt Siim , Vidjajev Nikon , Tõnisson Hannes 
Published: March 2022

Abstract
Wave buoys are a popular choice for measuring sea surface waves, and there is also an increasing interest for wave information from ice-covered water bodies. Such measurements require cost-effective, easily deployable, and robust devices. We have developed LainePoiss (LP)—an ice-resistant and lightweight wave buoy. It calculates the surface elevation by double integrating the data from the inertial sensors of the microelectromechanical system (MEMS), and transmits wave parameters and spectra in real time over cellular or satellite networks. LP was validated through 1) sensor tests, 2) wave tank experiments, 3) a field validation against a Directional Waverider, 4) an intercomparison of several buoys in the field, and 5) field measurements in the Baltic Sea marginal ice zone. These extensive field and laboratory tests confirmed that LP performed well (e.g., the bias of Hm0 in the field was 0.01 m, with a correlation of 0.99 and a scatter index of 8%; the mean absolute deviation of mean wave direction was 7°). LP was also deployed with an unmanned aerial vehicle and we present our experience of such operations. One issue that requires further development is the presence of low-frequency artifacts caused by the dynamic noise of the gyroscope. For now, a correction method is presented to deal with the noise.

Significance Statement
Operational wave buoys are large and therefore expensive and inconvenient to deploy. Many commercially available devices cannot measure short waves and are not tested in ice. Our purpose was to develop an affordable wave buoy that is lightweight, ice resistant, capable of measuring short waves, and also has a longer operating life than existing research buoys. The buoy is easily deployed with a small boat or even an industrial drone, thus reducing operating costs. The buoy is accurate, and captures waves that are too short for operational wave buoys. This is relevant for coastal planning in, e.g., archipelagos and narrow fjords. We measured waves in ice in the Baltic Sea, and are planning to extend these measurements to Antarctica.
Agent Transparency, Situation Awareness, Mental Workload, and Operator Performance: A Systematic Literature Review
Authors: van de Merwe Koen , Mallam Steven , Nazir Salman 
Published: March 2022

Objective In this review, we investigate the relationship between agent transparency, Situation Awareness, mental workload, and operator performance for safety critical domains. Background The advancement of highly sophisticated automation across safety critical domains poses a challenge for effective human oversight. Automation transparency is a design principle that could support humans by making the automation’s inner workings observable (i.e., “seeing-into”). However, experimental support for this has not been systematically documented to date. Method Based on the PRISMA method, a broad and systematic search of the literature was performed focusing on identifying empirical research investigating the effect of transparency on central Human Factors variables. Results Our final sample consisted of 17 experimental studies that investigated transparency in a controlled setting. The studies typically employed three human-automation interaction types: responding to agent-generated proposals, supervisory control of agents, and monitoring only. There is an overall trend in the data pointing towards a beneficial effect of transparency. However, the data reveals variations in Situation Awareness, mental workload, and operator performance for specific tasks, agent-types, and level of integration of transparency information in primary task displays. Conclusion Our data suggests a promising effect of automation transparency on Situation Awareness and operator performance, without the cost of added mental workload, for instances where humans respond to agent-generated proposals and where humans have a supervisory role. Application Strategies to improve human performance when interacting with intelligent agents should focus on allowing humans to see into its information processing stages, considering the integration of information in existing Human Machine Interface solutions.