bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance analysis of English hospitals during the first and second waves of the coronavirus pandemic
Authors: Kuosmanen Timo , Tan Yong , Dai Sheng
Published: May 2023

The coronavirus infection COVID-19 killed millions of people around the world in 2019-2022. Hospitals were in the forefront in the battle against the pandemic. This paper proposes a novel approach to assess the effectiveness of hospitals in saving lives. We empirically estimate the production function of COVID-19 deaths among hospital inpatients, applying Heckman’s two-stage approach to correct for the bias caused by a large number of zero-valued observations. We subsequently assess performance of hospitals based on regression residuals, incorporating contextual variables to convex quantile regression. Data of 187 hospitals in England over a 35-week period from April to December 2020 is divided in two sub-periods to compare the structural differences between the first and second waves of the pandemic. The results indicate significant performance improvement during the first wave, however, learning by doing was offset by the new mutated virus straits during the second wave. While the elderly patients were at significantly higher risk during the first wave, their expected mortality rate did not significantly differ from that of the general population during the second wave. Our most important empirical finding concerns large and systematic performance differences between individual hospitals: larger units proved more effective in saving lives, and hospitals in London had a lower mortality rate than the national average.
A Characterization of Van Hiele’s Level 5 of Geometric Reasoning Using the Delphi Methodology
Authors: Arnal-Bailera Alberto , Manero Víctor
Published: May 2023

The Van Hiele model of geometric reasoning establishes five levels of development, from level 1 (visual) to level 5 (rigor). Despite the fact that this model has been deeply studied, there are few research works concerning the fifth level. However, there are some works that point out the interest of working with activities at this level to promote the acquisition of previous levels. Our goal is to describe this level through the construction and validation of a list of indicators for each of the processes involved in geometrical reasoning (definition, proof, classification, and identification). Due to the lack of previous research, we have decided to use the Delphi methodology. This approach allowed us to collect information from a panel of experts to reach a consensus through a series of phases about the indicators that describe each of the processes. The final product of the iterative application of this method is a list of validated indicators of the fifth Van Hiele level of reasoning. In particular, proof and definition processes have turned out to be the most relevant processes at this level.
Service Re-Selection for Disruptive Events in Mobile Environments: A Heuristic Technique for Decision Support at Runtime
Authors: Bortlik Michael , Heinrich Bernd , Lohninger Daniel
Published: May 2023

Modern service-based processes in mobile environments are highly complex due to the necessary spatial–temporal coordination between multiple participating users and the consideration of context information. Due to the dynamic nature of mobile environments, disruptive events occur at runtime, which require a re-selection of the planned service compositions respecting multiple users and context-awareness. Thereby, when re-selecting services the features performance, solution quality, solution robustness and alternative solutions are essential and contribute to the efficacy of service systems. This paper presents an optimization-based heuristic technique based on a stateful representation that uses a region-based approach to re-select services considering multiple users, context information and in particular disruptive events at runtime. The evaluation results, which are based on a real-world scenario from the tourism domain, show that the proposed heuristic is superior compared to competing artifacts.
Subcutaneous Immunoglobulin 16.5% (Cutaquig®) in Primary Immunodeficiency Disease: Safety, Tolerability, Efficacy, and Patient Experience with Enhanced Infusion Regimens
Authors: Gupta Sudhir , DeAngelo James , Melamed Isaac , Walter Jolan E. , Kobayashi Ai-Lan , Bridges Tracy , Sublett J. Wesley , Bernstein Jonathan A. , Koterba Alan , Manning Michael , Maltese Joanna , Hoeller Sonja , Turpel-Kantor Eva , Kreuwel Huub , Kobayashi Roger H.
Published: May 2023

Purpose

To achieve reductions in infusion time, infusion sites, and frequency, a prospective, open-label, multicenter, Phase 3 study evaluated the safety, efficacy, and tolerability of subcutaneous immunoglobulin (SCIG) 16.5% (Cutaquig®, Octapharma) at enhanced infusion regimens.

Methods

Three separate cohorts received SCIG 16.5% evaluating volume, rate, and frequency: Cohort 1) volume assessment/site: up to a maximum 100 mL/site; Cohort 2) infusion flow rate/site: up to a maximum of 100 mL/hr/site or the maximum flow rate achievable by the tubing; Cohort 3) infusion frequency: every other week at twice the patient’s weekly dose.

Results

For Cohort 1 (n = 15), the maximum realized volume per site was 108 mL/site, exceeding the currently labeled (US) maximum (up to 40 mL/site for adults). In Cohort 2 (n = 15), the maximum realized infusion flow rate was 67.5 mL/hr/site which is also higher than the labeled (US) maximum (up to 52 mL/hr/site). In Cohort 3 (n = 34), the mean total trough levels for every other week dosing demonstrated equivalency to weekly dosing (p value = 0.0017). All regimens were well tolerated. There were no serious bacterial infections (SBIs). Most patients had mild (23.4%) or moderate (56.3%) adverse events. The majority of patients found the new infusion regimens to be better or somewhat better than their previous regimens and reported that switching to SCIG 16.5% was easy.

Conclusions

SCIG 16.5% (Cutaquig®), infusions are efficacious, safe, and well tolerated with reduced infusion time, fewer infusion sites, and reduced frequency. Further, the majority of patients found the new infusion regimens to be better or somewhat better than their previous regimens.
Fungal Keratitis Caused by Talaromyces coalescens: A Case Report
Authors: Todokoro Daisuke , Miyakubo Tomoko , Makimura Koichi , Tamura Takashi , Komori Aya , Akiyama Hideo
Published: May 2023

Fungal keratitis is a severe corneal infection, and the causative fungi include various rare fungal species. Fungal keratitis caused by Talaromyces species has yet to be reported, and there is no information about this fungus as a cause of keratitis. A 77-year-old man developed fungal keratitis while waiting for a donor cornea due to bullous keratopathy in his left eye. Fungal culture of a corneal scraping grew filamentous fungi, which were morphologically identified as Paecilomyces species. The corneal infection did not improve after topical administration of 1% voriconazole, and ribosomal DNA sequencing definitively verified the fungus to be Talaromyces coalescens. The lesion gradually improved after switching to topical 5% natamycin. Antifungal susceptibility tests determined the high minimum inhibitory concentrations of voriconazole to be > 8 μg/mL. This is the first report of Talaromyces fungal keratitis. Clinicians, especially those in ophthalmology, need to be aware of this rare fungus.
Using Concept Mapping to Explore the Perspectives of People with Mild to Borderline Intellectual Disabilities Toward Sexual Health
Authors: de Wit Wouter , Roeg Diana , Embregts Petri J. C. M.
Published: May 2023

People with mild to borderline intellectual disabilities face many barriers toward their sexual health. To promote sexual health and overcome these barriers, they need individualized forms of sexuality support and education. To align sexuality support and education insight is needed on their understanding of sexual health. The current paper aims to provide greater insight in what sexual health consists of according to people with mild to borderline intellectual disabilities. Nine people with a mild to borderline intellectual disability participated in a concept mapping procedure, consisting of brainstorming, sorting, and ranking the statements. The resulting clusters and concept map were interpreted by an expert group. Analysis resulted in five clusters which participants considered important for their sexual health. According to people with mild to borderline intellectual disability cluster pertaining to romantic relationships and sexual socialization were the most important. These were followed by clusters on sexual health and lastly sexual selfhood. These results have implications for the development of sexuality support and education, as well as further research.
Adaptive online variance estimation in particle filters: the ALVar estimator
Authors: Mastrototaro Alessandro , Olsson Jimmy
Published: May 2023

We present a new approach—the estimator—to estimation of asymptotic variance in sequential Monte Carlo methods, or, particle filters. The method, which adjusts adaptively the lag of the estimator proposed in Olsson and Douc (Bernoulli 25(2):1504–1535) applies to very general distribution flows and particle filters, including auxiliary particle filters with adaptive resampling. The algorithm operates entirely online, in the sense that it is able to monitor the variance of the particle filter in real time and with, on the average, constant computational complexity and memory requirements per iteration. Crucially, it does not require the calibration of any algorithmic parameter. Estimating the variance only on the basis of the genealogy of the propagated particle cloud, without additional simulations, the routine requires only minor code additions to the underlying particle algorithm. Finally, we prove that the estimator is consistent for the true asymptotic variance as the number of particles tends to infinity and illustrate numerically its superiority to existing approaches.
ADELA: a conversational virtual assistant to prevent delirium in hospitalized older persons
Authors: Alonso-Mencía Javier , Castro-Rodríguez Marta , Herrero-Pinilla Beatriz , Alonso-Weber Juan M. , Rodríguez-Mañas Leocadio , Pérez-Rodríguez Rodrigo
Published: May 2023

Delirium is a sudden mental state that causes confusion and disorientation, affecting a person's ability to think and remember clearly. Virtual assistants are a promising alternative for non-pharmacological interventions. This research aims to present a prototype of ADELA, a conversational assistant to prevent delirium in hospitalized older persons who speak Spanish. A co-creation process with medical experts to identify requirements was carried out to later develop the assistant iteratively and evaluate it from a technical and usability perspectives; the latest using the Spanish version of the System Usability Scale (SUS) and the Chatbot Usability Questionnaire (CUQ), supplemented by qualitative data. Mean values of 75.5 and 85.94 were obtained for SUS and CUQ, respectively. The technical evaluation helped defining the minimum environmental specifications required for deployment. Obtained results imply the assistant is usable and potentially accepted by the target population; useful information was extracted for refinement. Technical evaluation showed positive results, indicating it can be used in a real clinical environment.
Droplet Formation, Growth and Detachment at the Interface of a Coupled Free-FLow–Porous Medium System: A New Model Development and Comparison
Authors: Veyskarami Maziar , Michalkowski Cynthia , Bringedal Carina , Helmig Rainer
Published: May 2023

Coupled free-flow–porous medium systems are of great importance in various natural and industrial applications. Modeling of such systems is always challenging, especially when droplets form at the interface between the two domains. We propose a new concept to take droplet formation, growth and detachment at the interface into account. In this concept, we use pore-network modeling to describe the porous medium and the Navier–Stokes equations for the free-flow domain. New coupling conditions are developed which include droplet interactions with the free flow and the porous medium. Impacts of using different descriptions of the forces acting on the triple contact line and contact angle hysteresis on the predicted onset of the droplet detachment are examined. In addition, we compare the new approach with another model built using ANSYS Fluent based on the volume of fluid method. The results show that the new model is able to describe the droplet formation, growth and then detachment by the free flow. The proposed model provides a base for further developments to handle formation of multiple droplets at the interface between a free flow and a porous medium as well as to include the evaporation in future works.
Genetic polymorphism in European and African sheep breeds reared in Hungary based on 48 SNPs associated with resistance to gastrointestinal parasite infection using KASP-PCR technique
Authors: Astuti Putri Kusuma , Gavojdian Dinu , Ilie Daniela Elena , Wanjala George , Monori István , Bagi Zoltán , Kusza Szilvia
Published: May 2023

This pilot study used an alternative and economically efficient technique, the Kompetitive Allele-Specific Polymerase Chain Reaction (KASP-PCR) to examine 48 SNPs from 11 parasite-resistance genes found on 8 chromosomes in 110 animals from five sheep breeds reared in Hungary; Hungarian Tsigai, White Dorper, Dorper, Ile de France, and Hungarian Merino. Allele and genotype frequencies, fixation index, observed heterozygosity, expected heterozygosity, F statistic, and their relationship with the Hardy–Weinberg equilibrium (WHE) and the polymorphic information content (PIC) were determined, followed by principal component analysis (PCA). As much as 32 SNPs out of the 48 initially studied were successfully genotyped. A total of 9 SNPs, 4 SNPs in TLR5, 1 SNP in TLR8, and 4 SNPs in TLR2 genes, were polymorphic. The variable genotype and allele frequency of the TLRs gene indicated genetic variability among the studied sheep breeds, with the Hungarian Merino exhibiting the most polymorphisms, while Dorper was the population with the most SNPs departing from the HWE. According to the PIC value, the rs430457884-TLR2, rs55631273-TLR2, and rs416833129-TLR5 were found to be informative in detecting polymorphisms among individuals within the populations, whereas the rs429546187-TLR5 and rs424975389-TLR5 were found to have a significant influence in clustering the population studied. This study reported a moderate level of genetic variability and that a low to moderate within-breed diversity was maintained in the studied populations.
A tale of two events: Arctic rain-on-snow meteorological drivers
Authors: Voveris Jessica , Serreze Mark
Published: May 2023

Arctic rain-on-snow (ROS) events can have significant impacts on Arctic wildlife and socio-economic systems. This study addresses the meteorology of two different Arctic ROS events. The first, occurring near Nuuk, Greenland, generated significant impacts, including slush avalanches. The second, less severe, event occurred within the community of Iqaluit, Nunavut, Canada. This research utilizes atmospheric reanalysis, automated surface observation station data and atmospheric soundings to determine the meteorological conditions driving these events and the differences between each case. In both cases, atmospheric blocking played a leading role in ROS initiation, with atmospheric rivers – narrow bands of high water vapor transport, typically originating from the tropics and subtropics – having both direct and indirect effects. Cyclone-induced low-level jets and resultant ‘warm noses’ of higher air temperatures and moisture transport were other key features in ROS generation. To our knowledge, our study is the first to visualize how the varying strength and manifestation of these coupled features contribute to differences in the severity of Arctic ROS events. The meteorological drivers identified here find support from other studies on Arctic ROS events and are similar to weather features associated with Arctic precipitation events of extreme magnitude.
Antitrust as a Guardrail for Socially Responsible Neurotechnology Design
Authors: Nadler Roland
Published: May 2023

The neurotechnology sector is likely to develop under pressure towards commercialized, nonmedical products and may also undergo market consolidation. This possibility raises ethical, social, and policy concerns about the future responsibility of neurotechnology innovators and companies for high-consequence design decisions. Present-day internet technology firms furnish an instructive example of the problems that arise when providers of communicative technologies become too big for accountability. As a guardrail against the emergence of similar problems, concerned neurotechnologists may wish to draw inspiration from antitrust law and direct efforts, where appropriate, against undue consolidation in the commercial neurotechnology market.
Mapping the Landscape of Equitable Access to Advanced Neurotechnologies in Canada
Authors: Harding Louise , McFarlane Jacob , Honey Christopher R. , McDonald Patrick J. , Illes Judy
Published: May 2023

Geographic, social, political, and economic factors shape access to advanced neurotechnologies, yet little previous research has explored the barriers, enablers, and areas of opportunity for equitable and meaningful access for diverse patient communities across Canada. We applied a mixed-mode approach involving semi-structured interviews and rating scale questions to consult with 24 medical experts who are involved in the care of patients who undergo functional neurosurgery targeting the brain. Seven major themes emerged from the qualitative analysis: Health care system, Neurotechnology features, Patient demographics, Target condition features, Ethics, Upstream barriers and enablers, and Areas of opportunity. Descriptive statistics of the Likert-scale responses suggest that interviewees perceive a disparity between the imperative of access to advanced neurotechnologies for people living in rural and remote areas and the likelihood of achieving such access. The results depict a complex picture of access to functional neurosurgery in Canada with pockets of excellence and a motivation to improve the availability of care for vulnerable populations through the expansion of distributed care models, improved health care system efficiencies, increasing funding and support for patient travel, and increasing awareness about and advocacy for advanced neurotechnologies.
Concurrent dose-finding of a novel cancer drug with and without a second agent
Authors: Wages Nolan A. , Saleh Ramy R. , Braun Thomas M.
Published: May 2023

Introduction:

More complex research questions are being posed in early-phase oncology clinical trials, necessitating design strategies tailored to contemporary study objectives. This paper describes the proposed design of a Phase I trial concurrently evaluating the safety of a hematopoietic progenitor kinase-1 inhibitor (Agent A) as a single agent and in combination with an anti-PD-1 agent in patients with advanced malignancies. The study’s primary objective was to concurrently determine the maximum tolerated dose (MTD) of Agent A with and without anti-PD-1 therapy among seven possible study dose levels.

Methods:

Our solution to this challenge was to apply a continual reassessment method shift model to meet the research objectives of the study.

Results:

The application of this method is described herein, and a simulation study of the design’s operating characteristics is conducted. This work was developed through collaboration and mentoring between the authors at the American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO) annual AACR/ASCO Methods in Clinical Cancer Research Workshop.

Conclusions:

The aim of this manuscript is to highlight examples of novel design applications as a means of augmenting the implementation of innovative designs in the future and to demonstrate the flexibility of adaptive designs in satisfying modern design conditions. Although the design is presented using an investigation of Agent A with and without anti-PD-1 therapy as an illustrative example, the approach described is not specific to these agents and could be applied to other concurrent monotherapy and combination therapy studies with well-defined binary safety endpoints.
Dealing with the Facts of Life: The Management of Intra-Party Factionalism in the Iberian Radical Left Parties
Authors: Lourenço Pedro , Conceição Tiago , Jalali Carlos
Published: May 2023

Factionalism is an important element in parties' internal life, affecting their policies, strategies, electoral performance and even survival. Yet little is known about how parties manage factionalism. This study examines how radical left parties (RLPs) manage factionalism, drawing on a comparative case study of four RLPs – the Spanish Podemos and United Left (IU), and the Portuguese Left Bloc (BE) and Communist Party (PCP) – from 2010 to 2019. Drawing on original data collection, we find that parties adopt both formal and informal mechanisms to address factionalism. However, their approaches differ significantly. We identify two main approaches towards factionalism: apermissiveapproach, which allows internal pluralism, in the BE and IU; and aprohibitionistapproach, which actively fights factionalism, in Podemos and the PCP, withcompetitiveprohibitionism in the former andpre-emptiveprohibitionism in the latter. These approaches strongly correlate with parties' origins and political orientation, but neither fully prevents intra-party conflict or splintering.
SEMI-EQUATIONAL THEORIES
Authors: CHERNIKOV ARTEM , MENNEN ALEX
Published: May 2023

We introduce and study (weakly) semi-equational theories, generalizing equationality in stable theories (in the sense of Srour) to the NIP context. In particular, we establish a connection to distality via one-sided strong honest definitions; demonstrate that certain trees are semi-equational, while algebraically closed valued fields are not weakly semi-equational; and obtain a general criterion for weak semi-equationality of an expansion of a distal structure by a new predicate.
Ancient Human Mitogenome of the Beagle Channel (Tierra del Fuego): An Argentine Collaborative Project
Authors: Arencibia Valeria , Muñoz Hidalgo Marianne , Crespo Cristian , Maldonado Lucas , Lichtenstein Gabriel , Kamenetzky Laura , Vera Pablo , Zangrando Atilio F. , Tessone Augusto , Avena Sergio , Lia Verónica , Puebla Andrea , Dejean Cristina
Published: May 2023

The increasing use of massively parallel sequencing in the study of current and ancient human populations has enabled new approaches to bioanthropological and archaeological issues; however, its application to archaeological samples requires the use of technologies that are not easily accessible outside US and European research centers. To obtain an ancient mitogenome in Argentina, several institutions collaborated to apply massively parallel sequencing and bioinformatic methodologies on an enriched ancient DNA library of an individual from the Beagle Channel (dated 1504 ± 46 years BP), a region of particular interest for this line of inquiry. Phylogenetic reconstruction showed a close relationship with a Yamana from Navarino Island and an individual from Hoste Island (Chilean Antarctic Province): the three shared an ancestor who lived between 203 and 4,439 years ago. These three have mutations reported only for current and ancient individuals from the Beagle Channel, and their relationship with the rest of the D1g sub-haplogroups is unclear. The results obtained here are consistent with the reduction of mobility in the Fuegian archipelago around 4500 years BP that has been proposed based on archaeological evidence.
Accidental Conflict: America, China, and the Clash of False Narratives. By Stephen Roach. New Haven: Yale University Press, 2022. 448 pp. Illustrations. Hardcover, $32.50. ISBN: 978-0-300-25964-3. Mao and Markets: The Communist Roots of Chinese Enterprise. By Christopher Marquis and Kunyuan Qiao. New Haven: Yale University Press, 2022. 384 pp. Illustrations. Hardcover, $30.00. ISBN: 978-0-300-26338-1.
Authors: Friedman Jeremy S.
Published: May 2023

Few phrases in the discourse of the Chinese Communist Party (CCP) have proven as durable and pliable as “seeking truth from facts.” The phrase was first used by Mao Zedong in the 1930s as a way to legitimate the CCP's departure from Stalinist direction, and it was later mobilized by Deng Xiaoping to signal a shift from Maoism toward new avenues of policy experimentation. In recent years, as rising tensions in the US-China relationship have produced a burgeoning literature that seeks to understand and interpret Beijing's intentions for a Western audience, the phrase has become as applicable to the study of China as it has long been to the governance of China. This is not merely because the People's Republic of China (PRC) provides an endless source of raw material for speculation and analysis, obscured behind a veil of obfuscation, censorship, and propaganda constructed by the world's largest and most powerful political party. It is also because the stakes of the debate—coming at a time when the role of the West in general, and the United States in particular, has been thrown into doubt by social division, political dysfunction, and economic decline—seem to provide grounds for doubting the motives of anyone who aspires to take a stand on such a crucial yet ambiguous question as the true nature of CCP rule. With so many facts to choose from, how are we to know which will produce the right truths, and more importantly, who is doing the choosing and why?
Wheat seed demand assessment assisted by genotyping in Ethiopia
Authors: Habte Endeshaw , Yirga Chilot , Jaleta Moti , Tesfaye Kindie , Bekele Adam , Erenstein Olaf
Published: May 2023

This study examines the extent to which wheat varieties supplied by the formal seed system align with the varieties demanded and used by farmers in Ethiopia. The framework of stated and revealed preferences drawn from the consumer preference theory is used to analyze farmer demand for different wheat varieties. We used official data from the formal seed sector and representative survey data from wheat farm households in Ethiopia. The survey data allow to contrast the farmer reported varietal use with genotyping by sequencing (also known as DNA fingerprinting). Farmers’ reliance on informal seed sources and own saved seed, among others, contributes to the misidentification of the varieties they grow. Consequently, farmers are likely to misinform the formal seed demand assessment leading to either an over- or underestimation of actual seed demand for specific wheat varieties. Genotyping by sequencing, as opposed to farmer reports, established the persistence of old varieties. This also implies vulnerability of wheat production to disease dynamics depending on the longevity of disease resistance by the variety in use. Apart from narrowing the gap between the actual and stated demand and ensuring timely replacement of wheat varieties, genotyping-assisted estimates can save seed carry-over cost. Genotyping by sequencing is increasingly used as the new benchmark and gold standard for identifying and tracking the adoption of crop varieties. The technique has potential to enhance the performance of the seed sector through effective planning that can optimize resource commitments and accelerate the rate of varietal replacement.
Joint Inversion of Geodetic and Strong Motion Data for the 2012, Mw 6.1–6.0, May 20th and May 29th, Northern Italy Earthquakes: Source Models and Seismotectonic Interpretation
Authors: Improta L. , Cirella A. , Pezzo G. , Molinari I. , Piatanesi A.
Published: May 2023

We present the first rupture models of the two mainshocks of the 2012 northern Italy sequence, determined by jointly inverting seismic and geodetic data. We aim at providing new insights into the mainshocks for which contrasting seismotectonic interpretations are proposed in literature. Sources' geometric parameters were constrained by seismic reflection profiles, 3‐D relocations and focal mechanisms of mainshocks/aftershocks. Site‐specific velocity profiles were used to model accelerograms affected by strong propagation effects related to the Po basin. Our source models differ significantly from previous ones relying on either seismic or geodetic data. Their comparison against geological sections and aftershock distribution provides new insights about the ruptured thrust faults. The May 20th Mw6.1 mainshock activated the Middle Ferrara thrust‐ramp dipping ∼45° SSW‐wards, breaking a main eastern slip patch 4–15 km deep in Mesozoic carbonates (maximum slip 0.7–0.8 m) and Paleozoic‐Triassic basement rocks, and a small western patch in the basement. The May 29th Mw6.0 mainshock featured two separated asperities along the Mirandola thrust‐ramp dipping ∼42° S‐wards: an eastern asperity 4–15 km deep in Mesozoic carbonates and basement rocks (maximum slip 0.7 m) and a deeper western one (7–16 km depth) mainly in the basement (slip peak 0.8 m). On‐fault aftershocks were concentrated within the basement and Mesozoic carbonates, devoiding high‐slip zones. Slip and aftershock distribution was controlled by the rheological transition between Mesozoic carbonates and Cenozoic sediments. Unlike previous thin‐skinned tectonic interpretations, our results point to a complex rupture process along moderately dipping (40°–45°) thrust‐ramps deeply rooted into the Paleozoic crystalline basement.
A Tropical Cocktail of Organic Matter Sources: Variability in Supraglacial and Glacier Outflow Dissolved Organic Matter Composition and Age Across the Ecuadorian Andes
Authors: Holt Amy D. , Kellerman Anne M. , Battin Tom. I. , McKenna Amy M. , Hood Eran , Andino Patricio , Crespo‐Pérez Verónica , Peter Hannes , Schön Martina , De Staercke Vincent , Styllas Michail , Tolosano Matteo , Spencer Robert G. M.
Published: May 2023

The biogeochemistry of rapidly retreating Andean glaciers is poorly understood, and Ecuadorian glacier dissolved organic matter (DOM) composition is unknown. This study examined molecular composition and carbon isotopes of DOM from supraglacial and outflow streams (n = 5 and 14, respectively) across five ice capped volcanoes in Ecuador. Compositional metrics were paired with streamwater isotope analyses (δ18O) to assess if outflow DOM composition was associated with regional precipitation gradients and thus an atmospheric origin of glacier DOM. Ecuadorian glacier outflows exported ancient, biolabile dissolved organic carbon (DOC), and DOM contained a high relative abundance (RA) of aliphatic and peptide‐like compounds (≥27%RA). Outflows were consistently more depleted in Δ14C‐DOC (i.e., older) compared to supraglacial streams (mean −195.2 and −61.3‰ respectively), perhaps due to integration of spatially heterogenous and variably aged DOM pools across the supraglacial environment, or incorporation of aged subglacial OM as runoff was routed to the outflow. Across Ecuador, Δ14C‐DOC enrichment was associated with decreased aromaticity of DOM, due to increased contributions of organic matter (OM) from microbial processes or atmospheric deposition of recently fixed and subsequently degraded OM (e.g., biomass burning byproducts). There was a regional gradient between glacier outflow DOM composition and streamwater δ18O, suggesting covariation between regional precipitation gradients and the DOM exported from glacier outflows. Ultimately, this highlights that atmospheric deposition may exert a control on glacier outflow DOM composition, suggesting regional air circulation patterns and precipitation sources in part determine the origins and quality of OM exported from glacier environments.
Thank You to Our 2022 Peer Reviewers
Authors: Griffies Stephen M. , Fan Jiwen , MacBean Natasha , Schneider Tapio
Published: May 2023

The editors of Journal of Advances in Modeling Earth Systems thank the 702 reviewers who provided 1362 reviews during 2022. Their hard work and insights, typically done anonymously, benefits authors, readers, and the broader science community.
Design improvement of the conversion mechanism from balloon inflation to bending motion for inflatable film actuators
Authors: Hori Y. , Konishi S.
Published: May 2023

Various soft actuators have been investigated to overcome the drawbacks of conventional solid machines and explore the applications of soft robotics. In particular, and because they are expected to be applicable in minimally invasive medicine because of their safety, soft inflatable microactuators using an actuation conversion mechanism from balloon inflation to bending motion have been proposed for high-output bending motion. These microactuators could be applied to create an operation space by safely moving organs and tissues; however, the conversion efficiency could be further improved. This study aimed to improve conversion efficiency by investigating the design of the conversion mechanism. The contact conditions between the inflated balloon and conversion film were examined to improve the contact area for force transmission, with the contact area dependent on the length of the contact arc between the balloon and force conversion mechanism and on the amount of balloon deformation. In addition, surface contact friction between the balloon and film, which affects actuator performance, was also investigated. The generated force of the improved device is 1.21 N at 80 kPa when it bends 10 mm, which is 2.2 times the generated force of the previous design. This improved soft inflatable microactuator is expected to assist in performing operations in a limited space, such as in endoscopic or laparoscopic operations.
Glioma immunotherapy enhancement and CD8-specific sialic acid cleavage by isocitrate dehydrogenase (IDH)-1
Authors: Cordner Ryan , Jhun Michelle , Panwar Akanksha , Wang HongQiang , Gull Nicole , Murali Ramachandran , McAbee Joseph H. , Mardiros Armen , Sanchez-Takei Akane , Mazer Mia W. , Fan Xuemo , Jouanneau Emmanuel , Yu John S. , Black Keith L. , Wheeler Christopher J.
Published: May 2023

The promise of adaptive cancer immunotherapy in treating highly malignant tumors such as glioblastoma multiforme (GBM) can only be realized through expanding its benefits to more patients. Alleviating various modes of immune suppression has so far failed to achieve such expansion, but exploiting endogenous immune enhancers among mutated cancer genes could represent a more direct approach to immunotherapy improvement. We found that Isocitrate Dehydrogenase-1 (IDH1), which is commonly mutated in gliomas, enhances glioma vaccine efficacy in mice and discerns long from short survivors after vaccine therapy in GBM patients. Extracellular IDH1 directly enhanced T cell responses to multiple tumor antigens, and prolonged experimental glioma cell lysis. Moreover, IDH1 specifically bound to and exhibited sialidase activity against CD8. By contrast, mutant IDH1R132H lacked sialidase activity, delayed killing in glioma cells, and decreased host survival after immunotherapy. Overall, our findings identify IDH1 as an immunotherapeutic enhancer that mediates the known T cell-enhancing reaction of CD8 desialylation. This uncovers a new axis for immunotherapeutic improvement in GBM and other cancers, reveals novel physiological and molecular functions of IDH1, and hints at an unexpectedly direct link between lytic T cell function and metabolic activity in target cells.
Lysogenic bacteriophages encoding arsenic resistance determinants promote bacterial community adaptation to arsenic toxicity
Authors: Tang Xiang , Zhong Linrui , Tang Lin , Fan Changzheng , Zhang Baowei , Wang Mier , Dong Haoran , Zhou Chengyun , Rensing Christopher , Zhou Shungui , Zeng Guangming
Published: May 2023

Emerging evidence from genomics gives us a glimpse into the potential contribution of lysogenic bacteriophages (phages) to the environmental adaptability of their hosts. However, it is challenging to quantify this kind of contribution due to the lack of appropriate genetic markers and the associated controllable environmental factors. Here, based on the unique transformable nature of arsenic (the controllable environmental factor), a series of flooding microcosms was established to investigate the contribution of arsM-bearing lysogenic phages to their hosts’ adaptation to trivalent arsenic [As(III)] toxicity, where arsM is the marker gene associated with microbial As(III) detoxification. In the 15-day flooding period, the concentration of As(III) was significantly increased, and this elevated As(III) toxicity visibly inhibited the bacterial population, but the latter quickly adapted to As(III) toxicity. During the flooding period, some lysogenic phages re-infected new hosts after an early burst, while others persistently followed the productive cycle (i.e., lytic cycle). The unique phage-host interplay contributed to the rapid spread of arsM among soil microbiota, enabling the quick recovery of the bacterial community. Moreover, the higher abundance of arsM imparted a greater arsenic methylation capability to soil microbiota. Collectively, this study provides experimental evidence for lysogenic phages assisting their hosts in adapting to an extreme environment, which highlights the ecological perspectives on lysogenic phage-host mutualism.
Second haploidentical stem cell transplantation (HAPLO-SCT2) after relapse from a first HAPLO-SCT in acute leukaemia—a study on behalf of the Acute Leukaemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Filippini Velázquez Giuliano , Labopin Myriam , Tischer Johanna , Raiola Anna Maria , Angelucci Emanuele , Kulagin Alexander D. , Galieni Piero , Bermúdez Arancha , Bulabois Claude-Eric , Kröger Nicolaus , Díez-Martín José Luis , Kwon Mi , Nagler Arnon , Schmid Christoph , Ciceri Fabio , Mohty Mohamad
Published: May 2023

For patients with acute myeloid and lymphoblastic leukaemia (AML/ALL) lacking a matched sibling or unrelated donor, haploidentical stem cell transplantation (HAPLO-SCT) is increasingly used. However, available data on the treatment of relapse after HAPLO-SCT, including feasibility and efficacy of a second HAPLO-SCT (HAPLO-SCT2), is scarce. Hence, adults with AML/ALL, that had undergone HAPLO-SCT2 without ex-vivo manipulation after haematologic relapse from HAPLO-SCT1 were selected for a retrospective registry analysis. Eighty-two patients (AML, n = 63, ALL, n = 19, median follow-up: 33 months) were identified. Engraftment rate was 87%. At day +180, cumulative incidences of acute GvHD II-IV°/chronic GvHD were 23.9%/22.6%, respectively. Two-year overall survival/leukaemia-free survival (OS/LFS) were 34.3%/25.4%; 2-year non-relapse mortality (NRM) and relapse incidence (RI) were 17.6% and 57%. Leukaemia was the most frequent cause of death. Separated by disease, 2-year OS/LFS/NRM/RI were 28.7%/22.3%/16.2%/61.6% in AML, and 55.3%/38.4%/23.5%/38.2% in ALL patients. In a risk-factor analysis among patients with AML, stage at HAPLO-SCT1 and HAPLO-SCT2, and interval from HAPLO-SCT1 to relapse significantly influenced outcome. Our data demonstrate that HAPLO-SCT2 is a viable option in acute leukaemia relapse after HAPLO-SCT1. Engraftment, toxicity, risk factors and long-term outcome are comparable to data reported after allo-SCT2 in a matched donor setting.
Ti3C2Tx MXene as a growth template for amorphous RuOx in carbon nanofiber-based flexible electrodes for enhanced pseudocapacitive energy storage
Authors: Hwang Hyewon , Yang Sungeun , Yuk Seoyeon , Lee Kug-Seung , Byun Segi , Lee Dongju
Published: May 2023

A noble surface engineering method was developed to create a binder-free flexible electrode comprising Ti3C2Tx MXene/carbon nanofibers (MCNFs) covered by amorphous RuOx with a combined electrospinning and hydrothermal process. Utilizing the hydrophilicity of the MXene on/in the MCNFs, RuOx was easily coated on the surfaces of the MCNFs through oxygen-mediated chemical bonding between the functional groups of the MXene and Ru ions. A structural analysis revealed that the MXene acted as a growth template for RuOx and that the formed RuOx had an amorphous and disordered state in the composite electrode, which impacted the electrochemical performance. The electrochemical tests showed that these composite electrodes improved the electrochemical performance, with a two-fold increase in the gravimetric capacitance (279.4 F/g at 2 mV/s) relative to that of pristine MCNFs, a wide potential window (from 0.7 to 1 V) providing a superior energy density of 8.5 Wh/kg at a power density of 85.8 W/kg, as well as long-term cycling stability (99% after 10,000 cycles). The synergetic effect of the RuOx and MXene in the composite electrodes was attributed to an enhanced pseudocapacitive reaction. Our novel electrodes and fabrication method confirm the great potential of CNF-based composites for the development of high-performance binder-free electrodes for supercapacitors.
Negative interfacial energies of dynamic polymer brush interfaces: a discussion of the free energy balance
Authors: Saito Masayuki , Ito Kohzo , Yokoyama Hideaki
Published: May 2023

Interfacial energy is an important physical parameter for describing interfacial properties. However, quantifying the interfacial energy of a polymer–liquid interface is extremely difficult because numerous polymers reconstruct when exposed to liquids. A dynamic polymer brush is a reconstructed surface. When a hydrophobic elastomer containing amphiphilic block copolymers comes into contact with water, the copolymers spontaneously segregate at the elastomer–water interface to form a hydrophilic brush known as a dynamic polymer brush. We previously succeeded in analyzing the interfacial energy of a dynamic polymer brush interface by measuring the deformation of an ultrathin square elastomer film floating on water. However, the quantitativity remains debatable because the elastic modulus of a bulk elastomer sheet, rather than an ultrathin elastomer film, was used. In this study, we reanalyze the interfacial energy of a dynamic polymer brush system using the ultrathin-film modulus, which we recently measured via a film-on-water tensile test. Large negative interfacial energy was observed for the system of high-density stretched brushes. The free energy balance for the dynamic polymer brush system floating on water was calculated, and results validated the negative interfacial energy, which is a distinctive feature of dynamic polymer brushes.
Comparison of diabetic retinopathy severity grading on ETDRS 7-field versus ultrawide-field assessment
Authors: Attiku Yamini , Nittala Muneeswar Gupta , Velaga Swetha B. , Ramachandra Chaithanya , Bhat Sandeep , Solanki Kaushal , Jayadev Chaitra , Choudhry Netan , Orr Samantha Miyoko Ashlyn , Jiang Shangjun , He Ye , Sadda SriniVas R.
Published: May 2023

Objectives

To compare the diabetic retinopathy (DR) severity level determined when considering only the ETDRS 7-field region versus the entire ultrawidefield (UWF) image.

Methods

In this retrospective, cross-sectional study, UWF pseudocolor images were graded on the Eyenuk image viewing, grading, and annotation platform for the severity of DR considering only the regions within the ETDRS 7-fields as well as the entire UWF image using two different protocols: 1) the simple International Classification of Diabetic Retinopathy (ICDR) scale and 2) the more complex DRCR.net Protocol AA grading scale.

Results

A total of 250 eyes from 157 patients were included in this analysis. Six eyes (2.4%) demonstrated a discrepancy in severity level between the ETDRS 7-field region and the entire UWF image when using the ICDR classification system. The discrepancies were due to the presence of lesions [intraretinal haemorrhage (n = 2), neovascular disease (n = 4)] in the peripheral fields which were not identified in the ETDRS 7-fields. Fourteen eyes (5.6%) had a discrepancy in severity level between the ETDRS 7-field region and the entire UWF image when using the ETDRS DRSS Protocol AA grading scale. The discrepancies were due to the presence of a higher level of disease [intraretinal haemorrhage (n = 4), neovascularization (n = 4), preretinal haemorrhage (n = 2), scatter laser scars (n = 4)] in the peripheral fields.

Conclusion

Although considering regions outside of the ETDRS 7-fields altered the DR severity level assessment in <5% of cases in this cohort, significant and potentially vision-threatening lesions including neovascularization and preretinal haemorrhage were identified in these peripheral regions. This highlights the importance of evaluating the entire UWF region when assessing patients with diabetic retinopathy.
Loophole-free Bell inequality violation with superconducting circuits
Authors: Storz Simon , Schär Josua , Kulikov Anatoly , Magnard Paul , Kurpiers Philipp , Lütolf Janis , Walter Theo , Copetudo Adrian , Reuer Kevin , Akin Abdulkadir , Besse Jean-Claude , Gabureac Mihai , Norris Graham J. , Rosario Andrés , Martin Ferran , Martinez José , Amaya Waldimar , Mitchell Morgan W. , Abellan Carlos , Bancal Jean-Daniel , Sangouard Nicolas , Royer Baptiste , Blais Alexandre , Wallraff Andreas
Published: May 2023

Superposition, entanglement and non-locality constitute fundamental features of quantum physics. The fact that quantum physics does not follow the principle of local causality1–3 can be experimentally demonstrated in Bell tests4 performed on pairs of spatially separated, entangled quantum systems. Although Bell tests, which are widely regarded as a litmus test of quantum physics, have been explored using a broad range of quantum systems over the past 50 years, only relatively recently have experiments free of so-called loopholes5 succeeded. Such experiments have been performed with spins in nitrogen–vacancy centres6, optical photons7–9 and neutral atoms10. Here we demonstrate a loophole-free violation of Bell’s inequality with superconducting circuits, which are a prime contender for realizing quantum computing technology11. To evaluate a Clauser–Horne–Shimony–Holt-type Bell inequality4, we deterministically entangle a pair of qubits12 and perform fast and high-fidelity measurements13 along randomly chosen bases on the qubits connected through a cryogenic link14 spanning a distance of 30 metres. Evaluating more than 1 million experimental trials, we find an average S value of 2.0747 ± 0.0033, violating Bell’s inequality with a P value smaller than 10−108. Our work demonstrates that non-locality is a viable new resource in quantum information technology realized with superconducting circuits with potential applications in quantum communication, quantum computing and fundamental physics15.