bluuebunny/crossref_metadata_2025 huggingface dataset:
Bridging the gap: opportunities for transitions of care pharmacist review of outpatient parenteral antimicrobial therapy prescriptions prior to hospital discharge
Authors: Stashluk Sara , Ramos Michelle , Carettini Tyla , Cutrell James B. , Mathew Seana , Monogue Marguerite , Nguyen Jennifer , Sanders James M. , Golnabi Esther Y.
Published: April 2024

Purpose:

Pharmacist-led initiatives providing optimization of medications during transitions of care (TOC) have shown to have a positive impact on prescribing practices and patient outcomes. This study aims to evaluate the role and impact of TOC pharmacist review of outpatient parenteral antimicrobial therapy (OPAT) prescriptions prior to hospital discharge.

Methods:

In a retrospective chart review, patients with OPAT prescriptions between November 1, 2022 and January 31, 2023 were evaluated using prescription-specific and intervention-specific data points. Prescription-specific data points included intravenous antimicrobials prescribed, indication, prescribing team, and time from OPAT prescription to TOC pharmacist review. Intervention-specific data points included antimicrobial optimization (dose/frequency, duration, and other), prescription clarification, and laboratory monitoring.

Results:

Of the 137 OPAT prescriptions evaluated, 67 required intervention by TOC pharmacists (48.9%). The General Infectious Disease Consult team placed 71.5% of OPAT prescriptions and required interventions less frequently (42.9%) compared to the other teams. Antimicrobial optimization interventions accounted for 54.2% of interventions, which were primarily related to medication dose and frequency.

Conclusion:

The TOC pharmacists can play a key role in the evaluation of OPAT prescriptions at hospital discharge. This intervention demonstrated how TOC pharmacists can effectively collaborate with the OPAT team, which builds on prior evidence of the role and value of pharmacists in the transitional care setting.
Impact of COVID-19 on urgent care diagnoses and the new AXR metric
Authors: Hersh Adam L. , Stenehjem Edward A. , Fino Nora , Spivak Emily S.
Published: April 2024

We examined the antibiotic prescribing rate for respiratory diagnoses (AXR) before and after onset of the COVID-19 pandemic in urgent care clinics. At the onset, AXR declined substantially due to changes in case mix. Using AXR as a stewardship metric requires monitoring of changes in case mix.
Excitation and evolution of radiating modes in supersonic boundary layers. Part 1. Fundamental resonance with impinging sound waves
Authors: Qin Fufeng , Wu Xuesong
Published: April 2024

This paper investigates the linear and nonlinear evolution of radiating modes in supersonic boundary layers under the influence of impinging sound waves. It is found that the ensuing boundary-layer response is extraordinarily large for a subset of the sound frequency and incident angle, and the resonant over-reflection, corresponding to the reflection coefficient becoming infinite, occurs at a particular pairing of frequency and incident angle. At this point, the reflected wave coincides with a locally neutral radiating mode, which emits spontaneously sound in the form of Mach waves. A fundamental resonance takes place between the incident wave and the radiating mode. Viewed in a developing boundary layer, the response is rendered finite by introducing non-parallelism and nonlinear effects near the neutral location of the radiating mode, where the sound wave directly excites the radiating mode and/or acts on the pre-existing radiating mode. Inhomogeneous amplitude equations are derived to describe the excitation as well as the nonlinear development of the radiating mode in the two regimes where non-equilibrium and non-parallelism play a leading-order role, respectively. A composite amplitude equation is then constructed to take into account both non-parallelism and non-equilibrium effects. This amplitude equation is, with an appropriate initial condition, solved to quantify the impact of the impinging sound wave on the linear and nonlinear instability characteristics of the radiating mode. The far-field analysis shows that the Mach wave field of the radiating mode is changed significantly due to the incident sound.
Galaxy 3D shape recovery using mixture density network
Authors: Yong Suk Yee , Harborne K.E. , Foster Caroline , Bassett Robert , Poole Gregory B. , Cavanagh Mitchell
Published: April 2024

Since the turn of the century, astronomers have been exploiting the rich information afforded by combining stellar kinematic maps and imaging in an attempt to recover the intrinsic, three-dimensional (3D) shape of a galaxy. A common intrinsic shape recovery method relies on an expected monotonic relationship between the intrinsic misalignment of the kinematic and morphological axes and the triaxiality parameter. Recent studies have, however, cast doubt about underlying assumptions relating shape and intrinsic kinematic misalignment. In this work, we aim to recover the 3D shape of individual galaxies using their projected stellar kinematic and flux distributions using a supervised machine learning approach with mixture density network (MDN). Using a mock dataset of the EAGLE hydrodynamical cosmological simulation, we train the MDN model for a carefully selected set of common kinematic and photometric parameters. Compared to previous methods, we demonstrate potential improvements achieved with the MDN model to retrieve the 3D galaxy shape along with the uncertainties, especially for prolate and triaxial systems. We make specific recommendations for recovering galaxy intrinsic shapes relevant for current and future integral field spectroscopic galaxy surveys.
Bureaucratic Representation and Gender Mainstreaming in International Organizations: Evidence from the World Bank
Authors: HEINZEL MIRKO , WEAVER CATHERINE , JORGENSEN SAMANTHA
Published: April 2024

How does the representation of women in international organizations affect the implementation of gender mainstreaming policies? Many international organizations have adopted policies to prevent gender discrimination in their operations, but their implementation is often lackluster. We argue that these shortcomings appear due to a combination of institutional incentives and an underrepresentation of women in their staff. We test the argument in the case of the World Bank, drawing on highly disaggregated staffing data, an instrumental variable strategy, and an elite survey experiment. Our results show that most staff incorporate at least shallow gender mainstreaming in their projects. Deeper implementation of gender mainstreaming is more likely when women staff supervise projects, hold positions of authority, and are more represented as coworkers. These results contribute to understanding the disconnects between talk and action on mainstreaming policies and inform debates on representation in global governance.
Vitamin D status of pregnant women with obesity in the UK and its association with pregnancy outcomes: a secondary analysis of the UK Pregnancies Better Eating and Activity Trial (UPBEAT) study
Authors: O’Callaghan Karen M. , Nowak Katarzyna G. , Dalrymple Kathryn V. , Poston Lucilla , Rigutto-Farebrother Jessica , Quotah Ola F. , White Sara L. , Flynn Angela C. ,   UPBEAT Consortium
Published: April 2024

Prenatal vitamin D deficiency is widely reported and may affect perinatal outcomes. In this secondary analysis of the UK Pregnancies Better Eating and Activity Trial, we examined vitamin D status and its relationship with selected pregnancy outcomes in women with obesity (BMI ≥ 30 kg/m2) from multi-ethnic inner-city settings in the UK. Determinants of vitamin D status at a mean of 17 ± 1 weeks’ gestation were assessed using multivariable linear regression and reported as percent differences in serum 25-hydroxyvitamin D (25(OH)D). Associations between 25(OH)D and clinical outcomes were examined using logistic regression. Among 1089 participants, 67 % had 25(OH)D < 50 nmol/l and 26 % had concentrations < 25 nmol/l. In fully adjusted models accounting for socio-demographic and anthropometric characteristics, 25(OH)D was lower among women of Black (% difference = −33; 95 % CI: −39, −27), Asian (% difference = −43; 95 % CI: −51, −35) and other non-White (% difference = −26; 95 % CI: −35, −14) ethnicity compared with women of White ethnicity (n 1086; P < 0·001 for all). In unadjusted analysis, risk of gestational diabetes was greater in women with 25(OH)D < 25 nmol/l compared with ≥ 50 nmol/l (OR = 1·58; 95 % CI: 1·09, 2·31), but the magnitude of effect estimates was attenuated in the multivariable model (OR = 1·33; 95 % CI: 0·88, 2·00). There were no associations between 25(OH)D and risk of preeclampsia, preterm birth or small for gestational age or large-for-gestational-age delivery. These findings demonstrate low 25(OH)D among pregnant women with obesity and highlight ethnic disparities in vitamin D status in the UK. However, evidence for a greater risk of adverse perinatal outcomes among women with vitamin D deficiency was limited.
Effectiveness of Global Leadership Initiative on Malnutrition and Subjective Global Assessment for diagnosing malnutrition and predicting wound healing in patients with diabetic foot ulcers
Authors: Yuan Zhimin , Jiang Chunjie , Lao Guojuan , Zhang Yan , Wang Chunying , Zhu Yingying , Chen Chaogang , Ran Jianmin , Wang Chengzhi , Zhu Ping
Published: April 2024

Malnutrition significantly hampers wound healing processes. This study aimed to compare the effectiveness of the Global Leadership Initiative on Malnutrition (GLIM) and Subjective Global Assessment (SGA) in diagnosing malnutrition and predicting wound healing in patients with diabetic foot ulcers (DFU). GLIM criteria were evaluated for sensitivity (SE), specificity (SP), positive predictive value, negative predictive value and kappa (κ) against SGA as the reference. Modified Poisson regression model and the DeLong test investigated the association between malnutrition and non-healing ulcers over 6 months. This retrospective cohort study included 398 patients with DFU, with a mean age of 66·3 ± 11·9 years. According to SGA and GLIM criteria, malnutrition rates were 50·8 % and 42·7 %, respectively. GLIM criteria showed a SE of 67·3 % (95 % CI 60·4 %, 73·7 %) and SP of 82·7 % (95 % CI 76·6 %, 87·7 %) in identifying malnutrition, with a positive predictive value of 80·0 % and a negative predictive value of 71·1 % (κ = 0·50) compared with SGA. Multivariate analysis demonstrated that malnutrition, as assessed by SGA, was an independent risk factor for non-healing (relative risk (RR) 1·84, 95 % CI 1·45, 2·34), whereas GLIM criteria were associated with poorer ulcer healing in patients with estimated glomerular filtration rate ≥ 60 ml/min/1·73m2 (RR: 1·46, 95 % CI 1·10, 1·94). SGA demonstrated a superior area under the receiver’s operating characteristic curve for predicting non-healing compared with GLIM criteria (0·70 (0·65–0·75) v. 0·63 (0·58–0·65), P < 0·01). These findings suggest that both nutritional assessment tools effectively identify patients with DFU at increased risk, with SGA showing superior performance in predicting non-healing ulcers.
Widening the Arachis hypogaea seed chemical composition: the case of a recombinant inbred lines introgressed with genes from three different wild species
Authors: de Blas Francisco , Seijo José Guillermo , Costero Beatriz Del Pilar , Bressano Marina , Marchesino Mariana , Grosso Nelson Rubén
Published: April 2024

Peanut (Arachis hypogaea L.) is an important row crop rich in oil, protein, vitamins and other micro-nutrients. The intensive selection of the cultigen, a cultivated plant deliberately altered by humans through cultivation, has resulted in favourable changes in yield and biochemical composition. Nevertheless, it has generated a narrow genetic basis that limits the development of new varieties with resistance to pests, diseases and environmental stresses. In this study, we address this limitation by characterizing the proximate and fatty acid composition of a multi-disease-resistant interspecific recombinant inbred line (RIL) population derived from three wild Arachis species and a cultivated elite peanut line that is being used to widen the genetic basis of the crop. The population was also genotyped with the Axiom Arachis 48K SNP array and used to detect quantitative trait loci (QTL) for oil, protein content and oleic and linoleic fatty acid percentages. A wide range of proximate composition was found in the RIL population. Eighteen and 11 individuals had high oil and protein content, respectively, and no undesirable traits related to oil quality had been introduced into the population from wild species. The fatty acid composition of oleic and linoleic acids was found to be regulated by two major QTL. The discovery of markers within the major effect QTL for the most significant chemical traits provides new opportunities for the creation of resistant and extremely nutrient-dense peanut cultivars.
Afterword: Resonant Objects
Authors: Kaganovsky Lilya
Published: April 2024

The papers in this cluster—and sound studies more broadly—attune our ears to hearing and listening, to paying attention to that “other” important sense of modernity: the aural or sonic that so often is asked to play second fiddle to the visual. The challenge of sound studies, Jonathan Sterne reminds us, “is to think across sounds, to consider sonic phenomena in relationship to one another—as types of sonic phenomena rather than as things-in-themselves—whether they be music, voices, listening, media, buildings, performances, or another other path into sonic life.”
Cold War Networks and the Scholarly Byt: How Russian Formalism Became an American Thing
Authors: Tripiccione Lidia
Published: April 2024

This article centers on one key episode in the reception of Russian formalism in western academia, the 1955 publication of Victor Erlich's acclaimed Russian Formalism. History. Doctrine. The article discusses the appearance of the monograph in the young field of Slavic Studies through novel lenses and conceptualizes the monograph as the result of the activity of a network of heterogeneous actors that contributed to the formation and publication of the book. Methodologically, I develop the concept of the scholarly by hybridizing Boris Eikhenbaum's literaturnyi byt and Bruno Latour's Actor-Network-Theory. Finally, I suggest that the methodological framework developed in the article could be productively applied to further the study of Russian formalism reception.
Room for Noise in Soviet Sound Recording
Authors: Kendall Matthew
Published: April 2024

When he was nearing the end of his life, Viktor Shklovskii recorded an oral interview that was recently digitized and published by the Moscow oral history project (http://www.oralhistory.ru). During the audio encoding process, Shklovskii's voice and the contents of the interview were badly distorted. This article frames noise as an important force that impacts not only how sound documents become authoritative archival evidence, but also indexically points to the context of their creation. To do so, I compare the role that sound plays in Shklovskii's own writing with the history of the Soviet state's archival preservation of sound, a variety of amateur sound recording projects, and mainstream discussions of audio quality and sound recording in the Soviet press. Ultimately, I argue that for audio researchers, making room for noise allows us to see the emancipatory gesture embedded within amateur tape recording itself: the ambiguous noise that seemingly marred unpolished recordings can instead be heard as a sonic alternative to official narratives.
A “Common Enterprise”? The Role of Utility Infrastructure in the Divided City of Teschen, 1920–1938
Authors: Piskačová Zora
Published: April 2024

Teschen Silesia after the First World War is typically portrayed as a region of ethnic conflict and national rivalry. Focusing on gas, electricity, and water infrastructures of the divided city of Teschen, now Polish Cieszyn and Czech Český Těšín, this article shifts the focus from nationalist discourses of animosity and upheaval to stabilization and local cross-border cooperation. In examining the cities’ conjoined utility networks’ management as well as their partial reorientation towards domestic suppliers, it demonstrates that local interests and economic pragmatism often trumped national antagonism. Moreover, by allowing municipal politics to take central stage, the article shows that small town leaders on the periphery were not only obedient servants of their respective central governments. While the Polish and Czechoslovak nation-states attempted to curb transnational municipal dependency and thus erase all remnants of the Habsburg regime, small town leaders often acted as administrators first and nationalists second.
Absorption of Solar Radiation by Noctilucent Clouds in a Changing Climate
Authors: Lübken Franz‐Josef , Baumgarten Gerd , Grygalashvyly Mykhaylo , Vellalassery Ashique
Published: April 2024

The expected increase in climate change related methane emissions will result in an increase in middle atmospheric water vapor abundance. This will in turn amplify the brightness of noctilucent clouds (NLC). To examine how NLC will impact the absorption of solar radiation, we utilized both an atmospheric background model and a microphysical model spanning the period from 1950 to 2100. At a latitude of 69 ± 3°N, UV absorption at λ = 126 nm is projected to rise from ∼3% to ∼7%. In specific regions, the absorption may spike to approximately 30% by the year 2100. In the visible spectrum, we observe an absorption increase from 0.0030% in 1950 to 0.020% by 2100. Local absorption reach up to 0.35% by the year 2100. These trends are similar at 79 ± 3°N, but are smaller at 58 ± 3°N. Future average absorptions are comparable to solar cycle fluctuations, but local increases are significantly more pronounced. The ice mass contained in NLC is projected to surge from 677 to 1871 tons between 1950 and 2100.
An Updated Fault Coupling Model Along Major Block‐Bounding Faults on the Eastern and Northeastern Tibetan Plateau From a Stress‐Constrained Inversion of GPS and InSAR Data
Authors: Zhao Dezheng , Qu Chunyan , Shan Xinjian , Gong Wenyu , Weng Huihui , Chen Han , Wu Donglin
Published: April 2024

Large block‐bounding faults on the Tibetan plateau are significant geological structures that accommodate tectonic movements and accumulate stress, leading to large earthquakes. Quantifying the interseismic slip deficit rate helps to better assess the earthquake potential. We combine available InSAR (2015–2020) and interseismic GPS data to determine fault coupling along 14 major block‐bounding faults. Spatially dense InSAR measurements remarkably improve the resolution of the coupling model. Combined with a GPS‐constrained block model, we examine the performance of the inversion approach with the stress constraint and the common Laplacian smoothing based on both synthetic tests and real data. We suggest that, for continental strike‐slip faults, adding the stress constraint can mitigate unphysical coupling distributions due to unreasonable assumptions or modeling artifacts, reducing the model uncertainty and improving the accuracy of the coupling model. This is particularly useful for segments featured by a highly heterogeneous distribution of coupling along the transition zone from locking to creeping region, partially‐coupling segment, and junction zone between main and subsidiary faults. We present a large‐scale fault coupling map along the major block‐bounding faults on the northeastern and eastern Tibetan plateau, highlighting the distinct degrees of fault coupling and lateral variations. The collage of coupling maps along different faults demonstrates the kinematic features over a broad time scale during earthquake cycles ranging from early to late interseismic phases, such as the segments ruptured during the 2001 Kokoxili earthquake and the 1920 Haiyuan earthquake.
Examining Atmospheric River Life Cycles in East Antarctica
Authors: Wille Jonathan D. , Pohl Benjamin , Favier Vincent , Winters Andrew C. , Baiman Rebecca , Cavallo Steven M. , Leroy‐Dos Santos Christophe , Clem Kyle , Udy Danielle G. , Vance Tessa R. , Gorodetskaya Irina , Codron Francis , Berchet Antoine
Published: April 2024

During atmospheric river (AR) landfalls on the Antarctic ice sheet, the high waviness of the circumpolar polar jet stream allows for subtropical air masses to be advected toward the Antarctic coastline. These rare but high‐impact AR events are highly consequential for the Antarctic mass balance; yet little is known about the various atmospheric dynamical components determining their life cycle. By using an AR detection algorithm to retrieve AR landfalls at Dumont d'Urville and non‐AR analogs based on 700 hPa geopotential height, we examined what makes AR landfalls unique and studied the complete life cycle of ARs reaching Dumont d'Urville. ARs form in the mid‐latitudes/subtropics in areas of high surface evaporation, likely in response to tropical deep convection anomalies. These convection anomalies likely lead to Rossby wave trains that help amplify the upper‐tropospheric flow pattern. As the AR approaches Antarctica, condensation of isentropically lifted moisture causes latent heat release that—in conjunction with poleward warm air advection—induces geopotential height rises and anticyclonic upper‐level potential vorticity tendencies downstream. As evidenced by a blocking index, these tendencies lead to enhanced ridging/blocking that persist beyond the AR landfall time, sustaining warm air advection onto the ice sheet. Finally, we demonstrate a connection between tropopause polar vortices and mid‐latitude cyclogenesis in an AR case study. Overall, the non‐AR analogs reveal that the amplified jet pattern observed during AR landfalls is a result of enhanced poleward moisture transport and associated diabatic heating which is likely impossible to replicate without strong moisture transport.
Winter Insolation Modulates Boreal Tropical Monsoonal Temperatures in the Late Pleistocene
Authors: Dai Gaowen , Zhang Zhongshi , Otterå Odd Helge , Langebroek Petra M. , Yan Qing , Zhang Ran , Zhu Zongmin
Published: April 2024

During past glacial‐interglacial cycles, the boreal summer insolation is the most crucial external forcing for climate change. However, the question of whether summer insolation is a key forcing on temperatures in the boreal tropics remains under debate, hampering our understanding of climate change at low latitudes. To shed further light on this issue, we performed a series of equilibrium simulations with the NorESM‐L model over the past 425 ka. Our simulations show that in the boreal tropical monsoon region, the simulated annual temperature is anti‐phased towards the boreal summer insolation. This antiphase relation is also supported by some available geological data. Additional diagnostic analyses reveal that the tropical warmth throughout the year is more reliant on winter temperatures than on summer temperatures. This stands in contrast to the situation in middle to high latitudes, particularly in the Mediterranean region. Further correlation analysis and spectrum analysis suggest that the annual temperature in boreal tropics is highly linked to local winter insolation. Our results highlight complex hydrothermal configurations in the boreal tropics, suggesting a decoupling of temperature and precipitation. Specifically, variations in annual temperature and precipitation in the boreal tropics are driven by distinct patterns of seasonal insolation. We deduce that the unique hydrothermal configurations in North Africa may have influenced the dispersal of early humans out of Africa.
Net Primary Production of Ecoregions Across North America in Response to Drought and Wildfires From 2015 to 2022
Authors: Potter Christopher , Pass Stephanie , Ulrich Rachel
Published: April 2024

Ecosystem models are valuable tools to make climate‐related assessments of change when ground‐based measurements of water and carbon fluxes are not adequate to realistically capture regional variability. The Carnegie‐Ames‐Stanford Approach (CASA) is one such model based on satellite observations of monthly vegetation cover to estimate net primary production (NPP) of terrestrial ecosystems. CASA model predictions from 2015 to 2022 revealed several notable high and low periods in growing season NPP totals in certain biomes. Both Temperate Broadleaf and Boreal Forest production shifted from relatively high average NPP values in 2015 through 2019 to lower levels in 2020, typically representing a loss of 10%–14% of growing season NPP flux. This rapid decline in growing season NPP from 2019 to 2020–2021 was also estimated for the Temperate Grasslands and Savanna, Temperate Conifer Forest, and Tundra biomes. In contrast to the climate patterns in the temperate biomes that developed into severe widespread drought in 2020 and 2021 due to low precipitation totals and extreme hot temperatures, growing season NPP in the Tundra biome was depressed in these same years by colder temperature induced drought conditions at the high latitudes of North America. Drought severity classes were closely associated with different levels of decline in NPP in most biomes. Trends in NPP in areas of the largest wildfires in North America that burned between 2012 and 2021 were examined to assess recovery of vegetation and the resiliency of ecosystems during extreme drought periods.
Deepwater Renewal in a Large, Deep Lake (Lake Geneva): Identifying and Quantifying Winter Cooling Processes Using Heat Budget Decomposition
Authors: Peng N. , Lemmin U. , Mettra F. , Reiss R. S. , Barry D. A.
Published: April 2024

Wintertime deepwater renewal, which is important for heat–oxygen–nutrient exchange in lakes, is traditionally considered to be mainly driven by 1D vertical convective cooling. However, differential cooling between shallow and deep waters can produce density currents that flow into deep layers. In order to determine the role that these two cooling processes play in deepwater renewal, field measurements and 3D numerical modeling were combined to investigate heat content dynamics in Lake Geneva's large basin, the Grand Lac (maximum depth 309 m), during an exceptionally cold air spell in early 2012 where complete overturning had been reported. In a novel approach, the heat budget of the lake was decomposed, which allowed the identification and quantification of the heat budget components. The heat budget decomposition revealed that vertical convective cooling only penetrated to 200 m and that lateral advection was not only caused by density currents being discharged from the shallow littoral zone of the Grand Lac, but also from the Lake's shallow Petit Lac basin (maximum depth 75 m); the latter was found to be the main driver of heat content decrease in the deep layers of the Grand Lac below ∼200‐m depth. These findings provide unique insight into heat exchange processes that cannot be obtained from field data or numerical simulations alone. Heat budget decomposition proved to be a powerful, universally applicable tool for quantifying the contribution of alternative deepwater renewal processes. This is important, since deepwater renewal by convective cooling is weakening due to persistent global warming.
Anthropocene Activities Dramatically Alter Deep Underground Fluid Flux
Authors: Stanley Sarah
Published: April 2024

Scientists call for improved understanding of how our influence on deep subsurface fluids and microbes might affect the larger Earth system.
Monkeypox virus genomic accordion strategies
Authors: Monzón Sara , Varona Sarai , Negredo Anabel , Vidal-Freire Santiago , Patiño-Galindo Juan Angel , Ferressini-Gerpe Natalia , Zaballos Angel , Orviz Eva , Ayerdi Oskar , Muñoz-Gómez Ana , Delgado-Iribarren Alberto , Estrada Vicente , García Cristina , Molero Francisca , Sánchez-Mora Patricia , Torres Montserrat , Vázquez Ana , Galán Juan-Carlos , Torres Ignacio , Causse del Río Manuel , Merino-Diaz Laura , López Marcos , Galar Alicia , Cardeñoso Laura , Gutiérrez Almudena , Loras Cristina , Escribano Isabel , Alvarez-Argüelles Marta E. , del Río Leticia , Simón María , Meléndez María Angeles , Camacho Juan , Herrero Laura , Jiménez Pilar , Navarro-Rico María Luisa , Jado Isabel , Giannetti Elaina , Kuhn Jens H. , Sanchez-Lockhart Mariano , Di Paola Nicholas , Kugelman Jeffrey R. , Guerra Susana , García-Sastre Adolfo , Cuesta Isabel , Sánchez-Seco Maripaz P. , Palacios Gustavo
Published: April 2024

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome’s low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established “genomic accordion” evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.
Antiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment
Authors: Keller Michael D. , Hanley Patrick J. , Chi Yueh-Yun , Aguayo-Hiraldo Paibel , Dvorak Christopher C. , Verneris Michael R. , Kohn Donald B. , Pai Sung-Yun , Dávila Saldaña Blachy J. , Hanisch Benjamin , Quigg Troy C. , Adams Roberta H. , Dahlberg Ann , Chandrakasan Shanmuganathan , Hasan Hasibul , Malvar Jemily , Jensen-Wachspress Mariah A. , Lazarski Christopher A. , Sani Gelina , Idso John M. , Lang Haili , Chansky Pamela , McCann Chase D. , Tanna Jay , Abraham Allistair A. , Webb Jennifer L. , Shibli Abeer , Keating Amy K. , Satwani Prakash , Muranski Pawel , Hall Erin , Eckrich Michael J. , Shereck Evan , Miller Holly , Mamcarz Ewelina , Agarwal Rajni , De Oliveira Satiro N. , Vander Lugt Mark T. , Ebens Christen L. , Aquino Victor M. , Bednarski Jeffrey J. , Chu Julia , Parikh Suhag , Whangbo Jennifer , Lionakis Michail , Zambidis Elias T. , Gourdine Elizabeth , Bollard Catherine M. , Pulsipher Michael A.
Published: April 2024

Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST products were identified for 75 of 77 clinical queries. Clinical responses were achieved in 29 of 47 (62%) of patients post-HSCT including 73% of patients evaluable at 1-month post-infusion, meeting the primary efficacy endpoint (>52%). Secondary graft rejection occurred in one child following VST infusion as described in a companion article. Corticosteroids, graft-versus-host disease, transplant-associated thrombotic microangiopathy, and eculizumab treatment correlated with poor response, while uptrending absolute lymphocyte and CD8 T cell counts correlated with good response. This study highlights key clinical factors that impact response to VSTs and demonstrates the feasibility and efficacy of this therapy in pediatric HSCT.
Membrane to cortex attachment determines different mechanical phenotypes in LGR5+ and LGR5- colorectal cancer cells
Authors: Conti Sefora , Venturini Valeria , Cañellas-Socias Adrià , Cortina Carme , Abenza Juan F. , Stephan-Otto Attolini Camille , Middendorp Guerra Emily , Xu Catherine K. , Li Jia Hui , Rossetti Leone , Stassi Giorgio , Roca-Cusachs Pere , Diz-Muñoz Alba , Ruprecht Verena , Guck Jochen , Batlle Eduard , Labernadie Anna , Trepat Xavier
Published: April 2024

Colorectal cancer (CRC) tumors are composed of heterogeneous and plastic cell populations, including a pool of cancer stem cells that express LGR5. Whether these distinct cell populations display different mechanical properties, and how these properties might contribute to metastasis is poorly understood. Using CRC patient derived organoids (PDOs), we find that compared to LGR5- cells, LGR5+ cancer stem cells are stiffer, adhere better to the extracellular matrix (ECM), move slower both as single cells and clusters, display higher nuclear YAP, show a higher survival rate in response to mechanical confinement, and form larger transendothelial gaps. These differences are largely explained by the downregulation of the membrane to cortex attachment proteins Ezrin/Radixin/Moesin (ERMs) in the LGR5+ cells. By analyzing single cell RNA-sequencing (scRNA-seq) expression patterns from a patient cohort, we show that this downregulation is a robust signature of colorectal tumors. Our results show that LGR5- cells display a mechanically dynamic phenotype suitable for dissemination from the primary tumor whereas LGR5+ cells display a mechanically stable and resilient phenotype suitable for extravasation and metastatic growth.
Structural basis for antiepileptic drugs and botulinum neurotoxin recognition of SV2A
Authors: Yamagata Atsushi , Ito Kaori , Suzuki Takehiro , Dohmae Naoshi , Terada Tohru , Shirouzu Mikako
Published: April 2024

More than one percent of people have epilepsy worldwide. Levetiracetam (LEV) is a successful new-generation antiepileptic drug (AED), and its derivative, brivaracetam (BRV), shows improved efficacy. Synaptic vesicle glycoprotein 2a (SV2A), a putative membrane transporter in the synaptic vesicles (SVs), has been identified as a target of LEV and BRV. SV2A also serves as a receptor for botulinum neurotoxin (BoNT), which is the most toxic protein and has paradoxically emerged as a potent reagent for therapeutic and cosmetic applications. Nevertheless, no structural analysis on AEDs and BoNT recognition by full-length SV2A has been available. Here we describe the cryo-electron microscopy structures of the full-length SV2A in complex with the BoNT receptor-binding domain, BoNT/A2 HC, and either LEV or BRV. The large fourth luminal domain of SV2A binds to BoNT/A2 HC through protein-protein and protein-glycan interactions. LEV and BRV occupy the putative substrate-binding site in an outward-open conformation. A propyl group in BRV creates additional contacts with SV2A, explaining its higher binding affinity than that of LEV, which was further supported by label-free spectral shift assay. Numerous LEV derivatives have been developed as AEDs and positron emission tomography (PET) tracers for neuroimaging. Our work provides a structural framework for AEDs and BoNT recognition of SV2A and a blueprint for the rational design of additional AEDs and PET tracers.
Perceptography unveils the causal contribution of inferior temporal cortex to visual perception
Authors: Shahbazi Elia , Ma Timothy , Pernuš Martin , Scheirer Walter , Afraz Arash
Published: April 2024

Neurons in the inferotemporal (IT) cortex respond selectively to complex visual features, implying their role in object perception. However, perception is subjective and cannot be read out from neural responses; thus, bridging the causal gap between neural activity and perception demands independent characterization of perception. Historically, though, the complexity of the perceptual alterations induced by artificial stimulation of IT cortex has rendered them impossible to quantify. To address this old problem, we tasked male macaque monkeys to detect and report optical impulses delivered to their IT cortex. Combining machine learning with high-throughput behavioral optogenetics, we generated complex and highly specific images that were hard for the animal to distinguish from the state of being cortically stimulated. These images, named “perceptograms” for the first time, reveal and depict the contents of the complex hallucinatory percepts induced by local neural perturbation in IT cortex. Furthermore, we found that the nature and magnitude of these hallucinations highly depend on concurrent visual input, stimulation location, and intensity. Objective characterization of stimulation-induced perceptual events opens the door to developing a mechanistic theory of visual perception. Further, it enables us to make better visual prosthetic devices and gain a greater understanding of visual hallucinations in mental disorders.
Local environment in biomolecular condensates modulates enzymatic activity across length scales
Authors: Gil-Garcia Marcos , Benítez-Mateos Ana I. , Papp Marcell , Stoffel Florence , Morelli Chiara , Normak Karl , Makasewicz Katarzyna , Faltova Lenka , Paradisi Francesca , Arosio Paolo
Published: April 2024

The mechanisms that underlie the regulation of enzymatic reactions by biomolecular condensates and how they scale with compartment size remain poorly understood. Here we use intrinsically disordered domains as building blocks to generate programmable enzymatic condensates of NADH-oxidase (NOX) with different sizes spanning from nanometers to microns. These disordered domains, derived from three distinct RNA-binding proteins, each possessing different net charge, result in the formation of condensates characterized by a comparable high local concentration of the enzyme yet within distinct environments. We show that only condensates with the highest recruitment of substrate and cofactor exhibit an increase in enzymatic activity. Notably, we observe an enhancement in enzymatic rate across a wide range of condensate sizes, from nanometers to microns, indicating that emergent properties of condensates can arise within assemblies as small as nanometers. Furthermore, we show a larger rate enhancement in smaller condensates. Our findings demonstrate the ability of condensates to modulate enzymatic reactions by creating distinct effective solvent environments compared to the surrounding solution, with implications for the design of protein-based heterogeneous biocatalysts.
Position- and scale-invariant object-centered spatial localization in monkey frontoparietal cortex dynamically adapts to cognitive demand
Authors: Taghizadeh Bahareh , Fortmann Ole , Gail Alexander
Published: April 2024

Egocentric encoding is a well-known property of brain areas along the dorsal pathway. Different to previous experiments, which typically only demanded egocentric spatial processing during movement preparation, we designed a task where two male rhesus monkeys memorized an on-the-object target position and then planned a reach to this position after the object re-occurred at variable location with potentially different size. We found allocentric (in addition to egocentric) encoding in the dorsal stream reach planning areas, parietal reach region and dorsal premotor cortex, which is invariant with respect to the position, and, remarkably, also the size of the object. The dynamic adjustment from predominantly allocentric encoding during visual memory to predominantly egocentric during reach planning in the same brain areas and often the same neurons, suggests that the prevailing frame of reference is less a question of brain area or processing stream, but more of the cognitive demands.
Green moisture-electric generator based on supramolecular hydrogel with tens of milliamp electricity toward practical applications
Authors: Yang Su , Zhang Lei , Mao Jianfeng , Guo Jianmiao , Chai Yang , Hao Jianhua , Chen Wei , Tao Xiaoming
Published: April 2024

Moisture-electric generators (MEGs) has emerged as promising green technology to achieve carbon neutrality in next-generation energy suppliers, especially combined with ecofriendly materials. Hitherto, challenges remain for MEGs as direct power source in practical applications due to low and intermittent electric output. Here we design a green MEG with high direct-current electricity by introducing polyvinyl alcohol-sodium alginate-based supramolecular hydrogel as active material. A single unit can generate an improved power density of ca. 0.11 mW cm−2, a milliamp-scale short-circuit current density of ca. 1.31 mA cm−2 and an open-circuit voltage of ca. 1.30 V. Such excellent electricity is mainly attributed to enhanced moisture absorption and remained water gradient to initiate ample ions transport within hydrogel by theoretical calculation and experiments. Notably, an enlarged current of ca. 65 mA is achieved by a parallel-integrated MEG bank. The scalable MEGs can directly power many commercial electronics in real-life scenarios, such as charging smart watch, illuminating a household bulb, driving a digital clock for one month. This work provides new insight into constructing green, high-performance and scalable energy source for Internet-of-Things and wearable applications.
Illuminating the complete ß-cell mass of the human pancreas- signifying a new view on the islets of Langerhans
Authors: Lehrstrand Joakim , Davies Wayne I. L. , Hahn Max , Korsgren Olle , Alanentalo Tomas , Ahlgren Ulf
Published: April 2024

Pancreatic islets of Langerhans play a pivotal role in regulating blood glucose homeostasis, but critical information regarding their mass, distribution and composition is lacking within a whole organ context. Here, we apply a 3D imaging pipeline to generate a complete account of the insulin-producing islets throughout the human pancreas at a microscopic resolution and within a maintained spatial 3D context. These data show that human islets are far more heterogenous than previously accounted for with regards to their size distribution and cellular make up. By deep tissue 3D imaging, this in-depth study demonstrates that 50% of the human insulin-expressing islets are virtually devoid of glucagon-producing α-cells, an observation with significant implications for both experimental and clinical research.
Palladium anchored to BisPyP@bilayer-SiO2@NMP organic–inorganic hybrid as an efficient and recoverable novel nanocatalyst in suzuki and stille C–C coupling reactions
Authors: Abdalrazaq Eid Ahmed , Mohammed Hala Kh. , Voronkova Daria K. , Joshi Sanjeev Kumar , Saleh Ebraheem Abdu Musad , Kareem Anaheed Hussein , Kumar Abhinav , Alawadi Ahmed , Alslaami Ali , Fathollahi Rohollah
Published: April 2024

The palladium anchored to BisPyP@bilayer-SiO2@NMP organic–inorganic hybrid was employed as an effective and recyclable organometallic catalyst in Suzuki and Stille C–C coupling reactions. The structure of this magnetic nanocatalyst was determined using various techniques such as SEM, TEM, FT-IR, EDS, ICP-OES, VSM, N2 adsorption–desorption isotherms, XRD, and TGA. In both of the mentioned coupling paths, the yields of the products were very favorable and ranged from 90 to 98%. Also, they had significant features compared to previous reports, such as very short reaction time (5–15 and 7–20 min respectively in the Suzuki and Stille reactions), easy work-up, broad substrate scope, ease of separation of the catalyst using a magnet, suitable reproducibility of the catalyst in 6 runs, heterogeneous nature of the catalyst and not washing it during consecutive runs with confirmation of hot filtration and ICP-OES methods.
A novel flexible exponent power-X family of distributions with applications to COVID-19 mortality rate in Mexico and Canada
Authors: Shah Zubir , Khan Dost Muhammad , Khan Imad , Ahmad Bakhtiyar , Jeridi Mouna , Al-Marzouki Sanaa
Published: April 2024

This paper aims to introduce a novel family of probability distributions by the well-known method of the T–X family of distributions. The proposed family is called a “Novel Generalized Exponent Power X Family” of distributions. A three-parameters special sub-model of the proposed method is derived and named a “Novel Generalized Exponent Power Weibull” distribution (NGEP-Wei for short). For the proposed family, some statistical properties are derived including the hazard rate function, moments, moment generating function, order statistics, residual life, and reverse residual life. The well-known method of estimation, the maximum likelihood estimation method is used for estimating the model parameters. Besides, a comprehensive Monte Carlo simulation study is conducted to assess the efficacy of this estimation method. Finally, the model selection criterion such as Akaike information criterion (AINC), the correct information criterion (CINC), the Bayesian information criterion (BINC), the Hannan–Quinn information criterion (HQINC), the Cramer–von-Misses (CRMI), and the ANDA (Anderson–Darling) are used for comparison purpose. The comparison of the NGEP-Wei with other rival distributions is made by Two COVID-19 data sets. In terms of performance, we show that the proposed method outperforms the other competing methods included in this study.
Exploring the prognostic impact of absolute lymphocyte count in patients treated with immune-checkpoint inhibitors
Authors: Conroy M. R. , O’Sullivan H. , Collins D. C. , Bambury R. M. , Power D. , Grossman S. , O’Reilly S.
Published: April 2024

Background

The role of immune checkpoint inhibitors (ICI) expands but affordable and reproducible prognostic biomarkers are needed. We investigated the association between baseline and 3-month absolute lymphocyte count (ALC) and survival for patients on ICI.

Methods

A retrospective study investigated patients who received ICI July 2014—August 2019. Survival probabilities were calculated for lymphocyte subsets. Univariate and multivariate analyses were performed to investigate risk factors for lymphopenia.

Results

Among 179 patients, median age was 62 and 41% were female. The most common diagnoses were melanoma (41%) and lung cancer (40%). Median PFS was 6.5 months. 27% had baseline lymphopenia (ALC < 1 × 109cells/L) and no significant difference in PFS or OS to those with normal ALC. However, 31% had lymphopenia at 3 months and significantly shorter OS than those without (9.8 vs 18.3 months, p < 0.001). Those with baseline lymphopenia who recovered counts at 3 months had no difference in PFS (median NR vs 13.0 months, p = 0.48) or OS (22 vs 18.3 months, p = 0.548) to those never lymphopenic. The strongest risk factor for lymphopenia on multivariable analysis was previous radiation therapy (RT).

Conclusions

3-month lymphopenia is a negative prognostic marker in cancer patients on ICI. Previous RT is significantly associated with lymphopenia.
Structural chemistry of decalins and perfluorodecalins
Authors: Paska Bartłomiej , Cichowicz Grzegorz , Rzepiński Patryk , Cyrański Michał Ksawery , Dobrzycki Łukasz , Boese Roland
Published: April 2024

Crystaline phases of decalins and perfluorodecalins.
Salinity and pH effects on water–oil–calcite interfaces by using molecular dynamics
Authors: Arboleda-Lamus Anderson , Muñoz-Rugeles Leonardo , del Campo Jorge M. , Santos-Santos Nicolas , Pérez Julio , Mejía-Ospino Enrique
Published: April 2024

Smart water injection is a technology that allows changing the wettability of the oil rock by injecting water at different salinities, in a cheap and environmentally friendly way compared to other traditional methods.