bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review and meta-analysis of the effect of intravitreal VEGF inhibitors on cardiorenal outcomes
Authors: Lees Jennifer S , Dobbin Stephen J H , Elyan Benjamin M P , Gilmour David F , Tomlinson Laurie P , Lang Ninian N , Mark Patrick B 
Published: November 2022

ABSTRACT

Background
Vascular endothelial growth factor inhibitors (VEGFis) have transformed the treatment of many retinal diseases, including diabetic maculopathy. Increasing evidence supports systemic absorption of intravitreal VEGFi and development of significant cardiorenal side effects.

Methods
We conducted a systematic review and meta-analysis (PROSPERO: CRD42020189037) of randomised controlled trials of intravitreal VEGFi treatments (bevacizumab, ranibizumab and aflibercept) for any eye disease. Outcomes of interest were cardiorenal side effects (hypertension, proteinuria, kidney function decline and heart failure). Fixed effects meta-analyses were conducted where possible.

Results
There were 78 trials (81 comparisons; 13 175 participants) that met the criteria for inclusion: 47% were trials in diabetic eye disease. Hypertension (29 trials; 8570 participants) was equally common in VEGFi and control groups {7.3 versus 5.4%; relative risk [RR] 1.08 [95% confidence interval (CI) 0.91–1.28]}. New or worsening heart failure (10 trials; 3384 participants) had a similar incidence in VEGFi and control groups [RR 1.03 (95% CI 0.70–1.51)]. Proteinuria (5 trials; 1902 participants) was detectable in some VEGFi-treated participants (0.2%) but not controls [0.0%; RR 4.43 (95% CI 0.49–40.0)]. Kidney function decline (9 trials; 3471 participants) was similar in VEGFi and control groups. In participants with diabetic eye disease, the risk of all-cause mortality was higher in VEGFi-treated participants [RR 1.62 (95% CI 1.04–2.46)].

Conclusion
In trials of intravitreal VEGFi, we did not identify an increased risk of cardiorenal outcomes, although these outcomes were reported in only a minority of cases. There was an increased risk of death in VEGFi-treated participants with diabetic eye disease. Additional scrutiny of post-licensing observational data may improve the recognition of safety concerns in VEGFi-treated patients.
Squeezing microwaves by magnetostriction
Authors: Li Jie , Wang Yi-Pu , You Jian-Qiang , Zhu Shi-Yao 
Published: November 2022

ABSTRACT
Squeezed light finds many important applications in quantum information science and quantum metrology, and has been produced in a variety of physical systems involving optical non-linear processes. Here, we show how a non-linear magnetostrictive interaction in a ferrimagnet in cavity magnomechanics can be used to reduce quantum noise of the electromagnetic field. We show optimal parameter regimes where a substantial and stationary squeezing of the microwave output field can be achieved. Realization of the scheme is within reach of current technology in cavity electromagnonics and magnomechanics. Our work provides a new and practicable approach for producing squeezed vacuum states of electromagnetic fields, and may find promising applications in quantum information processing and quantum metrology.
Effect of Common ER Stress–Inducing Drugs on the Growth and Lipid Phenotypes of Chlamydomonas and Arabidopsis
Authors: Je Sujeong , Lee Yuree , Yamaoka Yasuyo 
Published: November 2022

Abstract
Endoplasmic reticulum (ER) stress is caused by the stress-induced accumulation of unfolded proteins in the ER. Several compounds are used to induce the unfolded protein response (UPR) in animals, with different modes of action, but which ER stress–inducing drugs induce ER stress in microalgae or land plants is unclear. In this study, we examined the effects of seven chemicals that were reported to induce ER stress in animals on the growth, UPR gene expression and fatty acid profiles of Chlamydomonas reinhardtii (Chlamydomonas) and Arabidopsis thaliana (Arabidopsis): 2-deoxyglucose, dithiothreitol (DTT), tunicamycin (TM), thapsigargin, brefeldin A (BFA), monensin (MON) and eeyarestatin I. In both model photosynthetic organisms, DTT, TM, BFA and MON treatment induced ER stress, as indicated by the induction of spliced bZIP1 and bZIP60, respectively. In Chlamydomonas, DTT, TM and BFA treatment induced the production of transcripts related to lipid biosynthesis, but MON treatment did not. In Arabidopsis, DTT, TM, BFA and MON inhibited seed germination and seedling growth with the activation of bZIP60. These findings lay the foundation for using four types of ER stress–inducing drugs in photosynthetic organisms, and they help uncover the mode of action of each compound.
In Situ Trace Elements in Quartz and K-Feldspar from Felsic Igneous Rocks: A Titanium-in-K-Feldspar Geothermometer for Natural Magmatic Systems
Authors: Zhang Yongmei , Gu Xuexiang , Rusk Brian , Mao Wei , Wang Jialin , Zheng Shaohua 
Published: November 2022

Abstract
Scanning electron microscope, cathodoluminescence (CL) imaging and laser ablation–inductively coupled plasma–mass spectrometry analyses were conducted on coexisting pairs of quartz and K-feldspar from 14 samples of various types of felsic igneous rocks. Difference of the concentration of trace elements in quartz and K-feldspar among plutonic, pegmatitic and volcanic rocks is closely related to the rock-forming process and P–T condition. In general, a decreasing Ti concentration and increasing Al, Li, and Ge concentrations from plutonic to pegmatitic quartz suggest a higher degree of magmatic fractionation and lower crystallization temperature. Sensitive elements to magma differentiation in K-feldspar such as Ba, Sr, and LREE show a decreasing trend from various granitic rocks to pegmatite, while Rb, Cs, Li, Ge, and P exhibit increasing trends. The K-feldspar from various types of felsic igneous rocks typically shows similar CL textures but relatively higher luminescence intensity compared with coexisting quartz. Both quartz and K-feldspar phenocrysts in the volcanic rhyolite have a bright rim and a dark core in CL images, corresponding to bimodal Ti concentrations. Among all samples, Ti concentrations in both quartz and coexisting K-feldspar positively correlate with their CL intensities, suggesting the activation of Ti-impurity in these minerals leads to increased CL intensity. Meanwhile, there is a good positive correlation between Ti concentrations in quartz and those in K-feldspar with an R2 value of 0.86. It is considered that Ti concentrations in the both minerals are mainly temperature dependent at relatively constant pressure on basis of a fair aTiO2 restriction. Here, for the first time, we calculated a titanium-in-K-feldspar (TitaniKfs) thermometer in the form of log (XTi, kfs/aTiO2) = −(3430 ± 268)/T(K) + (5.081 ± 0.298) for natural felsic magma systems. The Ti contents of K-feldspar (in ppm by weight) increase exponentially with reciprocal T at temperatures ranging from 500°C to 800°C, at 200–300 MPa. An application of this thermometer to granitic rocks from Xinjiang and Inner Mongolia in China fits well with other geothermometers. In addition, the present TitaniKfs thermometer is expected to be particularly useful in determining the temperature condition of K-feldspar-bearing extraterrestrial materials such as lunar rocks.
Degassing, Crystallization and Rheology of Hawaiitic Lava Flows: the Case of the 1669 AD Eruption of Mount Etna (Italy)
Authors: Lanzafame Gabriele , Giacomoni Pier Paolo , Casetta Federico , Mancini Lucia , Iezzi Gianluca , Coltorti Massimo , Ferlito Carmelo 
Published: November 2022

Abstract
Understanding lava flow dynamics during major effusive events is of paramount importance in volcanic areas characterized by a high risk of lava invasion. Mount Etna volcano (Sicily, Italy) has a long history of eruptions characterized by the emplacement of kilometer-wide lava fields, which have often reached the distal parts of the volcanic edifice, nowadays the location of numerous population centers. The 1669 eruption was one of the volcano’s most important events in historic times due to the low altitude of the eruptive vent and the high volume of emitted products (607 ± 105 × 106 m3), with lava flows that destroyed numerous villages located along their path. The flows reached the city of Catania, at a distance of &gt;16 km from the emission point. In this work, we investigate the products of the 1669 eruption through geochemical, mineralogical, 2D and 3D textural analyses with the aim of reconstructing the degassing, crystallization and rheological history of the magma and lavas in pre- to post-eruptive conditions. Combining geothermobarometric and hygrometric models allowed us to estimate magmatic water content (4.1 wt.%) before the eruption, whereas the syn-eruptive crystal content (10 vol.% at the onset of flowing) was retrieved through the textural analysis of pyroclasts sampled from the near-vent fallout. Finally, crystallization and degassing occurring at surface conditions were reconstructed using the textural and mineralogical analysis of lavas. Results were integrated in a three-phase (melt + crystal + bubble) rheological model indicating that lava viscosity, at the onset of the eruption, was low enough (&lt;3.51 log Pa s) to permit the development of a complex and extensive lava field. Flows reached numerous kilometers in length, thanks to the joint effects of lava tunneling, delayed crystal nucleation and growth, and the presence (up to 21.35 vol.%) of deformed bubbles. The combination of these processes maintained the high fluidity of the melt suspension, allowing the flow to arrive at considerable distances from the vent. Lastly, the results of this study highlight the necessity of an accurate real-time multi-analytical petrological characterization of active lavas during the monitoring of effusive eruptions, essential for reliable viscosity modeling of advancing flow units and therefore vital in predicting the direction of lava flows, especially in densely populated areas such as the southern flank of Mount Etna.
Redirecting Nonurgent Patients From the Pediatric Emergency Department to Their Pediatrician Office for a Same-Day Visit—A Quality Improvement Initiative
Authors: Wolski Thomas P. , Jamerino-Thrush Jennifer , Bigham Michael T. , Kline-Krammes Sarah , Patel Nirali , Lee Timothy J. , Pollauf Laura A. , Joyce Crystal N. , Kunka Sarah , McNinch Neil L. , Jacobs Michelle , White P. Cooper 
Published: November 2022

Objectives
Providing high-quality care in the appropriate setting to optimize value is a worthy goal of an efficient health system. Consequences of managing nonurgent complaints in the emergency department (ED) have been described including inefficiency, loss of the primary care–patient relationship, and delayed care for other ED patients. The purpose of this initiative was to redirect nonurgent patients arriving in the ED to their primary care office for a same-day visit, and the SMART AIM was to increase redirected patients from 0% of those eligible to 30% in a 12-month period.

Methods
The setting was a pediatric ED (PED) and primary care office of a tertiary care pediatric medical system. The initiative utilized the electronic health record to identify and mediate the redirection of patients to the patient's primary care office after ED triage. The primary measurement was the percentage of eligible patients redirected. Additional measures included health benefits during the primary care visit (vaccines, well-visits) and a balancing measure of patients returned to the PED.

Results
The SMART AIM of >30% redirection was achieved and sustained with a final redirection rate of 46%. In total, 216 of 518 eligible patients were redirected, with zero untoward outcomes. The encounter time for redirected patients was similar for those who remained in the PED, and additional health benefits were appreciated for redirected patients.

Conclusions
This initiative redirected nonurgent patients efficiently from a PED setting to their primary care office. The process is beneficial to patients and families and supports the patient-centered medical home. The balancing measure of no harm done to patients who accepted redirect reinforced the reliability of PED triage. The benefits achieved through the project highlight the value of the primary care–patient relationship and the continued need to improve access for patients and families.
Representation of Race and Ethnicity in a Contemporary US Health Cohort: TheAll of UsResearch Program
Authors: Kathiresan Nina , Cho So Mi Jemma , Bhattacharya Romit , Truong Buu , Hornsby Whitney , Natarajan Pradeep 
Published: November 2022

SummaryParticipation and inclusion in biomedical research remain disproportionate across sociodemographics limiting discoveries in genomic studies and contributing to systemic disparities in healthcare. To alleviate such inequities, the National Institute of Health initiated theAll of UsResearch Program (AoU), a prospective, population-based cohort to identify the root causes and consequences of health outcomes across diverse demographics. We quantify representation of key racial groups in the accruing AoU cohort of US adults aged ≥18 years and compare to their actual representation in the US. Of the 358,705 AoU participants to date, Hispanic or Latino participants were underrepresented by 0.85-fold, non-Hispanic Asian by 0.58-fold, non-Hispanic White by 0.98-fold, and Other by 0.43-fold. Meanwhile, individuals identifying as non-Hispanic Black or African American were overrepresented by 1.88-fold. While AoU representation better mirrors the US demographics compared to other cohorts, recruitment trends for the ongoing AoU underscore the need to further tailor participation initiatives for diverse populations.
Dual-mode near-infrared multispectral imaging system equipped with deep learning models improves the identification of cancer foci in breast cancer specimens
Authors: Liao Jun , Zhang Lingling , Wang Han , Bai Ziqi , Zhang Meng , Han Dandan , Jia Zhanli , Liu Yao , Qin Chenchen , Niu ShuYao , Bu Hong , Yao Jianhua , Liu Yueping 
Published: November 2022

AbstractFor surgically resected breast cancer samples, it is challenging to perform specimen sampling by visual inspection, especially when the tumor bed shrinks after neoadjuvant therapy in breast cancer. In this study, we developed a dual-mode near-infrared multispectral imaging system (DNMIS) to overcome the human visual perceptual limitations and obtain richer sample tissue information by acquiring reflection and transmission images covering visible to NIR-II spectrum range (400–1700 nm). Additionally, we used artificial intelligence (AI) for segmentation of the rich multispectral data. We compared DNMIS with the conventional sampling methods, regular visual inspection and a cabinet X-ray imaging system, using data from 80 breast cancer specimens. DNMIS demonstrated better tissue contrast and eliminated the interference of surgical inks on the breast tissue surface, helping pathologists find the tumor area which is easy to be overlooked with visual inspection. Statistically, AI-powered DNMIS provided a higher tumor sensitivity (95.9% vs visual inspection 88.4% and X-rays 92.8%), especially for breast samples after neoadjuvant therapy (90.3% vs visual inspection 68.6% and X-rays 81.8%). We infer that DNMIS can improve the breast tumor specimen sampling work by helping pathologists avoid missing out tumor foci.
In Silico, Brain Mesh Platform for Computing Topographic Dependent Internal Facets
Authors: Shaw Caleb , Riviere-Cazaux Cecile , Obrochta Dylan , Otto Stephanie , Ray Lawrence , Strother Lars , Burns Terry , Khan M. Rashed 
Published: November 2022

AbstractIndividualized and anatomically correct computational models of the brain can be leveraged to improve knowledge of drug dispersal following simulation of drug delivery. Using a patient’s magnetic resonance image (MRI) scans, we were able to reconstruct the pial surface of the brain of the left hemisphere with strong anatomic accuracy. We then established the major internal features, including the lateral ventricle, a tumor, and drug delivery catheters. These were able to include relevant tissue characteristics such as porosity and permeability in the Multiphysics platform COMSOL to create a platform for brain modeling. To test the performance of this platform, we simulated direct drug infusion in both a healthy patient brain and a diseased patient model, focusing on glioblastoma (GBM). Using this platform, we simulated perturbed convection enhanced delivery of a cancer medication (similar to temozolomide (TMZ) but modeled using methylene blue) to the tumor. Consequently, with our patient derived model, we are able to simulate solute dispersal and fluid flow representative ofin vivoconditions.
The power of geohistorical boundaries for modeling the genetic background of human populations: the case of the rural Catalan Pyrenees
Authors: Fibla Joan , Maceda Iago , Laplana Marina , Guerrero Montserrat , Álvarez Miguel Martín , Burgueño Jesús , Camps Agustí , Fàbrega Jordi , Felisart Josefina , Grané Joan , Luis Remón José , Serra Jordi , Moral Pedro , Lao Oscar 
Published: November 2022

AbstractThe genetic variation of the European population at a macro-geographic scale follows genetic gradients which reflect main migration events. However, less is known about factors affecting mating choices at a micro-geographic scale. In this study we have analyzed 726,718 autosomal SNPs in 435 individuals from the Catalan Pyrenees covering around 200 km of a vast and abrupt region in the north of the Iberian Peninsula, for which we have information about the geographic origin of all grand-parents and parents. At a macro-geographic scale, our analyses recapitulate the genetic gradient observed in Spain. However, we also identified the presence of micro-population substructure among the sampled individuals. Such micro-population substructure does not correlate with geographic barriers such as the expected by the orography of the considered region, but by the bishoprics present in the covered geographic area. These results support that, on top of main human migrations, long ongoing socio-cultural factors have also shaped the genetic diversity observed at rural populations.
Identifying endogenous peptide receptors by combining structure and transmembrane topology prediction
Authors: Teufel Felix , Refsgaard Jan C. , Kasimova Marina A. , Madsen Christian T. , Stahlhut Carsten , Grønborg Mads , Winther Ole , Madsen Dennis 
Published: November 2022

AbstractMany secreted endogenous peptides rely on signalling pathways to exert their function in the body. While peptides can be discovered through high throughput technologies, their cognate receptors typically cannot, hindering the understanding of their mode of action. We investigate the use of AlphaFold-Multimer for identifying the cognate receptors of secreted endogenous peptides in human receptor libraries without any prior knowledge about likely candidates. We find that AlphaFold’s predicted confidence metrics have strong performance for prioritizing true peptide-receptor interactions. By applying transmembrane topology prediction using DeepTMHMM, we further improve performance by detecting and filtering biologically implausible predicted interactions. In a library of 1112 human receptors, the method ranks true receptors in the top percentile on average for 11 benchmark peptide-receptor pairs.
Physics of sliding on water predicts morphological and behavioral allometry across a wide range of body sizes in water striders (Gerridae)
Authors: Kim Woojoo , Lee Jae Hong , Pham Thai H. , Tran Anh D. , Ha Jungmoon , Bang Sang Yun , Jablonski Piotr G. , Kim Ho-Young , Lee Sang-im 
Published: November 2022

AbstractLaws of physics shape morphological and behavioral adaptations to locomotion at different body sizes. Water striders serve as a model taxon to study how simple physical constraints of water-surface habitats affect their behavior and morphology, and hydrodynamics of rowing by midlegs on the surface is well understood. However, the physics of the subsequent passive sliding has been less explored. We created a model of sliding on the water surface to simulate the effect of body mass, striding type, and wetted leg lengths on an insect’s ability to float on the surface and on the sliding resistance. The model predicts that to support their weight on the surface during sliding, the heavy species should either develop long forelegs that support the frontal part of its body during symmetrical striding (when two midlegs thrust) or use asymmetrical striding (when one forward-extended midleg supports the body while the other midleg and contra-lateral hindleg thrust). These predictions are confirmed by the behavior and morphology of various Gerridae species. Hence, the results illustrate how simple physical processes specific to a certain habitat type have far-reaching consequences for the evolution of morphological and behavioral diversification associated with body size among biological organisms in these habitats.
Crystal ribcage: a platform for probing real-time lung function at cellular resolution in health and disease
Authors: Banerji Rohin , Grifno Gabrielle N. , Shi Linzheng , Smolen Dylan , LeBourdais Rob , Muhvich Johnathan , Eberman Cate , Hiller Bradley E. , Lee Jisu , Regan Kathryn , Zheng Siyi , Zhang Sue , Jiang John , Raslan Ahmed A. , Breda Julia C. , Pihl Riley , Traber Katrina , Mazzilli Sarah , Ligresti Giovanni , Mizgerd Joseph P. , Suki Béla , Nia Hadi T. 
Published: November 2022

AbstractUnderstanding the dynamic pathogenesis and treatment response in pulmonary diseases requires probing the lung at cellular resolution in real-time. Despite recent progress in intravital imaging, optical imaging of the lung during active respiration and circulation has remained challenging. Here, we introduce the crystal ribcage: a transparent ribcage that (i) allows truly multiscale optical imaging of the lung in health and disease from whole-organ to single cell, (ii) enables the modulation of lung biophysics and immunity through intravascular, intrapulmonary, intraparenchymal, and optogenetic interventions, and (iii) preserves the 3-D architecture, air-liquid interface, cellular diversity, and respiratory-circulatory functions of the lung. Utilizing these unprecedented capabilities on murine models of primary and metastatic lung tumors, respiratory infection, pulmonary fibrosis, emphysema, and acute lung injury we probed how disease progression remodels the respiratory-circulatory functions at the single alveolus and capillary levels. In cancer, we identified the earliest stage of tumorigenesis that compromises alveolar and capillary functions, a key state with consequences on tumor progression and treatment response. In pneumonia, we mapped mutual links between the recruited immune cells and the alveolar-capillary functions. We found that neutrophil migration is strongly and reversibly responsive to vascular pressure with implications for understanding of how lung physiology, altered by disease and anatomical location, affects immune cell activities. The crystal ribcage and its broad applications presented here will facilitate further studies of real-time remodeling of the alveoli and capillaries during pathogenesis of nearly any pulmonary disease, leading to the identification of new targets for treatment strategies.