bluuebunny/crossref_metadata_2025 huggingface dataset:
Volcanoes’ Future Climate Effects May Exceed Standard Estimates
Authors: Stanley Sarah
Published: June 2023

Future releases of sulfur dioxide from volcanoes will likely be higher than the reconstructed historical levels currently used for climate predictions.
Ozone Changes Due To Sudden Stratospheric Warming‐Induced Variations in the Intensity of Brewer‐Dobson Circulation: A Composite Analysis Using Observations and Chemical‐Transport Model
Authors: Veenus Venugopal , Das Siddarth Shankar , David Liji M.
Published: June 2023

We quantify the changes in the intensity of Brewer‐Dobson Circulation (BDC) during sudden stratospheric warming (SSW) and its impact on the tropical stratospheric thermal structure and ozone distribution by composite analysis using observations and a chemical‐transport model. An increase in the planetary wave activity and enhancement in BDC intensity before the central date of SSW is noticed. A positive ozone anomaly is observed in the tropical upper stratosphere. The tropical lower stratosphere shows a cooling (1–2 K) and negative ozone anomaly (∼0.1 ppmv) after ∼10 days from the central date. The polar stratosphere experiences a positive ozone anomaly, whereas the upper stratosphere shows ozone depletion due to the downwelling of NOx‐rich mesospheric air. The cold‐point tropopause temperature shows a cooling of ∼0.5 K for major warming which in turn dries the lower stratosphere.
Influence of the Polar Electrojet on Field‐Aligned Current Estimates From Single Satellite Magnetic Field Measurements
Authors: Xiong Chao , Wang Simin , Lühr Hermann , Wang Fengjue , Zhou Yunliang
Published: June 2023

The high‐resolution magnetic field measurements from European Space Agency's (ESA’s) Swarm satellite constellation provide a good opportunity for revisiting the mean properties of ionospheric currents. Among the Swarm Level‐2 data products, provided by European Space Agency, are field‐aligned current (FAC) estimates based on single‐spacecraft (single‐SC) and dual‐spacecraft (dual‐SC) solutions. For the more reliable dual‐SC approach only magnetic signatures from currents flowing through the integration loop are considered, while in the case of single‐SC FAC estimates the magnetic effects of all remote current systems contribute to the results. A direct comparison between the two FAC products at auroral latitudes reveals that the single‐SC estimates systematically overestimate the current density of region 2 (R2) FACs by about 15%, while underestimates the region 1 (R1) FACs by about 10%. The differences between the two FAC products appear closely related to the location and direction of the horizontal polar electrojet (PEJ) at auroral latitudes. A direct comparison of these two current systems suggests an influence of the PEJ induced magnetic field on the solutions from single‐SC FACs. Our preferred explanation is the effect of a partial diversion of the anti‐sunward flowing electrojet current into the polar cap region. The current deflection angle increases toward the pole. The B‐field of such a current flow geometry can explain the single‐SC differences. It is consistent with the general picture of the high‐latitude Hall current vortices. As a side aspect, we found that the mean PEJ intensities are almost identical in both hemispheres, but the latitudes of the current peaks differ between the two hemispheres in the morning/afternoon sectors by about 1°. The reason for this difference is not clear.
Endogenous oxytocin levels in children with autism: Associations with cortisol levels and oxytocin receptor gene methylation
Authors: Evenepoel Margaux , Moerkerke Matthijs , Daniels Nicky , Chubar Viktoria , Claes Stephan , Turner Jonathan , Vanaudenaerde Bart , Willems Lynn , Verhaeghe Johan , Prinsen Jellina , Steyaert Jean , Boets Bart , Alaerts Kaat
Published: June 2023

Alterations in the brain’s oxytocinergic system have been suggested to play an important role in the pathophysiology of autism spectrum disorder (ASD), but insights from pediatric populations are sparse. Here, salivary oxytocin was examined in the morning (AM) and afternoon (PM) in school-aged children with (n = 80) and without (n = 40) ASD (boys/girls 4/1), and also characterizations of DNA methylation (DNAm) of the oxytocin receptor gene (OXTR) were obtained. Further, cortisol levels were assessed to examine links between the oxytocinergic system and hypothalamic-pituitary-adrenal (HPA) axis signaling. Children with ASD displayed altered (diminished) oxytocin levels in the morning, but not in the afternoon, after a mildly stress-inducing social interaction session. Notably, in the control group, higher oxytocin levels at AM were associated with lower stress-induced cortisol at PM, likely reflective of aprotectivestress-regulatory mechanism for buffering HPA stress activity. In children with ASD, on the other hand, a significant rise in oxytocin levels from the morning to the afternoon was associated with a higher stress-induced cortisol release in the afternoon, likely reflective of a morereactivestress regulatory release of oxytocin for reactively coping with heightened HPA activity. Regarding epigenetic modifications, no overall pattern ofOXTRhypo- or hypermethylation was evident in ASD. In control children, a notable association betweenOXTRmethylation and levels of cortisol at PM was evident, likely indicative of a compensatory downregulation ofOXTRmethylation (higher oxytocin receptor expression) in children with heightened HPA axis activity. Together, these observations bear important insights into altered oxytocinergic signaling in ASD, which may aid in establishing relevant biomarkers for diagnostic and/or treatment evaluation purposes targeting the oxytocinergic system in ASD.
Exploratory genome-wide analyses of cortical inhibition, facilitation, and plasticity in late-life depression
Authors: Wathra Rafae A. , Men Xiaoyu , Elsheikh Samar S. M. , Marshe Victoria S. , Rajji Tarek K. , Lissemore Jennifer I. , Mulsant Benoit H. , Karp Jordan F. , Reynolds Charles F. , Lenze Eric J. , Daskalakis Zafiris J. , Müller Daniel J. , Blumberger Daniel M.
Published: June 2023

Late-life depression (LLD) is a heterogenous mood disorder influenced by genetic factors. Cortical physiological processes such as cortical inhibition, facilitation, and plasticity may be markers of illness that are more strongly associated with genetic factors than the clinical phenotype. Thus, exploring the relationship between genetic factors and these physiological processes may help to characterize the biological mechanisms underlying LLD and improve diagnosis and treatment selection. Transcranial magnetic stimulation (TMS) combined with electromyography was used to measure short interval intracortical inhibition (SICI), cortical silent period (CSP), intracortical facilitation (ICF), and paired associative stimulation (PAS) in 79 participants with LLD. We used exploratory genome-wide association and gene-based analyses to assess for genetic correlations of these TMS measures. MARK4 (which encodes microtubule affinity-regulating kinase 4) and PPP1R37 (which encodes protein phosphatase 1 regulatory subunit 37) showed genome-wide significant association with SICI. EGFLAM (which encodes EGF-like fibronectin type III and laminin G domain) showed genome-wide significant association with CSP. No genes met genome-wide significant association with ICF or PAS. We observed genetic influences on cortical inhibition in older adults with LLD. Replication with larger sample sizes, exploration of clinical phenotype subgroups, and functional analysis of relevant genotypes is warranted to better characterize genetic influences on cortical physiology in LLD. This work is needed to determine whether cortical inhibition may serve as a biomarker to improve diagnostic precision and guide treatment selection in LLD.
Notch1 promotes resistance to cisplatin by up-regulating Ecto-5′-nucleotidase (CD73) in triple-negative breast cancer cells
Authors: Qi Yuzhu , Li Meifang , Li Shaozhong , Zeng De , Xiao Yingsheng , Li Jiwei , Ye Qianqian , Bremer Edwin , Zhang Guo-jun
Published: June 2023

Triple-negative breast cancer (TNBC) is an aggressive molecular subtype that due to lack of druggable targets is treated with chemotherapy as standard of care. However, TNBC is prone to chemoresistance and associates with poor survival. The aim of this study was to explore the molecular mechanisms of chemoresistance in TNBC. Firstly, we found that the mRNA expression of Notch1 and CD73 in cisplatin-treated patient material associated with poor clinical outcome. Further, both were upregulated at the protein level in cisplatin-resistant TNBC cell lines. Overexpression of Notch1 intracellular domain (termed N1ICD) increased expression of CD73, whereas knockdown of Notch1 decreased CD73 expression. Using chromatin immunoprecipitation and Dual-Luciferase assay it was identified that N1ICD directly bound the CD73 promoter and activated transcription. Taken together, these findings suggest CD73 as a direct downstream target of Notch1, providing an additional layer to the mechanisms underlying Notch1-mediated cisplatin resistance in TNBC.
Zero-dimensionality of a scaled-down VO2 metal-insulator transition via high-resolution electrostatic gating
Authors: Yajima Takeaki , Samata Yusuke , Hamasuna Satoshi , Pati Satya Prakash , Toriumi Akira
Published: June 2023

An understanding of the phase transitions at the nanoscale is essential in state-of-the-art engineering1–5, instead of simply averaging the heterogeneous domains formed during phase transitions6,7. However, as materials are scaled down, the steepness of the phase transition rapidly increases8–13 and requires extremely high precision in the control method. Here, a three-terminal device, which could precisely control the phase transition electrically14–19, was applied for the first time to a scaled-down metal-insulator transition material VO2. The crossover from continuous to binary transitions with the scaled-down material was clarified, and the critical channel length was successfully elucidated via phase boundary energy. Notably, below the critical channel length, the spatial degrees of freedom degenerated, and the impact of drain voltage application disappeared in the phase transition, indicating zero-dimensionality of the VO2 channel. This zero-dimensionality could be the fundamental property in the scaled-down phase transition and have a significant impact on various fields that need nanoscale engineering.
Improving glaucoma staging in clinical practice by combining the ICD-10 glaucoma severity classification system and optical coherence tomography
Authors: Leshno Ari , Tsamis Emmanouil , Harizman Noga , De Moraes Carlos Gustavo , La Bruna Sol , Rai Anvit , Garg-Shukla Aakriti , Cioffi George A. , Wang Qing , Liebmann Jeffrey M. , Hood Donald C.
Published: June 2023

Objective

The International Classification of Disease, 10th revision (ICD-10) codes used for glaucoma severity classification are based on the 24-2 visual-field (VF) test. This study aim was to assess the added value of providing clinicians with optical coherence tomography (OCT) data, in addition to functional data, for glaucoma staging in clinical practice.

Exposure

Disease classification was determined for 54 glaucoma eyes, according to the principles of the ICD-10 guidelines. Eyes were independently graded in a masked fashion using the 24-2 VF test and 10-2 VF test, with and without OCT information. The reference standard (RS) for severity was determined using a previously published automated structure-function topographic agreement for glaucomatous damage using all available information.

Results

The RS classified eyes as mild, moderate and advanced in 3, 16 and 35 cases, respectively. Individual and combined 24-2 and 10-2 based gradings were significantly different from the RS (all P < 0.005), with Kappa agreements of 0.26, 0.45 and 0.42 respectively (P < 0.001). Classifications using OCT combined with either of the VF were not-significantly different from the RS (P > 0.3) with Kappa agreements of 0.56 and 0.57 respectively (P < 0.001). Combining 24-2 with OCT had less severity overestimations while 10-2 with OCT had fewer underestimations.

Conclusion

Combining OCT and VF data provides better staging of glaucoma severity than VF data alone. The 24-2 and OCT combination seems most appropriate given the high concordance with the RS and less overestimation of severity. Incorporating structural information into disease stages allows clinicians to set more appropriate severity-based treatment targets for individual patients.
Longitudinal body mass index and cancer risk: a cohort study of 2.6 million Catalan adults
Authors: Recalde Martina , Pistillo Andrea , Davila-Batista Veronica , Leitzmann Michael , Romieu Isabelle , Viallon Vivian , Freisling Heinz , Duarte-Salles Talita
Published: June 2023

Single body mass index (BMI) measurements have been associated with increased risk of 13 cancers. Whether life course adiposity-related exposures are more relevant cancer risk factors than baseline BMI (ie, at start of follow-up for disease outcome) remains unclear. We conducted a cohort study from 2009 until 2018 with population-based electronic health records in Catalonia, Spain. We included 2,645,885 individuals aged ≥40 years and free of cancer in 2009. After 9 years of follow-up, 225,396 participants were diagnosed with cancer. This study shows that longer duration, greater degree, and younger age of onset of overweight and obesity during early adulthood are positively associated with risk of 18 cancers, including leukemia, non-Hodgkin lymphoma, and among never-smokers, head and neck, and bladder cancers which are not yet considered as obesity-related cancers in the literature. Our findings support public health strategies for cancer prevention focussing on preventing and reducing early overweight and obesity.
High body temperature increases gut microbiota-dependent host resistance to influenza A virus and SARS-CoV-2 infection
Authors: Nagai Minami , Moriyama Miyu , Ishii Chiharu , Mori Hirotake , Watanabe Hikaru , Nakahara Taku , Yamada Takuji , Ishikawa Dai , Ishikawa Takamasa , Hirayama Akiyoshi , Kimura Ikuo , Nagahara Akihito , Naito Toshio , Fukuda Shinji , Ichinohe Takeshi
Published: June 2023

Fever is a common symptom of influenza and coronavirus disease 2019 (COVID-19), yet its physiological role in host resistance to viral infection remains less clear. Here, we demonstrate that exposure of mice to the high ambient temperature of 36 °C increases host resistance to viral pathogens including influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High heat-exposed mice increase basal body temperature over 38 °C to enable more bile acids production in a gut microbiota-dependent manner. The gut microbiota-derived deoxycholic acid (DCA) and its plasma membrane-bound receptor Takeda G-protein-coupled receptor 5 (TGR5) signaling increase host resistance to influenza virus infection by suppressing virus replication and neutrophil-dependent tissue damage. Furthermore, the DCA and its nuclear farnesoid X receptor (FXR) agonist protect Syrian hamsters from lethal SARS-CoV-2 infection. Moreover, we demonstrate that certain bile acids are reduced in the plasma of COVID-19 patients who develop moderate I/II disease compared with the minor severity of illness group. These findings implicate a mechanism by which virus-induced high fever increases host resistance to influenza virus and SARS-CoV-2 in a gut microbiota-dependent manner.
ssDNA accessibility of Rad51 is regulated by orchestrating multiple RPA dynamics
Authors: Ding Jiawei , Li Xiangting , Shen Jiangchuan , Zhao Yiling , Zhong Shuchen , Lai Luhua , Niu Hengyao , Qi Zhi
Published: June 2023

The eukaryotic single-stranded DNA (ssDNA)-binding protein Replication Protein A (RPA) plays a crucial role in various DNA metabolic pathways, including DNA replication and repair, by dynamically associating with ssDNA. While the binding of a single RPA molecule to ssDNA has been thoroughly studied, the accessibility of ssDNA is largely governed by the bimolecular behavior of RPA, the biophysical nature of which remains unclear. In this study, we develop a three-step low-complexity ssDNA Curtains method, which, when combined with biochemical assays and a Markov chain model in non-equilibrium physics, allow us to decipher the dynamics of multiple RPA binding to long ssDNA. Interestingly, our results suggest that Rad52, the mediator protein, can modulate the ssDNA accessibility of Rad51, which is nucleated on RPA coated ssDNA through dynamic ssDNA exposure between neighboring RPA molecules. We find that this process is controlled by the shifting between the protection mode and action mode of RPA ssDNA binding, where tighter RPA spacing and lower ssDNA accessibility are favored under RPA protection mode, which can be facilitated by the Rfa2 WH domain and inhibited by Rad52 RPA interaction.
TRPA1 activation in non-sensory supporting cells contributes to regulation of cochlear sensitivity after acoustic trauma
Authors: Vélez-Ortega A. Catalina , Stepanyan Ruben , Edelmann Stephanie E. , Torres-Gallego Sara , Park Channy , Marinkova Desislava A. , Nowacki Joshua S. , Sinha Ghanshyam P. , Frolenkov Gregory I.
Published: June 2023

TRPA1 channels are expressed in nociceptive neurons, where they detect noxious stimuli, and in the mammalian cochlea, where their function is unknown. Here we show that TRPA1 activation in the supporting non-sensory Hensen’s cells of the mouse cochlea causes prolonged Ca2+ responses, which propagate across the organ of Corti and cause long-lasting contractions of pillar and Deiters’ cells. Caged Ca2+ experiments demonstrated that, similar to Deiters’ cells, pillar cells also possess Ca2+-dependent contractile machinery. TRPA1 channels are activated by endogenous products of oxidative stress and extracellular ATP. Since both these stimuli are present in vivo after acoustic trauma, TRPA1 activation after noise may affect cochlear sensitivity through supporting cell contractions. Consistently, TRPA1 deficiency results in larger but less prolonged noise-induced temporary shift of hearing thresholds, accompanied by permanent changes of latency of the auditory brainstem responses. We conclude that TRPA1 contributes to the regulation of cochlear sensitivity after acoustic trauma.
Color multilayer holographic near-eye augmented reality display
Authors: Velez-Zea Alejandro , Barrera-Ramírez John Fredy
Published: June 2023

This study demonstrates a full-color near-eye holographic display capable of superimposing color virtual scenes with 2D, 3D, and multiple objects with extended depth upon a real scene, which also has the ability to present different 3D information depending on the focus of the user’s eyes using a single computer-generated hologram per color channel. Our setup makes use of a hologram generation method based on two-step propagation and the singular value decomposition of the Fresnel transform impulse response function to efficiently generate the holograms of the target scene. Then, we test our proposal by implementing a holographic display that makes use of a phase-only spatial light modulator and time-division multiplexing for color reproduction. We demonstrate the superior quality and computation speed of this approach compared with other hologram generation techniques with both numerical and experimental results.
Micro mercury trapped ion clock prototypes with 10$$^{-14}$$ frequency stability in 1-liter packages
Authors: Hoang Thai M. , Chung Sang K. , Le Thanh , Park Sehyun , Park Sung-Jin , Eden J. Gary , Holland Christopher , Wang Hao , Momeni Omeed , Bradley Russell , Crane Scott , Prestage John D. , Yu Nan
Published: June 2023

Modern communication and navigation systems are increasingly relying on atomic clocks. As timing precision requirements increase, demands for lower SWaP (size, weight, and power) clocks rise. However, it has been challenging to break through the general trade-off trend between the clock stability performance and SWaP. Here we demonstrate micro mercury trapped ion clock (M2TIC) prototypes integrated with novel micro-fabricated technologies to simultaneously achieve high performance and low SWaP. The M2TIC prototypes could reach the$$10^{-14}$$10-14-stability level in 1 day with a SWaP of 1.1 L, 1.2 kg, and under 6 W of power. This stability level is comparable to the widely used rack-mount Microchip 5071A cesium frequency standard. These standalone prototypes survived regular commercial shipping across the North American continent to a government laboratory, where their performance was independently tested. The M2TIC sets a new reference point for SWaP and performance and opens opportunities for high-performance clocks in terrestrial and space applications.
RETRACTED ARTICLE: Therapeutic effect of melatonin-loaded chitosan/lecithin nanoparticles on hyperglycemia and pancreatic beta cells regeneration in streptozotocin-induced diabetic rats
Authors: Alaa Habiba , Abdelaziz Mariam , Mustafa Maryam , Mansour Mustafa , Magdy Salma , Mohsen Salma , El-Karamany Yomna , Farid Alyaa
Published: June 2023

Nanotechnology is used to overcome fundamental flaws in today's marketed pharmaceuticals that obstruct therapy, like restricted solubility and quick release of drugs into the bloodstream. In both human and animal researches, melatonin was demonstrated to regulate glucose levels. Despite the fact that melatonin is quickly transported through the mucosa, its sensitivity to be oxidized creates a difficulty in achieving the required dose. Additionally, due to its variable absorption and poor oral bioavailability necessitates the development of alternative delivery methods. The study aimed to synthesize melatonin loaded chitosan/lecithin (Mel-C/L) nanoparticles to be assessed in the treatment of streptozotocin (STZ)-induced diabetes in rats. The antioxidant, anti-inflammatory, and cytotoxicity properties of nanoparticles were estimated to determine the safety of manufactured nanoparticles for in vivo studies. In addition, Mel-C/L nanoparticles were administered to rats for eight weeks after inducing hyperglycemia. The therapeutic effect of Mel-C/L nanoparticles was assessed in all experimental groups by detecting insulin and blood glucose levels; observing improvements in liver and kidney functions as well as histological and immunohistochemical evaluation of rats’ pancreatic sections. The results proved that Mel-C/L nanoparticles showed remarkable anti-inflammatory, anti-coagulant, and anti-oxidant effects, in addition to its efficiency in reducing blood glucose levels of STZ-induced diabetic rats and great ability to promote the regeneration of pancreatic beta (β)-cells. Furthermore, Mel-C/L nanoparticles elevated the insulin level; and decreased the elevated levels of urea, creatinine and cholesterol. In conclusion, nanoparticles application decreased the administrated melatonin dose that in turn can diminish the side effects of free melatonin administration.
Videos posted on the internet provide evidence for joint rushing in naturalistic social interactions
Authors: Wolf Thomas , Novák Tamás , Knoblich Günther
Published: June 2023

When people engage in rhythmic joint actions, they unintentionally increase their tempo. However, this phenomenon of joint rushing has so far been investigated only under very specific and somewhat artificial conditions. Therefore, it remains unclear whether joint rushing generalizes to other instances of rhythmic joint action. In this study our aim was to investigate whether joint rushing can also be observed in a wider range of naturalistic rhythmic social interactions. To achieve this, we retrieved videos of a wide range of rhythmic interactions from an online video-sharing platform. The data suggest that joint rushing indeed can also be observed in more naturalistic social interactions. Furthermore, we provide evidence that group size matters for how tempo unfolds in social interactions with larger groups showing a stronger tempo increase than smaller groups. Comparing the data from naturalistic interactions with data collected in a lab study further showed that unintended tempo changes in social interactions are reduced in naturalistic interactions compared to interactions in a lab context. It is an open question which factors led to this reduction. One possibility is that humans might have come up with strategies to reduce the effects of joint rushing.
Disabled and Romani passengers face similar levels of discrimination but different levels of open hostility in the sharing economy
Authors: Simonovits Borbála , Kurdi Benedek , Simonovits Gábor
Published: June 2023

This multimethod project investigates discrimination against members of two populous minority groups in the European Union: the Roma (numbering 6 million) and the disabled (numbering 100 million) on a leading Hungarian carpooling platform. In a field experiment, 1005 ride requests were sent to drivers, with passenger group membership (control, disabled, Roma) manipulated between participants. Widespread discrimination against both groups was apparent in significantly lower approval rates for disabled (56%) and Roma passengers (52%) relative to control (70%). Mechanisms driving anti-disabled and anti-Roma discrimination were probed using an experimental manipulation, natural language processing analysis of driver–passenger interactions, and an online survey (N = 398). Individuating information in the form of reviews did not mitigate unequal treatment, thus providing evidence against statistical (stereotype-based) discrimination. Militating against taste-based (attitudinal) discrimination, respondents reported negative attitudes toward Roma passengers but positive attitudes toward disabled passengers. Moreover, despite equivalent approval rates, disabled passengers were more likely to receive a response from drivers and received more polite responses than Roma passengers did. Overall, the observed patterns are most readily explained by intergroup emotions: Contempt toward Roma passengers likely engenders both passive and active harm, whereas pity toward disabled passengers likely engenders passive harm and active facilitation.
An investigation of simulated and real touch on feelings of loneliness
Authors: Gray Nicholas L. T. , Roberts S. Craig
Published: June 2023

As a social species, humans deprived of contact find loneliness a potentially distressing condition. Recent research emphasises the influence of touch on alleviating loneliness. This research found that touch reduces feelings of neglect, a subscale of loneliness. Affectionate touch, which demonstrates care or affection, has been previously linked to well-being in couples. Here, we investigated whether the effect of simulated touch during a video conversation might be sufficient to influence feelings of loneliness. Sixty participants answered a survey about their home life and relationships, including items that assessed the frequency of touch and feelings of loneliness. Following this, they participated in an online video call with three conditions: audio only, audio and video, or audio, video with simulated touch (a virtual ‘high-five’). Finally, immediately after the call, they repeated the loneliness questionnaire. We found that loneliness scores were reduced following the call, but there was no difference among conditions and no effect of a virtual touch. However, we did find a significant association between the frequency of touch in a relationship and the expression of loneliness, with individuals in low-touch relationships having loneliness scores more comparable to single participants than to those in high-touch relationships. Additionally, extraversion played a major role in moderating the effect of touch in relationships. These results emphasise the importance of physical contact in lowering feelings of loneliness within relationships and the ability of calls to lower feelings of loneliness, regardless of whether they include video or simulated touch.
Dapagliflozin and short-term changes on circulating antigen carbohydrate 125 in heart failure with reduced ejection fraction
Authors: Amiguet Martina , Palau Patricia , Domínguez Eloy , Seller Julia , Pinilla Jose Manuel Garcia , de la Espriella Rafael , Miñana Gema , Valle Alfonso , Sanchis Juan , Górriz Jose Luis , Bayés-Genís Antoni ,   DAPA VO2 investigators, Domíngueza Eloy , Sastre Clara , Miñana Gema , Santas Enrique , Mollar Anna , Civera Jose , Conesa Adriana , Zakarne Rim , Larumbe Ainoha , Pinilla Jose Manuel Garcia , Doblas Juan Jose Gómez , Mezcua Ainhoa Robles , Miñana Gema , Bodí Vicent , Pascual-Figal Domingo , Rubio Clara Jiménez , Cabeza Alejandro I. Pérez , Expósito Arancha Díaz , Carmona José David Martínez , Morales Manuel Luna , Sánchez Francisco J. Zafra , Trujillo Ángel Montiel , Climent Herminio Morillas , Núñez Julio
Published: June 2023

Circulating antigen carbohydrate 125 (CA125) has emerged as a proxy of fluid overload in heart failure. This study aimed to evaluate the effect of dapagliflozin on short-term CA125 levels in patients with stable heart failure with reduced ejection fraction (HFrEF) and whether these changes mediated the effects on peak oxygen consumption (peakVO2). This study is a post-hoc sub-analysis of a randomized, double-blinded clinical trial in which 90 stable patients with HFrEF were randomly assigned to receive either dapagliflozin or placebo to evaluate change in peakVO2 (NCT04197635). We used linear mixed regression analysis to compare changes in the natural logarithm of CA125 (logCA125) and percent changes from baseline (Δ%CA125). We used the “rwrmed” package to perform mediation analyses. CA125 was available in 87 patients (96.7%). LogCA125 significantly decreased in patients on treatment with dapagliflozin [1-month: Δ − 0.18, (CI 95% = − 0.33 to − 0.22) and 3-month: Δ − 0.23, (CI 95% = − 0.38 to − 0.07); omnibus p-value = 0.012]. Δ%CA125 decreased by 18.4% and 31.4% at 1 and 3-month, respectively (omnibus p-value = 0.026). Changes in logCA125 mediated the effect on peakVO2 by 20.4% at 1 month (p < 0.001). We did not find significant changes for natural logarithm of NTproBNP (logNT-proBNP) [1-month: Δ − 0.03, (CI 95% = − 0.23 to 0.17; p = 0.794), and 3-month: Δ 0.73, (CI 95% = − 0.13 to 0.28; p-value 0.489), omnibus p-value = 0.567]. In conclusion, in patients with stable HFrEF, dapagliflozin resulted in a significant reduction in CA125. Dapagliflozin was not associated with short-term changes in natriuretic peptides. These changes mediated the effects on peakVO2.
The concentration of particulate matter in the barn air and its influence on the content of heavy metals in milk
Authors: Nieckarz Zenon , Pawlak Krzysztof , Baran Agnieszka , Wieczorek Jerzy , Grzyb Jacek , Plata Patrycja
Published: June 2023

Heavy metals are one of the components of smog, which is mainly the product of burning fossil fuels in residential buildings. These elements, introduced into the body of cattle by inhalation, may enter the milk. The goal of this study was to assess the impact of particulate pollution in the atmospheric air on the concentration of particulate matter in the air of a dairy cattle barn and on the content of selected heavy metals in milk from cows present in the building. Measurements were taken between November and April (148 measurement days). The calculations carried out showed a high correlation (RS = + 0.95) between the concentrations of particulates measured outside and inside the barn, which is indicative of a significant impact of the atmospheric air on the particulate pollution level of the livestock building. The number of days in excess of the daily standard for PM10 inside was 51. The conducted analysis of the chemical composition of the milk collected under high particulate pollution (February) showed that the permitted lead level had been exceeded—21.93 µg/kg (norm 20.00 µg/kg).
Long-term surveillance provides real-world evidences of safety and effectiveness in intravitreal aflibercept treatment for age-related macular degeneration
Authors: Ozawa Yoko , Ohgami Kazuhiro , Sasaki Koji , Hirano Kazufumi , Sunaya Toshiyuki
Published: June 2023

This prospective, multicentre, postmarketing surveillance were conducted to report on the long-term safety and effectiveness of intravitreal aflibercept (IVT-AFL) treatment in clinical practice of Japanese patients with neovascular age-related macular degeneration (nAMD) who newly initiated IVT-AFL treatment. The primary outcomes were the incidence of adverse events (AEs) and of adverse drug reactions (ADRs) over 36 months. Number of injections, timing of ADR occurrence, and some effectiveness index were also summarised. A total of 3,872 patients received 7.2 ± 5.8 (mean ± standard deviation) injections, and AEs occurred in 5.73% of patients. ADRs were reported in 2.76% of patients, with ocular and nonocular ADRs in 2.07% and 0.72% of patients, respectively. Most vitreo-retinal events developed within 6 months of initial IVT-AFL treatment, and most instances of increased intraocular pressure and cerebral infarction developed after 6 months of follow-up. Mean best-corrected visual acuity and central retinal thickness were numerically better throughout the follow-up period compared with baseline. These results indicated acceptable tolerability and effectiveness of IVT-AFL treatment in patients with nAMD in clinical practice in Japan. Information regarding the risk and the timing of ADRs is valuable for safe and effective long-term treatment of patients with nAMD.

Trial registration number: NCT01756248.
A neonicotinoid pesticide alters Drosophila olfactory processing
Authors: Tatarko Anna R. , Leonard Anne S. , Mathew Dennis
Published: June 2023

Neonicotinoid pesticides are well-known for their sublethal effects on insect behavior and physiology. Recent work suggests neonicotinoids can impair insect olfactory processing, with potential downstream effects on behavior and possibly survival. However, it is unclear whether impairment occurs during peripheral olfactory detection, during information processing in central brain regions, or in both contexts. We used Drosophila melanogaster to explore the potential for neonicotinoids to disrupt olfaction by conducting electrophysiological analyses of single neurons and whole antennae of flies exposed to varying concentrations of the neonicotinoid imidacloprid (IMD) that were shown to cause relative differences in fly survival. Our results demonstrated that IMD exposure significantly reduced the activity of a single focal olfactory neuron and delayed the return to baseline activity of the whole antenna. To determine if IMD also impacts olfactory-guided behavior, we compared flies’ relative preference for odor sources varying in ethanol content. Flies exposed to IMD had a greater relative preference for ethanol-laced pineapple juice than control flies, demonstrating that neuronal shifts induced by IMD that we observed are associated with changes in relative preference. Given the interest in the sensory impacts of agrochemical exposure on wild insect behavior and physiology, we highlight the potential of Drosophila as a tractable model for investigating the effects of pesticides at scales ranging from single-neuron physiology to olfactory-guided behavior.
Application of structural equation modelling to inform best management strategies for Marek’s disease in Amhara region, Ethiopia
Authors: Birhan Mastewal , Berhane Nega , Ibrahim Saddam Mohammed , Dejene Haileyesus , Dessalegn Bereket , Woldemichael Wubet Weledemedhin , Gelaye Esayas , Getachew Belayneh , Abayneh Takele , Bitew Molalegne
Published: June 2023

Marek’s disease, a highly contagious and an economically significant oncogenic and paralytic viral diseases of poultry, is becoming a serious problem in Ethiopia’s poultry sector. The aim of the study was to examine the relationship between risk factors and their contribution to develop risk with the intentions to implement MD control measures in the different chicken production systems of Ethiopia using the SEM framework. A questionnaire was designed based on the framework and each model constructed was measured using a set of rating scale items. Thus, a sample size of 200 farmers from different production systems were chosen for the data collection. From the analysis, Cornbrash’s Alpha (coefficient of reliability) based on the average inter-item correlations were evaluated for each parameter. The result showed that when litter management goes up by 1, the number of sick goes down by 37.575, the number of staff goes up by 1, the number of sick goes down by 7.63, litter management goes up by 1, the number of deaths goes down by 2.505, flock size goes up by 1, the number of deaths goes down by 0.007 than the rest of the activities. The result of this structural equation modeling finding indicates that the data fit the model well (χ2 = 0.201, RMSEA = 0.000, CFI = 1.00, TLI = 1.496, Degrees of freedom = 2) and the model was appropriated. In conclusion, flock size, litter management and number of staff activities have more impact on the numbers of sick, drops in egg production and the number of deaths. Therefore, practicing regular awareness creation for producers regarding management techniques is recommended.
Engine performance and emissions evaluation of surfactant-free B30 biodiesel–diesel/water emulsion as alternative fuel
Authors: Mohd Tamam Mohamad Qayyum , Omi Md Reashed Tasvir , Yahya Wira Jazair , Ithnin Ahmad Muhsin , Abdul Rahman Hasbullah , Rahman Md. Mujibur , Abd Kadir Hasannuddin , Noge Hirofumi , Koga Tsuyoshi , Hong Chungpyo , Otaka Takeshi , Kinoshita Eiji
Published: June 2023

Malaysia is one of the top exporters of palm oil, and although currently facing fierce resistance towards palm oil imports in some parts of the globe, one of the ways to utilize this commodity is by increasing palm biodiesel content in local commercial diesel. However, due to the oxygen-rich nature of biodiesel, its utilization suffers from increased nitrogen oxides (NOx) emission compared to conventional diesel. To mitigate this issue and improve diesel engine performance and emissions using biodiesel–diesel blends, this study attempted to investigate implementation of a real-time non-surfactant emulsion fuel supply system (RTES) which produces water-in-diesel emulsion as fuel without surfactants. NOx reducing capability of water-in-diesel produced by RTES has been well documented. Therefore, in this study, 30% biodiesel–diesel (B30) was used as the base fuel while B30-derived emulsions consisting of 10 wt%, 15 wt% and 20 wt% water content were supplied into a 100 kVA, 5.9-L common rail turbocharged diesel engine electric generator. Fuel consumption and exhaust emissions were measured and compared with commercially available Malaysian low grade diesel fuel (D2M). Evidence suggested that emulsified B30 biodiesel–diesel produced by RTES was able to increase brake thermal efficiency (BTE) up to a maximum of 36% and reduce brake specific fuel consumption (BSFC) up to 8.70%. Furthermore, B30 biodiesel–diesel emulsions produced significantly less NOx, carbon monoxide and smoke at high engine load. In conclusion, B30 biodiesel–diesel emulsions can be readily utilized in current diesel engines without compromising on performance and emissions.
The impact of comorbidities and COVID-19 on the evolution of community onset sepsis
Authors: de Araújo Giovanna Colantuono , Pardini Andrea , Lima Camila
Published: June 2023

Sepsis is a disease with high mortality and morbidity despite advances in diagnostic procedures and therapeutic strategies. The aim of this study was to evaluate the profile and outcomes of community-onset sepsis. This retrospective, multicenter study included five 24-h health care units and was conducted from January 2018 to December 2021. Patients were diagnosed with sepsis or septic shock according to the Sepsis 3.0 criterion. A total of 2630 patients diagnosed as having sepsis (68.4%, 1800) or septic shock (31.6%, 830) in the 24-h health care unit were included; 43.76% of the patients were admitted to the intensive care unit, 12.2% died, 4.1% had sepsis and 30% had septic shock. The comorbidities that were independent predictors of septic shock were chronic kidney disease on dialysis (CKD-d), bone marrow transplantation and neoplasia. CKD and neoplasia were also independent predictors of mortality, with ORs of 2.00 (CI 1.10–3.68) p = 0.023 and 1.74 (CI 1.319–2.298) p =  < 0.0001, respectively. Mortality according to the focus of primary infection was as follows: pulmonary 40.1%; COVID-19 35.7%; abdominal 8.1% and urinary 6.2%. Mortality due to the COVID-19 outbreak had an OR of 4.94 (CI 3.08–8.13) p ≤ 0.0001. Even though community-onset sepsis can be potentially fatal, this study revealed that some comorbidities lead to an increased risk of septic shock (d-CKD and neoplasia) and mortality. COVID-19 infection as the primary focus was an independent predictor of mortality in patients with sepsis when compared to other foci.
The effects of IL-1β stimulated human umbilical cord mesenchymal stem cells on polarization and apoptosis of macrophages in rheumatoid arthritis
Authors: Zeng Ying-Xuan , Chou Kuang-Yi , Hwang Jeng-Jong , Wang Hwai-Shi
Published: June 2023

Macrophages play an important role in the pathogenesis of rheumatoid arthritis (RA), in which the functions of pro-inflammatory macrophages (M1) and anti-inflammatory macrophages (M2) are different. Our previous studies have demonstrated that interleukin-1β (IL-1β) stimulated human umbilical cord mesenchymal stem cells (hUCMSCs) increase the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and initiate breast cancer cell apoptosis via ligand to death receptor 4 (DR4) and DR5. In this study, we examined the effect of IL-1β stimulated hUCMSCs (IL-1β-hUCMSCs) on immunoregulation of M1 and M2 macrophages in vitro and in the RA mouse model. The results showed that IL-1β-hUCMSCs increased macrophage polarization into M2 macrophages and enhanced apoptosis of M1 macrophages in vitro. Moreover, the intravenous injected IL-1β-hUCMSCs in RA mice rehabilitated the imbalance of M1/M2 ratio and thus demonstrated the potential to reduce inflammation in RA. This study advances our knowledge of the underlying immunoregulatory mechanisms involved in IL-1β-hUCMSCs to induce M1 macrophage apoptosis and promote the anti-inflammatory polarization of M2 macrophages and demonstrates the potential of IL-1β-hUCMSCs to reduce inflammation in RA.
Seasonal prevalence of bacteria in the outflow of two full-scale municipal wastewater treatment plants
Authors: Domańska Magdalena , Kuśnierz Magdalena , Mackiewicz Katarzyna
Published: June 2023

Despite many modern wastewater treatment solutions, the most common is still the use of activated sludge (AS). Studies indicate that the microbial composition of AS is most often influenced by the raw sewage composition (especially influent ammonia), biological oxygen demand, the level of dissolved oxygen, technological solutions, as well as the temperature of wastewater related to seasonality. The available literature mainly refers to the relationship between AS parameters or the technology used and the composition of microorganisms in AS. However, there is a lack of data on the groups of microorganisms leaching into water bodies whose presence is a signal for possible changes in treatment technology. Moreover, sludge flocs in the outflow contain less extracellular substance (EPS) which interferes microbial identification. The novelty of this article concerns the identification and quantification of microorganisms in the AS and in the outflow by fluorescence in situ hybridization (FISH) method from two full-scale wastewater treatment plants (WWTPs) in terms of 4 key groups of microorganisms involved in the wastewater treatment process in the context of their potential technological usefulness. The results of the study showed that Nitrospirae, Chloroflexi and Ca. Accumulibacter phosphatis in treated wastewater reflect the trend in abundance of these bacteria in activated sludge. Increased abundance of betaproteobacterial ammonia-oxidizing bacteria and Nitrospirae in the outflow were observed in winter. Principal component analysis (PCA) showed that loadings obtained from abundance of bacteria in the outflow made larger contributions to the variance in the PC1 factorial axis, than loadings obtained from abundance of bacteria from activated sludge. PCA confirmed the reasonableness of conducting studies not only in the activated sludge, but also in the outflow to find correlations between technological problems and qualitative and quantitative changes in the outflow microorganisms.
Disparate dynamics of pathogen prevalence in Ixodes ricinus and Dermacentor reticulatus ticks occurring sympatrically in diverse habitats
Authors: Zając Zbigniew , Obregon Dasiel , Foucault-Simonin Angélique , Wu-Chuang Alejandra , Moutailler Sara , Galon Clemence , Kulisz Joanna , Woźniak Aneta , Bartosik Katarzyna , Cabezas-Cruz Alejandro
Published: June 2023

Ixodes ricinusandDermacentor reticulatusticks are important reservoirs and vectors of pathogens. The aim of the present study was to investigate the dynamic of the prevalence and genetic diversity of microorganisms detected in these tick species collected from two ecologically diverse biotopes undergoing disparate long-term climate condition. High-throughput real time PCR confirmed high prevalence of microorganisms detected in sympatrically occurring ticks species.D. reticulatusspecimens were the most often infected withFrancisella-like endosymbiont (FLE) (up to 100.0%) andRickettsiaspp. (up to 91.7%), while in case ofI. ricinusthe prevalence of Borreliaceae spirochetes reached up to 25.0%. Moreover, pathogens belonging to genera ofBartonella,Anaplasma,EhrlichiaandBabesiawere detected in both tick species regardless the biotope. On the other hand,Neoehrlichia mikurensiswas conformed only inI. ricinusin the forest biotope, while genetic material ofTheileriaspp. was found only inD. reticulatuscollected from the meadow. Our study confirmed significant impact of biotope type on prevalence of representatives of Borreliaceae and Rickettsiaceae families. The most common co-infection detected inD. reticulatuswasRickettsiaspp. + FLE, while Borreliaceae + R. helveticawas the most common inI. ricinus. Additionally, we found significant genetic diversity ofR. raoultii gltAgene across studied years, however such relationship was not observed in ticks from studied biotopes. Our results suggest that ecological type of biotope undergoing disparate long-term climate conditions have an impact on prevalence of tick-borne pathogens in adultD. reticulatusandI. ricinus.
Effectiveness of creating digital twins with different digital dentition models and cone-beam computed tomography
Authors: Lee Joo-Hee , Lee Hye-Lim , Park In-Young , On Sung-Woon , Byun Soo-Hwan , Yang Byoung-Eun
Published: June 2023

Distortion of dentition may occur in cone-beam computed tomography (CBCT) scans due to artifacts, and further imaging is frequently required to produce digital twins. The use of a plaster model is common; however, it has certain drawbacks. This study aimed to assess the feasibility of different digital dentition models over that of plaster casts. Plaster models, alginate impressions, intraoral scan (IOS) images, and CBCT images of 20 patients were obtained. The desktop model scanner was used to scan the alginate impression twice, five minutes and two hours after impression-making. Using an IOS, the full arch was scanned in segments using CS 3600 and simultaneously with i700 wireless. The digital twins obtained from the alginate impression and IOS were superimposed with those obtained from the plaster cast. The differences and distances at each reference point were measured. Scans of alginate impressions after two hours showed the greatest discrepancies, but these were all less than the CBCT voxel size of 0.39 mm. Alginate impression scans and IOS are suitable supplements to CBCT compared to the plaster model. Accuracy can be improved by scanning the alginate impression within five minutes or by intraoral scanning of the entire arch with segmentation.