bluuebunny/crossref_metadata_2025 huggingface dataset:
The Safety, Efficacy, and Expediency of Albuterol Nebulizer Administration by BLS Providers
Authors: Matthews Patrick J. , Ader Douglas R. , Harrison Cecelia K. , Ostahowski Paige J. , Nomura Jason T.
Published: March 2023

Introduction:

Many Emergency Medical Service (EMS) systems in the United States restrict albuterol therapy by scope of practice to Advanced Life Support (ALS). The State of Delaware has a two-tiered EMS system in which Basic Life Support (BLS) arrives on scene prior to ALS in the majority of respiratory distress calls.

Study Objective:

This study sought to evaluate the safety, efficacy, and expedience of albuterol administration by BLS compared to ALS.

Methods:

This retrospective observational study used data collected from July 2015 through January 2017 throughout a State BLS albuterol pilot program. Pilot BLS agencies participated in a training session on the indications and administration of albuterol, and were then authorized to carry and administer nebulized albuterol. Heart rate (HR), respiratory rate (RR), and pulse oximetry (spO2) were obtained before and after albuterol administration by BLS and ALS. The times from BLS arrival to the administration of albuterol by pilot BLS agencies versus ALS were compared. Study encounters required both BLS and ALS response. Data were analyzed using chi-square and t-test as appropriate.

Results:

Three hundred eighty-eight (388) incidents were reviewed. One hundred eighty-five (185) patients received albuterol by BLS pilot agencies and 203 patients received albuterol by ALS. Of note, the population treated by ALS was significantly older than the population treated by BLS (61.9 versus 51.6 years; P <.001). A comparison of BLS arrival time to albuterol administration time showed significantly shorter times in the BLS pilot group compared to the ALS group (3.50 minutes versus 8.00 minutes, respectively; P <.001). After albuterol administration, BLS pilot patients showed improvements in HR (P <.01), RR (P <.01), and spO2 (P <.01). Alternately, ALS treatment patients showed improvement in spO2 (P <.01) but not RR (P = .17) or HR (P = 1.00). Review by ALS or hospital staff showed albuterol was indicated in 179 of 185 BLS patients and administered correctly in 100% of these patients.

Conclusion:

Patients both received albuterol significantly sooner and showed superior improvements in vital signs when treated by BLS agencies carrying albuterol rather than by BLS agencies who required ALS arrival for albuterol. Two-tiered EMS systems should consider allowing BLS to carry and administer albuterol for safe, effective, and expedient treatment of respiratory distress patients amenable to albuterol therapy.
UNIFORM LOCAL CONSTANCY OF ÉTALE COHOMOLOGY OF RIGID ANALYTIC VARIETIES
Authors: Ito Kazuhiro
Published: March 2023

We prove some
$\ell $
-independence results on local constancy of étale cohomology of rigid analytic varieties. As a result, we show that a closed subscheme of a proper scheme over an algebraically closed complete non-archimedean field has a small open neighbourhood in the analytic topology such that, for every prime number
$\ell $
different from the residue characteristic, the closed subscheme and the open neighbourhood have the same étale cohomology with
${\mathbb Z}/\ell {\mathbb Z}$
-coefficients. The existence of such an open neighbourhood for each
$\ell $
was proved by Huber. A key ingredient in the proof is a uniform refinement of a theorem of Orgogozo on the compatibility of the nearby cycles over general bases with base change.
Exoskeletal solutions to enable mobility with a lower leg fracture in austere environments
Authors: Johnson W. Brett , Young Aaron , Goldman Stephen , Wilson Jon , Alderete Joseph F. , Childers W. Lee
Published: March 2023

The treatment and evacuation of people with lower limb fractures in austere environments presents unique challenges that assistive exoskeletal devices could address. In these dangerous situations, independent mobility for the injured can preserve their vital capabilities so that they can safely evacuate and minimize the need for additional personnel to help. This expert view article discusses how different exoskeleton archetypes could provide independent mobility while satisfying the requisite needs for portability, maintainability, durability, and adaptability to be available and useful within austere environments. The authors also discuss areas of development that would enable exoskeletons to operate more effectively in these scenarios as well as preserve the health of the injured limb so that definitive treatment after evacuation will produce better outcomes.
Immunotherapies: How Do They Work?
Authors: Quercia Kelly , Fernandez Eugenio
Published: March 2023

Abstract. The understanding of the immune system and the discovery of the proteins and processes involved in its regulation have enabled the emergence of new approaches against cancer. The development of antibodies (immune checkpoint inhibitors) able of blocking interactions that suppress the activation of T cells or their effector actions against cancer cells has modified the prognosis of several cancer forms. Bispecific antibodies as well as cellular immunotherapies (CARs/TILs) are new immunotherapy approaches that have already shown their effectiveness in certain onco-haematological diseases. Unfortunately, only a fraction of treated patients derives benefit from these treatments. The future challenge will be to understand the resistance mechanisms to immunotherapies so that treatment may be personalized for each patient.
Revisiting the Land‐Ocean Contrasts in Deep Convective Cloud Intensity Using Global Satellite Observations
Authors: Takahashi Hanii , Luo Zhengzhao Johnny , Stephens Graeme , Mulholland Jake P.
Published: March 2023

Tropical convection tends to be more intense over land than ocean, but why? Numerous previous studies have investigated the causes of this difference. This paper revisits this question using CloudSat data and focuses on interconnecting various environmental parameters and cloud properties, which have often been examined in a piecemeal way in the past. Our analysis shows that if convection is treated as a process by which potential energy (convective available potential energy) is converted to kinetic energy (vertical velocity), then the conversion is more efficient over land than ocean. A key factor that affects this conversion efficiency is the lifting condensation level (LCL). Higher LCLs over land give rise to broader dry boundary layer thermals that transition to wider deep convective cores. Wider cores, in turn, are better protected from the dilution by entrainment, thus leading to stronger updrafts. This study highlights the importance of the dry stage of convection.
Statistical Study of Release Time and Its Energy Dependence of In Situ Energetic Electrons in Impulsive Solar Flares
Authors: Wu Xiangyu , Li Gang , Zhao Lulu , Effenberger Frederic , Wang Linghua , Yao Shuo
Published: March 2023

Using the fraction velocity dispersion analysis method, it has been shown recently that in two impulsive solar energetic electron (SEE) events, the release times of near‐relativistic electrons at the Sun for outward‐propagating electrons are energy dependent and are delayed compared to those of the downward‐propagating electrons. In this work, we perform a statistical study of the release time and its energy dependence of near‐relativistic electrons in impulsive SEE events. We use in situ observations from the WIND spacecraft and remote hard X‐ray observations from the RHESSI and/or Fermi spacecraft. The difference in the release times between outward electrons and downward electrons for 29 events is obtained. In all events, the release of the outward‐propagating electrons is delayed from those precipitating downward. In 26 of the 29 events, the release times of outward‐propagating electrons also show clear energy dependence. In 15 of these 26 events, in situ electron data from more than five energy channels were available. The delay time as a function of energy for nine of these can be fitted by a form proposed by G. Li et al. (2021, https://doi.org/10.1029/2021GL095138). The implication of this energy‐dependent release on the Magnetohydrodynamics turbulence property at the electron acceleration site is discussed.
Net Climate Effects of Moose Browsing in Early Successional Boreal Forests by Integrating Carbon and Albedo Dynamics
Authors: Salisbury John , Hu Xiangping , Speed James D. M. , Iordan Cristina Maria , Austrheim Gunnar , Cherubini Francesco
Published: March 2023

Moose (Alces alces) is a large herbivore that can mediate boreal forest regeneration after timber harvest through selective browsing of tree species. Despite increasing evidence of moose browsing influence on tree growth in early successional forests, climate effects due to changes in carbon sequestration rates and biophysical factors such as albedo remain largely unexplored. We used 11 years of data from 44 pair‐sites of herbivore exclosures within clear‐cut forests in Norway to investigate how moose browsing alters aboveground tree biomass and albedo. We find a higher total aboveground tree biomass (mainly deciduous species) in unbrowsed than browsed forest plots, as moose browsing limited the growth of tree biomass. The effect of moose exclosure on relative tree abundances differed between sites, suggesting that moose browsing has stronger effects on forest structure than composition. At the same time, moose increased forest albedo relative to un‐browsed forests, driving biophysical cooling. When averaged at regional levels, climate effects due to changes in biomass and albedo are of similar magnitude, but contributions can diverge in specific locations. In a region with intensive forestry operations and high moose density, CO2 emissions from moose browsing in post‐harvested sites can be equal to about 40% of the annual emissions of fossil fuels from that region. Cooling effects from increased albedo can offset about two thirds of this impact. Given its influence on tree growth rates and climate impacts, management of moose browsing density should be integrated into forest management plans to optimize climate change mitigation and forest productivity.
The roles of N6-methyladenosine and its target regulatory noncoding RNAs in tumors: classification, mechanisms, and potential therapeutic implications
Authors: Liu Ziying , Gao Lei , Cheng Long , Lv Gaoyuan , Sun Bei , Wang Gang , Tang Qiushi
Published: March 2023

N6-methyladenosine (m6A) is one of the epigenetic modifications of RNA. The addition of this chemical mark to RNA molecules regulates gene expression by affecting the fate of the RNA molecules. This posttranscriptional RNA modification is reversible and regulated by methyltransferase “writers” and demethylase “erasers”. The fate of m6A-modified RNAs depends on the function of different “readers” that recognize and bind to them. Research on m6A methylation modification has recently increased due to its important role in regulating cancer progression. Noncoding RNAs (ncRNAs) are a class of RNA molecules that are transcribed from the genome but whose roles have been overlooked due to their lack of well-defined potential for translation into proteins or peptides. However, this misconception has now been completely overturned. ncRNAs regulate various diseases, especially tumors, and it has been confirmed that they play either tumor-promoting or tumor-suppressing roles in almost all types of tumors. In this review, we discuss the m6A modification of different types of ncRNA and summarize the mechanisms involved. Finally, we discuss the progress of research on clinical treatment and discuss the important significance of the m6A modification of ncRNAs in the clinical treatment of tumors.
Variable preterm oral microbiome stabilizes and reflects a full-term infant profile within three months
Authors: Selway Caitlin A. , Collins Carmel T. , Makrides Maria , Sullivan Thomas R. ,   N3RO Steering Committee, Gibson Robert A. , Penttila Irmeli , McPhee Andrew , Weyrich Laura S.
Published: March 2023

Background

Preterm infants suffer higher morbidity and mortality rates compared to full-term infants, but little is known about how changes to oral and respiratory tract microbiota may impact disease development.

Methods

Here, very preterm neonates (n = 50) were selected to study oral and respiratory microbiota development during the first few months post-birth, where 26 individuals were diagnosed with BPD and/or sepsis. These infants were compared to 14 healthy full-term infants and 16 adults. Microbiota diversity, composition, and species abundances were calculated from 16S ribosomal RNA gene sequences in buccal swabs and tracheal aspirates at two time points (within a week and 1–3 months post-birth).

Results

Collection time point was the biggest factor to significantly influence the preterm oral microbial diversity and composition. In addition, BPD and sepsis were linked to distinct preterm oral microbiota diversity and composition, and opportunistic pathogens previously associated with these diseases were identified in the initial sample for both healthy preterm neonates and those with the disease. Compared to the full-term infant and adult dataset, preterm infant diversity and composition was initially significantly different, but resembled full-term infant diversity and composition over time.

Conclusion

Overall, consequences of microbiota development need further examination in preterm infant infections and later development.

Impact

Non-gut microbiota research on preterm infants is limited.

At one week post-birth, preterm infants harbor distinct oral microbiota that are not shared with full-term children or adults, eventually becoming similar to full-term infants at 36 weeks postmenstrual age.

DNA from potential opportunistic pathogens was observed in the mouth and lungs of preterm infants within a week of birth, and microbes associated with BPD were identified in the lungs.

Oral microbiota in preterm infants over the first 2–3 months is unique and may be connected to short- and long-term health outcomes in these children.
Necroptosis of macrophage is a key pathological feature in biliary atresia via GDCA/S1PR2/ZBP1/p-MLKL axis
Authors: Yang Shen , Chang Na , Li Weiyang , Yang Ting , Xue Renmin , Liu Jing , Zhang Li , Yao Xingfeng , Chen Yajun , Wang Huanmin , Yang Lin , Huang Jinshi , Li Liying
Published: March 2023

Biliary atresia (BA) is a severe inflammatory and fibrosing neonatal cholangiopathy disease characterized by progressive obstruction of extrahepatic bile ducts, resulting in cholestasis and progressive hepatic failure. Cholestasis may play an important role in the inflammatory and fibrotic pathological processes, but its specific mechanism is still unclear. Necroptosis mediated by Z-DNA-binding protein 1 (ZBP1)/phosphorylated-mixed lineage kinase domain-like pseudokinase (p-MLKL) is a prominent pathogenic factor in inflammatory and fibrotic diseases, but its function in BA remains unclear. Here, we aim to determine the effect of macrophage necroptosis in the BA pathology, and to explore the specific molecular mechanism. We found that necroptosis existed in BA livers, which was occurred in liver macrophages. Furthermore, this process was mediated by ZBP1/p-MLKL, and the upregulated expression of ZBP1 in BA livers was correlated with liver fibrosis and prognosis. Similarly, in the bile duct ligation (BDL) induced mouse cholestatic liver injury model, macrophage necroptosis mediated by ZBP1/p-MLKL was also observed. In vitro, conjugated bile acid-glycodeoxycholate (GDCA) upregulated ZBP1 expression in mouse bone marrow-derived monocyte/macrophages (BMDMs) through sphingosine 1-phosphate receptor 2 (S1PR2), and the induction of ZBP1 was a prerequisite for the enhanced necroptosis. Finally, after selectively knocking down of macrophage S1pr2 in vivo, ZBP1/p-MLKL-mediated necroptosis was decreased, and further collagen deposition was markedly attenuated in BDL mice. Furthermore, macrophage Zbp1 or Mlkl specific knockdown also alleviated BDL-induced liver injury/fibrosis. In conclusion, GDCA/S1PR2/ZBP1/p-MLKL mediated macrophage necroptosis plays vital role in the pathogenesis of BA liver fibrosis, and targeting this process may represent a potential therapeutic strategy for BA.
Dying transplanted neural stem cells mediate survival bystander effects in the injured brain
Authors: Han Wei , Meißner Eva-Maria , Neunteibl Stefanie , Günther Madeline , Kahnt Jörg , Dolga Amalia , Xie Cuicui , Plesnila Nikolaus , Zhu Changlian , Blomgren Klas , Culmsee Carsten
Published: March 2023

Neural stem and progenitor cell (NSPC) transplants provide neuroprotection in models of acute brain injury, but the underlying mechanisms are not fully understood. Here, we provide evidence that caspase-dependent apoptotic cell death of NSPCs is required for sending survival signals to the injured brain. The secretome of dying NSPCs contains heat-stable proteins, which protect neurons against glutamate-induced toxicity and trophic factor withdrawal in vitro, and from ischemic brain damage in vivo. Our findings support a new concept suggesting a bystander effect of apoptotic NSPCs, which actively promote neuronal survival through the release of a protective “farewell” secretome. Similar protective effects by the secretome of apoptotic NSPC were also confirmed in human neural progenitor cells and neural stem cells but not in mouse embryonic fibroblasts (MEF) or human dopaminergic neurons, suggesting that the observed effects are cell type specific and exist for neural progenitor/stem cells across species.
A maximum-entropy model to predict 3D structural ensembles of chromatin from pairwise distances with applications to interphase chromosomes and structural variants
Authors: Shi Guang , Thirumalai D.
Published: March 2023

The principles that govern the organization of genomes, which are needed for an understanding of how chromosomes are packaged and function in eukaryotic cells, could be deciphered if the three-dimensional (3D) structures are known. Recently, single-cell imaging techniques have been developed to determine the 3D coordinates of genomic loci in vivo. Here, we introduce a computational method (Distance Matrix to Ensemble of Structures, DIMES), based on the maximum entropy principle, with experimental pairwise distances between loci as constraints, to generate a unique ensemble of 3D chromatin structures. Using the ensemble of structures, we quantitatively account for the distribution of pairwise distances, three-body co-localization, and higher-order interactions. The DIMES method can be applied to both small and chromosome-scale imaging data to quantify the extent of heterogeneity and fluctuations in the shapes across various length scales. We develop a perturbation method in conjunction with DIMES to predict the changes in 3D structures from structural variations. Our method also reveals quantitative differences between the 3D structures inferred from Hi-C and those measured in imaging experiments. Finally, the physical interpretation of the parameters extracted from DIMES provides insights into the origin of phase separation between euchromatin and heterochromatin domains.
Magnesium oxide-water compounds at megabar pressure and implications on planetary interiors
Authors: Pan Shuning , Huang Tianheng , Vazan Allona , Liang Zhixin , Liu Cong , Wang Junjie , Pickard Chris J. , Wang Hui-Tian , Xing Dingyu , Sun Jian
Published: March 2023

Magnesium Oxide (MgO) and water (H2O) are abundant in the interior of planets. Their properties, and in particular their interaction, significantly affect the planet interior structure and thermal evolution. Here, using crystal structure predictions and ab initio molecular dynamics simulations, we find that MgO and H2O can react again at ultrahigh pressure, although Mg(OH)2 decomposes at low pressure. The reemergent MgO-H2O compounds are: Mg2O3H2 above 400 GPa, MgO3H4 above 600 GPa, and MgO4H6 in the pressure range of 270–600 GPa. Importantly, MgO4H6 contains 57.3 wt % of water, which is a much higher water content than any reported hydrous mineral. Our results suggest that a substantial amount of water can be stored in MgO rock in the deep interiors of Earth to Neptune mass planets. Based on molecular dynamics simulations we show that these three compounds exhibit superionic behavior at the pressure-temperature conditions as in the interiors of Uranus and Neptune. Moreover, the water-rich compound MgO4H6 could be stable inside the early Earth and therefore may serve as a possible early Earth water reservoir. Our findings, in the poorly explored megabar pressure regime, provide constraints for interior and evolution models of wet planets in our solar system and beyond.
Oceanic climate changes threaten the sustainability of Asia’s water tower
Authors: Zhang Qiang , Shen Zexi , Pokhrel Yadu , Farinotti Daniel , Singh Vijay P. , Xu Chong-Yu , Wu Wenhuan , Wang Gang
Published: March 2023

Water resources sustainability in High Mountain Asia (HMA) surrounding the Tibetan Plateau (TP)—known as Asia’s water tower—has triggered widespread concerns because HMA protects millions of people against water stress1,2. However, the mechanisms behind the heterogeneous trends observed in terrestrial water storage (TWS) over the TP remain poorly understood. Here we use a Lagrangian particle dispersion model and satellite observations to attribute about 1 Gt of monthly TWS decline in the southern TP during 2003–2016 to westerlies-carried deficit in precipitation minus evaporation (PME) from the southeast North Atlantic. We further show that HMA blocks the propagation of PME deficit into the central TP, causing a monthly TWS increase by about 0.5 Gt. Furthermore, warming-induced snow and glacial melt as well as drying-induced TWS depletion in HMA weaken the blocking of HMA’s mountains, causing persistent northward expansion of the TP’s TWS deficit since 2009. Future projections under two emissions scenarios verified by satellite observations during 2020–2021 indicate that, by the end of the twenty-first century, up to 84% (for scenario SSP245) and 97% (for scenario SSP585) of the TP could be afflicted by TWS deficits. Our findings indicate a trajectory towards unsustainable water systems in HMA that could exacerbate downstream water stress.
Coastal phytoplankton blooms expand and intensify in the 21st century
Authors: Dai Yanhui , Yang Shangbo , Zhao Dan , Hu Chuanmin , Xu Wang , Anderson Donald M. , Li Yun , Song Xiao-Peng , Boyce Daniel G. , Gibson Luke , Zheng Chunmiao , Feng Lian
Published: March 2023

Phytoplankton blooms in coastal oceans can be beneficial to coastal fisheries production and ecosystem function, but can also cause major environmental problems1,2—yet detailed characterizations of bloom incidence and distribution are not available worldwide. Here we map daily marine coastal algal blooms between 2003 and 2020 using global satellite observations at 1-km spatial resolution. We found that algal blooms occurred in 126 out of the 153 coastal countries examined. Globally, the spatial extent (+13.2%) and frequency (+59.2%) of blooms increased significantly (P < 0.05) over the study period, whereas blooms weakened in tropical and subtropical areas of the Northern Hemisphere. We documented the relationship between the bloom trends and ocean circulation, and identified the stimulatory effects of recent increases in sea surface temperature. Our compilation of daily mapped coastal phytoplankton blooms provides the basis for global assessments of bloom risks and benefits, and for the formulation or evaluation of management or policy actions.
H3K4me3 regulates RNA polymerase II promoter-proximal pause-release
Authors: Wang Hua , Fan Zheng , Shliaha Pavel V. , Miele Matthew , Hendrickson Ronald C. , Jiang Xuejun , Helin Kristian
Published: March 2023

Trimethylation of histone H3 lysine 4 (H3K4me3) is associated with transcriptional start sites and has been proposed to regulate transcription initiation1,2. However, redundant functions of the H3K4 SET1/COMPASS methyltransferase complexes complicate the elucidation of the specific role of H3K4me3 in transcriptional regulation3,4. Here, using mouse embryonic stem cells as a model system, we show that acute ablation of shared subunits of the SET1/COMPASS complexes leads to a complete loss of all H3K4 methylation. Turnover of H3K4me3 occurs more rapidly than that of H3K4me1 and H3K4me2 and is dependent on KDM5 demethylases. Notably, acute loss of H3K4me3 does not have detectable effects on transcriptional initiation but leads to a widespread decrease in transcriptional output, an increase in RNA polymerase II (RNAPII) pausing and slower elongation. We show that H3K4me3 is required for the recruitment of the integrator complex subunit 11 (INTS11), which is essential for the eviction of paused RNAPII and transcriptional elongation. Thus, our study demonstrates a distinct role for H3K4me3 in transcriptional pause-release and elongation rather than transcriptional initiation.
Orbital period change of Dimorphos due to the DART kinetic impact
Authors: Thomas Cristina A. , Naidu Shantanu P. , Scheirich Peter , Moskovitz Nicholas A. , Pravec Petr , Chesley Steven R. , Rivkin Andrew S. , Osip David J. , Lister Tim A. , Benner Lance A. M. , Brozović Marina , Contreras Carlos , Morrell Nidia , Rożek Agata , Kušnirák Peter , Hornoch Kamil , Mages Declan , Taylor Patrick A. , Seymour Andrew D. , Snodgrass Colin , Jørgensen Uffe G. , Dominik Martin , Skiff Brian , Polakis Tom , Knight Matthew M. , Farnham Tony L. , Giorgini Jon D. , Rush Brian , Bellerose Julie , Salas Pedro , Armentrout William P. , Watts Galen , Busch Michael W. , Chatelain Joseph , Gomez Edward , Greenstreet Sarah , Phillips Liz , Bonavita Mariangela , Burgdorf Martin J. , Khalouei Elahe , Longa-Peña Penélope , Rabus Markus , Sajadian Sedighe , Chabot Nancy L. , Cheng Andrew F. , Ryan William H. , Ryan Eileen V. , Holt Carrie E. , Agrusa Harrison F.
Published: March 2023

The Double Asteroid Redirection Test (DART) spacecraft successfully performed the first test of a kinetic impactor for asteroid deflection by impacting Dimorphos, the secondary of near-Earth binary asteroid (65803) Didymos, and changing the orbital period of Dimorphos. A change in orbital period of approximately 7 min was expected if the incident momentum from the DART spacecraft was directly transferred to the asteroid target in a perfectly inelastic collision1, but studies of the probable impact conditions and asteroid properties indicated that a considerable momentum enhancement (β) was possible2,3. In the years before impact, we used lightcurve observations to accurately determine the pre-impact orbit parameters of Dimorphos with respect to Didymos4–6. Here we report the change in the orbital period of Dimorphos as a result of the DART kinetic impact to be −33.0 ± 1.0 (3σ) min. Using new Earth-based lightcurve and radar observations, two independent approaches determined identical values for the change in the orbital period. This large orbit period change suggests that ejecta contributed a substantial amount of momentum to the asteroid beyond what the DART spacecraft carried.
Distribution of dietary nitrate and its metabolites in rat tissues after 15N-labeled nitrate administration
Authors: Park Ji Won , Piknova Barbora , Walter Peter J. , Cai Hongyi , Upanan Supranee , Thomas Samantha M. , Tunau-Spencer Khalid J. , Schechter Alan N.
Published: March 2023

The reduction pathway of nitrate (NO3−) and nitrite (NO2−) to nitric oxide (NO) contributes to regulating many physiological processes. To examine the rate and extent of dietary nitrate absorption and its reduction to nitrite, we supplemented rat diets with Na15NO3-containing water (1 g/L) and collected plasma, urine and several tissue samples. We found that plasma and urine showed 8.8- and 11.7-fold increases respectively in total nitrate concentrations in 1-day supplementation group compared to control. In tissue samples—gluteus, liver and eyes—we found 1.7-, 2.4- and 4.2-fold increases respectively in 1-day supplementation group. These increases remained similar in 3-day supplementation group. LC–MS/MS analysis showed that the augmented nitrate concentrations were primarily from the exogenously provided 15N-nitrate. Overall nitrite concentrations and percent of 15N-nitrite were also greatly increased in all samples after nitrate supplementation; eye homogenates showed larger increases compared to gluteus and liver. Moreover, genes related to nitrate transport and reduction (Sialin, CLC and XOR) were upregulated after nitrate supplementation for 3 days in muscle (Sialin 2.3-, CLC1 1.3-, CLC3 2.1-, XOR 2.4-fold) and eye (XOR 1.7-fold) homogenates. These results demonstrate that dietary nitrate is quickly absorbed into circulation and tissues, and it can be reduced to nitrite in tissues (and likely to NO) suggesting that nitrate-enriched diets can be an efficient intervention to enhance nitrite and NO bioavailability.
NLRX1 knockdown attenuates pro-apoptotic signaling and cell death in pulmonary hyperoxic acute injury
Authors: Kim Hye Rin , Kim Mi Na , Kim Eun Gyul , Leem Ji Su , Baek Seung Min , Lee Yu Jin , Kim Kyung Won , Kang Min-Jong , Song Tae Won , Sohn Myung Hyun
Published: March 2023

Hyperoxia is frequently used for treating acute respiratory failure, but it can cause acute lung injury. Nucleotide-binding domain and leucine-rich-repeat-containing family member X1 (NLRX1) is localized in mitochondria and involved in production of reactive oxygen species, inflammation, and apoptosis, which are the features of hyperoxic acute lung injury (HALI). The contribution of NLRX1 to HALI has not previously been addressed. Thus, to investigate the role of NLRX1 in hyperoxia, we generated a murine model of HALI in wild-type (WT) and NLRX1−/− mice by exposure to > 95% oxygen for 72 h. As a result, NLRX1 expression was elevated in mice exposed to hyperoxia. In acute lung injury, levels of inflammatory cells, protein leakage, cell cytotoxicity, and pro-inflammatory cytokines were diminished in NLRX1−/− mice compared to WT mice. In a survival test, NLRX1−/− mice showed reduced mortality under hyperoxic conditions, and apoptotic cell death and caspase expression and activity were also lower in NLRX1−/− mice. Furthermore, levels of the MAPK signaling proteins ERK 1/2, JNK, and p38 were decreased in NLRX1-deficient mice than in WT mice exposed to hyperoxia. The study shows that a genetic deficit in NLRX1 can suppress hyperoxia-induced apoptosis, suggesting that NLRX1 acts as a pivotal regulator of HALI.
Individual personality predicts social network assemblages in a colonial bird
Authors: McCully Fionnuala R. , Rose Paul E.
Published: March 2023

Animal personalities manifest as consistent individual differences in the performance of specific behavioural expressions. Personality research has implications for zoo animal welfare, as it can further our understanding of how captive individuals may differ in their resource use and provide insight into improving individual and group social health. For group living species, personality may enable assortment based on similar behaviour and influence an individual’s interactions with conspecifics (e.g. social support). This research aimed to document how personality traits (aggressive, exploratory, submissive) influenced the social network structure of highly social animals in a captive environment. Data were collected from separate flocks of captive Caribbean (Phoenicopterus ruber) and Chilean flamingos (Phoenicopterus chilensis) to identify relationships between birds and examine opportunities for social support. The flocks associated non-randomly, and in both cases, personality was a substantial predictor of network structure. Personality also predicted key elements of Caribbean flamingo social role (degree, betweenness and average association strength) conflict outcome, and propensity to provide social support, however these patterns were not replicated within the Chilean flamingo network. While both species appear to assort by personality, the broader relationship between personality and social role may vary depending on species and context.
Financial constraint and perceptions of COVID-19
Authors: Trueblood Jennifer S. , Sussman Abigail B. , O’Leary Daniel , Holmes William R.
Published: March 2023

In early March 2020, two crises emerged: the COVID-19 public health crisis and a corresponding economic crisis resulting from business closures and skyrocketing job losses. While the link between socioeconomic status and infectious disease is well-documented, the psychological relationships among economic considerations, such as financial constraint and economic anxiety, and health considerations, such as perceptions of disease spread and preventative actions, is not well understood. Despite past research illustrating the strong link between financial fragility and a wide range of behaviors, surprisingly little research has examined the psychological relationship between the economic crisis and beliefs and behaviors related to the co-occurring health crisis. We show that financial constraint predicts people’s beliefs about both their personal risk of infection and the national spread of the virus as well as their social distancing behavior. In addition, we compare the predictive utility of financial constraint to two other commonly studied factors: political partisanship and local disease severity. We also show that negative affect partially mediates the relationship between financial constraint and COVID-19 beliefs and social distancing behaviors. These results suggest the economic crisis created by COVID-19 spilled over into people’s beliefs about the health crisis and their behaviors.
Fecal contamination of urban parks by domestic dogs and tragedy of the commons
Authors: Mori Kensuke , Rock Melanie , McCormack Gavin , Liccioli Stefano , Giunchi Dimitri , Marceau Danielle , Stefanakis Emmanuel , Massolo Alessandro
Published: March 2023

Contamination of public parks by dogs is a potential source of conflict among park users, causing “tragedy of the commons” problems. Besides the social conflict, feces can pose serious health risks to both dogs and humans. In this study we analyzed the extent and patterns of the distribution of dog feces in the urban parks of the City of Calgary. We collected dog feces from randomly selected locations in the urban parks. The average density of dog feces by the different dog leash policies of the parks and the distribution pattern of the fecal density within the parks were assessed, and the total contamination of the public parks for the entire city was estimated. We found off-leash parks to be significantly more contaminated than other types of parks. We estimated 127.23 g/ha of dog feces are left unpicked in city parks in total every week. Dog feces were found more often and in greater amount in off-leash parks, and near park entrances and parking lots, than in on-leash parks and away from the park entrances. These results suggest that public park visitors, especially those visiting off-leash parks, are likely to be exposed to large amounts of dog feces. Designation of parks as on-leash and educating dog-owners may be an effective approach for reducing the fecal contamination.
Association between genetic variants in TREM1, CXCL10, IL4, CXCL8 and TLR7 genes with the occurrence of congenital Zika syndrome and severe microcephaly
Authors: Santos Camilla Natália Oliveira , Magalhães Lucas Sousa , Fonseca Adriana Barbosa de Lima , Bispo Ana Jovina Barreto , Porto Roseane Lima Santos , Alves Juliana Cardoso , dos Santos Cliomar Alves , de Carvalho Jaira Vanessa , da Silva Angela Maria , Teixeira Mauro Martins , de Almeida Roque Pacheco , dos Santos Priscila Lima , de Jesus Amélia Ribeiro
Published: March 2023

Congenital Zika syndrome (CZS) is a cluster of malformations induced by Zika virus (ZIKV) infection and the underline mechanisms involved in its occurrence are yet not fully understood. Along with epidemiological and environmental factors, the genetic host factors are suggested as important to the CZS occurrence and development, however, few studies have evaluated this. This study enrolled a total of 245 individuals in a case–control association study compound a cohort of high specific interest constituted by 75 mothers who had delivered CZS infants, their 76 infants, and 47 mothers that had delivered healthy infants, and their 47 infants. Sixteen single-nucleotide polymorphisms on TREM1, CXCL10, IL4, CXCL8, TLR3, TLR7, IFNR1, CXCR1, IL10, CCR2 and CCR5 genes were genotyped to investigate their association as risk factors to CZS. The results show an association between C allele at TREM1 rs2234246 and C allele at IL4 rs224325 in mothers infected with ZIKV during pregnancy, with the increased susceptibility to CZS occurrence in their infants and the SNP CXCL8 rs4073 and the G allele at CXCL10 rs4508917 with presence of CZS microcephaly in the infants. Furthermore, the T allele at CXCL8 rs4073 and TRL7 rs179008 SNPs were associated with the severity of microcephaly in children with CZS. These results suggest that these polymorphisms in genes of innate immune responses addressed here are associated to increased risk of occurrence and severity of CZS in pregnant mothers infected with ZIKV and their CZS infants.
Comparative dosimetric analysis of volumetric modulated arc therapy based craniospinal irradiation plans between Halcyon ring gantry and TrueBeam C-arm linear accelerator
Authors: Sarkar Biplab , Biswal Subhra Snigdha , Shahid Tanweer , Ghosh Tanmoy , Bhattacharya Jibak , De Arundhati , Mukherjee Mukti , Ganesh Tharmarnadar , Cozzi Luca
Published: March 2023

This study evaluates the volumetric modulated arc therapy (VMAT) dosimetric comparison between Halcyon ring gantry and TrueBeam c-arm linear accelerators for craniospinal irradiation (CSI) of the neuro-axis. 25 patients, who received treatment for medulloblastoma and primitive neuro-ectodermal tumors between 2018 and 2021, were planned for VMAT in True Beam (TB), and Halcyon (HAL) linear accelerators using 6 MV unflattened (FFF) photon beams (HALFFF and TBFFF). Dose-volume statistics for the target and organs at risk (OARs) and the total number of monitoring units (MUs) in the treatment plans were compared which included dose received by 95% PTV volume (V95%), volume receiving ≥ 107% dose, homogeneity index (HI), conformity index (PI), MU and dose spillage (D10%, D30%, D50%, D70%, D90%). In all 26 OARs were considered of which five were serial and the remaining were parallel structures. For the former, the dose received by 0.2 cm3, volume = D0.2 cm3) were evaluated and for the latter mean dose were evaluated. Both arms were statistically compared with paired sample t-test with a significant value of ≤ 0.05. 11 patients received treatment with the Halcyon and the rest 14 in the TrueBeam C-arm linear accelerator. Patients in the low- and intermediate-risk category (n = 13) received 23.4 Gy in 13 fractions. The remaining patients were in the high-risk category and received 35 Gy in 21 fractions or 36 Gy in 20 fractions. For HALFFF and TBFFF, PTVV95% were 97.5 ± 0.8% and 97.4 ± 0.9% respectively (p = 0.371) while the V107% were 0.6 ± 0.4% and 0.5 ± 0.5 respectively (p = 0.504). However, the number of monitoring units showed statistical significance (p < 0.001) with values of 1331.9 ± 243.4 MU and 1089 ± 206.7 MU respectively for the HAL and TB plans. The differences in spillage dose were also statistically significant, favouring HAL plans at D30% (p = 0.002), D50% (p < 0.001), D70% (p = 0.039), and D90% (p = 0.01) level except for D10% (p = 0.090). Conformity index also showed statistical significance with PI_HAL = 0.9 ± 0.02 and PI_TB = 0.89 ± 0.03 (p = 0.029). For 10 of the 21 parallel structures, the mean dose differences were statistically significant in favouring of HAL plans. Halcyon based VMAT CSI plans are dosimetrically superior in terms of organ dose, especially for the large organs, and offer lower spillage doses than the TrueBeam plans. Plans generated by both linear accelerators are suitable for the patients’ treatments.
Subset of the periodontal ligament expressed leptin receptor contributes to part of hard tissue-forming cells
Authors: Oka Hirotsugu , Ito Shinichirou , Kawakami Mana , Sasaki Hodaka , Abe Shinichi , Matsunaga Satoru , Morita Sumiharu , Noguchi Taku , Kasahara Norio , Tokuyama Akihide , Kasahara Masataka , Katakura Akira , Yajima Yasutomo , Mizoguchi Toshihide
Published: March 2023

The lineage of periodontal ligament (PDL) stem cells contributes to alveolar bone (AB) and cementum formation, which are essential for tooth-jawbone attachment. Leptin receptor (LepR), a skeletal stem cell marker, is expressed in PDL; however, the stem cell capacity of LepR+ PDL cells remains unclear. We used a Cre/LoxP-based approach and detected LepR-cre-labeled cells in the perivascular around the root apex; their number increased with age. In the juvenile stage, LepR+ PDL cells differentiated into AB-embedded osteocytes rather than cementocytes, but their contribution to both increased with age. The frequency of LepR+ PDL cell-derived lineages in hard tissue was < 20% per total cells at 1-year-old. Similarly, LepR+ PDL cells differentiated into osteocytes following tooth extraction, but their frequency was < 9%. Additionally, both LepR+ and LepR− PDL cells demonstrated spheroid-forming capacity, which is an indicator of self-renewal. These results indicate that both LepR+ and LepR− PDL populations contributed to hard tissue formation. LepR− PDL cells increased the expression of LepR during spheroid formation, suggesting that the LepR− PDL cells may hierarchically sit upstream of LepR+ PDL cells. Collectively, the origin of hard tissue-forming cells in the PDL is heterogeneous, some of which express LepR.
Detecting red-lesions from retinal fundus images using unique morphological features
Authors: Monemian Maryam , Rabbani Hossein
Published: March 2023

One of the most important retinal diseases is Diabetic Retinopathy (DR) which can lead to serious damage to vision if remains untreated. Red-lesions are from important demonstrations of DR helping its identification in early stages. The detection and verification of them is helpful in the evaluation of disease severity and progression. In this paper, a novel image processing method is proposed for extracting red-lesions from fundus images. The method works based on finding and extracting the unique morphological features of red-lesions. After quality improvement of images, a pixel-based verification is performed in the proposed method to find the ones which provide a significant intensity change in a curve-like neighborhood. In order to do so, a curve is considered around each pixel and the intensity changes around the curve boundary are considered. The pixels for which it is possible to find such curves in at least two directions are considered as parts of red-lesions. The simplicity of computations, the high accuracy of results, and no need to post-processing operations are the important characteristics of the proposed method endorsing its good performance.
Sleep duration, hypnotic drug use, and risk factors: cross- sectional study
Authors: Jalali Nazanin , Khalili Parvin , Jamali Zahra , Jalali Zahra , Moghadam-Ahmadi Amir , Vakilian Alireza , Ayoobi Fatemeh
Published: March 2023

Both short sleep duration (SSD) and long sleep duration (LSD) are associated with an increased risk of morbidity and mortality. Here, we aimed to assess the prevalence of sleep duration disturbances among adults in association with demographic, medication use, personal habits, and chronic diseases, while also considering the impact of hypnotic drug use. We performed a cross-sectional study of 9991 adult participants of the Rafsanjan Cohort Study (RCS), as part of the Prospective epidemiological research studies in Iran (PERSIAN). Multivariate logistic regression analyses were conducted to assess the association between short (< 6 h) and long (> 9 h) sleep duration with demographic and lifestyle parameters and common non-communicable diseases. Additionally, we performed stratified analysis to investigate the association of sleep duration with the abovementioned factors and diseases, in groups with and without hypnotic drug use. We found higher odds of SSD significantly associated with age (P < 0.001), BMI (P < 0.001), physical activity (P < 0.001), and depression (P = 0.023). LSD displayed a positive association with the female sex (P < 0.001), opium consumption (P < 0.001), and history of MI (P = 0.045), and a reverse connection with education (P = 0.007), physical activity (P < 0.001) and alcohol consumption (P = 0.027). Stratifying for the hypnotic drug use, our sensitivity analyses indicated that in hypnotic drug users, education (P = 0.034) and physical activity (P < 0.001) were associated with LSD, in this group, significantly increased odds ratio of LSD were associated with opium consumption (P = 0.046) and thyroid dysfunction (P = 0.037). Our findings demonstrated the demographic and lifestyle factors and diseases associated with long and short sleep duration in the population of the RCS. Additionally, after stratifying for hypnotic drug use, our results indicated that some diseases are only associated with abnormal sleep duration upon using hypnotic drugs.
The interactions of monomeric acridines and unsymmetrical bisacridines (UAs) with DNA duplexes: an insight provided by NMR and MD studies
Authors: Laskowski Tomasz , Kosno Michał , Andrałojć Witold , Frackowiak Joanna E. , Borzyszkowska-Bukowska Julia , Szczeblewski Paweł , Radoń Nikola , Świerżewska Maria , Woźny Anna , Paluszkiewicz Ewa , Mazerska Zofia
Published: March 2023

Members of a novel class of anticancer compounds, exhibiting high antitumor activity, i.e. the unsymmetrical bisacridines (UAs), consist of two heteroaromatic ring systems. One of the ring systems is an imidazoacridinone moiety, with the skeleton identical to the structural base of Symadex. The second one is a 1-nitroacridine moiety, hence it may be regarded as Nitracrine’s structural basis. These monoacridine units are connected by an aminoalkyl linker, which vary in structure. In theory, these unsymmetrical dimers should act as double-stranded DNA (dsDNA) bis-intercalators, since the monomeric units constituting the UAs were previously reported to exhibit an intercalating mode of binding into dsDNA. On the contrary, our earlier, preliminary studies have suggested that specific and/or structurally well-defined binding of UAs into DNA duplexes might not be the case. In this contribution, we have revisited and carefully examined the dsDNA-binding properties of monoacridines C-1305, C-1311 (Symadex), C-283 (Ledakrin/Nitracrine) and C-1748, as well as bisacridines C-2028, C-2041, C-2045 and C-2053 using advanced NMR techniques, aided by molecular modelling calculations and the analysis of UV–VIS spectra, decomposed by chemometric techniques. These studies allowed us to explain, why the properties of UAs are not a simple sum of the features exhibited by the acridine monomers.