bluuebunny/crossref_metadata_2025 huggingface dataset:
Petrous internal carotid artery aneurysm rupture induced by Eustachian tube catheterisation: case report
Authors: Hyakusoku H , Tsuchiya Y , Matsushita Y , Nakayama M
Published: October 2022

Background

Petrous internal carotid artery aneurysms are very rare vascular lesions, which may present with otalgia and life-threatening massive otorrhoea.

Case report

An 84-year-old woman presented at a local otolaryngology clinic with progressive otalgia due to an acute exacerbation of chronic otitis media. She was referred with left-sided massive otorrhoea following Eustachian tube catheterisation. She suffered another massive otorrhoea with epistaxis during left-sided ear cleaning at a clinic visit. Contrast-enhanced computed tomography and computed tomography angiography revealed a left-sided aneurysm and adjacent stenosis at the left internal carotid artery. Coil embolisation of the petrous internal carotid artery aneurysm was performed with percutaneous transluminal angioplasty followed by dilatation of the stenosis.

Conclusion

Computed tomography angiography should be performed immediately when a patient reports massive otorrhoea. Endovascular occlusion is a treatment option as it avoids complications of open surgical ligation procedures.
Roe v. Wade and the Predatory State Interest in Protecting Future Cannon Fodder
Authors: Häyry Matti
Published: October 2022

The reversal of Roe v. Wade by the U.S. Supreme Court allowed the states to regulate terminations of pregnancy more autonomously than during 1973–2022. Those who think that women should be legally entitled to abortions at their own request are suggesting that annulling the reversal could be an option. This would mean continued reliance on the interpretation of privacy that Roe v. Wade stood on. The interpretation does not have the moral support that its supporters think. This can be shown by recalling the shortcomings of Judith Jarvis Thomson’s famous violinist example and its application to abortion laws. Philosophically better reasons for not restricting access to abortion can be found in a simple principle of fairness and in sensible theories on the value of human life. Whether or not philosophy has any use in the debate is another matter. Legal decisions to regulate terminations are probably based on pronatalist state interests, shared by the apparently disagreeing parties and immune to rational argumentation.
20 years of experience with the Fontan procedure: characteristics and clinical outcomes of children in a tertiary referral hospital
Authors: Gutiérrez-Gil Jaiber A. , Torres-Canchala Laura A. , Castro-Viáfara Leidy D. , Uribe-Mora Manuela , Vélez-Moreno Juan F. , Mejía-Quiñones Valentina , Mosquera-Álvarez Walter
Published: October 2022

Introduction:

Without participating in a contractile chamber, the Fontan procedure seeks to create a separation of oxygenated and deoxygenated blood in patients with univentricular heart, reducing the risks of long-term hypoxemia and improving their survival. This study describes the clinical outcomes of children undergoing the Fontan procedure between 2000 and 2020 in a tertiary referral hospital care centre in southwestern Colombia.

Materials and methods:

A retrospective observational descriptive study. The 81 patients who underwent the Fontan procedure were included. Categorical variables were presented with percentages and continuous variables with measures of central tendency according to the distribution of the data evaluated through the Shapiro–Wilk test. Sociodemographic, clinical, surgical variables, complications, and mortality were described.

Results:

Between 2000 and 2020, 81 patients underwent the Fontan procedure: 43 (53.1%) males and a median age of 5.3 years (interquartile range 4.3–6.6). The most common diagnosis was tricuspid atresia (49.4%). The median mean pulmonary arterial pressure was 12 mmHg (interquartile range 10–15), the Nakata index 272 mm2/m2 (interquartile range 204–327), and the McGoon index (interquartile range 1.86–2.3). Seventy-two (88.9%) patients underwent extracardiac Fontan and 44 (54.3%) patients underwent fenestration. The median hospitalisation days were 19 days. The main complication was coagulopathy (19.8%), mortality in the first month between 2000 and 2010 was 8.6%, and after 2010 was 1.2%.

Conclusion:

The Fontan procedure is a palliative surgery for children with complex heart disease. According to anatomical and physiological variables, the proper choice of patients determines the short- and long-term results.
Gender Identification and Survey Weighting: A Shifting Landscape
Authors: Urlacher Brian R.
Published: October 2022

In October 2021, the US Census Bureau piloted a new set of questions to operationalize sex and gender identity. This move follows a larger trend across the social sciences to rethink how surveys ask about sex and gender. Although this step is normatively positive, it complicates well-established protocols for weighting survey data. This article explores the likely pitfalls for survey researchers that accompany a shift in how the US Census Bureau measures gender. A preliminary empirical investigation of survey weighting indicates that using more inclusive gender categories will not negatively affect weighting metrics. Whereas the creation of a new set of US or even global best practices in measuring gender may be helpful to survey researchers, at this stage, there remain important empirical and ethical questions that are not well understood.
The Ultrastructure of Skeletal Muscle Capillaries of Streptozotocin Diabetic Rats and the Therapeutic Effect of Benfluorex
Authors: Gül Nursel , Cebesoy Suna , Özsoy Nesrin , Eskizengin Hakan , Özer Çiğdem
Published: October 2022

Diabetes mellitus is a serious disease worldwide and causes other associated diseases. In this study, we observed the effect of streptozotocin (STZ)-induced diabetes and benfluorex treatment on muscular capillary ultrastructure. Adult male rats were used as the test subjects and each individual was intraperitoneally injected with one dose of STZ (45 mg/kg) to induce diabetes. Doses (50 mg/kg) of benfluorex were given to the subjects with tap water by intragastric gavage application once daily for 21 days. At the end of day 21, muscle tissues were obtained from animals and examined under transmission electron microscopy. From the data obtained with the electron microscope, it was observed that the control group had typical continuous capillary vascular structures in their muscles, while STZ caused disruptive disorder of the muscle cells in the capillary wall of the STZ-diabetic group. Additionally, the thickening of the basement membrane around endothelial cells, loss of mitochondrial crista in the muscle cells, enlarged endothelial cells, and narrowed vessel lumen were observed in the muscle tissue. The findings of our study revealed that STZ-induced diabetes disrupted the vascular structure, while benfluorex partially improved it.
The Role of Judicial Craft in Improving Democracy’s Resilience: The Case of Party Bans in Czechia, Hungary and Slovakia
Authors: Steuer Max
Published: October 2022

The unsuccessful petition to ban Slovakia’s extreme right parliamentary party – the value of focusing on judicial craft for studies of militant democracy and courts – statutory frameworks as intervening variables and their overview in Czechia, Hungary and Slovakia – key components of judicial craft endogenous to courts: consistency, legal reasoning skills, problem-solving abilities, creativity – the cases of Workers’ Party (Czechia), Slovak Togetherness–National Party (Slovakia), People’s Party Our Slovakia (Slovakia) and Hungarian Guard (Hungary) – the decisions of the Czech Supreme Administrative Court (2009) and the Slovak Supreme Court (2019) – re-evaluating what counts as ‘success’ with party bans: judicial craft affects the effectiveness of the statutory framework for party bans – a court-centric perspective on militant democracy when courts face illiberal assaults
Rupture Nucleation on a Periodically Heterogeneous Interface
Authors: Gounon A. , Latour S. , Letort J. , El Arem S.
Published: October 2022

In this study we explore experimentally the effects of fault heterogeneity on the rupture nucleation. We conducted friction experiments between two polycarbonate plates, with a periodically heterogeneous friction interface. The rupture propagation is monitored with an ultra‐fast video camera by taking advantage of the photo‐elastic properties of the material used. We show that the nucleation process does not always consists of a monotonic growth of the rupture velocity. Instead, the rupture front advances with an alternation of slow and fast episodes that accelerates until it reaches a point at which fast propagation dominates. This complex nucleation process is compared to the results predicted by previous numerical studies on heterogeneous interfaces. Finally, we test whether it is possible to describe this complex nucleation process as a homogenized nucleation. We also point out a large variability in the rupture process due to the uncontrolled stress heterogeneity that occurs during the loading process.
Radon Dynamics and Effective Dose Estimation in a Touristic Volcanic Cave: La Cueva del Viento, Tenerife (Canary Islands, Spain)
Authors: Salazar‐Carballo Pedro A. , López‐Pérez María , Martín‐González María Esther , Hernández‐Suarez Francisco , Martín‐Luis M. Candelaria
Published: October 2022

La Cueva del Viento is a volcanic lava tube located in Tenerife Island (Canary Islands, Spain). Its touristic section, 180 m long, receives more than 28,200 visitants each year. According to the European and Spanish legislation, a radon monitoring program is required to minimize the radon exposition of workers, tourists, and cavers. In this work, we studied the radon concentration dynamics in the touristic section of the cave for ca. 1 year, using both passive and active radon detectors. Pluviometry and external air temperature played an important role in the seasonal and daily variations of indoor radon concentrations. Daily fluctuations during the dry season were analyzed using time series (Box‐Jenkins methodology) and frequency analysis (Fourier and Wavelet transforms) methods. The experimental radon time‐series was well‐fitted using a seasonal autoregressive integrated moving average model: Seasonal Auto‐Regressive Integrated Moving Average (2,0,1) (2,1,0)24, and its value, in a short‐time window (ca. 1 week) was conveniently forecasted. Finally, this work revealed that the annual effective doses received, during the observation period (1 year), by the touristic guides and visitors was ca. 2 mSv/yr and 4 μSv/hr, respectively. We concluded that the touristic exploitation of La Cueva del Viento is safe for both tourists and guides. However, based on our results, La Cueva del Viento had to be classified as a “Monitoring zone” and a regular monitoring program should be implemented.
Modeling Snow Dynamics and Stable Water Isotopes Across Mountain Landscapes
Authors: Carroll Rosemary W. H. , Deems Jeffrey , Sprenger Matthias , Maxwell Reed , Brown Wendy , Newman Alexander , Beutler Curtis , Williams Kenneth H.
Published: October 2022

A coupled hydrologic and snowpack stable water isotope model assesses controls on isotopic inputs across a mountainous basin. Annually, the most depleted isotope conditions occur in the upper subalpine where snow accumulation is high, and rainfall is low. Snowmelt isotopic evolution over time indicates fractionation processes account for <25% snowmelt enrichment. Meltwater isotopic inputs are largely determined by controls on the amount, phase and isotopic mass of precipitation coincident with the ablation period. Effect of vapor loss from the snowpack on d‐excess in snowmelt is a balance between energy and snow‐availability. It is highest above treeline, and in the grass and aspen‐dominated portions of the upper montane where vegetation shading is low. Deep snowpack in conifer forests limit the influence of vapor loss in the subalpine. Wet years reduce the effects of vapor loss on snowmelt across the basin, except in the lower montane where added snowfall bolsters snow‐limited conditions.
Acoustics Reveals Short‐Term Air Temperature Fluctuations Near Mars' Surface
Authors: Chide Baptiste , Bertrand Tanguy , Lorenz Ralph D. , Munguira Asier , Hueso Ricardo , Sánchez‐Lavega Agustin , Martinez German , Spiga Aymeric , Jacob Xavier , de la Torre Juarez Manuel , Lemmon Mark T. , Banfield Don , Newman Claire E. , Murdoch Naomi , Stott Alexander , Viúdez‐Moreiras Daniel , Pla‐Garcia Jorge , Larmat Carène , Lanza Nina L. , Rodríguez‐Manfredi José Antonio , Wiens Roger C.
Published: October 2022

Acoustics is new on Mars: it allows the characterization of turbulence at smaller scales than previously possible within the lowest part of the Planetary Boundary Layer. Sound speed measurements, by the SuperCam instrument and its microphone onboard the NASA Perseverance rover, allow the retrieval of atmospheric temperatures at 0.77 m above the ground, at 3 Hz, with a ∼10 ms response time that is 20–100 times shorter than for typical thermocouple sensors used on Mars. Here we report on the first measurements of the sound speed‐derived temperature and its fluctuations near the surface. Data highlight large and rapid fluctuations up to ±7 K/s, whose amplitude over such a timescale has never been reported, nor predicted by atmospheric models. These fluctuations follow the daytime pattern of the turbulence and highlight occasional high amplitude events that are likely due to the conjunction of low thermal inertia and strong winds.
Signature of the Contemporary Southwestern North American Megadrought in Mesopause Region Wave Activity
Authors: Gardner Chester S. , She Chiao‐Yao
Published: October 2022

The Southwestern North American megadrought began in 2000 and is now believed to be the driest 22‐year period in the region since 800 CE. The precipitation deficit during the megadrought (8.3% during 2000–2021) has been accompanied by a significant decrease in gravity waves observed in the upper atmosphere. Prior to the drought (1990–2000), the mean wave‐driven temperature fluctuation variances, between 85 and 100 km at Albuquerque and Ft. Collins, were comparable (62.2 ± 5.3 K2 and 60.5 ± 1.8 K2, respectively), with the largest variances occurring during winter and summer storm seasons. During the first decade of the drought (2001–2010), wave activity above Ft. Collins decreased by 28 ± 3%, mostly above 94 km, and changed from primarily semiannual to primarily annual variations. These changes may be related to reduced wave generation by tropospheric storms during the megadrought and to an altered geographic distribution of precipitation events in the western and mid‐western United States.
Blowing Hot and Cold: Glacier Microclimate can Help Understand Impacts of Climate Change on Forests Communities
Authors: Stoffel M.
Published: October 2022

Mountain regions cover roughly one‐fourth of the Earth's surface, store most snow and ice outside polar regions and are hotspots of species richness. Regrettably, they are also viewed as climate hotspots where change can anticipate/amplify what is occurring elsewhere on Earth. Current rates of warming are expected to double within decades, thereby becoming an order of magnitude faster than what most ecosystems have experienced over millennia. By monitoring contemporary microclimatic conditions around La Perouse Glacier (Alaska) and reconstructing locations of past ice margins, Gaglioti et al. (2022, https://doi.org/10.1029/2022GL098574) quantify local climate change over the last two centuries. Rates of cooling and warming at their site are beyond expectations, and outside human experience. Their “natural laboratory” experiment provides key insights into likely impacts of future climate change on tree vitality and growth and therefore is a stepping stone for the assessment of how trees have responded (and will likely respond) to fast‐paced warming.
Stochastic Downscaling of Hourly Precipitation Series From Climate Change Projections
Authors: Yu Ziwen , Montalto Franco , Jacobson Stefan , Lall Upmanu , Bader Daniel , Horton Radley
Published: October 2022

Stochastic precipitation generators (SPGs) are often used to produce synthetic precipitation series for water resource management. Typically, an SPG assumes a stationary climate. We present an hourly precipitation generation algorithm for nonstationary conditions informed by the global climate model (GCM) forecasted average monthly temperature (AMT). The physical basis for precipitation formation is considered explicitly in the design of the algorithm using hourly pressure change events (PCE) to define the relationship between hourly precipitation and AMT. The algorithm consists of a multivariable Markov Chain and a moving window driven by time, temperature, and pressure change. We demonstrate the methodology by generating a 100‐year, continuous, synthetic hourly precipitation time series using GCM AMT projections for the Northeast United States. When compared with historical observations, the synthetic results suggest that future precipitation in this region will be more variable, with more frequent mild events and fewer but intensified extremes, especially in warm seasons. The synthetic time series suggests that there will be less precipitation in the summers, while winters will be wetter, consistent with other research on climate change projections for the Northeast United States. This SPG provides physically plausible weather ensembles for water resource studies involving climate change.
DNA damage response revisited: the p53 family and its regulators provide endless cancer therapy opportunities
Authors: Abuetabh Yasser , Wu H. Helena , Chai Chengsen , Al Yousef Habib , Persad Sujata , Sergi Consolato M. , Leng Roger
Published: October 2022

Antitumor therapeutic strategies that fundamentally rely on the induction of DNA damage to eradicate and inhibit the growth of cancer cells are integral approaches to cancer therapy. Although DNA-damaging therapies advance the battle with cancer, resistance, and recurrence following treatment are common. Thus, searching for vulnerabilities that facilitate the action of DNA-damaging agents by sensitizing cancer cells is an active research area. Therefore, it is crucial to decipher the detailed molecular events involved in DNA damage responses (DDRs) to DNA-damaging agents in cancer. The tumor suppressor p53 is active at the hub of the DDR. Researchers have identified an increasing number of genes regulated by p53 transcriptional functions that have been shown to be critical direct or indirect mediators of cell fate, cell cycle regulation, and DNA repair. Posttranslational modifications (PTMs) primarily orchestrate and direct the activity of p53 in response to DNA damage. Many molecules mediating PTMs on p53 have been identified. The anticancer potential realized by targeting these molecules has been shown through experiments and clinical trials to sensitize cancer cells to DNA-damaging agents. This review briefly acknowledges the complexity of DDR pathways/networks. We specifically focus on p53 regulators, protein kinases, and E3/E4 ubiquitin ligases and their anticancer potential.
Suppression of obesity by melatonin through increasing energy expenditure and accelerating lipolysis in mice fed a high-fat diet
Authors: Xu Liang , Li Dandan , Li Haoran , Zhang Ouyang , Huang Yaxin , Shao Hengrong , Wang Yajiao , Cai Suili , Zhu Yuqin , Jin Shengnan , Ding Chunming
Published: October 2022

Backgrounds/objectives

Melatonin promotes brown adipose tissue (BAT) activity, leading to body mass reduction and energy expenditure. However, the mechanisms governing these beneficial effects are not well-established. This study aimed to assess the effects of (1) melatonin on BAT and energy metabolism, and (2) fibroblast growth factor 21 (FGF21) in BAT-mediated thermogenesis.

Methods

Male C57BL/6 J mice received a high-fat diet (HFD) or normal chow, accompanied by intraperitoneal injection of 20 mg/kg melatonin for 12 weeks. FGF21−/−mice consumed an HFD with or without melatonin for 8 weeks.

Results

Melatonin attenuated weight gain, insulin resistance, adipocyte hypertrophy, inflammation, and hepatic steatosis induced by the HFD and increased energy expenditure. Furthermore, melatonin improved cold tolerance by increasing BAT uncoupling protein 1 (UCP1) expression and producing heat. Notably, melatonin resulted in a shift in energy metabolism favouring the utilization of fat, and it increased FGF21 in circulating and metabolic tissues and skeletal muscle phosphorylation of AMP-activated protein kinase. However, melatonin did not protect against obesity, insulin resistance, and energy expenditure in HFD-fed FGF21−/−mice.

Conclusions

Melatonin suppressed obesity and insulin resistance resulting from the HFD by enhancing BAT activity and energy expenditure, and these effects were dependent on FGF21.
Serotonin and dopamine transporter availability in social anxiety disorder after combined treatment with escitalopram and cognitive-behavioral therapy
Authors: Hjorth Olof , Frick Andreas , Gingnell Malin , Engman Jonas , Björkstrand Johannes , Faria Vanda , Alaie Iman , Carlbring Per , Andersson Gerhard , Jonasson My , Lubberink Mark , Antoni Gunnar , Reis Margareta , Wahlstedt Kurt , Fredrikson Mats , Furmark Tomas
Published: October 2022

Selective serotonin reuptake inhibitors (SSRIs) and internet-based cognitive behavioral therapy (ICBT) are recommended treatments of social anxiety disorder (SAD), and often combined, but their effects on monoaminergic signaling are not well understood. In this multi-tracer positron emission tomography (PET) study, 24 patients with SAD were randomized to treatment with escitalopram+ICBT or placebo+ICBT under double-blind conditions. Before and after 9 weeks of treatment, patients were examined with positron emission tomography and the radioligands [11C]DASB and [11C]PE2I, probing the serotonin (SERT) and dopamine (DAT) transporter proteins respectively. Both treatment combinations resulted in significant improvement as measured by the Liebowitz Social Anxiety Scale (LSAS). At baseline, SERT-DAT co-expression was high and, in the putamen and thalamus, co-expression showed positive associations with symptom severity. SERT-DAT co-expression was also predictive of treatment success, but predictor-outcome associations differed in direction between the treatments. After treatment, average SERT occupancy in the SSRI + ICBT group was >80%, with positive associations between symptom improvement and occupancy in the nucleus accumbens, putamen and anterior cingulate cortex. Following placebo+ICBT, SERT binding increased in the raphe nuclei. DAT binding increased in both groups in limbic and striatal areas, but relations with symptom improvement differed, being negative for SSRI + ICBT and positive for placebo + ICBT. Thus, serotonin-dopamine transporter co-expression exerts influence on symptom severity and remission rate in the treatment of social anxiety disorder. However, the monoamine transporters are modulated in dissimilar ways when cognitive-behavioral treatment is given concomitantly with either SSRI-medication or pill placebo.
Combating the SARS-CoV-2 Omicron (BA.1) and BA.2 with potent bispecific antibodies engineered from non-Omicron neutralizing antibodies
Authors: Wang Yingdan , Zhang Xiang , Ma Yunping , Wang Yanqun , Zhan Wuqiang , Zheng Qinwen , Zhang Meng , Ji Ping , Liu Mei , Liu Qianying , Sun Tingting , Zhu Tongyu , Wen Yumei , Sun Lei , Zhao Jincun , Wu Fan , Chen Zhenguo , Huang Jinghe
Published: October 2022

The highly mutated and transmissible Omicron (BA.1) and its more contagious lineage BA.2 have provoked serious concerns over their decreased sensitivity to the current COVID-19 vaccines and evasion from most anti-SARS-CoV-2 neutralizing antibodies (NAbs). In this study, we explored the possibility of combating the Omicron and BA.2 by constructing bispecific antibodies based on non-Omicron NAbs. We engineered 10 IgG-like bispecific antibodies with non-Omicron NAbs named GW01, 16L9, 4L12, and REGN10987 by fusing the single-chain variable fragments (scFvs) of two antibodies through a linker and then connecting them to the Fc region of IgG1. Surprisingly, 8 out of 10 bispecific antibodies showed high binding affinities to the Omicron receptor-binding domain (RBD) and exhibited extreme breadth and potency against pseudotyped SARS-CoV-2 variants of concern (VOCs) including Omicron and BA.2, with geometric mean of 50% inhibitory concentration (GM IC50) values ranging from 4.5 ng/mL to 103.94 ng/mL, as well as the authentic BA.1.1. Six bispecific antibodies containing the cross-NAb GW01 not only neutralized Omicron and BA.2, but also neutralized the sarbecoviruses including SARS-CoV and SARS-related coronaviruses (SARSr-CoVs) RS3367 and WIV1, with GM IC50 ranging from 11.6 ng/mL to 103.9 ng/mL. Mapping analyses of 42 spike (S) variant single mutants of Omicron and BA.2 elucidated that these bispecific antibodies accommodated the S371L/F mutations, which were resistant to most of the non-Omicron NAbs. A cryo-electron microscopy (cryo-EM) structure study of the representative bispecific antibody GW01-16L9 (FD01) in its native full-length IgG form in complex with the Omicron S trimer revealed 5 distinct trimers and one novel trimer dimer conformation. 16L9 scFv binds the receptor-binding motif (RBM), while GW01 scFv binds a epitope outside the RBM. Two scFvs of the bispecific antibody synergistically induced the RBD-down conformation into 3 RBD-up conformation, improved the affinity between IgG and the Omicron RBD, induced the formation of trimer dimer, and inhibited RBD binding to ACE2. The trimer dimer conformation might induce the aggregation of virions and contribute to the neutralization ability of FD01. These novel bispecific antibodies are strong candidates for the treatment and prevention of infection with the Omicron, BA.2, VOCs, and other sarbecoviruses. Engineering bispecific antibodies based on non-Omicron NAbs could turn the majority of NAbs into a powerful arsenal to aid the battle against the pandemic.
Single-cell epigenome analysis reveals age-associated decay of heterochromatin domains in excitatory neurons in the mouse brain
Authors: Zhang Yanxiao , Amaral Maria Luisa , Zhu Chenxu , Grieco Steven Francis , Hou Xiaomeng , Lin Lin , Buchanan Justin , Tong Liqi , Preissl Sebastian , Xu Xiangmin , Ren Bing
Published: October 2022

Loss of heterochromatin has been implicated as a cause of pre-mature aging and age-associated decline in organ functions in mammals; however, the specific cell types and gene loci affected by this type of epigenetic change have remained unclear. To address this knowledge gap, we probed chromatin accessibility at single-cell resolution in the brains, hearts, skeletal muscles, and bone marrows from young, middle-aged, and old mice, and assessed age-associated changes at 353,126 candidatecis-regulatory elements (cCREs) across 32 major cell types. Unexpectedly, we detected increased chromatin accessibility within specific heterochromatin domains in old mouse excitatory neurons. The gain of chromatin accessibility at these genomic loci was accompanied by the cell-type-specific loss of heterochromatin and activation of LINE1 elements. Immunostaining further confirmed the loss of the heterochromatin mark H3K9me3 in the excitatory neurons but not in inhibitory neurons or glial cells. Our results reveal the cell-type-specific changes in chromatin landscapes in old mice and shed light on the scope of heterochromatin loss in mammalian aging.
TumorMet: A repository of tumor metabolic networks derived from context-specific Genome-Scale Metabolic Models
Authors: Granata Ilaria , Manipur Ichcha , Giordano Maurizio , Maddalena Lucia , Guarracino Mario Rosario
Published: October 2022

Studies about the metabolic alterations during tumorigenesis have increased our knowledge of the underlying mechanisms and consequences, which are important for diagnostic and therapeutic investigations. In this scenario and in the era of systems biology, metabolic networks have become a powerful tool to unravel the complexity of the cancer metabolic machinery and the heterogeneity of this disease. Here, we present TumorMet, a repository of tumor metabolic networks extracted from context-specific Genome-Scale Metabolic Models, as a benchmark for graph machine learning algorithms and network analyses. This repository has an extended scope for use in graph classification, clustering, community detection, and graph embedding studies. Along with the data, we developed and provided Met2Graph, an R package for creating three different types of metabolic graphs, depending on the desired nodes and edges: Metabolites-, Enzymes-, and Reactions-based graphs. This package allows the easy generation of datasets for downstream analysis.
A multi-omics longitudinal study of the murine retinal response to chronic low-dose irradiation and simulated microgravity
Authors: Kothiyal Prachi , Eley Greg , Ilangovan Hari , Hoadley Katherine A. , Elgart S. Robin , Mao Xiao W. , Eslami Parastou
Published: October 2022

The space environment includes unique hazards like radiation and microgravity which can adversely affect biological systems. We assessed a multi-omics NASA GeneLab dataset where mice were hindlimb unloaded and/or gamma irradiated for 21 days followed by retinal analysis at 7 days, 1 month or 4 months post-exposure. We compared time-matched epigenomic and transcriptomic retinal profiles resulting in a total of 4178 differentially methylated loci or regions, and 457 differentially expressed genes. Highest correlation in methylation difference was seen across different conditions at the same time point. Nucleotide metabolism biological processes were enriched in all groups with activation at 1 month and suppression at 7 days and 4 months. Genes and processes related to Notch and Wnt signaling showed alterations 4 months post-exposure. A total of 23 genes showed significant changes in methylation and expression compared to unexposed controls, including genes involved in retinal function and inflammatory response. This multi-omics analysis interrogates the epigenomic and transcriptomic impacts of radiation and hindlimb unloading on the retina in isolation and in combination and highlights important molecular mechanisms at different post-exposure stages.
Experimental considerations of acute heat stress assays to quantify coral thermal tolerance
Authors: Nielsen J. J. V. , Matthews G. , Frith K. R. , Harrison H. B. , Marzonie M. R. , Slaughter K. L. , Suggett D. J. , Bay L. K.
Published: October 2022

Understanding the distribution and abundance of heat tolerant corals across seascapes is imperative for predicting responses to climate change and to support novel management actions. Thermal tolerance is variable in corals and intrinsic and extrinsic drivers of tolerance are not well understood. Traditional experimental evaluations of coral heat and bleaching tolerance typically involve ramp-and-hold experiments run across days to weeks within aquarium facilities with limits to colony replication. Field-based acute heat stress assays have emerged as an alternative experimental approach to rapidly quantify heat tolerance in many samples yet the role of key methodological considerations on the stress response measured remains unresolved. Here, we quantify the effects of coral fragment size, sampling time point, and physiological measures on the acute heat stress response in adult corals. The effect of fragment size differed between species (Acropora tenuis and Pocillopora damicornis). Most physiological parameters measured here declined over time (tissue colour, chlorophyll-a and protein content) from the onset of heating, with the exception of maximum photosynthetic efficiency (Fv/Fm) which was surprisingly stable over this time scale. Based on our experiments, we identified photosynthetic efficiency, tissue colour change, and host-specific assays such as catalase activity as key physiological measures for rapid quantification of thermal tolerance. We recommend that future applications of acute heat stress assays include larger fragments (> 9 cm2) where possible and sample between 10 and 24 h after the end of heat stress. A validated high-throughput experimental approach combined with cost-effective genomic and physiological measurements underpins the development of markers and maps of heat tolerance across seascapes and ocean warming scenarios.
Partially coherent conical refraction promises new counter-intuitive phenomena
Authors: Mylnikov V. Yu. , Dudelev V. V. , Rafailov E. U. , Sokolovskii G. S.
Published: October 2022

In this paper, we extend the paraxial conical refraction model to the case of the partially coherent light using the unified optical coherence theory. We demonstrate the decomposition of conical refraction correlation functions into well-known conical refraction coherent modes for a Gaussian Schell-model source. Assuming randomness of the electrical field phase of the input beam, we reformulated and significantly simplified the rigorous conical refraction theory. This approach allows us to consider the propagation of light through a conical refraction crystal in exactly the same way as in the classical case of coherent radiation. Having this in hand, we derive analytically the conical refraction intensity both in the focal plane and in the far field, which allows us to explain and rigorously justify earlier experimental findings and predict new phenomena. The last include the counterintuitive effect of narrowing of the conical refraction ring width, disappearance of the dark Poggendorff’s ring in the Lloyd’s plane, and shift of Raman spots for the low-coherent conical refraction light. We also demonstrate a universal power-law dependence of conical refraction cones coherence degree on the input correlation length and diffraction-free propagation of the low-coherent conical refraction light in the far field.
Assessing the consequences of prolonged usage of disposable face masks
Authors: Buzzin Alessio , Domènech-Gil Guillem , Fraschetti Elena , Giovine Ennio , Puglisi Donatella , Caputo Domenico
Published: October 2022

Due to the SARS-CoV-2 outbreak, wearing a disposable face mask has become a worldwide daily routine, not only for medical operators or specialized personnel, but also for common people. Notwithstanding the undeniable positive effect in reducing the risk of virus transmission, it is important to understand if a prolonged usage of the same face mask can have effectiveness on filtering capability and potential health consequences. To this aim, we present three investigations. A survey, carried out in central Italy, offers an overview of the distorted public awareness of face mask usage. A functional study shows how prolonged wearing leads to substantial drops in humid air filtration efficiency. Finally, a morphological analysis reports the proliferation of fungal or bacteria colonies inside an improperly used mask. Our study highlights therefore that wearing a face mask is really beneficial only if it is used correctly.
Study on the interaction preference between CYCD subclass and CDK family members at the poplar genome level
Authors: He Chengcheng , Liang Jinghui , Wu Zhaoqun , Zhuge Xianglin , Xu Nan , Yang Hailing
Published: October 2022

Cyclin-dependent kinases (CDKs) control the progression of the cell cycle. D-type cyclin (CYCD) is generally believed to form a complex with CDK and control the G1/S transition. In plants, CYCD and CDK gene families can be divided into 6 (D1–D7) and 7 (CDKA–CDKG) subclasses, respectively. Different subclasses in the CYCD and CDK families have different numbers, structures and functions. In some heterologous woody plants, the functions of these subclass family members remain unclear. In this study, 43 CYCD and 27 CDK gene family members were identified in the allodiploid Populus tomentosa Carr. Phylogenetic analysis suggested that these CYCDs and CDKs were divided into 6 and 7 subclasses, respectively, which were the same as other species. The analysis of protein properties, gene structure, motifs, domains, cis-acting elements and tissue-specific expression of all members of these CYCDs and CDKs showed that the differences between members of different subclasses varied widely, but members of the same subclass especially in the CDK gene family were very similar. These findings also demonstrated a strong correlation between CYCD and CDK gene family members in response to hormones and specific expression. The collinear analysis of P. tomentosa, Populus trichocarpa and Arabidopsis thaliana showed that the expansion patterns of CYCD and CDK gene families were predominantly whole genome duplications (WGD). The protein interaction prediction results of different subclasses of CYCD and CDKs showed that the interaction between different subclasses of CYCD and CDKs was significantly different. Our previous study found that transgenic PtoCYCD2;1 and PtoCYCD3;3 poplars exhibited opposite phenotypes. Y2H and BIFC results showed that the interaction between PtoCYCD2;1 and PtoCYCD3;3 was significantly different with CDKs. This finding might suggest that the functional differences of different CYCD subclasses in plant growth and development were closely related to the different interactions between CYCD and CDK. Our results provide a good idea and direction for the functional study of CYCD and CDK proteins in woody plants.
M1 macrophages evoke an increase in polymeric immunoglobulin receptor (PIGR) expression in MDA-MB468 breast cancer cells through secretion of interleukin-1β
Authors: Asanprakit Wichitra , Lobo Dileep N. , Eremin Oleg , Bennett Andrew J.
Published: October 2022

High expression of polymeric immunoglobulin receptor (PIGR) in breast cancer is associated with increased 5-year survival rate. However, the factors influencing PIGR expression in breast cancer have not been elucidated. The aim of this study was to determine the role of macrophages and cytokines affecting expression of PIGR in two breast cancer cell lines. M1, M2 macrophage conditioned media (CM) and recombinant human cytokines were used to determine factors which increased PIGR expression in MCF7 (HTB-22) and MDA-MB468 (HTB-132) breast cancer cell lines. The level of PIGR expression in the cells and PIGR secretory component were evaluated by real-time quantitative polymerase chain reaction and Western blotting. M1 macrophage CM induced a dose-dependent increase in PIGR mRNA expression in MDA-MB468 cells, up to 20-fold. The level of PIGR expression in MCF7 cells was very low and not affected by M1 and M2 CM. Interferon gamma (IFN-γ) and interleukin (IL)-1β also increased PIGR expression in MDA-MB468 and MCF7 cells. However, IL-1β was demonstrated to increase in M1 macrophages, while IFN-γ was not. The role of IL-1β secreted from M1 macrophages in increasing expression of PIGR was confirmed by IL-1 receptor blockade, indicating that IL-1β was the major M1 macrophage-derived cytokine that enhanced PIGR expression. Elevated PIGR expression in breast cancer in vivo may reflect the polarization state of tumor-associated immune cells.
Possibilities of reducing the number of welds on rail vehicle doors
Authors: Sigmund Marian , Spichal Jan
Published: October 2022

The paper developed methods that can be employed to reduce the number of welds on a specific rail-vehicle frame door welded from the EN AW 6060 aluminum alloy profiles thermally processed into the T66 state. The profiles were welded by the GTAW method using an S Al 5087 (AlMg4,5MnZr) wire as the filler material. Tensile tests were performed on the supplied samples after welding to check the mechanical properties required. The resulting tensile test data were subsequently used as boundary values for a new design of the door frame having fewer welds. A FEM simulation was carried out using the Virtual Performance Solution software with PAM—Crash extension. The study's biggest achievement was reducing two welds on a real frame door without changing door frame stability. In view of saving welding and producing time and finance by reducing the number of loaded welds. In conclusion, this designed variant is evaluated and tested.
Temporal variation in the prokaryotic community of a nearshore marine environment
Authors: Korlević Marino , Markovski Marsej , Herndl Gerhard J. , Najdek Mirjana
Published: October 2022

Prokaryotic communities inhabiting surface waters of temperate areas exhibit patterns of seasonal succession. Generally, studies describing these temporal changes are not performed in the proximity to the coast. In the present study, temporal variation of these communities was determined in surface waters at two stations located in the close proximity to the eastern shore of the northern Adriatic Sea. Sequencing of the V4 region of the 16S rRNA gene identified the highest community richness in December with distinct shifts in community structure between periods from April to May, June to October, and November to March. Temperature was shown to be the main environmental force explaining community temporal variation. The NS5 marine group, uncultured Cryomorphaceae, SAR86 clade, and Synechococcus were present throughout the year. Members without know relatives within Rhodobacteraceae and the NS4 marine group were more pronounced in the period from April to May, the AEGEAN-169 marine group, SAR11 subclade III, and HIMB11 in the period from June to October, and SAR11 subclade Ia and Archaea in the period from November to March. Litoricola and OM60 (NOR5) clade were characteristic for both the community sampled from April to May and November to March. Taken together, prokaryotic communities inhabiting nearshore surface waters exhibit a general pattern in community structure similar to other surface associated assemblages of temperate areas. However, the identified specific community composition and temporal patterns differ from other coastal areas.
Switchable unidirectional waves on mono- and diatomic metamaterials
Authors: Yan Jiaruo , Radkovskaya Anna , Solymar Laszlo , Stevens Chris , Shamonina Ekaterina
Published: October 2022

We demonstrate switchable unidirectional propagation of slow waves of coupling within a metamaterial array of strongly coupled elements. We predict theoretically and verify experimentally that the direction of propagation of magnetoinductive waves for any chosen excitation pattern is dictated by the dispersion relations, with forward and backward waves propagating in opposite directions along a chain of meta-atoms. We further prove that the same fundamental phenomenon of direction selectivity due to the forward/backward wave nature is not limited to magnetoinductive waves: we predict analytically and verify numerically the same selective unidirectional signal propagation occurring in nanostructured metamaterial arrays with purely electric coupling. Generalising our method of unidirectional waveguiding to a diatomic magnetoinductive array featuring both forward-wave and backward-wave dispersion branches, switchable unidirectional signal propagation is achieved with distinct frequency bands with opposite directions of signal propagation. Finally, by expanding our technique of selective unidirectional waveguiding to a 2D metasurface, a selective directional control of waves in two dimensions is demonstrated opening up possibilities for directional wireless signal transfer via magnetoinductive surfaces. The observed phenomenon is analogous to polarisation-controlled near-field interference for unidirectional guiding of surface plasmon-polaritons.
Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond
Authors: Gaddis Nathan , Mathur Ravi , Marks Jesse , Zhou Linran , Quach Bryan , Waldrop Alex , Levran Orna , Agrawal Arpana , Randesi Matthew , Adelson Miriam , Jeffries Paul W. , Martin Nicholas G. , Degenhardt Louisa , Montgomery Grant W. , Wetherill Leah , Lai Dongbing , Bucholz Kathleen , Foroud Tatiana , Porjesz Bernice , Runarsdottir Valgerdur , Tyrfingsson Thorarinn , Einarsson Gudmundur , Gudbjartsson Daniel F. , Webb Bradley Todd , Crist Richard C. , Kranzler Henry R. , Sherva Richard , Zhou Hang , Hulse Gary , Wildenauer Dieter , Kelty Erin , Attia John , Holliday Elizabeth G. , McEvoy Mark , Scott Rodney J. , Schwab Sibylle G. , Maher Brion S. , Gruza Richard , Kreek Mary Jeanne , Nelson Elliot C. , Thorgeirsson Thorgeir , Stefansson Kari , Berrettini Wade H. , Gelernter Joel , Edenberg Howard J. , Bierut Laura , Hancock Dana B. , Johnson Eric Otto
Published: October 2022

Opioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (rg > 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10–9). Gene-based analyses identified novel genome-wide significant associations with PPP6C and FURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.
Missed Monteggia fractures in children treated by open reduction of the radial head and corrective osteotomy of the ulna
Authors: Cao Shu , Dong Zhong-Gen , Liu Li-Hong , Wei Jian-Wei , Luo Zhao-Biao , Peng Ping
Published: October 2022

Missed Monteggia fractures in children may cause pain, deformity, decreased range of motion, neurological symptoms, and late arthritis of the elbow. Numerous surgical techniques have been advocated to reconstruct missed Monteggia lesions. The purpose of the present study were first to evaluate the clinical and radiographic outcomes after open reduction of the radial head and corrective osteotomy of the ulna, second to identify the factors associated with the preoperative radial notch/head appearance and the postoperative radiographic results. This study investigated the preoperative MRI presentation and the treatment of 29 patients who were diagnosed missed Monteggia fracture. Radiologic and clinical results of these patients were evaluated retrospectively, and the patient’s and surgical factors related to preoperative radial notch/head appearance and the postoperative radiographic results were analyzed. Of the 29 patients, the average Kim elbow performance score at the last follow-up was 93.6, with 25 excellent, three good, one fair, and no poor results. 19 children had reduced radial heads, 8 had a subluxated radial head and 2 had dislocated radial heads at the last follow-up. The patient’s gender and age had no significant influence on the appearance of radial notch/head and final radiographic results. However, the appearance of radial notch/head can significantly affect the final radiographic result (P < 0.001). The interval time was an important factor which related with the appearance of radial notch/head and final radiographic results (P < 0.001). Treating a missed Monteggia fracture by open reduction of the radial head and corrective osteotomy of the ulna is generally successful and preoperative MRI is meaningful for evaluation of the condition of the radial head and the radial notch which is related with the final radiographic result. The interval time from injury to operation exceeds 6 months, the risk of radial notch/head abnormality and radial head subluxation/re-dislocation after operation significantly increase.