bluuebunny/crossref_metadata_2025 huggingface dataset:
Disease resistance in whitebark pine and potential for restoration of a threatened species
Authors: Sniezko Richard A. , Johnson Jeremy S. , Kegley Angelia , Danchok Robert
Published: October 2023

Societal impact statement

Forests world‐wide are being negatively affected by non‐native, invasive pathogens and pests, and some tree species face uncertain futures. To retain these species as components of future forests, the rare genetic resistance that exists needs to be identified and harnessed. The applied tree improvement program for whitebark pine (Pinus albicaulis), a threatened (in the United States) and endangered (in Canada) keystone species in many forests in western North America, provides an example of what can be accomplished in a relatively short timeframe. The level and frequency of resistance vary by location, and this information will be used to implement the national restoration plan.

Forest trees face serious threats from non‐native diseases and pests, often causing high mortality of both the existing trees and regeneration. Developing populations with genetic resistance can help restore forests and retain affected species. Resistance programs have historically focused on species of high economic importance; however, the threats to species of little direct economic value that provide other important ecosystem services are also great.

We examined the frequency, level, and geographic variation in genetic resistance to white pine blister rust in the threatened Pinus albicaulis (whitebark pine), a keystone species in high‐elevation ecosystems in western North America. In the two trials reported here, 2‐year‐old seedling progeny of 225 whitebark pine parent trees were inoculated with two geographic sources of the fungal pathogen Cronartium ribicola and evaluated over 5 years for an array of resistance traits. The trials focused primarily on parent trees from the Oregon and Washington populations.

We found unexpectedly high levels of quantitative resistance in some seedling families and populations, in stark contrast to levels observed in similar resistance programs with other North American white pine species such as Pinus monticola and Pinus lambertiana.

The level of resistance found in some whitebark pine populations provides optimism about potential recovery efforts for this species. Restoration efforts are underway by government agencies, tribes, and non‐government organizations in both the United States and Canada. These efforts may help boost support for applied genetic resistance programs in other forest tree species severely affected by non‐native pathogens or pests.
Coronaviruses spike glycoprotein endodomains: The sequence and structure‐based comprehensive study
Authors: Kumar Prateek , Bhardwaj Aparna , Mukherjee Bodhidipra , Joshi Richa , Giri Rajanish
Published: October 2023

Any protein's flexibility or region makes it available to interact with many biomolecules in the cell. Specifically, such interactions in viruses help them to perform more functions despite having a smaller genome. Therefore, these flexible regions can be exciting and essential targets to be explored for their role in pathogenicity and therapeutic developments as they achieve essential interactions. In the continuation with our previous study on disordered analysis of SARS‐CoV‐2 spike protein's cytoplasmic tail (CTR), or endodomain, here we have explored the endodomain's disordered potential of six other coronaviruses using multiple bioinformatics approaches and molecular dynamics simulations. Based on the comprehensive analysis of its sequence and structural composition, we report the varying disorder propensity in endodomains of spike proteins of coronaviruses. The observations of this study may help to understand the importance of spike glycoprotein endodomain and creating therapeutic interventions against them.
Effects of (−)‐MBP, a novel 5‐HT2C agonist and 5‐HT2A/2B antagonist/inverse agonist on brain activity: A phMRI study on awake mice
Authors: Sathe Preeti K. , Ramdasi Gargi R. , Giammatteo Kaylie , Beauzile Harvens , Wang Shuyue , Zhang Heng , Kulkarni Praveen , Booth Raymond G. , Ferris Craig F.
Published: October 2023

A novel serotonin ligand (−)‐MBP was developed for the treatment of schizophrenia that has 5‐HT2A/2B antagonist activity together with 5‐HT2C agonist activity. The multi‐functional activity of this novel drug candidate was characterized using pharmacological magnetic resonance imaging. It was hypothesized (−)‐MBP would affect activity in brain areas associated with sensory perception. Adult male mice were given one of three doses of (−)‐MBP (3.0, 10, 18 mg/kg) or vehicle while fully awake during the MRI scanning session and imaged for 15 min post I.P. injection. BOLD functional imaging was used to follow changes in global brain activity. Data for each treatment were registered to a 3D MRI mouse brain atlas providing site‐specific information on 132 different brain areas. There was a dose‐dependent decrease in positive BOLD signal in numerous brain regions, especially thalamus, cerebrum, and limbic cortex. The 3.0 mg/kg dose had the greatest effect on positive BOLD while the 18 mg/kg dose was less effective. Conversely, the 18 mg/kg dose showed the greatest negative BOLD response while the 3.0 mg/kg showed the least. The prominent activation of the thalamus and cerebrum included the neural circuitry associated with Papez circuit of emotional experience. When compared to vehicle, the 3.0 mg dose affected all sensory modalities, for example, olfactory, somatosensory, motor, and auditory except for the visual cortex. These findings show that (−)‐MBP, a ligand with both 5‐HT2A/2B antagonist and 5‐HT2C agonist activities, interacts with thalamocortical circuitry and impacts areas involved in sensory perception.
Toward improved predictions of pharmacokinetics of transported drugs in hepatic impairment: Insights from the extended clearance model
Authors: Storelli Flavia , Ladumor Mayur K. , Liang Xiaomin , Lai Yurong , Chothe Paresh P. , Enogieru Osatohanmwen J. , Evers Raymond , Unadkat Jashvant D.
Published: October 2023

Hepatic impairment (HI) moderately (<5‐fold) affects the systemic exposure (i.e., area under the plasma concentration–time curve [AUC]) of drugs that are substrates of the hepatic sinusoidal organic anion transporting polypeptide (OATP) transporters and are excreted unchanged in the bile and/or urine. However, the effect of HI on their AUC is much greater (>10‐fold) for drugs that are also substrates of cytochrome P450 (CYP) 3A enzymes. Using the extended clearance model, through simulations, we identified the ratio of sinusoidal efflux clearance (CL) over the sum of metabolic and biliary CLs as important in predicting the impact of HI on the AUC of dual OATP/CYP3A substrates. Because HI may reduce hepatic CYP3A‐mediated CL to a greater extent than biliary efflux CL, the greater the contribution of the former versus the latter, the greater the impact of HI on drug AUC ratio (AUCRHI). Using physiologically‐based pharmacokinetic modeling and simulation, we predicted relatively well the AUCRHI of OATP substrates that are not significantly metabolized (pitavastatin, rosuvastatin, valsartan, and gadoxetic acid). However, there was a trend toward underprediction of the AUCRHI of the dual OATP/CYP3A4 substrates fimasartan and atorvastatin. These predictions improved when the sinusoidal efflux CL of these two drugs was increased in healthy volunteers (i.e., before incorporating the effect of HI), and by modifying the directionality of its modulation by HI (i.e., increase or decrease). To accurately predict the effect of HI on AUC of hepatobiliary cleared drugs it is important to accurately predict all hepatobiliary pathways, including sinusoidal efflux CL.
Irrigation contrasts through the morning transition
Authors: Brooke J. K. , Best M. J. , Lock A. P. , Osborne S. R. , Price J. , Cuxart J. , Boone A. , Canut‐Rocafort G. , Hartogensis O. K. , Roy A.
Published: October 2023

The Land surface Interactions with the Atmosphere over the Iberian Semi‐arid Environment (LIAISE) campaign was conducted in July 2021, primarily to investigate the role of irrigation in modulating the boundary‐layer evolution in the Catalan region of northeastern Spain. Contrasts in near‐surface meteorological parameters and boundary‐layer thermodynamic profiles at an irrigated and rainfed (arid) site were established during the morning transition. Evapotranspriation dominated the flux partitioning at the irrigated site (Bowen ratio of 0.07–1.1), whilst sensible heat flux dominated at the rainfed (arid) site (Bowen ratio greater than 10.0). The cumulative evapotranspiration during July 2021 was a factor of 10 greater at the irrigated site than at the rainfed (arid) site. The presence of irrigation was shown to modulate the vertical gradients of turbulence, temperature, and moisture. Irrigation is shown to have a significant effect on the development of the boundary layer, including during the morning transition. The morning transition mean buoyancy flux was 2.8 times smaller at the irrigated site (1.1 ms) compared with the rainfed (arid) site (3.1 ms), with a resultant delay in the near‐surface buoyancy‐flux crossover time (30–90 min) at the irrigated site. At the start of the morning transition (sunrise), the average screen‐level (50‐m) temperature was  K ( K) colder at the irrigated site relative to the rainfed (arid) site. The colder temperatures at sunrise at the irrigated site are predominantly the result of a colder boundary‐layer thermodynamic profile from the previous day. At the end of the morning transition (convective onset), temperature differences between the two sites extend through much of the boundary layer and increase in magnitude. The average screen‐level (50‐m) temperature difference was  K ( K) colder at the irrigated site relative to the rainfed (arid) site. There was considerable day‐to‐day variability in temperature contrasts at a regional level ( to  K).
Two‐stage and three‐stage recursive gradient identification of Hammerstein nonlinear systems based on the key term separation
Authors: Lv Lei , Sun Wei , Pan Jian
Published: October 2023

This article explores recursive algorithms for parameter identification issues of Hammerstein output‐error systems. The proposed approach includes the key term separation auxiliary model recursive gradient algorithm, which utilizes the gradient search and the key term separation. To enhance computational efficiency, the system is decomposed into two or three subsystems through the hierarchical identification principle. Based on this, a key term separation based auxiliary model two‐stage recursive gradient algorithm and a key term separation based auxiliary model three‐stage recursive gradient algorithm are presented. The simulation results verify the validity of the obtained algorithms.
LGBTQIA+ victimization: A theoretical discourse
Authors: Sibanyoni Ephraim Kevin , Mkhize Simangele , Amali Sadiq Ewaoda
Published: October 2023

This paper draws on social construction and broken window theories as theoretical frameworks to explain how LGBTQIA+ are victimized due to discrimination and nonacceptance in their communities. Homosexual groups face a high risk of violence, discrimination, and prejudice because of their sexual orientation. They are stigmatized for their perceived sexual and/or gender “deviance” and rejected by the “straight” members of society, leading to discrimination and violation. This discrimination often leads to homophobia, which can result in violent attacks such as “corrective rape,” common assault, assault causing grievous bodily harm (GBH), and other crimes. Many people view homosexuality as a sickness, a sin, and even antihuman. The victimization of LGBTQIA+ is motivated by hate and intolerance toward their sexuality, leading to trauma, depression, isolation, and fear. This victimization has a significant impact on their lives, and many still live in fear, feeling unprotected. Consequently, many remain “in the closet” due to fear of victimization.
The impact of COVID‐19 trauma on healthcare workers: Examining the relationship between stress and growth through the lens of memory
Authors: Öner Sezin , Bilgin Ezgi , Çağlar Emine Şeyma
Published: October 2023

The COVID‐19 pandemic constituted tremendous traumatic stress among the frontline healthcare workers. In the present study, we investigated relationships of two types of rumination, namely brooding and reflection, with traumatic stress and post‐traumatic growth and the mediating role of recollective experience in these relationships. A total of 88 healthcare workers (75% female, Mage = 54.91) actively providing service to COVID‐19 patients reported two memories of events that impacted them the most at the first peak of the pandemic and rated their recollective experience (i.e., phenomenological characteristics of memories). We used structural equation modelling to test whether recollective experience mediated the link of brooding and reflection with post‐trauma reactions of stress and growth. The findings showed that brooding and reflection were associated with higher levels of traumatic stress and post‐traumatic growth. Importantly, recollective experience mediated the relationship of rumination with traumatic stress but this differed for the type of rumination. Higher brooding was associated with greater traumatic stress and that relationship was independent of how well the memories were recollected, while for reflection, high reflection was associated with stronger recollective experience, which predicted higher traumatic stress and post‐traumatic growth. The present study shows the functional dimensions of reflective rumination and presents novel findings that demonstrates the discrete mnemonic mechanisms underlying the association between brooding, reflection, and post‐trauma reactions.
Is boredom at work bad for your health? Examining the links between job boredom and autonomic nervous system dysfunction
Authors: Seppälä Piia , Harju Lotta , Virkkala Jussi , Hakanen Jari J.
Published: October 2023

Job boredom refers to an unpleasant state of passiveness at work that has been found to negatively relate to self‐reported health. To date, however, the relation between job boredom and physiological indicators of health has not been examined. The present study investigates whether job boredom relates to dysfunction in autonomic nervous system (ANS) activity as indicated by reduced heart rate variability (HRV) during night sleep. The sample of this study consisted of Finnish public sector workers (n = 125). Job boredom was assessed with an electronic questionnaire and HRV with an ambulatory monitoring period of two nights of sleep. The results supported the hypothesis by showing a negative relation between job boredom and HRV, after controlling for demographic and lifestyle factors. The findings extend previous knowledge on the detrimental consequences of job boredom by showing that it is related to dysfunction in ANS activity. Consequently, it is important to acknowledge boredom at work as a threat to occupational health and well‐being and pay more attention to how it can be prevented at workplaces.
The Influence of Precooling on Liquid Metal Embrittlement and Microstructure Properties of Galvanized 22MnB5 Tubes
Authors: Wang Xiaofeng , Sun Lei , Yuan Anying , Chu Guannan , Yao Shengjie , Zhao Long , Hou Deqi , Tang Qinghua
Published: October 2023

To address the issue of liquid metal embrittlement (LME) susceptibility in galvanized 22MnB5 steel during the hot stamping process, the material's performance is affected. This study proposes a method combining precooling and tube hydroforging to produce galvanized tubular hot stamping parts. The primary workflow comprises four distinct stages: the heating phase, thermal retention phase, precooling phase, and the tube hydroforging phase. Notably, the precooling stage employs two distinct approaches: air precooling and boiling water precooling. The composition and morphology of the zinc coating and the microstructure and mechanical properties of the 22MnB5 steel are investigated using two precooling methods at different hydroforging temperatures. The results show that when the initial hydroforging temperature is below 800 °C, the precooling combined with the tube hydroforging process eliminates LME. With increasing precooling time, the oxidation reaction forms ZnO and Fe2O3 on the coating. By comparing the composition, morphology, and mechanical properties of the coatings at hydroforging temperatures of 800 °C and 500 °C, it is concluded that the boiling water precooling aligns more effectively with the requirements of industrial production, with the optimal forming temperature being within the range of 750–800 °C.
Study on seismic performance test and calculation method of recycled steel fiber reinforced concrete shear wall
Authors: Li Yan , Li Dong‐yi , Zhao Shan‐mu , Wang Xiao‐peng
Published: October 2023

Recycled steel wire is taken from used tires, and by procedures like mechanical cutting and friction treatment, it can be converted into industrial recycled steel fiber that meets precise criteria. Such green fiber may effectively limit the growth of fractures in concrete and diffuse the fracture energy of concrete when incorporated into concrete. An investigation of the effects of materials and horizontal reinforcement spacing on the seismic performance of shear wall specimens is presented in this research. The test and numerical simulation findings indicate that the RSFRC (recycled steel fiber reinforced concrete) shear wall's fracture is substantially narrower than that of a conventional shear wall and that the shear carrying capacity and deformation ductility of the shear wall have been greatly enhanced. The energy dissipation capacity of the RSFRC shear wall specimen with varying horizontal reinforcement spacing is significantly enhanced when compared to the conventional shear wall, and the ultimate displacements are reduced. RSFRC shear wall specimen has higher stiffness in the early stage, and the overall stiffness decreases slowly. With the decrease of fiber volume fraction of RSFRC shear wall in a certain range, the shear bearing capacity and stiffness of the model will decrease slightly, but the ductility will increase significantly. Compared with the RSFRC shear wall with fiber aspect ratio of 40 and 25, the bearing capacity and ductility of the two are close, but the RSFRC shear wall with low aspect ratio is slightly insufficient. When the axial compression ratio is in the range of 0.2–0.4, the horizontal shear capacity of RSFRC shear wall increases with the increase of vertical load, but the maximum horizontal displacement becomes smaller, and the model is damaged by compression. Using theoretical calculation, this work also creates the simplified calculation method and restoring force model for the bearing capacity of the diagonal section of RSFRC shear wall. The observed findings correspond well with the test hysteresis curve and may serve as a benchmark for future study. This study provides a new research direction for the seismic performance of RSFRC structures, as well as a solid theoretical foundation and promotion for future research.
ATG16L1 rs2241880/T300A increases susceptibility to perianal Crohn's disease: An updated meta‐analysis on inflammatory bowel disease risk and clinical outcomes
Authors: Simovic Isidora , Hilmi Ida , Ng Ruey Terng , Chew Kee Seang , Wong Shin Yee , Lee Way Seah , Riordan Stephen , Castaño‐Rodríguez Natalia
Published: October 2023

Background

ATG16L1 plays a fundamental role in the degradative intracellular pathway known as autophagy, being a mediator of inflammation and microbial homeostasis. The variant rs2241880 can diminish these capabilities, potentially contributing to inflammatory bowel disease (IBD) pathogenesis.

Objectives

To perform an updated meta‐analysis on the association between ATG16L1 rs2241880 and IBD susceptibility by exploring the impact of age, ethnicity, and geography. Moreover, to investigate the association between rs2241880 and clinical features.

Methods

Literature searches up until September 2022 across 7 electronic public databases were performed for all case‐control studies on ATG16L1 rs2241880 and IBD. Pooled odds ratios (ORP) and 95% CI were calculated under the random effects model.

Results

Our analyses included a total of 30,606 IBD patients, comprising 21,270 Crohn's disease (CD) and 9336 ulcerative colitis (UC) patients, and 33,329 controls. ATG16L1 rs2241880 was significantly associated with CD susceptibility, where the A allele was protective (ORP: 0.74, 95% CI: 0.72–0.77, p‐value: <0.001), while the G allele was a risk factor (ORP: 1.23, 95% CI: 1.09–1.39, p‐value: 0.001), depending on the minor allele frequencies observed in this multi‐ancestry study sample. rs2241880 was predominantly relevant in Caucasians from North America and Europe, and in Latin American populations. Importantly, CD patients harbouring the G allele were significantly more predisposed to perianal disease (ORP: 1.21, 95% CI: 1.07–1.38, p‐value: 0.003).

Conclusions

ATG16L1 rs2241880 (G allele) is a consistent risk factor for IBD in Caucasian cohorts and influences clinical outcomes. As its role in non‐Caucasian populations remains ambiguous, further studies in under‐reported populations are necessary.
Turbulent heat and mass lines in finite difference regime
Authors: S P Suresha , Reddy G. Janardhana , Basha Hussain
Published: October 2023

Finite difference modelling of turbulent heat and mass flow visualization finds numerous applications in atmospheric flows/oceanic currents, wind turbines, thermal transfer in nuclear reactors, drag in oil pipelines, cooling of industrial machineries, and to investigate the complexity, dynamic and chaotic nature of the physical system. A turbulent phenomenon is effectively implemented in engineering, physics, earth sciences, bio‐engineering and medicine. Hence, motivated by the advantages of turbulence in various engineering fields, in the current article, a finite difference analysis is performed to demonstrate the k‐ε turbulence model‐based heat and mass lines visualization in boundary layer regime under turbulent buoyancy‐driven convective conditions along a cylinder. Turbulent flow characteristics are accurately explored by deploying the classical Newtonian flow model. Further, to accomplish a more sophisticated finite difference simulation, the effects of extra kinetic energy and its dissipation rate equations are considered. The produced Navier‐Stokes equations for time‐dependent turbulent heat and mass transmission are rendered to non‐dimensional by deploying suitable dimensionless numbers. The advanced coupled nonlinear turbulent unsteady buoyancy‐motivated vertical convection problem is then solved with a well‐sophisticated finite difference scheme such as Crank‐Nicolson technique using computational software. Authentication of current results with former solutions over a range of buoyancy number, Schmidt, and Prandtl parameters are presented. An extensive tabular and graphical discussion along with contours, heat and masslines visualization is included to enumerate the hydro‐dynamic, thermal and mass diffusion behaviour for the impact of emerged regulating numbers in the Prandtl regime. It is confirmed that, the accelerating turbulent buoyancy‐ratio number, maximizes the velocity, kinetic energy and dissipation rate at . Further, the numerical values of laminar thermal and mass diffusion rates are monotonically enhanced when compared to the turbulent values. Also, to verify the current findings, the authors compared the LRN k‐ε model turbulent results with the existing solutions and found good agreement. Further, the uniqueness and novelty of the current investigation is the exploration of heat and masslines in unsteady buoyancy‐driven convection regime under the influence of k‐ε turbulence model which extends the former studies and offers a more precise appraisal of the thermal and mass diffusion lines via the Crank‐Nicolson analysis.
Introduction
Authors: Ikeda Sanford
Published: October 2023

Jane Jacobs is renowned as a great urbanist who wrote about and profoundly influenced urban planning and design. This book is about the original and useful lessons we can learn about economics and social theory from Jacobs’s major works. This chapter contains an outline of the book and my reasons for writing it.
Coda
Authors: Ikeda Sanford
Published: October 2023

This chapter is a synopsis of the lessons learned from Jane Jacobs about economics, social theory, and policy. It also examines areas for future study, including action space, Jacobs Density, and the metaverse.
The Continuing Relevance of Jane Jacobs’s Economics and Social Theory
Authors: Ikeda Sanford
Published: October 2023

This chapter begins to argue the case that Jacobs made valuable and relevant contributions to economic theory. It describes the nature of her contributions and their relation in particular to market-process economics, and posits that the theory of society underlying market-process economics also underlies Jacobs’s economics and critique of planning. Subsequent chapters develop this argument in detail.
A City Is Not a Man-Made Thing
Authors: Ikeda Sanford
Published: October 2023

This chapter begins to uncover and develop Jacobs’s social theory, based squarely on the concept of “spontaneous order.” In particular, it explains the trade-off in planning between designed complexity and spontaneous complexity. It also defines several terms that are central to understanding that social theory.
The Life and Death of Cities
Authors: Ikeda Sanford
Published: October 2023

Here we explore in detail how and why, according to Jacobs, a living city is the principal social context within which innovation takes place. This chapter outlines and interprets Jacobs’s fundamental contributions to the theory and mechanics of economic development. We also identify the forces internal to the urban process itself that may retard development and contribute to its decline.
Cities of the Future
Authors: Ikeda Sanford
Published: October 2023

In the previous chapter, we examined the limits of urban micro-interventions from a Jacobsian Market Urbanist framework. Here we use that framework to address a different but related set of questions: To what extent is it feasible to consciously plan for “urban vitality”? How much political authority is needed to accomplish this? How workable are some of the recent, imaginative proposals for city planning and rebuilding? We also analyze the nature of different kinds of rules and how they relate to the difference between “governance” and “government,” which entails digging more deeply into some of the concepts we have already been using.
Prefixes of bargraph paths
Authors: Blecher Aubrey , Knopfmacher Arnold
Published: October 2023

We extend the notion of bargraphs as first quadrant, semi-perimeter defined lattice paths to that of a bargraph prefix where we relax the bargraph defining parameters and allow the bargraph to extend into negative territory. A bargraph prefix is any initial section of a bargraph. Generating functions for the prefixes which separately track the number of up, down and horizontal steps are found. The asymptotics for the average height of the last prefix step in the different bargraph extensions is given.
Tropopause folds over the Tibetan Plateau and their impact on water vapor in the upper troposphere-lower stratosphere
Authors: Zhang Yongpeng , Huang Qian , Guo Kun , Wang Mengyuan , Liao Huiren , Chou Yan , He Xin
Published: October 2023

As one of the most important greenhouse gases, water vapor in the upper troposphere and lower stratosphere (UTLS) has a significant impact on the global earth-atmosphere system. The Tibetan Plateau (TP) is an important high terrain which exerts a profound impact on the change of weather and climate, and mass exchange. Tropopause folds occur frequently over the TP due to the impact of the subtropical westerly jet, which affects water vapor transport between the stratosphere and the troposphere. In this paper, the spatial and temporal distribution characteristics of tropopause folds over the TP are examined by applying an improved three-dimensional (3D) labeling algorithm to the ERA5 reanalysis data (1979 to 2019). The effects of different fold depths in various regions over the TP on the variations of UTLS water vapor are further studied. The results of a case study (25 February 2008) suggest that there is a good continuity in identification of the fold depth for the same fold event using the improved 3D labeling algorithm. The fold depth and height are consistent with the results of radiosonde data and ERA5 reanalysis data. The fold frequency over the TP shows an increasing trend in the last 41 years, with slightly lower frequency of medium folds than that of shallow folds, and lowest frequency of deep folds. There is increasing water vapor in the UTLS over the TP due to tropopause folds. The results indicate that tropopause folds enhance the horizontal divergence of water vapor in the UTLS and increase the vertical water vapor flux in the UTLS region. The folding over the plateau leads to increased moisture in the UTLS. It is argued that vertical velocity anomalies in the vicinity of the fold and subgrid perturbations have a significant impact on the increase of UTLS water vapor over the TP. The results of this work provide a scientific basis for a better understanding of the stratosphere-troposphere exchanges due to tropopause folds over the TP.
Concordance between MITS and conventional autopsies for pathological and virological diagnoses
Authors: Schädler Julia , Azeke Akhator Terence , Ondruschka Benjamin , Steurer Stefan , Lütgehetmann Marc , Fitzek Antonia , Möbius Dustin
Published: October 2023

In pandemics or to further study highly contagious infectious diseases, new strategies are needed for the collection of post-mortem tissue samples to identify the pathogen as well as its morphological impact. In this study, an ultrasound-guided minimally invasive tissue sampling (MITS) protocol was developed and validated for post-mortem use. The histological and microbiological qualities of post-mortem specimens were evaluated and compared between MITS and conventional autopsy (CA) in a series of COVID-19 deaths. Thirty-six ultrasound-guided MITS were performed. In five cases more, specimens for histological and virological examination were also obtained and compared during the subsequently performed CA. Summary statistics and qualitative interpretations (positive, negative) were calculated for each organ tissue sample from MITS and CA, and target genes were determined for both human cell count (beta-globin) and virus (SARS-CoV-2 specific E gene). There are no significant differences between MITS and CA with respect to the detectability of viral load in individual organs, which is why MITS can be of utmost importance and an useful alternative, especially during outbreaks of infectious diseases.
Dynamic transcriptome analysis unravels key regulatory genes of maize root growth and development in response to potassium deficiency
Authors: Guo Song , Liu Zhigang , Sheng Huajin , Olukayode Toluwase , Zhou Zijun , Liu Yonghong , Wang Meng , He Mingjiang , Kochian Leon , Qin Yusheng
Published: October 2023

Main conclusion

Integrated root phenotypes and transcriptome analysis have revealed key candidate genes responsible for maize root growth and development in potassium deficiency.

Potassium (K) is a vital macronutrient for plant growth, but our understanding of its regulatory mechanisms in maize root system architecture (RSA) and K+ uptake remains limited. To address this, we conducted hydroponic and field trials at different growth stages. K+ deficiency significantly inhibited maize root growth, with metrics like total root length, primary root length, width and maximum root number reduced by 50% to 80% during early seedling stages. In the field, RSA traits exhibited maximum values at the silking stage but continued to decline thereafter. Furthermore, K deprivation had a pronounced negative impact on root morphology and RSA growth and grain yield. RNA-Seq analysis identified 5972 differentially expressed genes (DEGs), including 17 associated with K+ signaling, transcription factors, and transporters. Weighted gene co-expression network analysis revealed 23 co-expressed modules, with enrichment of transcription factors at different developmental stages under K deficiency. Several DEGs and transcription factors were predicted as potential candidate genes responsible for maize root growth and development. Interestingly, some of these genes exhibited homology to well-known regulators of root architecture or development in Arabidopsis, such as Zm00001d014467 (AtRCI3), Zm00001d011237 (AtWRKY9), and Zm00001d030862 (AtAP2/ERF). Identifying these key genes helps to provide a deeper understanding of the molecular mechanisms governing maize root growth and development under nutrient deficient conditions offering potential benefits for enhancing maize production and improving stress resistance through targeted manipulation of RSA traits in modern breeding efforts.
MicroRNAs in atrial fibrillation target genes in structural remodelling
Authors: van den Berg Nicoline W. E. , Kawasaki Makiri , Nariswari Fransisca A. , Fabrizi Benedetta , Neefs Jolien , van der Made Ingeborg , Wesselink Robin , van Boven Wim Jan P. , Driessen Antoine H. G. , Jongejan Aldo , de Groot Joris R.
Published: October 2023

We aim to elucidate how miRNAs regulate the mRNA signature of atrial fibrillation (AF), to gain mechanistic insight and identify candidate targets for future therapies. We present combined miRNA–mRNA sequencing using atrial tissues of patient without AF (n = 22), with paroxysmal AF (n = 22) and with persistent AF (n = 20). mRNA sequencing previously uncovered upregulated epithelial to mesenchymal transition, endothelial cell proliferation and extracellular matrix remodelling involving glycoproteins and proteoglycans in AF. MiRNA co-sequencing discovered miRNAs regulating the mRNA expression changes. Key downregulated miRNAs included miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p and key upregulated miRNAs were miR-144-3p, miR-15b-3p, miR-182-5p miR-18b-5p, miR-4306 and miR-206. MiRNA expression levels were negatively correlated with the expression levels of a multitude of predicted target genes. Downregulated miRNAs associated with increased gene expression are involved in upregulated epithelial and endothelial cell migration and glycosaminoglycan biosynthesis. In vitro inhibition of miR-135b-5p and miR-138-5p validated an effect of miRNAs on multiple predicted targets. Altogether, the discovered miRNAs may be explored in further functional studies as potential targets for anti-fibrotic therapies in AF.
Do pseudoxanthoma elasticum patients have higher prevalence of kidney stones on computed tomography compared to hospital controls?
Authors: Harmsen Iris M. , Kok Madeleine , Bartstra Jonas W. , de Jong Pim A. , Spiering Wilko , Foppen Wouter
Published: October 2023

Background

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by diminished inorganic plasma pyrophosphate (PPi), a strong calcification inhibitor. In addition to more typical calcification of skin, retina and arterial wall a diminished plasma PPi could lead to other ectopic calcification, such as formation of kidney stones.

Objective

To compare the prevalence of kidney stones between PXE patients and hospital controls on computed tomography (CT).

Method

Low-dose CT images of PXE patients and controls were assessed by one radiologist, who was blinded for the diagnosis PXE. The number of kidney stones, and the size of the largest stone was recorded. Odds ratios (ORs) for having kidney stone were calculated using multivariable adjusted logistic regression.

Results

Our study comprised 273 PXE patients and 125 controls. The mean age of PXE patients was 51.5 ± 15.9 years compared to 54.9 ± 14.2 in the control group (p = 0.04) and PXE patients more often were women (63 vs. 50%, p = 0.013). The prevalence of kidney stones on CT was similar: 6.9% in PXE patients, compared to 5.6% in controls (p = 0.6). In the multivariate analysis adjusting for age and sex, there was no significantly higher odds for PXE patients on having stones, compared to controls: OR 1.48 (95% CI 0.62–3.96).

Conclusion

There is no significant difference in the prevalence of incidental kidney stones on CT in PXE patients versus controls.
Therapeutic effectiveness of anlotinib combined with etoposide in extensive-stage small-cell lung cancer: a single-arm, phase II trial
Authors: Wu Yuan , Zhou Xuefeng , Zhao Weiqing , Wang Qiong , Han Zhengxiang , Wang Lifeng , Zhou Wenjie , Zhou Tong , Song Haizhu , Chen Yong , Yang Kaihua , Shi Lin , Pan Banzhou , Guo Renhong , Zhou Guoren , Jiang Feng , Feng Jifeng , Shen Bo
Published: October 2023

Background

Anlotinib plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC) achieves good efficacy, but there is still room for improvement. This clinical study examined the effectiveness of anlotinib plus etoposide for maintenance therapy in ES-SCLC.

Methods

The current single-arm, prospective phase II study was performed at Jiangsu Cancer Hospital (March 2019 to March 2022). After successful primary etoposide-based therapy, anlotinib was administered at 12 mg/day on days 1 to 14 of 21-day cycles until disease progression or consent withdrawal. All patients also received etoposide at 50 mg/day on days 1 to 14 of 21-day cycles for a maximum of six cycles. Progression-free survival (PFS) constituted the primary study endpoint. Secondary endpoints were overall survival (OS), objective remission rate (ORR), disease control rate (DCR), and safety. In addition, adverse events (AEs) were assessed.

Results

Twenty-eight patients were treated. Median PFS and OS were 8.02 (95%CI 5.36–10.67) and 11.04 (95%CI 10.37–11.68) months, respectively. Totally 9 and 18 participants showed a partial response and stable disease, respectively; ORR and DCR were 32.14% and 96.43%, respectively. The commonest all-grade AEs were fatigue (n = 11, 39.28%), hypertension (n = 11, 39.28%), loss of appetite (n = 9, 32.14%), oral mucositis (n = 7, 25.00%) and proteinuria (n = 6, 21.40%). Grade 3–4 AEs included fatigue (n = 4, 14.28%), hypertension (n = 2, 7.14%), hand and foot syndrome (n = 2, 7.14%), oral mucositis (n = 1, 3.57%), hemoptysis (n = 1, 3.57%), proteinuria (n = 1, 3.57%), gingival bleeding (n = 1, 3.57%), and serum creatinine elevation (n = 1, 3.57%).

Conclusion

Maintenance anlotinib plus etoposide achieves promising PFS and OS in clinical ES-SCLC.

Registration number

ChiCTR1800019421.
Detection of SARS-CoV-2 in high-efficiency particulate air (HEPA) filters of low-cost air purifiers in community-based organizations
Authors: Clarke Rachel D. , Garba Nana Aisha , Barbieri Manuel A. , Acuna Leonardo , Baum Marianna , Rodriguez Maribel Saad , Frias Hansel , Saldarriaga Paulina , Stefano Troy , Mathee Kalai , Narasimhan Giri , R. Brown David
Published: October 2023

This study aims to investigate the presence of SARS-CoV-2 in public spaces and assess the utility of inexpensive air purifiers equipped with high-efficiency particulate air (HEPA) filters for viral detection. Samples were collected from six community-based organizations in underserved minority neighborhoods in Northwest Miami, Florida, from February to May 2022. Reverse transcription–quantitative polymerase chain reaction (RT-qPCR) was used to detect SARS-CoV-2 in air purifier filters and surface swabs. Among 32 filters tested, three yielded positive results, while no positive surface swabs were found. Notably, positive samples were obtained exclusively from child daycare centers. These findings highlight the potential for airborne transmission of SARS-CoV-2 in indoor air, particularly in child daycare centers. Moreover, the study demonstrates the effectiveness of readily available HEPA filters in detecting the virus. Improving indoor ventilation and implementing air filtration systems are crucial in reducing COVID-19 transmission where people gather. Air filtration systems incorporating HEPA filters offer a valuable approach to virus detection and reducing transmission risks. Future research should explore the applicability of this technology for early identification and mitigation of viral outbreaks.
Dealing with the COVID-19 pandemic in Slovenia: simulations with a macroeconometric model
Authors: Weyerstrass Klaus , Blueschke Dmitri , Neck Reinhard , Verbič Miroslav
Published: October 2023

In this paper we analyse the effectiveness of fiscal policies with respect to macroeconomic stabilisation during the COVID-19 pandemic in the small open economy of Slovenia. Using SLOPOL11, an econometric model of the Slovenian economy, we simulate the development of the its economy during the 2020s under alternative assumptions about future pandemic-related shocks. We also determine optimal fiscal policies to combat the effects of the pandemic and to stabilise the economy under two scenarios for the future course of developments under COVID-19. Our simulations show that those public spending measures that entail both demand- and supply-side effects are more effective at stimulating real GDP and increasing employment than pure demand-side measures. Successful stabilisation policies should thus contain a supply-side component in addition to a demand-side component.
The Role of Nrf2 and Inflammation on the Dissimilar Cardiotoxicity of Doxorubicin in Two-Time Points: a Cardio-Oncology In Vivo Study Through Time
Authors: Reis-Mendes Ana , Ferreira Mariana , Padrão Ana Isabel , Duarte José Alberto , Duarte-Araújo Margarida , Remião Fernando , Carvalho Félix , Sousa Emília , Bastos Maria Lourdes , Costa Vera Marisa
Published: October 2023

Doxorubicin (DOX) is a topoisomerase II inhibitor used in cancer therapy. Despite its efficacy, DOX causes serious adverse effects, such as short- and long-term cardiotoxicity. This work aimed to assess the short- and long-term cardiotoxicity of DOX and the role of inflammation and antioxidant defenses on that cardiotoxicity in a mice model. Adult CD-1 male mice received a cumulative dose of 9.0 mg/kg of DOX (2 biweekly intraperitoneal injections (ip), for 3 weeks). One week (1W) or 5 months (5M) after the last DOX administration, the heart was collected. One week after DOX, a significant increase in p62, tumor necrosis factor receptor (TNFR) 2, glutathione peroxidase 1, catalase, inducible nitric oxide synthase (iNOS) cardiac expression, and a trend towards an increase in interleukin (IL)-6, TNFR1, and B-cell lymphoma 2 associated X (Bax) expression was observed. Moreover, DOX induced a decrease on nuclear factor erythroid-2 related factor 2 (Nrf2) cardiac expression. In both 1W and 5M, DOX led to a high density of infiltrating M1 macrophages, but only the 1W-DOX group had a significantly higher number of nuclear factor κB (NF-κB) p65 immunopositive cells. As late effects (5M), an increase in Nrf2, myeloperoxidase, IL-33, tumor necrosis factor-α (TNF-α), superoxide dismutase 2 (SOD2) expression, and a trend towards increased catalase expression were observed. Moreover, B-cell lymphoma 2 (Bcl-2), cyclooxygenase-2 (COX-2), and carbonylated proteins expression decreased, and a trend towards decreased p38 mitogen-activated protein kinase (MAPK) expression were seen. Our study demonstrated that DOX induces adverse outcome pathways related to inflammation and oxidative stress, although activating different time-dependent response mechanisms.

Graphical Abstract
Wellbeing at home: a mediation analysis of residential satisfaction, comfort, and home attachment
Authors: Wegener Bernd A. , Schmidt Peter
Published: October 2023

In the study of residential satisfaction in architectural design different physical comfort domains have received the most attention. But with this comfort-driven approach, residential satisfaction is reduced to a psychophysical relationship. Adding psychological substance to the design process, the paper argues that a distinction should be made between residential satisfaction and home attachment and that we need to consider home attachment as a mediator variable for comfort. The aim of the paper is to empirically assess whether the mediation, if it exists at all, is partial or complete. Distinguishing different forms of comfort, a set of alternative structural equation models are tested with data from a 14-nation population survey in Europe. The result of the model tests is that our wellbeing at home comes in two forms—satisfaction and attachment—and that there is partial as well as complete mediation of home attachment on satisfaction depending on the kind of comfort studied.
Evaluation of Prevention Programs for Grandparent Caregivers: a Systematic Review
Authors: Chan Athena Chung Yin , Piehler Timothy F.
Published: October 2023

This systematic review critically evaluates 21 grandparent-focused prevention programs designed to benefit grandparent caregivers or target grandparent caregivers as agents of change for grandchild development. These grandparent programs were published in 35 peer-reviewed articles in the last 31 years. For each program, we described the phase of development of program (i.e., feasibility, pilot, and efficacy), delivery characteristics, and adaptations of existing evidence-based programs to meet the needs of grandparent caregivers in diverse sociocultural backgrounds. For programs tested under a controlled trial design, we evaluated core components and preliminary effects on targeted outcomes. Most studies targeted grandparents who served as primary or custodial caregivers in the USA, while limited studies targeted supplementary grandparent caregivers. Thirteen programs which were evaluated using pretest–posttest designs demonstrated feasibility and acceptability of the grandparent programs. Moreover, eight programs which were evaluated using randomized-controlled trials (RCTs; 5 pilot and 3 full-scale efficacy trials) demonstrated promising outcomes. Additionally, we identified six core components and 17 specific elements in eight programs evaluated using RCT designs. Overall, we provide a comprehensive critique of this body of literature as well as directions for future studies, including the need to develop programing tailored to grandparent caregivers with unique needs.
Failed secular revolutions: religious belief, competition, and extremism
Authors: Carvalho Jean-Paul , Rubin Jared , Sacks Michael
Published: October 2023

All advanced economies have undergone secular revolutions in which religious belief and institutions have been subordinated to secular forms of authority. There are, however, numerous examples of failed secular transitions. To understand these failures, we present a religious club model with endogenous entry and cultural transmission of religious beliefs. A spike in the demand for religious belief, due for example to a negative economic shock, induces a new and more extreme organization to enter the religious market and exploit the dissatisfaction of highly religious types with the religious incumbent. The effect is larger where institutional secularization is more advanced, for example where the religious establishment has moderated itself or has been moderated by the political authority. The greater the moderation of the religious incumbent, the more extreme is the position chosen by the religious entrant, and the larger is the rise in religious participation. Hence, unanticipated shifts in religious demand can lead to the emergence of new and more extreme religious organizations and reverse previous trends toward secularization. Our model sheds light on the causes and consequences of failed secular revolutions and religious revivals in Latin America and Egypt.