bluuebunny/crossref_metadata_2025 huggingface dataset:
The Riemann Hypothesis is most likely true
Authors: Vega Frank
Published: November 2021

In mathematics, the Riemann hypothesis is a conjecture that the Riemann zeta function has its zeros only at the negative even integers and complex numbers with real part $\frac{1}{2}$. The Riemann hypothesis belongs to the David Hilbert's list of 23 unsolved problems and it is one of the Clay Mathematics Institute's Millennium Prize Problems. The Robin criterion states that the Riemann hypothesis is true if and only if the inequality $\sigma(n)< e^{\gamma } \times n \times \log \log n$ holds for all natural numbers $n> 5040$, where $\sigma(x)$ is the sum-of-divisors function and $\gamma \approx 0.57721$ is the Euler-Mascheroni constant. The Nicolas criterion states that the Riemann hypothesis is true if and only if the inequality $\prod_{q \leq q_{n}} \frac{q}{q-1} > e^{\gamma} \times \log\theta(q_{n})$ is satisfied for all primes $q_{n}> 2$, where $\theta(x)$ is the Chebyshev function. Using both inequalities, we show that the Riemann hypothesis is most likely true.
The Riemann Hypothesis Could Be True
Authors: Vega Frank
Published: November 2021

The Riemann hypothesis has been considered to be the most important unsolved problem in pure mathematics. The David Hilbert's list of 23 unsolved problems contains the Riemann hypothesis. Besides, it is one of the Clay Mathematics Institute's Millennium Prize Problems. The Robin criterion states that the Riemann hypothesis is true if and only if the inequality $\sigma(n)< e^{\gamma } \times n \times \log \log n$ holds for all natural numbers $n> 5040$, where $\sigma(x)$ is the sum-of-divisors function and $\gamma \approx 0.57721$ is the Euler-Mascheroni constant. The Nicolas criterion states that the Riemann hypothesis is true if and only if the inequality $\prod_{q \leq q_{n}} \frac{q}{q-1} > e^{\gamma} \times \log\theta(q_{n})$ is satisfied for all primes $q_{n}> 2$, where $\theta(x)$ is the Chebyshev function. Using both inequalities, we show that the Riemann hypothesis could be true.
“La justicia ambiental es para ti y para mí”: Translating Collective Struggles for Environmental and Energy Justice in Puerto Rico’s Jobos Bay Communities
Authors: Onís Catalina M. de
Published: November 2021

Rural, coastal communities in the Jobos Bay region of southeastern Puerto Rico confront disproportionate harms as an energy sacrifice zone. This space is constituted by imported fossil fuel dependency, economic and climate injustices, environmental racism, ecocide, US colonialism and imperialism, neoliberalism, and racial capitalism. In response, many grassroots actors mobilize against the toxic assault on their communities to push for alternatives beyond the suffocating status quo via apoyo mutuo [mutual support]. This survival work and movement building occur literally in “the outdoors” and in other intertwined multispecies environments, challenging narrow, oppressive colonial, and consumerist constructs that reduce “the outdoors” to recreation and thus erase the numerous ways that people labor in, honor, and defend places and spaces to lead good lives. Thus, critical examinations of communication and race/racism/racialization in and about this colonial US territory must grapple with the brutalities and pain caused by systemic and structural cruelties and translate how, where, and with whom self-determined and potentially liberatory environmental and energy justice advocacy takes shape to refuse a trauma-only narrative. Studying these embodied and emplaced efforts positions energy and power broadly construed, including in the form of collective action. This article centers on the collaborative energies of local grassroots actors and scholars who ideologically and politically align and who value working together toward anti-colonial praxis. To provide one example of how these collaborations can yield public-facing projects that contribute to struggles tied to the survival and well-being of the most impacted communities, this essay focuses on the creation of an environmental justice children’s book. This bilingual text documents and translates the pollution caused by a US-owned, coal-fired power plant and mobilizations to topple this corporate invader. The article concludes by reflecting on some of the difficulties and possibilities that emerged during multi-year coalitional relationships that inform and exceed the children’s book. To reject racist and colonial dominant assumptions and discourses about outdoor spaces as only privileged recreational areas or as a “blank slate” devoid of people and culture, this project narrates how grassroots organizers and scholars persist in continued study and struggle for power(ful) transformations in Jobos Bay and beyond.
Transplantation of Human Pluripotent Stem Cell-Derived Cardiomyocytes for Cardiac Regenerative Therapy
Authors: Silver Sophia E. , Barrs Ryan W. , Mei Ying
Published: November 2021

Cardiovascular disease is the leading cause of death worldwide and bears an immense economic burden. Late-stage heart failure often requires total heart transplantation; however, due to donor shortages and lifelong immunosuppression, alternative cardiac regenerative therapies are in high demand. Human pluripotent stem cells (hPSCs), including human embryonic and induced pluripotent stem cells, have emerged as a viable source of human cardiomyocytes for transplantation. Recent developments in several mammalian models of cardiac injury have provided strong evidence of the therapeutic potential of hPSC-derived cardiomyocytes (hPSC-CM), showing their ability to electromechanically integrate with host cardiac tissue and promote functional recovery. In this review, we will discuss recent developments in hPSC-CM differentiation and transplantation strategies for delivery to the heart. We will highlight the mechanisms through which hPSC-CMs contribute to heart repair, review major challenges in successful transplantation of hPSC-CMs, and present solutions that are being explored to address these limitations. We end with a discussion of the clinical use of hPSC-CMs, including hurdles to clinical translation, current clinical trials, and future perspectives on hPSC-CM transplantation.
Protocol for an Effectiveness-Implementation Hybrid Trial to Evaluate Scale up of an Evidence-Based Intervention Addressing Lifestyle Behaviours From the Start of Life: INFANT
Authors: Laws Rachel , Love Penelope , Hesketh Kylie D. , Koorts Harriet , Denney-Wilson Elizabeth , Moodie Marj , Brown Vicki , Ong Kok-Leong , Browne Jennifer , Marshall Sarah , Lioret Sandrine , Orellana Liliana , Campbell Karen J.
Published: November 2021

Introduction

Promoting healthy eating and active play in early life is critical, however few interventions have been delivered or sustained at scale. The evaluation of interventions at scale is a crucial, yet under-researched aspect of modifying population-level health behaviours. INFANT is an evidence-based early childhood healthy lifestyle intervention that aims to improve parents’ knowledge and skills around promoting optimal energy balance-related behaviours that, in turn, influence children’s diet, activity and adiposity. It consists of: 1) Four group sessions delivered via first time parent groups across the first 12 months of life; 2) access to the My Baby Now app from birth to 18 months of age. This research aims to assess real-world implementation, effectiveness and cost-effectiveness of INFANT when delivered at scale across Victoria, Australia.

Methods and Analysis

A hybrid type II implementation-effectiveness trial applying a mixed methods design will be conducted. INFANT will be implemented in collaboration with practice and policy partners including maternal and child health services, population health and Aboriginal health, targeting all local government areas (n=79) in Victoria, Australia. Evaluation is based on criteria from the ‘Outcomes for Implementation Research’ and ‘RE-AIM’ frameworks. Implementation outcomes will be assessed using descriptive quantitative surveys and qualitative interviews with those involved in implementation, and include intervention reach, organisational acceptability, adoption, appropriateness, cost, feasibility, penetration and sustainability. Process measures include organizational readiness, fidelity, and adaptation. Effectiveness outcomes will be assessed using a sample of INFANT participants and a non-randomized comparison group receiving usual care (1,500 infants in each group), recruited within the same communities. Eligible participants will be first time primary caregivers of an infant aged 0-3 months, owning a personal mobile phone and able to communicate in English. Effectiveness outcomes include infant lifestyle behaviours and BMIz at 12 and 18 months of age.

Impact

This is the first known study to evaluate the scale up of an evidence based early childhood obesity prevention intervention under real world conditions. This study has the potential to provide generalisable implementation, effectiveness and cost-effectiveness evidence to inform the future scale up of public health interventions both in Australia and internationally.

Clinical Trial Registration

Australian and New Zealand Clinical Trial Registry https://www.anzctr.org.au/, identifier ACTRN12620000670976.
Crosstalk Between Intestinal Serotonergic System and Pattern Recognition Receptors on the Microbiota–Gut–Brain Axis
Authors: Layunta Elena , Buey Berta , Mesonero Jose Emilio , Latorre Eva
Published: November 2021

Disruption of the microbiota–gut–brain axis results in a wide range of pathologies that are affected, from the brain to the intestine. Gut hormones released by enteroendocrine cells to the gastrointestinal (GI) tract are important signaling molecules within this axis. In the search for the language that allows microbiota to communicate with the gut and the brain, serotonin seems to be the most important mediator. In recent years, serotonin has emerged as a key neurotransmitter in the gut–brain axis because it largely contributes to both GI and brain physiology. In addition, intestinal microbiota are crucial in serotonin signaling, which gives more relevance to the role of the serotonin as an important mediator in microbiota–host interactions. Despite the numerous investigations focused on the gut–brain axis and the pathologies associated, little is known regarding how serotonin can mediate in the microbiota–gut–brain axis. In this review, we will mainly discuss serotonergic system modulation by microbiota as a pathway of communication between intestinal microbes and the body on the microbiota–gut–brain axis, and we explore novel therapeutic approaches for GI diseases and mental disorders.
Integrating Different Types of Knowledge to Understand Temporal Changes in Reef Landscapes
Authors: Quirino-Amador Maria Iohara , Longo Guilherme Ortigara , Freire Fúlvio Aurélio de Morais , Lopes Priscila F. M.
Published: November 2021

Reefs are highly diverse ecosystems threatened by anthropogenic actions that change their structure and dynamics. Many of these changes have been witnessed by different reef users who hold specific knowledge about the reefscape according to their experiences and uses. We aimed to understand whether fishers, divers, and reef scientists have different perceptions of general changes that have occurred in reefs and whether their knowledge converge, diverge or are complementary. We conducted 172 semi-structured interviews with stakeholders from Northeast and Southeast Brazil where either coral or rocky reefs occur, comprising most reefs occurring in the Southwestern Atlantic Ocean. Reef scientists and divers perceived corals have undergone the sharpest declines among reef species and indicate pollution and tourism as the major negative impacts on reefs. On the contrary, fishers noticed greater declines in fishing targets (i.e., groupers) and have hardly noticed differences in coral abundance or diversity over time. Divers had a broader view of changes in reef organisms, with some level of convergence with both reef scientists and fishers, while reef scientists and fishers provided information on more specific groups and economically relevant resources, respectively. The different stakeholders generally agree that reefscapes have undergone negative changes including diversity loss and abundance declines of reef organisms. The complementarity of information among different stakeholders enables a better understanding of how human behavior impact and perceive changes in natural ecosystems, which could be essential to manage reef environments, particularly those without baseline data.
Omics Technologies to Enhance Plant Based Functional Foods: An Overview
Authors: Nayak Spurthi N. , Aravind B. , Malavalli Sachin S. , Sukanth B. S. , Poornima R. , Bharati Pushpa , Hefferon Kathleen , Kole Chittaranjan , Puppala Naveen
Published: November 2021

Functional foods are natural products of plants that have health benefits beyond necessary nutrition. Functional foods are abundant in fruits, vegetables, spices, beverages and some are found in cereals, millets, pulses and oilseeds. Efforts to identify functional foods in our diet and their beneficial aspects are limited to few crops. Advances in sequencing and availability of different omics technologies have given opportunity to utilize these tools to enhance the functional components of the foods, thus ensuring the nutritional security. Integrated omics approaches including genomics, transcriptomics, proteomics, metabolomics coupled with artificial intelligence and machine learning approaches can be used to improve the crops. This review provides insights into omics studies that are carried out to find the active components and crop improvement by enhancing the functional compounds in different plants including cereals, millets, pulses, oilseeds, fruits, vegetables, spices, beverages and medicinal plants. There is a need to characterize functional foods that are being used in traditional medicines, as well as utilization of this knowledge to improve the staple foods in order to tackle malnutrition and hunger more effectively.
Role of Non-Coding RNAs in Post-Transcriptional Regulation of Lung Diseases
Authors: Soni Dharmendra Kumar , Biswas Roopa
Published: November 2021

Non-coding RNAs (ncRNAs), notably microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), have recently gained increasing consideration because of their versatile role as key regulators of gene expression. They adopt diverse mechanisms to regulate transcription and translation, and thereby, the function of the protein, which is associated with several major biological processes. For example, proliferation, differentiation, apoptosis, and metabolic pathways demand fine-tuning for the precise development of a specific tissue or organ. The deregulation of ncRNA expression is concomitant with multiple diseases, including lung diseases. This review highlights recent advances in the post-transcriptional regulation of miRNAs and lncRNAs in lung diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, and idiopathic pulmonary fibrosis. Further, we also discuss the emerging role of ncRNAs as biomarkers as well as therapeutic targets for lung diseases. However, more investigations are required to explore miRNAs and lncRNAs interaction, and their function in the regulation of mRNA expression. Understanding these mechanisms might lead to early diagnosis and the development of novel therapeutics for lung diseases.
Tpl2 Ablation Leads to Hypercytokinemia and Excessive Cellular Infiltration to the Lungs During Late Stages of Influenza Infection
Authors: Latha Krishna , Jamison Katelyn F. , Watford Wendy T.
Published: November 2021

Tumor progression locus 2 (Tpl2) is a serine-threonine kinase known to promote inflammation in response to various pathogen-associated molecular patterns (PAMPs), inflammatory cytokines and G-protein-coupled receptors and consequently aids in host resistance to pathogens. We have recently shown thatTpl2-/-mice succumb to infection with a low-pathogenicity strain of influenza (x31, H3N2) by an unknown mechanism. In this study, we sought to characterize the cytokine and immune cell profile of influenza-infectedTpl2-/-mice to gain insight into its host protective effects. AlthoughTpl2-/-mice display modestly impaired viral control, no virus was observed in the lungs ofTpl2-/-mice on the day of peak morbidity and mortality suggesting that morbidity is not due to virus cytopathic effects but rather to an overactive antiviral immune response. Indeed, increased levels of interferon-β (IFN-β), the IFN-inducible monocyte chemoattractant protein-1 (MCP-1, CCL2), Macrophage inflammatory protein 1 alpha (MIP-1α; CCL3), MIP-1β (CCL4), RANTES (CCL5), IP-10 (CXCL10) and Interferon-γ (IFN-γ) was observed in the lungs of influenza-infectedTpl2-/-mice at 7 days post infection (dpi). Elevated cytokine and chemokines were accompanied by increased infiltration of the lungs with inflammatory monocytes and neutrophils. Additionally, we noted that increased IFN-β correlated with increased CCL2, CXCL1 and nitric oxide synthase (NOS2) expression in the lungs, which has been associated with severe influenza infections. Bone marrow chimeras with Tpl2 ablation localized to radioresistant cells confirmed that Tpl2 functions, at least in part, within radioresistant cells to limit pro-inflammatory response to viral infection. Collectively, this study suggests that Tpl2 tempers inflammation during influenza infection by constraining the production of interferons and chemokines which are known to promote the recruitment of detrimental inflammatory monocytes and neutrophils.
A Systematic Approach for Semiconductor Half-Heusler
Authors: Lim Wei Yang Samuel , Zhang Danwei , Duran Solco Samantha Faye , Tan Xian Yi , Tan Chee Kiang Ivan , Xu Jianwei , Suwardi Ady
Published: November 2021

The key to designing a half-Heusler begins from the understanding of atomic interactions within the compound. However, this pool of knowledge in half-Heusler compounds is briefly segregated in many papers for specific explanations. The nature of the chemical bonding has been systematically explored for the large transition-metal branch of the half-Heusler family using density-of-states, charge-density, charge transfer, electron-localization-function, and crystal-orbital-Hamilton-population plots. This review aims to simplify the study of a conventional 18-electron configuration half-Heusler by applying rules proposed by renowned scientists to explain concepts such as Zintl-Klemm, hybridization, and valence electron content (VEC). Atomic and molecular orbital diagrams illustrate the electron orbital transitions and provide clarity to the semiconducting behavior (VEC = 18) of half-Heusler. Eighteen-electron half-Heusler usually exhibits good thermoelectric properties owing to favorable electronic structures such as narrow bandgap (<1.1 eV), thermal stability, and robust mechanical properties. The insights derived from this review can be used to design high-performance half-Heusler thermoelectrics.
Degradation of Sol-Gel Acrylic Coatings Based on Si and Zr Investigated Using Electrochemical Impedance, Infrared and X-Ray Photoelectron Spectroscopies
Authors: Rodič Peter , Zanna Sandrine , Milošev Ingrid , Marcus Philippe
Published: November 2021

This study aimed to synthesise and characterise two types of sol-gel acrylic coatings: one based on Si and the other based on Si and Zr. These coatings, which served as a barrier for corrosion protection of aluminium, were synthesised by sol-gel methodology using silicon precursors tetraethyl orthosilicate and organically modified silicon precursor 3-methacryloxypropyltrimethoxysilane, without and with the addition of zirconium(IV) n-propoxide chelated with methacrylic acid. The synthesis process was followed using real-time Fourier transform infrared spectroscopy, which confirmed the condensation reactions of Si–O–Si and Si–O–Zr networks, depending on the sol type. This was reflected in the composition of the coating as well, as shown by X-ray photoelectron spectroscopy. The coating topography, thickness and morphology were analysed using focused ion beam scanning electron microscopy. X-ray photoelectron spectroscopy was employed to follow the degradation of acrylic coatings upon immersion in sodium chloride solution. Corrosion properties, evaluated using electrochemical impedance spectroscopy in 0.1 M NaCl, confirmed high barrier protection of coated aluminium with acrylic coatings based on Si and even better for coating based on Si with Zr. The more durable corrosion protection of the latter was also confirmed by salt spray testing.
Research on Modeling Crystallographic Texture Evolution of Al Alloy 7075
Authors: Liu Hao , Zhao Man , Zhou Yufeng , Liu Gang
Published: November 2021

Crystallographic texture is related to the anisotropy or isotropy of material physical properties, including mechanical performance. The crystallographic effect in micromachining is more significant than that in macro-processing owing to that the depth of the cut and the grain size are in the same order. It is of great significance to model the crystallographic texture evolution induced by mechanical and thermal load during micro-machining to investigate the surface integrity and performance of the finished product. This study performed hot deformation experiments of Al alloy 7075 (AA7075) under various input parameters, including the temperature, temperature rate, stain rate, and strain, which was designed using the Taguchi method. Following that, crystallographic orientation of the samples before and after the deformation was tested using electron back-scattered diffraction (EBSD). Then, the crystallographic texture evolution was modeled with the parameters obtained by fitting a part of the experimental data. The crystallographic texture evolution of AA7075 under different levels of input parameters is studied and analyzed. Finally, the sensitivity of crystallographic orientation evolution to the process parameter is analyzed. The results indicate that these four input parameters have a significant impact on some crystallographic texture of the specimens. The proposed model is instructive in the future investigation of micromachining and microstructure evolution.
Stable Soil Microbial Functional Structure Responding to Biodiversity Loss Based on Metagenomic Evidences
Authors: Chen Huaihai , Ma Kayan , Huang Yu , Yao Zhiyuan , Chu Chengjin
Published: November 2021

Anthropogenic disturbances and global climate change are causing large-scale biodiversity loss and threatening ecosystem functions. However, due to the lack of knowledge on microbial species loss, our understanding on how functional profiles of soil microbes respond to diversity decline is still limited. Here, we evaluated the biotic homogenization of global soil metagenomic data to examine whether microbial functional structure is resilient to significant diversity reduction. Our results showed that although biodiversity loss caused a decrease in taxonomic species by 72%, the changes in the relative abundance of diverse functional categories were limited. The stability of functional structures associated with microbial species richness decline in terrestrial systems suggests a decoupling of taxonomy and function. The changes in functional profile with biodiversity loss were function-specific, with broad-scale metabolism functions decreasing and typical nutrient-cycling functions increasing. Our results imply high levels of microbial physiological versatility in the face of significant biodiversity decline, which, however, does not necessarily mean that a loss in total functional abundance, such as microbial activity, can be overlooked in the background of unprecedented species extinction.
Distinct Transcriptional Programs Underlie Differences in Virulence of Isolates on Host Plants in a Fungal Pathogen, Colletotrichum gloeosporioides
Authors: Cheon Wonsu , Kim Young Soo , Balaraju Kotnala , Lee Younmi , Kwon Hyeok Tae , Jeon Junhyun , Jeon Yongho
Published: November 2021

Susceptible host plants challenged by fungal pathogens can display different types of lesions, which can be attributed to environmental factors affecting the nature of interactions between the host and pathogen. During our survey of apple anthracnose in Korea, two distinct types of disease symptoms, designated as progressive (PS) and static symptoms (SS), were recognized. PS is a typical, rapidly enlarging symptom of apple anthracnose, while SS is a small, dark speck that does not expand further until the harvesting season. Isolation and genotyping of pathogens from disease lesions suggested that all of them belong toColletotrichum gloeosporioides, a well-known causal agent of apple anthracnose. Two types of isolates were comparable in growth on media, spore germination and appressorium formation, virulence test on fruits at various temperature conditions. Furthermore, they were analyzed at the molecular level by a phylogenetic tree, RNA-seq, and expression of virulence gene. However, the SS isolates were defective in appressorium-mediated penetration into the underlying substratum. RNA-seq analysis of PS and SS isolates showed that distinct transcriptional programs underlie the development of different types of anthracnose symptoms in host plants. One downregulated gene in SS encoded isocitrate lyase is essential for disease developmentviaits involvement in the glyoxylate cycle. It partly explains why SS is less virulent than PS on host plants. Overall, our work challenges the traditional view on the development of different lesion types and provides valuable insights into variations that exist in the pathogen population.
Sphingosine Kinase 1 Signaling in Breast Cancer: A Potential Target to Tackle Breast Cancer Stem Cells
Authors: Hii Ling-Wei , Chung Felicia Fei-Lei , Mai Chun-Wai , Ng Pei Yuen , Leong Chee-Onn
Published: November 2021

Sphingosine kinases (SPHKs) are conserved lipid enzymes that catalyze the formation of sphingosine-1-phosphate (S1P) through ATP-dependent phosphorylation of sphingosine. Two distinct SPHK isoforms, namely SPHK1 and SPHK2, have been identified to date, and the former has been implicated for its oncogenic roles in cancer development and progression. While SPHK1 signaling axis has been extensively studied in non-stem breast cancer cells, recent evidence has emerged to suggest a role of SPHK1 in regulating cancer stem cells (CSCs). With the clinical implications of CSCs in disease relapse and metastasis, it is believed that therapeutic approaches that can eradicate both non-stem cancer cells and CSCs could be a key to cancer cure. In this review, we first explore the oncogenic functions of sphingosine kinase 1 in human cancers and summarize current research findings of SPHK1 signaling with a focus on breast cancer. We also discuss the therapeutic potentials and perspectives of targeting SPHK1 signaling in breast cancer and cancer stem cells. We aim to offer new insights and inspire future studies looking further into the regulatory functions of SPHK1 in CSC-driven tumorigenesis, uncovering novel therapeutic avenues of using SPHK1-targeted therapy in the treatment of CSC-enriched refractory cancers.
Aberrant Changes in Cortical Complexity in Right-Onset Versus Left-Onset Parkinson’s Disease in Early-Stage
Authors: Zhang Lin , Shen Qin , Liao Haiyan , Li Junli , Wang Tianyu , Zi Yuheng , Zhou Fan , Song Chendie , Mao Zhenni , Wang Min , Cai Sainan , Tan Changlian
Published: November 2021

There is increasing evidence to show that motor symptom lateralization in Parkinson’s disease (PD) is linked to non-motor features, progression, and prognosis of the disease. However, few studies have reported the difference in cortical complexity between patients with left-onset of PD (LPD) and right-onset of PD (RPD). This study aimed to investigate the differences in the cortical complexity between early-stage LPD and RPD. High-resolution T1-weighted magnetic resonance images of the brain were acquired in 24 patients with LPD, 34 patients with RPD, and 37 age- and sex-matched healthy controls (HCs). Cortical complexity including gyrification index, fractal dimension (FD), and sulcal depth was analyzed using surface-based morphometry via CAT12/SPM12. Familywise error (FWE) peak-level correction at p < 0.05 was performed for significance testing. In patients with RPD, we found decreased mean FD and mean sulcal depth in the banks of the left superior temporal sulcus (STS) compared with LPD and HCs. The mean FD in the left superior temporal gyrus (STG) was decreased in RPD compared with HCs. However, in patients with LPD, we did not identify significantly abnormal cortical complex change compared with HCs. Moreover, we observed that the mean FD in STG was negatively correlated with the 17-item Hamilton Depression Scale (HAMD) among the three groups. Our findings support the specific influence of asymmetrical motor symptoms in cortical complexity in early-stage PD and reveal that the banks of left STS and left STG might play a crucial role in RPD.
Genetic Liability to Sedentary Behavior in Relation to Stroke, Its Subtypes and Neurodegenerative Diseases: A Mendelian Randomization Study
Authors: Yang Fangkun , Chen Songzan , Qu Zihao , Wang Kai , Xie Xiaojie , Cui Hanbin
Published: November 2021

Objective: To investigate the causal association of domain-specific sedentary behaviors with cerebrovascular diseases and neurodegenerative diseases, and the potential mediators among these associations.

Methods: Genetic instruments were identified for television watching, computer use and driving behavior from a genome-wide association study including 408,815 subjects. Mendelian randomization (MR) analysis was used to estimate the causal effect of sedentary behaviors on the cerebrovascular diseases and neurodegenerative diseases. Multivariable MR analysis was applied to adjust potential confounding factors, and mediation analysis was conducted to explore potential mediators.

Results: Genetically predisposition to 1.5 h/day increase in leisure time watching television was associated with increased risk of all-cause stroke [odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.15–1.52, p-value for MR-Egger method (PEgger) = 0.11, I2 = 37%, Cochrane’s Q = 212, p-value for Cochran Q test (PQ) < 0.001], and ischemic stroke (OR = 1.28, 95%CI = 1.10–1.49, PEgger = 0.04, I2 = 35%, Cochrane’s Q = 206, PQ = 0.002). Interestingly, television watching may decrease the risk of Parkinson’s disease (OR = 0.65, 95%CI = 0.50–0.84, PEgger = 0.47, I2 = 19%, Cochrane’s Q = 157, PQ = 0.04). Television watching was a detrimental factor of cognitive performance (estimate = −0.46, 95%CI = −0.55 – −0.37, PEgger = 0.001, I2 = 85%, Cochrane’s Q = 862, PQ < 0.001). Sensitivity analyses using leave out method and MR-PRESSO method suggested weak evidence of pleiotropy.

Conclusion: We provided genetic evidence for the causal association of television watching with increased risk of all-cause stroke and ischemic stroke, decreased risk of Parkinson’s disease, and worse cognitive performance. The results should be interpreted with caution considering the pleiotropy.
The Rate of Decrease in Brain Perfusion in Progressive Supranuclear Palsy and Corticobasal Syndrome May Be Impacted by Glycemic Variability—A Pilot Study
Authors: Alster Piotr , Dunalska Anna , Migda Bartosz , Madetko Natalia , Królicki Leszek
Published: November 2021

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are tauopathic parkinsonian syndromes, presently lacking disease-modifying treatments. Patients affected by these diseases suffer due to multidimensional deteriorations resulting in motor and cognitive impairment. Previously published research has confirmed risk factors that may impact the course of PSP and CBS, among them hypertension and diabetes. Less data is available regarding prediabetes and glycemic variability. In this study, 26 patients with clinical diagnoses of PSP and CBS were examined using glycated hemoglobin and perfusion single-photon emission tomography (SPECT). Patients were divided into two groups—PSP/CBS patients with glycated hemoglobin (HbA1c) below and above 5.7%. The results of the perfusion evaluation were compared with the values from healthy volunteers from the software's database. A decrease in perfusion in certain regions of interest was observed among patients affected by increased glycemic variability. A more pronounced decrement in perfusion was observed only in some regions of interest—the hippocampus, pons, left thalamus, right insula. The results indicated that, among PSP/CBS patients, individuals with more pronounced glycemic variability had more severe hypoperfusion in certain brain regions in comparison with PSP/CBS patients without carbohydrate metabolism disorders. Due to the fact that PSP and CBS are associated with cognitive impairment, an additional decrease in perfusion in the hippocampal area may impact the rate of cognitive deterioration.
Mapping Hebbian Learning Rules to Coupling Resistances for Oscillatory Neural Networks
Authors: Delacour Corentin , Todri-Sanial Aida
Published: November 2021

Oscillatory Neural Network (ONN) is an emerging neuromorphic architecture with oscillators representing neurons and information encoded in oscillator's phase relations. In an ONN, oscillators are coupled with electrical elements to define the network's weights and achieve massive parallel computation. As the weights preserve the network functionality, mapping weights to coupling elements plays a crucial role in ONN performance. In this work, we investigate relaxation oscillators based on VO2 material, and we propose a methodology to map Hebbian coefficients to ONN coupling resistances, allowing a large-scale ONN design. We develop an analytical framework to map weight coefficients into coupling resistor values to analyze ONN architecture performance. We report on an ONN with 60 fully-connected oscillators that perform pattern recognition as a Hopfield Neural Network.
Changes in the Use of Non-nutritive Sweeteners in the Chilean Food and Beverage Supply After the Implementation of the Food Labeling and Advertising Law
Authors: Zancheta Ricardo Camila , Corvalán Camila , Smith Taillie Lindsey , Quitral Vilma , Reyes Marcela
Published: November 2021

Reductions on the sugars content of the food supply have been described after the initial implementation Chilean Labeling Law, but it is unclear if sugars were replaced by non-caloric sweeteners (NNS). We evaluated changes in the NNSs use in foods and beverages after the initial implementation of the labeling law. We used longitudinal data on packaged foods and beverages collected in six major supermarkets and three candy distributors in Santiago, Chile, in January–February 2015/2016 and in January–February 2017. We included in the analysis beverages, dairy-based beverages, yogurts, breakfast cereals, desserts and ice creams, candies and sweet confectioneries, and sweet spreads with a market share ≥1% of their food groups (n = 999). We compared the use of any NNS, the number of different NNSs used, and the combined use of NNSs and ingredients adding sugars using non-parametric tests for matched samples. We evaluated the association between a reduction in sugars and starting NNS use in the post-implementation period using negative binomial regression. The use of any NNS increased from 37.9 to 43.6% (p < 0.001) after the law's implementation, NNSs increased among beverages, dairy-based beverages, yogurts, and desserts and ice creams (p < 0.05), driven mostly by increases in sucralose and stevia use (p < 0.05). We found that reformulated products that reduced the amount of sugars below the law's cutoff were more likely to start using an NNS in the post-implementation period (prevalence ratio: 12.1; 95%CI: 7.2–20.2; p < 0.001). Our results suggest that NNSs likely replaced sugars after the initial implementation of the law. Further analyses should explore how these changes may impact NNS consumption.
Predicting Flow Rate Escalation for Pediatric Patients on High Flow Nasal Cannula Using Machine Learning
Authors: Krachman Joshua A. , Patricoski Jessica A. , Le Christopher T. , Park Jina , Zhang Ruijing , Gong Kirby D. , Gangan Indranuj , Winslow Raimond L. , Greenstein Joseph L. , Fackler James , Sochet Anthony A. , Bergmann Jules P.
Published: November 2021

Background: High flow nasal cannula (HFNC) is commonly used as non-invasive respiratory support in critically ill children. There are limited data to inform consensus on optimal device parameters, determinants of successful patient response, and indications for escalation of support. Clinical scores, such as the respiratory rate-oxygenation (ROX) index, have been described as a means to predict HFNC non-response, but are limited to evaluating for escalations to invasive mechanical ventilation (MV). In the presence of apparent HFNC non-response, a clinician may choose to increase the HFNC flow rate to hypothetically prevent further respiratory deterioration, transition to an alternative non-invasive interface, or intubation for MV. To date, no models have been assessed to predict subsequent escalations of HFNC flow rates after HFNC initiation.

Objective: To evaluate the abilities of tree-based machine learning algorithms to predict HFNC flow rate escalations.

Methods: We performed a retrospective, cohort study assessing children admitted for acute respiratory failure under 24 months of age placed on HFNC in the Johns Hopkins Children's Center pediatric intensive care unit from January 2019 through January 2020. We excluded encounters with gaps in recorded clinical data, encounters in which MV treatment occurred prior to HFNC, and cases electively intubated in the operating room. The primary study outcome was discriminatory capacity of generated machine learning algorithms to predict HFNC flow rate escalations as compared to each other and ROX indices using area under the receiver operating characteristic (AUROC) analyses. In an exploratory fashion, model feature importance rankings were assessed by comparing Shapley values.

Results: Our gradient boosting model with a time window of 8 h and lead time of 1 h before HFNC flow rate escalation achieved an AUROC with a 95% confidence interval of 0.810 ± 0.003. In comparison, the ROX index achieved an AUROC of 0.525 ± 0.000.

Conclusion: In this single-center, retrospective cohort study assessing children under 24 months of age receiving HFNC for acute respiratory failure, tree-based machine learning models outperformed the ROX index in predicting subsequent flow rate escalations. Further validation studies are needed to ensure generalizability for bedside application.
Post-traumatic Stress Symptoms in Adolescents Exposed to the Earthquake in Lombok, Indonesia: Prevalence and Association With Maladaptive Trauma-Related Cognition and Resilience
Authors: Wahab Suzaily , Yong Li Ling , Chieng Wei Keong , Yamil Myristica , Sawal Noor Azah , Abdullah Nurul Qiyaam , Muhdisin Noor Cyntiya Rahmawati , Wd Wiredarma Siti Mardiyah , Ismail Rosnah , Othman Aisya Hanim , Damanhuri Hanafi Ahmad
Published: November 2021

Background: Natural disasters may physically and psychologically affect individuals and their surrounding community. This study determines the prevalence of post-traumatic stress (PTS) symptoms and its association with maladaptive trauma-related cognition and resilience among adolescents post-earthquake.

Materials and Methods: Data were collected, in this cross-sectional study, during an intervention program post-earthquake held in a state high school located at Lombok, Indonesia. The study sample engaged students 14–19 years of age using the purposive sampling method. The questionnaires used to measure PTS symptoms, maladaptive trauma-related cognition, and resilience were Children's Revised Impact of Event Scale-13 (CRIES-13), Child Post-Traumatic Cognitions Inventory (CPTCI), and Child and Youth Resilience Measure-Revised (CYRM-R), respectively.

Results: The prevalence of PTS symptoms was 69.9%. Among the respondents, 61.37% were female and 56.48% had mothers with lower educational levels. Using multiple linear regression, the final predictors of PTS symptoms were excessive reactions (e.g., wailing loudly, miserable shrieking) of proxy during earthquake (β = 3.283, p = 0.005), maladaptive trauma-related cognition (β = 0.224, p = 0.002), and resilience (β = 0.192, p < 0.001) with female gender (β = 7.350, p < 0.001) as a control variable. Through simple linear regression, victims who witnessed injury or death during the earthquake (p = 0.003), had a proxy died during the earthquake (p = 0.01), and trapped victims or those who had difficulty escaping (p = 0.01) were identified to potentially predict the occurrence of PTS symptoms, warranting further study.

Conclusion: The presence of excessive proxy reactions during the earthquake, maladaptive trauma-related cognition, and resilience in adolescents exposed to a natural disaster are worth targeting and prioritizing in future post-disaster interventions.
Stress-Related Behaviors in Companion Dogs Exposed to Common Household Noises, and Owners' Interpretations of Their Dogs' Behaviors
Authors: Grigg Emma K. , Chou Juliann , Parker Emily , Gatesy-Davis Anwyn , Clarkson Sara T. , Hart Lynette A.
Published: November 2021

Sudden, loud noises are one of the most common triggers for fearful behaviors in dogs, and many companion dogs suffer from noise sensitivity. Existing research focuses on dramatic infrequent sounds (e.g., thunderstorms, fireworks). Anecdotally, and based on reports of undesirable behaviors in response to noises in the home, many common household noises may also be causing fear and anxiety in companion dogs. However, these responses have not yet been studied in home environments. We surveyed 386 dog owners about their dogs' responses to household sounds, and recorded dog behaviors and human reactions from 62 videos and compilations available on an online video sharing platform, featuring dogs reacting to common household noises. Numerous signs of canine fear and anxiety were reported by survey respondents and observed in the videos, in response to both daily, and irregular but “normal,” household noises. Responses were significantly stronger to sounds characterized as high frequency intermittent than to sounds characterized as low frequency continuous. Respondents appeared to underestimate their dogs' fearfulness, and the majority of humans in the videos responded to their dogs' behaviors with amusement; welfare concerns were rarely expressed. While these videos cannot be used to calculate actual prevalence of these issues, our data support that some owners are underestimating fearfulness in their dogs in response to household noises, and responding inappropriately to dogs' expressions of fear and anxiety. Better education is required for dog owners to accurately interpret canine body language, to both safeguard dogs' welfare and minimize development of anxiety-related behavior problems.
Endoparasite Infections of the European Hedgehog (Erinaceus europaeus) in Central Italy
Authors: Mariacher Alessia , Santini Andrea , Del Lesto Irene , Tonon Sara , Cardini Elena , Barone Antonino , Eleni Claudia , Fichi Gianluca , Perrucci Stefania
Published: November 2021

The European hedgehog is a synanthropic mammal, widely distributed in Europe. This species usually inhabits the edges of deciduous or mixed woods, but it is also very common in private gardens and public parks. Despite its popularity and frequency of contacts both with humans and with wild and domestic animals, few studies have examined the endoparasitic fauna of the hedgehog in Italy. In the present study, endoparasites of naturally deceased hedgehogs (n = 40) from central Italy (Latium and Tuscany regions) were investigated, along with concurrent gross and histopathological lesions. The most prevalent identified endoparasites were Crenosoma striatum (45%), Capillaria erinacei (42.5%) and Brachylaemus erinacei (22.5%), in accordance with previous reports from hedgehogs in southern Italy. In few subjects, Physaloptera clausa, Acanthocephalans and Cystoisospora rastegaeivae coccidia were also identified. The infection by the lungworm C. striatum was found to be significantly associated (p < 0.01) with bronchial hyperplasia and peribronchiolitis upon histopathological examination. Awareness of the most common parasitic infections in the hedgehog and of their effects on the health of these animals is extremely important, especially in wildlife rescue centers, where European hedgehog represents the most frequently hospitalized mammal species.
Genetic Diversity of Hepatitis E Virus Type 3 in Switzerland—From Stable to Table
Authors: Vonlanthen-Specker Isabelle , Stephan Roger , Sidler Xaver , Moor Dominik , Fraefel Cornel , Bachofen Claudia
Published: November 2021

Hepatitis E caused by hepatitis E viruses of the genotype 3 (HEV-3) is a major health concern in industrialized countries and due to its zoonotic character requires a “One Health” approach to unravel routes and sources of transmission. Knowing the viral diversity present in reservoir hosts, i.e., pigs but also wild boars, is an important prerequisite for molecular epidemiology. The aim of this study was to gain primary information on the diversity of HEV-3 subtypes present along the food chain in Switzerland, as well as the diversity within these subtypes. To this end, samples of domestic pigs from slaughterhouses and carcass collection points, as well as from hunted wild boars, were tested for HEV RNA and antibodies. HEV positive meat products were provided by food testing labs. The HEV subtypes were determined using Sanger and next generation sequencing. The genetic analyses confirmed the predominance of a Swiss-specific cluster within subtype HEV-3h in pigs, meat products, and wild boars. This cluster, which may result from local virus evolution due to the isolated Swiss pig industry, supports fast differentiation of domestic and imported infections with HEV.
A Survey Study of Veterinary Student Opinions and Knowledge about Pet Reptiles and Their Welfare
Authors: Ostović Mario , Sabolek Ivana , Piplica Aneta , Žaja Ivona Žura , Menčik Sven , Nejedli Srebrenka , Mesić Željka
Published: November 2021

Exotic pet medicine is rapidly evolving, with reptiles becoming increasingly popular pet animals. Yet, there are only a few literature reports on veterinary perception of reptiles kept as pets. The aim of the study was to assess opinions and knowledge of the Croatian veterinarians-to-be about pet reptiles and their welfare. The questionnaire survey was conducted in the academic year 2019–2020 and included students of all six years of the integrated undergraduate and graduate study at the Faculty of Veterinary Medicine, University of Zagreb. First-year students were surveyed twice, before and after having attended the compulsory course on animal welfare. Questionnaire statements were 5-point Likert scale questions, requiring the students to express their opinions about turtles, lizards and snakes as pets, issues related to their welfare, risks they pose to the health and safety of humans, other animals and the environment, and their self-reported knowledge about pet reptiles. Although expressing higher opinions after having attended the course on animal welfare, first-year student responses remained neutral to most of the statements. Such a trend continued until the end of the study. Student responses revealed that they were uncertain about their knowledge of reptiles as pets, considering different educational areas observed. Study results emphasised the need of alterations in veterinary curriculum and additional student education in reptile medicine. The results obtained have broad implications involving not only the welfare of pet reptiles in clinical practice and elsewhere but also the health and safety of humans and other animals, as well as environmental protection.