bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of seasonality and normalization techniques for wastewater-based surveillance in Ontario, Canada
Authors: Dhiyebi Hadi A. , Abu Farah Joud , Ikert Heather , Srikanthan Nivetha , Hayat Samina , Bragg Leslie M. , Qasim Asim , Payne Mark , Kaleis Linda , Paget Caitlyn , Celmer-Repin Dominika , Folkema Arianne , Drew Stephen , Delatolla Robert , Giesy John P. , Servos Mark R. 
Published: August 2023

IntroductionWastewater-based surveillance is at the forefront of monitoring for community prevalence of COVID-19, however, continued uncertainty exists regarding the use of fecal indicators for normalization of the SARS-CoV-2 virus in wastewater. Using three communities in Ontario, sampled from 2021–2023, the seasonality of a viral fecal indicator (pepper mild mottle virus, PMMoV) and the utility of normalization of data to improve correlations with clinical cases was examined.MethodsWastewater samples from Warden, the Humber Air Management Facility (AMF), and Kitchener were analyzed for SARS-CoV-2, PMMoV, and crAssphage. The seasonality of PMMoV and flow rates were examined and compared by Season-Trend-Loess decomposition analysis. The effects of normalization using PMMoV, crAssphage, and flow rates were analyzed by comparing the correlations to clinical cases by episode date (CBED) during 2021.ResultsSeasonal analysis demonstrated that PMMoV had similar trends at Humber AMF and Kitchener with peaks in January and April 2022 and low concentrations (troughs) in the summer months. Warden had similar trends but was more sporadic between the peaks and troughs for PMMoV concentrations. Flow demonstrated similar trends but was not correlated to PMMoV concentrations at Humber AMF and was very weak at Kitchener (r = 0.12). Despite the differences among the sewersheds, unnormalized SARS-CoV-2 (raw N1–N2) concentration in wastewater (n = 99–191) was strongly correlated to the CBED in the communities (r = 0.620–0.854) during 2021. Additionally, normalization with PMMoV did not improve the correlations at Warden and significantly reduced the correlations at Humber AMF and Kitchener. Flow normalization (n = 99–191) at Humber AMF and Kitchener and crAssphage normalization (n = 29–57) correlations at all three sites were not significantly different from raw N1–N2 correlations with CBED.DiscussionDifferences in seasonal trends in viral biomarkers caused by differences in sewershed characteristics (flow, input, etc.) may play a role in determining how effective normalization may be for improving correlations (or not). This study highlights the importance of assessing the influence of viral fecal indicators on normalized SARS-CoV-2 or other viruses of concern. Fecal indicators used to normalize the target of interest may help or hinder establishing trends with clinical outcomes of interest in wastewater-based surveillance and needs to be considered carefully across seasons and sites.
Coverage and impact of influenza vaccination among children in Minhang District, China, 2013–2020
Authors: Zhang Zhaowen , Shi Liming , Liu Nian , Jia Biyun , Mei Kewen , Zhang Liping , Zhang XuanZhao , Lu Yihan , Lu Jia , Yao Ye 
Published: August 2023

BackgroundYoung children have a great disease burden and are particularly vulnerable to influenza. This study aimed to assess the direct effect of influenza vaccination among children and to evaluate the indirect benefit of immunizing children.MethodsThe influenza vaccination records for all children born during 2013–2019 in Minhang District and surveillance data for reported influenza cases were obtained from the Minhang CDC. 17,905 children were recorded in the vaccination system and included in this study. Descriptive epidemiology methods were used for data analysis, including an ecological approach to estimate the number of influenza cases averted by vaccination and linear regression to estimate the reduction in influenza cases in the general population per thousand additional childhood vaccination doses.ResultsDuring the study period, the annual vaccination coverage rate ranged from 10.40% in 2013–2014 to 27.62% in 2015–2016. The estimated number of influenza cases averted by vaccination ranged from a low of 0.28 (range: 0.23–0.34) during 2013–2014 (PF: 6.15%, range: 5.11–7.38%) to a high of 15.34 (range: 12.38–18.51) during 2017–2018 (PF: 16.54%, range: 13.79–19.30%). When increasing vaccination coverage rate by 10% in each town/street, a ratio of 7.27–10.69% cases could be further averted on the basis of observed cases. In four selected periods, the number of influenza cases in the general population was most significantly correlated with the cumulative childhood vaccination doses in the prior 2–5 months, and the reduction in influenza cases ranged from 0.73 to 3.18 cases per thousand additional childhood vaccination doses.ConclusionInfluenza vaccination among children is estimated to have direct effects in terms of averted cases and might provide an underlying indirect benefit to the general population. Vaccination coverage in high-coverage areas should be further expanded to avert more influenza cases.
Mapping the insomnia patient journey in Europe and Canada
Authors: O’Regan David , Garcia-Borreguero Diego , Gloggner Fenna , Wild Imane , Leontiou Chrysoula , Ferini-Strambi Luigi 
Published: August 2023

IntroductionInsomnia affects daily functioning and overall health, and is thus associated with significant individual, societal, and economic burden. The experience of patients living with insomnia, their perception of the condition, and its impact on their quality of life is not well documented. The objective of this study was to map the patient journey in insomnia and identify unmet needs.MethodsParticipants were individuals with insomnia, and healthcare professionals (HCPs) who treat insomnia, in the United Kingdom, France, Germany, Italy, and Canada. Qualitative interviews (50 patients, 70 HCPs) and a quantitative survey (700 patients, 723 HCPs) were conducted to inform the patient-journey mapping and obtain information on the emotions, perceptions, and experiences of patients and HCPs.ResultsThe patient journey comprises seven phases. The first defines the onset of insomnia symptoms. Phase 2 represents self-initiated behavior change to improve sleep (e.g., sleep hygiene, reducing caffeine, exercise). The next phase is characterized by use of over-the-counter (OTC) treatments, which generally fail to provide lasting relief. Phase 4 describes the first HCP consultation (occurring several months to several years after onset) and typically occurs at a crisis point for the patient; patients may be looking for an immediate solution (e.g., medication), which may not align with their HCP’s recommendation. The following stage comprises sleep hygiene/behavioral changes (±OTC treatment) under HCP guidance for many patients, although offering prescription treatments without a sleep hygiene stage under supervision is more common in some countries. Phase 6 describes prescription medication initiation, where patients fluctuate between relief/hopefulness and a sense of failure, while HCPs try to balance the need to provide relief for the patient while maintaining best medical practice and minimizing adverse effects. The final phase (living with long-term insomnia) represents an indefinite period during which sleep issues remain unresolved for many patients, with most of them continuing to use prescription treatments for longer than indicated and creating their own variable, self-managed regimens combining multiple modalities.ConclusionThis patient journey analysis for insomnia revealed seven distinct phases, highlighting different touchpoints where insomnia management could be optimized.
Exploration of the SIRT1-mediated BDNF–TrkB signaling pathway in the mechanism of brain damage and learning and memory effects of fluorosis
Authors: Wang Feiqing , Li Yanju , Tang Dongxin , Yang Bo , Tian Tingting , Tian Mengxian , Meng Na , Xie Wei , Zhang Chike , He Zhixu , Zhu Xiaodong , Ming Dong , Liu Yang 
Published: August 2023

IntroductionFluoride is considered an environmental pollutant that seriously affects organisms and ecosystems, and its harmfulness is a perpetual public health concern. The toxic effects of fluoride include organelle damage, oxidative stress, cell cycle destruction, inflammatory factor secretion, apoptosis induction, and synaptic nerve transmission destruction. To reveal the mechanism of fluorosis-induced brain damage, we analyzed the molecular mechanism and learning and memory function of the SIRT1-mediated BDNF–TrkB signaling pathway cascade reaction in fluorosis-induced brain damage through in vivo experiments.MethodsThis study constructed rat models of drinking water fluorosis using 50 mg/L, 100 mg/L, and 150 mg/L fluoride, and observed the occurrence of dental fluorosis in the rats. Subsequently, we measured the fluoride content in rat blood, urine, and bones, and measured the rat learning and memory abilities. Furthermore, oxidative stress products, inflammatory factor levels, and acetylcholinesterase (AchE) and choline acetyltransferase (ChAT) activity were detected. The pathological structural changes to the rat bones and brain tissue were observed. The SIRT1, BDNF, TrkB, and apoptotic protein levels were determined using western blotting.ResultsAll rats in the fluoride exposure groups exhibited dental fluorosis; decreased learning and memory abilities; and higher urinary fluoride, bone fluoride, blood fluoride, oxidative stress product, and inflammatory factor levels compared to the control group. The fluoride-exposed rat brain tissue had abnormal AchE and ChAT activity, sparsely arranged hippocampal neurons, blurred cell boundaries, significantly fewer astrocytes, and swollen cells. Furthermore, the nucleoli were absent from the fluoride-exposed rat brain tissue, which also contained folded neuron membranes, deformed mitochondria, absent cristae, vacuole formation, and pyknotic and hyperchromatic chromatin. The fluoride exposure groups had lower SIRT1, BDNF, and TrkB protein levels and higher apoptotic protein levels than the control group, which were closely related to the fluoride dose. The findings demonstrated that excessive fluoride caused brain damage and affected learning and memory abilities.DiscussionCurrently, there is no effective treatment method for the tissue damage caused by fluorosis. Therefore, the effective method for preventing and treating fluorosis damage is to control fluoride intake.
Gamified virtual reality exposure therapy for adolescents with public speaking anxiety: a four-armed randomized controlled trial
Authors: Kahlon Smiti , Lindner Philip , Nordgreen Tine 
Published: August 2023

Objective: Public Speaking Anxiety is highly prevalent among adolescents. However, few interventions have been developed specifically for this group. This four-armed randomized trial addressed the following research questions regarding interventions for adolescents with public speaking anxiety (PSA): 1) is Virtual Reality exposure therapy (VRET) more efficacious than online psychoeducation or waitlist, and 2) is VRET followed by online exposure therapy more efficacious than VRET alone or online psychoeducation followed by online exposure therapy?Methods: Adolescents, aged 13–16 with PSA were randomized to four groups: 1) VRET + no additional intervention (n = 20); 2) VRET + online exposure program (n = 20); 3) online psychoeducation program + exposure program (n = 40); or 4) waitlist (n = 20). Self-rated PSA symptoms served as primary outcome measure, with secondary outcomes covering other social anxiety symptoms.Results: Linear mixed models revealed that there was a significant difference in the decrease in PSA symptoms among adolescents receiving VRET compared with waiting list (p = 0.015), but no significant difference to the online psychoeducation program (p = 0.056). However, online psychoeducation program yielded smaller within-group effect sizes compared to VRET, d = 0.33 vs. d = 0.83 respectively. VRET + online exposure program had a significant decrease in PSA symptoms (p = 0.013), but no significant difference from VRET + no additional intervention or online psychoeducation + online exposure program. Symptom reduction remained stable at 3-month follow-up.Conclusion: The study shows the potential of delivering both gamified VRET as well as online psychoeducation and exposure programs as self-guided interventions for adolescents with PSA.Clinical trial registration:clinicaltrials.gov, identifier: NCT04396392
Observed and perceived benefits of providing physical activity opportunities in elementary schools: a qualitative study
Authors: Walker Timothy J. , Craig Derek W. , Pfledderer Christopher D. , Robertson Michael C. , Cuccaro Paula , Fumero Keisey , Bartholomew John B. 
Published: August 2023

IntroductionSchools play an important role in promoting physical activity for youth. However, school-based physical activity opportunities often compete with other academic priorities, limiting their implementation. The purpose of this study was to qualitatively explore elementary school teacher and staff perspectives on providing physical activity opportunities and how they impact students and learning.MethodsWe partnered with a school district in Texas to conduct semi-structured individual interviews. We used a purposeful sampling approach to recruit elementary teachers and staff knowledgeable about the physical activity opportunities provided at their school. Interviews included questions about participant opinions of providing physical activity opportunities and the types of opportunities provided. We analyzed data using a directed content analysis and iterative categorization approach.ResultsFifteen participants (4 teachers, 4 physical education teachers, 3 assistant principals, and 4 principals) completed interviews from 10 elementary schools. Participants discussed observed and perceived benefits when providing physical activity opportunities, which emerged into four themes and subthemes: (1) academic benefits (learning readiness, learning engagement, and academic performance); (2) social-emotional benefits (behavior, interpersonal and social skills, and classroom culture); (3) physical benefits (brain health, skill development, physical health); and (4) instructional benefits (quality teaching time, helpful teaching tools, and teacher-student relationships).ConclusionsTeachers and staff observed numerous benefits when students had opportunities to be physically active, including the positive impact on academic and social-emotional outcomes. Our findings highlight the alignment of physical activity with other school priorities. Physical activity programming can be used in ways to support academics, learning, behavior, and other important outcomes.
Viscoelastic behavior of gels obtained from five cultivars of quinoa at altitude gradient
Authors: Polo-Muñoz María Paula , Garcia-Parra Miguel Ángel , Roa-Acosta Diego Fernando 
Published: August 2023

BackgroundQuinoa consumption has created a challenge for producers and food processors. They need to study new cultivars and the functional properties of quinoa flours.MethodsThe structural and rheological properties of six quinoa cultivars (Titicaca, Blanca real, Soracá, Pasankalla, Puno and Nariño) grown at different altitudes were studied using Fourier Transform Infrared spectroscopy (FTIR) and dynamic oscillatory tests. The FTIR spectra revealed differences in the protein and starch structures among the cultivars, which could be related to their adaptation to different environmental conditions. The rheological analysis showed that the quinoa gels exhibited viscoelastic behavior, with a predominance of the elastic component (G’) over the viscous component (G”). The linear viscoelasticity range was determined by applying a strain sweep test (0.001–100%) at a constant frequency of 5 Hz. The frequency sweep test (0.01–100 Hz) at a constant strain amplitude of 0.1% within the linear regime was used to obtain the storage modulus (G’), the loss modulus (G”) and the complex viscosity (η*).ResultsThe Burgers model was fitted to the experimental data, and the four parameters (η1, η2, R1, and R2) were obtained for each cultivar. The results showed that the cultivar., the altitude and their interaction had significant effects on the rheological properties of the quinoa gels. The cultivars grown at higher altitudes tended to have higher G’, G”, and η* values than those grown at lower altitudes, indicating a stronger gel network. The cultivars also differed in their relaxation times, with Titicaca and Blanca real having the shortest and longest times, respectively. These differences could be attributed to the variations in the protein and starch structures of the quinoa flours, as well as the water absorption and gelation properties of the cultivars.ConclusionThe viscoelastic behavior of gels is influenced by the structural conformation of their components, such as proteins and starch. These components provide stiffness and elasticity to the gels. The structural conformation can change depending on the environmental conditions and the phenotypic characteristics of the components.
What predicts survival in glioblastoma? A population-based study of changes in clinical management and outcome
Authors: Fekete B. , Werlenius K. , Tisell M. , Pivodic A. , Smits A. , Jakola A. S. , Rydenhag B. 
Published: August 2023

BackgroundGlioblastoma is the most common and most aggressive primary brain tumor in adults. Despite multimodal treatment, the median survival time is 15–16 months and 5-year survival rate 5%–10%. The primary goal of this study was to identify prognostic factors for survival in an unselected population of patients operated for glioblastoma. The secondary goal was to explore changes in outcome and the clinical management of this patient group over time.MethodsWe identified 222 consecutive adults operated for glioblastoma between November 2012 and June 2016 at the Department of Neurosurgery, Sahlgrenska University Hospital in Gothenburg, serving a health care region in the western part of Sweden with 1.900.000 inhabitants. Clinical variables were identified and tested as predictors for prognosis in extended Poisson regression models. The results were compared with a previously published cohort from 2004 to 2008, before current standard of care based on molecular tumor diagnosis was fully implemented.ResultsMedian overall survival was 1.07 years, which was significantly longer than in the 2004–2008 cohort (1.07 vs. 0.73 y, age- and sex adjusted HR = 1.89, p &lt; 0.0001). Variables associated with longer survival in the multivariable model were MGMT promoter hypermethylation, non-central tumor location, complete resection of enhancing tumor, WHO performance status 0–1, unilateral tumor location, fewer lobes involved, younger age and no comorbidities.ConclusionThe median survival for patients with glioblastoma treated according to current standard treatment has moderately but significantly increased, with MGMT promoter hypermethylation as the strongest predictor for survival.
Isolation and genetic characterization of MERS-CoV from dromedary camels in the United Arab Emirates
Authors: Khalafalla Abdelmalik Ibrahim , Ishag Hassan Zackaria Ali , Albalushi Hamdoon Ismail Abdulla , Al-Hammadi Zulaikha Mohamed Abdel-Hameed , Al Yammahi Saeed Mohamed Saeed , Shah Asma Abdi Mohamed , Al Muhairi Salama Suhail Mohammed 
Published: August 2023

BackgroundThe study of coronaviruses has grown significantly in recent years.Middle East respiratory syndrome coronavirus (MERS-CoV) replicates in various cell types, and quick development has been made of assays for its growth and quantification. However, only a few viral isolates are now available for investigation with full characterization. The current study aimed to isolate MERS-CoV from nasal swabs of dromedary camels and molecularly analyze the virus in order to detect strain-specific mutations and ascertain lineage classification.MethodsWe isolated the virus in Vero cells and adapted it for in vitro cultivation. The isolates were subjected to complete genome sequencing using next-generation sequencing followed by phylogenetic, mutation, and recombination analysis of the sequences.ResultsA total of five viral isolates were obtained in Vero cells and adapted to in vitro cultures. Phylogenetic analysis classified all the isolates within clade B3. Four isolates clustered close to the MERS-CoV isolate camel/KFU-HKU-I/2017 (GenBank ID: MN758606.1) with nucleotide identity 99.90–99.91%. The later isolate clustered close to the MERS-CoV isolate Al-Hasa-SA2407/2016 (GenBank ID: MN654975.1) with a sequence identity of 99.86%. Furthermore, the isolates contained several amino acids substitutions in ORF1a (32), ORF1ab (25), S (2), ORF3 (4), ORF4b (4), M (3), ORF8b (1), and the N protein (1). The analysis further identified a recombination event in one of the reported sequences (OQ423284/MERS-CoV/dromedary/UAE-Al Ain/13/2016).ConclusionData presented in this study indicated the need for continuous identification and characterization of MERS-CoV to monitor virus circulation in the region, which is necessary to develop effective control measures. The mutations described in this investigation might not accurately represent the virus’s natural evolution as artificial mutations may develop during cell culture passage. The isolated MERS-CoV strains would be helpful in new live attenuated vaccine development and efficacy studies.
A cell-based, SARS-CoV-2 spike protein interaction assay to inform the neutralising capacity of recombinant and patient sera antibodies
Authors: Harrison Neale , Richardson Lauren , Pallini Chiara , Morano Ines , Jinks Elizabeth , Cowley Jamie , Chan Hujo , Hill Harriet J. , Tuekprakhon Aekkachai , Li Zhi , Matas de las Heras Cristina , Teodosio Ana , Lavado Andrea S. , Moring Robert , Ashraf Ayesha , Dafforn Timothy R. , Grammatopoulos Dimitris K. , Gordon John , Brady Catherine A. , Young Lawrence S. , Barnes Nicholas M. , Stamataki Zania , Qureshi Omar S. 
Published: August 2023

IntroductionThe engagement of the SARS-CoV-2 spike protein with ACE2 is a critical step for viral entry to human cells, and, therefore, blocking this interaction is a major determinant of the efficacy of monoclonal antibody therapeutics and vaccine elicited serum antibodies. The emergence of SARS-CoV-2 variants has necessitated the development of adaptable assays that can be applied to assess the effectiveness of antibody-based therapeutics.MethodsThrough the testing of a range of recombinant spike proteins, we have developed a cell-based, ACE2/spike protein interaction assay that characterises monoclonal anti-spike protein antibodies and neutralising antibodies in donor serum. The assay uses high-content imaging to quantify cell-bound spike protein fluorescence.ResultsUsing spike proteins from the original “Wuhan” SARS-CoV-2 strain and the Delta and Omicron variants, we identified differential blocking activity of three monoclonal antibodies directed against the spike receptor-binding domain. Importantly, biological activity in the spike interaction assay translated to efficacy in a SARS-CoV-2 infection assay.DiscussionThe spike protein interaction assay can be used to monitor anti-spike antibodies against the major known SARS-CoV-2 variants and is readily adaptable for quantification of the impact of antibodies against new and emerging SARS-CoV-2 variants.