bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcutaneous administration of a novel TRPM8 antagonist reverses cold hypersensitivity while attenuating the drop in core body temperature
Authors: Gold Michael S. , Pineda‐Farias Jorge B. , Close David , Patel Smith , Johnston Paul A. , Stocker Sean D. , Journigan V. Blair 
Published: May 2024

AbstractBackground and PurposeWe extend the characterization of the TRPM8 antagonist VBJ103 with tests of selectivity, specificity and distribution, therapeutic efficacy of systemic administration against oxaliplatin‐induced cold hyperalgesia and the impact of systemic administration on core body temperature (CBT).Experimental ApproachSelectivity at human TRPA1 and TRPV1 as well as in vitro safety profiling was determined. Effects of systemic administration of VBJ103 were evaluated in a model of oxaliplatin‐induced cold hyperalgesia. Both peripheral and centrally mediated effects of VBJ103 on CBT were assessed with radiotelemetry.Key ResultsVBJ103 had no antagonist activity at TRPV1 and TRPA1, but low potency TRPA1 activation. The only safety liability detected was partial inhibition of the dopamine transporter (DAT). VBJ103 delivered subcutaneously dose‐dependently attenuated cold hypersensitivity in oxaliplatin‐treated mice at 3, 10 and 30 mg·kg−1 (n = 7, P < 0.05). VBJ103 (30 mg·kg−1) antinociception was influenced by neither the TRPA1 antagonist HC‐030031 nor the DAT antagonist GBR12909. Subcutaneous administration of VBJ103 (3, 10 and 30 mg·kg−1, but not 100 or 300 mg·kg−1, n = 7) decreased CBT (2°C). Intraperitoneal (i.p.) administration of VBJ103 (3, 10 and 30 mg·kg−1) dose‐dependently decreased CBT to an extent larger than that detected with subcutaneous administration. Intracerebroventricular (i.c.v.) administration (306 nmol/1 μL; n = 5) did not alter CBT.Conclusions and ImplicationsWe achieve therapeutic efficacy with subcutaneous administration of a novel TRPM8 antagonist that attenuates deleterious influences on CBT, a side effect that has largely prevented the translation of TRPM8 as a target.
Phenotypic assessment of antiviral activity for spiro‐annulated oxepanes and azepenes
Authors: Osolodkin Dmitry I. , Kozlovskaya Liubov I. , Iusupov Ildar R. , Kurkin Alexander V. , Shustova Elena Y. , Orlov Alexey A. , Khvatov Evgeny V. , Mutnykh Elena S. , Kurashova Svetlana S. , Vetrova Anna N. , Yatsenko Darya O. , Goryashchenko Alexander S. , Ivanov Vladimir N. , Lukyanenko Evgeny R. , Karpova Evgenia V. , Stepanova Daria A. , Volok Viktor P. , Sotskova Svetlana E. , Dzagurova Tamara K. , Karganova Galina G. , Lukashev Alexander N. , Ishmukhametov Aydar A. 
Published: May 2024

AbstractEvolutionary potential of viruses can result in outbreaks of well‐known viruses and emergence of novel ones. Pharmacological methods of intervening the reproduction of various less popular, but not less important viruses are not available, as well as the spectrum of antiviral activity for most known compounds. In the framework of chemical biology paradigm, characterization of antiviral activity spectrum of new compounds allows to extend the antiviral chemical space and provides new important structure–activity relationships for data‐driven drug discovery. Here we present a primary assessment of antiviral activity of spiro‐annulated derivatives of seven‐membered heterocycles, oxepane and azepane, in phenotypic assays against viruses with different genomes, virion structures, and genome realization schemes: orthoflavivirus (tick‐borne encephalitis virus, TBEV), enteroviruses (poliovirus, enterovirus A71, echovirus 30), adenovirus (human adenovirus C5), hantavirus (Puumala virus). Hit compounds inhibited reproduction of adenovirus C5, the only DNA virus in the studied set, in the yield reduction assay, and did not inhibit reproduction of RNA viruses.
Autophagy‐associated non‐coding RNAs: Unraveling their impact on Parkinson's disease pathogenesis
Authors: Hussain Md Sadique , Moglad Ehssan , Afzal Muhammad , Sharma Shilpa , Gupta Gaurav , Sivaprasad G. V. , Deorari Mahamedha , Almalki Waleed Hassan , Kazmi Imran , Alzarea Sami I. , Shahwan Moyad , Pant Kumud , Ali Haider , Singh Sachin Kumar , Dua Kamal , Subramaniyan Vetriselvan 
Published: May 2024

AbstractBackgroundParkinson's disease (PD) is a degenerative neurological condition marked by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta. The precise etiology of PD remains unclear, but emerging evidence suggests a significant role for disrupted autophagy—a crucial cellular process for maintaining protein and organelle integrity.MethodsThis review focuses on the role of non‐coding RNAs (ncRNAs) in modulating autophagy in PD. We conducted a comprehensive review of recent studies to explore how ncRNAs influence autophagy and contribute to PD pathophysiology. Special attention was given to the examination of ncRNAs' regulatory impacts in various PD models and patient samples.ResultsFindings reveal that ncRNAs are pivotal in regulating key processes associated with PD progression, including autophagy, α‐synuclein aggregation, mitochondrial dysfunction, and neuroinflammation. Dysregulation of specific ncRNAs appears to be closely linked to these pathogenic processes.ConclusionncRNAs hold significant therapeutic potential for addressing autophagy‐related mechanisms in PD. The review highlights innovative therapeutic strategies targeting autophagy‐related ncRNAs and discusses the challenges and prospective directions for developing ncRNA‐based therapies in clinical practice. The insights from this study underline the importance of ncRNAs in the molecular landscape of PD and their potential in novel treatment approaches.
Intermittent hyperglycaemia induces macrophage dysfunction by extracellular regulated protein kinase‐dependent PKM2 translocation in periodontitis
Authors: Sun Yuezhang , Cui Aimin , Dong Hao , Nie Lulingxiao , Yue Ziqi , Chen Jiao , Leung Wai Keung , Wang Jian , Wang Qi 
Published: May 2024

AbstractEarly fluctuations in blood glucose levels increased susceptibility to macrophage dysfunction. However, the underlying pathological mechanisms linking glucose variations and macrophage dysregulation remains elusive. In current study, we established an animal model of transient intermittent hyperglycaemia (TIH) to simulate early fluctuations in blood glucose levels. Our findings revealed that both TIH and diabetic group exhibited more severe periodontal lesions and increased secretion of pro‐inflammatory cytokines compared to healthy controls. In immortalized bone marrow–derived macrophages (iBMDMs), phagocytosis and chemotaxis were impaired with transient and lasting hyperglycaemia, accompanied by enhanced glycolysis. We also found that TIH activated pyruvate kinase M2 (PKM2) through the phosphorylation of extracellular regulated protein kinase (ERK) in vivo, particularly at dimeric levels. In macrophage cultured with TIH, PKM2 translocated into the nucleus and involved in the regulating inflammatory genes, including TNF‐α, IL‐6 and IL‐1β. PKM2 translocation and secretion of inflammatory cytokines were attenuated by PD98059, while PKM2 tetramer activator TEPP‐46 prevented the formation of dimeric PKM2 in macrophages. Moreover, inhibition of glycolysis alleviated the TIH‐induced pro‐inflammatory cytokines. In conclusion, our manuscript provides a rationale for understanding how TIH modulates metabolic rewiring and dysfunction in macrophages via ERK‐dependent PKM2 nuclear translocation.
Measuring biodiversity with sound: How effective are acoustic indices for quantifying biodiversity in a tropical dry forest?
Authors: Kotian Mayuri , Biniwale Siddharth , Mourya Pravar , Burivalova Zuzana , Choksi Pooja 
Published: May 2024

AbstractLarge‐scale biodiversity conservation and management necessitate rapid assessment tools and technologies. Indices derived from passive acoustic data offer a novel solution for rapid biodiversity monitoring. Although these indices quantify vocalizing biodiversity at a site, previous studies indicate inconsistencies in the indices' performance across different biomes. We tested the efficacy of seven acoustic indices—acoustic complexity index, acoustic diversity index, bioacoustic index (BI), acoustic entropy index, total entropy (H), normalized difference soundscape index, and number of peaks in an understudied biome, tropical dry forests, in central India. We measured the relationship between every index and a combination of these indices with a biodiversity metric, avian species richness. We found a weak correlation between individual indices and species richness (0.00 ≤ R ≤ 0.35), while a combination of indices was comparatively better at predicting species richness (R2 = 0.54). Although BI performed better than all other indices, our results indicate that acoustic indices do not accurately quantify avian species richness in this forest in central India. However, combining multiple indices increases their efficacy, limitedly. We recommend evaluating the efficiency of acoustic indices, especially in underrepresented habitats, before their application in avifauna‐based rapid acoustic surveys.
Traits mediate environmental responses of benthic ciliates in dynamic coastal habitats
Authors: Xu Yuan , Fan Xinpeng , Soininen Janne 
Published: May 2024

AbstractAimUnderstanding how species' traits mediate environmental responses provides a mechanistic perspective on community assembly processes. Although traits that influence the response of multicellular organisms to environments have been studied, the identification of such traits in unicellular organisms, like ciliates, is underexplored. Since ciliates are dominant animals in coastal sandy sediments and contribute significantly to interstitial community respiration, identifying links between their occurrence and sandy‐coast characteristics is crucial for conserving biodiversity and protecting coastal habitats.LocationCoasts of China.MethodsWe used Hierarchical Modelling of Species Communities, a trait‐based joint species distribution model, to analyse ciliate community data collected from 344 sites belonging to 31 beaches across the Chinese coastline.ResultsWe found that physical variables play the most important role in determining ciliate occurrence. The beach index combines the tidal range, sediment grain size and beach slope of beach‐selected species based on body size as well as feeding type, while sediment grain size constrained different mobility types, with swimming species favouring fine sandy sediments. The significant contribution of phylogeny in explaining the residual variation among species responses indicates that there are phylogenetically conserved but unmeasured traits too that influence species' responses. Species richness of benthic ciliates was higher in dissipative beaches with high primary productivity.Main ConclusionsBased on our research, ciliate occurrence in coastal beaches is mediated by their traits which are filtered by local environmental variables. The beach index is essential in predicting distribution patterns and species richness of benthic ciliates. Nevertheless, further research is needed to identify additional traits that will enhance the accuracy of predicting ciliate niches. Our study provides insights into the mechanisms driving ciliate community assembly processes and has implications for the conservation of biodiversity in sandy coastal habitats.
Empowering Design in Revigrés: The Strategic Influence of the Chief Design Officer on an Organization's Future
Authors: Pinheiro Gisela , Franqueira Teresa 
Published: May 2024

By leveraging the CDO's role, Revigrés can drive innovation, enhance competitiveness, and position itself as a leader in the design‐driven economy.The presence of design leadership gives an organization an edge in driving innovation and strategic decision‐making in addition to enhancing its competitiveness.
Intellectual property protection, infringement disputes, and, corporate innovation investment persistence
Authors: Peng Hongxing , Mao Xinshu , Zhang Jun 
Published: May 2024

AbstractTo examine the important role of regional intellectual property (IP) protection, we empirically check the impact of infringement disputes on corporate innovation investment persistence. We document that IP protection enforcement can significantly and negatively mitigate the infringer's innovation investment persistence but positively enhance that of the infringed firm. This effect is more pronounced for non‐high‐tech or non‐state‐owned firms. Moreover, IP protection mainly reshapes a firm's perceptions of innovation investment persistence through the efficiency and fairness of law enforcement. Our findings provide insights into optimizing the IP protection environment, especially for emerging economies.
Accuracy assessment between computer‐guided surgery planning and actual tooth position during tooth autotransplantation
Authors: Zhang Jiaming , Han Yue , Zhong Haoyan 
Published: May 2024

AbstractBackground/AimThis study aims to evaluate the precision and efficacy of utilizing computer‐aided design (CAD) in combination with three‐dimensional printing technology for tooth transplantation.Material and MethodsThis study analysed 50 transplanted teeth from 48 patients who underwent tooth transplantation surgery with the aid of CAD and positional guides. A consistent coordinate system was established using preoperative and postoperative cone‐beam computed tomography images. Linear displacements and angular deviations were calculated by identifying key regions in both virtual designs and actual transplanted teeth. Additionally, an analysis was conducted to explore potential factors influencing these deviations.ResultsThe mean cervical deviation, apical deviation, and angular deviation among the 50 transplanted teeth were 1.16 ± 0.57 mm, 1.80 ± 0.94 mm, and 6.82 ± 3.14°, respectively. Cervical deviation was significantly smaller than apical deviation. No significant difference in deviation was observed among different recipient socket locations, holding true for both single‐root, and multi‐root teeth. However, a significant difference was noted in apical deviation between single‐root and multi‐root teeth. Our analysis identified a correlation between apical deviation and root length, leading to the development of a prediction model: Apical deviation = 0.1390 × (root length) + 0.2791.ConclusionsThe postoperative position of the donor teeth shows discrepancies compared to preoperative simulation when utilizing CAD and 3D printed templates during autotransplantation procedures. Continual refinement of preoperative design is a crucial endeavour.
Validating cognitive screening in young people with first‐episode psychosis: The CogScreen protocol
Authors: Stainton Alexandra , Bryce Shayden , Rattray Audrey , Pert Allie , Zbukvic Isabel , Fisher Evangeline , Anderson Debbie , Bowden Stephen C. , Chakma Symphony , Cheng Nicholas , Clark Scott , Crlenjak Caroline , Francey Shona , Gao Caroline , Gee Donna , Gelok Elle , Harris Anthony , Hatfield Lilianne , Hopkins Liza , Jensen Candice , Morell Rachel , O'Halloran Chris , Purdon Scot , Schubert K. Oliver , Scully Alana , Tang Hejun , Thomas Adrian , Thompson Andrew , Uren Jacqueline , Wood Stephen J. , Zhao Wendi , Allott Kelly 
Published: May 2024

AbstractAimCognitive impairments are a core feature of first‐episode psychosis (FEP) and one of the strongest predictors of long‐term psychosocial functioning. Cognition should be assessed and treated as part of routine clinical care for FEP. Cognitive screening offers the opportunity to rapidly identify and triage those in most need of cognitive support. However, there are currently no validated screening measures for young people with FEP. CogScreen is a hybrid effectiveness‐implementation study which aims to evaluate the classification accuracy (relative to a neuropsychological assessment as a reference standard), test–retest reliability and acceptability of two cognitive screening tools in young people with FEP.MethodsParticipants will be 350 young people (aged 12–25) attending primary and specialist FEP treatment centres in three large metropolitan cities (Adelaide, Sydney, and Melbourne) in Australia. All participants will complete a cross‐sectional assessment over two sessions including two cognitive screening tools (Screen for Cognitive Impairment in Psychiatry and Montreal Cognitive Assessment), a comprehensive neuropsychological assessment battery, psychiatric and neurodevelopmental assessments, and other supplementary clinical measures. To determine the test–retest reliability of the cognitive screening tools, a subset of 120 participants will repeat the screening measures two weeks later.ResultsThe protocol, rationale, and hypotheses for CogScreen are presented.Conclusions
CogScreen will provide empirical evidence for the validity and reliability of two cognitive screening tools when compared to a comprehensive neuropsychological assessment. The screening measures may later be incorporated into clinical practice to assist with rapid identification and treatment of cognitive deficits commonly experienced by young people with FEP.
Assessment of the knowledge, emotions and behaviours of secondary school students towards the environment and recycling in Southeastern Türkiye
Authors: Polat Meryem Betül , Karaçizmeli İzzettin Hakan , Atasoy Ayşe Dilek , Yeşilnacar Mehmet İrfan 
Published: May 2024

AbstractImproving the scope of environmental education given in schools and establishing environmental awareness among students are the most important steps to be taken to transfer this awareness to the next generations. The aim of this study is to examine the knowledge, emotions and behaviours of secondary school students ranging from 11 to 13 for environmental health and environmental protection. The study was carried out in the district of Karaköprü, a metropolitan settlement in Şanlıurfa for the 2020–2021 academic year, regarding environmental health and environmental protection, which has decreased with the effect of the pandemic. In this study, a questionnaire was applied to students and their attitudes were evaluated according to a 5‐point Likert scale. The attitudes of the students were detailed on the basis of ‘gender’ and ‘mother education level’ factors. It was found that the male students in the study group had more knowledge about environmental health and protection compared to the female students. However, no relationship was detected between students' environmental awareness and their mothers' educational levels.
Nerve cross‐sectional area from childhood to old age: A high‐resolution nerve ultrasound study
Authors: Philipps Jörg , Denz Robin , Tahmaz Melis , Yusuf Ifirae , Mork Hannah , Schellinger Peter Dieter , Fisse Anna Lena 
Published: May 2024

AbstractBackground and purposeNerve cross‐sectional area (CSA) is not constant over the human lifespan. The relationship between an increasing CSA and age has been described as a linear positive correlation, but few studies have found a linear decrease in nerve size with older age. The aim of the present study was to analyze the development of nerve CSA in a healthy population from early childhood to old age using high‐resolution ultrasound.MethodsThe median, ulnar, radial and sural nerves were examined bilaterally at 18 nerve sites in 110 healthy children, adolescents and adults aged between 2 and 98 years. The CSA of every nerve site was evaluated separately and in different age groups. The correlation of CSA with age, height and weight was analyzed in a linear, logarithmic and quadratic model and correlation coefficients were compared in a goodness‐of‐fit analysis. Models were then adjusted for weight and height.ResultsLinear CSA–age correlations showed the lowest correlation coefficients for all nerve sites. An inverted parabolic curve suggesting a quadratic correlation of CSA and age was the best‐fitting model. Weight and height had a higher predictive value than age in adjusted models.ConclusionsThere is an increase in nerve size during childhood and adolescence and a trend towards a decrease in old age, suggesting an inverted parabolic curve partly explained by age‐related changes in weight and height. Enlarged nerves in elderly individuals should not be attributed to age alone.
Hypogammaglobulinaemia during rituximab treatment in multiple sclerosis: A Swedish cohort study
Authors: Hallberg Susanna , Evertsson Björn , Lillvall Ellen , Boremalm Malin , de Flon Pierre , Wang Yunzhang , Salzer Jonatan , Lycke Jan , Fink Katharina , Frisell Thomas , Al Nimer Faiez , Svenningsson Anders 
Published: May 2024

AbstractBackground and purposeMechanisms behind hypogammaglobulinaemia during rituximab treatment are poorly understood.MethodsIn this register‐based multi‐centre retrospective cohort study of multiple sclerosis (MS) patients in Sweden, 2745 patients from six participating Swedish MS centres were identified via the Swedish MS registry and included between 14 March 2008 and 25 January 2021. The exposure was treatment with at least one dose of rituximab for MS or clinically isolated syndrome, including data on treatment duration and doses. The degree of yearly decrease in immunoglobulin G (IgG) and immunoglobulin M (IgM) levels was evaluated.ResultsThe mean decrease in IgG was 0.27 (95% confidence interval 0.17–0.36) g/L per year on rituximab treatment, slightly less in older patients, and without significant difference between sexes. IgG or IgM below the lower limit of normal (<6.7 or <0.27 g/L) was observed in 8.8% and 8.3% of patients, respectively, as nadir measurements. Six out of 2745 patients (0.2%) developed severe hypogammaglobulinaemia (IgG below 4.0 g/L) during the study period. Time on rituximab and accumulated dose were the main predictors for IgG decrease. Previous treatment with fingolimod and natalizumab, but not teriflunomide, dimethyl fumarate, interferons or glatiramer acetate, were significantly associated with lower baseline IgG levels by 0.80–1.03 g/L, compared with treatment‐naïve patients. Switching from dimethyl fumarate or interferons was associated with an additional IgG decline of 0.14–0.19 g/L per year, compared to untreated.ConclusionsAccumulated dose and time on rituximab treatment are associated with a modest but significant decline in immunoglobulin levels. Previous MS therapies may influence additional IgG decline.