bluuebunny/crossref_metadata_2025 huggingface dataset:
Asynchronous Encounters: Artistic Practice and Mediated Intimacy in the Space-Time of Lockdown
Authors: Goodwin Emily , Brophy Sarah
Published: May 2023

This essay engages with pandemic-era artistic practice, asking how digital technologies are being taken up out of desires and attempts to be intimate with, proximate to, ‘contemporary’ with one another. Drawing on theories of pandemic temporality and on media analysis approaches that highlight the digital’s materiality, affectivity, and self-reflexivity, we think with three first-person, visual-digital works composed, circulated, and archived during the COVID-19 pandemic: Ella Comberg’s research creation photo-essay on Google Street View, titled ‘Eye of the Storm,’ Bo Burnham’s Netflix streaming special Inside, and Richard Fung’s short documentary film ‘[…],’ shot on iPad. We suggest that these visual-digital pieces open onto the promises and limitations of mediated intimacies – with others, with ourselves, and with the space-time of lockdown. Their commitments to texture and tension draw out the ‘impurity’ ( Shotwell 2016 ) of our digital lifeworlds, while also attuning us to possibilities for ‘waiting with’ ( Baraitser and Salisbury 2020 ) one another amidst what Nadine Chan (2020) calls the ‘distal temporalities’ of late capitalism. To deliberately dwell in stuck or looped time and linger over the touch of distant, distal others – or what we call asynchronous encounters – is not to indulge or excuse the ways in which contemporary media platforms capitalise on affective and creative labour or surveil digital lifeworlds. Instead, we posit that the textures, glitches, and flickering bonds of mediated intimacy may offer new, multiple, reflexive and recursive pathways ‘toward inhabited futures that are not so distal’ ( Chan 2020 : 13.6).
Pengaruh Media Video Terhadap Tingkat Pengetahuan Tentang Kontrasepsi Intra Uterine Devices (IUD) Pada Pasangan Usia Subur
Authors: Herdiani Tria Nopi , Direja Ade Herman Surya , Nopisia Okta
Published: May 2023

Rendahnya penggunaan kontrasepsi IUD disebabkan oleh beberapa faktor, salah satunya adalah rendahnya tingkat pengetahuan. Puskesmas Anggut Atas termasuk Puskesmas dengan jumlah akseptor KB IUD  yang masih rendah sebanyak 4 akseptor yang memakai kontrasepsi IUD. Penelitian ini bertujuan untuk mempelajari pengaruh media video terhadap tingkat pengetahuan tentang kontrasepsi IUD pada pasangan usia subur di di Wilayah Puskesmas Anggut Atas Kota Bengkulu. Penelitian ini menggunakan desain pra eksperimen dengan pendekatan one group pre test-post test design. Populasi dalam penelitian ini adalah pasangan usia subur. Jumlah sampel sebanyak 64 responden diambil menggunakan teknik Purposive Sampling. Analisis data dilakukan dengan uji wilcoxon. Hasil penelitian menunjukkan tingkat pengetahuan PUS tentang IUD sebelum diberikan intevensi media video memiliki nilai rata-rata 3,83 (kurang), kemudian setelah diberikan intervensi media video rata-rata tingkat pengetahuan PUS meningkat menjadi 8,86 (baik). Ada pengaruh media video terhadap tingkat pengetahuan tentang kontrasepsi Intra Uterine Devices (IUD) pada pasangan usia subur di Puskesmas Anggut Atas Kota Bengkulu. Petugas kesehatan diharapkan dapat memberikan pendidikan kesehatan tentang kontraspesi AKDR kepada pasangan usia subur dengan menggunakan media video sehingga dapat meningkatkan pengetahuan tentang kontrasepsi IUD.
Cross-sectional properties of rib geometry from an adult population
Authors: Holcombe Sven , Huang Yuan
Published: May 2023

Introduction: Human body models (HBMs) play a key role in improving modern vehicle safety systems to protect broad populations. However, their geometry is commonly derived from single individuals chosen to meet global anthropometric targets, thus their internal anatomy may not fully represent the HBM’s target demographic. Past studies show sixth rib cross-sectional geometry differences between HBM ribs and population-derived ribs, and corrections to HBM ribs based on these data have improved HBM’s abilities to predict rib fracture locations.

Methods: We measure and report average and standard deviations (SDs) in rib cross-sectional geometric properties derived from live subject CT scans of 240 adults aged 18–90. Male and female results are given as functions of rib number and rib lengthwise position for ribs 2 through 11. Population means/SDs are reported for measures of rib total area, rib cortical bone area, and rib endosteal area, as well as inertial moment properties of these rib sections. These population corridors are compared between males and females, and against the baseline rib geometries defined in six current HBMs.

Results: Total cross-sectional area results found average males ribs to be larger than those of females by between approximately 1–2 SDs depending on rib number and position, and larger in cortical bone cross-sectional area by between 0–1 SDs. Inertial moment ratios showed female ribs being between approximately 0–1 SDs more elongated than male ribs, dependent again on rib number and position. Rib cross-sectional areas from 5 of the 6 HBMs were found to be overly large along substantial portions of most ribs when compared to average population corridors. Similarly, rib aspect ratios in HBMs deviated from average population data by up to 3 SDs in regions towards sternal rib ends.

Discussion: Overall, while most HBMs capture overall trends such as reductions in cross-section along shaft lengths, many also exhibit local variation that deviates from population trends. This study’s results provide the first reference values for assessing the cross-sectional geometry of human ribs across a wide range of rib levels. Results also further provide clear guidelines to improve rib geometry definitions present in current HBMs in order to better represent their target demographic.
A comparative life cycle assessment of fiber-reinforced polymers as a sustainable reinforcement option in concrete beams
Authors: Sbahieh Sami , Mckay Gordon , Al-Ghamdi Sami G.
Published: May 2023

Environmental awareness and the need for sustainable construction inspired researchers and practitioners to explore innovative alternatives that might reduce greenhouse gas emissions and energy use related to excessive structural work. One such alternative is the utilization of Fiber-Reinforced Polymer (FRP) bars as a reinforcement in reinforced concrete members. FRP bars possess favorable characteristics like high tensile strength, lightweight and corrosion resistance compared to steel. This feature makes FRP bars a potential solution for utilizing seawater instead of fresh water in concrete mixtures, especially in areas facing a harsh climate and water shortage like the Arabian Peninsula. This paper aims to assess and evaluate the environmental impacts through life cycle assessment of glass fiber-reinforced polymer bars, carbon fiber-reinforced polymer, and steel glass fiber reinforced polymer bars compared to steel bars. Moreover, another LCA was conducted comparing steel-reinforced beams made with desalinated fresh water to GFRP/CFRP reinforced beams made with seawater for the concrete mixture. The results indicate that the GFRP bar performed better than the steel bar in 10 out of 14 categories, while the carbon fiber-reinforced polymer bar performed worse than the steel bar in 10 out of 14 categories. The SGFRP bar had a result between the steel and GFRP bar, outperforming the steel bar in 10 categories. Furthermore, the GFRP beam exhibited better environmental performance than the steel beam in 9 out of 14 categories, while the CFRP beam performed better than the steel beam in 8 categories, attributed to the reduction in reinforcement ratio due to the high tensile strength of CFRP and GFRP bars compared to steel bars. Overall, this study sheds light on the possible environmental advantages of using FRP bars in construction and highlights the importance of sustainable construction practices in minimizing environmental impacts.
DNA methylation dynamics during pregnancy
Authors: Fradin Delphine , Tost Jorg , Busato Florence , Mille Clémence , Lachaux Fanny , Deleuze Jean-François , Apter Gisèle , Benachi Alexandra
Published: May 2023

Pregnancy is a state of multiple physiological adaptations. Since methylation of DNA is an epigenetic mechanism that regulates gene expression and contributes to adaptive phenotypic variations, we investigated methylation changes in maternal blood of a longitudinal cohort of pregnant women from the first trimester of gestation to the third. Interestingly, during pregnancy, we found a gain of methylation in genes involved in morphogenesis, such as ezrin, while we identified a loss of methylation in genes promoting maternal-infant bonding (AVP and PPP1R1B). Together, our results provide insights into the biological mechanisms underlying physiological adaptations during pregnancy.
Versatile gold-silver-PB nanojujubes for multi-modal detection and photo-responsive elimination against bacteria
Authors: Zhang Xining , Xiong Youlin , Cai Shuangfei , Wu Ting , Lian Zheng , Wang Chen , Zhang Wei , Yang Rong
Published: May 2023

Bacterial infections have become a serious threat to global public health. Nanomaterials have shown promise in the development of bacterial biosensing and antibiotic-free antibacterial modalities, but single-component materials are often less functional and difficult to achieve dual bacterial detection and killing. Herein, we report a novel strategy based on the effective integration of multi-modal bacterial detection and elimination, by constructing the versatile gold-silver-Prussian blue nanojujubes (GSP NJs) via a facile template etching method. Such incorporation of multi-components involves the utilization of cores of gold nanobipyramids with strong surface-enhanced Raman scattering (SERS) activity, the shells of Prussian blue as both an efficient bio-silent SERS label and an active peroxidase-mimic, and functionalization of polyvinyl pyrrolidone and vancomycin, respectively endowing them with good colloidal dispersibility and specificity against S. aureus. The GSP NJs show operational convenience in the SERS detection and excellent peroxidase-like activity for the sensitive colorimetric detection. Meanwhile, they exhibit robust near-infrared photothermal/photodynamic effects, and the photo-promoted Ag+ ions release, ultimately achieving a high antibacterial efficiency over 99.9% in 5 min. The NJs can also effectively eliminate complex biofilms. The work provides new insights into the design of multifunctional core-shell nanostructures for the integrated bacterial detection and therapy.
A novel, stain-free, natural auto-fluorescent signal, Sig M, identified from cytometric and transcriptomic analysis of infectivity of Cryptosporidium hominis and Cryptosporidium parvum
Authors: Ogbuigwe Paul , Roberts Joanna M. , Knox Matthew A. , Heiser Axel , Pita Anthony , Haack Neville A. , Garcia-Ramirez Juan Carlos , Velathanthiri Niluka , Biggs Patrick J. , French Nigel P. , Hayman David T. S.
Published: May 2023

Cryptosporidiosis is a worldwide diarrheal disease caused by the protozoan Cryptosporidium. The primary symptom is diarrhea, but patients may exhibit different symptoms based on the species of the Cryptosporidium parasite they are infected with. Furthermore, some genotypes within species are more transmissible and apparently virulent than others. The mechanisms underpinning these differences are not understood, and an effective in vitro system for Cryptosporidium culture would help advance our understanding of these differences. Using COLO-680N cells, we employed flow cytometry and microscopy along with the C. parvum-specific antibody Sporo-Glo™ to characterize infected cells 48 h following an infection with C. parvum or C. hominis. The Cryptosporidium parvum-infected cells showed higher levels of signal using Sporo-Glo™ than C. hominis-infected cells, which was likely because Sporo-Glo™ was generated against C. parvum. We found a subset of cells from infected cultures that expressed a novel, dose-dependent auto-fluorescent signal that was detectable across a range of wavelengths. The population of cells that expressed this signal increased proportionately to the multiplicity of infection. The spectral cytometry results confirmed that the signature of this subset of host cells closely matched that of oocysts present in the infectious ecosystem, pointing to a parasitic origin. Present in both C. parvum and C. hominis cultures, we named this Sig M, and due to its distinct profile in cells from both infections, it could be a better marker for assessing Cryptosporidium infection in COLO-680N cells than Sporo-Glo™. We also noted Sig M’s impact on Sporo-Glo™ detection as Sporo-Glo™ uses fluoroscein–isothiocynate, which is detected where Sig M also fluoresces. Lastly, we used NanoString nCounter® analysis to investigate the transcriptomic landscape for the two Cryptosporidium species, assessing the gene expression of 144 host and parasite genes. Despite the host gene expression being at high levels, the levels of putative intracellular Cryptosporidium gene expression were low, with no significant difference from controls, which could be, in part, explained by the abundance of uninfected cells present as determined by both Sporo-Glo™ and Sig M analyses. This study shows for the first time that a natural auto-fluorescent signal, Sig M, linked to Cryptosporidium infection can be detected in infected host cells without any fluorescent labeling strategies and that the COLO-680N cell line and spectral cytometry could be useful tools to advance the understanding of Cryptosporidium infectivity.
Application of hydrological model to simulate streamflow contribution on water balance in Himalaya river basin, Nepal
Authors: Budhathoki Bhumi Raj , Adhikari Tirtha Raj , Shrestha Suraj , Awasthi Ram Prasad
Published: May 2023

Hydrological models are widely used and often regarded as reliable tools for accurately estimating various components of the water balance. In a remote Himalayan catchment, such as Tamakoshi basin, where limited hydrometric dataset is available, such models often provide essential insights that are crucial to water researchers and planners. In this regard, we employed the semi-distributed HBV-light (version 4.0.0.25) hydrological model for glacierized Tamakoshi river basin and attempted to quantify various water balance components. For our model tests, using the daily streamflow records, we selected two distinct periods, i.e., 2004–2008 as a calibration period whilst 2011–2012 for model validation. Based on our findings, the model was able to reasonably predict the streamflow (validation efficiency: Nash-Sutcliffe Efficiency of 0.82 and percent bias −21%). At our site, HBV-light model predicted that the change in streamflow was mostly governed by monsoonal rain (62%) followed by baseflow (20%), glacier melt (13%) and snowmelt (5%). As expected, the streamflow peaked during the month of August where monsoon-induced rain and melting of glaciers significantly contributed to river flow. As a result, monsoon period showcased largest fluctuation in water storage while negligible change was observed during post-monsoon season. Nonetheless, our findings revealed that the baseflow contribution to streamflow was maximum during the month of October and lowest during February. Our findings indicated that the water balance of the Tamakoshi basin is largely influenced by monsoonal rain during June–September window as well as baseflow and glacier melt during the dry season. Runoff components contribution to streamflow was increasing but water storage changes was decreasing in recent decade (2011–2020). We believe our findings are crucial for future initiatives involving water resources, water-induced disaster management, and studies of climate change may benefit from the findings of this study, especially in a region with limited hydrometric data availability.
A review of integrating AI-based chatbots into flipped learning: new possibilities and challenges
Authors: Lo Chung Kwan , Hew Khe Foon
Published: May 2023

This mini review examines the emerging concept of integrating AI-based chatbots into flipped learning and its potential to enhance students’ learning experience. We investigate the design and practice of chatbot-supported flipped learning, as well as the benefits and challenges associated with this approach. Despite an extensive database search, only 10 empirical articles were found, indicating that this cutting-edge research topic requires further exploration. The findings of this review suggest that this emerging instructional approach could result in benefits such as increased student interaction with learning content, improved class preparation, and data-driven teaching and learning. However, potential challenges included limited technical functionality, lacking authenticity, and insufficient student motivation. The review offers insights into future research and development to advance the knowledge and practice of integrating AI chatbots into flipped learning.
Environmental protection or economic growth? The effects of preferences for individual freedoms
Authors: Čábelková Inna , Smutka Luboš , Mareš David , Ortikov Akhmadjon , Kontsevaya Stanislava
Published: May 2023

Environmental protection is often seen in conflict with individual freedom and economic growth. The proponents of environmental protection suggest that the environment is a global resource that must be protected for future generations, even at the expense of economic growth and individual freedoms. The opponents claim that environmental protection should not come at the expense of individual rights and liberties, economic growth included. This paper studies the associations between public preferences for environmental protection, economic growth, and individual freedoms in eleven post-soviet countries on a representative dataset (N = 20006, age 18+, M ± SD: 46,04 ± 17,07; 58% women, 46,8% upper education). Methodologically we rely on correlations, principal component analysis, and ordinal regression analyses. The results suggest that preferences for most personal freedoms studied predict environmental protection and economic growth preferences. In addition, preferences for civil rights, rights for democracy, gender equality, income inequality, and the low role of the army in politics predicted higher preferences for environmental protection and economic growth. Interestingly, the government’s right to video surveillance in public areas, though diminishing personal freedoms in terms of anonymity, predicted higher preferences for environmental protection and economic growth. The importance of God in lives proved to increase preferences for environmental protection but was negatively related to preferences for economic growth. We suggest the government communicate the need for environmental protection as a part of the rights for individual freedom to live in a clean environment.
The potential of sodium carbonate and Tiron extractions for the determination of silicon contents in plant samples—A method comparison using hydrofluoric acid digestion as reference
Authors: Puppe Daniel , Kaczorek Danuta , Buhtz Christian , Schaller Jörg
Published: May 2023

For the determination of silicon (Si) contents in plant materials several methods are in use, but as all of these methods exhibit specific advantages and drawbacks, none of them has become prevalent. Alkaline chemicals are widely used to extract Si from plant samples, because this method is comparably simple, fast, and cheap. However, a comprehensive method comparison between different alkaline extractions to different plant organs is still missing, as well as understanding of the relationship between Si content quantified with those methods and soil silicon availability. In our study we performed two different alkaline (sodium carbonate (Na2CO3) and Tiron) extractions to determine Si contents in husk and straw samples of winter wheat (Triticum aestivum). Results obtained from hydrofluoric (HF) acid digestion were used as reference as this method is assumed to completely dissolve Si in a plant material. We evaluated the efficacy of simple, single-step Na2CO3 and Tiron extractions in relation to complex, multistep HF extractions and analyzed the relationships between Si and phytolith contents in plant samples and plant available Si concentrations in corresponding soil samples. Irrespective of the plant material used (husk or straw) we found Tiron to be more efficient in Si extraction compared to Na2CO3. While Na2CO3 extractions systematically underestimated Si contents in the tested plant materials, the results of Tiron extractions were comparable to the results of HF digestions, at least for husk samples. Phytolith contents in plant samples were strongly positively correlated to Si contents obtained from extractions, especially in husk samples. Plant available Si in soil samples was also reflected best in husk Si contents. Based on our results we recommend the use of Tiron for the extraction of Si from plant materials as this method provided more reliable results compared to the Na2CO3 extraction.
The role of Raptor in lymphocytes differentiation and function
Authors: Tang Jianing , Yang Lu , Guan Fei , Miller Heather , Camara Niels Olsen Saraiva , James Louisa K. , Benlagha Kamel , Kubo Masato , Heegaard Steffen , Lee Pamela , Lei Jiahui , Zeng Hu , He Chengwei , Zhai Zhimin , Liu Chaohong
Published: May 2023

Raptor, a key component of mTORC1, is required for recruiting substrates to mTORC1 and contributing to its subcellular localization. Raptor has a highly conserved N-terminus domain and seven WD40 repeats, which interact with mTOR and other mTORC1-related proteins. mTORC1 participates in various cellular events and mediates differentiation and metabolism. Directly or indirectly, many factors mediate the differentiation and function of lymphocytes that is essential for immunity. In this review, we summarize the role of Raptor in lymphocytes differentiation and function, whereby Raptor mediates the secretion of cytokines to induce early lymphocyte metabolism, development, proliferation and migration. Additionally, Raptor regulates the function of lymphocytes by regulating their steady-state maintenance and activation.
Influence of smoke suppressant on the smoke inhibition effect and properties of different types of asphalt
Authors: Liang Hehao , Zhao Pu , Xu Ruifeng , Liang Xiayi , Xiao Xin , Shi Liwan , Lv Jin
Published: May 2023

The current understanding of the influence of smoke suppressants on the smoke inhibition effect and working performance of different types of asphalt is limited. In this study, portable gas detector (PGD) tests were used to investigate the influence of the smoke suppressant on different types of asphalt and the smoke purification effect. Subsequently, gas chromatography-mass spectrometry (GC-MS) was used to analyze the influence of the smoke suppressant on the volatile organic compounds (VOCs) in different types of asphalt fume, so as to compare and verify the PGD tests results. Finally, scanning electron microscopy and energy dispersive spectrometry were used to observe and analyze the influence of the smoke suppressant on the microstructure and element composition of different types of asphalt. The results show that the smoke suppressant can purify various harmful gases volatilized from different types of asphalt, but the effect and the optimal dosage of smoke suppressant are slightly different. The purification rate of the smoke suppressant for SO2 or H2S in the fumes of various asphalts can reach >70% and the NO and VOC purification rates can reach >40%. The influence of the smoke suppressant on the VOC purification rate of different asphalts detected through the GC-MS and PGD tests is similar. The smoke suppressant has little effect on the asphalt surface microstructure and on the changes in the element content in asphalt, indicating that it has no effect on the main properties of the asphalt itself. This study is helpful to further understand the relationship between smoke suppressants and the smoke inhibition effect and the working performance of different types of asphalt. Additionally, it provides basis and guidance for the development of low-smoke asphalt with a better emission reduction effect, which has a certain guiding and application significance.
Utility of MF-non coding region for measles molecular surveillance during post-elimination phase, Spain, 2017–2020
Authors: Jacqueline Camille , Gavilán Ana María , López-Perea Noemí , Penedos Ana Raquel , Masa-Calles Josefa , Echevarría Juan E. , Fernández-García Aurora ,   on behalf of the MMR Study Group
Published: May 2023

Background

In countries entering the post-elimination phase for measles, the study of variants by sequencing of 450 nucleotides of the N gene (N450) does not always allow the tracing of chains of transmission. Indeed, between 2017 and 2020, most measles virus sequences belonged to either the MVs/Dublin.IRL/8.16 (B3-Dublin) or the MVs/Gir Somnath.IND/42.16 (D8-Gir Somnath) variants. We evaluated the additional use of a non-coding region (MF-NCR) as a tool to enhance resolution and infer case origin, chains of transmission and characterize outbreaks.

Methods

We obtained 115 high-quality MF-NCR sequences from strains collected from Spanish patients infected with either B3-Dublin or D8-Gir Somnath variants between 2017 and 2020, performed epidemiological, phylogenetic and phylodynamic analyses and applied a mathematical model to determine relatedness among identified clades.

Results

Applying this model allowed us to identify phylogenetic clades potentially derived from concomitant importations of the virus rather than single chain of transmission, inferred based on only N450 and epidemiology data. In a third outbreak, we found two related clades that corresponded to two chains of transmission.

Discussion

Our results show the ability of the proposed method to improve identification of simultaneous importations in the same region which could trigger enhanced contact tracing. Moreover, the identification of further transmission chains indicates that the size of import-related outbreaks was smaller than previously found, supporting the interpretation that endemic measles transmission was absent in Spain between 2017 and 2020. We suggest considering the use of the MF-NCR region in conjunction with the study of N450 variants in future WHO recommendations for measles surveillance.
Potential effect of key soil bacterial taxa on the increase of rice yield under milk vetch rotation
Authors: Xia Mingming , Ma Xinling , Liu Jia , Wu Meng , Li Zhongpei , Liu Ming
Published: May 2023

Legume crop rotation is often adopted in rice cultivation to improve soil productivity. However, little is known about the role of microbes under legume rotation in affecting soil productivity. To elucidate this, a long-term paddy cropping experiment was set up to study the relationship between crop yield, soil chemical properties, and key microbial taxa under a double-rice and milk vetch rotation. Milk vetch rotation significantly improved soil chemical properties compared to no fertilization treatment, and soil phosphorus was a major factor correlated with crop yield. Long-term legume rotation increased soil bacterial alpha diversity and changed soil bacterial community. After milk vetch rotation, the relative abundances of Bacteroidota, Desulfobacterota, Firmicutes, and Proteobacteria increased while those of Acidobacteriota, Chloroflexi, and Planctomycetota decreased. Moreover, milk vetch rotation increased the relative abundance of phosphorus-related gene K01083 (bpp), which was significantly correlated with soil phosphorus content and crop yield. Network analysis showed that taxa of Vicinamibacterales were positively correlated with total phosphorus and available phosphorus, which was a potential taxon contributing to the availability of soil phosphorus stock. Our results indicated that milk vetch rotation could enrich key taxa with latent phosphate-solubilizing ability, increase the content of soil available phosphorus, and finally enhance crop yield. This could provide scientific guidance for better crop production.
Estimated glomerular filtration rate is a biomarker of cognitive impairment in Parkinson’s disease
Authors: Qu Yi , Qin Qi-Xiong , Wang Dan-Lei , Li Jiang-Ting , Zhao Jing-Wei , An Ke , Li Jing-Yi , Mao Zhi-Juan , Min Zhe , Xiong Yong-Jie , Xue Zheng
Published: May 2023

Backgrounds

The relationship between kidney function and cognitive impairment in Parkinson’s disease (PD) is poorly understood and underexplored. This study aims to explore whether renal indices can serve as indicators to monitor the cognitive impairment of PD.

Methods

A total of 508 PD patients and 168 healthy controls from the Parkinson’s Progression Markers Initiative (PPMI) were recruited, and 486 (95.7%) PD patients underwent longitudinal measurements. The renal indicators including serum creatinine (Scr), uric acid (UA), and urea nitrogen, as well as UA/Scr ratio and estimated glomerular filtration rate (eGFR), were measured. Cross-sectional and longitudinal associations between kidney function and cognitive impairment were evaluated using multivariable-adjusted models.

Results

eGFR was associated with lower levels of cerebrospinal fluid (CSF) Aβ1–42 (p = 0.0156) and α-synuclein (p = 0.0151) and higher serum NfL (p = 0.0215) in PD patients at baseline. Longitudinal results showed that decreased eGFR predicted a higher risk of cognitive impairment (HR = 0.7382, 95% CI = 0.6329–0.8610). Additionally, eGFR decline was significantly associated with higher rates of increase in CSF T-tau (p = 0.0096), P-tau (p = 0.0250), and serum NfL (p = 0.0189), as well as global cognition and various cognitive domains (p < 0.0500). The reduced UA/Scr ratio was also linked to higher NfL levels (p = 0.0282) and greater accumulation of T-tau (p = 0.0282) and P-tau (p = 0.0317). However, no significant associations were found between other renal indices and cognition.

Conclusion

eGFR is altered in PD subjects with cognitive impairment, and predict larger progression of cognitive decline. It may assist identifying patients with PD at risk of rapid cognitive decline and have the potential to monitoring responses to therapy in future clinical practice.
Identifying reproducible resting state networks and functional connectivity alterations following chronic restraint stress in anaesthetized rats
Authors: Dai Twain , Seewoo Bhedita J. , Hennessy Lauren A. , Bolland Samuel J. , Rosenow Tim , Rodger Jennifer
Published: May 2023

Background

Resting-state functional MRI (rs-fMRI) in rodent models have the potential to bridge invasive experiments and observational human studies, increasing our understanding of functional alterations in the brains of patients with depression. A major limitation in current rodent rs-fMRI studies is that there has been no consensus on healthy baseline resting-state networks (RSNs) that are reproducible in rodents. Therefore, the present study aimed to construct reproducible RSNs in a large dataset of healthy rats and then evaluate functional connectivity changes within and between these RSNs following a chronic restraint stress (CRS) model within the same animals.

Methods

A combined MRI dataset of 109 Sprague Dawley rats at baseline and after two weeks of CRS, collected during four separate experiments conducted by our lab in 2019 and 2020, was re-analysed. The mICA and gRAICAR toolbox were first applied to detect optimal and reproducible ICA components and then a hierarchical clustering algorithm (FSLNets) was applied to construct reproducible RSNs. Ridge-regularized partial correlation (FSLNets) was used to evaluate the changes in the direct connection between and within identified networks in the same animals following CRS.

Results

Four large-scale networks in anesthetised rats were identified: the DMN-like, spatial attention-limbic, corpus striatum, and autonomic network, which are homologous across species. CRS decreased the anticorrelation between DMN-like and autonomic network. CRS decreased the correlation between amygdala and a functional complex (nucleus accumbens and ventral pallidum) in the right hemisphere within the corpus striatum network. However, a high individual variability in the functional connectivity before and after CRS within RSNs was observed.

Conclusion

The functional connectivity changes detected in rodents following CRS differ from reported functional connectivity alterations in patients with depression. A simple interpretation of this difference is that the rodent response to CRS does not reflect the complexity of depression as it is experienced by humans. Nonetheless, the high inter-subject variability of functional connectivity within networks suggests that rats demonstrate different neural phenotypes, like humans. Therefore, future efforts in classifying neural phenotypes in rodents might improve the sensitivity and translational impact of models used to address aetiology and treatment of psychiatric conditions including depression.
A single intranasal dose of human mesenchymal stem cell-derived extracellular vesicles after traumatic brain injury eases neurogenesis decline, synapse loss, and BDNF-ERK-CREB signaling
Authors: Kodali Maheedhar , Madhu Leelavathi N. , Reger Roxanne L. , Milutinovic Bojana , Upadhya Raghavendra , Attaluri Sahithi , Shuai Bing , Shankar Goutham , Shetty Ashok K.
Published: May 2023

An optimal intranasal (IN) dose of human mesenchymal stem cell-derived extracellular vesicles (hMSC-EVs), 90 min post-traumatic brain injury (TBI), has been reported to prevent the evolution of acute neuroinflammation into chronic neuroinflammation resulting in the alleviation of long-term cognitive and mood impairments. Since hippocampal neurogenesis decline and synapse loss contribute to TBI-induced long-term cognitive and mood dysfunction, this study investigated whether hMSC-EV treatment after TBI can prevent hippocampal neurogenesis decline and synapse loss in the chronic phase of TBI. C57BL6 mice undergoing unilateral controlled cortical impact injury (CCI) received a single IN administration of different doses of EVs or the vehicle at 90 min post-TBI. Quantifying neurogenesis in the subgranular zone-granule cell layer (SGZ-GCL) through 5′-bromodeoxyuridine and neuron-specific nuclear antigen double labeling at ~2 months post-TBI revealed decreased neurogenesis in TBI mice receiving vehicle. However, in TBI mice receiving EVs (12.8 and 25.6 × 109 EVs), the extent of neurogenesis was matched to naive control levels. A similar trend of decreased neurogenesis was seen when doublecortin-positive newly generated neurons were quantified in the SGZ-GCL at ~3 months post-TBI. The above doses of EVs treatment after TBI also reduced the loss of pre-and post-synaptic marker proteins in the hippocampus and the somatosensory cortex. Moreover, at 48 h post-treatment, brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and phosphorylated cyclic AMP response-element binding protein (p-CREB) levels were downregulated in TBI mice receiving the vehicle but were closer to naïve control levels in TBI mice receiving above doses of hMSC-EVs. Notably, improved BDNF concentration observed in TBI mice receiving hMSC-EVs in the acute phase was sustained in the chronic phase of TBI. Thus, a single IN dose of hMSC-EVs at 90 min post-TBI can ease TBI-induced declines in the BDNF-ERK-CREB signaling, hippocampal neurogenesis, and synapses.
Prognostic and recurrent significance of SII in patients with pancreatic head cancer undergoing pancreaticoduodenectomy
Authors: Chen Qing , Ren Siqian , Cui Songping , Huang Jincan , Wang Di , Li Binglin , He Qiang , Lang Ren
Published: May 2023

Background

To investigate the clinical significance of preoperative inflammatory status in patients with pancreatic head carcinoma (PHC), we performed a single-center study to assess it.

Method

We studied a total of 164 patients with PHC undergoing PD surgery (with or without allogeneic venous replacement) from January 2018 to April 2022. Systemic immune-inflammation index (SII) was the most important peripheral immune index in predicting the prognosis according to XGBoost analysis. The optimal cutoff value of SII for OS was calculated according to Youden index based on the receiver operating characteristic (ROC) curve and the cohort was divided into Low SII group and High SII group. Demographic, clinical data, laboratory data, follow-up data variables were obtained and compared between the two groups. Kaplan-Meier curves, univariable and multivariable Cox regression models were used to determine the association between preoperative inflammation index, nutritional index and TNM staging system with OS and DFS respectively.

Results

The median follow-up time was 16 months (IQR 23), and 41.4% of recurrences occurred within 1 year. The cutoff value of SII was 563, with a sensitivity of 70.3%, and a specificity of 60.7%. Peripheral immune status was different between the two groups. Patients in High SII group had higher PAR, NLR than those in Low SII group (P <0.01, <0.01, respectively), and lower PNI (P <0.01). Kaplan–Meier analysis showed significantly poorer OS and DFS (P < 0.001, <0.001, respectively) in patients with high SII. By using the multivariable Cox regression model, high SII (HR, 2.056; 95% CI, 1.082–3.905, P=0.028) was significant predictor of OS. Of these 68 high-risk patients who recurrence within one year, patients with widespread metastasis had lower SII and worse prognosis (P <0.01).

Conclusion

High SII was significantly associated with poor prognosis in patients with PHC. However, in patients who recurrence within one year, SII was lower in patients at TNM stage III. Thus, care needs to be taken to differentiate those high-risk patients.
Real-world treatment patterns and outcomes among individuals receiving first-line pembrolizumab therapy for recurrent/metastatic head and neck squamous cell carcinoma
Authors: Black Christopher M. , Hanna Glenn J. , Wang Liya , Ramakrishnan Karthik , Goto Daisuke , Turzhitsky Vladimir , Hair Gleicy M.
Published: May 2023

Background

Pembrolizumab, a PD-1 immune checkpoint inhibitor, is approved as first-line (1L) treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) as monotherapy or in combination with platinum and 5-fluorouracil chemotherapy. Limited data exist on the use of these regimens in real-world settings.

Objective

Our primary objectives were to describe baseline characteristics and real-world overall survival (rwOS), time on treatment (rwToT), and time to next treatment (rwTTNT) among individuals with R/M HNSCC receiving approved 1L pembrolizumab therapies. We also aimed to identify baseline factors associated with choice of 1L pembrolizumab therapy and with rwOS.

Methods

This was a retrospective cohort study of adults with R/M HNSCC receiving 1L pembrolizumab monotherapy or pembrolizumab plus chemotherapy. We used Kaplan-Meier analyses to assess real-world outcomes, logistic regression modeling to identify factors associated with choice of 1L pembrolizumab therapy, and Cox proportional hazards models to identify factors associated with rwOS.

Results

The study population included 431 individuals receiving 1L pembrolizumab monotherapy and 215 receiving 1L pembrolizumab plus chemotherapy. The use of 1L pembrolizumab monotherapy was associated with higher baseline combined positive score for PD-L1 expression, older age, higher Eastern Cooperative Oncology Group performance status (ECOG PS), laryngeal tumor site, and human papillomavirus (HPV)-positive tumor status. The pembrolizumab monotherapy group had a median (95% CI) rwOS of 12.1 (9.2–15.1) months, rwToT of 4.2 (3.5–4.6) months, and rwTTNT of 6.5 (5.4–7.4) months. Among this group, HPV-positive tumor status and lower ECOG PS were associated with longer rwOS, and oral cavity tumor site with shorter rwOS. The pembrolizumab plus chemotherapy cohort had a median (95% CI) rwOS of 11.9 (9.0–16.0) months, rwToT of 4.9 (3.8–5.6) months, and rwTTNT of 6.6 (5.8–8.3) months. In this group, HPV-positive tumor status was associated with longer rwOS.

Conclusions

This study adds to clinical trial data by summarizing real-world treatment outcomes with 1L pembrolizumab-containing therapies in a more heterogeneous population. Overall survival outcomes in both treatment groups were similar to those observed in the registration clinical trial. These findings support the use of pembrolizumab as standard of care for R/M HNSCC.
A systematic review and meta-analysis for the association of the insulin-like growth factor1 pathway genetic polymorphisms with colorectal cancer susceptibility
Authors: Cheraghpour Makan , Askari Masomeh , Tierling Sascha , Shojaee Sajad , Sadeghi Amir , Ketabi Moghadam Pardis , Khazdouz Maryam , Asadzadeh Aghdaei Hamid , Piroozkhah Moein , Nazemalhosseini-Mojarad Ehsan , Fatemi Nayeralsadat
Published: May 2023

Background

The receptors, ligands, and associated proteins of the insulin-like growth factor (IGF) family are involved in cancer development. The IGF1 receptor and its accompanying signaling cascade are a crucial growth-regulatory mechanism that plays an important role in colorectal cancer (CRC) proliferation and differentiation. IRS1 (Insulin receptor substrate-1), a major substrate for the IGF1R, is involved in cell growth and promotes tumorigenesis. There are shreds of evidence from prior research suggesting that IGF system polymorphisms may influence susceptibility to CRC. However, the findings in this area were contradictory. Accordingly, we carried out a systematic literature search to identify all case-control, cross-sectional, and cohort studies on the association between various polymorphisms across four IGF1 pathway genes (IGF1, IGF1R, IRS1, and IRS2) and the risk of CRC.

Methods

We performed a comprehensive search strategy in PubMed, Scopus, and Web of Science databases for articles available until Aug 30, 2022. A total of 26 eligible studies with IGF1/IGF1R, IRS1 and IRS2 polymorphisms; met the inclusion criteria. All case-control studies for IGF1 rs6214C>T, IRS1 rs1801278G>A, and IRS2 rs1805097G>A comprising 22,084 cases and 29,212 controls were included in the current meta-analysis. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate relationships between the polymorphisms and CRC susceptibility. All statistical analyses were performed using STATA software version 14.0.

Results

The meta-analysis of available data for rs6214C>T, rs1801278G>A, and rs1805097G>A showed a significant association between these polymorphisms and an increased CRC risk in some of the comparisons studied (rs6214C>T, pooled OR for CC = 0.43, 95% CI 0.21- 0.87, P = 0.019; rs1801278G>A, OR for GA = 0.74, 95% CI 0.58-0.94, P = 0.016; rs1805097G>A, OR for GA = 0.83, 95% CI 0.71-0.96, P = 0.013). Nevertheless, the meta-analysis did not include other genetic variations in IGF1, IGF1R, IRS1, and IRS2 due to heterogeneity and limited sample size.

Conclusions

This systematic review and meta-analysis provide evidence that genetic variants in IGF1 rs6214C>T, IRS1 rs1801278G>A, and IRS2 rs1805097G>A are associated with an increased risk of CRC. These findings may contribute to a better understanding of the complex genetic mechanisms involved in CRC development and could inform future research on prevention and treatment strategies for this disease.
Inpatient prescribing patterns of long-acting injectables and their oral or short-acting injectable equivalent formulations
Authors: Liu Yifei , Patterson Mark E. , Sahil Suman , Stoner Steven C.
Published: May 2023

Background: Long-acting injectable (LAI) antipsychotics (APs) each have an oral equivalent formulation, while aripiprazole, olanzapine, and ziprasidone each also have a short-acting injectable (SAI) equivalent formulation. Inpatient prescribing patterns of LAIs and their oral/SAI equivalents are less characterized in populations other than Medicaid, Medicare, and Veterans Affairs populations. Mapping out inpatient prescribing patterns remains an important first step to ensure appropriate use of antipsychotics during this critical juncture of patient care prior to discharge. This study determined inpatient prescribing patterns of first- (FGA) and second-generation antipsychotic (SGA) LAIs and their oral/SAI formulations.

Methods: This was a large retrospective study using the Cerner Health Facts® database. Hospital admissions due to schizophrenia, schizoaffective disorder, or bipolar disorder from 2010 to 2016 were identified. AP utilization was defined as the proportion of inpatient stays during which at least 1 AP was administered to the total number of inpatient visits over the observed period. Descriptive analyses were used to determine prescribing patterns for APs. Chi-square tests were used to determine utilization differences across years.

Results: 94,989 encounters were identified. Encounters during which oral/SAI of SGA LAIs were administered were most common (n = 38,621, 41%). Encounters during which FGA LAIs or SGA LAIs were administered were the least common (n = 1,047, 1.1%). Prescribing patterns differed across years (p < 0.05) within the SGA LAI subgroup analysis (N = 6,014). Paliperidone palmitate (63%, N = 3,799) and risperidone (31%, N = 1,859) were the most frequently administered. Paliperidone palmitate utilization increased from 30% to 72% (p < 0.001), while risperidone utilization decreased from 70% to 18% (p < 0.001).

Conclusions: Compared with their oral or SAI formulations, LAIs were underutilized from 2010 to 2016. Among SGA LAIs, the prescribing patterns of paliperidone palmitate and risperidone changed significantly.
Development of a novel copper metabolism-related risk model to predict prognosis and tumor microenvironment of patients with stomach adenocarcinoma
Authors: Sun Dongjie , Zhang Haiying , Zhang Chi
Published: May 2023

Background: Stomach adenocarcinoma (STAD) is the fourth highest cause of cancer mortality worldwide. Alterations in copper metabolism are closely linked to cancer genesis and progression. We aim to identify the prognostic value of copper metabolism-related genes (CMRGs) in STAD and the characteristic of the tumor immune microenvironment (TIME) of the CMRG risk model.

Methods: CMRGs were investigated in the STAD cohort from The Cancer Genome Atlas (TCGA) database. Then, the hub CMRGs were screened out with LASSO Cox regression, followed by the establishment of a risk model and validated by GSE84437 from the Expression Omnibus (GEO) database. The hub CMRGs were then utilized to create a nomogram. TMB (tumor mutation burden) and immune cell infiltration were investigated. To validate CMRGs in immunotherapy response prediction, immunophenoscore (IPS) and IMvigor210 cohort were employed. Finally, data from single-cell RNA sequencing (scRNA-seq) was utilized to depict the properties of the hub CMRGs.

Results: There were 75 differentially expressed CMRGs identified, 6 of which were linked with OS. 5 hub CMRGs were selected by LASSO regression, followed by construction of the CMRG risk model. High-risk patients had a shorter life expectancy than those low-risk. The risk score independently predicted STAD survival through univariate and multivariate Cox regression analyses, with ROC calculation generating the highest results. This risk model was linked to immunocyte infiltration and showed a good prediction performance for STAD patients’ survival. Furthermore, the high-risk group had lower TMB and somatic mutation counters and higher TIDE scores, but the low-risk group had greater IPS-PD-1 and IPS-CTLA4 immunotherapy prediction, indicating a higher immune checkpoint inhibitors (ICIs) response, which was corroborated by the IMvigor210 cohort. Furthermore, those with low and high risk showed differential susceptibility to anticancer drugs. Based on CMRGs, two subclusters were identified. Cluster 2 patients had superior clinical results. Finally, the copper metabolism-related TIME of STAD was concentrated in endothelium, fibroblasts, and macrophages.

Conclusion: CMRG is a promising biomarker of prognosis for patients with STAD and can be used as a guide for immunotherapy.