bluuebunny/crossref_metadata_2025 huggingface dataset:
Encarceramento em Massa:
Authors: Cozza Sayão Sandro , Bezerra Acioly Dimitri Alexandre
Published: February 2024

Recebido: 08/04/2022

Aprovado: 06/09/2023

O encarceramento em massa é um dado da realidade brasileira aferível a partir da taxa de aprisionamento, que cresce vertiginosamente há duas décadas. Apesar disso, a opinião pública vê-se dominada por falas radicais que pretendem prender mais, por mais tempo e com maior rigor. Com base no conceito de enquadramento em Butler, o artigo defende que esse processo se alimenta da divisão entre pessoas que são consideradas dignas de amparo em detrimento das demais. Adota-se, então, perspectiva crítica a este paradigma, citando o trabalho de grupos religiosos na prisão como exemplo de ação contrária às vozes populistas. Numa perspectiva epistemológica sobre o problema, as ideias de duração em Bergson e alteridade na ética de Levinas são mobilizadas para rechaçar qualquer tentativa de mitigar a incidência dos direitos humanos na prisão e desconstruir a divisão essencialista entre criminoso e cidadão de bem.

Palavras-chave: Encarceramento em massa. Enquadramento. Alteridade. Duração.
Western Do Tempo Presente
Authors: Carreiro Marcelo , Alves Diogo
Published: February 2024

Recebido: 29/05/2021

Aprovado: 18/11/2023

Os jogos são uma fonte histórica, revelando através das suas técnicas de produção como os jogos representam grupos, ideais, política e sociedade em suas histórias, de maneira completamente diferente dos tradicionais livros e filmes. É através de documentos textuais, ou subjetivismo que os jogos representam valores simbólicos, que por sua vez podem ser intrínsecos a grupos específicos, que como as mulheres e os negros lutam pela legitimação de seus discursos – como defendemos ser o caso no jogo “Red Dead Redemption II”. Para resolver a questão metodológica de tratamento da mídia, foi necessário criar um ferramental que, a partir de uma série de documentos diegéticos ao jogo (como cartas e jornais), fosse capaz de revelar as representações sobre grupos e seus discursos. Através dessas premissas foi possível compreender como os jogos são capazes de criarem novas narrativas sobre grupos no passado, a partir do seu tempo de produção, bem como criar uma metodologia que auxilie novas pesquisas de jogos.

Palavras-chave: História; Modernidade; videogames.
Analysis of Conversational Implicature in “Burnt” Movie Directed by John Wells
Authors: Hamsah Silvana , Aso La , Martisa Ela
Published: February 2024

The objective of this research is to identify and describe the use of conversational implicature in the “Burnt” movie. The researcher used the implicature theory by Paul Grice to analyze the conversational implicature. The research methodology used in this research is a qualitative descriptive method. The source of this research is the data from the “Burnt” movie. To collect data, the researcher used several steps: watching the movie, pausing the movie that has conversational implicature, annotating the data, screenshotting the data, coding the data, and lastly reducing the data to present the needed data only. The result shows that both generalized and particularized conversational implicature is identified with the flouting maxim and the utterance that flouts the maxim has speech function. The use of conversational implicature in the character’s utterances is such as useful for conducting good communication in the workplace. The characters use conversational implicature to convey the intention conveyed politely and quickly.
Studi Kekerasan Dan Struktur Mikro Pada Komposit Paduan Serbuk AL+SN Berpenguat Resin
Authors: Asiri Muhammad Halim
Published: February 2024

Komposit merupakan salah satu bahan alternatif yang banyak digunakan untuk menggantikan bahan-bahan konvensional yang dari segi kuantitas dan kualitasnya semakin menurun. Salah satu dari bahan konvensional tersebut adalah alumunium (Al) dan timah (Sn) yang selama ini dikenal sebagai bahan yang mempunyai sifat fisika ringan, plastis, dan tahan terhadap korosi dengan memanfaatkan sistem proses pembuatan komposit serbuk metalurgi. Penelitian ini bertujuan untuk mengetahui kekerasan dan struktur mikro pada analisis paduan komposit serbuk logam Al+Sn berpenguat campuran resin. Metode penelitian yag dilakukan menggunakan metode Brinell merupakan metode pengukuran kekerasan suatu bahan yang paling banyak dilakukan. Hasil analisis pengamatan struktur mikro menunjukkan bahwa terdapat tiga jenis unsur yang terbentuk yaitu unsur Al+Sn berwarna kekuning- kuningan unsur Sn berwarna puti mengkilap dan terdapat porositas, Sehingga didapatkan perbandingan nilai kekerasan rata-rata yang berbeda pada masing-masing spesimen. Spesimen dengan komposisi Al 50% - Sn 50% nilai kekersan rata-rata sebesar 51,67 N/mm2, komposisi Al 60% - Sn 40% nilai kekersan rata-rata sebesar 55,86 N/mm2, komposisi Al 70% - Sn 30% nilai kekersan rata-rata sebesar 64,69 N/mm2, komposisi Al 80% - Sn 20% nilai kekerasan rata-rata sebesar 68,01 N/mm2, komposisi Al 90% - Sn 10% nilai kekerasan rata-rata sebesar 64,77 N/mm2, Dari hasil paduan yang dilakuakn menunjukan bahwa semakin besar presentase kandungan aluminum (Al) pada paduan timah (Sn) maka nilai kekerasan yang dihasilakn semakin meningkat
Vortex Temporum de Gérard Grisey sob a ótica do regente
Authors: Muniz André , Lima Erickinson
Published: February 2024

O presente trabalho nasce a partir da experiência docente e performativa dos autores, e suas linhas tentam trazer à luz as particularidades técnico-performativas da regência de Vortex Temporum de Gérard Grisey. Seguimos na contramão do pensamento comum, e estruturamos o percurso descritivo sob a óptica de Norman Del Mar para sugerir a construção performativa da obra. Em diálogo com essa perspectiva, propomos um modelo conceitual de edificação interpretativa embasada por cinco elos: contextualização, exploração emocional desse contexto, coativação, devir e posicionamento autocrítico. Por fim, complementando o método expositivo-dialogado, trazemos a voz dos instrumentistas que apontam o desvencilhar técnico no discurso dos instrumentos que compõem a composição.
Snowflake: visualizing microbiome abundance tables as multivariate bipartite graphs
Authors: Peeters Jannes , Bot Daniël M. , Rovelo Ruiz Gustavo , Aerts Jan
Published: February 2024

Current visualizations in microbiome research rely on aggregations in taxonomic classifications or do not show less abundant taxa. We introduce Snowflake: a new visualization method that creates a clear overview of the microbiome composition in collected samples without losing any information due to classification or neglecting less abundant reads. Snowflake displays every observed OTU/ASV in the microbiome abundance table and provides a solution to include the data’s hierarchical structure and additional information obtained from downstream analysis (e.g., alpha- and beta-diversity) and metadata. Based on the value-driven ICE-T evaluation methodology, Snowflake was positively received. Experts in microbiome research found the visualizations to be user-friendly and detailed and liked the possibility of including and relating additional information to the microbiome’s composition. Exploring the topological structure of the microbiome abundance table allows them to quickly identify which taxa are unique to specific samples and which are shared among multiple samples (i.e., separating sample-specific taxa from the core microbiome), and see the compositional differences between samples. An R package for constructing and visualizing Snowflake microbiome composition graphs is available at https://gitlab.com/vda-lab/snowflake.
Therapeutic effects and underlying mechanism of poly (L-glutamic acid)-g-methoxy poly (ethylene glycol)/combretastatin A4/BLZ945 nanoparticles on Renca renal carcinoma
Authors: Chen Jiaqi , Yin Min , Yang Chenguang , Wang Kun , Ma Lili , Yu Haiyang , Huang Yue , Liu Feng , Tang Zhaohui
Published: February 2024

Introduction: The prognosis of advanced renal carcinoma is not ideal, necessitating the exploration of novel treatment strategies. Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/Combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) possess the dual capability of CA4 (targeting blood vessels to induce tumor necrosis) and BLZ945 (inducing M2 macrophage apoptosis), thereby inhibiting tumor growth.

Methods: Here, the therapeutic effects and underlying mechanism was explored by CCK-8 cytotoxicity experiment, transwell cell invasion and migration experiment, H&E, western blot analysis, immunohistochemistry, flow cytometry, and other techniques.

Results: These results demonstrated that CB-NPs could inhibit the growth of Renca cells and subcutaneous tumors in mice, with an impressive tumor inhibition rate of 88.0%. Results suggested that CB-NPs can induce necrosis in renal carcinoma cells and tissues, downregulate VEGFA expression, promote renal carcinoma cell apoptosis, and reduce the polarization of M2 macrophages.

Discussion: These findings offer innovative perspectives for the treatment of advanced renal carcinoma.
Biomechanical evaluation on a new type of vertebral titanium porous mini-plate and mechanical comparison between cervical open-door laminoplasty and laminectomy: a finite element analysis
Authors: Lin Zhiwei , Lin Dongxin , Xu Lin , Chen Qiwei , Vashisth Manoj Kumar , Huang Xuecheng , Deng Yuping , Zhang Feihu , Huang Wenhua
Published: February 2024

Objective: Compare the spine’s stability after laminectomy (LN) and laminoplasty (LP) for two posterior surgeries. Simultaneously, design a new vertebral titanium porous mini plate (TPMP) to achieve firm fixation of the open-door vertebral LP fully. The objective is to enhance the fixation stability, effectively prevent the possibility of “re-closure,” and may facilitate bone healing.

Methods: TPMP was designed by incorporating a fusion body and porous structures, and a three-dimensional finite element cervical model of C2-T1 was constructed and validated. Load LN and LP finite element models, respectively, and analyze and simulate the detailed processes of the two surgeries. It was simultaneously implanting the TPMP into LP to evaluate its biomechanical properties.

Results: We find that the range of motion (ROM) of C4-C5 after LN surgery was greater than that of LP implanted with different plates alone. Furthermore, flexion-extension, lateral bending, and axial rotation reflect this change. More noteworthy is that LN has a much larger ROM on C2-C3 in axial rotation. The ROM of LP implanted with two different plates is similar. There is almost no difference in facet joint stress in lateral bending. The facet joint stress of LN is smaller on C2-C3 and C4-C5, and larger more prominent on C5-C6 in the flexion-extension. Regarding intervertebral disc pressure (IDP), there is little difference between different surgeries except for the LN on C2-C3 in axial rotation. The plate displacement specificity does not significantly differ from LP with vertebral titanium mini-plate (TMP) and LP with TPMP after surgery. The stress of LP with TPMP is larger in C4-C5, C5-C6. Moreover, LP with TMP shows greater stress in the C3-C4 during flexion-extension and lateral bending.

Conclusion: LP may have better postoperative stability when posterior approach surgery is used to treat CSM; at the same time, the new type of vertebral titanium mini-plate can achieve almost the same effect as the traditional titanium mini-plate after surgery for LP. In addition, it has specific potential due to the porous structure promoting bone fusion.
Is resource specialization the key?: some, but not all Red Crossbill call types associate with their key conifers in a diverse North American landscape
Authors: Centanni Caleb , Robinson W. Douglas , Young Matthew A.
Published: February 2024

Red Crossbills (Fringillidae: Loxia curvirostra) are finches specialized to pry open cones and extract seeds of coniferous trees. Within the species, variable bill morphology may provide more efficient foraging on some species of conifers than others. Subgroups also have distinctly different contact calls often given in flight (hereafter, call types). Variable morphology and discrete call types suggest the existence of distinct evolutionary lineages. Because coniferous trees produce seeds on irregular and unpredictable schedules, crossbills wander widely in search of food. The key conifer hypothesis suggests that each call type diverged by specializing on a single conifer species to maximize foraging efficiency, while other hypotheses have emphasized geographic isolation as a driver of lineage divergence. To quantify the degree to which call types occur with specific conifer species, we surveyed Red Crossbills in five ecoregions of western and central Oregon, USA, an area with high conifer diversity. Two of five call types (Types 5 and 10) were encountered in only one ecoregion and associated with their hypothesized key conifers. Three others (Types 2, 3, and 4) were found to wander widely and did not exclusively align geographically with their presumed key conifer species. Whereas types 2 and 3 were sometimes associated with their proposed key conifers, they wandered widely during our 2-year study and occurred with a wide variety of conifers. Type 4 was not significantly associated with its key conifer and also wandered widely during our study. Relationships of call types with key conifers were weaker in the winter and spring, when Types 3 and 4 were frequently encountered in hard-coned pines rather than their soft-coned key conifer species. In our study area, the key conifer hypothesis was strongly supported only for call type 10 as that call type was not encountered away from the coastal range of Sitka Spruce (Picea sitchensis). We found mixed support for the key conifer hypothesis based on our measure of geographic associations of crossbills with a diverse array of coniferous tree species. In most cases we observed, crossbills wandered widely and associated with multiple species of conifers.
Regulatory signaling pathways of osteoblast autophagy in periprosthetic osteolysis
Authors: Gu YingChu , Wu ZeRui , Xie Heng , Fang Tao , Wang QiuFei , Gu Ye
Published: February 2024

Periprosthetic osteolysis is a difficult-to-treat complication of arthroplasty. The pathological mechanisms of periprosthetic osteolysis are mainly weakened function of osteoblasts and excessive activation of osteoclasts. Many studies have demonstrated that the imbalance between the formation of bone by osteoblasts and the absorption of bone by osteoclasts is the direct cause of osteolytic diseases. Autophagy, as an important self-protective cellular mechanism, has significant effects on the regulation of osteoblast function, such as osteoblast differentiation, proliferation, and apoptosis. Osteoblasts, which play an important role in maintaining bone homeostasis, have attracted increasing attention in recent years. Up till now, Several signaling pathways have been proved to regulate autophagy of osteoblasts, including the AMPK, NF-κB, FoxO3 and other signaling pathways. This article reviews the recent progress in understanding osteoblast autophagy and mitophagy in the context of periprosthetic osteolysis and the signaling pathways which are involved in these processes. By summarizing previous studies describing the mechanism underlying osteoblast autophagy, we wish to contribute new therapeutic ideas and potential therapeutic targets for periprosthetic osteolysis.
Antiviral responses versus virus-induced cellular shutoff: a game of thrones between influenza A virus NS1 and SARS-CoV-2 Nsp1
Authors: Khalil Ahmed Magdy , Nogales Aitor , Martínez-Sobrido Luis , Mostafa Ahmed
Published: February 2024

Following virus recognition of host cell receptors and viral particle/genome internalization, viruses replicate in the host via hijacking essential host cell machinery components to evade the provoked antiviral innate immunity against the invading pathogen. Respiratory viral infections are usually acute with the ability to activate pattern recognition receptors (PRRs) in/on host cells, resulting in the production and release of interferons (IFNs), proinflammatory cytokines, chemokines, and IFN-stimulated genes (ISGs) to reduce virus fitness and mitigate infection. Nevertheless, the game between viruses and the host is a complicated and dynamic process, in which they restrict each other via specific factors to maintain their own advantages and win this game. The primary role of the non-structural protein 1 (NS1 and Nsp1) of influenza A viruses (IAV) and the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respectively, is to control antiviral host-induced innate immune responses. This review provides a comprehensive overview of the genesis, spatial structure, viral and cellular interactors, and the mechanisms underlying the unique biological functions of IAV NS1 and SARS-CoV-2 Nsp1 in infected host cells. We also highlight the role of both non-structural proteins in modulating viral replication and pathogenicity. Eventually, and because of their important role during viral infection, we also describe their promising potential as targets for antiviral therapy and the development of live attenuated vaccines (LAV). Conclusively, both IAV NS1 and SARS-CoV-2 Nsp1 play an important role in virus–host interactions, viral replication, and pathogenesis, and pave the way to develop novel prophylactic and/or therapeutic interventions for the treatment of these important human respiratory viral pathogens.
Effects of light therapy on sleep and circadian rhythm in older type 2 diabetics living in long-term care facilities: a randomized controlled trial
Authors: Wang Qin , Wu Shuang , Luo Zhenhua , Pu Lihui , Wang Xiaoxia , Guo Maoting , Zhang Mingjiao , Tang Hongxia , Chen Mengjie , Kong Laixi , Huang Ping , Chen Liyuan , Li Zhe , Zhao Dan , Xiong Zhenzhen
Published: February 2024

Background

Light influences the secretion of melatonin in the body and regulates circadian rhythms, which play an important role in sleep and mood. The light level of rooms in long-term care facilities is usually far below the threshold required to regulate the body’s circadian rhythm, and insufficient light can easily lead to sleep and mood disturbances among older residents in nursing homes. Therefore, the objective of this study was to investigate the effects of light therapy on sleep and circadian rhythm in older adults with type 2 diabetes residing in long-term care facilities.

Methods

This study was a prospective, single-blind, randomized controlled trial. Participants were randomly assigned to either the light therapy (LT) group or the control group and received the intervention for four weeks. Primary outcomes included the Pittsburgh Sleep Quality Index (PSQI) and objective sleep parameters recorded by a sleep monitoring bracelet, Morningness-Eveningness Questionnaire (MEQ). The secondary outcome included glycated serum protein (GSP). Data was collected at three time points: at baseline (T0), immediate post-treatment (T1), and 4-week follow-up (T2). A linear mixed model analysis was used to analyzed the data.

Results

We enrolled 45 long-term care residents. Compared with the control group, significant reductions in PSQI scores were observed at T1 and T2. At T2, the sleep score of objective sleep parameters was significantly higher in the LT group compared to the control group. Additionally, compared to the baseline T0, MEQ scores were significantly lower in the LT group at T1 and T2, with no significant difference in the control group. There was no significant difference between groups in glycated serum protein values at T1 and T2. However, compared to T0, glycated serum protein values decreased in the LT group while increased in the control group at T2.

Conclusion

Light therapy had a positive effect on subjective sleep quality and circadian rhythm time type in long-term care residents with type 2 diabetes, and had a possible delayed effect on objective sleep. However, no discernible alterations in blood glucose levels were detected in this study.
Characteristics of changes in plasma proteome profiling after sleeve gastrectomy
Authors: Zhang Yuying , Shi Chenye , Wu Haifu , Yan Hongmei , Xia Mingfeng , Jiao Heng , Zhou Di , Wu Wei , Zhong Ming , Lou Wenhui , Gao Xin , Bian Hua , Chang Xinxia
Published: February 2024

Bariatric surgery (BS), recognized as the most effective intervention for morbid obesity and associated metabolic comorbidities, encompasses both weight loss-dependent and weight loss-independent mechanisms to exert its metabolic benefits. In this study, we employed plasma proteomics technology, a recently developed mass spectrometric approach, to quantitatively assess 632 circulating proteins in a longitudinal cohort of 9 individuals who underwent sleeve gastrectomy (SG). Through time series clustering and Gene Ontology (GO) enrichment analysis, we observed that complement activation, proteolysis, and negative regulation of triglyceride catabolic process were the primary biological processes enriched in down-regulated proteins. Conversely, up-regulated differentially expressed proteins (DEPs) were significantly associated with negative regulation of peptidase activity, fibrinolysis, keratinocyte migration, and acute-phase response. Notably, we identified seven proteins (ApoD, BCHE, CNDP1, AFM, ITIH3, SERPINF1, FCN3) that demonstrated significant alterations at 1-, 3-, and 6-month intervals post SG, compared to baseline. These proteins play essential roles in metabolism, immune and inflammatory responses, as well as oxidative stress. Consequently, they hold promising potential as therapeutic targets for combating obesity and its associated comorbidities.
Tea intake and lung diseases: a Mendelian randomization study
Authors: Wu Zhengyan , Jiao Min , Shu Chenying , Li Chang , Zhu Yehan
Published: February 2024

Background

Existing studies on the relationship between tea intake and lung diseases have yielded inconsistent results, leading to an ongoing dispute on this issue. The impact of tea consumption on the respiratory system remained elucidating.

Materials and methods

We conducted a two-sample Mendelian randomization (MR) study to evaluate the associations between five distinct tea intake phenotypes and 15 different respiratory outcomes using open Genome-wide association study (GWAS) data. The inverse variance weighted (IVW) was used for preliminary screening and a variety of complementary methods were used as sensitivity analysis to validate the robustness of MR estimates. Pathway enrichment analysis was used to explore possible mechanisms.

Results

IVW found evidence for a causal effect of standard tea intake on an increased risk of lung squamous cell cancer (LSCC) (OR = 1.004; 95% CI = 1.001–1.007; P = 0.00299). No heterogeneity or pleiotropy was detected. After adjustment for potential mediators, including smoking, educational attainment, and time spent watching television, the association was still robust in multivariable MR. KEGG and GO enrichment predicted proliferation and activation of B lymphocytes may play a role in this causal relation. No causalities were observed when evaluating the effect of other kinds of tea intake on various pulmonary diseases.

Conclusion

Our MR estimates provide causal evidence of the independent effect of standard tea intake (black tea intake) on LSCC, which may be mediated by B lymphocytes. The results implied that the population preferring black tea intake should be wary of a higher risk of LSCC.
Adjuvant therapy provides no additional recurrence-free benefit for esophageal squamous cell carcinoma patients after neoadjuvant chemoimmunotherapy and surgery: a multi-center propensity score match study
Authors: Xie Shu-Han , Yang Li-Tao , Zhang Hai , Tang Zi-Lu , Lin Zhi-Wei , Chen Yi , Hong Zhi-Nuan , Xu Rong-Yu , Lin Wan-Li , Kang Ming-Qiang
Published: February 2024

Purpose

The need for adjuvant therapy (AT) following neoadjuvant chemoimmunotherapy (nICT) and surgery in esophageal squamous cell cancer (ESCC) remains uncertain. This study aims to investigate whether AT offers additional benefits in terms of recurrence-free survival (RFS) for ESCC patients after nICT and surgery.

Methods

Retrospective analysis was conducted between January 2019 and December 2022 from three centers. Eligible patients were divided into two groups: the AT group and the non-AT group. Survival analyses comparing different modalities of AT (including adjuvant chemotherapy and adjuvant chemoimmunotherapy) with non-AT were performed. The primary endpoint was RFS. Propensity score matching(PSM) was used to mitigate inter-group patient heterogeneity. Kaplan-Meier survival curves and Cox regression analysis were employed for recurrence-free survival analysis.

Results

A total of 155 nICT patients were included, with 26 patients experiencing recurrence. According to Cox analysis, receipt of adjuvant therapy emerged as an independent risk factor(HR:2.621, 95%CI:[1.089,6.310], P=0.032), and there was statistically significant difference in the Kaplan-Meier survival curves between non-AT and receipt of AT in matched pairs (p=0.026). Stratified analysis revealed AT bring no survival benefit to patients with pathological complete response(p= 0.149) and residual tumor cell(p=0.062). Subgroup analysis showed no significant difference in recurrence-free survival between non-AT and adjuvant chemoimmunotherapy patients(P=0.108). However, patients receiving adjuvant chemotherapy exhibited poorer recurrence survival compared to non-AT patients (p= 0.016).

Conclusion

In terms of recurrence-free survival for ESCC patients after nICT and surgery, the necessity of adjuvant therapy especially the adjuvant chemotherapy, can be mitigated.
In patients with mild disability NMOSD: is the alteration in the cortical morphological or functional network topological properties more significant
Authors: Ma Haotian , Zhu Yanyan , Liang Xiao , Wu Lin , Wang Yao , Li Xiaoxing , Qian Long , Cheung Gerald L. , Zhou Fuqing
Published: February 2024

Objective

To assess the alteration of individual brain morphological and functional network topological properties and their clinical significance in patients with neuromyelitis optica spectrum disorder (NMOSD).

Materials and methods

Eighteen patients with NMOSD and twenty-two healthy controls (HCs) were included. The clinical assessment of NMOSD patients involved evaluations of disability status, cognitive function, and fatigue impact. For each participant, brain images, including high-resolution T1-weighted images for individual morphological brain networks (MBNs) and resting-state functional MR images for functional brain networks (FBNs) were obtained. Topological properties were calculated and compared for both MBNs and FBNs. Then, partial correlation analysis was performed to investigate the relationships between the altered network properties and clinical variables. Finally, the altered network topological properties were used to classify NMOSD patients from HCs and to analyses time- to-progression of the patients.

Results

The average Expanded Disability Status Scale score of NMOSD patients was 1.05 (range from 0 to 2), indicating mild disability. Compared to HCs, NMOSD patients exhibited a higher normalized characteristic path length (λ) in their MBNs (P = 0.0118, FDR corrected) but showed no significant differences in the global properties of FBNs (p: 0.405-0.488). Network-based statistical analysis revealed that MBNs had more significantly altered connections (P< 0.01, NBS corrected) than FBNs. Altered nodal properties of MBNs were correlated with disease duration or fatigue scores (P< 0.05/6 with Bonferroni correction). Using the altered nodal properties of MBNs, the accuracy of classification of NMOSD patients versus HCs was 96.4%, with a sensitivity of 93.3% and a specificity of 100%. This accuracy was better than that achieved using the altered nodal properties of FBNs. Nodal properties of MBN significantly predicted Expanded Disability Status Scale worsening in patients with NMOSD.

Conclusion

The results indicated that patients with mild disability NMOSD exhibited compensatory increases in local network properties to maintain overall stability. Furthermore, the alterations in the morphological network nodal properties of NMOSD patients not only had better relevance for clinical assessments compared with functional network nodal properties, but also exhibited predictive values of EDSS worsening.
Divergent responses of the coral holobiont to deoxygenation and prior environmental stress
Authors: Swaminathan Sara D. , Meyer Julie L. , Johnson Maggie D. , Paul Valerie J. , Bartels Erich , Altieri Andrew H.
Published: February 2024

Ocean deoxygenation is intensifying globally due to human activities – and is emerging as a grave threat to coral reef ecosystems where it can cause coral bleaching and mass mortality. However, deoxygenation is one of many threats to coral reefs, making it essential to understand how prior environmental stress may influence responses to deoxygenation. To address this question, we examined responses of the coral holobiont (i.e., the coral host, Symbiodiniaceae, and the microbiome) to deoxygenation in corals with different environmental stress backgrounds. We outplanted Acropora cervicornis fragments of known genotypes from an in situ nursery to two sites in the Florida Keys spanning an inshore-offshore gradient. After four months, fragments from the outplanted corals were transferred to the laboratory, where we tested differences in survivorship, tissue loss, photosynthetic efficiency, Symbiodiniaceae cell density, and coral microbiome composition after persistent exposure to one of four oxygen treatments ranging from extreme deoxygenation (0.5 mg L-1) to normoxia (6 mg L-1). We found that, for the short duration of exposure tested in this study (four days), the entire coral holobiont was resistant to dissolved oxygen (DO) concentrations as low as 2.0 mg L-1, but that the responses of members of the holobiont decoupled at 0.5 mg L-1. In this most extreme treatment, the coral host showed decreased photosynthetic efficiency, tissue loss, and mortality, and lower Symbiodiniaceae densities in a bleaching response, but most microbial taxa remained stable. Although deoxygenation did not cause major community shifts in microbiome composition, the population abundance of some microbial taxa did respond. Site history influenced some responses of the coral host and endosymbiont, but not the coral microbiome, with corals from the more stressful inshore site showing greater susceptibility to subsequent deoxygenation. Our study reveals that coral holobiont members respond differently to deoxygenation, with greater sensitivity in the coral host and Symbiodiniaceae and greater resistance in the coral microbiome, and that prior stress exposure can decrease host tolerance to deoxygenation.
Patient perspective on living with mild hemophilia in Germany: results from a nationwide survey
Authors: Alesci Rosa Sonja , Goldmann Georg , Halimeh Susan , Holstein Katharina , Königs Christoph , Miesbach Wolfgang , Pfrepper Christian , Olivieri Martin
Published: February 2024

Introduction

The disease burden and bleeding risk of patients with mild hemophilia may be underestimated. Their health-related quality of life (QoL) may be negatively impacted by insufficient treatment and bleed-related joint damage connected to a potentially delayed diagnosis.

Aim

This study aims to gain information on the care reality and QoL of patients aged ≥12 years with mild hemophilia in Germany.

Methods

An anonymous cross-sectional patient survey using standardized questionnaires was conducted in a validated electronic patient-reported outcome system. Medical specialists, hemophilia centers, patient organizations, and support groups across Germany invited the patients.

Results

A total of 43 patients (35 patients with hemophilia A, 5 patients with hemophilia B, and 3 patients for whom the information was missing) with a median age of 33 years were analyzed. The median age at diagnosis was 6.0 years (interquartile range [IQR] 2.0–15.0), and the median factor activity was 14.0% (IQR 12.0–25.0). Nearly 85% of the patients received factor concentrates in the past, and the most common reasons for the treatment were surgery or joint bleeding (each 65.6%). Half of the patients who provided feedback experienced complications during bleeding episodes. Prophylactic treatment with factor concentrates was rare (10.3%). The patients had minor problems regarding their health status.

Conclusion

Bleeding complications and joint bleeding, in particular, may be highly underestimated in patients with mild hemophilia, highlighting a medical need in this population. Patients with a potential benefit from prophylaxis need to be identified. Mild hemophilia has a negative impact on patients’ QoL. Hemophilia centers satisfied the patients’ needs. Further research is needed to address the current lack of awareness and improve adequate treatment in the future.
Case report: Thrombotic thrombocytopenic purpura in a pregnant woman with lupus membranous nephropathy: a diagnostic challenge
Authors: Leiva Marina , Navarro Gustavo , Carpio J Daniel , Ardiles Leopoldo
Published: February 2024

A 27-year-old female at 20th week of pregnancy was admitted with edema, foamy urine, but normal blood pressure. Her blood count was normal, she had proteinuria of 3 g/day, creatinine 0.4 mg/dl, albumin 2.4 g/dl, and cholesterol 355 mg/dl. Antinuclear antibodies 1/160, but Anti-DNA, anticardiolipin antibodies and lupus anticoagulant were negative, with normal serum C3 and C4. A renal biopsy showed secondary membranous glomerulopathy, most likely lupus class V pure. Steroids, azathioprine, and aspirin were initiated, up to 28 weeks of pregnancy, when she developed severe hypertension, photopsia, headache, anasarca, extensive bruising of the extremities, severe anemia, thrombocytopenia, and creatinine rose to 2.09 mg/dl with preserved diuresis. A female infant, 1045 grams, was delivered by emergency caesarean section. Following the surgery, she experienced diplopia, dysarthria, bradypsychia, and sensory alterations in the lower extremities, necessitating emergency hemodialysis due to pulmonary congestion. Blood smear revealed schistocytes, LDH elevated at 1148 IU/L, while transaminases and liver function remained normal, suggesting thrombotic thrombocytopenic purpura. ADAMTS13 revealed 6% activity with the presence of inhibitor. Mycophenolate and daily plasmapheresis with fresh frozen plasma replacement yielded unsatisfactory response, unaffected by the addition of methylprednisolone pulses and rituximab. Eventually, intravenous cyclophosphamide was introduced, resulting in complete hematological remission and normalization of ADAMTS13, however dialysis-dependence persisted and four years later, right renal cancer prompted bilateral nephrectomy. After a total follow-up of six years, she remained free of neoplastic recurrence and lupus activity, receiving prednisone and hydroxychloroquine. The differential diagnosis of microangiopathic syndrome in a pregnant lupus patient is discussed.
The significance of metabolic disease in degenerative cervical myelopathy: a systematic review
Authors: Partha Sarathi Celine Iswarya , Sinha Amil , Rafati Fard Amir , Bhatti Faheem , Rujeedawa Tanzil , Ahmed Shahzaib , Akhbari Melika , Bhatti Aniqah , Nouri Aria , Kotter Mark R. , Davies Benjamin M. , Mowforth Oliver D.
Published: February 2024

Introduction

Degenerative cervical myelopathy (DCM) is a form of chronic spinal cord injury, with a natural history of potential for progression over time. Whilst driven by mechanical stress on the spinal cord from degenerative and congenital pathology, the neurological phenotype of DCM is likely to be modified by multiple systemic factors. The role of metabolic factors is therefore of interest, particularly given that ischaemia is considered a key pathological mechanism of spinal cord injury. The objective was therefore to synthesise current evidence on the effect of metabolism on DCM susceptibility, severity, and surgical outcomes.

Methods

A systematic review in MEDLINE and Embase was conducted following PRISMA guidelines. Full-text papers in English, with a focus on DCM and metabolism, including diabetes, cardiovascular disease, anaemia, and lipid profile, were eligible for inclusion. Risk of methodological bias was assessed using the Joanna Briggs Institute (JBI) critical assessment tools. Quality assessments were performed using the GRADE assessment tool. Patient demographics, metabolic factors and the relationships between metabolism and spinal cord disease, spinal column disease and post-operative outcomes were assessed.

Results

In total, 8,523 papers were identified, of which 57 met criteria for inclusion in the final analysis. A total of 91% (52/57) of included papers assessed the effects of diabetes in relation to DCM, of which 85% (44/52) reported an association with poor surgical outcomes; 42% of papers (24/57) discussed the association between cardiovascular health and DCM, of which 88% (21/24) reported a significant association. Overall, DCM patients with diabetes or cardiovascular disease experienced greater perioperative morbidity and poorer neurological recovery. They were also more likely to have comorbidities such as obesity and hyperlipidaemia.

Conclusion

Metabolic factors appear to be associated with surgical outcomes in DCM. However, evidence for a more specific role in DCM susceptibility and severity is uncertain. The pathophysiology and natural history of DCM are critical research priorities; the role of metabolism is therefore a key area for future research focus.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42021268814.
Improving the detection of sleep slow oscillations in electroencephalographic data
Authors: Dimulescu Cristiana , Donle Leonhard , Cakan Caglar , Goerttler Thomas , Khakimova Lilia , Ladenbauer Julia , Flöel Agnes , Obermayer Klaus
Published: February 2024

Study objectives

We aimed to build a tool which facilitates manual labeling of sleep slow oscillations (SOs) and evaluate the performance of traditional sleep SO detection algorithms on such a manually labeled data set. We sought to develop improved methods for SO detection.

Method

SOs in polysomnographic recordings acquired during nap time from ten older adults were manually labeled using a custom built graphical user interface tool. Three automatic SO detection algorithms previously used in the literature were evaluated on this data set. Additional machine learning and deep learning algorithms were trained on the manually labeled data set.

Results

Our custom built tool significantly decreased the time needed for manual labeling, allowing us to manually inspect 96,277 potential SO events. The three automatic SO detection algorithms showed relatively low accuracy (max. 61.08%), but results were qualitatively similar, with SO density and amplitude increasing with sleep depth. The machine learning and deep learning algorithms showed higher accuracy (best: 99.20%) while maintaining a low prediction time.

Conclusions

Accurate detection of SO events is important for investigating their role in memory consolidation. In this context, our tool and proposed methods can provide significant help in identifying these events.
Distinct roles for interleukin-23 receptor signaling in regulatory T cells in sporadic and inflammation-associated carcinogenesis
Authors: Jacobse Justin , Pilat Jennifer M. , Li Jing , Brown Rachel E. , Kwag Aaron , Buendia Matthew A. , Choksi Yash A. , Washington M. Kay , Williams Christopher S. , Markham Nicholas O. , Short Sarah P. , Goettel Jeremy A.
Published: February 2024

Introduction

The pro-inflammatory cytokine interleukin-23 (IL-23) has been implicated in colorectal cancer (CRC). Yet, the cell-specific contributions of IL-23 receptor (IL-23R) signaling in CRC remain unknown. One of the cell types that highly expresses IL-23R are colonic regulatory T cells (Treg cells). The aim of this study was to define the contribution of Treg cell-specific IL-23R signaling in sporadic and inflammation-associated CRC.

Methods

In mice, the role of IL-23R in Treg cells in colitis-associated cancer (CAC) was investigated using azoxymethane/dextran sodium sulphate in wild-type Treg cell reporter mice (WT, Foxp3YFP-iCre), and mice harboring a Treg cell-specific deletion of IL-23 (Il23rΔTreg). The role of IL-23R signaling in Treg cells in sporadic CRC was examined utilizing orthotopic injection of the syngeneic colon cancer cell line MC-38 submucosally into the colon/rectum of mice. The function of macrophages was studied using clodronate. Finally, single-cell RNA-seq of a previously published dataset in human sporadic cancer was reanalyzed to corroborate these findings.

Results

In CAC, Il23rΔTreg mice had increased tumor size and increased dysplasia compared to WT mice that was associated with decreased tumor-infiltrating macrophages. In the sporadic cancer model, Il23rΔTreg mice had increased survival and decreased tumor size compared to WT mice. Additionally, MC-38 tumors of Il23rΔTreg mice exhibited a higher frequency of pro-inflammatory macrophages and IL-17 producing CD4+ T cells. The decreased tumor size in Il23rΔTreg mice was macrophage-dependent. These data suggest that loss of IL-23R signaling in Treg cells permits IL-17 production by CD4+ T cells that in turn promotes pro-inflammatory macrophages to clear tumors. Finally, analysis of TCGA data and single-cell RNA-seq analysis of a previously published dataset in human sporadic cancer, revealed that IL23R was highly expressed in CRC compared to other cancers and specifically in tumor-associated Treg cells.

Conclusion

Inflammation in colorectal carcinogenesis differs with respect to the contribution of IL-23R signaling in regulatory T cells.
Comparison of remimazolam and propofol combined with low dose esketamine for pediatric same-day painless bidirectional endoscopy: a randomized, controlled clinical trial
Authors: Chu Tiantian , Zhou Siqi , Wan Yingfeng , Liu Qiuli , Xin Yueyang , Tian Zhang , Yan Tianqing , Xu Aijun
Published: February 2024

Background: Remimazolam has shown similar or even superior properties to propofol in procedural sedation in adults, but few studies have been conducted in pediatric populations. Thus, we aimed to compare the effect and safety of remimazolam and propofol combined with low dose esketamine for pediatric same-day bidirectional endoscopy (BDE).

Methods: Pediatrics <18 years scheduled for elective BDE under sedation were included and randomly assigned to remimazolam group (R group) or propofol group (P group). The primary outcome was the success rate of sedation. Secondary outcomes include sedation-related information and adverse events. Mean arterial pressure (MAP), heart rate (HR), and perfusion index (PI) were recorded during sedation.

Results: A total of 106 patients were enrolled and analyzed. The success rate of sedation was 100% in both groups. Compared with the P group, the induction time of the R group was significantly prolonged (p < 0.001), and the incidence of injection pain, intraoperative respiratory depression, hypotension and bradycardia was significantly lower (p < 0.001). The changes in MAP, HR and PI were relatively stable in the R group compared with the P group. Additionally, awake time significantly decreased with age by approximately 1.12 index points for each increase in age in the P group (p = 0.002) but not in the R group (p > 0.05). Furthermore, the decline in PI and PI ratio during BDE was related to body movement in the P group.

Conclusion: Remimazolam combined with low dose esketamine has a non-inferior sedative effect than propofol for pediatric BDE, with no injection pain, less respiratory depression, more stable hemodynamics. Moreover, early detection of the decline in PI may avoid harmful stimulation under light anesthesia.

Clinical trial registration:https://www.clinicaltrials.gov/study/NCT05686863?id=NCT05686863&rank=1, NCT05686863
Identification of molecular subtypes and diagnostic model in clear cell renal cell carcinoma based on collagen-related genes may predict the response of immunotherapy
Authors: Hong Yulong , Lv Zhengtong , Xing Zhuo , Xu Haozhe , Chand Harripersaud , Wang Jianxi , Li Yuan
Published: February 2024

Background: Collagen represents a prominent constituent of the tumor’s extracellular matrix (ECM). Nonetheless, its correlation with the molecular subtype attributes of clear cell renal cell carcinoma (ccRCC) remains elusive. Our objective is to delineate collagen-associated molecular subtypes and further construct diagnostic model, offering insights conducive to the precise selection of ccRCC patients for immunotherapeutic interventions.

Methods: We performed unsupervised non-negative matrix factorization (NMF) analysis on TCGA-KIRC samples, utilizing a set of 33 collagen-related differentially expressed genes (33CRDs) for clustering. Our analysis encompassed evaluations of subtype-associated differences in pathways, immune profiles, and somatic mutations. Through weighted gene co-expression network analysis (WGCNA) and four machine learning algorithms, two core genes were found and a diagnostic model was constructed. This was subsequently validated in a clinical immunotherapy cohort. Single cell sequencing analysis and experiments demonstrated the role of core genes in ccRCC. Finally, we also analyzed the roles of MMP9 and SCGN in pan-cancer.

Results: We described two novel collagen related molecular subtypes in ccRCC, designated subtype 1 and subtype 2. Compared with subtype 1, subtype 2 showed more infiltration of immune components, but had a higher TIDE (tumor immunedysfunctionandexclusion) score and increased levels of immune checkpoint molecules. Furthermore, reduced prognosis for subtype 2 was a consistent finding in both high and low mutation load subgroups. MMP9 and SCGN were identified as key genes for distinguishing subtype 1 and subtype 2. The diagnostic model based on them could better distinguish the subtype of patients, and the differentiated patients had different progression free survival (PFS) in the clinical immunotherapy cohort. MMP9 was predominantly expressed in macrophages and has been extensively documented in the literature. Meanwhile, SCGN, which was overexpressed in tumor cells, underwent experimental validation, emphasizing its role in ccRCC. In various cancers, MMP9 and SCGN were associated with immune-related molecules and immune cells.

Conclusion: Our study identifies two collagen-related molecular subtypes of ccRCC and constructs a diagnostic model to help select appropriate patients for immunotherapy.
The effective combination therapies with irinotecan for colorectal cancer
Authors: Chai Yun , Liu Jing-Li , Zhang Shuo , Li Na , Xu Ding-Qiao , Liu Wen-Juan , Fu Rui-Jia , Tang Yu-Ping
Published: February 2024

Colorectal cancer is the third most common type of cancer worldwide and has become one of the major human disease burdens. In clinical practice, the treatment of colorectal cancer has been closely related to the use of irinotecan. Irinotecan combines with many other anticancer drugs and has a broader range of drug combinations. Combination therapy is one of the most important means of improving anti-tumor efficacy and overcoming drug resistance. Reasonable combination therapy can lead to better patient treatment options, and inappropriate combination therapy will increase patient risk. For the colorectal therapeutic field, the significance of combination therapy is to improve the efficacy, reduce the adverse effects, and improve the ease of treatment. Therefore, we explored the clinical advantages of its combination therapy based on mechanism or metabolism and reviewed the rationale basis and its limitations in conducting exploratory clinical trials on irinotecan combination therapy, including the results of clinical trials on the combination potentiation of cytotoxic drugs, targeted agents, and herbal medicine. We hope that these can evoke more efforts to conduct irinotecan in the laboratory for further studies and evaluations, as well as the possibility of more in-depth development in future clinical trials.