bluuebunny/crossref_metadata_2025_split huggingface dataset:
MINANDO O AMBIENTE SEGURO DE VEDAÇÃO CONSTITUCIONAL DO ANONIMATO NA INTERNET
Authors: De Souza Delgado Joedson , Basso Ana Paula 
Published: October 2023

Durante as últimas duas décadas, as comunidades virtuais passaram por uma brusca mudança desde o desenvolvimento inicial da Internet baseada na comunicação anônima. O uso crescente das plataformas digitais e práticas relapsas de privacidade na Internet agora limitam ainda mais sua capacidade de usá-la anonimamente. O presente trabalho objetiva analisar a mudança do papel sociojurídico do anonimato na web ao identificar os principais atores e fatores que influenciam a desanonimização. O estudo proposto pelo método qualitativo e o uso de fontes secundárias busca responder quem e por que a Internet anônima incomoda e quais são os fatores macro e micro que contribuem para a sua vedação constitucional. Admite-se que a regulamentação da mídia – que a priori reconhece o anonimato online como indesejável – é prejudicial e até perigoso devido à ameaça aos direitos fundamentais de liberdade e privacidade e livre desenvolvimento da personalidade de uma pessoa natural. PALAVRAS CHAVE: Anonimato online. Democracia digital. Liberdade de Expressão e de Informação. Regulamentação da mídia. Vedação constitucional. ABSTRACT Over the past two decades, virtual communities have undergone a sharp shift since the early development of the Internet based on anonymous communication. The increasing use of digital platforms and internet privacy practices now further limit your ability to use it anonymously. This paper aims to analyze the change in the socio-legal role of anonymity on the web by identifying the main actors and factors that influence de-nonimization. The study proposed by the qualitative method and the use of secondary sources seeks to answer who and why the anonymous Internet bothers and what are the macro and micro factors that contribute to its constitutional fence. It is admitted that media regulation - which a priori recognizes online anonymity as undesirable - is harmful and even dangerous due to the threat to the fundamental rights of freedom and privacy and freedevelopment of a natural person’s personality. Keywords: Online anonymity. Digital democracy. Freedom of Expression and Information. Media regulation. Constitutional prohibition.
Identification of anti-pathogenic activity among in silico predicted small-molecule inhibitors of Pseudomonas aeruginosa LasR or nitric oxide reductase (NOR)
Authors: Gajera Gemini , Henriksen Niel , Cox Bryan , Kothari Vijay 
Published: October 2023

Introduction: Antibiotic-resistant Pseudomonas aeruginosa strains cause considerable morbidity and mortality globally. Identification of novel targets in this notorious pathogen is urgently warranted to facilitate discovery of new anti-pathogenic agents against it. This study attempted to identify small-molecule inhibitors of two important proteins LasR and nitric oxide reductase (NOR) in P. aeruginosa. ‘Las’ system can be said to be the ‘master’ regulator of quorum sensing in P. aeruginosa, whose receptor protein is LasR. Similarly, NOR is crucial to detoxification of reactive nitrogen species.
Methods: In silico identification of potential LasR or NOR inhibitors was attempted through a virtual screening platform AtomNet® to obtain a final subset of <100 top scoring compounds. These compounds were evaluated for their in vivo anti-pathogenic activity by challenging the model host Caenorhabditis elegans with P. aeruginosa in the presence or absence of test compounds. Survival of the worm population in 24-well assay plates was monitored over a period of 5 days microscopically.
Results: Of the 96 predicted LasR inhibitors, 11 exhibited anti-Pseudomonas activity (23%-96% inhibition of bacterial virulence as per third-day end-point) at 25-50 µg/mL. Of the 85 predicted NOR inhibitors, 8 exhibited anti-Pseudomonas activity (40%-85% inhibition of bacterial virulence as per second-day end-point) at 25-50 µg/mL.
Conclusion: Further investigation on molecular mode of action of compounds found active in this study is warranted. Virtual screening can be said to be a useful tool in narrowing down the list of compounds requiring actual wet-lab screening, saving considerable time and efforts for drug discovery.
Sosialisasi dan Pendampingan Pembelajaran Berbasis Video dengan Aplikasi ‘Screen O-Matic’ Bagi Guru Sekolah Dasar Kartika IV-6 Malang
Authors: Purwati Titik , Suhartatik Suhartatik , Agustina Wilyanti 
Published: October 2023

The aim of the activity is providing socialization and video-based learning assistance with "Screen O-Matic" application for teachers at SD Kartika IV-6 Malang. The agenda is presented in three stages, namely preparation, implementation, and evaluation. By implementing this stages, the teachers can develop online-based learning models and media using a variety of applications, including using the "Screen O-Matic" video application. The output targets achieved through this Community Service activity include: 1) increasing knowledge about video-based learning models and media for teaching at SD Kartika IV-6 Malang; 2) increasing learning innovation by developing video-based applications "Screen O-Matic".In conclusion by using "Screen O-Matic" video application, teaching learning process can be delivered in joyful learning, creative and innovative. Digital Literate is a must for Nowdays teachers.
The use of nanomaterials in advancing photodynamic therapy (PDT) for deep-seated tumors and synergy with radiotherapy
Authors: Dinakaran Deepak , Wilson Brian C. 
Published: October 2023

Photodynamic therapy (PDT) has been under development for at least 40 years. Multiple studies have demonstrated significant anti-tumor efficacy with limited toxicity concerns. PDT was expected to become a major new therapeutic option in treating localized cancer. However, despite a shifting focus in oncology to aggressive local therapies, PDT has not to date gained widespread acceptance as a standard-of-care option. A major factor is the technical challenge of treating deep-seated and large tumors, due to the limited penetration and variability of the activating light in tissue. Poor tumor selectivity of PDT sensitizers has been problematic for many applications. Attempts to mitigate these limitations with the use of multiple interstitial fiberoptic catheters to deliver the light, new generations of photosensitizer with longer-wavelength activation, oxygen independence and better tumor specificity, as well as improved dosimetry and treatment planning are starting to show encouraging results. Nanomaterials used either as photosensitizers per se or to improve delivery of molecular photosensitizers is an emerging area of research. PDT can also benefit radiotherapy patients due to its complementary and potentially synergistic mechanisms-of-action, ability to treat radioresistant tumors and upregulation of anti-tumoral immune effects. Furthermore, recent advances may allow ionizing radiation energy, including high-energy X-rays, to replace external light sources, opening a novel therapeutic strategy (radioPDT), which is facilitated by novel nanomaterials. This may provide the best of both worlds by combining the precise targeting and treatment depth/volume capabilities of radiation therapy with the high therapeutic index and biological advantages of PDT, without increasing toxicities. Achieving this, however, will require novel agents, primarily developed with nanomaterials. This is under active investigation by many research groups using different approaches.
25 Years of PI5P
Authors: Rameh Lucia E. , Blind Raymond D. 
Published: October 2023

The accidental discovery of PI5P (phosphatidylinositol-5-phosphate) was published 25 years ago, when PIP5K type II (phosphoinositide-4-phosphate 5-kinase) was shown to actually be a 4-kinase that uses PI5P as a substrate to generate PI(4,5)P2. Consequently, PIP5K type II was renamed to PI5P4K, or PIP4K for short, and PI5P became the last of the 7 signaling phosphoinositides to be discovered. Much of what we know about PI5P comes from genetic studies of PIP4K, as the pathways for PI5P synthesis, the downstream targets of PI5P and how PI5P affects cellular function all remain largely enigmatic. Nevertheless, PI5P and PI5P-dependent PI(4,5)P2 synthesis have been clearly implicated in metabolic homeostasis and in diseases such as cancer. Here, we review the past 25 years of PI5P research, with particular emphasis on the impact this small signaling lipid has on human health.
Causality of occupational exposure on rheumatoid arthritis and ankylosing spondylitis: a two-sample mendelian randomization study
Authors: Du Kai , Zhang Chen-Yu , Li Ao , Hu Jia-Ze , Guo Ren , Li Shu-Ming 
Published: October 2023

ObjectiveThis study aimed to explore the potential causal link between three specific types of occupational exposure on rheumatoid arthritis (RA) and ankylosing spondylitis (AS).MethodA Two-sample Mendelian randomization (TSMR) analysis, comprising univariate MR (UVMR) and multivariate MR (MVMR) analyses, was performed to investigate the potential causal association between three types of occupational exposures, jobs involving mainly walking or standing (JWS), jobs involving heavy manual or physical work (JMP), and jobs involving shift work(JSW) on RA and AS. Genetic variants for genome-wide association studies (GWAS) of occupational exposure and AS were obtained from the UK Biobank. GWAS summary data for RA were obtained from FinnGen Biobank analysis. For UVMR, six methods of Inverse Variance Weighted (IVW), MR-Egger, Weighted Mode, Weighted Median, Simple Mode, MR pleiotropy residual sum, and outlier (MR-PRESSO) were used for the analysis. The MVMR was analyzed using the IVW model as well as the MR-Egger model.ResultsThe UVMR suggested no causal relationship between the three occupational exposure and RA [IVW: P=0.59,0.21,0.63] or AS [IVW: P=0.43,0.57,0.04], as did the bidirectional MR [IVW: P=0.73,0.70,0.16], [IVW: P=0.65,0.68,0.74]. Although unadjusted MVMR suggested a causal relationship between JMP and AS [IVW: OR = 1.01, 95% CI = 1.00- 1.02, p = 0.02], the adjusted MVMR denied this relationship and concluded that there was no causal relationship between the other occupational exposure and either RA or AS.ConclusionOur MR analysis did not establish a direct causal relationship between certain occupational exposures and either RA or AS.
Immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcome
Authors: Röhl Louisa , Wellhausen Jana , Berszin Michael , Krücken Irene , Zebralla Veit , Pirlich Markus , Wiegand Susanne , Dietz Andreas , Wald Theresa , Wichmann Gunnar 
Published: October 2023

BackgroundImmune-checkpoint blockade (ICB) of programmed-death-1 (PD-1) with pembrolizumab or nivolumab is approved for treating recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). NadiHN and ADRISK are phase IIB trials investigating in locally advanced (LA) HNSCC having low or high risk of recurrence the potential benefits from adding nivolumab to post-operative radiotherapy or pembrolizumab to cisplatin-based radio-chemotherapy.MethodsAlong five randomized controlled ICB trials including NadiHN and ADRISK, blood samples were taken before and after starting ICB in n=25 patients. Concentrations of vascular endothelial growth factor A (VEGF), CCL2 (MCP-1), interleukin-6 (IL-6), IL-8, interferon-gamma (IFN-γ), and CXCL10 (IP-10) pre- and post-ICB in EDTA-anticoagulated plasma and serum were compared. We used receiver operating characteristic (ROC) curves to identify optimal cutoff for defining subgroups before analyzing overall survival (OS) applying Kaplan–Meier plots and multivariate Cox regression.ResultsWe detected huge heterogeneity between cytokine patterns in pre-and post-ICB plasma and serum. We observed high correlation between concentrations of some cytokines. Despite absent systematic OS differences after ICB with pembrolizumab or nivolumab or between LA-HNSCC versus R/M HNSCC patients, we noticed improved outcome of patients having lower IFN-γ concentrations pre- and post-ICB and following ICB reduced concentrations of VEGF, IL-6, and IL-8 but not MCP-1. Contrarily, increases in IL-6, IL-8, and VEGF levels correlated with impaired outcome. Multivariate Cox regression revealed five independent OS predictors among cytokines; using natural logarithms of their hazard ratios to estimate an individual’s risk of dying, three cytokine-expression pattern (CEP)-risk groups with no death within mean (95% confidence interval) follow-up of 29.2 (22.1–36.2) months and median OS of 11.3 (8.8–13.8) and 2.9 (0.4-5.4) months were found.ConclusionWhereas individual pre- or post-ICB cytokine concentrations in serum or plasma alone failed to predict the survivor group, CEP-risk groups may support the identification of individual patients with long-lasting benefit from ICB.
Distinct molecular subtypes of systemic sclerosis and gene signature with diagnostic capability
Authors: Wang Qi , Li Chen-Long , Wu Li , Hu Jing-Yi , Yu Qi , Zhang Sheng-Xiao , He Pei-Feng 
Published: October 2023

BackgroundAs Systemic Sclerosis (SSc) is a connective tissue ailment that impacts various bodily systems. The study aims to clarify the molecular subtypes of SSc, with the ultimate objective of establishing a diagnostic model that can inform clinical treatment decisions.MethodsFive microarray datasets of SSc were retrieved from the GEO database. To eliminate batch effects, the combat algorithm was applied. Immune cell infiltration was evaluated using the xCell algorithm. The ConsensusClusterPlus algorithm was utilized to identify SSc subtypes. Limma was used to determine differential expression genes (DEGs). GSEA was used to determine pathway enrichment. A support vector machine (SVM), Random Forest(RF), Boruta and LASSO algorithm have been used to select the feature gene. Diagnostic models were developed using SVM, RF, and Logistic Regression (LR). A ROC curve was used to evaluate the performance of the model. The compound-gene relationship was obtained from the Comparative Toxicogenomics Database (CTD).ResultsThe identification of three immune subtypes in SSc samples was based on the expression profiles of immune cells. The utilization of 19 key intersectional DEGs among subtypes facilitated the classification of SSc patients into three robust subtypes (gene_ClusterA-C). Gene_ClusterA exhibited significant enrichment of B cells, while gene_ClusterC showed significant enrichment of monocytes. Moderate activation of various immune cells was observed in gene_ClusterB. We identified 8 feature genes. The SVM model demonstrating superior diagnostic performance. Furthermore, correlation analysis revealed a robust association between the feature genes and immune cells. Eight pertinent compounds, namely methotrexate, resveratrol, paclitaxel, trichloroethylene, formaldehyde, silicon dioxide, benzene, and tetrachloroethylene, were identified from the CTD.ConclusionThe present study has effectively devised an innovative molecular subtyping methodology for patients with SSc and a diagnostic model based on machine learning to aid in clinical treatment. The study has identified potential molecular targets for therapy, thereby offering novel perspectives for the treatment and investigation of SSc.
Complement-activating donor-specific anti-HLA antibodies in solid organ transplantation: systematic review, meta-analysis, and critical appraisal
Authors: Al-Awadhi Solaf , Raynaud Marc , Louis Kevin , Bouquegneau Antoine , Taupin Jean-Luc , Aubert Olivier , Loupy Alexandre , Lefaucheur Carmen 
Published: October 2023

IntroductionSeveral studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.MethodsWe conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.ResultsIn total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p&lt;0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p&lt;0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss.DiscussionWe demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.
Resting-state EEG microstates as electrophysiological biomarkers in post-stroke disorder of consciousness
Authors: Yu Fang , Gao Yanzhe , Li Fenglian , Zhang Xueying , Hu Fengyun , Jia Wenhui , Li Xiaohui 
Published: October 2023

IntroductionIschemic stroke patients commonly experience disorder of consciousness (DOC), leading to poorer discharge outcomes and higher mortality risks. Therefore, the identification of applicable electrophysiological biomarkers is crucial for the rapid diagnosis and evaluation of post-stroke disorder of consciousness (PS-DOC), while providing supportive evidence for cerebral neurology.MethodsIn our study, we conduct microstate analysis on resting-state electroencephalography (EEG) of 28 post-stroke patients with awake consciousness and 28 patients with PS-DOC, calculating the temporal features of microstates. Furthermore, we extract the Lempel-Ziv complexity of microstate sequences and the delta/alpha power ratio of EEG on spectral. Statistical analysis is performed to examine the distinctions in features between the two groups, followed by inputting the distinctive features into a support vector machine for the classification of PS-DOC.ResultsBoth groups obtain four optimal topographies of EEG microstates, but notable distinctions are observed in microstate C. Within the PS-DOC group, there is a significant increase in the mean duration and coverage of microstates B and C, whereas microstate D displays a contrasting trend. Additionally, noteworthy variations are found in the delta/alpha ratio and Lempel-Ziv complexity between the two groups. The integration of the delta/alpha ratio with microstates’ temporal and Lempel-Ziv complexity features demonstrates the highest performance in the classifier (Accuracy = 91.07%).DiscussionOur results suggest that EEG microstates can provide insights into the abnormal brain network dynamics in DOC patients post-stroke. Integrating the temporal and Lempel-Ziv complexity microstate features with spectral features offers a deeper understanding of the neuro mechanisms underlying brain damage in patients with DOC, holding promise as effective electrophysiological biomarkers for diagnosing PS-DOC.
Effects of reducing free sugars on 24-hour glucose profiles and glycemic variability in subjects without diabetes
Authors: Pappe Christina Laeticia , Peters Beeke , Dommisch Henrik , Woelber Johan Peter , Pivovarova-Ramich Olga 
Published: October 2023

BackgroundThe Western diet, especially beverages and high processed food products, is high in sugars which are associated with the development of obesity and diabetes. The reduction of refined carbohydrates including free and added sugars improves glycemic control in individuals with diabetes, but the data regarding effects in subjects without diabetes are limited.ObjectiveThis study aimed to evaluate the effects of reducing free sugar intake on 24-h glucose profiles and glycemic variability using continuous glucose monitoring (CGM).MethodsIn the randomized controlled study, 21 normal weight and overweight/obese subjects (BMI 18–40 kg/m2) without diabetes were assigned to a 4-week reduced-sugar (RS) diet or control diet after a 2-week baseline phase. During the baseline phase, all participants were advised not to change their habitual diet. During the intervention phase, RS participants were asked to avoid added sugar and white flour products, whereas participants of the control group were requested to proceed their habitual diet. Anthropometric parameters and HbA1c were assessed before and at the end of the intervention phase. Interstitial glucose was measured using continuous glucose monitoring (CGM), and the food intake was documented by dietary records for 14 consecutive days during the baseline phase and for the first 14 consecutive days during the intervention phase. Mean 24-h glucose as well as intra- and inter-day indices of glucose variability, i.e., standard deviation (SD) around the sensor glucose level, coefficient of variation in percent (CV), mean amplitude of glucose excursions (MAGE), continuous overlapping net glycemic action (CONGA), and mean absolute glucose (MAG), were calculated for the baseline and intervention phases.ResultsDuring the intervention, the RS group decreased the daily intake of sugar (i.e., −22.4 ± 20.2 g, −3.28 ± 3.61 EN %), total carbohydrates (−6.22 ± 6.92 EN %), and total energy intake (−216 ± 108 kcal) and increased the protein intake (+2.51 ± 1.56 EN %) compared to the baseline values, whereby this intervention-induced dietary changes differed from the control group. The RS group slightly reduced body weight (−1.58 ± 1.33 kg), BMI, total fat, and visceral fat content and increased muscle mass compared to the baseline phase, but these intervention-induced changes showed no differences in comparison with the control group. The RS diet affected neither the 24-h mean glucose levels nor intra- and inter-day indices of glucose variability, HbA1c, or diurnal glucose pattern in the within- and between-group comparisons.ConclusionThe dietary reduction of free sugars decreases body weight and body fat which may be associated with reduced total energy intake but does not affect the daily mean glucose and glycemic variability in individuals without diabetes.Clinical trial registrationGerman Clinical Trials Register (DRKS); identifier: DRKS00026699.