bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-CCR4 treatment depletes regulatory T cells and leads to clinical activity in a canine model of advanced prostate cancer
Authors: Maeda Shingo , Motegi Tomoki , Iio Aki , Kaji Kenjiro , Goto-Koshino Yuko , Eto Shotaro , Ikeda Namiko , Nakagawa Takayuki , Nishimura Ryohei , Yonezawa Tomohiro , Momoi Yasuyuki 
Published: February 2022

BackgroundTargeting regulatory T cell (Treg) infiltration is an emerging strategy for cancer immunotherapy. However, its efficacy in advanced prostate cancer remains unclear. Here, we showed the therapeutic efficacy of anti-Treg treatment in a canine model of advanced prostate cancer.MethodsWe used dogs with naturally occurring prostate cancer to study the molecular mechanism underlying Treg infiltration and the effect of anti-Treg treatment. Tumor-infiltrating Tregs was evaluated by immunohistochemistry, and the association with prognosis was examined in dogs with spontaneous prostate cancer. The molecular mechanism of Treg infiltration was explored by RNA sequencing and protein analyses. A non-randomized canine clinical trial was conducted to define the therapeutic potential of anti-Treg treatment for advanced prostate cancer. Human prostate cancer datasets were analyzed to compare gene expression in dogs and humans.ResultsTumor-infiltrating Tregs were associated with poor prognosis in dogs bearing spontaneous prostate cancer. RNA sequencing and protein analyses showed a possible link between the CCL17–CCR4 pathway and the increase of tumor-infiltrating Tregs. Dogs with advanced prostate cancer responded to mogamulizumab, a monoclonal antibody targeting CCR4, with decreased circulating Tregs, improved survival, and low incidence of clinically relevant adverse events. Urinary CCL17 concentration and BRAFV595E mutation were independently predictive of the response to mogamulizumab. Analysis of a transcriptomic dataset of human prostate cancer showed that the CCL17–CCR4 axis correlated with Foxp3. In silico survival analyses revealed that high expression of CCL17 was associated with poor prognosis. Immunohistochemistry confirmed that tumor-infiltrating Tregs expressed CCR4 in human patients with prostate cancer.ConclusionsAnti-Treg treatment, through CCR4 blockade, may be a promising therapeutic approach for advanced prostate cancer in dogs and some population of human patients.
CD8+PD-1+ to CD4+PD-1+ ratio (PERLS) is associated with prognosis of patients with advanced NSCLC treated with PD-(L)1 blockers
Authors: Duchemann Boris , Naigeon Marie , Auclin Edouard , Ferrara Roberto , Cassard Lydie , Jouniaux Jean-Mehdi , Boselli Lisa , Grivel Jonathan , Desnoyer Aude , Danlos François-Xavier , Mezquita Laura , Caramella Caroline , Marabelle Aurelien , Besse Benjamin , Chaput Nathalie 
Published: February 2022

BackgroundProgrammed cell death protein-1 (PD-1) expression has been associated with activation and exhaustion of both the CD4 and CD8 populations in advanced non-small cell lung cancer (aNSCLC). Nevertheless, the impact of the balance between circulating CD8+PD-1+ and CD4+PD-1+ in patients treated with immune checkpoint blockers (ICB) is unknown.MethodsThe CD8+PD-1+ to CD4+PD-1+ ratio (PD-1-Expressing Ratio on Lymphocytes in a Systemic blood sample, or ‘PERLS’) was determined by cytometry in fresh whole blood from patients with aNSCLC before treatment with single-agent ICB targeting PD-1 or programmed cell death-ligand 1 (PD-L1 (discovery cohort). A PERLS cut-off was identified by log-rank maximization. Patients treated with ICB (validation cohort) or polychemotherapy (control cohort) were classified as PERLS+/− (above/below cut-off). Circulating immune cell phenotype and function were correlated with PERLS. A composite score (good, intermediate and poor) was determined using the combination of PERLS and senescent immune phenotype as previously described in aNSCLC.ResultsIn the discovery cohort (N=75), the PERLS cut-off was 1.91, and 11% of patients were PERLS+. PERLS + correlated significantly with median progression-free survival (PFS) of 9.63 months (95% CI 7.82 to not reached (NR)) versus 2.69 months (95% CI 1.81 to 5.52; p=0.03). In an independent validation cohort (N=36), median PFS was NR (95% CI 7.9 to NR) versus 2.00 months (95% CI 1.3 to 4.5; p=0.04) for PERLS + and PERLS−, respectively; overall survival (OS) followed a similar but non-significant trend. In the pooled cohort (N=111), PERLS + correlated significantly with PFS and OS. PERLS did not correlate with outcome in the polychemotherapy cohort. PERLS did not correlate with clinical characteristics but was significantly associated with baseline circulating naïve CD4+ T cells and the increase of memory T cells post-ICB treatment. Accumulation of memory T cells during treatment was linked to CD4+ T cell polyfunctionality. The composite score was evaluated in the pooled cohort (N=68). The median OS for good, intermediate and poor composite scores was NR (95% CI NR to NR), 8.54 months (95% CI 4.96 to NR) and 2.42 months (95% CI 1.97 to 15.5; p=0.001), respectively. The median PFS was 12.60 months (95% CI 9.63 to NR), 2.58 months (95% CI 1.74 to 7.29) and 1.76 months (95% CI 1.31 to 4.57; p<0.0001), respectively.ConclusionsElevated PERLS, determined from a blood sample before immunotherapy, was correlated with benefit from PD-(L)1 blockers in aNSCLC.
Polyclonal hypergammaglobulinaemia: towards definition of a threshold
Authors: Baillou Chloé , Jacomet Florence , Dejoie Thomas , Lureau Pierre , Beuvon Clément , Grados Aurélie , Martins Pauline , Roblot Pascal , Puyade Mathieu , Martin Mickael 
Published: February 2022

Abstract

Background
Polyclonal hypergammaglobulinaemia (PH) represents a classic diagnosis problem in internal medicine. However, there is no consensus threshold for PH. The aim of this study was to define a threshold for PH.

Methods
We conducted a retrospective multicentric study using laboratory biological databases between 1 January 2016 and 31 December 2016 in two university hospitals and one non-university hospital. All patients 18 years old or over and with at least one serum protein electrophoresis (SPE) available in 2016 were included. Exclusion criteria were monoclonal, biclonal, or oligoclonal spikes or, in case of hypogammaglobulinaemia, proven free light chain gammopathy. The main endpoint was to define the threshold values for PH in this population. Another objective was to define the 95th percentile of the distribution.

Results
20 766 SPEs were included in this cohort. The PH threshold on 95th percentile was 18.9 g/L. The threshold varied according to geographical areas.

Conclusions
This is the first study to scientifically define a PH threshold. The main limitation is that our threshold is only biological. The study was not designed to associate this threshold with a clinically active disease. In conclusion, while the 19 g/L cut-off seems the most relevant threshold, but it will need to be validated by prospective studies.
Production of anti-PF4 antibodies in antiphospholipid antibody-positive patients is not affected by COVID-19 vaccination
Authors: Lonati Paola Adele , Bodio Caterina , Scavone Mariangela , Martini Giuliana , Pesce Elisa , Bandera Alessandra , Lombardi Andrea , Gerosa Maria , Franceschini Franco , Tincani Angela , Podda Gianmarco , Abrignani Sergio , Grifantini Renata , Cattaneo Marco , Borghi Maria Orietta , Meroni Pier Luigi 
Published: February 2022

BackgroundAntibodies against cationic platelet chemokine, platelet factor 4 (PF4/CXCL4), have been described in heparin-induced thrombocytopenia (HIT), but also in patients positive for antiphospholipid antibodies (aPL) even in the absence of heparin treatment and HIT-related clinical manifestations. Anti-PF4 antibodies have been recently described also in subjects who developed thrombosis with thrombocytopenia syndrome (TTS) in association with adenoviral vector-based, but not with mRNA-based, COVID-19 vaccines.ObjectiveTo investigate whether COVID-19 vaccination affects the production of anti-PF4 antibodies in aPL-positive patients and in control groups.MethodsAnti-PF4 immunoglobulins were detected in patients’ and controls’ serum samples by ELISA and their ability to activate normal platelets was assessed by the platelet aggregation test.ResultsAnti-PF4 were found in 9 of 126 aPL-positive patients, 4 of 50 patients with COVID-19, 9 of 49 with other infections, and 1 of 50 aPL-negative patients with systemic lupus erythematosus. Clinical manifestations of TTS were not observed in any aPL patient positive for anti-PF4, whose serum failed to cause platelet aggregation. The administration of COVID-19 vaccines did not affect the production of anti-PF4 immunoglobulins or their ability to cause platelet aggregation in 44 aPL-positive patients tested before and after vaccination.ConclusionsHeparin treatment-independent anti-PF4 antibodies can be found in aPL-positive patients and asymptomatic carriers, but their presence, titre as well as in vitro effect on platelet activation are not affected by COVID-19 vaccination.
E-cigarette brands and social media influencers on Instagram: a social network analysis
Authors: Vassey Julia , Valente Tom , Barker Joshua , Stanton Cassandra , Li Dongmei , Laestadius Linnea , Cruz Tess Boley , Unger Jennifer B 
Published: February 2022

BackgroundExposure to visual posts featuring e-cigarette products on social media is associated with increased e-cigarette use among US adolescents. Instagram is the largest source of e-cigarette social media marketing, where influencers—for example, bloggers, brand ambassadors—post promotional materials. This study analysed the network of e-cigarette brands and influencers on Instagram, characterising the most central players in e-cigarette social media marketing.MethodsWe tracked influencers with public profiles on Instagram who posted promotional e-cigarette content in 2020, had over 1000 followers and high user engagement rate (ratio of likes and comments to followers) of 1%–25% per post. By conducting a social network analysis, we identified the most central (highly involved in promotional activities) influencers and e-cigarette brands. The number of the influencers’ followers aged 13–17 years old and the age verification practices restricting youth access were also assessed.ResultsThere is a highly interconnected network of engaging e-cigarette influencers (n=55) worldwide who collaborated with over 600 e-cigarette brands in 2020. The Asian and US influencers had five to six times more teenage followers compared with the European influencers. 75% of the influencers did not restrict youth access to their promotional content on Instagram. The brands Voopotech, Innokin, Geekvape, Lost Vape, Smok and Vaporesso collaborated with the largest number of influencers (mean n=20).ConclusionsIt is important to understand associations among influencers and e-cigarette use behaviours, especially youth, to inform effective public health communication and potential policies that could regulate social media marketing sponsored by e-cigarette companies.
Intelligent Building with Multi-Energy System Planning Method Considering Energy Supply Reliability
Authors: Qiao Guanghua 
Published: February 2022

Energy consumption is important to consume less power, reducing toxic fumes released by plants, preserving natural resources, and protecting ecosystems against damage. The challenging characteristics in energy supply include lack of renewable energy adoption, and policy and energy management are 0considered essential factors. An artificial intelligent building with a multi-energy planning method (AIBMEM) has been proposed to design multi-energy systems to achieve the best policy and energy management techniques. The intelligent construction problem with multi-energy is framed as a predictive energy model to minimize the overall utilization of energy levels. The normal distribution with the artificial intelligent model is introduced to solve the problem of renewable energy. The experimental results based on reliability, effectiveness, preservation, energy consumption, and control systems show that the suggested model is better than existing models, producing good performance analysis results.
Nanoelectrode Atomic Force Microscopy Probes Enable the in-Operando Measurement of Surface Electrochemical Potentials during Oxygen Evolution Catalysis
Authors: Nellist Michael R. , Laskowski Forrest A.L. , Qiu Jingjing , Boettcher Shannon W. 
Published: February 2022

Heterogeneous electrochemical processes, including (photo)electrochemical water splitting to evolve hydrogen via semiconductors and/or electrocatalysts, are driven by the accumulation of charge carriers and thus the interfacial electrochemical potential gradients that promote charge transfer. Conventional electrochemical techniques measure/control potentials at the conductive substrate, but are unable to isolate processes and electrochemical potentials at the surface during operation.1 In this talk, we will show that a nanoelectrode tip of an atomic force microscope cantilever can effectively sense the surface electrochemical potential of electrocatalysts in operando.2 First, we will discuss fundamental aspects and capabilities of the probes used.3 We then will show how the technique allows for measurement of the surface potential and thickness-dependent electronic properties of cobalt (oxy)hydroxide phosphate (CoPi). We show that when CoPi is deposited on illuminated photoanodes like hematite (a-Fe2O3), it acts as both a hole collector and an oxygen evolution catalyst. We highlight the versatility of the technique by comparing surface potentials of CoPi-decorated planar and mesoporous hematite, as well as bismuth vanadate photoelectrodes.
References:
(1) Nellist, M. R.; Laskowski, F. A. L.; Lin, F.; Mills, T. J.; Boettcher, S. W. Semiconductor-Electrocatalyst Interfaces: Theory, Experiment, and Applications in Photoelectrochemical Water Splitting. Acc. Chem. Res.
2016, 49, 733–740.
(2) Nellist, M. R.; Laskowski, F. A. L.; Qiu, J.; Hajibabaei, H.; Sivula, K.; Hamann, T. W.; Boettcher, S. W. Potential-Sensing Electrochemical Atomic Force Microscopy for In-Operando Analysis of Electrocatalysis During (Photo)electrochemical Water Splitting. Accepted, Nature Energy
2017.
(3) Nellist, M. R.; Chen, Y.; Mark, A.; Gödrich, S.; Stelling, C.; Jiang, J.; Poddar, R.; Li, C.; Kumar, R.; Papastavrou, G.; Retsch, M.; Brunschwig, B. S.; Huang, Z.; Xiang, C.; Boettcher, S. W. Atomic Force Microscopy with Nanoelectrode Tips for High Resolution Electrochemical, Nanoadhesion and Nanoelectrical Imaging. Nanotechnology
2017, 28, 95711.
Three-Dimensional Tin Oxide Nanohelix Structures with Thin Iron Oxide Layer for Efficient Visible Light Driven Water Splitting
Authors: Choi Il Yong , Jeon Tae Hwa , Chae Byeong-Gyu , Kim Dong Yeong , Park Chan-Gyung , Choi Wonyong , Kim Jong Kyu 
Published: February 2022

Solar-powered photoelectrochemical (PEC) water splitting has been a promising candidate for producing hydrogen in a clean and renewable way. Photoelectrodes are key components in PEC cells for efficient and stable hydrogen generation because they play crucial roles in absorption of photons, the separation and transportation of photo-generated charge carriers, as well as the chemical reactions with water. A variety of metal oxides for efficient photoelectrode have been intensively explored, but it is still challenging to find desirable materials to satisfy lots of requirements for PEC water splitting.
Iron oxide (hematite, Fe2O3) has recently attracted much attention due to its earth abundance, low cost as well as desirable material properties for PEC water oxidation including narrow band gap energy of 2.0~2.2eV for visible light absorption and proper energy band alignment, etc. However, Fe2O3 has very short hole diffusion length and low carrier mobility, which causes considerable recombination of photo-generated electrons and holes. A lot of approaches such as nanostructures, heterojunction with other materials, surface modification, etc. have been reported to improve electrical properties of Fe2O3 which unfortunately cause poor light absorption.
In this study, three-dimensional tin oxide (SnO2) nanohelix (NH) structures were fabricated as scaffolds for a thin Fe2O3 layer on fluorine-doped SnO2 glass substrate by oblique angle deposition method using electron beam evaporator. SnO2 NH structures based photoelectrode can simultaneously enhance light absorption and charge separation and transport for efficient PEC water splitting by trapping the incident light through strong light scattering effect as well as by providing pathways for charge separation and transport and large surface area. In addition, SnO2 NH structures are easy to be hybridized with Fe2O3 through only simple solution-based spin-coating method due to its high porosity, aspect ratio and large surface area. Thin Fe2O3 layer was coated along the surface of SnO2 NH structures forming a type-II band hetero-junction and these Fe2O3 coated SnO2 NH are significantly desirable for efficient visible light driven water splitting by simultaneously improving light absorption, charge separation and transport. Highly efficient PEC performance of our hybridized photoelectrode (including more than 5.0mAcm-2 photocurrent density at 1.23VRHE under AM1.5G solar spectrum and 1 sun illumination which is a significantly excellent performance for Fe2O3 based photoelectode) will be investigated and the advantages of three-dimensional SnO2 NH structures as scaffolds for very thin Fe2O3 layer as well as its potential for practical application will be discussed in detail based on electrochemical analysis, FEM simulation, angular-dependent reflectance, PEC analysis at different intensity of incident light, etc.
Editorial
Authors: Pacheco Ana Paula Sá e Souza , Silva Anderson Gonçalves da , Fonseca Maria Augusta Bernardes 
Published: February 2022

Na sala de aula, centra seu interesse na leituras de poemas, tendo como público-alvo, mas não apenas, os alunos de Introdução aos Estudos Literários (IEL 1), visando cobrir algumas lacunas deixadas pelas aulas remotas neste duro período em que se propagou violentamente a pandemia da Covid 19, tirando todos das aulas presenciais. O número está dividido em cinco partes: 1. Abertura. Aula, reprodução de manuscrito, depoimento e texto-homenagem; 2. Leitura de poemas: variedades; 3. Drummond em foco: múltiplas leituras; 4. Literatura contemporânea visadas analíticas. Pensando a sala de aula e lembrando a grande perda que tivemos em 31 de dezembro de 2020, com o falecimento do nosso querido colega Professor Doutor Eduardo Vieira Martins, a quem este número, dedicado à análise de poemas na sala de aula, rende homenagem.
A política de atenção à saúde do servidor público federal, o tratamento estatal sobre as doenças graves e raras e sua relação com a dignidade da pessoa humana, e os impactos da gestão gerencial e da automação nos processos de trabalho
Authors: Ribeiro Leonardo Coelho , Büttenbender Pedro Luís 
Published: February 2022

O artigo versa sobre a Política de Atenção à saúde do servidor público federal, sobre o tratamento estatal em relação às doenças graves e/ou raras e sobre a questão dos impactos que a implantação da gestão estratégica e da automação está trazendo nos processos de trabalho. Tem como objetivo analisar se há políticas públicas eficientes que protejam a saúde dos servidores, tutelem os portadores de doenças graves e/ou raras e verificar os impactos da gestão gerencial e da automação nos processos de trabalho na saúde dos servidores. O estudo conclui que as políticas públicas de atenção a saúde do servidor público federal e dos portadores de doenças graves tem sido muito ineficientes, demonstrando uma notória falta de interesse público, bem como a necessidade de criação de normas e da implantação de políticas públicas nessas áreas; e que o processo de automação, apesar de ser inevitável, precisa ser implantado de forma gradativa e melhor planejado, a fim de que não produza efeitos nocivos aos servidores e a toda a sociedade.
Cage 22
Authors: Tofoli Rejane do Nascimento 
Published: February 2022

O ensaio realizado no primeiro semestre de 2021, apresenta fotografias que foram captadas no período de lockdown em virtude da pandemia causada pelo coronavírus. As imagens foram capturadas a partir da janela do segundo andar do prédio em que reside a autora. As imagens refletem a liberdade dos pássaros contrastando com o caminho inverso ao do lockdown provocado pela pandemia. Não foram utilizados efeitos artísticos para que a própria natureza pudesse expressar seu estilo.
Palavras-chave: Pássaros, Gaiola, Lockdown, Pandemia, Liberdade.
Genome-Wide De Novo Variants in Congenital Heart Disease Are Not Associated With Maternal Diabetes or Obesity
Authors: Morton Sarah U. , Pereira Alexandre C. , Quiat Daniel , Richter Felix , Kitaygorodsky Alexander , Hagen Jacob , Bernstein Daniel , Brueckner Martina , Goldmuntz Elizabeth , Kim Richard W. , Lifton Richard P. , Porter George A. , Tristani-Firouzi Martin , Chung Wendy K. , Roberts Amy , Gelb Bruce D. , Shen Yufeng , Newburger Jane W. , Seidman J.G. , Seidman Christine E. 
Published: February 2022

Background:
Congenital heart disease (CHD) is the most common anomaly at birth, with a prevalence of ≈1%. While infants born to mothers with diabetes or obesity have a 2- to 3-fold increased incidence of CHD, the cause of the increase is unknown. Damaging de novo variants (DNV) in coding regions are more common among patients with CHD, but genome-wide rates of coding and noncoding DNVs associated with these prenatal exposures have not been studied in patients with CHD.

Methods:

DNV frequencies were determined for 1812 patients with CHD who had whole-genome sequencing and prenatal history data available from the Pediatric Cardiac Genomics Consortium’s CHD GENES study (Genetic Network). The frequency of DNVs was compared between subgroups using
t
test or linear model.

Results:

Among 1812 patients with CHD, the number of DNVs per patient was higher with maternal diabetes (76.5 versus 72.1,
t
test
P
=3.03×10
−11
), but the difference was no longer significant after including parental ages in a linear model (paternal and maternal correction
P
=0.42). No interaction was observed between diabetes risk and parental age (paternal and maternal interaction
P
=0.80 and 0.68, respectively). No difference was seen in DNV count per patient based on maternal obesity (72.0 versus 72.2 for maternal body mass index <25 versus maternal body mass index >30,
t
test
P
=0.86).

Conclusions:
After accounting for parental age, the offspring of diabetic or obese mothers have no increase in DNVs compared with other children with CHD. These results emphasize the role for other mechanisms in the cause of CHD associated with these prenatal exposures.

Registration:

URL:
https://clinicaltrials.gov
; NCT01196182.