bluuebunny/crossref_metadata_2025 huggingface dataset:
Análise textual de artigos nacionais de Educação Emocional e suas potencialidades em relação ao indicador de Felicidade Interna Bruta
Authors: Inês Boll Cíntia , Decarli Cecilia
Published: October 2022

Este artigo apresenta uma análise textual de trabalhos acadêmicos encaminhados ao Congresso Nacional de Educação (Conedu) no eixo Educação Emocional, relacionando-os às categorias propostas pelo indicador de Felicidade Interna Bruta (FIB). Os objetivos foram identificar os conceitos mais utilizados nos artigos e elencar as categorias do FIB que desenvolvem em maior potencial, para verificar a influência de atividades curriculares que desenvolvem as emoções para a vida em sociedade. Através do método de Classificação de Reinert do software IRAMUTEQ, separamos as palavras utilizadas nos artigos em quatro classes textuais e as classificamos de acordo com as categorias do FIB, no intuito de elencar relações entre os conceitos emocionais abordados na educação brasileira o indicador, potencializando práticas de educação emocional. A análise textual de conteúdo permitiu verificar que as relações entre as práticas escolares envolvendo a educação emocional e as classes identificadas contemplam o desenvolvimento ético, integral ecidadão do aluno. Vislumbra-se a aproximação da educação emocional com o FIB em futuras aplicações do indicador no país, relacionando, assim, saberes acadêmicos e da educação básica para o desenvolvimento do bem-estar social e a felicidade de uma nação
Experiências de aprendizagem, contextos de ensino e processos de interação: pistas para a educação pós-pandêmica
Authors: Lúcia Forneck Kári , Neumann Martins Silvana , Sullivan Faleiro Róger , Taís Werlang Carolina
Published: October 2022

Este estudo buscou investigar as percepções de estudantes de pós-graduação acerca das práticas de ensino e aprendizagem em um componente curricular ministrado de forma remota, com encontros síncronos. Para tanto, foram analisadas respostas coletadas através de um questionário elaborado no Google Forms, disponibilizado ao final da realização das aulas aos vinte estudantes matriculados. Numa aproximação com a metodologia de Análise Textual Discursiva (ATD), verificamos a emergência de três categorias de análise: experiências de aprendizagem; contextos de ensino; e processos de interação. A fim de tecermos as análises e ainda considerando os pressupostos metodológicos da ATD, ancoramos as reflexões em três bases conceituais, sendo elas: metacognição, metodologias ativas e linguagem e interação. Com base nessa interface, a análise desses dados apontou que a) mesmo em contexto digital, os estudantes experimentaram contextos de aprendizagem automonitorada; b) propostas metodológicas de ensino em contexto virtualizado são mais efetivas se partirem do pressuposto da aprendizagem ativa; e c) a interação síncrona é fundamental para fortalecer os processos de ensino e de aprendizagem, uma vez que discussões e atividades em grupo oferecem outras perspectivas e experiências. Essas percepções podem contribuir para enriquecer os debates sobre a virtualização das aulas em contexto pós-pandêmico.
Exploiting the resource-ratio (R*) hypothesis for weed management in legume crops: An example of volunteer Brassica napus in soybean
Authors: Geddes Charles M. , Gulden Robert H.
Published: October 2022

Poor competitive ability and sensitivity to many herbicides create challenges for weed management in legume production. The resource-ratio (R*) hypothesis may provide insight into how to manipulate the competitive balance between nitrogen (N)-fixing legume crops and non-leguminous weed species. A field study was conducted to test whether the level of soil mineral N affected yield loss of an annual legume crop, soybean [Glycine max (L.) Merr.], in the presence of four different populations of an interfering non-leguminous weed, volunteer canola (Brassica napus L.), compared with a weed-free control. The experiment consisted of banding five rates of urea fertilizer (0–180 kg N ha-1) prior to seeding soybean and volunteer canola, and was repeated in three environments in Manitoba, Canada. Soybean yield remained unaffected by N rate in the absence of volunteer canola. Interference from the volunteer canola populations caused a linear decline in soybean yield by 2.6 kg ha-1 for every 1 kg ha-1 increase in soil mineral N. In the presence of volunteer canola, soybean yield decreased by 17% from the lowest to the highest soil mineral N. In the lowest-N conditions (30 kg residual-N ha-1), soybean yield was greatest (3,350 kg ha-1) and volunteer canola seed production and aboveground biomass were lowest (decline in canola seed production by 19%, 50%, and 74% of the maximum seed production in the 2015i, 2015ii, and 2016 environments, respectively). Therefore, growing legume crops like soybean on fields with lower soil mineral N may reduce interference from unmanaged non-leguminous weeds. As N fertilization intensifies interference of many weed species, tailoring weed management in legume crops around their capacity for N-fixation could provide the crop with a competitive advantage, thereby minimizing the impact of weed interference on legume crop yield.
Profiling azole resistant haplotypes within Zymoseptoria tritici populations using nanopore sequencing
Authors: Gutierrez Vazquez Yaiza , Adams Ian P. , McGreig Sam , Walshaw John , van den Berg Femke , Sanderson Roy , Pufal Hollie , Conyers Chris , Langton David , Broadhead Ruth , Harrison Catherine , Boonham Neil
Published: October 2022

Zymoseptoria tritici is the causal agent of Septoria tritici blotch, the most important disease affecting wheat crops and responsible for up to 50% loss in yield. Azoles and SDHIs are the main groups of fungicides used to control the disease. The efficacy of these fungicides has decreased in recent years due to resistance development. Fungicide resistance can be a result of mutations in the target genes, mutations in upstream regulatory elements that result in over-expression of target proteins and the overexpression of transporters that remove toxic compounds from cells. In the current study nanopore sequencing was used to analyse isolates, mock communities and field samples to determine the pathogen population composition related to azole resistance. Despite the presence of sequencing errors, the method was able to effectively differentiate the sequences of different haplotypes present in both mock and field populations for haplotypes that were relatively common in the overall population. However, haplotypes present at a frequency lower than 5% of the total population, could not be accurately distinguished from haplotypes generated through background sequencing errors. The nanopore protocols are rapid and inexpensive, enabling the routine profiling of haplotypes within pathogen populations at the start of the season or between sprays, facilitating the selection of the most appropriate fungicide to control them, yet limit further selection for azole resistance.
Acidified diet is not effective in preventing hypocalcemia in dairy cows on French commercial farms
Authors: Aubineau Thomas , Boudon Anne , Guatteo Raphaël
Published: October 2022

The objective of this study was to assess, in the context of typical dairy farms in western France, the preventive effects of prepartum diet acidification (AcD) and mineral intake during late gestation on the incidence of subclinical hypocalcemia (SHC) and subclinical hypophosphatemia (SHP) after calving. We conducted a longitudinal study that followed a cohort of 371 Holstein cows from 26 French dairy farms; of these, 235 cows (15 farms) were supplied with anionic salts during late gestation, and 136 cows (11 farms) were not. Blood samples were collected from 1 to 22 cows per farm (average of 14.3 cows per farm) between 24 and 48 h after calving. Total calcium and inorganic phosphorus concentrations in plasma were then quantified by inductively coupled plasma - optical emission spectrometry. The effects of AcD on the incidence of SHC and SHP were assessed using mixed linear models that evaluated the cow-level factors parity, milk yield index, and individual health events/treatments, and the farm-level factors diet calcium and magnesium content, dietary phosphorus intake, vitamin D supply, diet crude protein content, and duration of AcD, with farm as a random effect. Approximately 55% of cows were diagnosed with SHC (calcium < 2.0 mmol/l, n = 203) and 37% with SHP (inorganic phosphorus < 1.3 mmol/l, n=136). The first model confirmed earlier findings that the risk of SHC is higher with increased parity (P ≤ 0.0001) and revealed a higher risk associated with high milk yield (P = 0.0005), high phosphorus intake (40–60 g/cow per day, OR = 3.5; ≥ 60 g/cow per day, OR = 7.3; P = 0.0003) and high vitamin D supply (≥ 19950 IU/cow per day, OR = 3, P = 0.007). The second model highlighted a greater risk of SHP with increasing parity (P = 0.03) and showed trends for the preventive effects of AcD (OR = 0.4, P = 0.07) and moderate amounts of phosphorus in the diet (OR = 0.4, P = 0.10). Overall, our results do not support the effectiveness of AcD in preventing SHC or SHP under field conditions examined here, probably resulting from insufficient diet acidification.
The diagnostic value of metagenomic next-generation sequencing for identifying Pneumocystis jirovecii infection in non-HIV immunocompromised patients
Authors: Zhao Mengyi , Yue Ruiming , Wu Xiaoxiao , Gao Zhan , He Miao , Pan Lingai
Published: October 2022

Background

Pneumocystis jirovecii pneumonia (PJP) remains an important cause of morbidity and mortality in non-HIV immunocompromised patients especially in transplant recipients. But its diagnosis remains challenging due to the insuffificient performance of conventional methods for diagnosing Pneumocystis jirovecii(P. jirovecii) infection. Therefore, the auxiliary diagnostic function of metagenomics next-generation sequencing (mNGS) in clinical practice is worth of exploring.

Method

34 non-HIV immunocompromised patients who were diagnosed as PJP by clinical manifestations, imaging findings, immune status of the host, and Methenamine silver staining were tested by mNGS from October 2018 to December 2020 in Sichuan Provincial People’s Hospital. The clinical performances of mNGS for P. jirovecii infection diagnosis were also evaluated with genome reads abundance and comparing with other traditional diagnostic methods.

Results

We diagnosed a total of 34 non-HIV PJP patients by the clinical composite diagnosis. Our data shows that, compared with the clinical microbiological test, the detection rate of mNGS for P. jirovecii in non-HIV infected PJP patients is significantly higher than that of Methenamine silver staining and serum 1-3-β-D-glucan. mNGS can be used as an auxiliary diagnostic tool to help diagnosis. The number of reads mapped to the genome of P. jirovecii and the duration of patients from onset to sampling collection were statistically significant between the two groups (Reads>100 and Reads ≤ 100) (8days vs. 23days, p=0.020). In addition, univariate analysis showed that C-reactive protein (15.8mg/L vs.79.56mg/L, p=0.016), lactate dehydrogenase (696U/l vs. 494U/l, p=0.030) and procalcitonin (0.09ng/ml vs. 0.59ng/ml, p=0.028) was also statistically significant between the two groups.

Conclusions

An effective detection rate was achieved in PJP patients using mNGS testing of bronchoalveolar lavage fluid (BALF) or blood. The study also confirmed that the abundance of reads of P. jirovecii is related to the interval between the onset and sample collection. And the inflammation status during simultaneous mNGS detection might determine the abundance of pathogens. Hence, we conclude that the mNGS strategy could benefit disease diagnosis as well as treatment when complicated clinical infections appeared.
The burden and predictors of latent tuberculosis infection among elder adults in high epidemic rural area of tuberculosis in Zhejiang, China
Authors: Wang Wei , Chen Xinyi , Chen Songhua , Zhang Mingwu , Wang Wei , Hao Xiaogang , Liu Kui , Zhang Yu , Wu Qian , Zhu Ping , Chen Bin
Published: October 2022

Diagnosis and treatment of latent tuberculosis infection (LTBI) is critical to tuberculosis (TB) control. Identifying the risk factors associated with LTBI can contribute to developing an optimized strategy for LTBI management. We conducted a survey of adults aged 65 years and older living in rural areas in Zhejiang Province during July 2021, followed by a one-year follow-up period to determine TB incidence. Participants underwent a physical examination and 5–6 mL of blood was drawn to test for Mycobacterium tuberculosis infection A total of 1856 individuals participated in the study, of whom 50.5% were men and 80.1% were married. Most participants (96.8%) often opened windows for ventilation at home. One-third (33.4%) of participants had abnormal chest radiographs and 34.9% had LTBI. Nine participants (0.5%) developed active TB patients during the one-year follow-up period. People who frequented closed entertainment places such as chess and card rooms had a relatively high percentage of LTBI (39.5%). Factors associated with a higher risk of LTBI in multivariable logistic regression analysis included being male (odds ratio [OR]:1.32; 95% confidence interval [CI] =:1.01-1.72), smoking (OR: 1.43; 95% CI:1.04-1.97), not opening windows for ventilation at home frequently (OR: 1.88; 95% CI: 1.10–3.22), and abnormal chest radiographs (OR; 1.48; 95% CI; 1.20–1.81). LTBI was prevalent among the elder adults living in high-epidemic rural areas of TB in Zhejiang province. Men, people who smoke, and people without the habit of ventilating at home should be targeted for LTBI screening to accelerate the decline of the TB epidemic in Zhejiang Province.
Differential effects of Akkermansia-enriched fecal microbiota transplant on energy balance in female mice on high-fat diet
Authors: Acharya Kalpana D. , Friedline Randall H. , Ward Doyle V. , Graham Madeline E. , Tauer Lauren , Zheng Doris , Hu Xiaodi , de Vos Willem M. , McCormick Beth A. , Kim Jason K. , Tetel Marc J.
Published: October 2022

Estrogens protect against weight gain and metabolic disruption in women and female rodents. Aberrations in the gut microbiota composition are linked to obesity and metabolic disorders. Furthermore, estrogen-mediated protection against diet-induced metabolic disruption is associated with modifications in gut microbiota. In this study, we tested if estradiol (E2)-mediated protection against obesity and metabolic disorders in female mice is dependent on gut microbiota. Specifically, we tested if fecal microbiota transplantation (FMT) from E2-treated lean female mice, supplemented with or without Akkermansia muciniphila, prevented high fat diet (HFD)-induced body weight gain, fat mass gain, and hyperglycemia in female recipients. FMT from, and cohousing with, E2-treated lean donors was not sufficient to transfer the metabolic benefits to the E2-deficient female recipients. Moreover, FMT from lean donors supplemented with A. muciniphila exacerbated HFD-induced hyperglycemia in E2-deficient recipients, suggesting its detrimental effect on the metabolic health of E2-deficient female rodents fed a HFD. Given that A. muciniphila attenuates HFD-induced metabolic insults in males, the present findings suggest a sex difference in the impact of this microbe on metabolic health.
Potential therapeutic role of pyroptosis mediated by the NLRP3 inflammasome in type 2 diabetes and its complications
Authors: Li Xiang , Xiao Gui-Ying , Guo Tao , Song Yu-Jie , Li Qiu-Mei
Published: October 2022

As a new way of programmed cell death, pyroptosis plays a vital role in many diseases. In recent years, the relationship between pyroptosis and type 2 diabetes (T2D) has received increasing attention. Although the current treatment options for T2D are abundant, the occurrence and development of T2D appear to continue, and the poor prognosis and high mortality of patients with T2D remain a considerable burden in the global health system. Numerous studies have shown that pyroptosis mediated by the NLRP3 inflammasome can affect the progression of T2D and its complications; targeting the NLRP3 inflammasome has potential therapeutic effects. In this review, we described the molecular mechanism of pyroptosis more comprehensively, discussed the most updated progress of pyroptosis mediated by NLRP3 inflammasome in T2D and its complications, and listed some drugs and agents with potential anti-pyroptosis effects. Based on the available evidence, exploring more mechanisms of the NLRP3 inflammasome pathway may bring more options and benefits for preventing and treating T2D and drug development.
Best Practices in PEC Water Splitting: How to Reliably Measure Solar-to-Hydrogen Efficiency of Photoelectrodes
Authors: Alley Olivia J. , Wyatt Keenan , Steiner Myles A. , Liu Guiji , Kistler Tobias , Zeng Guosong , Larson David M. , Cooper Jason K. , Young James L. , Deutsch Todd G. , Toma Francesca M.
Published: October 2022

Photoelectrochemical (PEC) water splitting, which utilizes sunlight and water to produce hydrogen fuel, is potentially one of the most sustainable routes to clean energy. One challenge to success is that, to date, similar materials and devices measured in different labs or by different operators lead to quantitatively different results, due to the lack of accepted standard operating procedures and established protocols for PEC efficiency testing. With the aim of disseminating good practices within the PEC community, we provide a vetted protocol that describes how to prepare integrated components and accurately measure their solar-to-hydrogen (STH) efficiency (ηSTH). This protocol provides details on electrode fabrication, ηSTH test device assembly, light source calibration, hydrogen evolution measurement, and initial material qualification by photocurrent measurements under monochromatic and broadband illumination. Common pitfalls in translating experimental results from any lab to an accurate STH efficiency under an AM1.5G reference spectrum are discussed. A III–V tandem photocathode is used to exemplify the process, though with small modifications, the protocol can be applied to photoanodes as well. Dissemination of PEC best practices will help those approaching the field and provide guidance for comparing the results obtained at different lab sites by different groups.
Lymphocyte antigen 6 complex locus G6D downregulation is a novel parameter for functional impairment of neutrophils in aged mice
Authors: Saito Suguru , Okuno Alato , Maekawa Toshio , Kobayashi Ryoki , Yamashita Osamu , Tsujimura Noriyuki , Inaba Morihiko , Kageyama Yasushi , Tsuji Noriko M.
Published: October 2022

Immunological aging is a critical event that causes serious functional impairment in the innate immune system. However, the identification markers and parameters are still poorly understood in immunological aging of myeloid lineage cells. Here, we show that a downregulation of lymphocyte antigen 6 complex locus G6D (Ly-6G) observed in aged mouse neutrophils could serve as a novel marker for the prediction of age-associated functional impairment in the neutrophils. Ly-6G expression was significantly downregulated in the bone marrow (BM) neutrophils of aged mice compared to young mice confirmed by flow cytometry analysis. In vitro experiments using BM-isolated neutrophils showed significant downregulations in their activities, such as phagocytosis, reactive oxygen species (ROS) production, interleukin (IL)-1β production, neutrophil extracellular trap (NET) formation, and migration as well as bacterial clearance, in the aged mouse neutrophils compared to those of young mice counterparts. Interestingly, the magnitudes of functional parameters were strongly correlated with the Ly-6G expression in the neutrophils. Thus, our results suggest that downregulation of Ly-6G reflects the age-associated functional attenuation of the neutrophils.
Insulin-regulated aminopeptidase contributes to setting the intensity of FcR-mediated inflammation
Authors: Bratti Manuela , Vibhushan Shamila , Longé Cyril , Koumantou Despoina , Ménasché Gaël , Benhamou Marc , Varin-Blank Nadine , Blank Ulrich , Saveanu Loredana , Ben Mkaddem Sanae
Published: October 2022

The function of intracellular trafficking in immune-complex triggered inflammation remains poorly understood. Here, we investigated the role of Insulin-Regulated Amino Peptidase (IRAP)-positive endosomal compartments in Fc receptor (FcR)-induced inflammation. Less severe FcγR-triggered arthritis, active systemic anaphylaxis and FcεRI-triggered passive systemic anaphylaxis were observed in IRAP-deficientversuswild-type mice. In mast cells FcεRI stimulation induced rapid plasma membrane recruitment of IRAP-positive endosomes. IRAP-deficient cells exhibited reduced secretory responses, calcium signaling and activating SykY519/520phosphorylation albeit receptor tyrosine phosphorylation on β and γ subunits was not different. By contrast, in the absence of IRAP, SHP1-inactivating phosphorylation on Ser591that controls Syk activity was decreased.Ex-vivocell profiling after FcγR-triggered anaphylaxis confirmed decreased phosphorylation of both SykY519/520and SHP-1S591in IRAP-deficient neutrophils and monocytes. Thus, IRAP-positive endosomal compartments, in promoting inhibition of SHP-1 during FcR signaling, control the extent of phosphorylation events at the plasma membrane and contribute to setting the intensity of immune-complex triggered inflammatory diseases.
Single-cell RNA sequencing reveals TCR+ macrophages in HPV-related head and neck squamous cell carcinoma
Authors: Jiang Yourong , Zhang Siwei , Tang Lu , Li Rui , Zhai Jinglei , Luo Suisui , Peng Yiman , Chen Xiaohang , Wei Lanlan
Published: October 2022

The prognosis of human papillomavirus (HPV)-infected head and neck squamous cell carcinoma (HNSCC) is often better than that of HPV- cancer, which is possibly caused by the differences in their immune microenvironments. The contribution of macrophage, as a principal innate immune cell, to this phenomenon is still unclear. In this study, a single-cell atlas of 4,388 high-quality macrophages from 18 HPV- and 8 HPV+ HNSCC patients was constructed with single-cell RNA sequencing data. Eight macrophage subsets were identified from HNSCC, whereas their functional properties and developmental trajectory were delineated based on HPV status. Our results demonstrated that macrophages in HPV+ HNSCC exhibit stronger phagocytic ability, although the infiltration rate of macrophages decreased. From the results, a unique macrophage subset with TCR and CD3-specific signatures was identified from HPV-related HNSCC. These TCR+ macrophages potentially participate in the regulation of the TCR signaling pathway and phagocytosis. In conclusion, our results suggested that HPV could affect the infiltration rate, function, and differentiation of macrophages in HNSCC, whereas TCR+ macrophages play a critical role in the HNSCC microenvironment. These results provide new insights into the immune microenvironment of HNSCC and offer a valuable resource for the understanding of the immune landscape of HPV-related HNSCC, which will in turn help the development of immunotherapy strategies for the disease.
The role of platelet mediated thromboinflammation in acute liver injury
Authors: Morris Sean M. , Chauhan Abhishek
Published: October 2022

Acute liver injuries have wide and varied etiologies and they occur both in patients with and without pre-existent chronic liver disease. Whilst the pathophysiological mechanisms remain distinct, both acute and acute-on-chronic liver injury is typified by deranged serum transaminase levels and if severe or persistent can result in liver failure manifest by a combination of jaundice, coagulopathy and encephalopathy. It is well established that platelets exhibit diverse functions as immune cells and are active participants in inflammation through processes including immunothrombosis or thromboinflammation. Growing evidence suggests platelets play a dualistic role in liver inflammation, shaping the immune response through direct interactions and release of soluble mediators modulating function of liver sinusoidal endothelial cells, stromal cells as well as migrating and tissue-resident leucocytes. Elucidating the pathways involved in initiation, propagation and resolution of the immune response are of interest to identify therapeutic targets. In this review the provocative role of platelets is outlined, highlighting beneficial and detrimental effects in a spatial, temporal and disease-specific manner.
Strategy of developing nucleic acid-based universal monkeypox vaccine candidates
Authors: Papukashvili Dimitri , Rcheulishvili Nino , Liu Cong , Wang Xingyun , He Yunjiao , Wang Peng George
Published: October 2022

Until May 2022, zoonotic infectious disease monkeypox (MPX) caused by the monkeypox virus (MPXV) was one of the forgotten viruses considered to be geographically limited in African countries even though few cases outside of Africa were identified. Central and West African countries are known to be endemic for MPXV. However, since the number of human MPX cases has rapidly increased outside of Africa the global interest in this virus has markedly grown. The majority of infected people with MPXV have never been vaccinated against smallpox virus. Noteworthily, the MPXV spreads fast in men who have sex with men (MSM). Preventive measures against MPXV are essential to be taken, indeed, vaccination is the key. Due to the antigenic similarities, the smallpox vaccine is efficient against MPXV. Nevertheless, there is no specific MPXV vaccine until now. Nucleic acid vaccines deserve special attention since the emergency approval of two messenger RNA (mRNA)-based coronavirus disease 2019 (COVID-19) vaccines in 2020. This milestone in vaccinology has opened a new platform for developing more mRNA- or DNA-based vaccines. Certainly, this type of vaccine has a number of advantages including time- and cost-effectiveness over conventional vaccines. The platform of nucleic acid-based vaccines gives humankind a huge opportunity. Ultimately, there is a strong need for developing a universal vaccine against MPXV. This review will shed the light on the strategies for developing nucleic acid vaccines against MPXV in a timely manner. Consequently, developing nucleic acid-based vaccines may alleviate the global threat against MPXV.
Intracellular monitoring by dendritic cells – a new way to stay informed – from a simple scavenger to an active gatherer
Authors: Herbst Christopher , Harshyne Larry A. , Igyártó Botond Z.
Published: October 2022

Dendritic cells (DCs) are required for the initiation of the adaptive immune response. Their ability to acquire antigens in the periphery is a critical step in this process. DCs express a wide variety of adhesion molecules and possess an extremely fluid plasma membrane that facilitates scavenging the extracellular environment and capturing material like exosomes, apoptotic bodies, and pathogens. Besides these standard routes, the acquisition of antigens by DCs can be further facilitated by tunneling nanotubes, trogocytosis, and gap junctions. However, in this article, we will argue that this is an incomplete picture, as certain observations in the literature cannot be explained if we assume DCs acquire antigens only through these means. Instead, it is more likely that DCs preferentially use adhesion molecules to form long-lasting cell-cell interactions to actively siphon material from cells they are in direct contact with. It is highly likely that DCs use this mechanism to continually capture membrane and cytosolic material directly from surrounding cells, which they scan to assess the health of the donor cell. Doing so would provide an array of advantages for the host immune system, as it would not be reliant on compromised cells to release antigens into the extracellular milieu. Therefore, we propose updating our view of DC antigen acquisition to include a process of active, contact-dependent capture of material directly from neighboring cell cytosol (cytocytosis), which we would term intracellular monitoring.
Neuroinflammation in retinitis pigmentosa: Therapies targeting the innate immune system
Authors: Zhao Ling , Hou Chen , Yan Naihong
Published: October 2022

Retinitis pigmentosa (RP) is an important cause of irreversible blindness worldwide and lacks effective treatment strategies. Although mutations are the primary cause of RP, research over the past decades has shown that neuroinflammation is an important cause of RP progression. Due to the abnormal activation of immunity, continuous sterile inflammation results in neuron loss and structural destruction. Therapies targeting inflammation have shown their potential to attenuate photoreceptor degeneration in preclinical models. Regardless of variations in genetic background, inflammatory modulation is emerging as an important role in the treatment of RP. We summarize the evidence for the role of inflammation in RP and mention therapeutic strategies where available, focusing on the modulation of innate immune signals, including TNFα signaling, TLR signaling, NLRP3 inflammasome activation, chemokine signaling and JAK/STAT signaling. In addition, we describe epigenetic regulation, the gut microbiome and herbal agents as prospective treatment strategies for RP in recent advances.
Cryoablation and immune synergistic effect for lung cancer: A review
Authors: Tian Yulong , Qi Xingshun , Jiang Xin , Shang Liqi , Xu Ke , Shao Haibo
Published: October 2022

The preferred treatment for lung cancer is surgical resection, but a large number of patients are not suitable for surgical resection in clinic. CT-guided cryoablation and immunotherapy can play an important role in patients with advanced lung cancer who are ineligible for surgery. CT-guided cryoablation has been widely used in the clinical treatment of lung tumors due to its advantages of less trauma, fewer complications, significant efficacy and rapid recovery. Cryoablation can not only cause tumor necrosis and apoptosis, but also promote the release of tumor-derived autoantigens into the blood circulation, and stimulate the host immune system to produce a good anti-tumor immune effect against primary and metastatic tumors. Since the study of immune checkpoint inhibitors has proved that lung cancer can be an immunotherapeutic response disease, the relationship between cryoablation and immunotherapy of lung cancer has been paid more attention. Therefore, we reviewed the literature on cryoablation for lung cancer, as well as the research progress of cryoablation combined with immunotherapy.
Construction of a B cell-related gene pairs signature for predicting prognosis and immunotherapeutic response in non-small cell lung cancer
Authors: Li Xuanzong , Wang Ruozheng , Wang Shijiang , Wang Linlin , Yu Jinming
Published: October 2022

Background

Accumulating evidence indicates that the B cells play important roles in anti-tumor immunity and shaping tumor development. This study aimed to explore the expression profiles of B cell marker genes and construct a B cell-related gene pairs (BRGPs) signature associated with the prognosis and immunotherapeutic efficiency in non-small cell lung cancer (NSCLC) patients.

Methods

B cell-related marker genes in NSCLC were identified using single-cell RNA sequencing data. TCGA and GEO datasets were utilized to identify the prognostic BRGPs based on a novel algorithm of cyclically single pairing along with a 0-or-1 matrix. BRGPs signature was then constructed using Lasso-Cox regression model. Its prognostic value, associated immunogenomic features, putative molecular mechanism and predictive ability to immunotherapy were investigated in NSCLC patients.

Results

The BRGPs signature was composed of 23 BRGPs including 28 distinct B cell-related genes. This predictive signature demonstrated remarkable power in distinguishing good or poor prognosis and can serve as an independent prognostic factor for NSCLC patients in both training and validation cohorts. Furthermore, BRGPs signature was significantly associated with immune scores, tumor purity, clinicopathological characteristics and various tumor-infiltrating immune cells. Besides, we demonstrated that the tumor mutational burden scores and TIDE scores were positively correlated with the risk score of the model implying immune checkpoint blockade therapy may be more effective in NSCLC patients with high-risk scores.

Conclusions

This novel BRGPs signature can be used to assess the prognosis of NSCLC patients and may be useful in guiding immune checkpoint inhibitor treatment in our clinical practice.
Bone marrow mesenchymal stem cells in premature ovarian failure: Mechanisms and prospects
Authors: Huang Yanjing , Zhu Mengdi , Liu Zhuo , Hu Runan , Li Fan , Song Yufan , Geng Yuli , Ma Wenwen , Song Kunkun , Zhang Mingmin
Published: October 2022

Premature ovarian failure (POF) is a common female reproductive disorder and characterized by menopause, increased gonadotropin levels and estrogen deficiency before the age of 40 years old. The etiologies and pathogenesis of POF are not fully clear. At present, hormone replacement therapy (HRT) is the main treatment options for POF. It helps to ameliorate perimenopausal symptoms and related health risks, but can’t restore ovarian function and fertility fundamentally. With the development of regenerative medicine, bone marrow mesenchymal stem cells (BMSCs) have shown great potential for the recovery of ovarian function and fertility based on the advantages of abundant sources, high capacity for self-renewal and differentiation, low immunogenicity and less ethical considerations. This systematic review aims to summarize the possible therapeutic mechanisms of BMSCs for POF. A detailed search strategy of preclinical studies and clinical trials on BMSCs and POF was performed on PubMed, MEDLINE, Web of Science and Embase database. A total of 21 studies were included in this review. Although the standardization of BMSCs need more explorations, there is no doubt that BMSCs transplantation may represent a prospective therapy for POF. It is hope to provide a theoretical basis for further research and treatment for POF.
Weak associations between personality and contraceptive choice
Authors: Pletzer Belinda , Lang Carmen , Derntl Birgit , Griksiene Ramune
Published: October 2022

Prospective randomized controlled trials on hormonal contraceptive (HC) effects on the brain are rare due to a number of methodological challenges. Thus, much of the evidence on HC effects on the brain comes from cross-sectional studies comparing HC-users to non-users. In interpreting these findings, it is of importance to be aware of potential confounds associated with women’s contraceptive choices. Previous studies have discussed age, education, social status, sexual orientation, relationship status, and tolerability of HC. Given the current trend toward a reduction in HC use and increased skepticism toward HC it seems relevant to also identify variables associated with women’s attitudes toward HC and whether they may represent confounds for neuroscientific studies. In the present study, we investigated whether women’s personality characteristics were associated with their choice to use or not use HC in the present, past and future and the type of HC chosen. 1,391 females aged 18–45 years participated in an online survey including the HEXACO-60 personality questionnaire, as well as two different measures of gender role, and provided information about their current and previous contraceptive status, as well as experiences with and attitudes toward contraceptive use. We compared (i) current, previous and never-users of HC, (ii) prospective users of HC to women who opposed future HC use, and (iii) current users of IUDs to current users of oral contraceptives. Results revealed that associations between personality and the decision to use or not use HC were negligible, while differences in personality were observed corresponding to contraceptive type. Current users of IUDs showed higher agreeableness and extraversion compared to current users of oral contraceptives. The results suggest that personality is more strongly associated to the choice of contraceptive type rather than the choice between hormonal and non-hormonal options.
Adult hamartoma of the chest wall: A case report
Authors: Bai Dong , Liu Yan-han
Published: October 2022

This paper retrospectively analyzed the case data of an adult hamartoma of the left chest wall, and combined with the literature analysis, to discuss the clinical characteristics, imaging diagnosis and differential diagnosis of hamartoma. CT and MRI findings of the patient showed medial occupation of the left serratius anterior muscle, with visible fat and calcification. Different from the previous reports of chest wall hamartoma in terms of age, location and imaging characteristics, this case had certain characteristics, and the diagnosis needed pathological confirmation after surgical resection.
Emerging target discovery and drug repurposing opportunities in chordoma
Authors: Freed Daniel M. , Sommer Josh , Punturi Nindo
Published: October 2022

The development of effective and personalized treatment options for patients with rare cancers like chordoma is hampered by numerous challenges. Biomarker-guided repurposing of therapies approved in other indications remains the fastest path to redefining the treatment paradigm, but chordoma’s low mutation burden limits the impact of genomics in target discovery and precision oncology efforts. As our knowledge of oncogenic mechanisms across various malignancies has matured, it’s become increasingly clear that numerous properties of tumors transcend their genomes – leading to new and uncharted frontiers of therapeutic opportunity. In this review, we discuss how the implementation of cutting-edge tools and approaches is opening new windows into chordoma’s vulnerabilities. We also note how a convergence of emerging observations in chordoma and other cancers is leading to the identification and evaluation of new therapeutic hypotheses for this rare cancer.
Survival and risk factors among upper tract urothelial carcinoma patients after radical nephroureterectomy in Northeast China
Authors: Gao Jianing , Liu Jingya , Liu Jianyu , Lin Shiyan , Ding Dexin
Published: October 2022

Objective

The study objective was to investigate the prognostic risk factors related to overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and metastasis-free survival (MFS) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Patients were then divided into different risk groups (based on their number of prognostic risk factors), and specific postoperative treatment plans were formulated for patients in different risk groups.

Methods

We retrospectively analyzed the data of 401 patients with UTUC who underwent RNU between 2010 and 2020. Univariate and multivariate Cox regression analyses were used to evaluate the associations of clinicopathological variables with prognosis among UTUC patients. Kaplan–Meier survival analysis of patients in different risk groups (based on their number of prognostic risk factors) was conducted.

Results

Multivariate Cox regression analysis showed that sex (being male), LVI, pT stage (>pT2), and lack of postoperative intravesical instillation were independent risk predictors of shorter OS, CSS, RFS, and MFS (all P<0.05). Laparoscopic RNU was also associated with shorter OS, CSS, and MFS, but not with shorter RFS (P=0.068). After risk stratification, the 5-year OS, CSS, RFS, and MFS in the high-risk group were 42.3%, 46.4%, 41%, and 46%, respectively.

Conclusions

Sex (being male), LVI, pT stage (>pT2), and intravesical instillation were independent predictors of OS, CSS, RFS, and MFS for UTUC. All were risk factors, except for intravesical instillation, which was a protective factor. Additionally, laparoscopic RNU was an independent risk factor for OS, CSS, and MFS. Patients in the high-risk group may benefit greatly from adjuvant or neoadjuvant chemotherapy.
MET-targeted therapies for the treatment of non-small-cell lung cancer: A systematic review and meta-analysis
Authors: Xu Linrui , Wang Faping , Luo Fengming
Published: October 2022

Background

Dysregulation of the mesenchymal epithelial transition (MET) pathway contributes to poor clinical outcomes in patients with non-small cell lung cancer (NSCLC). Numerous clinical trials are currently investigating several therapies based on modulation of the MET pathway.

Objectives

This study aimed to systematically evaluate the activity and safety of MET inhibitors in patients with NSCLC.

Methods

We searched PubMed, Embase, and the Cochrane Library from inception to June 02, 2022. The objective response rate (ORR) and disease control rate (DCR) were extracted as the main outcomes and pooled using the weighted mean proportion with fixed- or random-effects models in cases of significant heterogeneity (I2>50%). Safety analysis was performed based on adverse events reported in all studies.

Results

Eleven studies (882 patients) were included in the meta-analysis. The pooled ORR was 28.1% (95% confidence interval [CI], 0.223–0.354), while the pooled DCR was 69.1% (95% CI, 0.631–0.756). ORRs were higher for tepotinib (44.7% [95% CI, 0.365–0.530]) and savolitinib (42.9% [95% CI, 0.311–0.553]) than for other types of MET inhibitors. Patients with NSCLC with exon 14 skipping exhibited higher ORRs (39.3% (95% CI, 0.296–0.522)) and DCRs (77.8% (95% CI, 0.714–0.847)) than those with MET protein overexpression or amplification. Intracranial response rate and intracranial disease control rates were 40.1% (95% CI, 0.289–0.556) and 95.4% (95% CI, 0.892–0.100), respectively. Adverse events were mild (grade 1 to 2) in 87.2% of patients. Common adverse events above grade 3 included lower extremity edema (3.5% [95% CI, 0.027–0.044]), alanine aminotransferase (ALT) elevation (2.4% [95% CI, 0.014–0.033]), and lipase elevation (2.2% [95% CI, 0.016–0.031]).

Conclusion

MET inhibitors, which exhibited a satisfactory safety profile in the current study, may become a new standard of care for addressing MET dysregulation in patients with advanced or metastatic NSCLC, and even in those with brain metastases, particularly tepotinib, savolitinib and capmatinib. Further randomized trials are required to establish standard predictive biomarkers for MET therapies and to compare the effects of different MET inhibitors in NSCLC with MET dysregulation.
Trends in immune-related adverse events for colorectal cancer: A bibliometric analysis
Authors: Cui Jin , Xiong Ying , Sun Min , Gu Xinyue , Liu Yuting , Zhong Luhui , Hong Xiaohua , Liu Li
Published: October 2022

Purpose

We used bibliometric methods to assess the global scientific output on the IRAEs for colorectal cancer and to explore the current status and trends in the field over the last three decades.

Methods

Studies on immune-related adverse events for colorectal cancer published from 1996 to 2022 were retrieved from the Web of Science. For quantitative and qualitative assessments of publication outputs and author contributions, the R bibliometrix package was used. VOSviewer was used to construct networks based on the co-authorship of countries/institutions/authors, co-citation analysis of journals/references, citation analysis of documents, and co-occurrence of keywords.

Results

A total of 237 relevant articles were included in the final analysis. The number of publications has increased significantly over time. The countries and institutions that contributed most to the field were the USA and the University of Texas MD Anderson Cancer Center. Jefferey Schlom was the most productive author, ranking first in cited authors. The most cited document was Topalian et al. in The New England Journal of Medicine (2012). The journals with the highest number of selected articles and citations were The New England Journal of Medicine and the Journal of Clinical Oncology, respectively. Co-occurrence analysis showed that IRAEs for colorectal cancer were associated with immunotherapy, open-label, chemotherapy, nivolumab, and PD-1. Trend analysis showed that immune checkpoint inhibitors, gut-microbiota, inflammatory-bowel disease, and PD-1has been on the rise in recent years to IRAEs for colorectal cancer.

Conclusion

Our bibliometric analysis showed that studying IRAEs for colorectal cancer is increasingly a hot topic. The focus of the research had evolved from traditional treatment modalities such as targeted therapy to gut microbiota. Inflammatory bowel disease may be a future research hotspot of IRAEs for colorectal cancer.
Regulation, genomics, and clinical characteristics of cuproptosis regulators in pan-cancer
Authors: Zhou Cankun , Li Chaomei , Zheng Yuhua , Huang Xiaobin
Published: October 2022

Background

Cuproptosis, a copper-dependent controlled cell death, is a novel form of cell death that differs from known cell death mechanisms; however, its overall regulation in cancer remains elusive.

Methods

Multiple open-source bioinformatic platforms were used to comprehensively elucidate the expression levels, prognostic efficiency, potential biological functions, genomic and epigenetic characteristics, immune microenvironment, and drug sensitivity of cuproptosis regulators (ATP7A, ATP7B, DLAT, DLD, FDX1, GLS, LIAS, LIPT1, MTF1, NLRP3, PDHA1, PDHB, and SLC31A1) in pan-cancer.

Results

Cuproptosis-related genes (CRGs) were upregulated in most cancers tested. In KIRC, KIRP, LGG, MESO, and PCPG, most highly expressed CRGs predicted a better prognosis but poorer prognosis in patients with ACC, LIHC, and UCEC. Pathway analysis confirmed that cuproptosis regulators were associated with the metabolism-related pathways. The expression of MTF1, NLRP3, and SLC31A1 was positively related with ImmuneScore, StromalScore, and ESTIMATEScore in almost all types of tumor, whereas ATP7B, DLAT, DLD, LIAS, PDHA1, and PDHB were significantly negatively correlated with the scores. In addition, CRGs were significantly correlated with RNA stemness score, DNA stemness score, microsatellite instability, and tumor mutational burden. The expression of ATP7A, ATP7B, LIAS, and DLAT was significantly positively correlated with the drug sensitivity of Docetaxel. ATP7A, LIAS, and FDX1 were significantly negatively correlated with the drug sensitivity of UNC0638, XMD13−2, YM201636, and KIN001−260.

Conclusions

The altered genomic and clinical characteristics of cuproptosis regulators were comprehensively elucidated, providing a preliminary basis for understanding the functions of cuproptosis in pan-cancer.
Predicting a reduction in intraocular pressure in glaucoma patients in the early period after a trabeculectomy: Development and assessment of a new predictive nomogram
Authors: Wang Ruixue , Li Ning , Tan Yue , Chen Xiaoya
Published: October 2022

Purpose

To identify the factors associated with a reduction in intraocular pressure (IOP) in the early postoperative period after a trabeculectomy and to develop a predictive nomogram to guide clinical care.

Methods

This study included clinical data on 588 glaucoma patients (N = 588 eyes) who underwent a trabeculectomy in our hospital between January 2016 and December 2021. There were 412 eyes in a training cohort and 176 eyes in a validation cohort. We used logistic regression analysis to evaluate whether these factors were related to a decrease in IOP in the early period postsurgery and established a predictive model by combining features selected in a univariate analysis. We used external validation for evaluation. The standard for IOP reduction was that the IOP decreased to the normal range (10−21 mmHg) 1 month after the trabeculectomy.

Results

Among the patients in the training cohort, 82.8% met the standard for IOP lowering. There were 11 meaningful differences among the enrolled predictors, but the logistic regression analysis only showed significant differences with anterior chamber angle closed, age, preoperative IOP, axial length, and visual field mean sensitivity (MS). The C-index of the model was 0.910 (95% confidence interval [CI]: 0.869-0.951). The C-index was 0.956 for external validation of the model.

Conclusion

This new nomogram can be used to predict whether the IOP will reach the standard in the early stages after a trabeculectomy. The anterior chamber angle closed, age, preoperative IOP, axial length, and visual field MS are independent risk factors.