bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of ADAM17 by IL-15 Limits Human NK Cell Proliferation
Authors: Mishra Hemant K. , Dixon Kate J. , Pore Nabendu , Felices Martin , Miller Jeffrey S. , Walcheck Bruce
Published: July 2021

Natural killer (NK) cells are innate cytotoxic lymphocytes that can recognize assorted determinants on tumor cells and rapidly kill these cells. Due to their anti-tumor effector functions and potential for allogeneic use, various NK cell platforms are being examined for adoptive cell therapies. However, their limitedin vivopersistence is a current challenge. Cytokine-mediated activation of these cells is under extensive investigation and interleukin-15 (IL-15) is a particular focus since it drives their activation and proliferation. IL-15 efficacy though is limited in part by its induction of regulatory checkpoints. A disintegrin and metalloproteinase-17 (ADAM17) is broadly expressed by leukocytes, including NK cells, and it plays a central role in cleaving cell surface receptors, a process that regulates cell activation and cell-cell interactions. We report that ADAM17 blockade with a monoclonal antibody markedly increased human NK cell proliferation by IL-15 bothin vitroand in a xenograft mouse model. Blocking ADAM17 resulted in a significant increase in surface levels of the homing receptor CD62L on proliferating NK cells. We show that NK cell proliferationin vivoby IL-15 and the augmentation of this process upon blocking ADAM17 are dependent on CD62L. Hence, our findings reveal for the first time that ADAM17 activation in NK cells by IL-15 limits their proliferation, presumably functioning as a feedback system, and that its substrate CD62L has a key role in this processin vivo. ADAM17 blockade in combination with IL-15 may provide a new approach to improve NK cell persistence and function in cancer patients.
The Critical Role of PARPs in Regulating Innate Immune Responses
Authors: Zhu Huifang , Tang Yan-Dong , Zhan Guoqing , Su Chenhe , Zheng Chunfu
Published: July 2021

Poly (adenosine diphosphate-ribose) polymerases (PARPs) are a family of proteins responsible for transferring ADP-ribose groups to target proteins to initiate the ADP-ribosylation, a highly conserved and fundamental post-translational modification in all organisms. PARPs play important roles in various cellular functions, including regulating chromatin structure, transcription, replication, recombination, and DNA repair. Several studies have recently converged on the widespread involvement of PARPs and ADP-Ribosylation reaction in mammalian innate immunity. Here, we provide an overview of the emerging roles of PARPs family and ADP-ribosylation in regulating the host’s innate immune responses involved in cancers, pathogenic infections, and inflammations, which will help discover and design new molecular targets for cancers, pathogenic infections, and inflammations.
MaDCrow, a Citizen Science Infrastructure to Monitor Water Quality in the Gulf of Trieste (North Adriatic Sea)
Authors: Diviacco Paolo , Nadali Antonio , Iurcev Massimiliano , Carbajales Rodrigo , Busato Alessandro , Pavan Alessandro , Burca Mihai , Grio Lorenzo , Nolich Massimiliano , Molinaro Andrea , Malfatti Francesca
Published: July 2021

Within the United Nations Sustainable Development 2030 agenda, sustainable growth in the marine and maritime sector needs sea water quality monitoring. This is a very demanding and expensive task which results in the sea being largely undersampled. MaDCrow is a research and development project supported by the European Regional Development Fund, that involves citizens as data collectors while aiming to improve public environmental awareness and participation in scientific research. Its goal is to create an innovative technological infrastructure for real-time acquisition, integration and access of data, thus generating knowledge on sea water quality and marine ecosystem of the Gulf of Trieste. Data acquisition is based on an autonomous and removable device, developed within the project, that can be deployed on any small size sailing boat, recreational vessel, or fishing boat. The device holds low-cost sensors to measure pH, temperature, dissolved oxygen and salinity and the hardware and software to acquire, georeference and transmit the environmental data without interfering with the activities of the boats. In this work we analyze the use, capabilities and advantages of low-cost sensors but also their limitations, comparing, with a special focus on pH, their performances with those of the traditional ones. Applying the paradigm in a highly anthropized area such as the Gulf of Trieste, which is characterized also by a very high spatial and temporal variability of environments, we point out that this new approach allows to monitor sea water quality and highlight local anomalies with a resolution and spatial and temporal coverage that was not achievable with previous procedures, but yet at very low costs. Once received, data are then processed and submitted to a mediation flow that contextualizes and disseminates them for public use on a website. The final products have been customized to reach stakeholders such as tourists, fishermen and policy makers. The availability of information understandable to everyone, while fostering environmental awareness, stimulates, at the same time, involvement and participation of citizen scientists in the initiative. In the future, while committing to enlarge the number of participants, we will extend the analysis also toward other types of sensors.
The Role of Urbanness, Vegetation Structure, and Scale in Shaping Puerto Rico’s Acoustically Active Mangrove Fauna Communities
Authors: Branoff Benjamin L. , Campos-Cerqueira Marconi
Published: July 2021

The mangroves of Puerto Rico occupy a gradient of urbanization that offers a chance to test hypotheses on urban faunal communities. These hypotheses state that urban avifaunal communities have greater representation by generalists and that certain mangrove specialists can utilize urban landscapes. Much of this is said to be driven by food resources, with frugivores and nectarivores benefiting from abundant residential flowers and fruits, while insectivores are driven away by low food resources. This study used passive acoustic monitoring to identify the audible anuran and avifaunal species in mangroves across an urban gradient of Puerto Rico. Five anurans and thirty-one avian species were detected across all sites, with twenty-three species found at the most species rich site, and eight at the least rich site. Analyses on urban effects were conducted at an island-wide scale as well as a local scale with different results between the two. Island wide, the most urban faunal communities were more similar to each other in species composition relative to the least urban communities, and there was a significant difference in the community composition between the two. However, there were no differences in avian or anuran species richness between the least and most urban sites. Minimum canopy height was the strongest predictor of overall avian richness and avian invertivore richness, while the extent of mixed forest cover was the strongest predictor for increasing anuran richness. Some urban metrics, such as street density and the percent of surrounding urban and developed open space were strong predictors of certain avian feeding guilds and distribution groups. At the local scale, sites of maximum urbanness held 2–3 more bird species on average than corresponding sites of minimum urbanness at the same location, although there was no difference in anuran species and no differences in avian or anuran community composition between the two. Further, avian richness did increase significantly from the minimum to maximum urbanness site at six of the nine locations. These findings highlight that higher mangrove canopies are the strongest predictor of higher avian richness, but depending on the scale of observations, urbanness also plays a limited role in shaping mangrove faunal communities.
High-Frequency Motions in the Southeastern South China Sea During Winter–Spring 2018/2019
Authors: Zhang Zhipeng , Xu Hongzhou , Vetter Philip A. , Xie Qiang , Xie Xiaohui , Song Wei , Tian Chuan
Published: July 2021

High-frequency motions in the southeastern South China Sea (SCS) have rarely been investigated due to sparse field observations. The vertical distribution and temporal variation of internal tides (ITs) and near-inertial waves (NIWs) near the Nansha area in the southeastern SCS were studied using a mooring current dataset from December 2018 to June 2019 in this study. Results showed that ITs were mainly dominated by O1, K1, and M2. Tidal energy analysis indicates that the diurnal ITs were the most energetic components, followed by the semidiurnal ITs. Modal decomposition reveals that diurnal ITs were dominated by mode-3, rather than mode-1, as reported by previous studies. The horizontal kinetic energy (HKE) of diurnal ITs fluctuated within a limited range, almost unaffected by the background field. However, the HKE of semidiurnal ITs was dominated by mode-1 and more affected by the background field, especially at the end of March. Most observations showed the phase of the NIWs propagating upward and the energy propagating downward. During the northeast monsoon period, the near-inertial energy had a large magnitude due to strong wind forcing. In addition, the near-inertial energy peaked from the middle of March to the beginning of April because of the input of NIWs from afar. Overall, near-inertial energy was found concentrated above a 500–600 m depth in the southeastern SCS.
Tell a Story to Save a River: Assessing the Impact of Using a Children’s Book in the Classroom as a Tool to Promote Environmental Awareness
Authors: Aurélio Luísa , França Susana , Sequeira Vera , Boaventura Diana , Correia Maria João , Pinto Bruno , Amoroso Sandra , Feio Maria João , Brito Cristina , Chainho Paula , Chaves Luísa
Published: July 2021

Listening to a story stimulates children to understand concepts and vocabulary, while developing their background knowledge. Previous research indicates that the use of scientifically accurate literature helps children connect to the natural world. Promoting environmental education (EE) should be of utmost importance in school curricula, providing opportunities to students to improve their knowledge regarding the environment, and how to protect it. Particularly, marine ecosystems have been subject to increasing pressures, highlighting the importance of taking Ocean Literacy (OL) to the classroom. Drawing attention to more relatable environments, like a river, by tailoring OL activities to local contexts and community interests, might be an efficient strategy to raise awareness of ocean problems. A children’s book, written by a MARE (Marine and Environmental Sciences Centre, Portugal) researcher, with a macrobenthic invertebrate as the main character, was the springboard for an outreach project, developed with elementary school students. The project aimed to assess the impact of using a children’s book as a tool to promote environmental awareness, focusing on river basin ecological issues. Researchers conducted reading sessions of the book with 89 female and 87 male elementary school students (ages between 8–10). The target audience were students from two public and two private schools from an urban city and a city with a strong fishing tradition, aiming to assess if the reading session impacted students differently according to their background. A sequential explanatory mixed methodology was applied, using a pretest-posttest design, combined with focus group interviews in the last phase, to measure change in students’ knowledge, before and after the reading. Results demonstrated that there was an overall improvement in students’ knowledge regarding river basin biodiversity and anthropogenic threats they are subjected to. Furthermore, the idea that local impacts on rivers will also reach and influence the ocean was always present throughout the reading sessions. Students’ background, such as the type of school and region influenced higher posttest score results. In particular, students from Lisbon had higher scores in posttest results, while the same was observed for students from private schools. The present research revealed that a children’s book is an effective tool to improve environmental knowledge, while being an entertaining activity for students.
Use of Artificial Intelligence to Improve the Quality Control of Gastrointestinal Endoscopy
Authors: Song Ya-qi , Mao Xin-li , Zhou Xian-bin , He Sai-qin , Chen Ya-hong , Zhang Li-hui , Xu Shi-wen , Yan Ling-ling , Tang Shen-ping , Ye Li-ping , Li Shao-wei
Published: July 2021

With the rapid development of science and technology, artificial intelligence (AI) systems are becoming ubiquitous, and their utility in gastroenteroscopy is beginning to be recognized. Digestive endoscopy is a conventional and reliable method of examining and diagnosing digestive tract diseases. However, with the increase in the number and types of endoscopy, problems such as a lack of skilled endoscopists and difference in the professional skill of doctors with different degrees of experience have become increasingly apparent. Most studies thus far have focused on using computers to detect and diagnose lesions, but improving the quality of endoscopic examination process itself is the basis for improving the detection rate and correctly diagnosing diseases. In the present study, we mainly reviewed the role of AI in monitoring systems, mainly through the endoscopic examination time, reducing the blind spot rate, improving the success rate for detecting high-risk lesions, evaluating intestinal preparation, increasing the detection rate of polyps, automatically collecting maps and writing reports. AI can even perform quality control evaluations for endoscopists, improve the detection rate of endoscopic lesions and reduce the burden on endoscopists.
Impacts of Frailty on Prognosis in Lung Cancer Patients: A Systematic Review and Meta-Analysis
Authors: Dai Shuiping , Yang Ming , Song Juan , Dai Sisi , Wu Jinhui
Published: July 2021

Background: Frailty is a common geriatric syndrome and is described as a limited ability to compensate and recover from stressors. Lung cancer is largely diagnosed in old age, when frailty is common and might have predictive value on prognosis. Therefore, we performed a systematic review to evaluate the prognostic role of frailty in lung cancer.

Methods: The online PubMed, Web of Science, CNKI and Wanfang literature databases were searched to identify all related articles that reported the predictive value of frailty for mortality and therapeutic toxicity. Review Manager 5.3 was used to analyze results by standard meta-analysis methodology.

Results: Seven studies were included in this review, and only six studies with 2,359 patients were enrolled in meta-analysis. Patients in two studies received chemotherapy, two studies radiotherapy, two studies surgery, one study not reported. Compared to non-frail patients, frail patients had a higher risk of overall mortality [Hazard Ratio (HR) = 1.57, 95% confidence interval (CI), 1.32–1.87], and therapeutic toxicity [Odds Ratio (OR) = 2.60, 95% CI, 0.82–8.24]. Prefrail patients also showed higher overall mortality and therapeutic toxicity than non-frail patients (HR = 1.20, 95% CI, 1.05–1.38; OR = 1.72, 95% CI, 1.18–2.51, respectively).

Conclusions: Frailty is a powerful predictor of overall mortality and therapeutic toxicity in lung cancer patients.
Subcellular Localization of Epstein–Barr Virus BLLF2 and Its Underlying Mechanisms
Authors: Li Jingjing , Guo Yingjie , Deng Yangxi , Hu Li , Li Bolin , Deng Shenyu , Zhong Jiayi , Xie Li , Shi Shaoxuan , Hong Xuejun , Zheng Xuelong , Cai Mingsheng , Li Meili
Published: July 2021

Epstein–Barr virus (EBV), the pathogen of several human malignancies, encodes many proteins required to be transported into the nucleus for viral DNA reproduction and nucleocapsids assembly in the lytic replication cycle. Here, fluorescence microscope, mutation analysis, interspecies heterokaryon assays, co-immunoprecipitation assay, RNA interference, and Western blot were performed to explore the nuclear import mechanism of EBV encoded BLLF2 protein. BLLF2 was shown to be a nucleocytoplasmic shuttling protein neither by a chromosomal region maintenance 1 (CRM1)- nor by a transporter associated with antigen processing (TAP)-dependent pathway. Yet, BLLF2’s two functional nuclear localization signals (NLSs), NLS1 (16KRQALETVPHPQNRGR31) and NLS2 (44RRPRPPVAKRRRFPR58), were identified, whereas the predicted NES was nonfunctional. Finally, BLLF2 was proven to transport into the nucleus via a Ran-dependent and importin β1-dependent pathway. This mechanism may contribute to a more extensive insight into the assembly and synthesis of EBV virions in the nucleus, thus affording a new direction for the treatment of viruses.
Short-Chain and Unsaturated Fatty Acids Increase Sequentially From the Lag Phase During Cold Growth of Bacillus cereus
Authors: Français Marina , Bott Romain , Dargaignaratz Claire , Giniès Christian , Carlin Frédéric , Broussolle Véronique , Nguyen-Thé Christophe
Published: July 2021

Fatty acids of two mesophilic and one psychrotrophic strains of the foodborne pathogen Bacillus cereus were analyzed by gas chromatography coupled to mass spectrometry during growth at cold (10 and 12°C) vs. optimal (30°C) temperatures and during the whole growth process (6–7 sampling times) from lag to stationary phase. In all these strains, a sequential change of fatty acids during cold growth was observed. Fatty acids were modified as soon as the end of lag, with an increase of the short-chain fatty acids (less than 15 carbons), particularly i13. These short-chain fatty acids then reached a maximum at the beginning of growth and eventually decreased to their initial level, suggesting their importance as a rapid cold adaptation mechanism for B. cereus. In a second step, an increase in Δ5,10 di-saturated fatty acids and in monounsaturated fatty acids in Δ5 position, at the expense of unsaturation in Δ10, started during exponential phase and continued until the end of stationary phase, suggesting a role in growth consolidation and survival at cold temperatures. Among these unsaturated fatty acids, those produced by unsaturation of n16 increased in the three strains, whereas other unsaturated fatty acids increased in some strains only. This study highlights the importance of kinetic analysis of fatty acids during cold adaptation.
Population Diversity, Dynamics, and Differentiation of Wheat Stripe Rust Pathogen Puccinia striiformis f. sp. tritici From 2010 to 2017 and Comparison With 1968 to 2009 in the United States
Authors: Bai Qing , Wan Anmin , Wang Meinan , See Deven R. , Chen Xianming
Published: July 2021

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a serious disease on wheat in the United States, especially after 2000. In the present study, 2,247 Pst isolates collected over all stripe rust epidemiological regions in the United States from 2010 to 2017 were genotyped at 14 simple sequence repeat (SSR) loci to investigate the population diversity, dynamics, and differentiation. A total of 1,454 multilocus genotypes (MLGs) were detected. In general, the populations in the west (regions 1–6) had more MLGs and higher diversities than the populations in the east (regions 7–12). The populations of 2010 and 2011 were more different from the other years. Genetic variation was higher among years than among regions, indicating the fast changes of the population. The divergence (Gst) was bigger between the west population and east population than among regions within either the west or east population. Gene flow was stronger among the regional populations in the east than in the west. Clustering analyses revealed 3 major molecular groups (MGs) and 10 sub-MGs by combining the genotypic data of 2010–2017 isolates with those of 1968–2009. MG1 contained both 1968–2009 isolates (23.1%) and 2010–2017 isolates (76.9%). MG2 had 99.4% of isolates from 1968–2009. MG3, which was the most recent and distinct group, had 99.1% of isolates from 2010–2017. Of the 10 sub-MGs, 5 (MG1-3, MG1-5, MG3-2, MG3-3, and MG3-4) were detected only from 2011 to 2017. The SSR genotypes had a moderate, but significant correlation (r = 0.325; p < 0.0001) with the virulence phenotype data. The standard index values of association (rbarD = 0.11) based on either regional or yearly populations suggest clonal reproduction. This study indicated high diversity, fast dynamics, and various levels of differentiation of the Pst population over the years and among epidemiological regions, and the results should be useful for managing wheat stripe rust.
Divergent Genomic Adaptations in the Microbiomes of Arctic Subzero Sea-Ice and Cryopeg Brines
Authors: Rapp Josephine Z. , Sullivan Matthew B. , Deming Jody W.
Published: July 2021

Subzero hypersaline brines are liquid microbial habitats within otherwise frozen environments, where concentrated dissolved salts prevent freezing. Such extreme conditions presumably require unique microbial adaptations, and possibly altered ecologies, but specific strategies remain largely unknown. Here we examined prokaryotic taxonomic and functional diversity in two seawater-derived subzero hypersaline brines: first-year sea ice, subject to seasonally fluctuating conditions; and ancient cryopeg, under relatively stable conditions geophysically isolated in permafrost. Overall, both taxonomic composition and functional potential were starkly different. Taxonomically, sea-ice brine communities (∼105 cells mL–1) had greater richness, more diversity and were dominated by bacterial genera, including Polaribacter, Paraglaciecola, Colwellia, and Glaciecola, whereas the more densely inhabited cryopeg brines (∼108 cells mL–1) lacked these genera and instead were dominated by Marinobacter. Functionally, however, sea ice encoded fewer accessory traits and lower average genomic copy numbers for shared traits, though DNA replication and repair were elevated; in contrast, microbes in cryopeg brines had greater genetic versatility with elevated abundances of accessory traits involved in sensing, responding to environmental cues, transport, mobile elements (transposases and plasmids), toxin-antitoxin systems, and type VI secretion systems. Together these genomic features suggest adaptations and capabilities of sea-ice communities manifesting at the community level through seasonal ecological succession, whereas the denser cryopeg communities appear adapted to intense bacterial competition, leaving fewer genera to dominate with brine-specific adaptations and social interactions that sacrifice some members for the benefit of others. Such cryopeg genomic traits provide insight into how long-term environmental stability may enable life to survive extreme conditions.
Identification of Essential Genes Associated With Prodigiosin Production in Serratia marcescens FZSF02
Authors: Jia Xianbo , Liu Fangchen , Zhao Ke , Lin Junjie , Fang Yu , Cai Shouping , Lin Chenqiang , Zhang Hui , Chen Longjun , Chen Jichen
Published: July 2021

Prodigiosin is a promising secondary metabolite produced mainly by Serratia strains. To study the global regulatory mechanism of prodigiosin biosynthesis, a mutagenesis library containing 23,000 mutant clones was constructed with the EZ-Tn5 transposon, and 114 clones in the library showed altered prodigiosin production ability. For 37 of the 114 clones, transposon insertion occurred on the prodigiosin biosynthetic cluster genes; transposon inserted genes of the 77 clones belonged to 33 different outside prodigiosin biosynthetic cluster genes. These 33 genes can be divided into transcription-regulating genes, membrane protein-encoding genes, and metabolism enzyme-encoding genes. Most of the genes were newly reported to be involved in prodigiosin production. Transcriptional levels of the pigA gene were significantly downregulated in 22 mutants with different inserted genes, which was in accordance with the phenotype of decreased prodigiosin production. Functional confirmation of the mutant genes involved in the pyrimidine nucleotide biosynthesis pathway was carried out by adding orotate and uridylate (UMP) into the medium. Gene complementation confirmed the regulatory function of the EnvZ/OmpR two-component regulatory system genes envZ and ompR in prodigiosin production.
Developing a Radiomics Signature for Supratentorial Extra-Ventricular Ependymoma Using Multimodal MR Imaging
Authors: Safai Apoorva , Shinde Sumeet , Jadhav Manali , Chougule Tanay , Indoria Abhilasha , Kumar Manoj , Santosh Vani , Jabeen Shumyla , Beniwal Manish , Konar Subhash , Saini Jitender , Ingalhalikar Madhura
Published: July 2021

Rationale and Objectives: To build a machine learning-based diagnostic model that can accurately distinguish adult supratentorial extraventricular ependymoma (STEE) from similarly appearing high-grade gliomas (HGG) using quantitative radiomic signatures from a multi-parametric MRI framework.

Materials and Methods: We computed radiomic features on the preprocessed and segmented tumor masks from a pre-operative multimodal MRI dataset [contrast-enhanced T1 (T1ce), T2, fluid-attenuated inversion recovery (FLAIR), apparent diffusion coefficient (ADC)] from STEE (n = 15), HGG-Grade IV (HGG-G4) (n = 24), and HGG-Grade III (HGG-G3) (n = 36) patients, followed by an optimum two-stage feature selection and multiclass classification. Performance of multiple classifiers were evaluated on both unimodal and multimodal feature sets and most discriminative radiomic features involved in classification of STEE from HGG subtypes were obtained.

Results: Multimodal features demonstrated higher classification performance over unimodal feature set in discriminating STEE and HGG subtypes with an accuracy of 68% on test data and above 80% on cross validation, along with an overall above 90% specificity. Among unimodal feature sets, those extracted from FLAIR demonstrated high classification performance in delineating all three tumor groups. Texture-based radiomic features particularly from FLAIR were most important in discriminating STEE from HGG-G4, whereas first-order features from T2 and ADC consistently ranked higher in differentiating multiple tumor groups.

Conclusions: This study illustrates the utility of radiomics-based multimodal MRI framework in accurately discriminating similarly appearing adult STEE from HGG subtypes. Radiomic features from multiple MRI modalities could capture intricate and complementary information for a robust and highly accurate multiclass tumor classification.
Sex Differences are Reflected in Microstructural White Matter Alterations of Musical Sophistication: A Diffusion MRI Study
Authors: Mehrabinejad Mohammad-Mehdi , Rafei Parnian , Sanjari Moghaddam Hossein , Sinaeifar Zeinab , Aarabi Mohammad Hadi
Published: July 2021

Background: The human-specified ability to engage with different kinds of music in sophisticated ways is named “Musical Sophistication.” Herein, we investigated specific white matter (WM) tracts that are associated with musical sophistication and musicality in both genders, separately, using Diffusion MRI connectometry approach. We specifically aimed to explore potential sex differences regarding WM alterations correlated with musical sophistication.

Methods: 123 healthy participants [70 (56.9%) were male, mean age = 36.80 ± 18.86 year], who were evaluated for musical sophistication using Goldsmiths Musical Sophistication Index (Gold-MSI) self-assessment instrument from the LEMON database, were recruited in this study. The WM correlates of two Gold-MSI subscales (active engagement and music training) were analyzed. Images were prepared and analyzed with diffusion connectometry to construct the local connectome. Multiple regression models were then fitted to address the correlation of local connectomes with Gold-MSI components with the covariates of age and handedness.

Results: a significant positive correlation between WM integrity in the corpus callosum (CC), right corticospinal tract (CST), cingulum, middle cerebellar peduncle (MCP), bilateral parieto-pontine tract, bilateral cerebellum, and left arcuate fasciculus (AF) and both active engagement [false discovery rate (FDR) = 0.008] and music training (FDR = 0.057) was detected in males. However, WM integrity in the body of CC, MCP, and cerebellum in females showed an inverse association with active engagement (FDR = 0.046) and music training (FDR = 0.032).

Conclusion: WM microstructures with functional connection with motor and somatosensory areas (CST, cortico-pontine tracts, CC, cerebellum, cingulum, and MCP) and language processing area (AF) have significant correlation with music engagement and training. Our findings show that these associations are different between males and females, which could potentially account for distinctive mechanisms related to musical perception and musical abilities across genders.
Conceptual Framework for Insomnia: A Cognitive Model in Practice
Authors: Vaziri Zahra , Nami Mohammad , Leite João Pereira , Delbem Alexandre Cláudio Botazzo , Hyppolito Miguel Angelo , Ghodratitoostani Iman
Published: July 2021

Insomnia is a widespread neuropsychological sleep-related disorder known to result in various predicaments including cognitive impairments, emotional distress, negative thoughts, and perceived sleep insufficiency besides affecting the incidence and aggravation of other medical disorders. Despite the available insomnia-related theoretical cognitive models, clinical studies, and related guidelines, an evidence-based conceptual framework for a personalized approach to insomnia seems to be lacking. This study proposes a conceptual cognitive framework (CCF) providing insight into cognitive mechanisms involved in the predisposition, precipitation, and perpetuation of insomnia and consequent cognitive deficits. The current CCF for insomnia relies on evaluative conditional learning and appraisal which generates negative valence (emotional value) and arousal (cognitive value). Even with the limitations of this study, the suggested methodology is well-defined, reproducible, and accessible can help foster future high-quality clinical databases. During clinical insomnia but not the neutral one, negative mood (trait-anxiety) causes cognitive impairments only if mediating with a distorted perception of insomnia (Ind-1= 0.161, 95% CI 0.040–0.311). Further real-life testing of the CCF is intended to formulate a meticulous, decision-supporting platform for clinical interventions. Furthermore, the suggested methodology is expected to offer a reliable platform for CCF-development in other cognitive impairments and support the causal clinical data models. It may also improve our knowledge of psychological disturbances and complex comorbidities to help design rehabilitation interventions and comprehensive frameworks in line with the “preventive medicine” policies.
Relationship Between Dairy Products Intake and Risk of Endometriosis: A Systematic Review and Dose-Response Meta-Analysis
Authors: Qi Xiangying , Zhang Wenyan , Ge Mingxiu , Sun Qiang , Peng Lei , Cheng Wenke , Li Xuepeng
Published: July 2021

Objective: Diet lifestyle can influence the risk of endometriosis. Therefore, we conducted a systematic meta-analysis to investigate the association between dairy products and the risk of endometriosis. Besides, we performed a dose-response meta-analysis to evaluate the amount of dairy intake affecting the risk of endometriosis.

Methods: Relevant studies were searched from Pubmed, Embase databases, Cochrane Library, and Web of Science from the inception to November 6th, 2020. Also, the dose-response meta-analysis was conducted. All the pooled results were performed by risk ratios (RRs).

Results: Finally, seven high-quality studies were included in the present meta-analysis. Total dairy intake was inversely associated with the risk of endometriosis, and the risk of endometriosis tended to decrease with a decrease in the risk of endometriosis when dairy products intake was over 21 servings/week (RR 0.87, 95% CI 0.76–1.00; pnon−linearity = 0.04). Similarly, people who consumed more than 18 servings of high-fat dairy products per week had a reduced risk of endometriosis (RR 0.86, 95% CI 0.76–0.96). When stratified-analyses were conducted based on specific dairy product categories, it indicated that people with high cheese intake might have a reduced risk of endometriosis (RR 0.86, 95% CI 0.74–1.00). Other specific dairy products such as whole milk (RR 0.90, 95% CI 0.72–1.12), reduced-fat/skim milk (RR 0.83, 95% CI 0.50–1.73), ice cream (RR 0.83, 95% CI 0.50–1.73), and yogurt (RR 0.83, 95% CI 0.62–1.11) have not shown significant evidence of an association with the risk of endometriosis. However, there is a higher risk of endometriosis in the females with high butter intake compared to females with low butter intake (1.27, 95% CI 1.03–1.55).

Conclusions: Overall, dairy products intake was associated with a reduction in endometriosis, with significant effects when the average daily intake ≥3 servings. When analyzed according to the specific type of dairy product, it was shown that females with higher high-fat dairy and cheese intake might have a reduced risk of endometriosis. However, high butter intake might be associated to the increased risk of endometriosis. More future studies are needed to validate and add to this finding.
Dietary Interventions in Patients With Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
Authors: Houttu Veera , Csader Susanne , Nieuwdorp Max , Holleboom Adriaan G. , Schwab Ursula
Published: July 2021

Background: With no approved pharmacotherapy to date, the present therapeutic cornerstone for non-alcoholic fatty liver diseases (NAFLD) is a lifestyle intervention. Guidelines endorse weight loss through dietary modifications, physical exercise, or both. However, no consensus exists on the optimal dietary treatment.

Objectives: The aim of our systematic review and meta-analysis was to summarize and assess the evidence for applied types of dietary interventions on the liver and metabolic outcomes in patients with NAFLD, aside from any effects of exercise intervention.

Methods: This systematic review was conducted according to the Preferred Reporting Items of Systematic Reviews and Meta-analysis (PRISMA) statement guidelines. The search was conducted in PubMed, Scopus, and Cochrane databases in February 2020. Included were only dietary interventions without exercise. This study was registered at PROSPERO: CRD42020203573.

Results: Eight randomized controlled trials, seven with endpoint reduction of hepatic steatosis, one with an assessment of endpoint fibrosis, were included in this systematic review, five of which were included in the meta-analysis. Mediterranean dietary interventions without energy restriction (n = 3) showed significant reduction of intrahepatic lipid content (IHL) (SDM: −0.57, 95% CI: −1.04, −0.10), but there was no significant change in alanine transaminase (ALT) (SDM: 0.59, 95% CI: −0.5, −1.68). Hypocaloric dietary interventions with foods high in unsaturated fatty acids (n = 2) led to a significant decrease in ALT (SDM: −1.09, 95% CI: −1.49, −0.69) and aspartate aminotransferase (AST) (SDM: −0.75, 95% CI: −1.27, 0.23); yet effects on steatosis could not be aggregated due to different assessment techniques. Mediterranean diet did not lead to significant changes in concentrations of gamma-glutamyl transpeptidase (γGT), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), fasting glucose or insulin, or homeostatic assessment for insulin resistance.

Conclusions: In patients with NAFLD, Mediterranean and hypocaloric dietary interventions favoring unsaturated fatty acids result in improvements in IHL and transaminases. Since many dietary intervention studies are combined with exercise interventions and there is a paucity of ample-sized studies examining dietary interventions on the more advanced and clinically relevant stages of NAFLD, that is active and fibrotic NASH, with multiparametric imaging and liver histology as outcome measures, the optimal dietary invention in NAFLD remains to be defined.
Adenosquamous Carcinoma of the Cervix: A Population-Based Analysis
Authors: Cui Pengfei , Cong Xiaofeng , Chen Chen , Yang Lei , Liu Ziling
Published: July 2021

Background

Due to the rarity of adenosquamous carcinoma of the cervix (ASCC), studies on the incidence, prognostic factors, and treatment outcomes of ASCC remain scarce. Therefore, we performed a retrospective population-based study to systematically investigate the characteristics of ASCC patients.

Methods

Patients with a histopathologically confirmed diagnosis of ASCC were enrolled from the Surveillance, Epidemiology, and End Results database between 1975 and 2016. Univariate and multivariate Cox regression analyses were performed to identify the potential predictors of cancer-specific survival (CSS) in patients with ASCC. Selected variables were integrated to establish a predictive nomogram and the predictive performance of the nomogram was estimated using Harrell’s concordance index (C-index), calibration curve, and decision curve analysis (DCA).

Results

A total of 1142 ASCC patients were identified and included in this study and were further randomized into the training and validation cohorts in a 7:3 ratio. The age-adjusted incidence of ASCC declined from 0.19 to 0.09 cases per 100,000 person-years between 2000 and 2017, with an annual percentage change of -4.05% (P<0.05). We identified age, tumor grade, FIGO stage, tumor size, and surgical procedure as independent predictors for CSS in ASCC patients and constructed a nomogram to predict the 3- and 5-year CSS using these prognostic factors. The calibration curve indicated an outstanding consistency between the nomogram prediction and actual observation in both the training and testing cohorts. The C-index was 0.7916 (95% CI: 0.7990-0.8042) and 0.8148 (95% CI: 0.7954-0.8342) for the training and testing cohorts, respectively, indicating an excellent discrimination ability of the nomogram. The DCA showed that the nomogram exhibited more clinical benefits than the FIGO staging system.

Conclusions

We established and validated an accurate predictive nomogram for ASCC patients based on several clinical characteristics. This model might serve as a useful tool for clinicians to estimate the prognosis of ASCC patients.
Analysis of Adaptive Olaparib Resistance Effects on Cisplatin Sensitivity in Triple Negative Breast Cancer Cells
Authors: Gajan Ambikai , Sarma Ashapurna , Kim Seongho , Gurdziel Katherine , Wu Gen Sheng , Shekhar Malathy P.
Published: July 2021

Poly-(ADP)-ribose polymerase inhibitors (PARPi) and platinum-based drugs are promising therapies for triple negative breast cancers (TNBC) with BRCA1 or BRCA2 loss. PARPi(s) show better efficacies when combined with platinum-based therapy, however, acquisition of PARPi resistance has been linked with co-resistance to platinum-based drugs. Here, we show that TNBCs with constitutively hyperactivated PARP-1 display greater tolerances for the PARPi olaparib and cisplatin, and respond synergistically to olaparib/cisplatin combinations with increased cytotoxicity. Regardless of BRCA1 and PARP-1 activity status, upon gaining olaparib resistance (OlaR), OlaR MDA-MB-468 (BRCA1 wild-type) and SUM1315 (BRCA1 mutant) TNBC cells retain cisplatin sensitivities of their isogenic parental counterparts. OlaR TNBC cells express decreased levels of PARP-1 and Pol η, a translesion-synthesis polymerase important in platinum-induced interstrand crosslink repair. Although native RAD51 recombinase levels are unaffected, anti-RAD51 immunoreactive low molecular weight sbands are exclusively detected in OlaR cells. Despite normal BRCA1, RAD51 foci formation/recruitment to double-strand breaks are impaired in OlaR MDA-MB-468 cells, suggesting homologous-recombination impairment. RNA-seq and pathway analysis of cisplatin-affected genes revealed enrichment of G2/M cell cycle regulation and DNA repair pathways in parental and OlaR MDA-MB-468 cells whereas parental and OlaR SUM1315 cells showed enrichment of inflammatory stress response pathways associated with TNFR1/2, TWEAK and IL-17 signaling. These data show that TNBC models with wild type versus mutant BRCA1 exhibit differences in CDDP-induced cellular response pathways, however, the CDDP-induced signaling responses remain stable across the isogenic models of OlaR from the same lineage. These data also show that adaptive OlaR does not automatically promote cisplatin resistance, implicating the potential benefit of platinum-based therapy for OlaR TNBCs.
Reduction of Duration of Antibiotic Therapy for Suspected Early-Onset Sepsis in Late-Preterm and Term Newborns After Implementation of a Procalcitonin-Guided Algorithm: A Population-Based Study in Central Switzerland
Authors: Zihlmann-Ji Jennifer , Braun Christian , Buettcher Michael , Hodel Markus , Lehnick Dirk , Stocker Martin
Published: July 2021

Background: Suspected early-onset sepsis (EOS) is the main reason for antibiotic therapy at the start of life. Prolonged antibiotic therapy for culture-negative sepsis is often reported. Antibiotic stewardship is mandatory due to the potential negative effects of unnecessary antibiotics. Procalcitonin (PCT)-guided therapy is one possible strategy with published evidence to shorten antibiotic therapy. The aim of this study is to analyze the feasibility and the performance of the published PCT-algorithm in the clinical setting without study support.

Methods: This is a retrospective, population-based study regarding duration of antibiotic therapy for suspected EOS in Central Switzerland between 2014 and 2018. All neonates >34 0/7 weeks of gestational age started on antibiotic therapy for suspected EOS within the first 3 calendar days of life were included. The Procalcitonin-guided algorithm according to the NeoPInS study was used as strategy to determine duration of antibiotic therapy.

Results: In a population-based cohort of 35,642 life born neonates, the duration of antibiotic therapy of 879 neonates (2.5% of the cohort) treated for suspected EOS was 4 calendar days (median, IQR 2–5). We observed a statistically significant reduction from 4 (median, IQR 3–6) to 3 calendar days (median, IQR 2–4) from 2014 to 2018. Duration of antibiotic therapy was independent of gestational age (late-preterm vs. term neonates), of the presence of risk factors or clinical signs, but dependent on the presence of abnormal laboratory measurements (C-reactive protein > 10 mg/l or leukocytopenia <5 Giga/l) before start of antibiotic therapy (p < 0.01).

Conclusions: PCT-guided therapy using the NeoPInS algorithm is feasible and may lead to reduced duration of antibiotic therapy for suspected EOS as reported in the original study. We observed a learning curve to the new algorithm which may be explained as change process. The use of biomarker to guide duration of antibiotic therapy for suspected EOS may have unintended consequences with prolongation of antibiotic therapy in some cases.
Differential Dermatologic Adverse Events Associated With Checkpoint Inhibitor Monotherapy and Combination Therapy: A Meta-Analysis of Randomized Control Trials
Authors: Ge Yang , Zhang Huiyun , Weygant Nathaniel , Yao Jiannan
Published: July 2021

Background: As immune checkpoint inhibitors (ICIs) transition to the forefront of cancer treatment, a better understanding of immune related adverse events (IRAEs) is essential to promote safe clinical practice. Dermatologic adverse events are the most common IRAEs and can lead to drug withdrawal and decreased quality of life. This meta-analysis aimed to investigate the risk of the most prevalent dermatologic adverse events (pruritus and rash) among various ICI treatment regimens.

Methods: A systematic search of electronic databases was performed to identify qualified randomized controlled trials (RCTs). Data for any grade and high grade pruritus and rash were extracted for meta-analysis. Two reviewers independently assessed methodological quality. The relative risk summary and 95% confidence interval were calculated.

Results: 50 RCTs involving 29941 patients were analyzed. The risk of pruritus (2.15 and 4.21 relative risk respectively) and rash (1.61 and 3.89 relative risk respectively) developing from CTLA-4 or PD-1/-L1 inhibitor were increased compared to placebo, but this effect was not dose-dependent. PD-1/-L1 plus CTLA-4 inhibitor was associated with increased risk of pruritus (1.76 and 0.98 relative risk respectively) and rash (1.72 and 1.37 relative risk respectively) compared to either monotherapy. Compared with CTLA-4 inhibitor, PD-1/-L1 inhibitor had a significantly decreased risk of pruritus and rash in both monotherapy and combination therapy (0.65 and 0.29 relative risk respectively). No significant difference was found between PD-1/-L1 inhibitor combined with chemotherapy and PD-1/-L1 monotherapy in any grade and high grade rash (0.84 and 1.43 relative risk respectively). In subgroup analyses, PD-1 inhibitor was associated with reduced risk of pruritus and rash compared to PD-L1 inhibitor.

Conclusion: Our meta-analysis demonstrates a better safety profile for PD-1/-L1 inhibitor compared to CTLA-4 inhibitor in terms of pruritus and rash among both monotherapy and multiple combination therapies. PD-L1 inhibitor may contribute to an increased risk of pruritus and rash compared to PD-1 inhibitor.
Neferine Ameliorates Sepsis-Induced Myocardial Dysfunction Through Anti-Apoptotic and Antioxidative Effects by Regulating the PI3K/AKT/mTOR Signaling Pathway
Authors: Qi Zhen , Wang Renrong , Liao Rongheng , Xue Song , Wang Yongyi
Published: July 2021

Septic cardiomyopathy is a common complication of severe sepsis, which is one of the leading causes of death in intensive care units. Therefore, finding an effective therapy target is urgent. Neferine is an alkaloid extracted from the green embryos of mature seeds of Nelumbo nucifera Gaertn., which has been reported to exhibit various biological activities and pharmacological properties. This study aims to explore the protective effects of neferine against lipopolysaccharide (LPS)-induced myocardial dysfunction and its mechanisms. The LPS-induced cardiac dysfunction mouse model was employed to investigate the protective effects of neferine. In this study, we demonstrated that neferine remarkably improved cardiac function and survival rate and ameliorated morphological damage to heart tissue in LPS-induced mice. Neferine also improved cell viability and mitochondrial function and reduced cell apoptosis and the production of reactive oxygen species in LPS-treated H9c2 cells. In addition, neferine significantly upregulated Bcl-2 expression and suppressed cleaved caspase 3 activity in LPS-induced mouse heart tissue and H9c2 cells. Furthermore, neferine also upregulated the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) signaling pathway in vivo and in vitro. Conversely, LY294002 (a PI3K inhibitor) reversed the protective effect of neferine in LPS-induced H9c2 cells. Our findings thus demonstrate that neferine ameliorates LPS-induced cardiac dysfunction by activating the PI3K/AKT/mTOR signaling pathway and presents a promising therapeutic agent for the treatment of LPS-induced cardiac dysfunction.