bluuebunny/crossref_metadata_2025 huggingface dataset:
Host tree species effects on long-term persistence of epiphytic orchid populations
Authors: Ramírez-Martínez Adriana , Ticktin Tamara , Mondragon Demetria
Published: December 2022

The destinies of epiphytic orchids (about 70% of all orchids) are linked to their host trees. However, there is little information on if differences in host trees characteristics can affect the long-term persistence of orchid populations, and how this might vary under different climatic conditions. We compared the population dynamics of two epiphytic orchid species, Alamania punicea and Oncidium brachyandrum growing on two host trees with contrasting leaf phenologies: the deciduous Quercus martinezii and the semideciduous Q. rugosa, over 3 years with varying levels of rainfall, in a montane tropical oak forest in Oaxaca, Mexico. Using data from > 500 individuals growing on 63 host trees, we applied linear mixed effects models, Integral Projection Models, and Life Table Response Experiments to identify the effects of host tree on orchid vital rates and population growth rates. For both orchid species, survival and growth did not differ between host species during wettest year. However, during the driest year both vital rates were higher on the semi-deciduous host Q. rugosa than on the deciduous Q. martinezii. Host species did not affect fecundity for A. punicea, but for O. brachyandrum fecundity was higher on the deciduous host. For A. punicea, λ values were similar between hosts during the wettest and intermediate years, but significantly lower (Δ λ = 0.28) on the deciduous than on the semi-deciduous host during the driest year. This was due primarily to lower survival on the deciduous host. For O. brachyandrum, λ was slightly higher (Δ λ = 0.03) on the deciduous than the semideciduous host during the wettest year, due to higher growth and reproduction. However, during the intermediate and driest years, λ values were significantly higher on the semi-deciduous than on the deciduous host (Δ λ = 0.13 and 0.15, respectively). This was due to higher survival and growth. A. punicea populations appear more vulnerable to dry conditions than O. brachyandrum, likely due to its smaller pseudobulbs, and hence lower water-storing capacity. Our results show that host tree species can both influence the vital rates and the long-term dynamics of orchid populations, and these effects vary across orchids species and over time. Our results highlight the importance of maintaining a diversity of host trees to ensure long-term population persistence.
Major histocompatibility complex genomic investigation of endangered Chinese alligator provides insights into the evolution of tetrapod major histocompatibility complex and survival of critically bottlenecked species
Authors: He Ke , Zhu Ying , Yang Shang-Chen , Ye Qing , Fang Sheng-Guo , Wan Qiu-Hong
Published: December 2022

Background

The major histocompatibility complex (MHC) gene family, a vital immune gene family in vertebrates, helps animals defend against pathogens. The polymorphism of MHC genes is important for a species and is considered to be caused by the numerous alleles of MHC antigen-presenting genes. However, the mechanism of this process is unclear due to the lack of data on the MHC structure. The evolutionary trajectories of the tetrapod MHC are also unclear because of insufficient studies on the reptile MHC architecture. Here, we studied the Chinese alligator (Alligator sinensis), which experienced a population bottleneck, but the population increased rapidly in the past 30 years and is proposed to have a unique MHC system to face pathogenic challenges.

Results

We successfully constructed a 2 Mb MHC region using bacterial artificial chromosome (BAC) library and genome data of the Chinese alligator and checked the antigen-presenting genes using transcriptome data and the rapid amplification of cDNA ends (RACE) technique. The MHC architecture reported here uncovers adjacent Class I and Class II subregions and a unique CD1 subregion. This newly added information suggested that the Class I-II structure pattern was more ancient in tetrapods and helped reconstruct the evolution of the MHC region architecture. We also found multiple groups of MHC class I (MHC-I) (12 duplicated loci, belonging to three groups, two of which were novel) and MHC class II (MHC-II) (11 duplicated loci, belonging to two groups) inside the 2 Mb MHC region, and there were three more duplicated MHC-I loci outside it. These highly duplicated antigen-presenting loci had differences in expression, amino acid length of antigen-presenting exons, and splice signal of exon and intron, which together promoted the polymorphism of duplicated genes. Although the MHC antigen-presenting genes were identified as monomorphic or oligomorphic in our previous population study, the loci with high copy numbers and many differences can make up for this loss, presenting another mechanism for polymorphism in antigen presentation. These MHC-I and MHC-IIB loci with low polymorphism for each locus, but high numbers in all, may also contribute to MHC antigen-presenting binding variability in a population.

Conclusion

To summarize, the fine MHC region architecture of reptiles presented in this study completes the evolutionary trajectories of the MHC structure in tetrapods, and these distinctive MHC gene groups in the Chinese alligator may have helped this species to expand rapidly in the past recent years.
Metabolic responses of predators to prey density
Authors: Giacomini Henrique Corrêa
Published: December 2022

The metabolic cost of foraging is the dark energy of ecological systems. It is much harder to observe and to measure than its beneficial counterpart, prey consumption, yet it is not inconsequential for the dynamics of prey and predator populations. Here I define the metabolic response as the change in energy expenditure of predators in response to changes in prey density. It is analogous and intrinsically linked to the functional response, which is the change in consumption rate with prey density, as they are both shaped by adjustments in foraging activity. These adjustments are adaptive, ubiquitous in nature, and are implicitly assumed by models of predator–prey dynamics that impose consumption saturation in functional responses. By ignoring the associated metabolic responses, these models violate the principle of energy conservation and likely underestimate the strength of predator–prey interactions. Using analytical and numerical approaches, I show that missing this component of interaction has broad consequences for dynamical stability and for the robustness of ecosystems to persistent environmental or anthropogenic stressors. Negative metabolic responses – those resulting from decreases in foraging activity when more prey is available, and arguably the most common – lead to lower local stability of food webs and a faster pace of change in population sizes, including higher excitability, higher frequency of oscillations, and quicker return times to equilibrium when stable. They can also buffer the effects of press perturbations, such as harvesting, on target populations and on their prey through top-down trophic cascades, but are expected to magnify bottom-up cascades, including the effects of nutrient enrichment or the effects of altering lower trophic levels that can be caused by environmental forcing and climate change. These results have implications for any resource management approach that relies on models of food web dynamics, which is the case of many applications of ecosystem-based fisheries management. Finally, besides having their own individual effects, metabolic responses have the potential to greatly alter, or even invert, functional response-stability relationships, and therefore can be critical to an integral understanding of predation and its influence on population dynamics and persistence.
Biomarker-driven drug repurposing on biologically similar cancers with DNA-repair deficiencies
Authors: Munj Seeya Awadhut , Taz Tasnimul Alam , Arslanturk Suzan , Heath Elisabeth I.
Published: December 2022

Similar molecular and genetic aberrations among diseases can lead to the discovery of jointly important treatment options across biologically similar diseases. Oncologists closely looked at several hormone-dependent cancers and identified remarkable pathological and molecular similarities in their DNA repair pathway abnormalities. Although deficiencies in Homologous Recombination (HR) pathway plays a significant role towards cancer progression, there could be other DNA-repair pathway deficiencies that requires careful investigation. In this paper, through a biomarker-driven drug repurposing model, we identified several potential drug candidates for breast and prostate cancer patients with DNA-repair deficiencies based on common specific biomarkers and irrespective of the organ the tumors originated from. Normalized discounted cumulative gain (NDCG) and sensitivity analysis were used to assess the performance of the drug repurposing model. Our results showed that Mitoxantrone and Genistein were among drugs with high therapeutic effects that significantly reverted the gene expression changes caused by the disease (FDR adjusted p-values for prostate cancer =1.225e-4 and 8.195e-8, respectively) for patients with deficiencies in their homologous recombination (HR) pathways. The proposed multi-cancer treatment framework, suitable for patients whose cancers had common specific biomarkers, has the potential to identify promising drug candidates by enriching the study population through the integration of multiple cancers and targeting patients who respond poorly to organ-specific treatments.
Homozygous mutation in DNAAF4 causes primary ciliary dyskinesia in a Chinese family
Authors: Jiang Guoliang , Zou Lijun , Long Lingzhi , He Yijun , Lv Xin , Han Yuanyuan , Yao Tingting , Zhang Yan , Jiang Mao , Peng Zhangzhe , Tao Lijian , Xie Wei , Meng Jie
Published: December 2022

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder that affects the structure and function of motile cilia, leading to classic clinical phenotypes, such as situs inversus, chronic sinusitis, bronchiectasis, repeated pneumonia and infertility. In this study, we diagnosed a female patient with PCD who was born in a consanguineous family through classic clinical manifestations, transmission electron microscopy and immunofluorescence staining. A novel DNAAF4 variant NM_130810: c.1118G>A (p. G373E) was filtered through Whole-exome sequencing. Subsequently, we explored the effect of the mutation on DNAAF4 protein from three aspects: protein expression, stability and interaction with downstream DNAAF2 protein through a series of experiments, such as transfection of plasmids and Co-immunoprecipitation. Finally, we confirmed that the mutation of DNAAF4 lead to PCD by reducing the stability of DNAAF4 protein, but the expression and function of DNAAF4 protein were not affected.
Fatty acid composition and metabolic partitioning of α-linolenic acid are contingent on life stage in human CD3+ T lymphocytes
Authors: West Annette L. , von Gerichten Johanna , Irvine Nicola A. , Miles Elizabeth A. , Lillycrop Karen A. , Calder Philip C. , Fielding Barbara A. , Burdge Graham C.
Published: December 2022

Introduction

Immune function changes across the life course; the fetal immune system is characterised by tolerance while that of seniors is less able to respond effectively to antigens and is more pro-inflammatory than in younger adults. Lipids are involved centrally in immune function but there is limited information about how T cell lipid metabolism changes during the life course.

Methods and Results

We investigated whether life stage alters fatty acid composition, lipid droplet content and α-linolenic acid (18:3ω-3) metabolism in human fetal CD3+T lymphocytes and in CD3+T lymphocytes from adults (median 41 years) and seniors (median 70 years). Quiescent fetal T cells had higher saturated (SFA), monounsaturated fatty acid (MUFA), and ω-6 polyunsaturated fatty acid (PUFA) contents than adults or seniors. Activation-induced changes in fatty acid composition differed between life stages. The principal metabolic fates of [13C]18:3ω-3 were constitutive hydroxyoctadecatrienoic acid synthesis and β-oxidation and carbon recycling into SFA and MUFA. These processes declined progressively across the life course. Longer chain ω-3 PUFA synthesis was a relatively minor metabolic fate of 18:3ω-3 at all life stages. Fetal and adult T lymphocytes had similar lipid droplet contents, which were lower than in T cells from seniors. Variation in the lipid droplet content of adult T cells accounted for 62% of the variation in mitogen-induced CD69 expression, but there was no significant relationship in fetal cells or lymphocytes from seniors.

Discussion

Together these findings show that fatty acid metabolism in human T lymphocytes changes across the life course in a manner that may facilitate the adaptation of immune function to different life stages.
Effects of seawater acidification and solar ultraviolet radiation on photosynthetic performances and biochemical compositions of Rhodosorus sp. SCSIO-45730
Authors: Wang Na , Lv Jinting , Yang Fangfang , Li Tao , Wu Hualian , Li Chulin , Pei Haiwei , Wu Houbo , Xiang Wenzhou
Published: December 2022

Ocean acidification (OA) caused by rising atmospheric CO2 concentration and solar ultraviolet radiation (UVR) resulting from ozone depletion may affect marine organisms, but little is known regarding how unicellular Rhodosorus sp. SCSIO-45730, an excellent species resource containing various biological-active compounds, responds to OA and UVR. Therefore, we conducted a factorial coupling experiment to unravel the combined effects of OA and UVR on the growth, photosynthetic performances, biochemical compositions and enzyme activities of Rhodosorus sp. SCSIO-45730, which were exposed to two levels of CO2 (LC, 400 μatm, current CO2 level; HC, 1000 μatm, future CO2 level) and three levels of UVR (photosynthetically active radiation (PAR), PAR plus UVA, PAR plus UVB) treatments in all combinations, respectively. Compared to LC treatment, HC stimulated the relative growth rate (RGR) due to higher optimum and effective quantum yields, photosynthetic efficiency, maximum electron transport rates and photosynthetic pigments contents regardless of UVR. However, the presence of UVA had no significant effect but UVB markedly reduced the RGR. Additionally, higher carbohydrate content and lower protein and lipid contents were observed when Rhodosorus sp. SCSIO-45730 was cultured under HC due to the ample HCO3− applications and active stimulation of metabolic enzymes of carbonic anhydrase and nitrate reductase, thus resulting in higher TC/TN. OA also triggered the production of reactive oxygen species (ROS), and the increase of ROS coincided approximately with superoxide dismutase and catalase activities, as well as phenols contents. However, UVR induced photochemical inhibition and damaged macromolecules, making algal cells need more energy for self-protection. Generally, these results revealed that OA counteracted UVR-related inhibition on Rhodosorus sp. SCSIO-45730, adding our understanding of the red algae responding to future global climate changes.
Characteristics and survival of patients diagnosed with cardiac sarcoidosis: A case series
Authors: Brazile Tiffany L. , Saul Melissa , Nouraie Seyed Mehdi , Gibson Kevin
Published: December 2022

Background

Sarcoidosis is a multiorgan system granulomatous disease of unknown etiology. It is hypothesized that a combination of environmental, occupational, and/or infectious factors provoke an immunological response in genetically susceptible individuals, resulting in a diversity of manifestations throughout the body. In the United States, cardiac sarcoidosis (CS) is diagnosed in 5% of patients with systemic sarcoidosis, however, autopsy results suggest that cardiac involvement may be present in > 50% of patients. CS is debilitating and significantly decreases quality of life and survival. Currently, there are no gold-standard clinical diagnostic or monitoring criteria for CS.

Methods

We identified patients with a diagnosis of sarcoidosis who were seen at the Simmons Center from 2007 to 2020 who had a positive finding of CS documented with cardiovascular magnetic resonance (CMR) and/or endomyocardial biopsy as found in the electronic health record. Medical records were independently reviewed for interpretation and diagnostic features of CS including late gadolinium enhancement (LGE) patterns, increased signal on T2-weighted imaging, and non-caseating granulomas, respectively. Extracardiac organ involvement, cardiac manifestations, comorbid conditions, treatment history, and vital status were also abstracted.

Results

We identified 44 unique patients with evidence of CS out of 246 CMR reports and 9 endomyocardial biopsy pathology reports. The first eligible case was diagnosed in 2007. The majority of patients (73%) had pulmonary manifestations, followed by hepatic manifestations (23%), cutaneous involvement (23%), and urolithiasis (20%). Heart failure was the most common cardiac manifestation affecting 59% of patients. Of these, 39% had a documented left ventricular ejection fraction of < 50% on CMR. Fifty eight percent of patients had a conduction disease and 44% of patients had documented ventricular arrhythmias. Pharmacotherapy was usually initiated for extracardiac manifestations and 93% of patients had been prescribed prednisone. ICD implantation occurred in 43% of patients. Patients were followed up for a median of 5.4 (IQR: 2.4–8.5) years. The 10-year survival was 70%. In addition to age, cutaneous involvement was associated with an increased risk of death (age-adjusted OR 8.47, 95% CI = 1.11–64.73).

Conclusion

CMR is an important tool in the non-invasive diagnosis of CS. The presence of LGE on CMR in a pattern consistent with CS has been shown to be a predictor of mortality and likely contributed to a high proportion of patients undergoing ICD implantation to decrease risk of sudden cardiac death.

Clinical implications

Additional studies are necessary to develop robust criteria for the diagnosis of CS with CMR, assess the benefit of serial imaging for disease monitoring, and evaluate the effect of immunosuppression on disease progression.
Characteristics, pathogenic mechanism, zoonotic potential, drug resistance, and prevention of avian pathogenic Escherichia coli (APEC)
Authors: Hu Jiangang , Afayibo Dossêh Jean Apôtre , Zhang Beibei , Zhu Hong , Yao Lan , Guo Weiqi , Wang Xinyu , Wang Zhiyang , Wang Di , Peng Haoheng , Tian Mingxing , Qi Jingjing , Wang Shaohui
Published: December 2022

Although mostEscherichia coli(E. coli) strains are commensal and abundant, certain pathogenic strains cause severe diseases from gastroenteritis to extraintestinal infections. Extraintestinal pathogenicE.coli(ExPEC) contains newborn meningitisE.coli(NMEC), uropathogenicE.coli(UPEC), avian pathogenicE.coli(APEC), and septicemicE.coli(SEPEC) based on their original host and clinical symptom. APEC is a heterogeneous group derived from human ExPEC. APEC causes severe respiratory and systemic diseases in a variety of avians, threatening the poultry industries, food security, and avian welfare worldwide. APEC has many serotypes, and it is a widespread pathogenic bacterium in poultry. In addition, ExPEC strains share significant genetic similarities and similar pathogenic mechanisms, indicating that APEC potentially serves as a reservoir of virulence and resistance genes for human ExPEC, and the virulence and resistance genes can be transferred to humans through food animals. Due to economic losses, drug resistance, and zoonotic potential, APEC has attracted heightened awareness. Various virulence factors and resistance genes involved in APEC pathogenesis and drug resistance have been identified. Here, we review the characteristics, epidemiology, pathogenic mechanism zoonotic potential, and drug resistance of APEC, and summarize the current status of diagnosis, alternative control measures, and vaccine development, which may help to have a better understanding of the pathogenesis and resistance of APEC, thereby reducing economic losses and preventing the spread of multidrug-resistant APEC to humans.
Effects of chlorogenic acid on antimicrobial, antivirulence, and anti-quorum sensing of carbapenem-resistant Klebsiella pneumoniae
Authors: Wang Lingbo , Zhang Yi , Liu Yan , Xu Mengxin , Yao Zhuocheng , Zhang Xiaodong , Sun Yao , Zhou Tieli , Shen Mo
Published: December 2022

The rise in infections caused by the hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) is an emergent threat to public health. We assessed the effects of chlorogenic acid (CA), a natural phenolic compound, on antibacterial, antivirulence, and anti-quorum sensing (QS) of hv-CRKP. Five hv-CRKP were selected for antimicrobial susceptibility test and confirmed to carry virulence genes and carbapenem-resistant genes by polymerase chain reaction (PCR). Subsequently, a series of time-kill assay, determinations of protease activity and capsule content, biofilm-related experiment, scanning electron microscopy (SEM) and transmission electron microscope (TEM) observation, G. mellonella infection model, quantitative real-time PCR (qRT-PCR) of QS-related genes and biofilm formation genes, as well as AI-2 binding test were conduct to verify the effect of CA on hv-CRKP. Five CRKP strains showed varying degrees of resistance to antibacterial agents. All strains carried the blaKPC–2 gene, primarily carrying rmpA2, iucA, and peg-344. CA showed no effect on CRKP growth at the 1/2 minimum inhibitory concentration (MIC), 1/4 MIC, and 1/8 MIC, CA could reduce the production of extracellular protease and capsular polysaccharides, and improve the survival rate of larvae in Galleria mellonella (G. mellonella) infection model. By means of crystal violet staining and scanning electron microscopy experiments, we observed that CA can inhibit the formation of CRKP biofilm. On the quantitative real-time PCR analysis, the expression of the luxS, mrkA and wbbm genes in most CRKP strains appeared downregulated because of the CA treatment. Besides, CA significantly inhibited the effect of AI-2 activity of BB170. Our study suggests that CA can be an effective antimicrobial, antivirulent compound that can target QS in hv-CRKP infections, thus providing a new therapeutic direction for treating bacterial infections.
Nano-antivirals: A comprehensive review
Authors: Hussain Fayyaz Salih , Abro Naveed Qasim , Ahmed Naseer , Memon Saima Q. , Memon Najma
Published: December 2022

Nanoparticles can be used as inhibitory agents against various microorganisms, including bacteria, algae, archaea, fungi, and a huge class of viruses. The mechanism of action includes inhibiting the function of the cell membrane/stopping the synthesis of the cell membrane, disturbing the transduction of energy, producing toxic reactive oxygen species (ROS), and inhibiting or reducing RNA and DNA production. Various nanomaterials, including different metallic, silicon, and carbon-based nanomaterials and nanoarchitectures, have been successfully used against different viruses. Recent research strongly agrees that these nanoarchitecture-based virucidal materials (nano-antivirals) have shown activity in the solid state. Therefore, they are very useful in the development of several products, such as fabric and high-touch surfaces. This review thoroughly and critically identifies recently developed nano-antivirals and their products, nano-antiviral deposition methods on various substrates, and possible mechanisms of action. By considering the commercial viability of nano-antivirals, recommendations are made to develop scalable and sustainable nano-antiviral products with contact-killing properties.
An immediate-return reinforcement learning for the atypical Markov decision processes
Authors: Pan Zebang , Wen Guilin , Tan Zhao , Yin Shan , Hu Xiaoyan
Published: December 2022

The atypical Markov decision processes (MDPs) are decision-making for maximizing the immediate returns in only one state transition. Many complex dynamic problems can be regarded as the atypical MDPs, e.g., football trajectory control, approximations of the compound Poincaré maps, and parameter identification. However, existing deep reinforcement learning (RL) algorithms are designed to maximize long-term returns, causing a waste of computing resources when applied in the atypical MDPs. These existing algorithms are also limited by the estimation error of the value function, leading to a poor policy. To solve such limitations, this paper proposes an immediate-return algorithm for the atypical MDPs with continuous action space by designing an unbiased and low variance target Q-value and a simplified network framework. Then, two examples of atypical MDPs considering the uncertainty are presented to illustrate the performance of the proposed algorithm, i.e., passing the football to a moving player and chipping the football over the human wall. Compared with the existing deep RL algorithms, such as deep deterministic policy gradient and proximal policy optimization, the proposed algorithm shows significant advantages in learning efficiency, the effective rate of control, and computing resource usage.
Emergence of radial orientation selectivity: Effect of cell density changes and eccentricity in a layered network
Authors: Davey Catherine E. , Grayden David B. , Burkitt Anthony N.
Published: December 2022

We establish a simple mechanism by which radially oriented simple cells can emerge in the primary visual cortex. In 1986, R. Linsker. proposed a means by which radially symmetric, spatial opponent cells can evolve, driven entirely by noise, from structure in the initial synaptic connectivity distribution. We provide an analytical derivation of Linsker's results, and further show that radial eigenfunctions can be expressed as a weighted sum of degenerate Cartesian eigenfunctions, and vice-versa. These results are extended to allow for radially dependent cell density, from which we show that, despite a circularly symmetric synaptic connectivity distribution, radially biased orientation selectivity emerges in the third layer when cell density in the first layer, or equivalently, synaptic radius, changes with eccentricity; i.e., distance to the center of the lamina. This provides a potential mechanism for the emergence of radial orientation in the primary visual cortex before eye opening and the onset of structured visual input after birth.
Hotspots and frontier trends of diabetic associated cognitive decline research based on rat and mouse models from 2012 to 2021: A bibliometric study
Authors: Li Jie , Wang Zhen , Nan Xinyu , Yin Mingjie , Fang Hui
Published: December 2022

Background

The establishment of rodent models, such as rat and mouse models, plays a critical role in the study of diabetic associated cognitive decline. With the continuous growth of relevant literature information, it is difficult for researchers to accurately and timely capture the topics in this field. Therefore, this study aims to explore the current status and frontier trends of diabetic associated cognitive decline research based on rat and mouse models through a bibliometric analysis.

Methods

We collected 701 original articles on this subject from the Science Citation Index Expanded of the Web of Science Core Collection from 2012 to 2021. Then we utilized CiteSpace and VOSviewer for plotting knowledge maps and evaluating hotpots and trends.

Results

During this decade, except for a slight decline in 2020, the number of annual outputs on diabetes associated cognitive decline research using rat and mouse models increased every year. China (country), China Pharmaceutical University (institution), Gao, Hongchang (the author from the School of Pharmacy of Wenzhou Medical University, China), and Metabolic Brain Disease (journal) published the most papers in this research field. The analysis results of co-cited references and co-occurrence keywords indicated that “mechanisms and prevention and treatment methods”, especially “oxidative stress”, “potential association with Alzheimer's disease” and “spatial memory” are research focuses in this subject area. The bursts detection of references and keywords implied that “cognitive impairment of type 1 diabetes” and “autophagy and diabetes associated cognitive decline” will be potential directions for future research in this subject area.

Conclusion

This study systematically assessed general information, current status and emerging trends of diabetic associated cognitive decline research using rat and mouse models in the past decade based on a bibliometric analysis. The number of publications was annually increasing although a slight decline was observed in 2020. Contributions from different countries/regions, institutions, authors, co-cited authors, journals and co-cited journals were evaluated, which may also be used to guide future research. Through the analysis of references and keywords, we predicted the future research hotspots and trends in this field.
Comparative safety of multiple doses of erythropoietin for the treatment of traumatic brain injury: A systematic review and network meta-analysis
Authors: Zheng Qingyong , Duan Dan , Xu Jianguo , Wang Xing , Ge Yonggui , Xiong Lu , Yang Jingjing , Wulayin Saimire , Luo Xiaofeng
Published: December 2022

Introduction

Over the past few decades, advances in traumatic brain injury (TBI) pathology research have dynamically enriched our knowledge. Therefore, we aimed to systematically elucidate the safety and efficacy of erythropoietin (EPO) dosing regimens in patients with TBI.

Methods

Data search included PubMed, the Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov for related research published before July 2022. The network meta-analysis was conducted using ADDIS 1.16.8, and the CINeMA tool was used to assess the quality level of evidence.

Results

A total of six RCTs involving 981 patients were included in the network meta-analysis. EPO did not significantly reduce mortality in patients with TBI, but its risk of death decreased with increasing dosage (odds ratio (OR) of 12,000u vs. placebo = 0.98, 95% CI: 0.03–40.34; OR of group 30,000u vs. placebo = 0.56, 95% CI: 0.06–5.88; OR of 40,000u vs. placebo = 0.35, 95% CI: 0.01–9.43; OR of 70,000u vs. placebo = 0.29, 95% CI: 0.01–9.26; OR of group 80,000u vs. placebo = 0.22, 95% CI: 0.00–7.45). A total of three studies involving 739 patients showed that EPO did not increase the incidence of deep vein thrombosis in patients with TBI. However, the risk tended to rise as the dosage increased. Another two studies demonstrated that EPO did not increase the incidence of pulmonary embolism. The quality of evidence for all outcomes was low to moderate.

Conclusion

Although the efficacy of EPO was not statistically demonstrated, we found a trend toward an association between EPO dosage and reduced mortality and increased embolic events in patients with TBI. More high-quality original studies should be conducted to obtain strong evidence on the optimal dosage of EPO.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=272500. The study protocol was registered with PROSPERO (CRD42021272500).
Multibranch convolutional neural network with contrastive representation learning for decoding same limb motor imagery tasks
Authors: Phunruangsakao Chatrin , Achanccaray David , Izumi Shin-Ichi , Hayashibe Mitsuhiro
Published: December 2022

Introduction

Emerging deep learning approaches to decode motor imagery (MI) tasks have significantly boosted the performance of brain-computer interfaces. Although recent studies have produced satisfactory results in decoding MI tasks of different body parts, the classification of such tasks within the same limb remains challenging due to the activation of overlapping brain regions. A single deep learning model may be insufficient to effectively learn discriminative features among tasks.

Methods

The present study proposes a framework to enhance the decoding of multiple hand-MI tasks from the same limb using a multi-branch convolutional neural network. The CNN framework utilizes feature extractors from established deep learning models, as well as contrastive representation learning, to derive meaningful feature representations for classification.

Results

The experimental results suggest that the proposed method outperforms several state-of-the-art methods by obtaining a classification accuracy of 62.98% with six MI classes and 76.15 % with four MI classes on the Tohoku University MI-BCI and BCI Competition IV datasets IIa, respectively.

Discussion

Despite requiring heavy data augmentation and multiple optimization steps, resulting in a relatively long training time, this scheme is still suitable for online use. However, the trade-of between the number of base learners, training time, prediction time, and system performance should be carefully considered.
Discovery and functional characterization of neuropeptides in crinoid echinoderms
Authors: Aleotti Alessandra , Wilkie Iain C. , Yañez-Guerra Luis A. , Gattoni Giacomo , Rahman Tahshin A. , Wademan Richard F. , Ahmad Zakaryya , Ivanova Deyana A. , Semmens Dean C. , Delroisse Jérôme , Cai Weigang , Odekunle Esther , Egertová Michaela , Ferrario Cinzia , Sugni Michela , Bonasoro Francesco , Elphick Maurice R.
Published: December 2022

Neuropeptides are one of the largest and most diverse families of signaling molecules in animals and, accordingly, they regulate many physiological processes and behaviors. Genome and transcriptome sequencing has enabled the identification of genes encoding neuropeptide precursor proteins in species from a growing variety of taxa, including bilaterian and non-bilaterian animals. Of particular interest are deuterostome invertebrates such as the phylum Echinodermata, which occupies a phylogenetic position that has facilitated reconstruction of the evolution of neuropeptide signaling systems in Bilateria. However, our knowledge of neuropeptide signaling in echinoderms is largely based on bioinformatic and experimental analysis of eleutherozoans—Asterozoa (starfish and brittle stars) and Echinozoa (sea urchins and sea cucumbers). Little is known about neuropeptide signaling in crinoids (feather stars and sea lilies), which are a sister clade to the Eleutherozoa. Therefore, we have analyzed transcriptome/genome sequence data from three feather star species, Anneissia japonica, Antedon mediterranea, and Florometra serratissima, to produce the first comprehensive identification of neuropeptide precursors in crinoids. These include representatives of bilaterian neuropeptide precursor families and several predicted crinoid neuropeptide precursors. Using A. mediterranea as an experimental model, we have investigated the expression of selected neuropeptides in larvae (doliolaria), post-metamorphic pentacrinoids and adults, providing new insights into the cellular architecture of crinoid nervous systems. Thus, using mRNA in situ hybridization F-type SALMFamide precursor transcripts were revealed in a previously undescribed population of peptidergic cells located dorso-laterally in doliolaria. Furthermore, using immunohistochemistry a calcitonin-type neuropeptide was revealed in the aboral nerve center, circumoral nerve ring and oral tube feet in pentacrinoids and in the ectoneural and entoneural compartments of the nervous system in adults. Moreover, functional analysis of a vasopressin/oxytocin-type neuropeptide (crinotocin), which is expressed in the brachial nerve of the arms in A. mediterranea, revealed that this peptide causes a dose-dependent change in the mechanical behavior of arm preparations in vitro—the first reported biological action of a neuropeptide in a crinoid. In conclusion, our findings provide new perspectives on neuropeptide signaling in echinoderms and the foundations for further exploration of neuropeptide expression/function in crinoids as a sister clade to eleutherozoan echinoderms.
Neonatal oxytocin gives the tempo of social and feeding behaviors
Authors: Muscatelli Françoise , Matarazzo Valery , Chini Bice
Published: December 2022

The nonapeptide oxytocin (OT) is a master regulator of the social brain in early infancy, adolescence, and adult life. Here, we review the postnatal dynamic development of OT-system as well as early-life OT functions that are essential for shaping social behaviors. We specifically address the role of OT in neonates, focusing on its role in modulating/adapting sensory input and feeding behavior; both processes are involved in the establishing mother-infant bond, a crucial event for structuring all future social interactions. In patients and rodent models of Prader-Willi and Schaaf-Yang syndromes, two neurodevelopmental diseases characterized by autism-related features, sensory impairments, and feeding difficulties in early infancy are linked to an alteration of OT-system. Successful preclinical studies in mice and a phase I/II clinical trial in Prader-Willi babies constitute a proof of concept that OT-treatment in early life not only improves suckling deficit but has also a positive long-term effect on learning and social behavior. We propose that in early postnatal life, OT plays a pivotal role in stimulating and coordinating the maturation of neuronal networks controlling feeding behavior and the first social interactions. Consequently, OT therapy might be considered to improve feeding behavior and, all over the life, social cognition, and learning capabilities.
Brick tea consumption and its relationship with fluorosis in Tibetan areas
Authors: Wen Cai , Zhang Qing , Xie Fei , Jiang Jixin
Published: December 2022

Brick tea-type fluorosis (BTF) due to a high intake of brick tea is possible in Tibetan populations, and dental fluorosis (DF) and skeletal fluorosis (SF) are its primary manifestations. To determine the prevalence of DF and SF and their relationships with brick tea intake in Tibetan populations, a literature review was conducted for studies published between 1994 and 2021. The available evidence revealed that brick tea may be produced from older stems and leaves of the tea plant and that the fluoride content of brick tea exceeds the national standard. The harsh environment of the plateau has led to limited food sources for the local Tibetan people who form the habit of drinking tea leaves as a satiation solution to digest greasy food and replenish vitamins, and regular consumption of brick tea leads to excessive exposure of Tibetan residents to fluoride. Studies in Tibet showed that the prevalence of DF in children was 14.06–75.93% in different districts, and the overall pooled prevalence of DF was 26.08%. The prevalence of SF in adults was 19.90–74.77% in different Tibetan districts, and the overall pooled prevalence of SF was 33.84%. The analysis of risk factors showed that the prevalence of BTF may be related to high-altitude and different working and living conditions, and BTF in children may be associated with fluoride intake during mothers’ pregnancy and lactation. With the development of bioinformatics research, gene polymorphisms were suspected to be related to susceptibility to fluorosis in Tibetan populations. The study of BTF in Tibetan people needs to be further investigated and standardized, and additional studies evaluating the pathogenesis and preventive measures of BTF are warranted.
Evaluating breast ultrasound S-detect image analysis for small focal breast lesions
Authors: Xing Boyuan , Chen Xiangyi , Wang Yalin , Li Shuang , Liang Ying-Kui , Wang Dawei
Published: December 2022

Background

S-Detect is a computer-assisted, artificial intelligence-based system of image analysis that has been integrated into the software of ultrasound (US) equipment and has the capacity to independently differentiate between benign and malignant focal breast lesions. Since the revision and upgrade in both the breast imaging-reporting and data system (BI-RADS) US lexicon and the S-Detect software in 2013, evidence that supports improved accuracy and specificity of radiologists’ assessment of breast lesions has accumulated. However, such assessment using S-Detect technology to distinguish malignant from breast lesions with a diameter no greater than 2 cm requires further investigation.

Methods

The US images of focal breast lesions from 295 patients in our hospital from January 2019 to June 2022 were collected. The BI-RADS data were evaluated by the embedded program and as manually modified prior to the determination of a pathological diagnosis. The receiver operator characteristic (ROC) curves were constructed to compare the diagnostic accuracy between the assessments of the conventional US images, the S-Detect classification, and the combination of the two.

Results

There were 326 lesions identified in 295 patients, of which pathological confirmation demonstrated that 239 were benign and 87 were malignant. The sensitivity, specificity, and accuracy of the conventional imaging group were 75.86%, 93.31%, and 88.65%. The sensitivity, specificity, and accuracy of the S-Detect classification group were 87.36%, 88.28%, and 88.04%, respectively. The assessment of the amended combination of S-Detect with US image analysis (Co-Detect group) was improved with a sensitivity, specificity, and accuracy of 90.80%, 94.56%, and 93.56%, respectively. The diagnostic accuracy of the conventional US group, the S-Detect group, and the Co-Detect group using area under curves was 0.85, 0.88 and 0.93, respectively. The Co-Detect group had a better diagnostic efficiency compared with the conventional US group (Z = 3.882, p = 0.0001) and the S-Detect group (Z = 3.861, p = 0.0001). There was no significant difference in distinguishing benign from malignant small breast lesions when comparing conventional US and S-Detect techniques.

Conclusions

The addition of S-Detect technology to conventional US imaging provided a novel and feasible method to differentiate benign from malignant small breast nodules.
Targeted therapy of RET fusion-positive non-small cell lung cancer
Authors: Shen Zixiong , Qiu Binxu , Li Lin , Yang Bo , Li Guanghu
Published: December 2022

Lung cancer has very high morbidity and mortality worldwide, and the prognosis is not optimistic. Previous treatments for non-small cell lung cancer (NSCLC) have limited efficacy, and targeted drugs for some gene mutations have been used in NSCLC with considerable efficacy. The RET proto-oncogene is located on the long arm of chromosome 10 with a length of 60,000 bp, and the expression of RET gene affects cell survival, proliferation, growth and differentiation. This review will describe the basic characteristics and common fusion methods of RET genes; analyze the advantages and disadvantages of different RET fusion detection methods; summarize and discuss the recent application of non-selective and selective RET fusion-positive inhibitors, such as Vandetanib, Selpercatinib, Pralsetinib and Alectinib; discuss the mechanism and coping strategies of resistance to RET fusion-positive inhibitors.
Effects of metabolic cancer therapy on tumor microenvironment
Authors: Hyroššová Petra , Milošević Mirko , Škoda Josef , Vachtenheim Jr Jiří , Rohlena Jakub , Rohlenová Kateřina
Published: December 2022

Targeting tumor metabolism for cancer therapy is an old strategy. In fact, historically the first effective cancer therapeutics were directed at nucleotide metabolism. The spectrum of metabolic drugs considered in cancer increases rapidly – clinical trials are in progress for agents directed at glycolysis, oxidative phosphorylation, glutaminolysis and several others. These pathways are essential for cancer cell proliferation and redox homeostasis, but are also required, to various degrees, in other cell types present in the tumor microenvironment, including immune cells, endothelial cells and fibroblasts. How metabolism-targeted treatments impact these tumor-associated cell types is not fully understood, even though their response may co-determine the overall effectivity of therapy. Indeed, the metabolic dependencies of stromal cells have been overlooked for a long time. Therefore, it is important that metabolic therapy is considered in the context of tumor microenvironment, as understanding the metabolic vulnerabilities of both cancer and stromal cells can guide new treatment concepts and help better understand treatment resistance. In this review we discuss recent findings covering the impact of metabolic interventions on cellular components of the tumor microenvironment and their implications for metabolic cancer therapy.
Economic evaluation of first-line sugemalimab plus chemotherapy for metastatic non-small cell lung cancer in China
Authors: Wang Hao , Liao Li , Xu Yuan , Long Yunchun , Wang Ye , Zhou Yujie
Published: December 2022

Objective

To evaluate the economics of sugemalimab plus chemotherapy in the first-line treatment of metastatic non-small cell lung cancer, and to provide a reference for the formulation of relevant medical insurance policies and rational drug use.

Methods

From the perspective of the Chinese health system, a three-state partitioned survival model was constructed based on data from a phase III randomized clinical trial (GEMSTONE 302) to evaluate the cost-utility of sugemalimab plus chemotherapy compared with chemotherapy in first-line treatment of metastatic non-small cell lung cancer. Model results were expressed as total cost, life years, quality-adjusted life years, and incremental cost-effectiveness ratio. The robustness of the underlying analysis results was verified using one-way sensitivity analysis and probabilistic sensitivity analysis.

Results

The results of the base-case analysis showed that sugemalimab plus chemotherapy yielded 1.63 QALYs at a total cost of 130,667.70 USD, chemotherapy yielded 1.04 QALYs at a total cost of 64,001.02 USD, and the ICER was 113,155.52 USD/QALY, which was well above the current willingness-to-pay threshold in China (3 times 2021 per capita GDP) (36,203.88 USD).

Conclusion

This study suggests that sugemalimab in combination with a chemotherapy regimen is more effective but not economical for patients with metastatic non-small cell lung cancer receiving first-line therapy in China and that a reasonable reduction in drug prices could improve the probability of it being economical.