bluuebunny/crossref_metadata_2025 huggingface dataset:
The Application of CRISPR/Cas9 Technology for Cancer Immunotherapy: Current Status and Problems
Authors: Wang Luyao , Chen Yurong , Liu Xinrui , Li Ziyi , Dai Xiangpeng
Published: January 2022

Cancer is one of the main causes of disease-related deaths in the world. Although cancer treatment strategies have been improved in recent years, the survival time of cancer patients is still far from satisfied. Cancer immunotherapy, such as Oncolytic virotherapy, Immune checkpoints inhibition, Chimeric antigen receptor T (CAR-T) cell therapy, Chimeric antigen receptor natural killer (CAR-NK) cell therapy and macrophages genomic modification, has emerged as an effective therapeutic strategy for different kinds of cancer. However, many patients do not respond to the cancer immunotherapy which warrants further investigation to optimize this strategy. The clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9), as a versatile genome engineering tool, has become popular in the biology research field and it was also applied to optimize tumor immunotherapy. Moreover, CRISPR-based high-throughput screening can be used in the study of immunomodulatory drug resistance mechanism. In this review, we summarized the development as well as the application of CRISPR/Cas9 technology in the cancer immunotherapy and discussed the potential problems that may be caused by this combination.
A Finite Element Mesh Regrouping Strategy-Based Hybrid Light Transport Model for Enhancing the Efficiency and Accuracy of XLCT
Authors: Liu Yanqiu , Hu Xiangong , Chu Mengxiang , Guo Hongbo , Yu Jingjing , He Xiaowei
Published: January 2022

X-ray luminescence computed tomography (XLCT) is an emerging hybrid imaging modality in optical molecular imaging, which has attracted more attention and has been widely studied. In XLCT, the accuracy and operational efficiency of an optical transmission model play a decisive role in the rapid and accurate reconstruction of light sources. For simulation of optical transmission characteristics in XLCT, considering the limitations of the diffusion equation (DE) and the time and memory costs of simplified spherical harmonic approximation equation (SPN), a hybrid light transport model needs to be built. DE and SPN models are first-order and higher-order approximations of RTE, respectively. Due to the discontinuity of the regions using the DE and SPN models and the inconsistencies of the system matrix dimensions constructed by the two models in the solving process, the system matrix construction of a hybrid light transmission model is a problem to be solved. We provided a new finite element mesh regrouping strategy-based hybrid light transport model for XLCT. Firstly, based on the finite element mesh regrouping strategy, two separate meshes can be obtained. Thus, for DE and SPN models, the system matrixes and source weight matrixes can be calculated separately in two respective mesh systems. Meanwhile, some parallel computation strategy can be combined with finite element mesh regrouping strategy to further save the system matrix calculation time. Then, the two system matrixes with different dimensions were coupled though repeated nodes were processed according to the hybrid boundary conditions, the two meshes were combined into a regrouping mesh, and the hybrid optical transmission model was established. In addition, the proposed method can reduce the computational memory consumption than the previously proposed hybrid light transport model achieving good balance between computational accuracy and efficiency. The forward numerical simulation results showed that the proposed method had better transmission accuracy and achieved a balance between efficiency and accuracy. The reverse simulation results showed that the proposed method had superior location accuracy, morphological recovery capability, and image contrast capability in source reconstruction. In-vivo experiments verified the practicability and effectiveness of the proposed method.
Pseudocapsule-Based Resection for Pituitary Adenomas via the Endoscopic Endonasal Approach
Authors: Zhou Yuefei , Wei Jialiang , Feng Feng , Wang Jianguo , Jia Pengfei , Yang Shuangwu , Gao Dakuan
Published: January 2022

Introduction

The endoscopic endonasal approach (EEA) is a safe and effective treatment for pituitary adenomas (PAs). Since extracapsular resection (ER) of PAs improves tumor resection and endocrine remission rates, the interface between the pseudocapsule and gland draws increasing attention. However, it is difficult to precisely dissect the tumor along the exact boundary, and complete removal of the tumor increases the risks of normal tissue damage and cerebrospinal fluid (CSF) leakage. In this study, we investigated the extracapsular resection as well as the pseudocapsule histology to evaluate the effectiveness and safety of pseudocapsule-related surgical interventions.

Methods

From December 2017 to December 2019, 189 patients of PAs via EEA in our single center were analyzed retrospectively. The images, operative details, and clinical follow-up of patients were collected. Sixty-four patients underwent pseudocapsule-based ER, and 125 patients also underwent traditional intracapsular resection (IR) with or without intensive excision for FPAs. The clinical characteristics, tumor resection, endocrinological outcomes, and postoperative morbidities of the two groups were compared. Informed consent for publication of our article was obtained from each patient. Histological examination of pseudocapsule was performed using hematoxylin and eosin and reticulin staining.

Results

The gross total recession was 62 (96.9%) in the ER group and 107 (85.6%) cases in the IR group, whereas the endocrine remission rate was 29/31 (93.5%) and 40/53 (75.5%) cases, respectively. Anterior pituitary functions were not aggravated postoperatively in any patient, but transient diabetes insipidus (DI) occurred more in the IR group (64.0%) than in ER (48.4%). Pseudocapsule specimens were obtained in 93 patients, and clusters of small cell aggregation were detected in 11 pseudocapsule specimens (11.8%) whereas other patients showed no remarkable developed pseudocapsule. Intraoperative CSF leak occurred more in the ER group (28.1%) than in the IR group (13.6%), but no difference was seen between two groups postoperatively. No case of intracranial hematoma or pituitary crisis occurred in both groups. After a mean follow-up of 22.8 months, tumor recurrence was observed in 4 (2.1%) cases.

Conclusion

Pseudocapsule-based extracapsular resection of PAs via EEA is an effective and safe procedure to achieve complete resection with high and sustained endocrine remission and without deteriorating pituitary function.
Risk Factors for Central Lymph Node Metastases and Benefit of Prophylactic Central Lymph Node Dissection in Middle Eastern Patients With cN0 Papillary Thyroid Carcinoma
Authors: Parvathareddy Sandeep Kumar , Siraj Abdul K. , Ahmed Saeeda O. , DeVera Felisa , Al-Sobhi Saif S. , Al-Dayel Fouad , Al-Kuraya Khawla S.
Published: January 2022

Background

Prophylactic central lymph node dissection (PCLND) for adult patients with papillary thyroid carcinoma (PTC) is still a matter of debate. Data on incidence, risk and benefits of PCLND in Middle Eastern patients is lacking. Therefore, we aimed to identify the incidence and predictive clinico-pathological and molecular marker of PCLND in adult patients with clinically node negative (cN0) Middle Eastern PTC.

Methods

This retrospective study included 942 adult Middle Eastern patients with cN0 PTC who underwent total thyroidectomy (TT) or TT+PCLND. Clinico-pathological associations of central lymph node metastasis (CLNM) were assessed. Multivariate analysis was performed using logistic regression and Cox proportional hazards model.

Results

213 patients underwent PCLND and 38.0% (81/213) had positive CLNM. Multivariate analysis demonstrated age ≤55 years (Odds Ratio (OR) = 7.38; 95% Confidence Interval (CI) = 1.59 – 34.31; p = 0.0108), tumor bilaterality (OR = 3.01; 95% CI = 1.01 – 9.21; p = 0.0483), lymphovascular invasion (OR = 2.92; 95% CI = 1.18 – 7.23; p = 0.0206) and BRAF mutation (OR = 3.24; 95% CI = 1.41 – 7.49; p = 0.0058) were independent predictors of CLNM in adult PTC. Furthermore, patients who underwent PCLND showed significant association with improved recurrence-free survival (RFS; p = 0.0379). Multivariate analysis demonstrated that PCLND was an independent predictor of improved recurrence-free survival.

Conclusions

cN0 Middle Eastern PTC patients treated with PCLND showed a significantly better prognosis. PCLND was effective in improving RFS in Middle Eastern PTC patients and should be encouraged for patients with potential risk factors for CLNM.
Congenital Short-Bowel Syndrome Is Associated With a Novel Deletion Mutation in the CLMP Gene: Mutations in CLMP Caused CSBS
Authors: Ou Fen-fen , Li Ming-jie , Mei Li-bin , Lin Xin-Zhu , Wu Yan-an
Published: January 2022

Objective: To describe the clinical presentation and novel mutation in the coxsackie and adenovirus receptor-like membrane protein (CLMP) gene in a Chinese family with congenital short bowel syndrome (CSBS).

Methods: We collected clinical data from a Chinese family with inherited CSBS, and performed whole exon sequencing of the children and their parents. The pathogenic sites of candidate genes were targeted, and the detected exon deletions were verified by quantitative PCR.

Results: Two siblings in this family presented with bilious vomiting, and were diagnosed with CSBS on laparotomy. Two siblings and their parents underwent complete exome sequencing of the peripheral blood. Both children had CLMP gene exons 3–5 homozygous deletion mutation, while the parents had a heterozygous mutation.

Conclusion: This study identified a novel mutation of the CLMP gene in a Chinese family with CSBS. Identification of this mutation can help with genetic counseling and prenatal diagnosis of CSBS.
Study Protocol for Preventing Early-Onset Pneumonia in Young Children Through Maternal Immunisation: A Multi-Centre Randomised Controlled Trial (PneuMatters)
Authors: Chang Anne B. , Toombs Maree , Chatfield Mark D. , Mitchell Remai , Fong Siew M. , Binks Michael J. , Smith-Vaughan Heidi , Pizzutto Susan J. , Lust Karin , Morris Peter S. , Marchant Julie M. , Yerkovich Stephanie T. , O'Farrell Hannah , Torzillo Paul J. , Maclennan Carolyn , Simon David , Unger Holger W. , Ellepola Hasthika , Odendahl Jens , Marshall Helen S. , Swamy Geeta K. , Grimwood Keith
Published: January 2022

Background: Preventing and/or reducing acute lower respiratory infections (ALRIs) in young children will lead to substantial short and long-term clinical benefits. While immunisation with pneumococcal conjugate vaccines (PCV) reduces paediatric ALRIs, its efficacy for reducing infant ALRIs following maternal immunisation has not been studied. Compared to other PCVs, the 10-valent pneumococcal-Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) is unique as it includes target antigens from two common lower airway pathogens, pneumococcal capsular polysaccharides and protein D, which is a conserved H. influenzae outer membrane lipoprotein.

Aims: The primary aim of this randomised controlled trial (RCT) is to determine whether vaccinating pregnant women with PHiD-CV (compared to controls) reduces ALRIs in their infants' first year of life. Our secondary aims are to evaluate the impact of maternal PHiD-CV vaccination on different ALRI definitions and, in a subgroup, the infants' nasopharyngeal carriage of pneumococci and H. influenzae, and their immune responses to pneumococcal vaccine type serotypes and protein D.

Methods: We are undertaking a parallel, multicentre, superiority RCT (1:1 allocation) at four sites across two countries (Australia, Malaysia). Healthy pregnant Australian First Nation or Malaysian women aged 17–40 years with singleton pregnancies between 27+6 and 34+6 weeks gestation are randomly assigned to receive either a single dose of PHiD-CV or usual care. Treatment allocation is concealed. Study outcome assessors are blinded to treatment arms. Our primary outcome is the rate of medically attended ALRIs by 12-months of age. Blood and nasopharyngeal swabs are collected from infants at birth, and at ages 6- and 12-months (in a subset). Our planned sample size (n = 292) provides 88% power (includes 10% anticipated loss to follow-up).

Discussion: Results from this RCT potentially leads to prevention of early and recurrent ALRIs and thus preservation of lung health during the infant's vulnerable period when lung growth is maximum. The multicentre nature of our study increases the generalisability of its future findings and is complemented by assessing the microbiological and immunological outcomes in a subset of infants.

Clinical Trial Registration:https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374381, identifier: ACTRN12618000150246.
Renal Protective Effects of Inonotus obliquus on High-Fat Diet/Streptozotocin-Induced Diabetic Kidney Disease Rats: Biochemical, Color Doppler Ultrasound and Histopathological Evidence
Authors: Zhang Yan , Liao Hui , Shen Dayue , Zhang Xilan , Wang Jufang , Zhang Xiaohong , Wang Xiaocheng , Li Rongshan
Published: January 2022

Diabetic kidney disease (DKD) is the current leading cause of end-stage renal disease. Inonotus obliquus (chaga), a medicinal fungus, has been used in treatment of diabetes. Here, we aim to identify the renal protective effects of chaga extracts on a DKD rat model which was induced by a high-fat diet and streptozotocin injection. During the total 17-weeks experiment, the biological parameters of serum and urine were examined, and the color Doppler ultrasound of renal artery, the periodic acid-Schiff staining, and electron microscopy of kidney tissue were performed. The compositions of chaga extracts were analyzed and the intervention effects of the extracts were also observed. Compared with the normal control group, the biochemical research showed that insulin resistance was developed, blood glucose and total cholesterol were elevated, urinary protein excretion and serum creatinine levels were significantly increased in the DKD model. The ultrasound examinations confirmed the deteriorated blood flow parameters of the left renal interlobar artery in the rat models. Finally, histopathological data supported renal injury on the thickened glomerular basement membrane and fusion of the foot processes. 8 weeks intervention of chaga improved the above changes significantly, and the 100 mg/kg/d chaga group experienced significant effects compared with the 50 mg/kg/d in some parameters. Our findings suggested that Doppler ultrasound examinations guided with biochemical indicators played important roles in evaluating the renal injury as an effective, noninvasive, and repeatable method in rats. Based on biochemical, ultrasound, and histopathological evidence, we confirmed that chaga had pharmacodynamic effects on diabetes-induced kidney injury and the aforementioned effects may be related to delaying the progression of DKD.
A Nitrobenzoyl Sesquiterpenoid Insulicolide A Prevents Osteoclast Formation via Suppressing c-Fos-NFATc1 Signaling Pathway
Authors: Tan Yanhui , Ke Minhong , Li Zhichao , Chen Yan , Zheng Jiehuang , Wang Yiyuan , Zhou Xuefeng , Huang Gang , Li Xiaojuan
Published: January 2022

It is a viable strategy to inhibit osteoclast differentiation for the treatment of osteolytic diseases such as osteoporosis, rheumatoid arthritis and tumor bone metastases. Here we assessed the effects of insulicolide A, a natural nitrobenzoyl sesquiterpenoid derived from marine fungus, on receptor activator of nuclear factor-κB ligand (RANKL)-stimulated osteoclastogenesis in vitro and its protective effects on LPS-induced osteolysis mice model in vivo. The results demonstrated that insulicolide A inhibited osteoclastogenesis from 1 μM in vitro. Insulicolide A could prevent c-Fos and nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) nuclear translocation and attenuate the expression levels of osteoclast-related genes and DC-STAMP during RANKL-stimulated osteoclastogenesis but have no effects on NF-κB and MAPKs. Insulicolide A can also protect the mice from LPS-induced osteolysis. Our research provides the first evidence that insulicolide A may inhibit osteoclastogenesis both in vitro and in vivo, and indicates that it may have potential for the treatment of osteoclast-related diseases.
Activation of Autophagy Through the NLRP3/mTOR Pathway: A Potential Mechanism for Alleviation of Pneumonia by QingFei Yin
Authors: Sun Xiaozhou , Wang Dandan , Ding Lizhong , Xu Yan , Qi Wenxiu , Zhao Daqing , Liu Li , Yin Chengcheng , Cui Changsheng , Wang Zhongtian , Sun Liwei , Sun Liping
Published: January 2022

QingFei Yin (QFY), a Chinese traditional medicine recipe, is known for its excellent therapeutic pharmacological effects for the treatment of bacterial lung infections, although its molecular mechanism of action remains unknown. Here, QFY chemical composition was determined using a High-Performance Liquid Chromatography-Mass (HPLC-MS/MS)-based method then QFY was evaluated for protective pharmacological effects against pneumonia using two models: a Streptococcus pneumoniae-induced in vivo mouse model and an in vitro pneumolysin (PLY)-induced murine lung alveolar-derived MH-S cell line-based model. Notably, QFY exerted prominent anti-pneumonia effects both in vivo and in vitro. To further explore QFY protective effects, 4D label-free proteomics analysis, pathologic evaluation, and immunohistochemical (IHC) analysis were conducted to identify cellular pathways involved in QFY protection. Notably, our results indicated that NF-κB/NLRP3 and autophagy pathways may contribute to pharmacological effects associated with QFY-based protection. Briefly, QFY triggered autophagy via down-regulation of upstream NLRP3/mTOR signaling pathway events, resulting in the amelioration of inflammatory injury. Collectively, our results revealed molecular mechanisms underlying QFY protection against pneumonia as a foundation for the future development of novel treatments to combat this disease and reduce antibiotic abuse.
Inhibition of the Aquaporin-1 Cation Conductance by Selected Furan Compounds Reduces Red Blood Cell Sickling
Authors: Chow Pak Hin , Cox Charles D. , Pei Jinxin V. , Anabaraonye Nancy , Nourmohammadi Saeed , Henderson Sam W. , Martinac Boris , Abdulmalik Osheiza , Yool Andrea J.
Published: January 2022

In sickle cell disease (SCD), the pathological shift of red blood cells (RBCs) into distorted morphologies under hypoxic conditions follows activation of a cationic leak current (Psickle) and cell dehydration. Prior work showed sickling was reduced by 5-hydroxylmethyl-2-furfural (5-HMF), which stabilized mutant hemoglobin and also blocked the Psickle current in RBCs, though the molecular basis of this 5-HMF-sensitive cation current remained a mystery. Work here is the first to test the hypothesis that Aquaporin-1 (AQP1) cation channels contribute to the monovalent component of Psickle. Human AQP1 channels expressed in Xenopus oocytes were evaluated for sensitivity to 5-HMF and four derivatives known to have differential efficacies in preventing RBC sickling. Ion conductances were measured by two-electrode voltage clamp, and osmotic water permeability by optical swelling assays. Compounds tested were: 5-HMF; 5-PMFC (5-(phenoxymethyl)furan-2-carbaldehyde); 5-CMFC (5-(4-chlorophenoxymethyl)furan-2-carbaldehyde); 5-NMFC (5-(2-nitrophenoxymethyl)-furan-2-carbaldehyde); and VZHE006 (tert-butyl (5-formylfuran-2-yl)methyl carbonate). The most effective anti-sickling agent, 5-PMFC, was the most potent inhibitor of the AQP1 ion conductance (98% block at 100 µM). The order of sensitivity of the AQP1 conductance to inhibition was 5-PMFC > VZHE006 > 5-CMFC ≥ 5-NMFC, which corresponded with effectiveness in protecting RBCs from sickling. None of the compounds altered AQP1 water channel activity. Combined application of a selective AQP1 ion channel blocker AqB011 (80 µM) with a selective hemoglobin modifying agent 5-NMFC (2.5 mM) increased anti-sickling effectiveness in red blood cells from human SCD patients. Another non-selective cation channel known to be expressed in RBCs, Piezo1, was unaffected by 2 mM 5-HMF. Results suggest that inhibition of AQP1 ion channels and capacity to modify hemoglobin are combined features of the most effective anti-sickling agents. Future therapeutics aimed at both targets could hold promise for improved treatments for SCD.
Anlotinib Reverses Multidrug Resistance (MDR) in Osteosarcoma by Inhibiting P-Glycoprotein (PGP1) Function In Vitro and In Vivo
Authors: Wang Gangyang , Cao Lingling , Jiang Yafei , Zhang Tao , Wang Hongsheng , Wang Zhuoying , Xu Jing , Mao Min , Hua Yingqi , Cai Zhengdong , Ma Xiaojun , Hu Shuo , Zhou Chenghao
Published: January 2022

Overexpression of the multidrug resistance (MDR)-related protein P-glycoprotein (PGP1), which actively extrudes chemotherapeutic agents from cells and significantly decreases the efficacy of chemotherapy, is viewed as a major obstacle in osteosarcoma chemotherapy. Anlotinib, a novel tyrosine kinase inhibitor (TKI), has good anti-tumor effects in a variety of solid tumors. However, there are few studies on the mechanism of anlotinib reversing chemotherapy resistance in osteosarcoma. In this study, cellular assays were performed in vitro and in vivo to evaluate the MDR reversal effects of anlotinib on multidrug-resistant osteosarcoma cell lines. Drug efflux and intracellular drug accumulation were measured by flow cytometry. The vanadate-sensitive ATPase activity of PGP1 was measured in the presence of a range of anlotinib concentrations. The protein expression level of ABCB1 was detected by Western blotting and immunofluorescence analysis. Our results showed that anlotinib significantly increased the sensitivity of KHOSR2 and U2OSR2 cells (which overexpress PGP1) to chemotherapeutic agents in vitro and in a KHOSR2 xenograft nude mouse model in vivo. Mechanistically, anlotinib increases the intracellular accumulation of PGP1 substrates by inhibiting the efflux function of PGP1 in multidrug-resistant cell lines. Furthermore, anlotinib stimulated the ATPase activity of PGP1 but affected neither the protein expression level nor the localization of PGP1. In animal studies, anlotinib in combination with doxorubicin (DOX) significantly decreased the tumor growth rate and the tumor size in the KHOSR2 xenograft nude mouse model. Overall, our findings suggest that anlotinib may be useful for circumventing MDR to other conventional antineoplastic drugs.
Cancer Stem Cells in Intrahepatic Cholangiocarcinoma; Their Molecular Basis, and Therapeutic Implications
Authors: Tamai Keiichi , Fujimori Haruna , Mochizuki Mai , Satoh Kennichi
Published: January 2022

Cancer tissue consists of heterogenous cell types, and cancer stem cells (CSCs) are a subpopulation of the tissue which possess therapy resistance, tumor reconstruction capability, and are responsible for metastasis. Intrahepatic cholangiocarcinoma (iCCA) is one of the most common type of liver cancer that is highly aggressive with poor prognosis. Since no target therapy is efficient in improving patient outcomes, new therapeutic approaches need to be developed. CSC is thought to be a promising therapeutic target because of its resistance to therapy. Accumulating evidences suggests that there are many factors (surface marker, stemness-related genes, etc.) and mechanisms (epithelial-mesenchymal transition, mitochondria activity, etc.) which are linked to CSC-like phenotypes. Nevertheless, limited studies are reported about the application of therapy using these mechanisms, suggesting that more precise understandings are still needed. In this review, we overview the molecular mechanisms which modulate CSC-like phenotypes, and discuss the future perspective for targeting CSC in iCCA.
Association Mapping for Yield Attributing Traits and Yellow Mosaic Disease Resistance in Mung Bean [Vigna radiata (L.) Wilczek]
Authors: Rohilla Versha , Yadav Rajesh Kumar , Poonia Atman , Sheoran Ravika , Kumari Gita , Shanmugavadivel P. S. , Pratap Aditya
Published: January 2022

Mung bean [Vigna radiata(L.) Wilczek] is an important short-duration grain legume widely known for its nutritional, soil ameliorative, and cropping system intensification properties. This study aims at evaluating genetic diversity among mung bean genotypes and detecting genomic regions associated with various yield attributing traits and yellow mosaic disease (YMD) resistance by association mapping. A panel of 80 cultivars and advanced breeding lines was evaluated for 10 yield-related and YMD resistance traits duringkharif(monsoon) and summer seasons of 2018–2019 and 2019–2020. A total of 164 genome-wide simple sequence repeat (SSR) markers were initially screened, out of which 89 were found polymorphic which generated 317 polymorphic alleles with an average of 3.56 alleles per SSR locus. The number of alleles at each locus varied from 2 to 7. The population genetic structure analysis grouped different genotypes in three major clusters and three genetically distinct subpopulations (SPs) (i.e., SP-1, SP-2, and SP-3) with one admixture subpopulation (SP-4). Both cluster and population genetic structure analysis categorized the advanced mung bean genotypes in a single group/SP and the released varieties in other groups/SPs, suggesting that the studied genotypes may have common ancestral history at some level. The population genetic structure was also in agreement with the genetic diversity analysis. The estimate of the average degree of linkage disequilibrium (LD) present at the genome level in 80 mung bean genotypes unveiled significant LD blocks. Over the four seasons, 10 marker-trait associations were observed significant for YMD and four seed yield (SY)-related traitsviz., days to flowering, days to maturity, plant height, and number of pods per plant using the mixed linear model (MLM) method. These associations may be useful for marker-assisted mung bean yield improvement programs and YMD resistance.
Differential Maize Yield Hybrid Responses to Stand Density Are Correlated to Their Response to Radiation Reductions Around Flowering
Authors: Larrosa Federico H. , Borrás Lucas
Published: January 2022

Altered stand density affects maize yields by producing changes in both numerical yield components, kernel number per plant (KNP), and kernel weight (KW). Kernel number is determined by the accumulation of ear biomass during the flowering period, whereas KW is determined by the sink potential established during flowering and the capacity of the plant to fulfill this potential during effective grain filling. Here, we tested if different short shading treatments during different stages around flowering can help discriminate genotypic differences in eco-physiological parameters relevant for maize stand density yield response and associated yield components. Our specific objectives were to: (i) identify hybrids with differential shading stress response, (ii) explore shading effects over eco-physiological parameters mechanistically related to KNP and KW, and (iii) test if shading stress can be used for detecting differential genotypic yield responses to stand density. The objectives were tested using four commercial maize hybrids. Results indicated that KNP was the yield component most related to yield changes across the different shading treatments, and that the specific shading imposed soon after anthesis generated the highest yield reductions. Hybrids less sensitive to shading stress were those that reduced their plant growth rate the least and the ones that accumulated more ear biomass during flowering. Genotype susceptibility to shading stress around flowering was correlated to stand density responses. This indicated that specific shading stress treatments are a useful tool to phenotype for differential stand density responses of commercial hybrids.
Using Convolutional Neural Networks to Efficiently Extract Immense Phenological Data From Community Science Images
Authors: Reeb Rachel A. , Aziz Naeem , Lapp Samuel M. , Kitzes Justin , Heberling J. Mason , Kuebbing Sara E.
Published: January 2022

Community science image libraries offer a massive, but largely untapped, source of observational data for phenological research. The iNaturalist platform offers a particularly rich archive, containing more than 49 million verifiable, georeferenced, open access images, encompassing seven continents and over 278,000 species. A critical limitation preventing scientists from taking full advantage of this rich data source is labor. Each image must be manually inspected and categorized by phenophase, which is both time-intensive and costly. Consequently, researchers may only be able to use a subset of the total number of images available in the database. While iNaturalist has the potential to yield enough data for high-resolution and spatially extensive studies, it requires more efficient tools for phenological data extraction. A promising solution is automation of the image annotation process using deep learning. Recent innovations in deep learning have made these open-source tools accessible to a general research audience. However, it is unknown whether deep learning tools can accurately and efficiently annotate phenophases in community science images. Here, we train a convolutional neural network (CNN) to annotate images of Alliaria petiolata into distinct phenophases from iNaturalist and compare the performance of the model with non-expert human annotators. We demonstrate that researchers can successfully employ deep learning techniques to extract phenological information from community science images. A CNN classified two-stage phenology (flowering and non-flowering) with 95.9% accuracy and classified four-stage phenology (vegetative, budding, flowering, and fruiting) with 86.4% accuracy. The overall accuracy of the CNN did not differ from humans (p = 0.383), although performance varied across phenophases. We found that a primary challenge of using deep learning for image annotation was not related to the model itself, but instead in the quality of the community science images. Up to 4% of A. petiolata images in iNaturalist were taken from an improper distance, were physically manipulated, or were digitally altered, which limited both human and machine annotators in accurately classifying phenology. Thus, we provide a list of photography guidelines that could be included in community science platforms to inform community scientists in the best practices for creating images that facilitate phenological analysis.
Evolution and Stress Responses of CLO Genes and Potential Function of the GhCLO06 Gene in Salt Resistance of Cotton
Authors: Fu Xiaokang , Yang Yonglin , Kang Meng , Wei Hengling , Lian Boying , Wang Baoquan , Ma Liang , Hao Pengbo , Lu Jianhua , Yu Shuxun , Wang Hantao
Published: January 2022

The caleosin (CLO) protein family displays calcium-binding properties and plays an important role in the abiotic stress response. Here, a total of 107 CLO genes were identified in 15 plant species, while no CLO genes were detected in two green algal species. Evolutionary analysis revealed that the CLO gene family may have evolved mainly in terrestrial plants and that biological functional differentiation between species and functional expansion within species have occurred. Of these, 56 CLO genes were identified in four cotton species. Collinearity analysis showed that CLO gene family expansion mainly occurred through segmental duplication and whole-genome duplication in cotton. Sequence alignment and phylogenetic analysis showed that the CLO proteins of the four cotton species were mainly divided into two types: H-caleosins (class I) and L-caleosins (class II). Cis-acting element analysis and quantitative RT–PCR (qRT–PCR) suggested that GhCLOs might be regulated by abscisic acid (ABA) and methyl jasmonate (MeJA). Moreover, transcriptome data and qRT–PCR results revealed that GhCLO genes responded to salt and drought stresses. Under salt stress, gene-silenced plants (TRV: GhCLO06) showed obvious yellowing and wilting, higher malondialdehyde (MDA) content accumulation, and significantly lower activities of superoxide dismutase (SOD) and peroxidase (POD), indicating that GhCLO06 plays a positive regulatory role in cotton salt tolerance. In gene-silenced plants (TRV: GhCLO06), ABA-related genes (GhABF2, GhABI5, and GhNAC4) were significantly upregulated after salt stress, suggesting that the regulation of salt tolerance may be related to the ABA signaling pathway. This research provides an important reference for further understanding and analyzing the molecular regulatory mechanism of CLOs for salt tolerance.
Application of an Ovate Leaf Shape Model to Evaluate Leaf Bilateral Asymmetry and Calculate Lamina Centroid Location
Authors: Li Yirong , Zheng Yiwen , Ratkowsky David A. , Wei Hailin , Shi Peijian
Published: January 2022

Leaf shape is an important leaf trait, with ovate leaves common in many floras. Recently, a new leaf shape model (referred to as the MLRF equation) derived from temperature-dependent bacterial growth was proposed and demonstrated to be valid in describing leaf boundaries of many species with ovate leaf shape. The MLRF model’s parameters can provide valuable information of leaf shape, including the ratio of lamina width to length and the lamina centroid location on the lamina length axis. However, the model wasn’t tested on a large sample of a single species, thereby limiting its overall evaluation for describing leaf boundaries, for evaluating lamina bilateral asymmetry and for calculating lamina centroid location. In this study, we further test the model using data from two Lauraceae species,Cinnamomum camphoraandMachilus leptophylla, with >290 leaves for each species. The equation was found to be credible for describing those shapes, with all adjusted root-mean-square errors (RMSE) smaller than 0.05, indicating that the mean absolute deviation is smaller than 5% of the radius of an assumed circle whose area equals lamina area. It was also found that the larger the extent of lamina asymmetry, the larger the adjusted RMSE, with approximately 50% of unexplained variation by the model accounted for by the lamina asymmetry, implying that this model can help to quantify the leaf bilateral asymmetry in future studies. In addition, there was a significant difference between the two species in their centroid ratio, i.e., the distance from leaf petiole to the point on the lamina length axis associated with leaf maximum width to the leaf maximum length. It was found that a higher centroid ratio does not necessarily lead to a greater investment of mass to leaf petiole relative to lamina, which might depend on the petiole pattern.
Feedback and Trigger of Household Decision-Making to Ecological Protection Policies in Sanjiangyuan National Park
Authors: Su Xukun , Shen Yu , Dong Shikui , Liu Yuqing , Cheng Hao , Wan Lingfan , Liu Guohua
Published: January 2022

Ignoring the responses of local households to ecological protection policies can not only seriously limit sustainable development of the alpine grassland ecosystem, but also not improve livelihood on the Qinghai-Tibetan Plateau (QTP). It is of vital importance to clearly understand coupling feedback and trigger between household decision-making of local herdsmen with the implementation of ecological protection policies. We selected Sanjiangyuan National Park (SNP) as the study area which was in the hinterland of the QTP and the first national park in China. We used the global rangeland (G-Range) model to simulate alpine grassland changes and DEcisions under Conditions of Uncertainty by Modeled Agents (DECUMA) model to identify household decision-making of local herdsmen. Results showed that: (1) distribution of livestock density was basically consistent with the distribution of habitat suitability of local households in the SNP; (2) more than half of the uneducated households (52 and 70%) opposed the eco-compensation and eco-migration policies; (3) most of the households (53.7%) never traded livestock for maintaining their livelihood; and (4) When local households owed 65,000 yuan (≈10,000 dollars) in debts, as the critical value (trigger), they traded livestock to support their livelihood. We suggest that feedback and trigger of household decision-making should be fully considered by managers of national park and policymakers of local governments in planning ecological protection policies to maintain sustainable development of alpine grassland, which is of practical significance to long-term conservation and sustainable utilization of natural resources in the SNP.
Impact of Social Cognition on the Self-Rated Health of the Elderly and Its Mechanisms: Evidence From China’s Comprehensive Social Survey
Authors: Liu Yuan , Hu Yuqun , Nan Yan
Published: January 2022

Whether and how the differentiated social cognition of the elderly affects their self-rated health has not been deeply discussed. Based on social cognition theory and Chinese situation, this study constructs the social cognitive dimension of Chinese elderly including social attitude, class identity and perception of social relations. Using the data from Chinese General Social Survey in 2017, this study screens out 1,728 elderly people aged 60 and over, and discusses the impact mechanism of social cognition on self-rated health of Chinese elderly people aged 60 and over by the construction of structural equation model and mediation effect test method. The results show that social attitude, class identity and perceptions of social relationships have significantly positive effects on the self-rated health levels of elderly individuals. Among them, the path coefficient of social attitude to self-rated health was 0.049, the path coefficient of class identity to self-rated health was 0.171, and the path coefficient of social relationship perception to self-rated health was 0.248; both class identity and perception of social relationship have significant mediating effects on elderly self-rated health through social engagement. This study shows that social cognition rarely studied in existing literature has significant effects on the self-rated health of older adults, providing fruitful insights for enhancing the self-rated health level of elderly individuals.
From Something Old to Something New: Functionalist Lessons for the Cognitive Science of Scientific Creativity
Authors: Sanches de Oliveira Guilherme
Published: January 2022

An intuitive view is that creativity involves bringing together what is already known and familiar in a way that produces something new. In cognitive science, this intuition is typically formalized in terms of computational processes that combine or associate internally represented information. From this computationalist perspective, it is hard to imagine how non-representational approaches in embodied cognitive science could shed light on creativity, especially when it comes to abstract conceptual reasoning of the kind scientists so often engage in. The present article offers an entry point to addressing this challenge. The scientific project of embodied cognitive science is a continuation of work in the functionalist tradition in psychology developed over a century ago by William James and John Dewey, among others. The focus here is on how functionalist views on the nature ofmind, thought, andexperienceoffer an alternative starting point for cognitive science in general, and for the cognitive science of scientific creativity in particular. The result may seem paradoxical. On the one hand, the article claims that the functionalist conceptual framework motivates rejecting mainstream cognitive views of creativity as the combination or association of ideas. On the other hand, however, the strategy adopted here—namely, revisiting ideas from functionalist psychology to inform current scientific theorizing—can itself be described as a process of arriving at new, creative ideas from combinations of old ones. As is shown here, a proper understanding of cognition in light of the functionalist tradition resolves the seeming tension between these two claims.
Customer Concentration, Managerial Ability, and Corporate Performance
Authors: Jin Guanghui , Jiang Qingjuan , Liu Xiaolin
Published: January 2022

We examined whether and how managerial ability affects the relationship between customer concentration and corporate performance. Based on a novel measure of managerial ability, we found that customer concentration has a significant negative effect on corporate performance, while managerial ability can mitigate this effect. The negative effect of customer concentration is only significant in the subsample of low ability and lower efficiency in asset utilization, while the moderating effect of managerial ability is significant for all levels of asset utilization efficiency and more significant for firms with a lower gross margin. The results are robust to numerous robustness tests and endogeneity concerns. Additional analysis of mechanisms shows that in addition to superior operating ability, competent managers select major customers who are more beneficial to their company and decrease the sensitivity of their research and development (R&D) investment to customers. These findings indicate that the heterogeneity of managerial ability plays an important role in the supplier–customer context when the supplier firm generally faces one or more concentrated customers.
The Impact of the COVID-19 Pandemic on Affect, Fear, and Personality of Primary School Children Measured During the Second Wave of Infections in 2020
Authors: Matiz Alessio , Fabbro Franco , Paschetto Andrea , Urgesi Cosimo , Ciucci Enrica , Baroncelli Andrea , Crescentini Cristiano
Published: January 2022

In relation to the COVID-19 pandemic outbreak, a large body of research has identified a negative impact on individuals' affectivity, frequently documented by increased prevalence of anxiety and depression symptoms. For children, this research was less extensive, was mainly based on caregivers' reports and neglected personality assessment. In order to measure the impact of the pandemic, and the fears it caused, on primary school children's affect and personality, 323 (180 boys and 143 girls) Italian third, fourth and fifth graders were assessed between October and November 2020, namely during the second wave of COVID-19 infections in Italy, with validated self-reports of affect (Positive and Negative Affect Scale for Children, PANAS-C), fear of COVID-19 (Fear of COVID-19 Scale, FCV-19S) and personality (junior Temperament and Character Inventory, jTCI). In comparison with PANAS-C and jTCI normative scores collected prior to the pandemic, data obtained from children in 2020 showed unchanged affect scores in the overall sample, a decrease of Positive Affect in girls, and a decrease in the Harm Avoidance and an increase in the Self-Transcendence scales of personality. Fear of COVID-19 scores were positively correlated with Negative Affect scores and negatively predicted by children's personality profile of resilience (calculated using scores on the Harm Avoidance and the Self-Directedness scales of personality). These results suggested that Italian primary school children, especially boys, maintained their pre-pandemic levels of affect (or restored them after the first COVID-19 wave) and partially diverged from the typical development of personality in an apparently positive sense, namely toward more courageous/optimistic and spiritual profiles. This sort of children's post-traumatic growth might also be attributed to children's family and education systems, which should continue to be supported to promote and maintain community mental health.
Intranasal Oxytocin for Stimulant Use Disorder Among Male Veterans Enrolled in an Opioid Treatment Program: A Randomized Controlled Trial
Authors: Stauffer Christopher S. , Samson Salem , Hickok Alex , Hoffman William F. , Batki Steven L.
Published: January 2022

The increasing prevalence of illicit stimulant use among those in opioid treatment programs poses a significant risk to public health, stimulant users have the lowest rate of retention and poorest outcomes among those in addiction treatment, and current treatment options are limited. Oxytocin administration has shown promise in reducing addiction-related behavior and enhancing salience to social cues. We conducted a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin administered twice daily for 6 weeks to male Veterans with stimulant use disorder who were also receiving opioid agonist therapy and counseling (n = 42). There was no significant effect of oxytocin on stimulant use, stimulant craving, or therapeutic alliance over 6 weeks. However, participants receiving oxytocin (vs. placebo) attended significantly more daily opioid agonist therapy dispensing visits. This replicated previous work suggesting that oxytocin may enhance treatment engagement among individuals with stimulant and opioid use disorders, which would address a significant barrier to effective care.
The Experience of Insomnia in Patients With Schizophrenic Disorder: A Qualitative Study
Authors: Batalla-Martín David , Martorell-Poveda Maria-Antonia , Belzunegui-Eraso Angel , Miralles Garijo Eva , Del-Cuerpo Serratosa Ana , Valdearcos Pérez JuanCarlos , Montané Escobar Miquel , Lopez-Ruiz Marina
Published: January 2022

Background

Insomnia is a health problem that particularly affects people with schizophrenia. Its repercussions go beyond the disorder itself and affect many areas of life. The aim of the present study is to explore the clinical symptoms and consequences of insomnia in patients diagnosed with schizophrenic disorder and the perceptions of these patients regarding the care they receive.

Methods

The study takes a qualitative approach and uses semi-structured interviews to conduct a descriptive and interpretive analysis of 3 clinically different clusters of patients. These 3 clusters have been defined by using two-step cluster analysis based on the results of the ISI (Insomnia Severity Index) and EQ-5D scales (EuroQol-5D) and the presence of certain diagnostic symptoms in a sample of 170 patients. The final sample was 31 subjects. The analysis was based on a hermeneutic analysis of the patients' narratives regarding their experiences of insomnia.

Results

The patients' narratives show differences in the intensity and experience of insomnia depending on the severity, as well as its impact on their quality of life. Insomnia has a huge emotional impact. Participants describe ruminations and obsessive thoughts as a key factor hindering falling asleep. Some of the everyday actions they perform encourage the chronicity of insomnia. The desired health response must include interventions that are effective, such as cognitive-behavioural therapy, and powerful, such as pharmacological solutions. Psychoeducation and advice on sleep hygiene are highly valued tools as preventive strategies.

Conclusions

To know the experience of users gives us a more comprehensive understanding of insomnia complexities and brings some new intervention strategies in patients with mental disorders. It is important that health professionals intervene preventively to stop the disorder from becoming chronic.