bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated With the Presence of Tuberculous Empyema in Children With Pleural Tuberculosis
Authors: Wu Yan-Hua , Wang Jun-Li , Wang Mao-Shui
Published: October 2021

Background:Until now, the factor of tuberculous empyema (TE) in children with pleural tuberculosis (TB) remains unclear. Therefore, a retrospective study was conducted to assess the factors associated with the presence of TE in children.

Methods:Between January 2006 and December 2019, consecutive children patients (≤ 15 years old) with suspected pleural TB were selected for further analysis. Empyema was defined as grossly purulent pleural fluid. The demographic, clinical, laboratory, and radiographic features were collected from the electrical medical records retrospectively. Univariate and multivariate logistic regressions were used to explore the factors associated with the presence of TE in children with pleural TB.

Results:A total of 154 children with pleural TB (definite, 123 cases; possible, 31 cases) were included in our study and then were classified as TE (n= 27) and Non-TE (n= 127) groups. Multivariate analysis revealed that surgical treatment (age- and sex-adjusted OR = 92.0, 95% CI: 11.7, 721.3), cavity (age- and sex-adjusted OR = 39.2, 95% CI: 3.2, 476.3), pleural LDH (>941 U/L, age- and sex-adjusted OR = 14.8, 95% CI: 2.4, 90.4), and temperature (>37.2°C, age- and sex-adjusted OR = 0.08, 95% CI: 0.01, 0.53) were associated with the presence of TE in children with pleural TB.

Conclusion:Early detection of the presence of TE in children remains a challenge and several characteristics, such as surgical treatment, lung cavitation, high pleural LDH level, and low temperature, were identified as factors of the presence of TE in children with pleural TB. These findings may improve the management of childhood TE.
Therapeutic Potential of CUDC-907 (Fimepinostat) for Hepatocarcinoma Treatment Revealed by Tumor Spheroids-Based Drug Screening
Authors: Liao Wei , Yang Wanren , Xu Jiecheng , Yan Zhengming , Pan Mingxin , Xu Xiaoping , Zhou Shuqin , Zhu Yu , Lan Jianqiang , Zeng Min , Han Xu , Li Shao , Li Yang , Liang Kangyan , Gao Yi , Peng Qing
Published: October 2021

Background: Cancer is the second leading cause of death globally. However, most of the new anti-cancer agents screened by traditional drug screening methods fail in the clinic because of lack of efficacy. Choosing an appropriate in vitro tumor model is crucial for preclinical drug screening. In this study, we screened anti-hepatocarcinoma (HCC) drugs using a novel spheroid cell culture device.

Methods: Four HCC cell lines were three-dimensionally (3D) cultured to screen 19 small molecular agents. 3D-cultured primary HCC cells and a tumor-bearing mouse model were used to verify the candidate anti-hepatocarcinoma agent. Cell function experiments and western blotting were conducted to explore the anti-hepatocarcinoma mechanism of the candidate agent.

Results: We found that CUDC-907 can serve as a potent anti-hepatocarcinoma agent. The study data show that CUDC-907 (fimepinostat), a novel dual acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC), has potent inhibitory effects on HCC cell lines and primary HCC cells in vitro, Animal studies have shown that CUDC-907 can also suppress HCC cells in vivo. Furthermore, we found that CUDC-907 inhibits the PI3K/AKT/mTOR pathway and downregulates the expression of c-Myc, leading to the suppression of HCC cells.

Conclusion: Our results suggest that CUDC-907 can be a candidate anti-HCC drug, and the 3D in vitro drug screening method based on our novel spheroid culture device is promising for future drug screening efforts.
Comparison of Primary and Secondary Prophylaxis Using PEGylated Recombinant Human Granulocyte–Stimulating Factor as a Cost-Effective Measure in Malignant Neoplasms: A Multicenter Retrospective Study
Authors: Wu Qiuji , Li Qiu , Zhang Jun , Luo Zhumei , Zhou Jin , Chen Jing , Luo Yong
Published: October 2021

Purpose: The aim of the study was to evaluate the cost-effectiveness of PEGylated recombinant human granulocyte–stimulating factor (PEG-rhG-CSF) as a means of achieving primary and secondary prophylaxis against chemotherapy-induced neutropenia cancer cases.

Methods: Individuals who underwent PEG-rhG-CSF therapeutics were monitored for 12 months, together with thorough examination of individual medical records for extracting medical care costs. Both prophylaxis-based therapeutic options (primary/secondary) were scrutinized for cost-effectiveness, using a decision-making analysis model which derived the perspective of Chinese payers. One-way and probabilistic sensitivity analyses were used to assess the robustness of the model.

Results: In summary, 130 clinical cases treated using PEG-rhG-CSF prophylaxis were included in this study: 51 within the primary prophylaxis (PP) group and 79 within the secondary prophylaxis (SP) group. Compared with SP, PP-based PEG-rhG-CSF successfully contributed to a 14.3% reduction in febrile neutropenia. In general, PP was estimated to reduce costs by $4,701.81 in comparison to SP, with a gain of 0.02 quality-adjusted life years (QALYs). Equivalent results were found in differing febrile neutropenia (FN) risk subgroups. Sensitivity analyses found the model outputs to be most affected for the average time of hospitalization and for the cost of FN.

Conclusion: From the perspective of Chinese payers, PP with PEG-rhG-CSF should be considered cost-effective compared to SP strategies in patients who received chemotherapy regimens with a middle- to high-risk of FN.
Risk of Malignancy and Tuberculosis of Biological and Targeted Drug in Patients With Spondyloarthritis: Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Man Siliang , Hu Lidong , Ji Xiaojian , Wang Yiwen , Ma Yingpei , Wang Lei , Zhu Jian , Huang Feng
Published: October 2021

Objective: Concerns exist regarding the potential development of malignancy and tuberculosis in patients with spondyloarthritis (SpA) treated with biologics. We assessed the extent to which biologic therapy may increase the risk of malignancy and tuberculosis in patients with SpA by meta-analysis to derive estimates of sparse harmful events occurring in Randomized Controlled Trials (RCTs).

Methods: A systematic literature search was conducted in PubMed, EMbase, Web of Science, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating the risk of sparse harmful events of biologic therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto OR for malignancy and tuberculosis in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using Cochrane Risk of Bias tool.

Results: In total, 63 studies were included in this meta-analysis, and 83 patients and 7 patients developed malignancy and tuberculosis, respectively. Overall, the risk of malignancy and tuberculosis was increased in SpA patients treated with biologics compared to placebo (malignancy: Peto OR: 2.49, 95%CI: 1.61–3.87, p < 0.001; tuberculosis: Peto OR: 5.98, 95%CI: 1.29–27.76, p = 0.022). Remarkably, compared to placebo, there was higher risk of malignancy for IL-17 inhibitors (Peto OR: 3.68, 95%CI: 1.20–11.30, p = 0.023) and small molecule targeted drugs (Peto OR: 3.08, 95%CI: 1.37–6.90, p = 0.043) in peripheral SpA, and for TNF receptor-Fc fusion protein in axial SpA (Peto OR: 7.18, 95%CI: 1.21–42.69, p = 0.030). Besides, the risk of tuberculosis was higher for anti-TNFα antibody in axial SpA (Peto OR: 6.17, 95%CI: 1.03–37.13, p = 0.046).

Conclusion: This meta-analysis showed an elevated risk of malignancy in patients with peripheral SpA treated with biologics, especially for IL-17 inhibitors, and small molecule targeted drugs, a slightly increased risk of malignancy in TNF receptor-Fc fusion protein in axial SpA, and increased risk of tuberculosis in patients with axial SpA treated with anti-TNFα antibody. These findings need to be validated by studies with larger population and longer follow-up.
Metabolomic Analysis Reveals the Therapeutic Effects of MBT1805, a Novel Pan-Peroxisome Proliferator-Activated Receptor Agonist, on α-Naphthylisothiocyanate-Induced Cholestasis in Mice
Authors: Wang Chang , Peng Fei , Zhong Bohua , Shi Ying , Wang Xiaomei , Jin Xueyuan , Niu Junqi
Published: October 2021

Background and Aims: Therapeutic drugs that are used to treat cholestatic liver disease are limited; however, the results of clinical trials on primary biliary cholangitis treatment targeting peroxisome proliferator-activated receptors (PPARs) are encouraging. In this study, we aimed to identify the effects of MBT1805, a novel balanced PPARα/γ/δ agonist, on cholestasis induced by α-naphthylisothiocyanate (ANIT) and elucidate the underlying mechanisms through untargeted and bile acid-targeted metabolomic analysis.

Methods: Levels of serum biochemical indicators (transaminase, aspartate transaminase, alkaline phosphatase, and total bilirubin) and liver histopathology were analyzed to evaluate the therapeutic effects of MBT1805 on ANIT-induced cholestasis in C57BL/6 mice. Untargeted and bile acid-targeted metabolomic analysis of liver tissues was performed using ultrahigh-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-MC/MC). qRT-PCR and Western blot analysis were carried out to measure the expression of key enzymes and transporters regulating bile acid synthesis, biotransformation, and transport.

Results: MBT1805 significantly improved abnormal levels of liver biochemical indicators and gallbladder enlargement induced by ANIT. Histopathological analysis showed that MBT1805 effectively relieved ANIT-induced necrosis, vacuolation, and inflammatory infiltration. Untargeted metabolomic analysis identified 27 metabolites that were involved in the primary biliary acid biosynthesis pathway. In addition, bile acid-targeted metabolomics showed that MBT1805 could alleviate the abnormal bile acid content and composition induced by ANIT. Furthermore, qRT-PCR and Western blot results confirmed that MBT1805 could effectively regulate bile acid synthesis, biotransformation, and transport which helps relieve cholestasis.

Conclusions: MBT1805 is a potential candidate drug for cholestasis, with a balanced PPARα/γ/δ activation effect.
Research Progress of the Role of Anthocyanins on Bone Regeneration
Authors: Mao Wei , Huang Guowei , Chen Huan , Xu Liangliang , Qin Shengnan , Li Aiguo
Published: October 2021

Bone regeneration in osteoporosis and fragility fractures which are highly associated with age remains a great challenge in the orthopedic field, even though the bone is subjected to a continuous process of remodeling which persists throughout lifelong. Regulation of osteoblast and osteoclast differentiation is recognized as effective therapeutic targets to accelerate bone regeneration in osteopenic conditions. Anthocyanins (ACNs), a class of naturally occurring compounds obtained from colored plants, have received increasing attention recently because of their well-documented biological effects, such as antioxidant, anti-inflammation, and anti-apoptosis in chronic diseases, like osteoporosis. Here, we summarized the detailed research progress on ACNs on bone regeneration and their molecular mechanisms on promoting osteoblast differentiation as well as inhibiting osteoclast formation and differentiation to explore their promising therapeutic application in repressing bone loss and helping fragility fracture healing. Better understanding the role and mechanisms of ACNs on bone regeneration is helpful for the prevention or treatment of osteoporosis and also for the exploration of new bone regenerative medicine.
Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation
Authors: Xiang Yu , Chen Xiaying , Wang Wengang , Zhai Lijuan , Sun Xueni , Feng Jiao , Duan Ting , Zhang Mingming , Pan Ting , Yan Lili , Jin Ting , Gao Quan , Wen Chengyong , Ma Weirui , Liu Wencheng , Wang Deqiang , Wu Qibiao , Xie Tian , Sui Xinbing
Published: October 2021

Erianin, a natural product derived from Dendrobium chrysotoxum Lindl, has been proved to play antitumor activity in various cancers. However, the effects and molecular mechanisms of erianin in bladder cancer cells remain unexplored. In this study, we found that erianin triggered cell death and cell cycle arrest in bladder cancer cells. Then we demonstrated that erianin could promote the accumulation of lethal lipid-based reactive oxygen species (ROS) and the depletion of glutathione (GSH), suggesting the induction of ferroptosis. In the further study, the ferroptosis inhibitor deferoxamine (DFO), N-Acetylcysteine (NAC) and GSH but not necrostatin-1, CQ or Z-VAD-FMK rescued erianin-caused cell death, showing ferroptosis played a major role in erianin-caused cell death. In vivo, we also showed that erianin suppressed the tumor growth by inducing ferroptosis. Mechanistically, we demonstrated that nuclear factor E2-related factor 2 (NRF2) inactivation was a key determinant of ferroptosis caused by erianin. In bladder cancer cells, the compound tert-butylhydro-quinone (TBHQ), an activator of NRF2, suppressed erianin-induced ferroptosis. Whereas, NRF2 inhibition used shRNA augmented the ferroptosis response induced by erianin treatment. In conclusion, our data provide the first evidence that erianin can initiate ferroptosis-like cell death and lipid peroxidation in bladder cancer, which will hopefully become a promising anticancer compound for the treatment of bladder cancer.
The Effect of Moderate-Intensity Treadmill Exercise on Bone Mass and the Transcription of Peripheral Blood Mononuclear Cells in Ovariectomized Rats
Authors: Gao Li , Li Ye , Yang Yong-Jie , Zhang Dong-Yan
Published: October 2021

Objective: Using RNA-sequencing technology to screen the effect of moderate-intensity treadmill exercise on the sensitive genes that affect bone mass in the peripheral blood mononuclear cells (PBMCs) of ovariectomized (OVX) rats.

Methods: Three-month-old female Sprague-Dawley rats of Specific Pathogen Free (SPF) grade were randomly divided into the sham operation (SHAM) group, OVX group, and OVX combined exercise (OVX + EX) group. The OVX + EX group performed moderate-intensity treadmill exercise for 17 weeks. Then, the body composition and bone mineral density (BMD) were measured, and the bone microstructure of the femur was observed. PBMCs were collected from the abdominal aorta, and the differential genes were analyzed by transcriptome sequencing to further screen sensitive genes.

Results: (1) In the OVX group, the body weight and body fat content were significantly higher than in the SHAM group while the muscle content and BMD were significantly lower than the SHAM group. (2) The trabecular bone parameters in the OVX group were significantly lower than in the SHAM group, and they were significantly higher in the OVX + EX group than in the OVX group. When compared with the SHAM group, the microstructure of the distal femur trabecular in the OVX group was severely damaged, suggest that the morphological structure of trabecular bone is severely damaged, the number of trabecular bones is reduced, and the thickness becomes thinner, which lead to the widening of the trabecular bone space and the appearance of osteoporosis. The number and continuity of the trabecular bones were higher in the OVX + EX group than in the OVX group. (3) A Venn diagram showed that there were 58 common differential genes, and the differential genes were mainly enriched in the PI3K-Akt signaling pathway. Five sensitive genes were screened including CCL2, Nos3, Tgfb3, ITGb4, and LpL. The expression of CCL2, Nos3, and Tgfb3 genes was closely related to multiple bone parameters.

Conclusion: Moderate-intensity treadmill exercise may improve the body composition and bone mass of the OVX group by upregulating CCL2 and other genes of the PBMC. The PBMCs in the peripheral blood can be a useful tool for monitoring the effect of exercise on bone health in postmenopausal osteoporosis.
Moderate Physical Exercise Activates ATR2 Receptors, Improving Inflammation and Oxidative Stress in the Duodenum of 2K1C Hypertensive Rats
Authors: da Silva Alda Cássia Alves , Severo Juliana Soares , dos Santos Brenda Lois Barros , Mendes Pedro Henrique Moraes , Nobre Lívia Maria Soares , de Oliveira Ana Patrícia , Ferreira Francisco Cleber Silva , Medeiros Jand Venes Rolim , Lima-Junior Roberto Cesar , Havt Alexandre , Palheta-Junior Raimundo Campos , dos Santos Armênio Aguiar , Tolentino Moisés
Published: October 2021

Background: In addition to the cardiovascular and renal systems, the gastrointestinal tract also contains angiotensin ATR1a, ATR1b, and ATR2. We previously observed that the 2Kidney-1Clip hypertension model elicits physical exercise and gastrointestinal dysmotility, which is prevented by renin-angiotensin system blockers. Here, we investigate the effect of physical exercise on inflammation, stress biomarkers, and angiotensin II receptors in the duodenum of 2K1C rats.

Methods: Arterial hypertension was induced by the 2K1C surgical model. The rats were allocated in Sham, 2K1C, or 2K1C+Exercise groups. One week after surgery, they were submitted to a physical exercise protocol (running 5x/week, 60min/day). Next, we assessed their intestinal contractility, cytokine levels (TNF-α, IL-1β, and IL-6), oxidative stress levels (MPO, GSH, MDA, and SOD), and the gene expression of angiotensin receptors (ATR1A, ATR1B, and ATR2).

Results: In comparison with the Sham group, the 2K1C arterial hypertension decreased (p<0.05) the intestinal contractility. In comparison with 2K1C, the 2K1C+Exercise group exhibited lower (p<0.05) MPO activity (22.04±5.90 vs. 78.95±18.09 UMPO/mg tissue) and higher (p<0.05) GSH concentrations in intestinal tissues (67.63±7.85 vs. 31.85±5.90mg NPSH/mg tissue). The 2K1C+Exercise group showed lower (p<0.05) cytokine levels in the intestine than 2K1C rats. In comparison with the Sham group, the 2K1C+Exercise rats showed higher (p<0.05) gene expression of ATR2 in the duodenum.

Conclusion: 2K-1C hypertension elicits an oxidative stress and inflammation process in the duodenum. Physical exercise modulates the expression twice as much of ATR2 receptors, suggesting possible anti-inflammatory and antioxidant effects induced by exercise.
The Naturally Evolved EPSPS From Goosegrass Confers High Glyphosate Resistance to Rice
Authors: Ouyang Chao , Liu Wei , Chen Silan , Zhao Huimin , Chen Xinyan , Jin Xiongxia , Li Xinpeng , Wu Yongzhong , Zeng Xiang , Huang Peijin , He Xiuying , An Baoguang
Published: October 2021

Glyphosate-resistant crops developed by the CP4-EPSPS gene from Agrobacterium have been planted on a massive scale globally, which benefits from the high efficiency and broad spectrum of glyphosate in weed control. Some glyphosate-resistant (GR) genes from microbes have been reported, which might raise biosafety concerns. Most of them were obtained through a hygromycin-HPT transformation system. Here we reported the plant source with 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene from goosegrass endowed rice with high resistance to glyphosate. The integrations and inheritability of the transgenes in the rice genome were investigated within two generations. The EiEPSPS transgenic plants displayed similar growth and development to wild type under no glyphosate selection pressure but better reproductive performance under lower glyphosate selection pressure. Furthermore, we reconstructed a binary vector pCEiEPSPS and established the whole stage glyphosate selection using the vector. The Glyphosate-pCEiEPSPS selection system showed a significantly higher transformation efficiency compared with the hygromycin-HPT transformation system. Our results provided a promising alternative gene resource to the development of GR plants and also extended the plant transformation toolbox.
An OsKala3, R2R3 MYB TF, Is a Common Key Player for Black Rice Pericarp as Main Partner of an OsKala4, bHLH TF
Authors: Kim Da-Hye , Yang JuHee , Ha Sun-Hwa , Kim Jae Kwang , Lee Jong-Yeol , Lim Sun-Hyung
Published: October 2021

Rice (Oryza sativa) pericarp exhibits various colors due to the accumulation of anthocyanins and/or proanthocyanidins. Previous work revealed that the two basic helix-loop-helix (bHLH) transcription factors OsKala4 and OsRc are key regulators for the black and red pericarp traits, respectively, and their inactivation results in rice with white pericarp. However, their pericarp-specific R2R3 MYB partner remained unknown. Here, we characterized the role of the R2R3 MYB gene OsKala3 in rice pericarp pigmentation through genetic and molecular approaches. A rice protoplast transfection assay showed that OsKala3 is a nuclear-localized protein. Furthermore, OsKala3 physically interacted with OsKala4 in a yeast two-hybrid analysis. Co-transfection assays in rice protoplasts revealed that OsKala3 and OsKala4 mediate the activation of anthocyanin biosynthetic genes. Notably, the OsKala3 promoter region exhibited an insertion polymorphism specifically in rice cultivars with black pericarp, creating two tandem repeats while red and white varieties harbor only one. The number of repeats within the OsKala3 promoter correlated with increased transactivation by OsKala3, thus providing a rationale for the black pericarp characteristic of cultivars with two repeats. These results thus provide evidence for the molecular basis of anthocyanin biosynthesis in rice pericarp and may facilitate the introduction of this beneficial trait to other rice cultivars through marker-assisted breeding.
The Welleye: A Conceptual Framework for Understanding and Promoting Wellbeing
Authors: Dolan Paul , Laffan Kate , Kudrna Laura
Published: October 2021

We present the Welleye – a novel and conceptually clear framework that shows how attention links the objective circumstances of people’s lives and selves to how they spend their time and feel day to day. While existing wellbeing frameworks in policy contain many of the factors included in the Welleye, they all lack attention as the “lens” that determines the impact of these factors on how people feel. Policymakers and organizations can use the Welleye to better understand how people are faring and design and evaluate interventions aimed at making people better off.
Research on the Drivers of Entrepreneurship Education Performance of Medical Students in the Digital Age
Authors: Long Zehai , Zhao Guojing , Wang Jing , Zhang Mengting , Zhou Shaoyu , Zhang Ling , Huang Zhaoxin
Published: October 2021

COVID-19 has made the entire society pay more attention to medical students training. Medicine development is inseparable from the spirit of innovation, focusing on cultivating medical students' innovative awareness and improving entrepreneurship education performance, which has an irreplaceable effect on both the students themselves and the society. This study is based on the ridge regression model to study the driving factors of the entrepreneurship education performance of medical students. Compared with traditional multiple regression, it can improve the consistency of parameter estimation and obtain more realistic results. Based on a large sample of empirical survey data of 24,677 medical students in China, this study analyzed the driving factors of the entrepreneurship education performance of medical students and found that medical students of different genders have differences in entrepreneurship education performance; the digital economy impacts entrepreneurship education performance of medical students; entrepreneurship course, entrepreneurship faculty, entrepreneurship competition, entrepreneurship practice, and entrepreneurship policy have a driving effect on the entrepreneurship education performance of medical students. Meanwhile, the impact of entrepreneurship policy is the most obvious, followed by entrepreneurship practice and entrepreneurship competition, followed by entrepreneurship course and entrepreneurship faculty.
ESL/EFL Learners' Responses to Teacher Written Feedback: Reviewing a Recent Decade of Empirical Studies
Authors: Yu Rong , Yang Luxin
Published: October 2021

Teacher written feedback (TWF) has long been regarded as a necessary pedagogical tool for improving the writing proficiency of ESL/EFL learners, while student responses to this feedback can often reflect its effectiveness. This paper reviews 64 articles appearing in high-ranking journals during 2010–2021 in terms of research methodology, theoretical framework and main findings. Analysis of these articles reveals few studies adopted any theoretical frameworks to examine learner responses to TWF and suggests a need for longitudinal naturalistic studies adopting mixed methods and some theoretical framework such as sociocultural theory of mind (SCT) to better explain learners' dynamic engagement in response to TWF. The main findings of these previous studies reveal the diverse responses among learners at different language proficiency levels and in various sociocultural contexts. The results of the review indicate that future research could take classroom-based mixed-method research design to investigate learner variables.
The Role of Nonlinear Pedagogy in Supporting the Design of Modified Games in Junior Sports
Authors: Chow Jia Yi , Komar John , Seifert Ludovic
Published: October 2021

Nonlinear Pedagogy has been advocated as an approach that views acquisition of movement skills with a strong emphasis on exploratory behaviors and the development of individualized movement skills. Underpinned by Ecological Dynamics, Nonlinear Pedagogy provides key ideas on design principles to support a teaching and learning approach that accounts for dynamic interactions among constraints in the evolution of movement behaviors. In the context of junior sports, the manipulation of task constraints is central to how games can be re-designed for children to play that are age and body appropriate so that the games can still capture the key elements of representativeness as compared to the adult form of the game. Importantly, these games offer suitable affordances that promote sensible play that could be transferable to other contexts. In this paper, we provide an in-depth discussion on how Nonlinear Pedagogy is relevant in supporting the design and development of modified games in the context of junior sports. Practical implications are also provided to share how games can be modified for meaningful play to emerge.
Inflamed Mind: Multiple Genetic Variants of IL6 Influence Suicide Risk Phenotypes in Interaction With Early and Recent Adversities in a Linkage Disequilibrium-Based Clumping Analysis
Authors: Bokor Janos , Sutori Sara , Torok Dora , Gal Zsofia , Eszlari Nora , Gyorik Dorka , Baksa Daniel , Petschner Peter , Serafini Gianluca , Pompili Maurizio , Anderson Ian M. , Deakin Bill , Bagdy Gyorgy , Juhasz Gabriella , Gonda Xenia
Published: October 2021

Background: Understanding and predicting suicide remains a challenge, and a recent paradigm shift regarding the complex relationship between the immune system and the brain brought attention to the involvement of inflammation in neuropsychiatric conditions including suicide. Among cytokines, IL-6 has been most frequently implicated in suicide, yet only a few candidate gene studies and without considering the effect of stress investigated the role of IL6 in suicidal behaviour. Our study aimed to investigate the association of IL6 variation with a linkage disequilibrium-based clumping method in interaction with childhood adversities and recent stress on manifestations along the suicide spectrum.

Methods: One thousand seven hundred and sixty-two participants provided information on previous suicide attempts, current suicidal ideation, thoughts of death, and hopelessness, and were genotyped for 186 variants in IL6. Early childhood adversities were recorded with an instrument adapted from the Childhood Trauma Questionnaire, recent life events were registered using the List of Threatening Life Events. Following a 3-step quality control, logistic and linear regression models were run to explore the effect of genotype and gene-environment interactions on suicide phenotypes. All regression models were followed by a clumping process based on empirical estimates of linkage disequilibrium between clumps of intercorrelated SNPs. Interaction effects of distinct types of recent life events were also analysed.

Results: No clumps with significant main effects emerged, but we identified several clumps significantly interacting with childhood adversities on lifetime suicide attempts, current suicidal ideation, and current thoughts of death. We also identified clumps significantly interacting with recent negative life events on current suicidal ideation. We reported no clumps with significant effect on hopelessness either as a main effect or in interaction with childhood adversities or recent stress.

Conclusion: We identified variant clumps in IL6 influencing suicidal behaviour, but only in interaction with childhood or recent adversities. Our results may bring us a step further in understanding the role of neuroinflammation and specifically of IL-6 in suicide, towards identifying novel biological markers of suicidal behaviour especially in those exposed to stressful experiences, and to fostering the adaptation of a new paradigm and identifying novel approaches and targets in the treatment of suicidal behaviour.
Early Detection of COVID-19 Waves From Cases in a Neighboring Country With an Open Border
Authors: Kamat Anil , Sah Amrita
Published: October 2021

Border closure or travel restriction is a critical issue as closing the border early can badly affect the economy of the country, whereas substantial delay can put human lives at stake. While many papers discuss closing the border early in the pandemic, the question of when to close the border has not been addressed well. We have tried to estimate a date of closing the border by taking the reference of a neighboring country with a high correlation in Covid-19 incidence. Here we have used non-linear methods to probe the landscape of correlation between temporal COVID-19 incidences and deaths. We have tested our method on two neighboring countries, Nepal and India, with open borders, where closing the borders are among the top priorities to reduce the spread and spill-out of variants. We have selected these countries as they have close connectivity and intertwined socio-economic network with thousands of people crossing the border every day. We found the distance correlation for COVID-19 incidence between these countries to be statistically significant (p< 0.001) and there is a lag of 6 days for maximum correlation. In addition, we analyzed the correlation for each wave and found the distance correlation for the first phase is 0.8145 (p< 0.001) with a lag of 2 days, and the distance correlation for the second wave is 0.9685 (p< 0.001) without any lag. This study can be a critical planning tool for policymakers and public health practitioners to make an informed decision on border closure in the early days as it is critically associated with the legal and diplomatic agreements and regulations between two countries.
Varicocele-Associated Infertility and the Role of Oxidative Stress on Sperm DNA Fragmentation
Authors: Wood Guilherme Jacom Abdulmassih , Cardoso João Paulo Greco , Paluello Davi Vischi , Nunes Thiago Fagundes , Cocuzza Marcello
Published: October 2021

Varicocele has been extensively described and studied as the most important reversible cause of male infertility. Its impact on semen parameters, pregnancy rates, and assisted reproductive outcomes have been associated with multifactorial aspects, most of them converging to increase of reactive oxygen species (ROS). More recently, sperm DNA fragmentation has gained significant attention and potential clinical use, although the body of evidence still needs further evolution. The associations between sperm DNA damage and a variety of disorders, including varicocele itself, share common pathways to ROS increase. This mini-review discusses different aspects related to the etiology of ROS and its relation to varicocele and potential mechanisms of DNA damage.
Spondylodiscitis After Surgery for Pelvic Organ Prolapse: Description of a Rare Complication and Systematic Review of the Literature
Authors: Stabile Guglielmo , Romano Federico , Topouzova Ghergana A. , Mangino Francesco Paolo , Di Lorenzo Giovanni , Laganà Antonio Simone , De Manzini Nicolò , Ricci Giuseppe
Published: October 2021

Background: Spondylodiscitis can be a rare complication of gynecological surgery, typically of procedures involving the sacrum and the sacrospinous ligament. This report presents a case of spondylodiscitis arising after a laparoscopic sacrocolpopexy with a mesh. We also review the literature finding 52 cases of spondylodiscitis following sacrocolpopexy and (or) rectopexy with or without a mesh.

Methods: We performed a comprehensive search from the electronic databases MEDLINE (Pubmed), Scopus, Web of Science, Embase, CINAHL, and Google Scholar from 1990 to February 2021 in order to identify case reports or case series reporting on spondylodiscitis after rectopexy or sacrocolpopexy.

Results: We identified 52 total postoperative spondylodiscitis. We examined the mean age of patients, the surgical history, the time from initial surgery to spondylodiscitis, the presenting symptoms, the diagnostic tools, the medical and surgical treatment, the type of mesh used, the surgical access, and the possible causes of spondylodiscitis.

Conclusions: Diagnosis of spondylodiscitis may be challenging. From our review emerges that recurrent pelvic pain and lumbosciatalgia may be signals of lumbar spondylodiscitis. Magnetic resonance is the gold standard examination for spondylodiscitis. Surgical practice needs to be improved further in order to establish the best procedure to minimize the incidence of this complication. Awareness of symptoms, timely diagnosis, and treatment are fundamental to prevent irreversible complications.
DMFO-CD: A Discrete Moth-Flame Optimization Algorithm for Community Detection
Authors: Nadimi-Shahraki Mohammad H. , Moeini Ebrahim , Taghian Shokooh , Mirjalili Seyedali
Published: October 2021

In this paper, a discrete moth–flame optimization algorithm for community detection (DMFO-CD) is proposed. The representation of solution vectors, initialization, and movement strategy of the continuous moth–flame optimization are purposely adapted in DMFO-CD such that it can solve the discrete community detection. In this adaptation, locus-based adjacency representation is used to represent the position of moths and flames, and the initialization process is performed by considering the community structure and the relation between nodes without the need of any knowledge about the number of communities. Solution vectors are updated by the adapted movement strategy using a single-point crossover to distance imitating, a two-point crossover to calculate the movement, and a single-point neighbor-based mutation that can enhance the exploration and balance exploration and exploitation. The fitness function is also defined based on modularity. The performance of DMFO-CD was evaluated on eleven real-world networks, and the obtained results were compared with five well-known algorithms in community detection, including GA-Net, DPSO-PDM, GACD, EGACD, and DECS in terms of modularity, NMI, and the number of detected communities. Additionally, the obtained results were statistically analyzed by the Wilcoxon signed-rank and Friedman tests. In the comparison with other comparative algorithms, the results show that the proposed DMFO-CD is competitive to detect the correct number of communities with high modularity.
Estimation of Rate Constants and Mixing Characteristics in Flotation Columns
Authors: Park Chul-Hyun
Published: October 2021

The effect of mixing in a flotation column has long been recognized as an important factor in determining the performance of flotation. The paper presents the effects of mixing on the rate constant in a flotation column, and the establishment of relationships based on vessel dispersion numbers (Nd) that can describe axial dispersion. The rate constants were evaluated using models of plug flow, fully mixed tanks, and axial mixing for a coal cleaning operation. Results showed that fine particles are similar between each model; however, for coarse particles, the deviation is large in the case of perfect mixing, while axial mixing is suitable. It reveals the suitability of using an axial dispersion model for estimating the rate constants, particularly for coarser particles. A regression equation to determine the flotation rate constant was also developed with Nd values between 0.2 to 0.5. The ratio of particles to liquid the residence times time (τp/τL) decreases with particle size from small sizes to coarser sizes. Axial dispersion is increased by the superficial gas velocity while is suppressed by the wash water. The relationship between calculated and observed Nd can be used with a 94% accuracy for the coal cleaning application within the range of operating conditions of superficial gas velocity (0.7–1.6 cm/s), superficial wash water velocity (0.1–0.4 cm/s), and Hc/dc (26.8–32.7). The empirical relationship of Nd with significant variables along with the aspect ratio of the column was found to be applicable for coal beneficiation. It may be useful in terms of design and scale up of the columns.
Victorian Artists’ Letters: Rhetoric, Networks, and Social Capital
Authors: Codell Julie
Published: October 2021

Victorian artists were remarkably literate; they wrote autobiographies, diaries, and essays and befriended writers and journalists. Writing had become a way to present themselves on the open market and to generate a public image as individuals and collectively within the new professionalism emerging in the century. Letter writing was purposed to solidify and improve artists’ social capital, and their comments were always embedded in social relationships and practices. Thus, artists’ letters reveal much about the artworld structure; its players; and its overlapping spheres of social, economic, and professional identities. Their letters combined frankness with rhetorical pleading and contained their own press releases, studio invitations, and responses to criticism and were often intended for public consumption if used in critics’ reviews. Through letters, artists and critics revealed their reciprocal authority and agency and did not simply reflect the artworld but shaped that world. In their letters, economic gains were sublimated by artists’ desire for fame, Royal Academy acceptance, and a place in art history, then an emerging university discipline, seeking symbolic investments in their reputations and demonstrating that the market is cultural, not just economic. In their letters artists made clear that commodification does not destroy or pollute subjectivity.
The Race of CAR Therapies: CAR-NK Cells for Fighting B-Cell Hematological Cancers
Authors: Herrera Lara , Santos Silvia , Vesga Miguel Angel , Carrascosa Tomas , Garcia-Ruiz Juan Carlos , Pérez-Martínez Antonio , Juan Manel , Eguizabal Cristina
Published: October 2021

Acute lymphoblastic leukemia (ALL) and Chronic lymphocytic leukemia (CLL) are the most common leukemias in children and elderly people, respectively. Standard therapies, such as chemotherapy, are only effective in 40% of ALL adult patients with a five-year survival rate and therefore new alternatives need to be used, such as immunotherapy targeting specific receptors of malignant cells. Among all the options, CAR (Chimeric antigen receptor)-based therapy has arisen as a new opportunity for refractory or relapsed hematological cancer patients. CARs were designed to be used along with T lymphocytes, creating CAR-T cells, but they are presenting such encouraging results that they are already in use as drugs. Nonetheless, their side-effects and the fact that it is not possible to infuse an allogenic CAR-T product without causing graft-versus-host-disease, have meant using a different cell source to solve these problems, such as Natural Killer (NK) cells. Although CAR-based treatment is a high-speed race led by CAR-T cells, CAR-NK cells are slowly (but surely) consolidating their position; their demonstrated efficacy and the lack of undesirable side-effects is opening a new door for CAR-based treatments. CAR-NKs are now in the field to stay.
Er:YAG Laser Cleaning of Painted Surfaces: Functional Considerations to Improve Efficacy and Reduce Side Effects
Authors: Wang Cong , Cao Yijian , Tie Fude , Camaiti Mara
Published: October 2021

The restoration of paintings always involves the removal of darkened superficial layers, which are mainly due to dust deposition and aged varnishes. As cleaning is an irreversible and invasive treatment, physical methods (i.e., laser cleaning) instead of chemical ones are frequently suggested to reduce side effects on pictorial layers. Among the most employed laser systems, the free-running Er:YAG laser is considered very suitable for fine arts cleaning. This laser works at 2.94 μm, at which only –OH and –NH bonds in molecules are excited. This character can become a disadvantage when pigments with these functional groups are present. To understand the potential of the Er:YAG laser in such situations or in the presence of degradable pigments, the effectiveness of varnish removal from paintings prepared with egg yolk as the binder and cinnabar and lead white as the pigments were systematically investigated. Different cleaning conditions were used, and a hyperspectral sensor was innovatively used as a rapid, in situ and non-destructive technique to assess the effects of laser ablation, besides microscopic analysis. Though results obtained show all these pigments are sensitive to this laser radiation, satisfactory cleaning can be achieved without damaging the pictorial layer. The best cleaning conditions were 0.5 W of power (50 mJ and 10 Hz for energy and frequency), with 2-propanol as the wetting agent.
Breeding Density and Collision Mortality of Loggerhead Shrike (Lanius ludovicianus) in the Altamont Pass Wind Resource Area
Authors: Smallwood K. Shawn , Smallwood Noriko L.
Published: October 2021

Loggerhead shrike (Lanius ludovicianus) has declined across most or all of its geographic range. The species’ raptorial behavior requires maintenance of large territories, which means populations of breeding shrikes require large areas of habitat and are therefore sensitive to habitat loss and habitat fragmentation. We estimated breeding densities of loggerhead shrikes in the Altamont Pass Wind Resource Area (APWRA), California, where annual shrike mortality caused by wind turbine collisions was high until just before our study began in 2016. Based on surveys across an annual average 50 randomized sampling plots in 2016–2019, we estimated an average 129 breeding pairs/year across the 167.6-km2 APWRA. Relative to the size of the study area, density in the APWRA was relatively high compared to densities reported from other study sites across North America. It was higher than predicted by application of the Partners in Flight estimator, which was based on Breeding Bird Surveys along roads. We also found that loggerhead shrikes in the APWRA were limited by the availability of nest substrate and by California ground squirrels (Otospermophilus beecheyi) and their burrow complexes, which have keystone effects on vegetation and wildlife in the APWRA. To most effectively conserve loggerhead shrikes in the APWRA, wind turbine mortality should be minimized, ground squirrels conserved instead of eradicated as pests, and appropriate trees and shrubs cultivated where they are needed.
New and Poorly Known Species of Peniagone (Holothuroidea, Elpidiidae) from the Northwest Pacific Ocean with Discussion on Phylogeny of the Genus
Authors: Kremenetskaia Antonina , Gebruk Andrey , Alt Claudia H. S. , Budaeva Nataliya
Published: October 2021

The northwest Pacific fauna of Peniagone includes at least seven species. In the present study we considered the following six species: Peniagone dubia and P. mus are re-described, P. minuta and P. saveljevae are described as new to science, additional information is provided on P. vitrea and P. cf. purpurea. Peniagone japonica was not included in the analysis. A potentially new species Peniagone sp. “miniatura” was distinguished based on morphological and molecular data but not formally described due to insufficient material. In the northwest Pacific, the species of Peniagone are distributed from 2400 to 8200 m. The bathymetric range of most of the species is narrow except for P. mus being also one of the deepest representatives of the genus. Only one species, P. vitrea, is known outside the northwest Pacific region. Partial sequences of COI and 16S rDNA were obtained for provisionally ten species of the genus (four of them from the northwest Pacific) and two other species of Elpidiidae which were used as an outgroup in phylogenetic analyses. The phylogenetic analyses results suggest that the northwest Pacific species of Peniagone are not closely related.
Highly Productive Tropical Seagrass Beds Support Diverse Consumers and a Large Organic Carbon Pool in the Sediments
Authors: Lee Chen-Lu , Lin Wei-Jen , Liu Pi-Jen , Shao Kwang-Tsao , Lin Hsing-Juh
Published: October 2021

Tropical seagrass beds are productive coastal ecosystems that are important blue carbon sinks and crucial habitats and feeding grounds for consumers at high trophic levels. To understand how energy sustains the ecosystem from seagrass production, we constructed an Ecopath trophic model to reveal the possible pathways of energy flow in the tropical seagrass beds around Dongsha Island, South China Sea. The model indicates that Dongsha seagrass beds were developing but well-structured ecosystems. The productive seagrasses were rarely directly consumed by herbivores and, ultimately, flowed into detrital pools. Detritus was the main food source used to support diverse consumers in the food web. Nevertheless, the low cycling rate (2.74%) suggests that most detritus was not reused or exported and was stored as a large organic carbon pool in the sediments. The detritus-feeding invertebrates are keystone groups in the Dongsha seagrass beds, as they recycle energy from detritus and transfer to top predators such as sharks. The predation of top predators affected the biomasses of other compartments, leading to strong top-down control via a trophic cascade effect.
Thermodynamic Consistency of the Cushman Method of Computing the Configurational Entropy of a Landscape Lattice
Authors: Cushman Samuel A.
Published: October 2021

There has been a recent surge of interest in theory and methods for calculating the entropy of landscape patterns, but relatively little is known about the thermodynamic consistency of these approaches. I posit that for any of these methods to be fully thermodynamically consistent, they must meet three conditions. First, the computed entropies must lie along the theoretical distribution of entropies as a function of total edge length, which Cushman showed was a parabolic function following from the fact that there is a normal distribution of permuted edge lengths, the entropy is the logarithm of the number of microstates in a macrostate, and the logarithm of a normal distribution is a parabolic function. Second, the entropy must increase over time through the period of the random mixing simulation, following the expectation that entropy increases in a closed system. Third, at full mixing, the entropy will fluctuate randomly around the maximum theoretical value, associated with a perfectly random arrangement of the lattice. I evaluated these criteria in a test condition involving a binary, two-class landscape using the Cushman method of directly applying the Boltzmann relation (s = klogW) to permuted landscape configurations and measuring the distribution of total edge length. The results show that the Cushman method directly applying the classical Boltzmann relation is fully consistent with these criteria and therefore fully thermodynamically consistent. I suggest that this method, which is a direct application of the classical and iconic formulation of Boltzmann, has advantages given its direct interpretability, theoretical elegance, and thermodynamic consistency.