bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Applications of Porphyrin-Biomacromolecule Conjugates
Authors: Pathak Pravin , Zarandi Mohammad Amin , Zhou Xiao , Jayawickramarajah Janarthanan
Published: November 2021

With potential applications in materials and especially in light-responsive biomedicine that targets cancer tissue selectively, much research has focused on developing covalent conjugation techniques to tether porphyrinoid units to various biomacromolecules. This review details the key synthetic approaches that have been employed in the recent decades to conjugate porphyrinoids with oligonucleotides and peptides/proteins. In addition, we provide succinct discussions on the subsequent applications of such hybrid systems and also give a brief overview of the rapidly progressing field of porphyrin-antibody conjugates. Since nucleic acid and peptide systems vary in structure, connectivity, functional group availability and placement, as well as stability and solubility, tailored synthetic approaches are needed for conjugating to each of these biomacromolecule types. In terms of tethering to ONs, porphyrins are typically attached by employing bioorthogonal chemistry (e.g., using phosphoramidites) that drive solid-phase ON synthesis or by conducting post-synthesis modifications and subsequent reactions (such as amide couplings, hydrazide-carbonyl reactions, and click chemistry). In contrast, peptides and proteins are typically conjugated to porphyrinoids using their native functional groups, especially the thiol and amine side chains. However, bioorthogonal reactions (e.g., Staudinger ligations, and copper or strain promoted alkyne-azide cycloadditions) that utilizede novointroduced functional groups onto peptides/proteins have seen vigorous development, especially for site-specific peptide-porphyrin tethering. While the ON-porphyrin conjugates have largely been explored for programmed nanostructure self-assembly and artificial light-harvesting applications, there are some reports of ON-porphyrin systems targeting clinically translational applications (e.g., antimicrobial biomaterials and site-specific nucleic acid cleavage). Conjugates of porphyrins with proteinaceous moieties, on the other hand, have been predominantly used for therapeutic and diagnostic applications (especially in photodynamic therapy, photodynamic antimicrobial chemotherapy, and photothermal therapy). The advancement of the field of porphyrinoid-bioconjugation chemistry from basic academic research to more clinically targeted applications require continuous fine-tuning in terms of synthetic strategies and hence there will continue to be much exciting work on porphyrinoid-biomacromolecule conjugation.
Receptor-Interacting Protein Kinase 3 Inhibition Prevents Cadmium-Mediated Macrophage Polarization and Subsequent Atherosclerosis via Maintaining Mitochondrial Homeostasis
Authors: Zhang Jiexin , Feng Weijing , Li Minghui , Chen Peier , Ning Xiaodong , Ou Caiwen , Chen Minsheng
Published: November 2021

Chronic cadmium (Cd) exposure contributes to the progression of cardiovascular disease (CVD), especially atherosclerosis (AS), but the underlying mechanism is unclear. Since mitochondrial homeostasis is emerging as a core player in the development of CVD, it might serve as a potential mechanism linking Cd exposure and AS. In this study, we aimed to investigate Cd-mediated AS through macrophage polarization and know the mechanisms of Cd-caused mitochondrial homeostasis imbalance. In vitro, flow cytometry shows that Cd exposure promotes M1-type polarization of macrophages, manifested as the increasing expressions of nuclear Factor kappa-light-chain-enhancer of activated B (NF-kB) and NLR family pyrin domain containing 3 (NLRP3). Mitochondrial homeostasis tests revealed that decreasing mitochondrial membrane potential and mitophage, increasing the mitochondrial superoxide (mROS), and mitochondrial fission are involved in the Cd-induced macrophage polarization. The upregulated expressions of receptor-interacting protein kinase 3 (RIPK3) and pseudokinase-mixed lineage kinase domain-like protein (p-MLKL) were observed. Knocking out RIPK3, followed by decreasing the expression of p-MLKL, improves the mitochondrial homeostasis imbalance which effectively reverses macrophage polarization. In vivo, the oil red O staining showed that Cd with higher blood significantly aggravates AS. Besides, M1-type polarization of macrophages and mitochondrial homeostasis imbalance were observed in the aortic roots of the mice through immunofluorescence and western blot. Knocking out RIPK3 restored the changes above. Finally, the administered N-acetyl cysteine (NAC) or mitochondrial division inhibitor-1 (Mdivi-1), which decreased the mROS or mitochondrial fission, inhibited the expressions of RIPK3 and p-MLKL, attenuating AS and macrophage M1-type polarization in the Cd-treated group. Consequently, the Cd exposure activated the RIPK3 pathway and impaired the mitochondrial homeostasis, resulting in pro-inflammatory macrophage polarization and subsequent AS. Knocking out RIPK3 provided a potential therapeutic target for Cd-caused macrophage polarization and subsequent AS.
Understanding Teacher Education Students’ Research Competence Through Their Conceptions of Theory
Authors: Salmento Heidi , Murtonen Mari , Kiley Margaret
Published: November 2021

Learning a scientific way of thinking is a fundamental aim of university education. It means that there are certain thinking skills that students across all disciplines should learn during their studies. For example, critical thinking and reasoning skills are essential for all university graduates. In addition, students are expected to achieve certain skill levels related to scientific research, for example: learning the basic concepts of science and research methodology, understanding the research process and understanding the nature and origins of scientific knowledge. We call these skills research competence and see research competence as one of the main elements of scientific thinking. We assume that understanding the basic concepts of science is a starting point for the development of research competence and more broadly, for scientific thinking. However, previous studies have shown that scientific concepts are not easy for students to learn. The aim of this study is to increase our understanding of a particular aspect of university students’ research competence by exploring teacher education students’ (N = 179) conceptions of one of these challenging concepts, the concept of theory. The results illustrate that understanding the concept of theory is challenging even for graduating (fourth and fifth year) master students. Only half of them were able to describe the concept of theory in a scientific context suggesting that the other half had unscientific conceptions of theory, named here as non-scientific conceptions. When looking at the students’ who reported scientific conceptions of theory, one quarter of graduating students and a few early stage (first and second year) students had a declarative approach meaning that they were able to describe the concept of theory by using some basic scientific terms. About one fifth of graduating and early stage students had a procedural approach meaning that they were able to describe theory related to research as “doing”. Only a small number of students showed an understanding of the nature and origins of scientific knowledge and the role of research and theory, called here an epistemic approach.
Single-Cell RNA Sequencing Reveals B Cells Are Important Regulators in Fracture Healing
Authors: Zhang Hao , Wang Renkai , Wang Guangchao , Zhang Bo , Wang Chao , Li Di , Ding Chen , Wei Qiang , Fan Zhenyu , Tang Hao , Ji Fang
Published: November 2021

The bone marrow microenvironment is composed primarily of immune and stromal cells that play important roles in fracture healing. Although immune cells have been identified in mouse bone marrow, variations in their numbers and type during the fracture healing process remain poorly defined. In this study, single-cell RNA sequencing was used to identify immune cells in fracture tissues, including neutrophils, monocytes, T cells, B cells, and plasma cells. The number of B cells decreased significantly in the early stage of fracture healing. Furthermore, B cells in mice fracture models decreased significantly during the epiphyseal phase and then gradually returned to normal during the epiphyseal transformation phase of fracture healing. The B-cell pattern was opposite to that of bone formation and resorption activities. Notably, B-cell–derived exosomes inhibited bone homeostasis in fracture healing. In humans, a decrease in the number of B cells during the epiphyseal phase stimulated fracture healing. Then, as the numbers of osteoblasts increased during the callus reconstruction stage, the number of B cells gradually recovered, which reduced additional bone regeneration. Thus, B cells are key regulators of fracture healing and inhibit excessive bone regeneration by producing multiple osteoblast inhibitors.
Tri-Ponderal Mass Index Reference Values for Screening Metabolic Syndrome in Children and Adolescents: Results From Two National-Representative Cross-Sectional Studies in China and America
Authors: Wang Xijie , Chen Yanjun , Ma Jun , Dong Bin , Dong Yanhui , Zou Zhiyong , Ma Yinghua , Arnold Luke , Liang Wannian
Published: November 2021

Introduction

To ascertain the possible cut point of tri-ponderal mass index (TMI) in discriminating metabolic syndrome (MetS) and related cardio-metabolic risk factors in Chinese and American children and adolescents.

Methods

A total of 57,201 Chinese children aged 7-18 recruited in 2012 and and 10,441 American children aged 12-18 from National Health and Nutrition Examination Survey (NHANES 2001-2014) were included to fit TMI percentiles. Participants were randomly assigned to a derivation set (75%) and validation set (25%). The cut points of TMI with the lowest misclassification rate under the premise of the highest area under curves (AUC) were selected for each sex, which were additionally examined in the validation set. All of data analysis was conducted between September and December in 2019.

Results

TMI showed good capacity on discriminating MetS, with AUC of 0.7658 (95% CI: 0.7544-0.7770) to 0.8445 (95% CI: 0.8349-0.8537) in Chinese and 0.8871 (95% CI: 0.8663-0.9056) to 0.9329 (95% CI: 0.9166-0.9469) in American children. The optimal cut points were 14.46 kg/m3 and 13.91 kg/m3 for Chinese boys and girls, and 17.08 kg/m3 and 18.89 kg/m3 for American boys and girls, respectively. The corresponding misclassification rates were 17.1% (95% CI: 16.4-17.8) and 11.2% (95% CI: 9.9-12.6), respectively. Performance of these cut points were also examined in the validation set (sensitivity 67.7%, specificity 82.4% in Chinese; sensitivity 84.4%, specificity 88.7% in American children).

Conclusions

A sex- and ethnicity- specific single cut point of TMI could be used to distinguish MetS and elevated risk of cardio-metabolic factors in children and adolescents.
Municipal Solid Waste Forecasting in China Based on Machine Learning Models
Authors: Yang Liping , Zhao Yigang , Niu Xiaxia , Song Zisheng , Gao Qingxian , Wu Jun
Published: November 2021

As the largest producing country of municipal solid waste (MSW) around the world, China is always challenged by a lower utilization rate of MSW due to a lack of a smart MSW forecasting strategy. This paper mainly aims to construct an effective MSW prediction model to handle this problem by using machine learning techniques. Based on the empirical analysis of provincial panel data from 2008 to 2019 in China, we find that the Deep Neural Network (DNN) model performs best among all machine learning models. Additionally, we introduce the SHapley Additive exPlanation (SHAP) method to unravel the correlation between MSW production and socioeconomic features (e.g., total regional GDP, population density). We also find the increase of urban population and agglomeration of wholesales and retails industries can positively promote the production of MSW in regions of high economic development, and vice versa. These results can be of help in the planning, design, and implementation of solid waste management system in China.
Prognostic Model and Nomogram Construction Based on a Novel Ferroptosis-Related Gene Signature in Lower-Grade Glioma
Authors: Zhao Junsheng , Liu Zhengtao , Zheng Xiaoping , Gao Hainv , Li Lanjuan
Published: November 2021

Background: Low-grade glioma (LGG) is considered a fatal disease for young adults, with overall survival widely ranging from 1 to 15 years depending on histopathologic and molecular subtypes. As a novel type of programmed cell death, ferroptosis was reported to be involved in tumorigenesis and development, which has been intensively studied in recent years.

Methods: For the discovery cohort, data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were used to identify the differentially expressed and prognostic ferroptosis-related genes (FRGs). The least absolute shrinkage and selection operator (LASSO) and multivariate Cox were used to establish a prognostic signature with the above-selected FRGs. Then, the signature was developed and validated in TCGA and Chinese Glioma Genome Atlas (CGGA) databases. By combining clinicopathological features and the FRG signature, a nomogram was established to predict individuals’ one-, three-, and five-year survival probability, and its predictive performance was evaluated by Harrell’s concordance index (C-index) and calibration curves. Enrichment analysis was performed to explore the signaling pathways regulated by the signature.

Results: A novel risk signature contains seven FRGs that were constructed and were used to divide patients into two groups. Kaplan–Meier (K−M) survival curve and receiver-operating characteristic (ROC) curve analyses confirmed the prognostic performance of the risk model, followed by external validation based on data from the CGGA. The nomogram based on the risk signature and clinical traits was validated to perform well for predicting the survival rate of LGG. Finally, functional analysis revealed that the immune statuses were different between the two risk groups, which might help explain the underlying mechanisms of ferroptosis in LGG.

Conclusion: In conclusion, this study constructed a novel and robust seven-FRG signature and established a prognostic nomogram for LGG survival prediction.
Emergent Arboviruses: A Review About Mayaro virus and Oropouche orthobunyavirus
Authors: Pereira Thiago Nunes , Virginio Flávia , Souza Julia Isabela , Moreira Luciano Andrade
Published: November 2021

Arthropod-borne viruses have a significant impact on public health worldwide, and their (re) emergence put aside the importance of other circulating arboviruses. Therefore, this scoping review aims to identify and characterize the literature produced in recent years, focusing on aspects of two arboviruses: Mayaro virus and Oropouche orthobunyavirus. The Mayaro and Oropouche viruses were isolated for the first time in Trinidad and Tobago in 1954 and 1955, respectively, and have more recently caused numerous outbreaks. In addition, they have been incriminated as candidate diseases for human epidemics. These viruses have been drawing the attention of public health authorities worldwide following recent outbreaks. To determine the global epidemiological profile of these viruses, we used the Dimensions Database, which contains more than 100 million publications. In general, we identified 327 studies published from 1957 to 2020 for Mayaro virus, and 152 studies published from 1961 to 2020 for Oropouche orthobunyavirus. Interestingly, we observed that Mayaro and Oropouche had a significant increase in the number of publications in recent years. Thus, this comprehensive review will be helpful to guide future research based on the identified knowledge gaps.
Advances in Preclinical Platforms of Loa loa for Filarial Neglected Tropical Disease Drug and Diagnostics Research
Authors: Wanji Samuel , Chunda Valerine Chawa , Fombad Fanny Fri , Njouendou Abdel Jélil , Gandjui Narcisse Victor T. , Ritter Manuel , Enyong Peter A. , Mackenzie Charles , Taylor Mark J. , Hoerauf Achim , Turner Joseph D.
Published: November 2021

The tropical disease, loiasis, caused by the filarial parasite, Loa loa, has gained prominence in global public health as a cause of excess mortality and a barrier to the elimination of the related prioritized neglected tropical diseases (NTDs), lymphatic filariasis and onchocerciasis, within Central Africa. There are no effective drug cures or vaccines available to treat loiasis safely. Here we review recent advances in loiasis preclinical platform technologies, including novel in vitro culturing systems, animal models and innovations in experimental infections of the L. loa vector, Chrysops, that have facilitated access to all L. loa filarial life-cycle stages. We detail applications of these new model systems in anti-filarial drug screening, diagnostic development, immunology, and pathophysiology research. Finally, we provide an overview of how loiasis preclinical platforms may be further utilized in translational medicine applications to support the development of much needed new interventions against filarial NTDs.
Effects of Maternal Deprivation on the Prefrontal Cortex of Male Rats: Cellular, Neurochemical, and Behavioral Outcomes
Authors: Poleksic Joko , Aksic Milan , Kapor Slobodan , Aleksic Dubravka , Stojkovic Tihomir , Radovic Marina , Djulejic Vuk , Markovic Branka , Stamatakis Antonios
Published: November 2021

Stressful events experienced during early life are associated with increased vulnerability of developing psychopathology in adulthood. In the present study, we exposed 9-day-old Wistar rats to 24 h maternal deprivation (MD) with the aim to investigate the impact of early life stress (ELS) on morphological, biochemical, and functional aspects of the prefrontal cortex (PFC), a brain region particularly sensitive to stress. We found that in the superficial medial orbital cortex (MO), young adult male rats had reduced density of GAD67 and CCK immunopositive cells, while the rostral part of the ventral lateral orbital cortex (roVLO) showed a decrease in the density of GAD67 immunopositive cells in both superficial and deep layers. In addition, the superficial rostral part of area 1 of the cingulate cortex (roCg1) and deep prelimbic cortex (PrL) was also affected by MD indicated by the reduction in PV immunopositive cellular density. Furthermore, MD induced upregulation of brain-derived neurotrophic factor (BDNF), while it did not affect the overall expression of Iba1 in neonatal or young adult PFC as measured by Western blot, however, microglial activation in young adult MD rats was detected immunohistochemically in deep layers of MO and infralimbic cortex (IL). Interestingly, when young adult male rats were subjected to a behavioral flexibility test in a T-maze, MD rats showed a subtle impairment in T-maze reversal learning indicating a mildly affected PFC function. Taken together, our findings demonstrated that MD reduced the density of interneurons and induced microglial activation, in particular, PFC areas at young adulthood, and could alter synaptic plasticity accompanied by PFC dysfunction.
TUB and ZNF532 Promote the Atoh1-Mediated Hair Cell Regeneration in Mouse Cochleae
Authors: Xu Zhenhang , Rai Vikrant , Zuo Jian
Published: November 2021

Hair cell (HC) regeneration is a promising therapy for permanent sensorineural hearing loss caused by HC loss in mammals. Atoh1 has been shown to convert supporting cells (SCs) to HCs in neonatal cochleae; its combinations with other factors can improve the efficiency of HC regeneration. To identify additional transcription factors for efficient Atoh1-mediated HC regeneration, here we optimized the electroporation procedure for explant culture of neonatal mouse organs of Corti and tested multiple transcription factors, Six2, Ikzf2, Lbh, Arid3b, Hmg20 a, Tub, Sall1, and Znf532, for their potential to promote Atoh1-mediated conversion of SCs to HCs. These transcription factors are expressed highly in HCs but differentially compared to the converted HCs based on previous studies, and are also potential co-reprograming factors for Atoh1-mediated SC-to-HC conversion by literature review. P0.5 cochlear explants were electroporated with these transcription factors alone or jointly with Atoh1. We found that Sox2+ progenitors concentrated within the lateral greater epithelial ridge (GER) can be electroporated efficiently with minimal HC damage. Atoh1 ectopic expression promoted HC regeneration in Sox2+ lateral GER cells. Transcription factors Tub and Znf532, but not the other six tested, promoted the HC regeneration mediated by Atoh1, consistent with previous studies that Isl1 promotes Atoh1-mediated HC conversionex vivo and in vivo and that both Tub and Znf532 are downstream targets of Isl1. Thus, our studies revealed an optimized electroporation method that can transfect the Sox2+ lateral GER cells efficiently with minimal damage to the endogenous HCs. Our results also demonstrate the importance of the Isl1/Tub/Znf532 pathway in promoting Atoh1-mediated HC regeneration.
Optimizing Fixation Filters for Eye-Tracking on Small Screens
Authors: Trabulsi Julia , Norouzi Kian , Suurmets Seidi , Storm Mike , Ramsøy Thomas Zoëga
Published: November 2021

The study of consumer responses to advertising has recently expanded to include the use of eye-tracking to track the gaze of consumers. The calibration and validation of eye-gaze have typically been measured on large screens in static, controlled settings. However, little is known about how precise gaze localizations and eye fixations are on smaller screens, such as smartphones, and in moving feed-based conditions, such as those found on social media websites. We tested the precision of eye-tracking fixation detection algorithms relative to raw gaze mapping in natural scrolling conditions. Our results demonstrate that default fixation detection algorithms normally employed by hardware providers exhibit suboptimal performance on mobile phones. In this paper, we provide a detailed account of how different parameters in eye-tracking software can affect the validity and reliability of critical metrics, such as Percent Seen and Total Fixation Duration. We provide recommendations for producing improved eye-tracking metrics for content on small screens, such as smartphones, and vertically moving environments, such as a social media feed. The adjustments to the fixation detection algorithm we propose improves the accuracy of Percent Seen by 19% compared to a leading eye-tracking provider’s default fixation filter settings. The methodological approach provided in this paper could additionally serve as a framework for assessing the validity of applied neuroscience methods and metrics beyond mobile eye-tracking.
Non-human Primate Models to Explore the Adaptive Mechanisms After Stroke
Authors: Higo Noriyuki
Published: November 2021

The brain has the ability to reconstruct neural structures and functions to compensate for the brain lesions caused by stroke, although it is highly limited in primates including humans. Animal studies in which experimental lesions were induced in the brain have contributed to the current understanding of the neural mechanisms underlying functional recovery. Here, I have highlighted recent advances in non-human primate models using primate species such as macaques and marmosets, most of which have been developed to study the mechanisms underlying the recovery of motor functions after stroke. Cortical lesion models have been used to investigate motor recovery after lesions to the cortical areas involved in movements of specific body parts. Models of a focal stroke at the posterior internal capsule have also been developed to bridge the gap between the knowledge obtained by cortical lesion models and the development of intervention strategies because the severity and outcome of motor deficits depend on the degree of lesions to the region. This review will also introduce other stroke models designed to study the plastic changes associated with development and recovery from cognitive and sensory impairments. Although further validation and careful interpretation are required, considering the differences between non-human primate brains and human brains, studies using brain-lesioned non-human primates offer promise for improving translational outcomes.
Monitoring and Managing BTK Inhibitor Treatment-Related Adverse Events in Clinical Practice
Authors: O’Brien Susan M. , Brown Jennifer R. , Byrd John C. , Furman Richard R. , Ghia Paolo , Sharman Jeff P. , Wierda William G.
Published: November 2021

Bruton tyrosine kinase (BTK) inhibitors represent an important therapeutic advancement for B cell malignancies. Ibrutinib, the first-in-class BTK inhibitor, is approved by the US FDA to treat patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL; after ≥1 prior therapy); and by the European Medicines Agency (EMA) for adult patients with relapsed/refractory (R/R) MCL and patients with CLL. Ibrutinib treatment can be limited by adverse events (AEs) including atrial fibrillation, arthralgias, rash, diarrhea, and bleeding events, leading to drug discontinuation in 4%–26% of patients. Acalabrutinib, a second-generation BTK inhibitor, is approved by the FDA to treat adult patients with CLL/SLL or MCL (relapsed after 1 prior therapy); and by the EMA to treat adult patients with CLL or R/R MCL. The most common AE associated with acalabrutinib is headache of limited duration, which occurs in 22%–51% of patients, and is mainly grade 1–2 in severity, with only 1% of patients experiencing grade ≥3 headache. Furthermore, acalabrutinib is associated with a low incidence of atrial fibrillation. Zanubrutinib, a selective next-generation covalent BTK inhibitor, is approved by the FDA to treat adult patients with MCL who have received ≥1 prior therapy, and is under investigation for the treatment of patients with CLL. In the phase 3 SEQUOIA trial in patients with CLL, the most common grade ≥3 AEs were neutropenia/neutrophil count decreased and infections. This review provides an overview of BTK inhibitor-related AEs in patients with CLL, and strategies for their management.
Case Report: Potocki-Lupski Syndrome in Five Siblings
Authors: Grama Alina , Sîrbe Claudia , Miclea Diana , Cǎinap Simona Sorana , Huniadi Delia , Bulata Bogdan , Pop Tudor Lucian
Published: November 2021

Potocki-Lupski syndrome (PTLS) is a rare developmental disorder resulting from the partial duplication of the short arm of chromosome 17. Affected children may have hypotonia, facial dysmorphism, or neurological abnormalities. PTLS is also frequently associated with failure to thrive due to swallowing difficulties or growth hormone deficiency. We report the first Romanian family (a mother and her five children) diagnosed with PTLS (17p11.2 microduplication). Fortunately, they present a less severe form of the disease. The neurological manifestations (speech delay, mild intellectual disability) are associated with craniofacial dysmorphism (microcephaly, micrognathia, triangular face, broad forehead, long chin, prominent ears, dolichocephaly, down slanting palpebral fissures). The diagnostic was established using a multiplex ligation-dependent probe amplification technique (MLPA) test, which detected the duplication of three regions of the 17p11.2 chromosome (RAI1, DRC3-6, LLGL1-4RA). Children with PTLS have specific phenotypes (craniofacial dysmorphism or neurological manifestations), which must draw the pediatrician's attention to a possible genetic condition. However, every child with this disease is unique and may have a different clinical presentation. A multi-disciplinary team is needed for the management of these patients. The parent's counseling and genetic advice are essential for a family with children with PTLS.
Optimization of Initial Dose Regimen for Sirolimus in Pediatric Patients With Lymphangioma
Authors: Chen Xiao , Wang Dongdong , Wang Guangfei , Huang Yidie , Yu Xin , Lu Jinmiao , Zhai Xiaowen , Xu Hong , Li Zhiping
Published: November 2021

Sirolimus is an effective oral treatment for pediatric patients with lymphangioma. The present clinical study in 15 children (0.12–16.39 years of age) examines the effects of underlying factors on sirolimus concentrations through application of a population pharmacokinetic model. Using Monte Carlo simulation, an initial dose regimen for sirolimus in pediatric patients with lymphangioma is presented. It is found that the lower the body weight, the higher the clearance rate and sirolimus clearances are 0.31–0.17 L/h/kg in pediatric patients with lymphangioma whose weights are 5–60 kg, respectively. The doses of sirolimus, 0.07, 0.06, 0.05 mg/kg/day are recommended for weights of 5–10, 10–24.5 and 24.5–60 kg in children with lymphangioma. This study is the first to establish a population pharmacokinetic model for sirolimus and to recommend initial doses in pediatric patients with lymphangioma. Large scale, prospective studies are needed in the future.
Antihypertensive Drug Use and the Risk of Depression: A Systematic Review and Network Meta-analysis
Authors: Li Ying , Fan Yuanming , Sun Yangyang , Alolga Raphael N. , Xiao Pingxi , Ma Gaoxiang
Published: November 2021

Background: Although numerous cohort studies have reported an association between antihypertensives use and depression, the exact effect of antihypertensives on depression remains unclear.

Objective: To clarify the association between antihypertensives use and risk of depression.

Methods: We retrieved relevant literature using PubMed database until August 30, 2021. Four main classes of antihypertensives, thus, angiotensin antagonists, beta blockers, calcium channel blockers and diuretics were studied. The incidence of depression was pooled based on a single drug category. Network meta-analyses were conducted to comprehensively assess the effects of the four classes of antihypertensives on the risk of depression.

Results: A total of nine out of 9,557 studies involving 414,873 subjects were retrieved. The pooled results showed a positive association between the use of calcium channel blockers and symptoms of depression [odds ratio (OR): 1.09, 95% confidence interval (CI):1.06–1.13], while use of the angiotensin antagonists, beta blockers and diuretics was not associated with risk of depression. Subgroup analysis suggested a significant relationship between beta blockers usage and risk of depression in cohort studies (OR:1.21, 95% CI: 1.16–1.26). The results of network meta-analysis indicated that all other three classes of drugs increased the risk of depression: angiotensin antagonists (OR: 1.30, 95% CI: 1.04–1.63), beta blockers (OR: 1.53, 95% CI: 1.22–1.91), and calcium channel blockers (OR: 1.40, 95% CI: 1.12–1.75), compared with diuretics.

Conclusion: In conclusion, our results indicate that the use of angiotensin antagonists, beta blockers and calcium channel blockers are potential risk factors of depression.
Genome-Wide Analysis of CCT Transcript Factors to Identify Genes Contributing to Photoperiodic Flowering in Oryza rufipogon
Authors: Peng Xin , Tun Win , Dai Shuang-feng , Li Jia-yue , Zhang Qun-jie , Yin Guo-ying , Yoon Jinmi , Cho Lae-hyeon , An Gynheung , Gao Li-zhi
Published: November 2021

Photoperiod sensitivity is a dominant determinant for the phase transition in cereal crops. CCT (CONSTANS, CO-like, and TOC1) transcription factors (TFs) are involved in many physiological functions including the regulation of the photoperiodic flowering. However, the functional roles of CCT TFs have not been elucidated in the wild progenitors of crops. In this study, we identified 41 CCT TFs, including 19 CMF, 17 COL, and five PRR TFs in Oryza rufipogon, the presumed wild ancestor of Asian cultivated rice. There are thirty-eight orthologous CCT genes in Oryza sativa, of which ten pairs of duplicated CCT TFs are shared with O. rufipogon. We investigated daily expression patterns, showing that 36 OrCCT genes exhibited circadian rhythmic expression. A total of thirteen OrCCT genes were identified as putative flowering suppressors in O. rufipogon based on rhythmic and developmental expression patterns and transgenic phenotypes. We propose that OrCCT08, OrCCT24, and OrCCT26 are the strong functional alleles of rice DTH2, Ghd7, and OsPRR37, respectively. The SD treatment at 80 DAG stimulated flowering of the LD-grown O. rufipogon plants. Our results further showed that the nine OrCCT genes were significantly downregulated under the treatment. Our findings would provide valuable information for the construction of photoperiodic flowering regulatory network and functional characterization of the CCT TFs in both O. rufipogon and O. sativa.
The Totalising Nature of Secure and Forensic Mental Health Services in England and Wales
Authors: Markham Sarah
Published: November 2021

This evidence-based opinion piece explores the totalising risk averse nature of secure and forensic mental health services and associated iatrogenic harms in England and Wales. Drawing on the research literature I consider the various influences, both external and internal which impact on the provision of such services and how both the therapeutic alliance and recovery potential for patients may be improved. Especial attention is paid to the deployment of restrictive practise, practitioner attitudes, the potential for non-thinking, and how these may impact on decision-making and the care and treatment of mentally disordered offenders.
Dose-Effects Models for Space Radiobiology: An Overview on Dose-Effect Relationships
Authors: Strigari Lidia , Strolin Silvia , Morganti Alessio Giuseppe , Bartoloni Alessandro
Published: November 2021

Space radiobiology is an interdisciplinary science that examines the biological effects of ionizing radiation on humans involved in aerospace missions. The dose-effect models are one of the relevant topics of space radiobiology. Their knowledge is crucial for optimizing radioprotection strategies (e.g., spaceship and lunar space station-shielding and lunar/Mars village design), the risk assessment of the health hazard related to human space exploration, and reducing damages induced to astronauts from galactic cosmic radiation. Dose-effect relationships describe the observed damages to normal tissues or cancer induction during and after space flights. They are developed for the various dose ranges and radiation qualities characterizing the actual and the forecast space missions [International Space Station (ISS) and solar system exploration]. Based on a Pubmed search including 53 papers reporting the collected dose-effect relationships after space missions or in ground simulations, 7 significant dose-effect relationships (e.g., eye flashes, cataract, central nervous systems, cardiovascular disease, cancer, chromosomal aberrations, and biomarkers) have been identified. For each considered effect, the absorbed dose thresholds and the uncertainties/limitations of the developed relationships are summarized and discussed. The current knowledge on this topic can benefit from further in vitro and in vivo radiobiological studies, an accurate characterization of the quality of space radiation, and the numerous experimental dose-effects data derived from the experience in the clinical use of ionizing radiation for diagnostic or treatments with doses similar to those foreseen for the future space missions. The growing number of pooled studies could improve the prediction ability of dose-effect relationships for space exposure and reduce their uncertainty level. Novel research in the field is of paramount importance to reduce damages to astronauts from cosmic radiation before Beyond Low Earth Orbit exploration in the next future. The study aims at providing an overview of the published dose-effect relationships and illustrates novel perspectives to inspire future research.
When We Feel “Like-Minded” Is It Only in Our Minds?
Authors: Ravreby Inbal , Yeshurun Yaara
Published: November 2021

Much of our time is spent communicating with other people, including family, friends, and teachers. When we talk with others, we are interested in understanding one another, and we can often sense when the communication is good. Scientists suggest that synchronization—a state in which things happen simultaneously—contributes to good communication. Research has found that synchronization in facial expressions, ways of speaking, body movements, pulse, breath, and even brain activity, are related to positive communication. In this article, we will describe the role of synchronization and discuss the possibility that when we feel we are “riding on the same wave” with the person we are talking to, we actually are on the same physical and mental wave—synchronized.
Fusion of Technology in Cochlear Implantation Surgery: Investigation of Fluoroscopically Assisted Robotic Electrode Insertion
Authors: Jablonski Greg Eigner , Falkenberg-Jensen Benedicte , Bunne Marie , Iftikhar Muneera , Greisiger Ralf , Opheim Leif Runar , Korslund Hilde , Myhrum Marte , Sørensen Torquil Mcdonald
Published: November 2021

The HEARO cochlear implantation surgery aims to replace the conventional wide mastoidectomy approach with a minimally invasive direct cochlear access. The main advantage of the HEARO access would be that the trajectory accommodates the optimal and individualized insertion parameters such as type of cochlear access and trajectory angles into the cochlea. To investigate the quality of electrode insertion with the HEARO procedure, the insertion process was inspected under fluoroscopy in 16 human cadaver temporal bones. Prior to the insertion, the robotic middle and inner ear access were performed through the HEARO procedures. The status of the insertion was analyzed on the post-operative image with Siemens Artis Pheno (Siemens AG, Munich, Germany). The completion of the full HEARO procedure, including the robotic inner ear access and fluoroscopy electrode insertion, was possible in all 16 cases. It was possible to insert the electrode in all 16 cases through the drilled tunnel. However, one case in which the full cochlea was not visible on the post-operative image for analysis was excluded. The post-operative analysis of the electrode insertion showed an average insertion angle of 507°, which is equivalent to 1.4 turns of the cochlea, and minimal and maximal insertion angles were recorded as 373° (1 cochlear turn) and 645° (1.8 cochlear turn), respectively. The fluoroscopy inspection indicated no sign of complications during the insertion.
Mental Model of Malaysian Pig Farmers in Implementing Disease Prevention and Control Practices
Authors: Suit-B Yong , Hassan Latiffah , Krauss Steven Eric , Ooi Peck Toung , Ramanoon Siti Zubaidah , Yasmin Abd Rahaman , Epstein Jonathan H.
Published: November 2021

The 1998 Nipah virus outbreak in Malaysia resulted in major financial losses to the multi-million-dollar swine industry. While productivity and biosecurity of pig farms have improved since, biosecurity in some farms remains substandard with farmers struggling to adapt to current national pig farming policies. Farm viability and animal health depends on farmers' role as decision-makers in managing disease threats and other aspects of farm management. This study aimed to describe the mental model of farmers in making decisions about disease prevention and control measures during the 1998 Nipah virus outbreak, and in 2019, 20 years after the last reported Nipah case. Using a qualitative approach, in-depth, semi-structured interviews with 12 pig farmers (mostly small-scale or medium-scale farms) were conducted in three states in Malaysia. Data were analyzed via inductive content analysis. Thirty-six unique dimensions in the mental model were identified, representing six interrelated themes corresponding to participants' decision making related to disease prevention and control: drivers of action to prevent and control disease; perception of practice options; individual determinants of familiar practices; external social factors; external economic factors; and additional external factors. Key drivers of disease control and prevention responses during the Nipah outbreak included heightened perception of risk, emotions, perceived economic loss, and subjective norms whereas key drivers in 2019 included perception of risk, perceived effectiveness, perceived benefits, and other dimensions such as perception of the future, perceived economic cost, barriers, and loss. An unfavorable future outlook, perceived economic factors, and socio-political and personal factors currently hinders farm improvement and adoption of Pig Farming Areas (PFAs) and Modern Pig Farming (MPF) systems. Private sector service providers and veterinarians are highly influential in advocating for good biosecurity, herd health, and animal health intervention practices. Insights gained can inform the development of strategic policies and interventions.
Zero-Crossing Point Detection of Sinusoidal Signal in Presence of Noise and Harmonics Using Deep Neural Networks
Authors: Veeramsetty Venkataramana , Edudodla Bhavana Reddy , Salkuti Surender Reddy
Published: November 2021

Zero-crossing point detection is necessary to establish a consistent performance in various power system applications, such as grid synchronization, power conversion and switch-gear protection. In this paper, zero-crossing points of a sinusoidal signal are detected using deep neural networks. In order to train and evaluate the deep neural network model, new datasets for sinusoidal signals having noise levels from 5% to 50% and harmonic distortion from 10% to 50% are developed. This complete study is implemented in Google Colab using deep learning framework Keras. Results shows that the proposed deep learning model is able to detect zero-crossing points in a distorted sinusoidal signal with good accuracy.
In Situ Non-Destructive Temporal Measurements of the Rhizosphere Microbiome ‘Hot-Spots’ Using Metaproteomics
Authors: White Richard Allen , Rosnow Joshua , Piehowski Paul D. , Brislawn Colin J. , Moran James J.
Published: November 2021

Rhizosphere arguably embodies the most diverse microbial ecosystem on the planet, yet it is largely a functional ‘black box’ of belowground plant-microbiome interactions. The rhizosphere is the primary site of entry for subsurface injection of fixed carbon (C) into soil with impacts on local to global scale C biogeochemistry and ultimately Earth’s climate. While spatial organization of rhizosphere is central to its function, small scale and steep microbial and geochemical gradients within this dynamic region make it easily disrupted by sampling. The significant challenge presented by sampling blocks elucidation of discreet functions, drivers, and interactions within rhizosphere ecosystems. Here, we describe a non-destructive sampling method linked to metaproteomic analysis in order to measure temporal shifts in the microbial composition and function of rhizosphere. A robust, non-destructive method of sampling microbial hotspots within rhizosphere provides an unperturbed window into the elusive functional interactome of this system over time and space.
Integrative Effects of Treated Wastewater and Synthetic Fertilizers on Productivity, Energy Characteristics, and Elements Uptake of Potential Energy Crops in an Arid Agro-Ecosystem
Authors: Al-Suhaibani Nasser , Seleiman Mahmoud F. , El-Hendawy Salah , Abdella Kamel , Alotaibi Majed , Alderfasi Ali
Published: November 2021

Using wastewater in agriculture is a desirable alternative source of irrigation and is gaining attraction worldwide. Therefore, this study was designed to assess the effect of treated municipal wastewater (TWW) and groundwater (GW), along with half and full doses of the recommended NPK dose on the plant growth, total biomass, gross energy, and macro- and trace element content and uptake of safflower (Carthamus tinctorius L.), canola (Brassica napus L.), and triticale (X Triticosecale Wittmack) grown in old and virgin soil as potential bioenergy crops. The results showed that crops planted in old or virgin soil irrigated with TWW had higher values of plant height, leaf area per plant, total chlorophyll content, total biomass, and gross and net energy contents compared to those irrigated with GW grown in virgin soil. Similarly, crops grown in old soil irrigated with TWW showed higher concentrations in dry matter and uptake for both macronutrients (N, P, and K) and trace elements (B, Zn, Mn, Cu, Cd, Pb, and Ni) compared to those planted in virgin soil and irrigated with GW. Furthermore, the application of the recommended half dose of NPK in old and virgin soil irrigated with TWW showed occasionally comparable results to that of a full recommended dose of NPK for most of the measured parameters. Importantly, the recommended half dose applied to old soil irrigated with TWW resulted in a significant improvement in all measured parameters compared to virgin soil irrigated with GW, along with a full recommended dose of NPK. Briefly, TWW can be used to irrigate crops grown for bioenergy purposes, since it did not pose any harmful effect for energy crops. In addition, it provides additional nutrients to soil and thus decreases the required rate of synthetic fertilizer by up to 50% without any significant decreases in the final production of crops.
The Brown Marmorated Stink Bug (Halyomorpha halys Stål.) Influences Pungent and Non-Pungent Capsicum Cultivars’ Pre- and Post-Harvest Quality
Authors: Zamljen Tilen , Veberic Robert , Hudina Metka , Slatnar Ana
Published: November 2021

Halyomorpha halys is an important invasive pest that causes severe damage to fruits and vegetables. Peppers are susceptible to infestation by H. halys, resulting in yield losses. Plants respond to the insect infestation with a metabolic response. With this study, we attempted to determine the intensity of the metabolic response of infested peppers, how pungent and non-pungent peppers react to the infestation, and how the H. halys affects the post-harvest quality of both cultivars. The shelf life of the infested peppers did not change compared to the control treatments. We observed a drastic decrease in metabolite levels after storage in all three treatments in both cultivars, especially capsaicinoids, with an approximate decrease of 30% in the pericarp and 95% in the placenta of the pungent ‘Eris F1’. In some cases, the accumulation of metabolites was not limited to the fruit exposed to the H. halys infestation, but to the entire plant. We observed a 15-fold increase in capsaicinoid content in the infested fruits of cultivar ‘Eris F1’ and a 4-fold increase in the pericarp of cultivar ‘Lombardo tago’, which could lead to a possible further study on the defensive function of capsaicinoids and their use against H. halys.