bluuebunny/crossref_metadata_2025 huggingface dataset:
The Antiviral Activity of Bacterial, Fungal, and Algal Polysaccharides as Bioactive Ingredients: Potential Uses for Enhancing Immune Systems and Preventing Viruses
Authors: Chaisuwan Worraprat , Phimolsiripol Yuthana , Chaiyaso Thanongsak , Techapun Charin , Leksawasdi Noppol , Jantanasakulwong Kittisak , Rachtanapun Pornchai , Wangtueai Sutee , Sommano Sarana Rose , You SangGuan , Regenstein Joe M. , Barba Francisco J. , Seesuriyachan Phisit
Published: November 2021

Viral infections may cause serious human diseases. For instance, the recent appearance of the novel virus, SARS-CoV-2, causing COVID-19, has spread globally and is a serious public health concern. The consumption of healthy, proper, functional, and nutrient-rich foods has an important role in enhancing an individual's immune system and preventing viral infections. Several polysaccharides from natural sources such as algae, bacteria, and fungi have been considered as generally recognized as safe (GRAS) by the US Food and Drug Administration. They are safe, low-toxicity, biodegradable, and have biological activities. In this review, the bioactive polysaccharides derived from various microorganisms, including bacteria, fungi, and algae were evaluated. Antiviral mechanisms of these polysaccharides were discussed. Finally, the potential use of microbial and algal polysaccharides as an antiviral and immune boosting strategy was addressed. The microbial polysaccharides exhibited several bioactivities, including antioxidant, anti-inflammatory, antimicrobial, antitumor, and immunomodulatory activities. Some microbes are able to produce sulfated polysaccharides, which are well-known to exert a board spectrum of biological activities, especially antiviral properties. Microbial polysaccharide can inhibit various viruses using different mechanisms. Furthermore, these microbial polysaccharides are also able to modulate immune responses to prevent and/or inhibit virus infections. There are many molecular factors influencing their bioactivities, e.g., functional groups, conformations, compositions, and molecular weight. At this stage of development, microbial polysaccharides will be used as adjuvants, nutrient supplements, and for drug delivery to prevent several virus infections, especially SARS-CoV-2 infection.
OXCT1 Enhances Gemcitabine Resistance Through NF-κB Pathway in Pancreatic Ductal Adenocarcinoma
Authors: Ding Jinsheng , Li Hui , Liu Yang , Xie Yongjie , Yu Jie , Sun Huizhi , Xiao Di , Zhou Yizhang , Bao Li , Wang Hongwei , Gao Chuntao
Published: November 2021

Background

Pancreatic ductal adenocarcinoma (PDAC) is a type of malignant tumor with a five-year survival rate of less than 10%. Gemcitabine (GEM) is the most commonly used drug for PDAC chemotherapy. However, a vast majority of patients with PDAC develop resistance after GEM treatment.

Methods

We screened for GEM resistance genes through bioinformatics analysis. We used immunohistochemistry to analyze 3-oxoacid CoA-transferase 1 (OXCT1) expression in PDAC tissues. The survival data were analyzed using the Kaplan–Meier curve. The expression levels of the genes related to OXCT1 and the NF-κB signaling pathway were quantified using real−time quantitative PCR and western blot analyses. We performed flow cytometry to detect the apoptosis rate. Colony formation assay was performed to measure the cell proliferation levels. The cytotoxicity assays of cells were conducted using RTCA. The downstream pathway of OXCT1 was identified via the Gene Set Enrichment Analysis. Tumor growth response to GEM in vivo was also determined in mouse models.

Results

Bioinformatics analysis revealed that OXCT1 is the key gene leading to GEM resistance. Patients with high OXCT1 expression exhibited short relapse-free survival under GEM treatment. OXCT1 overexpression in PDAC cell lines exerted inhibitory effect on apoptosis after GEM treatment. However, the down-regulation of OXCT1 showed the opposite effect. Blocking the NF-κB signaling pathway also reduced GEM resistance of PDAC cells. Tumor growth inhibition induced by GEM in vivo reduced after OXCT1 overexpression. Moreover, the effect of OXCT1 on GEM refractoriness in PDAC cell lines was reversed through using an NF-κB inhibitor.

Conclusion

OXCT1 promoted GEM resistance in PDAC via the NF-κB signaling pathway both in vivo and in vitro. Our results suggest that OXCT1 could be used as a potential therapeutic target for patients with PDAC.
Primary Yolk Sac Tumor in the Cerebellar Hemisphere: A Case Report and Literature Review of the Rare Tumor
Authors: Wu Na , Chen Qiang , Chen Meng , Ning Jinbo , Peng Shulei , Zhang Taotao , Zhong Wen , Duan Song , Cheng Chongjie , Xie Yimin
Published: November 2021

Yolk sac tumor (YST) is one of rare malignant germ cell tumors (GCTs). Primary intracranial YST, also endodermal sinus tumor (EST), is a quite rare type of brain tumor. Here, we report a case of YST, review the relevant literature, and propose a treatment strategy for this rare tumor. A 6-year-old boy initially manifested symptoms of dizziness and vomiting. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large irregular oval tumor in the cerebellar hemisphere. We subtotally removed the tumor by microsurgery through the left suboccipital approach. Immunohistochemical staining showed that alpha fetoprotein (AFP) was positive and the Ki-67 proliferation index was high (60%), suggesting a germ cell tumor. After 3 months of follow-up, neither recurrence of tumor nor complications were found in the patient. The diagnosis of YST should be confirmed on the basis of clinical manifestations, neuroimaging and pathological findings. Gross total resection (GTR) is an ideal treatment for YST. However, due to the location of the tumor, GTR is usually difficult, and the rate of postoperative complications is high. This reported case shows that subtotal resection can be a good treatment strategy for YST.
Database-Guided Analysis for Immunophenotypic Diagnosis and Follow-Up of Acute Myeloid Leukemia With Recurrent Genetic Abnormalities
Authors: Aanei Carmen-Mariana , Veyrat-Masson Richard , Selicean Cristina , Marian Mirela , Rigollet Lauren , Trifa Adrian Pavel , Tomuleasa Ciprian , Serban Adrian , Cherry Mohamad , Flandrin-Gresta Pascale , Tardy Emmanuelle Tavernier , Guyotat Denis , Campos Catafal Lydia
Published: November 2021

Acute myeloid leukemias (AMLs) are hematologic malignancies with varied molecular and immunophenotypic profiles, making them difficult to diagnose and classify. High-dimensional analysis algorithms might increase the utility of multicolor flow cytometry for AML diagnosis and follow-up. The objective of the present study was to assess whether a Compass database-guided analysis can be used to achieve rapid and accurate diagnoses. We conducted this study to determine whether this method could be employed to pilote the genetic and molecular tests and to objectively identify different-from-normal (DfN) patterns to improve measurable residual disease follow-up in AML. Three Compass databases were built using Infinicyt 2.0 software, including normal myeloid-committed hematopoietic precursors (n = 20) and AML blasts harboring the most frequent recurrent genetic abnormalities (n = 50). The diagnostic accuracy of the Compass database-guided analysis was evaluated in a prospective validation study (125 suspected AML patients). This method excluded AML associated with the following genetic abnormalities: t(8;21), t(15;17), inv(16), and KMT2A translocation, with 92% sensitivity [95% confidence interval (CI): 78.6%–98.3%] and a 98.5% negative predictive value (95% CI: 90.6%–99.8%). Our data showed that the Compass database-guided analysis could identify phenotypic differences between AML groups, representing a useful tool for the identification of DfN patterns.
Integrative Radiogenomics Approach for Risk Assessment of Postoperative and Adjuvant Chemotherapy Benefits for Gastric Cancer Patients
Authors: Jin Yin , Xu Yilun , Li Yanyan , Chen Renpin , Cai Weiyang
Published: November 2021

Gastric cancer (GC) is a typical heterogeneous malignant tumor, whose insensitivity to chemotherapy is a common cause of tumor recurrence and metastasis. There is no doubt regarding the effectiveness of adjuvant chemotherapy (ACT) for GC, but the population for whom it is indicated and the selection of specific options remain the focus of present research. The conventional pathological TNM prediction focuses on cancer cells to predict prognosis, while they do not provide sufficient prediction. Enhanced computed tomography (CT) scanning is a validated tool that assesses the involvement of careful identification of the tumor, lymph node involvement, and metastatic spread. Using the radiomics approach, we selected the least absolute shrinkage and selection operator (LASSO) Cox regression model to build a radiomics signature for predicting the overall survival (OS) and disease-free survival (DFS) of patients with complete postoperative gastric cancer and further identifying candidate benefits from ACT. The radiomics trait-associated genes captured clinically relevant molecular pathways and potential chemotherapeutic drug metabolism mechanisms. Our results of precise surrogates using radiogenomics can lead to additional benefit from adjuvant chemotherapy and then survival prediction in postoperative GC patients.
Novel Nanoparticle-Based Cancer Treatment, Effectively Inhibits Lung Metastases and Improves Survival in a Murine Breast Cancer Model
Authors: Kraus Sarah , Khandadash Raz , Hof Raphael , Nyska Abraham , Sigalov Ekaterina , Eltanani Moshe , Rukenstein Pazit , Rabinovitz Ricarina , Kassem Rana , Antebi Adam , Shalev Ofer , Cohen-Erner Moshe , Goss Glenwood , Cyjon Arnoldo
Published: November 2021

Sarah Nanoparticles (SaNPs) are unique multicore iron oxide-based nanoparticles, developed for the treatment of advanced cancer, following standard care, through the selective delivery of thermal energy to malignant cells upon exposure to an alternating magnetic field. For their therapeutic effect, SaNPs need to accumulate in the tumor. Since the potential accumulation and associated toxicity in normal tissues are an important risk consideration, biodistribution and toxicity were assessed in naïve BALB/c mice. Therapeutic efficacy and the effect on survival were investigated in the 4T1 murine model of metastatic breast cancer. Toxicity evaluation at various timepoints did not reveal any abnormal clinical signs, evidence of alterations in organ function, nor histopathologic adverse target organ toxicity, even after a follow up period of 25 weeks, confirming the safety of SaNP use. The biodistribution evaluation, following SaNP administration, indicated that SaNPs accumulate mainly in the liver and spleen. A comprehensive pharmacokinetics evaluation, demonstrated that the total percentage of SaNPs that accumulated in the blood and vital organs was ~78%, 46%, and 36% after 4, 13, and 25 weeks, respectively, suggesting a time-dependent clearance from the body. Efficacy studies in mice bearing 4T1 metastatic tumors revealed a 49.6% and 70% reduction in the number of lung metastases and their relative size, respectively, in treated vs. control mice, accompanied by a decrease in tumor cell viability in response to treatment. Moreover, SaNP treatment followed by alternating magnetic field exposure significantly improved the survival rate of treated mice compared to the controls. The median survival time was 29 ± 3.8 days in the treated group vs. 21.6 ± 4.9 days in the control, p-value 0.029. These assessments open new avenues for generating SaNPs and alternating magnetic field application as a potential novel therapeutic modality for metastatic cancer patients.
Contribution of miRNAs in the Pathogenesis of Breast Cancer
Authors: Ghafouri-Fard Soudeh , Khanbabapour Sasi Ali , Abak Atefe , Shoorei Hamed , Khoshkar Ali , Taheri Mohammad
Published: November 2021

Breast cancer is the most frequently diagnosed cancer among females. Gene expression profiling methods have shown the deregulation of several genes in breast cancer samples and have confirmed the heterogeneous nature of breast cancer at the genomic level. microRNAs (miRNAs) are among the recently appreciated contributors in breast carcinogenic processes. These small-sized transcripts have been shown to partake in breast carcinogenesis through modulation of apoptosis, autophagy, and epithelial–mesenchymal transition. Moreover, they can confer resistance to chemotherapy. Based on the contribution of miRNAs in almost all fundamental aspects of breast carcinogenesis, therapeutic intervention with their expression might affect the course of this disorder. Moreover, the presence of miRNAs in the peripheral blood of patients potentiates these transcripts as tools for non-invasive diagnosis of breast cancer.
Comprehensive Analysis of the Expression and Prognosis for MMPs in Human Colorectal Cancer
Authors: Yu Jing , He Zhen , He Xiaowen , Luo Zhanhao , Lian Lei , Wu Baixing , Lan Ping , Chen Haitao
Published: November 2021

Background

Previous study implicated that genes of matrix metalloproteinase (MMP) family play an important role in tumor invasion, neoangiogenesis, and metastasis. However, the diverse expression patterns and prognostic values of 24 MMPs in colorectal cancer are yet to be analyzed.

Methods

In this study, by integrating public database and our data, we first investigated the expression levels and protein levels of MMPs in patients with colorectal cancer. Then, by using TCGA and GEO datasets, we evaluated the association of MMPs with clinicopathological parameters and prognosis of colorectal cancer. Finally, by using the cBioPortal online tool, we analyzed the alterations of MMPs and did the network and pathway analyses for MMPs and their nearby genes.

Results

We found that, MMP1, MMP3, MMP7, MMP9–MMP12, and MMP14 were consistently upregulated in public dataset and our samples. Whereas, MMP28 was consistently downregulated in public dataset and our samples. In the clinicopathological analyses, upregulated MMP11, MMP14, MMP16, MMP17, MMP19, and MMP23B were significantly associated with a higher tumor stage. In the survival analyses, upregulated MMP11, MMP14, MMP17, and MMP19 were significantly associated with a shorter progression-free survival (PFS) time and a shorter relapse-free (RFS) time.

Discussion

This study implied that MMP11, MMP14, MMP17, and MMP19 are potential targets of precision therapy for patients with colorectal cancer.
Evaluation of Caspase-1, Interleukin-1β, and Interleukin-18, in the Middle Ear Effusion in Children With Otitis Media With Effusion
Authors: Liu Shanshan , Guo Lining , Chen Min , Liu Wei , Li Yanhong , Wang Xiaoxu , Li Shilan , Zhang Jie , Ni Xin
Published: November 2021

Objectives: The present study aimed to assess the expression of caspase-1 and caspase-1-dependent processing of cytokines, such as interleukin (IL)-1β and IL-18, in the middle ear effusion of children with otitis media with effusion (OME) in order to identify the potential role of inflammasomes in OME.

Methods: This study included 29 children scheduled for myringotomy with the insertion of tympanostomy tubes due to OME. Middle ear effusion (MEE) was collected during the surgery. Caspase-1, IL-1β, and IL-18 were assayed using enzyme-linked immunosorbent assay kits. The levels were compared between those with mucoid and serous MEE and those with and without a history of ventilation tube insertion.

Results: Caspase-1, IL-1β, and IL-18 were detected in all samples. The caspase-1, IL-1β, and IL-18 levels did not significantly differ between mucoid samples and serous samples. No statistical significances were discovered in caspase-1, IL-1β, and IL-18 levels between with and without a history of ventilation tube groups. There was a significant negative correlation between IL-1β and IL-18 and the duration of OME (p < 0.05). However, no significant correlation was found between caspase-1 and disease duration.

Conclusions: Inflammasomes may participate in the inflammatory process of OME. IL-1β and IL-18 levels in the MEE decreased over time.
Aberrant Development of Enteric Glial Cells in the Colon of Hirschsprung's Disease
Authors: Zhou Tingting , Liu Wei , Yu Xiaofang , Cao Zengcai , Mu Weijing , Hou Peimin , Ren Chuantao , Li Aiwu
Published: November 2021

Objective: The aim of this study was to explore the development of enteric glial cells (EGCs) in different segments of Hirschsprung's disease (HSCR).

Methods: Colonic specimens from 35 children with HSCR were selected to analyze the relative expression of glial fibrillary acidic protein and S100 calcium-binding protein B using Western blotting and real-time fluorescence quantitative PCR. Immunofluorescence and immunohistochemical staining were performed to determine the distribution of myenteric EGCs and neuronal cells in different segments of HSCR.

Results: There was a trend of diminished protein and mRNA expression of glial fibrillary acidic protein and S100 calcium-binding protein B from the proximal, dilated, and transitional segments to the aganglionic segment (p < 0.05). Immunofluorescence and immunohistochemistry showed that the EGCs in the aganglionic, transitional, and dilated colonic muscles were morphologically abnormal, which was consistent with the dysplasia of myenteric neurons.

Conclusion: Aberrant development of myenteric EGCs was observed in the colon of HSCR, which may affect the survival of enteric neurons.
Screening for Coronavirus Disease 2019 (COVID-19) at the Pediatric Emergency Department During Different Pandemic Phases
Authors: Stacevičienė Indrė , Burokienė Sigita , Steponavičienė Aušra , Vaičiūnienė Daiva , Puronaitė Roma , Jankauskienė Augustina
Published: November 2021

The wide spectrum of COVID-19 symptoms complicates the selection of target groups for screening. We aimed to compare data of children screened for COVID-19 at the pediatric emergency department in Vilnius between different phases throughout 1 year (Phase I: March–May, 2020; Phase II: June–September, 2020; and Phase III: October, 2020–February, 2021) and to evaluate the possible predictors of the disease. SARS-CoV-2 PCR tests were positive for 2.7% of tested children (248/9,238), significantly higher during the Phase III (5.5%) compared with the Phase I (0.6%,p= 0.000) and Phase II (0.3%,p= 0.000). Infants and teenagers (12–17 years) accounted for a larger proportion of COVID-19 patients (24.6 and 26.2%, respectively) compared to other age groups: 1–2 years (18.9%), 3–6 years (14.9%), and 7–11 years (15.3%). There were more COVID-19 cases among children with a known SARS-CoV-2 exposure compared to those who did not declare any contact (18.2 vs. 1.1%,p= 0000). When symptoms were adjusted for age, gender and known exposure to SARS-CoV-2, we found that fever (OR 2.66; 95% CI 1.89–3.81), pharyngitis (OR 1.35; 95% CI 1.01–1.80), headache (OR 1.81; 95% CI 1.09–2.90), and anosmia/ageusia (OR 6.47; 95% CI 1.61–22.47) were the most significant predictors.

Conclusion:Although high numbers of testing were maintained throughout the year, the positive test results were significantly higher during the Phase III. Age (<1 year, 12–17 years), a history of exposure to SARS-CoV-2 and some symptoms, such as fever, pharyngitis, headache and anosmia/ageusia could aid in targeting groups for screening for COVID-19 in children.
Tubuloglomerular Disease With Cone-Shaped Epiphyses Associated With Hypomorphic Variant and a Novel p.Cys14Arg in the TTC21B Gene: A Case Report
Authors: Bezdíčka Martin , Zemková Dana , Skálová Sylva , Hovorková Eva , Podhola Miroslav , Burkert Jan , Zieg Jakub
Published: November 2021

Monogenic nephrotic syndrome (NS) is associated with a resistance to initial glucocorticoid therapy and causative variants, which may be found in several genes influencing podocyte stability and kidney development. The TTC21B gene, which encodes the retrograde intraflagellar transport protein IFT139, is found mostly in association with ciliopathies in humans. The role of this protein in podocyte cytoskeleton stability was confirmed later and the mutated TTC21B also may be associated with proteinuric diseases, such as nephrotic syndrome. Our patient manifested as an infant with brachydactyly, nephrotic-range proteinuria, and renal tubular acidosis, and a kidney biopsy revealed focal segmental glomerulosclerosis (FSGS). Multiple phalangeal cone-shaped epiphyses of the hand were seen on X-ray. Next-generation sequencing revealed the well-described p.Pro209Leu heterozygous variant and a novel heterozygous p.Cys14Arg variant in the TTC21B gene. Our finding confirmed that the causative variants in the TTC21B gene may contribute to a spectrum of clinical features, such as glomerular proteinuric disease with tubulointerstitial involvement and skeletal abnormalities.
Higher Risk of Cardiovascular Diseases in Rheumatoid Arthritis Patients Without Methotrexate Treatment
Authors: Hloch Karel , Doseděl Martin , Duintjer Tebbens Jurjen , Žaloudková Lenka , Medková Helena , Vlček Jiří , Soukup Tomáš , Pávek Petr
Published: November 2021

Cardiovascular diseases (CVDs) lead to higher morbidity and mortality in rheumatoid arthritis; thus, we aimed to determine whether patients who had discontinued methotrexate treatment before the study enrollment (group MTX 0) were at a higher risk of CVD than patients treated with methotrexate at the time of the data collection (group MTX 1). A retrospective, prospective, observational, cross-sectional study was conducted. A total of 125 patients were enrolled in the study. Patients from the MTX 0 group (n = 35) were not treated with methotrexate for 7.54 (SD ± 4.21) years in average. Medical documentation as well as information taken in patient examinations during regular rheumatologist visits was used to obtain the required data. The composite of any CVD occurred less frequently in patients in the MTX 1 group than in the MTX 0 group (18.8 vs. 40.0%, OR 0.35, 95% CI, 0.15 to 0.83; p = 0.017) with a non-significant trend after adjustment for other treatments, which differed between study groups at the baseline (p = 0.054). Significant difference was found for the reduction of myocardial infarction in the MTX 1 group compared to the MTX 0 group (3.5 vs. 14.3%, OR 0.22, 95% CI, 0.05 to 0.97; p = 0.046). There were 4 deaths (4.7%) in the MTX 1 group as compared with 7 (20.0%) in the MTX 0 group (OR 0.20, 95% CI, 0.05 to 0.73; p = 0.015). Our results demonstrate that patients who discontinued methotrexate treatment are at a significantly higher risk of CVD and all-cause mortality. Based on our findings, we recommend stricter control of CVD in cases of methotrexate discontinuation.
The Role of SGLT2 Inhibitors in Atherosclerosis: A Narrative Mini-Review
Authors: Pahud de Mortanges Aurélie , Salvador Jr. Dante , Laimer Markus , Muka Taulant , Wilhelm Matthias , Bano Arjola
Published: November 2021

Objective:Sodium glucose cotransporter 2 inhibitors (SGLT2-is) are antidiabetic drugs that improve glycemic control by limiting urinary glucose reuptake in the proximal tubule. SGLT2-is might suppress atherosclerotic processes and ameliorate the prognosis of patients with diabetes mellitus diagnosed with or at high risk of atherosclerotic cardiovascular disease (ASCVD). In this mini review, we examine the role of SGLT2-is in the development and progression of atherosclerosis throughout its spectrum, from subclinical atherosclerosis to ASCVD.

Data Sources—PubMed and Google Scholar were searched for publications related to SGLT2-is and atherosclerosis. All types of articles were considered, including clinical trials, animal studies,in vitroobservations, and reviews and meta-analyses. Data were examined according to their impact and clinical relevance.

Synopsis of Content—We first review the underlying mechanisms of SGLT2-is on the development and progression of atherosclerosis, including favorable effects on lipid metabolism, reduction of systemic inflammation, and improvement of endothelial function. We then discuss the putative impact of SGLT2-is on the formation, composition, and stability of atherosclerotic plaque. Furthermore, we evaluate the effects of SGLT2-is in subclinical atherosclerosis assessed by carotid intima media thickness and pulse wave velocity. Subsequently, we summarize the effects of SGLT2-is in ASCVD events, including ischemic stroke, angina pectoris, myocardial infarction, revascularization, and peripheral artery disease, as well as major adverse cardiovascular events, cardiovascular mortality, heart failure, and chronic kidney disease. Moreover, we examine factors that could modify the role of SGLT2-is in atherosclerosis, including sex, age, diabetes, glycemic control, ASCVD, and SGLT2-i compounds. Additionally, we propose future directions that can improve our understanding of SGLT2-is and atherosclerosis.
Adolescent Development of Biological Rhythms in Female Rats: Estradiol Dependence and Effects of Combined Contraceptives
Authors: Grant Azure D. , Wilbrecht Linda , Kriegsfeld Lance J.
Published: November 2021

Adolescence is a period of continuous development, including the maturation of endogenous rhythms across systems and timescales. Although, these dynamic changes are well-recognized, their continuous structure and hormonal dependence have not been systematically characterized. Given the well-established link between core body temperature (CBT) and reproductive hormones in adults, we hypothesized that high-resolution CBT can be applied to passively monitor pubertal development and disruption with high fidelity. To examine this possibility, we used signal processing to investigate the trajectory of CBT rhythms at the within-day (ultradian), daily (circadian), and ovulatory timescales, their dependence on estradiol (E2), and the effects of hormonal contraceptives. Puberty onset was marked by a rise in fecal estradiol (fE2), followed by an elevation in CBT and circadian power. This time period marked the commencement of 4-day rhythmicity in fE2, CBT, and ultradian power marking the onset of the estrous cycle. The rise in circadian amplitude was accelerated by E2 treatment, indicating a role for this hormone in rhythmic development. Contraceptive administration in later adolescence reduced CBT and circadian power and resulted in disruption to 4-day cycles that persisted after discontinuation. Our data reveal with precise temporal resolution how biological rhythms change across adolescence and demonstrate a role for E2 in the emergence and preservation of multiscale rhythmicity. These findings also demonstrate how hormones delivered exogenously in a non-rhythmic pattern can disrupt rhythmic development. These data lay the groundwork for a future in which temperature metrics provide an inexpensive, convenient method for monitoring pubertal maturation and support the development of hormone therapies that better mimic and support human chronobiology.
Generation and Export of Red Blood Cell ATP in Health and Disease
Authors: McMahon Timothy J. , Darrow Cole C. , Hoehn Brooke A. , Zhu Hongmei
Published: November 2021

Metabolic homeostasis in animals depends critically on evolved mechanisms by which red blood cell (RBC) hemoglobin (Hb) senses oxygen (O2) need and responds accordingly. The entwined regulation of ATP production and antioxidant systems within the RBC also exploits Hb-based O2-sensitivity to respond to various physiologic and pathophysiologic stresses. O2 offloading, for example, promotes glycolysis in order to generate both 2,3-DPG (a negative allosteric effector of Hb O2 binding) and ATP. Alternatively, generation of the nicotinamide adenine dinucleotide phosphate (NADPH) critical for reducing systems is favored under the oxidizing conditions of O2 abundance. Dynamic control of ATP not only ensures the functional activity of ion pumps and cellular flexibility, but also contributes to the availability of vasoregulatory ATP that can be exported when necessary, for example in hypoxia or upon RBC deformation in microvessels. RBC ATP export in response to hypoxia or deformation dilates blood vessels in order to promote efficient O2 delivery. The ability of RBCs to adapt to the metabolic environment via differential control of these metabolites is impaired in the face of enzymopathies [pyruvate kinase deficiency; glucose-6-phosphate dehydrogenase (G6PD) deficiency], blood banking, diabetes mellitus, COVID-19 or sepsis, and sickle cell disease. The emerging availability of therapies capable of augmenting RBC ATP, including newly established uses of allosteric effectors and metabolite-specific additive solutions for RBC transfusates, raises the prospect of clinical interventions to optimize or correct RBC function via these metabolite delivery mechanisms.
Portable Measurement System for in situ Estimation of Oxygen and Carbon Fluxes of Submerged Plants
Authors: Schrumpf Annika , Lengerer Andreas , Schmid Nicola , Kazda Marian
Published: November 2021

The metabolism of submerged plants is commonly characterized by oxygen development. The turnover rates of carbon dioxide and other inorganic carbon species, however, are assessed only at distinct points in time after incubation or calculated through shifts in pH and total alkalinity. A novel three parameter measurement system was developed in order to improve this issue and to gain a better understanding of the metabolism of aquatic plants. It allows the simultaneous and continuous assessment of oxygen concentration, partial pressure of carbon dioxide and pH with optical sensors without the need of taking water samples. Plants or plant parts can be enclosed in a chamber, while the surrounding water is either flushed through or circulated within the system. The method was evaluated in regards to measurement time and possible stress reactions during measurement. Its applicability in situ was confirmed with Elodea nuttallii and Ceratophyllum demersum. The measurement system will enable deeper insights into the metabolism and response of aquatic plants to changing environmental conditions, especially related to carbon fixation.
Poorly Conserved P15 Proteins of Cileviruses Retain Elements of Common Ancestry and Putative Functionality: A Theoretical Assessment on the Evolution of Cilevirus Genomes
Authors: Ramos-González Pedro L. , Pons Tirso , Chabi-Jesus Camila , Arena Gabriella Dias , Freitas-Astua Juliana
Published: November 2021

The genus Cilevirus groups enveloped single-stranded (+) RNA virus members of the family Kitaviridae, order Martellivirales. Proteins P15, scarcely conserved polypeptides encoded by cileviruses, have no apparent homologs in public databases. Accordingly, the open reading frames (ORFs) p15, located at the 5′-end of the viral RNA2 molecules, are considered orphan genes (ORFans). In this study, we have delved into ORFs p15 and the relatively poorly understood biochemical properties of the proteins P15 to posit their importance for viruses across the genus and theorize on their origin. We detected that the ORFs p15 are under purifying selection and that, in some viral strains, the use of synonymous codons is biased, which might be a sign of adaptation to their plant hosts. Despite the high amino acid sequence divergence, proteins P15 show the conserved motif [FY]-L-x(3)-[FL]-H-x-x-[LIV]-S-C-x-C-x(2)-C-x-G-x-C, which occurs exclusively in members of this protein family. Proteins P15 also show a common predicted 3D structure that resembles the helical scaffold of the protein ORF49 encoded by radinoviruses and the phosphoprotein C-terminal domain of mononegavirids. Based on the 3D structural similarities of P15, we suggest elements of common ancestry, conserved functionality, and relevant amino acid residues. We conclude by postulating a plausible evolutionary trajectory of ORFans p15 and the 5′-end of the RNA2 of cileviruses considering both protein fold superpositions and comparative genomic analyses with the closest kitaviruses, negeviruses, nege/kita-like viruses, and unrelated viruses that share the ecological niches of cileviruses.
Votes, Votes, Votes: Explaining the Long Road to Emigrant Enfranchisement in Ireland
Authors: Reidy Theresa
Published: November 2021

Enfranchisement of emigrant citizens living outside their home states has been a notable trend in recent decades. While emigrant voting rights are viewed by some as an important part of the wave of suffrage reforms that began in the 1970s, for others they are a contested development that rupture the essence of democracy by breaking the link between citizenship and residence. This article connects insights from the emigrant voting literature with historical institutionalism to argue that the longstanding avoidance of emigrant enfranchisement in the Republic of Ireland was overcome during the Great Recession because of an economic imperative, the need for greater investment from the emigrant community. Diaspora campaigners explicitly linked economic engagement with political rights and the pathway to the policy reform was set. The government gave a commitment in 2017 to hold a referendum to implement the emigrant franchise reform and it is scheduled for 2022, having been initially delayed by the Covid 19 pandemic.
Socio-Demographic Variables, Fear of COVID-19, Anxiety, and Depression: Prevalence, Relationships and Explanatory Model in the General Population of Seven Latin American Countries
Authors: Caycho-Rodríguez Tomás , Tomás José M. , Vilca Lindsey W. , Carbajal-León Carlos , Cervigni Mauricio , Gallegos Miguel , Martino Pablo , Barés Ignacio , Calandra Manuel , Anacona César Armando Rey , López-Calle Claudio , Moreta-Herrera Rodrigo , Chacón-Andrade Edgardo René , Lobos-Rivera Marlon Elías , del Carpio Perla , Quintero Yazmín , Robles Erika , Lombardo Macerlo Panza , Recalde Olivia Gamarra , Figares Andrés Buschiazzo , White Michael , Videla Carmen Burgos
Published: November 2021

The COVID-19 pandemic has gravely impacted Latin America. A model was tested that evaluated the contribution of socio-demographic factors and fear of COVID-19 on anxiety and depression in samples of residents in seven Latin American countries (Argentina, Ecuador, Mexico, Paraguay, Uruguay, Colombia, and El Salvador). A total of 4,881 individuals, selected by convenience sampling, participated in the study. Moderate and severe levels of depressive symptoms and anxiety were identified, as well as a moderate average level of fear of COVID-19. In addition, it was observed that about a quarter of the participants presented symptoms of generalized anxiety disorder and a major depressive episode. Fear of COVID-19 significantly and positively predicted anxiety and depressive symptoms, whereas the effects of socio-demographic variables are generally low [χ2(287) = 5936.96, p < 0.001; RMSEA = 0.064 [0.062, 0.065]; CFI = 0.947; and SRMR = 0.050]. This suggests the need for the implementation of preventive actions in the general population of these countries, with the aim of reducing the prevalence of depressive, anxious and fearful symptoms related to COVID-19.
Religiosity and Sexual Initiation Among Hispanic Adolescents: The Role of Sexual Attitudes
Authors: Calatrava Maria , Beltramo Carlos , Osorio Alfonso , Rodríguez-González Martiño , De Irala Jokin , Lopez-del Burgo Cristina
Published: November 2021

Introduction: Religiosity and sexuality present numerous interconnections. Little is known regarding the specific causal pathways between each religiosity dimension and sexual behavior. The objectives of this study were (1) to explore the relationship between religiosity (measured through attendance at religious services, salience, and prayer) and sexual initiation in adolescents and (2) to establish the role of sexual permissiveness as mediator of the impact produced by religiosity in sexual initiation.

Methods: This study analyzes data from an ongoing school-based international study examining what young people feel and think about relationships, love, and sexuality. An anonymous, self-administered online questionnaire was developed in Spanish. A total of 4,366 students, aged 14–18, completed the questionnaire. A final sample of 2,919 questionnaires was analyzed. Two unconditional logistic regression models were fit with religiosity variables and possible confounders as independent variables (with and without permissiveness, respectively). The dependent variable was sexual initiation. A final path analysis was performed to further understand the results.

Results: Our study highlights that, in predominantly Catholic and Spanish-speaking countries, the fact of attending church and praying may greatly contribute to postponing sexual relations during adolescence, even independently of their attitudes on sexual permissiveness. Conversely, the effect of salience on sexual initiation seems to be fostered only through the mediation of sexual permissiveness. Our findings point to an indirect effect of the three religiosity dimensions (and in particular, religious salience) through permissive attitudes.

Conclusion: Religiosity could be a relevant factor to explain sexual initiation during adolescence.
Clinical Trials and Outcome Measures in Adults With Hearing Loss
Authors: Munro Kevin J. , Whitmer William M. , Heinrich Antje
Published: November 2021

Clinical trials are designed to evaluate interventions that prevent, diagnose or treat a health condition and provide the evidence base for improving practice in health care. Many health professionals, including those working within or allied to hearing health, are expected to conduct or contribute to clinical trials. Recent systematic reviews of clinical trials reveal a dearth of high quality evidence in almost all areas of hearing health practice. By providing an overview of important steps and considerations concerning the design, analysis and conduct of trials, this article aims to give guidance to hearing health professionals about the key elements that define the quality of a trial. The article starts out by situating clinical trials within the greater scope of clinical evidence, then discusses the elements of a PICO-style research question. Subsequently, various methodological considerations are discussed including design, randomization, blinding, and outcome measures. Because the literature on outcome measures within hearing health is as confusing as it is voluminous, particular focus is given to discussing how hearing-related outcome measures affect clinical trials. This focus encompasses how the choice of measurement instrument(s) affects interpretation, how the accuracy of a measure can be estimated, how this affects the interpretation of results, and if differences are statistically, perceptually and/or clinically meaningful to the target population, people with hearing loss.
The Association Between Stress and Injury: A Prospective Cohort Study Among 186 First-Year Contemporary Dance Students
Authors: van Winden Diana , van Rijn Rogier M. , Savelsbergh Geert J. P. , Oudejans Raôul R. D. , Stubbe Janine H.
Published: November 2021

The demanding environment that contemporary dance students are exposed to could result in high stress levels, which can influence injury susceptibility. Therefore, this study aims to investigate the association between stress and injuries. In the period between September 2016 and March 2020, four cohorts of first-year dance students (N= 186; mean age 19.21 ± 1.35 years) were followed for one academic year. Each month, general stress was assessed on a 0–100 visual analogous scale. The Oslo Sports Trauma Research Center Questionnaire on Health Problems was used on a monthly basis to monitor injuries. Injuries were defined as “all injuries” (i.e., any physical complaint irrespective of the need for medical attention or time-loss from dance) and “substantial injuries” (i.e., leading to moderate/severe/complete reductions in training volume or performance). Mann–Whitney tests were performed to measure differences in general stress levels between injured and injury-free students, while repeated-measures ANOVA were performed to investigate whether general stress scores increased before and during injury occurrence. The overall average monthly general stress score over all cohorts for all students was 39.81. The monthly general stress scores ranged from 31.75 to 49.16. Overall, injured and substantially injured students reported higher stress scores than injury-free students, with significant differences in 3 out of the 9 months for all injuries (September, October, March,p< 0.05), and in 5 months for substantial injuries (September, October, November, December, April,p< 0.05). Within the 3-month period before and during injury occurrence, a (marginally) significant linear effect of general stress across the time periods was found for all injuries [F(1.87,216.49) = 3.10,p= 0.051] and substantial injuries [F(2,138) = 4.16,p= 0.018]. The results indicate an association between general stress and injuries. Future research should focus on effects of varying stress levels on injury risk using higher sampling frequency, for instance by measuring weekly since stress levels are likely to fluctuate daily. Practically, strategies aiming at stress reduction might have the potential to reduce the burden of dance injuries and may have positive outcomes for dancers, teachers, schools, and companies.
The Role of Teacher Autonomy Support on Students’ Academic Engagement and Resilience
Authors: Ma Qiangqiang
Published: November 2021

Learners have internal motivational resources that, when maintained, can enhance engagement, enthusiasm, resilience, and success. Learner engagement in educational tasks is a remarkable issue supporting the overall success of learners in higher education. Furthermore, building resilience in learners necessarily requires teachers’ efforts. Therefore, teacher support for autonomy is critical for augmenting appropriate outcomes, and it is deemed as a strong predictor of learners’ particular resources along with their motivational styles and educational achievement. As there is a dearth of studies that have considered teacher autonomy support and its noteworthy influence on learners’ resilience and engagement, the current review endeavors to concentrate on this motivational style in higher education. Successively, several implications are offered to illuminate the issue for teachers, students, teacher trainers, and educational administrators.
Is Cross-Shareholding Conducive to Corporate Sustainability? Evidence From the Environmental Investment of Chinese Listed Firms
Authors: Tian Jinfang , Cao Wei , Ji Xuzhao
Published: November 2021

This article examines the impact of cross-shareholding on corporate environmental investment (Env) using Chinese listed firms from 2014 to 2019 as the research setting. The results show that there is a positive impact of cross-shareholding on corporate environmental investment. The finding remains robust to a battery of robustness checks. In addition, the heterogeneity analysis illustrates that the positive impact of cross-shareholding on corporate environmental investment is more pronounced in state-owned firms and high-polluting industries when compared to non-state-owned firms and low-polluting industries, respectively. This study extends the research on cross-shareholding and provides practical implications for corporate sustainable development.
Modeling and Learning Constraints for Creative Tool Use
Authors: Fitzgerald Tesca , Goel Ashok , Thomaz Andrea
Published: November 2021

Improvisation is a hallmark of human creativity and serves a functional purpose in completing everyday tasks with novel resources. This is particularly exhibited in tool-using tasks: When the expected tool for a task is unavailable, humans often are able to replace the expected tool with an atypical one. As robots become more commonplace in human society, we will also expect them to become more skilled at using tools in order to accommodate unexpected variations of tool-using tasks. In order for robots to creatively adapt their use of tools to task variations in a manner similar to humans, they must identify tools that fulfill a set of task constraints that are essential to completing the task successfully yet are initially unknown to the robot. In this paper, we present a high-level process for tool improvisation (tool identification, evaluation, and adaptation), highlight the importance of tooltips in considering tool-task pairings, and describe a method of learning by correction in which the robot learns the constraints from feedback from a human teacher. We demonstrate the efficacy of the learning by correction method for both within-task and across-task transfer on a physical robot.
Control of Magnetopause Flux Rope Topology by Non-local Reconnection
Authors: Mejnertsen Lars , Eastwood Jonathan P. , Chittenden Jeremy P.
Published: November 2021

Dayside magnetic reconnection between the interplanetary magnetic field and the Earth’s magnetic field is the primary mechanism enabling mass and energy entry into the magnetosphere. During favorable solar wind conditions, multiple reconnection X-lines can form on the dayside magnetopause, potentially forming flux ropes. These flux ropes move tailward, but their evolution and fate in the tail is not fully understood. Whilst flux ropes may constitute a class of flux transfer events, the extent to which they add flux to the tail depends on their topology, which can only be measured in situ by satellites providing local observations. Global simulations allow the entire magnetospheric system to be captured at an instant in time, and thus reveal the interconnection between different plasma regions and dynamics on large scales. Using the Gorgon MHD code, we analyze the formation and evolution of flux ropes on the dayside magnetopause during a simulation of a real solar wind event. With a relatively strong solar wind dynamic pressure and southward interplanetary magnetic field, the dayside region becomes very dynamic with evidence of multiple reconnection events. The resulting flux ropes transit around the flank of the magnetosphere before eventually dissipating due to non-local reconnection. This shows that non-local effects may be important in controlling the topology of flux ropes and is a complicating factor in attempts to establish the overall contribution that flux ropes make in the general circulation of magnetic flux through the magnetosphere.