bluuebunny/crossref_metadata_2025 huggingface dataset:
Building the Bridge From Aquatic Nanotoxicology to Safety by Design Silver Nanoparticles
Authors: Corsi Ilaria , Desimone Martin Federico , Cazenave Jimena
Published: March 2022

Nanotechnologies have rapidly grown, and they are considered the new industrial revolution. However, the augmented production and wide applications of engineered nanomaterials (ENMs) and nanoparticles (NPs) inevitably lead to environmental exposure with consequences on human and environmental health. Engineered nanomaterial and nanoparticle (ENM/P) effects on humans and the environment are complex and largely depend on the interplay between their peculiar properties such as size, shape, coating, surface charge, and degree of agglomeration or aggregation and those of the receiving media/body. These rebounds on ENM/P safety and newly developed concepts such as thesafety by designare gaining importance in the field of sustainable nanotechnologies. This article aims to review the critical characteristics of the ENM/Ps that need to be addressed in thesafe by designprocess to develop ENM/Ps with the ablility to reduce/minimize any potential toxicological risks for living beings associated with their exposure. Specifically, we focused on silver nanoparticles (AgNPs) due to an increasing number of nanoproducts containing AgNPs, as well as an increasing knowledge about these nanomaterials (NMs) and their effects. We review the ecotoxicological effects documented on freshwater and marine species that demonstrate the importance of the relationship between the ENM/P design and their biological outcomes in terms of environmental safety.
Peptide Toxins as Biothreats and the Potential for AI Systems to Enhance Biosecurity
Authors: Lee Ying-Chiang J. , Cowan Alexis , Tankard Amari
Published: March 2022

Biological weapons have been used for thousands of years, but recent advances in synthesis technologies have made peptide and protein toxin production more accessible and pose a threat to biosecurity worldwide. Natural toxins such as conotoxins, certain hemolytic compounds, and enterotoxins are peptide agents that can be synthesized in an environment with weak biosecurity measures and rudimentarily weaponized for limited use against smaller targets for lethal or nonlethal effects. Technological advances are changing the threat landscape around biological weapons and potentially facilitating a shift from state sponsored to more micro-level threats stemming from terror cells, insider threats, and lone wolf attacks. Here, we present the reader with an overview of the threat of peptide and protein toxins, provide examples of potent peptide toxins, and introduce capabilities of a proposed biosecurity program utilizing artificial intelligence that unifies commercial nucleotide and peptide synthesis vendors.
The Impact of the Covid-19 Pandemic on the Well-Being and Diabetes Management of Adolescents With Type 1 Diabetes and Their Caregivers: A Scoping Review
Authors: Bassi Giulia , Mancinelli Elisa , Dell’Arciprete Gaia , Salcuni Silvia
Published: March 2022

The Covid-19 pandemic and its related restriction measures might negatively impact diabetes management and well-being of adolescents with Type 1 Diabetes Mellitus (T1DM) and their caregivers. Accordingly, the present scoping review is aimed at mapping the literature in line with the question “How has the Covid-19 influenced diabetes management and well-being of adolescents with T1DM and their caregivers?”. A systematic search has been conducted through three academic databases. Studies carried out during the Covid-19 pandemic focused on adolescents aged between 10 and 19 years with T1DM and/or their caregivers were included. A total of 9 studies, performed between 2020 and 2021, have been identified. In particular, N = 305 adolescents with T1DM and N = 574 caregivers were considered. Overall, studies were not specific in reporting adolescents’ age, and only 2 studies were primarily focused on the adolescent population with T1DM. In addition, studies were mainly focused on evaluating adolescents’ glycemic control, which remained stable or has improved throughout the pandemic. Contrarily, psychosocial variables have been marginally considered. Indeed, only one study investigated adolescents’ diabetes distress, which remained stable from pre-to during post-lockdown, albeit improving among girls, specifically. As regards caregivers of adolescents with T1DM, studies showed mixed results concerning their psychological state during the Covid-19 pandemic. Prevention measures, which are aimed at supporting adolescents with T1DM during the lockdown, were considered by one study only, showing the favorable role of telemedicine during lockdown for adolescents’ glycemic control. Altogether, the current scoping review has identified many shortcomings of the available literature, which are given by the limited specificity of the age group considered and by the limited consideration of psychosocial variables, particularly their interplay with the medical ones.
P2X7 Receptor Expression and Signaling on Dendritic Cells and CD4+ T Cells is Not Required but Can Enhance Th17 Differentiation
Authors: Yang Yin , Story Meaghan E. , Hao Xingxing , Sumpter Tina L. , Mathers Alicia R.
Published: March 2022

The purinergic receptor P2X7 (P2X7R) is important in inflammasome activation and generally considered to favor proinflammatory immune responses. However, there is still a limited understanding of the role of P2X7R signaling in Th cell differentiation, particularly, Th17 differentiation. Herein, the impact of P2X7R signaling on primary Th17 and Th1 cell responses was examined when P2X7R was expressed specifically on dendritic cells (DCs) and CD4+T cells. Surprisingly, global genetic ablation and pharmacological inhibition of the P2X7R did not affect the generation of Th17 and Th1 development in response to immunization with Complete Freund’s Adjuvant and the model antigens, keyhole limpet hemocyanin or OVA. However, in-depthin vitroandin vivoinvestigations revealed differences in the balance of Th1/Th17 differentiation when P2X7R blockade was restricted to either DCs or CD4+T cells. In this regard,in vitroDCs treated with a P2X7R agonist released more IL-6 and IL-1β and induced a more robust Th17 response in mixed leukocyte reactions when compared to controls. To test the hypothesis that P2X7R signaling specifically in DCs enhances Th17 responsesin vivo,DC-specific P2X7R deficient chimeras were immunized with CFA and OVA. In this model, the P2X7R expression on DCs decreased the Th1 response without impacting Th17 responses. Following an assessment of CD4+T cell P2X7R signaling, it was determined thatin vitroP2X7R sufficient T cells develop an increased Th17 and suppressed Th1 differentiation profile.In vivo, P2X7R expression on CD4+T cells had no effect on Th17 differentiation but likewise significantly suppressed the Th1 response, thereby skewing the immune balance. Interestingly, it appears that WT OT-II Th1 cells are more sensitive to P2X7R-induced cell death as evidence by a decrease in cell number and an increase in T cell death. Overall, these studies indicate thatin vitroP2X7R signaling does enhances Th17 responses, which suggests that compensatory Th17 differentiation mechanisms are utilizedin vivoin the absence of P2X7R signaling.
Growth Hormone Receptor Controls Adipogenic Differentiation of Chicken Bone Marrow Mesenchymal Stem Cells by Affecting Mitochondrial Biogenesis and Mitochondrial Function
Authors: Zhao Changbin , Hu Bowen , Liao Zhiying , Wei Haohui , Zhao Yongxia , Liang Jinping , Luo Wen , Nie Qinghua , Luo Qingbin , Zhang Dexiang , Zhang Xiquan , Li Hongmei
Published: March 2022

Growth hormone receptor (GHR) can activate several signaling pathways after binding to growth hormone (GH) to regulate cell growth and development. Sex-linked dwarf (SLD) chickens, normal protein functions are prevented because of exon mutations in the GHR gene, have more severe fat deposition. However, the specific molecular mechanisms responsible for this phenotype remains unclear. We therefore investigated the effect of the GHR gene on adipogenic differentiation of chicken bone marrow mesenchymal stem cells (BMSCs). We found that bone marrow fat deposition was more severe in SLD chickens compared to normal chickens, and the expression of genes related to adipogenic differentiation was enhanced in SLD chicken BMSCs. We also detected enhanced mitochondrial function of BMSCs in SLD chickens. In vitro, overexpression of GHR in chicken BMSCs increased mitochondrial membrane potential but decreased reactive oxygen and ATP contents, oxidative phosphorylation complex enzyme activity, and mitochondrial number. Expression of genes associated with mitochondrial biogenesis and function was repressed during adipogenic differentiation in chicken BMSCs, the adipogenic differentiation capacity of chicken BMSCs was also repressed. With knockdown of GHR, opposite results were observed. We concluded that GHR inhibited adipogenic differentiation of chicken BMSCs by suppressing mitochondrial biogenesis and mitochondrial function.
Key Players of the Immunosuppressive Tumor Microenvironment and Emerging Therapeutic Strategies
Authors: Park Kevin , Veena Mysore S. , Shin Daniel Sanghoon
Published: March 2022

The tumor microenvironment (TME) is a complex, dynamic battlefield for both immune cells and tumor cells. The advent of the immune checkpoint inhibitors (ICI) since 2011, such as the anti-cytotoxic T-lymphocyte associated protein (CTLA)-4 and anti-programmed cell death receptor (PD)-(L)1 antibodies, provided powerful weapons in the arsenal of cancer treatments, demonstrating unprecedented durable responses for patients with many types of advanced cancers. However, the response rate is generally low across tumor types and a substantial number of patients develop acquired resistance. These primary or acquired resistance are attributed to various immunosuppressive elements (soluble and cellular factors) and alternative immune checkpoints in the TME. Therefore, a better understanding of the TME is absolutely essential to develop therapeutic strategies to overcome resistance. Numerous clinical studies are underway using ICIs and additional agents that are tailored to the characteristics of the tumor or the TME. Some of the combination treatments are already approved by the Food and Drug Administration (FDA), such as platinum-doublet chemotherapy, tyrosine kinase inhibitor (TKI) -targeting vascular endothelial growth factor (VEGF) combined with anti-PD-(L)1 antibodies or immuno-immuno combinations (anti-CTLA-4 and anti-PD-1). In this review, we will discuss the key immunosuppressive cells, metabolites, cytokines or chemokines, and hypoxic conditions in the TME that contribute to tumor immune escape and the prospect of relevant clinical trials by targeting these elements in combination with ICIs.
Aberrant SKP1 Expression: Diverse Mechanisms Impacting Genome and Chromosome Stability
Authors: Thompson Laura L. , Rutherford Kailee A. , Lepage Chloe C. , McManus Kirk J.
Published: March 2022

The S-phase Kinase-Associated Protein 1 (SKP1) is a core component of the SKP1, Cullin 1, F-box protein (SCF) complex, an E3 ubiquitin ligase that serves to poly-ubiquitinate a vast array of protein targets as a signal for their proteasomal degradation, thereby playing a critical role in the regulation of downstream biological processes. Many of the proteins regulated by SKP1 and the SCF complex normally function within pathways that are essential for maintaining genome stability, including DNA damage repair, apoptotic signaling, and centrosome dynamics. Accordingly, aberrant SKP1 and SCF complex expression and function is expected to disrupt these essential pathways, which may have pathological implications in diseases like cancer. In this review, we summarize the central role SKP1 plays in regulating essential cellular processes; we describe functional models in which SKP1 expression is altered and the corresponding impacts on genome stability; and we discuss the prevalence of SKP1 somatic copy number alterations, mutations, and altered protein expression across different cancer types, to identify a potential link between SKP1 and SCF complex dysfunction to chromosome/genome instability and cancer pathogenesis. Ultimately, understanding the role of SKP1 in driving chromosome instability will expand upon our rudimentary understanding of the key events required for genome/chromosome stability that may aid in our understanding of cancer pathogenesis, which will be critical for future studies to establish whether SKP1 may be useful as prognostic indicator or as a therapeutic target.
SAGA Complex Subunits in Candida albicans Differentially Regulate Filamentation, Invasiveness, and Biofilm Formation
Authors: Rashid Saima , Correia-Mesquita Tuana Oliveira , Godoy Pablo , Omran Raha Parvizi , Whiteway Malcolm
Published: March 2022

SAGA (Spt-Ada-Gcn5-acetyltransferase) is a highly conserved, multiprotein co-activator complex that consists of five distinct modules. It has two enzymatic functions, a histone acetyltransferase (HAT) and a deubiquitinase (DUB) and plays a central role in processes such as transcription initiation, elongation, protein stability, and telomere maintenance. We analyzed conditional and null mutants of the SAGA complex module components in the fungal pathogen Candida albicans; Ngg1, (the HAT module); Ubp8, (the DUB module); Tra1, (the recruitment module), Spt7, (the architecture module) and Spt8, (the TBP interaction unit), and assessed their roles in a variety of cellular processes. We observed that spt7Δ/Δ and spt8Δ/Δ strains have a filamentous phenotype, and both are highly invasive in yeast growing conditions as compared to the wild type, while ngg1Δ/Δ and ubp8Δ/Δ are in yeast-locked state and non-invasive in both YPD media and filamentous induced conditions compared to wild type. RNA-sequencing-based transcriptional profiling of SAGA mutants reveals upregulation of hyphal specific genes in spt7Δ/Δ and spt8Δ/Δ strains and downregulation of ergosterol metabolism pathway. As well, spt7Δ/Δ and spt8Δ/Δ confer susceptibility to antifungal drugs, to acidic and alkaline pH, to high temperature, and to osmotic, oxidative, cell wall, and DNA damage stresses, indicating that these proteins are important for genotoxic and cellular stress responses. Despite having similar morphological phenotypes (constitutively filamentous and invasive) spt7 and spt8 mutants displayed variation in nuclear distribution where spt7Δ/Δ cells were frequently binucleate and spt8Δ/Δ cells were consistently mononucleate. We also observed that spt7Δ/Δ and spt8Δ/Δ mutants were quickly engulfed by macrophages compared to ngg1Δ/Δ and ubp8Δ/Δ strains. All these findings suggest that the SAGA complex modules can have contrasting functions where loss of Spt7 or Spt8 enhances filamentation and invasiveness while loss of Ngg1 or Ubp8 blocks these processes.
Integrin-Linked Kinase Reduces H3K9 Trimethylation to Enhance Herpes Simplex Virus 1 Replication
Authors: Tsai Meng-Shan , Chen Shun-Hua , Chang Chih-Peng , Hsiao Yi-Ling , Wang Li-Chiu
Published: March 2022

Histone modifications control the lytic gene expression of herpes simplex virus 1 (HSV-1). The heterochromatin mark, trimethylation of histone H3 on lysine (K) 9 (H3K9me3), is detected on HSV-1 genomes at early phases of infection to repress viral gene transcription. However, the components and mechanisms involved in the process are mostly unknown. Integrin-linked kinase (ILK) is activated by PI3K to phosphorylate Akt and promote several RNA virus infections. Akt has been shown to enhance HSV-1 infection, suggesting a pro-viral role of ILK in HSV-1 infection that has not been addressed before. Here, we reveal that ILK enhances HSV-1 replication in an Akt-independent manner. ILK reduces the accumulation of H3K9me3 on viral promoters and replication compartments. Notably, ILK reduces H3K9me3 in a manner independent of ICP0. Instead, we show an increased binding of H3K9 methyltransferase SUV39H1 and corepressor TRIM28 on viral promoters in ILK knockdown cells. Knocking down SUV39H1 or TRIM28 increases HSV-1 lytic gene transcription in ILK knockdown cells. These results show that ILK antagonizes SVU39H1- and TRIM28-mediated repression on lytic gene transcription. We further demonstrate that ILK knockdown reduces TRIM28 phosphorylation on serine 473 and 824 in HSV-1-infected cells, suggesting that ILK facilitates TRIM28 phosphorylation to abrogate its inhibition on lytic gene transcription. OSU-T315, an ILK inhibitor, suppresses HSV-1 replication in cells and mice. In conclusion, we demonstrate that ILK decreases H3K9me3 on HSV-1 DNA by reducing SUV39H1 and TRIM28 binding. Moreover, our results suggest that targeting ILK could be a broad-spectrum antiviral strategy for DNA and RNA virus infections, especially for DNA viruses controlled by histone modifications.
Unvaccinated Children Are an Important Link in the Transmission of SARS-CoV-2 Delta Variant (B1.617.2): Comparative Clinical Evidence From a Recent Community Surge
Authors: Li Hongru , Lin Haibin , Chen Xiaoping , Li Hang , Li Hong , Lin Sheng , Huang Liping , Chen Gongping , Zheng Guilin , Wang Shibiao , Hu Xiaowei , Huang Handong , Tu Haijian , Li Xiaoqin , Ji Yuejiao , Zhong Wen , Li Qing , Fang Jiabin , Lin Qunying , Yu Rongguo , Xie Baosong
Published: March 2022

Objective

To evaluate the necessity of Covid-19 vaccination in children aged < 12 y by comparing the clinical characteristics between unvaccinated children aged < 12 y and vaccinated patients aged ≥ 12y during the Delta surge (B.1.617.2) in Putian, Fujian, China.

Methods

A total of 226 patients with SARS-Cov-2 Delta variant (B.1.167.2; confirmed by Real-time PCR positivity and sequencing) were enrolled from Sep 10th to Oct 20th, 2021, including 77 unvaccinated children (aged < 12y) and 149 people aged ≥ 12y, mostly vaccinated. The transmission route was explored and the clinical data of two groups were compared; The effect factors for the time of the nucleic acid negativization (NAN) were examined by R statistical analysis.

Results

The Delta surge in Putian spread from children in schools to factories, mostly through family contact. Compared with those aged ≥ 12y, patients aged < 12y accounted for 34.07% of the total and showed milder fever, less cough and fatigue; they reported higher peripheral blood lymphocyte counts [1.84 (1.32, 2.71)×10^9/L vs. 1.31 (0.94, 1.85)×10^9/L; p<0.05), higher normal CRP rate (92.21% vs. 57.72%), lower IL-6 levels [5.28 (3.31, 8.13) vs. 9.10 (4.37, 15.14); p<0.05]. Upon admission, their COVID19 antibodies (IgM and IgG) and IgG in convalescence were lower [0.13 (0.00, 0.09) vs. 0.12 (0.03, 0.41), p<0.05; 0.02 (0.00, 0.14) vs. 1.94 (0.54, 6.40), p<0.05; 5.46 (2.41, 9.26) vs. 73.63 (54.63, 86.55), p<0.05, respectively], but longer NAN time (18 days vs. 16 days, p=0.13).

Conclusion

Unvaccinated children may be an important link in the transmission of SARS-CoV-2 delta variant (B1.617.2), which indicated an urgent need of vaccination for this particular population.
Design Thinking in Transitional Period
Authors: Özcan Oǧuzhan
Published: March 2022

In this speculative look of design thinking through the lens of the Renaissance, the author draws our attention to the shocking similarity between the transition in today's world and the Industrial Era. In this comparison, he emphasizes the similar role of “arts in Renaissance” concept and Design Thinking. In this perspective, the author's concern is not about discussing how the Design Thinking process will be in the new era, but just speculating its role as a tool in such a transitional period.
The Benefits of a Jeffersonian Transcript
Authors: Park Song Hee , Hepburn Alexa
Published: March 2022

Over the past 6 decades, researchers in conversation analysis have repeatedly shown that everyday social activities such as inviting a friend over, interviewing a police suspect, teaching a class, or cross-questioning in a courtroom–are achieved in orderly and reproducible ways. Jeffersonian transcription has been refined to both capture and crystallize the interactionally relevant specifics of how such tasks get done. Conversation analytic work has shown that by leaving out features like the timing of turns, and changes in prosody, volume and other vocal and embodied specifics of delivery, a standard orthographic transcript bleaches out crucial components of how humans perform discursive actions, and how they continuously analyze one another across sequences of talk. This short paper will overview some of the benefits of investing time in the Jeffersonian system. Rather than simply describing the system, we will illustrate the analytic usefulness of its systematic and detailed transcription practices; we show how transcription facilitates a clearer picture of how things get done in interaction.
Application of Metagenomic Next-Generation Sequencing in the Etiological Diagnosis of Infective Endocarditis During the Perioperative Period of Cardiac Surgery: A Prospective Cohort Study
Authors: Zeng Xiaodong , Wu Jinlin , Li Xin , Xiong Weiping , Tang Lili , Li Xueming , Zhuang Jian , Yu Ruoying , Chen Jimei , Jian Xuhua , Lei Liming
Published: March 2022

Objective

The present study aimed to prospectively evaluate the role of metagenomic next-generation sequencing (mNGS) in the etiological diagnosis of patients with perioperative infective endocarditis (IE).

Methods

From May 1st, 2019 to December 31st, 2020, a total of 99 patients with IE were enrolled in the present study according to the modified Duke criteria, etiological, and pathological results. 11 non-IE patients undergoing heart valve surgery in the same period were selected as the control group. A blood culture test was performed immediately after admission, and the valves harvested operatively were examined by blood culture and mNGS.

Results

In the IE group, there were 29 cases (29.3%) with positive blood culture, 16 cases (16.2%) with positive valve culture, and 85 cases (85.9%) with positive valve mNGS. Compared to culture-based detection, mNGS achieved better performance with a sensitivity, specificity, area under the curve (AUC) of 0.859, 0.727, and 0.793, respectively. The combined approach using culture and mNGS further improved the diagnostic accuracy (sensitivity 89.9%, specificity 72.7%, AUC 0.813). Preoperative white blood cell (P = 0.029) and neutrophils (P = 0.046) were identified as independent factors affecting the detection rate of mNGS. In the mNGS-positive group, 95 strains of pathogens were found and 10 cases were identified with mixed infection. There were 72 gram-positive bacteria and 14 gram-negative bacteria. mNGS positive group displayed higher species richness than mNGS negative group with enrichment of Streptococcus sanguis, Streptococcus buccalis, and Streptococcus griseus. Proteobacteria and Actinomycetes were enriched in mNGS negative group. Notably, six patients showed disconcordant results between culture and mNGS. Rothia aeria was identified in the blood culture, valve culture, and valve mNGS in one patient. Bartonella Quintana and Coxiella burnetii, which were fastidious intracellular bacteria, were found in two blood and valve culture-negative cases.

Conclusions

mNGS outperformed the conventional culture method and displayed high accuracy in detecting pathogens in IE patients. This study provided support for the use of mNGS in the etiological diagnosis of IE.
Early Detection of Cardiovascular Risk Factors and Definition of Psychosocial Profile in Women Through a Systematic Approach: The Monzino Women Heart Center's Experience
Authors: Gili Sebastiano , Giuliani Mattia , Santagostino Baldi Giulia , Teruzzi Giovanni , Pravettoni Gabriella , Montorsi Piero , Trabattoni Daniela
Published: March 2022

Introduction

Cardiovascular (CV) disease is the leading mortality cause among women, yet an alarming misrepresentation of women in CV studies and a low awareness of the impact of CV among women still persist to date. The Monzino Women Heart Center has been established as a clinical and research program dedicated to primary prevention of CV disease in women.

Methods

Patients aged between 35 and 60 years and with no history of CV disease underwent a comprehensive evaluation including a cardiologic outpatient visit with electrocardiogram, individual CV risk calculation, first-level cardiovascular examinations and a psychological assessment.

Results

A total of 635 women, with a mean age of 52.2 ± 6.4 participated to the project on a voluntary basis during the period January 2017–August 2021. Included patients had a high level of education (40.4% with a graduate or postgraduate university degree), the majority of them, in a stable couple and with children, were actively working. More than half of the patients performed physical activity on a regular basis. Prevalence of traditional CV risk factors were family history (70.2%), hypertension (46%), hypercholesterolemia (22%) and diabetes (14%). Early or premature menopause was reported by 17.7% of the patients, gestational hypertension and diabetes by 4.96 and 1.7%, respectively. Symptoms of depression were reported by 27%; nearly 36% of the participants rated high score of state anxiety and 41% of trait anxiety. Nearly 69% of the participants showed moderate-to-high perceived stress. The mean value of perceived general self-efficacy was moderate (mean = 28.78, SD = 4.69).

Conclusion

A CV prevention program dedicated to women can help identifying a considerable number of patients with risk factors for whom early interventions can help reducing the risk of developing CV disease. Psychological assessment might unmask depression or anxiety disorders, which might have a potential long-terme detrimental effect on CV health.
3D Visualization Monitoring and Early Warning System of a Tailings Dam—Gold Copper Mine Tailings Dam in Zijinshan, Fujian, China
Authors: Nie Wen , Luo Minghua , Wang Yunmin , Li Ruixiang
Published: March 2022

A 3D tailings dam visualization early warning system was developed based on GIS (geographic information system) combining ARIMA (autoregressive integrated moving average model) and 3S (RS, GIS, GPS) technology for prediction of phreatic line changes and tailing dam deformation. It was applied for monitoring and early warning for the gold–copper tailing dam in Zijinshan Dadongbei tailing pond. The system consists of equipment management, data management, prediction, monitoring and early warning, and 3D visualization modules. It is able to do data management, visualization and disaster prediction, and early warning based on 79 monitoring points of rainfall, infiltration line, and deformation of the tailing dam in the Zijinshan mine. The design and application of the system reflect its features of rich functionality, high practicality, intuitive effect, and high reference value. The system solves the problems of low visualization of monitoring data, poor management of multiple data, and feasible prediction and early warning of point–surface combination. It realizes high-precision prediction of key factors and real-time warning of disaster.
A MEN1 Patient Presenting With Multiple Parathyroid Adenomas and Transient Hypercortisolism: A Case Report and Literature Review
Authors: Chen Fuqiong , Xu Qinqin , Yue Wenzhu , Yu Xuefeng , Shao Shiying
Published: March 2022

Background

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary endocrine syndrome caused by mutations in MEN1 tumor suppressor gene.

Case Presentation

A 53-year-old Chinese female was admitted to Division of Endocrinology, Tongji Hospital, for hypercalcemic crisis. Increased level of parathyroid hormone (PTH) was confirmed by laboratory tests, and imaging examination showed multiple parathyroid adenomas. Based on gene analysis, the patient was diagnosed as MEN1 associated hyperparathyroidism (HPT) by gene analysis with c.1378C>T (p.Arg460Ter) mutation in MEN1 gene. Her condition was complicated by transient hypercortisolism, mammary mass and uterine leiomyoma. After subtotal parathyroidectomy, PTH and serum calcium levels returned to normal.

Conclusion

HPT with multiple parathyroid adenomas is an indication of MEN1 gene mutation. Serum cortisol and its circadian rhythm can be abnormal in the presence of hypercalcemia and high PTH. These parameters can return to normal after parathyroidectomy.
Relationship Between Subclinical Hypothyroidism in Pregnancy and Hypertensive Disorder of Pregnancy: A Systematic Review and Meta-Analysis
Authors: Han Yue , Wang Jun , Wang Xiaoying , Ouyang Ling , Li Yan
Published: March 2022

Objective

Studies have shown a high incidence of subclinical hypothyroidism in pregnancy, but the adverse pregnancy outcomes caused by it are not clear. Therefore, we conducted a systematic review and meta-analysis to evaluate the relationship between subclinical hypothyroidism in pregnancy and hypertensive disorders of pregnancy(HDP) to guide clinical practice.

Method

We searched the MEDLINE (PubMed), Cochrane Central, EMBASE, Web of Science, and SCOPUS databases and screened all studies evaluating the relationship between subclinical hypothyroidism in pregnancy and hypertensive disorders of pregnancy. Two researchers independently evaluated the quality of all eligible original studies using the Newcastle-Ottawa Scale (NOS). We also performed a meta-analysis using STATA15.1. Sensitivity analyses were also performed by examining the effects of individual studies as well as using different effect models and detecting any publication bias using the harbord test.

Results

Twenty-two studies were included in the final meta-analysis. Our results indicated that pregnant women with subclinical hypothyroidism had an increased risk of HDP (OR = 1.54(95% CI: 1.21-1.96) I²=67.1%), compared with euthyroidism. Subclinical hypothyroidism in pregnancy was not associated with hypertensive disorders of pregnancy at TSH diagnostic cut-off of less than 3.0 mIU/L (P = 0.077). Curiously, the risk of HDP increases when the TSH diagnostic cut-off value is higher or lower than 4 mIU/L. Although only 9 studies were above the threshold, the risk of developing HDP was still 1.69 times, which was highest in all subgroup analyses. This is consistent with the newly recommended diagnostic cut-off value of 4 mIU/L for TSH by the ATA. Our results consider that the risk of hypertensive disorder complicating pregnancy is increased regardless of the diagnosis of subclinical hypothyroidism at any stage of pregnancy. Unfortunately, there is insufficient evidence to support that patients can benefit from treatment with levothyroxine.

Conclusion

The results of this meta-analysis indicate that subclinical hypothyroidism in pregnancy is associated with an increased risk of developing HDP, and this association exists regardless of the gestational period. However, the available evidence cannot support these patients receiving thyroxine intervention can benefit from it, so routine screening is only recommended for pregnant women with risk factors for hypothyroidism. Further research is needed to validate more scientific and rigorous clinical studies to clarify the relationship between subclinical hypothyroidism and HDP to improve patient prognosis.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42021286405)
Predictive Factors for Catecholamine-Induced Cardiomyopathy in Patients with Pheochromocytoma and Paraganglioma
Authors: Wang Yi , Yu Xuerong , Huang Yuguang
Published: March 2022

Objective

To investigate possible predictive factors of catecholamine-induced cardiomyopathy in pheochromocytoma and paraganglioma (CICMPP) patients.

Methods

In all, 50 CICMPP patients and 152 pheochromocytoma and paraganglioma (PPGL) patients without CICMPP who were treated in our institution between August 2012 and April 2018 were included in this retrospective study to assess predictors of CICMPP.

Results

Patients with CICMPP reported younger onset age, more clinical symptoms and signs, more family history of hypertension, and higher maximum systolic, diastolic, and mean BP and maximum HR. Medical evaluation also showed higher level of blood hematocrit, blood glucose, 24-h urine catecholamines, larger diameter of the tumor and more comorbidities, von Hippel-Lindau syndromes, and metastatic tumors in these patients. Multivariable analysis identified maximum resting HR over 115 beats/min (OR 10.05, 95% CI 3.71–27.20), maximum resting systolic BP over 180 mmHg (OR 7.17, 95% CI 2.22–23.23), blood glucose over 8.0 mmol/L (OR 6.52, 95% CI 2.25–18.86), more than 3 symptoms and signs (OR 6.05, 95% CI 1.86–19.64), and onset age under 40 years (OR 3.74, 95% CI 1.37–10.20) as independent predictors of CICMPP. Female sex (OR 5.06, 95% CI 1.19–21.54), complaint of chest pain (OR 5.84, 95% CI 1.27–26.90), and extra-adrenal tumor (OR 8.64, 95% CI 1.82–40.94) were independent predictors of Takotsubo cardiomyopathy in CICMPP.

Conclusion

Maximum resting HR ≥115 beats/min, maximum resting systolic BP ≥180 mmHg, blood glucose ≥8.0 mmol/L, number of symptoms and signs ≥3, and onset age ≤40 years were found to be predictive factors for CICMPP.
The Hidden One: What We Know About Bitter Taste Receptor 39
Authors: Jalševac Florijan , Terra Ximena , Rodríguez-Gallego Esther , Beltran-Debón Raúl , Blay Maria Teresa , Pinent Montserrat , Ardévol Anna
Published: March 2022

Over thousands of years of evolution, animals have developed many ways to protect themselves. One of the most protective ways to avoid disease is to prevent the absorption of harmful components. This protective function is a basic role of bitter taste receptors (TAS2Rs), a G protein-coupled receptor family, whose presence in extraoral tissues has intrigued many researchers. In humans, there are 25 TAS2Rs, and although we know a great deal about some of them, others are still shrouded in mystery. One in this latter category is bitter taste receptor 39 (TAS2R39). Besides the oral cavity, it has also been found in the gastrointestinal tract and the respiratory, nervous and reproductive systems. TAS2R39 is a relatively non-selective receptor, which means that it can be activated by a range of mostly plant-derived compounds such as theaflavins, catechins and isoflavones. On the other hand, few antagonists for this receptor are available, since only some flavones have antagonistic properties (all of them detailed in the document). The primary role of TAS2R39 is to sense the bitter components of food and protect the organism from harmful compounds. There is also some indication that this bitter taste receptor regulates enterohormones and in turn, regulates food intake. In the respiratory system, it may be involved in the congestion process of allergic rhinitis and may stimulate inflammatory cytokines. However, more thorough research is needed to determine the precise role of TAS2R39 in these and other tissues.
Mechanism of Endoplasmic Reticulum Stress Pathway in the Osteogenic Phenotypic Transformation of Aortic Valve Interstitial Cells
Authors: Tao Yiming , Geng Yimin , Dang Wenpei , Xu Xinxin , Zhao Hui , Zou Lijuan , Li Yongsheng
Published: March 2022

Background and Purpose

Calcific Aortic Valve Disease (CAVD) is a crucial component of degenerative valvular disease in old age and with the increasing prevalence of the aging population. we hope that by modeling valvular osteogenesis and intervening with endoplasmic reticulum stress inhibitor TUDCA to observe the effect of endoplasmic reticulum stress on valve osteogenesis

Methods

In this study, rabbit heart valvular interstitial cells (VICs) were isolated and cultured. They treated with ox-LDL (Oxidized Low Density Lipoprotein) stimulation to establish a model of valvular osteogenic transformation. BMP2 (Bone Morphogenetic Protein 2), PERK (Protein kinase R-like endoplasmic reticulum kinase), CHOP (CCAAT/enhancer-binding protein homologous protein) and transcriptional regulatory factor ATF4 (Activating Transcription Factor 4 )were recorded after intervention with ER stress inhibitor TUDCA. The effects of er stress on valvular osteogenic transformation were analyzed.

Result

After stimulation of VICs with ox-LDL, the expression levels of BMP2, PERK, CHOP, and ATF4 increased. However, TUDCA treatment can alleviate the increased expression levels of BMP2, PERK ATF4, and CHOP under ox-LDL stimulation to a certain extent.

Conclusion

The endoplasmic reticulum stress signaling pathway is involved in ox-LDL-induced calcification of rabbit valve interstitial cells. Inhibition of endoplasmic reticulum stress using TUDCA can improve the progression of rabbit aortic valve calcification.
Mechanism and Experimental Verification of Luteolin for the Treatment of Osteoporosis Based on Network Pharmacology
Authors: Liang Guihong , Zhao Jinlong , Dou Yaoxing , Yang Yuan , Zhao Di , Zhou Zhanpeng , Zhang Rui , Yang Weiyi , Zeng Lingfeng
Published: March 2022

Purpose

To explore the molecular mechanism of luteolin in the treatment of osteoporosis (OP) by network pharmacological prediction and experimentation.

Methods

The target proteins of luteolin were obtained with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). OP-related proteins were extracted from the Comparative Toxicogenomics Database (CTD) and GeneCards and DisGeNET databases. We imported the common protein targets of luteolin and OP into the STRING database to obtain the relationships between the targets. The common target proteins of luteolin and OP were assessed by KEGG and GO enrichment analyses with the DAVID database. Animal experiments were conducted to verify the effect of luteolin on bone mineral density in ovariectomised (OVX) rats. Finally, the effects of luteolin on key signalling pathways were verified by cell experiments in vitro.

Results

Forty-four targets of luteolin involved in the treatment of OP, including key target proteins such as TP53, AKT1, HSP90AA1, JUN, RELA, CASP3, and MAPK1, were screened. KEGG enrichment analysis found that luteolin inhibits OP by regulating the PI3K-Akt, TNF, oestrogen and p53 signalling pathways. The results of animal experiments showed that bone mass in the low-dose luteolin group (Luteolin-L group, 10 mg/kg), high-dose luteolin group (Luteolin-H group, 50 mg/kg) and positive drug group was significantly higher than that in the OVX group (P<0.05). Western blot (WB) analysis showed that the protein expression levels of Collagen I, Osteopontin and RUNX2 in bone marrow mesenchymal stem cells (BMSCs) cultured with 0.5, 1 and 5 μM luteolin for 48 h were significantly higher than those in the dimethyl sulfoxide (DMSO) group (P<0.05). In vitro cell experiments showed that the p-PI3K/PI3K and p-Akt/Akt expression ratios in BMSCs cultured with 0.5, 1 and 5 μM luteolin for 48 h were also significantly higher than those in the DMSO group (P<0.05).

Conclusions

Luteolin has multitarget and multichannel effects in the treatment of OP. Luteolin could reduce bone loss in OVX rats, which may be due to its ability to promote the osteogenic differentiation of BMSCs by regulating the activity of the PI3K-Akt signalling pathway.
Bacteriological Quality of Bottled Drinking Water and Municipal Tap Water in Northeastern Ethiopia
Authors: Keleb Awoke , Ademas Ayechew , Sisay Tadesse , Lingerew Mistir , Adane Metadel
Published: March 2022

Objective: Water-borne diseases cause high morbidity and mortality in developing countries, like Ethiopia. Diarrheal disease and typhoid are one of the top five diseases that cause significant public health burden and economic cost in Dessie city. Thus, monitoring the quality of drinking water is crucial to prevent waterborne disease. This study aimed to determine the bacteriological quality of bottled drinking water and municipal tap water in Northeastern Ethiopia for proper planning, monitoring, and intervention purpose.

Methods: A laboratory-based cross-sectional study was conducted on 248 municipal tap water samples from point of collection (MTPOC), 248 water samples from a household water storage container (HHSC), 38 bottled water samples before packaging from manufacturing facilities (BPMF), and 38 bottle water samples from point of sale (POS) in Dessie city between March 15 to May 15, 2021. Water samples were collected by trained data collectors using a standard sampling protocol. Data were entered into Microsoft Excel and exported to SPSS version 25.0 for data cleaning and analysis. The commonest microbiological parameters, total coliforms (TC) and Escherichia coli (E. coli) were tested using the standard procedure. One-way ANOVA was used to compare the mean log concentration of E. coli and TC between sampling points and the Tukey post hoc test was also computed to identify statistically significant differences among sample types. The 95% confidence interval [CI] and p < 0.05 were taken as statistically significant.

Results: About 15.8 and 36.8% of the samples from BPMF and 26.3 and 55.3% of samples from POS were positive for E. coli and TC respectively while 47.2 and 65.7% of water sample from MTPOC and 48.8 and 98.8% of samples from HHSC were positive for E. coli and TC respectively. The mean log concentration of E. coli from the sample of MTPOC was significantly higher than BPMF. Similarly, water samples from HHSC had significantly higher E. coli and TC concentrations than BPMF and POS. Water samples from HHSC had also a significantly higher prevalence of log concentrations of TC than MTPOC.

Conclusion: Most values were beyond maximum tolerable limits recommended by World Health Organization (WHO). Thus, good water handling practices and water quality monitoring are essential to prevent bacteriological contamination.
The Evolution of Placentation in Flowering Plants: A Possible Role for Kin Selection
Authors: Shivaprakash K. Nagaraju , Bawa Kamaljit S.
Published: March 2022

Placentation refers to the mode of ovule attachment on the wall of the ovary. In multiovulate ovaries, placentation influences interactions among developing seeds with varying degrees of kinships. Placentation is a taxonomically informative character in flowering plants, yet little has been written about the origin and evolutionary trends of various placentation types in flowering plants since Puri’s and Stebbins’ work, over six decades and almost four decades ago, respectively. More recently, some authors have written about the evolution of placentation in certain groups, but an overall perspective for angiosperms is lacking. For 421 families of angiosperms, we collected data on placentation types and ovule number, and analyzed the data in the phylogenetic context using recent comprehensive phylogeny of angiosperms to test the hypotheses on the evolution of various placentation types and their association with ovule number. The distribution of placentation types across flowering plants suggests that axile placentation, followed by parietal and basal placentation, occurs more frequently than laminar and free central placentation that are very rare. Our results are more consistent with evolutionary trends proposed by Puri than by Stebbins and suggest that marginal placentation is the ancestral and most primitive placentation type, while axile is the most advanced. Placentation types show strong association with ovule number. Finally, our results on ovule number and placentation types indicate that most angiosperms may fall into two categories: one with one or few ovule(s) and basal placentation, and another with many ovules and parietal and axile placentation. Kin selection within ovaries may play a role in explaining the observed patterns. Overall, our results provide new insights into the evolution of placentation, particularly into the drivers underlying the diversification of various placentation types.
Feature Selection of OMIC Data by Ensemble Swarm Intelligence Based Approaches
Authors: Yao Zhaomin , Zhu Gancheng , Too Jingwei , Duan Meiyu , Wang Zhiguo
Published: March 2022

OMIC datasets have high dimensions, and the connection among OMIC features is very complicated. It is difficult to establish linkages among these features and certain biological traits of significance. The proposed ensemble swarm intelligence-based approaches can identify key biomarkers and reduce feature dimension efficiently. It is an end-to-end method that only relies on the rules of the algorithm itself, without presets such as the number of filtering features. Additionally, this method achieves good classification accuracy without excessive consumption of computing resources.
Neurodevelopment in Children Exposed to Zika in utero: Clinical and Molecular Aspects
Authors: Schuler-Faccini Lavínia , del Campo Miguel , García-Alix Alfredo , Ventura Liana O. , Boquett Juliano André , van der Linden Vanessa , Pessoa André , van der Linden Júnior Hélio , Ventura Camila V. , Leal Mariana Carvalho , Kowalski Thayne Woycinck , Rodrigues Gerzson Lais , Skilhan de Almeida Carla , Santi Lucélia , Beys-da-Silva Walter O. , Quincozes-Santos André , Guimarães Jorge A. , Garcez Patricia P. , Gomes Julia do Amaral , Vianna Fernanda Sales Luiz , Anjos da Silva André , Fraga Lucas Rosa , Vieira Sanseverino Maria Teresa , Muotri Alysson R. , Lopes da Rosa Rafael , Abeche Alberto Mantovani , Marcolongo-Pereira Clairton , Souza Diogo O.
Published: March 2022

Five years after the identification of Zika virus as a human teratogen, we reviewed the early clinical manifestations, collectively called congenital Zika syndrome (CZS). Children with CZS have a very poor prognosis with extremely low performance in motor, cognitive, and language development domains, and practically all feature severe forms of cerebral palsy. However, these manifestations are the tip of the iceberg, with some children presenting milder forms of deficits. Additionally, neurodevelopment can be in the normal range in the majority of the non-microcephalic children born without brain or eye abnormalities. Vertical transmission and the resulting disruption in development of the brain are much less frequent when maternal infection occurs in the second half of the pregnancy. Experimental studies have alerted to the possibility of other behavioral outcomes both in prenatally infected children and in postnatal and adult infections. Cofactors play a vital role in the development of CZS and involve genetic, environmental, nutritional, and social determinants leading to the asymmetric distribution of cases. Some of these social variables also limit access to multidisciplinary professional treatment.