bluuebunny/crossref_metadata_2025 huggingface dataset:
New insights into arsenic, lead, and iron neurotoxicity: Activation of MAPK signaling pathway and oxidative stress
Authors: Khedr Naglaa F. , Talkan Ola F. A.
Published: March 2022

Toxic metals cause neurodegeneration via formation of toxic complexes with the cellular compounds and production of highly reactive oxygen species. The present study aimed to investigate the role of mitogen‐activated protein kinase (MAPK) signaling pathway in iron, lead, and arsenic induced neurotoxicity. Also, to explore their effect on brain enzymes, inducible nitric oxide synthase (iNOS) and nuclear factor κB (NF‐κB) in rat brains. Rats were divided into four groups (n = 8): Control group, lead group (30 mg/kg lead acetate), arsenic group (5 mg/kg sodium arsenite), and iron group (100 mg/kg ferric hydroxide). Treatments were given three times/week orally for 2 months. Brain tissues were assessed for reduced glutathione and malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), alkaline phosphatase (ALP), acid phosphatase (ACP), Na+/K+activated adenosine 5′‐triphosphatase (Na+/K+‐ATPase) and acetylcholinesterase (AChE) activities, expression of iNOS and NF‐κB, and Western blot analysis of c‐Jun NH(2)‐terminal kinase (JNK) and extracellular signal‐regulated protein kinase (ERK) proteins. Levels of arsenic, iron, and lead were significantly (p = 0.000) increased in blood and brain tissues. Levels of MDA, SOD, CAT, iNOS, and NF‐κB gene expression, phosphorylated JNK and phosphorylated ERK proteins were increased significantly in lead, arsenic, and iron treated rat groups compared to control. ALP, ACP, AChE, and ATPase activities in brain were significantly altered in metal‐treated rat groups compared to control. Iron, lead, and arsenic induced neurotoxicity activated the pro‐inflammatory mediators NF‐κB, iNOS, and MAPK pathway and altered the activity of brain ALP, ACP, Na+/K+‐ATPase, CAT, SOD, and AChE.
HEPES‐buffering of bicarbonate‐containing culture medium perturbs lysosomal glucocerebrosidase activity
Authors: van der Lienden Martijn J. C. , Aten Jan , Boot Rolf G. , van Eijk Marco , Aerts Johannes M. F. G. , Kuo Chi‐Lin
Published: March 2022

Glucocerebrosidase (GCase), encoded by the GBA gene, degrades the ubiquitous glycosphingolipid glucosylceramide. Inherited GCase deficiency causes Gaucher disease (GD). In addition, carriers of an abnormal GBA allele are at increased risk for Parkinson's disease. GCase undergoes extensive modification of its four N‐glycans en route to and inside the lysosome that is reflected in changes in molecular weight as detected with sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. Fluorescent activity‐based probes (ABPs) that covalently label GCase in reaction‐based manner in vivo and in vitro allow sensitive visualization of GCase molecules. Using these ABPs, we studied the life cycle of GCase in cultured fibroblasts and macrophage‐like RAW264.7 cells. Specific attention was paid to the impact of 4‐(2‐hydroxyethyl)‐1‐piperazineethanesulfonic acid (HEPES) supplementation to bicarbonate‐buffered medium. Here, we report how HEPES‐buffered medium markedly influences processing of GCase, its lysosomal degradation, and the total cellular enzyme level. HEPES‐containing medium was also found to reduce maturation of other lysosomal enzymes (α‐glucosidase and β‐glucuronidase) in cells. The presence of HEPES in bicarbonate containing medium increases GCase activity in GD‐patient derived fibroblasts, illustrating how the supplementation of HEPES complicates the use of cultured cells for diagnosing GD.
Hsa_circ_0007142 contributes to cisplatin resistance in esophageal squamous cell carcinoma via miR‐494‐3p/LASP1 axis
Authors: Chang Na , Ge Ning , Zhao Yufei , Yang Liu , Qin Wei , Cui Yayun
Published: March 2022

Background

Chemoresistance is one of the major obstacles for tumor treatment. Circular RNAs (circRNAs) have been confirmed to play vital roles in chemoresistance of cancer, including esophageal squamous cell carcinoma (ESCC). We investigated the roles and mechanisms of circ_0007142 in cisplatin (DDP) resistance of ESCC.

Methods

Quantitative real‐time polymerase chain reaction (qRT‐PCR) was conducted to determine the levels of circ_0007142, DOCK1 mRNA, microRNA‐494‐3p (miR‐494‐3p) and LIM And SH3 Protein 1 (LASP1) mRNA. RNase R assay was conducted to analyze the characteristic of circ_0007142. Cell Counting Kit‐8 (CCK‐8) assay was performed to evaluate IC50 of DDP. Flow cytometry analysis, 5‐ethynyl‐2’‐deoxyuridine (EdU) assay and transwell assay were carried out to examine cell apoptosis, proliferation and invasion, respectively. Dual‐luciferase reporter assay was employed to verify the association between miR‐494‐3p and circ_0007142 or LASP1. Murine xenograft assay was conducted to investigate the role of circ_0007142 in DDP resistant in vivo. The protein level of LASP1 in tumors was measured by Immunohistochemistry (IHC) analysis.

Results

Circ_0007142 was upregulated in DDP‐resistant ESCC tissues and cells. Circ_0007142 knockdown improved DDP sensitivity, induced cell apoptosis and hampered cell proliferation and invasion in DDP‐resistant ESCC cells. Circ_0007142 functioned as the sponge for miR‐494‐3p and miR‐494‐3p inhibition reversed the impacts of circ_0007142 knockdown on DDP resistance, cell apoptosis, proliferation, and invasion. LASP1 was a target of miR‐494‐3p, and the effects on DDP resistance, cell apoptosis, growth, and invasion mediated by LASP1 downregulation were rescued by miR‐494‐3p inhibition. Moreover, circ_0007142 knockdown enhanced DDP sensitivity in vivo.

Conclusion

Circ_0007142 improved DDP resistance of ESCC by upregulating LASP1 via sponging miR‐494‐3p.
CircRNA hsa_circ_0018289 exerts an oncogenic role in cervical cancer progression through miR‐1294/ICMT axis
Authors: Li Yujuan , Gao Xiangrong , Yang Chaochao , Yan Hua , Li Cui
Published: March 2022

Background

circRNA hsa_circ_0018289‐mediated growth and metastasis of CC cells were investigated, as well as the mechanistic pathway.

Methods

Quantitative real‐time reverse transcription‐polymerase chain reaction (qRT‐PCR) was carried out to examine the expression of hsa_circ_0018289, microRNA (miR)‐1294, and isoprenylcysteine carboxyl methyltransferase (ICMT). CC cell proliferation, migration, and invasion were evaluated by 5‐ethynyl‐2’‐deoxyuridine (EdU) incorporation, colony formation, transwell assays, Western blot analysis of ICMT, and glycolysis‐associated proteins. Dual‐luciferase reporter or RNA pull‐down analysis of the target interaction between miR‐1294 and hsa_hsa_circ_0018289 or ICMT. Xenograft model assay was implemented to assess the role of hsa_circ_0018289 in vivo. Immunofluorescence (IHC) was employed to detect the level of Ki‐67.

Results

Hsa_circ_0018289 was elevated in CC tissues and cells, its deficiency could repress growth, metastasis, and glycolysis of CC cells in vitro, as well as hamper tumor growth in vivo. Hsa_circ_0018289 sponged miR‐1294 while miR‐1294 bound with ICMT, and the inhibition of miR‐1294 or addition of ICMT could partially relieve the effect caused by hsa_circ_0018289 depletion.

Conclusion

Hsa_circ_0018289 contributes to malignant development by regulating the miR‐1294/ICMT axis, affording novel insight into CC therapy.
Human adipose and synovial mesenchymal stem cells improve osteoarthritis in rats by reducing chondrocyte reactive oxygen species and inhibiting inflammatory response
Authors: Liu Xunzhi , Liu Yaqing , He Huabin , Xiang Weiwei , He Cheng
Published: March 2022

Background

We explored the therapeutic effects of Adipose‐derived mesenchymal stem cells (ADMSCs) and Synovial‐derived mesenchymal stem cells (SDMSCs) on osteoarthritis (OA).

Methods

SDMSCs and ADMSCs were co‐cultured with chondrocytes and stimulated with interleukin (IL)‐1β. An OA model was established on rats by intra‐articular injection with ADMSCs and SDMSCs. After 8 weeks, the joint diameter difference was detected, and histological staining was used to observe the pathological changes in cartilage tissue. Enzyme‐linked immunosorbent assay (ELISA) was used to detect the expressions of IL‐6, tumor necrosis factor (TNF)‐α and IL‐1β in joint fluid. The expressions of COL2A1, Aggrecan, Matrix metalloproteinase (MMP)‐13, SOX9, IL‐6, TNF‐α and IL‐1β were detected by qRT‐PCR and Western blotting in cartilage tissue. Reactive oxygen species (ROS) content in cells and cartilage tissues was detected by ROS kit.

Results

SDMSCs and ADMSCs co‐cultured with chondrocytes could reduce MMP‐13 expression, increase the expressions of COL2A1, Aggrecan and SOX9, as well as reverse the effects of IL‐1β on promoting ROS content and inflammatory factors levels. After the OA model was established, the injection of ADMSCs and SDMSCs reduced the differences in joint diameter and tissue lesions in OA rats. The OA model led to increased levels of IL‐6, TNF‐α and IL‐1β in joint fluid and cartilage tissue, while the injection of ADMSCs and SDMSCs inhibited the inflammatory factor levels in OA rats, and increased the expressions of COL2A1, Aggrecan and SOX9 in OA rats.

Conclusion

ADMSCs and SDMSCs improve osteoarthritis in rats by reducing chondrocyte ROS and inhibiting inflammatory response.
β‐catenin‐controlled tubular cell‐derived exosomes play a key role in fibroblast activation via the OPN‐CD44 axis
Authors: Chen Shuangqin , Zhang Meijia , Li Jiemei , Huang Jiewu , Zhou Shan , Hou Xiaotao , Ye Huiyun , Liu Xi , Xiang Shaowei , Shen Weiwei , Miao Jinhua , Hou Fan Fan , Liu Youhua , Zhou Lili
Published: March 2022

Tubular injury and peripheral fibroblast activation are the hallmarks of chronic kidney disease (CKD), suggesting intimate communication between the two types of cells. However, the underlying mechanisms remain to be determined. Exosomes play a role in shuttling proteins and other materials to recipient cells. In our study, we found that exosomes were aroused by β‐catenin in renal tubular cells. Osteopontin (OPN), especially its N‐terminal fragment (N‐OPN), was encapsulated in β‐catenin‐controlled tubular cell‐derived exosome cargo, and subsequently passed to fibroblasts. Through binding with CD44, exosomal OPN promoted fibroblast proliferation and activation. Gene deletion of β‐catenin in tubular cells (Ksp‐β‐catenin−/−) or gene ablation of CD44 (CD44−/−) greatly ameliorated renal fibrosis. Notably, N‐OPN was carried by exosome and secreted into the urine of patients with CKD, and negatively correlated with kidney function. The urinary exosomes from patients with CKD greatly accelerated renal fibrosis, which was blocked by CD44 deletion. These results suggest that exosome‐mediated activation of the OPN/CD44 axis plays a key role in renal fibrosis, which is controlled by β‐catenin.
Physiological stress responses to nonmimetic model brood parasite eggs: Leukocyte profiles and heat‐shock protein Hsp70 levels
Authors: Ruiz‐Raya Francisco , Abaurrea Teresa , Vigo Ramón , Soler Manuel
Published: March 2022

Obligate avian brood parasites lay their eggs in the nest of other bird species, known as hosts. Brood parasitism often imposes severe fitness costs on hosts, selecting for the evolution of effective antiparasitic defences, such as recognition and rejection of brood parasite eggs. Glucocorticoids have been recently found to mediate host physiological and behavioral adjustments in response to brood parasite eggs; however, it remains unclear whether brood parasitism triggers a general response involving multiple physiological elements. In this study, we experimentally investigated whether a salient brood parasitic stimulus (the presence of a nonmimetic model egg in the nest) causes physiological adjustments in adult Eurasian blackbirds (Turdus merula) at immune (leukocyte profiles) and cellular (heat‐shock protein Hsp70 synthesis) level. Also, we explored whether these physiological changes are mediated by variations in corticosterone (CORT) levels. We found that experimental brood parasitism caused an increase in heterophils and a decrease in lymphocytes, leading to higher heterophils and lymphocytes ratios in parasitized birds. Nevertheless, we did not find tradeoffs between immune function and CORT levels. Hsp70 synthesis was not affected by our experimental manipulation. Our findings provide evidence that brood parasite eggs trigger a general stress response in egg‐rejecter hosts, including changes in cellular immune profiles.
Clinical Feasibility of Structural and Functional MRI in Free‐Breathing Neonates and Infants
Authors: Zanette Brandon , Schrauben Eric M. , Munidasa Samal , Goolaub Datta S. , Singh Anuradha , Coblentz Ailish , Stirrat Elaine , Couch Marcus J. , Grimm Robert , Voskrebenzev Andreas , Vogel‐Claussen Jens , Seethamraju Ravi T. , Macgowan Christopher K. , Greer Mary‐Louise C. , Tam Emily W. Y. , Santyr Giles
Published: March 2022

Background

Evaluation of structural lung abnormalities with magnetic resonance imaging (MRI) has previously been shown to be predictive of clinical neonatal outcomes in preterm birth. MRI during free‐breathing with phase‐resolved functional lung (PREFUL) may allow for complimentary functional information without exogenous contrast.

Purpose

To investigate the feasibility of structural and functional pulmonary MRI in a cohort of neonates and infants with no cardiorespiratory disease. Macrovascular pulmonary blood flows were also evaluated.

Study Type

Prospective.

Population

Ten term infants with no clinically defined cardiorespiratory disease were imaged. Infants recruited from the general population and neonatal intensive care unit (NICU) were studied.

Field Strength/Sequence

T1‐weighted VIBE, T2‐weighted BLADE uncorrected for motion. Ultrashort echo time (UTE) and 3D‐flow data were acquired during free‐breathing with self‐navigation and retrospective reconstruction. Single slice 2D‐gradient echo (GRE) images were acquired during free‐breathing for PREFUL analysis. Imaging was performed at 3 T.

Assessment

T1, T2, and UTE images were scored according to the modified Ochiai scheme by three pediatric body radiologists. Ventilation/perfusion‐weighted maps were extracted from free‐breathing GRE images using PREFUL analysis. Ventilation and perfusion defect percent (VDP, QDP) were calculated from the segmented ventilation and perfusion‐weighted maps. Time‐averaged cardiac blood velocities from three‐dimensional‐flow were evaluated in major pulmonary arteries and veins.

Statistical Test

Intraclass correlation coefficient (ICC).

Results

The ICC of replicate structural scores was 0.81 (95% CI: 0.45–0.95) across three observers. Elevated Ochiai scores, VDP, and QDP were observed in two NICU participants. Excluding these participants, mean ± standard deviation structural scores were 1.2 ± 0.8, while VDP and QDP were 1.0% ± 1.1% and 0.4% ± 0.5%, respectively. Main pulmonary arterial blood flows normalized to body surface area were 3.15 ± 0.78 L/min/m2.

Data Conclusion

Structural and functional pulmonary imaging is feasible using standard clinical MRI hardware (commercial whole‐body 3 T scanner, table spine array, and flexible thoracic array) in free‐breathing infants.

Evidence Level

2

Technical Efficacy

Stage 1
Impact of three major risk factors on clinical outcomes in patients with nonvalvular atrial fibrillation receiving rivaroxaban: Sub‐analysis from the XAPASS study
Authors: Ikeda Takanori , Ogawa Satoshi , Kitazono Takanari , Nakagawara Jyoji , Minematsu Kazuo , Miyamoto Susumu , Murakawa Yuji , Tachiiri Michiya , Okayama Yutaka , Sunaya Toshiyuki , Hirano Kazufumi , Hayasaki Takanori
Published: March 2022

Background

To evaluate the impact of three risk factors (age [≥75 years], renal impairment [creatinine clearance <50 ml/min], and low body weight [≤50 kg]) on the risk of any bleeding events, all‐cause mortality, and stroke, non‐central nervous system (non‐CNS) systemic embolism (SE), and myocardial infarction (MI) in patients with nonvalvular atrial fibrillation (NVAF) treated with rivaroxaban in a real‐world clinical setting.

Methods

The Xarelto Post‐Authorization Safety and Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS) is a prospective, single‐arm, observational study. Enrolled patients were divided into four subgroups by the number of risk factors.

Results

Overall, 9823 patients were included: 4299 with low risk, 2816 with moderate risk, 1574 with high risk, and 1134 with very high risk. The hazard ratios (95% confidence interval) (reference: low risk) for the moderate‐, high‐, and very‐high‐risk groups were 1.62 (1.19, 2.21) (p = 0.002), 2.15 (1.47, 3.15) (p < 0.001), and 2.49 (1.60, 3.87) (p <0.001) for major bleeding, and 1.98 (1.47, 2.66), 2.29 (1.59, 3.29), and 2.74 (1.81, 4.16) (p <0.001 for all) for stroke/non‐CNS SE/MI, respectively.

Conclusions

Age ≥75 years and renal impairment, but not low body weight, were determinants for major bleeding. The accrual of three risk factors was associated with increased risk for major bleeding and stroke/non‐CNS SE/MI in patients with NVAF receiving rivaroxaban; there was no increase in the cumulative risk for these with an increasing number of risk factors.
Peering through the smokescreen: ESG disclosure and CEO personality
Authors: Dabbebi Ahlem , Lassoued Naima , Khanchel Imen
Published: March 2022

This study examines whether chief executive officer (CEO) with narcissistic tendencies are more likely to disclose ESG activities. Focusing on a sample of 118 US S&P 500‐listed companies over the period 2011–2018, the study uses the generalized estimating equation. The results indicate that a CEO with high narcissism is more likely to disclose social and corporate governance activities. These findings clarify the relationship between CEO personality traits and ESG disclosure to help investors and stakeholders with decision‐making. Further in light of these findings, regulators are recommended to reinforce the legal framework of ESG disclosure pushing for more transparency with high levels of supervision.
Effects of corporate social responsibility on pharmaceutical multinational enterprises performance: Research and development and business efficiency perspectives
Authors: Kao Fang Chen , Le Minh‐Hieu
Published: March 2022

This study employs an integrated two‐stage network data envelopment analysis, multiplicative efficiency aggregation in a second‐order cone programming approach, to assess efficiency scores of 41 pharmaceutical multinational enterprises (PMNEs). We also suggest a strategy for efficiently forecasting each PMNE's future efficiency score using a trend analysis technique. In particular, this study investigates how the three dimensions of corporate social responsibility (CSR) affect R&D efficiency and business efficiency. Results indicate that the governance pillar (social pillar) has a positive (negative) effect on the business efficiency of PMNEs. The findings give PMNE executives additional references to consider when deciding on CSR practices.
Targeting key proteins involved in transcriptional regulation for cancer therapy: Current strategies and future prospective
Authors: Pei Haixiang , Guo Weikai , Peng Yangrui , Xiong Hai , Chen Yihua
Published: March 2022

The key proteins involved in transcriptional regulation play convergent roles in cellular homeostasis, and their dysfunction mediates aberrant gene expressions that underline the hallmarks of tumorigenesis. As tumor progression is dependent on such abnormal regulation of transcription, it is important to discover novel chemical entities as antitumor drugs that target key tumor‐associated proteins involved in transcriptional regulation. Despite most key proteins (especially transcription factors) involved in transcriptional regulation are historically recognized as undruggable targets, multiple targeting approaches at diverse levels of transcriptional regulation, such as epigenetic intervention, inhibition of DNA‐binding of transcriptional factors, and inhibition of the protein–protein interactions (PPIs), have been established in preclinically or clinically studies. In addition, several new approaches have recently been described, such as targeting proteasomal degradation and eliciting synthetic lethality. This review will emphasize on accentuating these developing therapeutic approaches and provide a thorough conspectus of the drug development to target key proteins involved in transcriptional regulation and their impact on future oncotherapy.
Massachusetts BH resource database poised to support 988 MH crisis system
Authors: Canady Valerie A.
Published: March 2022

Network of Care Massachusetts (NoC MA), a free statewide online tool to help people with behavioral health needs find resources and treatment in their own communities, launched in March 2020. Little did behavioral health stakeholders know that following the planning and brainstorming that went into this initiative beginning in 2016 that it would formally commence right at the outset of a worldwide pandemic.
Texas judge halts investigations targeting gender‐affirming care
Authors: Enos Gary
Published: March 2022

A Texas state judge on March 11 issued an injunction blocking state investigations into youth health services for gender transitioning, probes that were launched after the state attorney general suggested that some of these procedures constitute child abuse. The state's recent actions had sent shock waves across a mental health provider community that considers gender‐affirming health services to be lifesaving care (see MHW, March 7).
Anterior intercostal artery perforator flap for immediate reconstruction following breast conservation surgery
Authors: Adler Neta , Carmon Einat , Chapchay Katya , Billig Allan
Published: March 2022

Introduction

Oncoplastic breast surgery following breast conservation surgery (BCS) utilizes aesthetic breast reduction techniques, and these reconstructions entail either volume displacement or volume replacement depending on the size and location of the excised tumor. The anterior Intercostal flap (AICAP) for immediate reconstruction after BCS is scarcely described in the literature. In this study, we present our experience with the Anterior Intercoastal Artery Perforator flap in 16 patients with small breast sizes.

Patients and Methods

Sixteen patients underwent lumpectomy followed by immediate reconstruction with Anterior ICAP flap between 2019 and 2021 at Hadassah University Hospital. Median age was 49 (range 28–67). Breast cup size, lumpectomy to breast size ration, defect measurements and location are provided. Flap design and flap in‐setting was planned and executed according to the size and location of the defect determined at the time of surgery. Surgical technique is described. Diagram of proposed reconstruction according to defect location is proposed.

Results

Flap dimensions clinically matched the defect size or were slightly larger due to anticipated shrinkage of tissue post radiation with mean of 5.4 × 3.9 × 3.75 cm (range of 2.5–13 × 2–13.2 × 0.8–4.5 cm). Complications, namely one seroma and one mild infection, were seen in two patients. Median follow up was 3 months after completion of radiation. All reconstructions were satisfactory by both surgeon and patient at last post‐operative follow‐up visit.

Conclusion

The anterior ICAP flap is an important addition to the armamentarium of immediate reconstruction options after BCS, particularly in patients smaller size breast sizes.
Dendrobium nobile Lindl polysaccharides improve testicular spermatogenic function in streptozotocin‐induced diabetic rats
Authors: Lei Xiaocan , Huo Peng , Xie Yuan‐jie , Wang Yaohui , Liu Guanghai , Tu Haoyan , Shi Qingxiang , Mo Zhong‐cheng , Zhang Shun
Published: March 2022

Dendrobium nobile Lindl polysaccharides (DNLP) exhibited various biological functions. This study aimed to investigate the protective effects of DNLP on testicular spermatogenic function in streptozotocin (STZ)‐induced diabetic rats in comparison with metformin. The blood glucose level was significantly increased and the homeostatic model assessment for insulin resistance (HOMA‐IR) aggravated markedly in diabetic rats. The weight of testis and epididymis, and the sperm number and motility were decreased in the diabetic rats. The pathologic changes occurred in the spermatogenic tubules along with the decreased number of spermatogenic cells, downregulated proliferating cell nuclear antigen (PCNA) and Sirtuin 1 (SIRT1) expression and increased cell apoptosis in the testes. Compared with the model group, DNLP and metformin treatment significantly decreased the level of blood glucose, improved the HOMA‐IR, and increased the weight of testis and epididymis, as well as the sperm number and sperm motility. Furthermore, the pathologic changes in the spermatogenic tubules improved significantly with increased number of spermatogenic cells, the upregulation of PCNA and SIRT1 and suppression of cell apoptosis in the testes. Collectively, our study for the first time examined the effects of DNLP on the male reproductive system of STZ‐induced diabetic rats, and indicated that DNLP was protective against diabetes mellitus‐induced testis injury via increasing the proliferation, inhibiting cell apoptosis and upregulating SIRT1 expression in testicular spermatogenic cells.
A physiologically relevant, estradiol‐17β [E2]‐responsive in vitro tissue‐engineered model of the vaginal epithelium for vaginal tissue research
Authors: Shafaat Sarah , Mangir Naside , Chapple Christopher , MacNeil Sheila , Hearnden Vanessa
Published: March 2022

Aims

There are many situations where preclinical models of the human vagina would be valuable for in vitro studies into the pathophysiology of vaginally transmitted diseases, microbicide efficacy, irritability testing, and particularly, for assessing materials to be inserted in the vagina for support of the pelvic floor. The aim of this study is to develop a physiologically relevant, low cost, and ethically suitable model of the vagina using sheep vaginal tissue (SVT) to reduce the need for animal testing in gynecological research.

Methods

Tissue‐engineered (TE) vaginal models were developed by culturing primary vaginal epithelial cells and vaginal fibroblasts, isolated from the native SVTs on decellularized sheep vaginal matrices at an air–liquid interface. Morphological analyses of the models were conducted by performing hematoxylin and eosin staining and further characterization was done by immunohistofluorescence (IHF) of structural proteins and cytokeratins.

Results

Histological analysis of the models revealed a gradual formation of a stratified epithelium on our decellularized matrices and cell metabolic activity remained high for 21 days as measured by the resazurin assay. Our models showed a dose‐dependent response to estradiol‐17β [E2] with an increase in the vaginal epithelium thickness and cellular proliferation under higher E2 concentrations (100–400 pg/ml). The physiological relevance of these results was confirmed by the IHF analysis of Ki67, and cytokeratins 10 and 19 expression.

Conclusion

In this study, we have developed an estradiol‐responsive TE vaginal model that closely mimics the structural and physiological properties of the native SVT.
Student nurses’ views on shift patterns: What do they prefer and why? Results from a Tweetchat
Authors: Dall’Ora Chiara , Sainsbury Jessica , Allen Chris
Published: March 2022

Aim

The main aim of the study was to understand student nurses’ views around shift patterns.

Design

Qualitative study.

Method

We held a Tweetchat in May 2019, where we asked questions around the frequency of 12‐hr shifts working on placement; schedule flexibility while on placement; which shift patterns they preferred and why. Data from the Tweetchat were analysed using reflexive thematic analysis to generate themes from initial codes.

Results

Seventy‐three nursing students participated in the Tweetchat. The majority reported that they work 12‐hr shifts on placements, particularly when based in a hospital. We identified three themes: ‘Achieving a personal equilibrium’; ‘Meeting the needs of the care environment’; ‘Factors affecting negotiation capacity’. Data highlighted a conflict for most students, where they preferred 12‐hr shifts because of more time off for study, paid work and leisure, while acknowledging 12‐hr shifts negatively affected their fatigue, exhaustion and led them to follow a poor diet and neglect exercise and sleep.
Marginalized adult learners faced different challenges during COVID‐19
Authors: Sutton Halley
Published: March 2022

SAN DIEGO, Cal. — “It's been my privilege to work with adult learners all the time,” Royce Ann Collins, Ph.D., Associate Professor of Adult Learning and Leadership at Kansas State University, said. Collins has worked with partner organizations, including working with the DeBruce Foundation, to conduct research on adult scholars at various programs, including the differences between adult learners and traditional students.
International student enrollment in the U.S. 2021–2022: Analysis and trends
Authors: Dennis Marguerite J.
Published: March 2022

Although the title of this article refers to current international student enrollment in the U.S., I think it is important to analyze current enrollment in light of the past years’ statistics and trends.
Reaffirmation: The critical partner to a resolution
Authors: Skipworth Stan
Published: March 2022

While 2020 and 2021 have been incredibly difficult in many ways, I look back at 2021 with a particular amount of pride for a rather important personal achievement.
Toughening and rapid self‐healing for carbon fiber/epoxy composites based on electrospinning thermoplastic polyamide nanofiber
Authors: Chen Boxue , Cai Haopeng , Mao Chi , Gan Yu , Wei Yinglong
Published: March 2022

This article fabricated toughening and self‐healing carbon/epoxy composites based on electrospinning thermoplastic polyamide nanofiber (PAnf). When the incorporation of PAnf was merely 1.2 wt%, the interlaminar shear and bending strength of composites increased by 17.6% and 14.7%. The two main toughening mechanisms were the entangled porous nanofiber structure with a large specific surface area and the strong interface resulting from the interaction between PAnf and epoxy. Multiple short beam shear cycles generating interlaminar fracture were conducted to evaluate the healing efficiency. The obtained results for three damage‐healing cycles achieved 110.4%, 88.4%, and 70.1%, respectively. The melting thermoplastic PAnf would thermally expand, flow across microcrack, and fill delamination at healing temperature. This process was the inherent characteristic of thermoplastic PAnf, and thus, the composites can heal the damaged region rapidly and repeatedly. Moreover, PAnf with low incorporation showed no adverse effect on the storage modulus and Tg of composites, which maintained their original properties.
Modeling analysis of elastic properties of graphene‐carbon nanotube (G‐C) reinforced composites
Authors: Zheng Weipeng , Guo Zhangxin , Wang Zhihua , Boay Chai Gin , Wang Xiaojun , Li Yongcun
Published: March 2022

This article describes in detail the research on the elastic properties of carbon nanotube reinforced composite materials and graphene‐carbon nanotube (G‐C) reinforced composite materials. Several different composite material models were established using finite element software ABAQUS to study the influence of the inclination angle, quantity and volume fraction of carbon nanotubes and graphene on the elastic modulus of reinforced composites. The results show that as the volume fraction of graphene and carbon nanotubes increases, the Young's modulus and shear modulus of the reinforced composite material increase significantly. In addition, the tilt angle and quantity of graphene and carbon nanotubes will also affect the elastic properties of the composite material. The Young's modulus E and the shear modulus G decrease with the increase of the inclination angle, and increase with the increase of the number of graphene and carbon nanotubes.
Supporting school‐community collaboration for the implementation of a multi‐tiered school mental health program: The Behavioral Health Team model
Authors: Raviv Tali , Smith Mashana , Hurwitz Laura , Gill Tara L. , Baker Sybil , Torres Stephanie A. , Bowen Iman E. , Cicchetti Colleen
Published: March 2022

Investing in school mental health programs has the potential to improve youths' access to mental health services. Barriers to the implementation of school mental health programs include limited workforce capacity, competing priorities, and lack of coordinated care. The current paper describes the history, development, and key components of the Behavioral Health Team (BHT) model that was established to promote implementation of school mental health programming. The BHT is a multi‐disciplinary team designed to maximize resources and collaboration, provide early identification of students with behavioral health needs, and match and connect students to the indicated interventions using data‐informed decision making. BHTs are tasked with selecting appropriate interventions, assuring fidelity of implementation, monitoring student progress and making adjustments based on data to enhance the sustainability and dissemination of evidence‐based prevention and intervention in schools. The paper reviews two case examples to illustrate how this model has been applied both within a large urban school district and a medium‐sized suburban school district. Results demonstrate that district support facilitates sustainability and expansion of the BHT model over time. Schools implementing this model demonstrate improvement in implementation of the BHT key components.
Ginkgo biloba extract ameliorates atherosclerosis via rebalancing gut flora and microbial metabolism
Authors: Wang Yun , Xu Yuanyuan , Xu Xiaowei , Wang Hong , Wang Dong , Yan Wenchao , Zhu Jiaying , Hao Haiping , Wang Guangji , Cao Lijuan , Zhang Jun
Published: March 2022

The Ginkgo biloba leave extract (GbE) is widely applied in the prevention and treatment of atherosclerotic cardiovascular diseases in clinical practice. However, its mechanism of actions has not been totally elucidated. In this study, we confirmed the beneficial effects of GbE in alleviating hypercholesterolemia, inflammation and atherosclerosis in Ldlr−/− mice, which were fed 12 weeks of Western diet (WD). Moreover, 16S rRNA sequencing revealed that GbE treatment reshaped the WD‐perturbed intestinal microbiota, particularly decreased the Firmicutes/Bacteroidetes ratio and elevated the abundance of Akkermansia, Alloprevotella, Alistipes, and Parabacteroides. Furthermore, GbE treatment downregulated the intestinal transcriptional levels of proinflammatory cytokines and enhanced the expression of tight junction proteins, exerting the roles of attenuating the intestinal inflammation as well as repairing the gut barrier. Meanwhile, the targeted metabolomic analysis displayed that GbE treatment significantly reversed the dysfunction of the microbial metabolic phenotypes, including promoting the production of short chain fatty acids, indole‐3‐acetate and secondary bile acids, which were correlated with the atherosclerotic plaque areas. Finally, we confirmed GbE‐altered gut microbiota was sufficient to alleviate atherosclerosis by fecal microbiota transplantation. In summary, our findings provide important insights into the pharmacological mechanism underlying the antiatherogenic efficacy of GbE.
The influence of women on SME innovation in emerging markets
Authors: Madison Kristen , Moore Curt B. , Daspit Joshua J. , Nabisaalu Joyce Komakech
Published: March 2022

Research Summary

Our study provides novel insights into how women influence SME innovation in emerging markets, despite the resource‐constrained and gender‐restrictive contexts in which they are embedded. Building from transactive memory (TM) theory and using data from 741 SMEs in 33 emerging markets, we develop and test a contextualized framework of SME innovation that considers gendered effects in ownership, workforce composition, and communication. Findings indicate that in emerging markets, female‐led SMEs employ more women than male‐led SMEs, and more women in SMEs (even at modest levels) enhance and enable the TM system to deliver more innovation outcomes. Findings also suggest that emerging‐market SMEs can be innovative through differing configurations of women in ownership and workforce composition, underscoring the importance of gendered and contextual considerations in innovation research.

Managerial Summary

Innovation is vital to the social progress and economic development of emerging markets. Even though institutionalized gender bias in emerging markets tends to constrain (rather than empower) women's entrepreneurial activities, our study reveals how women can be an important source of innovation. We find that women in emerging markets are stronger together: women in ownership advocate for and support other women by employing them in their SMEs, and in turn, as women's representation increases in SMEs, women are empowered to collectively share and leverage their endowed resources for innovation. Thus, our study challenges the general perception that men are more innovative than women by revealing that the presence of women in emerging‐market SMEs yields greater innovation outcomes.
Peptide‐Engineered AIE Nanofibers with Excellent and Precisely Adjustable Antibacterial Activity
Authors: Guo Kunzhong , Zhang Minjie , Cai Junyi , Ma Zunwei , Fang Zhou , Zhou Haiyan , Chen Junjian , Gao Meng , Wang Lin
Published: March 2022

Photosensitizers with aggregation‐induced emission properties (AIEgens) can produce reactive oxygen species (ROS) under irradiation, showing great potential in the antibacterial field. However, due to the limited molecular skeletons, the development of AIEgens with precisely adjustable antibacterial activity is still a daunting challenge. Herein, a series of AIE nanofibers (AIE‐NFs) based on the AIEgen of DTPM as the inner core and rationally designed peptides as bacterial recognition ligands (e.g., antimicrobial peptide (AMP) HHC36, ditryptophan, polyarginine, and polylysine) is developed. These AIE‐NFs show precisely adjustable antibacterial behaviors simply by changing the decorated peptides, which can regulate the aggregation and inhibition of different bacteria. By mechanistic analysis, it is demonstrated that this effect can be attributed to the synergistic antibacterial activities of the ROS and the peptides. It is noteworthy that the optimized AIE‐NFs, NFs‐K18, can efficiently aggregate bacteria to cluster and kill four types of clinical bacteria under irradiation in vitro, inhibit the infection of methicillin‐resistant Staphylococcus aureus (MRSA) and promote wound healing in vivo. To the authors’ knowledge, this is the first report of AIE‐NFs with precisely adjustable antibacterial activity, providing new opportunities for photodynamic therapy (PDT) treatment of infection.
State-Owned Gambling Operation in a Global Competitive Environment
Authors: Järvinen-Tassopoulos Johanna
Published: March 2022

This qualitative study examines what factors and measures may contribute to the success of a state-owned gambling company online. As each jurisdiction restricts online gambling offer and demand according to domestic legislation, there are few tools to limit the competition of online operators.

In order to understand how different stakeholders want to limit online competition and preserve the benefits guaranteed by a monopolistic gambling system, thematic interviews (N = 17) were conducted among the state-owned gambling company Veikkaus’ representatives and among public servants engaged in gambling regulation, ownership steering, the prevention of gambling harm, or the distribution and reception of gambling proceeds. Chantal Mouffe’s theorisation on ‘antagonism’ and ‘agonism’ is used to examine the impact of competition of these stakeholders.

The results show that the challenges of the Finnish state-owned gambling operator were related to competition (e.g., losing customers and proceeds to international competitors) and to regulation (e.g., channelling gambling and preventing gambling harms). The results also indicated that Veikkaus’ representatives seem to have an agonistic relationship with the regulators and the public servants interested in prevention of gambling harms. The only antagonism found in this study is based on the conflicting power relations of Veikkaus and the international online gambling companies.
Approximation Properties of the Double Fourier Sphere Method
Authors: Mildenberger Sophie , Quellmalz Michael
Published: March 2022

We investigate analytic properties of the double Fourier sphere (DFS) method, which transforms a function defined on the two-dimensional sphere to a function defined on the two-dimensional torus. Then the resulting function can be written as a Fourier series yielding an approximation of the original function. We show that the DFS method preserves smoothness: it continuously maps spherical Hölder spaces into the respective spaces on the torus, but it does not preserve spherical Sobolev spaces in the same manner. Furthermore, we prove sufficient conditions for the absolute convergence of the resulting series expansion on the sphere as well as results on the speed of convergence.
Diagnostic variation for febrile children in European emergency departments
Authors: Zanetto Lorenzo , van de Maat Josephine , Nieboer Daan , Moll Henriette , Gervaix Alain , Da Dalt Liviana , Mintegi Santiago , Bressan Silvia , Oostenbrink Rianne
Published: March 2022

The study aimed to explore the use of diagnostics for febrile children presenting to European emergency departments (EDs), the determinants of inter-hospital variation, and the association between test use and hospitalization. We performed a secondary analysis of a cross-sectional observational study involving 28 paediatric EDs from 11 countries. A total of 4560 children < 16 years were included, with fever as reason for consultation. We excluded neonates and children with relevant comorbidities. Our primary outcome was the proportion of children receiving testing after primary evaluation, by country and by focus of infection. Variability between hospitals and effects of blood testing on patient disposition were explored by multilevel regression analyses, adjusting for patient characteristics (age group, triage level, appearance, fever duration, focus of infection) and hospital type (academic, teaching, other). The use of routine diagnostics varied widely, mostly in the use of blood tests, ranging from 3 to 75% overall across hospitals. Age < 3 months, high-acuity triage level, ill appearance, and suspicion of urinary tract infection displayed the strongest association with blood testing (odds ratios (OR) of 8.71 (95% CI 5.23–14.53), 19.46 (3.66–103.60), 3.13 (2.29–4.26), 10.84 (6.35–18.50), respectively). Blood testing remained highly variable across hospitals (median OR of the final model 2.36, 1.98–3.54). A positive association was observed between blood testing and hospitalization (OR 13.62, 9.00–20.61).

Conclusion: the use of diagnostics for febrile children was highly variable across European EDs, yet patient and hospital characteristics could only partly explain inter-hospital variability. Focus groups of participating sites should help define reasons for unexpected variation.

What is Known:• Although previous research has shown variation in the emergency department (ED) management of febrile children, there is limited information on the use of diagnostics in European EDs.• A deeper knowledge of variability and its determinants can steer optimization of care.

What is New:• The use of diagnostics for febrile children was highly variable across European EDs, yet patient and hospital characteristics could only partly explain inter-hospital variability.• Data on between-centre comparison offer opportunities to further explore factors influencing unwarranted variation.
How cunning is the puppet-master? Cestode-infected fish appear generally fearless
Authors: Svensson P. Andreas , Eghbal Ramin , Eriksson Ramona , Nilsson Emelie
Published: March 2022

Trophically transmitted parasites have life cycles that require the infected host to be eaten by the correct type of predator. Such parasites should benefit from an ability to suppress the host’s fear of predators, but if the manipulation is imprecise the consequence may be increased predation by non-hosts, to the detriment of the parasite. Three-spined sticklebacks (Gasterosteus aculeatus) infected by the cestodeSchistocephalus solidusexpress reduced antipredator behaviours, but it is unknown whether this is an example of a highly precise manipulation, a more general manipulation, or if it can even be attributed to mere side effects of disease. In a series of experiments, we investigated several behaviours of infected and uninfected sticklebacks. As expected, they had weak responses to simulated predatory attacks compared to uninfected fish. However, our results suggest that the parasite induced a general fearlessness, rather than a precise manipulation aimed at the correct predators (birds). Infected fish had reduced responses also when attacked from the side and when exposed to odour from a fish predator, which is a “dead-end” for this parasite. We also tested whether the reduced anti-predator behaviours were mere symptoms of a decreased overall vigour, or due to parasite-induced hunger, but we found no support for these ideas. We propose that even imprecise manipulations of anti-predator behaviours may benefit parasites, for example, if other behaviours are altered in a way that increases the exposure to the correct predator.
Gene expression and epigenetic markers of prion diseases
Authors: Viré Emmanuelle A. , Mead Simon
Published: March 2022

Epigenetics, meaning the variety of mechanisms underpinning gene regulation and chromatin states, plays a key role in normal development as well as in disease initiation and progression. Epigenetic mechanisms like alteration of DNA methylation, histone modifications, and non-coding RNAs, have been proposed as biomarkers for diagnosis, classification, or monitoring of responsiveness to treatment in many diseases. In prion diseases, the profound associations with human aging, the effects of cell type and differentiation on in vitro susceptibility, and recently identified human risk factors, all implicate causal epigenetic mechanisms. Here, we review the current state of the art of epigenetics in prion diseases and its interaction with genetic determinants. In particular, we will review recent advances made by several groups in the field profiling DNA methylation and microRNA expression in mammalian prion diseases and the potential for these discoveries to be exploited as biomarkers.
A duality based 2-approximation algorithm for maximum agreement forest
Authors: Olver Neil , Schalekamp Frans , van der Ster Suzanne , Stougie Leen , van Zuylen Anke
Published: March 2022

We give a 2-approximation algorithm for the Maximum Agreement Forest problem on two rooted binary trees. This NP-hard problem has been studied extensively in the past two decades, since it can be used to compute the rooted Subtree Prune-and-Regraft (rSPR) distance between two phylogenetic trees. Our algorithm is combinatorial and its running time is quadratic in the input size. To prove the approximation guarantee, we construct a feasible dual solution for a novel exponential-size linear programming formulation. In addition, we show this linear program has a smaller integrality gap than previously known formulations, and we give an equivalent compact formulation, showing that it can be solved in polynomial time.