bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact and cost-effectiveness of 9-valent human papillomavirus vaccine in adolescent females in Hong Kong
Authors: Cheung Tak Hong , Cheng Sally Shuk Yee , Hsu Danny C. , Wong Queenie Wing-Lei , Pavelyev Andrew , Walia Anuj , Saxena Kunal , Prabhu Vimalanand S.
Published: November 2021

Introduction

In Hong Kong (HK), a single-cohort vaccination program for 10–12-year-old girls with the 9-valent human papillomavirus (HPV) vaccine (9vHPV; types 6/11/16/18/31/33/45/52/58) has been launched. This study assessed the public health impact and cost-effectiveness of implementing routine 9vHPV vaccination (12-year-olds) with or without catch-up 9vHPV vaccination (13–18-year-olds) in HK.

Methods

The health impact and costs of implementing routine 9vHPV vaccination with or without catch-up vaccination over a 100-year time horizon were evaluated using a validated HPV-type transmission dynamic model adapted to the HK population; analyses were performed from a healthcare payer perspective. Routine vaccination (12-year-old girls) and catch-up vaccination (13–18 years) assumed vaccine coverage rates of 70% (base case) and 30%, respectively. The model also assumed herd immunity, lifelong vaccine protection, a discount rate of 3%, and a cost per dose of HK dollars (HKD) 858 [United States dollars (USD) 110] and HKD 1390 (USD 179) for the 2-valent HPV (2vHPV) and 9vHPV vaccines, respectively. HPV disease-related incidence and the incremental cost-effectiveness ratio (ICER) per quality-adjusted-life-year (QALY) were estimated. Cost-effectiveness was determined at a ceiling threshold of HK dollars (HKD) 382,046 (USD 49,142) or 1.0 times the gross domestic product per capita of HK.

Results

Compared with routine 9vHPV alone, routine plus catch-up 9vHPV is projected to reduce cervical cancer incidence by 3.4%. Routine plus catch-up 9vHPV will also reduce genital warts incident cases for males/females by 2.6%/5.4%. The incremental cost-effectiveness ratios were HKD 29,911 (USD 3847)/quality-adjusted life-year (QALY) for routine plus catch-up 9vHPV versus routine 9vHPV alone and HKD 25,524 (USD 3283)/QALY for routine 9vHPV alone versus screening only. Sensitivity analyses indicated that routine plus catch-up 9vHPV compared with routine 9vHPV alone remained cost-effective at coverage rates of 30% and 90%.

Conclusions

This analysis predicts that the current HK vaccination strategy can be considered cost-effective and will provide maximum health benefit. These results support addition of the routine 9vHPV vaccine with or without catch-up 9vHPV vaccination to the regional vaccination program in HK.
Multiomic analysis on human cell model of wolfram syndrome reveals changes in mitochondrial morphology and function
Authors: Zmyslowska Agnieszka , Kuljanin Miljan , Malachowska Beata , Stanczak Marcin , Michalek Dominika , Wlodarczyk Aneta , Grot Dagmara , Taha Joanna , Pawlik Bartłomiej , Lebiedzińska-Arciszewska Magdalena , Nieznanska Hanna , Wieckowski Mariusz R. , Rieske Piotr , Mancias Joseph D. , Borowiec Maciej , Mlynarski Wojciech , Fendler Wojciech
Published: November 2021

Background

Wolfram syndrome (WFS) is a rare autosomal recessive syndrome in which diabetes mellitus and neurodegenerative disorders occur as a result of Wolframin deficiency and increased ER stress. In addition, WFS1 deficiency leads to calcium homeostasis disturbances and can change mitochondrial dynamics. The aim of this study was to evaluate protein levels and changes in gene transcription on human WFS cell model under experimental ER stress.

Methods

We performed transcriptomic and proteomic analysis on WFS human cell model—skin fibroblasts reprogrammed into induced pluripotent stem (iPS) cells and then into neural stem cells (NSC) with subsequent ER stress induction using tunicamycin (TM). Results were cross-referenced with publicly available RNA sequencing data in hippocampi and hypothalami of mice with WFS1 deficiency.

Results

Proteomic analysis identified specific signal pathways that differ in NSC WFS cells from healthy ones. Next, detailed analysis of the proteins involved in the mitochondrial function showed the down-regulation of subunits of the respiratory chain complexes in NSC WFS cells, as well as the up-regulation of proteins involved in Krebs cycle and glycolysis when compared to the control cells. Based on pathway enrichment analysis we concluded that in samples from mice hippocampi the mitochondrial protein import machinery and OXPHOS were significantly down-regulated.

Conclusions

Our results show the functional and morphological secondary mitochondrial damage in patients with WFS.

Graphical Abstract
Development of a real-time RT-PCR assay for the detection of pan-human parechoviruses
Authors: Lu Huanhuan , Xiao Jinbo , Zhang Keyi , Han Zhenzhi , Song Yang , Wang Dongyan , Ji Tianjiao , Yan Dongmei , Zhu Shuangli , Xu Wenbo , Zhang Yong
Published: November 2021

Background

Parechoviruses (PeV-As), which constitute a new genus within the family Picornaviridae, have been associated with numerous localized outbreaks of serious diseases, such as coryza, pneumonia, maculopapular exanthem, and conjunctivitis. However, to the best of our knowledge, only a few laboratories worldwide conduct tests for the identification of this group of viruses. Therefore, in this study, we aimed to develop and validate a real-time RT-PCR assay for the identification of PeV-As.

Methods

To design and validate a real-time PCR primer–probe targeting the 5′-UTR region of PeV-As, the 5′-UTR sequences of PeV-As available in GenBank were aligned using the MUSCLE algorithm in MEGA v7.0. Thereafter, the highly conserved 5′-UTR region was selected, and its primer–probe sequence was designed using Primer Premier v5.0. This primer–probe sequence was then evaluated for specificity, sensitivity, and repeatability, and for its validation, it was tested using fecal samples from 728 healthy children living in Beijing (China).

Results

The PeV-A real-time RT-PCR assay detected only the RNA-positive standards of PeV-A genotypes (1–8, 14, 17, and 18), whereas 72 serotypes of non-PeV-A EV viruses were undetected. In addition, the VP1 region of these 11 PeV-A genotypes that tested positive were amplified using the primers designed in this study. Typing results indicated that eight, one, and two strains of the 11 were PeV-A1, PeV-A4, and PeV-A6, respectively. We also determined and presented the genetic characterization and phylogenetic analyses results corresponding to these 11 VP1 region sequences. Furthermore, real-time RT-PCR assay showed good sensitivity with LOD of 102 copies/μL. Positive results in eight parallel experiments at each concentration gradient from 107 copies/μL to 102 copies/μL, indicating good repeatability.

Conclusion

Our findings suggested that the real-time RT-PCR assay developed in this study can be applied for routine PeV-A identification. We detected PeV-A1, 4 and 6 genotypes in the 728 faecal samples using this method. Additionally, we believe that our results will serve as a foundation for further studies on PeV-As and facilitate the expansion of the gene sequence information available in GenBank.
Association between maternal hepatitis B virus carrier and gestational diabetes mellitus: a retrospective cohort analysis
Authors: Yin Wanchang , Chen Bingjun , Yang Yilin , Li Xiuzi , Li Ruirui , Xie Jiangnan , Chen Guixian , He Fang , Chen Dunjin
Published: November 2021

Introduction

Given that many pregnant women have chronic hepatitis B virus (HBV) infection and that gestational diabetes mellitus (GDM) is linked to poor maternal and neonatal outcomes, we looked into the relationship between the hepatitis B surface antigen (HBsAg) and GDM to see if a high HBV DNA load is linked to a higher risk of GDM in chronic maternal HBsAg carriers.

Materials and methods

Our study included 39,539 pregnant women who gave birth at the Third Affiliated Hospital of Guangzhou Medical University in Guangzhou, China, between January 1, 2009, and December 31, 2019. The patients were divided into two groups: HBsAg negative (36,500) and positive (3039). The viral load levels of 1250 HBsAg-positive women who had tested their HBV DNA load during pregnancy were separated into three groups. We utilized univariate and multivariable logistical regression analysis to determine the relationship between maternal chronic HBsAg carrier and GDM.

Results

Being HBsAg positive was discovered to be an independent risk factor for GDM.Pre-pregnancy Obesity and advanced age were linked to an increased incidence of GDM. Those with a high HBV DNA load (> 106 IU/mL) had a higher risk of GDM than HBsAg-positive women with a low viral load (< 103 IU/mL). Pre-eclampsia and intrahepatic cholestasis of pregnancy (ICP) appeared to be more common in HBsAg-positive women than in uninfected women.

Conclusions

Being HBsAg positive, advanced age, and pre-pregnancy obesity were all revealed to be independent risk factors for GDM in our study. In HBsAg carrier, pregnant women, a high HBV DNA burden was linked to a greater risk of GDM. Furthermore, being an HBsAg carrier during pregnancy raised the risk of ICP and pre-eclampsia.
Case report: composite pancreatic intraductal papillary mucinous neoplasm and neuroendocrine tumor: a new mixed neuroendocrine-non-neuroendocrine neoplasm?
Authors: Chen Jingci , Wang Pengyan , Lv Ke , Zhou Weixun
Published: November 2021

Background

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) of the pancreas are extremely rare. Their pathogenesis and molecular landscape are largely unknown. Here, we report a case of mixed pancreatic intraductal papillary mucinous neoplasm (IPMN) and well-differentiated neuroendocrine tumor (NET) and identify its genetic alterations by next-generation sequencing (NGS).

Case presentation

A fifty-year-old male was admitted into the hospital for evaluation of a pancreatic lesion detected during a routine examination. Abdominal ultrasound indicated a hypoechoic mass of 2.6 cm at the head of the pancreas. Malignancy was suspected and partial pancreatectomy was performed. Thorough histopathological examination revealed a mixed IPMN-NET. In some areas, the two components were relatively separated, whereas in other areas IPMN and NET grew in a composite pattern: The papillae were lined with epithelial cells of IPMN, and there were clusters of NET nests in the stroma of papillary axis. NGS revealed shared somatic mutations (KRAS,PCK1,MLL3) in both components. The patient has been uneventful 21 months after the surgery.

Conclusions

Our case provides evidence of a common origin for mixed IPMN-NET with composite growth features. Our result and literature review indicate thatKRASmutation might be a driver event underlying the occurrence of MiNEN. We also recommend the inclusion of mixed non-invasive exocrine neoplasms and neuroendocrine neoplasms into MiNEN.
Morphological predictors for microsatellite instability in urothelial carcinoma
Authors: Sobrino-Reig Eduardo , Meizoso Telma , García Jesús , Varillas-Delgado David , Martin Yasmina B.
Published: November 2021

Introduction

Microsatellite instability occurs due to a series of mutations in the DNA pairing error repair (Mismatch repair; MMR) genes, which can affect germ cells as occurs in Lynch syndrome, whose patients are at high risk of developing multiple cancers. The loss of MMR protein is commonly determined by immunohistochemical studies. Although the relation between microsatellite instability and urothelial carcinomas has been widely studied, its evaluation is not currently performed in the analysis of urothelial carcinomas.

Methods

In this study, the microsatellite status of 139 urothelial carcinomas was analyzed and their clinicopathological characteristics were evaluated. We identified that 10.3% (13 patients) of urothelial carcinomas had loss of MMR protein expression (9 MLH1; 5 MSH2; 2 PMS2; 2 PSH6; n = 139).

Results

Results suggest that these tumors occur more frequently in males, are more frequently located in the bladder or ureters, and present a high tumor grade with a papillary histological pattern that does not infiltrate the lamina propria or, in the case of infiltrating tumors, that grows into perivesical tissues.

Conclusions

We identified patients with the aforementioned tumor characteristics as patients with a high probability of presenting loss of MMR protein expression, and consider that only these patients should undergo further immunohistochemical and molecular techniques for proper diagnosis. Therefore, we propose that the clinicopathological characteristics found in the present study could become possible markers to determine which cases should undergo additional tests.
Local control of bone metastases treated with external beam radiotherapy in recent years: a multicenter retrospective study
Authors: Makita Kenji , Hamamoto Yasushi , Kanzaki Hiromitsu , Kataoka Masaaki , Yamamoto Shuhei , Nagasaki Kei , Ishikawa Hirofumi , Takata Noriko , Tsuruoka Shintaro , Uwatsu Kotaro , Kido Teruhito
Published: November 2021

Background

Over the past decades, remarkable advancements in systemic drug therapy have improved the prognosis of patients with bone metastases. Individualization is required in external beam radiotherapy (EBRT) for bone metastases according to the patient’s prognosis. To establish individualized EBRT for bone metastases, we investigated factors that affect the local control (LC) of bone metastases.

Methods

Between January 2010 and December 2019, 536 patients received EBRT for 751 predominantly osteolytic bone metastases. LC at EBRT sites was evaluated with a follow-up computed tomography. The median EBRT dose was biologically effective dose (BED10) (39.0) (range of BED10: 14.4–71.7 Gy).

Results

The median follow-up time and median time of computed tomography follow-up were 11 (range 1–123) months and 6 (range 1–119) months, respectively. The 0.5- and 1-year overall survival rates were 73% and 54%, respectively. The 0.5- and 1-year LC rates were 83% and 79%, respectively. In multivariate analysis, higher age (≥ 70 years), non-vertebral bone metastases, unfavorable primary tumor sites (esophageal cancer, colorectal cancer, hepatobiliary/pancreatic cancer, renal/ureter cancer, sarcoma, melanoma, and mesothelioma), lower EBRT dose (BED10 < 39.0 Gy), and non-administration of bone-modifying agents (BMAs)/antineoplastic agents after EBRT were significantly unfavorable factors for LC of bone metastases. There was no statistically significant difference in the LC between BED10 = 39.0 and BED10 > 39.0 Gy.

Conclusions

Regarding tumor-related factors, primary tumor sites and the sites of bone metastases were significant for the LC. As for treatment-related factors, lower EBRT doses (BED10 < 39.0 Gy) and non-administration of BMAs/antineoplastic agents after EBRT were associated with poor LC. Dose escalation from BED10 = 39.0 Gy did not necessarily improve LC.
Music therapy and Sanfilippo syndrome: an analysis of psychological and physiological variables of three case studies
Authors: Pérez-Núñez P. , Lázaro E. , Amayra I. , López-Paz J. F. , Caballero P. , Martínez O. , Pérez M. , Berrocoso S. , Al-Rashaida M. , García M. , Rodríguez A. A. , Luna P. M.
Published: November 2021

Introduction

Mucopolysaccharidosis type III (MPS III) or Sanfilippo syndrome is a neurodegenerative disease caused by the accumulation of mucopolysaccharides in the body. As the symptoms are wide ranging, it is a challenge to provide a diagnosis and psychological treatment for affected children.

Method

The main objective of this study was to describe a form of music therapy treatment applied to three children diagnosed with MPS III. The psychological variables were evaluated by an ad hoc observation recording template, and the physiological variables were measured with a digital meter before and after each session. The perception of the parents was also considered through a semi-structured interview.

Results

An improvement in the psychological variables was shown in all cases. Changes in the physiological variables were also noted, although they varied according to each child. The parents report some benefit of music therapy and they share difficulty in assessing the extent of benefits of the music therapy.

Discussion

Findings indicate that music therapy can be a useful form of treatment with multiple benefits for children with conditions such as MPS III or similar conditions. However, further research is needed in this area and in the development of specific ways of evaluating music therapy.
Heterogeneity of BCSCs contributes to the metastatic organotropism of breast cancer
Authors: Wang Cenzhu , Xu Kun , Wang Runtian , Han Xin , Tang Jinhai , Guan Xiaoxiang
Published: November 2021

Breast cancer is one of the most-common female malignancies with a high risk of relapse and distant metastasis. The distant metastasis of breast cancer exhibits organotropism, including brain, lung, liver and bone. Breast cancer stem cells (BCSCs) are a small population of breast cancer cells with tumor-initiating ability, which participate in regulating distant metastasis in breast cancer. We investigated the heterogeneity of BCSCs according to biomarker status, epithelial or mesenchymal status and other factors. Based on the classical “seed and soil” theory, we explored the effect of BCSCs on the metastatic organotropism in breast cancer at both “seed” and “soil” levels, with BCSCs as the “seed” and BCSCs-related microenvironment as the “soil”. We also summarized current clinical trials, which assessed the safety and efficacy of BCSCs-related therapies. Understanding the role of BCSCs heterogeneity for regulating metastatic organotropism in breast cancer would provide a new insight for the diagnosis and treatment of advanced metastatic breast cancer.
The updated national research agenda 2021–2026 for prehospital emergency medical services in the Netherlands: a Delphi study
Authors: Vloet Lilian C. M. , Hesselink Gijs , Berben Sivera A. A. , Hoogeveen Margreet , Rood Paul J. T. , Ebben Remco H. A.
Published: November 2021

Background

In 2015, a national research agenda was established for Dutch prehospital EMS to underpin the evidence base of care delivery and inform policymakers and funders. The continuously increasing demand for ambulance care and the reorientation towards the role of EMS in recent years may have changed research priorities. Therefore, this study aimed to update the Dutch national EMS research agenda.

Methods

A three-round online Delphi survey was used to explore and discuss different viewpoints and to reach consensus on research priorities (i.e., themes and special interest groups, e.g. patient types who require specific research attention). A multidisciplinary expert panel (n = 62) was recruited in the field of prehospital EMS and delegates of relevant professional organizations and stakeholders participated. In round one, fifty-nine research themes and six special interest groups (derived from several resources) were rated on importance on a 5-point scale by the panel members. In round two, the panel selected their priority themes and special interest groups (yes/no), and those with a positive difference score were further assessed in round three. In this final round, appropriateness of the remaining themes and agreement within the panel was taken into account, following the RAND/UCLA appropriateness method, which resulted in the final list of research priorities.

Results

The survey response per round varied between 94 and 100 percent. In round one, a reduction from 59 to 25 themes and the selection of three special interest groups was realized. Round two resulted in the prioritization of six themes and one special interest group ('Vulnerable elderly'). Round three showed an adequate level of agreement regarding all six themes: 'Registration and (digital) exchange of patient data in the chain of emergency care'; 'Mobile care consultation/Non conveyance'; 'Care coordination'; 'Cooperation with professional partners within the care domain'; 'Care differentiation' and 'Triage and urgency classification'.

Conclusions

The updated Dutch national EMS research agenda builds further on the previous version and introduces new EMS research priorities that correspond with the future challenges prehospital EMS care is faced with. This agenda will guide researchers, policymakers and funding bodies in prioritizing future research projects.
Intravaginal electrical stimulation associated with pelvic floor muscle training for women with stress urinary incontinence: study protocol for a randomized controlled trial with economic evaluation
Authors: Reis Bianca Manzan , da Silva Jordana Barbosa , Rocha Ana Paula Rodrigues , Liebano Richard Eloin , Driusso Patricia
Published: November 2021

Introduction

Pelvic floor muscle training (PFMT) exercises and neuromuscular electrical stimulation (NMES) are described as conservative interventions to prevent or treat female stress urinary incontinence (SUI). However, it has not been described yet the effect of PFMT associated to intravaginal NMES which evaluated the cost-effectiveness and cost-utility of treating.

Aims

To evaluate the effects of intravaginal NMES associated with the PFMT protocol on urinary loss and quality of life in women with SUI and to evaluate the cost-effectiveness and cost-utility and pelvic floor muscle in women with SUI.

Methods

Randomized controlled trial study with economic evaluation. Inclusion criteria are woman (biological), aged ≥ 18 years old and with a report of SUI ≥ once/week. Exclusion criteria are presence of vaginal or urinary infection, virginity, being in the gestational or puerperium period, or neurological disease. Participants will undergo physical therapy assessment and intervention: anamnesis, pelvic floor muscle assessment by vaginal palpation and manometry (PeritronTM), questionnaires (Short-Form 6 Dimensions—Brazil (SF-6D), King's Health Questionnaire (KHQ) and King´s Health Questionnaire for Scoring Algorithm), health costs, and voiding diary. Participants will be randomly allocated into 3 groups: CG (control group), IG 1 (intervention group 1, PFMT), and IG2 (intervention group 2, PFMT + NMES). The statistical analysis will be performed by intention to treat, and multivariate analysis of mixed effects will be used to compare outcomes. Effect size measurements will be calculated and will be provided by Cohen’s d test. A significance level of 5% will be adopted. Additionally, the incremental cost-effectiveness and incremental cost-utility ratios will be used.

Discussion

This protocol can corroborate with the literature in order to identify the effect of techniques, based on the possibility of confirming the hypothesis that the NMES associated with PFMT performed concurrently will be the best treatment option; considering the effectiveness, cost-effectiveness, and cost-utility analysis, it will be used as an option for optimization of the treatment of SUI.

Trial registration

Brazilian Registry of Clinical Trials (ReBEC) ID: RBR-6gtzg4. Registered on September 3, 2019.
Effectiveness and safety of acupotomy for knee osteoarthritis: study protocol for a randomized controlled trial
Authors: Li Shu-Ming , Li Tian-Li , Guo Ren , Chen Ping , Du Wei-Shuai , Kang Si-Bo , Yan Ming-Zhe , Cheng Wu-Zhong
Published: November 2021

Background

Knee osteoarthritis (KOA) is one of the most common musculoskeletal disorders. Acupotomy may be effective for KOA, but the evidence is limited. This trial aims to determine the effectiveness and safety of acupotomy for KOA.

Methods/design

This is a parallel-group, assessor-blinded randomized controlled trial. Two hundred patients with KOA will be recruited and randomly assigned to two groups (group A or group D) in a 1:1 ratio. Patients in group A will receive acupotomy and topical diclofenac diethylamine for 4 weeks, while patients in group D will receive topical diclofenac diethylamine alone for 4 weeks. The primary outcome will be the response rate—the proportion of patients who achieve the minimal clinically important improvement in pain and function at week 4 compared with baseline. Secondary outcomes will include pain, function, quality of life, the use of rescue medicine (loxoprofen sodium), and adverse events at weeks 4, 8, and 24 after randomization. Besides, joint fluid and serum will be collected to assess the level of inflammatory cytokines, like TNF-α, IL-1β, and MMP-3.

Discussion

This study will contribute to a better understanding of the effectiveness and safety of acupotomy in combination with topical nonsteroidal anti-inflammatory drugs. If the hypothesis is confirmed, acupotomy may be recommended as adjunctive therapy for patients with KOA. Results of the study will be of great importance for the guidelines of clinical therapy.

Trial registration

Chinese Clinical Trial RegistryChiCTR2100043005Registered on 4 February 2021.
Evaluation of the interaction between insecticide resistance-associated genes and malaria transmission in Anopheles gambiae sensu lato in central Côte d’Ivoire
Authors: Wolie Rosine Z. , Koffi Alphonsine A. , Ahoua Alou Ludovic P. , Sternberg Eleanore D. , N’Nan-Alla Oulo , Dahounto Amal , Yapo Florent H. A. , Kanh Kpahe M. H. , Camara Soromane , Oumbouke Welbeck A. , Tia Innocent Z. , Nguetta Simon-Pierre A. , Thomas Matthew B. , NGuessan Raphael
Published: November 2021

Background

There is evidence that the knockdown resistance gene (Kdr) L1014F and acetylcholinesterase-1 gene (Ace-1R) G119S mutations involved in pyrethroid and carbamate resistance in Anopheles gambiae influence malaria transmission in sub-Saharan Africa. This is likely due to changes in the behaviour, life history and vector competence and capacity of An. gambiae. In the present study, performed as part of a two-arm cluster randomized controlled trial evaluating the impact of household screening plus a novel insecticide delivery system (In2Care Eave Tubes), we investigated the distribution of insecticide target site mutations and their association with infection status in wild An. gambiae sensu lato (s.l.) populations.

Methods

Mosquitoes were captured in 40 villages around Bouaké by human landing catch from May 2017 to April 2019. Randomly selected samples of An. gambiae s.l. that were infected or not infected with Plasmodium sp. were identified to species and then genotyped for Kdr L1014F and Ace-1R G119S mutations using quantitative polymerase chain reaction assays. The frequencies of the two alleles were compared between Anopheles coluzzii and Anopheles gambiae and then between infected and uninfected groups for each species.

Results

The presence of An. gambiae (49%) and An. coluzzii (51%) was confirmed in Bouaké. Individuals of both species infected with Plasmodium parasites were found. Over the study period, the average frequency of the Kdr L1014F and Ace-1R G119S mutations did not vary significantly between study arms. However, the frequencies of the Kdr L1014F and Ace-1R G119S resistance alleles were significantly higher in An. gambiae than in An. coluzzii [odds ratio (95% confidence interval): 59.64 (30.81–131.63) for Kdr, and 2.79 (2.17–3.60) for Ace-1R]. For both species, there were no significant differences in Kdr L1014F or Ace-1R G119S genotypic and allelic frequency distributions between infected and uninfected specimens (P > 0.05).

Conclusions

Either alone or in combination, Kdr L1014F and Ace-1R G119S showed no significant association with Plasmodium infection in wild An. gambiae and An. coluzzii, demonstrating the similar competence of these species for Plasmodium transmission in Bouaké. Additional factors including behavioural and environmental ones that influence vector competence in natural populations, and those other than allele measurements (metabolic resistance factors) that contribute to resistance, should be considered when establishing the existence of a link between insecticide resistance and vector competence.

Graphical Abstract
CircSMAD4 alleviates high glucose-induced inflammation, extracellular matrix deposition and apoptosis in mouse glomerulus mesangial cells by relieving miR-377-3p-mediated BMP7 inhibition
Authors: Wu Rina , Niu Zheli , Ren Guangwei , Ruan Lin , Sun Lijun
Published: November 2021

Background

Diabetic nephropathy (DN) is a common complication of diabetes mellitus. Accumulating studies suggest that the deregulation of circular RNA (circRNA) is involved in DN pathogenesis. This study aimed to investigate the role of circSMAD4 in DN models.

Methods

Mice were treated with streptozotocin to establish DN models in vivo. Mouse glomerulus mesangial cells (SV40-MES13) were treated with high glucose to establish DN models in vitro. The expression of circSMAD4, miR-377-3p and bone morphogenetic protein 7 (BMP7) mRNA was measured by quantitative real-time PCR (qPCR). The releases of inflammatory factors were examined by ELISA. The protein levels of fibrosis-related markers, apoptosis-related markers and BMP7 were checked by western blot. Cell apoptosis was monitored by flow cytometry assay. The predicted relationship between miR-377-3p and circSMAD4 or BMP7 was validated by dual-luciferase reporter assay or pull-down assay.

Results

CircSMAD4 was poorly expressed in DN mice and HG-treated SV40-MES13 cells. HG induced SV40-MES13 cell inflammation, extracellular matrix (ECM) deposition and apoptosis. CircSMAD4 overexpression alleviated, while circSMAD4 knockdown aggravated HG-induced SV40-MES13 cell injuries. MiR-377-3p was targeted by circSMAD4, and miR-377-3p enrichment partly reversed the effects of circSMAD4 overexpression. BMP7 was a target of miR-377-3p, and circSMAD4 regulated BMP7 expression by targeting miR-377-3p. MiR-377-3p overexpression aggravated HG-induced injuries by suppressing BMP7.

Conclusion

CircSMAD4 alleviates HG-induced SV40-MES13 cell inflammation, ECM deposition and apoptosis by relieving miR-377-3p-mediated inhibition on BMP7 in DN progression.
Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model
Authors: Morio Atsushi , Tsutsumi Rie , Satomi Shiho , Kondo Takashi , Miyoshi Hirotsugu , Kato Takahiro , Kuroda Masashi , Kitamura Tadahiro , Hara Kenta , Saeki Noboru , Sakaue Hiroshi , Tsutsumi Yasuo M.
Published: November 2021

Background

Coronary artery disease is a leading cause of morbidity and mortality among patients with diabetes. Previously, we demonstrated that branched-chain amino acids (BCAAs) showed cardioprotective effects against cardiac ischemia/reperfusion (I/R) injury. A recent study suggested that leucine (Leu), a BCAA, is a key amino acid involved in mammalian target of rapamycin (mTOR) activity and mitochondrial function. However, whether Leu has cardioprotective effects on diabetic hearts is unclear. In this study, we examined the preconditioning effect of Leu treatment on high-fat diet (HFD)-induced obese mouse which simulate prediabetic heart.

Methods

In vivo mice models of I/R injury were divided into the following groups: control, mTOR+/−, and high-fat diet (HFD)-induced obese groups. Mice were randomly administered with Leu, the mTOR inhibitor rapamycin (Rap), or Leu with Rap. Isolated rat cardiomyocytes were subjected to simulated I/R injury. Biochemical and mitochondrial functional assays were performed to evaluate the changes in mTOR activity and mitochondrial dynamics caused by Leu treatment.

Results

Leu-treated mice showed a significant reduction in infarct size when compared with the control group (34.8% ± 3.8% vs. 43.1% ± 2.4%, n = 7, p < 0.05), whereas Rap-treated mice did not show the protective effects of Leu. This preconditioning effect of Leu was attenuated in mTOR+/− mice. Additionally, Leu increased the percentage of fused mitochondria and the mitochondrial volume, and decreased the number of mitochondria per cell in isolated cardiomyocytes. In HFD-induced obese mice, Leu treatment significantly reduced infarct size (41.0% ± 1.1% vs. 51.0% ± 1.4%, n = 7, p < 0.05), which was not induced by ischemic preconditioning, and this effect was inhibited by Rap. Furthermore, we observed enhanced mTOR protein expression and mitochondrial fusion with decreased reactive oxygen species production with Leu treatment in HFD-induced obese mice, but not in mTOR+/− mice.

Conclusions

Leu treatment improved the damage caused by myocardial I/R injury by promoting mTOR activity and mitochondrial fusion on prediabetic hearts in mice.
Caspase-3/NLRP3 signaling in the mesenchymal stromal niche regulates myeloid-biased hematopoiesis
Authors: Zhang Jing , Chen Yaozhen , Yin Dandan , Feng Fan , An Qunxing , Liu Zhixin , An Ning , Xu Jinmei , Yi Jing , Gu Shunli , Yin Wen , Wang Yazhou , Hu Xingbin
Published: November 2021

Background

The fate of hematopoietic stem cells (HSCs) is determined by a complex regulatory network that includes both intrinsic and extrinsic signals. In the past decades, many intrinsic key molecules of HSCs have been shown to control hematopoiesis homeostasis. Non-hematopoietic niche cells also contribute to the self-renewal, quiescence, and differentiation of HSCs. Mesenchymal stromal cells (MSCs) have been identified as important components of the niche. However, the regulatory role of MSCs in hematopoiesis has not been fully understood.

Methods

Caspase-3 and NLRP3 gene knockout mice were generated respectively, and hematopoietic development was evaluated in the peripheral circulation and bone marrow by flow cytometry, colony formation assay, and bone marrow transplantation. Bone-associated MSCs (BA-MSCs) were then isolated from gene knockout mice, and the effect of Caspase-3/NLRP3 deficient BA-MSCs on hematopoiesis regulation was explored in vivo and ex vivo.

Results

We report that Caspase-3 deficient mice exhibit increased myelopoiesis and an aberrant HSC pool. Ablation of Caspase-3 in BA-MSCs regulates myeloid lineage expansion by altering the expression of hematopoietic retention cytokines, including SCF and CXCL12. Interestingly, NLRP3 gene knockout mice share phenotypic similarities with Caspase-3 deficient mice. Additionally, we found that NLRP3 may play a role in myeloid development by affecting the cell cycle and apoptosis of hematopoietic progenitors.

Conclusions

Our data demonstrate that the Caspase-3/NLRP3 signaling functions as an important regulator in physiological hematopoiesis, which provides new insights regarding niche signals that influence hematopoiesis regulation in the bone marrow.
Experimental Chlamydia gallinacea infection in chickens does not protect against a subsequent experimental Chlamydia psittaci infection
Authors: Heijne Marloes , van der Goot Jeanet , Buys Herma , Dinkla Annemieke , Roest Hendrik Jan , van Keulen Lucien , Koets Ad
Published: November 2021

Chlamydia psittaci was considered the predominant chlamydial species in poultry until Chlamydia gallinacea was discovered in 2009. C. psittaci is a zoonotic obligate intracellular bacterium reported in more than 465 bird species including poultry. In poultry, infections can result in asymptomatic disease, but also in more severe systemic illness. The zoonotic potential of C. gallinacea has yet to be proven. Infections in poultry appear to be asymptomatic and in recent prevalence studies C. gallinacea was the main chlamydial species found in chickens. The high prevalence of C. gallinacea resulted in the question if an infection with C. gallinacea might protect against an infection with C. psittaci. To investigate possible cross protection, chickens were inoculated with C. gallinacea NL_G47 and subsequently inoculated with either a different strain of C. gallinacea (NL_F725) or C. psittaci. Chickens that had not been pre-inoculated with C. gallinacea NL_G47 were used as a C. gallinacea or C. psittaci infection control. In the groups that were inoculated with C. psittaci, no difference in pharyngeal or cloacal shedding, or in tissue dissemination was observed between the control group and the pre-inoculated group. In the groups inoculated with C. gallinacea NL_F725, shedding in cloacal swabs and tissues dissemination was lower in the group pre-inoculated with C. gallinacea NL_G47. These results indicate previous exposure to C. gallinacea does not protect against an infection with C. psittaci, but might protect against a new infection of C. gallinacea.
Effect of exercise and diet intervention in NAFLD and NASH via GAB2 methylation
Authors: Wu Na , Yuan Fan , Yue Siran , Jiang Fengyan , Ren Decheng , Liu Liangjie , Bi Yan , Guo Zhenming , Ji Lei , Han Ke , Yang Xiao , Feng Mofan , Su Kai , Yang Fengping , Wu Xi , Lu Qing , Li Xingwang , Wang Ruirui , Liu Baocheng , Le Shenglong , Shi Yi , He Guang
Published: November 2021

Background

Nonalcoholic fatty liver disease (NAFLD) is a disorder that extends from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is effectively alleviated by lifestyle intervention. Nevertheless, DNA methylation mechanism underling the effect of environmental factors on NAFLD and NASH is still obscure. The aim of this study was to investigate the effect of exercise and diet intervention in NAFLD and NASH via DNA methylation of GAB2.

Methods

Methylation of genomic DNA in human NAFLD was quantified using Infinium Methylation EPIC BeadChip assay after exercise (Ex), low carbohydrate diet (LCD) and exercise plus low carbohydrate diet (ELCD) intervention. The output Idat files were processed using ChAMP package. False discovery rate on genome-wide analysis of DNA methylation (q < 0.05), and cytosine-guanine dinucleotides (CpGs) which are located in promoters were used for subsequent analysis (|Δβ|≥ 0.1). K-means clustering was used to cluster differentially methylated genes according to 3D genome information from Human embryonic stem cell. To quantify DNA methylation and mRNA expression of GRB2 associated binding protein 2 (GAB2) in NASH mice after Ex, low fat diet (LFD) and exercise plus low fat diet (ELFD), MassARRAY EpiTYPER and quantitative reverse transcription polymerase chain reaction were used.

Results

Both LCD and ELCD intervention on human NAFLD can induce same DNA methylation alterations at critical genes in blood, e.g., GAB2, which was also validated in liver and adipose of NASH mice after LFD and ELFD intervention. Moreover, methylation of CpG units (i.e., CpG_10.11.12) inversely correlated with mRNA expression GAB2 in adipose tissue of NASH mice after ELFD intervention.

Conclusions

We highlighted the susceptibility of DNA methylation in GAB2 to ELFD intervention, through which exercise and diet can protect against the progression of NAFLD and NASH on the genome level, and demonstrated that the DNA methylation variation in blood could mirror epigenetic signatures in target tissues of important biological function, i.e., liver and adipose tissue.

Trialregistration International Standard Randomized Controlled Trial Number Register (ISRCTN42622771)
On a power-type coupled system with mean curvature operator in Minkowski space
Authors: He Zhiqian , Zhao Yanzhong , Miao Liangying
Published: November 2021

We study the Dirichlet problem for the prescribed mean curvature equation in Minkowski space $$ \textstyle\begin{cases} \mathcal{M}(u)+ v^{\alpha }=0\quad \text{in } B, \\ \mathcal{M}(v)+ u^{\beta }=0\quad \text{in } B, \\ u|_{\partial B}=v|_{\partial B}=0, \end{cases} $$

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where $\mathcal{M}(w)=\operatorname{div} ( \frac{\nabla w}{\sqrt{1-|\nabla w|^{2}}} )$
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and B is a unit ball in $\mathbb{R}^{N} (N\geq 2)$

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. We use the index theory of fixed points for completely continuous operators to obtain the existence, nonexistence and uniqueness results of positive radial solutions under some corresponding assumptions on α, β.
The validation and reliability of a Japanese version of the Problematic Online Gaming Questionnaire (POGQ-J)
Authors: Inoue Kazuya , Yokomitsu Kengo , Irie Tomonari , Matsuyama Makoto , Tanaka Masanori
Published: November 2021

Background

The Problematic Online Gaming Questionnaire (POGQ) is an 18-item self-rated measure designed to assess the degree of problematic online gaming. This study translated the POGQ into Japanese (POGQ-J) and examined the POGQ-J’s factor structure, validity, and reliability for a Japanese population.

Method

A total of 285 undergraduate students (128 males, 157 females, Mage = 19.66, SD = 1.36) participated in this study.

Results

A confirmatory factor analysis indicated the appropriateness of the POGQ-J’s six-factor structure, χ2(129) = 106.027, p < .931; CFI = .957; RMSEA = .040; SRMR = .054. Regarding convergent validity, the POGQ-J was found to be related to the time spent on online gaming (r = .309), the Game Addiction Scale for Adolescents (r = .824), and Young’s Internet Addiction Test (r = .581). Finally, the POGQ-J was found to have a high test–retest reliability.

Conclusions

The POGQ-J is valid and reliable for assessing problematic online gaming in a Japanese population.
Web crawling based context aware recommender system using optimized deep recurrent neural network
Authors: Boppana Venugopal , Sandhya P.
Published: November 2021

Recommendation systems are obtaining more attention in various application fields especially e-commerce, social networks and tourism etc. The top items are recommended based on the ability of recommender system which predict the future preference out of the available items. Because of the internet, the people in the current society has too many options that’s why the recommendation system is very essential. The recommendation is achieved by the particular users who predict the ratings for numerous items and recommend those items to other users. Majorly, content and collaborative filtering techniques are employed in typical recommendation systems to find user preferences and provide final recommendations. But, these systems commonly lacks to take growing user preferences in various contextual factors. Context aware recommendation systems consider various contextual parameters into account and attempt to catch user preferences appropriately. The majority of the work in the recommender system domain focuses on increasing the recommendation accuracy by employing several proposed approaches where the main motive remains to maximize the accuracy of recommendations while ignoring other design objectives, such as a user’s an item’s context. Therefore, in this paper an effective deep learning based context aware recommendation model is proposed which can be act as an efficient recommender system by showing minimum error during recommendation. Initially, the dataset is pre-processed using Natural Language Tool Kit (NLTK) in Python platform. After pre-processing, the TF–IDF and word embedding model is used for every pre-processed reviews to extract the features and contextual information. The extracted feature is considered as an input of density based clustering to group the negative, neutral and positive sentiments of user reviews. Finally, deep recurrent neural Network (DRNN) is employed to get the most preferable user from every cluster. The recurrent neural network model parameter values are initialized through the fitness computation of Bald Eagle Search (BES) algorithm. The proposed model is implemented using NYC Restaurant Rich Dataset using Python programming platform and performance is evaluated based on the metrics of accuracy, precision, recall and compared with existing models. The proposed recommendation model achieves 99.6% accuracy which is comparatively higher than other machine learning models.
Stopover behavior of Red-eyed Vireos (Vireo olivaceus) during fall migration on the coast of the Yucatan Peninsula
Authors: Feldman Richard Evan , Celis-Murillo Antonio , Deppe Jill L. , Ward Michael P.
Published: November 2021

Background

For migrating birds, stopover requires spending time and energy that otherwise could be allocated to flying. Thus, birds optimally refuel their subsequent migratory flight by reducing stopover duration or foraging activity in food-rich environments. In coastal habitats, birds may forego refueling and take short stopovers irrespective of local food availability. Given the paucity of studies exploring how migrants adjust stopover behavior in response to temporal variation in food availability, especially in the Neotropics, we fixed radio tags to 51 Red-eyed Vireos (Vireo olivaceous) over two years at two sites on the coast of Mexico’s Yucatan Peninsula.

Methods

We applied VHF radio tags during the fall of 2016 and 2017, and tracked birds using automatic and manual receiving units. We estimated stopover duration and activity levels (one site only) for between six and fifteen birds, depending on site and year. We measured fruit availability weekly along the net lanes where we captured birds. We used a generalized linear model to estimate the relationships between stopover duration/activity level and fruit density, bird body mass and year. We interpreted relationships for the model with the lowest AICc value.

Results

We found that approximately half of the birds departed on the same day they were captured. For the birds that stayed longer, we could not discern whether they did so because they were light, or fruit density was high. On the other hand, lighter birds were more active than heavier birds but only in one of the two years.

Conclusions

Given our results, it is unlikely that Red-eyed Vireos refuel along the Yucatan coast. However, they still likely need to recuperate from crossing the Gulf of Mexico, which may necessitate foraging more often if in poor body condition. If the birds then move inland then stopover should be thought of as a large-scale phenomenon, where habitats with different functions may be spread out over a broad landscape.
Effect of sequential electrospinning and co-electrospinning on morphological and fluid mechanical wall properties of polycaprolactone and bovine gelatin scaffolds, for potential use in small diameter vascular grafts
Authors: Montoya Yuliet , Cardenas José , Bustamante John , Valencia Raúl
Published: November 2021

Background

Nowadays, the engineering vascular grafts with a diameter less than 6 mm by means of electrospinning, is an attracted alternative technique to create different three-dimensional microenvironments with appropriate physicochemical properties to promote the nutrient transport and to enable the bioactivity, dynamic growth and differentiation of cells. Although the performance of a well-designed porous wall is key for these functional requirements maintaining the mechanical function, yet predicting the flow rate and cellular transport are still not widely understood and many questions remain open about new configurations of wall can be used for modifying the conventional electrospun samples. The aim of the present study was to evaluate the effect of fabrication techniques on scaffolds composed of bovine gelatin and polycaprolactone (PCL) developed by sequential electrospinning and co-electrospinning, on the morphology and fluid-mechanical properties of the porous wall.

Methodology

For this purpose, small diameter tubular structures were manufactured and experimental tests were performed to characterize the crystallinity, morphology, wettability, permeability, degradability, and mechanical properties. Some samples were cross-linked with Glutaraldehyde (GA) to improve the stability of the gelatin fiber. In addition, it was analyzed how the characteristics of the scaffold favored the levels of cell adhesion and proliferation in an in vitro model of 3T3 fibroblasts in incubation periods of 24, 48 and 72 h.

Results

It was found that in terms of the morphology of tubular scaffolds, the co-electrospun samples had a better alignment with higher values of fiber diameters and apparent pore area than the sequential samples. The static permeability was more significant in the sequential scaffolds and the hydrophilic was higher in the co-electrospun samples. Therefore, the gelatin mass losses were less in the co-electrospun samples, which promote cellular functions. In terms of mechanical properties, no significant differences were observed for different types of samples.

Conclusion

This research concluded that the tubular scaffolds generated by sequential and co-electrospinning with modification in the microarchitecture could be used as a vascular graft, as they have better permeability and wettability, interconnected pores, and a circumferential tensile strength similar to native vessel compared to the commercial graft analyzed.