bluuebunny/crossref_metadata_2025 huggingface dataset:
Media optimization for SHuffle T7 Escherichia coli expressing SUMO-Lispro proinsulin by response surface methodology
Authors: Khalilvand Aida Bakhshi , Aminzadeh Saeed , Sanati Mohammad Hossein , Mahboudi Fereidoun
Published: January 2022

Background

SHuffle is a suitableEscherichia coli(E. coli) strain for high yield cytoplasmic soluble expression of disulfide-bonded proteins such as Insulin due to its oxidative cytoplasmic condition and the ability to correct the arrangement of disulfide bonds. Lispro is an Insulin analog that is conventionally produced inE. colias inclusion bodies (IBs) with prolonged production time and low recovery. Here in this study, we aimed to optimize cultivation media composition for high cell density fermentation of SHuffle T7E. coliexpressing soluble Lispro proinsulin fused to SUMO tag (SU-INS construct) to obtain high cell density fermentation.

Results

Factors including carbon and nitrogen sources, salts, metal ions, and pH were screened via Plackett–Burman design for their effectiveness on cell dry weight (CDW) as a measure of cell growth. The most significant variables of the screening experiment were Yeast extract and MgCl2concentration, as well as pH. Succeedingly, The Central Composite Design was utilized to further evaluate and optimize the level of significant variables. The Optimized media (OM-I) enhanced biomass by 2.3 fold in the shake flask (2.5 g/L CDW) that reached 6.45 g/L (2.6 fold increase) when applied in batch culture fermentation. The efficacy of OM-I media for soluble expression was confirmed in both shake flask and fermentor.

Conclusion

The proposed media was suitable for high cell density fermentation ofE. coliSHuffle T7 and was applicable for high yield soluble expression of Lispro proinsulin.
The unmet demand for point-of-care ultrasound among general pediatricians: a cross-sectional survey
Authors: McGinness Anelah , Lin-Martore Margaret , Addo Newton , Shaahinfar Ashkon
Published: January 2022

Background

Point-of-care ultrasound (POCUS) is a noninvasive bedside tool with many pediatric applications but is not currently a formal part of pediatric training and practice. Formal surveys of general pediatricians regarding POCUS training are lacking. We aimed to quantify the baseline ultrasound experience and training needs of general pediatricians and pediatric residents across different practice settings.

Methods

In 2020, we sent an online survey to 485 current faculty, residents, and graduates from an urban pediatric academic medical center in Northern California. Pediatric subspecialists were excluded. Survey questions about baseline experience, comfort, and perceived usefulness of 20 common POCUS applications were developed by two POCUS experts using existing literature. Chi-squared analysis was used to compare residents versus attendings and to compare attendings practicing in inpatient versus outpatient versus mixed settings.

Results

Response rate was 20% (98/485). Compared to attendings (n = 73), residents (n = 25) endorsed more exposure to POCUS in medical school (32% vs 5%, p = 0.003) and residency (12% vs 5%, p = 0.003). Respondents endorsed low comfort with POCUS (mean 1.3 out of 5 on Likert scale). Of 20 procedural and diagnostic applications, respondents identified abscess drainage, bladder catheterization, soft tissue, neck, advanced abdominal, and constipation as most useful. Overall, 50% of pediatricians (and 70% of pediatric residents) responded that there were opportunities to use POCUS multiple times a week or more in their clinical practice.

Conclusions

There is an unmet demand for POCUS training among general pediatricians and trainees in our study. Although the majority of respondents were not POCUS users, our results could guide future efforts to study the role of POCUS in general pediatrics and develop pediatric curricula.
Job satisfaction of graduates of rural oriented medical students training project in Jiangsu Province, China: a cross-sectional study
Authors: Yan Wenjun , Gao Xiuyin , Wang Wei , Zhou Zhengyu , Zou Chao , Lu Zhaojun
Published: January 2022

Background

The Chinese government has worked out the “Rural Oriented Medical Students Training Project” to address physician maldistribution, which attempted to train physicians for rural areas. The present study attempted to evaluate the job satisfaction of the graduates of this project in Jiangsu Province, China.

Methods

Online questionnaires were sent to the graduates of the “Rural Oriented Medical Students Training Project” (group A) and their colleagues, who were rural physicians recruited from different sources (group B). The study was approved by the Ethics Committee of Xuzhou Medical University, and the approval number was 2,018,057. Information on demographic characteristics, work conditions, and self-reported satisfaction was collected to compare the satisfaction differences between the two recruited rural physicians using the Chi-square test and Mann–Whitney U test. Additionally, factors correlated to the satisfaction of group A were assessed using multivariate linear regression. Statistical analysis was performed using SPSS 23.0 (SPSS Inc., Chicago, IL, USA). P < 0.05 was considered statistically significant.

Results

Group A exhibited moderate satisfaction (2.81 ± 0.687). The satisfaction score from the highest to the lowest was for occupational ecology, life satisfaction, stress, competency, and internal environment. Positive factors related to the satisfaction of group A were area, monthly income, working hours per week, professional title, and post.

Conclusion

The satisfaction of the graduates of the “Rural Oriented Medical Students Training Project” was moderate. Factors related to satisfaction included economic incentives, workload, and professional confidence. Possible solutions for increasing satisfaction should consist of economic support and possible ways to improve the professional identification of these graduates.
OSCE rater cognition – an international multi-centre qualitative study
Authors: Hyde Sarah , Fessey Christine , Boursicot Katharine , MacKenzie Rhoda , McGrath Deirdre
Published: January 2022

Introduction

This study aimed to explore the decision-making processes of raters during objective structured clinical examinations (OSCEs), in particular to explore the tacit assumptions and beliefs of raters as well as rater idiosyncrasies.

Methods

Thinking aloud protocol interviews were used to gather data on the thoughts of examiners during their decision-making, while watching trigger OSCE videos and rating candidates. A purposeful recruiting strategy was taken, with a view to interviewing both examiners with many years of experience (greater than six years) and those with less experience examining at final medical examination level.

Results

Thirty-one interviews were conducted in three centres in three different countries. Three themes were identified during data analysis, entitled ‘OSCEs are inauthentic’, ‘looking for glimpses of truth’ and ‘evolution with experience’.

Conclusion

Raters perceive that the shortcomings of OSCEs can have unwanted effects on student behaviour. Some examiners, more likely the more experienced group, may deviate from an organisations directions due to perceived shortcomings of the assessment. No method of assessment is without flaw, and it is important to be aware of the limitations and shortcomings of assessment methods on student performance and examiner perception. Further study of assessor and student perception of OSCE performance would be helpful.
Metabolic variables of obese dogs with insulin resistance supplemented with yeast beta-glucan
Authors: Ferreira Chayanne Silva , Vendramini Thiago Henrique Annibale , Amaral Andressa Rodrigues , Rentas Mariana Fragoso , Ernandes Mariane Ceschin , da Silva Flavio Lopes , Oba Patricia Massae , de Oliveira Roberti Filho Fernando , Brunetto Marcio Antonio
Published: January 2022

Background

Obesity is one of the most common nutritional disorders in dogs and cats and is related to the development metabolic comorbidities. Weight loss is the recommended treatment, but success is difficult due to the poor satiety control. Yeast beta-glucans are known as biological modifiers because of their innumerable functions reported in studies with mice and humans, but only one study with dogs was found. This study aimed to evaluate the effects of a diet supplemented with 0.1% beta-glucan on glucose, lipid homeostasis, inflammatory cytokines and satiety parameters in obese dogs. Fourteen dogs composed three experimental groups: Obese group (OG) with seven dogs with body condition score (BCS) 8 or 9; Lean group (LG) included seven non-obese dogs with a BCS of 5; and Supplemented Obese group (SOG) was the OG dogs after 90 days of consumption of the experimental diet.

Results

Compared to OG, SOG had lower plasma basal glycemic values (p = 0.05) and reduced serum cholesterol and triglyceride levels. TNF-α was lower in SOG than in OG (p = 0.05), and GLP-1 was increased in SOG compared to OG and LG (p = 0.02).

Conclusion

These results are novel and important for recognizing the possibility of using beta-glucan in obesity prevention and treatment.
Estimation of periodontal pocket surface area in small to medium dogs: a proof-of-concept study
Authors: Tamura Kazuya , Tokuzen-Tai Masako , Siddiqui Yasir Dilshad , Tamura-Naito Hitomi , Nagahara Yoshiharu , Hatanaka-Takeuchi Kazu , Yamamoto Tadashi , Takashiba Shogo
Published: January 2022

Background

Periodontal disease is the most common dental disease in dogs. Although the systemic effects of periodontal disease have not been clarified in veterinary science, it is necessary to evaluate the effects of periodontal disease in clinical trials in the future. There have been a few clinical attempts made, however, to assess the severity of periodontal inflammation and its impact on the systemic health of dogs. Meanwhile, in the field of dentistry for humans, the periodontal inflamed surface area (PISA) and periodontal epithelial surface area (PESA) have been used to quantitatively assess the degree of periodontal disease affecting a single tooth as well as the overall extent of periodontitis. Recent studies have also suggested the use of these assessments to examine the relationship between periodontal inflammation and systemic health.

Results

The estimation formula for a dog’s periodontal pocket surface area (PPSA), an alternative to PISA and PESA in humans, was established using body weight and periodontal pocket depth. Actual values were measured using extracted teeth from various dog breeds and sizes (2.3–25.0 kg of body weight) to obtain universal regression equations for PPSA. Altogether, 625 teeth from 73 dogs of 16 breeds were extracted and subsequently analyzed for morphological information.

PPSA was measured in 61 dogs of 10 breeds with periodontal disease using the established estimation formulas, and the correlation between PPSA and preoperative blood chemistry data was analyzed accordingly. A strong correlation was found between PPSA and serum globulin (r = 0.71) while moderate correlations were found for C-reactive protein (r = 0.54) and serum albumin (r = -0.51).

Conclusions

Estimation formulas using body weight and the 6-point probing depth were established for determining PPSA. Direct correlations between PPSA and several blood test results were observed in the study sample. Taken together, these results suggest that PPSA could be useful for evaluating the effects of periodontitis on systemic conditions in dogs.
TMT-based quantitative proteomic profiling of human monocyte-derived macrophages and foam cells
Authors: Zhang Yali , Fu Yu , Jia Linying , Zhang Chenyang , Cao Wenbin , Alam Naqash , Wang Rong , Wang Weirong , Bai Liang , Zhao Sihai , Liu Enqi
Published: January 2022

Background

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, most of which are caused by atherosclerosis. Discerning processes that participate in macrophage-to-foam cell formation are critical for understanding the basic mechanisms underlying atherosclerosis. To explore the molecular mechanisms of foam cell formation, differentially expressed proteins were identified.

Methods

Human peripheral blood mononuclear cells were stimulated with macrophage colony-stimulating factor, and obtained macrophages were transformed into foam cells by oxidized low-density lipoprotein. Tandem mass tag (TMT) labeling combined with mass spectrometry was performed to find associations between foam cell transformation and proteome profiles.

Results

Totally, 5146 quantifiable proteins were identified, among which 1515 and 182 differentially expressed proteins (DEPs) were found in macrophage/monocyte and foam cell/macrophage, respectively. Subcellular localization analysis revealed that downregulated DEPs of macrophages/monocytes were mostly located in the nucleus, whereas upregulated DEPs of foam cells/macrophages were mostly extracellular or located in the plasma membrane. Functional analysis of DEPs demonstrated that cholesterol metabolism-related proteins were upregulated in foam cells, whereas immune response-related proteins were downregulated in foam cells. The protein interaction network showed that the DEPs with the highest interaction scores between macrophages and foam cells were mainly concentrated in lysosomes and the endoplasmic reticulum.

Conclusions

Proteomics analysis suggested that cholesterol metabolism was upregulated, while the immune response was suppressed in foam cells. KEGG enrichment analysis and protein-protein interaction analysis indicated that DEPs located in the endoplasmic reticulum and lysosomes might be key drivers of foam cell formation. These data provide a basis for identifying the potential proteins associated with the molecular mechanism underlying macrophage transformation to foam cells.
Proteomic analysis of extracellular vesicles secreted by primary human epithelial endometrial cells reveals key proteins related to embryo implantation
Authors: Segura-Benítez Marina , Carbajo-García María Cristina , Corachán Ana , Faus Amparo , Pellicer Antonio , Ferrero Hortensia
Published: January 2022

Background

Successful implantation is dependent on coordination between maternal endometrium and embryo, and the role of EVs in the required cross-talk cell-to-cell has been recently established. In this regard, it has been reported that EVs secreted by the maternal endometrium can be internalized by human trophoblastic cells transferring their contents and enhancing their adhesive and invasive capacity. This is the first study to comprehensively evaluate three EV isolation methods on human endometrial epithelial cells in culture and to describe the proteomic content of EVs secreted by pHEECs from fertile women.

Methods

Ishikawa cells and pHEECs were in vitro cultured and hormonally treated; subsequently, conditioned medium was collected and EVs isolated. Ishikawa cells were used for the comparison of EVs isolation methods ultracentrifugation, ExoQuick-TC and Norgen Cell Culture Media Exosome Purification Kit (n = 3 replicates/isolation method). pHEECs were isolated from endometrial biopsies (n = 8/replicate; 3 replicates) collected from healthy oocyte donors with confirmed fertility, and protein content of EVs isolated by the most efficient methodology was analysed using liquid chromatography–tandem mass spectrometry. EV concentration and size were analyzed by nanoparticle tracking analysis, EV morphology visualized by transmission electron microscopy and protein marker expression was determined by Western blotting.

Results

Ultracentrifugation was the most efficient methodology for EV isolation from medium of endometrial epithelial cells. EVs secreted by pHEECs and isolated by ultracentrifugation were heterogeneous in size and expressed EV protein markers HSP70, TSG101, CD9, and CD81. Proteomic analysis identified 218 proteins contained in these EVs enriched in biological processes involved in embryo implantation, including cell adhesion, differentiation, communication, migration, extracellular matrix organization, vasculature development, and reproductive processes. From these proteins, 82 were selected based on their functional relevance in implantation success as possible implantation biomarkers.

Conclusions

EV protein cargos are implicated in biological processes related to endometrial receptivity, embryo implantation, and early embryo development, supporting the concept of a communication system between the embryo and the maternal endometrium via EVs. Identified proteins may define new biomarkers of endometrial receptivity and implantation success.
Circulating exosomal hsa_circRNA_0039480 is highly expressed in gestational diabetes mellitus and may be served as a biomarker for early diagnosis of GDM
Authors: Jiang Bao , Zhang Junfeng , Sun Xiubin , Yang Chunyan , Cheng Guanghui , Xu Mengru , Li Siyuan , Wang Lina
Published: January 2022

Background

Gestational diabetes mellitus (GDM) seriously affects the health of mothers and babies, and there are still no effective early diagnostic markers. Therefore, it is necessary to find diagnostic biomarkers for screening GDM in early pregnancy. Circular RNA (circRNA) is more stable than linear RNA, and can be encapsulated in exosomes and participate in the pathological process of various diseases, which makes it a better candidate biomarker for various diseases. In this study, we attempted to identify the exosomal circRNA biomarkers for detecting early GDM.

Methods

We performed microarray analysis to compare the plasma exosomal circRNA expression profiles of three GDM patients 48 h before and 48 h after delivery. The repeatability of the expression of circRNAs were randomly validated by RT-PCR analysis. Pearson correlation analysis was applied to evaluate the correlation between circRNAs and OGTT level. ROC curve was established to assess the diagnostic value of circRNAs for GDM at different stages.

Results

Plasma exosomal hsa_circRNA_0039480 and hsa_circRNA_0026497 were highly expressed in GDM patients before delivery (P < 0.05). The hsa_circRNA_0039480 expression was higher for GDM group than NGT group at different stages, and was also positively correlated with OGTT during the second trimester (P < 0.05). The expression of hsa_circRNA_0026497 was higher for GDM group during the third, and second trimesters. And there was a strong correlation between two circRNAs in GDM patients during the first-trimester (r = 0.496, P = 0.014). Hsa_circRNA_0039480 showed significant diagnostic value in the first, second, and third trimesters of pregnancy (AUC = 0.704, P = 0.005; AUC = 0.898, P < 0.001 and AUC = 0.698, P = 0.001, respectively). Notably, the combination of hsa_circRNA_0039480 and hsa_circRNA_0026497 exhibited promising discriminative effect on GDM in the first trimesters (AUC = 0.754, P < 0.001).

Conclusion

Plasma exosomal hsa_cirRNA_0039480 is highly expressed in GDM patients at different stages and may be served as a candidate biomarker for early detection of GDM.
Clinical efficiency of simultaneous CNV-seq and whole-exome sequencing for testing fetal structural anomalies
Authors: Chen Xinlin , Jiang Yulin , Chen Ruiguo , Qi Qingwei , Zhang Xiujuan , Zhao Sheng , Liu Chaoshi , Wang Weiyun , Li Yuezhen , Sun Guoqiang , Song Jieping , Huang Hui , Cheng Chen , Zhang Jianguang , Cheng Longxian , Liu Juntao
Published: January 2022

Background

Birth defects are responsible for approximately 7% of neonatal deaths worldwide by World Health Organization in 2004. Many methods have been utilized for examining the congenital anomalies in fetuses. This study aims to investigate the efficiency of simultaneous CNV-seq and whole-exome sequencing (WES) in the diagnosis of fetal anomaly based on a large Chinese cohort.

Methods

In this cohort study, 1800 pregnant women with singleton fetus in Hubei Province were recruited from 2018 to 2020 for prenatal ultrasonic screening. Those with fetal structural anomalies were transferred to the Maternal and Child Health Hospital of Hubei Province through a referral network in Hubei, China. After multidisciplinary consultation and decision on fetal outcome, products of conception (POC) samples were obtained. Simultaneous CNV-seq and WES was conducted to identify the fetal anomalies that can compress initial DNA and turnaround time of reports.

Results

In total, 959 couples were finally eligible for the enrollment. A total of 227 trios were identified with a causative alteration (CNV or variant), among which 191 (84.14%) were de novo. Double diagnosis of pathogenic CNVs and variants have been identified in 10 fetuses. The diagnostic yield of multisystem anomalies was significantly higher than single system anomalies (32.28% vs. 22.36%, P  = 0.0183). The diagnostic rate of fetuses with consistent intra- and extra-uterine phenotypes (172/684) was significantly higher than the rate of these with inconsistent phenotypes (17/116, P  = 0.0130).

Conclusions

Simultaneous CNV-seq and WES analysis contributed to fetal anomaly diagnosis and played a vital role in elucidating complex anomalies with compound causes.
The role of Exosomal miRNAs in cancer
Authors: Li Chuanyun , Zhou Tong , Chen Jing , Li Rong , Chen Huan , Luo Shumin , Chen Dexi , Cai Cao , Li Weihua
Published: January 2022

Exosomal miRNAs have attracted much attention due to their critical role in regulating genes and the altered expression of miRNAs in virtually all cancers affecting humans (Sun et al. in Mol Cancer 17(1):14, 2018). Exosomal miRNAs modulate processes that interfere with cancer immunity and microenvironment, and are significantly involved in tumor growth, invasion, metastasis, angiogenesis and drug resistance. Fully investigating the detailed mechanism of miRNAs in the occurrence and development of various cancers could help not only in the treatment of cancers but also in the prevention of malignant diseases. The current review highlighted recently published advances regarding cancer-derived exosomes, e.g., sorting and delivery mechanisms for RNAs. Exosomal miRNAs that modulate cancer cell-to-cell communication, impacting tumor growth, angiogenesis, metastasis and multiple biological features, were discussed. Finally, the potential role of exosomal miRNAs as diagnostic and prognostic molecular markers was summarized, as well as their usefulness in detecting cancer resistance to therapeutic agents.
SNHG15 is a negative regulator of inflammation by mediating TRAF2 ubiquitination in stroke-induced immunosuppression
Authors: Sun Huiling , Li Shuo , Xu Zhaohan , Liu Chengfang , Gong Pengyu , Deng Qiwen , Yan Fuling
Published: January 2022

Background

Abnormal expression of long noncoding RNAs (lncRNAs) has been reported in the acute stage of acute ischemic stroke (AIS). This study aimed to explore differential lncRNA expression in the subpopulations of peripheral blood mononuclear cells (PBMCs) from AIS patients and further evaluate its underlying mechanisms in stroke-induced immunosuppression.

Methods

We reanalyzed lncRNA microarray data and investigated abnormally expressed lncRNAs in the subpopulations of PBMCs by magnetic cell sorting and real-time quantitative PCR. The potential mechanism of small nucleolar RNA host gene 15 (SNHG15) was explored through in vitro and in vivo approaches.

Results

The stroke-induced SNHG15 acted as a checkpoint to inhibit peripheral inflammatory responses. Functional studies showed that SNHG15 promoted M2 macrophage polarization. Mechanistically, SNHG15 expression was dysregulated through the Janus kinase (JAK)-signal transducer and activator of transcription 6 (STAT6) signaling pathway. SNHG15, localized in the cytoplasm, interfered with K63-linked ubiquitination of tumor necrosis factor receptor-associated factor 2 and thereby repressed the activation of mitogen-activated protein kinase and nuclear factor kappa-B signaling pathways and prevented the production of proinflammatory cytokines. Administration of an adenovirus targeting SNHG15 improved stroke-induced immunosuppression in mice.

Conclusions

This study identified SNHG15 as a negative regulator of inflammation in stroke-induced immunosuppression, suggesting it as a novel biomarker and therapeutic target in stroke-associated infection.

Trial registrationClinicalTrials.gov NCT04175691. Registered November 25, 2019,https://www.clinicaltrials.gov/ct2/show/NCT04175691.
The immunosenescence-related factor DOCK11 is involved in secondary immune responses of B cells
Authors: Sugiyama Yuma , Fujiwara Mitsuhiro , Sakamoto Akihiko , Tsushima Hiromichi , Nishikimi Akihiko , Maruyama Mitsuo
Published: January 2022

Background

Memory B cells are an antigen-experienced B-cell population with the ability to rapidly differentiate into antibody-producing cells by recall responses. We recently found that dedicator of cytokinesis 11 (DOCK11) contributes to the expansion of antigen-specific populations among germinal center B cells upon immunization. In comparison, limited information is available on the contribution of DOCK11 to secondary humoral immune responses.

Results

In this study, effects of the DOCK11 deficiency in B cells were examined on secondary immune responses to protein antigen. The lack of DOCK11 in B cells resulted in the impaired induction of antibody-producing cells upon secondary immunization with protein antigen. DOCK11 was dispensable for the recall responses of antigen-experienced B cells, as demonstrated by the comparable induction of antibody-producing cells in mice given transfer of antigen-experienced B cells with no DOCK11 expression. Instead, the lack of DOCK11 in B cells resulted in the impaired secondary immune responses in a B cell-extrinsic manner, which was recovered by the adoptive transfer of cognate T cells.

Conclusions

We addressed that intrinsic and extrinsic effects of DOCK11 expression in B cells may contribute to secondary humoral immune responses in manner of the induction of cognate T-cell help.
Comparison of the efficacy of intranasal ketamine versus intravenous ketorolac on acute non-traumatic headaches: a randomized double-blind clinical trial
Authors: Sarvari Hooman Rafiei , Baigrezaii Hamidreza , Nazarianpirdosti Mohammad , Meysami Amirhossein , Safari-Faramani Roya
Published: January 2022

Introduction

Non - traumatic headaches are one of the most common causes of referral to hospital emergency. This study aimed to compare the efficacy of intranasal ketamine and intravenous ketorolac on acute non-traumatic headaches.

Methods

This randomized and double-blind clinical trial was conducted in 2019. One hundred and forty samples were randomly divided into intranasal ketamine (A) and intravenous ketorolac (B). Group (A) received ketamine intranasal (0.75 mg/kg, max 75 mg), and group B received intravenous ketorolac (30 mg). Headache severity was measured on arrival, 30, 60, and 120 min after intervention with Visual Analogue Scale (VAS). The side effects were recorded an hour after the intervention.

Result

The mean difference of pain intensity 30, 60, and 120 min after the intervention between the two groups was statistically significant (p < 0.001). In the first 30 min, significant changes were observed in the VAS levels of the two groups. These changes were significantly greater in the intranasal ketamine group (p < 0.001). Side effects such as fatigue, dizziness, general discomfort, nausea, increased heart rate, and hypertension were significantly higher in the ketamine group (p < 0.05).

Conclusion

Intranasal ketamine and intravenous ketorolac both effectively reduced headaches. However, more analgesic effects of intranasal ketamine in a short time can be considered as a selective approach to reducing headaches.

Trial registration

IRCT20180108038276N3, Registered 29 September 2019.

Ethics committee reference number

IR.KUMS.REC.1398.068.
The m6A methyltransferase METTL3 affects autophagy and progression of nasopharyngeal carcinoma by regulating the stability of lncRNA ZFAS1
Authors: Peng Jiaojiao , Zheng Hong , Liu Feng , Wu Qi , Liu Shixi
Published: January 2022

Background

Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the epithelial cells of the nasopharyngeal mucosa of the head and neck. The role of long non-coding RNA and RNA methylation in NPC has received increasing attention. Therefore, this study aims to investigate the mechanism of lncRNA ZFAS1 in NPC and its relationship with RNA methylation, providing evidence for targeted therapy of NPC.

Methods

Microarray arrays were used to screen the differentially expressed miRNAs in normal tissues and tumor tissues. QRT-PCR was used to quantify ZFAS1, miR-100-3p, ATG10, autophagy and epithelial-mesenchymal transition related genes. The interactive relationship between ZFAS1 and miR-100-3p was verified using dual-luciferase reporter gene assay and RIP assay. CCK-8, transwell and apoptosis were used to detect the occurrence of tumor cells after different treatments. The m6A modification test is used to verify the effect of METTL3 on ZFAS1. BALB/c mice and BALB/c nude mice are used to detect the effects of different treatments on tumor growth and immune escape in vivo.

Results

ZFAS1 is upregulated in tumor tissues and NPC cells. N (6)-methyladenosine (m6A) is highly enriched in ZFAS1 and enhances its RNA stability. ZFAS1 is used as an oncogenic lncRNA, which can promote NPC cell proliferation, migration and tumor growth. In terms of mechanism, ZFAS1 up-regulates the expression of ATG10 by competitively adsorbing miR-100-3p and regulates the level of autophagy by inhibiting the PI3K/Akt signaling pathway to promote the proliferation and migration of NPC cells.

Conclusion

In short, our study verified the cancer-promoting effect of ZFAS1 in NPC and explained part of the reason for its upregulation. In addition, we confirmed that ZFAS1 can regulate the autophagy level of NPC cells through the PI3K/AKT pathway through miR-100-3p/ATG10 to affect tumor progression.
Impact of telelactation services on breastfeeding outcomes among Black and Latinx parents: protocol for the Tele-MILC randomized controlled trial
Authors: Uscher-Pines Lori , Demirci Jill , Waymouth Molly , Lawrence Rebecca , Parks Amanda , Mehrotra Ateev , Ray Kristin , DeYoreo Maria , Kapinos Kandice
Published: January 2022

Background

Breastfeeding offers many medical and neurodevelopmental advantages for birthing parents and infants; however, the majority of parents stop breastfeeding before it is recommended. Professional lactation support by the International Board Certified Lactation Consultants (IBCLCs) increases breastfeeding rates; however, many communities lack access to IBCLCs. Black and Latinx parents have lower breastfeeding rates, and limited access to professional lactation support may contribute to this disparity. Virtual “telelactation” consults that use two-way video have the potential to increase access to IBCLCs among disadvantaged populations. We present a protocol for the digital Tele-MILC trial, which uses mixed methods to evaluate the impact of telelactation services on breastfeeding outcomes. The objective of this pragmatic, parallel design randomized controlled trial is to assess the impact of telelactation on breastfeeding duration and exclusivity and explore how acceptability of and experiences with telelactation vary across Latinx, Black, and non-Black and non-Latinx parents to guide future improvement of these services.

Methods

2400 primiparous, pregnant individuals age > 18 who intend to breastfeed and live in the USA underserved by IBCLCs will be recruited. Recruitment will occur via Ovia, a pregnancy tracker mobile phone application (app) used by over one million pregnant individuals in the USA annually. Participants will be randomized to (1) on-demand telelactation video calls on personal devices or (2) ebook on infant care/usual care. Breastfeeding outcomes will be captured via surveys and interviews and compared across racial and ethnic groups. This study will track participants for 8 months (including 6 months postpartum). Primary outcomes include breastfeeding duration and breastfeeding exclusivity. We will quantify differences in these outcomes across racial and ethnic groups. Both intention-to-treat and as-treated (using instrumental variable methods) analyses will be performed. This study will also generate qualitative data on the experiences of different subgroups of parents with the telelactation intervention, including barriers to use, satisfaction, and strengths and limitations of this delivery model.

Discussion

This is the first randomized study evaluating the impact of telelactation on breastfeeding outcomes. It will inform the design and implementation of future digital trials among pregnant and postpartum people, including Black and Latinx populations which are historically underrepresented in clinical trials.

Trial registration

ClinicalTrials.gov NCT04856163. Registered on April 23, 2021
Deltamethrin interacts with Culex quinquefasciatus odorant-binding protein: a novel potential resistance mechanism
Authors: Shen Rui-xin , Wang Yi-ting , Wu Jia-hong , Zhang Ning , Zhang Heng-duan , Xing Dan , Chen Yan , Li Chun-xiao , Zhao Tong-yan
Published: January 2022

Background

Odorant-binding proteins (OBPs) play important roles in many physiological processes of mosquitoes. Previous high-throughput sequencing studies have revealed that some OBPs of Culex quinquefasciatus might be involved in the development of resistance to insecticides.

Methods

Based on the results of sequencing analyses, the OBP28 gene was selected for evaluation in this study. Three laboratory strains of Cx. quinquefasciatus [susceptible strain (SS), deltamethrin-resistant strain 1 (HN) and deltamethrin-resistant strain 2 (RR)] were first examined by using the Centers for Disease Control and Prevention bottle bioassay, after which the expression level of the OBP28 gene in the susceptible and deltamethrin-resistant strains was determined by real-time quantitative polymerase chain reaction. The OBP28 gene in deltamethrin-resistant strain RR was silenced using RNA interference technology. The expression level of OBP28 and the resistance level were tested in the silenced strain and control strain after microinjection of double-stranded RNA for a 48-h interference period. Four field-collected strains (henceforth ‘field strains’) of Cx. quinquefasciatus were also examined for their resistance to deltamethrin and levels of OBP28 expression. Finally, a correlation analysis between deltamethrin resistance and gene expression was carried out for all seven strains, i.e. the four field strains and the three laboratory strains.

Results

In the bioassay, the mortality of SS, HN and RR was 100%, 21.33% and 1.67%, respectively. The relative expression levels of OBP28 in strains HN and RR were 6.30- and 6.86-fold higher, respectively, than that of strain SS. After silencing of the OBP28 gene, the mortality of strain RR was 72.20% and that of the control strain 26.32%. The mortality of strain RR increased significantly after interference compared to that of the control strain. There was a negative correlation between OBP28 gene expression and mortality in adult mosquitoes after exposure to deltamethrin.

Conclusions

To our knowledge, this study shows for the first time a correlation between the expression of a gene coding for OBP and insecticide resistance in mosquitoes. The potential resistance mechanism that was elucidated provides a new target gene for the surveillance of resistance in mosquitoes.

Graphical abstract
Accelerometer-based prediction of ground reaction force in head-out water exercise with different exercise intensity countermovement jump
Authors: Chien Kuei-Yu , Chang Wei-Gang , Chen Wan-Chin , Liou Rong-Jun
Published: January 2022

Background

Water jumping exercise is an alternative method to achieve maintenance of bone health and reduce exercise injuries. Clarifying the ground reaction force (GRF) of moderate and high cardiopulmonary exercise intensities for jumping movements can help quantify the impact force during different exercise intensities. Accelerometers have been explored for measuring skeletal mechanical loading by estimating the GRFs. Predictive regression equations for GRF using ACC on land have already been developed and performed outside laboratory settings, whereas a predictive regression equation for GRF in water exercises is not yet established. The purpose of this study was to determine the best accelerometer wear-position for three exercise intensities and develop and validate the ground reaction force (GRF) prediction equation.

Methods

Twelve healthy women (23.6 ± 1.83 years, 158.2 ± 5.33 cm, 53.1 ± 7.50 kg) were recruited as participants. Triaxial accelerometers were affixed 3 cm above the medial malleolus of the tibia, fifth lumbar vertebra, and seventh cervical vertebra (C7). The countermovement jump (CMJ) cadence started at 80 beats/min and increased by 5 beats per 20 s to reach 50%, 65%, and 80% heart rate reserves, and then participants jumped five more times. One-way repeated analysis of variance was used to determine acceleration differences among wear-positions and exercise intensities. Pearson’s correlation was used to determine the correlation between the acceleration and GRF per body weight on land (GRFVLBW). Backward regression analysis was used to generate GRFVLBW prediction equations from full models with C7 acceleration (C7 ACC), age, percentage of water deep divided by body height (PWDH), and bodyweight as predictors. Paired t-test was used to determine GRFVLBW differences between values from the prediction equation and force plate measurement during validation. Lin’s CCC and Bland–Altman plots were used to determine the agreement between the predicted and force plate-measured GRFVLBW.

Results

The raw full profile data for the resultant acceleration showed that the acceleration curve of C7 was similar to that of GRFv. The predicted formula was − 1.712 + 0.658 * C7ACC + 0.016 * PWDH + 0.008 * age + 0.003*weight. Lin’s CCC score was 0.7453, with bias of 0.369%.

Conclusion

The resultant acceleration measured at C7 was identified as the valid estimated GRFVLBW during CMJ in water.
A survey of elite and pre-elite athletes’ perceptions of key support, lifestyle and performance factors
Authors: Burns Lauren , Weissensteiner Juanita R. , Cohen Marc , Bird Stephen R.
Published: January 2022

Background

Success at the elite level in sport is often attributed to physical prowess, technical skill, and mental attitude. However, underpinning these factors are various lifestyle, support and social factors that may contribute to successful performance, but which may be absent from athlete development programs.

Methods

An online survey was used to investigate athlete perceptions of lifestyle practices and support services amongst 135 Australian Olympic, Paralympic, National, and state-level athletes across 25 Olympic sports.

Results

International athletes perceived psychological skills and attributes, along with strong interpersonal relationships as vital to their success, and they also rated ‘Recovery practices’ as very important and made extensive use of available support services. These athletes also indicated that they would have liked access to these services earlier in their careers, a wish that was reiterated by the sub-elite athletes. Furthermore, athletes wanted greater knowledge, mentoring, and autonomy earlier in their careers, and the importance of ‘athlete wellbeing’ as well as ‘athletic performance’ was evident in a number of contexts.

Conclusions

An athlete development system into which these are included may assist in generating an environment that facilitates athlete success, repeated podium performances, retain athletes in high-performance sport for longer, encourage human-flourishing, wellbeing and smooth transitions for retiring athletes.
Effects of consecutive days of matchplay on maximal hip abductor and adductor strength in female field hockey players
Authors: Sánchez-Migallón Violeta , López-Samanes Álvaro , Del Coso Juan , Navandar Archit , Aagaard Per , Moreno-Pérez Víctor
Published: January 2022

Background

The purpose of this study was to examine the effects of two competitive field hockey matches, played on consecutive days, on maximal isometric hip adductor and abductor strength, wellness and fatigue.

Methods

Fourteen professional female field hockey players (age: 20.4 ± 5.4 years; body mass: 60.7 ± 7.2 kg; height: 167.0 ± 1.0 cm) volunteered to participate in this investigation. Maximal isometric hip adductor and abductor strength were obtained before (pre-match 1) and after the first match (post-match 1), after the second match (post-match 2), and 48 h after the second match. Locomotion patterns during the matches were obtained with portable Global Positioning System (GPS) and perceived exertion (RPE) was assessed after each match. In addition, Wellness Questionnaire (5-WQ) and the Total Quality Recovery Scale (TQR) were employed before the matches and 48 h after the second match.

Results

For the non-dominant limb, the maximal isometric hip adductor and abductor strength were lower after post-match 2 when compared to pre-match 1 (p = 0.011). Hip abductor strength in the non-dominant limb remained reduced 48 h after post-match 2 (p < 0.001). There were no differences in the total distance covered when comparing match 1 and match 2. Players reported more acute fatigue (5-WQ, p = 0.009) and increased muscle soreness on pre-match 2 compared to pre-match 1 (p = 0.015), while fatigue returned to pre-competition levels 48 h after post-match 2 (p = 0.027). No changes were observed in the TQR.

Conclusion

The assessment of maximal adductor and abductor strength before and after competitive matches, in addition to evaluating self-perceived fatigue by a wellness questionnaire can help to identify field hockey players with excessive fatigue responses during tournaments with a congested match program.
How innovation can be defined, evaluated and rewarded in health technology assessment
Authors: Rejon-Parrilla Juan Carlos , Espin Jaime , Epstein David
Published: January 2022

Background

What constitutes innovation in health technologies can be defined and measured in a number of ways and it has been widely researched and published about. However, while many countries mention it as a criterion for pricing or reimbursement of health technologies, countries differ widely in how they define and operationalise it.

Methods

We performed a literature review, using a snowballing search. In this paper, we explore how innovation has been defined in the literature in relation to health technology assessment. We also describe how a selection of countries (England, France, Italy, Spain and Japan) take account of innovation in their health technology assessment frameworks and explore the key methodologies that can capture it as a dimension of value in a new health technology. We propose a way of coming to, and incorporating into health technology assessment systems, a definition of innovation for health technologies that is independent of other dimensions of value that they already account for in their systems, such as clinical benefit. We use Spain as an illustrative example of how innovation might be operationalised as a criterion for decision making in health technology assessment.

Results

The countries analysed here can be divided into 2 groups with respect to how they define innovation. France, Japan and Italy use features such as severity, unmet need and therapeutic added value as indicators of the degree of innovation of a health technology, while England, Spain consider the degree of innovation as a separate and additional criterion from others. In the case of Spain, a notion of innovation might be constructed around concepts of `step-change’, `convenience’, `strength of evidence base’ and `impact on future research & development’.

Conclusions

If innovation is to be used as operational criteria for adoption, pricing and reimbursement of health technologies, the concept must be clearly defined, and it ought to be independent from other value dimensions already captured in their health technology assessment systems.
Understanding out-of-pocket spending and financial hardship among patients who succumb to cancer and their caregivers
Authors: Tur-Sinai Aviad , Urban Damien , Azoulay Daniel , Bar-Sela Gil , Bentur Netta
Published: January 2022

Background

In most countries, including those with national health insurance or comprehensive public insurance, some expenses for cancer treatment are borne by the ill and their families.

Objectives

This study aims to identify the areas of out-of-pocket (OOP) spending in the last half-year of the lives of cancer patients and examine the extent of that spending; to examine the probability of OOP spending according to patients’ characteristics; and to examine the financial burden on patients’ families.

Methods

491 first-degree relatives of cancer patients (average age: 70) who died 3–6 months before the study were interviewed by telephone. They were asked about their OOP payments during the last-half year of the patient's life, the nature of each payment, and whether it had imposed a financial burden on them. A logistic regression and ordered logit models were used to estimate the probability of OOP expenditure and the probability of financial burden, respectively.

Results

Some 84% of cancer patients and their relatives incurred OOP expenses during the last half-year of the patient’s life. The average levels of expenditure were US$5800on medicines, $8000 on private caregivers, and $2800 on private nurses. The probability of paying OOP for medication was significantly higher among patients who were unable to remain alone at home and those who were less able to make ends meet. The probability of spending OOP on a private caregiver or private nurse was significantly higher among those who were incapacitated, unable to remain alone, had neither medical nor nursing-care insurance, and were older. The probability of a financial burden due to OOP was higher among those unable to remain alone, the incapacitated, and those without insurance, and lower among those with above-average income, those with better education, and patients who died at home.

Conclusions

The study yields three main insights. First, it is crucial that oncology services provide cancer patients with detailed information about their entitlements and refer them to the National Insurance Institute so that they can exercise those rights. Second, oncologists should relate to the financial burden associated with OOP care at end of life. Finally, it is important to sustain the annual increase in budgeting for technologies and pharmaceuticals in Israel and to allocate a significant proportion of those funds to the addition new cancer treatments to the benefits package; this can alleviate the financial burden on patients who need such treatments and their families.