bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interplay between Müller cells and microglia aggravates retinal inflammatory response in experimental glaucoma
Authors: Hu Xin , Zhao Guo-Li , Xu Meng-Xi , Zhou Han , Li Fang , Miao Yanying , Lei Bo , Yang Xiong-Li , Wang Zhongfeng 
Published: December 2021

Abstract
Background
Glaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells (RGCs). Although the mechanisms underlying RGC apoptosis in glaucoma are extremely complicated, an abnormal cross-talk between retinal glial cells and RGCs is generally thought to be involved. However, how interaction of Müller cells and microglia, two types of glial cells, contributes to RGC injury is largely unknown.

Methods
A mouse chronic ocular hypertension (COH) experimental glaucoma model was produced. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), transwell co-culture of glial cells, flow cytometry assay, ELISA, Ca2+ image, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the interaction of Müller cells and microglia, and its underlying mechanisms in COH retina.

Results
We first showed that Müller cell activation in mice with COH induced microglia activation through the ATP/P2X7 receptor pathway. The activation of microglia resulted in a significant increase in mRNA and protein levels of pro-inflammatory factors, such as tumor necrosis factor-α and interleukin-6. These inflammatory factors in turn caused the up-regulation of mRNA expression of pro-inflammatory factors in Müller cells through a positive feedback manner.

Conclusions
These findings provide robust evidence, for the first time, that retinal inflammatory response may be aggravated by an interplay between activated two types of glial cells. These results also suggest that to reduce the interplay between Müller cells and microglia could be a potential effective strategy for preventing the loss of RGCs in glaucoma.
Maximizing community participation and engagement: lessons learned over 2 decades of field trials in rural Ghana
Authors: Newton Sam , Asbroek Guus Ten , Hill Zelee , Agyemang Charlotte Tawiah , Soremekun Seyi , Etego Seeba Amenga , Kirkwood Betty 
Published: December 2021

Abstract
Background
Successful implementation of community-based research is dominantly influenced by participation and engagement from the local community without which community members will not want to participate in research and important knowledge and potential health benefits will be missed. Therefore, maximising community participation and engagement is key for the effective conduct of community-based research. In this paper, we present lessons learnt over two decades of conducting research in 7 rural districts in the Brong Ahafo region of Ghana with an estimated population of around 600,000. The trials which were mainly in the area of Maternal, Neonatal and Child Health were conducted by the Kintampo Health Research Centre (KHRC) in collaboration with the London School of Hygiene and Tropical Medicine (LSHTM).

Methods
The four core strategies which were used were formative research methods, the formation of the Information, Education and Communication (IEC) team to serve as the main link between the research team and the community, recruitment of field workers from the communities within which they lived, and close collaboration with national and regional stakeholders.

Results
These measures allowed trust to be built between the community members and the research team and ensured that potential misconceptions which came up in the communities were promptly dealt with through the IEC team. The decision to place field workers in the communities from which they came and their knowledge of the local language created trust between the research team and the community. The close working relationship between the District health authorities and the Kintampo Health Research Centre supported the acceptance of the research in the communities as the District Health Authorities were respected and trusted.

Conclusion
The successes achieved during the past 2 decades of collaboration between LSHTM and KHRC in conducting community-based field trials were based on involving the community in research projects. Community participation and engagement helped not only to identify the pertinent issues, but also enabled the communities and research team to contribute towards efforts to address challenges.
Evaluation of a treatment planning system developed for clinical boron neutron capture therapy and validation against an independent Monte Carlo dose calculation system
Authors: Hu Naonori , Tanaka Hiroki , Kakino Ryo , Yoshikawa Syuushi , Miyao Mamoru , Akita Kazuhiko , Isohashi Kayako , Aihara Teruhito , Nihei Keiji , Ono Koji 
Published: December 2021

AbstractBoron neutron capture therapy (BNCT) for the treatment of unresectable, locally advanced, and recurrent carcinoma of the head and neck cancer has been approved by the Japanese government for reimbursement under the national health insurance as of June 2020. A new treatment planning system for clinical BNCT has been developed by Sumitomo Heavy Industries, Ltd. (Sumitomo), NeuCure® Dose Engine. To safely implement this system for clinical use, the simulated neutron flux and gamma ray dose rate inside a water phantom was compared against experimental measurements. Furthermore, to validate and verify the new planning system, the dose distribution inside an anthropomorphic head phantom was compared against a BNCT treatment planning system SERA and an in-house developed Monte Carlo dose calculation program. The simulated results closely matched the experimental results, within 5% for the thermal neutron flux and 10% for the gamma ray dose rate. The dose distribution inside the head phantom closely matched with SERA and the in-house developed dose calculation program, within 3% for the tumour and a difference of 0.3 Gyw for the brain.
Patient understanding regarding opioid use in an orthopaedic trauma surgery population: a survey study
Authors: Xu Amy L. , Dunham Alexandra M. , Enumah Zachary O. , Humbyrd Casey J. 
Published: December 2021

Abstract
Background
Prior studies have assessed provider knowledge and factors associated with opioid misuse; similar studies evaluating patient knowledge are lacking. The purpose of this study was to assess the degree of understanding regarding opioid use in orthopaedic trauma patients. We also sought to determine the demographic factors and clinical and personal experiences associated with level of understanding.

Methods
One hundred and sixty-six adult orthopaedic trauma surgery patients across two clinical sites of an academic institution participated in an internet-based survey (2352 invited, 7.1% response rate). Demographic, clinical, and personal experience variables, as well as perceptions surrounding opioid use were collected. Relationships between patient characteristics and opioid perceptions were identified using univariate and multivariable logistic regressions. Alpha = 0.05.

Results
Excellent recognition (> 85% correct) of common opioids, side effects, withdrawal symptoms, and disposal methods was demonstrated by 29%, 10%, 30%, and 2.4% of patients; poor recognition (< 55%) by 11%, 56%, 33%, and 52% of patients, respectively. Compared with white patients, non-white patients had 7.8 times greater odds (95% confidence interval [CI] 1.9–31) of perceiving addiction discrepancy (p = 0.004). Employed patients with higher education levels were less likely to have excellent understanding of side effects (adjusted odds ratio [aOR] 0.06, 95% CI 0.006–0.56; p = 0.01) and to understand that dependence can occur within 2 weeks (aOR 0.28, 95% CI 0.09–0.86; p = 0.03) than unemployed patients. Patients in the second least disadvantaged ADI quartile were more knowledgeable about side effects (aOR 8.8, 95% CI 1.7–46) and withdrawal symptoms (aOR 2.7, 95% CI 1.0–7.2; p = 0.046) than those in the least disadvantaged quartile. Patients who knew someone who was dependent or overdosed on opioids were less likely to perceive addiction discrepancy (aOR 0.24, 95% CI 0.07–0.76; p = 0.02) as well as more likely to have excellent knowledge of withdrawal symptoms (aOR 2.6, 95% CI 1.1–6.5, p = 0.03) and to understand that dependence can develop within 2 weeks (aOR 3.8, 95% CI 1.5–9.8, p = 0.005).

Conclusions
Level of understanding regarding opioid use is low among orthopaedic trauma surgery patients. Clinical and personal experiences with opioids, in addition to demographics, should be emphasized in the clinical history.
The degradation of Rap1GAP via E6AP-mediated ubiquitin-proteasome pathway is associated with HPV16/18-infection in cervical cancer cells
Authors: Wang Yinghui , Xie Yihang , Sun Boxuan , Guo Yuwei , Song Ling , Mohammednur Dawit Eman , Zhao Chunyan 
Published: December 2021

Abstract
Background
Cervical cancers are closely associated with persistent high-risk human papillomaviruses (HR HPV) infection. The main mechanism involves the targeting of tumor suppressors, such as p53 and pRB, for degradation by HR HPV-encoded oncoproteins, thereby leading to tumorigenesis. Rap1GAP, a tumor suppressor gene, is down-regulated in many cancers. Previous studies have revealed that down-regulation of Rap1GAP is correlated with HPV16/18 infection in cervical cancer. However, the molecular mechanism remains unclear. In this study, we aimed to address the degradation pathway of Rap1GAP in HPV-positive cervical cancer cells.

Methods
HPV-positive (HeLa and SiHa) and negative (C33A) cervical cancer cells were used to analyze the pathways of Rap1GAP degradation. MG132 (carbobenzoxy-leucyl-leucyl-leucine) was used to inhibit protein degradation by proteasome. Co-immunoprecipitation (co-IP) was used to detect the interaction between Rap1GAP and E6AP. siRNA for E6AP was used to silence the expression of E6AP. Rapamycin was used to induce cell autophagy. Western blotting was used to check the levels of proteins.

Results
Following treatment with MG132, the levels of Rap1GAP were increased in the HR HPV-positive HeLa and SiHa cells, but not in the HPV-negative C33A cells. Co-immunoprecipitation assay revealed ubiquitinated Rap1GAP protein in HeLa and SiHa cells, but not in C33A cells. E6-associated protein (E6AP) mediated the ubiquitination of Rap1GAP by binding to it in HeLa and SiHa cells, but not in C33A cells. However, the levels of Rap1GAP were decreased in HeLa and SiHa cells after knocking down E6AP by siRNA. Silencing of E6AP did not affect the levels of Rap1GAP in C33A cells. Autophagy marker p62 was decreased and LC3 II/LC3 I was increased after knocking down E6AP in HeLa cells, but not in C33A cells. The levels of Rap1GAP were decreased after treating the cells with rapamycin to induce cell autophagy in HeLa and C33A cells.

Conclusion
Rap1GAP may be degraded by autophagy in cervical cancer cells, but HPV infection can switch the degradation pathway from autophagy to E6AP-mediated ubiquitin-proteasome degradation. E6AP may be a key component of the switch.
Protocol of investigation into reporting quality of RCT abstracts on COVID-19 pursuant to CONSORT (CoCo study)—a review
Authors: Tulka Sabrina , Baulig Christine , Knippschild Stephanie 
Published: December 2021

Abstract
Background
In 2020, the COVID-19 pandemic developed into a global crisis, the enormity and urgency of which accelerated research activities in the field. At the same time, manuscripts describing these research projects underwent fast-track peer review procedures and were published in freely accessible formats. Although full texts about COVID-19 are currently available for free, abstracts continue to play a key role since they provide essential information and possibly a decision basis for therapies. Abstracts are particularly important in case the full texts are not free, not all reports have been published in English and in emergency situations when there is less time for comprehensive analysis of all full texts. It is therefore necessary to ensure that abstracts—as publications in miniature format—contain comprehensive and transparent information. The CONSORT statement for abstracts (CONSORT-A) offers guidelines to authors how to include all necessary information in an abstract.
Prior to the COVID-19 pandemic, the quality of reporting in medical research had already been the object of debate and criticism. The current crisis makes comprehensive documentation all the more important. Abstracts of COVID-19 RCTs should therefore report the criteria listed in the CONSORT-A statement fully and verifiably. The objective of this study is to check the completeness of abstracts of all COVID-19 RTCs published to date.

Methods
Based on a literature search in PubMed, Embase and the Cochrane Library, all publications up to 29 October 2020 are identified and examined in terms of the subject matter (reported results from COVID-19 studies) and their study design (RTC). Subsequently, suitable publications are examined for completeness and quality of abstracts. The CONSORT checklist for RTC abstracts serves as a basis in this procedure. The primary endpoint of the study is the percentage of correctly implemented items of the CONSORT statement for abstracts. The frequency of correct reporting of each individual item is checked in a second step.

Discussion
The study is expected to contribute to evaluating the reporting quality on COVID-19 studies, and specifically the completeness of abstracts of RTCs. It may thus support the assessment of current research into COVID-19.

Trial registration
Registration was not required as the study investigated existing literature.
Isolation of infectious Theileria parva sporozoites secreted by infected Rhipicephalus appendiculatus ticks into an in vitro tick feeding system
Authors: Vimonish Rubikah , Dinkel Kelcey D. , Fry Lindsay M. , Johnson Wendell C. , Capelli-Peixoto Janaina , Bastos Reginaldo G. , Scoles Glen A. , Knowles Donald P. , Madder Maxime , Chaka George , Ueti Massaro W. 
Published: December 2021

Abstract
Background
Vector-borne diseases pose an increasing threat to global food security. Vaccines, diagnostic tests, and therapeutics are urgently needed for tick-borne diseases that affect livestock. However, the inability to obtain significant quantities of pathogen stages derived from ticks has hindered research. In vitro methods to isolate pathogens from infected tick vectors are paramount to advance transcriptomic, proteomic, and biochemical characterizations of tick-borne pathogens.

Methods
Nymphs of Rhipicephalus appendiculatus were infected with Theileria parva by feeding on a calf during an acute infection. Isolation of sporozoites was accomplished by feeding infected adult ticks on an in vitro tick feeding system. Sporozoite viability was tested using in vitro bovine lymphocytes.

Results
We isolated infectious T. parva sporozoites secreted into an in vitro tick feeding system. Infected adult R. appendiculatus ticks attached to and successfully fed on silicone membranes in the in vitro tick feeding system. Bovine blood in the receptacle was replaced with cell-free medium and the ticks were allowed to feed for 3 h to collect secreted T. parva sporozoites. Secreted sporozoites infected in vitro bovine lymphocytes, demonstrating that isolated sporozoites remained viable and infectious.

Conclusions
This work is the first to report the isolation of mature infectious T. parva sporozoites using an in vitro tick feeding system, which represents a significant step towards the development of a more efficient control strategy for T. parva. Isolation of infectious tick-stage parasites will facilitate the examination of the vector-pathogen interface, thereby accelerating the development of next-generation vaccines and treatment interventions for tick-borne pathogens.

Graphical Abstract
CTLA4-Ig treatment induces M1–M2 shift in cultured monocyte-derived macrophages from healthy subjects and rheumatoid arthritis patients
Authors: Cutolo Maurizio , Soldano Stefano , Gotelli Emanuele , Montagna Paola , Campitiello Rosanna , Paolino Sabrina , Pizzorni Carmen , Sulli Alberto , Smith Vanessa , Tardito Samuele 
Published: December 2021

Abstract
Background
In rheumatoid arthritis (RA), macrophages play an important role in modulating the immunoinflammatory response through their polarisation into “classically” (M1) or “alternatively activated” (M2) phenotypes. In RA, CTLA4-Ig (abatacept) reduces the inflammatory activity of macrophages by interacting with the costimulatory molecule CD86. The study aimed to investigate the efficacy of CTLA4-Ig treatment to induce an M2 phenotype both in M1-polarised monocyte-derived macrophages (MDMs) obtained from healthy subjects (HS) and in cultured MDMs obtained from active RA patients.

Methods
Cultured MDMs were obtained from peripheral blood mononuclear cells of 7 active RA patients and from 10 HS after stimulation with phorbol myristate acetate (5 ng/mL) for 24 h. HS-MDMs were then stimulated with lipopolysaccharide (LPS, 1 mg/mL) for 4 h to induce M1-MDMs. M1-MDMs and RA-MDMs were treated with CTLA4-Ig (100 μM and 500 μM) for 3, 12, 24, and 48 h. The gene expression of CD80, CD86, and TLR4 (M1 markers); CD163, CD204, and CD206 (surface M2 markers); and MerTK (functional M2 marker) was evaluated by qRT-PCR. The protein synthesis of surface M2 markers was investigated by Western blotting. The statistical analysis was performed by the Wilcoxon t-test.

Results
In LPS-induced HS-M1-MDMs, CTLA4-Ig 100 μM and 500 μM significantly downregulated the gene expression of M1 markers (3 h p<0.01 for all molecules; 12 h p<0.05 for TLR4 and CD86) and significantly upregulated that of M2 markers, primarily after 12 h of treatment (CD163: p < 0.01 and p < 0.05; CD206: p < 0.05 and p < 0.01; CD204: p < 0.05 by 100 mg/mL). Moreover, in these cells, CTLA4-Ig 500 μM increased the protein synthesis of surface M2 markers (p < 0.05). Similarly, in RA-MDMs, the CTLA4-Ig treatment significantly downregulated the gene expression of M1 markers at both concentrations primarily after 12 h (p < 0.05). Furthermore, both concentrations of CTLA4-Ig significantly upregulated the gene expression of CD206 (after 3 h of treatment; p < 0.05), CD163, and MerTK (after 12 h of treatment, p < 0.05), whereas CD204 gene expression was significantly upregulated by the high concentration of CTLA4-Ig (p < 0.05). The protein synthesis of all surface markers was increased primarily by CTLA4-Ig 500 μM, significantly for CD204 and CD206 after 24 h of treatment (p < 0.05).

Conclusions
CTLA4-Ig treatment seems to induce the in vitro shift from M1 to M2 macrophages, of both HS-M1-MDMs and RA-MDMs, as observed by the significant downregulation exerted on selected M1 markers and the upregulation of selected M2 markers suggesting an additional mechanism for its modulation of the RA inflammatory process.
Dietary supplementation of inulin alleviates metabolism disorders in gestational diabetes mellitus mice via RENT/AKT/IRS/GLUT4 pathway
Authors: Miao Miao , Dai Yongmei , Rui Can , Fan Yuru , Wang Xinyan , Fan Chong , Mu Juan , Hou Wenwen , Dong Zhiyong , Li Ping , Sun Guiju , Zeng Xin 
Published: December 2021

Abstract
Background
Gestational diabetes mellitus (GDM) has significant short and long-term health consequences for both the mother and child. There is limited but suggestive evidence that inulin could improve glucose tolerance during pregnancy. This study assessed the effect of inulin on glucose homeostasis and elucidated the molecular mechanisms underlying the inulin-induced antidiabetic effects during pregnancy.

Method
Female C57BL/6 mice were randomized to receive either no treatment, high-dose inulin and low-dose inulin for 7 weeks with measurement of biochemical profiles. A real-time2 (RT2) profiler polymerase chain reaction (PCR) array involved in glycolipid metabolism was measured.

Results
Inulin treatment facilitated glucose homeostasis in a dose-dependent manner by decreasing fasting blood glucose, advanced glycation end products and total cholesterol, and improving glucose tolerance. Suppressing resistin (RETN) expression was observed in the inulin treatment group and the expression was significantly correlated with fasting blood glucose levels. The ratios of p-IRS to IRS and p-Akt to Akt in liver tissue and the ratio of p-Akt to Akt in adipose tissue as well as the expression level of GLUT4 increased significantly after inulin treatment.

Conclusions
Our findings indicated improvement of glucose and lipid metabolism by inulin was to activate glucose transport through the translocation of GLUT4 which was mediated by insulin signaling pathway repairment due to decreased expression of RETN and enhanced phosphorylation of IRS and Akt in GDM mice.
Epidemiological characteristics and genetic diversity of norovirus infections among outpatient children with diarrhea under 5 years of age in Beijing, China, 2011–2018
Authors: Li Weihong , Yan Hanqiu , Liu Baiwei , Tian Yi , Chen Yanwei , Jia Lei , Gao Zhiyong , Wang Quanyi 
Published: December 2021

Abstract
Background
Human noroviruses are the leading cause of sporadic cases and outbreaks of viral acute gastroenteritis in all age groups worldwide.

Methods
Epidemiological data and fecal specimens were collected between January 2011 and December 2018 from 4911 children < 5 years of age with diarrhea in three districts of Beijing. From 2011 to 2013, One-Step Reverse Transcription Polymerase Chain Reaction (RT-PCR) was used to detect noroviruses, and from January 2014 to December 2018, norovirus GI and GII were screened using duplex quantitative real-time RT-PCR (qRT-PCR). One-Step RT-PCR and RT-seminested PCR were performed to amplify the RNA-dependent polymerase and capsid genes of noroviruses in positive sample. Amplified products were sequenced directly; norovirus was typed using the online Norovirus Genotyping Tool v2.0 and phylogenetic analyses were conducted using MEGA-X.

Results
From 2011 to 2018, noroviruses were detected in 16.5% of specimens from children with diarrhea. The highest prevalence was observed in children aged 12 to 23 months (22.4%, 319/1421), followed by children aged 6 to 11 months (17.6%, 253/1441). The highest prevalence of norovirus infections occurred in autumn followed by winter, spring, and summer. From 2011 to 2018, the most prevalent dual types (genotype and polymerase type) were GII.4 Sydney[P31] (51.6%, 239/463), followed by GII.3[P12] (24.0%, 111/463), GII.4 2006b[P4 2006b] (7.3%, 34/463), GII.2[P16] (5.0%, 23/463), GII.17[P17] (2.6%, 12/463) and GII.6[P7] (2.6%, 12/463). GII.4 2006b[P4 2006b] predominated in 2011 and 2012. GII.4 Sydney[P31] predominated from 2013 to 2018. In total, 15 genotypes, 15 P-types and 19 dual types were detected in this study, reflecting the genetic diversity.

Conclusions
There were significant epidemiological characteristics and genetic diversity among outpatient children with norovirus infections < 5 years of age in Beijing from 2011 to 2018. These characteristics differ from those of norovirus outbreaks in Beijing. The complete genome sequences of each genotype are needed to better understand norovirus evolutionary mechanisms.