bluuebunny/crossref_metadata_2025 huggingface dataset:
The biological function of tumor-derived extracellular vesicles on metabolism
Authors: Fu Xiaoyu , Song Junlong , Yan Wei , Downs Bradley M. , Wang Weixing , Li Juanjuan
Published: June 2023

Multiple studies have shown that extracellular vesicles (EVs) play a key role in the process of information transfer and material transport between cells. EVs are classified into different types according to their sizes, which includes the class of exosomes. In comparison to normal EVs, tumor-derived EVs (TDEs) have both altered components and quantities of contents. TDEs have been shown to help facilitate an environment conducive to the occurrence and development of tumor by regulation of glucose, lipids and amino acids. Furthermore, TDEs can also affect the host metabolism and immune system. EVs have been shown to have multiple clinically useful properties, including the use of TDEs as biomarkers for the early diagnosis of diseases and using the transport properties of exosomes for drug delivery. Targeting the key bioactive cargoes of exosomes could be applied to provide new strategies for the treatment of tumors. In this review, we summarize the finding of studies focused on measuring the effects of TDE on tumor-related microenvironment and systemic metabolism.
Islets in the body are never flat: transitioning from two-dimensional (2D) monolayer culture to three-dimensional (3D) spheroid for better efficiency in the generation of functional hPSC-derived pancreatic β cells in vitro
Authors: Diane Abdoulaye , Mohammed Layla Ibrahim , Al-Siddiqi Heba H.
Published: June 2023

Diabetes mellitus (DM), currently affecting more than 537 million people worldwide is a chronic disease characterized by impaired glucose metabolism resulting from a defect in insulin secretion, action, or both due to the loss or dysfunction of pancreatic β cells. Since cadaveric islet transplantation using Edmonton protocol has served as an effective intervention to restore normoglycaemia in T1D patients for months, stem cell-derived β cells have been explored for cell replacement therapy for diabetes. Thus, great effort has been concentrated by scientists on developing in vitro differentiation protocols to realize the therapeutic potential of hPSC-derived β cells. However, most of the 2D traditional monolayer culture could mainly generate insulin-producing β cells with immature phenotype. In the body, pancreatic islets are 3D cell arrangements with complex cell–cell and cell–ECM interactions. Therefore, it is important to consider the spatial organization of the cell in the culture environment. More recently, 3D cell culture platforms have emerged as powerful tools with huge translational potential, particularly for stem cell research. 3D protocols provide a better model to recapitulate not only the in vivo morphology, but also the cell connectivity, polarity, and gene expression mimicking more physiologically the in vivo cell niche. Therefore, the 3D culture constitutes a more relevant model that may help to fill the gap between in vitro and in vivo models. Interestingly, most of the 2D planar methodologies that successfully generated functional hPSC-derived β cells have switched to a 3D arrangement of cells from pancreatic progenitor stage either as suspension clusters or as aggregates, suggesting the effect of 3D on β cell functionality. In this review we highlight the role of dimensionality (2D vs 3D) on the differentiation efficiency for generation of hPSC-derived insulin-producing β cells in vitro. Consequently, how transitioning from 2D monolayer culture to 3D spheroid would provide a better model for an efficient generation of fully functional hPSC-derived β cells mimicking in vivo islet niche for diabetes therapy or drug screening.
Potassium ion channels as a molecular target to reduce virus infection and mortality of honey bee colonies
Authors: Fellows Christopher J. , Simone-Finstrom Michael , Anderson Troy D. , Swale Daniel R.
Published: June 2023

Declines in managed honey bee populations are multifactorial but closely associated with reduced virus immunocompetence and thus, mechanisms to enhance immune function are likely to reduce viral infection rates and increase colony viability. However, gaps in knowledge regarding physiological mechanisms or ‘druggable’ target sites to enhance bee immunocompetence has prevented therapeutics development to reduce virus infection. Our data bridge this knowledge gap by identifying ATP-sensitive inward rectifier potassium (KATP) channels as a pharmacologically tractable target for reducing virus-mediated mortality and viral replication in bees, as well as increasing an aspect of colony-level immunity. Bees infected with Israeli acute paralysis virus and provided KATP channel activators had similar mortality rates as uninfected bees. Furthermore, we show that generation of reactive oxygen species (ROS) and regulation of ROS concentrations through pharmacological activation of KATP channels can stimulate antiviral responses, highlighting a functional framework for physiological regulation of the bee immune system. Next, we tested the influence of pharmacological activation of KATP channels on infection of 6 viruses at the colony level in the field. Data strongly support that KATP channels are a field-relevant target site as colonies treated with pinacidil, a KATP channel activator, had reduced titers of seven bee-relevant viruses by up to 75-fold and reduced them to levels comparable to non-inoculated colonies. Together, these data indicate a functional linkage between KATP channels, ROS, and antiviral defense mechanisms in bees and define a toxicologically relevant pathway that can be used for novel therapeutics development to enhance bee health and colony sustainability in the field.
Perilipin5 protects against non-alcoholic steatohepatitis by increasing 11-Dodecenoic acid and inhibiting the occurrence of ferroptosis
Authors: Xu Xinming , Qiu Jin , Li Xiaoya , Chen Juntong , Li Yue , Huang Xinmei , Zang Shufei , Ma Xinran , Liu Jun
Published: June 2023

Background

Non-alcoholic steatohepatitis (NASH) is a major contributor to liver cirrhosis and hepatocellular carcinoma. There remains no effective pharmacological therapy. The hepatic lipid metabolism and fatty acid β-oxidation are regulated by Perilipin5 (Plin5). However, it is yet unknown how Plin5 affects NASH and the molecular process.

Methods

High-fat, high-cholesterol and high-fructose (HFHC) diets were used to mimic the progression of NASH in wild type (WT) mice and Plin5 knockout (Plin5 KO) mice. The degree of ferroptosis was measured by detecting the expression of key genes of ferroptosis and the level of lipid peroxide. The degree of NASH was judged by observing the morphology of the liver, detecting the expression of inflammation and fibrosis related genes of liver damage. Plin5 was overexpressed in the liver of mice by tail vein injection of adenovirus, and the process of NASH was simulated by methionine choline deficiency (MCD) diet. The occurrence of ferroptosis and NASH was detected by the same detection method. Targeted lipidomics sequencing was used to detect the difference in free fatty acid expression in the WT Plin5 KO group. Finally, it was verified in cell experiments to further study the effect of free fatty acids on ferroptosis of hepatocytes.

Results

In various NASH models, hepatic Plin5 was dramatically reduced. Plin5 knockout (KO) worsened NASH-associated characteristics in mice given a high-fat/high-cholesterol (HFHC) diet, such as lipid accumulation, inflammation and hepatic fibrosis. It has been shown that ferroptosis is involved in NASH progression. We revealed that Plin5 KO in mice aggravated the degree of ferroptosis in NASH models. Conversely, overexpression of Plin5 significantly alleviated ferroptosis and further ameliorated progression of MCD-induced NASH. Analysis of livers obtained from HFHC diet-fed mice by targeted lipidomics revealed that 11-Dodecenoic acid was significantly decreased in Plin5 KO mice. Addition of 11-Dodecenoia acid to Plin5 knockdown hepatocytes effectively prevented ferroptosis.

Conclusion

Our study demonstrates that Plin5 protects against NASH progression by increasing 11-Dodecenoic acid level and further inhibiting ferroptosis, suggesting that Plin5 has therapeutic potential as a target for the management of NASH.
Patient with composite haemangioendothelioma containing angiosarcoma-like areas in the setting of congenital lymphoedema mimicking Stewart-Treves syndrome: a case report
Authors: Balko Jan , Ozaniak Andrej , Krskova Lenka , Strizova Zuzana , Lischke Robert , Zamecnik Josef
Published: June 2023

Background

Composite haemangioendothelioma is a rare vascular neoplasm with indolent to intermediate malignant potential. Diagnosis of this disease relays on histopathological identification of at least two different morphologically distinctive vascular components in proper clinical settings. Exceedingly rare cases of this neoplasm can exhibit areas resembling high-grade angiosarcoma, which does not change the biological behaviour. Such lesions tend to occur in the setting of chronic lymphoedema and thus, can mimic Stewart-Treves syndrome, which has a much worse clinical outcome and prognosis.

Case presentation

We present a case of 49 years old male suffering from chronic lymphoedema of the left lower extremity who had developed a composite haemangioendothelioma with high grade angiosarcoma-like areas mimicking the Stewart-Treves syndrome. Given the multifocality of the disease, the only potentially curable surgical treatment would be hemipelvectomy, which was refused by the patient. The patient has been followed-up, with no signs of local progression of the remaining disease, nor a distant spread outside the involved extremity for two years.

Conclusions

Composite haemangioendothelioma represents a rare malignant vascular tumour, with significantly more favourable biological behaviour than angiosarcoma, even in cases where angiosarcoma-like areas are present. For that reason, composite haemangioendothelioma can be easily misdiagnosed as true angiosarcoma. The rarity of this disease unfortunately hampers the development of clinical practice guidelines and the implementation of treatment recommendations. Most of the patients with localized tumour are treated by wide surgical resection, without neo- or adjuvant radiotherapy or chemotherapy. However, in the case of this diagnosis, the watch-and-wait approach is better than mutilating procedure, highlighting the necessity of establishing of the correct diagnosis.
Patients’ perspectives on the use of artificial intelligence in dentistry: a regional survey
Authors: Ayad Nasim , Schwendicke Falk , Krois Joachim , van den Bosch Stefanie , Bergé Stefaan , Bohner Lauren , Hanisch Marcel , Vinayahalingam Shankeeth
Published: June 2023

The use of artificial intelligence (AI) in dentistry is rapidly evolving and could play a major role in a variety of dental fields. This study assessed patients’ perceptions and expectations regarding AI use in dentistry. An 18-item questionnaire survey focused on demographics, expectancy, accountability, trust, interaction, advantages and disadvantages was responded to by 330 patients; 265 completed questionnaires were included in this study. Frequencies and differences between age groups were analysed using a two-sided chi-squared or Fisher’s exact tests with Monte Carlo approximation. Patients’ perceived top three disadvantages of AI use in dentistry were (1) the impact on workforce needs (37.7%), (2) new challenges on doctor–patient relationships (36.2%) and (3) increased dental care costs (31.7%). Major expected advantages were improved diagnostic confidence (60.8%), time reduction (48.3%) and more personalised and evidencebased disease management (43.0%). Most patients expected AI to be part of the dental workflow in 1–5 (42.3%) or 5–10 (46.8%) years. Older patients (> 35 years) expected higher AI performance standards than younger patients (18–35 years) (p < 0.05). Overall, patients showed a positive attitude towards AI in dentistry. Understanding patients’ perceptions may allow professionals to shape AI-driven dentistry in the future.
Determinants of early initiation of breastfeeding in The Gambia: a population-based study using the 2019–2020 demographic and health survey data
Authors: Darboe Muhammed L , Jeyakumar Angeline , Mansour Salma M. A. , Valawalkar Shahanara
Published: June 2023

Background

Early initiation of breastfeeding within the first hour of life prevents neonatal and infant mortality. Sustainable Development Goals (SDGs) Target 3.2 aims to reduce neonatal mortality and under 5 mortality globally. The decline in the early initiation of breastfeeding in The Gambia coincides with deviations from the SDGs, due to poor indicators of child survival. Our work studied the determinants of early initiation of breastfeeding in The Gambia.

Methods

We used the 2019–2020 Gambia Demographic Health Survey (GDHS) conducted across all regions of the country. Since our population of interest was children born two years preceding the study, we only included children less than 24 months of age, living with an eligible respondent. Thus, a weighted sample of 5691 mother-child pairs was applied in the analysis. We reported summary statistics of individuals’ sociodemographic, obstetrics and antenatal, household, and community-level factors. A logistic regression model was used to determine associations between early initiation of breastfeeding and covariates.

Results

The prevalence of early initiation of breastfeeding was 64.3% (n = 3659). Mothers who had secondary education or higher educational level had higher odds of early initiation of breastfeeding (AOR 1.22; 95% CI 1.07, 1.40). Regions with rural population notably Lower and Central and Upper River Region had lower odds of early initiation of breastfeeding [Mansakonko (AOR 0.37; 95% CI 0.26, 0.15), Kerewan (AOR 0.26; 95% CI 0.19, 0.36), Kuntaur (AOR 0.39; 95% CI 0.28, 0.54), Janjanbureh (AOR 0.48; 95% CI 0.35, 0.66) and Basse (AOR 0.64; 95%CI 0.49, 0.85)]. Also, women in the high quintile of the wealth index were more likely to initiate breastfeeding early (AOR 1.29; 95% CI 1.06, 1.57). Four or more antenatal care visits did not increase early initiation of breastfeeding.

Conclusions

The results of the analyses demand affirmative action to improve maternal education, reduce poverty and inequality and empower rural communities in The Gambia. The IYCF component in antenatal care needs to be strengthened. Programs and policies on IYCF must resonate to address determinants of timely breastfeeding initiation to chart progress towards the SDG.
Improving outcomes for hospitalised First Nations peoples through greater cultural safety and better communication: the Communicate Study Partnership study protocol
Authors: Ralph Anna P. , McGrath Stuart Yiwarr , Armstrong Emily , Herdman Rarrtjiwuy Melanie , Ginnivan Leah , Lowell Anne , Lee Bilawara , Gorham Gillian , Taylor Sean , Hefler Marita , Kerrigan Vicki
Published: June 2023

Background

The Communicate Study is a partnership project which aims to transform the culture of healthcare systems to achieve excellence in culturally safe care for First Nations people. It responds to the ongoing impact of colonisation which results in First Nations peoples experiencing adverse outcomes of hospitalisation in Australia’s Northern Territory. In this setting, the majority of healthcare users are First Nations peoples, but the majority of healthcare providers are not. Our hypotheses are that strategies to ensure cultural safety can be effectively taught, systems can become culturally safe and that the provision of culturally safe healthcare in first languages will improve experiences and outcomes of hospitalisation.

Methods

We will implement a multicomponent intervention at three hospitals over 4 years. The main intervention components are as follows: cultural safety training called ‘Ask the Specialist Plus’ which incorporates a locally developed, purpose-built podcast, developing a community of practice in cultural safety and improving access to and uptake of Aboriginal language interpreters. Intervention components are informed by the ‘behaviour change wheel’ and address a supply–demand model for interpreters. The philosophical underpinnings are critical race theory, Freirean pedagogy and cultural safety. There are co-primary qualitative and quantitative outcome measures: cultural safety, as experienced by First Nations peoples at participating hospitals, and proportion of admitted First Nations patients who self-discharge. Qualitative measures of patient and provider experience, and patient-provider interactions, will be examined through interviews and observational data. Quantitative outcomes (documentation of language, uptake of interpreters (booked and completed), proportion of admissions ending in self-discharge, unplanned readmission, hospital length of stay, costs and cost benefits of interpreter use) will be measured using time-series analysis. Continuous quality improvement will use data in a participatory way to motivate change. Programme evaluation will assess Reach, Effectiveness, Adoption, Implementation and Maintenance (‘RE-AIM’).

Discussion

The intervention components are innovative, sustainable and have been successfully piloted. Refinement and scale-up through this project have the potential to transform First Nations patients’ experiences of care and health outcomes.

Trial registration

Registered with ClinicalTrials.gov Protocol Record 2008644
Arthroscopic-assisted reduction and internal fixation for complex tibial plateau fracture: radiographic and clinical outcomes with 2- to 15-year follow-up
Authors: Cheng You-Hung , Yang Cheng-Pang , Chang Shih-Sheng , Weng Chun-Jui , Chiu Chih-Hao , Chan Yi-Sheng
Published: June 2023

Background

To investigate the radiologic and prognostic outcomes after using arthroscopic-assisted reduction and internal fixation (ARIF) in complex tibial plateau fractures with mid- to long-term follow-up.

Methods

This retrospective study reviewed complex tibial plateau fractures that underwent ARIF from 1999 to 2019. Radiologic outcomes, including tibial plateau angle (TPA), posterior slope angle (PSA), Kellgren–Lawrence classification and Rasmussen radiologic assessment, were measured and evaluated. The prognosis and complications were assessed by the Rasmussen clinical assessment with a minimum follow-up of 2 years.

Results

Ninety-two consecutive patients (mean age: 46.9 years) with a mean follow-up of 74.8 months (24–180) were included in our series. Using AO classification, there were 20 type C1 fractures, 21 type C2 fractures, and 51 type C3 fractures. All the fractures achieved solid union. TPA was maintained well on average at the last follow-up and showed no significant difference compared to postoperatively (p = 0.208). In the sagittal plane, the mean PSA increased from 9.3 ± 2.9° to 9.6 ± 3.1° (p = 0.092). A statistically significant increase in PSA was also noted in the C3 group (p = 0.044). Superficial or deep infection was noted in 4 cases (4.3%), and total knee arthroplasty (TKA) was performed in 2 cases (2.2%) due to grade 4 osteoarthritis (OA). Ninety (97.8%) and 89 (96.7%) patients had good or excellent results in the Rasmussen radiologic assessment and Rasmussen clinical assessment, respectively.

Conclusions

The complex tibial plateau fracture could be treated successfully using arthroscopy-assisted reduction and internal fixation. Most patients achieve excellent and good clinical outcomes with low complication rates. In our experience, a higher incidence of increased slope was noted, especially in type C3 fractures. Reduction of the posterior fragment should be done cautiously during the operation.

Levels of evidence

Level III.
Nutrition management of PKU with pegvaliase therapy: update of the web-based PKU nutrition management guideline recommendations
Authors: Cunningham Amy , Rohr Fran , Splett Patricia , Mofidi Shideh , Bausell Heather , Stembridge Adrya , Kenneson Aileen , Singh Rani H.
Published: June 2023

Background

The web-based GMDI/SERN PKU Nutrition Management Guideline, published before approval of pegvaliase pharmacotherapy, offers guidance for nutrition management of individuals with phenylketonuria (PKU) treated with dietary therapy and/or sapropterin. An update of this guideline aims to provide recommendations that improve clinical outcomes and promote consistency and best practice in the nutrition management of individuals with PKU receiving pegvaliase therapy. Methodology includes: formulation of a research question; review, critical appraisal, and abstraction of peer-reviewed studies and unpublished practice literature; expert input through Delphi surveys and a Nominal Group process; and external review by metabolic experts.

Results

Recommendations, summary statements, and strength of evidence are included for each of the following topics: (1) initiating a pegvaliase response trial, (2) monitoring therapy response and nutritional status, (3) managing pegvaliase treatment after response to therapy, (4) education and support for optimal nutrition with pegvaliase therapy, and (5) pegvaliase therapy during pregnancy, lactation, and adolescence. Findings, supported by evidence and consensus, provide guidance for nutrition management of individuals receiving pegvaliase therapy for PKU. Recommendations focus on nutrition management by clinicians, as well as the challenges for individuals with PKU as a result of therapy changes.

Conclusions

Successful pegvaliase therapy allows the possibility for individuals with PKU to consume an unrestricted diet while still maintaining the benefits of blood phenylalanine control. This necessitates a perspective change in education and support provided to individuals in order to achieve healthy nutrient intake that supports optimal nutritional status. The updated guideline, and companion Toolkit for practical implementation of recommendations, is web-based, allowing for utilization by health care providers, researchers, and collaborators who advocate and care for individuals with PKU. These guidelines are meant to be followed always taking into account the provider’s clinical judgement and considering the individual’s specific circumstances. Open access is available at the Genetic Metabolic Dietitians International (https://GMDI.org) and Southeast Regional Genetics Network (https://managementguidelines.net) websites.
Cryptosporidium parvum: an emerging occupational zoonosis in Finland
Authors: Enbom Tuulia , Suominen Kristiina , Laitinen Sirpa , Ollgren Jukka , Autio Tiina , Rimhanen-Finne Ruska
Published: June 2023

Background

Cryptosporidiosis has increased in recent years in Finland. We aimed to identify risk factors for human cryptosporidiosis and to determine the significance of Cryptosporidium parvum as a causative agent. Based on notifications to the Finnish Infectious Disease Register (FIDR), we conducted a case-control study and genotyped Cryptosporidium species from patient samples from July to December 2019. We also retrieved the occupational cryptosporidiosis cases from 2011 to 2019 from the Finnish Register of Occupational Diseases (FROD).

Results

Of 272 patient samples analyzed, 76% were C. parvum and 3% C. hominis. In the multivariable logistic regression analysis of 82 C. parvum cases and 218 controls, cryptosporidiosis was associated with cattle contact (OR 81, 95% confidence interval (CI) 26–251), having a family member with gastroenteritis (OR 34, 95% CI 6.2–186), and spending time at one’s own vacation home (OR 15, 95% CI 4.2–54). Of the cases, 65% had regular cattle contact. The most common gp60 subtypes identified were IIaA15G2R1 and IIaA13G2R1. In FROD, 68 recognized occupational cryptosporidiosis cases were registered in 2011–2019.

Conclusions

C. parvum is the most common Cryptosporidium species found in humans in Finland and poses a moderate to high risk of occupational infection for people working with cattle. The number of occupational notifications of cryptosporidiosis increased between 2011 and 2019. Cryptosporidiosis should be recognized as an important occupational disease among persons working with livestock in Finland, criteria to identify occupational cryptosporidiosis need to be created, and occupational safety in cattle-related work should be improved.
A survey for antibodies against Fasciola hepatica in cattle and sheep in Finland indicates a low level of exposure
Authors: Gröning Heini , Oksanen Antti , Skrzypczak Teresa , Autio Tiina
Published: June 2023

Background

Fasciolosis is a parasitic infection caused by the liver fluke Fasciola hepatica that can have a major economic impact on livestock industry. The prevalence of the disease has recently been increasing in many North European countries. The objective of this study was to determine the prevalence of antibody against F. hepatica in Finnish cattle herds and sheep flocks during 2019 by using a commercial enzyme-linked immunosorbent assay (ELISA). Randomly selected bulk tank milk samples were obtained from 660 dairy herds. Blood samples were collected at slaughterhouses from 1944 suckler cows from 309 herds and from 1120 sheep from 95 flocks.

Results

Antibodies against F. hepatica were found in 0.45% (95% confidence interval (CI): 0.15–1.33) of the dairy herds and 0.97% (95% CI: 0.33–2.82) of the suckler cow herds. The seropositive herds were located in eastern and central Finland. None of the sampled sheep flocks tested had antibodies against F. hepatica (95% CI: 0–3.89). The results of the assays were compared with meat inspection data received from the slaughterhouses. All positive herds also had liver condemnations due to F. hepatica based on the meat inspection reports.

Conclusions

Compared to other North European countries, the prevalence of fasciolosis in Finland can be considered low, and according to meat inspection reports, there are no indications of the prevalence increasing in Finland.
Small RNA modifications: regulatory molecules and potential applications
Authors: Xiong Qunli , Zhang Yaguang
Published: June 2023

Small RNAs (also referred to as small noncoding RNAs, sncRNA) are defined as polymeric ribonucleic acid molecules that are less than 200 nucleotides in length and serve a variety of essential functions within cells. Small RNA species include microRNA (miRNA), PIWI-interacting RNA (piRNA), small interfering RNA (siRNA), tRNA-derived small RNA (tsRNA), etc. Current evidence suggest that small RNAs can also have diverse modifications to their nucleotide composition that affect their stability as well as their capacity for nuclear export, and these modifications are relevant to their capacity to drive molecular signaling processes relevant to biogenesis, cell proliferation and differentiation. In this review, we highlight the molecular characteristics and cellular functions of small RNA and their modifications, as well as current techniques for their reliable detection. We also discuss how small RNA modifications may be relevant to the clinical applications for the diagnosis and treatment of human health conditions such as cancer.
Effectiveness of laparoscopic removal of isolated superficial peritoneal endometriosis for the management of chronic pelvic pain in women (ESPriT2): protocol for a multi-centre randomised controlled trial
Authors: Mackenzie Scott C. , Stephen Jacqueline , Williams Linda , Daniels Jane , Norrie John , Becker Christian M. , Byrne Dominic , Cheong Ying , Clark T. Justin , Cooper Kevin G. , Cox Emma , Doust Ann M. , Fernandez Priscilla , Hawe Jeremy , Holland Tom , Hummelshoj Lone , Jackson Louise J. , King Kathleen , Maheshwari Abha , Martin Dan C. , Sutherland Lauren , Thornton Jim , Vincent Katy , Vyas Sanjay , Horne Andrew W. , Whitaker Lucy H. R.
Published: June 2023

Background

Endometriosis affects 190 million women and those assigned female at birth worldwide. For some, it is associated with debilitating chronic pelvic pain. Diagnosis of endometriosis is often achieved through diagnostic laparoscopy. However, when isolated superficial peritoneal endometriosis (SPE), the most common endometriosis subtype, is identified during laparoscopy, limited evidence exists to support the common decision to surgically remove it via excision or ablation. Improved understanding of the impact of surgical removal of isolated SPE for the management of chronic pelvic pain in women is required. Here, we describe our protocol for a multi-centre trial to determine the effectiveness of surgical removal of isolated SPE for the management of endometriosis-associated pain.

Methods

We plan to undertake a multi-centre participant-blind parallel-group randomised controlled clinical and cost-effectiveness trial with internal pilot. We plan to randomise 400 participants from up to 70 National Health Service Hospitals in the UK. Participants with chronic pelvic pain awaiting diagnostic laparoscopy for suspected endometriosis will be consented by the clinical research team. If isolated SPE is identified at laparoscopy, and deep or ovarian endometriosis is not seen, participants will be randomised intraoperatively (1:1) to surgical removal (by excision or ablation or both, according to surgeons’ preference) versus diagnostic laparoscopy alone. Randomisation with block-stratification will be used. Participants will be given a diagnosis but will not be informed of the procedure they received until 12 months post-randomisation, unless required. Post-operative medical treatment will be according to participants’ preference. Participants will be asked to complete validated pain and quality of life questionnaires at 3, 6 and 12 months after randomisation. Our primary outcome is the pain domain of the Endometriosis Health Profile-30 (EHP-30), via a between randomised group comparison of adjusted means at 12 months. Assuming a standard deviation of 22 points around the pain score, 90% power, 5% significance and 20% missing data, 400 participants are required to be randomised to detect an 8-point pain score difference.

Discussion

This trial aims to provide high quality evidence of the clinical and cost-effectiveness of surgical removal of isolated SPE.

Trial registration

ISRCTN registry ISRCTN27244948. Registered 6 April 2021.
Non-COVID-19 UK clinical trials and the COVID-19 pandemic: impact, challenges and possible solutions
Authors: Lorenc Ava , Rooshenas Leila , Conefrey Carmel , Wade Julia , Farrar Nicola , Mills Nicola , Paramasivan Sangeetha , Realpe Alba , Jepson Marcus
Published: June 2023

Introduction

The COVID-19 pandemic impacted the operationalisation of non-COVID-19 clinical trials globally, particularly site and participant recruitment and trial success/stoppage. Trials which anticipate recruitment challenges may embed methods such as the QuinteT Recruitment Intervention (QRI) to help identify and understand the sources of challenges. Such interventions can help shed light on pandemic-related challenges. This paper reports our experience of the impact of the COVID-19 pandemic on conducting clinical trials with an embedded QRI, highlighting how the QRI aided in identifying challenges and potential solutions, particularly related to the site set-up and participant recruitment.

Main body

We report on 13 UK clinical trials which included a QRI. Information is from QRI data and researchers’ experience and reflections. In most trials, recruitment was lower than even the lowest anticipated rates. The flexibility of the QRI facilitated rapid data collection to understand and document, and in some instances respond to, operational challenges. Challenges were mostly logistical, pandemic-related and beyond the control of the site or central trial teams. Specifically: disrupted and variable site opening timelines —often due to local research and development (R&D) delays— shortages of staff to recruit patients; fewer eligible patients or limited access to patients; and intervention-related factors. Almost all trials were affected by pandemic-related staffing issues including redeployment, prioritisation of COVID-19 care and research, and COVID-19-related staff illness and absence. Trials of elective procedures were particularly impacted by the pandemic, which caused changes to care/recruitment pathways, deprioritisation of services, reduced clinical and surgical capacity and longer waiting lists. Attempted solutions included extra engagement with staff and R&D departments, trial protocol changes (primarily moving online) and seeking additional resourcing.

Conclusion

We have highlighted wide-ranging, extensive and consistent pandemic-related challenges faced by UK clinical trials, which the QRI helped to identify and, in some cases, address. Many challenges were insurmountable at individual trials or trials unit level. This overview highlights the need to streamline trial regulatory processes, address staffing crises, improve recognition of NHS research staff and for clearer, more nuanced central guidance on the prioritisation of studies and how to deal with the backlog. Pre-emptively embedding qualitative work and stakeholder consultation into trials with anticipated difficulties, moving some processes online, and flexible trial protocols may improve the resilience of trials in the current challenging context.
Evaluating the completeness of the reporting of abstracts since the publication of the CONSORT extension for abstracts: an evaluation of randomized controlled trial in ten nursing journals
Authors: He Yan , Zhang Rong , Shan Wenjing , Yin Yuhuan , Zhang Xiaoli , Zhang Yiyin , Wang Xiaoping
Published: June 2023

Background

As a practice-oriented discipline, strict adherence to reporting guidelines is particularly important in randomized controlled trial (RCT) abstracts of the nursing area. However, whether abstract reports after 2010 have complied with the Consolidated Standards of Reporting Trials for Abstracts (CONSORT-A) guideline is unclear. This study aimed to evaluate whether the publication of CONSORT-A has improved abstract reporting in nursing and explores the factors associated with better adherence to the guidelines.

Methods

We searched the Web of Science for 200 RCTs randomly selected from ten nursing journals. We used a data extraction form based on CONSORT-A, including 16 items, to analyze the reporting adherence to the guidelines, and the reporting rate of each item and the total score for each abstract were used to indicate adherence and overall quality score (OQS, range 0–16). A comparison of the total mean score between the two periods was made, and affecting factors were analyzed.

Results

In the studies we included, 48 abstracts were published pre-CONSORT-A whereas 152 post-CONSORT-A. The overall mean score for reporting adherence to 16 items was 7.41 ± 2.78 and 9.16 ± 2.76 for pre- and post-CONSORT-A, respectively (total score: 16). The most poorly reported items are “harms (0%),” “outcomes in method (8.5%),” “randomization (25%),” and “blinding (6.5%).” Items including the year of publication, impact factor, multiple center trial, word count, and structured abstract are significantly associated with higher adherence.

Conclusions

The adherence to abstract reporting in nursing literature has improved since the CONSORT-A era, but the overall completeness of RCT abstracts remained low. A joint effort by authors, editors, and journals is necessary to improve reporting quality of RCT abstracts.
Pregabalin as an effective treatment for acute postoperative pain following spinal surgery without major side effects: protocol for a prospective, randomized controlled, double-blinded trial
Authors: Park Ki-Hoon , Chung Nam-Su , Chung Hee-Woong , Kim Tae Young , Lee Han-Dong
Published: June 2023

Background

Patients experience considerable postoperative pain after spinal surgery. As the spine is located at the centre of the body and supports body weight, severe postoperative pain hinders upper body elevation and gait which can lead to various complications, including pulmonary deterioration and pressure sores. It is important to effectively control postoperative pain to prevent such complications. Gabapentinoids are widely used as preemptive multimodal analgesia, but their effects and side effects are dose-dependent. This study was designed to examine the efficacy and side effects of varying doses of postoperative pregabalin for the treatment of postoperative pain after spinal surgery.

Methods

This is a prospective, randomized controlled, double-blind study. A total of 132 participants will be randomly assigned to the placebo (n = 33) group or to the pregabalin 25 mg (n = 33), 50 mg (n = 33), or 75 mg (n = 33) groups. Each participant will be administered placebo or pregabalin once prior to surgery and every 12 h after surgery for 72 h. The primary outcome will be the visual analogue scale pain score, total dose of administered intravenous patient-controlled analgesia, and frequency of rescue analgesic administered for 72 h from arrival to the general ward after surgery, subdivided into four periods: 1–6 h, 6–24 h, 24–48 h, and 48–72 h. The secondary outcomes will be the incidence and frequency of nausea and vomiting due to intravenous patient-controlled analgesia. Safety will be assessed by monitoring the occurrence of side effects such as sedation, dizziness, headache, visual disturbance, and swelling.

Discussion

Pregabalin is already widely used as preemptive analgesia and, unlike nonsteroidal anti-inflammatory drugs, is not associated with a risk of nonunion after spinal surgery. A recent meta-analysis demonstrated the analgesic efficacy and opioid-sparing effect of gabapentinoids with significantly decreased risks of nausea, vomiting, and pruritus. This study will provide evidence for the optimal dosage of pregabalin for the treatment of postoperative pain after spinal surgery.

Trial registration

ClinicalTrials.gov NCT05478382. Registered on 26 July 2022.
Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus
Authors: Torell Agnes , Stockfelt Marit , Larsson Gunilla , Blennow Kaj , Zetterberg Henrik , Leonard Dag , Rönnblom Lars , Saleh Muna , Sjöwall Christopher , Strevens Helena , Jönsen Andreas , Bengtsson Anders A. , Trysberg Estelle , Sennström Maria Majcuk , Zickert Agneta , Svenungsson Elisabet , Gunnarsson Iva , Christenson Karin , Bylund Johan , Jacobsson Bo , Rudin Anna , Lundell Anna-Carin
Published: June 2023

Background

An increased risk of pregnancy complications is seen in women with systemic lupus erythematosus (SLE), but the specific immunopathological drivers are still unclear. Hallmarks of SLE are granulocyte activation, type I interferon (IFN) overproduction, and autoantibodies. Here we examined whether low-density granulocytes (LDG) and granulocyte activation increase during pregnancy, and related the results to IFNα protein levels, autoantibody profile, and gestational age at birth.

Methods

Repeated blood samples were collected during pregnancy in trimesters one, two, and three from 69 women with SLE and 27 healthy pregnant women (HC). Nineteen of the SLE women were also sampled late postpartum. LDG proportions and granulocyte activation (CD62L shedding) were measured by flow cytometry. Plasma IFNα protein concentrations were quantified by single molecule array (Simoa) immune assay. Clinical data were obtained from medical records.

Results

Women with SLE had higher LDG proportions and increased IFNα protein levels compared to HC throughout pregnancy, but neither LDG fractions nor IFNα levels differed during pregnancy compared to postpartum in SLE. Granulocyte activation status was higher in SLE relative to HC pregnancies, and it was increased during pregnancy compared to after pregnancy in SLE. Higher LDG proportions in SLE were associated with antiphospholipid positivity but not to IFNα protein levels. Finally, higher LDG proportions in trimester three correlated independently with lower gestational age at birth in SLE.

Conclusion

Our results suggest that SLE pregnancy results in increased peripheral granulocyte priming, and that higher LDG proportions late in pregnancy are related to shorter pregnancy duration but not to IFNα blood levels in SLE.
Immunohistochemical detection of MUC5AC and MUC5B mucins in ferrets
Authors: Meyerholz David K. , Leidinger Mariah R. , Adam Goeken J. , Businga Thomas R. , Vizuett Sebastian , Akers Allison , Evans Idil , Zhang Yan , Engelhardt John F.
Published: June 2023

Objective

Cystic fibrosis (CF) is a genetic condition that causes abnormal mucus secretions in affected organs. MUC5AC and MUC5B are gel-forming mucins and frequent targets for investigations in CF tissues. Our objective was to qualify MUC5AC and MUC5B immunohistochemical techniques to provide a useful tool to identify, localize and interpret mucin expression in ferret tissues.

Results

MUC5AC and MUC5B mucins were detected most commonly in large airways and least in small airways, consistent with reported goblet cell density in airway surface epithelia. We evaluated whether staining method affected the detection of goblet cell mucins in serial sections of bronchial surface epithelia. Significant differences between stains were not observed suggesting common co-expression MUC5AC and MUC5B proteins in goblet cells of airway surface epithelia. Gallbladder and stomach tissues are reported to have differential mucin enrichment, so we tested these tissues in wildtype ferrets. Stomach tissues were enriched in MUC5AC and gallbladder tissues enriched in MUC5B, mucin enrichment similar to human tissues. Mucin immunostaining techniques were further qualified for specificity using lung tissue from recently generated MUC5AC−/− and MUC5B−/− ferrets. Qualified techniques for MUC5AC and MUC5B immunohistochemistry will be useful tools for mucin tissue studies in CF and other ferret models.
Monitoring the growth dynamics of Tetragenococcus halophilus strains in lupine moromi fermentation using a multiplex-PCR system
Authors: Link Tobias , Ehrmann Matthias A.
Published: June 2023

Objective

The microbiota of a seasoning sauce fermentation process is usually complex and includes multiple species and even various strains of one species. Moreover, composition and cell numbers of individual strains vary over the course of the entire fermentation. This study demonstrates the applicability of a multiplex PCR system to monitor growth dynamics of Tetragenococcus (T.) halophilus strains in order to evaluate their performance and help to select the most competitive starter strain.

Results

In a previous study we isolated T. halophilus strains from multiple lupine moromi fermentation processes and characterized them. In this study we wanted to monitor the growth dynamics of these strains in a competitive lupine moromi model fermentation process using a multiplex PCR system. Therefore, pasteurized lupine koji was inoculated with eight different T. halophilus strains, six from lupine moromi, one from an experimental buckwheat moromi fermentation process and the type strain DSM 20,339T, to create the inoculated lupine moromi pilot scale fermentation process. With the multiplex PCR system, we could detect that all strains could grow in lupine moromi but, that TMW 2.2254 and TMW 2.2264 outperformed all other strains. Both strains dominated the fermentation after three weeks with cell counts between 4 × 106 to 4 × 107 CFU/mL for TMW 2.2254 and 1 × 107 to 5 × 107 CFU/mL for TMW 2.2264. The pH dropped to value below 5 within the first 7 days, the selection of these strains might be related to their acid tolerance.
Parallel-in-time optimization of induction motors
Authors: Hahne Jens , Polenz Björn , Kulchytska-Ruchka Iryna , Friedhoff Stephanie , Ulbrich Stefan , Schöps Sebastian
Published: June 2023

Parallel-in-time (PinT) methods were developed to accelerate time-domain solution of evolutionary problems using modern parallel computer architectures. In this paper we incorporate one of the efficient PinT approaches, in particular, the asynchronous truncated multigrid-reduction-in-time algorithm, into a bound constrained optimization procedure applied to an induction machine. Calculation of an optimal motor geometry with respect to its efficiency in the steady state is thus parallelized at each iteration of the optimization algorithm. As a result, a more efficient motor model is obtained about 11 times faster compared to optimization using the standard sequential time stepping.
Device association and trajectory planning for UAV-assisted MEC in IoT: a matching theory-based approach
Authors: Zhang Xinjun , Zhang Guopeng , Wang Kezhi , Yang Kun
Published: June 2023

Unmanned aircraft vehicles (UAVs)-enabled mobile edge computing (MEC) can enable Internet of Things devices (IoTD) to offload computing tasks to them. Considering this, we study how multiple aerial service providers (ASPs) compete with each other to provide edge computing services to multiple ground network operators (GNOs). An ASP owning multiple UAVs aims to achieve the maximum profit from providing MEC service to the GNOs, while a GNO operating multiple IoTDs aims to seek the computing service of a certain ASP to meet its performance requirements. To this end, we first quantify the conflicting interests of the ASPs and GNOs by using different profit functions. Then, the UAV scheduling and resource allocation is formulated as a multi-objective optimization problem. To address this problem, we first solve the UAV trajectory planning and resource allocation problem between one ASP and one GNO by using the Lagrange relaxation and successive convex optimization (SCA) methods. Based on the obtained results, the GNOs and ASPs are then associated in the framework based on the matching theory, which results in a weak Pareto optimality. Simulation results show that the proposed method achieves the considerable performance.
A survey on the handover management in 5G-NR cellular networks: aspects, approaches and challenges
Authors: Haghrah Amiraslan , Abdollahi Mehran Pourmohammad , Azarhava Hosein , Niya Javad Musevi
Published: June 2023

With the purpose of providing higher data rate and ultra-reliable and low-latency communications for the users, employing the small cells in the upcoming Fifth-Generation-New Radio (5G-NR) cellular networks and beyond is leading to the serious challenges in mobility management due to dynamicity of the user equipments (UEs). Among different issues related to the mobility of the UEs, the handover management is one of the key procedures to let the UEs experience a high quality of service (QoS)/quality of experience (QoE). So far, many protocols and algorithms have been proposed to enhance the mobility management in 5G-NR from various aspects, but still a thorough survey has not been incorporated to summarize the recent advances and future directions of the mentioned issue. Thus, the handover management and the corresponding challenges stand in the center of concentrations in this paper, with a glance on 4G to the advancements of 5G-NR. The challenges include QoS/QoE, throughput, delay, traffic load, the attacks during authentication process and resource allocation. To overcome the mentioned challenges, the handover procedure is evaluated by some key performance indicators such as handover ratio, handover failure, radio link failure and such like which depend on the received signal quality. The lack of new advancements and novel aspects of handover plus the separation of security and handover issues in previous works are perceived as research gaps and motivations for the current paper. In this regard, this paper aims to specify and analyze the technical issues, to provide an overview on the proposed methods and recent advances and to bring the future directions into the limelight. We categorize the concurrent standards and methods about the handover, and then, we survey the proposed algorithms including theoretical, algorithm-based and pattern-capturing approaches following the authentication process along with the vulnerabilities and the algorithms to counteract the attacks during handover. Also, we study various issues corresponding to network performance during the handover procedure. Finally, we discuss the open problems and future research directions.