bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of manual chest compressions according to the updated cardiopulmonary resuscitation guidelines and the impact of feedback devices in an educational resuscitation course
Authors: Urushibata Nao , Murata Kiyoshi , Endo Hideki , Yoshiyuki Ayako , Otomo Yasuhiro
Published: June 2020

Background

The cardiopulmonary resuscitation guidelines revised in 2015 recommend target chest compression rate (CCR) and chest compression depth (CCD) of 100–120 compressions per minute (cpm) and 5–6 cm, respectively. We hypothesized that the new guidelines are harder to comply with, even with proper feedback.

Methods

This prospective observational study using data collected from the participants of an Immediate Cardiac Life Support course included the evaluation of chest compressions using performance data from a feedback device after the completion of the course. Participants completed chest compressions for 1 min and were provided with feedback, after which they performed another cycle of CC. Primary outcome measures were CCR and CCD as well as the correct CCR percentage and CCD percentage for pre and post feedback.

Results

The study included a total of 88 participants. The median pre-CCR was 112.5 cpm (interquartile range [IQR] 108–116 cpm), and the median correct pre-CCR percentage was 96% (IQR 82.5–99.5%). After the feedback, there was a slight increase in the correct CCR percentage (99% [IQR 92.5–100%]). Conversely, the median pre-CCD was 5.4 cm (IQR 4.9–5.8 cm), and the median pre-correct CCD percentage was 66% (IQR 18.5–90%). The increase in the median post-correct CCD percentage to 72% (IQR 27–94%) observed after the feedback was not statistically significant (P = 0.361).

Conclusions

Compliance with the new guidelines for chest compressions, especially those regarding the CCD, might be difficult. However, whether the changes in guidelines affect outcomes in actual clinical settings is uncertain and requires further investigation.
Using online technologies to improve diversity and inclusion in cognitive interviews with young people
Authors: Upadhyay Ushma D. , Lipkovich Heather
Published: June 2020

Background

We aimed to assess the feasibility of using multiple technologies to recruit and conduct cognitive interviews among young people across the United States to test items measuring sexual and reproductive empowerment. We sought to understand whether these methods could achieve a diverse sample of participants. With more researchers turning to approaches that maintain social distancing in the context of COVID-19, it has become more pressing to refine these remote research methods.

Methods

We used several online sites to recruit for and conduct cognitive testing of survey items. To recruit potential participants we advertised the study on the free online bulletin board, Craigslist, and the free online social network, Reddit. Interested participants completed an online Qualtrics screening form. To maximize diversity, we purposefully selected individuals to invite for participation. We used the video meeting platform, Zoom, to conduct the cognitive interviews. The interviewer opened a document with the items to be tested, shared the screen with the participant, and gave them control of the mouse and keyboard. After the participant self-administered the survey, the interviewer asked about interpretation and comprehension. After completion of the interviews we sent participants a follow-up survey about their impressions of the research methods and technologies used. We describe the processes, the advantages and disadvantages, and offer recommendations for researchers.

Results

We recruited and interviewed 30 young people from a range of regions, gender identities, sexual orientations, ages, education, and experiences with sexual activity. These methods allowed us to recruit a purposefully selected diverse sample in terms of race/ethnicity and region. It also may have offered potential participants a feeling of safety and anonymity leading to greater participation from gay, lesbian, and transgender people who would not have agreed to participate in-person. Conducting the interviews using video chat may also have facilitated the inclusion of individuals who would not volunteer for in-person meetings. Disadvantages of video interviewing included participant challenges to finding a private space for the interview and problems with electronic devices.

Conclusions

Online technologies can be used to achieve a diverse sample of research participants, contributing to research findings that better respond to young people’s unique identities and situations.
Hygiene promotion might be better than serological screening to deal with Cytomegalovirus infection during pregnancy: a methodological appraisal and decision analysis
Authors: Billette de Villemeur Agathe , Tattevin Pierre , Salmi Louis-Rachid ,   the French Haut Conseil de la santé publique Working Group, Alain S. , Antona D. , Aujard Y. , Bégué A. , Barjat T. , Billaud E. , de Villemeur Billette A. , Colson S. , Dufour V. , Jean D. , Gehanno J. F. , des Fontaines Halley V. , Mandelbrot L. , Matheron S. , Minodier P. , Marseille Roussey M. , Royère D. , Salmi L. R. , Scemama O. , Tattevin P. , Teurnier F. , Trastour C. , Vauloup-Fellous C.
Published: June 2020

Background

Cytomegalovirus infection is the most frequent viral congenital infection, with possible consequences such as deafness, or psychomotor retardation. In 2016, the French High Council of Public Health was mandated to update recommendations regarding prevention of cytomegalovirus infection in pregnant women. We summarize a critical appraisal of knowledge and deterministic decision analysis comparing the current no-screening situation to serological screening during pregnancy, and to hygiene promotion.

Methods

Screening was defined as systematic serological testing, during the first trimester, with repeated tests as needed, to all pregnant women. Outcomes were: 1) severe sequela: intellectual deficiency with IQ ≤ 50 or hearing impairment < 70 dB or sight impairment (≤ 3/10 at best eye); 2) moderate sequela: any level of intellectual, hearing or sight deficiency; and 3) death or termination of pregnancy. We simulated the one-year course of cytomegalovirus infection in a cohort of 800,000 pregnant women. We developed a deterministic decision model, using best and min-max estimates, extracted from systematic reviews or original studies.

Results

Relevant data were scarce or imprecise. We estimated that 4352 maternal primary infections would result in 1741 foetal infections, and an unknown number of maternal reinfections would result in 1699 foetal infections. There would be 788 cytomegalovirus-related consequences, including 316 foetal deaths or terminations of pregnancy, and 424 moderate and 48 severe sequelae. Screening would result in a 1.66-fold increase of poor outcomes, mostly related to a 2.93-fold increase in deaths and terminations of pregnancy, not compensated by the decrease in severe symptomatic newborns. The promotion of hygiene would result in a 0.75-fold decrease of poor outcomes, related to both a decrease in severe sequelae among symptomatic newborns (RR = 0.75; min-max: 1.00–0.68), and in deaths and terminations of pregnancy (RR = 0.75; min-max: 0.97–0.68).

Conclusions

Prevention of cytomegalovirus infection during pregnancy should promote hygiene; serological screening should not be recommended.
Detailed registration of care in midwifery practices in the Netherlands: an opportunity for research within a healthy pregnant population
Authors: Pouwels A. , Offerhaus P. , Merkx A. , Zeegers B. , Nieuwenhuijze M. J.
Published: June 2020

Background

Research in maternity care is often conducted in mixed low and high-risk or solely high-risk populations. This limits generalizability to the low-risk population of pregnant women receiving care from Dutch midwives. To address this limitation, 24 midwifery practices in the Netherlands bring together routinely collected data from medical records of pregnant women and their offspring in the VeCaS database. This database offers possibilities for research of physiological pregnancy and childbirth. This study explores if the pregnant women in VeCaS are a representative sample for the national population of women who receive primary midwife-led care in the Netherlands.

Methods

In VeCaS we selected a low risk population in midwife-led care who gave birth in 2015. We compared population characteristics and birth outcomes in this study cohort with a similarly defined national cohort, using Chi Square and two side t-test statistics. Additionally, we describe some birth outcomes and lifestyle factors.

Results

Midwifery practices contributing to VeCaS are spread over the Netherlands, although the western region is underrepresented. For population characteristics, the VeCaS cohort is similar to the national cohort in maternal age (mean 30.4 years) and parity (nulliparous women: 47.1% versus 45.9%). Less often, women in the VeCaS cohort have a non-Dutch background (15.7% vs 24.4%), a higher SES (9.9% vs 23.7%) and live in an urbanised surrounding (4.9% vs 24.8%). Birth outcomes were similar to the national cohort, most women gave birth at term (94.9% vs 94.5% between 37 + 0–41+ 6 weeks), started labour spontaneously (74.5% vs 75.5%) and had a spontaneous vaginal birth (77.4% vs 77.6%), 16.9% had a home birth. Furthermore, 61.1% had a normal pre-pregnancy BMI, and 81.0% did not smoke in pregnancy.

Conclusions

The VeCaS database contains data of a population that is mostly comparable to the national population in primary midwife-led care in the Netherlands. Therefore, the VeCaS database is suitable for research in a healthy pregnant population and is valuable to improve knowledge of the physiological course of pregnancy and birth. Representativeness of maternal characteristics may be improved by including midwifery practices from the urbanised western region in the Netherlands.
A psychological intervention for suicide applied to non-affective psychosis: the CARMS (Cognitive AppRoaches to coMbatting Suicidality) randomised controlled trial protocol
Authors: Gooding Patricia A. , Pratt Daniel , Awenat Yvonne , Drake Richard , Elliott Rachel , Emsley Richard , Huggett Charlotte , Jones Steven , Kapur Navneet , Lobban Fiona , Peters Sarah , Haddock Gillian
Published: June 2020

Background

Suicide is a leading cause of death globally. Suicide deaths are elevated in those experiencing severe mental health problems, including schizophrenia. Psychological talking therapies are a potentially effective means of alleviating suicidal thoughts, plans, and attempts. However, talking therapies need to i) focus on suicidal experiences directly and explicitly, and ii) be based on testable psychological mechanisms. The Cognitive AppRoaches to coMbatting Suicidality (CARMS) project is a Randomised Controlled Trial (RCT) which aims to investigate both the efficacy and the underlying mechanisms of a psychological talking therapy for people who have been recently suicidal and have non-affective psychosis.

Methods

The CARMS trial is a two-armed single-blind RCT comparing a psychological talking therapy (Cognitive Behavioural Suicide Prevention for psychosis [CBSPp]) plus Treatment As Usual (TAU) with TAU alone. There are primary and secondary suicidality outcome variables, plus mechanistic, clinical, and health economic outcomes measured over time. The primary outcome is a measure of suicidal ideation at 6 months after baseline. The target sample size is 250, with approximately 125 randomised to each arm of the trial, and an assumption of up to 25% attrition. Hence, the overall recruitment target is up to 333. An intention to treat analysis will be used with primary stratification based on National Health Service (NHS) recruitment site and antidepressant prescription medication. Recruitment will be from NHS mental health services in the North West of England, UK. Participants must be 18 or over; be under the care of mental health services; have mental health problems which meet ICD-10 non-affective psychosis criteria; and have experienced self-reported suicidal thoughts, plans, and/or attempts in the 3 months prior to recruitment. Nested qualitative work will investigate the pathways to suicidality, experiences of the therapy, and identify potential implementation challenges beyond a trial setting as perceived by numerous stake-holders.

Discussion

This trial has important implications for countering suicidal experiences for people with psychosis. It will provide definitive evidence about the efficacy of the CBSPp therapy; the psychological mechanisms which lead to suicidal experiences; and provide an understanding of what is required to implement the intervention into services should it be efficacious.

Trial registration

ClinicalTrials.gov(NCT03114917), 14th April 2017. ISRCTN (reference ISRCTN1777666610.1186/ISRCTN17776666); 5th June 2017). Registration was recorded prior to participant recruitment commencing.
Practice and technique of using face mask amongst adults in the community: a cross-sectional descriptive study
Authors: Lee Linda Yin-king , Lam Evangeline Pui-wah , Chan Chiu-kiu , Chan Sum-yi , Chiu Man-ki , Chong Wing-hei , Chu Kin-wai , Hon Man-sze , Kwan Lok-ki , Tsang Kit-lam , Tsoi Siu-lai , Wu Chung-wai
Published: June 2020

Background

The proper use of face mask comprises the correct practice and wearing technique and is important in preventing the spread of respiratory infections. Previous studies have addressed only the aspect of practice and failed to provide a detailed account of face mask usage amongst community-based populations. This study examined the practice and technique of using face mask amongst adults.

Methods

A cross-sectional descriptive design was adopted. A quota sample of 1500 adults was recruited in Hong Kong during a nonepidemic state between January and February 2017. The participants’ practice of using face mask in five given situations was assessed using a questionnaire. Their technique in using face mask, including 12 steps, was assessed using an observation checklist. Statistical tests were used to compare the differences in practice and technique amongst adults of different gender and age groups.

Results

Findings revealed that the performance of the participants in both categories was unsatisfactory. In terms of practice, less than one-fifth of the participants reported that they always wore face mask when taking care of family members with fever (14.7%) or respiratory infections (19.5%). Male adults and those aged 55–64 reported low frequency in using face mask during required situations. In terms of technique, none of the participants performed all the required steps in using face mask correctly. More than 90% of the participants did not perform hand hygiene before putting on (91.5%), taking off (97.3%), or after disposing (91.5%) face mask. Adults aged 55 and above performed poorer than adults in the younger age groups.

Conclusion

Compared with previous findings obtained during an epidemic, the performance of the participants during a nonepidemic state was less satisfactory. The possibility of developing fatigue after exposure to repeated epidemics was discussed. This study contributes to a comprehensive understanding of the use of face mask in a community and reveals the underperformed areas. Effort is required to enhance the proper practice of using face mask, convey the message that hand hygiene is an essential step in wearing and taking off a face mask and increase the public’s general concern in the value of using face mask.
Creatine kinase elevation after robotic surgery for rectal cancer due to a prolonged lithotomy position
Authors: Tsuchiya Yuki , Munakata Shinya , Tsukamoto Ryoichi , Okazawa Yu , Mizukoshi Kosuke , Sugimoto Kiichi , Takahashi Makoto , Tomiki Yutaka Kojima Yuichi , Sakamoto Kazuhiro
Published: June 2020

Background

Robotic surgery for rectal cancer, which is now performed worldwide, can be associated with elevated creatine kinase levels postoperatively. In this study, we compared postoperative complications between patients undergoing robotic surgery and laparoscopic surgery.

Methods

We identified 66 consecutive patients who underwent curative resection for rectal cancer at Juntendo University Hospital between January 2016 and February 2019. Patients were divided into a conventional laparoscopic surgery (CLS) group (n = 38) and a robotic-assisted laparoscopic surgery (RALS) group (n = 28) before comparing various clinicodemographic factors between the groups.

Results

Patient age and gender, surgical approach (CLS/RALS), pathological T factor, pathological stage, duration of postoperative hospital stay, and postoperative complications were not significantly different between the RALS and CLS groups. However, the operation time was significantly longer in the RALS group (407 min) than in the CLS group (295 min; p < 0.001). Notably, the serum level of creatine kinase on postoperative day 1 was significantly higher in the CLS group (154 IU/L) than in the RALS group (525 IU/L; p < 0.001), despite there being no significant differences in the incidence of rhabdomyolysis. The multivariate analysis showed that RALS/CLS (HR 6.0 95% CI 1.3–27.5, p = 0.02) and operation time (HR 15.9 95% CI 3.79–67.4, p = 0.001) remained independent factors of CK elevation on postoperative day 1.

Conclusions

Clinically relevant positioning injuries and rhabdomyolysis may occur in patients who are subjected to a prolonged and extreme Trendelenburg position or who have extra force applied to the abdominal wall because of remote center displacement. The creatine kinase value should therefore be measured after RALS to monitor for the sequelae of these potential positioning injuries.
Diabetes conversation map - a novel tool for diabetes management self-efficacy among type 2 diabetes patients in Pakistan: a randomized controlled trial
Authors: Qasim Rubina , Masih Sarfaraz , Yousafzai Mohammad Tahir , shah Hakim , Manan Abdul , Shah Yousaf , Yaqoob Muhammad , Razzaq Abida , Khan Ajmal , Rohilla Atiya Rahman Khan
Published: June 2020

Background

This study aimed to measure the effect of diabetes education using the novel method of “diabetes conversation map (DCM)” as compared to routine counselling (RC) on diabetes management self-efficacy (DMSE) among patients living with type 2 diabetes in Karachi, Pakistan.

Methods

A parallel arm randomized controlled trial among patients with type 2 diabetes aged 30–60 years, with HbA1c > 7%, diagnosed for at least 5 yrs., was conducted at the national institute of diabetes and endocrinology in Karachi, Pakistan. A total 123 type 2 diabetes patients were randomized into DCM (n = 62) or RC (n = 61). Four weekly diabetes control sessions of 40 min each using the DCM or RC was provided. DMSE was measured using a validated Urdu language DMSE tool at baseline and after three months of the randomization. Change in DMSE and HbA1c levels within groups (pre-post) and between the groups after 3 months of enrollment was compared.

Results

Baseline characteristics except HbA1c were similar between the two arms. After 3 months of enrollment, there was no change in the DMSE score in the RC arm however, significant increase in DMSE score was noted in the DCM arm (P = < 0.001). The average difference (95% confidence interval) in DMSE score between the DCM and RC arm was 33.7(27.3, 40.0; p = < 0.001) after 3 months of the enrollment. Difference in HbA1c within groups was not significant.

Conclusions

DCM significantly improved DMSE among type 2 diabetes patients in a developing country setting like Pakistan. Healthcare workers caring for type 2 diabetes patients need to be trained on DCM to effectively utilize this novel tool for educating diabetes patients.

Trial registration

This trial was prospectively registered. ClinicalTrials.gov Identifier: NCT03747471. Date of registration: Nov 20. 2018.
Development of the prototype concise safe systems checklist tool for general practice
Authors: Litchfield Ian , Spencer Rachel , Bell Brian G. , Avery Anthony , Perryman Katherine , Marsden Kate , Greenfield Sheila , Campbell Stephen
Published: June 2020

Background

In the course of producing a patient safety toolkit for primary care, we identified the need for a concise safe-systems checklist designed to address areas of patient safety which are under-represented in mandatory requirements and existing tools. This paper describes the development of a prototype checklist designed to be used in busy general practice environments to provide an overview of key patient safety related processes and prompt practice wide-discussion.

Methods

An extensive narrative review and a survey of world-wide general practice organisations were used to identify existing primary care patient safety issues and tools. A RAND panel of international experts rated the results, summarising the findings for importance and relevance. The checklist was created to include areas that are not part of established patient safety tools or mandatory and legal requirements. Four main themes were identified: information flow, practice safety information, prescribing, and use of IT systems from which a 13 item checklist was trialled in 16 practices resulting in a nine item prototype checklist, which was tested in eight practices. Qualitative data on the utility and usability of the prototype was collected through a series of semi-structured interviews.

Results

In testing the prototype four of nine items on the checklist were achieved by all eight practices. Three items were achieved by seven of eight practices and two items by six of eight practices. Participants welcomed the brevity and ease of use of the prototype, that it might be used within time scales at their discretion and its ability to engage a range of practice staff in relevant discussions on the safety of existing processes. The items relating to prescribing safety were considered particularly useful.

Conclusions

As a result of this work the concise patient safety checklist tool, specifically designed for general practice, has now been made available as part of an online Patient Safety Toolkit hosted by the Royal College of General Practitioners. Senior practice staff such as practice managers and GP partners should find it a useful tool to understand the safety of less explored yet important safety processes within the practice.
Trends and seasonal variation of hospitalization and mortality of interstitial lung disease in the United States from 2006 to 2016
Authors: Ho An Thi Nhat , Shmelev Artem , Charbek Edward
Published: June 2020

Background

In the recent years, the overall trends in hospital admission and mortality of interstitial lung disease (ILD) are unknown. In addition, there was some evidence that interstitial lung disease death rate highest in the winter but this finding was only available in one study. This study will investigate the trend and seasonal variations in hospital admission and mortality rates of ILD from 2006 to 2016.

Method

From the Nationwide Inpatient Sample database, we collected all cases with the International Classification of Diseases (ICD)-9 or ICD-10 codes of ILD excluding identifiable external causes (drug, organic or inorganic dusts) from 2006 to 2016. Hospitalization rates of each year were calculated based on U.S Census population data. Monthly hospitalization and in-hospital mortality rates were analyzed by seasonal and trend decomposition. Subgroups of idiopathic interstitial fibrosis (IPF), acute respiratory failure (ARF), pneumonia were analyzed.

Results

From 2006 to 2016, all-cause hospital admission rate of patients with interstitial lung disease (ILD) and IPF-only subgroup declined but their overall mortality remained unchanged (except IPF subgroup and acute respiratory failure subgroup). Acute respiratory failure related admission account for 23% of all causes and pneumonia 17.6%. Mortality of ILD in general and subgroup of ILD with ARF was highest in winter, up to 8.13% ± 0.60 and 26.3% ± 10.2% respectively. The seasonal variations of hospital admission and mortality of ILD in general was not changed when infectious pneumonia cases were ruled out. All cause admission rates were highest in months from January to April. Subgroup analysis also showed seasonal variations with highest hospitalization rates for all subgroups (IPF, ARF, pneumonia) in the months from December to April (winter to early Spring).

Conclusion

From 2006 to 2016, admission rates of ILD of all causes and IPF subgroup declined but in-hospital mortality of ILD of all causes remained unchanged. Mortality of IPF subgroup and acute respiratory failure subgroup trended down. All-cause hospital admissions and mortality of ILD have a strong seasonal variation. Hospitalization rates for all subgroups (IPF, ARF, pneumonia) were highest in the months from December to April.
Knockdown of LINC00662 represses AK4 and attenuates radioresistance of oral squamous cell carcinoma
Authors: Chen Yangzong , Bao Chunchun , Zhang Xiuxing , Lin Xinshi , Fu Yimou
Published: June 2020

Background

LncRNAs play crucial roles in the development of carcinomas. However, the investigation of LINC00662 in Oral squamous cell carcinoma (OSCC) is still elusive.

Methods

qRT-PCR assay tested the expression levels of LINC00662, hnRNPC and AK4. With exposure to irradiation, CCK-8, colony formation, flow cytometry and western blot experiments, respectively determined the function of LINC00662 in the radiosensitivity of OSCC cells. Then RIP and western blot assays affirmed the interaction between hnRNPC protein and LINC00662 or AK4. Finally, rescue assays validated the regulation mechanism of LINC00662 in the radioresistance of OSCC.

Results

In the present report, LINC00662 was overexpressed in OSCC and its silencing could alleviate radioresistance of OSCC. Furthermore, the interaction between hnRNPC protein and LINC00662 or AK4 was uncovered. Besides, LINC00662 regulated AK4 mRNA stability through binding to hnRNPC protein. To sum up, LINC00662 modulated the radiosensitivity of OSCC cells via hnRNPC-modulated AK4.

Conclusion

The molecular mechanism of the LINC00662/hnRNPC/AK4 axis was elucidated in OSCC, which exhibited a promising therapeutic direction for patients with OSCC.
LncRNA ZFAS1 promotes pancreatic adenocarcinoma metastasis via the RHOA/ROCK2 pathway by sponging miR-3924
Authors: Liu Jinyang , Zhu Yaqin , Ge Chunlin
Published: June 2020

Background

The mortality and morbidity rates of pancreatic adenocarcinoma have been increasing over the past two decades, and an understanding of the mechanisms underlying pancreatic adenocarcinoma progression is urgently needed. The long non-coding RNA ZFAS1 has been demonstrated to be an oncogene in some cancers, but its function and mechanism in pancreatic adenocarcinoma remain unclear.

Methods

The ZFAS1 expression level in pancreatic adenocarcinoma was predicted by bioinformatic analysis, and the expression level of ZFAS1 in pancreatic adenocarcinoma tissue samples and cell lines was further detected by quantitative real-time PCR and in situ hybridization. The functions of ZFAS1 in pancreatic adenocarcinoma in vitro and in vivo were investigated by further bioinformatic analysis. Dual-luciferase reporter assays were used to confirm the binding of ZFAS1/miR-3924 and miR-3924/ROCK2, and rescue assays were performed to further investigate the underlying mechanism.

Results

ZFAS1 overexpression in pancreatic adenocarcinoma was predicted and experimentally verified. ZFAS1 silencing inhibited pancreatic adenocarcinoma metastasis in vitro and in vivo. The competing endogenous RNA mechanism of ZFAS1 was also identified.

Conclusions

Our results demonstrated the promotive effect of ZFAS1 on pancreatic adenocarcinoma metastasis and suggested its potential role as a novel regulator of ROCK2.
Methods and indicators for measuring patterns of human exposure to malaria vectors
Authors: Monroe April , Moore Sarah , Okumu Fredros , Kiware Samson , Lobo Neil F. , Koenker Hannah , Sherrard-Smith Ellie , Gimnig John , Killeen Gerry F.
Published: June 2020

Background

Effective targeting and evaluation of interventions that protect against adult malaria vectors requires an understanding of how gaps in personal protection arise. An improved understanding of human and mosquito behaviour, and how they overlap in time and space, is critical to estimating the impact of insecticide-treated nets (ITNs) and determining when and where supplemental personal protection tools are needed. Methods for weighting estimates of human exposure to bitingAnophelesmosquitoes according to where people spend their time were first developed over half a century ago. However, crude indoor and outdoor biting rates are still commonly interpreted as indicative of human-vector contact patterns without any adjustment for human behaviour or the personal protection effects of ITNs.

Main text

A small number of human behavioural variables capturing the distribution of human populations indoors and outdoors, whether they are awake or asleep, and if and when they use an ITN over the course of the night, can enable a more accurate representation of human biting exposure patterns. However, to date no clear guidance is available on what data should be collected, what indicators should be reported, or how they should be calculated. This article presents an integrated perspective on relevant indicators of human-vector interactions, the critical entomological and human behavioural data elements required to quantify human-vector interactions, and recommendations for collecting and analysing such data.

Conclusions

If collected and used consistently, this information can contribute to an improved understanding of how malaria transmission persists in the context of current intervention tools, how exposure patterns may change as new vector control tools are introduced, and the potential impact and limitations of these tools. This article is intended to consolidate understanding around work on this topic to date and provide a consistent framework for building upon it. Additional work is needed to address remaining questions, including further development and validation of methods for entomological and human behavioural data collection and analysis.
Macrophage-cancer hybrid membrane-coated nanoparticles for targeting lung metastasis in breast cancer therapy
Authors: Gong Chunai , Yu Xiaoyan , You Benming , Wu Yan , Wang Rong , Han Lu , Wang Yujie , Gao Shen , Yuan Yongfang
Published: June 2020

Cell membrane- covered drug-delivery nanoplatforms have been garnering attention because of their enhanced bio-interfacing capabilities that originate from source cells. In this top-down technique, nanoparticles (NPs) are covered by various membrane coatings, including membranes from specialized cells or hybrid membranes that combine the capacities of different types of cell membranes. Here, hybrid membrane-coated doxorubicin (Dox)-loaded poly(lactic-co-glycolic acid) (PLGA) NPs (DPLGA@[RAW-4T1] NPs) were fabricated by fusing membrane components derived from RAW264.7(RAW) and 4T1 cells (4T1). These NPs were used to treat lung metastases originating from breast cancer. This study indicates that the coupling of NPs with a hybrid membrane derived from macrophage and cancer cells has several advantages, such as the tendency to accumulate at sites of inflammation, ability to target specific metastasis, homogenous tumor targeting abilities in vitro, and markedly enhanced multi-target capability in a lung metastasis model in vivo. The DPLGA@[RAW-4T1] NPs exhibited excellent chemotherapeutic potential with approximately 88.9% anti-metastasis efficacy following treatment of breast cancer-derived lung metastases. These NPs were robust and displayed the multi-targeting abilities of hybrid membranes. This study provides a promising biomimetic nanoplatform for effective treatment of breast cancer metastasis.
Patient reported symptoms, coping and quality of life during somatostatin analogue treatment for metastatic small- intestinal neuroendocrine tumours
Authors: Sorbye Halfdan , Meyer Liv Sylvi , Mordal Kjersti Elisabeth , Myhre Simen , Thiis-Evensen Espen
Published: June 2020

Background

Patients with metastatic small-intestinal neuroendocrine tumours (NET) have been shown to have a reduced quality of life compared to the general population and many have disabling symptoms during somatostatin analogue (SSA) treatment. The aim of this prospective study was to document the patient-reported symptoms, coping and quality of life during SSA treatment and to measure patients’ fat-soluble vitamin levels.

Methods

Patients with metastatic small-intestinal NET on treatment with long-acting SSA were included. Data on patient characteristics, blood samples, questionnaires (EORTC-QLQ-C30 and GI.NET-21) and structured patient interviews were collected at inclusion and after 1 year.

Results

Eighty-eight patients were included, 77 (88%) attended 1 year follow-up. Approximately 50% of patients reported symptoms, the most common symptoms at baseline and after 1 year follow-up were diarrhoea, flatulence, fatigue, abdominal discomfort and sore injection lumps. Diarrhoea and fatigue were reported as their main complaint, 23% had > 5 daily episodes of diarrhoea and 59% reported fatigue. However, patients reported a high perceived quality of life, high daily activity, coped with their symptoms and managed their daily life well. Deficiency of vitamin D (27%) and A (13%) were observed.

Conclusions

Patients with metastatic small-intestinal NET on SSA treatment reported a high frequency of symptoms. Minor improvements were seen after 1-year of follow-up, illustrating that many symptoms might be difficult to improve, or may not be recognised by the health service. Patients, however, generally reported a high quality of life. Care for NET patients on SSA treatment should include a regular systematic symptom registration and vitamin measurements.
β-Catenin and TCFs/LEF signaling discordantly regulate IL-6 expression in astrocytes
Authors: Robinson KaReisha F. , Narasipura Srinivas D. , Wallace Jennillee , Ritz Ethan M. , Al-Harthi Lena
Published: June 2020

Background

The Wnt/β-catenin signaling pathway is a prolific regulator of cell-to-cell communication and gene expression. Canonical Wnt/β-catenin signaling involves partnering of β-catenin with members of the TCF/LEF family of transcription factors (TCF1, TCF3, TCF4, LEF1) to regulate gene expression. IL-6 is a key cytokine involved in inflammation and is particularly a hallmark of inflammation in the brain. Astrocytes, specialized glial cells in the brain, secrete IL-6. How astrocytes regulate IL-6 expression is not entirely clear, although in other cells NFκB and C/EBP pathways play a role. We evaluated here the interface between β-catenin, TCFs/LEF and C/EBP and NF-κB in relation to IL-6 gene regulation in astrocytes.

Methods

We performed molecular loss and/or gain of function studies of β-catenin, TCF/LEF, NFκB, and C/EBP to assess IL-6 regulation in human astrocytes. Specifically, siRNA mediated target gene knockdown, cDNA over expression of target gene, and pharmacological agents for regulation of target proteins were used. IL-6 levels was evaluated by real time quantitative PCR and ELISA. We also cloned the IL-6 promoter under a firefly luciferase reporter and used bioinformatics, site directed mutagenesis, and chromatin immunoprecipitation to probe the interaction between β-catenin/TCFs/LEFs and IL-6 promoter activity.

Results

β-catenin binds to TCF/LEF to inhibits IL-6 while TCFs/LEF induce IL-6 transcription through interaction with ATF-2/SMADs. β-catenin independent of TCFs/LEF positively regulates C/EBP and NF-κB, which in turn activate IL-6 expression. The IL-6 promoter has two putative regions for TCFs/LEF binding, a proximal site located at -91 nt and a distal site at -948 nt from the transcription start site, both required for TCF/LEF induction of IL-6 independent of β-catenin.

Conclusion

IL-6 regulation in human astrocytes engages a discordant interaction between β-catenin and TCF/LEF. These findings are intriguing given that no role for β-catenin nor TCFs/LEF to date is associated with IL-6 regulation and suggest that β-catenin expression in astrocytes is a critical regulator of anti-inflammatory responses and its disruption can potentially mediate persistent neuroinflammation.

Graphical abstract
Mesenchymal stem cells activate Notch signaling to induce regulatory dendritic cells in LPS-induced acute lung injury
Authors: Lu Zhonghua , Meng Shanshan , Chang Wei , Fan Shanwen , Xie Jianfeng , Guo Fengmei , Yang Yi , Qiu Haibo , Liu Ling
Published: June 2020

Background

Mesenchymal stem cells (MSCs) have been shown to alleviate acute lung injury (ALI) and induce the production of regulatory dendritic cells (DCregs), but the potential link between these two cell types remains unclear. The goal of this study was to investigate the effect and mechanism of MSC-induced regulatory dendritic cells in ALI mice.

Material/methods

In vivo experiments, C57BL/6 wild-type male mice were sacrificed at different times after intratracheal injection of LPS to observe changes in lung DC maturation and pathological damage. MSCs, DCregs or/and carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled DCs were administered to the mice by tail vein, and flow cytometry was performed to measure the phenotype of lung DCs and T cells. Lung injury was estimated by the lung wet weight/body weight ratio and histopathological analysis. In vitro, Western blotting or flow cytometry was used to detect the expression of Notch ligand or receptor in MSCs or DCs after coculture or LPS stimulation. Finally, in vivo and in vitro, we used the Notch signaling inhibitor DAPT to verify the effect of the Notch pathway on MSC-induced DCregs and their pulmonary protection.

Results

We showed significant accumulation and maturation of lung DCs 2 h after intratracheal injection of LPS, which were positively correlated with the lung pathological injury score. MSC treatment alleviated ALI lung injury, accompanied by a decrease in the number and maturity of classical DCs in the lungs. CFSE-labeled DCs migrated to the lungs of ALI mice more than those of the normal group, and the elimination of CFSE-labeled DCs in the blood was slower. MSCs inhibited the migration of CFSE-labeled DCs to the lung and promoted their elimination in the blood. DCregs, which are obtained by contact coculture of mDCs with MSCs, expressed reduced levels of MHCII, CD86, CD40 and increased levels of PD-L1, and had a reduced ability to stimulate lymphocyte proliferation and activation (expression of CD44 and CD69). mDCs expressing Notch2 significantly increased after coculture with MSCs or rhJagged1, and MSCs expressed more Jagged1 after LPS stimulation. After stimulation of mDCs with recombinant Jagged1, DCs with low expression of MHCII, CD86 and CD40 were also induced, and the effects of both rhJagged1 and MSCs on DCs were blocked by the Notch inhibitor DAPT. Intra-airway DAPT reversed the inhibitory effect of mesenchymal stem cells on DC recruitment to the lungs and its maturation.

Conclusions

Our results suggested that the recruitment and maturation of lung DCs is an important process in early ALI, MSCs attenuate LPS-induced ALI by inducing the production of DCregs by activating Notch signaling.
Serum IgG-induced microglial activation enhances neuronal cytolysis via the NO/sGC/PKG pathway in children with opsoclonus-myoclonus syndrome and neuroblastoma
Authors: Ding Xu , Yang Wei , Ren Qinghua , Hu Jiajian , Yang Shen , Han Wei , Wang Jing , Wang Xu , Wang Huanmin
Published: June 2020

Background

Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disease. Some children with OMS also have neuroblastoma (NB). We and others have previously documented that serum IgG from children with OMS and NB induces neuronal cytolysis and activates several signaling pathways. However, the mechanisms underlying OMS remain unclear. Here, we investigated whether nitric oxide (NO) from activated microglias and its cascade contribute to neuronal cytolysis in pediatric OMS.

Methods

The activation of cultured cerebral cortical and cerebellar microglias incubated with sera or IgG isolated from sera of children with OMS and NB was measured by the expression of the activation marker, cytokines, and NO. Neuronal cytolysis was determined after exposing to IgG-treated microglia-conditioned media. Using inhibitors and activators, the effects of NO synthesis and its intracellular cascade, namely soluble guanylyl cyclase (sGC) and protein kinase G (PKG), on neuronal cytolysis were evaluated.

Results

Incubation with sera or IgG from children with OMS and NB increased the activation of cerebral cortical and cerebellar microglias, but not the activation of astrocytes or the cytolysis of glial cells. Moreover, the cytolysis of neurons was elevated by conditioned media from microglias incubated with IgG from children with OMS and NB. Furthermore, the expression of NO, sGC, and PKG was increased. Neuronal cytolysis was relieved by the inhibitors of NO signaling, while neuronal cytolysis was exacerbated by the activators of NO signaling but not proinflammatory cytokines. The cytolysis of neurons was suppressed by pretreatment with the microglial inhibitor minocycline, a clinically tested drug. Finally, increased microglial activation did not depend on the Fab fragment of serum IgG.

Conclusions

Serum IgG from children with OMS and NB potentiates microglial activation, which induces neuronal cytolysis through the NO/sGC/PKG pathway, suggesting an applicability of microglial inhibitor as a therapeutic candidate.
A comparison of two personalization and adaptive cognitive rehabilitation approaches: a randomized controlled trial with chronic stroke patients
Authors: Faria Ana Lúcia , Pinho Maria Salomé , Bermúdez i Badia Sergi
Published: June 2020

Background

Paper-and-pencil tasks are still widely used for cognitive rehabilitation despite the proliferation of new computer-based methods, like VR-based simulations of ADL’s. Studies have established construct validity of VR assessment tools with their paper-and-pencil version by demonstrating significant associations with their traditional construct-driven measures. However, VR rehabilitation intervention tools are mostly developed to include mechanisms such as personalization and adaptation, elements that are disregarded in their paper-and-pencil counterparts, which is a strong limitation of comparison studies. Here we compare the clinical impact of a personalized and adapted paper-and-pencil training and a content equivalent and more ecologically valid VR-based ADL’s simulation.

Methods

We have performed a trial with 36 stroke patients comparing Reh@City v2.0 (adaptive cognitive training through everyday tasks VR simulations) with Task Generator (TG: content equivalent and adaptive paper-and-pencil training). The intervention comprised 12 sessions, with a neuropsychological assessment pre, post-intervention and follow-up, having as primary outcomes: general cognitive functioning (assessed by the Montreal Cognitive Assessment - MoCA), attention, memory, executive functions and language specific domains.

Results

A within-group analysis revealed that the Reh@City v2.0 improved general cognitive functioning, attention, visuospatial ability and executive functions. These improvements generalized to verbal memory, processing speed and self-perceived cognitive deficits specific assessments. TG only improved in orientation domain on the MoCA, and specific processing speed and verbal memory outcomes. However, at follow-up, processing speed and verbal memory improvements were maintained, and a new one was revealed in language. A between-groups analysis revealed Reh@City v2.0 superiority in general cognitive functioning, visuospatial ability, and executive functions on the MoCA.

Conclusions

The Reh@City v2.0 intervention with higher ecological validity revealed higher effectiveness with improvements in different cognitive domains and self-perceived cognitive deficits in everyday life, and the TG intervention retained fewer cognitive gains for longer.

Trial registration

The trial is registered at ClinicalTrials.gov, number NCT02857803. Registered 5 August 2016, .
Performance of commercially available anti-HDV enzyme-linked immunosorbent assays in Taiwan
Authors: Lin Guan-Yu , Wu Yi-Le , Wang Cheng-Si , Ko Chia-Yun , Chen Chien-Hung , Chen Pei-Jer , Peng Po-Hsin , Hsu Chao-Wei
Published: June 2020

Background

Hepatitis D virus (HDV) infection is a major global health issue around the world. There are approximately 15–20 million individuals infected with HDV worldwide. HDV infection usually causes increased mortality compared with infection with hepatitis B virus (HBV) alone. However, testing for the detection of HDV is not widely available in Taiwan. Therefore, the General Biologicals Corporation (GB) HDV Ab kit was developed for detecting anti-HDV antibodies.

Methods

A total of 913 serum and 462 EDTA-treated plasma samples were obtained from HBsAg-positive individuals in three hospitals in Taiwan from June 2014 to November 2017. We used three commercially available ELISA kits, DiaPro HDV Ab, DiaSorin ETI-AB-DELTAK-2 and GB HDV Ab, which were utilized strictly according to the instructions of the manufacturers.

Results

A comparative study of the results from the GB HDV Ab kit and the other commercial ELISA kits (DiaPro and DiaSorin) was performed to determine their efficacy for anti-HDV detection. The results indicated that the sensitivity of the GB HDV Ab kit for serum and EDTA samples was 100% compared to that of the DiaPro and DiaSorin kits, whereas the specificity for serum and EDTA samples was 99.3 and 98.1%, respectively. In addition, the overall agreement of the results of the GB HDV Ab kit for the serum and EDTA samples was 99.3 and 98.3%, respectively. It is worth noting that the performance of the GB HDV Ab kit was not affected by interference from triglyceride, bilirubin, hemoglobin, or human anti-mouse antibody. The limit of detection of the GB HDV Ab kit is approximately 100-fold lower than that of the other two commercial kits.

Conclusions

The GB HDV Ab kit, which presented equivalent sensitivity and specificity compared to both certified anti-HDV kits, would be a suitable kit for HDV diagnosis in Taiwan.