bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors related to implementation of an interprofessional communication concept in thoracic oncology: a mixed-methods study
Authors: Krug Katja , Bossert Jasmin , Möllinger Sophia , Deis Nicole , Unsöld Laura , Siegle Anja , Villalobos Matthias , Hagelskamp Laura , Jung Corinna , Thomas Michael , Wensing Michel
Published: May 2022

Background

An innovative patient-centred interprofessional communication concept with advanced lung cancer patients (Heidelberg Milestone Communication Approach, MCA) has been developed and implemented. Role changes and interprofessional communication are challenging in a busy outpatient oncology service. The aim of the study was to present attitudes to interprofessional collaboration of professions in thoracic oncology during the implementation of MCA and to explore factors and experiences healthcare team members associate with its implementation.

Methods

In a longitudinal study, 3 of the 4 subscales of the validated German translation of the University of the West of England Interprofessional Questionnaire (UWE-IP-D) were collected prior to implementation of MCA (t0) with follow-up data collections at 4 months (t1), 10 months (t2) and 17 months (t3). Descriptive analysis included calculating subscale sum scores and categorizing each subscale into positive, neutral and negative attitudes. Interviews and focus groups on implementation and interprofessional collaboration in the context of MCA were conducted with healthcare staff. The topics were analysed deductively, guided by the Professional Interactions factor of the Tailored Implementation for Chronic Diseases (TICD) framework.

Results

The survey with 87 staff (44 nurses, 13 physicians, 12 psycho-social staff, 7 therapists, and 11 others) participating at least once found heterogeneous attitudes. ‘Communication and Teamwork’ and ‘Interprofessional Relationships’ were characterized by primarily positive attitudes. Neutral attitudes to ‘Interprofessional Interaction’ were indicated by the majority of respondents. There were no differences between collection times. Fifteen staff members participated in the interviews and focus groups. The main interprofessional interaction factors associated with implementation concerned the knowledge of the MCA and the impact of the intervention on team roles, on information sharing and on transfer processes between wards. Adaptive processes led to a shift in the perception of responsibilities and interprofessional collaboration.

Conclusions

Positive experiences and potential shortfalls in the implementation were observed. Future introductions of interprofessional communication concepts require further activities which should address the attitudes of healthcare professionals towards interprofessional care.

Trial registration

DRKS00013469 / Date of registration: 22/12/2017.
A phenomenographic study exploring the conceptions of stakeholders on their teaching and learning roles in nursing education
Authors: Munangatire Takaedza , McInerney Patricia
Published: May 2022

Background

Nursing education involves a number of stakeholders in the teaching and learning process, and these are student nurses, lecturers, clinical instructors and nurses. The role that each of these parties play in the teaching and learning process is dependent on each other and is key to the development of competence among student nurses. However, there is scanty literature on the discourse of how these stakeholders conceptualise their roles to maximise student learning. The objective of this study was to explore the conceptions of stakeholders on their teaching and learning roles in nursing education.

Methods

Thirty-eight semi-structured interviews and three focus group discussions were conducted with nursing students, lecturers, clinical educators at a Namibian nursing college and nurses at teaching hospitals. Phenomenographic data analysis approach was applied.

Results

Four conceptions were constructed that described the level of involvement of the different parties in teaching and learning. These were initiating, supporting, becoming part of and owning the teaching and learning role. Three dimensions of variation marked the differences among the conceptions: responsibility and accountability, priorities and level of collaboration.

Conclusions

The parties involved in the teaching and learning in nursing education have qualitatively different understating of their roles and those of others. There is a pattern transcending from being at the periphery of teaching and learning to taking ownership of teaching and learning. And a movement from limited responsibility and collaboration to that of being responsible, accountable and high level of collaboration in the teaching and learning of nursing students. The conceptions in this study add more ways of enhancing collaboration between theoretical and clinical sites in nursing education, by ensuring that those involved are aware of their role and that of others and work collaboratively at the micro-level.
Mind your language: the importance of english language skills in an International Medical Programme (IMP)
Authors: Chan Sharon Min Hui , Mamat Norul Hidayah , Nadarajah Vishna Devi
Published: May 2022

Background

Language proficiency is crucial for doctors as they communicate with patients, peers and other healthcare professionals. Although proficiency in English is part of admission requirements, there is a gap in the knowledge of medical students’ perception of factors enhancing English language (EL) skills during training in international medical programmes (IMPs). The gap prevents educators and policy makers from helping students who struggle with communication skills during medical training. This study therefore explores the importance of English language skills from medical students’ perspectives.

Methods

Six focus group interviews with 24 medical students were conducted in an IMP. Data were analysed using Braun and Clarke’s framework of thematic analysis.

Results

Results established three themes that constitute the importance of EL skills, namely the use of EL in medical training and practice, influence of university culture in EL mastery and individual EL proficiency as perceived by medical students.

Conclusions

Findings of this study demonstrate how students perceived the importance of EL skills as a professional and social requirement during medical training and for future practice. It also informs that setting English language admission pre requisites needs to be complemented with opportunities to practice context specific communication skills. Thus, international medical programmes should embed diverse and inclusive strategies to support and develop medical students’ English language skills.
Process evaluation of an academic-community-government partnership to reduce liver diseases attributable to hepatitis B virus
Authors: Le Daisy , Jeon Min Jeong , Ciceron Annie Coriolan , Yang Y. Tony , Pan Jane , Juon Hee-Soon , Wallington Sherrie F.
Published: May 2022

Background

Racial/ethnic minorities have higher incidence and mortality rates of liver cancer, or hepatocellular carcinoma, than non-Hispanic Whites. As such, the Washington-Baltimore Metropolitan Area Hepatitis B Virus (WB-HBV) Demonstration Project, a community-based participatory research (CBPR)-driven academic-community-government (ACG) partnership, was established in 2019 to address disparities and implement strategies to improve the HBV screening and vaccination infrastructure for at-risk communities. CBPR is a partnership of community members, organizational leaders, and academic researchers with a common aim to collectively share and contribute their input at every phase of the project.

Herein, we describe the process evaluation of the WB-HBV Project and extract themes and insights to benefit future ACG partnerships and community-engaged research. The process evaluation has been conducted to determine whether CBPR-driven partnership and programmatic activities have been implemented as intended and have resulted in building expanded research capacity for future ACG partnership HBV community-level initiatives.

Methods

A WB-HBV Project Task Force was convened and comprised of eight organizations: four community organizations, three government organizations, and one academic institution. Through a mixed-methods process evaluation, an online survey and key informant interviews were conducted to provide context for program implementation barriers and facilitators. Descriptive statistics were conducted, and interviews were recorded, transcribed, and thematically coded.

Results

The survey was completed by 14 of 20 partnership members (70.0%): two academic, eight community, and four government members. Partnership members showed general agreement across 14 domains: organization and structure of meetings; trust; decisions; impact; general satisfaction; strategic planning; ACG policy impact; community-based participatory research and government; participation in meetings; assessment of participation; partnership operations and capacity; communication; challenges/limitations associated with ACG involvement; and benefits compared to challenges associated with ACG involvement. Qualitative interviews were conducted with 15 of the 20 members (75.0%): two academic, nine community, and four government members. Four themes emerged: partnership involvement, project goals and accomplishments, project challenges and barriers, and partnership involvement in government or policy.

Conclusions

The process evaluation presents insights into developing strategies to enhance partnership functioning and increase the ability of present and future ACG partnerships to improve community health outcomes.
A strategy to identify event specific hospitalizations in large health claims databases
Authors: Lambert Joshua , Sandhu Harpal , Kean Emily , Xavier Teenu , Brokman Aviv , Steckler Zachary , Park Lee , Stromberg Arnold
Published: May 2022

Background

Health insurance claims data offer a unique opportunity to study disease distribution on a large scale. Challenges arise in the process of accurately analyzing these raw data. One important challenge to overcome is the accurate classification of study outcomes. For example, using claims data, there is no clear way of classifying hospitalizations due to a specific event. This is because of the inherent disjointedness and lack of context that typically come with raw claims data.

Methods

In this paper, we propose a framework for classifying hospitalizations due to a specific event. We then tested this framework in a private health insurance claims database (Symphony) with approximately 4 million US adults who tested positive with COVID-19 between March and December 2020. Our claims specific COVID-19 related hospitalizations proportion is then compared to nationally reported rates from the Centers for Disease Control by age.

Results

Across all ages (18 +) the total percentage of Symphony patients who met our definition of hospitalized due to COVID-19 was 7.3% which was similar to the CDC’s estimate of 7.5%. By age group, defined by the CDC, our estimates vs. the CDC’s estimates were 18–49: 2.7% vs. 3%, 50–64: 8.2% vs. 9.2%, and 65 + : 14.6% vs. 28.1%.

Conclusions

The proposed methodology is a rigorous way to define event specific hospitalizations in claims data. This methodology can be extended to many different types of events and used on a variety of different types of claims databases.
Associations of maternal iron deficiency with malaria infection in a cohort of pregnant Papua New Guinean women
Authors: Unger Holger W. , Bleicher Andie , Ome-Kaius Maria , Aitken Elizabeth H. , Rogerson Stephen J.
Published: May 2022

Background

Iron deficiency (ID) is common in malaria-endemic settings. Intermittent preventative treatment of malaria in pregnancy (IPTp) and iron supplementation are core components of antenatal care in endemic regions to prevent adverse pregnancy outcomes. ID has been associated with reduced risk of malaria infection, and correspondingly, iron supplementation with increased risk of malaria infection, in some studies.

Methods

A secondary analysis was conducted amongst 1888 pregnant women enrolled in a malaria prevention trial in Papua New Guinea. Maternal ID was defined as inflammation-corrected plasma ferritin levels < 15 μg/L at antenatal enrolment. Malaria burden (Plasmodium falciparum,Plasmodium vivax) was determined by light microscopy, polymerase chain reaction, and placental histology. Multiple logistic and linear regression analyses explored the relationship of ID or ferritin levels with indicators of malaria infection. Models were fitted with interaction terms to assess for modification of iron-malaria relationships by gravidity or treatment arm.

Results

Two-thirds (n = 1226) and 13.7% (n = 258) of women had ID and peripheral parasitaemia, respectively, at antenatal enrolment (median gestational age: 22 weeks), and 18.7% (120/1,356) had evidence of malaria infection on placental histology. Overall, ID was associated with reduced odds of peripheral parasitaemia at enrolment (adjusted odds ratio [aOR] 0.50; 95% confidence interval [95% CI] 0.38, 0.66, P < 0.001); peripheral parasitaemia at delivery (aOR 0.68, 95% CI 0.46, 1.00; P = 0.050); and past placental infection (aOR 0.35, 95% CI 0.24, 0.50; P < 0.001). Corresponding increases in the odds of infection were observed with two-fold increases in ferritin levels. There was effect modification of iron-malaria relationships by gravidity. At delivery, ID was associated with reduced odds of peripheral parasitaemia amongst primigravid (AOR 0.44, 95% CI 0.25, 0.76; P = 0.003), but not multigravid women (AOR 1.12, 95% CI 0.61, 2.05; P = 0.720). A two-fold increase in ferritin associated with increased odds of placental blood infection (1.44, 95% CI 1.06, 1.96; P = 0.019) and active placental infection on histology amongst primigravid women only (1.24, 95% CI 1.00, 1.54; P = 0.052).

Conclusions

Low maternal ferritin at first antenatal visit was associated with a lower risk of malaria infection during pregnancy, most notably in primigravid women. The mechanisms by which maternal iron stores influence susceptibility to infection withPlasmodiumspecies require further investigation.

Trial registration
PIK3CA mutations-mediated downregulation of circLHFPL2 inhibits colorectal cancer progression via upregulating PTEN
Authors: Chong Xiaodan , Chen Jingde , Zheng Nanxin , Zhou Zhuqing , Hai Yanan , Chen Shiqing , Zhang Yu , Yu Qingzhuo , Yu Shijun , Chen Zhiqin , Bao Wenfang , Quan Ming , Chen Zhe-Sheng , Zhan Yangyang , Gao Yong
Published: May 2022

Background

PIK3CA mutation and PTEN suppression lead to tumorigenesis and drug resistance in colorectal cancer (CRC). There is no research on the role of circular RNAs (circRNAs) in regulating PIK3CA mutation and MEK inhibitor resistance in CRC.

Methods

The expression of circLHFPL2 in PIK3CA-mutant and wild-type cells and tissues was quantified by RNA-sequencing and qRT-PCR. CCK-8 assay and colony formation assay were used to evaluate cell viability. Annexin V/PI staining was implemented to assess cell apoptosis. Luciferase assay, biotin-coupled microRNA capture, and RIP assay were used to validate the interaction among potential targets. Western blotting and qRT-PCR assays were used to evaluate the expression of involved targets. Xenograft tumor in a nude mouse model was used to explore the role of circRNAs in vivo.

Results

RNA sequencing defined downregulated expression of circLHFPL2 in both PIK3CAH1047R (HCT116) and PIK3CAE545K (DLD1) cells. CircLHFPL2 was also downregulated in PIK3CA-mutant CRC primary cells and tissues, which was correlated with poor prognosis. CircLHFPL2 was mainly localized in the cytoplasm and its downregulation was attributed to the PI3K/AKT signaling pathway activated by phosphorylating Foxo3a. CircLHFPL2 inhibited PI3KCA-Mut CRC progression both in vitro and in vivo. Furthermore, our work indicated that circLHFPL2 acts as a ceRNA to sponge miR-556-5p and miR-1322 in CRC cells and in turn modulate the expression of PTEN. Importantly, circLHFPL2 was able to overcome PIK3CA-mediated MEK inhibitor resistance in CRC cells.

Conclusions

Downregulation of circLHFPL2 sustains the activation of the PI3K/AKT signaling pathway via a positive feedback loop in PIK3CA-mutant CRC. In addition, downregulation of circLHFPL2 leads to MEK inhibitor resistance in CRC. Therefore, targeting circLHFPL2 could be an effective approach for the treatment of CRC patients harboring oncogenic PIK3CA mutations.
What do Iranian physicians value most when choosing a specialty? Evidence from a discrete choice experiment
Authors: Sarikhani Yaser , Ghahramani Sulmaz , Edirippulige Sisira , Fujisawa Yoshikazu , Bambling Matthew , Bastani Peivand
Published: May 2022

Background

Choosing a specialty by physicians is fundamentally linked to the performance of health systems and public health outcomes. Identifying the determinants of specialty selection is important to health policy for targeting resources and planning the development of services. This study examined preferences of Iranian physicians for medical specialty using a discrete choice experiment (DCE) method.

Methods

In this study, the attributes of the DCE were determined using rigorous qualitative approach. Then we applied D-efficiency criteria to design the DCE and validated it at a pilot study. In the final survey, we recruited participants from six Iranian provinces and analyzed data using conditional logit model. We estimated willingness to pay (WTP) for non-monetary attributes.

Results

The WTP analysis revealed that the most important non-monetary attributes in the selection of a specialty were job burnout, opportunity for procedural activities, and job prestige. The results imply that the attributes that were related to the quality of personal life was more important only for physicians who preferred to choose non-surgical specialties.

Conclusions

The findings demonstrate that traditional gender patterns of specialty selection are changing and quality of personal life characteristics might be the most important factor when developing policies to recruit physicians into non-surgical specialties.
Synergistic effect of the commonest residual risk factors, remnant cholesterol, lipoprotein(a), and inflammation, on prognosis of statin-treated patients with chronic coronary syndrome
Authors: Liu Hui-Hui , Guo Yuan-Lin , Zhu Cheng-Gang , Wu Na-Qiong , Gao Ying , Xu Rui-Xia , Dong Qian , Qian Jie , Dou Ke-Fei , Li Jian-Jun
Published: May 2022

Background

Currently, remnant cholesterol (RC), lipoprotein(a) [Lp(a)], and inflammation are considered the principal residual cardiovascular risk (RCVR) factors. This study sought to evaluate the combined impact of RC, Lp(a), and inflammation on prognosis of statin-treated patients with chronic coronary syndrome (CCS), which has not been investigated.

Methods

A total of 6839 patients with CCS were consecutively enrolled. Baseline RC, Lp(a), and high-sensitivity C-reactive protein (hsCRP) concentrations were measured and their medians were used for categorizations. All patients were followed for the major adverse cardiovascular events (MACEs), including cardiovascular death, non-fatal myocardial infarction, and stroke. The individual and combined effects of RC, Lp(a), and hsCRP on MACEs were examined and stratification analysis according to low-density lipoprotein cholesterol (LDL-C) was performed.

Results

Over an average of 54.93 ± 18.59 months follow-up, 462 MACEs were recorded. Multivariate Cox analysis showed that elevated RC and Lp(a) levels were significantly associated with an increased risk of MACEs, while high hsCRP levels were related to a slightly but non-significantly increased MACEs risk. Moreover, when participants were subgrouped according to RC, Lp(a), and hsCRP levels together, only High RC-High Lp(a)-High hsCRP group had significantly higher risk of MACEs [hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.15–3.47] compared with the reference group (Low RC-Low Lp(a)-Low hsCRP), especially in patients with LDL-C < 2.6 mmol/L.

Conclusions

The combination of elevated levels of RC, Lp(a), and hsCRP potentiated the adverse effect on MACEs among statin-treated patients with CCS, suggesting that multiple RCVR factors assessment may be a better strategy to improve stratification in very-high risk population.
Association between mitochondrial DNA haplogroups J and K, serum branched-chain amino acids and lowered capability for endurance exercise
Authors: Kiiskilä Jukka M. , Hassinen Ilmo E. , Kettunen Johannes , Kytövuori Laura , Mikkola Ilona , Härkönen Pirjo , Jokelainen Jari J. , Keinänen-Kiukaanniemi Sirkka , Perola Markus , Majamaa Kari
Published: May 2022

Background

Endurance exercise training promotes the catabolism of branched-chain amino acids (BCAAs) in skeletal muscles. We have previously shown that mitochondrial DNA (mtDNA) haplogroups J and K are markers of low responders in endurance training. In this paper, we hypothesize that BCAA catabolism is a surrogate marker of lower respiratory chain activity attributed to these haplogroups. We evaluated whether exercise-induced changes in amino acid concentrations differ between subjects harbouring mtDNA haplogroups J or K and those with non-JK haplogroups.

Methods

Finnish male conscripts (N = 633) undertook the 12-min Cooper running test at the beginning and end of their military service. The intervention during the service mainly included endurance aerobic exercise and sports-related muscle training. Concentrations of seven amino acids were analysed in the serum using a high-throughput 1H NMR metabolomics platform. Total DNA was extracted from whole blood, and restriction fragment analysis was used to determine mtDNA haplogroups J and K.

Results

The concentrations of the seven amino acids were higher following the intervention, with the exception of phenylalanine; interestingly, the increase in the concentrations of three BCAAs was larger in subjects with haplogroup J or K than in subjects with non-JK haplogroups (p = 0.029). MtDNA haplogroups J and K share two common nonsynonymous variants. Structural analysis based on crystallographic data on bovine complexes I and III revealed that the Leu18 variant in cytochrome b encoded by m.14798T > C may interfere with ubiquinone binding at the Qi site in complex III.

Conclusions

The increase in the concentrations of serum BCAAs following exercise intervention differs between subjects harbouring mtDNA haplogroup J or K and those harbouring non-JK haplogroups. Lower response in endurance training and difference in exercise-induced increase in the concentrations of serum BCAAs suggest decreased respiratory chain activity. Haplogroups J and K share m.14798T > C in MT-CYB, which may hamper the function of complex III.
A randomized controlled clinical trial of the effects of range of motion exercises and massage on muscle strength in critically ill patients
Authors: Rahiminezhad Elham , Sadeghi Mehdi , Ahmadinejad Mehdi , Mirzadi Gohari Seyed Iman , Dehghan Mahlagha
Published: May 2022

Background

Atrophy and muscle weakness is a common problem in critically ill patients admitted to the intensive care unit (ICU). Muscle weakness in severe cases can lead to tetraplegia, reduced or lost tendon reflexes, delayed weaning from mechanical ventilation, physical disability, and increased mortality. The aim of this study was to compare the effects of range of motion exercises (ROM) and massage on muscle strength of the patients admitted to ICUs.

Methods

This study was a single-blinded randomized controlled trial conducted in ICUs of Afzalipour hospital in Kerman, southeastern Iran. Ninety conscious ICU patients were randomly divided into three groups (massage, ROM exercises and control). The researcher/co-researcher massaged or did ROM exercises on the patients’ extremities once a day for seven consecutive days. Using a hand-held dynamometer, the co-researcher, rated the muscle strength before, on the fourth and seventh days of intervention at 8 p.m.

Results

The mean muscles strength of the right arm in the ROM exercise and massage groups increased by 0.63 kg, and 0.29 kg, respectively after the intervention compared with before the intervention. The muscle strength of the right arm in the control group reduced by 0.55 kg. The mean muscles strength of the left arm in the ROM exercise and massage groups increased by 0.61 kg and 0.28 kg after the intervention, respectively while it reduced by 0.56 kg in the control group. The mean muscles strength of the right leg in the ROM exercise and massage groups increased by 0.53 kg and 0.27 kg after the intervention compared with before the intervention while it reduced by 0.70 kg in the control group. The mean muscles strength of the left leg in the ROM exercise and massage groups increased by 0.54 kg and 0.26 kg after the intervention compared with before the intervention while it reduced by 0.71 kg in the control group.

Conclusion

The results of the present study showed that ROM exercises and massage were effective interventions in increasing muscle strength of the critically ill patients admitted to intensive care units.
Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: a pilot study
Authors: Zhu Ying-Gang , Shi Meng-meng , Monsel Antoine , Dai Cheng-xiang , Dong Xuan , Shen Hong , Li Su-ke , Chang Jing , Xu Cui-li , Li Ping , Wang Jing , Shen Mei-ping , Ren Cheng-jie , Chen De-chang , Qu Jie-Ming
Published: May 2022

Background

Existing clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19.

Methods

The MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0 × 108 nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging.

Results

Seven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (interquartile range (IQR), 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61 × 109/L vs. 1.78 × 109/L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients.

Conclusions

Our trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0 × 109 nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population.

Trial Registration: MEXCOVID, NCT04276987.
Assay establishment and validation of a high-throughput organoid-based drug screening platform
Authors: Li Xiaomeng , Fu Guoxiang , Zhang Long , Guan Ruoyu , Tang Peiyuan , Zhang Jialing , Rao Xinxin , Chen Shengzhi , Xu Xiaoya , Zhou Yi , Deng Yun , Lv Tao , He Xingfeng , Mo Shaobo , Mu Peiyuan , Gao Jianjun , Hua Guoqiang
Published: May 2022

Background

Organoids are three-dimensional structures that closely recapitulate tissue architecture and cellular composition, thereby holding great promise for organoid-based drug screening. Although growing in three-dimensional provides the possibility for organoids to recapitulate main features of corresponding tissues, it makes it incommodious for imaging organoids in two-dimensional and identifying surviving organoids from surrounding dead cells after organoids being treated by irradiation or chemotherapy. Therefore, significant work remains to establish high-quality controls to standardize organoid analyses and make organoid models more reproducible.

Methods

In this study, the Z-stack imaging technique was used for the imaging of three-dimensional organoids to gather all the organoids’ maximum cross sections in one imaging. The combination of live cell staining fluorescent dye Calcein-AM and ImageJ assessment was used to analyze the survival of organoids treated by irradiation or chemotherapy.

Results

We have established a novel quantitative high-throughput imaging assay that harnesses the scalability of organoid cultures. Using this assay, we can capture organoid growth over time, measure multiple whole-well organoid readouts, and show the different responses to drug treatments.

Conclusions

In summary, combining the Z-stack imaging technique and fluorescent labeling methods, we established an assay for the imaging and analysis of three-dimensional organoids. Our data demonstrated the feasibility of using organoid-based platforms for high-throughput drug screening assays.

Graphical Abstract
The ventromedial hypothalamic nucleus: watchdog of whole-body glucose homeostasis
Authors: Tu Longlong , Fukuda Makoto , Tong Qingchun , Xu Yong
Published: May 2022

The brain, particularly the ventromedial hypothalamic nucleus (VMH), has been long known for its involvement in glucose sensing and whole-body glucose homeostasis. However, it is still not fully understood how the brain detects and responds to the changes in the circulating glucose levels, as well as brain-body coordinated control of glucose homeostasis. In this review, we address the growing evidence implicating the brain in glucose homeostasis, especially in the contexts of hypoglycemia and diabetes. In addition to neurons, we emphasize the potential roles played by non-neuronal cells, as well as extracellular matrix in the hypothalamus in whole-body glucose homeostasis. Further, we review the ionic mechanisms by which glucose-sensing neurons sense fluctuations of ambient glucose levels. We also introduce the significant implications of heterogeneous neurons in the VMH upon glucose sensing and whole-body glucose homeostasis, in which sex difference is also addressed. Meanwhile, research gaps have also been identified, which necessities further mechanistic studies in future.
Application and prospect of targeting innate immune sensors in the treatment of autoimmune diseases
Authors: Liu Jun , Zhang Hui , Su Yanhong , Zhang Baojun
Published: May 2022

Dysregulation of auto-reactive T cells and autoantibody-producing B cells and excessive inflammation are responsible for the occurrence and development of autoimmune diseases. The suppression of autoreactive T cell activation and autoantibody production, as well as inhibition of inflammatory cytokine production have been utilized to ameliorate autoimmune disease symptoms. However, the existing treatment strategies are not sufficient to cure autoimmune diseases since patients can quickly suffer a relapse following the end of treatments. Pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), Nod-like receptors (NLRs), RIG-I like receptors (RLRs), C-type lectin receptors (CLRs) and various nucleic acid sensors, are expressed in both innate and adaptive immune cells and are involved in the development of autoimmune diseases. Here, we have summarized advances of PRRs signaling pathways, association between PRRs and autoimmune diseases, application of inhibitors targeting PRRs and the corresponding signaling molecules relevant to strategies targeting autoimmune diseases. This review emphasizes the roles of different PRRs in activating both innate and adaptive immunity, which can coordinate to trigger autoimmune responses. The review may also prompt the formulation of novel ideas for developing therapeutic strategies against autoimmune diseases by targeting PRRs-related signals.
DQN-based mobile edge computing for smart Internet of vehicle
Authors: Zhang Lianhong , Zhou Wenqi , Xia Junjuan , Gao Chongzhi , Zhu Fusheng , Fan Chengyuan , Ou Jiangtao
Published: May 2022

In this paper, we investigate a multiuser mobile edge computing (MEC)-aided smart Internet of vehicle (IoV) network, where one edge server can help accomplish the intensive calculating tasks from the vehicular users. For the MEC networks, most existing works mainly focus on minimizing the system latency to guarantee the user’s quality of service (QoS) through designing some offloading strategies, which, however, fail to consider the pricing from the server and hence fail to take into account the budget constraint from the users. To address this issue, we jointly incorporate the budget constraint into the system design of the MEC-based IoV networks and then propose a joint deep reinforcement learning (DRL) approach combined with the convex optimization algorithm. Specifically, a deep Q-network (DQN) is firstly used to make the offloading decision, and then, the Lagrange multiplier method is employed to allocate the calculating capability of the server to multiple users. Simulations are finally presented to demonstrate that the proposed schemes outperform the conventional ones. In particular, the proposed scheme can effectively reduce the system latency by up to 56% compared to the conventional schemes.
External validation of 5A score model for predicting in-hospital mortality among the accidental hypothermia patients: JAAM-Hypothermia study 2018–2019 secondary analysis
Authors: Okada Yohei , Matsuyama Tasuku , Hayashida Kei , Takauji Shuhei , Kanda Jun , Yokobori Shoji
Published: May 2022

Background

The 5A score including five components “Age, Activities of daily living, Arrest, Acidemia and Albumin” was developed as an easy-to-use screening tool for predicting in-hospital mortality among patients with accidental hypothermia. However, the external validity of the 5A score has not yet been evaluated. We aimed to perform an external validation of the 5A score model.

Method

This secondary analysis of the multicenter, prospective cohort Japanese Association for Acute Medicine-Hypothermia Study (2018–2019), which was conducted at 87 and 89 institutions throughout Japan, collected data from December 2018 to February 2019 and from December 2019 to February 2020. Adult accidental hypothermia patients whose body temperature was 35 °C or less were included in this analysis. The probability of in-hospital mortality was calculated using a logistic regression model of the 5A score. The albumin was not recorded in this database; thus, it was imputed by estimation. Predictions were compared with actual observations to evaluate the calibration of the model. Furthermore, decision-curve analysis was used to evaluate the clinical usefulness.

Results

Of the 1363 patients registered in the database, data of 1139 accidental hypothermia patients were included for analysis. The median [interquartile range] age was 79 [68–87] years, and there were 625 men (54.9%) in the study cohort. The predicted probability and actual observation by risk groups produced the following results: low 7% (5.4–8.6), mild 19.1% (17.4–20.8), moderate 33.2% (29.9–36.5), and high 61.9% (55.9–67.9) predicted risks, and the low 12.4% (60/483), mild 17.7% (59/334), moderate 32.6% (63/193), and high 69% (89/129) observed mortality. These results indicated that the model was well calibrated. Decision-curve analysis visually indicated the clinical utility of the 5A score model.

Conclusion

This study indicated that the 5A score model using estimated albumin value has external validity in a completely different dataset from that used for the 5A model development. The 5A score is potentially helpful to predict the mortality risk and may be one of the valuable information for discussing the treatment strategy with patients and their family members.
A description of self-medication with cannabis among adults with legal access to cannabis in Quebec, Canada
Authors: Asselin Antoine , Lamarre Olivier Beauparlant , Chamberland Richard , McNeil Sarah-Jeanne , Demers Eric , Zongo Arsène
Published: May 2022

Objective

Cannabis is increasingly used for medical purposes, particularly in countries like Canada where cannabis was recently legalized for recreational use. We aimed to assess self-medication with cannabis post-cannabis legalization among adults in the Canadian province of Quebec.

Methods

This is a cross-sectional online survey of a self-selected convenience sample conducted in Quebec, Canada, from November 2020 to January 2021. Individuals aged ≥ 21 years who endorsed using cannabis bought in legal recreational cannabis stores to self-medicate a health condition were included. Data were analyzed using descriptive statistics and stratified according to sex, age, and the type of cannabis use (exclusively medical versus medical and recreational use).

Results

Four hundred eighty-nine participants were included. The median age was 34 years, and 48% were women. About 25% reported exclusive medical use of cannabis. Treated conditions included anxiety (70%), insomnia (56%), pain (53%), depression (37%), and many others. Reasons for not consulting in cannabis clinics included lack of information (52%), the complexity of the process (39%), accessibility of cannabis clinics (23%), and others.

Tetrahydrocannabinol (THC) dosage > 20% was reported by 32%. Smoking was the main route of use (81%). Possession of prescribed drugs was reported by 56%. Professionals consulted for information on cannabis included recreational cannabis store agents (36%), physicians (29%), and others.

Overall, significant differences were observed for many of the comparisons according to sex, age, and the type of cannabis use.

Conclusions

Many conditions are self-medicated with cannabis. The use of high doses of cannabis, smoking as a preferred method of use, and concurrent use of other medications may pose some risks to individuals. Addressing the reported barriers to medical access to cannabis is urgently needed.
Neonatal orally administered curcumin: impact on the metabolic response and renal histology of Sprague-Dawley rats fed a high-fructose diet until adolescence
Authors: Ibrahim Kasimu Ghandi , Chivandi Eliton , Nkomozepi Pilani , Erlwanger Kennedy Honey
Published: May 2022

Background

Fructose-rich diets are linked to the epidemic of metabolic syndrome and co-morbidities including nephropathy. Phytochemicals are increasingly being used for medicinal purposes due to their perceived safety compared to conventional drugs. Although previously shown to beneficially programme metabolism, these phytochemicals might have a negative impact on metabolic health when introduced early in life. We investigated whether neonatal administration of curcumin to rats would impact their response in adolescence to a high-fructose diet. Sprague-Dawley pups (n = 128) were administered either 0.5% dimethyl sulphoxide, curcumin (500 mg kg−1), fructose (20%, w/v) or a combination of curcumin and fructose from post-natal day 6 to 21. Each group was then subdivided into two; one had tap water, while the other had fructose (20%, w/v) to drink for 6 weeks.

Results

There were no differences (p > 0.05) in the fasting blood glucose, triglycerides, cholesterol, plasma insulin and adiponectin concentrations across the groups. The renal corpuscular, glomerular tuft and Bowman capsular areas were similar (p > 0.05) across the treatment groups, in both sexes. Post-weaning fructose alone induced tubular secretions and mesangial proliferation in the kidneys which were prevented by curcumin.

Conclusions

Despite the observed benefits in adolescence, the impact of curcumin on renal health beyond adolescence needs to be explored.
Targeted isolation of biocontrol agents from plants through phytopathogen co-culture and pathogen enrichment
Authors: Wang Bozhen , Li Li , Lin Yuheng , Shen Danyu , Shao Xiaolong , Zhong Caihong , Qian Guoliang
Published: May 2022

In a long-term symbiotic relationship between plants and pathogens, plants have evolved to harbor beneficially endophytic microbiomes, thereby conferring them the ability to resist infection by pathogens. This prompted us to establish a phytopathogen-based co-culture platform for the targeted isolation of potential biocontrol agents from plants via specific pathogen enrichment. In this study, we investigated three different phytopathogenic systems, including kiwifruit, turfgrass, and rice, and their infectious bacterial and/or fungal pathogens. By using the developed mono- or co-enrichment platform, we efficiently isolated three antimicrobial agents, including Bacillus safensis ZK-1 against Pseudomonas syringae pv. actinidiae that causes kiwifruit canker, Pseudomonas alcaligenes ZK-2 against Clarireedia paspali that causes dollar spot disease in turfgrass, and Bacillus velezensis ZK-3 against rice bacterial blight pathogen Xanthomonas oryzae pv. oryzae and rice blast fungus Magnaporthe oryzae. We believe that the phytopathogenic co-culture and pathogen enrichment platform developed here is versatile and effective for the isolation of potential biocontrol agents with specific or broad-spectrum antimicrobial activities from plants of interest in a targeted and large-scale manner.
The exploration and utilization of functional substances in edible insects: a review
Authors: Qian Lei , Deng Pan , Chen Fajun , Cao Ye , Sun Hongwu , Liao Huaijian
Published: May 2022

Edible insects as food have been considered as a core future protein source. Not only are edible insects abundant in nutrient value, but also have numbers of functional substances, which could provide a multiple valuable benefits for humans. This review examines and summarizes the functional substances in edible insects and their special effects for people, as well as the use and prospects for these functional substances. There are many functional substances in edible insects, such as antimicrobial peptides, interferon, sex attractant hormones, cordycepin, active polysaccharides, microelement, chitin/chitosan, steroidal material, vitamin, lecithin, etc., which could provide multiple benefits for human beings. These special functional substances could help people enhance immunity, inhibit tumor, regulate intestinal function, relieve fatigue, anti oxidation, protect against colds, improve sleeping, promote the growth and development, as well as reducing blood sugar and blood pressure, among others. According to these valuable efficacies, the functional substances extracted from edible insects can be exploited mainly in three ways: edible insects are used to discover new medicines or health care products for people; and edible insects are applied in chemical, agricultural, food technology, pollutant treatment and textile sectors; as well as being consumed as animal feedstuff for livestock and other animals, which indirectly meet the different requirements for humans. Currently, edible insects have generated global interest to be developed as different forms of products and has promoted more research and development. However, pupae and larvae are still the main consumption ways in the market, which is unacceptable to most people. It is expected that the edible insect industry would be prosperous and sustainable by integrating the power of beneficial policies and regulations, huge consumer demand and proper strategies of promotion and production.

Graphical Abstract
PPP-RTK considering the ionosphere uncertainty with cross-validation
Authors: Li Pan , Cui Bobin , Hu Jiahuan , Liu Xuexi , Zhang Xiaohong , Ge Maorong , Schuh Harald
Published: May 2022

With the high-precision products of satellite orbit and clock, uncalibrated phase delay, and the atmosphere delay corrections, Precise Point Positioning (PPP) based on a Real-Time Kinematic (RTK) network is possible to rapidly achieve centimeter-level positioning accuracy. In the ionosphere-weighted PPP–RTK model, not only the a priori value of ionosphere but also its precision affect the convergence and accuracy of positioning. This study proposes a method to determine the precision of the interpolated slant ionospheric delay by cross-validation. The new method takes the high temporal and spatial variation into consideration. A distance-dependent function is built to represent the stochastic model of the slant ionospheric delay derived from each reference station, and an error model is built for each reference station on a five-minute piecewise basis. The user can interpolate ionospheric delay correction and the corresponding precision with an error function related to the distance and time of each reference station. With the European Reference Frame (EUREF) Permanent GNSS (Global Navigation Satellite Systems) network (EPN), and SONEL (Système d'Observation du Niveau des Eaux Littorales) GNSS stations covering most of Europe, the effectiveness of our wide-area ionosphere constraint method for PPP-RTK is validated, compared with the method with a fixed ionosphere precision threshold. It is shown that although the Root Mean Square (RMS) of the interpolated ionosphere error is within 5 cm in most of the areas, it exceeds 10 cm for some areas with sparse reference stations during some periods of time. The convergence time of the 90th percentile is 4.0 and 20.5 min for horizontal and vertical directions using Global Positioning System (GPS) kinematic solution, respectively, with the proposed method. This convergence is faster than those with the fixed ionosphere precision values of 1, 8, and 30 cm. The improvement with respect to the latter three solutions ranges from 10 to 60%. After integrating the Galileo navigation satellite system (Galileo), the convergence time of the 90th percentile for combined kinematic solutions is 2.0 and 9.0 min, with an improvement of 50.0% and 56.1% for horizontal and vertical directions, respectively, compared with the GPS-only solution. The average convergence time of GPS PPP-RTK for horizontal and vertical directions are 2.0 and 5.0 min, and those of GPS + Galileo PPP-RTK are 1.4 and 3.0 min, respectively.
The application of rapid test paper technology for pesticide detection in horticulture crops: a comprehensive review
Authors: Ghosh Soumya , AlKafaas Samar Sami , Bornman Charné , Apollon Wilgince , Hussien Aya Misbah , Badawy Ahmed Emad , Amer Mohamed Hussein , Kamel Manar Bakr , Mekawy Eman Ahmed , Bedair Heba
Published: May 2022

Background

The ever increasing pests and diseases occurring during vegetable crop production is a challenge for agronomists and farmers. One of the practices to avoid or control the attack of the causal agents is the use of pesticides, including herbicides, insecticides nematicides, and molluscicides. However, the use of these products can result in the presence of harmful residues in horticultural crops, which cause several human diseases such as weakened immunity, splenomegaly, renal failure, hepatitis, respiratory diseases, and cancer. Therefore, it was necessary to find safe and effective techniques to detect these residues in horticultural crops and to monitor food security.

Main body

The review discusses the use of conventional methods to detect pesticide residues on horticultural crops, explain the sensitivity of nanoparticle markers to detect a variety of pesticides, discuss the different methods of rapid test paper technology and highlight recent research on rapid test paper detection of pesticides.

Conclusions

The methodologies discussed in the current review can be used in a certain situation, and the variety of methods enable detection of different types of pesticides in the environment. Notably, the highly sensitive immunoassay, which offers the advantages of being low cost, highly specific and sensitive, allows it to be integrated into many detection fields to accurately detect pesticides.