bluuebunny/crossref_metadata_2025 huggingface dataset:
Transferring the sandwich principle to instructional videos: is it worth the effort?
Authors: Bock Anna , Thomas Christina , Heitzer Marius , Winnand Philipp , Peters Florian , Lemos Martin , Hölzle Frank , Modabber Ali
Published: October 2021

Background

The sandwich principle is an educational concept that regularly alternates between collective and individual learning phases within one learning unit. Applying sandwich principle to lectures has proven to be more effective for learning outcomes than classical lectures. Supposedly, this teaching format also leads to a beneficial knowledge transfer when applied to other teaching formats. Therefore, the aim of this study was to investigate the effect of the sandwich principle on instructional videos and how its use was evaluated by students.

Methods

Participants (n = 51) were randomly allocated into two groups. Both groups were given a test to assess the baseline level of knowledge. Afterwards, the control group watched the normal instructional video on cleft lips and palates, while the sandwich group watched the same video modified according to the sandwich principle. The participants then had to answer 30 single-choice questions to assess their knowledge gain and evaluate the instructional video. Long-term retention of the knowledge was tested again 6 months later using the same test questions. The unpaired t-test and ANOVA were used to compare the results.

Results

Comparison of the pre-test and post-test results of both groups showed significantly increased test scores (p < 0.0001). Regarding long-term retention, the mean test scores were still significantly higher in both groups than before watching the video (p < 0.0001). For all test results, there was no significant difference between the groups (p > 0.05). The evaluation showed that the students highly appreciated the modified video and found the interruptions for repetition of previously learned knowledge useful.

Conclusion

The hypothesis that the modification of instructional videos according to the sandwich principle would lead to an improved learning outcome could not be proved subjectively or objectively. Nevertheless, the teaching format was highly appreciated by the students and may have increased their motivation to learn with instructional videos.
Advance research directives: avoiding double standards
Authors: Heinrichs Bert
Published: October 2021

Background

Advance research directives (ARD) have been suggested as a means by which to facilitate research with incapacitated subjects, in particular in the context of dementia research. However, established disclosure requirements for study participation raise an ethical problem for the application of ARDs: While regular consent procedures call for detailed information on a specific study (“token disclosure”), ARDs can typically only include generic information (“type disclosure”). The introduction of ARDs could thus establish a double standard in the sense that within the context of ARDs, type disclosure would be considered sufficient, while beyond this context, token disclosure would remain necessary.

Main body

This paper provides an ethical analysis of ARDs, taking into account the results of numerous empirical studies that have been performed so far. It will be argued that a revised understanding of informed consent can allow for context-sensitive disclosure standards. As a consequence, ARDs that include type disclosure can be acceptable under suitable circumstances. Such an approach raises a number of objections. A thorough examination shows, however, that they are not sufficient to justify a rejection of the approach.

Conclusion

The approach presented in this paper avoids introducing a double standard. It is, therefore, more suitable for the implementation of ARDs than established approaches.
Evaluation of learning environment among Nursing undergraduates in state universities, Sri Lanka
Authors: Jayaweera Patalee , Thilakarathne Abisheka , Ratnayaka Madushanka , Shashikala Tharangi , Arachchige Rushani , Galgamuwa Lahiru Sandaruwan , Karunathilaka Nimantha , Amarasekara Thamara
Published: October 2021

Background

The learning environment is a vital part of the undergraduate curriculum which enable to delivery of quality education in the stipulated time. Therefore, this study aimed to evaluate the learning environment among BSc. Nursing undergraduates in Sri Lankan state universities.

Methods

A descriptive cross-sectional study was conducted among 161 final year BSc. Nursing undergraduates in six state universities. Socio-demographic characteristics were collected using a self-administered questionnaire. The Dundee Ready Educational Environment Measure (DREEM) questionnaire was used to evaluate the learning environment in Perception of learning (SPL), Perceptions of teaching (SPT), Academic self-perceptions (SASP), Perceptions of the atmosphere (SPA), and Social self-perceptions (SSP). Based on the SPL, SPT, SASP, SPA, and SSP domains, the overall score of learning environment was ranged from 0 to 200 and then the overall score was classified into four categories such as poor (0–50), many problems (51–100), more positive than negative (101–150) and excellent (151–200). One-way Analysis of Variance (ANOVA) and t-test were used to determine the difference in the subscales and the overall scale.

Results

The mean age of the students was 24.9 ± 0.9 years. The overall score of the learning environment was 127.1 ± 14.3. Student’s Perception of learning showed the highest mean score of 31.1 ± 3.9 while the social self-perception showed the lowest score (mean 16.4 ± 3.1). A significant group effect was observed in SPL and SPT subdomains among state universities while no significant group effect was observed in other subdomains. Furthermore, participating in extracurricular activities, travelling time to the faculty, and gender were observed as associated factors for the learning environment among BSc. Nursing undergraduates in state universities.

Conclusions

Although the overall learning environment of BSc. Nursing undergraduates in state universities in Sri Lanka was within more positive than negative category, none of the university reaches to the excellent category. Therefore, each university should have improved their subdomains of learning environment to reach excellent category through addressing the gaps of curricular and extracurricular activities in the future.
Patients' assessment of care for type 2 diabetes: Results of the Patient Assessment of Chronic Illness Care scale in a Danish population
Authors: Frølich Anne , Nielsen Ann , Glümer Charlotte , Eriksen Christian U , Maindal Helle Terkildsen , Kleist Bodil Helbech , Birke Hanne , Stockmarr Anders
Published: October 2021

Background

The Patient Assessment of Chronic Illness Care (PACIC) scale is the most appropriate for assessing self-reported experience in chronic care. We aimed to validate the PACIC questionnaire by (1) assess patients’ perception of the quality of care for Danish patients with type 2 diabetes, (2) identify which factors are most important to the quality of care designated by the five subscales in PACIC, and (3) the validity of the questionnaire.

Methods

A survey of 7,745 individuals randomly selected from the National Diabetes Registry. Descriptive statistics inter-item and item-rest correlations and factor analysis assessed the PACIC properties. Quality of care was analysed with descriptive statistics; linear and multiple regression assessed the effect of forty-nine covariates on total and subscale scores.

Results

In total, 2,696 individuals with type 2 diabetes completed ≥ 50 % of items. The floor effect for individual items was 8.5–74.5 %; the ceiling effect was 4.1–47.8 %. Cronbach’s alpha was 0.73–0.86 for the five subscales. The comparative fit index (CFI) and the Tucker–Lewis index (TLI) were 0,87, and 0,84, respectively. Mean PACIC score was 2.44 (± 0.04). Respondents, who receive diabetes care primarily at general practice and outpatient clinics had higher scores compared to those receiving care at a private specialist. Receiving rehabilitation was followed by higher scores in all subscales. Those 70 years or older had lower mean total and subscale scores compared to younger patient groups.

A higher number of diabetes visits were associated with higher total scores; a higher number of emergency department visits were associated with lower total scores. The effects of healthcare utilisation on subscale scores varied.

Conclusions

These results provide insight into variations in the quality of provided care and can be used for targeting initiatives towards improving diabetes care. Factors important to the quality of perceived care are having a GP or hospital outpatient clinic as the primary organization. Also having a higher number of visits to the two organizations are perceived as higher quality of care as well as participating in a rehabilitation program. Floor and ceiling effects were comparable to an evaluation of the PACIC questionnaire in a Danish population. Yet, floor effects suggest a need for further evaluation and possible improvement of the PACIC questionnaire in a Danish setting. Total PACIC scores were lower than in other healthcare systems, possible being a result of different contexts and cultures, and of a need for improving diabetes care in Denmark.
A qualitative study on the implementation of a holistic care package for control and management of lymphoedema: experience from a pilot intervention in northern Ethiopia
Authors: Ali Oumer , Kinfe Mersha , Semrau Maya , Tora Abebayehu , Tesfaye Abraham , Mengiste Asrat , Davey Gail , Fekadu Abebaw
Published: October 2021

Background

Neglected Tropical Diseases (NTDs) such as podoconiosis, lymphatic filariasis (LF) and leprosy mainly affect communities in low resource settings. These diseases are associated with physical disability due to lymphoedema as well as poor mental health and psychosocial outcomes. Integration of care across these NTDs at primary health care level, which includes mental health and psychosocial care alongside physical health care, is increasingly recommended.

Methods

A holistic integrated care package was developed and piloted as part of the EnDPoINT project in Gusha district, Awi zone, Ethiopia. The intervention was conducted at the health care organization, health facility and community levels. To assess the impact of the care package in terms of acceptability, scalability, sustainability and barriers to implementation, a qualitative study was conducted in January 2020. This included four focus group discussions (29 participants) and ten key informant interviews with decision makers, health professionals, patients, and community representatives.

Results

The integrated lymphoedema care package was found to be efficient compared to vertical programs in saving time and resources. It also resulted in improved awareness of the causes, treatment and prevention of lymphoedema, in marked improvements in the lymphoedema, and in reduced stigma and discrimination. The care package was found to be acceptable to patients, health professionals and decision makers. The barriers to integrated care were unrealistic patient expectations, inadequate dissemination across health workers, and poor transportation access. Health professionals, decision makers and patients believed the integrated lymphoedema care package to be scalable and sustainable.

Conclusion

The integrated holistic care package was found to be acceptable to patients, health professionals and decision makers. We recommend its scale-up to other endemic districts.
Comparison of the accumulation of macro- and microelements in the bone marrow and bone of wild and farmed red deer (Cervus elaphus)
Authors: Tajchman Katarzyna , Ukalska-Jaruga Aleksandra , Bogdaszewski Marek , Pecio Monika , Janiszewski Pawel
Published: October 2021

Background

The cells of the entire body, including the skeletal system, especially of young animals, may derive from the bone marrow in which they multiply. Therefore, it is important to assess whether the diet and quality of life of deer have a significant impact on the elemental composition of bone and bone marrow, which can directly affect their health and growth. The aim of this study was to determine the concentrations of macro- (Ca, calcium, P, phosphorus, Mg, magnesium, K, potassium, Na, sodium) and microelements (Li, lithium, Cr, chromium, Mn, manganese, Co, cobalt, Cu, copper, Zn, zinc, Se, selenium, Mo, molybdenum, and Sn, tin) accumulated in the bone marrow and bones of deer (Cervus elaphus). The study was carried out on 15 young stags divided into two groups: farmed and wild animals. The concentrations of macro- and microelements were analysed using the inductively coupled plasma mass spectrometry technique. This research expands our knowledge on this topic, which so far has not been extensively studied.

Results

The mean content of K, Na, Zn and Se in the bone marrow of farmed animals was significantly higher than in wild deer, whereas the mean content of Ca, P, Mg, K, Na and Li in the bones was higher in wild animals than in farmed individuals (p < 0.05). In addition, the mean concentration of Cr, Mn, Cu, Se and Mo in the bones of the analysed animals differed significantly (p < 0.05) and was higher in the farmed deer. The mean concentration of Se in the bone marrow of wild deer decreased with the increase of the body weight (p < 0.05). In turn, the mean content of Mn in the bone marrow and of Mo in the bones of the animals was significantly positively correlated with the animals’ body weight (p < 0.05).

Conclusions

The obtained results indicated different levels of micro- and macro-components in the body of farmed and wild deer, though without clear and strong variations. Generally, the higher level of macronutrients in the bones of wild deer may be related to the higher physiological importance of these minerals for life activities in the natural environment and to the limited supply of balanced food. On the other hand, the higher levels of microelements in the tissues of farmed animals may result from their significantly better nutritional status in the first year of life, achieved through appropriate nutrition as well as diet supplementation of adult females.
Reciprocal deregulation of NKX3.1 and AURKA axis in castration-resistant prostate cancer and NEPC models
Authors: Sooreshjani Moloud Aflaki , Kamra Mohini , Zoubeidi Amina , Shah Kavita
Published: October 2021

Background

NKX3.1, a prostate-specific tumor suppressor, is either genomically lost or its protein levels are severely downregulated, which are invariably associated with poor prognosis in prostate cancer (PCa). Nevertheless, a clear disconnect exists between its mRNA and protein levels, indicating that its post-translational regulation may be critical in maintaining its protein levels. Similarly, AURKA is vastly overexpressed in all stages of prostate cancer (PCa), including castration-resistant PCa (CRPC) and neuroendocrine PCa (NEPC), although its transcripts are only increased in ~ 15% of cases, hinting at additional mechanisms of deregulation. Thus, identifying the upstream regulators that control AURKA and NKX3.1’s levels and/or their downstream effectors offer an alternative route to inhibit AURKA and upregulate NKX3.1 in highly fatal CRPC and NEPC. AURKA and NKX3.1 have not linked to each other in any study to date.

Methods

A chemical genetic screen revealed NKX3.1 as a direct target of AURKA. AURKA-NKX3.1 cross-talk was analyzed using several biochemical techniques in CRPC and NEPC cells.

Results

We uncovered a reciprocal loop between AURKA and NKX3.1 in CRPC and NEPC cells. We observed that AURKA-mediated NKX3.1 downregulation is a major mechanism that drives CRPC pathogenesis and NEPC differentiation. AURKA phosphorylates NKX3.1 at three sites, which degrades it, but AURKA does not regulate NKX3.1 mRNA levels. NKX3.1 degradation drives highly aggressive oncogenic phenotypes in cells. NKX3.1 also degrades AURKA in a feedback loop. NKX3.1-AURKA loop thus upregulates AKT, ARv7 and Androgen Receptor (AR)-signaling in tandem promoting highly malignant phenotypes. Just as importantly, we observed that NKX3.1 overexpression fully abolished synaptophysin and enolase expression in NEPC cells, uncovering a strong negative relationship between NKX3.1 and neuroendocrine phenotypes, which was further confirmed be measuring neurite outgrowth. While WT-NKX3.1 inhibited neuronal differentiation, 3A-NKX3.1 expression obliterated it.

Conclusions

NKX3.1 loss could be a major mechanism causing AURKA upregulation in CRPC and NEPC and vice versa. NKX3.1 genomic loss requires gene therapy, nonetheless, targeting AURKA provides a powerful tool to maintain NKX3.1 levels. Conversely, when NKX3.1 upregulation strategy using small molecules comes to fruition, AURKA inhibition should work synergistically due to the reciprocal loop in these highly aggressive incurable diseases.
Heterologous production of novel and rare C30-carotenoids using Planococcus carotenoid biosynthesis genes
Authors: Takemura Miho , Takagi Chiharu , Aikawa Mayuri , Araki Kanaho , Choi Seon-Kang , Itaya Mitsuhiro , Shindo Kazutoshi , Misawa Norihiko
Published: October 2021

Background

Members of the genus Planococcus have been revealed to utilize and degrade solvents such as aromatic hydrocarbons and alkanes, and likely to acquire tolerance to solvents. A yellow marine bacterium Planococcus maritimus strain iso-3 was isolated from an intertidal sediment that looked industrially polluted, from the Clyde estuary in the UK. This bacterium was found to produce a yellow acyclic carotenoid with a basic carbon 30 (C30) structure, which was determined to be methyl 5-glucosyl-5,6-dihydro-4,4′-diapolycopenoate. In the present study, we tried to isolate and identify genes involved in carotenoid biosynthesis from this marine bacterium, and to produce novel or rare C30-carotenoids with anti-oxidative activity in Escherichia coli by combinations of the isolated genes.

Results

A carotenoid biosynthesis gene cluster was found out through sequence analysis of the P. maritimus genomic DNA. This cluster consisted of seven carotenoid biosynthesis candidate genes (orf1–7). Then, we isolated the individual genes and analyzed the functions of these genes by expressing them in E. coli. The results indicated that orf2 and orf1 encoded 4,4′-diapophytoene synthase (CrtM) and 4,4′-diapophytoene desaturase (CrtNa), respectively. Furthermore, orf4 and orf5 were revealed to code for hydroxydiaponeurosporene desaturase (CrtNb) and glucosyltransferase (GT), respectively. By utilizing these carotenoid biosynthesis genes, we produced five intermediate C30-carotenoids. Their structural determination showed that two of them were novel compounds, 5-hydroxy-5,6-dihydro-4,4′-diaponeurosporene and 5-glucosyl-5,6-dihydro-4,4′-diapolycopene, and that one rare carotenoid 5-hydroxy-5,6-dihydro-4,4′-diapolycopene is included there. Moderate singlet oxygen-quenching activities were observed in the five C30-carotenoids including the two novel and one rare compounds.

Conclusions

The carotenoid biosynthesis genes from P. maritimus strain iso-3, were isolated and functionally identified. Furthermore, we were able to produce two novel and one rare C30-carotenoids in E. coli, followed by positive evaluations of their singlet oxygen-quenching activities.
High value-added products derived from crude glycerol via microbial fermentation using Yarrowia clade yeast
Authors: Rakicka-Pustułka Magdalena , Miedzianka Joanna , Jama Dominika , Kawalec Sylwia , Liman Kamila , Janek Tomasz , Skaradziński Grzegorz , Rymowicz Waldemar , Lazar Zbigniew
Published: October 2021

Background

Contemporary biotechnology focuses on many problems related to the functioning of developed societies. Many of these problems are related to health, especially with the rapidly rising numbers of people suffering from civilization diseases, such as obesity or diabetes. One factor contributing to the development of these diseases is the high consumption of sucrose. A very promising substitute for this sugar has emerged: the polyhydroxy alcohols, characterized by low caloric value and sufficient sweetness to replace table sugar in food production.

Results

In the current study, yeast belonging to the Yarrowia clade were tested for erythritol, mannitol and arabitol production using crude glycerol from the biodiesel and soap industries as carbon sources. Out of the 13 tested species, Yarrowia divulgata and Candida oslonensis turned out to be particularly efficient polyol producers. Both species produced large amounts of these compounds from both soap-derived glycerol (59.8–62.7 g dm−3) and biodiesel-derived glycerol (76.8–79.5 g dm−3). However, it is equally important that the protein and lipid content of the biomass (around 30% protein and 12% lipid) obtained after the processes is high enough to use this yeast in the production of animal feed.

Conclusions

The use of waste glycerol for the production of polyols as well as utilization of the biomass obtained after the process for the production of feed are part of the development of modern waste-free technologies.
EZR promotes pancreatic cancer proliferation and metastasis by activating FAK/AKT signaling pathway
Authors: Xu Jian , Zhang Wei
Published: October 2021

Background

As a member of the ERM (ezrin-radixin-moesin) protein family, EZR has been recognized as a regulator of adhesion signal pathways by researchers. Moreover, EZR was thought to play irreplaceable roles in invasion and metastasis of versatile cancers. In this study, we managed to undermine the effect of EZR on proliferation and metastasis in pancreatic cancer (PC).

Methods

To analyze the impact of EZR expression on overall survival and free diseases survival of PC patients, we screened abnormally expressed EZR in PC using the Gene Expression Omnibus database (GEO database) and The Cancer Genome Atlas (TCGA) database. Following, Gene Ontology (GO)-based functional analysis and Gene set enrichment analysis (GSEA) was performed to predicate the possible biological processes in which EZR were involved. The clinicopathological characteristics and prognosis of PC patients were analyzed according to clinical data. Further, immunohistochemistry, western blotting and real time PCR analysis were conducted to analyze the expression level of EZR in PC and paired paracancerous tissues. The effect of EZR on proliferation of PC cell lines were detected by Cell Counting Kit-8 assay, and meanwhile, Transwell assay was performed to detect the effect of EZR on invasion and migration of PC cell.

Result

EZR exhibited higher expression level in pancreatic cancer tissues and cell than paracancerous tissues and cell, and its expression level was positively correlated with poor overall survival and diseases-free survival in PC patients. CCK8 assay indicated that EZR facilitated the proliferation of PC cells, meanwhile, Transwell assay showed that EZR promoted the migration and invasion of PC cells. The GO analysis predicated that EZR was involved in biological processes including cell adhesion, ameboidal-type cell migration, cell junction assembly. Through GSEA analysis, pancreatic cancer pathway, and the adhesion junction pathway were screened as the mostly enriched pathways in EZR-regulated pathological process. The inhibition of EZR suppressed proliferation and migration of PC cells. Western blot experiment revealed a positive correlation between EZR and FAK, the proliferation invasion and migration ability of PC cells were significantly decreased after knockdown of EZR.

Conclusion

Our finding revealed EZR accelerated the progression of PC via FAK/AKT signaling pathway.
Identification and validation of a pyroptosis-related prognostic signature for thyroid cancer
Authors: Wu Pu , Shi Jinyuan , Sun Wei , Zhang Hao
Published: October 2021

Background

Pyroptosis is a form of programmed cell death triggered by inflammasomes. However, the roles of pyroptosis-related genes in thyroid cancer (THCA) remain still unclear.

Objective

This study aimed to construct a pyroptosis-related signature that could effectively predict THCA prognosis and survival.

Methods

A LASSO Cox regression analysis was performed to build a prognostic model based on the expression profile of each pyroptosis-related gene. The predictive value of the prognostic model was validated in the internal cohort.

Results

A pyroptosis-related signature consisting of four genes was constructed to predict THCA prognosis and all patients were classified into high- and low-risk groups. Patients with a high-risk score had a poorer overall survival (OS) than those in the low-risk group. The area under the curve (AUC) of the receiver operator characteristic (ROC) curves assessed and verified the predictive performance of this signature. Multivariate analysis showed the risk score was an independent prognostic factor. Tumor immune cell infiltration and immune status were significantly higher in low-risk groups, which indicated a better response to immune checkpoint inhibitors (ICIs). Of the four pyroptosis-related genes in the prognostic signature, qRT-PCR detected three of them with significantly differential expression in THCA tissues.

Conclusion

In summary, our pyroptosis-related risk signature may have an effective predictive and prognostic capability in THCA. Our results provide a potential foundation for future studies of the relationship between pyroptosis and the immunotherapy response.
Role of RhoC in cancer cell migration
Authors: Lou Yingyue , Jiang Yuhan , Liang Zhen , Liu Bingzhang , Li Tian , Zhang Duo
Published: October 2021

Migration is one of the five major behaviors of cells. Although RhoC—a classic member of the Rho gene family—was first identified in 1985, functional RhoC data have only been widely reported in recent years. Cell migration involves highly complex signaling mechanisms, in which RhoC plays an essential role. Cell migration regulated by RhoC—of which the most well-known function is its role in cancer metastasis—has been widely reported in breast, gastric, colon, bladder, prostate, lung, pancreatic, liver, and other cancers. Our review describes the role of RhoC in various types of cell migration. The classic two-dimensional cell migration cycle constitutes cell polarization, adhesion regulation, cell contraction and tail retraction, most of which are modulated by RhoC. In the three-dimensional cell migration model, amoeboid migration is the most classic and well-studied model. Here, RhoC modulates the formation of membrane vesicles by regulating myosin II, thereby affecting the rate and persistence of amoeba-like migration. To the best of our knowledge, this review is the first to describe the role of RhoC in all cell migration processes. We believe that understanding the detail of RhoC-regulated migration processes will help us better comprehend the mechanism of cancer metastasis. This will contribute to the study of anti-metastatic treatment approaches, aiding in the identification of new intervention targets for therapeutic or genetic transformational purposes.
Safety monitoring experience of single-low dose primaquine co-administered with artemether–lumefantrine among providers and patients in routine healthcare practice: a qualitative study in Eastern Tanzania
Authors: Mosha Dominic , Kakolwa Mwaka A. , Mahende Muhidin K. , Masanja Honorati , Abdulla Salim , Drakeley Chris , Gosling Roland , Wamoyi Joyce
Published: October 2021

Background

Primaquine is a gametocytocidal drug recommended by the World Health Organization (WHO) in a single-low dose combined with artemisinin-based combination therapy (ACT) for the treatment and prevention ofPlasmodium falciparummalaria transmission. Safety monitoring concerns and the lack of a universal validated and approved primaquine pharmacovigilance tool is a challenge for a national rollout in many countries. This study aimed to explore the acceptance, reliability and perceived effectiveness of the primaquine roll out monitoring pharmacovigilance tool (PROMPT).

Methods

This study was conducted in three dispensaries in the Coastal region of Eastern Tanzania. The study held six in-depth interviews with healthcare providers and six participatory focus group discussions with malaria patients (3) and parents/guardians of sick children (3). Participants were purposively sampled. Thematic analysis was conducted with the aid of NVivo qualitative analysis software.

Results

The respondents’ general acceptance and perceived effectiveness of the single-low dose primaquine and PROMPT was good. Screening procedure for treatment eligibility and explaining to patients about the possible adverse events was considered very useful for safety reasons. Crushing and dissolving of primaquine tablet to get the appropriate dose, particularly in children, was reported by all providers to be challenging. Transport costs and poor access to the health facility were the main reasons for a patient failing to return to the clinic for a scheduled follow-up visit. Treatment was perceived to be safe by both providers and patients and reported no case of a severe adverse event. Some providers were concerned with the haemoglobin drop observed on day 7.

Conclusion

Single-low dose primaquine was perceived to be safe and acceptable among providers and patients. PROMPT demonstrated to be a reliable and user-friendly tool among providers. Further validation of the tool by involving the National Malaria Control Programme is pivotal to addressing key challenges and facilitating primaquine adoption in the national policy.
Risk factors associated with house entry of malaria vectors in an area of Burkina Faso with high, persistent malaria transmission and high insecticide resistance
Authors: Yaro Jean Baptiste , Tiono Alfred B. , Sanou Antoine , Toe Hyacinthe K. , Bradley John , Ouedraogo Alphonse , Ouedraogo Z. Amidou , Guelbeogo Moussa W. , Agboraw Efundem , Worrall Eve , Sagnon N.’Fale , Lindsay Steven W. , Wilson Anne L.
Published: October 2021

Background

In rural Burkina Faso, the primary malaria vector Anopheles gambiae sensu lato (s.l.) primarily feeds indoors at night. Identification of factors which influence mosquito house entry could lead to development of novel malaria vector control interventions. A study was therefore carried out to identify risk factors associated with house entry of An. gambiae s.l. in south-west Burkina Faso, an area of high insecticide resistance.

Methods

Mosquitoes were sampled monthly during the malaria transmission season using CDC light traps in 252 houses from 10 villages, each house sleeping at least one child aged five to 15 years old. Potential risk factors for house entry of An. gambiae s.l. were measured, including socio-economic status, caregiver’s education and occupation, number of people sleeping in the same part of the house as the child, use of anti-mosquito measures, house construction and fittings, proximity of anopheline aquatic habitats and presence of animals near the house. Mosquito counts were compared using a generalized linear mixed-effect model with negative binomial and log link function, adjusting for repeated collections.

Results

20,929 mosquitoes were caught, of which 16,270 (77.7%) were An. gambiae s.l. Of the 6691 An. gambiae s.l. identified to species, 4101 (61.3%) were An. gambiae sensu stricto and 2590 (38.7%) Anopheles coluzzii. Having a metal-roof on the child’s sleeping space (IRR = 0.55, 95% CI 0.32–0.95, p = 0.03) was associated with fewer malaria vectors inside the home.

Conclusion

This study demonstrated that the rate of An. gambiae s.l. was 45% lower in sleeping spaces with a metal roof, compared to those with thatch roofs. Improvements in house construction, including installation of metal roofs, should be considered in endemic areas of Africa to reduce the burden of malaria.
Genetic variation of Plasmodium falciparum histidine-rich protein 2 and 3 in Assosa zone, Ethiopia: its impact on the performance of malaria rapid diagnostic tests
Authors: Alemayehu Gezahegn Solomon , Messele Alebachew , Blackburn Kayla , Lopez Karen , Lo Eugenia , Janies Daniel , Golassa Lemu
Published: October 2021

Background

Rapid diagnostic tests (RDT) are commonly used for the diagnosis of malaria caused by Plasmodium falciparum. However, false negative results of RDT caused by genetic variation of P. falciparum histidine-rich protein 2 and 3 genes (pfhrp2/3) threaten existing malaria case management and control efforts. The main objective of this study was to investigate the genetic variations of the pfhrp2/3 genes.

Methods

A cross-sectional study was conducted from malaria symptomatic individuals in 2018 in Assosa zone, Ethiopia. Finger-prick blood samples were collected for RDT and microscopic examination of thick and thin blood films. Dried blood spots (DBS) were used for genomic parasite DNA extraction and molecular detection. Amplification of parasite DNA was made by quantitative PCR. DNA amplicons of pfhrp2/3 were purified and sequenced.

Results

The PfHRP2 amino acid repeat type isolates were less conserved compared to the PfHRP3 repeat type. Eleven and eight previously characterized PfHRP2 and PfHRP3 amino acid repeat types were identified, respectively. Type 1, 4 and 7 repeats were shared by PfHRP2 and PfHRP3 proteins. Type 2 repeats were found only in PfHRP2, while types 16 and 17 were found only in PfHRP3 with a high frequency in all isolates. 18 novel repeat types were found in PfHRP2 and 13 novel repeat types were found in PfHRP3 in single or multiple copies per isolate. The positivity rate for PfHRP2 RDT was high, 82.9% in PfHRP2 and 84.3% in PfHRP3 sequence isolates at parasitaemia levels > 250 parasites/µl. Using the Baker model, 100% of the isolates in group A (If product of types 2 × type 7 repeats ≥ 100) and 73.7% of the isolates in group B (If product of types 2 × type 7 repeats 50–99) were predicted to be detected by PfHRP2 RDT at parasitaemia level > 250 parasite/μl.

Conclusion

The findings of this study indicate the presence of different PfHRP2 and PfHRP3 amino acid repeat including novel repeats in P. falciparum from Ethiopia. These results indicate that there is a need to closely monitor the performance of PfHRP2 RDT associated with the genetic variation of the pfhrp2 and pfhrp3 gene in P. falciparum isolates at the country-wide level.
Multiple overlapping stent-assisted coiling improves efficacy and safety of treatment for complex intracranial aneurysms: a randomized trial
Authors: You Lingtong , Huang Jiaxin , Zhang Jinning , Jiang Zhixian
Published: October 2021

Background

Intracranial aneurysm rupture is the main cause of subarachnoid hemorrhage, leading to high disability and mortality. This study aimed to evaluate the clinical treatment effects of multiple overlapping stent-assisted coiling for complex intracranial aneurysms.

Methods

We conducted a randomized, controlled, single-blinded clinical trial among 168 patients diagnosed with complex intracranial aneurysms. Treatment allocation to either single stent (SS) group or multiple stent (MS) group was randomized at 1:1 ratio using a Web-based platform. The O’Kelly–Marotta (OKM) grading scale was used to evaluate the degree of aneurysm occlusion after operation and during follow-up. Good aneurysm occlusion was defined as OKM grade C–D. The modified Rankin Scale (mRS) was used to evaluate the neurological status and the clinical outcome of patients.

Results

Efficacy comparative analysis demonstrated that major recurrence of aneurysms was significantly reduced in the MS group (P = 0.012). In addition, the MS group displayed significantly reduced number of patients with mRS between 3 and 6 (P = 0.007) and increased number of patients with mRS between 0 and 1 (P = 0.034). Furthermore, the MS group showed increased percentage of patients with OKM grade C–D (P = 0.041). Compared with the SS group, the MS group exhibited decreased mortality (P = 0.037) and morbidity (P = 0.035).

Conclusions

Multiple overlapping stent-assisted coiling significantly improved the clinical treatment effects and provided a new method for complex intracranial aneurysms.
Comparison of obesity-related indices for identifying nonalcoholic fatty liver disease: a population-based cross-sectional study in China
Authors: Xie Fangfei , Pei Yuyu , Zhou Quan , Cao Deli , Wang Yun
Published: October 2021

Background

The relationship between nonalcoholic fatty liver disease (NAFLD) and obesity-related indices has been analyzed separately thus far, and evidence comparing these indices together is still lacking, especially in China. This study aimed to comprehensively evaluate the predictive performance of anthropometric and metabolic indices to identify NAFLD in Chinese adults.

Methods

This study recruited a total of 1748 participants who were 18 years or older in southeastern China. The systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL), waist circumference (WC), a body shape index (ABSI), atherogenic index of plasma (AIP), abdominal volume index (AVI), body adiposity index (BAI), body mass index (BMI), body roundness index (BRI), conicity index (CI), triglyceride glucose (TyG), waist hip ratio (WHR), and waist height ratio (WHtR) were measured. The association between these indices and NAFLD was analyzed via logistic analyses with odds ratios (ORs). Receiver operating characteristic (ROC) curves and areas under the curve (AUCs) were used to compare the predictive performance of these indices to identify NAFLD.

Results

BMI had the greatest total AUC (AUC = 0.841) in the ROC curve analysis. However, BRI and BMI both had the best diagnostic ability in males (AUC = 0.812), and BRI had the best diagnostic ability in females (AUC = 0.849). Furthermore, AVI had the greatest AUC for patients who were ~ 20 (AUC = 0.892) and ~ 40 years old (AUC = 0.831), while TyG showed a higher predictive ability than AVI in those who were ~ 60 years old (AUC = 0.766).

Conclusion

This study identified sex- and age-specific indices for predicting NAFLD in Chinese subjects. Compared with indices for all age groups, sex- and age-specific indices can provide more accurate assistance for clinical diagnosis and treatment.
Accumulation of cholesterol, triglycerides and ceramides in hepatocellular carcinomas of diethylnitrosamine injected mice
Authors: Haberl Elisabeth M. , Pohl Rebekka , Rein-Fischboeck Lisa , Höring Marcus , Krautbauer Sabrina , Liebisch Gerhard , Buechler Christa
Published: October 2021

Background

Dysregulated lipid metabolism is critically involved in the development of hepatocellular carcinoma (HCC). The respective metabolic pathways affected in HCC can be identified using suitable experimental models. Mice injected with diethylnitrosamine (DEN) and fed a normal chow develop HCC. For the analysis of the pathophysiology of HCC in this model a comprehensive lipidomic analysis was performed.

Methods

Lipids were measured in tumor and non-tumorous tissues by direct flow injection analysis. Proteins with a role in lipid metabolism were analysed by immunoblot. Mann-Whitney U-test or paired Student´s t-test were used for data analysis.

Results

Intra-tumor lipid deposition is a characteristic of HCCs, and di- and triglycerides accumulated in the tumor tissues of the mice. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha, lipoprotein lipase and hepatic lipase protein were low in the tumors whereas proteins involved in de novo lipogenesis were not changed. Higher rates of de novo lipogenesis cause a shift towards saturated acyl chains, which did not occur in the murine HCC model. Besides, LDL-receptor protein and cholesteryl ester levels were higher in the murine HCC tissues. Ceramides are cytotoxic lipids and are low in human HCCs. Notably, ceramide levels increased in the murine tumors, and the simultaneous decline of sphingomyelins suggests that sphingomyelinases were involved herein. DEN is well described to induce the tumor suppressor protein p53 in the liver, and p53 was additionally upregulated in the tumors.

Conclusions

Ceramides mediate the anti-cancer effects of different chemotherapeutic drugs and restoration of ceramide levels was effective against HCC. High ceramide levels in the tumors makes the DEN injected mice an unsuitable model to study therapies targeting ceramide metabolism. This model is useful for investigating how tumors evade the cytotoxic effects of ceramides.
Association of lipid accumulation product with chronic kidney disease in Chinese community adults: a report from the REACTION study
Authors: Yan Pijun , Xu Yong , Miao Ying , Tang Qian , Wu Yuru , Bai Xue , Zhang Zhihong , Li Qian , Wan Qin
Published: October 2021

Background

Limited studies regarding the correlation of lipid accumulation product (LAP) with a decreased estimated glomerular filtration rate (eGFR) have yielded conflicting findings, and no report has demonstrated the relationship of LAP with chronic kidney disease (CKD), defined as the presence of albuminuria and/or a decreased eGFR. The purpose of this study was to estimate the possible correlation of LAP with CKD prevalence in Chinese community adults.

Method

In this cross-sectional study, LAP level of 7202 participants (age ≥ 40 years) was determined, and its possible association with CKD was evaluated by a multiple logistic regression model.

Results

Compared with subjects with non-CKD, non-albuminuria, and high eGFR, LAP levels significantly increased in female not male subjects with CKD, albuminuria, and low eGFR, respectively (all P < 0.001). The univariate logistic regression analysis revealed that LAP level of female not male subjects were significantly and positively associated with the prevalence of CKD (P < 0.001). The multivariate logistic regression analysis showed that the risk of CKD prevalence in female not male subjects progressively increased across LAP quartiles (P for trend < 0.01), and the risk of CKD prevalence of subjects in Q4 significantly increased compared to those in Q1 after adjustment for potential confounding factors in Models 4 (odds ratio [OR]: 1.382, 95% confidence intervals [CI] 1.002–1.906, P < 0.05). Stratified analysis revealed positive associations of LAP quartiles with risk of CKD prevalence in people with the following characteristics: women, older, overweight, with hypertension, normal glucose tolerance, appropriate low-density lipoprotein cholesterol, nonsmokers, nondrinkers, and no cardiovascular disease events.

Conclusions

High LAP levels might be significantly associated with risk of CKD prevalence in community-dwelling Chinese female adults, which may inform both public health recommendations and clinical practice.
Investigating the response scale of the EORTC QLQ-C30 in German cancer patients and a population survey
Authors: Koller Michael , Müller Karolina , Nolte Sandra , Schmidt Heike , Harvey Christina , Mölle Ulrike , Boehm Andreas , Engeler Daniel , Metzger Jürg , Sztankay Monika , Holzner Bernhard , Groenvold Mogens , Kuliś Dagmara , Bottomley Andrew ,   the EORTC Quality of Life Group
Published: October 2021

Background

The European Organization for research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) scales are scored on a 4-point response scale, ranging from not at all to very much. Previous studies have shown that the German translation of the response option quite a bit as mäßig violates interval scale assumptions, and that ziemlich is a more appropriate translation. The present studies investigated differences between the two questionnaire versions.

Methods

The first study employed a balanced cross-over design and included 450 patients with different types of cancer from three German-speaking countries. The second study was a representative survey in Germany including 2033 respondents. The main analyses included compared the ziemlich and mäßig version of the questionnaire using analyses of covariance adjusted for sex, age, and health burden.

Results

In accordance with our hypothesis, the adjusted summary score was lower in the mäßig than in the ziemlich version; Study 1: − 4.5 (95% CI − 7.8 to − 1.3), p = 0.006, Study 2: − 3.1 (95% CI − 4.6 to − 1.5), p < 0.001. In both studies, this effect was pronounced in respondents with a higher health burden; Study 1: − 6.8 (95% CI − 12.2 to − 1.4), p = 0.013; Study 2: − 4.5 (95% CI − 7.3 to − 1.7), p = 0.002.

Conclusions

We found subtle but consistent differences between the two questionnaire versions. We recommend to use the optimized response option for the EORTC QLQ-C30 as well as for all other German modules.

Trial registration: The study was retrospectively registered on the German Registry for Clinical Studies (reference number DRKS00012759, 04th August 2017, https://www.drks.de/DRKS00012759).
Regional brain tissue changes in patients with cystic fibrosis
Authors: Roy Bhaswati , Woo Marlyn S. , Vacas Susana , Eshaghian Patricia , Rao Adupa P. , Kumar Rajesh
Published: October 2021

Background

Cystic fibrosis (CF) patients present with a variety of symptoms, including mood and cognition deficits, in addition to classical respiratory, and autonomic issues. This suggests that brain injury, which can be examined with non-invasive magnetic resonance imaging (MRI), is a manifestation of this condition. However, brain tissue integrity in sites that regulate cognitive, autonomic, respiratory, and mood functions in CF patients is unclear. Our aim was to assess regional brain changes using high-resolution T1-weighted images based gray matter (GM) density and T2-relaxometry procedures in CF over control subjects.

Methods

We acquired high-resolution T1-weighted images and proton-density (PD) and T2-weighted images from 5 CF and 15 control subjects using a 3.0-Tesla MRI. High-resolution T1-weighted images were partitioned to GM-tissue type, normalized to a common space, and smoothed. Using PD- and T2-weighted images, whole-brain T2-relaxation maps were calculated, normalized, and smoothed. The smoothed GM-density and T2-relaxation maps were compared voxel-by-voxel between groups using analysis of covariance (covariates, age and sex; SPM12, p < 0.001).

Results

Significantly increased GM-density, indicating tissues injury, emerged in multiple brain regions, including the cerebellum, hippocampus, amygdala, basal forebrain, insula, and frontal and prefrontal cortices. Various brain areas showed significantly reduced T2-relaxation values in CF subjects, indicating predominant acute tissue changes, in the cerebellum, cerebellar tonsil, prefrontal and frontal cortices, insula, and corpus callosum.

Conclusions

Cystic fibrosis subjects show predominant acute tissue changes in areas that control mood, cognition, respiratory, and autonomic functions and suggests that tissue changes may contribute to symptoms resulting from ongoing hypoxia accompanying the condition.