bluuebunny/crossref_metadata_2025 huggingface dataset:
Malnutrition and other risk factors of geriatric depression: a community-based comparative cross-sectional study in older adults in rural Bangladesh
Authors: Islam Md. Ziaul , Disu Tasnim Rahman , Farjana Sharmin , Rahman Mohammad Meshbahur
Published: October 2021

Background

Malnutrition and depression are highly prevalent in older adults and can lead to disparaging outcomes. Analytical studies on geriatric depression (GD) and its association with malnutrition are very scarce in Bangladesh, although the size of the older population is increasing fast in the country. The current study aimed to assess the association between malnutrition and depression and associated risk factors in rural older adults.

Methods

A community-based comparative cross-sectional study was conducted in 600 older adult residents (aged ≥60 years) of three rural communities of Bangladesh from January to October 2019. The study enrolled two groups of participants; 300 depressed as cases and another 300 non-depressed older adults as a comparison group matching their age and living area. We used a semi-structured questionnaire to collect data through a face-to-face interview. Geriatric Depression Scale-15 was used to determine depression, and a score of ≥5 was considered as depressed. We used the Bangla version of the Mini-Nutritional Assessment-Short Form to assess nutritional status, which comprised questions related to appetite, weight loss, mobility, recent illness/stress, dementia/depression, and BMI, and considered a score of 0–7 as the cutoff score for malnutrition. Measures included baseline and personal characteristics, malnutrition, GD, and its associated risk factors. A binary logistic regression model was fitted to identify variables associated with the risk of GD.

Results

The study found no significant difference in gender (male Vs. female) between depressed (44.0% Vs. 56.0%) and non-depressed (46.0% Vs. 54.0%) older individuals. The study revealed that malnutrition was significantly (p < 0.01) higher in depressed (56.0%) than in non-depressed (18.0%) rural older adults. The malnourished older adults had around three times (AOR = 3.155; 95% CI: 1.53–6.49, p = 0.002) more risk of having depression than the well-nourished older individuals. Older adults who were unemployed (AOR = 4.964; 95% CI: 2.361–10.440; p = 0.0001) and from lower and middle class (AOR = 3.654; 95% CI: 2.266–7.767; p = 0.001) were more likely to experience depression. Older adults having a ‘poor diet’ were more likely to experience depression (AOR = 3.384; 95% CI: 1.764–6.703; p = 0.0001). The rural older adults who were single (AOR = 2.368; 95% CI: 1.762–6.524; p = 0.001) and tobacco users (AOR = 2.332; 95% CI: 1.663–5.623; p = 0.003) were found more likely to experience depression.

Conclusions

A significant association between malnutrition and depression was evident by the current study in the rural older individuals of Bangladesh. It will be a prolific initiative if policymakers merge malnutrition and the risk factors associated with geriatric depression in providing universal health care for better health and well-being of the rural older populations.
IL-18 and IL-18 binding protein are related to disease severity and parasitemia during falciparum malaria
Authors: Otterdal Kari , Berg Aase , Michelsen Annika E. , Yndestad Arne , Patel Sam , Gregersen Ida , Halvorsen Bente , Ueland Thor , Langeland Nina , Aukrust Pål
Published: October 2021

Background

Several inflammatory molecules participate in the immune response to malaria. Interleukin (IL)-18 is an inflammatory cytokine activated by NLRP3 inflammasomes. In clinical falciparum malaria, with and without HIV co-infection, data on IL-18 and in particular on its binding protein, IL-18bp, is scarce.

Methods

Clinical data and blood samples were collected from adults in Mozambique with P. falciparum infection, with (n = 70) and without (n = 61) HIV co-infection, from HIV-infected patients with similar symptoms without malaria (n = 58) and from healthy controls (n = 52). In vitro studies were performed in endothelial cells using hemozoin crystals.

Results

(i) IL-18 and IL-18bp were markedly up-regulated during falciparum malaria with particular high levels in malaria patients co-infected with HIV and severe malaria disease. (ii) In the malaria group as a whole, both IL-18 and IL-18bp were positively correlated with disease severity, parasitemia, and endothelial cell activation as assessed by vWF in plasma. (iii) Whereas there was no change in IL-18 levels in malaria patients co-infected with HIV during follow-up, the patients with malaria only had slightly increased IL-18 levels. Further, the IL-18pb levels declined and thereby contributed to an increase in IL-18/IL-18bp ratio in all subgroups of malaria patients. (iv) IL-27, previously shown to be up-regulated in this malaria cohort, markedly induced a release of IL-18bp from endothelial cells in vitro, and notably, this presumably anti-inflammatory effect was counteracted by hemozoin.

Conclusions

Our findings suggest that the IL-18 system could be an important mediator in the immune pathogenesis during falciparum malaria, potentially also representing a target for therapy.
Exploring the clinical value of preoperative serum gamma-glutamyl transferase levels in the management of patients with hepatocellular carcinoma receiving postoperative adjuvant transarterial chemoembolization
Authors: Ke Qiao , Xiang Fu , Xiao Chunhong , Huang Qizhen , Liu Xiaolong , Zeng Yongyi , Wang Lei , Liu Jingfeng
Published: October 2021

Background

Preoperative serum gamma-glutamyl transferase (γ-GT) levels is significantly related to the prognosis of hepatocellular carcinoma (HCC), but its clinical value in the management of postoperative adjuvant transarterial chemoembolization (PA-TACE) has rarely been explored. This study aimed to investigate whether γ-GT levels could be taken as a biomarker to guide the management of PA-TACE in resectable HCC.

Methods

HCC patients receiving radical resection were identified through the primary liver cancer big data (PLCBD) from December 2012 to December 2015. Prognostic factors of overall survival (OS) and disease-free survival (DFS) were identified by univariate and multivariate cox analyses, and subgroup analysis was conducted between PA-TACE group and non-TACE stratified by γ-GT levels before and after 1:1 propensity score matching (PSM).

Results

γ-GT level was found to be an independent risk factor of OS and DFS in 1847 HCC patients receiving radical resection (both P < 0.05), and patients with elevated γ-GT(> 54.0 U/L) have a shortened median OS and DFS, compared with those with normal γ-GT (both P < 0.001). In the subgroup of patients with normal γ-GT, there were no significant differences between groups of PA-TACE and non-TACE in terms of median OS and DFS before and after PSM (all P > 0.05), and PA-TACE was not a significant prognostic factor of both OS and DFS before and after PSM (all P > 0.05). In the subgroup of patients with elevated γ-GT, significant differences were found between groups of PA-TACE and non-TACE in terms of median OS and DFS before and after PSM (all P < 0.05), and PA-TACE was an independent prognostic factor of both OS and DFS (all P < 0.05).

Conclusion

Currently, we concluded that patients with more advanced HCC also have more elevated γ-GT, and these patients with elevated γ-GT would be benefited more from PA-TACE after radical resection.
TFEB, SIRT1, CARM1, Beclin-1 expression and PITX2 methylation in breast cancer chemoresistance: a retrospective study
Authors: Bertozzi Serena , Londero Ambrogio P. , Viola Luigi , Orsaria Maria , Bulfoni Michela , Marzinotto Stefania , Corradetti Bruna , Baccarani Umberto , Cesselli Daniela , Cedolini Carla , Mariuzzi Laura
Published: October 2021

Background

Breast cancer chemoresistance is attributed to a wide variety of mechanisms, including autophagy. Transcription factor EB (TFEB) has been recently identified and characterized as one major regulator of autophagy and lysosomal genesis.

Objective

This study aims to evaluate the prognostic impact of TFEB and its pathway in breast cancer chemoresistance.

Methods

This retrospective study analyzes the expression of TFEB, CARM1, SIRT1, and Beclin-1 and the methylation of PITX2 in breast carcinoma. A group of breast cancer patients treated with chemotherapy, who relapsed within 12 months from treatment initiation, were compared to a sub-cohort of chemo-treated patients who did not recur within 12 months of follow-up. The expression of TFEB, CARM1, SIRT1, and Belcin-1 was analyzed using immunohistochemistry or RT-PCR on formalin-fixed paraffin-embedded samples. PITX2 methylation was tested with the diagnostic CE-marked kit Therascreen PITX2 RGQ PCR. In the final model, 136 cases of chemo-treated breast cancer were included.

Results

A higher TFEB and Beclin-1 expression correlate with shorter survival in patients with chemo-treated invasive breast cancer (respectively HR 3.46, CI.95 1.27–9.47,p < 0.05 and 7.11, CI.95 2.54–19.9). TFEB, CARM1, and SIRT1 are positively correlated with Beclin-1. The protein expression of SIRT1 is significantly associated with TFEB and CARM1 so that a very low SIRT1 expression (lower than the first quartile of the H-score distribution) correlates with a low expression of TFEB and CARM1 and with longer survival. SIRT1 seems to have a lower H-score in the basal-like and HER2-enriched tumors than the luminal subtypes. Beclin-1 and TFEB seem to have a higher H-score in the basal-like and HER2-enriched tumors than the luminal subtypes. PITX2 methylation analysis was feasible only in 65% of the selected samples, but no significant differences between cases and controls were found, and there was also no correlation with the expression of the TFEB pathway.

Conclusions

TFEB, SIRT1, and Beclin-1 seem to have a potential prognostic significance in patients with chemo-treated breast cancer, likely because of their role in the regulation of autophagy. In addition, no correlation between TFEB and PITX2 methylation was found, likely because they perform two different roles within the autophagy process.
Evaluating the impact of 18F-FDG-PET-CT on risk stratification and treatment adaptation for patients with muscle-invasive bladder cancer (EFFORT-MIBC): a phase II prospective trial
Authors: Verghote Flor , Poppe Lindsay , Verbeke Sofie , Dirix Piet , Albersen Maarten , De Meerleer Gert , Berghen Charlien , Ost Piet , Villeirs Geert , De Visschere Pieter , De Man Kathia , De Maeseneer Daan , Rottey Sylvie , Van Praet Charles , Decaestecker Karel , Fonteyne Valérie
Published: October 2021

Background

The outcome of patients with muscle-invasive bladder cancer (MIBC) remains poor, despite aggressive treatments. Inadequate primary staging, classically performed by computed tomography (CT)-imaging, could lead to inappropriate treatment and might contribute to these poor results. Although not (yet) adapted by international guidelines, several reports have indicated the superiority of 18F-fluorodeoxyglucose-positron emission tomography-CT (18F-FDG-PET-CT) compared to CT in the detection of lymph node and distant metastases. Thereby the presence of extra-vesical disease on 18F-FDG-PET-CT has been correlated with a worse overall survival. This supports the hypothesis that 18F-FDG-PET-CT is useful in stratifying MIBC patients and that adapting the treatment plan accordingly might result in improved outcome.

Methods

EFFORT-MIBC is a multicentric prospective phase II trial aiming to include 156 patients. Eligible patients are patients with histopathology-proven MIBC or ≥ T3 on conventional imaging treated with MIBC radical treatment, without extra-pelvic metastases on conventional imaging (thoracic CT and abdominopelvic CT/ magnetic resonance imaging (MRI)). All patients will undergo radical local therapy and if eligible neo-adjuvant chemotherapy. An 18F-FDG-PET-CT will be performed in addition to and at the timing of the conventional imaging. In case of presence of extra-pelvic metastasis on 18F-FDG-PET-CT, appropriate intensification of treatment with metastasis-directed therapy (MDT) (in case of ≤3 metastases) or systemic immunotherapy (> 3 metastases) will be provided. The primary outcome is the 2-year overall survival rate. Secondary endpoints are progression-free survival, distant metastasis-free survival, disease-specific survival and quality of life. Furthermore, the added diagnostic value of 18F-FDG-PET-CT compared to conventional imaging will be evaluated and biomarkers in tumor specimen, urine and blood will be correlated with primary and secondary endpoints.

Discussion

This is a prospective phase II trial evaluating the impact of 18F-FDG-PET-CT in stratifying patients with primary MIBC and tailoring the treatment accordingly. We hypothesize that the information on the pelvic nodes can be used to guide local treatment and that the presence of extra-pelvic metastases enables MDT or necessitates the early initiation of immunotherapy leading to an improved outcome.

Trial registration

The Ethics Committee of the Ghent University Hospital (BC-07456) approved this study on 11/5/2020. The trial was registered on ClinicalTrials.gov (NCT04724928) on 21/1/2021.
Modelling the impact of travel restrictions on COVID-19 cases in Hong Kong in early 2020
Authors: Kwok Wang-Chun , Wong Chun-Ka , Ma Ting-Fung , Ho Ka-Wai , Fan Louis Wai-Tong , Chan King-Pui Florence , Chan Samuel Shung-Kay , Tam Terence Chi-Chun , Ho Pak-Leung
Published: October 2021

Background

Coronavirus Disease 2019 (COVID-19) led to pandemic that affected almost all countries in the world. Many countries have implemented border restriction as a public health measure to limit local outbreak. However, there is inadequate scientific data to support such a practice, especially in the presence of an established local transmission of the disease.

Objective

To apply a metapopulation Susceptible-Exposed-Infectious-Recovered (SEIR) model with inspected migration to investigate the effect of border restriction as a public health measure to limit outbreak of coronavirus disease 2019.

Methods

We apply a modified metapopulation SEIR model with inspected migration with simulating population migration, and incorporating parameters such as efficiency of custom inspection in blocking infected travelers in the model. The population sizes were retrieved from government reports, while the number of COVID-19 patients were retrieved from Hong Kong Department of Health and China Centre for Disease Control (CDC) data. The R0 was obtained from previous clinical studies.

Results

Complete border closure can help to reduce the cumulative COVID-19 case number and mortality in Hong Kong by 13.99% and 13.98% respectively. To prevent full occupancy of isolation facilities in Hong Kong; effective public health measures to reduce local R0 to below 1.6 was necessary, apart from having complete border closure.

Conclusions

Early complete travel restriction is effective in reducing cumulative cases and mortality. However, additional anti-COVID-19 measures to reduce local R0 to below 1.6 are necessary to prevent COVID-19 cases from overwhelming hospital isolation facilities.
Analysis of the relationship between the HbA1c screening results and the development and worsening of diabetes among adults aged over 40 years: a 4-year follow-up study of 140,000 people in Japan – the Shizuoka study
Authors: Nomura Shuhei , Sakamoto Haruka , Rauniyar Santosh Kumar , Shimada Koki , Yamamoto Hiroyuki , Kohsaka Shun , Ichihara Nao , Kumamaru Hiraku , Miyata Hiroaki
Published: October 2021

Background

Hemoglobin A1c (HbA1c) levels are routinely measured during health check-ups and are used as an indicator of glycemic control in Japan. However, only a few studies have followed up individuals to assess the risk of diabetes development and worsening based on HbA1c screening results. This study evaluated the relationship between HbA1c screening results and the risk of diabetes development and worsening.

Methods

Data were collected from the Shizuoka Kokuho Database, a Japanese administrative claims database of insured individuals aged > 40 years. We included individuals available for follow-up from April 2012 to March 2018 who had not received any diabetes treatment before March 2014. HbA1c screening results were categorized into 4 groups based on the HbA1c levels at the 2012 and 2013 health check-ups: group A, those whose HbA1c levels were < 6.5% in 2012 and 2013; group B, those whose HbA1c levels > 6.5% in 2012 but < 6.5% in 2013; group C, those whose HbA1c levels were > 6.5% in 2012 and 2013; and group D, those whose HbA1c levels were < 6.5% in 2012 and > 6.5% in 2013. Logistic regression models were used to analyze diabetes development and worsening, defined as the initiation of diabetes treatment by March 2018 and the use of injection drugs by participants who initiated diabetes treatment by March 2018.

Results

Overall, 137,852 individuals were analyzed. After adjusting for covariates, compared with group A, group B was more likely to initiate treatment within 4 years (odds ratio: 22.64; 95% confidence interval: 14.66–34.99). In patients who initiated diabetes treatment by March 2018, injection drugs were less likely used by group D than by group A (odds ratio: 0.28; 95% confidence interval: 0.12–0.61).

Conclusions

Our study suggests that although HbA1c levels measured during health check-ups were correlated with the risk of diabetes development and worsening, HbA1c levels in a single year may not necessarily provide sufficient information to consider these future risks.
Measurements of quality of village-level care and patients’ healthcare-seeking behaviors in rural China
Authors: Rao Sihang , Xue Hao , Teuwen Dirk E. , Shi Haonan , Yi Hongmei
Published: October 2021

Background

Although the progress in global health initiatives has improved the availability of primary health care (PHC), unqualified healthcare remains a serious challenge in low- and middle-income countries, where PHC is often underutilized. This study examines factors associated with patients’ healthcare-seeking behaviors in rural Chin—seeking healthcare at village-level PHC providers, at higher-level health facilities, self-medicating, and refraining from seeking medical help. We focus on provider-side factors, including (1) the unobservable quality indicator, (2) the observable quality indicator, and (3) the observable signal indicator.

Methods

We analyzed 1578 episodes of healthcare-seeking behaviors of patients with diarrhea or cough/runny nose symptom from surveys conducted in July 2017 and January 2018 in 114 villages of the Yunnan province. We investigated the correlation between quality-related factors with patients’ healthcare-seeking behaviors by multinomial logit regression.

Results

We found that rural patients were insensitive to the unobservable quality of healthcare providers, as measured by standardized clinical vignettes, which might be attributable to the credence nature of PHC. The observable quality indicator, whether the clinician has received full-time junior college formal medical education, was associated with patients’ healthcare choices. Patients, however, were more likely to select healthcare based on the observable signal indicator, which was measured by the availability of medicines. Additionally, the observable signal indicator had no significant association with two quality indicators. Notably, socioeconomically-disadvantaged patients relied more on the village-level PHC, which emphasized the role of PHC in promoting the welfare of rural populations.

Conclusions

Our study found an inconsistency between objective quality of healthcare provided by providers and subjective quality perceived by patients. Patients could not identify the actual quality of PHC precisely, while they were more likely to make decisions based on the observable signal indicator. Therefore, the quality of PHC should be more observable to patients. This study not only supplements the literature on healthcare-seeking choices by examining four types of behaviors simultaneously but also clarifies rural patients’ perceptions of the quality of PHC for policy decision-making on increasing the utilization of PHC and improving the medical welfare of the vulnerable.
Role of psychosocial factors on the effect of physical activity on physical function in patients after lumbar spine surgery
Authors: Master Hiral , Castillo Renan , Wegener Stephen T. , Pennings Jacquelyn S. , Coronado Rogelio A. , Haug Christine M. , Skolasky Richard L. , Riley Lee H. , Neuman Brian J. , Cheng Joseph S. , Aaronson Oran S. , Devin Clinton J. , Archer Kristin R.
Published: October 2021

Background

The purpose of this study was to investigate the longitudinal postoperative relationship between physical activity, psychosocial factors, and physical function in patients undergoing lumbar spine surgery.

Methods

We enrolled 248 participants undergoing surgery for a degenerative lumbar spine condition. Physical activity was measured using a triaxial accelerometer (Actigraph GT3X) at 6-weeks (6wk), 6-months (6M), 12-months (12M) and 24-months (24M) following spine surgery. Physical function (computerized adaptive test domain version of Patient-Reported Outcomes Measurement Information System) and psychosocial factors (pain self-efficacy, depression and fear of movement) were assessed at preoperative visit and 6wk, 6M, 12M and 24M after surgery. Structural equation modeling (SEM) techniques were utilized to analyze data, and results are represented as standardized regression weights (SRW). Overall SRW were computed across five imputed datasets to account for missing data. The mediation effect of each psychosocial factor on the effect of physical activity on physical function were computed [(SRW for effect of activity on psychosocial factor X SRW for effect of psychosocial factor on function) ÷ SRW for effect of activity on function]. Each SEM model was tested for model fit by assessing established fit indexes.

Results

The overall effect of steps per day on physical function (SRW ranged from 0.08 to 0.19, p<0.05) was stronger compared to the overall effect of physical function on steps per day (SRW ranged from non-existent to 0.14, p<0.01 to 0.3). The effect of steps per day on physical function and function on steps per day remained consistent after accounting for psychosocial factors in each of the mediation models. Depression and fear of movement at 6M mediated 3.4% and 5.4% of the effect of steps per day at 6wk on physical function at 12M, respectively. Pain self-efficacy was not a statistically significant mediator.

Conclusions

The findings of this study suggest that the relationship between physical activity and physical function is stronger than the relationship of function to activity. However, future research is needed to examine whether promoting physical activity during the early postoperative period may result in improvement of long-term physical function. Since depression and fear of movement had a very small mediating effect, additional work is needed to investigate other potential mediating factors such as pain catastrophizing, resilience and exercise self-efficacy.
Right pneumonectomy for primary large acinic cell carcinoma (AciCC) with severe mediastinal deviation: a case report and literature review
Authors: Chen Xueyu , Zhang Yajie , Luo Fangxiu , Li Hecheng
Published: October 2021

Background

Primary lung acinic cell carcinoma is very rare. Here we report a young female patient who suffered the largest primary lung acinic cell carcinoma with severe mediastinal deviation which has never been reported before. We also reviewed data and features of 20 previously reported cases of primary lung acinic cell carcinoma who underwent lobectomy.

Case presentation

A 27-year-old female patient presented with recurrent coughing and hemoptysis for more than 10 years came to our hospital. A chest computed tomography (CT) showed a giant space-occupying lesion in the hilum of right lung. After a thorough and detailed preoperative examination, the patient then was performed a radical right pneumonectomy with mediastinal lymph node dissection. The size of the tumor was about 8.6 × 4.5 × 4.4 cm. The pathological results demonstrated a primary acinic cell carcinoma of right lung. The immunohistochemistry of the tumor showed AE1/AE3 (+), Ki-67 (2% +), CK7 (+), Vimentin (+), CK19 (+), α1-ACT (+), AB-PAS (+), S-100 (−), TTF-1 (−). The patient was discharged less than 2 weeks after the operation. So far, the patient has been followed-up for 2 years, and no evidence of tumor recurrence or metastasis was observed.

Conclusions

The primary acinic cell carcinoma of lung in this case is the biggest one ever reported and also the first case treated with radical right pneumonectomy. In addition, the patient had a very rare condition of severe mediastinal deviation at the same time. After surgical treatment, the patient recovered uneventfully and had stable disease without recurrence and metastasis after 2 years of follow-up. This case together with the reported case indicate that primary acinic cell carcinoma of lung is of low malignancy, the prognosis and therapy effect of surgical treatment are relatively satisfactory.
Deterioration of diabetic nephropathy via stimulating secretion of cytokines by atrial natriuretic peptide
Authors: Liu Chenxiao , Li Qi , Feng Xiu , Zhu Jian , Li Qian
Published: October 2021

Background

Atrial natriuretic peptide (ANP) is a cardiovascular and metabolic hormone that has been identified recently as being associated with chronic kidney disease (CKD) without diabetes. Cytokines such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and adiponectin (ADP) contribute to the development of type 2 diabetes (T2DM). The aim here was to investigate the relationships of ANP with cytokine levels and clinical variables in T2DM nephropathy patients.

Methods

A total of 81 participants with T2DM were recruited, including 37 patients with normoalbuminuria, 23 patients with microalbuminuria and 21 patients with macroalbuminuria. Serum concentrations of ANP and cytokines were measured using enzyme-linked immunosorbent assay (ELISA) kits. The correlations between ANP and clinical variables were analyzed. Multiple linear regression and logistic regression models were constructed to test the associations between ANP and the severity and presence of albuminuria.

Results

The macroalbuminuria patients exhibited higher plasma levels of ANP, TNF-α, IL-6, and ADP; higher serum creatinine (Cr) and blood urea nitrogen (BUN); and longer duration of diabetes mellitus (DM) than the patients with normoalbuminuria and microalbuminuria. Plasma ANP level was significantly associated with TNF-α (r = 0.876, p < 0.001), IL-6 (r = 0.816, p < 0.001) and ADP (r = 0.772, p < 0.001), independent of the duration of DM or the BUN concentration.

Conclusion

ANP is higher in type 2 diabetes mellitus nephropathy subjects, especially those who have macroalbuminuria, which is associated with compensatory responses to inflammation.
Neonatal nursing led research activity in the UK: a survey of current practice
Authors: Gallagher Katie , Petty Julia , Cooper Joanne , Marlow Neil
Published: October 2021

Background

Neonatal nurses are ideally placed in practice to undertake research enhancing the care of families. More information is required, however, around neonatal nursing led research to advance leadership in this area. The aim of this study was to determine neonatal nursing led research activity within the UK.

Methods

The study used a web-based survey design and neonatal nurses were eligible if they were working at or towards Masters or Doctoral level qualification in the UK. The survey was distributed to members of the Neonatal Nurses Association, UK Schools of Nursing and shared on social media pages of authors and professional organisations. Results were analysed using descriptive and frequency statistics and content analysis.

Results

Of the 56 respondents, 14% (n = 8) had a Doctoral level qualification and 43% (n = 24) of participants held a Masters qualification. Lack of time and funding knowledge was the largest barrier to research. Only 30% (n = 3) of participants had a research mentor and only 18% (n = 3) were from a neonatal nursing background.

Conclusions

There are limited numbers of neonatal nurses undertaking or leading nursing research in the UK. Further support is required to enhance clinical academic career trajectories to ensure research is a viable pathway for future generations of neonatal nurses.
The cost-saving effect of continuity of care (COC): an analysis of institutional COC on diabetic treatment costs using panel 2SLS regressions
Authors: Wen Yu-Ping , Liu Sandra S. , Sheu Ji-Tian , Wang Hong-Huei , Becker Edmund R. , Lu Jui-fen Rachel
Published: October 2021

Background

The high costs of chronic conditions call for new treatment approaches that reduce costs while ensuring desirable health outcomes. There has been a growing transformation of care delivery models from conventional referral systems to integrated care models. This study seeks to evaluate the cost-saving impact of integrated care delivery model under pay-for-performance (P4P) scheme with continuity of care at institution level (ICOC).

Methods

We analyzed the Taiwan National Health Insurance claim data of 21,725 diabetic patients who visited clinics and/or hospitals at least four times a year for 8 years. Using average local provider P4P participation rate (for each accreditation level) as an instrumental variable in two-stage least squares (2SLS) regressions, we have estimated consistent estimates of the ICOC elasticities for all-cause inpatient and outpatient costs.

Results

Our results show that ICOC significantly reduced inpatient costs but increased outpatient costs with the elasticity for treatment costs of -11.6 and 1.03, respectively. The decrease in inpatient costs offset the increase in outpatient costs and the resulting total cost saving showed significant association with ICOC. The saving effect of ICOC is especially robust among patients who used clinics as their principal source of care.

Conclusions

Institutional continuity of care has a substantial impact on the treatment costs of diabetes patients. In the context where inpatient care costs are significantly higher than that of the outpatient care, ICOC would lead to a meaningful cost-saving effect. For new diabetes patients, care by clinics demonstrated the strongest saving effect.
SaferBirths bundle of care protocol: a stepped-wedge cluster implementation project in 30 public health-facilities in five regions, Tanzania
Authors: Kamala Benjamin A. , Ersdal Hege L. , Mduma Estomih , Moshiro Robert , Girnary Sakina , Østrem Ole Terje , Linde Jørgen , Dalen Ingvild , Søyland Elsa , Bishanga Dunstan R. , Bundala Felix Ambrose , Makuwani Ahmad M. , Richard Boniphace Marwa , Muzzazzi Pius David , Kamala Ivony , Mdoe Paschal F.
Published: October 2021

Background

The burden of stillbirth, neonatal and maternal deaths are unacceptably high in low- and middle-income countries, especially around the time of birth. There are scarce resources and/or support implementation of evidence-based training programs. SaferBirths Bundle of Care is a well-proven package of innovative tools coupled with data-driven on-the-job training aimed at reducing perinatal and maternal deaths. The aim of this project is to determine the effect of scaling up the bundle on improving quality of intrapartum care and perinatal survival.

Methods

The project will follow a stepped-wedge cluster implementation design with well-established infrastructures for data collection, management, and analysis in 30 public health facilities in regions in Tanzania. Healthcare workers from selected health facilities will be trained in basic neonatal resuscitation, essential newborn care and essential maternal care. Foetal heart rate monitors (Moyo), neonatal heart rate monitors (NeoBeat) and skills trainers (NeoNatalie Live) will be introduced in the health facilities to facilitate timely identification of foetal distress during labour and improve neonatal resuscitation, respectively. Heart rate signal-data will be automatically collected by Moyo and NeoBeat, and newborn resuscitation training by NeoNatalie Live.

Given an average of 4000 baby-mother pairs per year per health facility giving an estimate of 240,000 baby-mother pairs for a 2-years duration, 25% reduction in perinatal mortality at a two-sided significance level of 5%, intracluster correlation coefficient (ICC) to be 0.0013, the study power stands at 0.99.

Discussion

Previous reports from small-scale Safer Births Bundle implementation studies show satisfactory uptake of interventions with significant improvements in quality of care and lives saved. Better equipped and trained birth attendants are more confident and skilled in providing care. Additionally, local data-driven feedback has shown to drive continuous quality of care improvement initiatives, which is essential to increase perinatal and maternal survival. Strengths of this research project include integration of innovative tools with existing national guidelines, local data-driven decision-making and training. Limitations include the stepwise cluster implementation design that may lead to contamination of the intervention, and/or inability to address the shortage of healthcare workers and medical supplies beyond the project scope.

Trial registration

Name of Trial Registry: ISRCTN Registry.

Trial registration number: ISRCTN30541755.

Date of Registration: 12/10/2020.

Type of registration: Prospectively Registered.
Non-destructive quantification of anaerobic gut fungi and methanogens in co-culture reveals increased fungal growth rate and changes in metabolic flux relative to mono-culture
Authors: Leggieri Patrick A. , Kerdman-Andrade Corey , Lankiewicz Thomas S. , Valentine Megan T. , O’Malley Michelle A.
Published: October 2021

Background

Quantification of individual species in microbial co-cultures and consortia is critical to understanding and designing communities with prescribed functions. However, it is difficult to physically separate species or measure species-specific attributes in most multi-species systems. Anaerobic gut fungi (AGF) (Neocallimastigomycetes) are native to the rumen of large herbivores, where they exist as minority members among a wealth of prokaryotes. AGF have significant biotechnological potential owing to their diverse repertoire of potent lignocellulose-degrading carbohydrate-active enzymes (CAZymes), which indirectly bolsters activity of other rumen microbes through metabolic exchange. While decades of literature suggest that polysaccharide degradation and AGF growth are accelerated in co-culture with prokaryotes, particularly methanogens, methods have not been available to measure concentrations of individual species in co-culture. New methods to disentangle the contributions of AGF and rumen prokaryotes are sorely needed to calculate AGF growth rates and metabolic fluxes to prove this hypothesis and understand its causality for predictable co-culture design.

Results

We present a simple, microplate-based method to measure AGF and methanogen concentrations in co-culture based on fluorescence and absorbance spectroscopies. Using samples of < 2% of the co-culture volume, we demonstrate significant increases in AGF growth rate and xylan and glucose degradation rates in co-culture with methanogens relative to mono-culture. Further, we calculate significant differences in AGF metabolic fluxes in co-culture relative to mono-culture, namely increased flux through the energy-generating hydrogenosome organelle. While calculated fluxes highlight uncertainties in AGF primary metabolism that preclude definitive explanations for this shift, our method will enable steady-state fluxomic experiments to probe AGF metabolism in greater detail.

Conclusions

The method we present to measure AGF and methanogen concentrations enables direct growth measurements and calculation of metabolic fluxes in co-culture. These metrics are critical to develop a quantitative understanding of interwoven rumen metabolism, as well as the impact of co-culture on polysaccharide degradation and metabolite production. The framework presented here can inspire new methods to probe systems beyond AGF and methanogens. Simple modifications to the method will likely extend its utility to co-cultures with more than two organisms or those grown on solid substrates to facilitate the design and deployment of microbial communities for bioproduction and beyond.
Establishment of a co-culture system using Escherichia coli and Pichia pastoris (Komagataella phaffii) for valuable alkaloid production
Authors: Urui Miya , Yamada Yasuyuki , Ikeda Yoshito , Nakagawa Akira , Sato Fumihiko , Minami Hiromichi , Shitan Nobukazu
Published: October 2021

Background

Plants produce a variety of specialized metabolites, many of which are used in pharmaceutical industries as raw materials. However, certain metabolites may be produced at markedly low concentrations in plants. This problem has been overcome through metabolic engineering in recent years, and the production of valuable plant compounds using microorganisms such as Escherichia coli or yeast cells has been realized. However, the development of complicated pathways in a single cell remains challenging. Additionally, microbial cells may experience toxicity from the bioactive compounds produced or negative feedback effects exerted on their biosynthetic enzymes. Thus, co-culture systems, such as those of E. coli–E. coli and E. coli-Saccharomyces cerevisiae, have been developed, and increased production of certain compounds has been achieved. Recently, a co-culture system of Pichia pastoris (Komagataella phaffii) has gained considerable attention due to its potential utility in increased production of valuable compounds. However, its co-culture with other organisms such as E. coli, which produce important intermediates at high concentrations, has not been reported.

Results

Here, we present a novel co-culture platform for E. coli and P. pastoris. Upstream E. coli cells produced reticuline from a simple carbon source, and the downstream P. pastoris cells produced stylopine from reticuline. We investigated the effect of four media commonly used for growth and production of P. pastoris, and found that buffered methanol-complex medium (BMMY) was suitable for P. pastoris cells. Reticuline-producing E. coli cells also showed better growth and reticuline production in BMMY medium than that in LB medium. De novo production of the final product, stylopine from a simple carbon source, glycerol, was successful upon co-culture of both strains in BMMY medium. Further analysis of the initial inoculation ratio showed that a higher ratio of E. coli cells compared to P. pastoris cells led to higher production of stylopine.

Conclusions

This is the first report of co-culture system established with engineered E. coli and P. pastoris for the de novo production of valuable compounds. The co-culture system established herein would be useful for increased production of heterologous biosynthesis of complex specialized plant metabolites.
UBTF facilitates melanoma progression via modulating MEK1/2-ERK1/2 signalling pathways by promoting GIT1 transcription
Authors: Zhang Jian , Zhang Jiaojiao , Liu Wenli , Ge Rui , Gao Tianyuan , Tian Qiong , Mu Xin , Zhao Lingyu , Li Xu
Published: October 2021

Background

UBTF is an HMGB-box DNA binding protein and a necessary Pol I/Pol II basal transcription factor. It has been found that UBTF involves in carcinogenesis and progression of a few cancers. Nevertheless, the the biological function and potential molecular mechanism of UBTF in melanoma are still not clear and need to be clarified.

Methods

UBTF and GIT1 expressions in melanoma specimens and cell lines were examined by quantitative real-time PCR (qRT-PCR) and Western blot. MTT and colony formation assays were used to investigate the effects of UBTF and GIT1 on melanoma cell proliferation. Cell cycle and apoptosis assays were detected by flow cytometry. Tumor formation assay was used to analyze the effect of UBTF on melanoma growth. Bioinformatics predicting, chromatin immunoprecipitation (ChIP)-qRT-PCR and reporter gene assay were fulfilled for verifing GIT1 as UBTF targeting gene.

Results

Here we reported that UBTF mRNA and protein expressions were upregulated in primary melanoma specimens and cell lines. UBTF overexpression facilitated melanoma cell proliferation and cell cycle progression and restrained. Silencing UBTF suppressed cell multiplication, cell cycle progression and tumor growth, and promoted apoptosis. UBTF expression was positively related with GIT1 expression in human melanoma tissues. It was verified that UBTF promoted GIT1 transcription in melanoma cells through binding to the promoter region of GIT1. Furthermore, GIT1 overexpression promoted melanoma cell growth and suppressed apoptosis. Knockdown of GIT1 inhibited cell multiplication and induced apoptosis. Overexpression of GIT1 eliminated the effects of silencing UBTF on melanoma cells. Importantly, UBTF activated MEK1/2-ERK1/2 signalling pathways by upregulating GIT1 expression.

Conclusions

Our study demonstrates that UBTF promotes melanoma cell proliferation and cell cycle progression by promoting GIT1 transcription, thereby activating MEK1/2-ERK1/2 signalling pathways. The findings indicate that UBTF plays a crucial function in melanoma and may be a potential therapeutic target for the treatment of this disease.
Chitosan as possible inhibitory agents and delivery systems in leukemia
Authors: Zivarpour Parinaz , Hallajzadeh Jamal , Asemi Zatollah , Sadoughi Fatemeh , Sharifi Mehran
Published: October 2021

Leukemia is a lethal cancer in which white blood cells undergo proliferation and immature white blood cells are seen in the bloodstream. Without diagnosis and management in early stages, this type of cancer can be fatal. Changes in protooncogenic genes and microRNA genes are the most important factors involved in development of leukemia. At present, leukemia risk factors are not accurately identified, but some studies have pointed out factors that predispose to leukemia. Studies show that in the absence of genetic risk factors, leukemia can be prevented by reducing the exposure to risk factors of leukemia, including smoking, exposure to benzene compounds and high-dose radioactive or ionizing radiation. One of the most important treatments for leukemia is chemotherapy which has devastating side effects. Chemotherapy and medications used during treatment do not have a specific effect and destroy healthy cells besides leukemia cells. Despite the suppressing effect of chemotherapy against leukemia, patients undergoing chemotherapy have poor quality of life. So today, researchers are focusing on finding more safe and effective natural compounds and treatments for cancer, especially leukemia. Chitosan is a valuable natural compound that is biocompatible and non-toxic to healthy cells. Anticancer, antibacterial, antifungal and antioxidant effects are examples of chitosan biopolymer properties. The US Food and Drug Administration has approved the use of this compound in medical treatments and the pharmaceutical industry. In this article, we take a look at the latest advances in the use of chitosan in the treatment and improvement of leukemia.
Exosomal transfer of miR-769-5p promotes osteosarcoma proliferation and metastasis by targeting DUSP16
Authors: Liu Wanshun , Wang Binyu , Duan Ao , Shen Kai , Zhang Qi , Tang Xiaolu , Wei Yongzhong , Tang Jian , Zhang Sheng
Published: October 2021

Background

Osteosarcoma (OS) is a malignant tumor originating from mesenchymal stem cells, and has an extremely high fatality rate and ability to metastasize. Although mounting evidence suggests that miR-769-5p is strongly associated with the malignant progression and poor prognosis of various tumors, the exact role of miR-769-5p in OS is still unclear. Therefore, this study aimed to explore the relationship between miR-769-5p and the malignant progression of OS, and its underlying mechanism of action.

Methods

miR-769-5p expression was analyzed in GSE28423 from the GEO database and measured in OS clinical specimens and cell lines. The effects of miR-769-5p on OS proliferation, migration and invasion were measured both in vivo and in vitro. In addition, bioinformatics analyses and luciferase reporter assays were used to explore the target genes of miR-769-5p. Rescue experiments were also conducted. Moreover, a co-culture model was used to test the cell interaction between bone mesenchymal stem cells (BMSC) and OS cells.

Results

We found that miR-769-5p is highly expressed in OS clinical specimens and cell lines. In vivo and in vitro experiments also showed that miR-769-5p significantly promoted the proliferation, migration and invasion of OS cells. Dual-specific phosphatase 16 (DUSP16) was negatively associated with miR-769-5p expression in OS cells and tissue samples and was validated as the downstream target by luciferase reporter assay and western blotting. Rescue experiments showed that DUSP16 reverses the effect of miR-769-5p on OS cells by negatively regulating the JNK/p38 MAPK signaling pathway. Additionally, the results of the co-culture of BMSCs and OS cells confirmed that miR-769-5p was transferred from BMSCs to OS cells through exosomes.

Conclusions

In summary, this study demonstrates for the first time that BMSC-derived exosomal miR-769-5p promotes OS proliferation and metastasis by targeting DUSP16 and activating the JNK/p38 MAPK signaling pathway, which could provide rationale for a new therapeutic strategy for OS.
Cost-effectiveness analysis of integrated community case management delivery models utilizing drug sellers and community health workers for treatment of under-five febrile cases of malaria, pneumonia, diarrhoea in rural Uganda
Authors: Lubogo Patrick , Lukyamuzi John Edward , Kyambadde Deo , Komakech Alex Aboda , Kitutu Freddy Eric , Mulogo Edgar Mugema
Published: October 2021

Background

Malaria, pneumonia and diarrhoea continue to be the leading causes of death in children under the age of five years (U5) in Uganda. To combat these febrile illnesses, integrated community case management (iCCM) delivery models utilizing community health workers (CHWs) or drug sellers have been implemented. The purpose of this study is to compare the cost-effectiveness of delivering iCCM interventions via drug sellers versus CHWs in rural Uganda.

Methods

This study was a cost-effectiveness analysis to compare the iCCM delivery model utilizing drug sellers against the model using CHWs. The effect measure was the number of appropriately treated U5 children, and data on effectiveness came from a quasi-experimental study in Southwestern Uganda and the inSCALE cross-sectional household survey in eight districts of mid-Western Uganda. The iCCM interventions were costed using the micro-costing (ingredients) approach, with costs expressed in US dollars. Cost and effect data were linked together using a decision tree model and analysed using the Amua modelling software.

Results

The costs per 100 treated U5 children were US$591.20 and US$298.42 for the iCCM trained-drug seller and iCCM trained-CHW models, respectively, with 30 and 21 appropriately treated children in the iCCM trained-drug seller and iCCM trained-CHW models. When the drug seller arm (intervention) was compared to the CHW arm (control), an incremental effect of 9 per 100 appropriately treated U5 children was observed, as well as an incremental cost of US$292.78 per 100 appropriately treated children, resulting in an incremental cost-effectiveness ratio (ICER) of US$33.86 per appropriately treated U5 patient.

Conclusion

Since both models were cost-effective compared to the do-nothing option, the iCCM trained-drug seller model could complement the iCCM trained-CHW intervention as a strategy to increase access to quality treatment.